FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Zile, MR Mehurg, SM Arroyo, JE Stroud, RE DeSantis, SM Spinale, FG AF Zile, Michael R. Mehurg, Shannon M. Arroyo, Jazmine E. Stroud, Robert E. DeSantis, Stacia M. Spinale, Francis G. TI Relationship Between the Temporal Profile of Plasma microRNA and Left Ventricular Remodeling in Patients After Myocardial Infarction SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE myocardial infarction; remodeling; microRNA ID CIRCULATING MICRORNAS; DISEASE; EXPRESSION; BIOMARKERS; HEART; FIBROSIS; MARKERS; CANCER; OCCURS; BLOOD AB Background-microRNAs (miRs) are small noncoding RNAs that recognize and bind to mRNAs and inhibit protein translation or degrade mRNA. Studies in animal models have suggested that miRs play a translational or posttranslational regulatory role in myocardial growth, fibrosis, viability, and remodeling. However, whether specific temporal changes in miRs occur in patients during the left ventricular (LV) remodeling process that follows a myocardial infarction (post-MI) remains unknown. The current pilot study tested the hypotheses that plasma miRs could be reliably measured in post-MI patients and that there is a relationship between temporal changes in specific miRs and post-MI LV structural remodeling. Methods and Results-LV end-diastolic volume (echocardiography) and plasma miR were measured in age-matched referent controls (CTLs, n = 12) and post-MI patients (n = 12) from day 2 through day 90 post-MI. Selected miRs (miR-1, miR-21, miR-29a, miR-133a, and miR-208) were measured using quantitative reverse transcription-polymerase chain reaction and normalized for endogenous small nuclear RNA U6. After MI, LV end-diastolic volume increased progressively compared with CTL; this was accompanied by time-dependent changes in specific miRs. For example, miR-21 initially decreased 2 days post-MI (0.3 +/- 0.1-fold versus CTL; P<0.05), increased 5 days post-MI (2 +/- 1-fold versus CTL; P<0.05), and returned to CTL values at later post-MI time points. In contrast, miR-29a increased 5 days post-MI (4 +/- 1-fold versus CTL; P<0.05) and then decreased to CTL at later time points. miR-208 increased 5 days post-MI (3 +/- 1-fold versus CTL; P<0.05) and remained elevated up to 90 days post-MI. Conclusions-A time-dependent change in miRs occurred in post-MI patients, including an early and robust increase in miRs that has affected myocardial growth, fibrosis, and viability. Thus, serially profiling miRs in the plasma of post-MI patients may hold both mechanistic and prognostic significance. (Circ Cardiovasc Genet. 2011;4:614-619.) C1 [Zile, Michael R.; Mehurg, Shannon M.] Med Univ S Carolina, Dept Med, Div Cardiol, Charleston, SC 29425 USA. [Arroyo, Jazmine E.; Stroud, Robert E.; Spinale, Francis G.] Med Univ S Carolina, Div Cardiothorac Surg, Dept Surg, Charleston, SC 29425 USA. [DeSantis, Stacia M.] Med Univ S Carolina, Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC 29425 USA. [DeSantis, Stacia M.] Med Univ S Carolina, Dept Biostat Bioinformat & Epidemiol, Charleston, SC 29425 USA. RP Zile, MR (reprint author), Med Univ S Carolina, Dept Med, Div Cardiol, Ashley River Towers,25 Courtenay Dr,Room 7067, Charleston, SC 29425 USA. EM zilem@musc.edu FU Doris Duke Foundation and Health Sciences of South Carolina; Research Service of the Department of Veterans Affairs; National Institutes of Health [HL057952, HL059165, HL095608] FX This study was supported by the Doris Duke Foundation and Health Sciences of South Carolina (Dr Zile); the Research Service of the Department of Veterans Affairs (Drs Zile and Spinale); grants HL057952, HL059165, and HL095608 from the National Institutes of Health (Dr Spinale). NR 24 TC 60 Z9 66 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1942-325X J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD DEC PY 2011 VL 4 IS 6 BP 614 EP 619 DI 10.1161/CIRCGENETICS.111.959841 PG 6 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA 866VR UT WOS:000298414800007 PM 21956146 ER PT J AU Lucas, G Lluis-Ganella, C Subirana, I Senti, M Willenborg, C Musameh, MD Schwartz, SM O'Donnell, CJ Melander, O Salomaa, V Elosua, R AF Lucas, Gavin Lluis-Ganella, Carla Subirana, Isaac Senti, Mariano Willenborg, Christina Musameh, Muntaser D. Schwartz, Stephen M. O'Donnell, Christopher J. Melander, Olle Salomaa, Veikko Elosua, Roberto CA CARDIoGRAM Consortium TI Post-Genomic Update on a Classical Candidate Gene for Coronary Artery Disease: ESR1 SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE coronary artery disease; estrogen receptor alpha; menopause; polymorphism; single nucleotide; genetic association studies; meta-analysis ID POSTMENOPAUSAL HORMONE-THERAPY; ESTROGEN PLUS PROGESTIN; HEART-DISEASE; MYOCARDIAL-INFARCTION; CARDIOVASCULAR-DISEASE; WIDE ASSOCIATION; COMMON DISEASE; 5 COHORTS; POLYMORPHISMS; WOMEN AB Background-After age, sex is the most important risk factor for coronary artery disease (CAD). The mechanism through which women are protected from CAD is still largely unknown, but the observed sex difference suggests the involvement of the reproductive steroid hormone signaling system. Genetic association studies of the gene-encoding Estrogen Receptor alpha (ESR1) have shown conflicting results, although only a limited range of variation in the gene has been investigated. Methods and Results-We exploited information made available by advanced new methods and resources in complex disease genetics to revisit the question of ESR1's role in risk of CAD. We performed a meta-analysis of 14 genome-wide association studies (CARDIoGRAM discovery analysis, N = approximate to 87 000) to search for population-wide and sex-specific associations between CAD risk and common genetic variants throughout the coding, noncoding, and flanking regions of ESR1. In addition to samples from the MIGen (N = approximate to 6000), WTCCC (N = approximate to 7400), and Framingham (N = approximate to 3700) studies, we extended this search to a larger number of common and uncommon variants by imputation into a panel of haplotypes constructed using data from the 1000 Genomes Project. Despite the widespread expression of ER alpha in vascular tissues, we found no evidence for involvement of common or low-frequency genetic variation throughout the ESR1 gene in modifying risk of CAD, either in the general population or as a function of sex. Conclusions-We suggest that future research on the genetic basis of sex-related differences in CAD risk should initially prioritize other genes in the reproductive steroid hormone biosynthesis system. (Circ Cardiovasc Genet. 2011;4:647-654.) C1 [Lucas, Gavin; Lluis-Ganella, Carla; Subirana, Isaac; Senti, Mariano; Elosua, Roberto] IMIM, Cardiovasc Epidemiol & Genet Grp, Barcelona 08003, Spain. [Subirana, Isaac; Elosua, Roberto] CIBERESP, Epidemiol & Publ Hlth Network, Madrid, Spain. [Senti, Mariano] Pompeu Fabra Univ, Barcelona, Spain. [Willenborg, Christina] Univ Lubeck, Inst Med Biometrie & Stat, Lubeck, Germany. Univ Lubeck, Med Klin 2, Lubeck, Germany. [Musameh, Muntaser D.] Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England. [Musameh, Muntaser D.] Glenfield Hosp, Leicester Cardiovasc Biomed Res Unit, Leicester, Leics, England. [Schwartz, Stephen M.] Univ Washington, Dept Med, Seattle, WA USA. [Schwartz, Stephen M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Schwartz, Stephen M.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [O'Donnell, Christopher J.] NHLBI, Framingham, MA USA. [O'Donnell, Christopher J.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [O'Donnell, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Melander, Olle] Lund Univ, Malmo Univ Hosp, Dept Clin Sci Hypertens & Cardiovasc Dis, Malmo, Sweden. [Salomaa, Veikko] Natl Inst Hlth & Welf, Helsinki, Finland. RP Lucas, G (reprint author), IMIM, Cardiovasc Epidemiol & Genet Grp, C Doctor Aiguader 88, Barcelona 08003, Spain. EM glucas@imim.es RI Willenborg, Christina/D-2668-2012; Lucas, Gavin/D-4346-2012; Lluis-Ganella, Carla/G-5998-2012; Senti, M/D-4309-2014; Gudnason, Vilmundur/K-6885-2015; Meitinger, Thomas/O-1318-2015; OI Willenborg, Christina/0000-0001-5217-6882; Lluis-Ganella, Carla/0000-0001-7609-5497; Gudnason, Vilmundur/0000-0001-5696-0084; ELOSUA, ROBERTO/0000-0001-8235-0095; Senti, Mariano/0000-0002-6983-3831; Kleber, Marcus/0000-0003-0663-7275 FU National Institutes of Health [R01 HL087676]; Wellcome Trust [085475]; National Heart, Lung, and Blood institute; Boston University [N01-HC-25195]; European Regional Development Fund; Spanish Ministry of Science and Innovation through the Carlos III Health Institute [CIBER Epidemiolog a y Salud Publica, Red HERACLES] [RD06/0009, PI061254, PI09/90506]; Catalan Research and Technology Innovation Interdepartmental Commission [SGR 1195]; Juan de la Cierva Program, Ministerio de Educacion [JCI-2009-04684]; [ACC1O (RD08-1-0024)] FX Information on funding sources for the studies that contributed to The CARDIoGRAM Consortium were provided previously.21 The Myocardial Infarction Genetics (MIGen) Consortium24 was funded by grant R01 HL087676 from the National Institutes of Health. The Wellcome Trust Case-Control Consortium 2 was funded by the Wellcome Trust under award 085475. The Framingham Heart Study is conducted and supported by the National Heart, Lung, and Blood institute in collaboration with Boston University (Contract No. N01-HC-25195). This work was supported by a grant from ACC1O (RD08-1-0024), the European Regional Development Fund, the Spanish Ministry of Science and Innovation through the Carlos III Health Institute [CIBER Epidemiolog a y Salud Publica, Red HERACLES RD06/0009, PI061254, PI09/90506], and by the Catalan Research and Technology Innovation Interdepartmental Commission [SGR 1195]. Dr Lucas was funded by the Juan de la Cierva Program, Ministerio de Educacion (JCI-2009-04684). NR 36 TC 1 Z9 2 U1 1 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1942-325X J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD DEC PY 2011 VL 4 IS 6 BP 647 EP U357 DI 10.1161/CIRCGENETICS.111.960583 PG 27 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA 866VR UT WOS:000298414800011 PM 21984528 ER PT J AU Freedman, RA Bullitt, E Sun, LX Gelman, R Harris, G Ligibel, JA Krop, IE Partridge, AH Eisenberg, E Winer, EP Lin, NU AF Freedman, Rachel A. Bullitt, Elizabeth Sun, Lixian Gelman, Rebecca Harris, Gordon Ligibel, Jennifer A. Krop, Ian E. Partridge, Ann H. Eisenberg, Emily Winer, Eric P. Lin, Nancy U. TI A Phase II Study of Sagopilone (ZK 219477; ZK-EPO) in Patients With Breast Cancer and Brain Metastases SO CLINICAL BREAST CANCER LA English DT Article DE Central nervous system; Epothilone; Metastases; ZK-EPO ID FULLY SYNTHETIC EPOTHILONE; NERVOUS-SYSTEM METASTASES; SOLID TUMORS; VESSEL TORTUOSITY; IXABEPILONE BMS-247550; CLINICAL DEVELOPMENT; B ANALOG; TRIAL; CARCINOMA; LAPATINIB AB Treatments for women with recurrent brain metastases from breast cancer are limited. In this phase II study, we administered sagopilone to patients with breast cancer and brain metastases. We observed modest activity with a central nervous system objective response rate of 13.3%; however, median PFS was disappointing. Further studies should focus on other agents to treat this challenging clinical problem. Background: Patients with progressive metastatic breast cancer to the central nervous system (CNS) have limited treatment options. Patients and Methods: We conducted a phase II study of sagopilone, an epothilone B analogue that crosses the blood-brain barrier, in patients with breast cancer brain metastases. Women were treated with 16 mg/m(2) or 22 mg/m(2) intravenously every 21 days. The primary endpoint was CNS objective response rate (ORR). Secondary endpoints included toxicity, progression-free survival (PFS), and overall survival (OS). Using modified, high-resolution magnetic resonance angiography (MRA), we also evaluated changes in vessel tortuosity with treatment. Results: Fifteen women were enrolled; all had progressive CNS disease despite whole-brain radiotherapy. Two patients achieved a partial response (ORR, 13.3%) and remained in the study for 6 cycles. Responses were not associated with normalization of tumor-associated vessels on correlative imaging studies. Median PFS and OS were 1.4 months and 5.3 months, respectively. The most common grade 3 toxicities were lymphopenia and fatigue. Enrollment was stopped prematurely because of limited observed activity and slow accrual. Conclusions: Sagopilone was associated with modest CNS activity in patients with breast cancer; however median PFS was disappointing. Further studies should examine other potentially active agents and/or combinations for this challenging clinical problem. Clinical Breast Cancer, Vol. 11, No. 6, 376-83 (C) 2011 Elsevier Inc. All rights reserved. C1 [Freedman, Rachel A.; Ligibel, Jennifer A.; Krop, Ian E.; Partridge, Ann H.; Eisenberg, Emily; Winer, Eric P.; Lin, Nancy U.] Harvard Univ, Dana Farber Canc Inst, Dept Med Oncol, Sch Med, Boston, MA 02115 USA. [Bullitt, Elizabeth] Univ N Carolina, Dept Neurosurg, Chapel Hill, NC USA. [Sun, Lixian; Gelman, Rebecca] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Harris, Gordon] Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Sch Med, Boston, MA 02115 USA. RP Freedman, RA (reprint author), Harvard Univ, Dana Farber Canc Inst, Dept Med Oncol, Sch Med, 44 Binney St, Boston, MA 02115 USA. EM rafreedman@partners.org FU American Society of Clinical Oncology; National Cancer Institute of Research Excellence in Breast Cancer at Dana-Farber/Harvard Cancer Center [CA89393]; Karen Webster and David Evans Research Fund; Breast Cancer Research Foundation; Dana-Farber/Harvard Cancer Center [CA006516]; National Institutes of Health [R01 CA124608, R01 EB000219]; Bayer HealthCare Pharmaceuticals FX This work was supported by the American Society of Clinical Oncology Career Development Award (Nancy Lin), the National Cancer Institute Specialized Program of Research Excellence in Breast Cancer at Dana-Farber/Harvard Cancer Center (CA89393), the Karen Webster and David Evans Research Fund (Nancy Lin, Eric Winer); the Breast Cancer Research Foundation (Nancy Linn) the Dana-Farber/Harvard Cancer Center grant CA006516 (Lixian Sun, Rebecca Gelman), the National Institutes of Health (R01 CA124608 and R01 EB000219) [E. B.], and Bayer HealthCare Pharmaceuticals. NR 40 TC 25 Z9 25 U1 2 U2 6 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1526-8209 J9 CLIN BREAST CANCER JI Clin. Breast Cancer PD DEC PY 2011 VL 11 IS 6 BP 376 EP 383 DI 10.1016/j.clbc.2011.03.024 PG 8 WC Oncology SC Oncology GA 863JQ UT WOS:000298159200005 PM 21697017 ER PT J AU Tonon, G Anderson, KC AF Tonon, Giovanni Anderson, Kenneth C. TI Disentangling the Myeloma Web SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID GENE-EXPRESSION PROFILES; MULTIPLE-MYELOMA; NETWORKS AB Gene expression profiling in patients with multiple myeloma has identified gene signatures linked to prognosis. However, because of their heterogeneity, there is currently no consensus about which signatures represent the best predictive and prognostic markers. Novel computational tools are now helping investigators integrate heterogeneous data sets to identify universal and robust classifiers. Clin Cancer Res; 17(23); 7210-2. (C)2011 AACR. C1 [Tonon, Giovanni] Ist Sci San Raffaele, Div Mol Oncol, Funct Genom Canc Unit, I-20132 Milan, Italy. [Anderson, Kenneth C.] Dana Farber Canc Inst, Jerome Lipper Ctr Multiple Myeloma Res, Dept Med Oncol, Boston, MA 02115 USA. [Anderson, Kenneth C.] Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, Dept Med Oncol, Boston, MA 02115 USA. RP Tonon, G (reprint author), Ist Sci San Raffaele, Div Mol Oncol, Funct Genom Canc Unit, Via Olgettina, I-20132 Milan, Italy. EM tonon.giovanni@hsr.it; kenneth_anderson@dfci.harvard.edu NR 12 TC 2 Z9 2 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 1 PY 2011 VL 17 IS 23 BP 7210 EP 7212 DI 10.1158/1078-0432.CCR-11-2316 PG 3 WC Oncology SC Oncology GA 862ZW UT WOS:000298133600002 PM 21989063 ER PT J AU Sasaki, T Janne, PA AF Sasaki, Takaaki Jaenne, Pasi A. TI New Strategies for Treatment of ALK-Rearranged Non-Small Cell Lung Cancers SO CLINICAL CANCER RESEARCH LA English DT Article ID EML4-ALK FUSION GENE; TRANSBRONCHIAL NEEDLE ASPIRATION; TYROSINE KINASE INHIBITORS; RESISTANCE; LYMPHOMA; IMMUNOHISTOCHEMISTRY; ADENOCARCINOMA; ONCOGENE; MUTATION; FEATURES AB The identification of oncogenic alterations in subsets of patients with non-small cell lung cancer (NSCLC) is transforming clinical care. Genomic rearrangements in anaplastic lymphoma kinase (ALK) are detected in 3% to 7% of patients with NSCLC. The ALK tyrosine kinase inhibitor crizotinib has demonstrated clinical efficacy in ALK-rearranged NSCLC patients and was recently approved by the U. S. Food and Drug Administration. Crizotinib is currently under additional phase III clinical development as both initial and second-line therapy for advanced ALK-rearranged NSCLC. However, new challenges in the diagnosis and treatment of this subset of NSCLC have emerged, including the need to determine the most effective means of diagnosing ALK-rearranged NSCLC and the emergence of acquired drug resistance to crizotinib. In this review, we discuss current strategies for treatment and diagnosis, as well as the current knowledge about mechanisms of acquired resistance to crizotinib. Finally, we discuss the strategies that are underway to clinically overcome acquired drug resistance. Clin Cancer Res; 17(23); 7213-8. (C)2011 AACR. C1 [Jaenne, Pasi A.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02215 USA. [Jaenne, Pasi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Jaenne, Pasi A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Jaenne, Pasi A.] Harvard Univ, Sch Med, Boston, MA USA. [Sasaki, Takaaki] Asahikawa Med Univ, Resp Ctr, Asahikawa, Hokkaido, Japan. RP Janne, PA (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, M422,450 Brookline Ave, Boston, MA 02215 USA. EM pjanne@partners.org OI Sasaki, Takaaki/0000-0002-6505-8786 FU NIH [R01CA136851]; National Cancer Institute Lung SPORE [P50CA090578]; Cammarata Family Foundation FX NIH (R01CA136851), National Cancer Institute Lung SPORE (P50CA090578), and the Cammarata Family Foundation Research Fund (all to P.A. Janne). NR 30 TC 39 Z9 42 U1 1 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 1 PY 2011 VL 17 IS 23 BP 7213 EP 7218 DI 10.1158/1078-0432.CCR-11-1404 PG 6 WC Oncology SC Oncology GA 862ZW UT WOS:000298133600003 PM 22010214 ER PT J AU Cheema, TA Kanai, R Kim, GW Wakimoto, H Passer, B Rabkin, SD Martuza, RL AF Cheema, Tooba A. Kanai, Ryuichi Kim, Geon Woo Wakimoto, Hiroaki Passer, Brent Rabkin, Samuel D. Martuza, Robert L. TI Enhanced Antitumor Efficacy of Low-Dose Etoposide with Oncolytic Herpes Simplex Virus in Human Glioblastoma Stem Cell Xenografts SO CLINICAL CANCER RESEARCH LA English DT Article ID RECURRENT MALIGNANT GLIOMA; ORAL ETOPOSIDE; PHASE-II; METRONOMIC CHEMOTHERAPY; TOPOISOMERASE-I; CANCER-CELLS; DEATH; EXPRESSION; REPLICATION; INHIBITORS AB Purpose: Glioblastoma (GBM) inevitably recurs despite surgery, radiation, and chemotherapy. A subpopulation of tumor cells, GBM stem cells (GSC), has been implicated in this recurrence. The chemotherapeutic agent etoposide is generally reserved for treating recurrent tumors; however, its effectiveness is limited due to acute and cumulative toxicities to normal tissues. We investigate a novel combinatorial approach of low-dose etoposide with an oncolytic HSV to enhance antitumor activity and limit drug toxicity. Experimental Design: In vitro, human GBM cell lines and GSCs were treated with etoposide alone, oncolytic herpes simplex virus (oHSV) G47 Delta alone, or the combination. Cytotoxic interactions were analyzed using the Chou-Talalay method, and changes in caspase-dependent apoptosis and cell cycle were determined. In vivo, the most etoposide-resistant human GSC, BT74, was implanted intracranially and treated with either treatment alone or the combination. Analysis included effects on survival, therapy-associated adverse events, and histologic detection of apoptosis. Results: GSCs varied in their sensitivity to etoposide by over 50-fold in vitro, whereas their sensitivity to G47 Delta was similar. Combining G47 Delta with low-dose etoposide was moderately synergistic in GSCs and GBM cell lines. This combination did not enhance virus replication, but significantly increased apoptosis. In vivo, the combination of a single cycle of low-dose etoposide with G47 Delta significantly extended survival of mice-bearing etoposide-insensitive intracranial human GSC-derived tumors. Conclusions: The combination of low-dose etoposide with G47 Delta increases survival of mice-bearing intracranial human GSC-derived tumors without adverse side effects. These results establish this as a promising combination strategy to treat resistant and recurrent GBM. Clin Cancer Res; 17(23); 7383-93. (C)2011 AACR. C1 [Martuza, Robert L.] Massachusetts Gen Hosp, Dept Neurosurg, Brain Tumor Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Martuza, RL (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, Brain Tumor Res Ctr, 55 Fruit St,GB502, Boston, MA 02114 USA. EM rmartuza@partners.org RI rabkin, samuel/C-2443-2012 OI rabkin, samuel/0000-0003-2344-2795 FU NIH [NS-032677]; Joelle Syverson American Brain Tumor Basic Research Fellowship FX These studies were supported by NIH grant NS-032677 (R.L. Martuza) and Joelle Syverson American Brain Tumor Basic Research Fellowship (T.A. Cheema). NR 50 TC 23 Z9 25 U1 1 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 1 PY 2011 VL 17 IS 23 BP 7383 EP 7393 DI 10.1158/1078-0432.CCR-11-1762 PG 11 WC Oncology SC Oncology GA 862ZW UT WOS:000298133600020 PM 21976549 ER PT J AU O'Leary, TJ AF O'Leary, Timothy J. TI "Research Use Only" Reagents: Is There an Imperative for Increased FDA Oversight? SO CLINICAL CHEMISTRY LA English DT Article C1 Vet Hlth Adm, Off Res & Dev, US Dept Vet Affairs, Washington, DC 20420 USA. RP O'Leary, TJ (reprint author), Vet Hlth Adm, Off Res & Dev, US Dept Vet Affairs, 810 Vermont Ave NW, Washington, DC 20420 USA. EM timothy.oleary@va.gov NR 3 TC 1 Z9 1 U1 0 U2 2 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD DEC PY 2011 VL 57 IS 12 BP 1681 EP 1683 DI 10.1373/clinchem.2011.174268 PG 3 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 862UM UT WOS:000298119600009 PM 21998341 ER PT J AU Litsas, G AF Litsas, Georgia TI Nursing Perspectives on Fulvestrant for the Treatment of Postmenopausal Women With Metastatic Breast Cancer SO CLINICAL JOURNAL OF ONCOLOGY NURSING LA English DT Article ID ENDOCRINE THERAPY; PURE ANTIESTROGEN; DOUBLE-BLIND; ANASTROZOLE; MODEL; TRIAL; ADHERENCE AB Fulvestrant is an estrogen receptor antagonist indicated for the treatment of hormone receptor-positive metastatic breast cancer (MBC) in postmenopausal women with disease progression following antiestrogen therapy. Fulvestrant has a different mechanism of action than other hormonal therapies, including aromatase inhibitors and tamoxifen. In clinical trials of postmenopausal women with MBC, fulvestrant was effective and well tolerated compared to anastrozole after failure of tamoxifen. The monthly injection regimen of fulvestrant provides nurses with an additional opportunity to improve patient adherence to hormonal therapy, reinforce patient education, and monitor side effects. Several ongoing trials will elucidate the role of fulvestrant in the treatment of MBC. Issues that are being addressed in those trials include alternative doses and schedules, efficacy and safety in other patient populations, and the development of novel treatment combinations. This article provides oncology nurses with the knowledge needed to educate patients on the use of fulvestrant, to effectively administer this medication, and to prevent and manage potential side effects. C1 Dana Farber Canc Inst, Dept Med Oncol, Breast Oncol Ctr, Boston, MA 02115 USA. RP Litsas, G (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Breast Oncol Ctr, Boston, MA 02115 USA. EM georgia_litsas@dfci.harvard.edu NR 35 TC 0 Z9 0 U1 1 U2 2 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 1092-1095 J9 CLIN J ONCOL NURS JI Clin. J. Oncol. Nurs. PD DEC PY 2011 VL 15 IS 6 BP 674 EP 681 DI 10.1188/11.CJON.674-681 PG 8 WC Oncology; Nursing SC Oncology; Nursing GA 862WR UT WOS:000298125300014 PM 22119979 ER PT J AU Muhammed, KI Morledge, T Sachar, R Zeldin, A Wolski, K Bhatt, DL AF Muhammed, Kamran I. Morledge, Thomas Sachar, Ravish Zeldin, Annette Wolski, Kathy Bhatt, Deepak L. TI Treatment with omega-3 fatty acids reduces serum C-reactive protein concentration SO CLINICAL LIPIDOLOGY LA English DT Article DE omega-3 fatty acids; C-reactive protein; fish oils; inflammation; prevention ID POLYUNSATURATED FATTY-ACIDS; HEART-RATE-VARIABILITY; SUDDEN CARDIAC DEATH; CARDIOVASCULAR-DISEASE; FISH CONSUMPTION; STATIN THERAPY; MYOCARDIAL-INFARCTION; DOCOSAHEXAENOIC ACID; CONTROLLED-TRIAL; CORONARY EVENTS AB Background: Studies have demonstrated that patients with diets high in omega-3 fatty acids have a lower risk of adverse cardiovascular events. C-reactive protein (CRP), a marker of inflammation, is a strong predictor of future cardiovascular events. omega-3 fatty acids have been shown to have anti-inflammatory properties. However, there is a paucity of data examining the effect of omega-3 fatty acids on CRP levels. This randomized, double-blind, placebo-controlled trial tested the hypothesis that treatment with omega-3 polyunsaturated fatty acids (n-3 PUFAs) would reduce serum high-sensitivity CRP levels. Materials & methods: Fifty three patients with elevated baseline CRP (>= 3 mg/l) were randomized to n-3 PUFA (27 patients) or placebo (26 patients). Patients with active infection, inflammatory disease, baseline CRP >= 10 mg/l or those started on HMG-CoA reductase inhibitor therapy during the study period were excluded. The primary end point was CRP level following 8 weeks of treatment. Results: After 8 weeks of treatment with the study drug, the median CRP level in the n-3 PUFA group was 3.4 mg/l compared with 4.0 mg/l in the placebo group (p = 0.36). After controlling for baseline CRP, there was a significant percentage decrease in CRP from baseline in the n-3 PUFA group (-40.3%; p = 0.009) but not in the placebo group (-16.4%; p = 0.32) Conclusion: Treatment for 8 weeks with omega-3 fatty acids resulted in a significant percentage reduction of CRP levels as compared with baseline, a finding not seen with placebo. C1 [Muhammed, Kamran I.] Oklahoma Heart Inst, Tulsa, OK 74104 USA. [Morledge, Thomas] Cleveland Clin Wellness Enterprise, Lyndhurst, OH 44124 USA. [Sachar, Ravish] Wake Heart & Vasc, Raleigh, NC 27610 USA. [Zeldin, Annette; Wolski, Kathy] Cleveland Clin, Cleveland, OH 44195 USA. RP Bhatt, DL (reprint author), VA Boston Healthcare Syst, 1400 VPW Pkwy, Boston, MA 02132 USA. EM dlbhattmd@post.harvard.edu FU Amarin; Astra Zeneca; Bristol-Myers Squibb; Eisai; Ethicon; Medtronic; Sanofi Aventis; Medicines Company FX DL Bhatt has received research grants from Amarin, Astra Zeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi Aventis, and The Medicines Company. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 53 TC 2 Z9 2 U1 1 U2 5 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1758-4299 J9 CLIN LIPIDOL JI Clin. Lipidol. PD DEC PY 2011 VL 6 IS 6 BP 723 EP 729 DI 10.2217/CLP.11.54C PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 875GM UT WOS:000299018400014 ER PT J AU Akinkuolie, AO Ngwa, JS Meigs, JB Djousse, L AF Akinkuolie, Akintunde O. Ngwa, Julius S. Meigs, James B. Djousse, Luc TI Omega-3 polyunsaturated fatty acid and insulin sensitivity: A meta-analysis of randomized controlled trials SO CLINICAL NUTRITION LA English DT Review DE Insulin sensitivity; Diabetes; Omega-3 polyunsaturated fatty acids; Randomized controlled trials; Meta-analysis ID DEPENDENT DIABETES-MELLITUS; FISH-OIL SUPPLEMENTATION; HEPATIC GLUCOSE-PRODUCTION; BLOOD-PRESSURE; DIETARY SUPPLEMENTATION; CARDIOVASCULAR-DISEASE; METABOLIC SYNDROME; GLYCEMIC CONTROL; LINOLEIC-ACID; RESISTANCE AB Background &aim: n-3 PUFA has been shown to decrease the risk of several components of the metabolic syndrome; however, the role of n-3 PUFA on glucose metabolism is not clear. Our aim was to systematically review the effect of n-3 PUFA on IS by conducting a meta-analysis of available RCTs. Methods: We followed the guidelines of Cochrane's review of systematic interventions. We searched MEDLINE, EMBASE, CENTRAL and clinicaltrials.gov from the beginning of each database until October 2010. Meta-analysis was performed using a random effects model to estimate a pooled SMD and the corresponding 95% Cl. Results: From 303 screened citations, 11 RCTs (n = 618) were eligible for inclusion in the analysis. In a pooled estimate, n-3 PUFA intervention had no effects on IS compared to placebo (SMD 0.08, 95% Cl -0.11-0.28). Similarly, n-3 PUFA had no effects on IS in sub-group analyses (Type 2 diabetes vs. other population; QUICKI and other test subgroups). In the HOMA subgroup, n-3 PUFA was associated with a statistically significant increase in IS (SMD 0.30, Cl 0.03-0.58) when compared to placebo. Conclusion: This meta-analysis is consistent with a lack of n-3 PUFA effects on IS. (C) 2011 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved. C1 [Akinkuolie, Akintunde O.; Ngwa, Julius S.] Boston Univ, Sch Publ Hlth, Boston, MA 02118 USA. [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Meigs, James B.; Djousse, Luc] Harvard Univ, Sch Med, Boston, MA USA. [Djousse, Luc] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA. [Djousse, Luc] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol & Informat Res Ctr MA, Boston, MA USA. RP Akinkuolie, AO (reprint author), Boston Univ, Sch Publ Hlth, Boston, MA 02118 USA. EM tunde@bu.edu RI Djousse, Luc/F-5033-2017 OI Djousse, Luc/0000-0002-9902-3047 FU NHLBI NIH HHS [N01 HC025195] NR 58 TC 69 Z9 69 U1 1 U2 27 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0261-5614 J9 CLIN NUTR JI Clin. Nutr. PD DEC PY 2011 VL 30 IS 6 BP 702 EP 707 DI 10.1016/j.clnu.2011.08.013 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 874EY UT WOS:000298939400002 PM 21959352 ER PT J AU Merida-Puga, J Ramirez-Bermudez, J Aguilar-Venegas, LC Fricchione, GL Espinola-Nadurille, M AF Merida-Puga, Jorge Ramirez-Bermudez, Jesus Aguilar-Venegas, Luis Carlos Fricchione, Gregory L. Espinola-Nadurille, Mariana TI Westphal Variant Huntington Disease and Refractory Catatonia: A Case Report SO COGNITIVE AND BEHAVIORAL NEUROLOGY LA English DT Article DE Huntington disease; Westphal variant; amantadine; levodopa; resistant catatonia ID NEUROPSYCHIATRIC ASPECTS; MALIGNANT CATATONIA; ECT; THERAPY; LEVODOPA AB A young woman with Westphal variant (juvenile) Huntington disease (HD) also developed catatonia. Catatonia is an underdiagnosed psychomotor syndrome often associated with neurological and psychiatric disorders, but it has rarely been documented in patients with HD. Catatonia usually responds to standard treatment with benzodiazepines and electroconvulsive therapy; however, this patient's catatonic syndrome did not improve until we augmented the standard treatment with amantadine and levodopa. The underlying pathophysiology and a neurochemical hypothesis of HD and catatonia can explain their comorbidity and the refractoriness of catatonia to treatment. Both conditions are linked to dysregulation of neurotransmitters in the striatocortical and corticocortical pathways. This understanding may serve as a guide for the use of nonstandard treatments. Our evidence also suggests that electroconvulsive therapy can be useful and safe in the treatment of HD. C1 [Merida-Puga, Jorge; Ramirez-Bermudez, Jesus; Aguilar-Venegas, Luis Carlos; Espinola-Nadurille, Mariana] Natl Inst Neurol & Neurosurg Mexico, Dept Neuropsychiat, Colonia La Fama 14269, Chiapas, Mexico. [Espinola-Nadurille, Mariana] Natl Inst Neurol & Neurosurg Mexico, Dept Social Psychiat, Colonia La Fama 14269, Chiapas, Mexico. [Ramirez-Bermudez, Jesus] Univ Nacl Autonoma Mexico, Sch Med, Mexico City, DF, Mexico. [Fricchione, Gregory L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Espinola-Nadurille, M (reprint author), Natl Inst Neurol & Neurosurg Mexico, Dept Neuropsychiat, Insurgentes Sur 3877, Colonia La Fama 14269, Chiapas, Mexico. EM menadu2002@yahoo.com.mx NR 26 TC 3 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1543-3633 J9 COGN BEHAV NEUROL JI Cogn. Behav. Neurol. PD DEC PY 2011 VL 24 IS 4 BP 204 EP 208 DI 10.1097/WNN.0b013e318240080d PG 5 WC Behavioral Sciences; Clinical Neurology SC Behavioral Sciences; Neurosciences & Neurology GA 863GQ UT WOS:000298151200005 PM 22123587 ER PT J AU Mukete, BN Atlas, SA AF Mukete, Bertrand N. Atlas, Steven A. TI Implications of Changes in Plasma Asymmetric Dimethylarginine During Treatment of Hypertension SO CURRENT HYPERTENSION REPORTS LA English DT Editorial Material DE Dimethylarginine; Hypertension; Treatment; Clinical trial; Nebivolol; Metoprolol; Beta-blockers; Nitric oxide synthase; Arginine; Antihypertensive agents ID BETA(3)-ADRENOCEPTOR AGONISTS; NEBIVOLOL; DRUGS C1 [Mukete, Bertrand N.; Atlas, Steven A.] James J Peters VA Med Ctr, Bronx, NY 10468 USA. [Mukete, Bertrand N.; Atlas, Steven A.] Mt Sinai Sch Med, New York, NY 10028 USA. RP Atlas, SA (reprint author), James J Peters VA Med Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM steven.atlas@va.gov NR 9 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1522-6417 J9 CURR HYPERTENS REP JI Curr. Hypertens. Rep. PD DEC PY 2011 VL 13 IS 6 BP 406 EP 408 DI 10.1007/s11906-011-0233-8 PG 3 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 874ZA UT WOS:000298996300004 PM 22045470 ER PT J AU Wucherpfennig, KW Noelle, RJ AF Wucherpfennig, Kai W. Noelle, Randolph J. TI Untitled SO CURRENT OPINION IN IMMUNOLOGY LA English DT Editorial Material C1 [Wucherpfennig, Kai W.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Wucherpfennig, Kai W.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Noelle, Randolph J.] Kings Coll London, Dept Nephrol & Transplantat, MRC Ctr Transplantat, Guys Hosp, London SE1 9RT, England. [Noelle, Randolph J.] Dartmouth Med Sch, Dept Microbiol & Immunol, Lebanon, NH 03756 USA. RP Wucherpfennig, KW (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 450 Brookline Ave, Boston, MA 02115 USA. EM kai_wucherpfennig@dfci.harvard.edu; rjn@dartmouth.edu FU Medical Research Council [G0802651]; NCCIH NIH HHS [R01 AT005382]; Wellcome Trust [091823] NR 0 TC 1 Z9 1 U1 0 U2 3 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD DEC PY 2011 VL 23 IS 6 BP 699 EP 701 DI 10.1016/j.coi.2011.10.003 PG 3 WC Immunology SC Immunology GA 869UG UT WOS:000298623100001 PM 22056155 ER PT J AU Pillai, S Mattoo, H Cariappa, A AF Pillai, Shiv Mattoo, Hamid Cariappa, Annaiah TI B cells and autoimmunity SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; REGULATORY T-CELLS; LYN-DEFICIENT MICE; RHEUMATOID-ARTHRITIS; ULCERATIVE-COLITIS; PHASE-II; IN-VIVO; TOLERANCE CHECKPOINTS; LYMPHOCYTE DEPLETION; INADEQUATE RESPONSE AB There is a growing appreciation for the role for B cells in autoimmune disorders in which inflammation is driven by T cells, in addition to the well-established role for B cells in autoimmune disorders characterized by pathogenic auto-antibodies. Current information on tolerance checkpoints in B cells, B cell depletion, BAFF blockade, regulatory B cells and clonal ignorance mediated by the SIAE/Siglec pathway will be reviewed. C1 [Pillai, Shiv] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Pillai, S (reprint author), Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02129 USA. EM pillai@helix.mgh.harvard.edu FU NIH [AI076505, AR058481, AI064930]; Alliance for Lupus Research FX This work was supported by grants AI076505, AR058481, and AI064930 from the NIH and a grant from the Alliance for Lupus Research. NR 106 TC 48 Z9 49 U1 0 U2 8 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD DEC PY 2011 VL 23 IS 6 BP 721 EP 731 DI 10.1016/j.coi.2011.10.007 PG 11 WC Immunology SC Immunology GA 869UG UT WOS:000298623100005 PM 22119110 ER PT J AU Ibrahimi, OA Sharon, V Eisen, DB AF Ibrahimi, Omar A. Sharon, Victoria Eisen, Daniel B. TI Surgical-Site Infections and Routes of Bacterial Transfer: Which Ones Are Most Plausible? SO DERMATOLOGIC SURGERY LA English DT Review ID RESISTANT STAPHYLOCOCCUS-AUREUS; MOHS MICROGRAPHIC SURGERY; HIGH-SPEED PHOTOGRAPHY; OPERATING-ROOM; WOUND INFECTIONS; PROPHYLACTIC ANTIBIOTICS; DERMATOLOGICAL SURGERY; GLOVE PERFORATION; POSTOPERATIVE INFECTIONS; STREPTOCOCCUS-PYOGENES AB BACKGROUND Surgical-site infections (SSIs) are an unfortunate consequence of cutaneous surgery. Their incidence can be a significant problem for patients and surgeons. Most SSIs are presumed to originate from the patient and operating room staff. OBJECTIVES To review the potential routes of iatrogenic bacterial transfer during cutaneous surgery. METHODS A review of the medical literature. CONCLUSIONS Potential routes of bacterial transfer during surgery include respiratory droplets and nuclei, skin scales carried on air currents, direct contact with the surgical team's skin, and contaminated fomites. The route with the most significant potential for iatrogenic bacterial transfer is direct physical contact. Strategies that minimize contact with infected fomites and with the surgical team would probably have the best chances of reducing the incidence of SSIs. C1 [Eisen, Daniel B.] Univ Calif Davis, Dept Dermatol, Sacramento, CA 95817 USA. [Ibrahimi, Omar A.] Univ Connecticut, Ctr Hlth, Dept Dermatol, Farmington, CT USA. [Ibrahimi, Omar A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. [Sharon, Victoria] Oregon Hlth & Sci Univ, Dept Dermatol, Portland, OR USA. RP Eisen, DB (reprint author), UC Davis, Dept Dermatol, Sacramento, CA 95816 USA. EM deisen123@gmail.com OI Sharon, Victoria/0000-0002-5108-8757; Eisen, Daniel/0000-0001-6741-3182 NR 110 TC 2 Z9 2 U1 1 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1076-0512 J9 DERMATOL SURG JI Dermatol. Surg. PD DEC PY 2011 VL 37 IS 12 BP 1709 EP 1720 DI 10.1111/j.1524-4725.2011.02183.x PG 12 WC Dermatology; Surgery SC Dermatology; Surgery GA 866BS UT WOS:000298355200001 PM 22092583 ER PT J AU Egede, LE Gebregziabher, M Lynch, CP Gilbert, GE Echols, C AF Egede, Leonard E. Gebregziabher, Mulugeta Lynch, Cheryl P. Gilbert, Gregory E. Echols, Carrae TI Longitudinal ethnic differences in multiple cardiovascular risk factor control in a cohort of US adults with diabetes SO DIABETES RESEARCH AND CLINICAL PRACTICE LA English DT Article DE Diabetes; Cardiovascular disease; Risk factor control; Ethnicity; Veterans ID OF-VETERANS-AFFAIRS; HEALTH-CARE-SYSTEM; INTERMEDIATE OUTCOMES; DISEASE RISK; PREVENTION; POPULATION; PREVALENCE; QUALITY; TRIAD AB Aim: To examine longitudinal differences in multiple cardiovascular risk factor control (glycemia, blood pressure, and lipids) by race/ethnicity. Methods: Data were analyzed on a cohort of 11,203 veterans with type 2 diabetes. Primary outcome was odds of none of the risk factors out of control vs. having at least one out of control (HbA1c > 8.0%, BP > 140/90 mmHg, and LDL > 100 mg/dL). Secondary outcome was odds of having none out of control vs. having one, two or three risk factors out of control, respectively. Generalized linear mixed models assessed the relationship between race/ethnicity and multiple risk factor control adjusted for covariates. Results: Adjusted models for primary outcome showed that NHB had two-fold (95% CI 1.8-2.3) and Hispanics had 48% higher (95% CI 1.3-1.7) odds of multiple risk factors out of control over time compared to NHW. Adjusted models for secondary outcome showed that NHB and Hispanics also had higher odds of having one, two, and three risk factors out of control over time compared to NHW. Conclusions: Ethnic minority veterans with diabetes are less likely to have multiple cardiovascular risk factor control over time compared to whites. Thus, greater risk reduction efforts are needed to reduce the heavier disease burden among ethnic minorities. (C) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Egede, Leonard E.; Gebregziabher, Mulugeta; Lynch, Cheryl P.] Med Univ S Carolina, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. [Egede, Leonard E.; Lynch, Cheryl P.; Gilbert, Gregory E.; Echols, Carrae] Ralph H Johnson Vet Affairs Med Ctr, Ctr Dis Prevent & Hlth Intervent Diverse Populat, Charleston, SC USA. [Gebregziabher, Mulugeta] Med Univ S Carolina, Div Biostat & Epidemiol, Charleston, SC 29425 USA. RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Hlth Dispar Res, 135 Rutledge Ave,Room 280H,POB 250593, Charleston, SC 29425 USA. EM egedel@musc.edu RI Gilbert, Gregory/C-7735-2016; OI Gilbert, Gregory/0000-0003-0879-5496; Gebregziabher, Mulugeta/0000-0002-4826-481X FU Center for Disease Prevention and Health Interventions for Diverse Populations [REA 08-261]; Veterans Affairs Health Services Research and Development (PI - Leonard Egede) FX This study was supported by Grant # REA 08-261, Center for Disease Prevention and Health Interventions for Diverse Populations funded by Veterans Affairs Health Services Research and Development (PI - Leonard Egede). NR 31 TC 13 Z9 13 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-8227 J9 DIABETES RES CLIN PR JI Diabetes Res. Clin. Pract. PD DEC PY 2011 VL 94 IS 3 BP 385 EP 394 DI 10.1016/j.diabres.2011.08.003 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 863EA UT WOS:000298144400019 PM 21903291 ER PT J AU Birk, JL Dennis, TA Shin, LM Urry, HL AF Birk, Jeffrey L. Dennis, Tracy A. Shin, Lisa M. Urry, Heather L. TI Threat Facilitates Subsequent Executive Control During Anxious Mood SO EMOTION LA English DT Article DE low-level threat; executive control; state anxiety; trait anxiety; dual competition framework ID ATTENTIONAL CONTROL-THEORY; ANTERIOR CINGULATE CORTEX; SELECTIVE ATTENTION; NEGATIVE AFFECT; COGNITIVE PERFORMANCE; EMOTIONAL ATTENTION; PREFRONTAL CORTEX; VISUAL-ATTENTION; POSITIVE AFFECT; TRAIT ANXIETY AB Dual competition framework (DCF) posits that low-level threat may facilitate behavioral performance by influencing executive control functions. Anxiety is thought to strengthen this effect by enhancing threat's affective significance. To test these ideas directly, we examined the effects of low-level threat and experimentally induced anxiety on one executive control function, the efficiency of response inhibition. In Study 1, briefly presented stimuli that were mildly threatening (i.e., fearful faces) relative to nonthreatening (i.e., neutral faces) led to facilitated executive control efficiency during experimentally induced anxiety. No such effect was observed during an equally arousing, experimentally induced happy mood state. In Study 2, we assessed the effects of low-level threat, experimentally induced anxiety, and individual differences in trait anxiety on executive control efficiency. Consistent with Study 1, fearful relative to neutral faces led to facilitated executive control efficiency during experimentally induced anxiety. No such effect was observed during an experimentally induced neutral mood state. Moreover, individual differences in trait anxiety did not moderate the effects of threat and anxiety on executive control efficiency. The findings are partially consistent with the predictions of DCF in that low-level threat improved executive control, at least during a state of anxiety. C1 [Birk, Jeffrey L.; Shin, Lisa M.; Urry, Heather L.] Tufts Univ, Dept Psychol, Medford, MA 02155 USA. [Dennis, Tracy A.] CUNY Hunter Coll, Dept Psychol, New York, NY 10021 USA. [Shin, Lisa M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Psychiat Neuroimaging Grp, Cambridge, MA 02138 USA. RP Urry, HL (reprint author), Tufts Univ, Dept Psychol, 490 Boston Ave, Medford, MA 02155 USA. EM heather.urry@tufts.edu NR 64 TC 10 Z9 11 U1 3 U2 20 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1528-3542 J9 EMOTION JI Emotion PD DEC PY 2011 VL 11 IS 6 BP 1291 EP 1304 DI 10.1037/a0026152 PG 14 WC Psychology, Experimental SC Psychology GA 860BO UT WOS:000297921200003 PM 22059518 ER PT J AU O'Sullivan, ES Vegas, A Anderson, DG Weir, GC AF O'Sullivan, Esther S. Vegas, Arturo Anderson, Daniel G. Weir, Gordon C. TI Islets Transplanted in Immunoisolation Devices: A Review of the Progress and the Challenges that Remain SO ENDOCRINE REVIEWS LA English DT Review ID TYPE-1 DIABETES-MELLITUS; BETA-CELL MASS; ISOLATED PANCREATIC-ISLETS; INSULIN-PRODUCING CELLS; EMBRYONIC STEM-CELLS; PORCINE ISLETS; IN-VIVO; BIOARTIFICIAL PANCREAS; ENCAPSULATED ISLETS; LIVING CELLS AB The concept of using an immunoisolation device to facilitate the transplantation of islets without the need for immunosuppression has been around for more than 50 yr. Significant progress has been made in developing suitable materials that satisfy the need for biocompatibility, durability, and permselectivity. However, the search is ongoing for a device that allows sufficient oxygen transfer while maintaining a barrier to immune cells and preventing rejection of the transplanted tissue. Separating the islets from the rich blood supply in the native pancreas takes its toll. The immunoisolated islets commonly suffer from hypoxia and necrosis, which in turn triggers a host immune response. Efforts have been made to improve the supply of nutrients by using proangiogenic factors to augment the development of a vascular supply in the transplant site, by using small islet cell aggregates to reduce the barrier to diffusion of oxygen, or by creating scaffolds that are in close proximity to a vascular network such as the omental blood supply. Even if these efforts are successful, the shortage of donor islet tissue available for transplantation remains a major problem. To this end, a search for a renewable source of insulin-producing cells is ongoing; whether these will come from adult or embryonic stem cells or xenogeneic sources remains to be seen. Herein we will review the above issues and chart the progress made with various immunoisolation devices in small and large animal models and the small number of clinical trials carried out to date. (Endocrine Reviews 32: 827-844, 2011) C1 [O'Sullivan, Esther S.; Weir, Gordon C.] Joslin Diabet Ctr, Div Res, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. [Vegas, Arturo; Anderson, Daniel G.] MIT, Dept Chem Engn, Div Hlth Sci & Technol, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. RP Weir, GC (reprint author), Joslin Diabet Ctr, Div Res, Sect Islet Transplantat & Cell Biol, 1 Joslin Pl, Boston, MA 02215 USA. EM gordon.weir@joslin.harvard.edu FU National Institutes of Health [RO1 DK 50657]; Juvenile Diabetes Research Foundation; Diabetes Research and Wellness Foundation; National University of Ireland FX This work was supported by Grant RO1 DK 50657 from the National Institutes of Health, the Juvenile Diabetes Research Foundation, and the Diabetes Research and Wellness Foundation. E.S.O. was the recipient of a traveling studentship from the National University of Ireland. NR 152 TC 73 Z9 76 U1 2 U2 43 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD DEC PY 2011 VL 32 IS 6 BP 827 EP 844 DI 10.1210/er.2010-0026 PG 18 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 865XI UT WOS:000298343800005 PM 21951347 ER PT J AU Ritaccio, A Boatman-Reich, D Brunner, P Cervenka, MC Cole, AJ Crone, N Duckrow, R Korzeniewska, A Litt, B Miller, KJ Moran, DW Parvizi, J Viventi, J Williams, J Schalk, G AF Ritaccio, Anthony Boatman-Reich, Dana Brunner, Peter Cervenka, Mackenzie C. Cole, Andrew J. Crone, Nathan Duckrow, Robert Korzeniewska, Anna Litt, Brian Miller, Kai J. Moran, Daniel W. Parvizi, Josef Viventi, Jonathan Williams, Justin Schalk, Gerwin TI Proceedings of the Second International Workshop on Advances in Electrocorticography SO EPILEPSY & BEHAVIOR LA English DT Review DE Electrocorticography; Brain-computer interface; High-frequency oscillations; Brain mapping; Seizure detection; Gamma-frequency electroencephalography; Neuroprosthetics; Subdural grid ID BRAIN-COMPUTER-INTERFACE; TEMPORAL-LOBE EPILEPSY; HUMAN SENSORIMOTOR CORTEX; GAMMA-BAND; SPECTRAL-ANALYSIS; INTRACRANIAL EEG; FIELD POTENTIALS; HUMANS; POWER; OSCILLATIONS AB The Second International Workshop on Advances in Electrocorticography (ECoG) was convened in San Diego, CA, USA, on November 11-12, 2010. Between this meeting and the inaugural 2009 event, a much clearer picture has been emerging of cortical ECoG physiology and its relationship to local field potentials and single-cell recordings. Innovations in material engineering are advancing the goal of a stable long-term recording interface. Continued evolution of ECoG-driven brain-computer interface technology is determining innovation in neuroprosthetics. Improvements in instrumentation and statistical methodologies continue to elucidate ECoG correlates of normal human function as well as the ictal state. This proceedings document summarizes the current status of this rapidly evolving field. (C) 2011 Elsevier Inc. All rights reserved. C1 [Ritaccio, Anthony] Albany Med Coll, Dept Neurol, Albany, NY 12208 USA. [Boatman-Reich, Dana; Cervenka, Mackenzie C.; Crone, Nathan; Korzeniewska, Anna] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Brunner, Peter; Schalk, Gerwin] New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA. [Cole, Andrew J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cole, Andrew J.] Harvard Univ, Sch Med, Boston, MA USA. [Duckrow, Robert] Yale Univ, New Haven, CT USA. [Litt, Brian] Univ Penn, Pittsburgh, PA USA. [Miller, Kai J.; Parvizi, Josef] Stanford Univ, Stanford, CA 94305 USA. [Moran, Daniel W.] Washington Univ, St Louis, MO USA. [Viventi, Jonathan] NYU, Polytech Inst, Brooklyn, NY USA. [Williams, Justin] Univ Wisconsin, Madison, WI USA. RP Ritaccio, A (reprint author), Albany Med Coll, Dept Neurol, Albany, NY 12208 USA. EM RitaccA@mail.amc.edu OI Brunner, Peter/0000-0002-2588-2754 FU NIH [R01-NS40596, K24-DC010028, R01-EB000856, R01-EB006356]; U.S. Army Research Office [W911NF-07-1-0415, W911NF-08-1-0216]; NASA; Stanford University FX This research was partially supported by the NIH (R01-NS40596 (N.C.), K24-DC010028 (D.B.), R01-EB000856 (G.S.), R01-EB006356 (G.S.)), the U.S. Army Research Office (W911NF-07-1-0415 (G.S.) and W911NF-08-1-0216 (G.S.)), the NASA graduate student research program (K.J.M.), and the Stanford University Neuro Ventures Program (J.P.). NR 81 TC 12 Z9 14 U1 1 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD DEC PY 2011 VL 22 IS 4 BP 641 EP 650 DI 10.1016/j.yebeh.2011.09.028 PG 10 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA 862CO UT WOS:000298067600003 PM 22036287 ER PT J AU Kharbouch, A Shoeb, A Guttag, J Cash, SS AF Kharbouch, Alaa Shoeb, Ali Guttag, John Cash, Sydney S. TI An algorithm for seizure onset detection using intracranial EEG SO EPILEPSY & BEHAVIOR LA English DT Article DE Seizure detection; Intracranial electroencephalography; Patient specific ID EPILEPTIC SEIZURES; PREDICTION AB This article addresses the problem of real-time seizure detection from intracranial EEG (IEEG). One difficulty in creating an approach that can be used for many patients is the heterogeneity of seizure IEEG patterns across different patients and even within a patient. In addition, simultaneously maximizing sensitivity and minimizing latency and false detection rates has been challenging as these are competing objectives. Automated machine learning systems provide a mechanism for dealing with these hurdles. Here we present and evaluate an algorithm for real-time seizure onset detection from IEEG using a machine-learning approach that permits a patient-specific solution. We extract temporal and spectral features across all intracranial EEG channels. A pattern recognition component is trained using these feature vectors and tested against unseen continuous data from the same patient. When tested on more than 875 hours of IEEG data from 10 patients, the algorithm detected 97% of 67 test seizures of several types with a median detection delay of 5 seconds and a median false alarm rate of 0.6 false alarms per 24-hour period. The sensitivity was 100% for 8 of 10 patients. These results indicate that a sensitive, specific, and relatively short-latency detection system based on machine learning can be employed for seizure detection from EEG using a full set of intracranial electrodes to individual patients. This article is part of a Supplemental Special Issue entitled The Future of Automated Seizure Detection and Prediction. (C) 2011 Elsevier Inc. All rights reserved. C1 [Kharbouch, Alaa; Guttag, John] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Shoeb, Ali; Cash, Sydney S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Cash, Sydney S.] Harvard Univ, Sch Med, Boston, MA USA. RP Kharbouch, A (reprint author), MIT, Dept Elect Engn & Comp Sci, 32 Vassar St,Room 32-G915, Cambridge, MA 02139 USA. EM aak@mit.edu FU Center for Integration of Medicine & Innovative Technology; Quanta Computer, Inc; Cyberonics, Inc.; National Institute of Neurological Disorders and Stroke (NINDS) [NS062092] FX A.K. was supported by grants from the Center for Integration of Medicine & Innovative Technology as well as funds from Quanta Computer, Inc and Cyberonics, Inc. SSC was supported by the Center for Integration of Medicine & Innovative Technology and the National Institute of Neurological Disorders and Stroke (NINDS-NS062092). The authors thank the reviewers for their comments. NR 21 TC 15 Z9 15 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD DEC PY 2011 VL 22 SU 1 BP S29 EP S35 DI 10.1016/j.yebeh.2011.08.031 PG 7 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA 862CQ UT WOS:000298067800006 PM 22078515 ER PT J AU Shoeb, A Kharbouch, A Soegaard, J Schachter, S Guttag, J AF Shoeb, Ali Kharbouch, Alaa Soegaard, Jacqueline Schachter, Steven Guttag, John TI A machine-learning algorithm for detecting seizure termination in scalp EEG SO EPILEPSY & BEHAVIOR LA English DT Article DE Seizure detection; Machine learning; Seizure termination; Postictal state ID POSTICTAL STATE AB Efforts to develop algorithms that can robustly detect the cessation of seizure activity within scalp EEGs are now underway. Such algorithms can facilitate novel clinical applications such as the estimation of a seizure's duration: the delivery of therapies designed to mitigate postictal period symptoms: or detection of the presence of status epilepticus. In this article, we present and evaluate a novel, machine learning-based method for detecting the termination of electrographic seizure activity. When tested on 133 seizures from a public database, our method successfully detected the end of 132 seizures within 10.3 +/- 5.5 seconds of the time determined by an electroencephalographer to represent the electrographic end of seizure. Furthermore, by pairing our seizure end detector with a previously published seizure onset detector, we could automatically estimate the duration of 85% of test electrographic seizures within a 15-second error margin compared with electroencephalographer determinations. This article is part of a Supplemental Special Issue entitled The Future of Automated Seizure Detection and Prediction. (C) 2011 Elsevier Inc. All rights reserved. C1 [Shoeb, Ali] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Kharbouch, Alaa; Guttag, John] MIT, Dept Elect Engn & Comp Sci, Boston, MA USA. [Soegaard, Jacqueline] MIT, Dept Bioengn, Boston, MA USA. [Schachter, Steven] Ctr Integrat Med & Innovat Technol, Neurotechnol Program, Boston, MA USA. RP Shoeb, A (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. EM ashoeb81@gmail.com FU Quanta Computer, Inc.; Center for Integration of Medicine and Innovative Technology under U.S. Army [DAMD17-02-2-0006, W81XWH-07-2-0011, W81XWH-09-2-0001] FX The authors thank the following programs and organizations for supporting this research: the MGH-MIT Career Development Postdoctoral Fellowship in Translational Research; Quanta Computer, Inc.; and the Center for Integration of Medicine and Innovative Technology under U.S. Army Medical Research Acquisition Activity Cooperative Agreements DAMD17-02-2-0006, W81XWH-07-2-0011, and W81XWH-09-2-0001. The information contained herein does not necessarily reflect the position or policy of the government, and no official endorsement should be inferred. NR 17 TC 18 Z9 18 U1 3 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 EI 1525-5069 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD DEC PY 2011 VL 22 SU 1 BP S36 EP S43 DI 10.1016/j.yebeh.2011.08.040 PG 8 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA 862CQ UT WOS:000298067800007 PM 22078516 ER PT J AU Kohling, R Staley, K AF Koehling, Ruediger Staley, Kevin TI Network mechanisms for fast ripple activity in epileptic tissue SO EPILEPSY RESEARCH LA English DT Article DE Ripples; Fast ripples; Oscillations; Hippocampus; Neocortex; Epilepsy; GABA ID HIGH-FREQUENCY OSCILLATIONS; HZ ELECTRICAL OSCILLATIONS; RAT SOMATOSENSORY CORTEX; TEMPORAL-LOBE EPILEPSY; BEHAVING RAT; HIPPOCAMPUS; BRAIN; SEIZURES; SYNCHRONIZATION; RELIABILITY AB Fast ripples are high-frequency, 250-600 Hz field potential oscillations which can be recorded from hippocampal or neocortical structures. In the neocortex, fast ripples occur during both sensory information processing and under pathological, epileptic conditions. In the hippocampus and entorhinal cortex, fast ripples are exclusively associated with epilepsy and perhaps even mark the epileptogenic focus. In contrast to ripples, which regularly also occur in normal tissue and which are thought to reflect population spike bursts at 100-200 Hz paced and synchronised by recurrent inhibition, the fast ripple frequency range exceeds the maximal firing frequency of most neurones. Hence, particularly in the hippocampus, fast ripples must emerge as a network phenomenon and cannot reflect the activity of single spiking neurones. In this review, current views on the mechanisms and processes underlying fast ripples are discussed. (C) 2011 Elsevier B.V. All rights reserved. C1 [Koehling, Ruediger] Univ Rostock, Oscar Langendorff Inst Physiol, D-18057 Rostock, Germany. [Staley, Kevin] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Kohling, R (reprint author), Univ Rostock, Oscar Langendorff Inst Physiol, Gertrudenstr 9, D-18057 Rostock, Germany. EM ruediger.koehling@uni-rostock.de RI Kohling, Rudiger/K-8647-2013 OI Kohling, Rudiger/0000-0003-3330-4898 FU NINDS NIH HHS [R01 NS074772-02, R01 NS074772, R01 NS074772-01] NR 35 TC 14 Z9 14 U1 0 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 J9 EPILEPSY RES JI Epilepsy Res. PD DEC PY 2011 VL 97 IS 3 SI SI BP 318 EP 323 DI 10.1016/j.eplepsyres.2011.03.006 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 868ND UT WOS:000298529100013 PM 21470826 ER PT J AU Dudek, FE Staley, KJ AF Dudek, F. Edward Staley, Kevin J. TI Seizure probability in animal models of acquired epilepsy: A perspective on the concept of the preictal state SO EPILEPSY RESEARCH LA English DT Article DE Seizure probability; Preictal ID TEMPORAL-LOBE EPILEPSY; SPONTANEOUS RECURRENT SEIZURES; SPONTANEOUS MOTOR SEIZURES; RAT MODEL; STATUS EPILEPTICUS; ISCHEMIC ENCEPHALOPATHY; HYPOXIA-ISCHEMIA; KAINATE; REORGANIZATION AB The concept of a preictal state is based on the belief that it may be possible to predict seizures before they occur. The preictal state is viewed as a time period when a seizure is practically inevitable, or at least a period of greatly increased seizure probability. Changes in seizure frequency may provide insight into how seizure probability increases after brain injury. Here, time-dependent changes in the frequency of spontaneous recurrent seizures after brain injury are summarized from published, nearly continuous, electrographic (EEG) recordings of kainate-treated rats and neonatal rats subjected to hypoxia-ischemia. For these animal models, seizure frequency and thus seizure probability was a sigmoid function of time after the brain injury. This observation differs from the traditional view, where the development of epilepsy after brain injury is a step-function of time, and the latent period is the time between a brain injury and the first spontaneous seizure. Based on backward extrapolation of the plots of seizure frequency versus time, these data suggest that seizure probability increases continuously during the latent period. Also, spontaneous recurrent seizures frequently occurred in clusters, suggesting that the intra-cluster seizure intervals are periods of high seizure probability. Thus, seizure probability progressively increases as a function of time after an epileptogenic brain injury, and is particularly high between seizures within a cluster, as compared to the time between clusters. These data suggest that the detectors of the preictal state need to be accurate (and tested) over a very wide range of seizure probabilities, and that studies on the physiological events that occur during seizure clusters may provide insight on the properties of the preictal state. (C) 2011 Published by Elsevier B.V. C1 [Dudek, F. Edward] Univ Utah, Sch Med, Dept Physiol, Salt Lake City, UT 84108 USA. [Staley, Kevin J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Dudek, FE (reprint author), Univ Utah, Sch Med, Dept Physiol, 420 Chipeta Way,Suite 1700, Salt Lake City, UT 84108 USA. EM ed.dudek@hsc.utah.edu; kstaley@partners.org FU NINDS; American Heart Association FX Supported by the NINDS and the American Heart Association. We thank Phil Williams, Shilpa Kadam, Andrew White, D.J. Ferraro, Suzanne Clark, and Walde Swiercz; the data described here were derived from collaborative experiments with them. NR 39 TC 11 Z9 11 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 J9 EPILEPSY RES JI Epilepsy Res. PD DEC PY 2011 VL 97 IS 3 SI SI BP 324 EP 331 DI 10.1016/j.eplepsyres.2011.10.017 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 868ND UT WOS:000298529100014 PM 22094446 ER PT J AU Nett, JE Sanchez, H Cain, MT Ross, KM Andes, DR AF Nett, Jeniel E. Sanchez, Hiram Cain, Michael T. Ross, Kelly M. Andes, David R. TI Interface of Candida albicans Biofilm Matrix-Associated Drug Resistance and Cell Wall Integrity Regulation SO EUKARYOTIC CELL LA English DT Article ID ANTIFUNGAL AGENTS; SACCHAROMYCES-CEREVISIAE; FLUCONAZOLE RESISTANCE; GENE DISRUPTION; BETA-GLUCANS; EFFLUX PUMPS; IN-VIVO; SUSCEPTIBILITY; INFECTIONS; PATHWAY AB Candida albicans frequently infects medical devices by growing as a biofilm, i.e., a community of adherent organisms entrenched in an extracellular matrix. During biofilm growth, Candida spp. acquire the ability to resist high concentrations of antifungal drugs. One recently recognized biofilm resistance mechanism involves drug sequestration by matrix beta-1,3 glucan. Using a candidate gene approach, we investigated potential C. albicans beta-1,3-glucan regulators, based on their homology to Saccharomyces cerevisiae, including SMI1 and protein kinase C (PKC) pathway components. We identified a role for the SMI1 in biofilm matrix glucan production and development of the associated drug resistance phenotype. This pathway appears to act through transcription factor Rlmp and glucan synthase Fks1p. The phenotypes of these mutant biofilms mimicked those of the smi1 Delta/smi1 Delta biofilm, and overexpression of FKS1 in the smi1 Delta/smi1 Delta mutant restored the biofilm resistant phenotype. However, control of this pathway is distinct from that of the upstream PKC pathway because the pkc1 Delta/pkc1 Delta, bck1 Delta/bck1 Delta, mkk2 Delta/mkk2 Delta, and mkc1 Delta/mkc1 Delta biofilms retained the resistant phenotype of the parent strain. In addition, resistance to cell-perturbing agents and gene expression data do not support a significant role for the cell wall integrity pathway during the biofilm formation. Here we show that Smi1p functions in conjunction with Rlm1p and Fks1p to produce drug-sequestering biofilm beta-glucan. Our work provides new insight into how the C. albicans biofilm matrix production and drug resistance pathways intersect with the planktonic cell wall integrity pathway. This novel connection helps explain how pathogens in a multicellular biofilm community are protected from anti-infective therapy. C1 [Nett, Jeniel E.; Sanchez, Hiram; Cain, Michael T.; Ross, Kelly M.; Andes, David R.] Univ Wisconsin, Dept Med, Madison, WI 53705 USA. [Andes, David R.] Univ Wisconsin, Dept Med Microbiol & Immunol, Madison, WI 53705 USA. [Nett, Jeniel E.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Andes, DR (reprint author), Univ Wisconsin, Dept Med, 5211 UW Med Fdn Centennial Bldg,1685 Highland Ave, Madison, WI 53705 USA. EM dra@medicine.wisc.edu FU National Institutes of Health [RO1 AI073289-01]; Veteran Women's Health Fellowship FX This work was supported by the National Institutes of Health (grant RO1 AI073289-01) and the Veteran Women's Health Fellowship. NR 52 TC 45 Z9 53 U1 2 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1535-9778 J9 EUKARYOT CELL JI Eukaryot. Cell PD DEC PY 2011 VL 10 IS 12 BP 1660 EP 1669 DI 10.1128/EC.05126-11 PG 10 WC Microbiology; Mycology SC Microbiology; Mycology GA 863HN UT WOS:000298153500007 PM 21666076 ER PT J AU Tannir, NM Wong, YN Kollmannsberger, CK Ernstoff, MS Perry, DJ Appleman, LJ Posadas, EM Cho, D Choueiri, TK Coates, A Gupta, N Pradhan, R Qian, J Chen, JH Scappaticci, FA Ricker, JL Carlson, DM Michaelson, MD AF Tannir, Nizar M. Wong, Yu-Ning Kollmannsberger, Christian K. Ernstoff, Marc S. Perry, David J. Appleman, Leonard J. Posadas, Edwin M. Cho, Daniel Choueiri, Toni K. Coates, Andrew Gupta, Neeraj Pradhan, Rajendra Qian, Jiang Chen, Jihong Scappaticci, Frank A. Ricker, Justin L. Carlson, Dawn M. Michaelson, M. Dror TI Phase 2 trial of linifanib (ABT-869) in patients with advanced renal cell cancer after sunitinib failure SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE Renal cell carcinoma; Sunitinib; ABT-869; VEGFR; Angiogenesis inhibitors ID INTERFERON-ALPHA; DOUBLE-BLIND; III TRIAL; CARCINOMA; SURVIVAL AB Purpose: This study assessed the efficacy and safety of linifanib in patients with advanced renal cell carcinoma (RCC) who were previously treated with sunitinib. Materials and methods: This open-label, multicentre, phase 2 trial of oral linifanib 0.25 mg/kg/day enrolled patients who had prior nephrectomy and adequate organ function. The primary end-point was objective response rate (ORR) per response evaluation criteria in solid tumors (RECIST) by central imaging. Secondary end-points were progression-free survival (PFS), overall survival (OS) and time to progression (TTP). Safety was also assessed. Results: Fifty-three patients, median age 61 years (range 40-80) were enrolled (August 2007 to October 2008) across 12 North-American centres. Median number of prior therapies was 2 (range 1-4); 43 patients (81%) had clear-cell histology. ORR was 13.2%, median PFS was 5.4 months (95% Confidence Interval (Cl): 3.6, 6.0) and TIP was the same; median OS was 14.5 months (95% CI: 10.8, 24.1). The most common treatment-related adverse events (AEs) were diarrhoea (74%), fatigue (74%) and hypertension (66%), and the most common treatment-related Grade 3/4 AE was hypertension (40%). Conclusions: Linifanib demonstrated clinically meaningful activity in patients with advanced RCC after sunitinib failure. At 0.25 mg/kg/day, significant dose modifications were required. An alternative, fixed-dosing strategy is being evaluated in other trials. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Tannir, Nizar M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Wong, Yu-Ning] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Kollmannsberger, Christian K.] Vancouver Canc Ctr, British Columbia Canc Agcy, Vancouver, BC, Canada. [Ernstoff, Marc S.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [Perry, David J.] Washington Canc Inst, Washington, DC USA. [Appleman, Leonard J.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Posadas, Edwin M.] Cedar Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA USA. [Cho, Daniel] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Choueiri, Toni K.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Coates, Andrew; Gupta, Neeraj; Pradhan, Rajendra; Qian, Jiang; Chen, Jihong; Ricker, Justin L.; Carlson, Dawn M.] Abbott Labs, Abbott Pk, IL 60064 USA. [Scappaticci, Frank A.] Genentech Inc, San Francisco, CA USA. [Michaelson, M. Dror] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Tannir, NM (reprint author), Univ Texas MD Anderson Canc Ctr, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM ntannir@mdanderson.org OI Michaelson, Dror/0000-0001-9249-6338; Appleman, Leonard/0000-0003-4951-7388 FU Abbott; Abbott Laboratories, IL, USA; Genentech, Inc., CA, USA FX N.M.T. has had a consultant/advisory role for Abbott, Novartis, Genentech, Seattle Genetics and Aveo Pharmaceuticals, Inc., and has conducted research funded by Abbott, Pfizer, Novartis, Lilly, Amgen and Seattle Genetics. M.S.E. has had a consultant/advisory role for Abbott, owns stock in Abbott and conducted research funded by Abbott. D.J.P. conducted research funded by Abbott, and attended a Genentech advisory board. L.J.A. received research funding from Abbott. D.C. has had a consultant/advisory role for Genentech Inc., T.K.C. has had a consultant/advisory role for Abbott. A.C., R.P., J.Q., J.L.R. and D.M.C. are employees of Abbott and own Abbott stock. N.G. and J.C. are former employees of Abbott and own Abbott stock; N.G. is currently employed at Millennium: The Takeda Oncology Company, Cambridge, MA, and J.C. is currently employed at Astellas Pharma Global Development, Inc., Deerfield, IL. F.A.S. is an employee of Genentech, Inc., South San Francisco, CA, and owns stock in Roche. M.D.M. has had a consultant/advisory role for Abbott and Pfizer, and received honoraria from Wyeth. The other authors have no conflict of interest.; This work was supported by Abbott Laboratories, IL, USA and Genentech, Inc., CA, USA. Abbott participated with study investigators in the development of the study design, the collection, analysis, and interpretation of data, the writing of the manuscript and the decision to submit for publication. NR 37 TC 20 Z9 22 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD DEC PY 2011 VL 47 IS 18 BP 2706 EP 2714 DI 10.1016/j.ejca.2011.09.002 PG 9 WC Oncology SC Oncology GA 867LW UT WOS:000298456900006 PM 22078932 ER PT J AU Dong, CZ Tian, SM Madani, N Choi, WT Kumar, S Liu, DX Sodroski, JG Huang, ZW An, J AF Dong, Chang-Zhi Tian, Shaomin Madani, Navid Choi, Won-Tak Kumar, Santosh Liu, Dongxiang Sodroski, Joseph G. Huang, Ziwei An, Jing TI Role of CXCR4 internalization in the anti-HIV activity of stromal cell-derived factor-1 alpha probed by a novel synthetically and modularly modified-chemokine analog SO EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article DE HIV-1; AIDS; CXCR4; chemokines; SDF-1 alpha; vMIP-II ID SMM-CHEMOKINES; FACTOR-I; RECEPTOR; ENTRY; LIGAND; INHIBITION; PEPTIDES; BINDING; SDF-1; DISSOCIATION AB The natural ligands of two major human immunodeficiency virus type 1 (HIV-1) co-receptors, CXCR4 and CCR5, can profoundly inhibit the replication of HIV-1 that uses these co-receptors for entry into the target cells. It has been postulated that these natural chemokines inhibit HIV-1 infection by blocking common binding sites on CXCR4 or CCR5 that are required for HIV-1 envelope glycoprotein gp120 interaction with its co-receptor and/or by inducing receptor internalization. To investigate whether receptor internalization caused by stromal cell-derived factor (SDF)-1 alpha, a natural ligand of CXCR4, plays a role in its anti-HIV activity, we applied the SMM (synthetically and modularly modified)chemokine approach to generate a functional probe of SDF-1 alpha that retains significant CXCR4 binding but does not induce CXCR4 internalization. The antiviral study of this functional probe analog versus wild-type SDF-1 alpha showed that, despite the significant CXCR4 binding activity, this probe analog displayed a complete loss of effect in causing CXCR4 internalization and greatly diminished antiviral activity. Interestingly, this new analog also showed a decreased number of overlapping binding sites with HIV-1 on CXCR4 transmembrane and extracellular domains. The correlation of the decrease in the anti-HIV activity with the loss of CXCR4 internalization observed with this probe molecule suggests that receptor internalization may play an important role in the anti-HIV activity of SDF-1 alpha and possibly other natural chemokines. This further implies that any modifications in SDF-1a that result in a reduction or loss of internalization activity may result in analogs that are not suitable as effective HIV-1 inhibitors that target CXCR4, unless such modifications also result in improved CXCR4 interaction with increased number of overlapping binding sites with HIV-1, thus leading to more effective steric hindrance against HIV-1. C1 [Huang, Ziwei; An, Jing] SUNY Syracuse, SUNY Upstate Canc Res Inst, Dept Pharmacol, Syracuse, NY 13210 USA. [Dong, Chang-Zhi; Tian, Shaomin; Choi, Won-Tak; Kumar, Santosh; Liu, Dongxiang] Univ Illinois, Dept Biochem, Urbana, IL 61801 USA. [Madani, Navid; Sodroski, Joseph G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Huang, ZW (reprint author), SUNY Syracuse, SUNY Upstate Canc Res Inst, Dept Pharmacol, 750 E Adams St, Syracuse, NY 13210 USA. EM huangz@upstate.edu; anji@upstate.edu FU National Institutes of Health FX This work was supported by grants from the National Institutes of Health. NR 27 TC 5 Z9 5 U1 0 U2 2 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 1535-3702 J9 EXP BIOL MED JI Exp. Biol. Med. PD DEC PY 2011 VL 236 IS 12 BP 1413 EP 1419 DI 10.1258/ebm.2011.011260 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 875KI UT WOS:000299028400010 PM 22101518 ER PT J AU Quiroz, YT Lopera, F Budson, AE AF Quiroz, Yakeel T. Lopera, Francisco Budson, Andrew E. TI Charting the path for early diagnosis and prevention of Alzheimer's disease SO EXPERT REVIEW OF NEUROTHERAPEUTICS LA English DT Editorial Material DE early diagnosis; presenilin-1; presymptomatic Alzheimer's disease; prevention ID PRESYMPTOMATIC CARRIERS; MUTATION; ATROPHY; RISK; MRI C1 [Budson, Andrew E.] VA Boston Healthcare Syst, Boston, MA USA. [Budson, Andrew E.] Boston Univ, Sch Med, Dept Neurol, Alzheimers Dis Ctr, Boston, MA 02118 USA. [Quiroz, Yakeel T.] Boston Univ, Dept Psychol, Ctr Memory & Brain, Boston, MA 02215 USA. [Quiroz, Yakeel T.; Lopera, Francisco] Univ Antioquia, Grp Neurociencias, Medellin, Colombia. RP Budson, AE (reprint author), VA Boston Healthcare Syst, Boston, MA USA. EM abudson@bu.edu NR 17 TC 0 Z9 0 U1 0 U2 6 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7175 J9 EXPERT REV NEUROTHER JI Expert Rev. Neurother. PD DEC PY 2011 VL 11 IS 12 BP 1665 EP 1667 DI 10.1586/ERN.11.162 PG 3 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 873AD UT WOS:000298851800002 PM 22091590 ER PT J AU Jang, C Choi, JK Na, YJ Jang, B Wasco, W Buxbaum, JD Kim, YS Choi, EK AF Jang, Changhwan Choi, Jin-Kyu Na, Yeo-Jung Jang, Byungki Wasco, Wilma Buxbaum, Joseph D. Kim, Yong-Sun Choi, Eun-Kyoung TI Calsenilin regulates presenilin 1/gamma-secretase-mediated N-cadherin epsilon-cleavage and beta-catenin signaling SO FASEB JOURNAL LA English DT Article DE adhesion molecule; SH-SY5Y neuroblastoma cells ID GAMMA-SECRETASE COMPLEX; CELL-CELL ADHESION; AMYLOID PRECURSOR PROTEIN; TRANS-GOLGI NETWORK; C-TERMINAL FRAGMENT; ALZHEIMERS-DISEASE; TRANSCRIPTIONAL REPRESSOR; NUCLEAR TRANSLOCATION; ENDOPLASMIC-RETICULUM; PLASMA-MEMBRANE AB Presenilin 1 (PS1) is a component of the gamma-secretase complex that cleaves a variety of type I membrane proteins, including the beta-amyloid precursor protein (beta-APP), Notch, and neuronal (N)- and epithelial (E)-cadherins. N-cadherin is an essential adhesion molecule that forms a complex with, and is cleaved by, PS1/gamma-secretase and beta-catenin in the plasma membrane. The purpose of this study was to determine whether calsenilin, a presenilin-interacting protein, has a functional role in PS1/gamma-secretase-mediated N-cadherin epsilon-cleavage using Western blot analysis, RT-PCR, immunoprecipitation, subcellular fractionation, biotinylation, and a luciferase reporter assay in SH-SY5Y neuroblastoma cells. Here, we demonstrate that the expression of calsenilin leads to a disruption of PS1/gamma-secretase-mediated epsilon-cleavage of N-cadherin, which results in the significant accumulation of N-cadherin C-terminal fragment 1 (Ncad/CTF1), the reduction of cytoplasmic Ncad/CTF2 release, and a deceleration of PS1-CTF delivery to the cell surface. Interestingly, we also found that the expression of calsenilin is associated with the redistribution of beta-catenin from the cell surface to a cytoplasmic pool, as well as with the negative regulation of genes that are targets of T-cell factor/beta-catenin nuclear signaling. Taken together, our findings suggest that calsenilin is a novel negative regulator of N-cadherin processing that plays an important role in beta-catenin signaling.-Jang, C., Choi, J.-K., Na, Y.-J., Jang, B., Wasco, W., Buxbaum, J. D., Kim, Y.-S., Choi, E.-K. Calsenilin regulates presenilin 1/gamma-secretase-mediated N-cadherin epsilon-cleavage and beta-catenin signaling. FASEB J. 25, 4174-4183 (2011). www.fasebj.org C1 [Choi, Eun-Kyoung] Hallym Univ, Ilsong Inst Life Sci, Lab Cellular Aging & Neurodegenerat, Anyang 431060, Gyeonggi Do, South Korea. [Jang, Changhwan; Kim, Yong-Sun] Hallym Univ, Coll Med, Dept Microbiol, Chunchon, South Korea. [Wasco, Wilma] Harvard Univ, Sch Med, Mass Gen Inst Neurodegenerat Dis, Massachusetts Gen Hosp,Genet & Aging Res Unit,Dep, Charlestown, MA USA. [Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Psychiat & Neurobiol, Lab Mol Neuropsychiat, New York, NY USA. RP Choi, EK (reprint author), Hallym Univ, Ilsong Inst Life Sci, Lab Cellular Aging & Neurodegenerat, 1605-4 Gwanyang Dong, Anyang 431060, Gyeonggi Do, South Korea. EM ekchoi@hallym.ac.kr FU National Research Foundation of Korea (NRF); Ministry of Education, Science and Technology [2011-0006204] FX The authors thank Dr. J. H. Boo (Seoul National University, Seoul, Korea) and Dr. H. G. Lee (Case Western Reserve University, Cleveland, OH, USA) for technical advice and helpful discussions. This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2011-0006204). NR 67 TC 12 Z9 12 U1 1 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD DEC PY 2011 VL 25 IS 12 BP 4174 EP 4183 DI 10.1096/fj.11-185926 PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 863BP UT WOS:000298138100011 PM 21852538 ER PT J AU De Rienzo, G Bishop, JA Mao, YW Pan, LY Ma, TP Moens, CB Tsai, LH Sive, H AF De Rienzo, Gianluca Bishop, Joshua A. Mao, Yingwei Pan, Luyuan Ma, Taylur P. Moens, Cecilia B. Tsai, Li-Huei Sive, Hazel TI Disc1 regulates both beta-catenin-mediated and noncanonical Wnt signaling during vertebrate embryogenesis SO FASEB JOURNAL LA English DT Article DE Disc1; zebrafish; brain; neurons; GSK3 beta; pcp; mutant ID SCHIZOPHRENIA 1; ZEBRAFISH GASTRULATION; EXTENSION MOVEMENTS; CELL POLARITY; ADULT BRAIN; MECHANISM; EXPRESSION; DISRUPTED-IN-SCHIZOPHRENIA-1; HINDBRAIN; XENOPUS AB Disc1 is a schizophrenia risk gene that engages multiple signaling pathways during neurogenesis and brain development. Using the zebrafish as a tool, we analyze the function of zebrafish Disc1 (zDisc1) at the earliest stages of brain and body development. We define a "tool" as a biological system that gives insight into mechanisms underlying a human disorder, although the system does not phenocopy the disorder. A zDisc1 peptide binds to GSK3 beta, and zDisc1 directs early brain development and neurogenesis, by promoting beta-catenin-mediated Wnt signaling and inhibiting GSK3 beta activity. zDisc1 loss-of-function embryos additionally display a convergence and extension phenotype, demonstrated by abnormal movement of dorsolateral cells during gastrulation, through changes in gene expression, and later through formation of abnormal, U-shaped muscle segments, and a truncated tail. These phenotypes are caused by alterations in the noncanonical Wnt pathway, via Daam and Rho signaling. The convergence and extension phenotype can be rescued by a dominant negative GSK3 beta construct, suggesting that zDisc1 inhibits GSK3 beta activity during noncanonical Wnt signaling. This is the first demonstration that Disc1 modulates the noncanonical Wnt pathway and suggests a previously unconsidered mechanism by which Disc1 may contribute to the etiology of neuropsychiatric disorders.-De Rienzo, G., Bishop, J. A., Mao, Y., Pan, L., Ma, T. P., Moens, C. B., Tsai, L. H., Sive, H. Disc1 regulates both beta-catenin-mediated and noncanonical Wnt signaling during vertebrate embryogenesis. FASEB J. 25, 4184 -4197 (2011). www.fasebj.org C1 [De Rienzo, Gianluca; Sive, Hazel] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Bishop, Joshua A.; Tsai, Li-Huei] Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Bishop, Joshua A.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Mao, Yingwei] Penn State Univ, Dept Biol, State Coll, PA USA. [Pan, Luyuan; Ma, Taylur P.; Moens, Cecilia B.] Fred Hutchinson Canc Res Ctr, Howard Hughes Med Inst, Div Basic Sci, Seattle, WA 98104 USA. [Tsai, Li-Huei] Howard Hughes Med Inst, Dept Brain & Cognit Sci, Picower Inst Learning & Memory, Cambridge, MA USA. [Sive, Hazel] MIT, Dept Biol, Cambridge, MA USA. RP Sive, H (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. EM sive@wi.mit.edu FU Stanley Medical Research Institute; U.S. National Institutes of Health (NIH) [R01 HG002995]; NIH [RO1 MH091115] FX The authors thank the members of the H.S. laboratory for discussion, and Olivier Paugois for expert fish husbandry. The authors are grateful to Ed Scolnick, Stephen Haggarty, Pamela Sklar, and other members of the Stanley Center for input. The authors thank the following colleagues for generous gifts of reagents, as noted in Materials and Methods: Anand Chandrasekhar (University of Missouri, Columbia, MO, USA), Jeremy Green (Dana-Farber Cancer Institute, Boston, MA, USA), Raymond Habas (Temple University, Philadelphia, PA, USA), Stephen Haggarty (Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA), Xi He (Harvard Medical School, Cambridge, MA, USA), David Kimelman (University of Washington, Seattle, WA, USA), Jim Smith (Gurdon Institute, Cambridge, UK), Randall Moon (University of Washington School of Medicine, Seattle, WA, USA), Steven Wilson (University College London, London, UK), Rudi Winklbauer (University of Toronto, Toronto, ON, Canada), and Karen Symes (Boston University, Boston, MA, USA). This work was supported by the Stanley Medical Research Institute, via a grant to the Stanley Center for Psychiatric Research at the Broad Institute. The Disc1fh291 and Disc1fh292 mutants were identified with the support of U.S. National Institutes of Health (NIH) grant R01 HG002995 to C.B.M. This work was partially supported by NIH grant RO1 MH091115 to L.-H.T. NR 51 TC 16 Z9 16 U1 3 U2 13 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD DEC PY 2011 VL 25 IS 12 BP 4184 EP 4197 DI 10.1096/fj.11-186239 PG 14 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 863BP UT WOS:000298138100012 PM 21859895 ER PT J AU Kwon, JY De Asla, RJ AF Kwon, John Y. De Asla, Richard J. TI The Use of Flexor to Extensor Transfers for the Correction of the Flexible Hammer Toe Deformity SO FOOT AND ANKLE CLINICS LA English DT Article DE Hammer toe; Clawtoe; Flexion deformity; Foot ID 2ND METATARSOPHALANGEAL JOINT; BREVIS TENDON TRANSFER; DIGITORUM LONGUS; OPERATIVE REPAIR; INSTABILITY AB Flexor to extensor transfer is a useful means for the correction of a flexible hammer toe deformity. Although satisfaction rates have varied in the literature, this technique remains a useful tool in the surgeon's armamentarium to improve toe deformity, decrease pain, and aid in shoe wear. C1 [Kwon, John Y.; De Asla, Richard J.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Foot & Ankle Div, Boston, MA 02114 USA. [Kwon, John Y.; De Asla, Richard J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Kwon, JY (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Foot & Ankle Div, 55 Fruit St, Boston, MA 02114 USA. EM johnkwonmd@gmail.com NR 31 TC 4 Z9 4 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1083-7515 J9 FOOT ANKLE CLIN JI Foot Ankle Clin. PD DEC PY 2011 VL 16 IS 4 BP 573 EP 582 DI 10.1016/j.fcl.2011.08.005 PG 10 WC Orthopedics SC Orthopedics GA 871UX UT WOS:000298764300005 PM 22118230 ER PT J AU Coleman, JJ Muhammed, M Kasperkovitz, PV Vyas, JM Mylonakis, E AF Coleman, Jeffrey J. Muhammed, Maged Kasperkovitz, Pia V. Vyas, Jatin M. Mylonakis, Eleftherios TI Fusarium pathogenesis investigated using Galleria mellonella as a heterologous host SO FUNGAL BIOLOGY LA English DT Article DE Antifungal agent; Fusariosis; Fusarium; Galleria; Heterologous host; Thermotolerance ID SOLANI SPECIES COMPLEX; SECONDARY METABOLIC PRODUCTS; SMALL-GRAIN CEREALS; ASPERGILLUS-FUMIGATUS; MURINE MODEL; INFECTIONS; FUNGUS; PATHOGENICITY; MYCOTOXINS; VIRULENCE AB Members of the fungal genus Fusarium are capable of manifesting in a multitude of clinical infections, most commonly in immunocompromised patients. In order to better understand the interaction between the fungus and host, we have developed the larvae of the greater wax moth, Galleria mellonella, as a heterologous host for fusaria. When conidia are injected into the haemocoel of this Lepidopteran system, both clinical and environmental isolates of the fungus are able to kill the larvae at 37 degrees C, although killing occurs more rapidly when incubated at 30 degrees C. This killing was dependent on several other factors besides temperature, including the Fusarium strain, the number of conidia injected, and the conidia. morphology, where macroconidia are more virulent than their microconidia counterpart. There was a correlation in the killing rate of Fusarium spp. when evaluated in G. mellonella and a murine model. In vivo studies indicated G. mellonella haemocytes were capable of initially phagocytosing both conidial morphologies. The G. mellonella system was also used to evaluate antifungal agents, and amphotericin B was able to confer a significant increase in survival to Fusarium-infected larvae. The G. mellonella Fusarium pathogenicity system revealed that virulence of Fusarium spp. is similar, regardless of the origin of the isolate, and that mammalian endothermy is a major deterrent for Fusarium infection and therefore provides a suitable alternative to mammalian models to investigate the interaction between the host and this increasingly important fungal pathogen. (C) 2011 British Mycological Society. Published by Elsevier Ltd. All rights reserved. C1 [Coleman, Jeffrey J.; Muhammed, Maged; Kasperkovitz, Pia V.; Vyas, Jatin M.; Mylonakis, Eleftherios] Harvard Univ, Div Infect Dis, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Mylonakis, E (reprint author), Harvard Univ, Div Infect Dis, Massachusetts Gen Hosp, Sch Med, 55 Fruit St,Gray Jackson Rm 504, Boston, MA 02114 USA. EM jjcoleman@partners.org; mmuhammed@partners.org; kasperkovitz.pia@mgh.harvard.edu; jvyas@partners.org; emylonakis@partners.org RI Coleman, Jeffrey/E-2981-2015; Vyas, Jatin/Q-1627-2016; OI Vyas, Jatin/0000-0002-9985-9565; Coleman, Jeffrey/0000-0001-8579-1996 FU National Institutes of Health [AI075286, AI079569, AI07061] FX We would like to thank Evan Mojica in the MGH clinical mycology laboratory for kindly providing Fusarium isolates and Beth Burgwyn Fuchs for insightful discussions. This research was supported by a National Institutes of Health R01 award (AI075286) and a R21 award (AI079569) to EM and a T32 award (AI07061) to BC. NR 56 TC 21 Z9 21 U1 0 U2 18 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1878-6146 J9 FUNGAL BIOL-UK JI Fungal Biol. PD DEC PY 2011 VL 115 IS 12 BP 1279 EP 1289 DI 10.1016/j.funbio.2011.09.005 PG 11 WC Mycology SC Mycology GA 873PF UT WOS:000298894600009 PM 22115447 ER PT J AU Peer, D Lieberman, J AF Peer, D. Lieberman, J. TI Special delivery: targeted therapy with small RNAs SO GENE THERAPY LA English DT Review DE siRNA; drug; liposome; nanoparticle; aptamer ID SMALL INTERFERING RNA; IN-VIVO DELIVERY; APTAMER-SIRNA CHIMERAS; MAMMALIAN-CELLS; EFFICIENT DELIVERY; SYSTEMIC DELIVERY; GENE DELIVERY; PROTECTS MICE; CANCER; GROWTH AB Harnessing RNA interference using small RNA-based drugs has great potential to develop drugs designed to knock down expression of any disease-causing gene, thereby greatly expanding the universe of possible drug targets. However, delivering small RNAs into specific tissues and cells is still a hurdle. Here, we review recent progress in overcoming systemic, local and cellular barriers to RNA drug delivery, focusing on strategies for targeted uptake. Gene Therapy (2011) 18, 1127-1133; doi:10.1038/gt.2011.56; published online 14 April 2011 C1 [Lieberman, J.] Harvard Univ, Sch Med, Dept Pediat, Immune Dis Inst,Program Cellular & Mol Med,Childr, Boston, MA 02115 USA. [Peer, D.] Tel Aviv Univ, Lab Nanomed, Dept Cell Res & Immunol, GS Wise Fac Life Sci, IL-69978 Tel Aviv, Israel. [Peer, D.] Tel Aviv Univ, Ctr Nanosci & Nanotechnol, IL-69978 Tel Aviv, Israel. RP Lieberman, J (reprint author), Harvard Univ, Sch Med, Dept Pediat, Immune Dis Inst,Program Cellular & Mol Med,Childr, 200 Longwood Ave, Boston, MA 02115 USA. EM peer@post.tau.ac.il; Lieberman@idi.harvard.edu RI Peer, Dan/A-1785-2011; Lieberman, Judy/A-2717-2015 OI Peer, Dan/0000-0001-8238-0673; FU Alon Foundation; European Union; Levy Family Trust; ISF [181/10]; US Department of Defense; BSF [2009107] FX This work was supported, in part, by grants from the Alon Foundation, the Marie Curie IRG-FP7 of the European Union, Levy Family Trust and ISF (181/10) to DP, the Breast Cancer Research Program of the US Department of Defense to JL, and by a joint BSF grant (2009107) to DP and JL. NR 63 TC 72 Z9 76 U1 1 U2 55 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD DEC PY 2011 VL 18 IS 12 BP 1127 EP 1133 DI 10.1038/gt.2011.56 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 865XZ UT WOS:000298345500005 PM 21490679 ER PT J AU Pike, LS Tannous, BA Deliolanis, NC Hsich, G Morse, D Tung, CH Sena-Esteves, M Breakefield, XO AF Pike, L. S. Tannous, B. A. Deliolanis, N. C. Hsich, G. Morse, D. Tung, C-H Sena-Esteves, M. Breakefield, X. O. TI Imaging gene delivery in a mouse model of congenital neuronal ceroid lipofuscinosis SO GENE THERAPY LA English DT Article DE fluorescence; lysosomal storage disease; cathepsin D; central nervous system; AAV; neurologic disease ID CATHEPSIN-D DEFICIENCY; ADENOASSOCIATED VIRUS VECTOR; LYSOSOMAL STORAGE DISEASES; PROTEASE ACTIVITY; AMPLICON VECTOR; NEONATAL MICE; PHASE-I; BRAIN; FLUORESCENCE; THERAPY AB Adeno-associated virus (AAV)-mediated gene replacement for lysosomal disorders have been spurred by the ability of some serotypes to efficiently transduce neurons in the brain and by the ability of lysosomal enzymes to cross-correct among cells. Here, we explored enzyme replacement therapy in a knock-out mouse model of congenital neuronal ceroid lipofuscinosis (NCL), the most severe of the NCLs in humans. The missing protease in this disorder, cathepsin D (CathD) has high levels in the central nervous system. This enzyme has the potential advantage for assessing experimental therapy in that it can be imaged using a near-infrared fluorescence (NIRF) probe activated by CathD. Injections of an AAV2/rh8 vector-encoding mouse CathD (mCathD) into both cerebral ventricles and peritoneum of newborn knock-out mice resulted in a significant increase in lifespan. Successful delivery of active CathD by the AAV2/rh8-mCathD vector was verified by NIRF imaging of mouse embryonic fibroblasts from knock-out mice in culture, as well as by ex vivo NIRF imaging of the brain and liver after gene transfer. These studies support the potential effectiveness and imaging evaluation of enzyme replacement therapy to the brain and other organs in CathD null mice via AAV-mediated gene delivery in neonatal animals. Gene Therapy (2011) 18, 1173-1178; doi:10.1038/gt.2011.118; published online 8 September 2011 C1 [Pike, L. S.; Tannous, B. A.; Hsich, G.; Morse, D.; Sena-Esteves, M.; Breakefield, X. O.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Pike, L. S.; Tannous, B. A.; Hsich, G.; Morse, D.; Sena-Esteves, M.; Breakefield, X. O.] Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. [Tannous, B. A.; Tung, C-H; Breakefield, X. O.] Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Boston, MA 02114 USA. [Deliolanis, N. C.] Helmholtz Zentrum Muenchen, Inst Biol & Med Imaging, Neuherberg, Germany. [Hsich, G.] Cleveland Clin, Ctr Pediat Neurol, Cleveland, OH 44106 USA. [Tung, C-H] Methodist Hosp, Res Inst, Weill Cornell Med Coll, Dept Radiol, Houston, TX 77030 USA. [Sena-Esteves, M.] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA USA. [Sena-Esteves, M.] Univ Massachusetts, Sch Med, Gene Therapy Ctr, Worcester, MA USA. RP Tannous, BA (reprint author), Massachusetts Gen Hosp E, Mol Neurogenet Unit, 13th St,Bldg 149, Boston, MA 02129 USA. EM btannous@hms.harvard.edu OI Deliolanis, Nikolaos/0000-0002-6392-3035; Tung, Ching-Hsuan/0000-0001-6648-6195 FU Howard Hughes Fellowship; NIH/NINDS [NS24279, NS045776]; NIH/NCI [CA86355] FX This work was supported by a Howard Hughes Fellowship (GH), NIH/NINDS NS24279 (XOB) and NS045776 (BAT), as well as NIH/NCI CA86355 (XOB and BAT). We thank Suzanne McDavitt for skilled editorial assistance. NR 53 TC 8 Z9 8 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD DEC PY 2011 VL 18 IS 12 BP 1173 EP 1178 DI 10.1038/gt.2011.118 PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 865XZ UT WOS:000298345500011 PM 21900963 ER PT J AU Wu, H Zhang, Y AF Wu, Hao Zhang, Yi TI Mechanisms and functions of Tet protein-mediated 5-methylcytosine oxidation SO GENES & DEVELOPMENT LA English DT Review DE Tet; 5-methylcytosine; 5-hydroxymethylcytosine; DNA demethylation; embryonic stem cells; leukemia ID EMBRYONIC STEM-CELLS; ACTIVE DNA DEMETHYLATION; ACUTE MYELOID-LEUKEMIA; ZYGOTIC PATERNAL GENOME; PRIMORDIAL GERM-CELLS; BASE EXCISION-REPAIR; METHYLTRANSFERASE GENE; BINDING PROTEIN; MAMMALIAN DNA; CPG ISLANDS AB Ten-eleven translocation 1-3 (Tet1-3) proteins have recently been discovered in mammalian cells to be members of a family of DNA hydroxylases that possess enzymatic activity toward the methyl mark on the 5-position of cytosine (5-methylcytosine [5mC]), a well-characterized epigenetic modification that has essential roles in regulating gene expression and maintaining cellular identity. Tet proteins can convert 5mC into 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) through three consecutive oxidation reactions. These modified bases may represent new epigenetic states in genomic DNA or intermediates in the process of DNA demethylation. Emerging biochemical, genetic, and functional evidence suggests that Tet proteins are crucial for diverse biological processes, including zygotic epigenetic reprogramming, pluripotent stem cell differentiation, hematopoiesis, and development of leukemia. Insights into how Tet proteins contribute to dynamic changes in DNA methylation and gene expression will greatly enhance our understanding of epigenetic regulation of normal development and human diseases. C1 [Wu, Hao; Zhang, Yi] Univ N Carolina, Lineberger Comprehens Canc Ctr, Howard Hughes Med Inst, Chapel Hill, NC 27599 USA. [Wu, Hao; Zhang, Yi] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA. [Wu, Hao] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Wu, Hao] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. RP Zhang, Y (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, Howard Hughes Med Inst, Chapel Hill, NC 27599 USA. EM yi_zhang@med.unc.edu RI Wu, Hao/G-4145-2013 OI Wu, Hao/0000-0002-1256-6891 FU NIH [GM68804, U01DK089565]; Jane Coffin Childs post-doctoral fellowship FX We thank Susan Wu for critical reading of the manuscript. We also thank reviewers for their constructive comments and suggestions. We apologize to colleagues whose work cannot be cited owing to space constrains. This work was supported by NIH grants GM68804 and U01DK089565 (to Y.Z.). H.W. is supported by a Jane Coffin Childs post-doctoral fellowship. Y.Z. is an Investigator of the Howard Hughes Medical Institute. NR 121 TC 275 Z9 285 U1 12 U2 89 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD DEC 1 PY 2011 VL 25 IS 23 BP 2436 EP 2452 DI 10.1101/gad.179184.111 PG 17 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 865WS UT WOS:000298342200003 PM 22156206 ER PT J AU Bugeon, L Taylor, HB Progatzky, F Lin, MI Ellis, CD Welsh, N Smith, E Vargesson, N Gray, C Renshaw, SA Chico, TJA Zon, LI Lamb, J Dallman, MJ AF Bugeon, Laurence Taylor, Harriet B. Progatzky, Fraenze Lin, Michelle I. Ellis, Charles D. Welsh, Natalie Smith, Emma Vargesson, Neil Gray, Caroline Renshaw, Stephen A. Chico, Timothy J. A. Zon, Leonard I. Lamb, Jonathan Dallman, Margaret J. TI The NOTCH pathway contributes to cell fate decision in myelopoiesis SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Article DE NOTCH signaling; hematopoiesis; myelopoiesis; cell fate ID IN-VIVO; GRANULOCYTIC DIFFERENTIATION; ZEBRAFISH; EXPRESSION; INFLAMMATION; ACTIVATION; HEMATOPOIESIS; MACROPHAGES; PROMOTER; GENE AB Background Controversy persists regarding the role of Notch signaling in myelopoiesis. We have used genetic approaches, employing two Notch zebrafish mutants deadly seven (DES) and beamter (BEA) with disrupted function of notch1a and deltaC, respectively, and Notch1a morphants to analyze the development of leukocyte populations in embryonic and mature fish. Design and Methods Myelomonocytes were quantified in early embryos by in situ hybridization using a myeloper-oxidase (mpx) probe. Morpholinos were used to knock down expression of Notch1a or DeltaC. Wound healing assays and/or flow cytometry were used to quantify myelomonocytes in 5-day post-fertilization (dpf) Notch mutants (BEA and DES), morphants or pu.1:GFP, mpx:GFP and fms:RFP transgenic embryos. Flow cytometry was performed on 2-3 month old mutant fish. Results The number of mpx(+) cells in embryos was reduced at 48 hpf (but not at 26 hpf) in DES compared to WT. At 5 dpf this was reflected by a reduction in the number of myelomonocytic cells found at the wound site in mutants and in Notch1a morphants. This was due to a reduced number of myelomonocytes developing rather than a deficit in the migratory ability since transient inhibition of Notch signaling using DAPT had no effect. The early deficit in myelopoiesis was maintained into later life, 2-3 month old BEA and DES fish having a decreased proportion of myelomonocytes in both the hematopoietic organ (kidney marrow) and the periphery (coelomic cavity). Conclusions Our results indicate that defects in Notch signaling affect definitive hematopoiesis, altering myelopoiesis from the early stages of development into the adult. C1 [Dallman, Margaret J.] Univ London Imperial Coll Sci Technol & Med, Fac Nat Sci, Dept Life Sci, Div Cell & Mol Biol, London SW7 2AZ, England. [Lin, Michelle I.; Zon, Leonard I.] Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. [Lin, Michelle I.; Zon, Leonard I.] Childrens Hosp, Div Haematol Oncol, Boston, MA 02115 USA. [Lin, Michelle I.; Zon, Leonard I.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Vargesson, Neil] Univ London Imperial Coll Sci Technol & Med, Fac Med, NHLI Div, London SW7 2AZ, England. [Gray, Caroline; Renshaw, Stephen A.; Chico, Timothy J. A.] Univ Sheffield, MRC Ctr Dev & Biomed Genet, Sheffield, S Yorkshire, England. RP Dallman, MJ (reprint author), Univ London Imperial Coll Sci Technol & Med, Fac Nat Sci, Dept Life Sci, Div Cell & Mol Biol, L3 Fac Bldg,S Kensington Campus, London SW7 2AZ, England. EM m.dallman@imperial.ac.uk RI Renshaw, Stephen/E-6192-2010; OI Renshaw, Stephen/0000-0003-1790-1641; Vargesson, Neil/0000-0001-8027-114X FU GlaxoSmithKline; MRC FX this work was supported by GlaxoSmithKline and the MRC. NR 39 TC 5 Z9 5 U1 0 U2 3 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD DEC PY 2011 VL 96 IS 12 BP 1753 EP 1760 DI 10.3324/haematol.2011.044115 PG 8 WC Hematology SC Hematology GA 868SB UT WOS:000298544400007 PM 21933862 ER PT J AU Seyyedi, M Eddington, DK Nadol, JB AF Seyyedi, Mohammad Eddington, Donald K. Nadol, Joseph B., Jr. TI Interaural comparison of spiral ganglion cell counts in profound deafness SO HEARING RESEARCH LA English DT Article ID COCHLEAR IMPLANTATION; CHARGE SYNDROME; HISTOPATHOLOGY AB Objectives: This study is designed to measure the degree to which spiral ganglion cell (SGC) survival in the left and right ears is similar in profoundly hearing-impaired human patients with symmetric (right/left) etiology and sensitivity. This is of interest because a small difference between ears would imply that one ear could be used as a control ear in temporal bone studies evaluating the impact on SGC survival of a medical intervention in the other ear. Materials and methods: Forty-two temporal bones from 21 individuals with bilaterally symmetric profound hearing impairment were studied. Both ears in each individual were impaired by the same etiology. Rosenthal's canal was reconstructed in two dimensions and segmental and total SGCs were counted. Correlation analysis and t-tests were used to compare segmental and total counts of left and right ears. Statistical power calculations illustrate how the results can be used to estimate the effect size (right/left difference in SGC count) that can be reliably identified as a function of sample size. Results: Left counts (segmental and total) were significantly correlated with those in the right ears (p < 0.01) and the coefficients of determination for segments 1 to 4 and total count were respectively 0.64, 0.91, 0.93, 0.91 and 0.98. The hypothesis that mean segmental and total counts of right and left are the same could not be rejected by paired t-test. Conclusion: The variance in the between-ear difference across the temporal bones studied indicates that useful effect sizes can be reliably identified using subject numbers that are practical for temporal bone studies. For instance, there is 95% likelihood that an interaural difference in SGC count of approximately 1000 cells associated with a treatment/manipulation of one ear will be reliably detected in a bilaterally-symmetric profound hearing loss population of temporal bones from approximately 10 subjects. (C) 2011 Elsevier B.V. All rights reserved. C1 [Seyyedi, Mohammad; Eddington, Donald K.; Nadol, Joseph B., Jr.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. [Seyyedi, Mohammad; Eddington, Donald K.; Nadol, Joseph B., Jr.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Seyyedi, Mohammad; Eddington, Donald K.; Nadol, Joseph B., Jr.] Massachusetts Eye & Ear Infirm, Cochlear Implant Res Lab, Boston, MA 02114 USA. [Eddington, Donald K.; Nadol, Joseph B., Jr.] MIT, Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02139 USA. RP Nadol, JB (reprint author), Harvard Univ, Sch Med, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02114 USA. EM joseph_nadol@meei.harvard.edu FU National Institute of Deafness and Other Communication Disorders [R01-DC00152] FX This work was supported by grant R01-DC00152 from the National Institute of Deafness and Other Communication Disorders. NR 12 TC 5 Z9 5 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD DEC PY 2011 VL 282 IS 1-2 BP 56 EP 62 DI 10.1016/j.heares.2011.10.002 PG 7 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 871FW UT WOS:000298724300006 PM 22008826 ER PT J AU Steensma, DP AF Steensma, David P. TI Oddballs: Acute Leukemias of Mixed Phenotype and Ambiguous Origin SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Acute leukemia; Leukemia pathology; lmmunophenotype; Leukemias of ambiguous lineage; Bilineage; Biphenotypic; Mixed phenotype acute leukemia; Acute undifferentiated leukemia ID ACUTE MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; BIPHENOTYPIC ACUTE-LEUKEMIA; TERMINAL DEOXYNUCLEOTIDYL TRANSFERASE; ACUTE UNDIFFERENTIATED LEUKEMIA; ACUTE PROMYELOCYTIC LEUKEMIA; ABL TYROSINE KINASE; FLOW-CYTOMETRY; PHILADELPHIA-CHROMOSOME; CD79A EXPRESSION AB Historically, acute leukemias that do not fit neatly into the broad categories of "acute myeloid leukemia" or "acute lymphoblastic leukemia" have caused considerable confusion and frustration for clinicians and pathologists. These misfit cases include bilineage and biphenotypic leukemias (collectively termed "mixed phenotype acute leukemias" in the 2008 World Health Organization Classification of Tumors of Hematopoietic and Lymphoid Tissues), as well as acute undifferentiated leukemias and other miscellaneous atypical cases. In this review, the author discusses the definitions, history, clinical behavior, and current treatment approaches to acute leukemias of Sambiguous lineage. C1 Dana Farber Canc Inst, Adult Leukemia Program, Dept Med Oncol, Boston, MA 02215 USA. RP Steensma, DP (reprint author), Dana Farber Canc Inst, Adult Leukemia Program, Dept Med Oncol, 450 Brookline Ave,Suite D1B30,Mayer 1B21, Boston, MA 02215 USA. EM david_steensma@dfci.harvard.edu OI Steensma, David/0000-0001-5130-9284 NR 88 TC 5 Z9 5 U1 1 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD DEC PY 2011 VL 25 IS 6 BP 1235 EP + DI 10.1016/j.hoc.2011.09.014 PG 20 WC Oncology; Hematology SC Oncology; Hematology GA 865KL UT WOS:000298309700007 PM 22093585 ER PT J AU Pantaleo, MA Astolfi, A Nannini, M Ceccarelli, C Formica, S Santini, D Heinrich, MC Corless, C Dei Tos, AP Paterini, P Catena, F Maleddu, A Saponara, M Di Battista, M Biasco, G AF Pantaleo, Maria A. Astolfi, Annalisa Nannini, Margherita Ceccarelli, Claudio Formica, Serena Santini, Donatella Heinrich, Michael C. Corless, Christopher Dei Tos, Angelo Paolo Paterini, Paola Catena, Fausto Maleddu, Alessandra Saponara, Maristella Di Battista, Monica Biasco, Guido TI Differential expression of neural markers in KIT and PDGFRA wild-type gastrointestinal stromal tumours SO HISTOPATHOLOGY LA English DT Article DE gene expression profiling; GIST; ICC; ICC mature; ICC precursor; IGF1R; KIT; PDGFRA ID INTERSTITIAL-CELLS; C-KIT; THERAPEUTIC TARGET; MUTATIONS; CAJAL; GISTS; STOMACH; COMMON; RECEPTOR; SIZE AB Aims: To compare the genomic signatures of wildtype (WT) and mutated GISTs and the murine interstitial cells of Cajal (ICCs) to find markers of cell differentiation and other functions that may identify cells that give rise to WT tumours. Methods and results: We analysed the gene expression profiles of a total of 30 tumour samples (four WT GISTs and 26 mutated GISTs), selected the genes most differentially expressed (P < 0.001: 448 probe sets) and validated these results by quantitative polymerase chain reaction (PCR) and immunohistochemistry. In addition, we conducted a meta-analysis merging data from human GISTs with a genomic data set from murine ICCs. The gene expression profiles of WT and mutated GISTs differed profoundly, especially in the expression of those genes restricted primarily to neural tissues. We found that mature ICCs are more similar to mutated GISTs than WT GISTs. Conclusions: WT GISTs have different genomic profiles from both mutated GISTs and murine mature ICCs. Considering that IGF1R expression is common to both WT GISTs and putative precursor ICCs, this study suggests that WT GISTs may derive either from ICCs at a different step of differentiation or from a different cell of origin. C1 [Pantaleo, Maria A.; Nannini, Margherita; Maleddu, Alessandra; Saponara, Maristella; Di Battista, Monica; Biasco, Guido] Univ Bologna, S Orsola Malpighi Hosp, Dept Hematol & Oncol Sci LA Seragnoli, I-40138 Bologna, Italy. [Pantaleo, Maria A.; Astolfi, Annalisa; Formica, Serena; Paterini, Paola; Biasco, Guido] Univ Bologna, Interdept Ctr Canc Res G Prodi, I-40138 Bologna, Italy. [Ceccarelli, Claudio; Santini, Donatella] Univ Bologna, S Orsola Malpighi Hosp, Dept Radiol & Histopathol Sci, Surg Pathol Unit, I-40138 Bologna, Italy. [Heinrich, Michael C.; Corless, Christopher] Portland VA Med Ctr, Dept Med, Portland, OR USA. [Heinrich, Michael C.; Corless, Christopher] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. [Dei Tos, Angelo Paolo] Gen Hosp Treviso, Dept Oncol, Treviso, Italy. [Catena, Fausto] Univ Bologna, S Orsola Malpighi Hosp, Emergency Surg & Transplant Dept, I-40138 Bologna, Italy. RP Pantaleo, MA (reprint author), Univ Bologna, S Orsola Malpighi Hosp, Dept Hematol & Oncol Sci LA Seragnoli, Via Massarenti 9, I-40138 Bologna, Italy. EM maria.pantaleo@unibo.it RI Saponara, Maristella/J-9904-2016; nannini, margherita/J-9866-2016; OI Saponara, Maristella/0000-0003-0715-171X; PANTALEO, MARIA ABBONDANZA/0000-0002-0177-6957; DEI TOS, ANGELO/0000-0002-1228-8940; Ceccarelli, Claudio/0000-0003-0743-2087; NANNINI, MARGHERITA/0000-0002-2103-1960; astolfi, annalisa/0000-0002-2732-0747 FU Fondazione Cassa di Risparmio of Bologna (CARISBO), Italy; Fondazione Giuseppe Alazio; Palermo Italy; Fondazione Vanini-Cavagnino, Bologna, Italy FX Research programmes on GIST are supported by Fondazione Cassa di Risparmio of Bologna (CARISBO), Italy, Fondazione Giuseppe Alazio, Palermo Italy and Fondazione Vanini-Cavagnino, Bologna, Italy. NR 30 TC 10 Z9 10 U1 1 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0309-0167 J9 HISTOPATHOLOGY JI Histopathology PD DEC PY 2011 VL 59 IS 6 BP 1071 EP 1080 DI 10.1111/j.1365-2559.2011.04071.x PG 10 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 866CT UT WOS:000298358000005 PM 22175887 ER PT J AU Putcha, D O'Keefe, K LaViolette, P O'Brien, J Greve, D Rentz, DM Locascio, J Atri, A Sperling, R AF Putcha, Deepti O'Keefe, Kelly LaViolette, Pete O'Brien, Jackie Greve, Doug Rentz, Dorene M. Locascio, Joseph Atri, Alireza Sperling, Reisa TI Reliability of Functional Magnetic Resonance Imaging Associative Encoding Memory Paradigms in Non-Demented Elderly Adults SO HUMAN BRAIN MAPPING LA English DT Article DE test-retest; hippocampus; precuneus; reliability; mild cognitive impairment; aging ID MILD COGNITIVE IMPAIRMENT; TEST-RETEST RELIABILITY; CONSCIOUS RESTING STATE; BOLD-FMRI SIGNAL; ALZHEIMERS-DISEASE; HIPPOCAMPAL ACTIVATION; BRAIN ACTIVITY; OLDER-ADULTS; DEFAULT NETWORK; WORKING-MEMORY AB Functional magnetic resonance imaging (fMRI) holds significant potential to aid in the development of early interventions to improve memory function, and to assess longitudinal change in memory systems in aging and early Alzheimer's disease (AD). However, the test-retest reliability of hippocampal activation and of "beneficial" deactivation in the precuneus has yet to be fully established during memory encoding tasks in older subjects. Using a mixed block and event-related face-name associative encoding paradigm, we assessed the reliability of hippocampal activation and default network deactivation over a 4- to 6-week interscan interval in 27 older individuals who were cognitively normal [Clinical Dementia Rating (CDR) Scale = 0; n = 18] or mildly impaired (CDR = 0.5; n = 9). Reliability was assessed in whole brain maps and regions of interest using both a full-task paradigm of six functional runs as well as an abbreviated paradigm of the first two functional runs, which would be advantageous for use in clinical trials. We found reliable hippocampal signal response across both block-and event-related designs in the right hippocampus. Comparable reliability in hippocampal activation was found in the full and the abbreviated paradigm. Similar reliability in hippocampal activation was observed across both CDR groups overall, but the CDR 0.5 group was more variable in left hippocampal activity. Task-related deactivation in the precuneus demonstrated much greater variability than hippocampal activation in all analyses. Overall, these results are encouraging for the utility of fMRI in "Proof of Concept" clinical trials investigating the efficacy of potentially therapeutic agents for treatment of age-related memory changes, cognitive impairment, and early AD. Hum Brain Mapp 32:2027-2044, 2011. (C) 2011 Wiley Periodicals, Inc. C1 [Putcha, Deepti; O'Keefe, Kelly; O'Brien, Jackie; Rentz, Dorene M.; Sperling, Reisa] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Alzheimer Res & Treatment,Dept Neurol, Boston, MA 02115 USA. [Putcha, Deepti; O'Keefe, Kelly; LaViolette, Pete; O'Brien, Jackie; Greve, Doug; Atri, Alireza; Sperling, Reisa] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Putcha, Deepti; O'Keefe, Kelly; LaViolette, Pete; O'Brien, Jackie; Greve, Doug; Rentz, Dorene M.; Locascio, Joseph; Atri, Alireza; Sperling, Reisa] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Atri, Alireza] Bedford Vet Adm Med Ctr, Geriatr Res Educ Ctr, Ctr Cognit Translat Neurosci, Bedford, MA USA. RP Sperling, R (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Alzheimer Res & Treatment,Dept Neurol, 221 Longwood Ave, Boston, MA 02115 USA. EM reisa@rics.bwh.harvard.edu OI Atri, Alireza/0000-0003-4405-6973 FU National Institute on Aging [R01 AG-027435, P01 AG036694, K23 AG027171, P50 AG005134] FX Contract grant sponsor: National Institute on Aging; Contract grant numbers: R01 AG-027435, P01 AG036694, K23 AG027171, P50 AG005134. NR 68 TC 14 Z9 14 U1 2 U2 12 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD DEC PY 2011 VL 32 IS 12 BP 2027 EP 2044 DI 10.1002/hbm.21166 PG 18 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 860AT UT WOS:000297918500001 PM 21259385 ER PT J AU Panchamoorthy, G Rehan, H Kharbanda, A Ahmad, R Kufe, D AF Panchamoorthy, Govind Rehan, Hala Kharbanda, Akriti Ahmad, Rehan Kufe, Donald TI A Monoclonal Antibody Against the Oncogenic Mucin 1 Cytoplasmic Domain SO HYBRIDOMA LA English DT Article ID MUC1-C ONCOPROTEIN; REGULATORY LOOP; LUNG-CANCER; BREAST; REACTIVITY; ACTIVATION; CELLS; DF3 AB Mucin 1 (MUC1) is a heterodimeric protein that is aberrantly overexpressed in diverse human carcinomas and certain hematologic malignancies. The transmembrane MUC1-C subunit confers tumorigenicity and is a target for anti-cancer drug development. In this regard, the MUC1-C cytoplasmic domain interacts with multiple effectors that have been linked to transformation. Here we report on the generation of a mouse monoclonal antibody (MAb) against the human MUC1-C cytoplasmic domain (MUC1-CD). This IgG1 MAb, designated anti-MUC1-CD, reacts with the NYGQLDIFP epitope. We show that anti-MUC1-CD is useful in immunoblotting and immunoprecipitation experiments. In addition, anti-MUC1-CD can be used to detect expression of the MUC1-C subunit in formalin-fixed, paraffin-embedded tissues. The MUC1-C inhibitor has entered Phase I evaluation for patients with refractory solid tumors. The present results indicate that the anti-MUC1-CD antibody could be useful as a biomarker to identify patients with tumors that may be responsive to MUC1-C inhibitors. C1 [Kufe, Donald] Harvard Univ, Dana Farber Canc Inst, Dept Med Oncol, Sch Med, Boston, MA 02215 USA. [Panchamoorthy, Govind; Rehan, Hala; Kharbanda, Akriti] Genus Oncol, Boston, MA USA. RP Kufe, D (reprint author), Harvard Univ, Dana Farber Canc Inst, Dept Med Oncol, Sch Med, 450 Brookline Ave, Boston, MA 02215 USA. EM donald_kufe@dfci.harvard.edu FU National Cancer Institute [CA42802, CA97098] FX This work was supported in part by grants awarded by the National Cancer Institute (nos. CA42802 and CA97098). NR 19 TC 13 Z9 13 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1554-0014 J9 HYBRIDOMA JI Hybridoma PD DEC PY 2011 VL 30 IS 6 BP 531 EP 535 DI 10.1089/hyb.2011.0070 PG 5 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Immunology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology GA 865DV UT WOS:000298291900005 PM 22149278 ER PT J AU Takahashi, K Saha, D Shattino, I Pavlov, VI Stahl, GL Finnegan, P Melo, MFV AF Takahashi, Kazue Saha, Dalia Shattino, Ivany Pavlov, Vasile I. Stahl, Gregory L. Finnegan, Paul Melo, Marcos F. Vidal TI Complement 3 is involved with ventilator-induced lung injury SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Article DE Complement; Coagulation; Matrix metalloproteinase; Complement; Acute lung injury; Humanized cobra venom factor ID MANNOSE-BINDING LECTIN; RESPIRATORY-DISTRESS-SYNDROME; REPERFUSION INJURY; INDUCED ARTHRITIS; MATRIX METALLOPROTEINASES; PSEUDOMONAS-AERUGINOSA; PULMONARY COAGULOPATHY; ADHESION MOLECULES; EPITHELIAL-CELLS; ACTIVATION AB Humoral molecules can trigger injury on mechanically stressed and damaged tissue. We have studied the role of complement 3 (C3) in a mouse model of ventilator-induced lung injury (VILI). Compared with shamtreated wild type (WT) mice, ventilated WT mice have reduced total bronchoalveolar lavage (BAL) cells; and elevated activities of thrombin and matrix metalloproteinases (MMPs), such as gelatinase/collagenase in the BAL fluid. In contrast, these parameters in ventilated C3 null mice are not significantly different from sham-treated WT and C3 null mice. In mechanically ventilated mice, thrombin activity and MMPs are lower in 0 null mice than in WT mice and are inversely correlated with total single BAL cells. C3 activation is associated with MMP activation in vitro. Pretreatment of WT mice with humanized cobra venom factor, which inactivates C3, reduces 0 deposition in the lung and increases total BAL cells in VILI We propose that C3 is involved with VILI and inhibition of complement activation may be a potential therapeutic strategy. (C) 2011 Elsevier B.V. All rights reserved. C1 [Takahashi, Kazue] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Dev Immunol,Dept Pediat, Boston, MA USA. [Saha, Dalia; Shattino, Ivany; Melo, Marcos F. Vidal] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. [Pavlov, Vasile I.; Stahl, Gregory L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Expt Therapeut & Reperfus Injury,Dept Anesthe, Boston, MA 02115 USA. [Finnegan, Paul] Incode Biopharmaceut, La Jolla, CA USA. RP Takahashi, K (reprint author), 55 Fruit St,GRJ1402, Boston, MA 02114 USA. EM ktakahashi1@partners.org FU NIH [UO1 AI074503-01, R21 AI077081-01A1, 5RO1HL086827] FX The authors thank Dr. Michael Carroll for providing C3 null mice breeding pairs. This work was in part supported by NIH grants UO1 AI074503-01, R21 AI077081-01A1, and 5RO1HL086827. NR 49 TC 13 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-5769 J9 INT IMMUNOPHARMACOL JI Int. Immunopharmacol. PD DEC PY 2011 VL 11 IS 12 BP 2138 EP 2143 DI 10.1016/j.intimp.2011.09.008 PG 6 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA 867NI UT WOS:000298460700025 PM 21979496 ER PT J AU Buhlmann, U Greenberg, JL Wilhelm, S AF Buhlmann, Ulrike Greenberg, Jennifer L. Wilhelm, Sabine TI Recent Advances in BDD: The Role of Risk Factors and Cognitive-Behavioral Therapy Introduction to the Special Section SO INTERNATIONAL JOURNAL OF COGNITIVE THERAPY LA English DT Editorial Material ID BODY DYSMORPHIC DISORDER C1 [Buhlmann, Ulrike] Univ Berlin, Dept Clin Psychol, D-12489 Berlin, Germany. [Greenberg, Jennifer L.; Wilhelm, Sabine] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Greenberg, Jennifer L.; Wilhelm, Sabine] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Buhlmann, U (reprint author), Univ Berlin, Dept Clin Psychol, Rudower Chaussec 18, D-12489 Berlin, Germany. EM ulrike.buhlmann@hu-berlin.de NR 7 TC 0 Z9 0 U1 0 U2 3 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 1937-1209 J9 INT J COGN THER JI Int. J. Cogn. Ther. PD DEC PY 2011 VL 4 IS 4 BP 339 EP 341 PG 3 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 860OK UT WOS:000297957400001 ER PT J AU Buhlmann, U Wilhelm, S Glaesmer, H Mewes, R Brahler, E Rief, W AF Buhlmann, Ulrike Wilhelm, Sabine Glaesmer, Heide Mewes, Ricarda Braehler, Elmar Rief, Winfried TI Perceived Appearance-Related Teasing in Body Dysmorphic Disorder: A Population-Based Survey SO INTERNATIONAL JOURNAL OF COGNITIVE THERAPY LA English DT Article ID PREVALENCE; IMAGE AB Body dysmorphic disorder (BDD) is characterized by perceived defects in one's physical appearance (e.g., facial asymmetry). Cognitive-behavioral models of BDD suggest that several factors, including negative appearance-related beliefs and life experiences, such as teasing, might be related to BDD's unique symptomatology Research on perceived teasing in BDD is still limited, and the relationships previously found have been based on small sample sizes. In the current study, we investigated perceived appearance-related teasing in the German population (total N = 2,510; BDD group: n = 45; age and gender-matched non-BDD group: n = 45). As expected, the BDD group reported significantly more teasing than did the non-BDD group (40.0% vs 15.6%). Whereas no group difference was obtained regarding the years of age at the first teasing incident, the BDD group remembered the teasing experience more vividly (p =.008) and as more traumatic (p =.002). This study provides further evidence for perceived teasing in BDD. C1 [Buhlmann, Ulrike] Univ Berlin, Dept Clin Psychol, D-12489 Berlin, Germany. [Wilhelm, Sabine] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wilhelm, Sabine] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Glaesmer, Heide; Braehler, Elmar] Univ Leipzig, Leipzig, Germany. [Mewes, Ricarda; Rief, Winfried] Univ Marburg, D-35032 Marburg, Germany. RP Buhlmann, U (reprint author), Univ Berlin, Dept Clin Psychol, Rudower Chaussee 18, D-12489 Berlin, Germany. EM ulrike.buhlmann@hu-berlin.de NR 19 TC 8 Z9 8 U1 1 U2 10 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 1937-1209 J9 INT J COGN THER JI Int. J. Cogn. Ther. PD DEC PY 2011 VL 4 IS 4 BP 342 EP 348 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 860OK UT WOS:000297957400002 ER PT J AU Greenberg, JL Wilhelm, S AF Greenberg, Jennifer L. Wilhelm, Sabine TI Cognitive-Behavioral Therapy for Body Dysmorphic Disorder: A Review and Future Directions SO INTERNATIONAL JOURNAL OF COGNITIVE THERAPY LA English DT Review ID OBSESSIVE-COMPULSIVE DISORDER; POPULATION-BASED SURVEY; RESPONSE PREVENTION; CLINICAL-FEATURES; EXPOSURE THERAPY; FOLLOW-UP; DYSMORPHOPHOBIA; PREVALENCE; MAINTENANCE; RELIABILITY AB Theoretical and empirical rationale support cognitive behavioral therapy (CBT) as the psychological treatment of choice for body dysmorphic disorder (BDD). The aim of this article is to review the evidence from published outcome studies of cognitive, behavioral, and cognitive-behavioral interventions for BDD. The literature on CBT for BDD is sparse but promising. Evidence suggests that CBT for BDD is associated with symptom improvement, generally performs better than wait-list controls, and is associated with improvement in associated features, including functioning, depression, anxiety, and delusional beliefs. However, the small number of studies and methodological limitations hamper definitive conclusions about the efficacy of CBT for BDD. We propose directions for future research. C1 [Greenberg, Jennifer L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Greenberg, JL (reprint author), Massachusetts Gen Hosp, Simches Res Bldg,185 Cambridge St,Suite 2200, Boston, MA 02114 USA. EM jlgreenberg@partners.org NR 53 TC 4 Z9 4 U1 1 U2 23 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 1937-1209 J9 INT J COGN THER JI Int. J. Cogn. Ther. PD DEC PY 2011 VL 4 IS 4 BP 349 EP 362 PG 14 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 860OK UT WOS:000297957400003 ER PT J AU Weingarden, H Marques, L Fang, A LeBlanc, N Buhlmann, U Phillips, KA Wilhelm, S AF Weingarden, Hilary Marques, Luana Fang, Angela LeBlanc, Nicole Buhlmann, Ulrike Phillips, Katharine A. Wilhelm, Sabine TI Culturally Adapted Cognitive Behavioral Therapy for Body Dysmorphic Disorder: Case Examples SO INTERNATIONAL JOURNAL OF COGNITIVE THERAPY LA English DT Article ID OBSESSIVE-COMPULSIVE SCALE; TREATMENT-RESISTANT PTSD; POPULATION-BASED SURVEY; CAMBODIAN REFUGEES; ASIAN-AMERICAN; PANIC-ATTACKS; PREVALENCE; RELIABILITY; IMAGE; VALIDITY AB Individuals with body dysmorphic disorder (BDD) have distressing or impairing preoccupations with imagined or slight defects in their appearance (e.g., nose too big). BDD is a severe psychiatric disorder often associated with high rates of suicidality as well as social and occupational impairment (Phillips, Coles, Menard, Yen, Fay, & Weisberg, 2005). Researchers have only recently begun to investigate psychological treatments for BDD, with available data suggesting that cognitive behavioral therapy (CBT) appears efficacious for BDD (Williams, Hadjistavropoulos, & Sharpe, 2006). To our knowledge there are no reports of whether CBT for BDD can be effectively generalized to ethnic minority and other special populations. We suggest specific modifications within the CBT for BDD framework that might improve the effectiveness and retention rates of CBT among ethnic minority patients with BDD. Specifically, the cases of Ben, a 40-year-old, Jewish, married male, and John, a 30-year-old, African American, single male, both with a primary diagnosis of BDD, are described. Various treatment techniques were used the course of CBT more culturally responsive. This case report illustrates the challenges and benefits of integrating cultural variables into a CBT framework for BDD, and it highlights the need for more work in this area. C1 [Marques, Luana] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Weingarden, Hilary] George Mason Univ, Fairfax, VA 22030 USA. [Fang, Angela] Boston Univ, Boston, MA 02215 USA. [Buhlmann, Ulrike; Phillips, Katharine A.] Univ Berlin, Rhode Isl Hosp, Berlin, Germany. [Buhlmann, Ulrike; Phillips, Katharine A.] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA. RP Marques, L (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, 1 Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM lmarques@partners.org FU NIMH NIH HHS [R34 MH070490] NR 40 TC 3 Z9 3 U1 3 U2 7 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 1937-1209 J9 INT J COGN THER JI Int. J. Cogn. Ther. PD DEC PY 2011 VL 4 IS 4 BP 381 EP 396 PG 16 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 860OK UT WOS:000297957400005 PM 25346783 ER PT J AU McClintock, SM Husain, MM Bernstein, IH Wisniewski, SR Trivedi, MH Morris, D Alpert, J Warden, D Luther, JF Kornstein, SG Biggs, MM Fava, M Rush, AJ AF McClintock, Shawn M. Husain, Mustafa M. Bernstein, Ira H. Wisniewski, Stephen R. Trivedi, Madhukar H. Morris, David Alpert, Jonathan Warden, Diane Luther, James F. Kornstein, Susan G. Biggs, Melanie M. Fava, Maurizio Rush, A. John TI Assessing anxious features in depressed outpatients SO INTERNATIONAL JOURNAL OF METHODS IN PSYCHIATRIC RESEARCH LA English DT Article DE depression; anxiety; rating scales; STAR(star)D; measurement-based care ID STAR-ASTERISK-D; SEQUENCED TREATMENT ALTERNATIVES; DIAGNOSTIC SCREENING QUESTIONNAIRE; NATIONAL COMORBIDITY SURVEY; ITEM RESPONSE THEORY; RATING-SCALE; QUICK INVENTORY; SELF-REPORT; PSYCHOMETRIC EVALUATION; SYMPTOMATOLOGY IDS AB Both the 17-item Hamilton Rating Scale for Depression (HRSD(17)) and 30-item Inventory of Depressive Symptomatology - Clinician-rated (IDS-C(30)) contain a subscale that assesses anxious symptoms. We used classical test theory and item response theory methods to assess and compare the psychometric properties of the two anxiety subscales (HRSD(ANX) and IDS-C(ANX)) in a large sample (N = 3453) of outpatients with non-psychotic major depressive disorder in the Sequenced Treatment Alternatives to Relieve Depression (STAR(star)D) study. Approximately 48% of evaluable participants had at least one concurrent anxiety disorder by the self-report Psychiatric Diagnostic Screening Questionnaire (PDSQ). The HRSD(ANX) and IDS-C(ANX) were highly correlated (r = 0.75) and both had moderate internal consistency given their limited number of items (HRSD(ANX) Cronbach's alpha = 0.48; IDS-C(ANX) Cronbach's alpha = 0.58). The optimal threshold for ascribing the presence/absence of anxious features was found at a total score of eight or nine for the HRSD(ANX) and seven or eight for the IDS-C(ANX). It would seem beneficial to delete item 17 (loss of insight) from the HRSD(ANX) as it negatively correlated with the scale's total score. Both the HRSD(ANX) and IDS-C(ANX) subscales have acceptable psychometric properties and can be used to identify anxious features for clinical or research purposes. Copyright (C) 2011 John Wiley & Sons, Ltd. C1 [McClintock, Shawn M.; Husain, Mustafa M.; Trivedi, Madhukar H.; Morris, David; Warden, Diane; Biggs, Melanie M.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [McClintock, Shawn M.] Columbia Univ, Dept Psychiat, New York State Psychiat Inst, New York, NY USA. [Bernstein, Ira H.] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA. [Wisniewski, Stephen R.; Luther, James F.] Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA USA. [Alpert, Jonathan; Fava, Maurizio] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Kornstein, Susan G.] Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA USA. [Biggs, Melanie M.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA. [Rush, A. John] Duke NUS Grad Med Sch, Off Clin Sci, Singapore, Singapore. RP McClintock, SM (reprint author), Univ Texas SW Med Ctr Dallas, Dept Psychiat, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM shawn.mcclintock@utsouthwestern.edu OI Wisniewski, Stephen/0000-0002-3877-9860; Alpert, Jonathan/0000-0002-4332-908X; Rush, Augustus/0000-0003-2004-2382 FU National Institute of Mental Health (NIMH) [N01MH90003]; National Institutes of Health (NIH); National Alliance for Research on Schizophrenia and Depression (NARSAD); Abbott Laboratories; Alkermes; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; Aspect Medical Systems; Astra-Zeneca; Bristol-Myers Squibb Company; Cephalon; Cyberonics; Eli Lilly Company; Forest Pharmaceuticals Inc.; GlaxoSmithkline; J & J Pharmaceuticals; Novartis; Organon Inc.; PamLab; LLC; Pfizer Inc; Pharmavite; Roche; Sanofi/Synthelabo; Solvay Pharmaceuticals, Inc.; Wyeth-Ayerst Laboratories; National Institute of Mental Health; Stanley Medical Research Institute; Cyberonics, Inc.; Neuronetics, Inc.; Magstim; Advanced Neuromodulation Systems; Department of Health and Human Services; Pfizer, Inc.; Lilly, Inc.; Forest Laboratories, Inc.; GlaxoSmithKline, Inc.; Mitsubishi-Tokyo; Merck, Inc.; Biovail Laboratories, Inc.; Wyeth, Inc.; Berlex Laboratories; Novartis Pharmaceuticals, Inc.; Sepracor, Inc.; Boehringer-Ingelheim; Sanofi-Synthelabo FX This project was funded by the National Institute of Mental Health (NIMH) under contract N01MH90003 to the University of Texas Southwestern Medical Center at Dallas (A.J. Rush, principal investigator). The NIMH had no further role in the study design; in the collection, analysis and interpretation of the data; in the writing of the report; or in the decision to submit the paper for publication. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. Also, we thank Bristol-Myers Squibb, Forest Laboratories, GlaxoSmithKline, King Pharmaceuticals, Organon, Pfizer, and Wyeth for providing medications at no cost for this trial. Trial Registration: clinicaltrials.govIdentifier: NCT00021528; The authors would like to acknowledge Dr Anna Brandon at University of Texas Southwestern Medical Center and Ms Sara Mlynarchek at the University of Pittsburgh Graduate School of Public Health for input into this manuscript. The authors would like to acknowledge the editorial support of Mr Jon Kilner, MS, MA (Pittsburgh, PA).; Dr McClintock has received research support from the National Institutes of Health (NIH) and the National Alliance for Research on Schizophrenia and Depression (NARSAD). Dr Alpert has received research support from Abbott Laboratories, Alkermes, Lichtwer Pharma GmbH, Lorex Pharmaceuticals; Aspect Medical Systems, Astra-Zeneca, Bristol-Myers Squibb Company, Cephalon, Cyberonics, Eli Lilly & Company, Forest Pharmaceuticals Inc., GlaxoSmithkline, J & J Pharmaceuticals, Novartis, Organon Inc., PamLab, LLC, Pfizer Inc, Pharmavite, Roche, Sanofi/Synthelabo, Solvay Pharmaceuticals, Inc., and Wyeth-Ayerst Laboratories. He has received speakers' honoraria from Eli Lilly & Company, Janssen, Organon. Dr Husain has received research support from the National Institute of Mental Health, Stanley Medical Research Institute, Cyberonics, Inc., Neuronetics, Inc., Magstim, and Advanced Neuromodulation Systems. Dr Kornstein has received research support from the Department of Health and Human Services, National Institute of Mental Health, Pfizer, Inc., Bristol-Myers Squibb Company, Lilly, Inc., Forest Laboratories, Inc., GlaxoSmithKline, Inc., Mitsubishi-Tokyo, Merck, Inc., Biovail Laboratories, Inc., Wyeth, Inc., Berlex Laboratories, Novartis Pharmaceuticals, Inc., Sepracor, Inc., Boehringer-Ingelheim, Sanofi-Synthelabo, and Astra-Zeneca.; Dr Alpert has served as in the advisor/consultative relationship role with Eli Lilly & Company, Pamlab LLC, and Pharmavite LLC. Dr Biggs has served as a consultant for Bristol-Meyers Squibb, Eli Lilly, GlaoxSmithKline, Merck, and Pfizer. Dr Fava has provided scientific consultation to or served on the Advisory Boards for Aspect Medical Systems, Astra-Zeneca, Bayer AG, Biovail Pharmaceuticals, Inc., BrainCells, Inc. Bristol-Myers Squibb Company, Cephalon, Compellis, Cypress Pharmaceuticals, Dov Pharmaceuticals, Eli Lilly & Company, EPIX Pharmaceuticals, Fabre-Kramer Pharmaceuticals, Inc., Forest Pharmaceuticals Inc., GlaxoSmithKline, Grunenthal GmBH, Janssen Pharmaceutica, Jazz Pharmaceuticals, J & J Pharmaceuticals, Knoll Pharmaceutical Company, Lundbeck, MedAvante, Inc., Neuronetics, Novartis, Nutrition 21, Organon Inc., PamLab, LLC, Pfizer Inc, PharmaStar, Pharmavite, Roche, Sanofi/Synthelabo, Sepracor, Solvay Pharmaceuticals, Inc., Somaxon, Somerset Pharmaceuticals, Wyeth-Ayerst Laboratories. He has been on speaker bureaus for Astra-Zeneca, Boehringer-Ingelheim, BristolMyers Squibb Company, Cephalon, Eli Lilly & Company, Forest Pharmaceuticals Inc., GlaxoSmithKline, Novartis, Organon Inc., Pfizer Inc, PharmaStar, Wyeth-Ayerst Laboratories. He has received research/grant support from Abbott Laboratories, Alkermes, Aspect Medical Systems, Astra-Zeneca, Bristol-Myers Squibb Company, Cephalon, Eli Lilly & Company, Forest Pharmaceuticals Inc., GlaxoSmithKline, J & J Pharmaceuticals, Lichtwer Pharma GmbH, Lorex Pharmaceuticals, Novartis, Organon Inc., PamLab, LLC, Pfizer Inc, Pharmavite, Roche, Sanofi/Synthelabo, Solvay Pharmaceuticals, Inc., Wyeth-Ayerst Laboratories. He has equity holdings in Compellis, MedAvante. Dr Husain has served on Advisory Boards for AstraZeneka, VersusMed, Avinar, Boston Scientific, MEASURE, Bristol-Meyer-Squibb, and Clinical Advisors and on speakers bureaus for Cyberonics, Inc., Avinar, Inc., Cerebrio, Inc., AstraZeneka, Bristol-Meyers-Squibb, Optima/Forrest Pharmaceuticals, Glaxo-Smith-Kline, Forrest Pharmaceuticals, and Janssen. Dr Kornstein has served on Advisory Boards/recieved honoraria from Pfizer, Inc., Wyeth, Inc., Lilly, Inc., Bristol-Myers Squibb Company, Warner-Chilcott, Inc., Biovail Laboratories, Berlex Laboratories, Forest Laboratories, Neurocrine, and Sepracor, Inc. She has received book royalties from Guilford Press. Dr Morris has been a consultant for Pfizer. Dr Rush has provided scientific consultation to or served on Advisory Boards for Advanced Neuromodulation Systems, Inc.; Best Practice Project Management, Inc.; Bristol-Myers Squibb Company; Cyberonics, Inc.; Forest Pharmaceuticals, Inc.; Gerson Lehman Group; GlaxoSmithKline; Jazz Pharmaceuticals; Eli Lilly & Company; Merck & Co., Inc.; Neuronetics; Ono Pharmaceutical; Organon USA Inc.; Personality Disorder Research Corp.; Pfizer Inc.; The Urban Institute; and Wyeth-Ayerst Laboratories Inc. He has received royalties from Guilford Press and Healthcare Technology Systems and research/grant support from the Robert Wood Johnson Foundation, the National Institute of Mental Health, and the Stanley Foundation; has been on speaker bureaus for Cyberonics, Inc., Forest Pharmaceuticals Inc., GlaxoSmithKline, and Eli Lilly & Company; and owns stock in Pfizer Inc. Dr Trivedi has received research support from Bristol-Myers Squibb Company; Cephalon, Inc.; Corcept Therapeutics, Inc.; Cyberonics, Inc.; ; Eli Lilly & Company; Forest Pharmaceuticals; GlaxoSmithKline; Janssen Pharmaceutica; Merck; National Institute of Mental Health; National Alliance for Resarch in Schizophrenia and Depression; Novartis; Pfizer Inc.; Pharmacia & Upjohn; Predix Pharmaceuticals; Solvay Pharmaceuticals, Inc.; and Wyeth-Ayerst Laboratories. He has served on Advisory Boards for or provided consultation to Abbott Laboratories, Inc.; Akzo (Organon Pharmaceuticals Inc.); Bayer; Bristol-Myers Squibb Company; Cephalon, Inc.; Cyberonics, Inc.; Forest Pharmaceuticals; GlaxoSmithKline; Janssen Pharmaceutica Products, LP; Johnson & Johnson PRD; Eli Lilly & Company; Meade Johnson; Parke-Davis Pharmaceuticals, Inc.; Pfizer, Inc.; Pharmacia & Upjohn; Sepracor; Solvay Pharmaceuticals, Inc.; and Wyeth-Ayerst Laboratories and has been on speaker's bureaus for Akzo (Organon Pharmaceuticals Inc.); Bristol-Myers Squibb Company; Cephalon, Inc.; Cyberonics, Inc.; Forest Pharmaceuticals; Janssen Pharmaceutica Products, LP; Eli Lilly & Company; Pharmacia & Upjohn; Solvay Pharmaceuticals, Inc.; and WyethAyerst Laboratories. Dr. Warden currently owns stock in Pfizer and previously owned stock in Bristol Myers Squibb. Dr Wisniewski has served as a consultant for Cyberonics Inc. (2005-2005) and ImaRx Therapeutics, Inc. (2006). The remaining authors report no competing interests. NR 64 TC 7 Z9 8 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1049-8931 J9 INT J METH PSYCH RES JI Int. J. Methods Psychiatr. Res. PD DEC PY 2011 VL 20 IS 4 BP E69 EP E82 DI 10.1002/mpr.353 PG 14 WC Psychiatry SC Psychiatry GA 860XW UT WOS:000297982800001 PM 22057975 ER PT J AU Azizi, B Ziaei, A Fuchsluger, T Schmedt, T Chen, YM Jurkunas, UV AF Azizi, Behrooz Ziaei, Alireza Fuchsluger, Thomas Schmedt, Thore Chen, Yuming Jurkunas, Ula V. TI p53-Regulated Increase in Oxidative-Stress-Induced Apoptosis in Fuchs Endothelial Corneal Dystrophy: A Native Tissue Model SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID P53; CELLS; PATHOGENESIS; EXPRESSION AB PURPOSE. This study compared susceptibility of Fuchs endothelial corneal dystrophy (FECD) and normal corneal endothelial cells (CECs) to oxidative stress, and studied the mechanism of oxidative-stress-induced apoptosis in FECD-affected endothelium. METHODS. For in vitro studies, immortalized normal and FECD human corneal endothelial cell lines (HCECi and FECDi, respectively) were exposed to tert-butyl hydroperoxide (tBHP). Apoptotic cell populations were distinguished using flow cytometry. Reactive oxygen species production was measured by a horseradish peroxidase assay. For ex vivo studies, CECs were exposed to tBHP. Oxidative DNA damage and apoptosis were assessed by anti-8-hydroxydeoxyguanosine antibody and TUNEL assay, respectively. p53 and phospho-p53 levels were assessed by Western blot and immunohistochemistry. RESULTS. Flow cytometry revealed a higher rate of apoptosis in FECDi than that in HCECi after exposure to 0.5 mM (P = 0.010) and 1.0 mM tBHP (P = 0.041). Further analysis showed increased production of H(2)O(2) by FECDi than that by HCECi. Oxidative DNA damage increased in both normal and FECD CECs after exposure to 0.5 mM tBHP (P = 0.031 and 0.022, respectively), leading to a 21% increase in TUNEL-positive CECs in FECD (P = 0.015) but no change in normal. Baseline p53 expression was twofold higher in FECD than that in normal endothelium (P = 0.002). Immunofluorescence revealed an increase in p53 and phospho-p53 levels in FECD compared with that in normal endothelium. CONCLUSIONS. FECD CECs are more susceptible to oxidative DNA damage and oxidative-stress-induced apoptosis than normal. Increased activation of p53 in FECD suggests that it mediates cell death in susceptible CECs. The authors conclude that p53 plays a critical role in complex mechanisms regulating oxidative-stress-induced apoptosis in FECD. (Invest Ophthalmol Vis Sci. 2011; 52: 9291-9297) DOI: 10.1167/iovs.11-8312 C1 [Azizi, Behrooz; Ziaei, Alireza; Fuchsluger, Thomas; Schmedt, Thore; Chen, Yuming; Jurkunas, Ula V.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst,Dept Ophthalmol, Boston, MA 02114 USA. RP Jurkunas, UV (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst,Dept Ophthalmol, 20 Staniford St, Boston, MA 02114 USA. EM ula_jurkunas@meei.harvard.edu FU Eye Bank Association; National Eye Institute/National Institutes of Health [R01 EY20581]; Research to Prevent Blindness FX Supported in part by an award from the Eye Bank Association (BA and TS); National Eye Institute/National Institutes of Health Grant R01 EY20581; and a Research to Prevent Blindness Award (UVJ). NR 16 TC 34 Z9 34 U1 1 U2 5 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD DEC PY 2011 VL 52 IS 13 BP 9291 EP 9297 DI 10.1167/iovs.11-8312 PG 7 WC Ophthalmology SC Ophthalmology GA 869WC UT WOS:000298628200001 PM 22064994 ER PT J AU Verter, EE Gisel, TE Yang, PG Johnson, AJ Redmond, RW Kochevar, IE AF Verter, E. Eri Gisel, Thomas E. Yang, Penggao Johnson, Anthony J. Redmond, Robert W. Kochevar, Irene E. TI Light-Initiated Bonding of Amniotic Membrane to Cornea SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID PHOTODYNAMIC CROSS-LINKING; PHOTOCHEMICAL KERATODESMOS; SINGLET OXYGEN; FIBRIN GLUE; INCISIONS; COLLAGEN; REPAIR; SKIN; TEMPERATURE; MODEL AB PURPOSE. Suturing amniotic membrane to cornea during surgery is time consuming, and sutures may further damage the eye. The authors introduce a novel sutureless, light-activated technique that securely attaches amnion to cornea through protein-protein crosslinks. METHODS. Cryopreserved human amniotic membrane, stained with Rose Bengal (RB), was placed over a full-thickness wound in deepithelialized rabbit cornea and was treated with green laser. The intraocular pressure that broke the seal (IOP(L)) was measured, and adhesion was measured with a peel test. The influences on bonding strength of fluence, irradiance, RB concentration, and amnion surface bonded were measured. Epithelial cell migration on treated amnion and keratocyte viability after bonding were also measured. The involvement in the bonding mechanism of oxygen, singlet oxygen, and association of RB with stromal collagen was investigated. RESULTS. Sealing amniotic membrane over cornea using 0.1% RB and 150 J/cm(2) at 532 nm produced an IOP L of 261 +/- 77 mm Hg ex vivo and 448 mm +/- 212 mm Hg in vivo. The ex vivo IOP L increased with increasing fluence (50-150 J/cm(2)). Equivalent IOP L was produced for bonding basement membrane or stromal amnion surfaces. The bonding treatment was not toxic to keratocytes but slightly reduced the migration of corneal epithelial cells on amnion ex vivo. Mechanism studies indicated that RB forms two complexes with amnion stromal collagen, that bonding requires oxygen, and that singlet oxygen mediates protein crosslinking. CONCLUSIONS. A rapid, light-activated technique produces strong, immediate bonding between amnion and cornea and merits further evaluation for ocular surface surgeries. (Invest Ophthalmol Vis Sci. 2011;52:9470-9477) DOI:10.1167/iovs.11-7248 C1 [Verter, E. Eri; Gisel, Thomas E.; Yang, Penggao; Redmond, Robert W.; Kochevar, Irene E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. [Yang, Penggao] 3 Peoples Hosp, Dept Burns & Plast Surg, Shanghai, Peoples R China. [Johnson, Anthony J.] Brooke Army Med Ctr, Dept Ophthalmol, San Antonio, TX USA. RP Kochevar, IE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Thier Bldg,Room 212,55 Fruit St, Boston, MA 02114 USA. EM kochevar@helix.mgh.harvard.edu FU US Department of the Army [W81XWH-09-2-0050]; Air Force Office of Scientific Research [FA9550-10-1-0537] FX Supported by US Department of the Army Award number W81XWH-09-2-0050 and Air Force Office of Scientific Research Grant FA9550-10-1-0537. NR 37 TC 19 Z9 21 U1 4 U2 8 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD DEC PY 2011 VL 52 IS 13 BP 9470 EP 9477 DI 10.1167/iovs.11-7248 PG 8 WC Ophthalmology SC Ophthalmology GA 869WC UT WOS:000298628200027 PM 22058339 ER PT J AU Todani, A Behlau, I Fava, MA Cade, F Cherfan, DG Zakka, FR Jakobiec, FA Gao, YQ Dohlman, CH Melki, SA AF Todani, Amit Behlau, Irmgard Fava, Mark A. Cade, Fabiano Cherfan, Daniel G. Zakka, Fouad R. Jakobiec, Frederick A. Gao, Yuqing Dohlman, Claes H. Melki, Samir A. TI Intraocular Pressure Measurement by Radio Wave Telemetry SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID GLAUCOMA; RABBITS; APPLANATION; TONOMETRY; TONOPEN; ACCURACY; GOLDMANN; OFFICE AB PURPOSE. To determine the biocompatibility of a new wireless intraocular pressure (IOP) transducer (WIT) in rabbit eyes and to correlate its measurements with other pressure-measuring devices. METHODS. The WIT is a ring-shaped intraocular device that allows wireless IOP measurements through radiofrequency. It was implanted into six eyes of New Zealand White rabbits after extracapsular lens extraction. A sham rabbit eye with no transducer implanted was used as a control. The animals were observed and examined by microscopy at various intervals up to 25 months after surgery. IOP was measured at various intervals by pneumotonometry, tonometry, WIT, and manometry. The data from the various devices were compared and analyzed for reproducibility. Two eyes were enucleated at 5.5 and 20 months after implantation and analyzed by histology. RESULTS. The WIT appears to be well tolerated in the rabbit eye, with no evidence of significant inflammation or scar formation by microscopic in vivo examination. Histology did not reveal intraocular inflammation or membrane formation. Repeated IOP measurements with pneumotonometry, tonometry, and the WIT resulted in SDs of 2.70 mm Hg, 3.35 mm Hg, and 0.81 mm Hg, respectively. The concordance between the WIT and direct manometry measurements was high. A downward drift in IOP measured by the WIT was noted in three rabbits, necessitating recalibration. CONCLUSIONS. The WIT is well tolerated by the rabbit eye. Its measurements are reproducible and in close concordance with manometry. A downward IOP drift warrants further investigation. (Invest Ophthalmol Vis Sci. 2011; 52:9573-9580) DOI: 10.1167/iovs.11-7878 C1 [Todani, Amit; Behlau, Irmgard; Cade, Fabiano; Zakka, Fouad R.; Jakobiec, Frederick A.; Dohlman, Claes H.; Melki, Samir A.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Brookline, MA 02445 USA. [Todani, Amit; Fava, Mark A.; Cherfan, Daniel G.; Gao, Yuqing; Melki, Samir A.] Boston Eye Grp, Boston, MA USA. RP Melki, SA (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, 1101 Beacon St 6W, Brookline, MA 02445 USA. EM samir_melki@meei.harvard.edu FU Massachusetts Eye and Ear Infirmary, Boston, Massachusetts FX Supported by the Keratoprosthesis Fund, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts. NR 30 TC 25 Z9 26 U1 1 U2 7 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD DEC PY 2011 VL 52 IS 13 BP 9573 EP 9580 DI 10.1167/iovs.11-7878 PG 8 WC Ophthalmology SC Ophthalmology GA 869WC UT WOS:000298628200043 PM 22039243 ER PT J AU Lowe, HC Narula, J Fujimoto, JG Jang, IK AF Lowe, Harry C. Narula, Jagat Fujimoto, James G. Jang, Ik-Kyung TI Intracoronary Optical Diagnostics Current Status, Limitations, and Potential SO JACC-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE atherosclerosis; coronary stent; intravascular imaging ID SIROLIMUS-ELUTING STENTS; ACUTE MYOCARDIAL-INFARCTION; CORONARY-ARTERY-DISEASE; 6-MONTH FOLLOW-UP; BARE-METAL STENTS; COHERENCE TOMOGRAPHY; INTRAVASCULAR ULTRASOUND; NEOINTIMAL COVERAGE; IN-VIVO; PLAQUE MORPHOLOGY AB Optical coherence tomography (OCT), is a novel intravascular imaging modality analogous to intravascular ultrasound but uses light instead of sound. This review details the background, development, and status of current investigation using OCT, and discusses advantages, limitations, and likely future developments. It provides indications for possible future clinical use, and places OCT in the context of current intravascular imaging in what is a rapidly changing field of investigation. (J Am Coll Cardiol Intv 2011;4:1257-70) (C) 2011 by the American College of Cardiology Foundation C1 [Jang, Ik-Kyung] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Lowe, Harry C.] Concord Repatriat Gen Hosp, Sydney, NSW, Australia. [Lowe, Harry C.] Univ Sydney, Sydney, NSW 2006, Australia. [Narula, Jagat] Univ Calif Irvine, Sch Med, Irvine, CA 92717 USA. [Fujimoto, James G.] MIT, Cambridge, MA 02139 USA. [Jang, Ik-Kyung] Harvard Univ, Sch Med, Boston, MA USA. RP Jang, IK (reprint author), Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St,GRB 800, Boston, MA 02114 USA. EM ljang@partners.org FU LightLab Imaging; Abbott Vascular; Johnson Johnson FX Dr. Jang has received research grants from LightLab Imaging, Abbott Vascular, and Johnson & Johnson; and he has received royalties front IP owned by MIT and licenced to LightLab Imaging/St. Jude Medical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 100 TC 37 Z9 38 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-8798 EI 1876-7605 J9 JACC-CARDIOVASC INTE JI JACC-Cardiovasc. Interv. PD DEC PY 2011 VL 4 IS 12 BP 1257 EP 1270 DI 10.1016/j.jcin.2011.08.015 PG 14 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 872ST UT WOS:000298830500001 PM 22192367 ER PT J AU Bao, Y Michaud, DS Spiegelman, D Albanes, D Anderson, KE Bernstein, L van den Brandt, PA English, DR Freudenheim, JL Fuchs, CS Giles, GG Giovannucci, E Goldbohm, RA Hakansson, N Horn-Ross, PL Jacobs, EJ Kitahara, CM Marshall, JR Miller, AB Robien, K Rohan, TE Schatzkin, A Stevens, VL Stolzenberg-Solomon, RZ Virtamo, J Wolk, A Ziegler, RG Smith-Warner, SA AF Bao, Ying Michaud, Dominique S. Spiegelman, Donna Albanes, Demetrius Anderson, Kristin E. Bernstein, Leslie van den Brandt, Piet A. English, Dallas R. Freudenheim, Jo L. Fuchs, Charles S. Giles, Graham G. Giovannucci, Edward Goldbohm, R. Alexandra Hakansson, Niclas Horn-Ross, Pamela L. Jacobs, Eric J. Kitahara, Cari M. Marshall, James R. Miller, Anthony B. Robien, Kim Rohan, Thomas E. Schatzkin, Arthur Stevens, Victoria L. Stolzenberg-Solomon, Rachael Z. Virtamo, Jarmo Wolk, Alicja Ziegler, Regina G. Smith-Warner, Stephanie A. TI Folate Intake and Risk of Pancreatic Cancer: Pooled Analysis of Prospective Cohort Studies SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Review ID FOOD FREQUENCY QUESTIONNAIRE; COLORECTAL-CANCER; MALE SMOKERS; DUCTAL ADENOCARCINOMA; CALIFORNIA TEACHERS; DIETARY ASSESSMENT; MULTIPLE GENES; FOLIC-ACID; WOMEN; METAANALYSIS AB Background Epidemiological studies evaluating the association between folate intake and risk of pancreatic cancer have produced inconsistent results. The statistical power to examine this association has been limited in previous studies partly because of small sample size and limited range of folate intake in some studies. Methods We analyzed primary data from 14 prospective cohort studies that included 319 716 men and 542 948 women to assess the association between folate intake and risk of pancreatic cancer. Folate intake was assessed through a validated food-frequency questionnaire at baseline in each study. Study-specific relative risks (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models and then pooled using a random effects model. All statistical tests were two-sided. Results During 7-20 years of follow-up across studies, 2195 pancreatic cancers were identified. No association was observed between folate intake and risk of pancreatic cancer in men and women (highest vs lowest quintile: dietary folate intake, pooled multivariable RR = 1.06, 95% CI = 0.90 to 1.25, P-trend = .47; total folate intake [dietary folate and supplemental folic acid], pooled multivariable RR = 0.96, 95% CI = 0.80 to 1.16, P-trend = .90). No between-study heterogeneity was observed (for dietary folate, P-heterogeneity = .15; for total folate, P-heterogeneity = .22). Conclusion Folate intake was not associated with overall risk of pancreatic cancer in this large pooled analysis. C1 [Bao, Ying; Giovannucci, Edward] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Bao, Ying; Giovannucci, Edward] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Michaud, Dominique S.] Brown Univ, Dept Community Hlth, Providence, RI 02912 USA. [Spiegelman, Donna] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Spiegelman, Donna; Giovannucci, Edward; Smith-Warner, Stephanie A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Giovannucci, Edward; Smith-Warner, Stephanie A.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Albanes, Demetrius; Kitahara, Cari M.; Schatzkin, Arthur; Stolzenberg-Solomon, Rachael Z.; Ziegler, Regina G.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Anderson, Kristin E.; Robien, Kim] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Anderson, Kristin E.; Robien, Kim] Univ Minnesota, Mason Canc Ctr, Minneapolis, MN USA. [Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Duarte, CA 91010 USA. [van den Brandt, Piet A.] Maastricht Univ, Sch Oncol & Dev Biol, Dept Epidemiol, GROW, Maastricht, Netherlands. [English, Dallas R.; Giles, Graham G.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia. [Freudenheim, Jo L.] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA. [Fuchs, Charles S.] Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. [Goldbohm, R. Alexandra] TNO Qual Life, Dept Prevent & Hlth, Leiden, Netherlands. [Hakansson, Niclas; Wolk, Alicja] Karolinska Inst, Div Nutr Epidemiol, Natl Inst Environm Med, Stockholm, Sweden. [Horn-Ross, Pamela L.] Canc Prevent Inst Calif, Fremont, CA USA. [Jacobs, Eric J.; Stevens, Victoria L.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Marshall, James R.] Roswell Pk Canc Inst, Dept Canc Prevent & Populat Sci, Buffalo, NY 14263 USA. [Miller, Anthony B.] Univ Toronto, Div Epidemiol, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada. [Rohan, Thomas E.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. RP Smith-Warner, SA (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. EM pooling@hsphsun2.harvard.edu RI Hakansson, Niclas/L-7913-2013; Michaud, Dominique/I-5231-2014; Albanes, Demetrius/B-9749-2015; Kitahara, Cari/R-8267-2016; OI Hakansson, Niclas/0000-0001-7673-5554; Robien, Kim/0000-0002-2120-2280; Giles, Graham/0000-0003-4946-9099; English, Dallas/0000-0001-7828-8188 FU National Cancer Institute, National Institutes of Health, Bethesda, MD [CA55075, CA124908] FX This study was supported by grants from the National Cancer Institute, National Institutes of Health, Bethesda, MD (CA55075 to W. C. Willett and CA124908 to C.S.F.). NR 49 TC 16 Z9 16 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-. Natl. Cancer Inst. PD DEC PY 2011 VL 103 IS 24 BP 1840 EP 1850 DI 10.1093/jnci/djr431 PG 11 WC Oncology SC Oncology GA 866OQ UT WOS:000298391000009 PM 22034634 ER PT J AU Jakobiec, FA Zakka, FR D'Amato, R DeAngelis, MM Walton, DS Rao, RC AF Jakobiec, Frederick A. Zakka, Fouad R. D'Amato, Robert DeAngelis, Margaret M. Walton, David S. Rao, Rajesh C. TI Unilateral sporadic retinal dysplasia: Results of histopathologic, immunohistochemical, chromosomal, genetic, and VEGF-A analyses SO JOURNAL OF AAPOS LA English DT Article ID NORRIE-DISEASE GENE; FAMILIAL EXUDATIVE VITREORETINOPATHY; ENDOTHELIAL GROWTH-FACTOR; GLUCOSE-TRANSPORTER; NDP GENE; ANGIOGENESIS; MUTATION; RETINOPATHY; MICE; RETINOBLASTOMA AB PURPOSE To describe new findings in a case of unilateral retinal dysplasia. METHODS Histopathologic evaluation of an enucleated globe and analysis with immunohistochemical probes, karyotyping, and genetic analysis for the Norrie gene, and aqueous assay for vascular endothelial growth factor A (VEGF-A). RESULTS Histopathological examination of the globe revealed retinal dysplasia with pseudorosette formation, abnormal or absent retinal nuclear lamination, a paucity of disorganized retinal microvasculature, retinal infoldings, advanced gliosis, persistent hyperplastic vitreous, exuberant neovascularization of the vitreous, and iris neovascularization (identical to the findings observed in bilateral Norrie disease). Immunohistochemistry disclosed GFAP-positive and GLUT-1-positive gliosis and retinal and persistent hyperplastic vitreous microvessels that were CD34-positive and GLUT-1-negative. Ki-67-positive retinal cells were polarized toward the subretinal space and absent in the retinal invaginations and pseudorosettes. A normal karyotype was found, and DNA sequencing revealed no known mutation in the region of the Norrie gene (NDP) in sputum or retinal DNA. Aqueous obtained immediately after enucleation contained an exceptionally high concentration of VEGF-A (4.5 ng/mL). CONCLUSIONS Despite the failure to find an abnormal ND P allele, other unexplored NDP regions, an undetected defect restricted to retinal tissues, or an autosomal mutation coupled with disrupted signaling pathways may be responsible for the condition. High aqueous VEGF-A suggests that this cytokine may play a role in pathogenesis in conjunction with other pathways. (J AAPOS 2011;15:579-586) C1 [Jakobiec, Frederick A.; Zakka, Fouad R.; Rao, Rajesh C.] Harvard Univ, Sch Med, David G Cogan Lab Ophthalm Pathol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [D'Amato, Robert] Harvard Univ, Sch Med, Childrens Hosp Boston, Vasc Biol Program, Boston, MA 02114 USA. [D'Amato, Robert] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Surg, Boston, MA 02114 USA. [D'Amato, Robert] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Ophthalmol, Boston, MA 02114 USA. [DeAngelis, Margaret M.] Univ Utah, Sch Med, Dept Ophthalmol, Moran Eye Ctr, Salt Lake City, UT USA. RP Jakobiec, FA (reprint author), Harvard Univ, Sch Med, David G Cogan Lab Ophthalm Pathol, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM fred_jakobiec@meei.harvard.edu RI DeAngelis, e/J-7863-2015; OI Rao, Rajesh/0000-0002-5776-8366 FU NEI NIH HHS [P30 EY014800] NR 53 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1091-8531 J9 J AAPOS JI J. AAPOS PD DEC PY 2011 VL 15 IS 6 BP 579 EP 586 DI 10.1016/j.jaapos.2011.08.009 PG 8 WC Ophthalmology; Pediatrics SC Ophthalmology; Pediatrics GA 867GO UT WOS:000298443100016 PM 22153404 ER PT J AU Lai, YY Chen, B Shi, JB Palmer, JN Kennedy, DW Cohen, NA AF Lai, Yinyan Chen, Bei Shi, Jianbo Palmer, James N. Kennedy, David W. Cohen, Noam A. TI Inflammation-mediated upregulation of centrosomal protein 110, a negative modulator of ciliogenesis, in patients with chronic rhinosinusitis SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Chronic rhinosinusitis; ciliated epithelial cell; ciliogenesis; cytokine; inflammation; centrosomal protein 110 ID LIQUID INTERFACE CULTURES; CHRONIC SINUSITIS; NASAL POLYPOSIS; PSEUDOMONAS-AERUGINOSA; HUMAN-CELLS; EXPRESSION; CILIA; CENTRIOLE; INTERLEUKIN-5; EPITHELIUM AB Background: Sinonasal mucosa in patients with chronic rhinosinusitis (CRS) is often devoid of motile cilia. This defect is presumed to result from prolonged inflammation, infection, or both. However, the mechanism underlying this observation is unknown. Recently, centrosomal protein 110 (Cp110) was shown to prevent the terminal step in ciliary maturation (ie, elongation), suggesting that Cp110 might be involved in pathological states in which ciliation is abnormal. Objectives: First, we sought to investigate the expression of Cp110 in sinonasal mucosa from patients with CRS and control subjects. Second, we sought to determine the extent that inflammatory cytokines modulate Cp110 expression and ciliary maturation in vitro. Methods: Sinonasal mucosal specimens from patients with and without CRS were analyzed for Cp110 mRNA and protein expression. Furthermore, human and murine nasal respiratory epithelial cultures were used to investigate Cp110 expression under normal growth conditions and in the presence of exogenous proinflammatory cytokines. Results: Increased Cp110 mRNA and protein expression was found in sinonasal mucosal specimens from patients with CRS compared with that seen in control specimens. During ciliogenesis in vitro, the expression of Cp110 gradually decreased in cultures derived from patients without CRS but remained increased in cultures derived from patients with CRS. Furthermore, cultures grown in the presence of proinflammatory cytokines demonstrated increased levels of Cp110 expression with concomitant inhibition of ciliogenesis. Conclusion: Increased Cp110 expression in mucosa from patients with CRS might contribute to the poor ciliation observed in patients with CRS. Exogenous cytokine exposure maintains increased levels of Cp110 expression. Regulation of Cp110 expression by inflammation warrants additional investigation because it might offer a novel target in the management of respiratory tract diseases. (J Allergy Clin Immunol 2011;128:1207-15.) C1 [Lai, Yinyan; Chen, Bei; Palmer, James N.; Kennedy, David W.; Cohen, Noam A.] Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, Philadelphia, PA 19104 USA. [Lai, Yinyan; Shi, Jianbo] Sun Yat Sen Univ, Otorhinolaryngol Hosp, Affiliated Hosp 1, Guangzhou 510275, Guangdong, Peoples R China. [Palmer, James N.; Cohen, Noam A.] Philadelphia Vet Affairs Med Ctr, Surg Serv, Div Otolaryngol, Philadelphia, PA USA. RP Cohen, NA (reprint author), Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, Ravdin Bldg,5th Floor,3400 Spruce St, Philadelphia, PA 19104 USA. EM cohenn@uphs.upenn.edu OI Cohen, Noam/0000-0002-9462-3932 FU China Scholarship Council; Flight Attendant Medical Research Institute [082478] FX Supported by the China Scholarship Council and the Flight Attendant Medical Research Institute Clinical Innovator Award (082478; to N.A.C.). NR 42 TC 31 Z9 33 U1 0 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD DEC PY 2011 VL 128 IS 6 BP 1207 EP U526 DI 10.1016/j.jaci.2011.09.001 PG 10 WC Allergy; Immunology SC Allergy; Immunology GA 865WX UT WOS:000298342700008 PM 21982113 ER PT J AU Perez, JE Smith, AR Norris, RL Canenguez, KM Tracey, EF DeCristofaro, SB AF Perez, John E. Smith, Amy Rex Norris, Rebecca L. Canenguez, Katia M. Tracey, Elizabeth F. DeCristofaro, Susan B. TI Types of prayer and depressive symptoms among cancer patients: the mediating role of rumination and social support SO JOURNAL OF BEHAVIORAL MEDICINE LA English DT Article DE Religion; Spirituality; Prayer; Coping; Depression; Rumination; Social support; Cancer ID SELF-REPORTED HEALTH; LATE-LIFE; MEDICALLY ILL; WELL; GRATITUDE; MORTALITY; SURVIVORS; ADULTS; RELIGIOUSNESS; METAANALYSIS AB We examined the association between different types of prayer and depressive symptoms-with rumination and social support as potential mediators-in a sample of predominantly White, Christian, and female ambulatory cancer patients. In a cross-sectional design, 179 adult cancer outpatients completed measures of prayer, rumination, social support, depressive symptoms, and demographic variables. Type and stage of cancer were collected from electronic medical charts. Depressive symptoms were negatively correlated with adoration prayer (r = -.15), reception prayer (r = -.17), thanksgiving prayer (r = -.29), and prayer for the well-being of others (r = -.26). In the path analysis, rumination fully mediated the link between thanksgiving prayer and depressive symptoms (beta for indirect effect = -.05), whereas social support partially mediated the link between prayer for others and depressive symptoms (beta for indirect effect = -.05). These findings suggest that unique mechanisms may link different prayer types to lower depressive symptoms among cancer patients. C1 [Perez, John E.] Univ San Francisco, Dept Psychol, San Francisco, CA 94117 USA. [Smith, Amy Rex] Univ Massachusetts, Dept Nursing, Boston, MA 02125 USA. [Norris, Rebecca L.; Canenguez, Katia M.] Univ Massachusetts, Dept Psychol, Boston, MA 02125 USA. [Tracey, Elizabeth F.] Hosp Care SW Connecticut, Stamford, CT USA. [Tracey, Elizabeth F.; DeCristofaro, Susan B.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Perez, JE (reprint author), Univ San Francisco, Dept Psychol, 2130 Fulton St, San Francisco, CA 94117 USA. EM jperez6@usfca.edu FU NCI NIH HHS [U56 CA118635] NR 65 TC 12 Z9 12 U1 3 U2 11 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0160-7715 J9 J BEHAV MED JI J. Behav. Med. PD DEC PY 2011 VL 34 IS 6 BP 519 EP 530 DI 10.1007/s10865-011-9333-9 PG 12 WC Psychology, Clinical SC Psychology GA 857QH UT WOS:000297733100011 PM 21487725 ER PT J AU Udelson, JE Bilsker, M Hauptman, PJ Sequeira, R Thomas, I O'Brien, T Zimmer, C Orlandi, C Konstam, MA AF Udelson, James E. Bilsker, Martin Hauptman, Paul J. Sequeira, Rafael Thomas, Ignatius O'Brien, Terrence Zimmer, Christopher Orlandi, Cesare Konstam, Marvin A. TI A Multicenter, Randomized, Double-blind, Placebo-controlled Study of Tolvaptan Monotherapy Compared to Furosemide and the Combination of Tolvaptan and Furosemide in Patients With Heart Failure and Systolic Dysfunction SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE Heart failure; diuretics; vasopressin ID LEFT-VENTRICULAR DYSFUNCTION; NEONATAL-RAT CARDIOMYOCYTE; VASOPRESSIN ANTAGONIST; RENAL-FUNCTION; RECEPTOR ANTAGONIST; PROTEIN-SYNTHESIS; DIURETIC THERAPY; ACTIVATION; SODIUM; TRIAL AB Background: Increased vasopressin levels may be present in patient with chronic heart failure (HF) and contribute to pathophysiology through effects on the vasopressin V2 receptor. The presence of background diuretic therapy may confound evaluations of vasopressin receptor antagonists (VRA). Methods and Results: Eligible patients had FIF (New York Heart Association Class 11411), systolic dysfunction (left ventricular ejection fraction <= 0.40) and signs of congestion (eg, edema, rales). At screening, patients were removed from baseline diuretic therapy and placed on a low-sodium diet (2 g/day). After a 2-day run-in period, 83 patients were randomized to placebo (n = 21), monotherapy with the vasopressin V2 receptor antagonist tolvaptan (TLV) 30 mg (n = 20), monotherapy with furosernide 80 mg (FURO, n = 22) or both TLV 30 mg and FURO 80 mg (n = 20) once daily for 7 days. Patients were on standard background therapy and not fluid-restricted throughout the study. A decrease in body weight of -1.37 +/- 1.61, -0.54 +/- 1.59, and -1.13 +/- 1.49 kg was observed versus baseline for TLV, FURO, and TLV+FURO, respectively, at day 8. At the same point, the placebo group showed a body weight increase of +0.72 +/- 2.42 kg versus baseline (P = .0006 for TLV versus placebo). Increases in urine volume from baseline were greater with TLV alone (2646 +/- 1503 mL/24 hours) than with FURO (894 +/- 853 mL/24 hours, P < .001), or PLC (423 +/- 786 mL/24 hours, P < .001), and similar to TLV+FURO (2585 2119 mL/24 hours). An increase in serum sodium within the normal range was also observed in TLV-treated patients (P < .02 versus placebo; P < .01 versus FURO). No changes in serum potassium, other laboratory values, or blood pressure were observed. TLV therapy was well tolerated. Conclusions: In patients with HF and signs of volume overload, TLV monotherapy without concomitant loop diuretic therapy reduced body weight when compared to placebo without adverse changes in serum electrolytes, during a sodium restricted diet while on background medications including angiotensin-converting enzyme inhibitors and beta-blockers. (J Cardiac Fail 2011;17:973-981) C1 [Udelson, James E.; Konstam, Marvin A.] Tufts Med Ctr, Div Cardiol, Boston, MA 02111 USA. [Udelson, James E.; Konstam, Marvin A.] Tufts Med Ctr, CardioVasc Ctr, Boston, MA 02111 USA. [Bilsker, Martin; Sequeira, Rafael] Univ Miami, Jackson Mem Hosp, Div Cardiol, Miami, FL 33136 USA. [Hauptman, Paul J.] St Louis Univ, Sch Med, St Louis, MO USA. [Thomas, Ignatius] Med Res Inst, Slidell, LA USA. [O'Brien, Terrence] Ralph H Johnson Vet Adm Med Ctr, Charleston, SC USA. [Zimmer, Christopher; Orlandi, Cesare] Otsuka Maryland Res Inst, Rockville, MD USA. RP Udelson, JE (reprint author), Tufts Med Ctr, Div Cardiol, 750 Washington St,Box 70, Boston, MA 02111 USA. EM JUdelson@tuftsmedicalcenter.org NR 32 TC 22 Z9 24 U1 1 U2 5 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD DEC PY 2011 VL 17 IS 12 BP 973 EP 981 DI 10.1016/j.cardfail.2011.08.005 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 864AB UT WOS:000298208300001 PM 22123358 ER PT J AU Choi, JH Ke, QG Bae, S Lee, JY Kim, YJ Kim, UK Arbeeny, C Thadhani, R Kang, PM AF Choi, Jun H. Ke, Qingen Bae, Soochan Lee, Ji Yoo Kim, Yu Jin Kim, Ui Kyoung Arbeeny, Cynthia Thadhani, Ravi Kang, Peter M. TI Doxercalciferol, a Pro-hormone of Vitamin D, Prevents the Development of Cardiac Hypertrophy in Rats SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE Heart failure; high salt; Dahl rats; cardiac dysfunction ID CONGESTIVE-HEART-FAILURE; KINASE-C-ALPHA; SALT-SENSITIVE RATS; D-RECEPTOR; D DEFICIENCY; VENTRICULAR HYPERTROPHY; CARDIOVASCULAR-DISEASE; CLINICAL EPIDEMIOLOGY; EXPRESSION; PROLIFERATION AB Background: Activated vitamin D analog, paricalcitol, has been shown to attenuate the development of cardiac hypertrophy in Dahl salt sensitive (DSS) rats. To determine whether an antihypertrophic effect is class specific, we tested if doxercalciferol (a pro-hormone vitamin D2 analog) could also attenuate the development of cardiac hypertrophy in DSS rats. Methods and Results: Male DSS rats were fed a high salt (HS) diet for 6 weeks beginning at 6 weeks of age. Doxercalciferol was administered intraperitoneally at 150 ng, 3 times per week (Monday, Wednesday, Friday) for 6 weeks. Pathological and echocardiographic findings demonstrated that rats on HS diet with doxercalciferol administration had significant decrease in cardiac hypertrophy and improved cardiac function compared to the HS + vehicle. In addition, there was a significant decrease in plasma brain natriuretic peptide (BNP) level and tissue atrial natriuretic factor (ANF) mRNA level with doxercalciferol treatment. Doxercalciferol also significantly reduced the level of protein kinase C-alpha (PKC alpha) suggesting that PKC-mediated cardiac hypertrophy may be associated with vitamin D deficiency. Conclusions: Administration of doxercalciferol attenuated the development of HS diet induced cardiac hypertrophy and cardiac dysfunction in DSS rats. (J Cardiac Fail 2011;17:1051-1058) C1 [Choi, Jun H.; Ke, Qingen; Bae, Soochan; Lee, Ji Yoo; Kim, Yu Jin; Kim, Ui Kyoung; Kang, Peter M.] Beth Israel Deaconess Med Ctr, Div Cardiovasc, Boston, MA 02215 USA. [Arbeeny, Cynthia] Genzyme Corp, Cambridge, MA USA. [Thadhani, Ravi] Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. RP Kang, PM (reprint author), Beth Israel Deaconess Med Ctr, Div Cardiovasc, 3 Blackfan Circle,Room 910, Boston, MA 02215 USA. EM pkang@bidmc.harvard.edu FU National Institutes of Health [RO1 HL091998]; Genzyme Corporation FX Supported in part by the grants from National Institutes of Health RO1 HL091998 and Genzyme Corporation (P.M.K.). Supported in part by Genzyme Corporation, which employs C.A. Doxercalciferol (brand name Hectorol) is marketed by Genzyme Corporation. NR 31 TC 12 Z9 12 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD DEC PY 2011 VL 17 IS 12 BP 1051 EP 1058 DI 10.1016/j.cardfail.2011.08.006 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 864AB UT WOS:000298208300013 PM 22123370 ER PT J AU Diaz-Gomez, JL Satyapriya, A Satyapriya, SV Mascha, EJ Yang, DS Krakovitz, P Mossad, EB Eikermann, M Doyle, DJ AF Diaz-Gomez, Jose L. Satyapriya, Anand Satyapriya, Sree V. Mascha, Edward J. Yang, Dongsheng Krakovitz, Paul Mossad, Emad B. Eikermann, Matthias Doyle, D. John TI Standard clinical risk factors for difficult laryngoscopy are not independent predictors of intubation success with the GlideScope SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Article DE Airway management; Difficult intubation; GlideScope; Mallampati airway class; Morbid obesity; Preoperative anesthesia assessment ID IMPOSSIBLE MASK VENTILATION; MORBIDLY OBESE-PATIENTS; TRACHEAL INTUBATION; VIDEOLARYNGOSCOPE GLIDESCOPE(R); MACINTOSH LARYNGOSCOPE; FIBEROPTIC INTUBATION; AIRWAY; MANAGEMENT; PERFORMANCE; METAANALYSIS AB Study Objectives: To determine whether the first-attempt tracheal intubation incidence using the GlideScope videolaryngoscope is higher in patients with predicted increased risk of difficult laryngoscopy, and to assess the ability of other a priori defined standard risk factors to predict first-attempt intubation success, in aggregate and by forming scores. Design: Prospective study. Setting: Operating room in a tertiary-care academic center. Patients: 357 patients intubated with the GlideScope for nonernergent general anesthesia. Interventions and Measurements: Mallampati airway class was used to create two groups of patients, one with higher and the other, lower, potential difficult laryngoscopy (Mallampati classes 3-4 and 1-2, respectively). Intubation success on the first attempt with the GlideScope videolaryngoscope in patients with a Mallampati class 3 or 4 airway versus those with Mallampati class 1 or 2 airway was tested. We also evaluated the predictive ability of the Mallampati airway class (1 and 2 vs 3 and 4) along with 9 other possible predictors of difficult intubation on first-attempt intubation success: gender, age, body mass index, level of training within our anesthesia residency program (Clinical Anesthesia Resident years 1, 2, and 3), ASA physical status, mouth opening, thyromental distance, neck flexion, and neck extension. Main Results: None of the standard predictors of difficult intubation was significantly associated with outcome after adjusting for other predictors. A multivariable model containing the aggregate set of variables predicted outcome significantly better than a risk score formed as the sum of 10 predictors ("Risk 10"; P = 0.0176). Conclusions: With GlideScope-assisted tracheal intubation, Mallampati airway class is not an independent risk factor for difficult intubation. Other standard clinical risk factors of difficulty with direct laryngoscopy also do not appear to be individually predictive of first-attempt success of tracheal intubation. (C) 2011 Elsevier Inc. All rights reserved. C1 [Diaz-Gomez, Jose L.; Satyapriya, Anand; Satyapriya, Sree V.; Doyle, D. John] Cleveland Clin, Dept Cardiothorac Anesthesiol, Inst Anesthesiol, Cleveland, OH 44195 USA. [Mascha, Edward J.; Yang, Dongsheng] Cleveland Clin, Dept Outcomes Res, Inst Anesthesiol, Cleveland, OH 44195 USA. [Mascha, Edward J.] Cleveland Clin, Lerner Res Inst, Dept Quantitat Hlth Sci, Cleveland, OH 44195 USA. [Krakovitz, Paul] Cleveland Clin, Head & Neck Inst, Cleveland, OH 44195 USA. [Mossad, Emad B.] Texas Childrens Hosp, Baylor Coll Med, Div Pediat Cardiovasc Anesthesia, Houston, TX 77030 USA. [Eikermann, Matthias] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Eikermann, Matthias] Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02115 USA. RP Diaz-Gomez, JL (reprint author), Cleveland Clin, Dept Cardiothorac Anesthesiol, Inst Anesthesiol, 9500 Euclid Ave,J4-331, Cleveland, OH 44195 USA. EM diazj@ccf.org NR 38 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0952-8180 J9 J CLIN ANESTH JI J. Clin. Anesth. PD DEC PY 2011 VL 23 IS 8 BP 603 EP 610 DI 10.1016/j.jclinane.2011.03.006 PG 8 WC Anesthesiology SC Anesthesiology GA 863ZX UT WOS:000298207900001 PM 22137510 ER PT J AU Yao, JC Pavel, M Phan, AT Kulke, MH Hoosen, S Peter, JS Cherfi, A Oberg, KE AF Yao, James C. Pavel, Marianne Phan, Alexandria T. Kulke, Matthew H. Hoosen, Sakina Peter, Jessica St. Cherfi, Azzeddine Oberg, Kjell E. TI Chromogranin A and Neuron-Specific Enolase as Prognostic Markers in Patients with Advanced pNET Treated with Everolimus SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ISLET-CELL CARCINOMA; GASTROENTEROPANCREATIC NEUROENDOCRINE TUMORS; PANCREATIC ENDOCRINE TUMORS; ANTITUMOR-ACTIVITY; OCTREOTIDE LAR; MTOR PATHWAY; STREPTOZOCIN; DOXORUBICIN; FLUOROURACIL; EFFICACY AB Context: Everolimus, an oral inhibitor of mammalian target of rapamycin, significantly prolongs progression-free survival (PFS) in patients with advanced pancreatic neuroendocrine tumors (pNET). Chromogranin A (CgA) and neuron-specific enolase (NSE) are considered general biomarkers of these tumors. Objective: The objective of the study was to evaluate the prognostic value of CgA and NSE in patients with pNET treated with everolimus. Patients and Methods: Patients with low-to intermediate-grade advanced pNET enrolled in two phase 2 studies [RAD001 in Advanced Neuroendocrine Tumors (RADIANT-1) and single institution phase II study at The University of Texas M. D. Anderson Cancer Center] received everolimus. Blood samples were collected and analyzed by a central laboratory at baseline and monthly thereafter. PFS and overall survival (OS) were evaluated in patients with elevated and nonelevated baseline CgA/NSE levels. Results: In RADIANT-1, elevated vs. nonelevated baseline CgA was associated with shorter median PFS (8.34 vs. 15.64 months; P = 0.03) and OS (16.95 months vs. not reached; P < 0.001). Elevated vs. nonelevated baseline NSE resulted in shorter median PFS (7.75 vs. 12.29 months; P = 0.01) and OS (13.96 vs. 24.90 months; P = 0.005). Median PFS was prolonged in patients with early CgA or NSE response (11.0 vs. 5.0 months) compared with those without early biomarker response. More patients with CgA (87 vs. 50%) or NSE (81 vs. 14%) response experienced tumor shrinkage compared with those without response. CgA response data from the single-institution phase II study at The University of Texas M. D. Anderson Cancer Center study are consistent with data from the RADIANT-1 study. Conclusions: Elevated baseline CgA/NSE provided prognostic information on PFS and survival; early CgA/NSE responses are potential prognostic markers for treatment outcomes in patients with advanced pNET. (J Clin Endocrinol Metab 96: 3741-3749, 2011) C1 [Yao, James C.; Phan, Alexandria T.] Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX 77030 USA. [Pavel, Marianne] Charite, Campus Virchow Klinikum, Dept Gastroenterol & Hepatol, D-13353 Berlin, Germany. [Kulke, Matthew H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Hoosen, Sakina] Novartis Pharmaceut, Dept Licensing Clin Evaluat, Florham Pk, NJ 07932 USA. [Peter, Jessica St.] Novartis Pharmaceut, Dept Oncol Clin Dev, E Hanover, NJ 07936 USA. [Cherfi, Azzeddine] Novartis Pharma AG, Dept Biometr & Data Management, CH-4056 Basel, Switzerland. [Oberg, Kjell E.] Univ Uppsala Hosp, Dept Endocrine Oncol, SE-75185 Uppsala, Sweden. RP Yao, JC (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, 1515 Holcombe Blvd,Box 426, Houston, TX 77030 USA. EM jyao@mdanderson.org FU Novartis Pharma AG, Basel, Switzerland FX J.C.Y. has received research funding (to his institution) and honoraria from Novartis Pharma AG, Basel, Switzerland, and has acted as a consultant to Novartis Pharma. M. P. has acted as an adviser to Novartis Pharma. M. H. K. has acted as a consultant and an adviser to and has received honoraria from Novartis Pharma. K.E.O. is a member of neuroendocrine tumor advisory boards for Novartis, Ipsen, and Pfizer, has received honoraria from all, and is on the speakers' bureau for Novartis. S. H. and J.S.P. are employed by Novartis Pharmaceuticals Corporation, and A. C. is employed by Novartis Pharma AG; all have shares in Novartis Pharma AG. A. T. P. has nothing to disclose. NR 29 TC 73 Z9 74 U1 0 U2 6 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 2011 VL 96 IS 12 BP 3741 EP 3749 DI 10.1210/jc.2011-0666 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 865FA UT WOS:000298295200048 PM 21994954 ER PT J AU Lopez, X Cypess, A Manning, R O'Shea, S Kulkarni, RN Goldfine, AB AF Lopez, Ximena Cypess, Aaron Manning, Raquel O'Shea, Sheila Kulkarni, Rohit N. Goldfine, Allison B. TI Exogenous Insulin Enhances Glucose-Stimulated Insulin Response in Healthy Humans Independent of Changes in Free Fatty Acids SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PANCREATIC BETA-CELLS; NONDIABETIC SUBJECTS; DOSE-RESPONSE; HUMAN ISLETS; PHOSPHATIDYLINOSITOL 3-KINASE; RECEPTOR SUBSTRATE-1; DIABETES-MELLITUS; INDUCED APOPTOSIS; SKELETAL-MUSCLE; GENE-EXPRESSION AB Context: Islet beta-cells express both insulin receptors and insulin signaling proteins. Recent studies suggest insulin signaling is physiologically important for glucose sensing. Objective: Preexposure to insulin enhances glucose-stimulated insulin secretion (GSIS) in healthy humans. We evaluated whether the effect of insulin to potentiate GSIS is modulated through regulation of free fatty acids (FFA). Design and Setting: Subjects were studied on three occasions in this single-site study at an academic institution clinical research center. Patients: Subjects included nine healthy volunteers. Interventions: Glucose-induced insulin response was assessed on three occasions after 4 h saline (low insulin/sham) or isoglycemic-hyperinsulinemic (high insulin) clamps with or without intralipid and heparin infusion, using B28 Asp-insulin that could be distinguished from endogenous insulin immunologically. During the last 80 min of all three clamps, additional glucose was administered to stimulate insulin secretion (GSIS) with glucose concentrations maintained at similar concentrations during all studies. Main Outcome Measure: beta-Cell response to glucose stimulation was assessed. Results: Preexposure to exogenous insulin increased the endogenous insulin-secretory response to glucose by 32% compared with sham clamp (P = 0.001). This was accompanied by a drop in FFA during hyperinsulinemic clamp compared with the sham clamp (0.06 +/- 0.02 vs. 0.60 +/- 0.09 mEq/liter, respectively), which was prevented during the hyperinsulinemic clamp with intralipid/heparin infusion (1.27 +/- 0.17 mEq/liter). After preexposure to insulin with intralipid/heparin infusion to maintain FFA concentration, GSIS was 21% higher compared with sham clamp (P < 0.04) and similar to preexposure to insulin without intralipid/heparin (P = 0.2). Conclusions: Insulin potentiates glucose-stimulated insulin response independent of FFA concentrations in healthy humans. (J Clin Endocrinol Metab 96: 3811-3821, 2011) C1 [Lopez, Ximena; Cypess, Aaron; Manning, Raquel; O'Shea, Sheila; Kulkarni, Rohit N.; Goldfine, Allison B.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Lopez, Ximena; Cypess, Aaron; Kulkarni, Rohit N.; Goldfine, Allison B.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Lopez, Ximena] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Goldfine, AB (reprint author), 1 Joslin Pl, Boston, MA 02215 USA. EM Allison.Goldfine@Joslin.Harvard.Edu FU American Diabetes Association [06-CD-07]; National Institutes of Health [R01 DK070648, R01 DK070648-03S, RO1 DK067536]; Joslin Diabetes and Endocrinology Research Center [P30-DK36836]; General Clinical Research Center [M01-RR001032]; Beth Israel Deaconess Medical Center-Harvard/ MIT Health Sciences and Technology, in collaboration with Pfizer and Merck; Joslin Clinical Research Center FX This work was supported by many funding sources including the American Diabetes Association 06-CD-07 (to A. B. G.), National Institutes of Health R01 DK070648 (to A. B. G.), R01 DK070648-03S (to X. L.), RO1 DK067536 (to R.N.K.), the Joslin Diabetes and Endocrinology Research Center P30-DK36836, and General Clinical Research Center M01-RR001032, and the Clinical Investigator Training Program, Beth Israel Deaconess Medical Center-Harvard/ MIT Health Sciences and Technology, in collaboration with Pfizer and Merck (to A. C.). Joslin acknowledges support for the Joslin Clinical Research Center from its philanthropic donors. NR 73 TC 14 Z9 14 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 2011 VL 96 IS 12 BP 3811 EP 3821 DI 10.1210/jc.2011-0627 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 865FA UT WOS:000298295200056 PM 21956413 ER PT J AU Goedecke, JH Evans, J Keswell, D Stimson, RH Livingstone, DEW Hayes, P Adams, K Dave, JA Victor, H Levitt, NS Lambert, EV Walker, BR Seckl, JR Olsson, T Kahn, SE AF Goedecke, Julia H. Evans, Juliet Keswell, Dheshnie Stimson, Roland H. Livingstone, Dawn E. W. Hayes, Philip Adams, Kevin Dave, Joel A. Victor, Hendriena Levitt, Naomi S. Lambert, Estelle V. Walker, Brian R. Seckl, Jonathan R. Olsson, Tommy Kahn, Steven E. TI Reduced Gluteal Expression of Adipogenic and Lipogenic Genes in Black South African Women Is Associated with Obesity-Related Insulin Resistance SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ADIPOSE-TISSUE; IMPAIRED ADIPOGENESIS; BODY-FAT; DIFFERENTIATION; SENSITIVITY; PROFILE; PREADIPOCYTES; INFLAMMATION; HEALTH; MUSCLE AB Context: Black South African women are less insulin sensitive than their White counterparts, despite less central and greater peripheral fat deposition. We hypothesized that this paradox may be explained, in part, by differences in the adipogenic capacity of sc adipose tissue (SAT). Objective: Our objective was to measure adipogenic and lipogenic gene expression in abdominal and gluteal SAT depots and determine their relationships with insulin sensitivity (S(I)) in South African women. Participants and Design: Fourteen normal-weight [body mass index (BMI) <25 kg/m(2)] Black, 13 normal-weight White, 14 obese (BMI >30 kg/m(2)) Black, and 13 obese White premenopausal South African women participated in this cross-sectional study. Main outcomes: S(I) (frequently sampled iv glucose tolerance test) in relation to expression of adipogenic and lipogenic genes in abdominal and gluteal SAT depots. Results: With increasing BMI, Black women had less visceral fat (P = 0.03) and more abdominal (P = 0.017) and gynoid (P = 0.041) SAT but had lower S(I) (P < 0.01) than White women. The expression of adipogenic and lipogenic genes was proportionately lower with obesity in Black but not White women in the gluteal and deep SAT depots (P < 0.05 for ethnicity x BMI effect). In Black women only, the expression of these genes correlated positively with S(I) (all P < 0.05), independently of age and fat mass. Conclusions: Obese Black women have reduced SAT expression of adipogenic and lipogenic genes compared with White women, which associates with reduced S(I). These findings suggest that obesity in Black women impairs SAT adipogenesis and storage, potentially leading to insulin resistance and increased risk of type 2 diabetes. (J Clin Endocrinol Metab 96: E2029-E2033, 2011) C1 [Goedecke, Julia H.; Evans, Juliet; Keswell, Dheshnie; Victor, Hendriena; Lambert, Estelle V.] Univ Cape Town, Med Res Council Res Unit Exercise Sci & Sports Me, ZA-7725 Newlands, South Africa. [Hayes, Philip; Adams, Kevin] Univ Cape Town, Dept Human Biol, ZA-7725 Newlands, South Africa. [Dave, Joel A.; Levitt, Naomi S.] Univ Cape Town, Plast Surg Units, Dept Med, ZA-7725 Newlands, South Africa. [Dave, Joel A.; Levitt, Naomi S.] Univ Cape Town, Endocrine Units, Dept Med, ZA-7725 Newlands, South Africa. [Goedecke, Julia H.] S African MRC, ZA-7505 Tygerberg, South Africa. [Stimson, Roland H.; Livingstone, Dawn E. W.; Walker, Brian R.; Seckl, Jonathan R.] Univ Edinburgh, Endocrinol Unit, Univ British Heart Fdn Ctr Cardiovasc Sci, Edinburgh EH16 4TJ, Midlothian, Scotland. [Olsson, Tommy] Umea Univ, Dept Med, SE-90187 Umea, Sweden. [Kahn, Steven E.] Univ Washington, Div Metab Endocrinol & Nutr, Dept Med, Seattle, WA 98108 USA. [Kahn, Steven E.] Univ Washington, Div Metab Endocrinol & Nutr, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Goedecke, JH (reprint author), Univ Cape Town, Med Res Council Res Unit Exercise Sci & Sports Me, 3rd Floor Sports Sci Inst S Africa,POB 115, ZA-7725 Newlands, South Africa. EM julia.goedecke@uct.ac.za RI Seckl, Jonathan/C-3555-2013; Goedecke, Julia/J-8628-2013; Goedecke, Julia/E-1820-2016; OI Goedecke, Julia/0000-0001-6795-4771; Goedecke, Julia/0000-0001-6795-4771; Olsson, Tommy/0000-0001-7768-1076; Kahn, Steven/0000-0001-7307-9002 FU South African Medical Research Council; International Atomic Energy Agency; National Research Foundation of South Africa; Royal Society SA-UK; University of Cape Town; British Heart Foundation; Wellcome Trust; U.S. Department of Veterans Affairs FX This work was supported by the South African Medical Research Council, International Atomic Energy Agency, National Research Foundation of South Africa and Royal Society SA-UK Science Networks Program, University of Cape Town, British Heart Foundation, Wellcome Trust, and U.S. Department of Veterans Affairs. NR 20 TC 11 Z9 11 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 2011 VL 96 IS 12 BP E2029 EP E2033 DI 10.1210/jc.2011-1576 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 865FA UT WOS:000298295200016 PM 21956425 ER PT J AU Mitsiades, N Pazaitou-Panayiotou, K Aronis, KN Moon, HS Chamberland, JP Liu, XW Diakopoulos, KN Kyttaris, V Panagiotou, V Mylvaganam, G Tseleni-Balafouta, S Mantzoros, CS AF Mitsiades, Nicholas Pazaitou-Panayiotou, Kalliopi Aronis, Konstantinos N. Moon, Hyun-Seuk Chamberland, John P. Liu, Xiaowen Diakopoulos, Kalliope N. Kyttaris, Vasileios Panagiotou, Vasiliki Mylvaganam, Geetha Tseleni-Balafouta, Sofia Mantzoros, Christos S. TI Circulating Adiponectin Is Inversely Associated with Risk of Thyroid Cancer: In Vivo and in Vitro Studies SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BREAST-CANCER; PLASMA ADIPONECTIN; PROSTATE-CANCER; MYELODYSPLASTIC-SYNDROME; GROWTH; RESISTIN; LEPTIN; CELLS; EXPRESSION; CARCINOMA AB Context: Circulating adiponectin has been inversely associated with risk for several malignancies. Its association with thyroid cancer has not yet been evaluated. Objective/Methods: We measured circulating adiponectin levels in 175 thyroid carcinoma patients and 107 controls. We also examined the expression of adiponectin receptors (AdipoR1 and AdipoR2) using immunohistochemistry in 82 thyroid carcinoma tissues and using RT-qPCR in 40 human thyroid carcinoma tissues (32 papillary, six follicular/Hurthle, one anaplastic, one medullary), four normal human thyroid tissue specimens, and the BHP7 and SW579 thyroid cancer cell lines. We then utilized these thyroid cancer cell lines to investigate whether adiponectin could directly regulate cell cycle or apoptosis. Results: Thyroid cancer patients had lower circulating adiponectin levels than controls (17.00 +/- 6.32 vs. 19.26 +/- 6.28 +/- mu g/ml; P < 0.001). Subjects in the highest tertile of circulating adiponectin concentrations had significantly lower odds of developing any type of thyroid carcinoma (odds ratio = 0.29; 95% confidence interval, 0.16-0.55), or papillary thyroid carcinoma (odds ratio = 0.27; 95% confidence interval, 0.14-0.55), before and after adjustment for potential confounders. Both thyroid carcinoma cell lines and tissues expressed AdipoR1 and AdipoR2. Recombinant adiponectin did not exert a clinically significant direct effect on cell cycle, proliferation, or apoptosis in thyroid cancer cell lines in vitro. Conclusions: Circulating adiponectin is independently and inversely associated with the risk of thyroid cancer. Human thyroid carcinomas and cell lines express adiponectin receptors. However, in the absence of a major direct effect of adiponectin on thyroid cancer cell lines in vitro, the negative association observed herein may be attributed to the metabolic effects of adiponectin. (J Clin Endocrinol Metab 96: E2023-E2028, 2011) C1 [Mantzoros, Christos S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Dept Internal Med,Med Sch, Boston, MA 02215 USA. [Diakopoulos, Kalliope N.; Panagiotou, Vasiliki] Theagenio Canc Hosp, Div Endocrinol Endocrine Oncol, Thessaloniki 54630, Greece. [Tseleni-Balafouta, Sofia] Univ Athens, Dept Pathol, Athens 10671, Greece. [Mantzoros, Christos S.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Dept Internal Med, Boston, MA 02130 USA. RP Mantzoros, CS (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Dept Internal Med,Med Sch, 330 Brookline Ave,FD 875, Boston, MA 02215 USA. EM cmantzor@bidmc.harvard.edu RI Aronis, Konstantinos/F-3586-2012; Moon, Hyun-Seuk/G-8576-2015; Aronis, Konstantinos/J-6582-2014 OI Chamberland, John/0000-0002-7862-1371; Diakopoulos, Kalliope/0000-0002-9236-0489; Aronis, Konstantinos/0000-0001-7189-8434; Moon, Hyun-Seuk/0000-0002-5216-2090; FU Beth Israel Deaconess Medical Center; National Institute of Diabetes and Digestive and Kidney Diseases [DK058785, DK079929, DK081913]; National Institute on Aging [AG032030] FX This work was supported by a discretionary grant from Beth Israel Deaconess Medical Center (to C.S.M.). The Mantzoros Lab is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (Grants DK058785, DK079929, and DK081913), the National Institute on Aging (Grant AG032030), and a discretionary grant from Beth Israel Deaconess Medical Center. NR 25 TC 17 Z9 17 U1 0 U2 6 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 2011 VL 96 IS 12 BP E2023 EP E2028 DI 10.1210/jc.2010-1908 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 865FA UT WOS:000298295200015 PM 21937620 ER PT J AU Schafer, AL Sellmeyer, DE Schwartz, AV Rosen, CJ Vittinghoff, E Palermo, L Bilezikian, JP Shoback, DM Black, DM AF Schafer, Anne L. Sellmeyer, Deborah E. Schwartz, Ann V. Rosen, Clifford J. Vittinghoff, Eric Palermo, Lisa Bilezikian, John P. Shoback, Dolores M. Black, Dennis M. TI Change in Undercarboxylated Osteocalcin Is Associated with Changes in Body Weight, Fat Mass, and Adiponectin: Parathyroid Hormone (1-84) or Alendronate Therapy in Postmenopausal Women with Osteoporosis (the PaTH Study) SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID VITAMIN-K STATUS; SERUM OSTEOCALCIN; PLASMA-GLUCOSE; METABOLISM; PROTEIN; MEN AB Context: The undercarboxylated form of the osteoblast-secreted protein osteocalcin has favorable effects on fat and glucose metabolism in mice. In human subjects, cross-sectional studies suggest a relevant association. Objective: We investigated whether changes in undercarboxylated osteocalcin (ucOC) during osteoporosis treatment are associated with changes in metabolic parameters. Design, Setting, Participants, and Interventions: We measured ucOC in sera from a subset of osteoporotic postmenopausal women who were treated with PTH(1-84) or alendronate (n = 64 and n = 33, respectively) during the Parathyroid Hormone and Alendronate study. Main Outcome Measures: We measured serum adiponectin, leptin, and insulin and analyzed existing data on body weight, fat mass, and serum glucose concentration. Three-month changes in ucOC levels were evaluated as predictors of 12-month changes in indices of fat and glucose metabolism. Results: ucOC levels increased with PTH(1-84) and decreased with alendronate administration (P <= 0.01 for both treatment groups). Three-month change in ucOC was inversely associated with 12-month changes in body weight (standardized beta = -0.25, P = 0.04) and fat mass (beta = -0.23, P = 0.06), after adjustment for the treatment group. Three-month change in ucOC was positively associated with a 12-month change in adiponectin (beta = 0.30, P = 0.01), independent of change in fat mass. There were no interactions between treatment and change in ucOC on changes in weight, fat mass, or adiponectin. Conclusions: PTH(1-84) increases and alendronate decreases ucOC levels. Changes in ucOC induced by PTH(1-84) and alendronate are associated with changes in metabolic indices. These associations are consistent with observations from animal models and support a role for ucOC in the skeletal regulation of energy metabolism in humans. (J Clin Endocrinol Metab 96: E1982-E1989, 2011) C1 [Schafer, Anne L.; Shoback, Dolores M.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Schwartz, Ann V.; Vittinghoff, Eric; Palermo, Lisa; Black, Dennis M.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Schafer, Anne L.; Shoback, Dolores M.] San Francisco VA Med Ctr, Med Serv, Endocrine Res Unit, San Francisco, CA 94121 USA. [Sellmeyer, Deborah E.] Johns Hopkins Univ, Dept Med, Baltimore, MD 21224 USA. [Rosen, Clifford J.] Maine Med Ctr, Res Inst, Scarborough, ME 04074 USA. [Bilezikian, John P.] Columbia Univ, Coll Phys & Surg, New York, NY 10032 USA. RP Schafer, AL (reprint author), 4150 Clement St,Box 111N, San Francisco, CA 94121 USA. EM anne.schafer@ucsf.edu FU National Institute of Arthritis and Musculoskeletal and Skin Diseases [NIAMS-045, N01-AR-9-2245]; Veterans Affairs; Department of Veterans Affairs; Amgen; Novartis; Merck; Roche FX The PaTH study was supported by a contract with the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS-045, N01-AR-9-2245; to D.M.B.). The study drugs were supplied by NPS Pharmaceuticals, Inc. [PTH(1-84)] and Merck & Co., Inc. (alendronate). The authors have full control of all primary data. This ancillary study was supported by the Veterans Affairs Research Enhancement Award Program. Additional support for A.L.S. came from the Department of Veterans Affairs, through a Health Issues of Women Veterans Fellowship and a Career Development Award.; D.E.S. has received research support from Amgen and Novartis. A.V.S. has received research support from Merck. L.P. has consulted for NPS Pharmaceuticals, Inc. and Nycomed. D.M.B. has received research support from Amgen, Merck, Novartis, and Roche and has consulted for Nycomed. NR 20 TC 55 Z9 59 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 2011 VL 96 IS 12 BP E1982 EP E1989 DI 10.1210/jc.2011-0587 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 865FA UT WOS:000298295200009 PM 21994958 ER PT J AU Bloch, MJ Basile, JN AF Bloch, Michael J. Basile, Jan N. TI UK Guidelines Call for Routine 24-Hour Ambulatory Blood Pressure Monitoring in All Patients to Make the Diagnosis of HypertensionuNot Ready for Prime Time in the United States SO JOURNAL OF CLINICAL HYPERTENSION LA English DT Editorial Material C1 [Bloch, Michael J.] St Marys Reg Med Ctr, Risk Reduct Ctr, Reno, NV 89503 USA. [Bloch, Michael J.] Univ Nevada, Sch Med, Dept Internal Med, Reno, NV 89557 USA. [Basile, Jan N.] Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Seinsheimer Cardiovasc Hlth Program, Div Gen Internal Med Geriatr, Charleston, SC 29425 USA. RP Bloch, MJ (reprint author), St Marys Reg Med Ctr, Risk Reduct Ctr, 645 N Arlington St,Suite 460, Reno, NV 89503 USA. EM mbloch@aol.com NR 1 TC 6 Z9 6 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1524-6175 J9 J CLIN HYPERTENS JI J. Clin. Hypertens. PD DEC PY 2011 VL 13 IS 12 BP 871 EP 872 DI 10.1111/j.1751-7176.2011.00551.x PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 859DJ UT WOS:000297854700003 PM 22142345 ER PT J AU Roshan, B Ganda, OP DeSilva, R Ganim, RB Ward, E Haessler, SD Polisecki, EY Asztalos, BF Schaefer, EJ AF Roshan, Bijan Ganda, Om P. DeSilva, Rani Ganim, Rose B. Ward, Edmund Haessler, Sarah D. Polisecki, Eliana Y. Asztalos, Bela F. Schaefer, Ernst J. TI Homozygous lecithin:cholesterol acyltransferase (LCAT) deficiency due to a new loss of function mutation and review of the literature SO JOURNAL OF CLINICAL LIPIDOLOGY LA English DT Review DE Apolipoprotein; High density lipoprotein; Lecithin:cholesterol acyltransferase; Corneal pacification; Anemia; Renal disease ID CORONARY-HEART-DISEASE; PRIMARY BILIARY-CIRRHOSIS; LECITHIN; HDL; PATIENT; PARTICIPANTS; INHIBITION; METABOLISM; EXPRESSION; STATES AB BACKGROUND: A case of homozygous familial lecithin:cholesterol acyltransferase (LCAT) deficiency with a novel homozygous LCAT missense mutation (replacement of methionine by arginine at position 293 in the amino acid sequence of the LCAT protein) is reported. METHODS AND RESULTS: The probable diagnosis was suggested by findings of marked high density lipoprotein (HDL) deficiency, corneal opacification, anemia, and renal insufficiency. The diagnosis was confirmed by two dimensional gel electrophoresis of HDL, the measurement of free and esterified cholesterol, and sequencing of the LCAT gene. CONCLUSIONS: In our view the most important aspects of therapy to prevent the kidney disease that these patients develop is careful control of blood pressure and lifestyle measures to optimize non HDL lipoproteins. In the future replacement therapy by gene transfer or other methods may become available. (C) 2011 Published by Elsevier Inc. on behalf of National Lipid Association. C1 [Asztalos, Bela F.; Schaefer, Ernst J.] Tufts Univ, Lipid Metab Lab, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [Asztalos, Bela F.; Schaefer, Ernst J.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Roshan, Bijan; Ganda, Om P.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [DeSilva, Rani] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Ganim, Rose B.; Haessler, Sarah D.] Baystate Med Ctr, Springfield, MA USA. [Ward, Edmund; Polisecki, Eliana Y.; Asztalos, Bela F.; Schaefer, Ernst J.] Boston Heart Diagnost, Framingham, MA USA. RP Schaefer, EJ (reprint author), Tufts Univ, Lipid Metab Lab, Human Nutr Res Ctr Aging, 711 Washington St, Boston, MA 02111 USA. EM ernst.schaefer@tufts.edu FU National Institutes of Health [P30DK36836]; National Institutes of Health, Bethesda, MD [HL-60935, HL 74753, PO50HL083813]; US Department of Agriculture, Washington DC [53-3K06-5-10] FX Dr. Ganda's research is partially supported by a National Institutes of Health Diabetes Enrichment Core (P30DK36836). Drs. Schaefer and Asztalos are supported by research grants to the Lipid Metabolism Laboratory at Tufts University from the National Institutes of Health, Bethesda, MD (HL-60935, HL 74753, PO50HL083813) and the US Department of Agriculture, Washington DC (53-3K06-5-10). Drs. Polisecki, Asztalos, and Schaefer receive partial salary support from Boston Heart Laboratory, Framingham, MA. There are no other conflicts of interest for the rest of the authors. NR 33 TC 7 Z9 7 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1933-2874 J9 J CLIN LIPIDOL JI J. Clin. Lipidol. PD DEC PY 2011 VL 5 IS 6 BP 493 EP 499 DI 10.1016/j.jacl.2011.07.002 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 862WZ UT WOS:000298126100010 PM 22108153 ER PT J AU Patel, M Gonzalez, R Halford, C Lewinski, MA Landaw, EM Churchill, BM Haake, DA AF Patel, Mayank Gonzalez, Rodrigo Halford, Colin Lewinski, Michael A. Landaw, Elliot M. Churchill, Bernard M. Haake, David A. TI Target-Specific Capture Enhances Sensitivity of Electrochemical Detection of Bacterial Pathogens SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID GENOMIC DNA; URINE; UROPATHOGENS; GUIDELINES; SPECIMENS; DIAGNOSIS; WOMEN AB We report the concentration and purification of bacterial 16S rRNA by the use of a biotinylated DNA target-specific capture (TSC) probe. For both cultivated bacterial and urine specimens from urinary tract infection patients, TSC resulted in a 5- to 8-fold improvement in the sensitivity of bacterial detection in a 16S rRNA electrochemical sensor assay. C1 [Haake, David A.] VA Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA 90073 USA. [Patel, Mayank; Halford, Colin; Churchill, Bernard M.; Haake, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA. [Landaw, Elliot M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biomath, Los Angeles, CA 90095 USA. [Lewinski, Michael A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Haake, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Haake, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA. RP Haake, DA (reprint author), VA Greater Los Angeles Healthcare Syst, Div Infect Dis, 111F,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM DHAAKE@UCLA.EDU FU National Institute of Allergy and Infectious Diseases [AI075565]; Wendy and Ken Ruby Fund for Excellence in Pediatric Urology Research FX This study was supported by Cooperative Agreement Award AI075565 (to D.A.H.) from the National Institute of Allergy and Infectious Diseases and by the Wendy and Ken Ruby Fund for Excellence in Pediatric Urology Research. B.M.C. is the Judith and Robert Winston Chair in Pediatric Urology. NR 15 TC 5 Z9 5 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD DEC PY 2011 VL 49 IS 12 BP 4293 EP 4296 DI 10.1128/JCM.01261-11 PG 4 WC Microbiology SC Microbiology GA 862SC UT WOS:000298113400043 PM 21940468 ER PT J AU Simon, MV AF Simon, Mirela V. TI Neurophysiologic Intraoperative Monitoring of the Vestibulocochlear Nerve SO JOURNAL OF CLINICAL NEUROPHYSIOLOGY LA English DT Review DE Vestibulocochlear nerve; Brainstem; Brainstem auditory evoked potentials; Intraoperative monitoring ID AUDITORY-EVOKED-POTENTIALS; ACOUSTIC NEUROMA SURGERY; BRAIN-STEM RESPONSES; VESTIBULAR SCHWANNOMA SURGERY; PRODUCT OTOACOUSTIC EMISSIONS; HEARING PRESERVATION; CEREBELLOPONTINE ANGLE; MICROVASCULAR DECOMPRESSION; RETROSIGMOID APPROACH; 8TH NERVE AB Neurosurgical procedures involving the skull base and structures within can pose a significant risk of damage to the brain stem and cranial nerves. This can have life-threatening consequences and/or result in devastating neurologic deficits. Over the past decade, intraoperative neurophysiology has significantly evolved and currently offers a great tool for live monitoring of the integrity of nervous structures. Thus, dysfunction can be identified early and prompt modification of the surgical management or operating conditions, leads to avoidance of permanent structural damage. Along these lines, the vestibulocochlear nerve (CN VIII) and, to a greater extent, the auditory pathways as they pass through the brain stem are especially at risk during cerebelopontine angle (CPA), posterior/middle fossa, or brain stem surgery. CN VIII can be damaged by several mechanisms, from vascular compromise to mechanical injury by stretch, compression, dissection, and heat injury. Additionally, cochlea itself can be significantly damaged during temporal bone drilling, by noise, mechanical destruction, or infarction, and because of rupture, occlusion, or vasospasm of the internal auditory artery. CN VIII monitoring can be successfully achieved by live recording of the function of one of its parts, the cochlear or auditory nerve (AN), using the brain stem auditory evoked potentials (BAEPs), electrocochleography (ECochG), and compound nerve action potentials (CNAPs) of the cochlear nerve. This is a review of these techniques, their principle, applications, methodology, interpretation of the evoked responses, and their change from baseline, within the context of surgical and anesthesia environments, and finally the appropriate management of these changes. C1 [Simon, Mirela V.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Simon, Mirela V.] Harvard Univ, Sch Med, Boston, MA USA. RP Simon, MV (reprint author), 55 Fruit St, Boston, MA 02114 USA. EM mvsimon@partners.org NR 92 TC 11 Z9 11 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0736-0258 J9 J CLIN NEUROPHYSIOL JI J. Clin. Neurophysiol. PD DEC PY 2011 VL 28 IS 6 BP 566 EP 581 PG 16 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 872PL UT WOS:000298821700005 PM 22146352 ER PT J AU Haffty, BG Hunt, KK Harris, JR Buchholz, TA AF Haffty, Bruce G. Hunt, Kelly K. Harris, Jay R. Buchholz, Thomas A. TI Positive Sentinel Nodes Without Axillary Dissection: Implications for the Radiation Oncologist SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID INVASIVE BREAST-CANCER; LYMPH-NODES; PREOPERATIVE THERAPY; TANGENTIAL FIELDS; BIOPSY; RADIOTHERAPY; IRRADIATION; SURGERY; METAANALYSIS; RECURRENCE C1 [Haffty, Bruce G.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Canc Inst New Jersey, New Brunswick, NJ USA. [Hunt, Kelly K.; Buchholz, Thomas A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Harris, Jay R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Haffty, BG (reprint author), Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Canc Inst New Jersey, New Brunswick, NJ USA. NR 33 TC 59 Z9 63 U1 1 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 1 PY 2011 VL 29 IS 34 BP 4479 EP 4481 DI 10.1200/JCO.2011.36.1667 PG 3 WC Oncology SC Oncology GA 863AZ UT WOS:000298136500012 PM 22042942 ER PT J AU Kurian, AW Gong, GD John, EM Johnston, DA Felberg, A West, DW Miron, A Andrulis, IL Hopper, JL Knight, JA Ozcelik, H Dite, GS Apicella, C Southey, MC Whittemore, AS AF Kurian, Allison W. Gong, Gail D. John, Esther M. Johnston, David A. Felberg, Anna West, Dee W. Miron, Alexander Andrulis, Irene L. Hopper, John L. Knight, Julia A. Ozcelik, Hilmi Dite, Gillian S. Apicella, Carmel Southey, Melissa C. Whittemore, Alice S. TI Breast Cancer Risk for Noncarriers of Family-Specific BRCA1 and BRCA2 Mutations: Findings From the Breast Cancer Family Registry SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID SENSITIVE GEL-ELECTROPHORESIS; GENETIC EPIDEMIOLOGY; OVARIAN-CANCER; PHENOCOPIES; PENETRANCE; CARRIERS; RELATIVES; MODELS; WOMEN AB Purpose Women with germline BRCA1 and BRCA2 mutations have five- to 20-fold increased risks of developing breast and ovarian cancer. A recent study claimed that women testing negative for their family-specific BRCA1 or BRCA2 mutation (noncarriers) have a five-fold increased risk of breast cancer. We estimated breast cancer risks for noncarriers by using a population-based sample of patients with breast cancer and their female first-degree relatives (FDRs). Patients and Methods Patients were women with breast cancer and their FDRs enrolled in the population-based component of the Breast Cancer Family Registry; patients with breast cancer were tested for BRCA1 and BRCA2 mutations, as were FDRs of identified mutation carriers. We used segregation analysis to fit a model that accommodates familial correlation in breast cancer risk due to unobserved shared risk factors. Results We studied 3,047 families; 160 had BRCA1 and 132 had BRCA2 mutations. There was no evidence of increased breast cancer risk for noncarriers of identified mutations compared with FDRs from families without BRCA1 or BRCA2 mutations: relative risk was 0.39 (95% CI, 0.04 to 3.81). Residual breast cancer correlation within families was strong, suggesting substantial risk heterogeneity in women without BRCA1 or BRCA2 mutations, with some 3.4% of them accounting for roughly one third of breast cancer cases. Conclusion These results support the practice of advising noncarriers that they do not have any increase in breast cancer risk attributable to the family-specific BRCA1 or BRCA2 mutation. J Clin Oncol 29:4505-4509. (C) 2011 by American Society of Clinical Oncology C1 [Whittemore, Alice S.] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA. [John, Esther M.; West, Dee W.] Canc Prevent Inst Calif, Fremont, CA USA. [Miron, Alexander] Dana Farber Canc Inst, Boston, MA 02115 USA. [Andrulis, Irene L.; Knight, Julia A.; Ozcelik, Hilmi] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Andrulis, Irene L.; Ozcelik, Hilmi] Univ Toronto, Toronto, ON M5S 1A1, Canada. [Andrulis, Irene L.] Canc Care Ontario, Toronto, ON, Canada. [Hopper, John L.; Dite, Gillian S.; Apicella, Carmel; Southey, Melissa C.] Univ Melbourne, Melbourne, Vic, Australia. RP Whittemore, AS (reprint author), Stanford Univ, Sch Med, Dept Hlth Res & Policy, HRP Redwood Bldg,Room T204,259 Campus Dr, Stanford, CA 94305 USA. EM alicesw@stanford.edu RI Knight, Julia/A-6843-2012; Andrulis, Irene/E-7267-2013; OI Dite, Gillian/0000-0002-2448-2548 FU National Cancer Institute, National Institutes of Health (NIH) [RFA-CA-06-503]; NIH [CA69417, CA94069]; Cancer Care Ontario [U01 CA69467]; Cancer Prevention Institute of California [U01 CA694117]; University of Melbourne [U01 CA69638] FX Supported by Grants No. RFA-CA-06-503 from the National Cancer Institute, National Institutes of Health (NIH), No. CA69417 and CA94069 from NIH, No. U01 CA69467 from Cancer Care Ontario, No. U01 CA694117 from the Cancer Prevention Institute of California, and No. U01 CA69638 from the University of Melbourne, and through cooperative agreements with members of the Breast Cancer Family Registry and principal investigators. NR 29 TC 19 Z9 20 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 1 PY 2011 VL 29 IS 34 BP 4505 EP 4509 DI 10.1200/JCO.2010.34.4440 PG 5 WC Oncology SC Oncology GA 863AZ UT WOS:000298136500016 PM 22042950 ER PT J AU Ramalingam, SS Spigel, DR Chen, D Steins, MB Engelman, JA Schneider, CP Novello, S Eberhardt, WEE Crino, L Habben, K Liu, L Janne, PA Brownstein, CM Reck, M AF Ramalingam, Suresh S. Spigel, David R. Chen, David Steins, Martin B. Engelman, Jeffrey A. Schneider, Claus-Peter Novello, Silvia Eberhardt, Wilfried E. E. Crino, Lucio Habben, Kai Liu, Lian Jaenne, Pasi A. Brownstein, Carrie M. Reck, Martin TI Randomized Phase II Study of Erlotinib in Combination With Placebo or R1507, a Monoclonal Antibody to Insulin-Like Growth Factor-1 Receptor, for Advanced-Stage Non-Small-Cell Lung Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ACQUIRED-RESISTANCE; SOLID TUMORS; GEFITINIB; EXPRESSION; IGF-1R; SENSITIVITY; BREAST AB Purpose R1507 is a selective, fully human, recombinant monoclonal antibody (immunoglobulin G1 subclass) against insulin-like growth factor-1 receptor (IGF-1R). The strong preclinical evidence supporting coinhibition of IGF-1R and epidermal growth factor receptor (EGFR) as anticancer therapy prompted this study. Patients and Methods Patients with advanced-stage non-small-cell lung cancer (NSCLC) with progression following one or two prior regimens, Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2, and measurable disease were eligible. Patients were randomly assigned to receive erlotinib (150 mg orally once a day) in combination with either placebo, R1507 9 mg/kg weekly, or R1507 16 mg/kg intravenously once every 3 weeks. Treatment cycles were repeated every 3 weeks. The primary end point was comparison of the 12-week progression-free survival (PFS) rate. Results In all, 172 patients were enrolled: median age, 61 years; female, 33%; never-smokers, 12%; and performance status 0 or 1, 88%. The median number of R1507 doses was six for the weekly arm and 3.5 for the every-3-weeks arm. Grades 3 to 4 adverse events occurred in 37%, 44%, and 48% of patients with placebo, R1507 weekly, and R1507 every 3 weeks, respectively. The 12-week PFS rates were 39%, 37%, and 44%, and the median overall survival was 8.1, 8.1, and 12.1 months for the three groups, respectively, with statistically nonsignificant hazard ratios. The 12-week PFS rate in patients with KRAS mutation was 36% with R1507 compared with 0% with placebo. Conclusion The combination of R1507 with erlotinib did not provide PFS or survival advantage over erlotinib alone in an unselected group of patients with advanced NSCLC. Predictive biomarkers are essential for further development of combined inhibition of IGF-1R and EGFR. J Clin Oncol 29:4574-4580. (C) 2011 by American Society of Clinical Oncology C1 [Ramalingam, Suresh S.] Emory Univ, Sch Med, Winship Canc Inst, Atlanta, GA 30322 USA. [Spigel, David R.] Sarah Cannon Res Inst, Nashville, TN USA. [Spigel, David R.] Tennessee Oncol, Nashville, TN USA. [Chen, David; Habben, Kai; Liu, Lian; Brownstein, Carrie M.] Roche Pharmaceut, Nutley, NJ USA. [Steins, Martin B.] Univ Heidelberg, Heidelberg, Germany. [Schneider, Claus-Peter] Cent Clin Bad Berka, Bad Berka, Germany. [Eberhardt, Wilfried E. E.] Univ Duisburg Essen, Univ Hosp Essen, Essen, Germany. [Reck, Martin] Hosp Grosshansdorf, Grosshansdorf, Germany. [Engelman, Jeffrey A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Jaenne, Pasi A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Novello, Silvia] Univ Turin, Orbassano, Italy. [Crino, Lucio] Univ Perugia, I-06100 Perugia, Italy. RP Ramalingam, SS (reprint author), Emory Univ, Sch Med, Winship Canc Inst, 1365 Clifton Rd NE,Suite C-3090, Atlanta, GA 30322 USA. EM suresh.ramalingam@emory.edu FU NCI NIH HHS [U10 CA180864, U10 CA180950] NR 25 TC 66 Z9 66 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 1 PY 2011 VL 29 IS 34 BP 4574 EP 4580 DI 10.1200/JCO.2011.36.6799 PG 7 WC Oncology SC Oncology GA 863AZ UT WOS:000298136500026 PM 22025157 ER PT J AU Mischoulon, D AF Mischoulon, David TI The Impact of Omega-3 Fatty Acids on Depressive Disorders and Suicidality: Can We Reconcile 2 Studies With Seemingly Contradictory Results? SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Editorial Material ID POLYUNSATURATED FATTY-ACIDS; DOUBLE-BLIND; DOCOSAHEXAENOIC ACID; CONTROLLED-TRIALS; BIPOLAR DISORDER; MAJOR DEPRESSION; METAANALYSIS; EFFICACY; ANTIDEPRESSANTS; RATES C1 [Mischoulon, David] Massachusetts Gen Hosp, Depress Clin & Res Program, Dept Psychiat, Boston, MA 02114 USA. [Mischoulon, David] Harvard Univ, Sch Med, Boston, MA USA. RP Mischoulon, D (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, Dept Psychiat, 1 Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM dmischoulon@partners.org FU NIMH NIH HHS [R01 MH074085] NR 26 TC 6 Z9 6 U1 2 U2 2 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD DEC PY 2011 VL 72 IS 12 BP 1574 EP 1576 DI 10.4088/JCP.11com07463 PG 3 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 872AJ UT WOS:000298778500001 PM 22244020 ER PT J AU Topor, DR Swenson, LP Liguori, GM Spirito, A Lowenhaupt, EA Hunt, JI AF Topor, David R. Swenson, Lance P. Liguori, Gina M. Spirito, Anthony Lowenhaupt, Elizabeth A. Hunt, Jeffrey I. TI Problematic Video Game Use Scale: Initial Psychometric Properties With Psychiatrically Hospitalized Adolescents SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID HOPELESSNESS SCALE; INTERNET USE; CHILDREN; ADDICTION; VALIDITY; PLAY AB Objective: Excessive video game use among youth has been a growing concern in the United States and elsewhere. The aims of this study are to establish validity of a video game measure in a large adolescent inpatient sample, identify clinical factors underlying problem video game use, and identify associations with measures of psychopathology. Method: Three hundred eighty participants admitted to an adolescent inpatient psychiatric unit between November 2007 and March 2009 were administered a battery of self-report measures, including a questionnaire developed for this study that assessed reinforcers and consequences of past-year video game use (ie, Problematic Video Game Use Scale). Factor analysis was used to identify the underlying structure of behaviors associated with problem video game use. Results: A factor analysis of the Problematic Video Game Use Scale indicated 2 primary factors. One was associated with engaging in problem behaviors that impaired the adolescent's functioning as a result of playing video games and one reflected the reinforcing effects of playing video games. Both factors were associated with measures of psychopathology, although associations were generally stronger for impairment in functioning than for reinforcing effects. Both factors were significantly correlated with self-reported daily video game use (P < .001). Conclusions:Two underlying factors emerged to account for problem video game playing: impairment in functioning and reinforcing effects. Initial evidence of the content validity of the video game measure was established. Findings highlight the importance of assessing video game use among an adolescent population, the factors associated with video game use, and associations with symptoms of psychopathology. Limitations include a common reporter for multiple measures and cross-sectional data that do not allow for causal links to be made. J Clin Psychiatry 2011;72(12):1611-1615 (C) Copyright 2011 Physicians Postgraduate Press, Inc. C1 [Topor, David R.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Dept Psychiat, Brockton, MA 02301 USA. [Swenson, Lance P.] Suffolk Univ, Dept Psychol, Boston, MA 02114 USA. [Liguori, Gina M.; Hunt, Jeffrey I.] Bradley Hosp, Providence, RI USA. [Spirito, Anthony; Lowenhaupt, Elizabeth A.; Hunt, Jeffrey I.] Brown Univ, Alpert Med Sch, Dept Psychiat & Human Behav, Providence, RI 02912 USA. RP Topor, DR (reprint author), Harvard Univ, Sch Med, VA Boston Healthcare Syst, Dept Psychiat, 940 Belmont St,Bldg 22-PRRC, Brockton, MA 02301 USA. EM David.Topor@va.gov FU Bradley Hospital; Department of Psychiatry and Human Behavior, Warren Alpert Medical School of Brown University, Providence, Rhode Island FX Bradley Hospital and the Department of Psychiatry and Human Behavior, Warren Alpert Medical School of Brown University, Providence, Rhode Island. NR 28 TC 6 Z9 6 U1 2 U2 11 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD DEC PY 2011 VL 72 IS 12 BP 1611 EP 1615 DI 10.4088/JCP.11m07040 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 872AJ UT WOS:000298778500006 PM 22244022 ER PT J AU Tedeschini, E Levkovitz, Y Iovieno, N Ameral, VE Nelson, JC Papakostas, GI AF Tedeschini, Enrico Levkovitz, Yeciel Iovieno, Nadia Ameral, Victoria E. Nelson, J. Craig Papakostas, George I. TI Efficacy of Antidepressants for Late-Life Depression: A Meta-Analysis and Meta-Regression of Placebo-Controlled Randomized Trials SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID WHITE-MATTER HYPERINTENSITIES; CONTROLLED-RELEASE PAROXETINE; DOUBLE-BLIND; MAJOR DEPRESSION; GERIATRIC DEPRESSION; EXCLUSION CRITERIA; ELDERLY-PATIENTS; CLINICAL-TRIALS; EXECUTIVE DYSFUNCTION; DIAGNOSTIC CRITERIA AB Objective: Late-life depression is an important public health issue, given the growing proportion of the elderly relative to the general population in the developed world. The purpose of this study was to examine the efficacy of antidepressants for the treatment of major depressive disorder (MDD) in elderly patients. Data Sources: PubMed/MEDLINE was searched for randomized, double-blind, placebo-controlled trials of antidepressants for treatment of both adult (nonelderly) MDD (patients aged < 65 years) and late-life MDD (patients aged >= 55 years). The search was limited to articles published between January 1, 1980, and March 3, 2010 (inclusive). The year 1980 was used as a cutoff in our search to decrease diagnostic variability, since the DSM-III was introduced in 1980. Our search cross-referenced the term placebo with each of the following antidepressants: amitriptyline, nortriptyline, imipramine, desipramine, clomipramine, trimipramine, protriptyline, dothiepin, doxepin, lofepramine, amoxapine, maprotiline, amineptine, nomifensine, bupropion, phenelzine, tranylcypromine, isocarboxazid, moclobemide, brofaromine, fluoxetine, sertraline, paroxetine, citalopram, escitalopram, fluvoxamine, zimelidine, tianeptine, trazodone, nefazodone, agomelatine, venlafaxine, desvenlafaxine, duloxetine, milnacipran, reboxetine, mirtazapine, and mianserin. We also reviewed the reference lists of all studies identified through the PubMed/MEDLINE search. Study Selection: Articles were selected that reported on randomized, double-blind, placebo-controlled trials of antidepressants used as monotherapy for treatment of MDD and that met numerous a priori criteria pertaining to MDD diagnosis criteria, study duration, study design, drug formulation, original data, age thresholds, primary and secondary outcome measures, and exclusions of other disorders. Final inclusion of articles was determined by consensus between the authors. Seventy-four articles were found eligible for inclusion in our analysis (15 late-life MDD trials and 59 adult MDD trials). Results: Antidepressants were found to be efficacious for late-life MDD (age 55 and older; P <.0001), although there was evidence for heterogeneity across studies (Q(22)=67.302, P <.001). However, antidepressants were not found to be efficacious in the subset of studies using age thresholds of 65 years or older (older late-life MDD) (P=.265). Finally, when we controlled for study design characteristics, antidepressant but not placebo response rates were lower among late-life MDD patients than among adult MOD patients. Conclusions: The present meta-analysis suggests that antidepressants are efficacious in late-life MDD, but significant study heterogeneity suggests that other factors may contribute to these findings. A secondary analysis raises the possibility that efficacy of these agents may be reduced in trials involving patients aged 65 years or older. Why antidepressants may be less efficacious in elderly versus younger subjects remains unclear. J Clin Psychiatry 2011;72(12):1660-1668 (C) Copyright 2011 Physicians Postgraduate Press, Inc. C1 [Tedeschini, Enrico] Univ Modena & Reggio Emilia, Dept Psychiat, I-41100 Modena, Italy. [Tedeschini, Enrico; Levkovitz, Yeciel; Iovieno, Nadia; Ameral, Victoria E.; Papakostas, George I.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Tedeschini, Enrico; Levkovitz, Yeciel; Iovieno, Nadia; Ameral, Victoria E.; Papakostas, George I.] Harvard Univ, Sch Med, Boston, MA USA. [Levkovitz, Yeciel] Shalvata Mental Hlth Ctr, Emot Cognit Res Ctr, Hod Hasharon, Israel. [Levkovitz, Yeciel] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. [Nelson, J. Craig] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. RP Tedeschini, E (reprint author), Univ Modena & Reggio Emilia, Dept Psychiat, 71 Pozzo Rd, I-41100 Modena, Italy. EM enricoted@hotmail.it RI Papakostas, George/I-6905-2013 OI Papakostas, George/0000-0002-2465-5103 FU National Institute of Mental Health (NIMH); Health Resources and Services Administration; Bristol-Myers Squibb; Forest; Pamlab; Pfizer; Ridge Diagnostics FX Dr Nelson has served as a consultant for Bristol-Myers Squibb, Corcept, Covidien, Eli Lilly, Forest, Lundbeck, Medtronics, Merck, Orexigen, Otsuka, Pfizer, and Sanofi-Aventis; has received honoraria from Eli Lilly Global, Otsuka Asia, and Schering-Plough/Merck (Japan and China); has received research support from the National Institute of Mental Health (NIMH) and the Health Resources and Services Administration; has been a member of the speakers bureaus for Bristol-Myers Squibb and Pfizer; has served as an advisor to Bristol-Myers Squibb, Eli Lilly, Labopharm, and Otsuka; and is a stock shareholder of Atossa Genetics. Dr Papakostas has served as a consultant for Abbott, AstraZeneca, Brainsway, Bristol-Myers Squibb, Cephalon, Eli Lilly, GlaxoSmithKline, Evotec, Inflabloc, Jazz, Otsuka, Pamlab, Pfizer, Pierre Fabre, Ridge Diagnostics (formerly known as Precision Human Biolaboratories), Shire, and Wyeth; has received honoraria from Abbott, AstraZeneca, Bristol-Myers Squibb, Brainsway, Cephalon, Eli Lilly, Evotec, GlaxoSmithKline, Inflabloc, Jazz, Lundbeck, Otsuka, Pamlab, Pfizer, Pierre Fabre, Ridge Diagnostics, Shire, Titan, and Wyeth; has received research support from Bristol-Myers Squibb, Forest, NIMH, Pamlab, Pfizer, and Ridge Diagnostics; and has served (in the past, but not currently) on the speakers bureaus for Bristol-Myers Squibb and Pfizer. Drs Tedeschini, Levkovitz, and Iovieno and Ms Ameral report no competing interests relative to the subject of this article. NR 51 TC 58 Z9 61 U1 3 U2 30 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD DEC PY 2011 VL 72 IS 12 BP 1660 EP 1668 DI 10.4088/JCP.10r06531 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 872AJ UT WOS:000298778500013 PM 22244025 ER PT J AU Chen, JA Papakostas, GI Youn, SJ Baer, L Clain, AJ Fava, M Mischoulon, D AF Chen, Justin A. Papakostas, George I. Youn, Soo Jeong Baer, Lee Clain, Alisabet J. Fava, Maurizio Mischoulon, David TI Association Between Patient Beliefs Regarding Assigned Treatment and Clinical Response: Reanalysis of Data From the Hypericum Depression Trial Study Group SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID DOUBLE-BLIND; ANTIDEPRESSANT RESPONSE; ALTERNATIVE MEDICINE; ORTHODOX MEDICINE; PLACEBO; EXPECTATIONS; PERFORATUM; EFFICACY; DESIGN; SCALE AB Objective: To reanalyze data from a 2002 study by the Hypericum Depression Trial Study Group to determine whether patients who believed they were receiving active therapy rather than placebo obtained greater improvement, independent of treatment. Method:Three hundred forty adults with major depressive disorder (according to the Structured Clinical Interview for DSM-IV) and baseline scores of >= 20 on the 17-item Hamilton Depression Rating Scale (HDRS-17) were randomized to Hypericum perforatum 900-1,500 mg/d, sertraline 50-100 mg/d, or placebo and were asked to guess their assigned treatment after 8 weeks. This reanalysis of data was performed from October 1, 2009, to April 15, 2011 The intent-to-treat sample included 207 subjects (mean age = 44 years) who had (1) at least 1 postbaseline visit; (2) adherence data based on serum levels of hyperforin, sertraline, and desmethylsertraline; and (3) guess data. Univariate factorial analysis of variance was used to determine whether treatment assignment affected clinical improvement according to HDRS-17 score and whether this effect was moderated by patient guess of sertraline, Hypericum, or placebo. Analysis of covariance was used to determine whether side effects mediated improvement in the context of patient guess and assigned treatment. chi(2) analyses compared response rates (>= 50% decrease in HDRS-17 score) between the guess groups and between the treatment groups within each guess group. Results: Assigned treatment had no significant effect on clinical improvement (P=.65), but patient guess was significantly associated with improvement (P <.001), and treatment and guess interacted significantly (P=.005). Among subjects who guessed placebo, clinical improvement was small and did not differ significantly across treatments. Among subjects who guessed Hypericum, improvement was large and did not differ significantly across treatments. Among subjects who guessed sertraline, those who received placebo or sertraline had large improvements, but those who received Hypericum had significantly less improvement (P <.001). Similar findings were obtained for response rates. Conclusions: Patient beliefs regarding treatment may have a stronger association with clinical outcome than the actual medication received, and the strength of this association may depend upon the particular combination of treatment guessed and treatment received. J Clin Psychiatry 2011;72(12):1669-1676 (C) Copyright 2011 Physicians Postgraduate Press, Inc. C1 [Chen, Justin A.; Papakostas, George I.; Youn, Soo Jeong; Baer, Lee; Clain, Alisabet J.; Fava, Maurizio; Mischoulon, David] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Depress Clin & Res Program, Boston, MA 02114 USA. RP Mischoulon, D (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Depress Clin & Res Program, 1 Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM dmischoulon@partners.org RI Papakostas, George/I-6905-2013 OI Papakostas, George/0000-0002-2465-5103 FU Bristol-Myers Squibb; Forest; National Institute of Mental Health (NIMH) [N01 MH070007]; Pamlab; Pfizer; Ridge Diagnostics; Abbott; Alkermes; Aspect Medical Systems; AstraZeneca; BioResearch; BrainCells; CeNeRx BioPharma; Cephalon; Clinical Trial Solutions; Clintara; Covidien; Eli Lilly; EnVivo; Euthymics Bioscience; Ganeden; GlaxoSmithKline; Icon Clinical Research; i3 Innovus/Ingenix; Johnson Johnson; Lichtwer; Lorex; NARSAD; National Center for Complementary and Alternative Medicine (NCCAM); National Institute on Drug Abuse; Novartis; Organon; Pharmavite; PhotoThera; Roche; RCT Logic; Sanofi-Aventis; Shire; Solvay; Synthelabo; Wyeth-Ayerst; Nordic Naturals; Fisher Wallace; Back Bay Scientific for PMS Escape; Lippincott Williams & Wilkins for the textbook Natural Medications for Psychiatric Disorders; MGH; NCCAM FX Dr Papakostas has served as a consultant for AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Evotec, Inflabloc, Jazz, Otsuka, Pamlab, Pfizer, Pierre Fabre, Shire, and Wyeth; has received honoraria from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Evotec, GlaxoSmithKline, Inflabloc, Jazz, Lundbeck, Otsuka, Pamlab, Pfizer, Pierre Fabre, Shire, Titan, and Wyeth; has received research support from Bristol-Myers Squibb, Forest, the National Institute of Mental Health (NIMH), Pamlab, Pfizer, and Ridge Diagnostics (formerly known as Precision Human Biolaboratories); and has served on the speakers bureaus of Bristol-Myers Squibb and Pfizer. Dr Fava has received research support from Abbott, Alkermes, Aspect Medical Systems, AstraZeneca, BioResearch, BrainCells, Bristol-Myers Squibb, CeNeRx BioPharma, Cephalon, Clinical Trial Solutions, Clintara, Covidien, Eli Lilly, EnVivo, Euthymics Bioscience, Forest, Ganeden, GlaxoSmithKline, Icon Clinical Research, i3 Innovus/Ingenix, Johnson & Johnson, Lichtwer, Lorex, NARSAD, National Center for Complementary and Alternative Medicine (NCCAM), National Institute on Drug Abuse, NIMH, Novartis, Organon, Pamlab, Pfizer, Pharmavite, PhotoThera, Roche, RCT Logic, Sanofi-Aventis, Shire, Solvay, Synthelabo, and Wyeth-Ayerst; has served as an advisor and consultant to Abbott, Affectis, Alkermes, Amarin, Aspect Medical Systems, AstraZeneca, Auspex, Bayer, Best Practice Project Management, BioMarin, Biovail, BrainCells, Bristol-Myers Squibb, CeNeRx BioPharma, Cephalon, Clinical Trials Solutions, CNS Response, Compellis, Cypress, Dainippon Sumitomo, DOV, Edgemont, Eisai, Eli Lilly, ePharmaSolutions, EPIX, Euthymics Bioscience, Fabre-Kramer, Forest, Genomind, GlaxoSmithKline, Grunenthal, i3 Innovus/Ingenix, Janssen, Jazz, Johnson 8c Johnson, Knoll, Labopharm, Lorex, Lundbeck, MedAvante, Merck, Methylation Sciences, Naurex, Neuronetics, NextWave, Novartis, Nutrition 21, Orexigen, Organon, Otsuka, Pamlab, Pfizer, PharmaStar, Pharmavite, PharmoRx Therapeutics, Precision Human Biolaboratory, Prexa, PureTech Ventures, PsychoGenics, Psylin Neurosciences, Rexahn, Ridge Diagnostics, Roche, RCT Logic, Sanofi-Aventis, Sepracor, Servier, Schering-Plough, Solvay, Somaxon, Somerset, Sunovion, Supernus, Synthelabo, Takeda, Tal Medical, Tetragenex, TransForm, Transcept, Vanda, and Wyeth-Ayerst; has received speaking and publishing honoraria from Adamed, Advanced Meeting Partners, American Psychiatric Association, American Society of Clinical Psychopharmacology, AstraZeneca, Belvoir Media Group, Boehringer-Ingelheim, Bristol-Myers Squibb, Cephalon, CME Institute/Physicians Postgraduate Press, Eli Lilly, Forest, GlaxoSmithKline, Imedex, Novartis, Organon, Pfizer, PharmaStar, MGH Psychiatry Academy/PRIMEDIA Healthcare, MGH Psychiatry Academy/Reed Elsevier, UBC, and Wyeth-Ayerst; holds equity in Compellis; holds a patent for Sequential Parallel Comparison Design (SPCD); holds a patent for research and licensing of SPCD with RCT Logic, Lippincott Williams & Wilkins, and World Scientific Publishing; has a patent application for a combination of azapirones and bupropion in major depressive disorder; and has received copyright royalties for the MGH Cognitive and Physical Functioning Questionnaire, Sexual Functioning Inventory, Antidepressant Treatment Response Questionnaire, Discontinuation-Emergent Signs and Symptoms scale, and SAFER Criteria Interview diagnostic instruments.; Dr Mischoulon has received research support from Nordic Naturals, Fisher Wallace, and Ganeden; has served as a consultant to Bristol-Myers Squibb; hs received writing honoraria from Pamlab; has received royalties from Back Bay Scientific for PMS Escape and from Lippincott Williams & Wilkins for the textbook Natural Medications for Psychiatric Disorders: Considering the Alternatives, for which he is co-editor; and has received honoraria from Reed Medical Education (a company working as a logistics collaborator for MGH Psychiatry Academy) (the education programs conducted by MGH Psychiatry Academy were supported through independent medical education grants from pharmaceutical companies cosupporting programs along with participant tuition; commercial entities currently supporting the MGH Psychiatry Academy are listed on the Academy's website at www.mghcme.org). Drs Chen and Baer and Mss Youn and Clain report no competing interests in relation to the subject of this article.; This reanalysis was supported by the MGH Depression Clinical and Research Program's clinical practice revenues. The original clinical study "Treatment of Major Depression With St John's Wort (Hypericum)" (clinicaltrials.gov Identifier: NCT00005013) was conducted and supported by NIMH (grant N01 MH070007) and NCCAM in collaboration with the study investigators. NR 34 TC 15 Z9 15 U1 1 U2 16 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD DEC PY 2011 VL 72 IS 12 BP 1669 EP 1676 DI 10.4088/JCP.10m06453 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 872AJ UT WOS:000298778500014 PM 22053942 ER PT J AU Lowe, MR Berner, LA Swanson, SA Clark, VL Eddy, KT Franko, DL Shaw, JA Ross, S Herzog, DB AF Lowe, Michael R. Berner, Laura A. Swanson, Sonja A. Clark, Vicki L. Eddy, Kamryn T. Franko, Debra L. Shaw, Jena A. Ross, Stephanie Herzog, David B. TI Weight Suppression Predicts Time to Remission From Bulimia Nervosa SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article DE bulimia nervosa; weight suppression; remission; outcome ID FOLLOW-UP; REPORTED WEIGHT; ACCURACY; RISK AB Objective: To investigate whether, at study entry, (a) weight suppression (WS), the difference between highest past adult weight and current weight, prospectively predicts time to first full remission from bulimia nervosa (BN) over a follow-up period of 8 years, and (b) weight change over time mediates the relationship between WS and time to first full remission. Method: A well-characterized sample of women with BN (N = 110; M age = 25.58 years, SD = 6.48) from the Massachusetts General Hospital Longitudinal Study of Eating Disorders was interviewed at 6-12 month intervals over 8 years. The main outcome measure, a "time to first full remission" variable, was based on psychiatric status ratings generated from the Eating Disorders Longitudinal Interval Follow-up Evaluation. Results: WS was significantly associated with time to first full remission (p = .01; hazard ratio = .89; 95% confidence interval [0.82, 0.97]), indicating that women who were more weight suppressed at study entry took longer to recover. Weight change did not mediate the relationship between WS and time to remission. Conclusions: Results add to a growing body of evidence that WS predicts maintenance of BN symptoms and extend previous short-term findings by demonstrating, over a period of approximately 8 years, that WS predicts longer time to first full remission. Beyond absolute weight status, WS level may significantly inform the treatment of BN. C1 [Lowe, Michael R.; Berner, Laura A.; Clark, Vicki L.; Shaw, Jena A.] Drexel Univ, Dept Psychol, Philadelphia, PA 19102 USA. [Lowe, Michael R.] Renfrew Ctr Eating Disorders, Dept Res, Philadelphia, PA USA. [Swanson, Sonja A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Cambridge, MA 02138 USA. [Franko, Debra L.] Northeastern Univ, Dept Psychiat, Massachusetts Gen Hosp, Dept Counseling & Appl Educ Psychol, Boston, MA 02115 USA. [Eddy, Kamryn T.; Franko, Debra L.; Herzog, David B.] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. RP Lowe, MR (reprint author), Drexel Univ, Dept Psychol, 245 N 15th St,Mail Stop 626, Philadelphia, PA 19102 USA. EM lowe@drexel.edu OI Shaw, Jena/0000-0003-3587-4130 FU NIMH NIH HHS [5R01 MH38333 05, F31 MH097406] NR 21 TC 17 Z9 17 U1 0 U2 3 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD DEC PY 2011 VL 79 IS 6 BP 772 EP 776 DI 10.1037/a0025714 PG 5 WC Psychology, Clinical SC Psychology GA 855FG UT WOS:000297548600006 PM 22004302 ER PT J AU Susser, E Buka, S Schaefer, CA Andrews, H Cirillo, PM Factor-Litvak, P Gillman, M Goldstein, JM Henry, PI Lumey, LH McKeague, IW Michels, KB Terry, MB Cohn, BA AF Susser, E. Buka, S. Schaefer, C. A. Andrews, H. Cirillo, P. M. Factor-Litvak, P. Gillman, M. Goldstein, J. M. Henry, P. Ivey Lumey, L. H. McKeague, I. W. Michels, K. B. Terry, M. B. Cohn, B. A. CA EDAH Team TI The Early Determinants of Adult Health Study SO JOURNAL OF DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE LA English DT Review DE early determinants of adult health; EDAH; pregnancy cohorts; sibling pairs ID FOR-GESTATIONAL-AGE; BIRTH-WEIGHT; PRENATAL DETERMINANTS; GENETIC VULNERABILITY; AFFECTIVE PSYCHOSES; CIGARETTE-SMOKING; MATERNAL-SMOKING; BREAST-CANCER; HIGH-RISK; SCHIZOPHRENIA AB This issue of the Journal features collaborative follow-up studies of two unique pregnancy cohorts recruited during 1959-1966 in the United States. Here we introduce the Early Determinants of Adult Health (EDAH) study. EDAH was designed to compare health outcomes in midlife (age 40s) for same-sex siblings discordant on birthweight for gestational age. A sufficient sample of discordant siblings could only be obtained by combining these two cohorts in a single follow-up study. All of the subsequent six papers are either based upon the EDAH sample or are related to it in various ways. For example, three papers report results from studies that significantly extended the 'core' EDAH sample to address specific questions. We first present the overall design of and rationale for the EDAH study. Then we offer a synopsis of past work with the two cohorts to provide a context for both EDAH and the related studies. Next, we describe the recruitment and assessment procedures for the core EDAH sample. This includes the process of sampling and recruitment of potential participants; a comparison of those who were assessed and not assessed based on archived data; the methods used in the adult follow-up assessment; and the characteristics at follow-up of those who were assessed. We provide online supplementary tables with much further detail. Finally, we note further work in progress on EDAH and related studies, and draw attention to the broader implications of this endeavor. C1 [Susser, E.; Factor-Litvak, P.; Lumey, L. H.; Terry, M. B.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA. [Susser, E.] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. [Andrews, H.] New York State Psychiat Inst & Hosp, Data Coordinating Ctr, New York, NY 10032 USA. [Susser, E.; Factor-Litvak, P.; Lumey, L. H.; McKeague, I. W.; Terry, M. B.] Columbia Univ, Mailman Sch Publ Hlth, Imprints Ctr Genet & Environm Life Course Studies, New York, NY 10032 USA. [Buka, S.] Brown Univ, Dept Epidemiol, Providence, RI 02912 USA. [Schaefer, C. A.] Kaiser Permanente Div Res, Oakland, CA USA. [Andrews, H.; McKeague, I. W.] Columbia Univ, Dept Biostat, New York, NY 10032 USA. [Cirillo, P. M.; Cohn, B. A.] Inst Publ Hlth, Ctr Res Women & Childrens Hlth Child Hlth & Dev S, Berkeley, CA USA. [Gillman, M.] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA USA. [Gillman, M.] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Goldstein, J. M.] Brigham & Womens Hosp, Connors Ctr Womens Hlth & Gender Biol, Div Womens Hlth, Dept Psychiat, Boston, MA 02115 USA. [Goldstein, J. M.] Brigham & Womens Hosp, Dept Med, Div Womens Hlth, Connors Ctr Womens Hlth & Gender Biol, Boston, MA 02115 USA. [Goldstein, J. M.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Goldstein, J. M.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Goldstein, J. M.] Massachusetts Gen Hosp, Dept Psychiat, Div Psychiat Neurosci, Boston, MA 02114 USA. [Henry, P. Ivey] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Michels, K. B.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Obstet,Obstet & Gynecol Epidemiol Ctr, Boston, MA 02115 USA. [Michels, K. B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Michels, K. B.] Univ Freiburg, Comprehens Canc Ctr Freiburg, Div Canc Epidemiol, D-79106 Freiburg, Germany. RP Susser, E (reprint author), Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, 722 W 168th St,Off 1030, New York, NY 10032 USA. EM ess8@columbia.edu RI Buka, Stephen/H-7335-2014 OI Buka, Stephen/0000-0002-8578-9308 FU NIA [P01 AG023028] FX This work was supported by NIA P01 AG023028 (E. Susser, overall PI, S. Buka, co-PI, B.Cohn, co-PI). Many individuals contributed to the success of this study. The authors would like to specially acknowledge Melissa Begg, Michaeline Bresnahan, Sara Cherkerzian, George Davey Smith, Ana Diez-Roux, Kim Fader, Tammy Kouffman, Bill Lasley, Thomas Matte, Sunita Miles, Sharon O'Toole, Eleonora Raviglione, Janet Rich-Edwards and Patricia A. Zybert. The study could not have been properly designed and conducted without the generous contributions of these individuals. NR 60 TC 15 Z9 15 U1 1 U2 5 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 2040-1744 J9 J DEV ORIG HLTH DIS JI J. Dev. Orig. Health Dis. PD DEC PY 2011 VL 2 IS 6 SI SI BP 311 EP 321 DI 10.1017/S2040174411000663 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 864UF UT WOS:000298264900001 PM 25126404 ER PT J AU Goldstein, JM Cherkerzian, S Buka, SL Fitzmaurice, G Hornig, M Gillman, M O'Toole, S Sloan, RP AF Goldstein, J. M. Cherkerzian, S. Buka, S. L. Fitzmaurice, G. Hornig, M. Gillman, M. O'Toole, S. Sloan, R. P. TI Sex-specific impact of maternal-fetal risk factors on depression and cardiovascular risk 40 years later SO JOURNAL OF DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE LA English DT Article DE autonomic nervous system; cardiovascular disease; depression; fetal programming; fetal risk; sex differences ID HEART-RATE-VARIABILITY; LOW-BIRTH-WEIGHT; FOR-GESTATIONAL-AGE; MAJOR AFFECTIVE-DISORDER; HIGH BLOOD-PRESSURE; OBSTETRIC COMPLICATIONS; MYOCARDIAL-INFARCTION; SOCIOECONOMIC-STATUS; GROWTH RESTRICTION; AUTONOMIC FUNCTION AB Major depressive disorder (MDD) and cardiovascular disease (CVD) represent leading causes of morbidity and mortality worldwide. We tested the hypothesis that growth restriction and preeclampsia (referred to as fetal risk) are significant predictors of these conditions, with women at higher risk in adulthood. Adult offspring exposed to fetal risk factors and their discordant siblings were from two prenatal cohorts, whose mothers were followed through pregnancy and whom we recruited as adults 40 years later (n = 538; 250 males and 288 females). Subjects were psychiatrically diagnosed and underwent a stress challenge during which parasympathetic regulation was assessed by electrocardiogram, operationalized as high-frequency R-R interval variability (HF-RRV). Linear mixed models and generalized estimating equations were used to examine the relationship of fetal risk on HF-RRV, MDD and comorbidity of low HF-RRV (lowest 25th percentile) and MDD, including interactions with sex and socioeconomic status (SES). Fetal risk was significantly associated with low HF-RRV response (F = 3.64, P = 0.05), particularly among low SES (interaction: F = 4.31, P < 0.04). When stratified by MDD, the fetal risk impact was three times greater among MDD compared with non-MDD subjects (effect size: 0.21 v. 0.06). Females had a significantly higher risk for the comorbidity of MDD and low HF-RRV than males (relative risk (RR) = 1.36, 95% CI: 1.07-1.73), an association only seen among those exposed to fetal risk (RR = 1.38, 95% CI: 1.04-1.83). Findings suggest that these are shared fetal antecedents to the comorbidity of MDD and CVD risk 40 years later, an association stronger in females than in males. C1 [Goldstein, J. M.] Brigham & Womens Hosp, Div Womens Hlth, Connors Ctr Womens Hlth & Gender Biol, Boston, MA 02120 USA. [Goldstein, J. M.; Cherkerzian, S.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Goldstein, J. M.; Cherkerzian, S.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Goldstein, J. M.] Massachusetts Gen Hosp, Dept Psychiat, Div Psychiat Neurosci, Boston, MA 02114 USA. [Buka, S. L.] Brown Univ, Dept Epidemiol, Providence, RI 02912 USA. [Fitzmaurice, G.] Harvard Univ, McLean Hosp, Sch Med, Dept Psychiat, Belmont, MA USA. [Hornig, M.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. [Hornig, M.] Columbia Univ, Mailman Sch Publ Hlth, Ctr Infect & Immun, New York, NY USA. [Gillman, M.] Harvard Univ, Sch Med, Dept Populat Hlth, Cambridge, MA 02138 USA. [Sloan, R. P.] Columbia Univ, Dept Psychiat, New York State Psychiat Inst, Med Ctr, New York, NY USA. RP Goldstein, JM (reprint author), Brigham & Womens Hosp, Div Womens Hlth, Connors Ctr Womens Hlth & Gender Biol, 1 Brigham Circle,3rd Floor,1620 Tremont St, Boston, MA 02120 USA. EM jill_goldstein@hms.harvard.edu RI Buka, Stephen/H-7335-2014 OI Buka, Stephen/0000-0002-8578-9308 FU NIMH-NHLBI [RO1 MH074679]; NIA [P01 AG023028]; ORWH-NIMH [P50 MH082679] FX This study was supported by NIMH-NHLBI RO1 MH074679 [Goldstein, principal investigator (PI)] and NIA P01 AG023028 (Susser, overall PI) and, in part, by ORWH-NIMH P50 MH082679 (Goldstein, P.I.). The authors thank Harlin Aizley, Ed.M., for her clinical diagnostic interviewing expertise and collection of RRV data; Jo-Ann Donatelli, Ph.D. for her clinical expertise in training and quality control of psychiatric and cognitive data; Christiana Provencale, MA, for her efforts in managing the recruitment team at Brown; Howard Andrews, Ph.D., for his contribution to data management; Catherine Schaefer, Ph.D., for overseeing the original NIA work in California; and Kim Fader for her administrative help in maintaining connections between multiple sites involved in this study. NR 112 TC 13 Z9 13 U1 2 U2 4 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 2040-1744 J9 J DEV ORIG HLTH DIS JI J. Dev. Orig. Health Dis. PD DEC PY 2011 VL 2 IS 6 SI SI BP 353 EP 364 DI 10.1017/S2040174411000651 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 864UF UT WOS:000298264900005 PM 23378891 ER PT J AU Factor-Litvak, P Straka, N Cherkerzian, S Richards, M Liu, X Sher, A Neils, G Goldstein, J AF Factor-Litvak, P. Straka, N. Cherkerzian, S. Richards, M. Liu, X. Sher, A. Neils, G. Goldstein, J. TI Associations between birth weight, preeclampsia and cognitive functions in middle-aged adults SO JOURNAL OF DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE LA English DT Article DE fetal programming; neurocognition; fetal growth ID SEX-DIFFERENCES; GESTATIONAL-AGE; HUMAN BRAIN; NEUROPSYCHOLOGICAL FUNCTIONS; SOCIOECONOMIC POSITION; GONADAL-HORMONES; FEMALE BRAIN; IN-VIVO; CHILDREN; COHORT AB Both reductions in birth weight and preeclampsia (PE) have been associated with decrements in scores on tests of intelligence in children and adolescents. We examined whether these decrements persist into middle adulthood and expand into other domains of cognitive functioning. Using data from the Early Determinants of Adult Health project and from the ancillary project, Fetal Antecedents of Major Depression and Cardiovascular Disease, we selected term same-sex sibling sets or singletons from these sets, from the New England Family Study (NEFS) and the Child Health and Development Studies (CHDS), discordant on either fetal growth or PE, to test the hypotheses that prenatal exposure to inflammation was associated with decrements in attention, learning and executive function 40 years later. Exposure was defined as a continuous measure of percentile birth weight for gestational age, reduced fetal growth (<20th percentile of birth weight for gestational age) or maternal PE. Given that the sample was comprised, in part, of sibling sets, the analyses were performed using mixed models to account for the inter-sibling correlations. Analyses were performed separately by study site (i.e. NEFS and CHDS). We found few statistically significant associations (suggesting a possible type II error) consistent with previous literature, suggesting that the associations with low birth weight do not persist into midlife. We discuss the possible reasons for the lack of associations, which include the possible mediating effects of the postnatal environment. C1 [Factor-Litvak, P.; Straka, N.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10027 USA. [Cherkerzian, S.; Goldstein, J.] Brigham & Womens Hosp, Dept Psychiat, Div Womens Hlth, Connors Ctr Womens Hlth & Gender Biol, Boston, MA 02115 USA. [Cherkerzian, S.] Brigham & Womens Hosp, Dept Med, Div Womens Hlth, Connors Ctr Womens Hlth & Gender Biol, Boston, MA 02115 USA. [Cherkerzian, S.; Goldstein, J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Cherkerzian, S.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Richards, M.] Med Res Council MRC Unit Lifelong Hlth & Aging, London, England. [Richards, M.] UCL, Dept Epidemiol & Publ Hlth, London, England. [Liu, X.] Columbia Univ, Mailman Sch Publ Hlth, Dept Biostat, New York, NY USA. [Sher, A.] ICSD USA, Millburn, NJ USA. [Neils, G.] Columbia Univ, Gertrude H Sergievsky Ctr, Coll Phys & Surg, New York, NY 10027 USA. [Goldstein, J.] Massachusetts Gen Hosp, Dept Psychiat, Div Psychiat Neurosci, Boston, MA 02114 USA. RP Factor-Litvak, P (reprint author), Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10027 USA. EM prf1@columbia.edu FU NIMH-NHLBI [RO1 MH074679]; NIA [P01 AG023028]; ORWH-NIMH [P50 MH082679] FX This work was supported by NIMH-NHLBI RO1 MH074679 (Goldstein, P.I.) and NIA P01 AG023028 (Susser, overall PI) and, partly, by ORWH-NIMH P50 MH082679 (Goldstein, P.I.). The authors thank Harlin Aizley, Ed.M. for her clinical diagnostic interviewing expertise and collection of RRV data, Jo-Ann Donatelli, Ph.D. for her clinical expertise in training and quality control of psychiatric and cognitive data, Christiana Provencale, M.A. for her efforts in managing the recruitment team at Brown, Barbara Cohn, Ph.D. and Piera Cirillo M.P.H. for providing access to the CHDS archived data and for providing the sample from the CHDS, Howard Andrews, Ph.D. for his contribution to data management, Catherine Schaefer, Ph.D. for overseeing the original NIA work in California and Kim Fader, M.A. for her administrative help in maintaining connections between multiple sites involved in this work. NR 69 TC 3 Z9 3 U1 1 U2 5 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 2040-1744 J9 J DEV ORIG HLTH DIS JI J. Dev. Orig. Health Dis. PD DEC PY 2011 VL 2 IS 6 SI SI BP 365 EP 374 DI 10.1017/S2040174411000596 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 864UF UT WOS:000298264900006 PM 25140487 ER PT J AU Capp, R Chang, YC Brown, DFM AF Capp, Roberta Chang, Yuchiao Brown, David F. M. TI EFFECTIVE ANTIBIOTIC TREATMENT PRESCRIBED BY EMERGENCY PHYSICIANS IN PATIENTS ADMITTED TO THE INTENSIVE CARE UNIT WITH SEVERE SEPSIS OR SEPTIC SHOCK: WHERE IS THE GAP? SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE septic shock; severe sepsis; guidelines; antibiotics ID INADEQUATE ANTIMICROBIAL TREATMENT; COMMUNITY-ACQUIRED PNEUMONIA; BLOOD-STREAM INFECTIONS; CLINICAL-OUTCOMES; ESCHERICHIA-COLI; MATCHED COHORT; THERAPY; HEALTH; EPIDEMIOLOGY; GUIDELINES AB Background: Antibiotic selection made within the first hour of recognition of severe sepsis and septic shock has been shown to decrease mortality. Objective: The purpose of this study was to determine what antibiotics are being prescribed and to identify factors influencing ineffective antibiotic coverage in patients with severe sepsis or septic shock. In addition, we explore an alternative method for antibiotic selection that could improve organism coverage. Methods: This was a retrospective review of emergency department (ED) patients admitted to an intensive care unit (ICU) over a 12-month period with a culture-positive diagnosis of either severe sepsis or septic shock. Appropriate antibiotic therapy was defined as effective coverage of the offending organism based on final culture results. Results: Of the 1400 patients admitted to the ICU, 137 patients were culture positive and met the criteria for severe sepsis or septic shock. Effective antibiotic coverage was prescribed by emergency physicians in 82% (95% confidence interval [CI] .74-.88) of cases. Of the 25 patients who received ineffective antibiotics, the majority had infections caused by resistant Gram-negative organisms. Health care-associated pneumonia guidelines were applied to all patients, regardless of the source of infection, and were 100% sensitive (95% CI .93-1) for selecting patients who had infections caused by highly resistant organisms. Conclusion: Emergency physicians achieved 82% effective antibiotic coverage in patients with severe sepsis or septic shock. The gap seems to be in coverage of highly resistant Gram-negative organisms. An alternative approach to antibiotic prescription, utilizing a set of guidelines for community- and health care-associated infections, was found to be 100% sensitive in selecting patients who had infections caused by the more resistant organisms. (C) 2011 Elsevier Inc. C1 [Capp, Roberta] Brigham & Womens Hosp, Boston, MA 02115 USA. [Chang, Yuchiao; Brown, David F. M.] Massachusetts Gen Hosp, Dept Emergency Serv, Boston, MA 02114 USA. [Capp, Roberta; Chang, Yuchiao; Brown, David F. M.] Harvard Univ, Sch Med, Boston, MA USA. RP Capp, R (reprint author), Brigham & Womens Hosp, 75 Francis St,Neville House, Boston, MA 02115 USA. NR 33 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD DEC PY 2011 VL 41 IS 6 BP 573 EP 580 DI 10.1016/j.jemermed.2010.10.024 PG 8 WC Emergency Medicine SC Emergency Medicine GA 869BZ UT WOS:000298572000001 PM 21371846 ER PT J AU Soremekun, OA Takayesu, JK Bohan, SJ AF Soremekun, Olanrewaju A. Takayesu, James K. Bohan, Stephen J. TI FRAMEWORK FOR ANALYZING WAIT TIMES AND OTHER FACTORS THAT IMPACT PATIENT SATISFACTION IN THE EMERGENCY DEPARTMENT SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE emergency department; patient satisfaction ID CUSTOMER SATISFACTION; MODEL; COMMUNICATION AB Background: Wait times and patient satisfaction are important administrative metrics in emergency departments (EDs), as they are critical to return patronage, liability, and remuneration. Although several factors have been shown to impact patient satisfaction, little attention has been paid to understanding the psychology of waiting and patient satisfaction. Objective: We utilize concepts that have been applied in other service industries to conceptualize factors that impact patient satisfaction. We focus on wait times, a key factor in patient satisfaction, and describe how these concepts can be applied in research and daily practice. Discussion: Patient satisfaction can be conceptualized as the difference between a patient's perceptions and their expectations. Perception is the psychological process by which an individual understands and interprets sensory information. Changes in the wait experience can decrease the perceived wait times without a change in actual wait times. Other changes such as improved staff interpersonal and communication skills that provide patients with an increased sense of the staff's dedication as well as a greater understanding of their care, can also affect patient perceptions of their care quality. These changes in patient perception can synergize with more expensive investments such as state-of-the-art facilities and increased ED beds to magnify their impact on patient satisfaction. Expectation is the level of service a patient believes they will receive during their ED visit. Patients arrive with expectations around the component of their care such as wait times, needed diagnostic tests, and overall time in the ED. These expectations are affected by individual-specific, pre-encounter, and intra-encounter factors. When these factors are identified and understood, they can be managed during the care process to improve patient satisfaction. Conclusion: Interventions to decrease perception of wait times and increase the perception of service being provided, when combined with management of patient expectations, can improve patient satisfaction. (C) 2011 Elsevier Inc. C1 [Soremekun, Olanrewaju A.; Bohan, Stephen J.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Soremekun, Olanrewaju A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Takayesu, James K.; Bohan, Stephen J.] Harvard Univ, Sch Med, Boston, MA USA. [Takayesu, James K.] Massachusetts Gen Hosp, Dept Emergency Serv, Boston, MA 02114 USA. RP Soremekun, OA (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St,Neville House,Room 236A, Boston, MA 02115 USA. NR 25 TC 21 Z9 21 U1 6 U2 21 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD DEC PY 2011 VL 41 IS 6 BP 686 EP 692 DI 10.1016/j.jemermed.2011.01.018 PG 7 WC Emergency Medicine SC Emergency Medicine GA 869BZ UT WOS:000298572000024 PM 21440402 ER PT J AU Peters, ME Vaidya, V Drye, LT Rosenberg, PB Martin, BK Porsteinsson, AP Frangakis, CE Mintzer, J Weintraub, D Schneider, LS Rabins, PV Munro, CA Meinert, CL Lyketsos, CG Dimitri, A AF Peters, Matthew E. Vaidya, Vijay Drye, Lea T. Rosenberg, Paul B. Martin, Barbara K. Porsteinsson, Anton P. Frangakis, Constantine E. Mintzer, Jacobo Weintraub, Daniel Schneider, Lon S. Rabins, Peter V. Munro, Cynthia A. Meinert, Curtis L. Lyketsos, Constantine G. Dimitri, Avramopoulos CA DIADS-2 Res Grp TI Sertraline for the Treatment of Depression in Alzheimer Disease: Genetic Influences SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Article DE Alzheimer disease; sertraline; depression; randomized trial; dementia; antidepressant ID DOUBLE-BLIND; NEUROPSYCHIATRIC SYMPTOMS; CLINICAL-TRIAL; POLYMORPHISM; DEMENTIA; PREVALENCE; PSYCHOSIS; EFFICACY; CRITERIA AB Objective. To assess the potential for genetic influences on sertraline treatment efficacy for depression of Alzheimer disease (dAD). Four functional genetic variants were studied: 2 serotonin receptors (HTR2A-T102C and HTR2C-Cys23Ser), the serotonin transporter (5HTT-LPR), and brain-derived neurotrophic factor (BDNF-Val66Met). Treatment response by genotype was measured by (1) the modified Alzheimer's Disease Cooperative Study Clinical Global Impression of Change, (2) the Cornell scale for Depression in Dementia, and (3) remission of depression. Methods. We utilized data from the Depression in Alzheimer's Disease Study 2 (DIADS-2), a 24-week, randomized, multicenter trial showing no significant treatment effect of sertraline on dAD. Proportional odds logistic regression and mixed effects models were used to examine the above mentioned outcome measures. Results. No significant interactions were seen between any of the genetic polymorphisms and the selected outcomes above at 12 or 24 weeks. Discussion. Treatment outcomes in the DIADS-2 trial were not significantly influenced by genetic variation at the loci that were assessed. Future studies should continue to examine the interaction of depression-related genetic variants with antidepressant treatment in Alzheimer disease patients with depression. C1 [Peters, Matthew E.; Rosenberg, Paul B.; Rabins, Peter V.; Munro, Cynthia A.; Lyketsos, Constantine G.; Dimitri, Avramopoulos] Johns Hopkins Univ, Baltimore, MD 21224 USA. [Vaidya, Vijay; Drye, Lea T.; Martin, Barbara K.; Frangakis, Constantine E.; Meinert, Curtis L.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Porsteinsson, Anton P.] Univ Rochester, Rochester, NY USA. [Mintzer, Jacobo] Med Univ S Carolina, Charleston, SC 29425 USA. [Mintzer, Jacobo] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Weintraub, Daniel] Univ Penn, Philadelphia, PA 19104 USA. [Schneider, Lon S.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. RP Lyketsos, CG (reprint author), Johns Hopkins Univ, 5300 Alpha Commons Dr, Baltimore, MD 21224 USA. EM kostas@jhmi.edu OI Drye, Lea/0000-0002-2964-1878 FU National Institute of Mental Health [1U01MH066136, 1U01MH068014, 1U01MH066174, 1U01MH066175, 1U01MH066 176, 1U01MH066177]; National Institutes of Health; Michael J. Fox Foundation for Parkinson's Research; Baxter; Bristol-Myers Squibb; Elan Pharmaceuticals; Janssen Alzheimer Initiative; Medivation Inc; Pfizer Inc; Toyama; Eisai Inc; Eli Lilly; Forest Laboratories; Janssen; GlaxoSmithKline; Merck; Mitsubishi; Myriad; Neurochem; Ono Pharma; Wyeth; Alzheimer's Disease Cooperative Study Group [NIA-U01AG10483]; Alzheimer's Disease Neuroimaging Initiative [NIA-U01AG024904]; ADAPT-FS [NIA-U01AG15477]]; CitAD [NIMH-R01AG031348]; DIADS-2 [NIMH-U01MH066177]; NIA; Pfizer; Janssen Alzheimer's Immunotherapy; Genentech; NIMH; Associated Jewish Federation of Baltimore; Weinberg Foundation; Forest; Eisai; Astra-Zeneca; Lilly; Ortho-McNeil; BristolMyers; Novartis; National Football League; Elan FX The authors disclosed receipt of the following financial support for the research, authorship and/or publication of this article: This work was supported by National Institute of Mental Health, 1U01MH066136, 1U01MH068014, 1U01MH066174, 1U01MH066175, 1U01MH066 176, 1U01MH066177. DW has received grants or research funding from National Institutes of Health and the Michael J. Fox Foundation for Parkinson's Research. APP received research support from Baxter, Bristol-Myers Squibb, Elan Pharmaceuticals, Janssen Alzheimer Initiative, Medivation Inc, Pfizer Inc, Toyama, Eisai Inc, Eli Lilly, Forest Laboratories, Janssen, GlaxoSmithKline, Merck, Mitsubishi, Myriad, Neurochem, Ono Pharma, Wyeth, the Alzheimer's Disease Cooperative Study Group (NIA-U01AG10483), Alzheimer's Disease Neuroimaging Initiative NIA-U01AG024904, ADAPT-FS (NIA-U01AG15477], CitAD study (NIMH-R01AG031348), and DIADS-2 study (NIMH-U01MH066177). JM received research support from NIA, Eli Lilly, Pfizer, Janssen Alzheimer's Immunotherapy, and Genentech. CGL received grant support (research or CME) from NIMH, NIA, Associated Jewish Federation of Baltimore, Weinberg Foundation, Forest, GlaxoSmithKline, Eisai, Pfizer, Astra-Zeneca, Lilly, Ortho-McNeil, BristolMyers, Novartis, National Football League, and Elan. NR 34 TC 6 Z9 7 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0891-9887 EI 1552-5708 J9 J GERIATR PSYCH NEUR JI J. Geriatr. Psychiatry Neurol. PD DEC PY 2011 VL 24 IS 4 BP 222 EP 228 DI 10.1177/0891988711422527 PG 7 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 873BJ UT WOS:000298855400007 PM 22228829 ER PT J AU Forrest, GN Arnold, RS Gammie, JS Gilliam, BL AF Forrest, Graeme N. Arnold, Ryan S. Gammie, James S. Gilliam, Bruce L. TI Single center experience of a vancomycin resistant enterococcal endocarditis cohort SO JOURNAL OF INFECTION LA English DT Article DE Vancomycin resistant enterococci; Hemodialysis; Organ transplantation; Endocarditis ID INFECTIVE ENDOCARDITIS; STAPHYLOCOCCUS-AUREUS; RISK-FACTORS; ANTIMICROBIAL THERAPY; BACTEREMIA; FAECALIS; SAFETY; SURVEILLANCE; DAPTOMYCIN; DIAGNOSIS AB Objectives: Vancomycin resistant enterococcus (VRE) infective endocarditis (IE) is an increasing nosocomial problem. We describe the clinical management and outcomes of a cohort of patients with VRE IE at a tertiary endocarditis referral center. Methods: Retrospective review of all proven cases of VRE IE, from July 2000 through January 2008 was performed. Demographics, comorbidities and therapeutic details were collected and analyzed to assess for risk factors and clinical outcomes. Results: Fifty cases of VRE IE were identified: 26 (52%) were Enterococcus faecium and 24 were Enterococcus faecalis. Vancomycin resistant E. faecalis IE was associated with the presence of a central venous line, liver transplantation, and mitral valve infection while VR E. faecium IE was significantly associated with tricuspid valve infection (p = 0.03). The median duration of bacteremia was 14 days for E. faecium and 4 days for E. faecalis, respectively (p = 0.002). Factors associated with mortality on bivariate analysis were hemodialysis via a catheter with VR E. faecium (OR = 11.7. CI 1.1-122, p = 0.02) and liver transplantation with both species. Combination antimicrobial therapy (OR = 0.5 CI = 0.06-3.2, p = 0.1) and valve surgery (OR 1.3 CI 0.8-20, p = 0.02) trended toward improved survival with E. faecalis on bivariate analysis. On multivariate analysis, none of the associations were significant. Conclusions: Hemodialysis and liver transplantation were factors associated with acquisition of VRE IE. There was a higher mortality and prolonged bacteremia with VR E. faecium IE than VR E. faecalis IE. Although not significant, combination antimicrobial therapy and surgical intervention trended toward improved survival. Published by Elsevier Ltd on behalf of The British Infection Association. C1 [Forrest, Graeme N.] Portland VA Med Ctr, Div Infect Dis, Portland, OR 97239 USA. [Arnold, Ryan S.] Univ Maryland, Sch Med, Div Infect Dis, Baltimore, MD 21201 USA. [Gammie, James S.] Univ Maryland, Sch Med, Div Cardiac Surg, Baltimore, MD 21201 USA. [Gilliam, Bruce L.] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA. RP Forrest, GN (reprint author), Portland VA Med Ctr, Div Infect Dis, 3710 SW US Vet Hosp Rd,P3-ID, Portland, OR 97239 USA. EM forrestg@ohsu.edu FU Cubist Pharmaceuticals, Inc. FX Graeme Forrest has received research funding from Cubist Pharmaceuticals, Inc. Bruce Gilliam has been a speaker for Cubist Pharmaceuticals, Inc. NR 26 TC 9 Z9 10 U1 0 U2 1 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0163-4453 J9 J INFECTION JI J. Infect. PD DEC PY 2011 VL 63 IS 6 BP 420 EP 428 DI 10.1016/j.jinf.2011.08.014 PG 9 WC Infectious Diseases SC Infectious Diseases GA 869GP UT WOS:000298586100187 PM 21920382 ER PT J AU Liu, Q Li, Y Yang, GB Dai, JJ Ruprecht, RM Shao, YM AF Liu, Qiang Li, Yue Yang, GuiBo Dai, JieJie Ruprecht, Ruth M. Shao, Yiming TI Molecularly cloned SHIV-CN97001: a replication-competent, R5 simian/human immunodeficiency virus containing env of a primary Chinese HIV-1 clade C isolate SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Article DE clade C; passage; rhesus macaques; SHIV ID T-LYMPHOCYTE DEPLETION; PIG-TAILED MACAQUES; SUBTYPE-E ENVELOPE; CORECEPTOR SWITCH; RHESUS MACAQUES; SHIV CHALLENGE; PERSISTENT INFECTION; SHIV89.6P CHALLENGE; VACCINE PROTECTION; TYPE-1 ISOLATE AB Background The increasing prevalence of human immunodeficiency virus type 1 (HIV-1) subtype C infection worldwide calls for efforts to develop a relevant animal model for evaluating AIDS candidate vaccines. In China, the prevalent HIV strains comprise a circulating recombinant form, BC (CRF07_BC), in which the envelope belongs to subtype C. Methods To evaluate potential AIDS vaccines targeting Chinese viral strains in non-human primate models, we constructed a simian/ human immunodeficiency virus (SHIV) carrying most of the envelope sequence of a primary HIV-1 clade C strain isolated from an HIV-positive intravenous drug user from YunNan province in China. Furthermore, to determine whether in vivo adaptation would enhance the infectivity of SHIVCN97001, the parental infectious strain was serially passaged through eight Chinese rhesus macaques. Results Infection of six Chinese rhesus macaques with SHIV-CN97001 resulted in a low level of viremia and no significant alteration in CD4+ T-lymphocyte counts. However, the hallmarks of SHIV infectivity developed gradually, as shown by the increasingly elevated peak viremia with each passage. Conclusion These findings establish that the R5-tropic SHIV-CN97001/ Chinese rhesus macaque model should be very useful for the evaluation of HIV-1 subtype C vaccines in China. C1 [Liu, Qiang; Yang, GuiBo; Shao, Yiming] Chinese Ctr Dis Control & Prevent, Natl Ctr AIDS STD Control & Prevent, China CDC, Beijing 102206, Peoples R China. [Liu, Qiang] Natl Inst Food & Drug Control, Beijing, Peoples R China. [Li, Yue] Nankai Univ, Coll Life Sci, Tianjin 300071, Peoples R China. [Dai, JieJie] CAMS, Inst Med Biol, Kuming, Peoples R China. [Ruprecht, Ruth M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ruprecht, Ruth M.] Harvard Univ, Sch Med, Boston, MA USA. RP Shao, YM (reprint author), Chinese Ctr Dis Control & Prevent, Natl Ctr AIDS STD Control & Prevent, China CDC, Beijing 102206, Peoples R China. EM yshao@bbn.cn FU Kuming Institute of Medical Biology; Institute of Laboratory Animal Science [SHIV-CN97001]; China Comprehensive Integrated Programs for Research on AIDS (CIPRA) [U19AI51915]; National Institute of Allergy and Infectious Diseases, National Institutes of Health, USA; China Ministry of Science and Technology [2008ZX10001-010] FX We thank Dr. Shan Yi and Dr. Xiaomei Sun from the Kuming Institute of Medical Biology and the Institute of Laboratory Animal Science for providing strong support in SHIV-CN97001 challenge and sample collection. We thank the Kuming Institute of Medical Biology and Institute of Laboratory Animal Science veterinary and clinical staff for providing excellent animal care, Min Li for flow analysis, and Dr. Maosheng Sun for coordination and shipping of samples. This research was supported by the China Comprehensive Integrated Programs for Research on AIDS (CIPRA, U19AI51915), the National Institute of Allergy and Infectious Diseases, National Institutes of Health, USA, the National Mega Projects on Key Infectious Disease Control (2008ZX10001-010) of the China Ministry of Science and Technology. NR 40 TC 5 Z9 6 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD DEC PY 2011 VL 40 IS 6 BP 427 EP 436 DI 10.1111/j.1600-0684.2011.00497.x PG 10 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 860LL UT WOS:000297949700007 PM 21895680 ER PT J AU Harder, LH Chen, S Baker, DG Chow, B McFall, M Saxon, A Smith, MW AF Harder, Laura H. Chen, Shuo Baker, Dewleen G. Chow, Bruce McFall, Miles Saxon, Andrew Smith, Mark W. TI The Influence of Posttraumatic Stress Disorder Numbing and Hyperarousal Symptom Clusters in the Prediction of Physical Health Status in Veterans With Chronic Tobacco Dependence and Posttraumatic Stress Disorder SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE Health-related quality of life; PTSD; numbing; hyperarousal; avoidance; smoking; tobacco; SF-36 ID QUALITY-OF-LIFE; ADMINISTERED PTSD SCALE; WAR VETERANS; PRIMARY-CARE; NICOTINE DEPENDENCE; VIETNAM VETERANS; FEMALE VETERANS; OLDER-ADULTS; SMOKING; RISK AB Smoking and PTSD are predictors of poor physical health status. This study examined the unique contribution of PTSD symptoms in the prediction of the SF-36 physical health status subscales accounting for cigarette smoking, chronic medical conditions, alcohol and drug use disorders, and depression. This study examined baseline interview and self-report data from a national tobacco cessation randomized, controlled trial (Veterans Affairs Cooperative Study 519) that enrolled tobacco-dependent veterans with chronic PTSD (N = 943). A series of blockwise multiple regression analyses indicated that PTSD numbing and hyperarousal symptom clusters explained a significant proportion of the variance across all physical health domains except for the Physical Functioning subscale, which measures impairments in specific physical activities. Our findings further explain the impact of PTSD on health status by exploring the way PTSD symptom clusters predict self-perceptions of health, role limitations, pain, and vitality. C1 [Harder, Laura H.; Baker, Dewleen G.] VA San Diego Healthcare Syst, San Diego, CA 92161 USA. [Chen, Shuo; Smith, Mark W.] Vet Affairs Palo Alto Hlth Care Syst, Hlth Econ Resource Ctr, Menlo Pk, CA USA. [Baker, Dewleen G.] VA San Diego, Vet Affairs Ctr Excellence Stress & Mental Hlth, San Diego, CA USA. [Baker, Dewleen G.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Chow, Bruce] Vet Affairs Palo Alto Hlth Care Syst, Cooperat Studies Program, Mountain View, CA USA. [McFall, Miles; Saxon, Andrew] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [McFall, Miles; Saxon, Andrew] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Smith, Mark W.] Stanford Med Sch, Ctr Primary Care & Outcomes Res, Stanford, CA USA. RP Harder, LH (reprint author), VA San Diego Healthcare Syst, 3350 La Jolla Village Dr 151, San Diego, CA 92161 USA. EM Laura.Harder@va.gov RI Smith, Mark/G-1522-2012; Schueter, nicos/A-3625-2014 OI Smith, Mark/0000-0002-4582-9088; FU Clinical Science Research and Development Service, US Department of Veterans Affairs [519, NCT00118534]; Tobacco-Related Disease Research Program [19DT-0003]; Department of Defense (Navy BUMED) [CDMRP PTO 090738]; DVA [HSRD SDR09-128]; VA Center of Excellence for Stress and Mental Health; VA Merit [821]; NIAAA [1 P20 AA017839-01]; NIDA [5 U10 DA013714-08]; TRA [05-081]; CPS [636F4574119] FX This study was supported by the Cooperative Studies Program of the Clinical Science Research and Development Service, US Department of Veterans Affairs (DVA; CSP #519, NCT00118534). Ms. Harder is supported in part by the Tobacco-Related Disease Research Program 19DT-0003. Dr. Baker receives research support from the Department of Defense (Navy BUMED and CDMRP PTO 090738) and the DVA (HSR&D SDR09-128) and is supported in part by the VA Center of Excellence for Stress and Mental Health. Dr. McFall receives research support from VA Merit #821 and DVA. Dr. Saxon receives research support from NIAAA (1 P20 AA017839-01) and NIDA (5 U10 DA013714-08). Dr. Smith is supported in part by TRA 05-081 and CPS #636F4574119. NR 43 TC 11 Z9 11 U1 3 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD DEC PY 2011 VL 199 IS 12 BP 940 EP 945 DI 10.1097/NMD.0b013e3182392bfb PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 863CD UT WOS:000298139500008 PM 22134452 ER PT J AU Connorton, E Perry, MJ Hemenway, D Miller, M AF Connorton, Ellen Perry, Melissa J. Hemenway, David Miller, Matthew TI Occupational Trauma and Mental Illness-Combat, Peacekeeping, or Relief Work and the National Co-Morbidity Survey Replication SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; HUMANITARIAN AID WORKERS; COMORBIDITY SURVEY; UN PEACEKEEPERS; HEALTH STATUS; VETERANS; EXPOSURE; SUICIDE; PERSONNEL; SYMPTOMS AB Objective: Peacekeepers, relief workers, and military members experience multiple traumas, and trauma is believed to increase risk for psychiatric distress. We examined whether combat and/or peacekeeping or relief work was associated with subsequent mental illness. Methods: Using data from the US National Co-morbidity Survey Replication (n = 2383), we estimated whether combat, peacekeeping, or relief work was associated with increased prevalence of mental illness through bivariate cross-tabulations and multivariate logistic regression. Results: Combat was associated with increased subsequent posttraumatic stress disorder (PTSD) and alcohol or drug issues more than peacekeeping or relief work. Conclusions: Combat, alone or combined with peacekeeping/relief work, appears to be a risk factor for subsequent PTSD and issues with drugs and alcohol. Peacekeeping/relief work without combat does not appear to be associated with these diagnoses. Clinical Significance: We found an association between combat and subsequent PTSD and drug and alcohol issues. Absent combat, peacekeeping, or relief work were not associated with mental illness. Previous diagnoses and trauma exposure may increase potential for subsequent mental health problems. C1 [Connorton, Ellen; Hemenway, David; Miller, Matthew] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02215 USA. [Connorton, Ellen; Hemenway, David; Miller, Matthew] Dana Farber Canc Inst, Boston, MA USA. [Perry, Melissa J.] George Washington Univ, Sch Publ Hlth, Dept Environm & Occupat Hlth, Washington, DC 20052 USA. [Perry, Melissa J.] George Washington Univ, Hlth Serv, Washington, DC 20052 USA. [Perry, Melissa J.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02215 USA. RP Connorton, E (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, 450 Brookline Ave,LW 750, Boston, MA 02215 USA. EM connort@hsph.harvard.edu FU National Institute for Occupational Safety and Health (NIOSH) Educational Research Center, Harvard University [T42 OH008416]; National Institutes of Health (NIH) [R25CA057713]; Harvard Injury Control Research Center (HICRC) FX This research was supported by a National Institute for Occupational Safety and Health (NIOSH) Educational Research Center, Harvard University grant (T42 OH008416); a National Institutes of Health (NIH) Harvard Education Program in Cancer Prevention and Control grant (R25CA057713); and the Harvard Injury Control Research Center (HICRC). NR 30 TC 3 Z9 3 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD DEC PY 2011 VL 53 IS 12 BP 1360 EP 1363 DI 10.1097/JOM.0b013e318234e2ec PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 861DR UT WOS:000297999700007 PM 22173283 ER PT J AU Hansen, L Penko, J Guzman, D Bangsberg, DR Miaskowski, C Kushel, MB AF Hansen, Luke Penko, Joanne Guzman, David Bangsberg, David R. Miaskowski, Christine Kushel, Margot B. TI Aberrant Behaviors With Prescription Opioids and Problem Drug Use History in a Community-Based Cohort of HIV-Infected Individuals SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Pain; substance use disorders; substance misuse; aberrant behavior; opioids; addiction; pseudoaddiction ID CHRONIC NONCANCER PAIN; CLINICAL-PRACTICE GUIDELINE; CHRONIC NONMALIGNANT PAIN; AMBULATORY AIDS PATIENTS; SUBSTANCE-ABUSE; TAKING BEHAVIORS; AMERICAN ACADEMY; NONMEDICAL USE; SAN-FRANCISCO; RISK-FACTORS AB Context. The treatment of pain in patients with substance use disorders creates tensions for clinicians between undertreating pain and enabling opioid analgesic misuse. Objectives. To characterize prevalence and factors associated with aberrant opioid analgesic behaviors in a cohort of HIV-infected individuals who are at high risk for opioid analgesic misuse. Methods. We assessed pain and substance use disorders in a cross-sectional study that enrolled 296 participants from the Research on Access to Care in the Homeless cohort, a community-based sample of indigent HIV-infected adults. We measured aberrant opioid behaviors, defined as major or minor depending on level of risk of harm to patients, using Audio Computer-Assisted Self-Interview technology. Results. Most participants (91.2%) reported pain in the week before interview, with the majority of these experiencing severe pain (53.7%). More than two-thirds (69.2%) of the participants met criteria for a lifetime history of cocaine, amphetamine, or heroin/opioid use disorder as defined by the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition). More than one-third of the sample (37.4%) had a history of aberrant opioid behavior within 90 days of interview. One-fifth (18.5%) had a history of "major" aberrant behaviors. Conclusion. In this high-risk population, severe pain is common and aberrant opioid behaviors are prevalent but not universal. As recommended by American Pain Society and American Academy of Pain Medicine guidelines, when prescribing opioid analgesics, clinicians must consider variation in the severity of aberrant behaviors, particularly aberrant behaviors that may represent undertreatment of pain. J Pain Symptom Manage 2011;42:893-902. (C) 2011 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved. C1 [Hansen, Luke] Northwestern Univ, Div Hosp Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Penko, Joanne; Guzman, David; Kushel, Margot B.] Univ Calif San Francisco, Div Gen Internal Med, San Francisco Gen Hosp, San Francisco, CA 94143 USA. [Bangsberg, David R.] Harvard Univ, Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, Med Sch,Harvard Initiat Global Hlth, Boston, MA USA. [Miaskowski, Christine] Univ Calif San Francisco, Sch Nursing, San Francisco, CA 94143 USA. RP Hansen, L (reprint author), Northwestern Univ, Div Hosp Med, Feinberg Sch Med, 211 E Ontario St,Suite 700, Chicago, IL 60611 USA. EM l-hansen@northwestern.edu FU Robert Wood Johnson Foundation; National Institute on Drug Abuse (NIDA) [R01DA022550]; National Institute of Mental Health (NIMH) [R01MH54907]; National Institutes of Health/National Center for Research Resources University of California San Francisco-Clinical and Translational Science Institute [UL1 RR024131] FX Dr. Hansen was supported by the Robert Wood Johnson Foundation Clinical Scholars Program. Dr. Kushel, Dr. Miaskowski, Dr. Bangsberg, Mr. Guzman, and Ms. Penko received support from the National Institute on Drug Abuse (NIDA R01DA022550); Drs. Kushel and Bangsberg received support from the National Institute of Mental Health (NIMH R01MH54907).; This project was supported by NIDA R01DA022550, NIMH R01MH54907, and National Institutes of Health/National Center for Research Resources University of California San Francisco-Clinical and Translational Science Institute grant number UL1 RR024131. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. NR 60 TC 20 Z9 20 U1 2 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD DEC PY 2011 VL 42 IS 6 BP 893 EP 902 DI 10.1016/j.jpainsymman.2011.02.026 PG 10 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 865WU UT WOS:000298342400011 PM 21802896 ER PT J AU Bekelman, DB Nowels, CT Retrum, JH Allen, LA Shakar, S Hutt, E Heyborne, T Main, DS Kutner, JS AF Bekelman, David B. Nowels, Carolyn T. Retrum, Jessica H. Allen, Larry A. Shakar, Simon Hutt, Evelyn Heyborne, Theresa Main, Deborah S. Kutner, Jean S. TI Giving Voice to Patients' and Family Caregivers' Needs in Chronic Heart Failure: Implications for Palliative Care Programs SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID PHYSICAL IMPAIRMENT; COLLABORATIVE CARE; CHRONIC ILLNESS; DEPRESSION; CANCER; ASSOCIATION; MANAGEMENT; STATEMENT; AMERICAN; SERVICES AB Background: The American College of Cardiology Foundation/American Heart Association (ACC/AHA) Guidelines for the Management of Heart Failure recommend palliative care in the context of Stage D HF or at the end of life. Previous studies related to heart failure (HF) palliative care provide useful information about patients' experiences, but they do not provide concrete guidance for what palliative care needs are most important and how a palliative care program should be structured. Objectives: Describe HF patients' and their family caregivers' major concerns and needs. Explore whether, how, and when palliative care would be useful to them. Design and participants: Qualitative study using in-depth interviews of 33 adult outpatients with symptomatic HF identified using purposive sampling and 20 of their family caregivers. Approach: Interviews were transcribed verbatim and analyzed using the constant comparative method. Key results: Overall, patients and caregivers desired early support adjusting to the limitations and future course of illness, relief of a number of diverse symptoms, and the involvement of family caregivers using a team approach. A diverse group of participants desired these elements of palliative care early in illness, concurrent with their disease-specific care, coordinated by a provider who understood their heart condition and knew them well. Some diverging needs and preferences were found based on health status and age. Conclusions: HF patients and their family caregivers supported early integration of palliative care services, particularly psychosocial support and symptom control, using a collaborative team approach. Future research should test the feasibility and effectiveness of integrating such a program into routine HF care. C1 [Bekelman, David B.; Hutt, Evelyn] Dept Vet Affairs Med Ctr, Res Sect, Denver, CO USA. [Bekelman, David B.; Hutt, Evelyn] Dept Vet Affairs Med Ctr, Genet Sect, Denver, CO USA. [Bekelman, David B.; Nowels, Carolyn T.; Hutt, Evelyn; Kutner, Jean S.] Univ Colorado, Sch Med, Dept Med, Div Gen Internal Med, Aurora, CO USA. [Bekelman, David B.; Allen, Larry A.] Colorado Cardiovasc Outcomes Res, Denver, CO USA. [Retrum, Jessica H.] Univ Colorado, Sch Publ Affairs, Denver, CO 80202 USA. [Allen, Larry A.; Shakar, Simon] Univ Colorado, Sch Med, Dept Med, Div Cariol, Aurora, CO USA. [Main, Deborah S.] Univ Colorado, Dept Hlth & Behav Sci, Denver, CO 80202 USA. RP Bekelman, DB (reprint author), Denver VA Med Ctr, 1055 Clermont St, Denver, CO 80220 USA. EM david.bekelman@va.gov FU University of Colorado Denver Hartford/Jahnigen Center for Excellence in Geriatric Medicine; Mordecai Palliative Care Grants Fund; Department of Veterans Affairs [HSRD CDA 08-022] FX This research was funded by the University of Colorado Denver Hartford/Jahnigen Center for Excellence in Geriatric Medicine and the Mordecai Palliative Care Grants Fund. Dr. Bekelman is funded by a Department of Veterans Affairs Career Development Award (HSR&D CDA 08-022). The funding organizations had no role in any part of the study. We thank Sheldon Gottlieb, MD, for contributing to the title, and Traci Yamashita, MA, for assistance with survey data. The views in this article are those of the authors and do not necessarily reflect the views of the Department of Veterans Affairs. NR 40 TC 34 Z9 34 U1 0 U2 6 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD DEC PY 2011 VL 14 IS 12 BP 1317 EP 1324 DI 10.1089/jpm.2011.0179 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 863EO UT WOS:000298145800010 PM 22107107 ER PT J AU Krimshtein, NS Luhrs, CA Puntillo, KA Cortez, TB Livote, EE Penrod, JD Nelson, JE AF Krimshtein, Nina S. Luhrs, Carol A. Puntillo, Kathleen A. Cortez, Therese B. Livote, Elayne E. Penrod, Joan D. Nelson, Judith E. TI Training Nurses for Interdisciplinary Communication with Families in the Intensive Care Unit: An Intervention SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID OF-LIFE CARE; PALLIATIVE CARE; CRITICALLY-ILL; MORAL DISTRESS; FOLLOW-UP; END; SKILLS; PHYSICIANS; EFFICACY; MEETINGS AB Background: Critical care nurse communication training has largely been limited to didactic materials, interactive training for nurse supervisors, or brief participatory learning programs within the context of comprehensive end-of-life care educational seminars. Preliminary evidence suggests that an interactive approach can also be effective in communication skills training for intensive care unit (ICU) nurses. Methods: We implemented a 1-day educational intervention in five acute care hospitals within Veterans Integrated Service Network (VISN) 3 (New York-New Jersey region) of the Department of Veterans Affairs and focused solely on communication skills and targeted specifically to nurses providing bedside care for critically ill patients. A "learner centered'' approach to skills training that has several integral components was employed. Among these are: a cognitive, evidence-based foundation upon which to build new skills; a method such as role-play that allows participants to practice newly learned skills; and an affective component, during which trainees can freely discuss their impressions of the exercise or explore difficulties that may have been encountered. Before and after the program we conducted a detailed assessment of participants' self-rated communication skills and of the techniques and materials we used. Results and conclusions: Post-program responses documented significant improvement in self-evaluated skills for each of the core tasks we assessed. Evidence suggests that communication with patients and families in the ICU can be most effectively approached in an interdisciplinary way. For nurses to fully realize their potential for optimal communication as members of the multidisciplinary team, they must be equipped with the necessary skills. We believe this new program helps to expand the range of approaches for training nurses in essential communication skills. C1 [Krimshtein, Nina S.; Nelson, Judith E.] Mt Sinai Sch Med, Div Pulm & Crit Care, New York, NY 10029 USA. [Luhrs, Carol A.; Cortez, Therese B.] New York Harbor Healthcare Syst, Dept Vet Affairs, Brooklyn, NY USA. [Puntillo, Kathleen A.] Univ Calif San Francisco, Dept Physiol Nursing, San Francisco, CA USA. [Livote, Elayne E.; Penrod, Joan D.] James J Peters VA Med Ctr, Bronx, NY USA. RP Nelson, JE (reprint author), Mt Sinai Sch Med, Div Pulm & Crit Care, 1 Gustave Levy Pl, New York, NY 10029 USA. EM judith.nelson@mountsinai.org FU Veterans Integrated Service Network (VISN); Center for the Study of Health Care Across Systems and Sites of Care at the James J. Peters VA Medical Center, Bronx, New York; National Institute on Aging [AG04234] FX This project was supported by the Veterans Integrated Service Network (VISN) 3 Palliative Care Program and by the Center for the Study of Health Care Across Systems and Sites of Care at the James J. Peters VA Medical Center, Bronx, New York. Additional organizational support for the program was provided by nursing leadership within the hospitals participating in the program. Dr. Nelson is the recipient of a K07 Academic Career Leadership Award (AG04234) from the National Institute on Aging. NR 41 TC 30 Z9 30 U1 5 U2 17 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD DEC PY 2011 VL 14 IS 12 BP 1325 EP 1332 DI 10.1089/jpm.2011.0225 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 863EO UT WOS:000298145800011 PM 22132740 ER PT J AU Stone, SC Mohanty, S Grudzen, CR Shoenberger, J Asch, S Kubricek, K Lorenz, KA AF Stone, Susan C. Mohanty, Sarita Grudzen, Corita R. Shoenberger, Jan Asch, Steve Kubricek, Katrina Lorenz, Karl A. TI Emergency Medicine Physicians' Perspectives of Providing Palliative Care in an Emergency Department SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID CONTROLLED-TRIAL; OF-LIFE; CONSULTATION; COST AB This study describes emergency physicians' perspectives on the challenges and benefits to providing palliative care in an academic, urban, public hospital in Los Angeles. Participants underwent a semi-structured interview on their training and experiences related to palliative care, perceptions of providing palliative care, and their recommendations for education and training in this area. Overall, respondents felt that palliative care is not prioritized appropriately, leading patients to be unaware of their options for end-of-life care. Providing educational materials and courses that have been developed from the ED perspective should be included in ongoing continuing medical education. Having a palliative care team that is responsive to the needs of the ED will further enhance collaboration with the ED. Future research should focus on understanding the range of benefits to having palliative care in the ED. C1 [Stone, Susan C.] Univ Calif Los Angeles, Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Lorenz, Karl A.] Univ Calif Los Angeles, W Los Angeles VA, Los Angeles, CA 90048 USA. [Shoenberger, Jan] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Grudzen, Corita R.] Mt Sinai Sch Med, New York, NY USA. [Asch, Steve] Stanford Univ, Sch Med, Palo Alto VA, Stanford, CA 94305 USA. [Kubricek, Katrina] Childrens Hosp Los Angeles, Los Angeles, CA USA. RP Stone, SC (reprint author), Univ Calif Los Angeles, Cedars Sinai Med Ctr, 8700 Beverly Blvd, Los Angeles, CA 90048 USA. EM sstone.90064@yahoo.com OI Grudzen, Corita/0000-0003-3039-8497 FU Archstone Foundation FX This study was funded by the Archstone Foundation. NR 15 TC 19 Z9 19 U1 1 U2 4 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD DEC PY 2011 VL 14 IS 12 BP 1333 EP 1338 DI 10.1089/jpm.2011.0106 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 863EO UT WOS:000298145800012 PM 22136262 ER PT J AU Moore, MS AF Moore, Mary S. TI Re: A Simple Thank You SO JOURNAL OF PERIANESTHESIA NURSING LA English DT Letter C1 S Texas Vet Healthcare Syst, San Antonio, TX USA. RP Moore, MS (reprint author), S Texas Vet Healthcare Syst, San Antonio, TX USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1089-9472 J9 J PERIANESTH NURS JI J. PeriAnesthesia Nurs. PD DEC PY 2011 VL 26 IS 6 BP 370 EP 370 DI 10.1016/j.jopan.2011.09.010 PG 1 WC Nursing SC Nursing GA 864WM UT WOS:000298271200002 PM 22099126 ER PT J AU Mikuls, TR LeVan, TD Sayles, H Yu, F Caplan, L Cannon, GW Kerr, GS Reimold, AM Johnson, DS Thiele, GM AF Mikuls, Ted R. LeVan, Tricia D. Sayles, Harlan Yu, Fang Caplan, Liron Cannon, Grant W. Kerr, Gail S. Reimold, Andreas M. Johnson, Dannette S. Thiele, Geoffrey M. TI Soluble CD14 and CD14 Polymorphisms in Rheumatoid Arthritis SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE SOLUBLE CD14; RHEUMATOID ARTHRITIS; ACUTE-PHASE RESPONSE; DISEASE SEVERITY; DISEASE ACTIVITY; POLYMORPHISMS ID SINGLE-NUCLEOTIDE POLYMORPHISMS; DISEASE-ACTIVITY; LIPOPOLYSACCHARIDE; ASSOCIATION; PERIODONTITIS; PROTEIN; PLASMA; LPS; VALIDATION; ACTIVATION AB Objective. Soluble CD14 (sCD14) is involved in innate immune responses and has been implicated to play a pathogenic role in inflammatory diseases including rheumatoid arthritis (RA). No studies have identified the specific factors that influence sCD14 expression in RA. We used cross-sectional data to evaluate the relationship of sCD14 concentrations in RA with measures of disease activity and severity. We hypothesized that sCD14 concentrations would be elevated in subjects with greater RA disease severity and markers of disease activity, compared to subjects with lower disease activity. We also examined whether well-defined polymorphisms in CD14 are associated with sCD14 expression in RA. Methods. Soluble CD14 concentrations were measured using banked serum from patients with RA (n = 1270) and controls (n = 186). Associations of patient factors including demographics, measures of RA disease activity/severity, and select CD14 single-nucleotide polymorphisms (SNP) with sCD14 concentration were examined in patients with RA using ordinal logistic regression. Results. Circulating concentrations of sCD14 were higher in patients with RA compared to controls (p < 0.0001). Factors significantly and independently associated with higher sCD14 levels in patients with RA included older age, being white (vs African American), lower body mass index, elevated high sensitivity C-reactive protein, and higher levels of disease activity based on the Disease Activity Score (DAS28). There were no significant associations of CD14 tagging SNP with sCD14 level in either univariate or multivariable analyses. Conclusion. Circulating levels of sCD14 are increased in RA and are highest in patients with increased levels of RA disease activity. In the context of RA, sCD14 concentrations also appear to be strongly influenced by specific patient factors including older age and race but not by genetic variation in CD14. (First Release Sept 15 2011; J Rheumatol 2011;38:2509-16; doi:10.3899/jrheum.110378) C1 [Mikuls, Ted R.] Omaha VA Med Ctr, Dept Med, Div Rheumatol & Immunol, Omaha, NE USA. [LeVan, Tricia D.] Omaha VA Med Ctr, Dept Epidemiol, Omaha, NE USA. [Sayles, Harlan] Omaha VA Med Ctr, Dept Biostat, Omaha, NE USA. [Caplan, Liron] Denver VAMC, Denver, CO USA. [Caplan, Liron] Univ Colorado, Boulder, CO 80309 USA. [Cannon, Grant W.] Salt Lake City VAMC, Salt Lake City, UT USA. [Kerr, Gail S.] VAMC, Georgetown, Guyana. [Kerr, Gail S.] Howard Univ Hosp, Washington, DC 20059 USA. [Reimold, Andreas M.] Dallas VAMC, Dallas, TX USA. [Reimold, Andreas M.] Univ Texas SW Med Ctr, Dallas, TX USA. [Johnson, Dannette S.] Sonny Montgomery VAMC, Montgomery, AL USA. RP Mikuls, TR (reprint author), Omaha VA Med Ctr, Dept Med, Div Rheumatol & Immunol, Omaha, NE USA. EM tmikuls@unmc.edu RI Yu, Fang/B-9874-2013; OI Thiele, Geoffrey/0000-0001-5688-8596 FU VA CSRD; VA HSRD Program FX Supported by a Merit Grant from VA CSR&D. The Veterans Affairs Rheumatoid Arthritis registry has received research support from the VA HSR&D Program. NR 47 TC 10 Z9 10 U1 0 U2 2 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD DEC PY 2011 VL 38 IS 12 BP 2509 EP 2516 DI 10.3899/jrheum.110378 PG 8 WC Rheumatology SC Rheumatology GA 868NU UT WOS:000298530800004 PM 21921097 ER PT J AU Liu, HY Potter, MP Woodworth, KY Yorks, DM Petty, CR Wozniak, JR Biederman, J Faraone, SV AF Liu, Howard Y. Potter, Mona P. Woodworth, K. Yvonne Yorks, Dayna M. Petty, Carter R. Wozniak, Janet R. Biederman, Joseph Faraone, Stephen V. TI Pharmacologic Treatments for Pediatric Bipolar Disorder reply SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Letter C1 [Liu, Howard Y.] Univ Nebraska Med Ctr, Omaha, NE USA. [Potter, Mona P.] McLean Hosp, Belmont, MA 02178 USA. [Woodworth, K. Yvonne; Yorks, Dayna M.; Petty, Carter R.; Wozniak, Janet R.; Biederman, Joseph] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Syracuse, NY USA. RP Liu, HY (reprint author), Univ Nebraska Med Ctr, Omaha, NE USA. EM jbiederman@partners.org NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD DEC PY 2011 VL 50 IS 12 BP 1290 EP 1291 DI 10.1016/j.jaac.2011.09.001 PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 857KA UT WOS:000297716200013 ER PT J AU Hillis, LD Smith, PK Anderson, JL Bittl, JA Bridges, CR Byrne, JG Cigarroa, JE DiSesa, VJ Hiratzka, LF Hutter, AM Jessen, ME Keeley, EC Lahey, SJ Lange, RA London, MJ Mack, MJ Patel, MR Puskas, JD Sabik, JF Selnes, O Shahian, DM Trost, JC Winniford, MD AF Hillis, L. David Smith, Peter K. Anderson, Jeffrey L. Bittl, John A. Bridges, Charles R. Byrne, John G. Cigarroa, Joaquin E. DiSesa, Verdi J. Hiratzka, Loren F. Hutter, Adolph M., Jr. Jessen, Michael E. Keeley, Ellen C. Lahey, Stephen J. Lange, Richard A. London, Martin J. Mack, Michael J. Patel, Manesh R. Puskas, John D. Sabik, Joseph F. Selnes, Ola Shahian, David M. Trost, Jeffrey C. Winniford, Michael D. TI 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery: Executive Summary A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the American Association for Thoracic Surgery, Society of Cardiovascular Anesthesiologists, and Society of Thoracic Surgeons SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE ACCF/AHA Practice Guidelines; acute coronary syndromes; anticoagulants; antiplatelet agents; arrhythmias, cardiac; coronary angiography; coronary artery revascularization interventions: stents; drug therapy; heart diseases; myocardial revasularization; platelet aggregation inhibitor; ultrasound ID ACUTE MYOCARDIAL-INFARCTION; LONG-TERM SURVIVAL; RANDOMIZED-CONTROLLED-TRIAL; VACUUM-ASSISTED CLOSURE; ACUTE-RENAL-FAILURE; HIGH-RISK PATIENTS; LEFT-VENTRICULAR DYSFUNCTION; PREOPERATIVE STATIN THERAPY; DRUG-ELUTING STENTS; TRANSMYOCARDIAL LASER REVASCULARIZATION AB The medical profession should play a central role in evaluating the evidence related to drugs, devices, and procedures for the detection, management, and prevention of disease. When properly applied, expert analysis of available data on the benefits and risks of these therapies and procedures can improve the quality of care, optimize patient outcomes, and favorably affect costs by focusing resources on the most effective strategies. An organized and directed approach to a thorough review of evidence has resulted in the production of clinical practice guidelines that assist physicians in selecting the best management strategy for an individual patient. Moreover, clinical practice guidelines can provide a foundation for other applications, such as performance measures, appropriate use criteria, and both quality improvement and clinical decision support tools. The American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA) have jointly produced guidelines in the area of cardiovascular disease since 1980. The ACCF/AHA Task Force on Practice Guidelines (Task Force), charged with developing, updating, and revising practice guidelines for cardiovascular diseases and procedures, directs and oversees this effort. Writing committees are charged with regularly reviewing and evaluating all available evidence to develop balanced, patient-centric recommendations for clinical practice. Experts in the subject under consideration are selected by the ACCF and AHA to examine subject-specific data and write guidelines in partnership with representatives from other medical organizations and specialty groups. Writing committees are asked to perform a formal literature review; weigh the strength of evidence for or against particular tests, treatments, or procedures; and include estimates of expected outcomes where such data exist. Patient-specific modifiers, comorbidities, and issues of patient preference that may influence the choice of tests or therapies are considered. When available, information from studies on cost is considered, but data on efficacy and outcomes constitute the primary basis for the recommendations contained herein. In analyzing the data and developing recommendations and supporting text, the writing committee uses evidence-based methodologies developed by the Task Force (1). The Class of Recommendation (COR) is an estimate of the size of the treatment effect considering risks versus benefits in addition to evidence and/or agreement that a given treatment or procedure is or is not useful/effective or in some situations may cause harm. The Level of Evidence (LOE) is an estimate of the certainty or precision of the treatment effect. The writing committee reviews and ranks evidence supporting each recommendation with the weight of evidence ranked as LOE A, B, or C according to specific definitions that are included in Table 1. Studies are identified as observational, retrospective, prospective, or randomized where appropriate. For certain conditions for which inadequate data are available, recommendations are based on expert consensus and clinical experience and are ranked as LOE C. When recommendations at LOE C are supported by historical clinical data, appropriate references (including clinical reviews) are cited if available. For issues for which sparse data are available, a survey of current practice among the clinicians on the writing committee is the basis for LOE C recommendations, and no references are cited. The schema for COR and LOE is summarized in Table 1, which also provides suggested phrases for writing recommendations within each COR. A new addition to this methodology is separation of the Class III recommendations to delineate if the recommendation is determined to be of "no benefit" or is associated with "harm" to the patient. In addition, in view of the increasing number of comparative effectiveness studies, comparator verbs and suggested phrases for writing recommendations for the comparative effectiveness of one treatment or strategy versus another have been added for COR I and IIa, LOE A or B only. In view of the advances in medical therapy across the spectrum of cardiovascular diseases, the Task Force has designated the term guideline-directed medical therapy (GDMT) to represent optimal medical therapy as defined by ACCF/AHA guideline-recommended therapies (primarily Class I). This new term, GDMT, will be used herein and throughout all future guidelines. Because the ACCF/AHA practice guidelines address patient populations (and healthcare providers) residing in North America, drugs that are not currently available in North America are discussed in the text without a specific COR. For studies performed in large numbers of subjects outside North America, each writing committee reviews the potential influence of different practice patterns and patient populations on the treatment effect and relevance to the ACCF/AHA target population to determine whether the findings should inform a specific recommendation. The ACCF/AHA practice guidelines are intended to assist healthcare providers in clinical decision making by describing a range of generally acceptable approaches to the diagnosis, management, and prevention of specific diseases or conditions. The guidelines attempt to define practices that meet the needs of most patients in most circumstances. The ultimate judgment regarding the care of a particular patient must be made by the healthcare provider and patient in light of all the circumstances presented by that patient. As a result, situations may arise for which deviations from these guidelines may be appropriate. Clinical decision making should involve consideration of the quality and availability of expertise in the area where care is provided. When these guidelines are used as the basis for regulatory or payer decisions, the goal should be improvement in quality of care. The Task Force recognizes that situations arise in which additional data are needed to inform patient care more effectively; these areas will be identified within each respective guideline when appropriate. Prescribed courses of treatment in accordance with these recommendations are effective only if followed. Because lack of patient understanding and adherence may adversely affect outcomes, physicians and other healthcare providers should make every effort to engage the patient's active participation in prescribed medical regimens and lifestyles. In addition, patients should be informed of the risks, benefits, and alternatives to a particular treatment and be involved in shared decision making whenever feasible, particularly for COR IIa and IIb, where the benefit-to-risk ratio may be lower. The Task Force makes every effort to avoid actual, potential, or perceived conflicts of interest that may arise as a result of industry relationships or personal interests among the members of the writing committee. All writing committee members and peer reviewers of the guideline are required to disclose all such current relationships, as well as those existing 12 months previously. In December 2009, the ACCF and AHA implemented a new policy for relationships with industry and other entities (RWI) that requires the writing committee chair plus a minimum of 50% of the writing committee to have no relevant RWI (Appendix 1 for the ACCF/AHA definition of relevance). These statements are reviewed by the Task Force and all members during each conference call and meeting of the writing committee and are updated as changes occur. All guideline recommendations require a confidential vote by the writing committee [GRAPHICS] and must be approved by a consensus of the voting members. Members are not permitted to write, and must rescue themselves from voting on, any recommendation or section to which their RWI apply. Members who recused themselves from voting are indicated in the list of writing committee members, and section recusals are noted in Appendix 1. Authors' and peer reviewers' RWI pertinent to this guideline are disclosed in Appendixes 1 and 2, respectively. Additionally, to ensure complete transparency, writing committee members' comprehensive disclosure information-including RWI not pertinent to this document-is available as an online supplement. Comprehensive disclosure information for the Task Force is also available online at www. cardiosource. org/ACC/About-ACC/Leadership/Guidelines-and-Documents-Task-Forces.aspx. The work of the writing committee was supported exclusively by the ACCF and AHA without commercial support. Writing committee members volunteered their time for this activity. In an effort to maintain relevance at the point of care for practicing physicians, the Task Force continues to oversee an ongoing process improvement initiative. As a result, in response to pilot projects, evidence tables (with references linked to abstracts in PubMed) have been added. In April 2011, the Institute of Medicine released 2 reports: Finding What Works in Health Care: Standards for Systematic Reviews and Clinical Practice Guidelines We Can Trust (2,3). It is noteworthy that the ACCF/AHA guidelines are cited as being compliant with many of the proposed standards. A thorough review of these reports and of our current methodology is under way, with further enhancements anticipated. The recommendations in this guideline are considered current until they are superseded by a focused update or the full-text guideline is revised. Guidelines are official policy of both the ACCF and AHA. C1 [Hillis, L. David; Lange, Richard A.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Smith, Peter K.; Patel, Manesh R.] Duke Univ, Med Ctr, Durham, NC 27706 USA. [Bridges, Charles R.] Univ Penn, Med Ctr, Philadelphia, PA 19104 USA. [Byrne, John G.] Vanderbilt Univ, Med Ctr, Div Cardiac Surg, Nashville, TN USA. [Cigarroa, Joaquin E.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [DiSesa, Verdi J.] Johns Hopkins Univ Hosp, Div Cardiac Surg, Baltimore, MD 21287 USA. [Hutter, Adolph M., Jr.; Shahian, David M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Keeley, Ellen C.] Univ Virginia, Charlottesville, VA 22903 USA. [Lahey, Stephen J.] Univ Connecticut, Storrs, CT USA. [London, Martin J.] Univ Calif San Francisco, Vet Affairs Med Ctr, San Francisco, CA 94143 USA. [Puskas, John D.] Emory Univ Emory Healthcare, Atlanta, GA USA. [Sabik, Joseph F.] Cleveland Clin Fdn, Cleveland, OH USA. [Selnes, Ola] Johns Hopkins Univ Hosp, Dept Neurol, Baltimore, MD 21287 USA. [Winniford, Michael D.] Univ Mississippi, Med Ctr, University, MS 38677 USA. RP Hillis, LD (reprint author), Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. NR 493 TC 19 Z9 24 U1 2 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD DEC PY 2011 VL 58 IS 24 BP 2584 EP 2614 DI 10.1016/j.jacc.2011.08.008 PG 31 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 862ZJ UT WOS:000298132300025 ER PT J AU Hillis, LD Smith, PK Anderson, JL Bittl, JA Bridges, CR Byrne, JG Cigarroa, JE DiSesa, VJ Hiratzka, LF Hutter, AM Jessen, ME Keeley, EC Lahey, SJ Lange, RA London, MJ Mack, MJ Patel, MR Puskas, JD Sabik, JF Selnes, O Shahian, DM Trost, JC Winniford, MD AF Hillis, L. David Smith, Peter K. Anderson, Jeffrey L. Bittl, John A. Bridges, Charles R. Byrne, John G. Cigarroa, Joaquin E. DiSesa, Verdi J. Hiratzka, Loren F. Hutter, Adolph M., Jr. Jessen, Michael E. Keeley, Ellen C. Lahey, Stephen J. Lange, Richard A. London, Martin J. Mack, Michael J. Patel, Manesh R. Puskas, John D. Sabik, Joseph F. Selnes, Ola Shahian, David M. Trost, Jeffrey C. Winniford, Michael D. TI 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the American Association for Thoracic Surgery, Society of Cardiovascular Anesthesiologists, and Society of Thoracic Surgeons SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE ACCF/AHA Practice Guidelines; acute coronary syndromes; anticoagulants; antiplatelet agents; arrhythmias, cardiac; coronary angiography; coronary artery revascularization interventions: stents; drug therapy; heart diseases; myocardial revasularization; platelet aggregation inhibitor; ultrasound ID ACUTE MYOCARDIAL-INFARCTION; INTERNAL-MAMMARY-ARTERY; LONG-TERM SURVIVAL; RANDOMIZED-CONTROLLED-TRIAL; HIGH-RISK PATIENTS; ACUTE-RENAL-FAILURE; DRUG-ELUTING STENTS; NEW-YORK-STATE; STERNAL WOUND-INFECTION; ST-SEGMENT ELEVATION AB The medical profession should play a central role in evaluating the evidence related to drugs, devices, and procedures for the detection, management, and prevention of disease. When properly applied, expert analysis of available data on the benefits and risks of these therapies and procedures can improve the quality of care, optimize patient outcomes, and favorably affect costs by focusing resources on the most effective strategies. An organized and directed approach to a thorough review of evidence has resulted in the production of clinical practice guidelines that assist physicians in selecting the best management strategy for an individual patient. Moreover, clinical practice guidelines can provide a foundation for other applications, such as performance measures, appropriate use criteria, and both quality improvement and clinical decision support tools. The American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA) have jointly produced guidelines in the area of cardiovascular disease since 1980. The ACCF/AHA Task Force on Practice Guidelines (Task Force), charged with developing, updating, and revising practice guidelines for cardiovascular diseases and procedures, directs and oversees this effort. Writing committees are charged with regularly reviewing and evaluating all available evidence to develop balanced, patient-centric recommendations for clinical practice. Experts in the subject under consideration are selected by the ACCF and AHA to examine subject-specific data and write guidelines in partnership with representatives from other medical organizations and specialty groups. Writing committees are asked to perform a formal literature review; weigh the strength of evidence for or against particular tests, treatments, or procedures; and include estimates of expected outcomes where such data exist. Patient-specific modifiers, comorbidities, and issues of patient preference that may influence the choice of tests or therapies are considered. When available, information from studies on cost is considered, but data on efficacy and outcomes constitute the primary basis for the recommendations contained herein. In analyzing the data and developing recommendations and supporting text, the writing committee uses evidence-based methodologies developed by the Task Force (1). The Class of Recommendation (COR) is an estimate of the size of the treatment effect considering risks versus benefits in addition to evidence and/or agreement that a given treatment or procedure is or is not useful/effective or in some situations may cause harm. The Level of Evidence (LOE) is an estimate of the certainty or precision of the treatment effect. The writing committee reviews and ranks evidence supporting each recommendation with the weight of evidence ranked as LOE A, B, or C according to specific definitions that are included in Table 1. Studies are identified as observational, retrospective, prospective, or randomized where appropriate. For certain conditions for which inadequate data are available, recommendations are based on expert consensus and clinical experience and are ranked as LOE C. When recommendations at LOE C are supported by historical clinical data, appropriate references (including clinical reviews) are cited if available. For issues for which sparse data are available, a survey of current [GRAPHICS] practice among the clinicians on the writing committee is the basis for LOE C recommendations, and no references are cited. The schema for COR and LOE is summarized in Table 1, which also provides suggested phrases for writing recommendations within each COR. A new addition to this methodology is separation of the Class III recommendations to delineate if the recommendation is determined to be of "no benefit" or is associated with "harm" to the patient. In addition, in view of the increasing number of comparative effectiveness studies, comparator verbs and suggested phrases for writing recommendations for the comparative effectiveness of one treatment or strategy versus another have been added for COR I and IIa, LOE A or B only. In view of the advances in medical therapy across the spectrum of cardiovascular diseases, the Task Force has designated the term guideline-directed medical therapy (GDMT) to represent optimal medical therapy as defined by ACCF/AHA guideline-recommended therapies (primarily Class I). This new term, GDMT, will be used herein and throughout all future guidelines. Because the ACCF/AHA practice guidelines address patient populations (and healthcare providers) residing in North America, drugs that are not currently available in North America are discussed in the text without a specific COR. For studies performed in large numbers of subjects outside North America, each writing committee reviews the potential influence of different practice patterns and patient populations on the treatment effect and relevance to the ACCF/AHA target population to determine whether the findings should inform a specific recommendation. The ACCF/AHA practice guidelines are intended to assist healthcare providers in clinical decision making by describing a range of generally acceptable approaches to the diagnosis, management, and prevention of specific diseases or conditions. The guidelines attempt to define practices that meet the needs of most patients in most circumstances. The ultimate judgment regarding the care of a particular patient must be made by the healthcare provider and patient in light of all the circumstances presented by that patient. As a result, situations may arise for which deviations from these guidelines may be appropriate. Clinical decision making should involve consideration of the quality and availability of expertise in the area where care is provided. When these guidelines are used as the basis for regulatory or payer decisions, the goal should be improvement in quality of care. The Task Force recognizes that situations arise in which additional data are needed to inform patient care more effectively; these areas will be identified within each respective guideline when appropriate. Prescribed courses of treatment in accordance with these recommendations are effective only if followed. Because lack of patient understanding and adherence may adversely affect outcomes, physicians and other healthcare providers should make every effort to engage the patient's active participation in prescribed medical regimens and lifestyles. In addition, patients should be informed of the risks, benefits, and alternatives to a particular treatment and be involved in shared decision making whenever feasible, particularly for COR IIa and IIb, where the benefit-to-risk ratio may be lower. The Task Force makes every effort to avoid actual, potential, or perceived conflicts of interest that may arise as a result of industry relationships or personal interests among the members of the writing committee. All writing committee members and peer reviewers of the guideline are required to disclose all such current relationships, as well as those existing 12 months previously. In December 2009, the ACCF and AHA implemented a new policy for relationships with industry and other entities (RWI) that requires the writing committee chair plus a minimum of 50% of the writing committee to have no relevant RWI (Appendix 1 for the ACCF/AHA definition of relevance). These statements are reviewed by the Task Force and all members during each conference call and meeting of the writing committee and are updated as changes occur. All guideline recommendations require a confidential vote by the writing committee and must be approved by a consensus of the voting members. Members are not permitted to write, and must recuse themselves from voting on, any recommendation or section to which their RWI apply. Members who recused themselves from voting are indicated in the list of writing committee members, and section recusals are noted in Appendix 1. Authors' and peer reviewers' RWI pertinent to this guideline are disclosed in Appendixes 1 and 2, respectively. Additionally, to ensure complete transparency, writing committee members' comprehensive disclosure information-including RWI not pertinent to this document-is available as an online supplement. Comprehensive disclosure information for the Task Force is also available online at www.cardiosource.org/ACC/About-ACC/Leadership/Guidelinesand-Documents-Task-Forces.aspx. The work of the writing committee was supported exclusively by the ACCF and AHA without commercial support. Writing committee members volunteered their time for this activity. In an effort to maintain relevance at the point of care for practicing physicians, the Task Force continues to oversee an ongoing process improvement initiative. As a result, in response to pilot projects, evidence tables (with references linked to abstracts in PubMed) have been added. In April 2011, the Institute of Medicine released 2 reports: Finding What Works in Health Care: Standards for Systematic Reviews and Clinical Practice Guidelines We Can Trust (2,3). It is noteworthy that the ACCF/AHA guidelines are cited as being compliant with many of the proposed standards. A thorough review of these reports and of our current methodology is under way, with further enhancements anticipated. The recommendations in this guideline are considered current until they are superseded by a focused update or the full-text guideline is revised. Guidelines are official policy of both the ACCF and AHA. C1 [Hillis, L. David; Lange, Richard A.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Smith, Peter K.] Duke Univ, Med Ctr, Private Diagnost Clin, Durham, NC 27706 USA. [Bridges, Charles R.] Univ Penn, Med Ctr, Philadelphia, PA 19104 USA. [Byrne, John G.] Vanderbilt Univ, Med Ctr, Div Cardiac Surg, Nashville, TN 37203 USA. [Cigarroa, Joaquin E.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [DiSesa, Verdi J.] Johns Hopkins Univ Hosp, Div Cardiac Surg, Baltimore, MD 21287 USA. [Hutter, Adolph M., Jr.; Shahian, David M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jessen, Michael E.] UT SW Med Ctr, Dallas, TX 75390 USA. [Keeley, Ellen C.] Univ Virginia, Charlottesville, VA 22903 USA. [Lahey, Stephen J.] Univ Connecticut, Storrs, CT 06269 USA. [London, Martin J.] Univ Calif San Francisco, Vet Affairs Med Ctr, San Francisco, CA 94143 USA. [Puskas, John D.] Emory Univ, Atlanta, GA 30322 USA. [Sabik, Joseph F.] Cleveland Clin Fdn, Cleveland, OH USA. [Selnes, Ola] Johns Hopkins Univ Hosp, Dept Neurol, Baltimore, MD 21287 USA. [Winniford, Michael D.] Univ Mississippi, Med Ctr, University, MS 38677 USA. RP Hillis, LD (reprint author), Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. NR 1259 TC 171 Z9 184 U1 8 U2 41 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD DEC PY 2011 VL 58 IS 24 BP E123 EP E210 DI 10.1016/j.jacc.2011.08.009 PG 88 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 862ZJ UT WOS:000298132300003 ER PT J AU Field, TS Bosco, JLF Prout, MN Gold, HT Cutrona, S Pawloski, PA Yood, MU Quinn, VP Thwin, SS Silliman, RA AF Field, Terry S. Bosco, Jaclyn L. F. Prout, Marianne N. Gold, Heather T. Cutrona, Sarah Pawloski, Pamala A. Yood, Marianne Ulcickas Quinn, Virginia P. Thwin, Soe Soe Silliman, Rebecca A. TI Age, Comorbidity, and Breast Cancer Severity: Impact on Receipt of Definitive Local Therapy and Rate of Recurrence among Older Women with Early-Stage Breast Cancer SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID CONSERVING SURGERY; RADIATION-THERAPY; RANDOMIZED-TRIAL; ADJUVANT RADIOTHERAPY; FOLLOW-UP; CONSERVATION THERAPY; ELDERLY-WOMEN; CARCINOMA; MASTECTOMY; MORBIDITY AB BACKGROUND: The definitive local therapy options for early-stage breast cancer are mastectomy and breast-conserving surgery followed by radiation therapy. Older women and those with comorbidities frequently receive breast-conserving surgery alone. The interaction of age and comorbidity with breast cancer severity and their impact on receipt of definitive therapy have not been well-studied. STUDY DESIGN: In a cohort of 1,837 women aged 65 years and older receiving treatment for early-stage breast cancer in 6 integrated health care delivery systems in 1990-1994 and followed for 10 years, we examined predictors of receiving nondefinitive local therapy and assessed the impact on breast cancer recurrence within levels of severity, defined as level of risk for recurrence. RESULTS: Age and comorbidity were associated with receipt of nondefinitive therapy. Compared with those at low risk, women at the highest risk were less likely to receive nondefinitive therapy (odds ratio = 0.32; 95% CI, 0.22-0.47), and women at moderate risk were about half as likely (odds ratio = 0.54; 95% CI, 0.35-0.84). Nondefinitive local therapy was associated with higher rates of recurrence among women at moderate (hazard ratio = 5.1; 95% CI, 1.9-13.5) and low risk (hazard ratio = 3.2; 95% CI, 1.1-8.9). The association among women at high risk was weak (hazard ratio = 1.3; 95% CI, 0.75-2.1). CONCLUSIONS: Among these older women with early-stage breast cancer, decisions about therapy partially balanced breast cancer severity against age and comorbidity. However, even among women at low risk, omitting definitive local therapy was associated with increased recurrence. (J Am Coll Surg 2011;213:757-765. (C) 2011 by the American College of Surgeons) C1 [Field, Terry S.; Cutrona, Sarah] Meyers Primary Care Inst, Worcester, MA 01605 USA. [Bosco, Jaclyn L. F.; Silliman, Rebecca A.] Boston Univ, Med Ctr, Sect Geriatr, Boston, MA USA. [Prout, Marianne N.; Yood, Marianne Ulcickas] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Gold, Heather T.] Weill Cornell Med Coll, Dept Publ Hlth, New York, NY USA. [Pawloski, Pamala A.] HealthPartners Res Fdn, Minneapolis, MN USA. [Quinn, Virginia P.] Kaiser Permanente So Calif, Res & Evaluat, Pasadena, CA USA. [Thwin, Soe Soe] VA Boston Healthcare Syst, Brockton, MA USA. RP Field, TS (reprint author), Meyers Primary Care Inst, 630 Plantat St, Worcester, MA 01605 USA. EM Terry.Field@umassmed.edu OI Prout, Marianne/0000-0001-8747-6199; Ulcickas Yood, Marianne/0000-0003-4204-0871 FU National Cancer Institute [R01 CA093772] FX Funded by the National Cancer Institute (R01 CA093772, R Silliman, principal investigator). NR 58 TC 19 Z9 19 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD DEC PY 2011 VL 213 IS 6 BP 757 EP 765 DI 10.1016/j.jamcollsurg.2011.09.010 PG 9 WC Surgery SC Surgery GA 861FD UT WOS:000298003700012 PM 22014658 ER PT J AU Lee, BT Duggan, MM Keenan, MT Kamatkar, S Quinlan, RM Hergrueter, CA Hertl, MC Shin, JH Truppin, NB Chun, YS AF Lee, Bernard T. Duggan, Margaret M. Keenan, Maureen T. Kamatkar, Suyog Quinlan, Robert M. Hergrueter, Charles A. Hertl, M. Catherine Shin, Joseph H. Truppin, Nicola B. Chun, Yoon S. CA Massachusetts Board Registration TI Commonwealth of Massachusetts Board of Registration in Medicine Expert Panel on Immediate Implant-Based Breast Reconstruction Following Mastectomy for Cancer: Executive Summary, June 2011 SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID SURGEONS 12-YEAR EXPERIENCE; SURGICAL DECISION-MAKING; PATIENT SATISFACTION; TISSUE EXPANDER; RISK-FACTORS; COMPLICATIONS; INFECTION; OUTCOMES; OPTIONS; IMPACT C1 [Lee, Bernard T.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Plast & Reconstruct Surg,Dept Surg, Boston, MA 02215 USA. [Hergrueter, Charles A.; Chun, Yoon S.] Brigham & Womens Hosp, Dept Surg, Faulkner Hosp, Div Plast Surg, Boston, MA 02115 USA. [Keenan, Maureen T.; Kamatkar, Suyog] Massachusetts Board Registrat Med, Qual & Patient Safety Div, Boston, MA USA. [Quinlan, Robert M.] Univ Massachusetts, Mem Med Ctr, Dept Surg, Worcester, MA 01605 USA. [Hertl, M. Catherine] Massachusetts Gen Hosp, N Shore Med Ctr, Div Plast Surg, Salem, MA USA. [Shin, Joseph H.] Baystate Med Ctr, Div Plast Surg, Springfield, MA USA. [Truppin, Nicola B.] Hlth Navigator Partners, Newton, MA USA. RP Lee, BT (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Plast & Reconstruct Surg,Dept Surg, 110 Francis St,Suite 5A, Boston, MA 02215 USA. EM blee3@bidmc.harvard.edu RI Lee, Bernard/K-1106-2016; OI Lee, Bernard/0000-0002-5533-3166; KAMATKAR, SUYOG/0000-0002-2944-3142 NR 58 TC 5 Z9 5 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD DEC PY 2011 VL 213 IS 6 BP 800 EP 805 DI 10.1016/j.jamcollsurg.2011.08.014 PG 6 WC Surgery SC Surgery GA 861FD UT WOS:000298003700018 PM 21958509 ER PT J AU Kong, A Beresford, SAA Alfano, CM Foster-Schubert, KE Neuhouser, ML Johnson, DB Duggan, C Wang, CY Xiao, LR Bain, CE McTiernan, A AF Kong, Angela Beresford, Shirley A. A. Alfano, Catherine M. Foster-Schubert, Karen E. Neuhouser, Marian L. Johnson, Donna B. Duggan, Catherine Wang, Ching-Yun Xiao, Liren Bain, Carolyn E. McTiernan, Anne TI Associations between Snacking and Weight Loss and Nutrient Intake among Postmenopausal Overweight to Obese Women in a Dietary Weight-Loss Intervention SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID LOOK-AHEAD ACTION; ENERGY-INTAKE; FOOD-INTAKE; EATING OCCASIONS; US ADULTS; PATTERNS; HEALTH; FREQUENCY; MEAL; BMI AB Snacking may play a role in weight control. The associations of timing and frequency of snacking with observed weight change and nutrient intake were assessed in an ancillary study to a 12-month randomized controlled trial in Seattle, WA. Overweight-to-obese postmenopausal women (n=123) enrolled in the two dietary weight-loss arms from 2007 to 2008 with complete data at 12 months were included in these analyses.. Generalized linear models were used to test the associations between snacking and weight loss (percent) and nutrient intake at the 12-month time point. Participants were, on average, 58 years old and mainly non-Hispanic white (84%). Ninety-seven percent reported one or more snacks per day. Weight loss (percent) was significantly lower among mid-morning (10:30 AM to 11:29 Am) snackers (7.0%, 95% confidence interval: 4.3 to 9.7) compared to non mid-morning snackers (11.4%, 95% confidence interval: 10.2 to 12.6; P=0.005). A higher proportion of mid-morning snackers reported more than one snack per day (95.7%), compared to afternoon (82.8%) and evening (80.6%) snackers, although differences were not statistically significant (P>0.05). Women who reported two or more snacks per day vs one or no snacks per day had higher fiber intake (P=0.027). Afternoon snackers had higher fruit and vegetable intake compared to non-afternoon-snackers (P=0.035). These results suggest that snack meals can be a source for additional fruits, vegetables, and fiber-rich foods; however, snacking patterns might also reflect unhealthy eating habits and impede weight-loss progress. Future dietary weight-loss interventions should evaluate the effects of timing, frequency, and quality of snacks on weight loss. J Am Diet Assoc. 2011;111:1898-1903. C1 [McTiernan, Anne] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Prevent Ctr, Seattle, WA 98109 USA. [Kong, Angela] Univ Illinois, Inst Hlth Res & Policy, Canc Educ & Career Dev Program, Chicago, IL USA. [Beresford, Shirley A. A.] Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. [Alfano, Catherine M.] NCI, Off Canc Survivorship, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [Foster-Schubert, Karen E.] Univ Washington, VA Puget Sound Hlth Care, Seattle, WA 98195 USA. [Duggan, Catherine] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, Seattle, WA 98109 USA. [Johnson, Donna B.] Univ Washington, Ctr Publ Hlth Nutr, Seattle, WA 98195 USA. RP McTiernan, A (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Prevent Ctr, 1100 Fairview Ave N,M4-B874,POB 19024, Seattle, WA 98109 USA. EM amctiern@fhcrc.org RI Duggan, Catherine/F-9414-2015 OI Duggan, Catherine/0000-0001-7369-4021 FU National Cancer Institute (NCI) National Institutes of Health (NIH) [R01 CA105204-01A1, U54-CA116847]; NIH [5KL2RR025015-03]; NCI [R25CA094880, 2R25CA057699-16] FX This study was funded by National Cancer Institute (NCI) National Institutes of Health (NIH) grants R01 CA105204-01A1 and U54-CA116847 (Transdisciplinary Research on Energetics and Cancer). K.E.F.-S. received support from NIH 5KL2RR025015-03 and A.K. was supported by NCI R25CA094880 at the time of this study and is currently supported by NCI 2R25CA057699-16. NR 32 TC 6 Z9 6 U1 0 U2 4 PU AMER DIETETIC ASSOC PI CHICAGO PA 120 S RIVERSIDE PLZ, STE 2000, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD DEC PY 2011 VL 111 IS 12 BP 1898 EP 1903 DI 10.1016/j.jada.2011.09.012 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 872RY UT WOS:000298828200016 PM 22117666 ER PT J AU Burgio, KL Goode, PS Johnson, TM Hammontree, L Ouslander, JG Markland, AD Colli, J Vaughan, CP Redden, DT AF Burgio, Kathryn L. Goode, Patricia S. Johnson, Theodore M., II Hammontree, Lee Ouslander, Joseph G. Markland, Alayne D. Colli, Janet Vaughan, Camille P. Redden, David T. TI Behavioral Versus Drug Treatment for Overactive Bladder in Men: The Male Overactive Bladder Treatment in Veterans (MOTIVE) Trial SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Urological-Association CY JUN 06, 2010 CL San Francisco, CA SP Amer Urol Assoc DE overactive bladder; behavioral treatment; drug therapy; lower urinary tract symptoms; urinary incontinence ID URINARY-TRACT SYMPTOMS; BENIGN PROSTATIC HYPERPLASIA; RANDOMIZED CONTROLLED-TRIAL; SIDED TESTS PROCEDURE; OLDER WOMEN; INCONTINENT WOMEN; MANAGEMENT; THERAPY; COMBINATION; EFFICACY AB OBJECTIVES: To compare the effectiveness of behavioral treatment with that of antimuscarinic therapy in men without bladder outlet obstruction who continue to have overactive bladder (OAB) symptoms with alpha-blocker therapy. DESIGN: The Male Overactive Bladder Treatment in Veterans (MOTIVE) Trial was a two-site randomized, controlled, equivalence trial with 4-week alpha-blocker run-in. SETTING: Veterans Affairs Medical Center outpatient clinics. PARTICIPANTS: Volunteer sample of 143 men aged 42 to 88 who continued to have urgency and more than eight voids per day, with or without incontinence, after run-in. INTERVENTIONS: Participants were randomized to 8 weeks of behavioral treatment (pelvic floor muscle exercises, urge suppression techniques, delayed voiding) or drug therapy (individually titrated, extended-release oxybutynin, 5-30 mg/d). MEASUREMENTS: Seven-day bladder diaries and a validated urgency scale were used to calculate changes in 24-hour voiding frequency, nocturia, urgency, and incontinence. Secondary outcomes were global patient ratings and American Urological Association Symptom Index. RESULTS: Mean voids per day decreased from 11.3 to 9.1 (- 18.8%) with behavioral treatment and 11.5 to 9.5 (- 16.9%) with drug therapy. Equivalence analysis indicated that posttreatment means were equivalent (P <.01). After treatment, 85% of participants rated themselves as much better or better; more than 90% were completely or somewhat satisfied, with no betweengroup differences. The behavioral group showed greater reductions in nocturia (mean = -0.70 vs - 0.32 episodes/ night; P =.05). The drug group showed greater reductions in maximum urgency scores (mean = -0.44 vs -0.12; P =.02). Other between-group differences were nonsignificant. CONCLUSION: Behavioral and antimuscarinic therapy are effective when added to alpha-blocker therapy for OAB in men without outlet obstruction. Behavioral treatment is at least as effective as antimuscarinic therapy. J Am Geriatr Soc 59: 2209-2216, 2011. C1 [Burgio, Kathryn L.; Goode, Patricia S.; Johnson, Theodore M., II; Hammontree, Lee; Markland, Alayne D.; Colli, Janet; Vaughan, Camille P.; Redden, David T.] Birmingham Atlanta Geriatr Res Educ & Clin Ctr, Dept Vet Affairs, Birmingham, AL USA. [Burgio, Kathryn L.; Goode, Patricia S.; Markland, Alayne D.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. [Hammontree, Lee; Colli, Janet] Univ Alabama, Dept Surg, Birmingham, AL 35294 USA. [Redden, David T.] Univ Alabama, Dept Biostat, Birmingham, AL 35294 USA. [Johnson, Theodore M., II; Vaughan, Camille P.] Emory Univ, Atlanta, GA 30322 USA. [Ouslander, Joseph G.] Florida Atlantic Univ, Charles E Schmidt Coll Biomed Sci, Dept Clin Biomed Sci, Miami, FL USA. RP Burgio, KL (reprint author), Birmingham VA Med Ctr, Geriatr Res Educ & Clin Ctr, 11G,700 S 19th St, Birmingham, AL 35233 USA. EM kburgio@aging.uab.edu RI Vaughan, Camille/I-3758-2014 NR 39 TC 34 Z9 34 U1 3 U2 11 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD DEC PY 2011 VL 59 IS 12 BP 2209 EP 2216 DI 10.1111/j.1532-5415.2011.03724.x PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 869LU UT WOS:000298600300003 PM 22092152 ER PT J AU Blackwell, T Yaffe, K Ancoli-Israel, S Redline, S Ensrud, KE Stefanick, ML Laffan, A Stone, KL AF Blackwell, Terri Yaffe, Kristine Ancoli-Israel, Sonia Redline, Susan Ensrud, Kristine E. Stefanick, Marcia L. Laffan, Alison Stone, Katie L. CA Osteoporotic Fractures Men Study TI Associations Between Sleep Architecture and Sleep-Disordered Breathing and Cognition in Older Community-Dwelling Men: The Osteoporotic Fractures in Men Sleep Study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE sleep architecture; sleep-disordered breathing; cognitive function; hypoxemia ID APNEA SYNDROME; ALZHEIMERS-DISEASE; CPAP TREATMENT; HEART HEALTH; REM-SLEEP; MEMORY; DYSFUNCTION; CONSOLIDATION; PERFORMANCE; IMPROVEMENT AB OBJECTIVES: To examine the association between sleep architecture, sleep-disordered breathing, and cognition in older men. DESIGN: Population-based cross-sectional study. SETTING: Six clinical sites in the United States. PARTICIPANTS: Two thousand nine hundred nine community- dwelling men aged 67 and older who were not selected on the basis of sleep problems or cognitive impairment. MEASUREMENTS: Predictors were measured using in-home polysomnography: sleep architecture, nocturnal hypoxemia (any sleep time with arterial oxygen saturation < 80%), apnea-hypopnea index (AHI), and arousal index. Cognitive outcomes were measured using the modified Mini-Mental State Examination (3MS), Trail-Making Test Part B (TMT-B), and the Digit Vigilance Test (DVT). RESULTS: Analyses adjusted for age, race, education, body mass index, lifestyle, comorbidities, and medication use showed that participants who spent less percentage of time in rapid eye movement (REM) sleep had lower levels of cognition; participants in the lowest quartile (< 14.8%) took an average of 5.9 seconds longer on the TMT-B and 20.1 seconds longer on the DVT than those in the highest quartile (>= 23.7%). Similarly, greater percentage of time spent in Stage 1 sleep was related to poorer cognitive function. Participants in the highest quartile of Stage 1 sleep (>= 8.6%) had worse cognitive scores on average than those in the lowest quartile (< 4.0%). Those with nocturnal hypoxemia took an average of 22.3 seconds longer to complete the DVT than those without, but no associations were found with 3MS or the TMT-B. CONCLUSION: Spending less percentage of time in REM sleep and greater percentage of time in Stage 1 sleep and having higher levels of nocturnal hypoxemia were associated with poorer cognition in older men. Further studies are needed to clarify the direction of these associations and to explore potential mechanisms. J Am Geriatr Soc 59: 2217-2225, 2011. C1 [Blackwell, Terri; Laffan, Alison; Stone, Katie L.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. [Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. [Ancoli-Israel, Sonia] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Redline, Susan] Harvard Univ, Brigham & Womens Hosp, Dept Med, Sch Med, Boston, MA 02115 USA. [Redline, Susan] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Ensrud, Kristine E.] Vet Affairs Med Ctr, Ctr Chron Dis Outcomes Res, Minneapolis, MN USA. [Ensrud, Kristine E.] Univ Minnesota, Dept Med, Div Epidemiol & Community Hlth, Minneapolis, MN 55455 USA. [Stefanick, Marcia L.] Stanford Univ, Dept Med, Sch Med, Stanford Prevent Res Ctr, Stanford, CA 94305 USA. RP Blackwell, T (reprint author), San Francisco Coordinating Ctr, 185 Berry St,Lobby 5,Suite 5700, San Francisco, CA 94107 USA. EM tblackwell@sfcc-cpmc.net FU National Institutes of Health (NIH); National Institute of Arthritis and Musculoskeletal and Skin Diseases; National Institute on Aging; National Cancer Institute; National Center for Research Resources; NIH Roadmap for Medical Research [U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01 AG18197, U01-AG027810, UL1 RR024140, AG08415]; National Heart, Lung, and Blood Institute [R01 HL071194, R01 HL070848, R01 HL070847, R01 HL070842, R01 HL070841, R01 HL070837, R01 HL070838, R01 HL070839]; Sepracor; Litebook FX Conflict of Interest: MrOS is supported by National Institutes of Health (NIH) funding. The following institutes provide support: the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the National Institute on Aging, the National Cancer Institute, the National Center for Research Resources, and NIH Roadmap for Medical Research under Grants U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01 AG18197, U01-AG027810, UL1 RR024140, and AG08415.; The National Heart, Lung, and Blood Institute provides funding for the MrOS Sleep ancillary study "Out-comes of Sleep Disorders in Older Men" under Grants R01 HL071194, R01 HL070848, R01 HL070847, R01 HL070842, R01 HL070841, R01 HL070837, R01 HL070838, and R01 HL070839. Dr. Yaffe received funding from K 24 grant AG031155.; Dr. Ancoli-Israel has consulted for or is on the advisory board of Ferring Pharmaceuticals, GlaxoSmithKline, Merck, NeuroVigil, Pfizer, Philips Respironics, Sanofi-Aventis, Sepracor, Scherling-Plough, and Perdue, and has received research support from Sepracor and Litebook. NR 50 TC 36 Z9 36 U1 4 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD DEC PY 2011 VL 59 IS 12 BP 2217 EP 2225 DI 10.1111/j.1532-5415.2011.03731.x PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 869LU UT WOS:000298600300004 PM 22188071 ER PT J AU Gray, SL Boudreau, RM Newman, AB Studenski, SA Shorr, RI Bauer, DC Simonsick, EM Hanlon, JT AF Gray, Shelly L. Boudreau, Robert M. Newman, Anne B. Studenski, Stephanie A. Shorr, Ronald I. Bauer, Douglas C. Simonsick, Eleanor M. Hanlon, Joseph T. CA Hlth Aging Body Composition Study TI Angiotensin-Converting Enzyme Inhibitor and Statin Use and Incident Mobility Limitation in Community-Dwelling Older Adults: The Health, Aging and Body Composition Study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE medications; mobility; pharmacoepidemiology ID PERIPHERAL ARTERIAL-DISEASE; RANDOMIZED CONTROLLED-TRIAL; LOWER-EXTREMITY FUNCTION; C-REACTIVE PROTEIN; WOMEN AGED 65; PHYSICAL FUNCTION; WALKING PERFORMANCE; VASCULAR-DISEASE; PRAVASTATIN; ATORVASTATIN AB OBJECTIVES: To evaluate whether the use of angiotensin- converting enzyme (ACE) inhibitors and statins is associated with a lower risk of incident mobility limitation in older community dwelling adults. DESIGN: Longitudinal cohort study. SETTING: Health, Aging and Body Composition (Health ABC) study. PARTICIPANTS: Three thousand fifty-five participants who were well functioning at baseline (no mobility limitations). MEASUREMENTS: Summated standardized daily doses (low, medium, high) and duration of ACE inhibitor and statin use were computed. Mobility limitation (two consecutive self-reports of having any difficulty walking onequarter of a mile or climbing 10 steps without resting) was assessed every 6 months after baseline. Multivariable Cox proportional hazards analyses were conducted, adjusting for demographics, health status, and health behaviors. RESULTS: At baseline, 15.2% used ACE inhibitors and 12.9% used statins; use of both was greater than 25% by Year 6. Over 6.5 years of follow-up, 49.8% had developed mobility limitation. In separate multivariable models, neither ACE inhibitor (multivariate hazard ratio (HR) = 0.95, 95% confidence interval (CI) = 0.82-1.09) nor statin use (multivariate HR = 1.02, 95% CI = 0.87-1.17) was associated with lower risk of mobility limitation. Similar findings were seen in analyses examining dose-response and duration-response relationships and a sensitivity analysis restricted to those with hypertension. CONCLUSION: ACE inhibitors and statins widely prescribed to treat hypertension and hypercholesterolemia, respectively, do not lower risk of mobility limitation, an important indicator of quality of life. J Am Geriatr Soc 59: 2226-2232, 2011. C1 [Gray, Shelly L.] Univ Washington, Sch Pharm, Seattle, WA 98195 USA. [Boudreau, Robert M.; Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Sch Publ Hlth, Pittsburgh, PA 15261 USA. [Newman, Anne B.; Studenski, Stephanie A.; Hanlon, Joseph T.] Univ Pittsburgh, Sch Med, Dept Med, Div Geriatr, Pittsburgh, PA USA. [Hanlon, Joseph T.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15261 USA. [Studenski, Stephanie A.; Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Geriatr Res Educ, Pittsburgh, PA USA. [Studenski, Stephanie A.; Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Clin, Pittsburgh, PA USA. [Shorr, Ronald I.] N Florida S Georgia Vet Hlth Syst, Geriatr Res Educ & Clin Ctr, Gainesville, FL USA. [Bauer, Douglas C.] Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94143 USA. [Simonsick, Eleanor M.] NIA, Intramural Res Program, Baltimore, MD 21224 USA. RP Gray, SL (reprint author), Univ Washington, Sch Pharm, Box 357630, Seattle, WA 98195 USA. EM slgray@u.washington.edu RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Boudreau, Robert/0000-0003-0162-5187 FU National Institutes of Health, National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; NIA [R01AG027017, P30AG024827, T32 AG021885, K07AG033174, R56AG027017, R01AG034056]; National Institute of Mental Health [R34 MH082682]; National Institute of Nursing Research [R01 NR010135]; Agency for Healthcare Research and Quality [R01 HS017695, R01 HS018721, K12 HS019461]; Veterans Affairs Health Services Research [IIR-06-062]; Merck; Novartis; GTX; Hazzard Text McGraw Hill FX This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute on Aging (NIA) and Contracts N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106. The authors were also supported by NIA Grants and Contracts R01AG027017, P30AG024827, T32 AG021885, K07AG033174, R56AG027017, and R01AG034056; National Institute of Mental Health Grant R34 MH082682; National Institute of Nursing Research Grant R01 NR010135; Agency for Healthcare Research and Quality Grants R01 HS017695, R01 HS018721, and K12 HS019461; and Veterans Affairs Health Services Research Grant IIR-06-062.; Dr. Studenski received institutional grant support, travel expenses, and consultancy fees from Merck; consultancy fees from Novartis and GTX; and royalties from Hazzard Text McGraw Hill. NR 37 TC 14 Z9 14 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD DEC PY 2011 VL 59 IS 12 BP 2226 EP 2232 DI 10.1111/j.1532-5415.2011.03721.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 869LU UT WOS:000298600300005 PM 22092102 ER PT J AU Feil, DG Rajan, M Soroka, O Tseng, CL Miller, DR Pogach, LM AF Feil, Denise G. Rajan, Mangala Soroka, Orysya Tseng, Chin-Lin Miller, Donald R. Pogach, Leonard M. TI Risk of Hypoglycemia in Older Veterans with Dementia and Cognitive Impairment: Implications for Practice and Policy SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE diabetes mellitus; dementia; cognitive impairment; glycemic control; hypoglycemia ID TYPE-2 DIABETES-MELLITUS; BLOOD-GLUCOSE CONTROL; ADVERSE DRUG EVENTS; GLYCEMIC CONTROL; CARE; PERFORMANCE; INSULIN; HEALTH; COMPLICATIONS; SULFONYLUREAS AB OBJECTIVES: To examine the relationship between management of diabetes mellitus and hypoglycemia in older adults with and without dementia and cognitive impairment. DESIGN: Cross-sectional database analysis of veterans aged 65 years and older stratified according to dementia, cognitive impairment, age, antiglycemic medications, and glycosylated hemoglobin (Hba1c) level. SETTING: Research database with linked clinical, laboratory, pharmacy, and International Classification of Diseases, Ninth Revision, Clinical Modification, codes. PARTICIPANTS: Four hundred ninety-seven thousand nine hundred veterans aged 65 and older with diabetes mellitus who obtained services from the Department of Veterans Affairs in fiscal years (FYs) 2002 and 2003. MEASUREMENTS: Hypoglycemia, the outcome variable, was identified from outpatient visits, emergency department and inpatient admission codes in FY2003. Independent variables (FY2002-03) included dementia and cognitive impairment, comorbid conditions, extended care and nursing home stays, demographics, antiglycemic medication, and HbA1c levels. RESULTS: Prevalence of combined dementia and cognitive impairment was 13.1% for individuals aged 65 to 74 and 24.2% for those aged 75 and older. Mean HbA1c levels were 7.0 +/- 1.3% for all participants and 6.9 +/- 1.3% for those with dementia. The proportion of participants taking insulin was higher in those with dementia or cognitive impairment (30%) than in those with neither condition (24%). Of all participants taking insulin, more with dementia (26.5%) and cognitive impairment (19.5%) were hypoglycemic than of those with neither condition (14.4%). For all participants, unadjusted odds ratios (ORs) for hypoglycemia were 2.42 (95% confidence interval (CI) = 2.36-2.48) for dementia and 1.72 (95% CI = 1.65-1.79) for cognitive impairment; adjusted ORs were 1.58 (95% CI = 1.53-1.62) for dementia and 1.13 (95% CI = 1.08-1.18) for cognitive impairment. CONCLUSION: Diabetes mellitus was managed more intensively in older veterans with dementia and cognitive impairment, and dementia and cognitive impairment were independently associated with greater risk of hypoglycemia. J Am Geriatr Soc 59: 2263-2272, 2011. C1 [Feil, Denise G.] Univ Calif Los Angeles, Div Geriatr Psychiat, W Los Angeles Vet Affairs Healthcare Ctr, Los Angeles, CA USA. [Feil, Denise G.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Rajan, Mangala; Soroka, Orysya; Tseng, Chin-Lin; Pogach, Leonard M.] Ctr Healthcare Knowledge Management, Dept Vet Affairs New Jersey Healthcare Syst, E Orange, NJ USA. [Miller, Donald R.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Miller, Donald R.] Bedford Vet Affairs Med Ctr Hlth Qual Outcomes &, Bedford, MA USA. [Tseng, Chin-Lin; Pogach, Leonard M.] Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. RP Pogach, LM (reprint author), VA New Jersey Healthcare Syst, VA HSR&D Ctr Healthcare Knowledge Management Res, 385 Tremont Ave, E Orange, NJ 07018 USA. EM leonard.pogach@va.gov FU VA Health Services Research and Development (HSRD); VA HSRD Diabetes Quality Enhancement Research Initiative FX Dr. Feil received grant support from a VA Health Services Research and Development (HSRD) Career Development Award. Dr. Pogach and Dr. Miller report funding from the VA HSRD Diabetes Quality Enhancement Research Initiative. NR 51 TC 35 Z9 35 U1 4 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD DEC PY 2011 VL 59 IS 12 BP 2263 EP 2272 DI 10.1111/j.1532-5415.2011.03726.x PG 10 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 869LU UT WOS:000298600300010 PM 22150156 ER PT J AU Kelley, AS Ettner, SL Wenger, NS Sarkisian, CA AF Kelley, Amy S. Ettner, Susan L. Wenger, Neil S. Sarkisian, Catherine A. TI Determinants of Death in the Hospital Among Older Adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE hospital use; end-of-life care; health services ID OF-LIFE CARE; TERMINALLY-ILL PATIENTS; TREATMENT INTENSITY; ETHNIC-DIFFERENCES; FAMILY-MEMBERS; END; PLACE; PREFERENCES; CANCER; QUALITY AB OBJECTIVES: To investigate patient-level determinants of in-hospital death, adjusting for patient and regional characteristics. DESIGN: Using multivariable regression, the relationship between in-hospital death and participants' social, functional, and health characteristics was investigated, controlling for regional Hospital Care Intensity Index (HCI) from the Dartmouth Atlas of Health Care. SETTING: The Health and Retirement Study, a longitudinal nationally representative cohort of older adults. PARTICIPANTS: People aged 67 and older who died between 2,000 and 2,006 (N = 3,539) were sampled. MEASUREMENTS: In-hospital death. RESULTS: Thirty-nine percent (n = 1,380) of participants died in the hospital (range 34% in Midwest to 45% in Northeast). Nursing home residence, functional dependence, and cancer or dementia diagnosis, among other characteristics, were associated with lower adjusted odds of in-hospital death. Being black or Hispanic, living alone, and having more medical comorbidities were associated with greater adjusted odds, as was higher HCI. Sex, education, net worth, and completion of an advance directive did not correlate with in-hospital death. CONCLUSION: Black race, Hispanic ethnicity, and other functional and social characteristics are correlates of inhospital death, even after controlling for the role of HCI. Further work must be done to determine whether preferences, provider characteristics and practice patterns, or differential access to medical and community services drive this difference. J Am Geriatr Soc 59: 2321-2325, 2011. C1 [Kelley, Amy S.] Mt Sinai Sch Med, Dept Geriatr & Palliat Med, New York, NY USA. [Ettner, Susan L.; Wenger, Neil S.] Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA. [Sarkisian, Catherine A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Geriatr, Los Angeles, CA 90095 USA. [Sarkisian, Catherine A.] Vet Affairs Greater Los Angeles Healthcare Syst, Geriatr Res Educ Clin Ctr, Los Angeles, CA USA. RP Kelley, AS (reprint author), 1 Gustave L Levy Pl,Box 1070, New York, NY 10029 USA. EM amy.kelley@mssm.edu FU Univeristy of California at Los Angeles; Veterans Affairs Greater Los Angeles Healthcare System Geriatric Research Education Clinical Center FX The authors report no financial or personal conflicts of interest. While conducting this work, Dr. Kelley was supported by the National Research Service Award Fellowship Program at the Univeristy of California at Los Angeles and the Brookdale Leadership in Aging Fellowship. Dr. Sarkisian is supported by the Veterans Affairs Greater Los Angeles Healthcare System Geriatric Research Education Clinical Center. NR 23 TC 9 Z9 9 U1 2 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD DEC PY 2011 VL 59 IS 12 BP 2321 EP 2325 DI 10.1111/j.1532-5415.2011.03718.x PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 869LU UT WOS:000298600300017 PM 22092014 ER PT J AU Potosky, AL Malin, JL Kim, B Chrischilles, EA Weeks, JC AF Potosky, Arnold L. Malin, Jennifer L. Kim, Benjamin Chrischilles, Elizabeth A. Weeks, Jane C. TI Re: Personalized Medicine and Cancer Supportive Care: Appropriate Use of Colony-Stimulating Factor Support of Chemotherapy SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter ID NON-HODGKINS-LYMPHOMA; CELL LUNG-CANCER; RANDOMIZED CONTROLLED-TRIAL; PHASE-III TRIAL; BREAST-CANCER; ADJUVANT CHEMOTHERAPY; ADVERSE EVENTS; DOSE-INTENSITY; DOUBLE-BLIND; LENOGRASTIM C1 [Potosky, Arnold L.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC 20007 USA. [Malin, Jennifer L.; Kim, Benjamin] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Malin, Jennifer L.; Kim, Benjamin] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Div Gen Internal Med, Hlth Serv Res, Los Angeles, CA 90024 USA. [Malin, Jennifer L.; Kim, Benjamin] RAND Corp, RAND Grad Sch, RAND Hlth & Pardee, Santa Monica, CA USA. [Chrischilles, Elizabeth A.] Univ Iowa, Dept Epidemiol, Coll Publ Hlth, Iowa City, IA USA. [Weeks, Jane C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Potosky, AL (reprint author), Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Oncol, 3300 Whitehaven St NW,Ste 4100, Washington, DC 20007 USA. EM alp49@george-town.edu FU NCI NIH HHS [U01 CA093329, U01 CA093332, U01 CA093348, U01 CA093324, U01 CA093326, U01 CA093339, U01 CA093344] NR 35 TC 1 Z9 1 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC PY 2011 VL 103 IS 24 BP 1899 EP 1901 DI 10.1093/jnci/djr439 PG 3 WC Oncology SC Oncology GA 866OQ UT WOS:000298391000014 PM 22036767 ER PT J AU Krishnan, A Pasquini, MC Logan, B Stadtmauer, EA Vesole, DH Alyea, E Antin, JH Comenzo, R Goodman, S Hari, P Laport, G Qazilbash, MAH Rowley, S Sahebi, F Somlo, G Vogl, DT Weisdorf, D Ewell, M Wu, J Geller, NL Horowitz, MM Giralt, S Maloney, DG AF Krishnan, Amrita Pasquini, Marcelo C. Logan, Brent Stadtmauer, Edward A. Vesole, David H. Alyea, Edwin, III Antin, Joseph H. Comenzo, Raymond Goodman, Stacey Hari, Parameswaran Laport, Ginna Qazilbash, Muzaffar H. Rowley, Scott Sahebi, Firoozeh Somlo, George Vogl, Dan T. Weisdorf, Daniel Ewell, Marian Wu, Juan Geller, Nancy L. Horowitz, Mary M. Giralt, Sergio Maloney, David G. CA Blood Marrow Transplant Clinical TI Autologous haemopoietic stem-cell transplantation followed by allogeneic or autologous haemopoietic stem-cell transplantation in patients with multiple myeloma (BMT CTN 0102): a phase 3 biological assignment trial SO LANCET ONCOLOGY LA English DT Article ID BONE-MARROW-TRANSPLANTATION; NEWLY-DIAGNOSED MYELOMA; CLINICAL-TRIALS; THALIDOMIDE; DEXAMETHASONE; CHEMOTHERAPY; MAINTENANCE; SURVIVAL; SINGLE AB Background Autologous haemopoietic stem-cell transplantation (HSCT) improves survival in patients with multiple myeloma, but disease progression remains an issue. Allogeneic HSCT might reduce disease progression, but can be associated with high treatment-related mortality. Thus, we aimed to assess effectiveness of allogeneic HSCT with non-myeloablative conditioning after autologous HSCT compared with tandem autologous HSCT. Methods In our phase 3 biological assignment trial, we enrolled patients with multiple myeloma attending 37 transplant centres in the USA. Patients (<70 years old) with adequate organ function who had completed at least three cycles of systemic antimyeloma therapy within the past 10 months were eligible for inclusion. We assigned patients to receive an autologous HSCT followed by an allogeneic HSCT (auto-allo group) or tandem autologous HSCTs (auto-auto group) on the basis of the availability of an HLA-matched sibling donor. Patients in the auto-auto group subsequently underwent a random allocation (1: 1) to maintenance therapy (thalidomide plus dexamethasone) or observation. To avoid enrolment bias, we classified patients as standard risk or high risk on the basis of cytogenetics and beta 2-microglobulin concentrations. We used the Kaplan-Meier method to estimate differences in 3-year progression-free survival (PFS; primary endpoint) between patients with standard-risk disease in the auto-allo group and the best results from the auto-auto group (maintenance, observation, or pooled). This study is registered with ClinicalTrials.gov, number NCT00075829. Findings Between Dec 17, 2003, and March 30, 2007, we enrolled 710 patients, of whom 625 had standard-risk disease and received an autologous HSCT. 156 (83%) of 189 patients with standard-risk disease in the auto-allo group and 366 (84%) of 436 in the auto-auto group received a second transplant. 219 patients in the auto-auto group were randomly assigned to observation and 217 to receive maintenance treatment, of whom 168 (77%) completed this treatment. PFS and overall survival did not differ between maintenance and observation groups and pooled data were used. Kaplan-Meier estimates of 3-year PFS were 43% (95% CI 36-51) in the auto-allo group and 46% (42-51) in the auto-auto group (p=0.671); overall survival also did not differ at 3 years (77% [95% CI 72-84] vs 80% [77-84]; p=0.191). Within 3 years, 87 (46%) of 189 patients in the auto-allo group had grade 3-5 adverse events as did 185 (42%) of 436 patients in the auto-auto group. The adverse events that differed most between groups were hyperbilirubinaemia (21 [11%] patients in the auto-allo group vs 14 [3%] in the auto-auto group) and peripheral neuropathy (11 [6%] in the auto-allo group vs 52 [12%] in the auto-auto group). Interpretation Non-myeloablative allogeneic HSCT after autologous HSCT is not more effective than tandem autologous HSCT for patients with standard-risk multiple myeloma. Further enhancement of the graft versus myeloma effect and reduction in transplant-related mortality are needed to improve the allogeneic HSCT approach. C1 [Maloney, David G.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Krishnan, Amrita; Sahebi, Firoozeh; Somlo, George] City Hope Canc Ctr, Los Angeles, CA USA. [Pasquini, Marcelo C.; Logan, Brent; Hari, Parameswaran; Horowitz, Mary M.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Stadtmauer, Edward A.; Vogl, Dan T.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Vesole, David H.; Rowley, Scott] Hackensack Univ Med Ctr, Hackensack, NJ USA. [Alyea, Edwin, III; Antin, Joseph H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Comenzo, Raymond] Tufts Univ & Med Ctr, Boston, MA USA. [Goodman, Stacey] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Goodman, Stacey] Vet Affairs Tennessee Valley Healthcare Syst, Nashville, TN USA. [Laport, Ginna] Stanford Univ, Stanford, CA 94305 USA. [Qazilbash, Muzaffar H.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Weisdorf, Daniel] Univ Minnesota, Minneapolis, MN USA. [Ewell, Marian; Wu, Juan] EMMES Corp, Rockville, MD USA. [Geller, Nancy L.] NHLBI, Bethesda, MD 20892 USA. [Giralt, Sergio] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Maloney, DG (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,D1-100,POB 19024, Seattle, WA 98109 USA. EM dmaloney@fhcrc.org OI Vogl, Dan/0000-0002-2935-2566; Hari, Parameswaran/0000-0002-8800-297X FU US National Heart, Lung, and Blood Institute; National Cancer Institute; Celgene Pharmaceuticals FX US National Heart, Lung, and Blood Institute and the National Cancer Institute.; AK is on the speakers' bureau for Celgene Pharmaceuticals and Millennium Pharmaceutics and has consulted for Celgene Pharmaceuticals. DGM is a consultant for Celgene Pharmaceuticals. GS is on the Advisory of Board of Celgene Pharmaceuticals. SGi is on the Advisory of board of Celgene, Millennium, AMGEN and ONYX Pharmaceuticals; and receives research support from Celgene Pharmaceuticals. The other authors declare that they have no conflicts of interest. NR 28 TC 103 Z9 105 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD DEC PY 2011 VL 12 IS 13 BP 1195 EP 1203 DI 10.1016/S1470-2045(11)70243-1 PG 9 WC Oncology SC Oncology GA 863GG UT WOS:000298150200021 PM 21962393 ER PT J AU Ertman, N Andreano, JM Cahill, L AF Ertman, Nicole Andreano, Joseph M. Cahill, Larry TI Progesterone at encoding predicts subsequent emotional memory SO LEARNING & MEMORY LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; NATIONAL-COMORBIDITY-SURVEY; MENSTRUAL-CYCLE MODULATION; HEALTHY-YOUNG WOMEN; CROSS-SEX HORMONES; ORAL-CONTRACEPTIVES; CORTISOL RESPONSES; ANXIETY DISORDERS; ESTROUS-CYCLE; CONSOLIDATION AB Significant sex differences in the well-documented relationship between stress hormones and memory have emerged in recent studies. The potentiating effects of glucocorticoids on memory vary across the menstrual cycle, suggesting a potential interaction between these stress hormones and endogenously cycling sex hormones. Here, we show that memory for emotional materials changes significantly in accordance with hormonal changes across the menstrual cycle, suggesting that ovarian sex hormones influence the modulation of emotional memories. Sixty healthy, naturally cycling women rated 120 images on arousal and valence. One week later they completed free recall and recognition memory tests. Their menstrual cycle phases were estimated by self-report and confirmed by salivary assay of 17 beta-estradiol and progesterone. Memory for emotional items only was significantly better in the high hormone (luteal) phase compared with the low hormone (follicular) phase on the free recall test; on both tests memory correlated positively with progesterone collected at the time of encoding. These findings suggest that emotional memory performance changes across the menstrual cycle, and that this change is in part mediated by endogenous progesterone cycling. C1 [Ertman, Nicole; Andreano, Joseph M.; Cahill, Larry] Univ Calif Irvine, Ctr Neurobiol Learning & Memory, Dept Neurobiol & Behav, Irvine, CA 92697 USA. [Andreano, Joseph M.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02139 USA. RP Ertman, N (reprint author), Univ Calif Irvine, Ctr Neurobiol Learning & Memory, Dept Neurobiol & Behav, Irvine, CA 92697 USA. EM nertman@uci.edu FU NIMH [R01MH057508] FX This research was supported by NIMH grant R01MH057508 to L.C. NR 58 TC 35 Z9 35 U1 2 U2 12 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1072-0502 J9 LEARN MEMORY JI Learn. Mem. PD DEC PY 2011 VL 18 IS 12 BP 759 EP 763 DI 10.1101/lm.023267.111 PG 5 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 874PD UT WOS:000298969700004 PM 22101178 ER PT J AU Zhang, X Reis, M Khoriaty, R Li, Y Ouillette, P Samayoa, J Carter, H Karchin, R Li, M Diaz, LA Velculescu, VE Papadopoulos, N Kinzler, KW Vogelstein, B Malek, SN AF Zhang, X. Reis, M. Khoriaty, R. Li, Y. Ouillette, P. Samayoa, J. Carter, H. Karchin, R. Li, M. Diaz, L. A., Jr. Velculescu, V. E. Papadopoulos, N. Kinzler, K. W. Vogelstein, B. Malek, S. N. TI Sequence analysis of 515 kinase genes in chronic lymphocytic leukemia SO LEUKEMIA LA English DT Letter ID HIGH-THROUGHPUT ANNOTATION; SOMATIC MUTATIONS; HUMAN CANCER; B-RAF; MECHANISMS C1 [Zhang, X.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Reis, M.; Li, M.; Diaz, L. A., Jr.; Velculescu, V. E.; Papadopoulos, N.; Kinzler, K. W.; Vogelstein, B.] Ludwig Ctr Canc Genet & Therapeut, Baltimore, MD USA. [Reis, M.; Li, M.; Diaz, L. A., Jr.; Velculescu, V. E.; Papadopoulos, N.; Kinzler, K. W.; Vogelstein, B.] Howard Hughes Med Inst Johns Hopkins, Baltimore, MD USA. [Khoriaty, R.; Li, Y.; Ouillette, P.; Malek, S. N.] Univ Michigan, Dept Internal Med, Div Hematol & Oncol, Ann Arbor, MI 48109 USA. [Samayoa, J.; Carter, H.; Karchin, R.] Johns Hopkins Univ, Dept Biomed Engn, Inst Computat Med, Baltimore, MD USA. RP Zhang, X (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. EM smalek@med.umich.edu RI Karchin, Rachel/A-3385-2010; Reis, Marcelo/H-9370-2012; Papadopoulos, Nickolas/K-7272-2012 OI Reis, Marcelo/0000-0002-4706-1041; FU NCI NIH HHS [5 P30 CA46592, CA 43460, CA135877, CA136537, P30 CA046592, R01 CA136537, R21 CA135877, R37 CA043460] NR 18 TC 18 Z9 19 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD DEC PY 2011 VL 25 IS 12 BP 1908 EP 1910 DI 10.1038/leu.2011.163 PG 4 WC Oncology; Hematology SC Oncology; Hematology GA 866TG UT WOS:000298405500016 PM 21701494 ER PT J AU Li, XH Zhang, D Liu, B AF Li, Xinhua Zhang, Da Liu, Bob TI Comment on "In-patient to isocenter KERMA ratios in CT" [Med. Phys. 38, 5362-5369 (2011)] SO MEDICAL PHYSICS LA English DT Letter DE biological organs; computerised tomography; dosimetry; phantoms; radiation therapy C1 [Li, Xinhua; Zhang, Da; Liu, Bob] Massachusetts Gen Hosp, Dept Radiol, Div Diagnost Imaging Phys, Boston, MA 02114 USA. RP Li, XH (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Diagnost Imaging Phys, Boston, MA 02114 USA. EM bliu7@bics.bwh.harvard.edu NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD DEC PY 2011 VL 38 IS 12 BP 6787 EP 6788 DI 10.1118/1.3663667 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 864OS UT WOS:000298250100046 PM 22149860 ER PT J AU Afaq, F Katiyar, SK AF Afaq, F. Katiyar, S. K. TI Polyphenols: Skin Photoprotection and Inhibition of Photocarcinogenesis SO MINI-REVIEWS IN MEDICINAL CHEMISTRY LA English DT Review DE Polyphenols; photoprotection; photocarcinogenesis; proliferation; skin cancer; inflammation; immunosuppression; DNA repair; cellular signaling pathway; reactive oxygen species; ultraviolet radiation ID GREEN TEA POLYPHENOLS; SKH-1 HAIRLESS MICE; FACTOR-KAPPA-B; HUMAN EPIDERMAL-KERATINOCYTES; ACTIVATED PROTEIN-KINASES; INDUCED OXIDATIVE STRESS; RADIATION-INDUCED IMMUNOSUPPRESSION; INDUCED IMMUNE SUPPRESSION; UV-INDUCED IMMUNOSUPPRESSION; HUMAN RECONSTITUTED SKIN AB Polyphenols are a large family of naturally occurring plant products and are widely distributed in plant foods, such as, fruits, vegetables, nuts, flowers, bark and seeds, etc. These polyphenols contribute to the beneficial health effects of dietary products. Clinical and epidemiological studies suggest that exposure of the skin to environmental factors/pollutants, such as solar ultraviolet (UV) radiation induce harmful effects and leads to various skin diseases including the risk of melanoma and non-melanoma skin cancers. The incidence of non-melanoma skin cancer, comprising of squamous cell carcinoma and basal cell carcinoma, is a significant public health concern world-wide. Exposure of the skin to solar UV radiation results in inflammation, oxidative stress, DNA damage, dysregulation of cellular signaling pathways and immunosuppression thereby resulting in skin cancer. The regular intake of natural plant products, especially polyphenols, which are widely present in fruits, vegetables, dry legumes and beverages have gained considerable attention as protective agents against the adverse effects of UV radiation. In this article, we first discussed the impact of polyphenols on human health based on their structure-activity relationship and bioavailability. We then discussed in detail the photoprotective effects of some selected polyphenols on UV-induced skin inflammation, proliferation, immunosuppression, DNA damage and dysregulation of important cellular signaling pathways and their implications in skin cancer management. The selected polyphenols include: green tea polyphenols, pomegranate fruit extract, grape seed proanthocyanidins, resveratrol, silymarin, genistein and delphinidin. The new information on the mechanisms of action of these polyphenols supports their potential use in skin photoprotection and prevention of photocarcinogenesis in humans. C1 [Afaq, F.; Katiyar, S. K.] Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA. [Katiyar, S. K.] Birmingham Vet Affairs Med Ctr, Birmingham, AL 35294 USA. RP Afaq, F (reprint author), Univ Alabama, Dept Dermatol, 1670 Univ Blvd,Volker Hall 557, Birmingham, AL 35294 USA. EM fafaq@uab.edu; skatiyar@uab.edu FU National Institutes of Health [R21 AT002429-02, CA104428, CA140832, AT002536]; Veterans Administration FX This work was supported by funds from the National Institutes of Health [(R21 AT002429-02, F.A.) (CA104428, CA140832, AT002536, S.K.K.)] and Veterans Administration Merit Review Award (S.K.K.). The content of this article does not necessarily reflect the views or policies of the funding agencies. NR 109 TC 58 Z9 60 U1 3 U2 43 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-5575 J9 MINI-REV MED CHEM JI Mini-Rev. Med. Chem. PD DEC PY 2011 VL 11 IS 14 BP 1200 EP 1215 PG 16 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 869YH UT WOS:000298635800004 PM 22070679 ER PT J AU Moon, HS Chamberland, JP Aronis, K Tseleni-Balafouta, S Mantzoros, CS AF Moon, Hyun-Seuk Chamberland, John P. Aronis, Konstantinos Tseleni-Balafouta, Sofia Mantzoros, Christos S. TI Direct Role of Adiponectin and Adiponectin Receptors in Endometrial Cancer: In Vitro and Ex Vivo Studies in Humans SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID CIRCULATING ADIPONECTIN; CARCINOMA-CELLS; RISK; EXPRESSION; PROTEIN; LEPTIN; PATHWAY; CYCLE; PTEN AB Low adiponectin levels are an independent risk factor for and mediate the effect of obesity on endometrial cancer in epidemiology studies. The direct or indirect mechanisms underlying these findings remain to be elucidated. We first examined the expression of adiponectin receptor 1 (AdipoR1) and 2 (AdipoR2) in normal human endometrium and in endometrial cancer tissues ex vivo. We then used KLE and RL95-2 human endometrial cancer cell lines in vitro to study relative expression of AdipoRs, to investigate the effect of adiponectin on activating intracellular signaling pathways, and to assess its potential to alter malignant properties. We report for the first time that the relative expression level of AdipoR1 is higher than AdipoR2 in human endometrial cancer tissue, but the expression of AdipoRs is not statistically different from nonneoplastic tissues. We also show for the first time in endometrial cancer cell lines in vitro that adiponectin suppresses endometrial cancer proliferation acting through AdipoRs. Adiponectin also increases the expression of the adaptor molecule LKB1, which is required for adiponectin-mediated activation of AMPK/S6 axis and modulation of cell proliferation, colony formation, adhesion, and invasion of KLE and RL95-2 cell lines. These novel mechanistic studies provide for the first time in vitro and ex vivo evidence for a causal role of adiponectin in endometrial cancer. Mol Cancer Ther; 10(12); 2234-43. (C)2011 AACR. C1 [Moon, Hyun-Seuk; Chamberland, John P.; Aronis, Konstantinos; Mantzoros, Christos S.] Harvard Univ, Div Endocrinol Diabet & Metab, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Chamberland, John P.; Mantzoros, Christos S.] Harvard Univ, Endocrinol Sect, Boston VA Healthcare Syst, Sch Med, Boston, MA 02215 USA. [Tseleni-Balafouta, Sofia] Univ Athens, Dept Pathol, Fac Med, Athens, Greece. RP Mantzoros, CS (reprint author), Harvard Univ, Div Endocrinol Diabet & Metab, Beth Israel Deaconess Med Ctr, Sch Med, FD-876,330 Brookline Ave, Boston, MA 02215 USA. EM cmantzor@bidmc.harvard.edu RI Aronis, Konstantinos/F-3586-2012; Moon, Hyun-Seuk/G-8576-2015; OI Aronis, Konstantinos/0000-0001-7189-8434; Moon, Hyun-Seuk/0000-0002-5216-2090; Chamberland, John/0000-0002-7862-1371 FU NIH [DK081913]; VA Merit award; Beth Israel Deaconess Medical Center FX This work was supported by the NIH (DK081913) and a VA Merit award. The Mantzoros Laboratory is also supported by a discretionary grant from Beth Israel Deaconess Medical Center. NR 20 TC 32 Z9 37 U1 1 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2011 VL 10 IS 12 BP 2234 EP 2243 DI 10.1158/1535-7163.MCT-11-0545 PG 10 WC Oncology SC Oncology GA 865XO UT WOS:000298344400003 PM 21980131 ER PT J AU Cloninger, C Bernath, A Bashir, T Holmes, B Artinian, N Ruegg, T Anderson, L Masri, J Lichtenstein, A Gera, J AF Cloninger, Cheri Bernath, Andrew Bashir, Tariq Holmes, Brent Artinian, Nicholas Ruegg, Teresa Anderson, Lauren Masri, Janine Lichtenstein, Alan Gera, Joseph TI Inhibition of SAPK2/p38 Enhances Sensitivity to mTORC1 Inhibition by Blocking IRES-Mediated Translation Initiation in Glioblastoma SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID ACTIVATED PROTEIN-KINASE; P38 MAP KINASE; NUCLEAR RIBONUCLEOPROTEIN A1; SIGNAL-REGULATING KINASE-1; ENDOTHELIAL GROWTH-FACTOR; MAMMALIAN TARGET; CYCLIN D1; MULTIPLE-MYELOMA; AKT ACTIVITY; RAPAMYCIN AB A variety of mechanisms confer hypersensitivity of tumor cells to the macrolide rapamycin, the prototypic mTORC1 inhibitor. Several studies have shown that the status of the AKT kinase plays a critical role in determining hypersensitivity. Cancer cells in which AKT activity is elevated are exquisitely sensitive to mTORC1 inhibitors while cells in which the kinase is quiescent are relatively resistant. Our previous work has shown that a transcript-specific protein synthesis salvage pathway is operative in cells with quiescent AKT levels, maintaining the translation of crucial mRNAs involved in cell-cycle progression in the face of global eIF-4E-mediated translation inhibition. The activation of this salvage pathway is dependent on SAPK2/p38-mediated activation of IRES-dependent initiation of the cyclin D1 and c-MYC mRNAs, resulting in the maintenance of their protein expression levels. Here, we show that both genetic and pharmacologic inhibition of SAPK2/p38 in glioblastoma multiforme cells significantly reduces rapamycin-induced IRES-mediated translation initiation of cyclin D1 and c-MYC, resulting in increased G(1) arrest in vitro and inhibition of tumor growth in xenografts. Moreover, we observed that the AKT-dependent signaling alterations seen in vitro are also displayed in engrafted tumors cells and were able to show that combined inhibitor treatments markedly reduced the mRNA translational state of cyclin D1 and c-MYC transcripts in tumors isolated from mice. These data support the combined use of SAPK2/p38 and mTORC1 inhibitors to achieve a synergistic antitumor therapeutic response, particularly in rapamycin-resistant quiescent AKT-containing cells. Mol Cancer Ther; 10(12); 2244-56. (C)2011 AACR. C1 [Cloninger, Cheri; Bernath, Andrew; Bashir, Tariq; Holmes, Brent; Artinian, Nicholas; Ruegg, Teresa; Anderson, Lauren; Masri, Janine; Lichtenstein, Alan; Gera, Joseph] Greater Los Angeles Vet Affairs Healthcare Syst, Dept Res & Dev, Los Angeles, CA USA. [Lichtenstein, Alan; Gera, Joseph] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Lichtenstein, Alan; Gera, Joseph] Jonsson Comprehens Canc Ctr, Los Angeles, CA 90034 USA. [Gera, Joseph] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90024 USA. RP Gera, J (reprint author), Greater Los Angeles VA Healthcare Syst, Dept Res & Dev, 16111 Plummer St 151, Sepulveda, CA 91343 USA. EM jgera@mednet.ucla.edu FU NIH [CA16042, AI28697, R01CA111448, R01CA109312]; Jonsson Comprehensive Cancer Center; UCLA AIDS Institute; David Geffen School of Medicine at UCLA; Veterans Administration FX We thank members of the Lichtenstein and Gera labs for helpful discussions and Dr. Robert Nishimura for comments on the manuscript. We also thank Alex Funk and Jonathan Li for technical assistance. Flow cytometry was performed in the UCLA Jonsson Comprehensive Cancer Center and Center for AIDS Research, Janis Giorgi Flow Cytometry Core Facility (supported by NIH grants CA16042 and AI28697 and by the Jonsson Comprehensive Cancer Center, the UCLA AIDS Institute and the David Geffen School of Medicine at UCLA). We thank Ardella Sherwood for excellent administrative assistance.; This work was supported, in whole or in part, by NIH grants R01CA111448 (A. Lichtenstein), R01CA109312 (J. Gera), and funds from the Veterans Administration. NR 41 TC 8 Z9 8 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2011 VL 10 IS 12 BP 2244 EP 2256 DI 10.1158/1535-7163.MCT-11-0478 PG 13 WC Oncology SC Oncology GA 865XO UT WOS:000298344400004 PM 21911485 ER PT J AU Jin, JF Samuvel, DJ Zhang, XM Li, YC Lu, ZY Lopes-Virella, MF Huang, Y AF Jin, Junfei Samuvel, Devadoss J. Zhang, Xiaoming Li, Yanchun Lu, Zhongyang Lopes-Virella, Maria F. Huang, Yan TI Coactivation of TLR4 and TLR2/6 coordinates an additive augmentation on IL-6 gene transcription via p38MAPK pathway in U937 mononuclear cells SO MOLECULAR IMMUNOLOGY LA English DT Article DE Toll-like receptor; Interleukin 6; p38 mitogen-activated protein kinase; Inflammation ID ACTIVATED PROTEIN-KINASE; TOLL-LIKE RECEPTOR-2; NF-KAPPA-B; P38 MAPK; ASP299GLY POLYMORPHISM; SIGNALING PATHWAYS; INSULIN-RESISTANCE; MMP-1 EXPRESSION; DENDRITIC CELLS; TNF-ALPHA AB Studies have demonstrated that TLR4 and TLR2 expression by monocytes and the blood levels of TLR4 and TLR2 ligand in diabetic patients are significantly incased compared to nondiabetic patients, indicating that more monocytes in diabetic patients may have coactivation of TLR4 and TLR2. Although it has been shown that either TLR4 or TLR2 activation leads to increased expression of proinflammatory cytokines, the effect of coactivation of TLR2 and TLR4 in mononuclear cells on proinflammatory cytokine expression and the underlying molecular mechanisms remain largely unknown. In this study, we found that while TLR1, TLR2, TLR4 and TLR6 were expressed by U937 mononuclear cells, TLR4 was expressed at the highest level. Interestingly, results showed that while activation of either TLR4 or TLR2/6 (TLR2dimerized with TLR6), but not TLR2/1 (TLR2dimerized with TLR1), significantly increased IL-6 expression by U937 mononuclear cells, coactivation of TLR4 and TLR2/6, but not TLR4 and TLR2/1, led to a further augmentation on IL-6 expression by increasing IL-6 transcriptional activity, but not mRNA stability. To explore the signaling mechanisms involved in the augmentation, we found that p38MAPK and NF kappa B pathways, but not ERK and JNK pathways, were required for the augmentation of IL-6 expression by coactivation of TLR4 and TLR2/6. Furthermore, we found that coactivation of TLR4 and TLR2/6 increased p38 phosphorylation, but not NFkB activity, as compared to activation of TLR4or TLR2/6 alone. Taken together, this study showed that coactivation of TLR4 and TLR2/6 coordinates an additive augmentation of IL-6 gene transcription via p38MAPK pathway in U937 mononuclear cells. Published by Elsevier Ltd. C1 [Lopes-Virella, Maria F.; Huang, Yan] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. [Jin, Junfei; Samuvel, Devadoss J.; Zhang, Xiaoming; Li, Yanchun; Lu, Zhongyang; Lopes-Virella, Maria F.; Huang, Yan] Med Univ S Carolina, Div Endocrinol Diabet & Med Genet, Dept Med, Charleston, SC 29425 USA. RP Huang, Y (reprint author), Med Univ S Carolina, Div Endocrinol Diabet & Med Genet, Dept Med, 114 Doughty St, Charleston, SC 29403 USA. EM huangyan@musc.edu FU NIH [DE016353]; Department of Veterans Affairs FX This work was supported by NIH grant DE016353 and a Merit Review Grant from Department of Veterans Affairs (to Y.H.). NR 52 TC 16 Z9 16 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD DEC PY 2011 VL 49 IS 3 BP 423 EP 432 DI 10.1016/j.molimm.2011.08.026 PG 10 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 872AV UT WOS:000298779700002 PM 22030478 ER PT J AU Sharma, SK Chiang, LY Hamblin, MR AF Sharma, Sulbha K. Chiang, Long Y. Hamblin, Michael R. TI Photodynamic therapy with fullerenes in vivo: reality or a dream? SO NANOMEDICINE LA English DT Article DE antimicrobial photosensitizers; functionalized fullerenes; hydroxyl radicals; invasive wound infection; mouse models; peritoneal carcinomatosis; photodynamic therapy; singlet oxygen ID 2-PHOTON EXCITATION; SUBACUTE TOXICITY; ELECTRON-TRANSFER; MALONIC-ACID; C-60; WATER; DERIVATIVES; CANCER; CELLS; BUCKMINSTERFULLERENE AB Photodynamic therapy (PDT) employs the combination of nontoxic photosensitizers and visible light that is absorbed by the chromophore to produce long-lived triplet states that can carry out photochemistry in the presence of oxygen to kill cells. The closed carbon-cage structure found in fullerenes can act as a photosensitizer, especially when functionalized to impart water solubility. Although there are reports of the use of fullerenes to carry out light-mediated destruction of viruses, microorganisms and cancer cells in vitro, the use of fullerenes to mediate PDT of diseases such as cancer and infections in animal models is less well developed. It has recently been shown that fullerene PDT can be used to save the life of mice with wounds infected with pathogenic Gram-negative bacteria. Fullerene PDT has also been used to treat mouse models of various cancers including disseminated metastatic cancer in the peritoneal cavity. In vivo PDT with fullerenes represents a new application in nanomedicine. C1 [Sharma, Sulbha K.; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Chiang, Long Y.] Univ Massachusetts, Dept Chem, Lowell, MA USA. [Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu OI Hamblin, Michael/0000-0001-6431-4605 FU NIH [R01AI050875, R01CA137108, R44CA103177] FX This work was funded by the NIH (grants R01AI050875 to MR Hamblin; R01CA137108 to LY Chiang and R44CA103177 to Lynntech Inc.). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 92 TC 59 Z9 61 U1 5 U2 50 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1743-5889 J9 NANOMEDICINE-UK JI Nanomedicine PD DEC PY 2011 VL 6 IS 10 BP 1813 EP 1825 DI 10.2217/NNM.11.144 PG 13 WC Biotechnology & Applied Microbiology; Nanoscience & Nanotechnology SC Biotechnology & Applied Microbiology; Science & Technology - Other Topics GA 867XW UT WOS:000298489100016 PM 22122587 ER PT J AU O'Donnell, MA Perez-Jimenez, E Oberst, A Ng, A Massoumi, R Xavier, R Green, DR Ting, AT AF O'Donnell, Marie Anne Perez-Jimenez, Eva Oberst, Andrew Ng, Aylwin Massoumi, Ramin Xavier, Ramnik Green, Douglas R. Ting, Adrian T. TI Caspase 8 inhibits programmed necrosis by processing CYLD SO NATURE CELL BIOLOGY LA English DT Article ID RECEPTOR-INTERACTING PROTEIN; CELL-DEATH PATHWAY; TNF-ALPHA; NECROTIC CELLS; T-CELLS; APOPTOSIS; RIP1; ACTIVATION; REGULATOR; PHOSPHATIDYLSERINE AB Caspase 8 initiates apoptosis downstream of TNF death receptors by undergoing autocleavage and processing the executioner caspase 3 (ref. 1). However, the dominant function of caspase 8 is to transmit a pro-survival signal that suppresses programmed necrosis (or necroptosis) mediated by RIPK1 and RIPK3 (refs 2-6) during embryogenesis and haematopoiesis(7-9). Suppression of necrotic cell death by caspase 8 requires its catalytic activity but not the autocleavage essential for apoptosis(10); however, the key substrate processed by caspase 8 to block necrosis has been elusive. A key substrate must meet three criteria: it must be essential for programmed necrosis; it must be cleaved by caspase 8 in situations where caspase 8 is blocking necrosis; and mutation of the caspase 8 processing site on the substrate should convert a pro-survival response to necrotic death without the need for caspase 8 inhibition. We now identify CYLD as a substrate for caspase 8 that satisfies these criteria. Following TNF stimulation, caspase 8 cleaves CYLD to generate a survival signal. In contrast, loss of caspase 8 prevented CYLD degradation, resulting in necrotic death. A CYLD substitution mutation at Asp 215 that cannot be cleaved by caspase 8 switches cell survival to necrotic cell death in response to TNF. C1 [O'Donnell, Marie Anne; Perez-Jimenez, Eva; Ting, Adrian T.] Mt Sinai Sch Med, Inst Immunol, New York, NY 10029 USA. [Oberst, Andrew; Green, Douglas R.] St Jude Childrens Hosp, Dept Immunol, Memphis, TN 38105 USA. [Ng, Aylwin; Xavier, Ramnik] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Massoumi, Ramin] Lund Univ, Dept Lab Med, Clin Res Ctr, SE-205 Malmo, Sweden. RP O'Donnell, MA (reprint author), Mt Sinai Sch Med, Inst Immunol, New York, NY 10029 USA. EM marie.a.odonnell@mssm.edu; adrian.ting@mssm.edu RI Knecht, Erwin/A-9366-2014; Perez-Jimenez, Eva/K-4345-2014 OI Perez-Jimenez, Eva/0000-0001-7076-9577 FU National Institutes of Health [AI052417, AI44828]; Crohn's and Colitis Foundation of America; Irma T. Hirschl Career Scientist Award FX We are indebted to a number of colleagues for providing reagents used in these studies. We thank X. Wang (UT Southwestern, Dallas, Texas, USA) for his gift of SMAC mimetics and human RIPK3 antibody, M. Kelliher (UMASS, Worcester, Massachusetts, USA) for Ripk1+/+ and Ripk1-/- MEFs, J. Chipuk (Mount Sinai School of Medicine, New York, USA) for suggesting the use of MCF7 cells and S. Aaronson (Mount Sinai School of Medicine, New York, USA) for providing these cells. This work was supported by National Institutes of Health grants AI052417 (A.T.T.) and AI44828 (D.R.G.). M.A.O'D. is a recipient of a Research Fellowship Award from the Crohn's and Colitis Foundation of America. A.T.T. is a recipient of the Irma T. Hirschl Career Scientist Award. NR 33 TC 178 Z9 182 U1 4 U2 30 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD DEC PY 2011 VL 13 IS 12 BP 1437 EP U132 DI 10.1038/ncb2362 PG 17 WC Cell Biology SC Cell Biology GA 863JB UT WOS:000298157500011 PM 22037414 ER PT J AU Pinheiro, AV Han, DR Shih, WM Yan, H AF Pinheiro, Andre V. Han, Dongran Shih, William M. Yan, Hao TI Challenges and opportunities for structural DNA nanotechnology SO NATURE NANOTECHNOLOGY LA English DT Review ID DOUBLE-CROSSOVER MOLECULES; GOLD NANOPARTICLE ARRAYS; CONDUCTIVE NANOWIRES; ORIGAMI NANOTUBES; HIGH-THROUGHPUT; PROTEIN ARRAYS; PHOTONIC WIRES; FINITE-SIZE; NANOSTRUCTURES; SINGLE AB DNA molecules have been used to build a variety of nanoscale structures and devices over the past 30 years, and potential applications have begun to emerge. But the development of more advanced structures and applications will require a number of issues to be addressed, the most significant of which are the high cost of DNA and the high error rate of self-assembly. Here we examine the technical challenges in the field of structural DNA nanotechnology and outline some of the promising applications that could be developed if these hurdles can be overcome. In particular, we highlight the potential use of DNA nanostructures in molecular and cellular biophysics, as biomimetic systems, in energy transfer and photonics, and in diagnostics and therapeutics for human health. C1 [Pinheiro, Andre V.; Han, Dongran; Yan, Hao] Arizona State Univ, Biodesign Inst, Ctr Single Mol Biophys, Tempe, AZ 85287 USA. [Han, Dongran; Yan, Hao] Arizona State Univ, Dept Chem & Biochem, Tempe, AZ 85287 USA. [Shih, William M.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Shih, William M.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Shih, William M.] Harvard Univ, Wyss Inst Biol Inspired Engn, Cambridge, MA 02138 USA. RP Pinheiro, AV (reprint author), Arizona State Univ, Biodesign Inst, Ctr Single Mol Biophys, Tempe, AZ 85287 USA. EM William_Shih@dfci.harvard.edu; hao.yan@asu.edu FU Office of Naval Research (ONR); Army Research office; National Science Foundation; National Institutes of Health (NIH); Department of Energy; Arizona State University; Agilent Technologies; Wyss Institute for Biologically Inspired Engineering FX We thank K. Gothelf and T. LaBean for discussions. H.Y. acknowledges funding support from the Office of Naval Research (ONR), the Army Research office, the National Science Foundation, the National Institutes of Health (NIH), the Department of Energy, Sloan Research Fellowship and Arizona State University. W.M.S acknowledges funding support from ONR, NIH, Agilent Technologies and the Wyss Institute for Biologically Inspired Engineering. We also thank J. Nangreave for proofreading the manuscript. NR 150 TC 449 Z9 453 U1 83 U2 571 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1748-3387 J9 NAT NANOTECHNOL JI Nat. Nanotechnol. PD DEC PY 2011 VL 6 IS 12 BP 763 EP 772 DI 10.1038/NNANO.2011.187 PG 10 WC Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Science & Technology - Other Topics; Materials Science GA 864OA UT WOS:000298248300007 PM 22056726 ER PT J AU Ogino, S Galon, J Fuchs, CS Dranoff, G AF Ogino, Shuji Galon, Jerome Fuchs, Charles S. Dranoff, Glenn TI Cancer immunology-analysis of host and tumor factors for personalized medicine SO NATURE REVIEWS CLINICAL ONCOLOGY LA English DT Review ID ISLAND METHYLATOR PHENOTYPE; CELL LUNG-CANCER; MOLECULAR PATHOLOGICAL EPIDEMIOLOGY; MICROSATELLITE-INSTABILITY STATUS; METASTATIC COLORECTAL-CANCER; DEFECTIVE MISMATCH REPAIR; RESISTANT PROSTATE-CANCER; POPULATION-BASED SAMPLE; NEGATIVE BREAST-CANCER; RESECTED COLON-CANCER AB Immune cells in the tumor microenvironment have an important role in regulating tumor progression. Therefore, stimulating immune reactions to tumors can be an attractive therapeutic and prevention strategy. Cancer cells and host cells constantly interact with each other in the tumor microenvironment; thus, cancer immunology is an interdisciplinary area where integrated analysis of both host and tumor factors is needed. Cancer represents a heterogeneous group of diseases with different genetic and epigenetic alterations; therefore, molecular classification of cancer (for example lung, prostate and breast cancers) is an important component in clinical decision making. However, most studies on antitumor immunity and clinical outcome lack analysis of tumor molecular biomarkers. In this Review, we discuss colorectal cancer as a prototypical example of cancer. Common molecular classifiers of colon cancer include KRAS, BRAF and PIK3CA mutations, microsatellite instability, LINE-1 methylation, and CpG island methylator phenotype. Since tumor molecular features and immune reactions are inter-related, a comprehensive assessment of these factors is critical. Examining the effects of tumor-host interactions on clinical outcome and prognosis represents an evolving interdisciplinary field of molecular pathological epidemiology. Pathological immunity evaluation may provide information on prognosis and help identify patients who are more likely to benefit from immunotherapy. C1 [Ogino, Shuji; Fuchs, Charles S.; Dranoff, Glenn] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02215 USA. [Ogino, Shuji; Fuchs, Charles S.; Dranoff, Glenn] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Galon, Jerome] Ctr Rech Cordeliers, INSERM, Integrat Canc Immunol Lab, F-75006 Paris, France. RP Ogino, S (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM shuji_ogino@dfci.harvard.edu FU US NIH [R01 CA151993, P50 CA127003]; DF/HCC GI SPORE; [R01 CA143083] FX This work was supported by grants from the US NIH (R01 CA151993 [to S. Ogino], P50 CA127003 [DF/HCC GI SPORE to C. S. Fuchs], DF/HCC GI SPORE Developmental Project Award [to S. Ogino], and R01 CA143083 [to G. Dranoff]). The content is solely the responsibility of the authors and does not necessarily represent the official views of NCI or NIH. Funding agencies did not have any role in the decision to submit the manuscript for publication, or the writing of the manuscript. NR 149 TC 112 Z9 116 U1 3 U2 42 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4774 J9 NAT REV CLIN ONCOL JI Nat. Rev. Clin. Oncol. PD DEC PY 2011 VL 8 IS 12 BP 711 EP 719 DI 10.1038/nrclinonc.2011.122 PG 9 WC Oncology SC Oncology GA 863EZ UT WOS:000298146900006 PM 21826083 ER PT J AU Shaw, AT Yasothan, U Kirkpatrick, P AF Shaw, Alice T. Yasothan, Uma Kirkpatrick, Peter TI Crizotinib SO NATURE REVIEWS DRUG DISCOVERY LA English DT Article ID CELL LUNG-CANCER; ANAPLASTIC LYMPHOMA KINASE; INHIBITORS; GENE C1 [Shaw, Alice T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Yasothan, Uma] IMS Hlth, London NW1 6JB, England. RP Shaw, AT (reprint author), Massachusetts Gen Hosp, Ctr Canc, 32 Fruit St, Boston, MA 02114 USA. EM ashaw1@partners.org; UYasothan@imscg.com; p.kirkpatrick@nature.com NR 10 TC 46 Z9 46 U1 0 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1776 EI 1474-1784 J9 NAT REV DRUG DISCOV JI Nat. Rev. Drug Discov. PD DEC PY 2011 VL 10 IS 12 BP 897 EP 898 DI 10.1038/nrd3600 PG 2 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 862TP UT WOS:000298117300013 PM 22129984 ER PT J AU Grskovic, M Javaherian, A Strulovici, B Daley, GQ AF Grskovic, Marica Javaherian, Ashkan Strulovici, Berta Daley, George Q. TI Induced pluripotent stem cells - opportunities for disease modelling and drug discovery SO NATURE REVIEWS DRUG DISCOVERY LA English DT Review ID HUMAN IPS CELLS; SPINAL MUSCULAR-ATROPHY; HUMAN SOMATIC-CELLS; LINEAGE-SPECIFIC DIFFERENTIATION; PATIENT-SPECIFIC IPSCS; HUMAN CORD BLOOD; LONG-QT SYNDROME; MOTOR-NEURONS; REPROGRAMMING FACTORS; HUMAN FIBROBLASTS AB The ability to generate induced pluripotent stem cells (iPSCs) from patients, and an increasingly refined capacity to differentiate these iPSCs into disease-relevant cell types, promises a new paradigm in drug development - one that positions human disease pathophysiology at the core of preclinical drug discovery. Disease models derived from iPSCs that manifest cellular disease phenotypes have been established for several monogenic diseases, but iPSCs can likewise be used for phenotype-based drug screens in complex diseases for which the underlying genetic mechanism is unknown. Here, we highlight recent advances as well as limitations in the use of iPSC technology for modelling a'disease in a dish' and for testing compounds against human disease phenotypes in vitro. We discuss how iPSCs are being exploited to illuminate disease pathophysiology, identify novel drug targets and enhance the probability of clinical success of new drugs. C1 [Daley, George Q.] Childrens Hosp, Manton Ctr Orphan Dis Res, Div Pediat Haematol Oncol, Stem Cell Transplantat Program, Boston, MA 02115 USA. [Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Strulovici, Berta] Weizmann Inst Sci, IL-76100 Rehovot, Israel. [Grskovic, Marica; Javaherian, Ashkan] IPierian, San Francisco, CA 94080 USA. [Grskovic, Marica; Javaherian, Ashkan; Daley, George Q.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. [Daley, George Q.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. [Daley, George Q.] Harvard Univ, Dept Biol Chem & Mol Pharmacol, Harvard Stem Cell Inst, Sch Med, Boston, MA 02115 USA. [Daley, George Q.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. RP Daley, GQ (reprint author), Childrens Hosp, Manton Ctr Orphan Dis Res, Div Pediat Haematol Oncol, Stem Cell Transplantat Program, 300 Longwood Ave, Boston, MA 02115 USA. EM George.Daley@childrens.harvard.edu NR 174 TC 199 Z9 203 U1 13 U2 130 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1776 J9 NAT REV DRUG DISCOV JI Nat. Rev. Drug Discov. PD DEC PY 2011 VL 10 IS 12 BP 915 EP 929 DI 10.1038/nrd3577 PG 15 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 862TP UT WOS:000298117300020 PM 22076509 ER PT J AU Sperling, R AF Sperling, Reisa TI The potential of functional MRI as a biomarker in early Alzheimer's disease SO NEUROBIOLOGY OF AGING LA English DT Article DE Alzheimer's disease; Biomarker; Cognitive impairment; Dementia; fMRI; Functional magnetic resonance imaging ID MILD COGNITIVE IMPAIRMENT; RESTING-STATE NETWORKS; DEFAULT-MODE NETWORK; APOLIPOPROTEIN-E EPSILON-4; TEST-RETEST RELIABILITY; HIPPOCAMPAL ACTIVATION; BRAIN ACTIVITY; OLDER-ADULTS; CHOLINERGIC ENHANCEMENT; PARIETAL DEACTIVATION AB Functional magnetic resonance imaging (fMRI) is a relative newcomer in the field of biomarkers for Alzheimer's disease (AD). fMRI has several potential advantages, particularly for clinical trials, as it is a noninvasive imaging technique that does not require the injection of contrast agent or radiation exposure and thus can be repeated many times during a longitudinal study. fMRI has relatively high spatial and reasonable temporal resolution, and can be acquired in the same session as structural magnetic resonance imaging. Perhaps most importantly, fMRI may provide useful information about the functional integrity of brain networks supporting memory and other cognitive domains, including the neural correlates of specific behavioral events, such as successful versus failed memory formation. (C) 2011 Elsevier Inc. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Brigham & Womens Hosp, Sch Med,Ctr Alzheimer Res & Treatment, Boston, MA 02115 USA. RP Sperling, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Brigham & Womens Hosp, Sch Med,Ctr Alzheimer Res & Treatment, 221 Longwood Ave, Boston, MA 02115 USA. EM reisa@rics.bwh.harvard.edu FU NIA NIH HHS [K24 AG035007, K24 AG035007-02, P01 AG036694, P01 AG036694-02, P50 AG005134, P50 AG005134-29] NR 96 TC 43 Z9 44 U1 5 U2 24 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD DEC PY 2011 VL 32 SU 1 BP S37 EP S43 DI 10.1016/j.neurobiolaging.2011.09.009 PG 7 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 860EW UT WOS:000297932600005 PM 22078171 ER PT J AU Pelak, VS Smyth, SF Boyer, PJ Filley, CM AF Pelak, Victoria S. Smyth, Shawn F. Boyer, Philip J. Filley, Christopher M. TI Computerized visual field defects in posterior cortical atrophy SO NEUROLOGY LA English DT Article ID ALZHEIMERS-DISEASE; DEMENTIA; CONSORTIUM; DIAGNOSIS; SERIES AB Background and objective: Posterior cortical atrophy (PCA) is a progressive neurodegenerative syndrome that presents with cortical visual dysfunction and relatively preserved memory. Although higher cortical visual syndromes are well known in PCA, visual field defects detected by computerized visual field (CVF) perimetry have not been systematically described. The objective of this study was to describe CVF defects measured by threshold perimetry in PCA. Methods: This was a retrospective case series of patients meeting proposed PCA diagnostic criteria seen in the Neuro-ophthalmology and Neurobehavior Clinics at the University of Colorado during 2002 to 2006. History, examination, neuroimaging, autopsy, and CVF studies were analyzed. Results: Nine of 11 patients who met the criteria for PCA and had CVF testing were included. Seven of the 9 patients had homonymous hemianopia or quadrantanopia, and 2 had bilateral constriction. All patients progressed to dementia. Criteria were met for probable Alzheimer disease (AD) in 7, definite AD in 1, and definite dementia with Lewy bodies associated with AD pathology in 1. Seven of 9 patients had early and prominent complaints of difficulty driving. Conclusions: CVF defects were characterized by homonymous visual field defects or bilateral constriction. Eight of 9 patients progressed to probable or definite AD, but the CVF defects were distinctly different from those in typical AD. This observation probably reflects a posterior shift of cortical pathology to the primary and early secondary visual cortices in PCA. CVF testing should be considered in older patients with unexplained visual complaints, particularly when associated with difficulty driving, which may indicate the possibility of PCA and prompt early neurobehavioral evaluation. Neurology (R) 2011; 77:2119-2122 C1 [Pelak, Victoria S.; Smyth, Shawn F.; Filley, Christopher M.] Univ Colorado Denver Sch Med, Dept Neurol, Denver, CO USA. [Boyer, Philip J.] Univ Colorado Denver Sch Med, Dept Pathol, Denver, CO USA. [Pelak, Victoria S.] Univ Colorado Denver Sch Med, Dept Ophthalmol, Denver, CO USA. [Filley, Christopher M.] Univ Colorado Denver Sch Med, Dept Psychiat, Denver, CO USA. [Pelak, Victoria S.; Filley, Christopher M.] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Pelak, VS (reprint author), Acad Off 1,Mailstop B185,12631 E 17th Ave,Room 52, Aurora, CO 80045 USA. EM victoria.pelak@ucdenver.edu FU UpToDate, Inc.; NIH; Alzheimer's Association; University Press of Colorado; Behavioral Neurology of White Matter (Oxford University Press); University of Colorado Alzheimer's Disease and Cognition Center (ADCC); NIH/NIAMSD FX Dr. Pelak receives publishing royalties from UpToDate, Inc.; serves as a consultant for Anthem Blue Cross and Blue Shield; receives research support from the NIH and the Alzheimer's Association; and has given expert testimony in medico-legal cases. Dr. Smyth reports no disclosures. Dr. Boyer serves on the editorial board of the Journal of Pathology Informatics and has given expert testimony in medico-legal cases. Dr. Filley receives publishing royalties for Neurobehavioral Anatomy, 2nd ed.(University Press of Colorado, 2001) and The Behavioral Neurology of White Matter (Oxford University Press, 2001); receives research support from University of Colorado Alzheimer's Disease and Cognition Center (ADCC), Alzheimer's Association, and the NIH/NIAMSD; and has given expert testimony in medico-legal cases. NR 18 TC 12 Z9 12 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC PY 2011 VL 77 IS 24 BP 2119 EP 2122 DI 10.1212/WNL.0b013e31823e9f2a PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 865PT UT WOS:000298323500015 PM 22131540 ER PT J AU McGinnis, KA Brandt, CA Skanderson, M Justice, AC Shahrir, S Butt, AA Brown, ST Freiberg, MS Gibert, CL Goetz, MB Kim, JW Pisani, MA Rimland, D Rodriguez-Barradas, MC Sico, JJ Tindle, HA Crothers, K AF McGinnis, Kathleen A. Brandt, Cynthia A. Skanderson, Melissa Justice, Amy C. Shahrir, Shahida Butt, Adeel A. Brown, Sheldon T. Freiberg, Matthew S. Gibert, Cynthia L. Goetz, Matthew Bidwell Kim, Joon Woo Pisani, Margaret A. Rimland, David Rodriguez-Barradas, Maria C. Sico, Jason J. Tindle, Hilary A. Crothers, Kristina TI Validating Smoking Data From the Veteran's Affairs Health Factors Dataset, an Electronic Data Source SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID HIV-NEGATIVE VETERANS; INFECTION; MORTALITY; COHORT; DISEASE; SYSTEM; IMPACT AB We assessed smoking data from the Veterans Health Administration (VHA) electronic medical record (EMR) Health Factors dataset. To assess the validity of the EMR Health Factors smoking data, we first created an algorithm to convert text entries into a 3-category smoking variable (never, former, and current). We compared this EMR smoking variable to 2 different sources of patient self-reported smoking survey data: (a) 6,816 HIV-infected and -uninfected participants in the 8-site Veterans Aging Cohort Study (VACS-8) and (b) a subset of 13,689 participants from the national VACS Virtual Cohort (VACS-VC), who also completed the 1999 Large Health Study (LHS) survey. Sensitivity, specificity, and kappa statistics were used to evaluate agreement of EMR Health Factors smoking data with self-report smoking data. For the EMR Health Factors and VACS-8 comparison of current, former, and never smoking categories, the kappa statistic was .66. For EMR Health Factors and VACS-VC/LHS comparison of smoking, the kappa statistic was .61. Based on kappa statistics, agreement between the EMR Health Factors and survey sources is substantial. Identification of current smokers nationally within the VHA can be used in future studies to track smoking status over time, to evaluate smoking interventions, and to adjust for smoking status in research. Our methodology may provide insights for other organizations seeking to use EMR data for accurate determination of smoking status. C1 [McGinnis, Kathleen A.; Skanderson, Melissa] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15206 USA. [Brandt, Cynthia A.; Justice, Amy C.; Sico, Jason J.] VA Connecticut Healthcare Syst, West Haven, CT USA. [Brandt, Cynthia A.] Yale Univ, Sch Med, Dept Emergency Med, New Haven, CT USA. [Justice, Amy C.; Pisani, Margaret A.] Yale Univ, Dept Med, New Haven, CT 06520 USA. [Shahrir, Shahida; Crothers, Kristina] Univ Washington, Harborview Med Ctr, Dept Med, Seattle, WA 98104 USA. [Butt, Adeel A.; Freiberg, Matthew S.; Tindle, Hilary A.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA USA. [Brown, Sheldon T.; Kim, Joon Woo] James J Peterson VAMC, Bronx, NY USA. [Gibert, Cynthia L.] VA Med Ctr, Washington, DC USA. [Goetz, Matthew Bidwell] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Goetz, Matthew Bidwell] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Rimland, David] Emory Univ, Sch Med, Atlanta, GA USA. [Rimland, David] VA Med Ctr, Atlanta, GA USA. [Rodriguez-Barradas, Maria C.] Michael E DeBakey VAMC, Infect Dis Sect, Houston, TX USA. [Rodriguez-Barradas, Maria C.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Sico, Jason J.] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA. RP McGinnis, KA (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, 7180 Highland Dr 151C-H, Pittsburgh, PA 15206 USA. EM kathleen.mcginnis3@va.gov OI Goetz, Matthew/0000-0003-4542-992X FU VAHS HSRD [RCD 04-125-1]; National Institute on Aging (NIA) [K08 AG00826]; National Institute of Mental Health; National Institute on Alcohol Abuse and Alcoholism [U01-13566]; NIH/NHLBI [1R01 HL090342] FX Supported by VAHS HSR&D RCD 04-125-1, NIA K08 AG00826, an interagency agreement between the National Institute on Aging and the National Institute of Mental Health, and the National Institute on Alcohol Abuse and Alcoholism (Grant No. U01-13566; ACJ); NIH/NHLBI 1R01 HL090342 (KC). NR 23 TC 37 Z9 37 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD DEC PY 2011 VL 13 IS 12 BP 1233 EP 1239 DI 10.1093/ntr/ntr206 PG 7 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 852RY UT WOS:000297376400009 PM 21911825 ER PT J AU Powis, KM Kitch, D Ogwu, A Hughes, MD Lockman, S Leidner, J van Widenfelt, E Moffat, C Moyo, S Makhema, J Essex, M Shapiro, RL AF Powis, Kathleen M. Kitch, Douglas Ogwu, Anthony Hughes, Michael D. Lockman, Shahin Leidner, Jean van Widenfelt, Erik Moffat, Claire Moyo, Sikhulile Makhema, Joseph Essex, Max Shapiro, Roger L. TI Increased Risk of Preterm Delivery Among HIV-Infected Women Randomized to Protease Versus Nucleoside Reverse Transcriptase Inhibitor-Based HAART During Pregnancy EDITORIAL COMMENT SO OBSTETRICAL & GYNECOLOGICAL SURVEY LA English DT Editorial Material AB The World Health Organization recommends the use of highly active antiretroviral therapy (HAART) for prevention of mother-to-child transmission of human immunodeficiency virus during pregnancy and breast-feeding. Some observational studies have reported that use of protease inhibitor (PI)-based HAART is associated with preterm delivery, but others have reported no such association. This retrospective analysis of a previously published randomized trial was designed to determine whether the use of PI for prevention of mother-to-child transmission in late pregnancy increases the risk for preterm delivery (<37 weeks' gestation). Maternal weight gain in late pregnancy was also evaluated as a potentially associated risk factor for preterm delivery. The study subjects were 560 human immunodeficiency virus-infected, HAART-naive pregnant women with CD4+ counts (plus is superior) >= 200 cells/mm(3). Between 26 and 34 weeks of gestation, the women were randomized to receive either lopinavir/ritonavir/zidovudine/lamivudine (PI group, n = 267) or abacavir/zidovudine/lamivudine (nucleoside reverse transcriptase inhibitor [NRTI] group, n = 263). With univariate analysis, the rate of preterm delivery was found to be significantly higher in the PI group compared with the NRTI group (21.4% vs. 11.8%, P = 0 0.003). Multivariate analysis showed that use of the PI-based HAART regimen was associated with a 2-fold higher rate of preterm delivery compared with the NRTI-based regimen; the adjusted odds ratio was 2.02, with a 95% confidence interval of 1.26 to 3.27; P = 0.004. The mean change in maternal body mass index 1 month after HAART initiation (surrogate for weight gain) was significantly lower in the PI group than in the NRTI group (P < 0.001). The reduced weight gain, however, was not significantly associated with preterm delivery. There was no difference in the frequency of infant hospitalizations or mortality between the regimens until 6 months of life. These findings show an association between use of a PI-based HAART regimen in late pregnancy and preterm delivery. C1 [Powis, Kathleen M.] Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. Brigham & Womens Hosp, Infect Dis Unit, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA. Botswana Harvard AIDS Inst Partnership, Gaborone, Botswana. RP Powis, KM (reprint author), Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. RI Moyo, Sikhulile/E-1464-2015 OI Moyo, Sikhulile/0000-0003-3821-4592 NR 1 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7828 J9 OBSTET GYNECOL SURV JI Obstet. Gynecol. Surv. PD DEC PY 2011 VL 66 IS 12 BP 751 EP 753 DI 10.1097/OGX.0b013e3182402506 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 870IN UT WOS:000298662700009 ER PT J AU Udayakumar, D Zhang, G Ji, Z Njauw, CN Mroz, P Tsao, H AF Udayakumar, D. Zhang, G. Ji, Z. Njauw, C-N Mroz, P. Tsao, H. TI Epha2 is a critical oncogene in melanoma SO ONCOGENE LA English DT Article DE melanoma; EphA2; survival ID RECEPTOR TYROSINE KINASE; VASCULOGENIC MIMICRY; PROSTATE-CANCER; CELL-MIGRATION; OVARIAN-CANCER; TUMOR-CELLS; OVEREXPRESSION; EXPRESSION; INVASION; GROWTH AB EphA2 is a member of the Eph family of receptor tyrosine kinases and is highly expressed in many aggressive cancer types, including melanoma. We recently showed that EphA2 is also upregulated by ultraviolet radiation and is able to induce apoptosis. These findings suggest that EphA2 may have different, even paradoxical, effects on viability depending on the cellular context and that EphA2 mediates a delicate balance between life and death of the cell. To functionally clarify EphA2's role in melanoma, we analyzed a panel of melanoma cell lines and found that EphA2 levels are elevated in a significant fraction of the samples. Specific depletion of EphA2 in high-expressing melanoma cells using short hairpin RNA led to profound reductions in cellular viability, colony formation and migration in vitro and a dramatic loss of tumorigenic potential in vivo. Stable introduction of EphA2 into low-expressing cell lines enhanced proliferation, colony formation and migration, further supporting its pro-malignant phenotype. Interestingly, transient expression of EphA2 and/or Braf(V600E) in non-transformed melanocytes led to significant and additive apoptosis. These results verify that EphA2 is an important oncogene and potentially a common source of 'addiction' for many melanoma cells. Moreover, acute induction of EphA2 may purge genetically susceptible cells, thereby uncovering a more aggressive population that is in fact dependent on the oncogene. Oncogene (2011) 30, 4921-4929; doi:10.1038/onc.2011.210; published online 13 June 2011 C1 [Udayakumar, D.; Ji, Z.; Mroz, P.; Tsao, H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA 02114 USA. [Udayakumar, D.; Ji, Z.; Njauw, C-N; Mroz, P.; Tsao, H.] Massachusetts Gen Hosp, Dept Dermatol, Wellman Ctr Photomed, Boston, MA 02114 USA. [Zhang, G.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Surg,Ctr Vasc Biol Res, Boston, MA 02114 USA. [Tsao, H.] Massachusetts Gen Hosp, Melanoma & Pigmented Les Ctr, Boston, MA 02114 USA. RP Tsao, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Bartlett 622,48 Blossom St, Boston, MA 02114 USA. EM htsao@partners.org FU National Institutes of Health [1R21ES013964]; Dermatology Foundation; American Skin Association; Melanoma Research Alliance FX This work was supported by the National Institutes of Health (1R21ES013964; HT), the Dermatology Foundation (DU), the American Skin Association (HT and DU), the Melanoma Research Alliance (to HT) and the generous philanthropic donors at MGH. We thank Dr Jie Zhao and other members of the Wellman Center Pathology core facility for their help with the tissue sections and confocal analysis. We also thank Dr Michael Hamblin for his support in mice tumor studies. NR 41 TC 36 Z9 38 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD DEC PY 2011 VL 30 IS 50 BP 4921 EP 4929 DI 10.1038/onc.2011.210 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 865YJ UT WOS:000298346500001 PM 21666714 ER PT J AU Aiello, LP Beck, RW Bressler, NM Browning, DJ Chalam, KV Davis, M Ferris, FL Glassman, AR Maturi, RK Stockdale, CR Topping, TM AF Aiello, Lloyd Paul Beck, Roy W. Bressler, Neil M. Browning, David J. Chalam, K. V. Davis, Matthew Ferris, Frederick L., III Glassman, Adam R. Maturi, Raj K. Stockdale, Cynthia R. Topping, Trexler M. CA Diabetic Retinopathy Clinical Res TI Rationale for the Diabetic Retinopathy Clinical Research Network Treatment Protocol for Center-Involved Diabetic Macular Edema SO OPHTHALMOLOGY LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; LASER; PHOTOCOAGULATION AB Objective: To describe the underlying principles used to develop a web-based algorithm that incorporated intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment for diabetic macular edema (DME) in a Diabetic Retinopathy Clinical Research Network (DRCR.net) randomized clinical trial. Design: Discussion of treatment protocol for DME. Participants: Subjects with vision loss resulting from DME involving the center of the macula. Methods: The DRCR.net created an algorithm incorporating anti-VEGF injections in a comparative effectiveness randomized clinical trial evaluating intravitreal ranibizumab with prompt or deferred (>= 24 weeks) focal/grid laser treatment in eyes with vision loss resulting from center-involved DME. Results confirmed that intravitreal ranibizumab with prompt or deferred laser provides superior visual acuity outcomes compared with prompt laser alone through at least 2 years. Duplication of this algorithm may not be practical for clinical practice. To share their opinion on how ophthalmologists might emulate the study protocol, participating DRCR.net investigators developed guidelines based on the algorithm's underlying rationale. Main Outcome Measures: Clinical guidelines based on a DRCR.net protocol. Results: The treatment protocol required real-time feedback from a web-based data entry system for intravitreal injections, focal/grid laser treatment, and follow-up intervals. Guidance from this system indicated whether treatment was required or given at investigator discretion and when follow-up should be scheduled. Clinical treatment guidelines, based on the underlying clinical rationale of the DRCR.net protocol, include repeating treatment monthly as long as there is improvement in edema compared with the previous month or until the retina is no longer thickened. If thickening recurs or worsens after discontinuing treatment, treatment is resumed. Conclusions: Duplication of the approach used in the DRCR.net randomized clinical trial to treat DME involving the center of the macula with intravitreal ranibizumab may not be practical in clinical practice, but likely can be emulated based on an understanding of the underlying rationale for the study protocol. Inherent differences between a web-based treatment algorithm and a clinical approach may lead to differences in outcomes that are impossible to predict. The closer the clinical approach is to the algorithm used in the study, the more likely the outcomes will be similar to those published. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2011; 118: e5-e14 (C) 2011 by the American Academy of Ophthalmology. C1 [Beck, Roy W.; Glassman, Adam R.; Stockdale, Cynthia R.] Jaeb Ctr Hlth Res, Tampa, FL 33647 USA. [Aiello, Lloyd Paul] Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Ophthalmol, Boston, MA 02115 USA. [Bressler, Neil M.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA. [Browning, David J.] Charlotte Eye Ear Nose & Throat Associates PA, Charlotte, NC USA. [Chalam, K. V.] Univ Florida, Hlth Sci Ctr Jacksonville, Dept Ophthalmol, Coll Med, Jacksonville, FL 32209 USA. [Davis, Matthew] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI USA. [Ferris, Frederick L., III] NEI, NIH, Bethesda, MD 20892 USA. [Topping, Trexler M.] Ophthalm Consultants Boston, Boston, MA USA. RP Stockdale, CR (reprint author), Jaeb Ctr Hlth Res, 15310 Amberly Dr,Suite 350, Tampa, FL 33647 USA. EM drcrnetstat5@jaeb.org OI Chalam, kakarla/0000-0001-9325-8665 FU National Institutes of Health; National Eye Institute; National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, United States Department of Health and Human Services [EY14231, EY14229, EY018817] FX The funding organization (National Institutes of Health) participated in oversight of the conduct of the study and review of the manuscript but not directly in the design or conduct of the study, nor in the collection, management, analysis, or interpretation of the data, or in the preparation of the manuscript. A complete list of all DRCR.net investigator financial disclosures can be found at www.drcr.net.; Supported through a cooperative agreement from the National Eye Institute and the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, United States Department of Health and Human Services (grant nos.: EY14231, EY14229, and EY018817). NR 9 TC 33 Z9 34 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD DEC PY 2011 VL 118 IS 12 BP E5 EP E14 DI 10.1016/j.ophtha.2011.09.058 PG 10 WC Ophthalmology SC Ophthalmology GA 863BO UT WOS:000298138000001 ER PT J AU Lee, WM Yun, SH AF Lee, W. M. Yun, S. H. TI Adaptive aberration correction of GRIN lenses for confocal endomicroscopy SO OPTICS LETTERS LA English DT Article ID OPTICS; MICROSCOPE AB Graded-index (GRIN) lenses serve as a key component for miniature endoscopes because of their small diameters and ease of assembly. However, the nonaplanatic nature of GRIN lenses causes inherent spatial aberrations that lower image resolution and sharpness. Here we present the diagnosis of the aberrations in GRIN probes and the use of adaptive optics to compensate for the wavefront errors in the endoscope. Two different operation schemes based on preset and in situ measurements are demonstrated, both resulting in a substantial reduction of the wavefront error from 0.42 to < 0.1 mu m. (C) 2011 Optical Society of America C1 [Yun, S. H.] Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Yun, SH (reprint author), Harvard Univ, Sch Med, 40 Blossom St, Boston, MA 02114 USA. EM syun@hms.harvard.edu RI lee, Woei Ming "Steve"/C-7035-2009; OI Lee, W M Steve/0000-0002-3912-6095 FU National Institutes of Health (NIH) [R21AI081010, RC1DK086242, RC2DK088661, U54CA143837, R01AI081734] FX We acknowledge the generous loan from P. Clemens with Imagine Optics, Inc., and thank J. Kim, M. Gather, and P. Kim for materials and discussions. This work is funded by the National Institutes of Health (NIH) (R21AI081010, RC1DK086242, RC2DK088661, U54CA143837, R01AI081734). NR 14 TC 10 Z9 10 U1 1 U2 9 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD DEC 1 PY 2011 VL 36 IS 23 BP 4608 EP 4610 PG 3 WC Optics SC Optics GA 863OI UT WOS:000298174400048 PM 22139258 ER PT J AU Matlock, DD Nowels, CT Masoudi, FA Sauer, WH Bekelman, DB Main, DS Kutner, JS AF Matlock, Dan D. Nowels, Carolyn T. Masoudi, Frederick A. Sauer, William H. Bekelman, David B. Main, Deborah S. Kutner, Jean S. TI Patient and Cardiologist Perceptions on Decision Making for Implantable Cardioverter-Defibrillators: A Qualitative Study SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Article DE Implantable cardioverter-defibrillators; qualitative research; medical decision making ID HEART-FAILURE; OF-LIFE; PROPHYLACTIC IMPLANTATION; CARE; DEACTIVATION; CONSEQUENCES; AMIODARONE; MANAGEMENT; THERAPY; CHOICE AB Background: Although implantable cardioverter-defibrillators (ICDs) reduce mortality in selected patients, they are also associated with potential risks. Periprocedural decision making requires understanding both benefits and risks. Methods: This qualitative study aims to understand cardiologists' and patients' perspectives about decision making surrounding ICD implantation using semi-structured, in-depth interviews. We interviewed 11 cardiologists (including four electrophysiologists) and 20 patients (14 with ICDs; six who declined ICDs). The data were analyzed through the theoretical lens of patient-centered care using the constant comparative method. Results: Cardiologists emphasized the benefits of ICD therapy but varied substantially in the extent to which they emphasized the various risks associated with ICD implantation with patients. Cardiologists indicated that they were influenced by the benefits of therapy as presented in published guidelines. Many patients who chose to receive an ICD indicated that they followed the advice of their physician without questioning the risks and benefits of the device. Some ICD recipients described not learning many of the risks until after device implantation or when they experienced these side effects. Patients who declined ICD implantation were concerned that the ICD was unnecessary or believed that the risks related to sudden death without an ICD did not apply to them. Only one patient considered the trade-off between dying quickly versus living longer with progressive heart failure. Conclusions: In our sample, cardiologists' desire to adhere to published guidelines appears to inhibit shared decision making. The marked variability in the discussions surrounding ICD decisions highlights a need for an improved process of ICD decision making. (PACE 2011; 34: 1634-1644) C1 [Matlock, Dan D.] Univ Colorado, Acad Off 1, Dept Med, Div Gen Internal Med,Sch Med, Aurora, CO 80045 USA. [Matlock, Dan D.; Masoudi, Frederick A.; Bekelman, David B.] Univ Colorado, Colorado Cardiovasc Outcomes Res Grp, Denver, CO 80202 USA. [Matlock, Dan D.; Masoudi, Frederick A.] Univ Colorado, Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO 80202 USA. [Bekelman, David B.] Univ Colorado, Denver Vet Affairs Med Ctr, Denver, CO 80202 USA. [Main, Deborah S.] Univ Colorado, Dept Hlth & Behav Sci, Denver, CO 80202 USA. RP Matlock, DD (reprint author), Univ Colorado, Acad Off 1, Dept Med, Div Gen Internal Med,Sch Med, 12631 E 17th Ave,Campus Box B-180, Aurora, CO 80045 USA. EM daniel.matlock@ucdenver.edu FU Foundation for Informed Medical Decision Making (FIMDM) FX Financial support for this study was provided by a George Bennett Postdoctoral Research Grant from the Foundation for Informed Medical Decision Making (FIMDM) awarded to Dr. Matlock. The views in this article are those of the authors and do not necessarily reflect the views of the Department of Veterans Affairs. NR 38 TC 25 Z9 26 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0147-8389 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD DEC PY 2011 VL 34 IS 12 BP 1634 EP 1644 DI 10.1111/j.1540-8159.2011.03237.x PG 11 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA 860HZ UT WOS:000297940700013 PM 21972983 ER PT J AU Arnstein, P Broglio, K Wuhrman, E Kean, MB AF Arnstein, Paul Broglio, Kathleen Wuhrman, Elsa Kean, Mary Beth TI Use of Placebos in Pain Management SO PAIN MANAGEMENT NURSING LA English DT Article ID CLINICAL-PRACTICE; POSITION STATEMENT AB The American Society for Pain Management Nursing (ASPMN) holds the position that a placebo should not be used by any method to assess and/or manage an individual's pain regardless of their age or diagnosis. The only justifiable use of placebos is for participants enrolled in a blinded clinical trial. These clinical trials must be Institutional Review Board (or equivalent) approved with participants clearly informed that they may receive a placebo before they consent to participate and actually have the sham treatment administered. (C) 2011 by the American Society for Pain Management Nursing C1 [Arnstein, Paul] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Broglio, Kathleen] NYU, Sch Med, New York, NY USA. [Wuhrman, Elsa] Columbia Univ, Med Ctr, New York, NY USA. [Kean, Mary Beth] Seton Med Ctr, Austin, TX USA. RP Arnstein, P (reprint author), Massachusetts Gen Hosp, GRB-1034,55 Fruit St, Boston, MA 02114 USA. EM pmarnstein@partners.org NR 22 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1524-9042 J9 PAIN MANAG NURS JI Pain Manag. Nurs. PD DEC PY 2011 VL 12 IS 4 BP 225 EP 229 DI 10.1016/j.pmn.2010.10.033 PG 5 WC Nursing SC Nursing GA 860PJ UT WOS:000297959900006 PM 22117754 ER PT J AU Naik, AD Teal, CR Rodriguez, E Haidet, P AF Naik, Aanand D. Teal, Cayla R. Rodriguez, Elisa Haidet, Paul TI Knowing the ABCs: A comparative effectiveness study of two methods of diabetes education SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE Diabetes education; Self-management; Patient empowerment; Team-based learning; Group clinics ID SELF-MANAGEMENT EDUCATION; GLYCEMIC CONTROL; HYPERTENSION CONTROL; PATIENT EMPOWERMENT; VULNERABLE PATIENTS; CARE; A1C; KNOWLEDGE; OUTCOMES; ADULTS AB Objective: To test an active-learning, empowerment approach to teaching patients about the "diabetes ABCs" (hemoglobin A(1)C, systolic blood pressure, and low density lipoprotein cholesterol). Methods: 84 (97%) diabetic patients who participated in a randomized effectiveness trial of two clinic-based group educational methods and completed a post-intervention assessment. The empowerment arm participated in a group session that incorporated two educational innovations (a conceptual metaphor to foster understanding, and team-based learning methods to foster active learning). The traditional diabetes education arm received a didactic group session focused on self-management and educational materials about the diabetes ABCs. Participants in both arms received individual review of their current ABC values. Results: A questionnaire evaluated knowledge, understanding, and recall of the diabetes ABCs was administered three months after enrollment in the study. At three months, participants in the empowerment group demonstrated greater understanding of the diabetes ABCs (P < 0.0001), greater knowledge of their own values (P < 0.0001), and greater knowledge of guideline-derived target goals for the ABCs compared with participants in the traditional arm (P < 0.0001). Conclusion: An active-learning, empowerment-based approach applied to diabetes education can lead to greater understanding and knowledge retention. Practice implications: An empowerment approach to education can facilitate informed, activated patients and increase performance of self-management behaviors. Published by Elsevier Ireland Ltd. C1 [Naik, Aanand D.; Rodriguez, Elisa] Michael E DeBakey VA Med Ctr, Houston Hlth Serv Res & Dev Ctr Excellence, Houston, TX USA. [Naik, Aanand D.; Teal, Cayla R.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Haidet, Paul] Penn State Univ, Coll Med, Off Med Educ, Hershey, PA USA. [Haidet, Paul] Penn State Univ, Coll Med, Dept Med, Hershey, PA USA. [Haidet, Paul] Penn State Univ, Coll Med, Dept Humanities, Hershey, PA USA. [Naik, Aanand D.; Rodriguez, Elisa; Haidet, Paul] Houston Ctr Res & Educ Therapeut, Houston, TX USA. [Teal, Cayla R.] Baylor Coll Med, Off Undergrad Med Educ, Houston, TX 77030 USA. RP Naik, AD (reprint author), Michael E DeBakey VA Med Ctr 152, Houston Hlth Serv Res & Dev Ctr Excellence, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM anaik@bcm.edu RI Herring, Anna/L-7859-2014 FU Agency for Healthcare Research and Quality [U18HS016093]; Centers for Research and Education on Therapeutics (Houston CERT. Suarez-Almazor, PI); Doris Duke Charitable Foundation; National Institute on Aging [K23AG027144] FX This work was supported by a grant from the Agency for Healthcare Research and Quality (#U18HS016093), Centers for Research and Education on Therapeutics (Houston CERT. Suarez-Almazor, PI). The authors acknowledge additional project support from a Clinical Scientist Development Award from the Doris Duke Charitable Foundation and resources in the preparation of this manuscript from the Houston Health Services Research and Development Center of Excellence (HFP90-020) at the Michael E. DeBakey VA Medical Center. Dr. Naik receives additional support from the National Institute on Aging (K23AG027144). These sources had no role in the preparation, review, or approval of the manuscript. The authors thank Andrea Price, BA, and Donna Rochon, PhD, for their assistance with patient recruitment, retention and project support, Teresa Zhang, PhD, and Annette Walder, MS with data analysis. NR 29 TC 6 Z9 6 U1 0 U2 13 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD DEC PY 2011 VL 85 IS 3 BP 383 EP 389 DI 10.1016/j.pec.2011.01.010 PG 7 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 864EM UT WOS:000298219800008 PM 21300516 ER PT J AU Galarce, EM Ramanadhan, S Weeks, J Schneider, EC Gray, SW Viswanath, K AF Galarce, Ezequiel M. Ramanadhan, Shoba Weeks, Jane Schneider, Eric C. Gray, Stacy W. Viswanath, Kasisomayajula TI Class, race, ethnicity and information needs in post-treatment cancer patients SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE Health information seeking; Health communication; Health disparities; Communication disparities; Shared decision making; Cancer ID TREATMENT DECISION-MAKING; HEALTH-INFORMATION; BREAST-CANCER; PROSTATE-CANCER; SEEKING BEHAVIORS; SELF-EFFICACY; PATIENTS WANT; WOMEN; PREFERENCES; MEN AB Objective: Health information-seeking behaviors (HISBs) are associated with active participation in cancer care decisions which, in turn, may positively impact health outcomes. The goal of this study was to develop a taxonomy of topics for which post-treatment cancer patients sought information, and to explore HISB patterns by sociodemographic factors and cancer type. Methods: We examined how health information seeking is associated with social determinants in a survey of 521 post-treatment cancer patients. Results: Four major topics of interest were found: disease/treatment, self-care management, health services, and work/finance. Assessment of the relationship between social determinants and these four topics showed associations for (1) HISBs on disease/treatment topics decreased with age and increased with education; (2) HISBs on self-care management increased with education and varied by cancer type; (3) HISBs on health services increased with education; and (4) HISBs on work/finance decreased with age and wealth, but increased with debt. Conclusion: These results demonstrate one pathway through which social determinants may drive communication inequalities, which may result in increased disparities in health outcomes. Practice implications: Further exploration of the relationship between social determinants and information-seeking among post-treatment cancer patients may contribute to the development of strategies to reduce health disparities. (C) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Galarce, Ezequiel M.; Viswanath, Kasisomayajula] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. [Weeks, Jane; Schneider, Eric C.] Harvard Univ, Sch Med, Boston, MA USA. RP Galarce, EM (reprint author), Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, 44 Binney St,LW601, Boston, MA 02115 USA. EM ezequiel_galarce@dfci.harvard.edu OI Schneider, Eric/0000-0002-1132-5084 FU Lance Armstrong Foundation FX This work was supported by the Lance Armstrong Foundation to Dr. Viswanath (PI). NR 67 TC 17 Z9 17 U1 1 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD DEC PY 2011 VL 85 IS 3 BP 432 EP 439 DI 10.1016/j.pec.2011.01.030 PG 8 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 864EM UT WOS:000298219800015 PM 21354761 ER PT J AU Price, EL MacKenzie, TD Metlay, JP Camargo, CA Gonzales, R AF Price, Erika Leemann MacKenzie, Thomas D. Metlay, Joshua P. Camargo, Carlos A., Jr. Gonzales, Ralph TI A computerized education module improves patient knowledge and attitudes about appropriate antibiotic use for acute respiratory tract infections SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE Acute respiratory infection; Respiratory tract infection; Patient education; Appropriate antibiotic use; Interactive computerized education module; Educational computer kiosk ID PATIENTS EXPECTATIONS; EMERGENCY-DEPARTMENTS; UNITED-STATES; ADULTS; PRINCIPLES; QUESTIONNAIRE; MANAGEMENT; CHILDREN; BEHAVIOR; ILLNESS AB Background: Over-use of antibiotics for acute respiratory infections (ARIs) increases antimicrobial resistance, treatment costs, and side effects. Patient desire for antibiotics contributes to over-use. Objective: To explore whether a point-of-care interactive computerized education module increases patient knowledge and decreases desire for antibiotics. Methods: Bilingual (English/Spanish) interactive kiosks were available in 8 emergency departments as part of a multidimensional intervention to reduce antibiotic prescribing for ARIs. The symptom-tailored module included assessment of symptoms, knowledge about ARIs (3 items), and desire for antibiotics on a 10-point visual analog scale. Multivariable analysis assessed predictors of change in desire for antibiotics. Results: Of 686 adults with ARI symptoms. 63% initially thought antibiotics might help. The proportion of patients with low (1-3 on the scale) desire for antibiotics increased from 22% pre-module to 49% post-module (p < .001). Self-report of "learning something new" was associated with decreased desire for antibiotics, after adjusting for baseline characteristics (p = .001). Conclusion: An interactive educational kiosk improved knowledge about antibiotics and ARIs. Learning correlated with changes in personal desire for antibiotics. Practice implications: By reducing desire for antibiotics, point-of-care interactive educational computer technology may help decrease inappropriate use for antibiotics for ARIs. (C) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Price, Erika Leemann; Gonzales, Ralph] Univ Calif San Francisco, Dept Med, Div Gen Internal Med, San Francisco, CA USA. [MacKenzie, Thomas D.] Denver Hlth & Hosp Author, Denver, CO USA. [Metlay, Joshua P.] Univ Penn, Dept Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Price, EL (reprint author), UCSF Box 0320, San Francisco, CA 94143 USA. EM erika.price@ucsf.edu NR 30 TC 12 Z9 12 U1 0 U2 10 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD DEC PY 2011 VL 85 IS 3 BP 493 EP 498 DI 10.1016/j.pec.2011.02.005 PG 6 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 864EM UT WOS:000298219800024 PM 21392929 ER PT J AU Naik, AD Street, RL Castillo, D Abraham, NS AF Naik, Aanand D. Street, Richard L., Jr. Castillo, Diana Abraham, Neena S. TI Health literacy and decision making styles for complex antithrombotic therapy among older multimorbid adults SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE Aging; Drugs; Prevention; Literacy; Doctor-patient relationship ID PATIENT PARTICIPATION; IDENTIFY PATIENTS; COMMUNICATION; PREFERENCES; QUESTIONS; ENCOUNTER; OUTCOMES; CANCER; RISK AB Objectives: To evaluate the effect of functional health literacy (FHL) on preferences for decision-making; and among those initially preferring a passive decision-making role, to explore how preferences change if their physician actively encourages their involvement. Methods: Consecutive older adults with cardiovascular disease receiving complex antithrombotic therapy completed a comprehensive assessment including measures of FHL and preferences for shared decision making. Results: Half of all participants had inadequate or marginal FHL. Those with inadequate FHL were more likely (P = 0.01) to prefer passive rather than active decision making styles even after controlling for age, education, and numeracy. However, 40% of patients preferring passive styles had adequate FHL and these patients were significantly more likely to change their preference to more active styles (odds ratio = 7.17, P < .01) if their physician "was more supportive or encouraged participation". Conclusions: Screening FHL can provide insight into patients' preferences for active participation in decision making. Clinicians' encouragement of participation can increase engagement by patients with adequate FHL. Practice implications: We propose an algorithm for screening FHL and preferences for participating in decisions about complex medication regimens. Published by Elsevier Ireland Ltd. C1 [Naik, Aanand D.; Street, Richard L., Jr.; Castillo, Diana; Abraham, Neena S.] Michael E DeBakey VA Med Ctr, Houston HSR&D Ctr Excellence, Houston, TX USA. [Naik, Aanand D.; Abraham, Neena S.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Street, Richard L., Jr.] Texas A&M Univ, Dept Commun, College Stn, TX USA. RP Naik, AD (reprint author), Michael E DeBakey VA Med Ctr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM anaik@bcm.tmc.edu FU Houston Veterans Affairs Health Sciences Research and Development Center of Excellence [HFP90-020]; National Institute on Aging [K23AG027144]; Doris Duke Charitable Foundation; American Gastroenterological Association Foundation-Sucampo-Association; Department of Veterans Affairs [VA IIR 08-028] FX This study was supported by a locally funded pilot grant and use of facilities at the Houston Veterans Affairs Health Sciences Research and Development Center of Excellence (HFP90-020). Dr. Naik is also supported by a National Institute on Aging Career Development Award (K23AG027144) and a Doris Duke Charitable Foundation Clinical Scientist Development Award. Dr. Abraham is supported by an American Gastroenterological Association Foundation-Sucampo-Association of Specialty Professors Designated Research Award in Geriatric Gastroenterology and by a Merit Review Award from the Department of Veterans Affairs (VA IIR 08-028). No funding agencies had a role in the design and conduct of the study, analysis and interpretation of data, or preparation and approval of the manuscript. The views expressed herein are those of the authors and do not necessarily reflect those of the Department of Veterans Affairs or Baylor College of Medicine. NR 32 TC 18 Z9 18 U1 3 U2 7 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD DEC PY 2011 VL 85 IS 3 BP 499 EP 504 DI 10.1016/j.pec.2010.12.015 PG 6 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 864EM UT WOS:000298219800025 PM 21251788 ER PT J AU Arjomandi, M Galanter, JM Choudhry, S Eng, C Hu, DL Beckman, K Chapela, R Rodriguez-Santana, JR Rodriguez-Cintron, W Ford, J Avila, PC Burchard, EG AF Arjomandi, Mehrdad Galanter, Josh M. Choudhry, Shweta Eng, Celeste Hu, Donglei Beckman, Kenneth Chapela, Rocio Rodriguez-Santana, Jose R. Rodriguez-Cintron, William Ford, Jean Avila, Pedro C. Burchard, Esteban G. TI Polymorphism in Osteopontin Gene (SPP1) Is Associated with Asthma and Related Phenotypes in a Puerto Rican Population SO PEDIATRIC ALLERGY IMMUNOLOGY AND PULMONOLOGY LA English DT Article ID MURINE MODEL; MICE LACKING; EXPRESSION; DISEASE; RISK; TNF-ALPHA-308; EPIDEMIOLOGY; EOSINOPHILS; MACROPHAGES; ACTIVATION AB Recent studies have shown that osteopontin, a cytokine with suggested immunoregulatory functions, may contribute to pathogenesis of asthma. To determine whether single-nucleotide polymorphisms (SNPs) in SPP1, the gene encoding osteopontin, are associated with risk of asthma, we genotyped 6 known SNPs in SPP1 in the well-characterized Genetics of Asthma in Latino Americans population of 294 Mexican and 365 Puerto Rican parent-child asthma trios. The associations between SNPs and asthma or asthma-related phenotypes were examined by transmission disequilibrium tests as implemented in the family-based association test program. Three polymorphisms, 1 in exon 7 (rs1126616C) and 2 in the 3'-untranslated region (rs1126772A and rs9138A) of SPP1, were associated with diagnosis of asthma, severity of asthma, asthma in subjects with elevated immunoglobulin E (IgE) (IgE > 100 IU/mL), and postbronchodilator FEV(1) in Puerto Ricans (P values = 0.00007-0.04). The CC genotype of rs1126616 conferred an odds ratio of 1.7 (95% CI = [1.3, 2.3], P value adjusted for multiple comparisons = 0.001) for asthma compared with the CT and TT genotypes. Furthermore, haplotype analysis identified rs1126616C-rs1126772A-rs9138A to be associated with an increased risk for asthma, severity of asthma, and asthma in subjects with elevated IgE (P = 0.03). There was no association between the SPP1 SNPs and asthma outcomes in Mexicans. Our findings suggest that the SPP1 gene is a risk factor for asthma and asthma-related phenotypes in Puerto Ricans, and are consistent with previous animal and human studies on the role of osteopontin in pathogenesis of asthma. C1 [Arjomandi, Mehrdad] Univ Calif San Francisco, Div Pulm & Crit Care Med, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94121 USA. [Arjomandi, Mehrdad] Univ Calif San Francisco, Human Exposure Lab, San Francisco, CA 94121 USA. [Galanter, Josh M.; Choudhry, Shweta; Eng, Celeste; Hu, Donglei; Burchard, Esteban G.] Univ Calif San Francisco, Dept Med, Lung Biol Ctr, San Francisco, CA 94121 USA. [Choudhry, Shweta; Eng, Celeste; Hu, Donglei; Burchard, Esteban G.] Univ Calif San Francisco, Dept Epidemiol & Biostat, Inst Human Genet, San Francisco, CA 94121 USA. [Beckman, Kenneth] Univ Minnesota, Biomed Genom Ctr, Minneapolis, MN USA. [Chapela, Rocio] Inst Nacl Enfermedades Resp, Mexico City, DF, Mexico. [Rodriguez-Santana, Jose R.; Rodriguez-Cintron, William] CSP, Ctr Neumol Pediat, San Juan, PR USA. [Ford, Jean] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Avila, Pedro C.] Northwestern Univ, Div Allergy Immunol, Chicago, IL 60611 USA. [Burchard, Esteban G.] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94121 USA. RP Arjomandi, M (reprint author), Univ Calif San Francisco, Div Pulm & Crit Care Med, San Francisco Vet Affairs Med Ctr, Bldg 203,Room 3A-128,Mailstop 111-D,4150 Clement, San Francisco, CA 94121 USA. EM mehrdad.arjomandi@ucsf.edu FU NIH/NHLBI [HL083099]; GALA [HL078885, HL088133]; tobacco-related disease research program (TRDRP) (GALA) [15KT-0008]; Northern California Institute for Research and Education (Arjomandi); University of California San Francisco Cardiovascular Research Institute Faculty (Arjomandi) FX This study was supported by NIH/NHLBI HL083099 (Arjomandi K23 award), HL078885, and HL088133 (GALA funding), tobacco-related disease research program (TRDRP) 15KT-0008 (GALA funding), Northern California Institute for Research and Education (Arjomandi), and University of California San Francisco Cardiovascular Research Institute Faculty Development Funds (Arjomandi). NR 51 TC 9 Z9 11 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 2151-321X J9 PEDIAT ALLER IMM PUL JI Pediatr. Allergy Immunol. Pulmonol. PD DEC PY 2011 VL 24 IS 4 BP 207 EP 214 DI 10.1089/ped.2011.0095 PG 8 WC Allergy; Immunology; Pediatrics; Respiratory System SC Allergy; Immunology; Pediatrics; Respiratory System GA 864IT UT WOS:000298234100005 ER PT J AU Rhodes, ET Prosser, LA Lieu, TA Songer, TJ Ludwig, DS Laffel, LM AF Rhodes, Erinn T. Prosser, Lisa A. Lieu, Tracy A. Songer, Thomas J. Ludwig, David S. Laffel, Lori M. TI Preferences for type 2 diabetes health states among adolescents with or at risk of type 2 diabetes mellitus SO PEDIATRIC DIABETES LA English DT Article DE adolescents; microvascular; SG; T2DM; utilities ID QUALITY-OF-LIFE; BODY-MASS INDEX; INSULIN-RESISTANCE; CARDIOVASCULAR-DISEASE; COST-EFFECTIVENESS; GLYCEMIC CONTROL; SELF-MANAGEMENT; UTILITY SCORES; US ADOLESCENTS; CHILDREN AB Objective: We evaluated how adolescents with or at risk of type 2 diabetes (T2DM) and their parent/guardians (parents) value health states associated with T2DM. Methods: We interviewed overweight/obese [Body Mass Index (BMI) >= 85th percentile], 12-18-yr old adolescents with T2DM, prediabetes, or insulin resistance (IR) and a parent. The standard gamble (SG) method elicited preferences (utilities) for seven hypothetical T2DM health states reported on a scale from 0 (dead) to 1 (perfect health). Adolescent's current health was evaluated with the SG and Health Utilities Index (HUI). Results: There were 70 adolescents and 69 parents. Adolescents were 67.1% female and 15.5 +/- 2.2 yr old; 30% had T2DM, 30% prediabetes, and 40% IR. Almost half (48.6%) had a BMI > 99th percentile. Parents (83% mothers) were 45.1 +/- 7.3 yr old and 75% had at least some college/technical school education. Adolescents and parents rated T2DM with no complications treated with diet as most desirable [median (IQR); adolescent 0.72 (0.54, 0.98); parent 1.0 (0.88, 1.0)] and end-stage renal disease as least desirable [adolescent 0.51 (0.31, 0.70); parent 0.80 (0.65, 0.94)]. However, adolescents' utilities were significantly lower (p <= 0.001) than parents for all health states assessed. Adolescents' assessments of their current health with the SG and HUI were not correlated. Conclusions: Adolescents with or at risk of T2DM rated treatments and sequelae of diabetes as significantly worse than their parents. These adolescent utilities should be considered in the evaluation of treatment strategies for youth with T2DM. Family-based programs for T2DM must also be prepared to address conflicting preferences in order to promote shared decision-making. C1 [Rhodes, Erinn T.; Ludwig, David S.] Childrens Hosp Boston, Div Endocrinol, Boston, MA 02115 USA. [Rhodes, Erinn T.; Ludwig, David S.; Laffel, Lori M.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Prosser, Lisa A.] Univ Michigan, Div Gen Pediat, Child Hlth Evaluat & Res Unit, Ann Arbor, MI 48109 USA. [Prosser, Lisa A.; Lieu, Tracy A.] Harvard Pilgrim Hlth Care Inst, Dept Populat Med, Ctr Child Hlth Care Studies, Boston, MA USA. [Lieu, Tracy A.] Childrens Hosp Boston, Div Gen Pediat, Boston, MA 02115 USA. [Songer, Thomas J.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Laffel, Lori M.] Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, Boston, MA 02215 USA. RP Rhodes, ET (reprint author), Childrens Hosp Boston, Div Endocrinol, 333 Longwood Ave 6th Floor, Boston, MA 02115 USA. EM Erinn.Rhodes@childrens.harvard.edu OI Songer, Thomas/0000-0002-5253-2514 FU Centers for Disease Control and Prevention [K01DP000089]; Katherine Adler Astrove Youth Education Fund; Maria Griffin Drury Fund; National Institute of Diabetes and Digestive and Kidney Diseases [K24DK082730]; New Balance Foundation; Bayer FX The study was supported by the Centers for Disease Control and Prevention grant K01DP000089 (Rhodes, Ludwig, Prosser). Additional support to investigators included the Katherine Adler Astrove Youth Education Fund (Laffel); Maria Griffin Drury Fund (Laffel); National Institute of Diabetes and Digestive and Kidney Diseases grant K24DK082730 (Ludwig), and the New Balance Foundation (Rhodes). This work was published, in part, at the American Diabetes Association 68th Annual Scientific Sessions, June 6-10, 2008, San Francisco, CA. We would like to thank our research assistants Tessa Gonzalez AB, Kaitlin Rawluk BA, and Roula Zoghbi MPH for their work on this project; the Clinical Research Program at Children's Hospital Boston for project management, database development, and statistical support; and members of our Data and Safety Monitoring Board for their careful review and feedback.; Dr Rhodes was formerly Chief Medical Officer for Pediatric Weight Management Centers, LLC's Great Moves! Program, a company privately owned and operated in collaboration with the physicians of Children's Hospital Boston. Dr Rhodes provided contracted clinical and administrative services for the company but neither had nor has equity or other economic interest in the business. Dr Rhodes also received salary support from an unrestricted, philanthropic grant from the New Balance Foundation. Dr Laffel is on the Speaker's Bureau for Sanofi-Aventis, Menarini, and Johnson&Johnson. She is also a consultant for Lilly, Sanofi-Aventis, Bristol Myers Squibb, Menarini, and Astra Zeneca and receives grant support from Bayer. The remaining authors have no disclosures. NR 49 TC 6 Z9 6 U1 4 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1399-543X J9 PEDIATR DIABETES JI Pediatr. Diabetes PD DEC PY 2011 VL 12 IS 8 BP 724 EP 732 DI 10.1111/j.1399-5448.2011.00772.x PG 9 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 863NB UT WOS:000298170000009 PM 21489091 ER PT J AU Baca, CB Vickrey, BG Caplan, R Vassar, SD Berg, AT AF Baca, Christine B. Vickrey, Barbara G. Caplan, Rochelle Vassar, Stefanie D. Berg, Anne T. TI Psychiatric and Medical Comorbidity and Quality of Life Outcomes in Childhood-Onset Epilepsy SO PEDIATRICS LA English DT Article DE epilepsy; psychiatric comorbidity; quality of life; Child Health Questionnaire; child and adolescent health ID WELL-CONTROLLED EPILEPSY; NEWLY-DIAGNOSED EPILEPSY; LONG-TERM PROGNOSIS; PEDIATRIC EPILEPSY; DEPRESSIVE SYMPTOMS; SPECTRUM DISORDER; CHILDREN; HEALTH; ADOLESCENTS; SEIZURE AB OBJECTIVE: We compared associations of epilepsy remission status and severity as well as psychiatric and other comorbidities with child and parent-proxy reports of health-related quality of life (HRQoL) in adolescents previously diagnosed with epilepsy. METHODS: In a prospective, community-based study of newly diagnosed childhood epilepsy, HRQoL of 277 children was assessed 8 to 9 years after diagnosis by using child and parent-proxy versions of the Child Health Questionnaire (CHQ). Multiple linear regression models adjusted for age and gender were used to compare associations of epilepsy remission and "complicated" epilepsy (secondary to an underlying neurologic insult or epileptic encephalopathy) status and psychiatric and other comorbidities with HRQoL. RESULTS: Mean age of epilepsy onset was 4.4 years (SD: 2.6). At the 9-year reassessment, children were, on average, 13.0 years old (SD: 2.6); 64% were seizure-free for 5 years, 31% were taking antiepileptic drugs, and 19% had a complicated epilepsy. Prevalence of comorbidities at follow-up were 26% psychiatric diagnosis; 39% neurodevelopmental spectrum disorder (NDSD); 24% chronic medical illness; and 15% migraine. In multivariable analysis, having a psychiatric disorder was broadly associated with child (6 of 11 scales) and parent-proxy (7 of 12 scales) HRQoL (P <= .0125). Five-year remission and complicated epilepsy status had few or no associations with HRQoL. Although parent-proxy HRQoL was strongly associated with NDSD (6 of 11 scales), child-reported HRQoL was not (2 of 11 scales). CONCLUSIONS: Psychiatric comorbidities are strongly associated with long-term HRQoL in childhood-onset epilepsy, which suggests that comprehensive epilepsy care must include screening and treatment for these conditions, even if seizures remit. Pediatrics 2011;128:e1532-e1543 C1 [Baca, Christine B.; Vickrey, Barbara G.; Vassar, Stefanie D.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90095 USA. [Baca, Christine B.; Vickrey, Barbara G.; Vassar, Stefanie D.] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90095 USA. [Caplan, Rochelle] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Berg, Anne T.] NW Childrens Hosp, Chicago, IL USA. RP Baca, CB (reprint author), Univ Calif Los Angeles, Dept Neurol, Box 951769,C-239 RNRC, Los Angeles, CA 90095 USA. EM cbower@mednet.ucla.edu FU National Institutes of Health (NIH); National Institutes of Health, National Institute of Neurological Disorders and Stroke [R37-NS31146]; Robert Wood Johnson Foundation [59982] FX Funded by the National Institutes of Health (NIH).; This work was supported by National Institutes of Health, National Institute of Neurological Disorders and Stroke grant R37-NS31146 (principal investigator Dr Berg). Dr Baca was supported by Robert Wood Johnson Foundation Clinical Scholars Program grant 59982. NR 77 TC 56 Z9 57 U1 2 U2 13 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD DEC PY 2011 VL 128 IS 6 BP E1532 EP E1543 DI 10.1542/peds.2011-0245 PG 12 WC Pediatrics SC Pediatrics GA 862ZA UT WOS:000298131400021 PM 22123895 ER PT J AU Maturo, S Hill, C Bunting, G Baliff, C Ramakrishna, J Scirica, C Fracchia, S Donovan, A Hartnick, C AF Maturo, Stephen Hill, Courtney Bunting, Glenn Baliff, Cathy Ramakrishna, Jyoti Scirica, Christina Fracchia, Shannon Donovan, Abigail Hartnick, Christopher TI Pediatric Paradoxical Vocal-Fold Motion: Presentation and Natural History SO PEDIATRICS LA English DT Article ID CORD DYSFUNCTION; ADOLESCENTS; CHILDREN; HYPNOSIS; THERAPY; ASTHMA AB OBJECTIVES: To describe (1) a cohort of children with paradoxical vocal-fold motion (PVFM) who were referred to a multidisciplinary airway center and (2) the outcomes of various treatment modalities including speech therapy, gastroesophageal reflux disease treatment, and psychiatric treatment. PATIENTS AND METHODS: This was a case series with chart review of children younger than 18 years with PVFM evaluated at a tertiary care pediatric airway center over a 36-month period. RESULTS: Fifty-nine children with PVFM were evaluated. The cohort had a mean age of 13.64 years (range: 8-18 years) and a female-to-male ratio of 3:1. Speech therapy as an initial treatment resulted in a 63% (24 of 38) success rate after an average of 3.7 treatment sessions. Speech therapy was a more successful treatment than antireflux therapy (P = .001). Ten percent (6 of 59) of the children presented with a known psychiatric diagnosis, and 30% (18 of 59) of children in the cohort were ultimately diagnosed with a psychiatric condition. Children with inspiratory stridor at rest had a lower initial success rate with speech therapy (56%), a higher rate of underlying psychiatric disorders (75%), and a high rate of success after psychiatric treatment (100%) that required, on average, 3 sessions over a 2-month period. CONCLUSIONS: To our knowledge, this is the largest study to date on pediatric PVFM. The majority of children with PVFM improve with speech therapy. Children with PVFM at rest may be better treated with psychiatric therapy than speech therapy. Furthermore, children who present with symptoms at rest may have a higher likelihood of underlying psychiatric disease. Pediatrics 2011;128:e1443-e1449 C1 [Hill, Courtney; Hartnick, Christopher] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA. [Bunting, Glenn; Baliff, Cathy] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Voice & Speech Lab, Boston, MA 02114 USA. [Maturo, Stephen] Uniformed Serv Univ Hlth Sci, Dept Otolaryngol, San Antonio Uniformed Serv Hlth Educ Consortium, Bethesda, MD 20814 USA. [Ramakrishna, Jyoti; Scirica, Christina; Fracchia, Shannon] Massachusetts Gen Hosp Children, Dept Pediat, Boston, MA USA. [Donovan, Abigail] Massachusetts Gen Hosp Children, Dept Psychiat, Boston, MA USA. RP Hartnick, C (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02114 USA. EM christopher_hartnick@meei.harvard.edu NR 23 TC 15 Z9 15 U1 0 U2 5 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD DEC PY 2011 VL 128 IS 6 BP E1443 EP E1449 DI 10.1542/peds.2011-1003 PG 7 WC Pediatrics SC Pediatrics GA 862ZA UT WOS:000298131400010 PM 22123871 ER PT J AU Randolph, AG Vaughn, F Sullivan, R Rubinson, L Thompson, BT Yoon, G Smoot, E Rice, TW Loftis, LL Helfaer, M Doctor, A Paden, M Flori, H Babbitt, C Graciano, AL Gedeit, R Sanders, RC Giuliano, JS Zimmerman, J Uyeki, TM AF Randolph, Adrienne G. Vaughn, Frances Sullivan, Ryan Rubinson, Lewis Thompson, B. Taylor Yoon, Grace Smoot, Elizabeth Rice, Todd W. Loftis, Laura L. Helfaer, Mark Doctor, Allan Paden, Matthew Flori, Heidi Babbitt, Christopher Graciano, Ana Lia Gedeit, Rainer Sanders, Ronald C. Giuliano, John S. Zimmerman, Jerry Uyeki, Timothy M. CA Pediat Acute Lung Injury Sepsis In Natl Heart Lung & Blood Inst ARDS TI Critically III Children During the 2009-2010 Influenza Pandemic in the United States SO PEDIATRICS LA English DT Article DE influenza; intensive care unit; pediatric; mortality; pandemic; MRSA ID COMMUNITY-ACQUIRED PNEUMONIA; A H1N1 VIRUS; STAPHYLOCOCCUS-AUREUS COINFECTION; INFECTIOUS-DISEASES-SOCIETY; CLINICAL CHARACTERISTICS; NEW-ZEALAND; CASE SERIES; A(H1N1); MYOCARDITIS; DEATHS AB BACKGROUND: The 2009 pandemic influenza A (H1N1) (pH1N1) virus continues to circulate worldwide. Determining the roles of chronic conditions and bacterial coinfection in mortality is difficult because of the limited data for children with pH1N1-related critical illness. METHODS: We identified children (<21 years old) with confirmed or probable pH1N1 admitted to 35 US PICUs from April 15, 2009, through April 15, 2010. We collected data on demographics, baseline health, laboratory results, treatments, and outcomes. RESULTS: Of 838 children with pH1N1 admitted to a PICU, the median age was 6 years, 58% were male, 70% had >= 1 chronic health condition, and 88.2% received oseltamivir (5.8% started before PICU admission). Most patients had respiratory failure with 564 (67.3%) receiving mechanical ventilation; 162 (19.3%) received vasopressors, and 75 (8.9%) died. Overall, 71 (8.5%) of the patients had a presumed diagnosis of early (within 72 hours after PICU admission) Staphylococcus aureus coinfection of the lung with 48% methicillin-resistant S aureus (MRSA). In multivariable analyses, preexisting neurologic conditions or immunosuppression, encephalitis (1.7% of cases), myocarditis (1.4% of cases), early presumed MRSA lung coinfection, and female gender were mortality risk factors. Among 251 previously healthy children, only early presumed MRSA coinfection of the lung (relative risk: 8 [95% confidence interval: 3.1-20.6]; P < .0001) remained a mortality risk factor. CONCLUSIONS: Children with preexisting neurologic conditions and immune compromise were at increased risk of pH1N1-associated death after PICU admission. Secondary complications of pH1N1, including myocarditis, encephalitis, and clinical diagnosis of early presumed MRSA coinfection of the lung, were mortality risk factors. Pediatrics 2011;128:e1450-e1458 C1 [Randolph, Adrienne G.; Sullivan, Ryan; Yoon, Grace] Childrens Hosp Boston, Dept Anesthesia Perioperat & Pain Med, Boston, MA 02115 USA. [Randolph, Adrienne G.] Harvard Univ, Sch Med, Boston, MA USA. [Vaughn, Frances; Rubinson, Lewis] Natl Disaster Med Syst, Off Preparedness & Emergency Operat, Off Assistant Secretary Preparedness & Response, Dept Hlth & Human Serv, Washington, DC USA. [Thompson, B. Taylor] Massachusetts Gen Hosp, ARDSNet Coordinating Ctr, Dept Med, Boston, MA 02114 USA. [Rice, Todd W.] Vanderbilt Univ, Sch Med, Dept Med, Vanderbilt, TN USA. [Loftis, Laura L.] Texas Childrens Hosp, Dept Pediat, Houston, TX 77030 USA. [Helfaer, Mark] Childrens Hosp Philadelphia, Dept Anesthesia & Crit Care, Philadelphia, PA 19104 USA. [Doctor, Allan] St Louis Childrens Hosp, Dept Pediat, St Louis, MO 63110 USA. [Paden, Matthew] Childrens Healthcare Atlanta Egleston, Dept Pediat, Atlanta, GA USA. [Flori, Heidi] Childrens Hosp Oakland, Dept Pediat, Oakland, CA USA. [Babbitt, Christopher] Miller Childrens Hosp, Dept Pediat, Long Beach, CA USA. [Graciano, Ana Lia] Childrens Hosp Cent Calif, Dept Pediat, Madera, CA USA. [Gedeit, Rainer] Childrens Hosp Wisconsin, Dept Pediat, Milwaukee, WI 53201 USA. [Sanders, Ronald C.] Arkansas Childrens Hosp, Dept Pediat, Little Rock, AR 72202 USA. [Giuliano, John S.] Yale Childrens Hosp, Dept Pediat, New Haven, CT USA. [Zimmerman, Jerry] Seattle Childrens Hosp, Div Pediat Crit Care Med, Seattle, WA USA. [Uyeki, Timothy M.] Ctr Dis Control & Prevent, Influenza Div, Atlanta, GA USA. RP Randolph, AG (reprint author), Childrens Hosp Boston, Dept Anesthesia Perioperat & Pain Med, 300 Longwood Ave,Bader 634, Boston, MA 02115 USA. EM adrienne.randolph@childrens.harvard.edu RI Hall, Mark/E-3193-2011 FU National Institutes of Health (NIH); National Institutes of Health, National Heart, Lung, and Blood Institute, Department of Health and Human Services [N01 HR 56179] FX Funded by the National Institutes of Health (NIH).; This work was supported by National Institutes of Health, National Heart, Lung, and Blood Institute, Department of Health and Human Services (contract N01 HR 56179). NR 54 TC 80 Z9 81 U1 2 U2 10 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD DEC PY 2011 VL 128 IS 6 BP E1450 EP E1458 DI 10.1542/peds.2011-0774 PG 9 WC Pediatrics SC Pediatrics GA 862ZA UT WOS:000298131400011 PM 22065262 ER PT J AU Goldstein, MA Dechant, EJ Beresin, EV AF Goldstein, Mark A. Dechant, Esther J. Beresin, Eugene V. TI Eating Disorders SO PEDIATRICS IN REVIEW LA English DT Review ID RANDOMIZED CONTROLLED-TRIALS; ANOREXIA-NERVOSA; BONE-DENSITY; ADOLESCENT GIRLS; BULIMIA-NERVOSA AB Objectives After completing this article, readers should be able to: 1. Identify behaviors in an adolescent that suggest an underlying eating disorder. 2. Recognize the physical findings that can be seen in patients who have an eating disorder. 3. Understand the medical complications seen in teens who have anorexia and bulimia. 4. Be informed about the types of therapies available for adolescents who have anorexia and bulimia. 5. Know the definition of the female athlete triad. A 15-year-old girl is admitted to the pediatric intensive care unit with a long history of weight loss and a serum sodium concentration of 189 mmol/L. She has been following a meal plan to gain weight and recently has stopped running 5 miles a day. Her fluid intake is approximately 16 oz of water a day. She denies fear of weight gain and body image disturbances, and a symptom review is negative. Physical examination reveals an alert and cooperative adolescent girl. Weight is 68 lb (<< 3%); height, 62.75 in (34%); body mass index (BMI), 12.14 (<< 3%); blood pressure, 113/74 mm Hg; heart beat, 67 beats/minute; and axillary temperature, 36 C. She has no signs of pubertal development and is mildly dehydrated. After extensive evaluation, she is determined to have an underlying eating disorder with no primary medical diagnosis. She is discharged from the hospital on day 16 without any complications, with follow-up care by an adolescent medicine specialist and therapist. C1 [Goldstein, Mark A.; Beresin, Eugene V.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Goldstein, Mark A.] MassGen Hosp Children, Div Adolescent & Young Adult Med, Boston, MA USA. [Dechant, Esther J.] Harvard Univ, Sch Med, Belmont, MA 02178 USA. [Dechant, Esther J.] McLean Hosp, Klarman Eating Disorders Ctr, Belmont, MA 02178 USA. [Beresin, Eugene V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Goldstein, MA (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 20 TC 1 Z9 1 U1 5 U2 20 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0191-9601 J9 PEDIATR REV JI Pediatr. Rev. PD DEC PY 2011 VL 32 IS 12 BP 508 EP 521 DI 10.1542/pir.32-12-508 PG 14 WC Pediatrics SC Pediatrics GA 863NK UT WOS:000298170900004 PM 22135421 ER PT J AU Buchbinder, D Casillas, J Krull, KR Goodman, P Leisenring, W Recklitis, C Alderfer, MA Robison, LL Armstrong, GT Kunin-Batson, A Stuber, M Zeltzer, LK AF Buchbinder, David Casillas, Jacqueline Krull, Kevin R. Goodman, Pam Leisenring, Wendy Recklitis, Christopher Alderfer, Melissa A. Robison, Leslie L. Armstrong, Gregory T. Kunin-Batson, Alicia Stuber, Margaret Zeltzer, Lonnie K. TI Psychological outcomes of siblings of cancer survivors: a report from the Childhood Cancer Survivor Study SO PSYCHO-ONCOLOGY LA English DT Article ID LONG-TERM SURVIVORS; QUALITY-OF-LIFE; BRIEF SYMPTOM INVENTORY-18; ADULT SURVIVORS; ADOLESCENT SURVIVORS; ADAPTATION; CHILDREN; DISTRESS; ADJUSTMENT; SOMATIZATION AB Objective: To identify risk factors for adverse psychological outcomes among adult siblings of long-term survivors of childhood cancer. Methods: Cross-sectional, self-report data from 3083 adult siblings (mean age 29 years, range 18-56 years) of 5+year survivors of childhood cancer were analyzed to assess psychological outcomes as measured by the Brief Symptom Inventory-18 (BSI-18). Socio-demographic and health data, reported by both the siblings and their matched cancer survivors, were explored as risk factors for adverse sibling psychological outcomes through multivariable logistic regression. Results: Self-reported symptoms of psychological distress, as measured by the global severity index of the BSI-18, were reported by 3.8% of the sibling sample. Less than 1.5% of siblings reported elevated scores on two or more of the subscales of the BSI-18. Risk factors for sibling depression included having a survivor brother (OR 2.22, 95% CI 1.42-3.55), and having a survivor with impaired general health (OR 2.15, 95% CI 1.18-3.78). Siblings who were younger than the survivor reported increased global psychological distress (OR 1.81, 95% CI 1.05-3.12), as did siblings of survivors reporting global psychological distress (OR 2.32, 95% CI 1.08-4.59). Siblings of sarcoma survivors reported more somatization than did siblings of leukemia survivors (OR 2.07, 95% CI 1.05-3.98). Conclusions: These findings suggest that siblings of long-term childhood cancer survivors are psychologically healthy in general. There are, however, small subgroups of siblings at risk for long-term psychological impairment who may benefit from preventive risk-reduction strategies during childhood while their sibling with cancer is undergoing treatment. Copyright (C) 2010 John Wiley & Sons, Ltd. C1 [Buchbinder, David] CHOC Childrens Hosp, Dept Pediat, Orange, CA 92868 USA. [Buchbinder, David] CHOC Childrens Hosp, Div Hematol, Orange, CA 92868 USA. [Casillas, Jacqueline; Stuber, Margaret; Zeltzer, Lonnie K.] Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90024 USA. [Casillas, Jacqueline; Stuber, Margaret; Zeltzer, Lonnie K.] Univ Calif Los Angeles, David Geffen Sch Med, Div Canc Prevent & Control Res, Los Angeles, CA 90095 USA. [Casillas, Jacqueline; Stuber, Margaret; Zeltzer, Lonnie K.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. [Krull, Kevin R.; Robison, Leslie L.; Armstrong, Gregory T.] St Jude Childrens Hosp, Dept Epidemiol & Canc Control, Memphis, TN 38105 USA. [Goodman, Pam; Leisenring, Wendy] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98104 USA. [Recklitis, Christopher] Dana Farber Canc Inst, Dept Psychiat, Boston, MA 02115 USA. [Recklitis, Christopher] Dana Farber Canc Inst, Perini Family Survivors Ctr, Boston, MA 02115 USA. [Alderfer, Melissa A.] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA. [Alderfer, Melissa A.] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. [Kunin-Batson, Alicia] Univ Minnesota, Dept Pediat, Div Neuropsychol, Minneapolis, MN 55455 USA. RP Buchbinder, D (reprint author), CHOC Childrens Hosp, Dept Pediat, 455 S Main St, Orange, CA 92868 USA. EM dbuchbinder@choc.org OI Zeltzer, Lonnie/0000-0001-9306-9450 FU UCLA Jonsson Cancer Center Foundation; Stein Oppenhiemer Endowment Award; American Society of Clinical Oncology; National Cancer Institute [U24 CA55727]; American Lebanese Syrian Associated Charities (ALSAC); Gwynne Hazen Cherry Memorial Laboratories FX Work on this study was supported by a post-doctoral fellowship award from the UCLA Jonsson Cancer Center Foundation (to D. Buchbinder and sponsor L. Zeltzer), a Stein Oppenhiemer Endowment Award (to D. Buchbinder and sponsor M. Stuber), a American Society of Clinical Oncology Young Investigator Award (to D. Buchbinder and sponsor D. Nugent) and by grant U24 CA55727 (L. L. Robison, Principal Investigator) from the National Cancer Institute, and by support to St. Jude Children's Research Hospital from the American Lebanese Syrian Associated Charities (ALSAC). The authors are grateful to the participants of the CCSS. We would also like to acknowledge the support of the Gwynne Hazen Cherry Memorial Laboratories and the assistance of Ron D. Hayes, MD PhD; Patricia Ganz, MD; and Roshan Bastani, PhD at the UCLA School of Public Health for their assistance in the preparation of this manuscript. NR 46 TC 27 Z9 27 U1 2 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD DEC PY 2011 VL 20 IS 12 BP 1259 EP 1268 DI 10.1002/pon.1848 PG 10 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 863MS UT WOS:000298169100003 PM 22114043 ER PT J AU Wolf, EJ Harrington, KM Miller, MW AF Wolf, Erika J. Harrington, Kelly M. Miller, Mark W. TI Psychometric Properties of the Schedule for Nonadaptive and Adaptive Personality in a PTSD Sample SO PSYCHOLOGICAL ASSESSMENT LA English DT Article DE Schedule for Nonadaptive and Adaptive Personality; Multidimensional Personality Questionnaire; International Personality Disorder Exam; psychometric; posttraumatic stress disorder ID POSTTRAUMATIC-STRESS-DISORDER; 5-FACTOR MODEL; ANXIETY DISORDERS; COMBAT VETERANS; INTERNALIZING SUBTYPES; DIMENSIONAL MODELS; AXIS-II; DSM-V; SCALES; MOOD AB This study evaluated the psychometric characteristics of the Schedule for Nonadaptive and Adaptive Personality (SNAP; Clark, 1996) in 280 individuals who screened positive for posttraumatic stress disorder (PTSD). The SNAP validity, trait, temperament, and personality disorder (PD) scales were compared with scales on the Brief Form of the Multidimensional Personality Questionnaire (Patrick, Curtin, & Tellegen, 2002). In a subsample of 86 veterans, the SNAP PD, trait, and temperament scales were also evaluated in comparison to the International Personality Disorder Examination (IPDE; Loranger, 1999), a semistructured diagnostic interview. Results revealed that the SNAP scales have good convergent validity, as evidenced by their pattern of associations with related measures of personality and PD. However, evidence for their discriminant validity in relationship to other measures of personality and PD was more mixed, and test scores on the SNAP trait and temperament scales left much unexplained variance in IPDE-assessed PDs. The diagnostic scoring of the SNAP PD scales greatly inflated prevalence estimates of PDs relative to the IPDE and showed poor agreement with the IPDE. In contrast, the dimensional SNAP scores yielded far stronger associations with continuous scores on the IPDE. The SNAP scales also largely evidenced expected patterns of association with a measure of PTSD severity. Overall, findings support the use of this measure in this population and contribute to our conceptualization of the association between temperament, PTSD, and Axis II psychopathology. C1 VA Natl Ctr PTSD, Boston, MA USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. RP Miller, MW (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD 116B2, 150 S Huntington Ave, Boston, MA 02130 USA. EM mark.miller5@va.gov RI Schueter, nicos/A-3625-2014; Miller, Mark/G-7322-2011; OI Miller, Mark/0000-0001-6393-8563; Wolf, Erika/0000-0003-2666-2435 FU CSRD VA [I01 CX000431]; Intramural VA [CDA-2-067-10S]; NIMH NIH HHS [5F31MH074267, 5R01MH079806), F31 MH074267, R01 MH079806, R01 MH079806-01, T32 MH019836, T32MH019836] NR 61 TC 2 Z9 2 U1 2 U2 5 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1040-3590 J9 PSYCHOL ASSESSMENT JI Psychol. Assess. PD DEC PY 2011 VL 23 IS 4 BP 911 EP 924 DI 10.1037/a0023985 PG 14 WC Psychology, Clinical SC Psychology GA 856IN UT WOS:000297633000010 PM 21767029 ER PT J AU Broyles, LM Rodriguez, KL Price, PA Bayliss, NK Sevick, MA AF Broyles, Lauren Matukaitis Rodriguez, Keri L. Price, Patrice A. Bayliss, Nichole K. Sevick, Mary Ann TI Overcoming Barriers to the Recruitment of Nurses as Participants in Health Care Research SO QUALITATIVE HEALTH RESEARCH LA English DT Article DE alcohol / alcoholism; focus groups; health care; health care, acute / critical; nursing; relationships, research; research participation; research, access to participants; research, qualitative; sensitive topics ID QUALITY-OF-LIFE; NURSING-RESEARCH; FOCUS GROUPS; PERCEPTIONS; EXPERIENCES; INTERVIEWS; STRATEGIES; PROVIDERS; EMPLOYEES; HEART AB Adequate participant recruitment is critical for the successful execution of research studies involving human subjects. Participant recruitment can be particularly challenging when the intended study participants are health care providers as opposed to patients. Discussions of the challenges and successful strategies associated with provider recruitment are limited, particularly regarding providers other than physicians and settings outside of primary care. Using a case study format, we present our experiences recruiting inpatient nurses into a study which involved focus group methodology at a United States Veterans Health Administration facility. We describe the initial logistical and ethical issues involved, various challenges we encountered, and five successful action strategies used during a second recruitment wave addressing logistical issues; on-site recruitment; increased scheduling flexibility and peer-to-peer recruitment; attention to the sensitive nature of the research topic; and increased involvement of stakeholders. In conclusion, we advocate for multimodal recruitment strategies that facilitate ongoing investigator-clinician partnerships. C1 [Broyles, Lauren Matukaitis; Rodriguez, Keri L.; Bayliss, Nichole K.; Sevick, Mary Ann] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15206 USA. [Broyles, Lauren Matukaitis] VA Pittsburgh Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Pittsburgh, PA 15206 USA. [Rodriguez, Keri L.; Sevick, Mary Ann] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15206 USA. [Price, Patrice A.] VA Pittsburgh Healthcare Syst, Crit Care Serv Line, Pittsburgh, PA 15206 USA. RP Broyles, LM (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, 7180 Highland Dr,151C-H, Pittsburgh, PA 15206 USA. EM Lauren.Broyles@va.gov NR 53 TC 7 Z9 7 U1 0 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1049-7323 J9 QUAL HEALTH RES JI Qual. Health Res. PD DEC PY 2011 VL 21 IS 12 BP 1705 EP 1718 DI 10.1177/1049732311417727 PG 14 WC Information Science & Library Science; Social Sciences, Interdisciplinary; Social Sciences, Biomedical SC Information Science & Library Science; Social Sciences - Other Topics; Biomedical Social Sciences GA 854VJ UT WOS:000297522600009 PM 21844286 ER PT J AU Barnes, TA Kacmarek, RM Durbin, CG AF Barnes, Thomas A. Kacmarek, Robert M. Durbin, Charles G., Jr. TI Survey of Respiratory Therapy Education Program Directors in the United States SO RESPIRATORY CARE LA English DT Article DE respiratory care; respiratory therapist; survey; education; credentials; accreditation AB OBJECTIVE: As background for the American Association for Respiratory Care (AARC) third 2015 and Beyond conference, we sought information and opinions on the ability of the current respiratory therapy education infrastructure to make changes that would assure competent respiratory therapists in the envisioned healthcare future. METHODS: After pilot testing and refining the questions, we invited the directors of 435 respiratory therapy programs (based in 411 colleges) that were fully accredited or in the process of being accredited by the Commission on Accreditation for Respiratory Care as of May, 2010, to participate in the survey. RESULTS: Three-hundred forty-eight program directors (80%) provided valid survey responses. Three of the 5 competencies related to evidence-based medicine and respiratory care protocols were taught less often in the associate-degree programs than in the baccalaureate-degree programs. Eighty percent of the baccalaureate-degree programs, compared to 42% of the associate-degree programs, instruct students how to critique published research (P < .001). Only 34% of the associate-degree programs teach students the general meaning of statistical tests, compared to 78% of the baccalaureate-degree programs (P < .001). Ninety-four percent of the baccalaureate-degree programs, versus 81% of the associate-degree programs, teach the students to apply evidence-based medicine to clinical practice (P = .01). Teaching students how to describe healthcare and financial reimbursement systems and the need to reduce the cost of delivering respiratory care (a leadership competency identified by the second 2015 and Beyond conference) was significantly more common in the baccalaureate-degree programs (72%) than in the associate-degree programs (56%) (P = .03). Other competencies showed trends toward differences, and the baccalaureate-degree programs reported higher percentages of success than the associate-degree programs. CONCLUSIONS: There are important differences between the baccalaureate-degree and associate-degree programs. C1 [Barnes, Thomas A.] Northeastern Univ, Dept Hlth Sci, Boston, MA 02115 USA. [Kacmarek, Robert M.] Massachusetts Gen Hosp, Dept Anesthesiol, Boston, MA 02114 USA. [Kacmarek, Robert M.] Harvard Univ, Sch Med, Boston, MA USA. [Durbin, Charles G., Jr.] Univ Virginia, Dept Anesthesiol, Charlottesville, VA USA. RP Barnes, TA (reprint author), Northeastern Univ, Dept Hlth Sci, 316 Robinson Hall,360 Huntington Ave, Boston, MA 02115 USA. EM t.barnes@neu.edu NR 10 TC 6 Z9 6 U1 0 U2 0 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESP CARE JI Respir. Care PD DEC PY 2011 VL 56 IS 12 BP 1906 EP 1915 DI 10.4187/respcare.01259 PG 10 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 868IF UT WOS:000298516300005 PM 21535914 ER PT J AU Duan, M Berra, L Kumar, A Wilcox, S Safford, S Goulet, R Lander, M Schmidt, U AF Duan, Melissa Berra, Lorenzo Kumar, Asheesh Wilcox, Susan Safford, Steve Goulet, Robert Lander, Michelle Schmidt, Ulrich TI Use of Hypothermia to Allow Low-Tidal-Volume Ventilation in a Patient With ARDS SO RESPIRATORY CARE LA English DT Article DE acute respiratory distress syndrome; ARDS; mechanical ventilation; lung-protective ventilation; tidal volume; hypothermia; permissive hypercapnia ID RESPIRATORY-DISTRESS-SYNDROME; PULMONARY VENTILATION; FAILURE AB Low-tidal-volume ventilation reduces mortality in patients with ARDS, but there are often challenges in implementing lung-protective ventilation, such as acidosis from hypercapnia. In a patient with severe ARDS we achieved adequate ventilation with a very low tidal volume (4 mL/kg ideal body weight) by inducing mild hypothermia (body temperature 35-36 degrees C). C1 [Duan, Melissa; Berra, Lorenzo; Kumar, Asheesh; Wilcox, Susan; Safford, Steve; Goulet, Robert; Lander, Michelle; Schmidt, Ulrich] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Surg Intens Care Unit,Dept Anesthesia Crit Care &, Boston, MA 02114 USA. RP Schmidt, U (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Surg Intens Care Unit,Dept Anesthesia Crit Care &, 55 Fruit St,Gray 4, Boston, MA 02114 USA. EM uschmidt@partners.org OI Wilcox, Susan/0000-0001-7477-7531 NR 9 TC 6 Z9 7 U1 1 U2 2 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESP CARE JI Respir. Care PD DEC PY 2011 VL 56 IS 12 BP 1956 EP 1958 DI 10.4187/respcare.01211 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 868IF UT WOS:000298516300013 PM 21682985 ER PT J AU Grayson, PC Sloan, JM Niles, JL Monach, PA Merkel, PA AF Grayson, Peter C. Sloan, J. Mark Niles, John L. Monach, Paul A. Merkel, Peter A. TI Antineutrophil Cytoplasmic Antibodies, Autoimmune Neutropenia, and Vasculitis SO SEMINARS IN ARTHRITIS AND RHEUMATISM LA English DT Review DE vasculitis; neutropenia; antineutrophil cytoplasmic antibody (ANCA) ID ANCA-ASSOCIATED VASCULITIS; LEVAMISOLE-TAINTED COCAINE; DRUG-INDUCED NEUTROPENIA; WEGENERS-GRANULOMATOSIS; FELTYS-SYNDROME; LUPUS SYNDROME; PROPYLTHIOURACIL; AUTOANTIBODIES; NEUTROPHILS; FEATURES AB Objectives: Reports of an association between antineutrophil cytoplasmic antibodies (ANCA) and autoimmune neutropenia have rarely included cases of proven vasculitis. A case of ANCA-associated vasculitis (AAV) with recurrent neutropenia is described and relevant literature on the association between ANCA, neutropenia, and vasculitis is reviewed. Methods: Longitudinal clinical assessments and laboratory findings are described in a patient with AAV and recurrent episodes of profound neutropenia from December 2008 to October 2010. A PubMed database search of the medical literature was performed for articles published from 1960 through October 2010 to identify all reported cases of ANCA and neutropenia. Results: A 49-year-old man developed recurrent neutropenia, periodic fevers, arthritis, biopsyproven cutaneous vasculitis, sensorineural hearing loss, epididymitis, and positive tests for ANCA with specificity for antibodies to both proteinase 3 and myeloperoxidase. Antineutrophil membrane antibodies were detected during an acute neutropenic phase and were not detectable in a postrecovery sample, whereas ANCA titers did not seem to correlate with neutropenia. An association between ANCA and neutropenia has been reported in 74 cases from 24 studies in the context of drug/toxin exposure, underlying autoimmune disease, or chronic neutropenia without underlying autoimmune disease. In these cases, the presence of atypical ANCA patterns and other antibodies were common; however, vasculitis was uncommon and when it occurred was usually limited to the skin and in cases of underlying toxin exposure. Conclusions: ANCA is associated with autoimmune neutropenia, but systemic vasculitis rarely occurs in association with ANCA and neutropenia. The interaction between neutrophils and ANCA may provide insight into understanding both autoimmune neutropenia and AAV. (C) 2011 Elsevier Inc. All rights reserved. Semin Arthritis Rheum 41:424-433 C1 [Grayson, Peter C.; Monach, Paul A.; Merkel, Peter A.] Boston Univ, Med Ctr, Clin Epidemiol Unit, Dept Med, Boston, MA 02118 USA. [Sloan, J. Mark] Boston Univ, Hematol Oncol Sect, Dept Med, Boston, MA 02118 USA. [Niles, John L.] Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. [Grayson, Peter C.; Monach, Paul A.; Merkel, Peter A.] Boston Univ, Sch Med, Vasculitis Ctr, Rheumatol Sect,Med Ctr, Boston, MA 02118 USA. RP Grayson, PC (reprint author), Boston Univ, Sch Med, Vasculitis Ctr, Rheumatol Sect,Med Ctr, 72 E Concord St, Boston, MA 02118 USA. EM pgrayson@bu.edu OI Sloan, John/0000-0001-7069-4528 FU NIH [AR 007598]; Arthritis Foundation FX This work was supported by Grants NIH T32 (AR 007598) Training Program in Rheumatic Disease (P. Grayson); and the Arthritis Foundation Arthritis Investigator Award (P. Monach). NR 45 TC 5 Z9 5 U1 0 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0049-0172 J9 SEMIN ARTHRITIS RHEU JI Semin. Arthritis Rheum. PD DEC PY 2011 VL 41 IS 3 BP 424 EP 433 DI 10.1016/j.semarthrit.2011.02.003 PG 10 WC Rheumatology SC Rheumatology GA 864BK UT WOS:000298211800012 PM 21507463 ER PT J AU Tsai, AC Bangsberg, DR Emenyonu, N Senkungu, JK Martin, JN Weiser, SD AF Tsai, Alexander C. Bangsberg, David R. Emenyonu, Nneka Senkungu, Jude K. Martin, Jeffrey N. Weiser, Sheri D. TI The social context of food insecurity among persons living with HIV/AIDS in rural Uganda SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE Uganda; HIV/AIDS; International health; Social support; Stigma; Food security ID HIV-INFECTED INDIVIDUALS; RESOURCE-CONSTRAINED SETTINGS; AIDS-RELATED STIGMA; ANTIRETROVIRAL THERAPY; SOUTH-AFRICA; POLITICAL-ECONOMY; PUBLIC-HEALTH; POSITIVE INDIVIDUALS; DEVELOPING-COUNTRIES; SAN-FRANCISCO AB HIV/AIDS and food insecurity are two of the leading causes of morbidity and mortality in sub-Saharan Africa, with each heightening the vulnerability to, and worsening the severity of, the other. Less research has focused on the social determinants of food insecurity in resource-limited settings, including social support and HIV-related stigma. In this study, we analyzed data from a cohort of 456 persons from the Uganda AIDS Rural Treatment Outcomes study, an ongoing prospective cohort of persons living with HIV/AIDS (PLWHA) initiating HIV antiretroviral therapy in Mbarara, Uganda. Quarterly data were collected by structured interviews. The primary outcome, food insecurity, was measured with the Household Food Insecurity Access Scale. Key covariates of interest included social support, internalized HIV-related stigma, HIV-related enacted stigma, and disclosure of HIV serostatus. Severe food insecurity was highly prevalent overall (38%) and more prevalent among women than among men. Social support, HIV disclosure, and internalized HIV-related stigma were associated with food insecurity; these associations persisted after adjusting for household wealth, employment status, and other previously identified correlates of food insecurity. The adverse effects of internalized stigma persisted in a lagged specification, and the beneficial effect of social support further persisted after the inclusion of fixed effects. International organizations have increasingly advocated for addressing food insecurity as part of HIV/AIDS programming to improve morbidity and mortality. This study provides quantitative evidence on social determinants of food insecurity among PLWHA in resource-limited settings and suggests points of intervention. These findings also indicate that structural interventions to improve social support and/or decrease HIV-related stigma may also improve the food security of PLWHA. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Tsai, Alexander C.] Harvard Univ, Robert Wood Johnson Hlth & Soc Scholars Program, Cambridge, MA 02138 USA. [Bangsberg, David R.] Harvard Univ, Sch Med, Boston, MA USA. [Bangsberg, David R.] Harvard Initiat Global Hlth, Cambridge, MA USA. [Bangsberg, David R.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Bangsberg, David R.; Senkungu, Jude K.] Mbarara Univ Sci & Technol, Mbarara, Uganda. [Bangsberg, David R.] Massachusetts Gen Hosp, Massachusetts Inst Technol, Phillip T & Susan M Ragon Inst, Charlestown, MA USA. [Bangsberg, David R.] Harvard Univ, Charlestown, MA USA. [Bangsberg, David R.] Brigham & Womens Hosp, Div Global Hlth Equ, Boston, MA 02115 USA. [Emenyonu, Nneka] Univ N Carolina, Sch Publ Hlth, Dept Hlth Policy & Management, Chapel Hill, NC USA. [Martin, Jeffrey N.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Weiser, Sheri D.] Univ Calif San Francisco, Div HIV AIDS, San Francisco, CA 94143 USA. [Weiser, Sheri D.] Univ Calif San Francisco, Ctr AIDS Prevent Studies, San Francisco, CA 94143 USA. RP Tsai, AC (reprint author), Harvard Ctr Populat & Dev Studies, 9 Bow St, Cambridge, MA 02138 USA. EM atsai@hsph.harvard.edu RI Nguyen, Giang/D-9027-2016; OI Tsai, Alexander/0000-0001-6397-7917 FU U.S. National Institutes of Health [K23 MH-79713, MH-79713-03S1, R01 MH-054907, P30 AI27763]; Tim and Jane Meyer Family Foundation; Robert Wood Johnson Foundation [K24 MH-087227]; Burke Family Foundation FX We thank the Uganda AIDS Rural Treatment Outcomes study participants who made this study possible by sharing their experiences; Annet Kawuma and Annet Kembabazi for providing study coordination and support: and Doreen Akello, Marcy Mutumba, Christine Ngabirano, Ruth Ssentongo, and Florence Turyashemererwa for research assistance. Edward Frongillo, Jessica Haberer, Peter W. Hunt, and F.B. Nozmo Mukiibi provided invaluable input on study design and implementation. While these individuals are acknowledged for their assistance, no endorsement of manuscript contents or conclusions should be inferred. The study was funded by U.S. National Institutes of Health K23 MH-79713 and MH-79713-03S1 (PI: Weiser), R01 MH-054907 (PI: Bangsberg), P30 AI27763 (UCSF-Gladstone Institute Center for AIDS Research), and the Tim and Jane Meyer Family Foundation. The authors acknowledge the following additional sources of support: Robert Wood Johnson Foundation Health & Society Scholars Program (Tsai), K24 MH-087227 (Bangsberg), and the Burke Family Foundation (Weiser). NR 98 TC 47 Z9 47 U1 4 U2 24 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD DEC PY 2011 VL 73 IS 12 BP 1717 EP 1724 DI 10.1016/j.socscimed.2011.09.026 PG 8 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 863YF UT WOS:000298203500006 PM 22019367 ER PT J AU Nehs, MA Lin, CI Kozono, DE Whang, EE Cho, NL Zhu, K Moalem, J Moore, FD Ruan, DT AF Nehs, Matthew A. Lin, Chi-Iou Kozono, David E. Whang, Edward E. Cho, Nancy L. Zhu, Kaya Moalem, Jacob Moore, Francis D., Jr. Ruan, Daniel T. TI Necroptosis is a novel mechanism of radiation-induced cell death in anaplastic thyroid and adrenocortical cancers SO SURGERY LA English DT Article ID CARCINOMA; RADIOTHERAPY; SURVIVAL; MITOTANE; RECURRENCE; EFFICACY; SURGERY; PATHWAY; KINASE; RIP AB Background. Necroptosis is a recently described mechanism of programmed cellular death. We hypothesize that necroptosis plays an important role in radiation-induced cell death in endocrine cancers. Methods. Thyroid and adrenocortical carcinoma cell lines were exposed to increasing doses of radiation in the presence of necroptosis inhibitor Nec-1 and/or apoptosis-inhibitor zVAD. H295R cells deficient in receptor interacting protein 1 (RIP1), an essential kinase for necroptosis, were used as controls. Survival curves were generated at increasing doses of radiation. Results. Nec-1 and zVAD increased cellular survival with increasing doses of radiotherapy in 8505c, TPC-1, and SW13. Both inhibitors used together had an additive effect. At 6 Gy, 8505c, TPC-1, and SW13 cell survival was significantly increased compared to controls by 40%; 33%, and 31% with Nec-1 treatment, by 53%, 47%, and 44% with zVAD treatment, and by 80%, 70%, and 65% with both compounds, respectively (P < .05). H295R showed no change in survival with Nec-1 treatment. The radiobiologic parameter quasithreshold dose was significantly increased in 8505c, TPC-1, and SW13 cells when both Nec-1 and WAD were used in combination to inhibit necroptosis and apoptosis together, revealing resistance to standard doses of fractionated therapeutic radiation. Conclusion. Necroptosis contributes to radiation-induced cell death. Future studies should investigate ways to promote the activation of necroptosis to improve radiosensitivity. (Surgery 2011;150:1032-9.) C1 [Nehs, Matthew A.; Lin, Chi-Iou; Whang, Edward E.; Cho, Nancy L.; Moore, Francis D., Jr.; Ruan, Daniel T.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. [Kozono, David E.; Zhu, Kaya] Harvard Univ, Sch Med, Dana Farber Canc Ctr, Boston, MA 02115 USA. [Moalem, Jacob] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. RP Ruan, DT (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, 75 Francis St,ASB2, Boston, MA 02115 USA. EM druan@partners.org FU Department of Surgery at Brigham and Women's Hospital FX Supported by an Osteen Junior Faculty Research Grant (to D.T.R.) from the Department of Surgery at Brigham and Women's Hospital. NR 24 TC 27 Z9 31 U1 1 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD DEC PY 2011 VL 150 IS 6 BP 1032 EP 1038 DI 10.1016/j.surg.2011.09.012 PG 7 WC Surgery SC Surgery GA 865UX UT WOS:000298337500004 PM 22136818 ER PT J AU Yip, DT Hassan, M Pazaitou-Panayiotou, K Ruan, DT Gawande, AA Gaz, RD Moore, FD Hodin, RA Stephen, AE Sadow, PM Daniels, GH Randolph, GW Parangi, S Lubitz, CC AF Yip, Dana T. Hassan, Maria Pazaitou-Panayiotou, Kalliopi Ruan, Daniel T. Gawande, Atul A. Gaz, Randall D. Moore, Francis D., Jr. Hodin, Richard A. Stephen, Antonia E. Sadow, Peter M. Daniels, Gilbert H. Randolph, Gregory W. Parangi, Sareh Lubitz, Carrie C. TI Preoperative basal calcitonin and tumor stage correlate with postoperative calcitonin normalization in patients undergoing initial surgical management of medullary thyroid carcinoma SO SURGERY LA English DT Article ID SERUM CALCITONIN; ROUTINE MEASUREMENT; BIOCHEMICAL CURE; NODE DISSECTION; UNITED-STATES; MEN 2; CANCER; DIAGNOSIS; IMPACT; PERSISTENT AB Background. The optimal initial operative management of medullary thyroid cancer (MTC) and the use of biomarkers to guide the extent of operation remain controversial. We hypothesized that preoperative serum levels of calcitonin and carcinoembryonic antigen (CEA) correlate with extent of disease and postoperative levels reflect the extent of operation performed. Methods. We assessed retrospectively clinical and pathologic factors among patients with MTC undergoing at least total thyroidectomy; these factors were correlated with biomarkers using regression analyses. Results. Data were obtained from 104 patients, 28% with hereditary MTC. Preoperative calcitonin correlated with tumor size (P < .001) and postoperative serum calcitonin levels (P = .01) after multivariable adjustment for lymph node positivity, extent of operation, and hereditary MTC. No patient with a preoperative calcitonin level of <53 pg/ml (n = 20) had lymph node metastases. TNM stage (P = .001) and preoperative calcitonin levels (P = .04), but not extent of operation, independently correlated with the failure to normalize postoperative calcitonin. Postoperative CEA correlated with positive margins (adjusted P = 04). Neither preoperative nor postoperative CEA was correlated with lymph node positivity or extent of surgery. Conclusion. Preoperative serum calcitonin and TMN stage, but not extent of operation, were independent predictors of postoperative normalization of serum calcitonin levels. Future studies should evaluate preoperative serum calcitonin levels as a determinate of the extent of initial operation. (Surgery 2011; 150:1168-77.) C1 [Yip, Dana T.; Hassan, Maria; Pazaitou-Panayiotou, Kalliopi; Gaz, Randall D.; Hodin, Richard A.; Stephen, Antonia E.; Sadow, Peter M.; Daniels, Gilbert H.; Parangi, Sareh; Lubitz, Carrie C.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Yip, Dana T.; Hassan, Maria; Pazaitou-Panayiotou, Kalliopi; Gaz, Randall D.; Hodin, Richard A.; Stephen, Antonia E.; Sadow, Peter M.; Daniels, Gilbert H.; Parangi, Sareh; Lubitz, Carrie C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Yip, Dana T.; Hassan, Maria; Pazaitou-Panayiotou, Kalliopi; Gaz, Randall D.; Hodin, Richard A.; Stephen, Antonia E.; Sadow, Peter M.; Daniels, Gilbert H.; Parangi, Sareh; Lubitz, Carrie C.] Massachusetts Gen Hosp, Thyroid Unit, Boston, MA 02114 USA. [Ruan, Daniel T.; Gawande, Atul A.; Moore, Francis D., Jr.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Randolph, Gregory W.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Yip, DT (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. EM danayip@gmail.com OI Gawande, Atul/0000-0002-1824-9176 FU NCI NIH HHS [R01 CA149738] NR 27 TC 14 Z9 15 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD DEC PY 2011 VL 150 IS 6 BP 1168 EP 1176 DI 10.1016/j.surg.2011.09.043 PG 9 WC Surgery SC Surgery GA 865UX UT WOS:000298337500039 PM 22136837 ER PT J AU Abi-Haidar, Y Gupta, K Strymish, J Williams, SA Itani, KMF AF Abi-Haidar, Youmna Gupta, Kalpana Strymish, Judith Williams, Sandra A. Itani, Kamal M. F. TI Factors Associated with Post-Operative Conversion to Methicillin-Resistant Staphylococcus Aureus Positivity or Infection in Initially MRSA-Negative Patients SO SURGICAL INFECTIONS LA English DT Article ID SURGICAL SITE INFECTION; INTENSIVE-CARE-UNIT; RISK-FACTORS; CARDIAC-SURGERY; ANTIMICROBIAL RESISTANCE; NOSOCOMIAL TRANSMISSION; POVIDONE-IODINE; WOUND-INFECTION; CRITICALLY-ILL; US HOSPITALS AB Background: Hospital-acquired methicillin-resistant Staphylococcus aureus (MRSA) is associated with morbid, invasive infections and has been implicated in nearly every type of nosocomial infection. Our aim was to identify the risk factors for patient conversion from MRSA negativity pre-operatively to MRSA positivity post-operatively. Methods: We retrospectively reviewed all patients at the Veterans Affairs-Boston Health Care System who underwent clean or clean-contaminated surgical procedures during the years 2008 and 2009 and had documented pre-operative nasal polymerase chain reaction (PCR) testing for MRSA. We abstracted post-operative MRSA microbiologic testing results, MRSA infections, surgical site infections (SSIs), surgical prophylaxis data, and SSI risk index, as calculated using the Veterans Affairs Surgical Quality Improvement Project (VASQIP) database variables. All patients who had a negative nasal MRSA PCR result in the 31-day pre-operative period and did not have any positive MRSA clinical swab or culture in the 1-year pre-operative period were defined as MRSA-negative. These patients were classified as converters to MRSA positivity if they had at least one documented positive nasal MRSA PCR swab, culture, nosocomial infection, or SSI within 31 days post-operatively. Results: Among 4,238 eligible patients, 3,890 (92%) qualified as MRSA-negative pre-operatively. A total of 1,432 (37%) of these patients were assessed in the VASQIP database, of whom 34 (2%) converted to MRSA positivity post-operatively. On multivariable logistic regression analysis of the VASQIP sample, age (odds ratio [OR] 1.049; 95% confidence interval [CI] 1.016, 1.083), SSI risk index (OR 2.863; 95% CI 1.251-6.554), and vancomycin prophylaxis alone or in combination (OR 3.223; 95% CI 1.174-8.845) were significantly associated with conversion to MRSA positivity. Conclusion: In pre-operatively MRSA-negative patients, age, SSI risk index, and vancomycin prophylaxis were significant factors for conversion to MRSA positivity post-operatively. Alternatives to vancomycin prophylaxis in non-colonized patients and optimization of patients' SSI risk factors should be considered before elective surgery. C1 [Abi-Haidar, Youmna; Itani, Kamal M. F.] Vet Affairs Boston Healthcare Syst, Dept Surg, Boston, MA USA. [Gupta, Kalpana; Strymish, Judith] Vet Affairs Boston Healthcare Syst, Dept Med, Boston, MA USA. [Williams, Sandra A.] Vet Affairs Boston Healthcare Syst, Ctr Org Leadership & Management Res, Boston, MA USA. [Abi-Haidar, Youmna; Gupta, Kalpana; Itani, Kamal M. F.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Strymish, Judith; Itani, Kamal M. F.] Harvard Univ, Sch Med, Boston, MA USA. RP Itani, KMF (reprint author), VA Boston HCS, 1400 VFW Pkwy,Rm 1B-130, W Roxbury, MA 02132 USA. EM kamal.itani@va.gov FU Merck Pharmaceuticals; Sanofi-Aventis Pharmaceuticals FX Dr. Itani has received research support from Merck Pharmaceuticals and from Sanofi-Aventis Pharmaceuticals. NR 49 TC 3 Z9 3 U1 1 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-2964 J9 SURG INFECT JI Surg. Infect. PD DEC PY 2011 VL 12 IS 6 BP 435 EP 442 DI 10.1089/sur.2011.040 PG 8 WC Infectious Diseases; Surgery SC Infectious Diseases; Surgery GA 872VI UT WOS:000298837400004 PM 22142319 ER PT J AU Thompson, GR Wickes, BL Herrera, ML Haman, TC Lewis, JS Jorgensen, JH AF Thompson, G. R., III Wickes, B. L. Herrera, M. L. Haman, T. C. Lewis, J. S., II Jorgensen, J. H. TI Disseminated Burkholderia gladioli infection in a lung transplant recipient with underlying hypocomplementemic urticarial vasculitis SO TRANSPLANT INFECTIOUS DISEASE LA English DT Article DE hypocomplementemic urticarial vasculitis; Burkholderia gladioli; Burkholderia; lung transplantation ID CHRONIC GRANULOMATOUS-DISEASE; CYSTIC-FIBROSIS; PSEUDOMONAS-AERUGINOSA; IDENTIFICATION; CEPACIA; ANTIBODIES; PCR AB Burkholderia gladioli is difficult to definitively identify within the laboratory using phenotypic testing alone. We describe a case of recurrent B. gladioli infection in a lung transplant recipient with underlying hypocomplementemic urticarial vasculitis syndrome, discuss the difficulties encountered with laboratory identification, provide a review of the methodology required for definitive identification, and discuss potential pathophysiologic mechanisms in this patient responsible for the difficulty in treatment. C1 [Thompson, G. R., III] Univ Calif Davis, Coccidioidomycosis Serol Lab, Dept Med Microbiol & Immunol, Davis, CA 95616 USA. [Thompson, G. R., III] Univ Calif Davis, Dept Internal Med, Div Infect Dis, Davis, CA 95616 USA. [Wickes, B. L.; Herrera, M. L.; Jorgensen, J. H.] Univ Texas San Antonio, Dept Microbiol, Hlth Sci Ctr San Antonio, San Antonio, TX USA. [Haman, T. C.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Lewis, J. S., II] Univ Hlth Syst, Dept Pharm, San Antonio, TX USA. RP Thompson, GR (reprint author), Univ Calif Davis, Coccidioidomycosis Serol Lab, Dept Med Microbiol & Immunol, 1 Shields Ave,Tupper Hall, Davis, CA 95616 USA. EM george.thompson@ucdmc.ucdavis.edu NR 24 TC 1 Z9 1 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1398-2273 J9 TRANSPL INFECT DIS JI Transpl. Infect. Dis. PD DEC PY 2011 VL 13 IS 6 BP 641 EP 645 DI 10.1111/j.1399-3062.2011.00638.x PG 5 WC Immunology; Infectious Diseases; Transplantation SC Immunology; Infectious Diseases; Transplantation GA 865RL UT WOS:000298327900013 PM 21504528 ER PT J AU Walensky, LD Gavathiotis, E AF Walensky, Loren D. Gavathiotis, Evripidis TI BAX unleashed: the biochemical transformation of an inactive cytosolic monomer into a toxic mitochondrial pore SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Review ID PROGRAMMED CELL-DEATH; CYTOCHROME-C RELEASE; CHANNEL-FORMING ACTIVITY; BCL-2 FAMILY PROTEINS; PROAPOPTOTIC BAX; BH3 DOMAIN; E1B 19K; TRANSGENIC MICE; DEFICIENT MICE; IN-VIVO AB BAX, the BCL-2-associated X protein, is a cardinal proapoptotic member of the BCL-2 family, which regulates the critical balance between cellular life and death. Because so many medical conditions can be categorized as diseases of either too many or too few cells, dissecting the biochemistry of BCL-2 family proteins and developing pharmacological strategies to target them have become high priority scientific objectives. Here, we focus on BAX, a latent, cytosolic and monomeric protein that transforms into a lethal mitochondrial oligomer in response to cellular stress. New insights into the structural location of BAX's 'on switch', and the multi-step conformational changes that ensue upon BAX activation, are providing fresh opportunities to modulate BAX for potential benefit in human diseases characterized by pathologic cell survival or unwanted cellular demise. C1 [Walensky, Loren D.] Harvard Univ, Sch Med, Dept Pediat Oncol, Boston, MA 02115 USA. [Walensky, Loren D.] Harvard Univ, Childrens Hosp Boston, Program Canc Chem Biol, Dana Farber Canc Inst,Sch Med, Boston, MA 02115 USA. [Gavathiotis, Evripidis] Albert Einstein Coll Med, Dept Biochem & Med, Wilf Family Cardiovasc Res Inst, Bronx, NY 10461 USA. RP Walensky, LD (reprint author), Harvard Univ, Sch Med, Dept Pediat Oncol, Boston, MA 02115 USA. EM Loren_Walensky@dfci.harvard.edu; Evripidis.Gavathiotis@einstein.yu.edu FU NIH [5R01CA50239, 1K99HL095929] FX We thank E. Smith for figure design. This work was supported by NIH grant 5R01CA50239 to L.D.W. and 1K99HL095929 to E.G. NR 114 TC 80 Z9 89 U1 1 U2 14 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD DEC PY 2011 VL 36 IS 12 BP 642 EP 652 DI 10.1016/j.tibs.2011.08.009 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 867KF UT WOS:000298452600003 PM 21978892 ER PT J AU Krim, SR Vivo, RP Krim, NR Cox, M Hernandez, AF Peterson, ED Fonarow, GC Pina, IL Schwamm, LH Bhatt, DL AF Krim, Selim R. Vivo, Rey P. Krim, Nassim R. Cox, Margueritte Hernandez, Adrian F. Peterson, Eric D. Fonarow, Gregg C. Pina, Ileana L. Schwamm, Lee H. Bhatt, Deepak L. TI Regional differences in clinical profile, quality of care, and outcomes among Hispanic patients hospitalized with acute myocardial infarction in the Get with Guidelines-Coronary Artery Disease (GWTG-CAD) Registry SO AMERICAN HEART JOURNAL LA English DT Article ID ASSOCIATION TASK-FORCE; HEART-ASSOCIATION; AMERICAN-COLLEGE; PERFORMANCE-MEASURES; ETHNIC-DIFFERENCES; MEXICAN-AMERICANS; MORTALITY; PROGRAM; ELEVATION; PROJECT AB Background Although Hispanics constitute the largest minority in the United States, it is unknown whether regional differences in quality of care and outcomes exist among Hispanic patients hospitalized with acute myocardial infarction (MI). Methods Using the GWTG-CAD Registry, clinical characteristics, conformity with quality measures, and in-hospital outcomes were assessed among Hispanic patients from different geographic regions admitted for acute MI in participating hospitals. Results A total of 11,299 Hispanic patients treated for acute MI at 277 hospitals from 4 regions were included in the study. Midwestern Hispanics were more likely to be younger, with male predominance in all regions. Northeastern Hispanics were more often insured with Medicaid. All subgroups showed high rates of hypertension, dyslipidemia, diabetes, and smoking, with the highest rates observed in the northeast region. Northeastern Hispanics were more likely to be discharged on angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers, and statin or other lipid-lowering therapy. No significant regional differences were observed in aspirin, clopidogrel, and guideline-recommended door-to-balloon and door-to-thrombolysis times. Although Hispanics in the south and northeast were more likely to have a longer hospital stay compared with the west, there were no regional differences in in-hospital mortality. Conclusions Among Hispanics with acute MI enrolled in the GWTG-CAD program, there were modest regional differences in clinical profile; high rates of use and, with few exceptions, no regional differences in guideline-recommended therapies; and no regional variation in in-hospital mortality. (Am Heart J 2011;162:988-995.e4.) C1 [Krim, Selim R.] Ochsner Heart & Vasc Inst, New Orleans, LA 70121 USA. [Vivo, Rey P.] Univ Texas Med Branch, Galveston, TX USA. [Vivo, Rey P.] Methodist DeBakey Heart & Vasc Ctr, Houston, TX USA. [Krim, Nassim R.] Montefiore Med Ctr, Bronx, NY 10467 USA. [Cox, Margueritte; Hernandez, Adrian F.; Peterson, Eric D.] Duke Clin Res Inst, Durham, NC USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. [Pina, Ileana L.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. RP Krim, SR (reprint author), Ochsner Heart & Vasc Inst, 1514 Jefferson Highway, New Orleans, LA 70121 USA. EM krimselim@hotmail.com RI Hernandez, Adrian F./A-7818-2016 OI Schwamm, Lee/0000-0003-0592-9145; Hernandez, Adrian F./0000-0003-3387-9616 NR 26 TC 5 Z9 7 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD DEC PY 2011 VL 162 IS 6 BP 988 EP U63 DI 10.1016/j.ahj.2011.09.006 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 861QC UT WOS:000298033300005 PM 22137071 ER PT J AU Chin, CT Weintraub, WS Dai, D Mehta, RH Rumsfeld, JS Anderson, HV Messenger, JC Kutcher, MA Peterson, ED Brindis, RG Rao, SV AF Chin, Chee Tang Weintraub, William S. Dai, David Mehta, Rajendra H. Rumsfeld, John S. Anderson, H. Vernon Messenger, John C. Kutcher, Michael A. Peterson, Eric D. Brindis, Ralph G. Rao, Sunil V. TI Trends and predictors of length of stay after primary percutaneous coronary intervention: A report from the CathPCI Registry SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; CARDIOVASCULAR DATA REGISTRY; EARLY DISCHARGE; PRIMARY ANGIOPLASTY; COST-EFFECTIVENESS; MORTALITY; OUTCOMES AB Background Post hoc analyses of clinical trials suggest that certain patients are eligible for early discharge after ST-segment elevation myocardial infarction. The extent to which ST-segment elevation myocardial infarction patients are discharged early after primary percutaneous coronary intervention (PPCI) in current practice is unknown. Methods We examined 115,113 patients in the CathPCI Registry to assess temporal trends in length of stay (LOS) after PPCI. Baseline characteristics were compared between patients with LOS <= 2 and >2 days. Predictors of LOS >2 days were determined by logistic regression and adjusted for clustering among centers. Patterns of discharge within 2 days for low-risk patients with no inhospital complications were examined. Results From January 2005 through March 2009, mean LOS (4.0 +/- 3.0 to 3.6 +/- 2.7 days) (P for trend <.001) and the proportion of patients discharged after 2 days decreased (72.0%-65.9%), while predicted inhospital mortality risk remained unchanged. Patients with LOS >2 days (n = 77,471; 67.3%) were older and more likely to have had an intra-aortic balloon pump, cardiogenic shock, transfusions, and post-PPCI complications. Of 958 hospitals, 437 (45.6%) discharged at least half of their low-risk patients with no inhospital complications within 2 days. Conclusions While the predicted risk profile has remained stable, there has been a significant decrease in LOS after PPCI. Nevertheless, hospitals vary in discharging low-risk and uncomplicated patients early. Discharge within 2 days was associated with specific patient, procedure, and hospital factors. Further study is needed to determine the safety of early discharge among patients undergoing PPCI. (Am Heart J 2011;162:1052-61.) C1 [Chin, Chee Tang] Natl Heart Ctr Singapore, Singapore 168752, Singapore. [Chin, Chee Tang; Dai, David; Mehta, Rajendra H.; Peterson, Eric D.; Rao, Sunil V.] Duke Clin Res Inst, Durham, NC USA. [Weintraub, William S.] Christiana Care Hlth Syst, Newark, DE USA. [Rumsfeld, John S.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Anderson, H. Vernon] Univ Texas Houston, Hlth Sci Ctr, Houston, TX USA. [Messenger, John C.] Univ Colorado, Denver Sch Med, Aurora, CO USA. [Kutcher, Michael A.] Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. [Brindis, Ralph G.] No Calif Kaiser Permanente, Oakland, CA USA. RP Chin, CT (reprint author), Natl Heart Ctr Singapore, 17 3rd Hosp Ave, Singapore 168752, Singapore. EM chin.chee.tang@nhcs.com.sg FU Agency for Healthcare Research and Quality (AHRQ) [U18HS016964] FX This project was supported by grant number U18HS016964 from the Agency for Healthcare Research and Quality (AHRQ). The content is solely the responsibility of the authors and does not necessarily represent the official views of the AHRQ. The funding source had no role in the design or implementation of the study, or in the decision to seek publication. NR 16 TC 9 Z9 9 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD DEC PY 2011 VL 162 IS 6 BP 1052 EP 1061 DI 10.1016/j.ahj.2011.09.008 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 861QC UT WOS:000298033300013 PM 22137079 ER PT J AU Donohue, JM Zhang, YT Men, AM Perera, S Lave, JR Hanlon, JT Reynolds, CF AF Donohue, Julie M. Zhang, Yuting Men, Aiju Perera, Subashan Lave, Judith R. Hanlon, Joseph T. Reynolds, Charles F. TI Impact of Medicare Part D on Antidepressant Treatment, Medication Choice, and Adherence Among Older Adults With Depression SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE Adherence; depression; insurance coverage; medicare ID PRIMARY-CARE PATIENTS; MAJOR DEPRESSION; HEALTH-SERVICES; DRUG; SYMPTOMS; COST; NONADHERENCE; BENEFICIARIES; MORTALITY; TRIAL AB Objectives: Depression in older adults is often undertreated due, in part, to medication costs. We examined the impact of improved prescription drug coverage under Medicare Part D on use of antidepressants, medication choice, and adherence. Design, Setting and Participants: Observational claims-based study of older adults with depression (ICD-9: 296.2, 296.3, 311, 300.4) continuously enrolled in a Medicare managed care plan between 2004 and 2007. Three groups with limited ($ 150 or $ 350 quarterly caps) or no drug coverage in 2004-2005 obtained Part D benefits in 2006. A comparison group had stable employer-sponsored coverage throughout. Measurements: Any antidepressant prescription fill, antidepressant choice (tricyclics or monoamine oxidase inhibitors versus newer antidepressants), and adherence (80% of days covered) in the first 6 months of treatment. Results: Part D was associated with increased odds of any antidepressant use among those who previously lacked coverage (odds ratio [OR] 1.61, 95% confidence interval [CI] 1.41-1.85) but odds of use did not change among those with limited prior coverage. Use of older antidepressant agents did not change with Part D. All three groups whose coverage improved with Part D had significantly higher odds of 80% of days covered with an antidepressant (OR = 1.86 [95% CI: 1.44-2.39] for no coverage, 1.74 [95% CI: 1.25% 3.42] for $ 150 cap; and 1.19 [95% CI: 1.06-1.34] for the $ 350 cap groups). Conclusions: Medicare Part D was associated with improvements in antidepressant use and adherence in depressed older adults who previously had no or limited drug coverage but not with changes in use of older agents. use and adherence in depressed older adults who previously had no or limited drug coverage but not with changes in use of older agents. (Am J Geriatr Psychiatry 2011; 19:989-997) C1 [Donohue, Julie M.; Zhang, Yuting; Lave, Judith R.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Hlth Policy & Management, Pittsburgh, PA 15261 USA. [Donohue, Julie M.; Reynolds, Charles F.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15261 USA. [Perera, Subashan; Hanlon, Joseph T.] Univ Pittsburgh, Sch Med, Dept Geriatr Med, Pittsburgh, PA 15261 USA. [Perera, Subashan; Hanlon, Joseph T.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Hanlon, Joseph T.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15261 USA. [Hanlon, Joseph T.] Univ Pittsburgh, Clin & Translat Sci Inst, Ctr Hlth Equ Res, Pittsburgh, PA 15261 USA. [Hanlon, Joseph T.] Univ Pittsburgh, Ctr Geriatr Res Educ & Clin, Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA 15261 USA. [Donohue, Julie M.; Reynolds, Charles F.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. RP Donohue, JM (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Hlth Policy & Management, 130 DeSoto St,Crabtree Hall A613, Pittsburgh, PA 15261 USA. EM jdonohue@pitt.edu RI Perera, Subashan/D-7603-2014; OI Donohue, Julie/0000-0003-2418-6017; Zhang, Yuting/0000-0002-6460-6779 FU National Center for Research Resources, National Institutes of Health (NIH) [KL2 RR-024154-04]; Agency for Healthcare Research and Quality [R01HS017695]; NIH [R34 MH082682, R01AG027017, P30AG024827, P30MH71944, T32AG021885, K07AG033174, R01AG034056]; Veterans Administration Health Services Research and Development Service [IIR-06-062]; UPMC endowment in geriatric psychiatry; John A. Hartford Foundation FX This publication was supported by the National Center for Research Resources, National Institutes of Health (NIH) (KL2 RR-024154-04), Agency for Healthcare Research and Quality (R01HS017695), NIH grants (R34 MH082682, R01AG027017, P30AG024827, P30MH71944, T32AG021885, K07AG033174, R01AG034056), the Veterans Administration Health Services Research and Development Service (IIR-06-062), the UPMC endowment in geriatric psychiatry, and John A. Hartford Foundation. NR 32 TC 16 Z9 16 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD DEC PY 2011 VL 19 IS 12 BP 989 EP 997 DI 10.1097/JGP.0b013e3182051a9b PG 9 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 857ES UT WOS:000297699600002 PM 22123272 ER PT J AU Jack, CR Vemuri, P Wiste, HJ Weigand, SD Aisen, PS Trojanowski, JQ Shaw, LM Bernstein, MA Petersen, RC Weiner, MW Knopman, DS AF Jack, Clifford R., Jr. Vemuri, Prashanthi Wiste, Heather J. Weigand, Stephen D. Aisen, Paul S. Trojanowski, John Q. Shaw, Leslie M. Bernstein, Matthew A. Petersen, Ronald C. Weiner, Michael W. Knopman, David S. CA Alzheimer's Dis Neuroimaging Initi TI Evidence for Ordering of Alzheimer Disease Biomarkers SO ARCHIVES OF NEUROLOGY LA English DT Article ID MILD COGNITIVE IMPAIRMENT; PITTSBURGH COMPOUND-B; CEREBROSPINAL-FLUID A-BETA(42); NORMAL OLDER-ADULTS; ASSOCIATION WORKGROUPS; DIAGNOSTIC GUIDELINES; NATIONAL INSTITUTE; CSF BIOMARKERS; A-BETA; AMYLOID DEPOSITION AB Objective: To empirically assess the concept that Alzheimer disease (AD) biomarkers significantly depart from normality in a temporally ordered manner. Design: Validation sample. Setting: Multisite, referral centers. Participants: A total of 401 elderly participants in the Alzheimer's Disease Neuroimaging Initiative who were cognitively normal, who had mild cognitive impairment, or who had AD dementia. We compared the proportions of 3 AD biomarker values (the A beta 42 level in cerebrospinal fluid [CSF], the total tau level in CSF, and the hippocampal volume adjusted for intracranial volume [hereafter referred to as the adjusted hippocampal volume]) that were abnormal as cognitive impairment worsened. Cut points demarcating normal vs abnormal for each biomarker were established by maximizing diagnostic accuracy in independent autopsy samples. Main Outcome Measures: Three AD biomarkers (ie, the CSF A beta 42 level, the CSF total tau level, and the adjusted hippocampal volume). Results: Within each clinical group of the entire sample (n=401), the CSF A beta 42 level was abnormal more often than was the CSF total tau level or the adjusted hippocampal volume. Among the 298 participants with both baseline and 12-month data, the proportion of participants with an abnormal A beta 42 level did not change from baseline to 12 months in any group. The proportion of participants with an abnormal total tau level increased from baseline to 12 months in cognitively normal participants (P=.05) but not in participants with mild cognitive impairment or AD dementia. For 209 participants with an abnormal CSF A beta 42 level at baseline, the percentage with an abnormal adjusted hippocampal volume but normal CSF total tau level increased from baseline to 12 months in participants with mild cognitive impairment. No change in the percentage of MCI participants with an abnormal total tau level was seen between baseline and 12 months. Conclusions: A reduction in the CSF A beta 42 level denotes a pathophysiological process that significantly departs from normality (ie, becomes dynamic) early, whereas the CSF total tau level and the adjusted hippocampal volume are biomarkers of downstream pathophysiological processes. The CSF total tau level becomes dynamic before the adjusted hippocampal volume, but the hippocampal volume is more dynamic in the clinically symptomatic mild cognitive impairment and AD dementia phases of the disease than is the CSF total tau level. Arch Neurol. 2011; 68(12): 1526-1535. Published online August 8, 2011. doi:10.1001/archneurol.2011.183 C1 [Jack, Clifford R., Jr.; Vemuri, Prashanthi; Bernstein, Matthew A.] Mayo Clin & Mayo Fdn Med Educ & Res, Dept Radiol, Rochester, MN 55905 USA. [Wiste, Heather J.; Weigand, Stephen D.] Mayo Clin & Mayo Fdn Med Educ & Res, Div Biomed Stat & Informat, Rochester, MN 55905 USA. [Petersen, Ronald C.; Knopman, David S.] Mayo Clin & Mayo Fdn Med Educ & Res, Dept Neurol, Rochester, MN 55905 USA. [Aisen, Paul S.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. [Weiner, Michael W.] Univ Calif San Francisco, Ctr Imaging Neurodegenerat Dis, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. [Weiner, Michael W.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Trojanowski, John Q.; Shaw, Leslie M.] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Trojanowski, John Q.; Shaw, Leslie M.] Univ Penn, Sch Med, Inst Aging, Philadelphia, PA 19104 USA. RP Jack, CR (reprint author), Mayo Clin & Mayo Fdn Med Educ & Res, Dept Radiol, 200 1st St SW, Rochester, MN 55905 USA. EM jack.clifford@mayo.edu RI Jack, Clifford/F-2508-2010; Vemuri, Prashanthi/K-7030-2012; OI Jack, Clifford/0000-0001-7916-622X; Bernstein, Matt/0000-0003-3770-0441 FU Pfizer; Baxter International Inc; Merck; Avid; Elan Pharmaceuticals; Forest Pharmaceuticals; Baxter Healthcare; National Institutes of Health [AG11378]; ADNI FX Dr Aisen serves on a scientific advisory board for NeuroPhage; serves as a consultant to Elan Corporation, Wyeth, Eisai Inc, Bristol-Myers Squibb, Eli Lilly and Company, NeuroPhage, Merck, Roche, Amgen, Abbott, Pfizer, Novartis, Bayer, Astellas, Dainippon, Biomarin, Solvay, Otsuka, Daiichi, AstraZeneca, Janssen, and Medivation Inc; receives research support from Pfizer and Baxter International Inc; and has received stock options from Medivation Inc and NeuroPhage. Dr Petersen reports serving as a consultant for Elan Pharmaceuticals and GE Healthcare and serving on data monitoring committees for Pfizer and Janssen Alzheimer Immunotherapy. Dr Weiner reports serving on the advisory boards of Elan/Wyeth, Novartis, Banner, Lilly, VACO, Biogen Idec, Araclon, and Pfizer. He serves as a consultant to Elan/Wyeth, Novartis, Forest, Ipsen, Daiichi Sankyo Inc, AstraZeneca, Araclon, Pfizer, TauRx Therapeutics, Bayer, Biogen Idec, Exonhit Therapeutics, Servier, and Synarc. He has received honoraria from the American Academy of Neurology, Ipsen, NeuroVigil Inc, and the Institut Catala de Neurociencies Aplicades. He receives research funding from Merck and Avid. He owns stock in Synarc and Elan. He serves on the editorial advisory board for Alzheimer's & Dementia and the Journal of Magnetic Resonance Imaging. Dr Knopman reports that he serves on a Data Safety Monitoring Board for Lilly Pharmaceuticals and is an investigator for clinical trials sponsored by Elan Pharmaceuticals, Forest Pharmaceuticals, and Baxter Healthcare. He is deputy editor of Neurology and receives compensation for editorial services.; This work was support by the National Institutes of Health (grant AG11378) and the ADNI. Online-Only Material: The eTables and eFigures are available at http://www.archneurol.com. NR 86 TC 104 Z9 104 U1 4 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD DEC PY 2011 VL 68 IS 12 BP 1526 EP 1535 DI 10.1001/archneurol.2011.183 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 861BJ UT WOS:000297993500005 PM 21825215 ER PT J AU Weintraub, D Doshi, J Koka, D Davatzikos, C Siderowf, AD Duda, JE Wolk, DA Moberg, PJ Xie, SX Clark, CM AF Weintraub, Daniel Doshi, Jimit Koka, Deepthi Davatzikos, Christos Siderowf, Andrew D. Duda, John E. Wolk, David A. Moberg, Paul J. Xie, Sharon X. Clark, Christopher M. TI Neurodegeneration Across Stages of Cognitive Decline in Parkinson Disease SO ARCHIVES OF NEUROLOGY LA English DT Article ID ALZHEIMERS-DISEASE; LEWY BODIES; PATTERN-CLASSIFICATION; ELASTIC REGISTRATION; BRAIN ATROPHY; MCI PATIENTS; DEMENTIA; IMPAIRMENT; HIPPOCAMPAL; MRI AB Objective: To assess regions and patterns of brain atrophy in patients with Parkinson disease (PD) with normal cognition (PD-NC), mild cognitive impairment (PD-MCI), and dementia-level cognitive deficits (PDD). Design: Images were quantified using a region-ofinterest approach and voxel-based morphometry analysis. We used a high-dimensional pattern classification approach to delineate brain regions that collectively formed the Spatial Pattern of Abnormalities for Recognition of PDD. Setting: The Parkinson's Disease and Movement Disorders Center at the University of Pennsylvania. Subjects: Eighty-four PD patients (61 PD-NC, 12 PD-MCI, and 11 PDD) and 23 healthy control subjects (HCs) underwent magnetic resonance imaging of the brain. Results: The PD-NC patients did not demonstrate significant brain atrophy compared with HCs. Compared with PD-NC patients, PD-MCI patients had hippocam-pal atrophy (beta=-0.37; P=.001), and PDD patients demonstrated hippocampal (beta=-0.32; P=.004) and additional medial temporal lobe atrophy (beta=-0.36; P=.003). The PD-MCI patients had a different pattern of atrophy compared with PD-NC patients (P=.04) and a similar pattern to that of PDD patients (P=.81), characterized by hippocampal, prefrontal cortex gray and white matter, occipital lobe gray and white matter, and parietal lobe white matter atrophy. In nondemented PD patients, there was a correlation between memory-encoding performance and hippocampal volume. Conclusions: Hippocampal atrophy is a biomarker of initial cognitive decline in PD, including impaired memory encoding and storage, suggesting heterogeneity in the neural substrate of memory impairment. Use of a pattern classification approach may allow identification of diffuse regions of cortical gray and white matter atrophy early in the course of cognitive decline. Arch Neurol. 2011; 68(12):1562-1568 C1 [Weintraub, Daniel; Moberg, Paul J.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Weintraub, Daniel; Siderowf, Andrew D.; Duda, John E.; Wolk, David A.; Clark, Christopher M.] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Doshi, Jimit; Koka, Deepthi; Davatzikos, Christos] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. [Xie, Sharon X.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Weintraub, Daniel; Duda, John E.; Moberg, Paul J.] Philadelphia Vet Affairs Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA USA. [Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr, Philadelphia, PA USA. [Clark, Christopher M.] Avid Radiopharmaceut, Philadelphia, PA USA. RP Weintraub, D (reprint author), Univ Penn, Dept Psychiat, 3615 Chestnut St,Ste 330, Philadelphia, PA 19104 USA. EM daniel.weintraub@uphs.upenn.edu FU Department of Health of the Commonwealth of Pennsylvania [SAP4100027296]; National Institute of Neurological Disorders and Stroke (Penn Udall Center) [P50 NS053488]; National Institute on Aging [R01-14971, P30-AG10124] FX This study was supported by health research grant SAP4100027296 from the Department of Health of the Commonwealth of Pennsylvania from the Tobacco Master Settlement Agreement under Act 200177; by P50 NS053488 from the National Institute of Neurological Disorders and Stroke (Penn Udall Center); and by grants R01-14971 and P30-AG10124 from the National Institute on Aging. NR 52 TC 78 Z9 79 U1 1 U2 12 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD DEC PY 2011 VL 68 IS 12 BP 1562 EP 1568 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 861BJ UT WOS:000297993500010 PM 22159053 ER PT J AU Singhal, AB AF Singhal, Aneesh B. TI Reversible Cerebral Vasoconstriction Syndrome and Hemorrhagic Events: Who Precedes Whom? Reply SO ARCHIVES OF NEUROLOGY LA English DT Letter C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Singhal, AB (reprint author), Massachusetts Gen Hosp, Dept Neurol, ACC-729-C,55 Fruit St, Boston, MA 02114 USA. EM asinghal@partners.org NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD DEC PY 2011 VL 68 IS 12 BP 1615 EP 1615 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 861BJ UT WOS:000297993500026 ER PT J AU Panigrahy, D Greene, ER Pozzi, A Wang, DW Zeldin, DC AF Panigrahy, Dipak Greene, Emily R. Pozzi, Ambra Wang, Dao Wen Zeldin, Darryl C. TI EET signaling in cancer SO CANCER AND METASTASIS REVIEWS LA English DT Review DE Cytochrome P450 epoxygenase; EETs; Cancer; Metastasis; Arachidonic acid ID SOLUBLE EPOXIDE HYDROLASE; ARACHIDONIC-ACID EPOXYGENASE; ACTIVATED-RECEPTOR-ALPHA; ENDOTHELIAL-CELL PROLIFERATION; ASTROCYTIC EPOXYEICOSATRIENOIC ACID; GLUTATHIONE-S-TRANSFERASE; SUPPRESSES TUMOR-GROWTH; NF-KAPPA-B; 20-HYDROXYEICOSATETRAENOIC ACID; BREAST-CANCER AB Inflammation and angiogenesis in the tumor microenvironment are increasingly implicated in tumorigenesis. Endogenously produced lipid autacoids, locally acting small-molecule mediators, play a central role in inflammation and tissue homeostasis. These lipid mediators, collectively referred to as eicosanoids, have recently been implicated in cancer. Although eicosanoids, including prostaglandins and leukotrienes, are best known as products of arachidonic acid metabolism by cyclooxygenases and lipoxygenases, arachidonic acid is also a substrate for another enzymatic pathway, the cytochrome P450 (CYP) system. This eicosanoid pathway consists of two main branches: omega-hydroxylases which converts arachidonic acid to hydroxyeicosatetraenoic acids (HETEs) and epoxygenases which converts it to four regioisomeric epoxyeicosatrienoic acids (EETs; 5,6-EET, 8,9-EET, 11,12-EET, and 14,15-EET). EETs regulate inflammation and vascular tone. The bioactive EETs are produced predominantly in the endothelium and are mainly metabolized by soluble epoxide hydrolase to less active dihydroxyeicosatrienoic acids. EET signaling was originally studied in conjunction with inflammatory and cardiovascular disease. Arachidonic acid and its metabolites have recently stimulated great interest in cancer biology. To date, most research on eicosanoids in cancer has focused on the COX and LOX pathways. In contrast, the role of cytochrome P450-derived eicosanoids, such as EETs and HETEs, in cancer has received little attention. While CYP epoxygenases are expressed in human cancers and promote human cancer metastasis, the role of EETs (the direct products of CYP epoxygenases) in cancer remains poorly characterized. In this review, the emerging role of EET signaling in angiogenesis, inflammation, and cancer is discussed. C1 [Zeldin, Darryl C.] NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. [Panigrahy, Dipak; Greene, Emily R.] Harvard Univ, Sch Med, Dana Farber Canc Inst,Div Pediat Oncol, Vasc Biol Program,Boston Childrens Hosp, Boston, MA 02115 USA. [Pozzi, Ambra] Vanderbilt Univ, Dept Med & Canc Biol, Div Nephrol & Hypertens, Nashville, TN USA. [Wang, Dao Wen] Huazhong Univ Sci & Technol, Dept Internal Med, Wuhan 430030, Peoples R China. [Wang, Dao Wen] Huazhong Univ Sci & Technol, Gene Therapy Ctr, Tongji Hosp, Tongji Med Coll, Wuhan 430030, Peoples R China. RP Zeldin, DC (reprint author), NIEHS, Div Intramural Res, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM dipak.panigrahy@childrens.harvard.edu; emily.greene@childrens.harvard.edu; ambra.pozzi@vanderbilt.edu; dwwang@tjh.tjmu.edu.cn; zeldin@niehs.nih.gov FU National Cancer Institute [RO1CA148633-O1A1, 2PO1DK38226]; Division of Intramural Research of the NIH, National Institute of Environmental Health [Z01 ES025034, Z01 ES050167] FX We thank Sui Huang and Arja Kaipainen for suggestions in preparing the manuscript; Kristin Johnson for preparation of figures. This work was supported by National Cancer Institute grant RO1CA148633-O1A1 (DP); 2PO1DK38226 (AP); Division of Intramural Research of the NIH, National Institute of Environmental Health Sciences - Z01 ES025034 and Z01 ES050167 (DCZ). NR 166 TC 36 Z9 37 U1 0 U2 16 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-7659 J9 CANCER METAST REV JI Cancer Metastasis Rev. PD DEC PY 2011 VL 30 IS 3-4 BP 525 EP 540 DI 10.1007/s10555-011-9315-y PG 16 WC Oncology SC Oncology GA 861TS UT WOS:000298042700019 PM 22009066 ER PT J AU Bernt, KM Armstrong, SA AF Bernt, Kathrin M. Armstrong, Scott A. TI A role for DOT1L in MLL-rearranged leukemias SO EPIGENOMICS LA English DT Editorial Material DE chromatin; DOT1L; epigenetic regulation; histone code; MLL-rearranged leukemias; transcriptional elongation ID MIXED-LINEAGE LEUKEMIA; H3K79 METHYLATION; TRANSCRIPTIONAL ELONGATION; FUSION PROTEINS; CHROMATIN; METHYLTRANSFERASE; LEUKEMOGENESIS; COMPLEX; CELLS C1 [Bernt, Kathrin M.; Armstrong, Scott A.] Childrens Hosp Boston, Div Pediat Hematol Oncol, Boston, MA USA. [Bernt, Kathrin M.; Armstrong, Scott A.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA USA. [Bernt, Kathrin M.; Armstrong, Scott A.] Karp Family Res Labs, Boston, MA 02215 USA. RP Bernt, KM (reprint author), Childrens Hosp Boston, Div Pediat Hematol Oncol, Boston, MA USA. EM kathrin.bernt@childrens.harvard.edu RI Bernt, Kathrin/L-1826-2016 OI Bernt, Kathrin/0000-0002-5400-0482 NR 18 TC 24 Z9 24 U1 0 U2 5 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1750-1911 J9 EPIGENOMICS-UK JI Epigenomics PD DEC PY 2011 VL 3 IS 6 BP 667 EP 670 DI 10.2217/EPI.11.98 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 861SF UT WOS:000298038800001 PM 22126283 ER PT J AU Takahashi, K AF Takahashi, Kazue TI Mannose-binding lectin and the balance between immune protection and complication SO EXPERT REVIEW OF ANTI-INFECTIVE THERAPY LA English DT Review DE coagulation; complement; deficiency; infection; inflammation; mannose-binding lectin; MASP; pattern recognition molecules ID DISSEMINATED INTRAVASCULAR COAGULATION; PATTERN-RECOGNITION MOLECULES; INFLUENZA-A VIRUS; NATURALLY-OCCURRING MUTATIONS; AGE-DEPENDENT ASSOCIATION; TRANSMITTANCE WAVE-FORM; DEFICIENT MICE DISPLAY; SURFACTANT PROTEIN-A; INTENSIVE-CARE-UNIT; C-REACTIVE PROTEIN AB The innate immune system is evolutionarily ancient and biologically primitive. Historically, it was first identified as an element of the immune system that provides the first-line response to pathogens, and increasingly it is recognized for its central housekeeping role and its essential functions in tissue homeostasis, including coagulation and inflammation, among others. A pivotal link between the innate immune system and other functions is mannose-binding lectin (MBL), a pattern recognition molecule. Multiple studies have demonstrated that MBL deficiency increases susceptibility to infection, and the mechanisms associated with this susceptibility to infection include reduced opsonophagocytic killing and reduced activation of the lectin complement pathway. Results from our laboratory have demonstrated that MBL and MBL-associated serine protease (MASP)-1/3 together mediate coagulation factor-like activities, including thrombin-like activity. MBL and/or MASP-1/3-deficient hosts demonstrate in vivo evidence that MBL and MASP-1/3 are involved with hemostasis following injury. Staphylococcus aureus-infected MBL null mice developed disseminated intravascular coagulation, which was associated with elevated blood IL-6 levels (but not TNF-alpha) and systemic inflammatory responses. Infected MBL null mice also develop liver injury. These findings suggest that MBL deficiency may manifest as disseminated intravascular coagulation and organ failure with infection. Beginning from these observations, this review focuses on the interaction of innate immunity and other homeostatic systems, the derangement of which may lead to complications in infection and other inflammatory states. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. RP Takahashi, K (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat, 55 Fruit St,GRJ1402, Boston, MA 02114 USA. EM ktakahashi1@partners.org FU NIH [U01 AI074503] FX The author's work was supported in part by grants from NIH U01 AI074503. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 143 TC 19 Z9 21 U1 0 U2 15 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1478-7210 J9 EXPERT REV ANTI-INFE JI Expert Rev. Anti-Infect. Ther. PD DEC PY 2011 VL 9 IS 12 BP 1179 EP 1190 DI 10.1586/ERI.11.136 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 861QM UT WOS:000298034300018 PM 22114968 ER PT J AU LeBlanc, JK Al-Haddad, M McHenry, L Sherman, S Juan, M McGreevy, K Johnson, C Howard, TJ Lillemoe, KD DeWitt, J AF LeBlanc, Julia K. Al-Haddad, Mohammad McHenry, Lee Sherman, Stuart Juan, Michelle McGreevy, Kathleen Johnson, Cynthia Howard, Thomas J. Lillemoe, Keith D. DeWitt, John TI A prospective, randomized study of EUS-guided celiac plexus neurolysis for pancreatic cancer: one injection or two? SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID PAIN; MANAGEMENT; BLOCK AB Background: The technique of alcohol injection during EUS-guided celiac plexus neurolysis (CPN) in patients with pancreatic cancer-related pain has not been standardized. Objective: To compare pain relief and safety of alcohol given as 1 versus 2 injections during EUS-guided CPN (EUS-CPN). Secondary outcomes examined were characteristics that predict response and survival. Design: Single-blinded, prospective, randomized, parallel-group study. Setting: Tertiary-care center. Patients: This study involved patients with pancreatic cancer-related pain. Intervention: EUS-CPN done by injecting 20 mL of 0.75% bupivacaine and 10 mL 98% alcohol into 1 or 2 sites at the celiac trunk. Participants were interviewed by telephone at 24 hours and weekly thereafter. Main Outcome Measurements: Time until onset of pain relief, duration of pain relief, complications. Results: Fifty patients (mean age 63 years; 24 men) were enrolled and randomized (29 in 1-injection, 21 in 2-injections groups). Pain relief was observed in 37 (74%) patients: 20 (69%) in the 1-injection group and 17 (81%) in the 2-injection group (chi-square P = .340). Median onset of pain relief was 1 day for both 1-injection (range 1-28 days) and 2-injection (range 1-21 days) groups (Mann-Whitney P = .943). Median duration of pain relief in the 1-injection and 2-injection groups was 11 weeks and 14 weeks, respectively (log-rank P = .612). Complete pain relief was observed in 4 (8%) patients total, 2 in each group. There were no long-term complications. Limitations: Single-blinded study. Conclusion: There were no differences in onset or duration of pain relief when either 1 or 2 injections were used. There was no difference in safety or survival between the 2 groups. (Clinical trial registration number: NCT00583479.) (Gastrointest Endosc 2011;74:1300-7.) C1 [LeBlanc, Julia K.; Al-Haddad, Mohammad; McHenry, Lee; Sherman, Stuart; Juan, Michelle; McGreevy, Kathleen; DeWitt, John] Indiana Univ, Med Ctr, Div Gastroenterol & Hepatol, Indianapolis, IN USA. [Johnson, Cynthia] IU Hlth, Dept Biostat, Indianapolis, IN USA. [Howard, Thomas J.] Indiana Univ, Dept Surg, Indianapolis, IN 46204 USA. [Lillemoe, Keith D.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP LeBlanc, JK (reprint author), 550 N Univ Blvd,UH 4100, Indianapolis, IN 46202 USA. EM juleblan@iupui.edu NR 19 TC 32 Z9 34 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD DEC PY 2011 VL 74 IS 6 BP 1300 EP 1307 DI 10.1016/j.gie.2011.07.073 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 861AX UT WOS:000297992300017 PM 22000795 ER PT J AU Isong, IA Silk, H Rao, SR Perrin, JM Savageau, JA Donelan, K AF Isong, Inyang A. Silk, Hugh Rao, Sowmya R. Perrin, James M. Savageau, Judith A. Donelan, Karen TI Provision of Fluoride Varnish to Medicaid-Enrolled Children by Physicians: The Massachusetts Experience SO HEALTH SERVICES RESEARCH LA English DT Article DE Children; preventive dental care; fluoride varnish; Medicaid; physicians ID EARLY-CHILDHOOD CARIES; ORAL-HEALTH; CARE PROVIDERS; SYSTEMATIC REVIEWS; NATIONAL-SURVEY; US CHILDREN; DENTAL-CARE; ACCESS; SERVICES; IMPLEMENTATION AB Objectives. To evaluate the impact of a 2008 Medicaid policy in Massachusetts (MA), regarding reimbursing physicians for providing fluoride varnish (FV) to eligible children in medical settings. Data Source. Survey of a sample of primary care physicians in MA. Study Design. Cross-sectional survey of a sample of physicians who provide care to MassHealth (MA Medicaid) enrolled-children. Dependent variables: history of completed preventive dental skills training, and FV provision. Independent variables: oral health knowledge, FV-attitudes, and physician and practice characteristics. Principal Findings. Overall, 19 percent of respondents had completed the training required to be eligible to bill for FV provision. Only 5 percent of physicians were providing FV. Most respondents (63 percent) were not familiar with the new policy, and only 25 percent felt that FV should be provided during well-child visits. Most physicians (60 percent) did not feel that the reimbursement rate of U. S.$26/application was sufficient; 17 percent said that they would not provide FV, regardless of payment. Most common barriers to FV provision were a lack of time and logistical challenges. Conclusions. Our findings suggest that simply reimbursing physicians for FV provision is insufficient to ensure provider participation. Success of this policy will likely require addressing several barriers identified. C1 [Isong, Inyang A.; Perrin, James M.; Donelan, Karen] Harvard Univ, Sch Med, Ctr Child & Adolescent Hlth Policy, Massachusetts Gen Hosp Children, Boston, MA 02114 USA. [Silk, Hugh] Univ Massachusetts, Med Sch & Family Med Residency, Hahnemann Family Hlth Ctr, Worcester, MA 01605 USA. [Rao, Sowmya R.] Univ Massachusetts, Sch Med, Ctr Hlth Qual Outcomes & Econ Res, Vet Adm, Worcester, MA 01605 USA. [Savageau, Judith A.] Univ Massachusetts, Sch Med, Dept Family Med & Community Hlth, Worcester, MA USA. [Donelan, Karen] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. RP Isong, IA (reprint author), Harvard Univ, Sch Med, Ctr Child & Adolescent Hlth Policy, Massachusetts Gen Hosp Children, 50 Staniford St,Suite 901, Boston, MA 02114 USA. EM iisong@partners.org FU DentaQuest Foundation; Health Resources and Services Administration, Department of Health and Human Services [T32 HP10018] FX Joint Acknowledgment/Disclosure Statement: This study was supported by a grant from the DentaQuest Foundation to the University of Massachusetts Office of Community Programs. Drs. Donelan and Rao were paid as consultants by the University of Massachusetts for their effort on this project. Dr. Isong's work is supported by a National Research Service Award (T32 HP10018) from the Health Resources and Services Administration, Department of Health and Human Services. We would like to thank Ellen Sachs Leicher for her coordination efforts, Heather-Lyn Haley for her on-line survey work, and Joanne Dombrowski for her efforts with our paper survey. NR 32 TC 6 Z9 6 U1 1 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD DEC PY 2011 VL 46 IS 6 BP 1843 EP 1862 DI 10.1111/j.1475-6773.2011.01289.x PN 1 PG 20 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 851BT UT WOS:000297244000009 PM 21762142 ER PT J AU Wang, V Liu, CF Bryson, CL Sharp, ND Maciejewski, ML AF Wang, Virginia Liu, Chuan-Fen Bryson, Christopher L. Sharp, Nancy D. Maciejewski, Matthew L. TI Does Medication Adherence Following a Copayment Increase Differ by Disease Burden? SO HEALTH SERVICES RESEARCH LA English DT Article DE Cost sharing; medication adherence; diabetes; hypertension; veterans ID ACUTE MYOCARDIAL-INFARCTION; MANAGED CARE; PRESCRIPTION DRUGS; PHARMACY BENEFITS; STATIN THERAPY; RETROSPECTIVE COHORT; HEALTH-INSURANCE; RISK ADJUSTMENT; CHRONICALLY ILL; PART-D AB Objectives. To compare changes in medication adherence between patients with high- or low-comorbidity burden after a copayment increase. Methods. We conducted a retrospective observational study at four Veterans Affairs (VA) medical centers by comparing veterans with hypertension or diabetes required to pay copayments with propensity score-matched veterans exempt from copayments. Disease cohorts were stratified by Diagnostic Cost Group risk score: low-(<1) and high-comorbidity (>1) burden. Medication adherence from February 2001 to December 2003, constructed from VA pharmacy claims data based on the ReComp algorithm, were assessed using generalized estimating equations. Results. Veterans with lower comorbidity were more responsive to a U.S.$5 copayment increase than higher comorbidity veterans. In the lower comorbidity groups, veterans with diabetes had a greater reduction in adherence than veterans with hypertension. Adherence trends were similar for copayment-exempt and nonexempt veterans with higher comorbidity. Conclusion. Medication copayment increases are associated with different impacts for low- and high-risk patients. High-risk patients incur greater out-of-pocket costs from continued adherence, while low- risk patients put themselves at increased risk for adverse health events due to greater nonadherence. C1 [Wang, Virginia] Duke Univ, Ctr Hlth Serv Res Primary Care, Durham VA Med Ctr, Dept Med,Div Gen Internal Med, Durham, NC 27705 USA. [Liu, Chuan-Fen; Bryson, Christopher L.; Sharp, Nancy D.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Liu, Chuan-Fen; Bryson, Christopher L.; Sharp, Nancy D.] VA Puget Sound Hlth Care Syst, NW Ctr Outcomes Res Older Adults, Seattle, WA USA. [Maciejewski, Matthew L.] Duke Univ, Div Gen Internal Med, Dept Med, Durham, NC 27706 USA. [Maciejewski, Matthew L.] Durham VA Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC USA. RP Wang, V (reprint author), Duke Univ, Ctr Hlth Serv Res Primary Care, Durham VA Med Ctr, Dept Med,Div Gen Internal Med, 508 Fulton St 152, Durham, NC 27705 USA. EM virginia.wang@duke.edu FU Office of Research and Development, Health Services Research and Development Service, Department of Veterans Affairs [IIR 03-200]; Department of Veteran Affairs Office of Academic Affiliations; AHRQ [K12 HS 019479] FX This research was supported by Office of Research and Development, Health Services Research and Development Service, Department of Veterans Affairs, project number IIR 03-200, Department of Veteran Affairs Office of Academic Affiliations, and AHRQ grant number K12 HS 019479. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veteran Affairs, AHRQ, University of Washington, or Duke University Health System. NR 73 TC 10 Z9 10 U1 5 U2 11 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD DEC PY 2011 VL 46 IS 6 BP 1963 EP 1985 DI 10.1111/j.1475-6773.2011.01286.x PN 1 PG 23 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 851BT UT WOS:000297244000015 PM 21689097 ER PT J AU Contreras-Valdes, FM Heist, EK Danik, SB Barrett, CD Blendea, D Brugge, WR Ptaszek, L Ruskin, JN Mansour, M AF Contreras-Valdes, Fernando M. Heist, E. Kevin Danik, Stephan B. Barrett, Conor D. Blendea, Dan Brugge, William R. Ptaszek, Leon Ruskin, Jeremy N. Mansour, Moussa TI Severity of esophageal injury predicts time to healing after radiofrequency catheter ablation for atrial fibrillation SO HEART RHYTHM LA English DT Article DE Atrial fibrillation; Radiofrequency catheter ablation; Esophageal injury; Temperature monitoring; Severity of esophageal injury; Esophageal healing; Complications; Endoscopy; Atrioesophageal fistula ID PULMONARY VEIN ISOLATION; CAPSULE ENDOSCOPY; TEMPERATURE; FISTULA; RISK; LESIONS; DAMAGE; COMPLICATIONS; PREVALENCE; STRATEGIES AB BACKGROUND The delivery of radiofrequency (RF) energy to the posterior left atrium creates a risk of injury to the adjacent esophagus. Esophageal endoscopy (EGD) is used to screen patients at risk for esophageal thermal injury after RF ablation. OBJECTIVE The purpose of this study was to analyze the macroscopic features of the severity of esophageal injuries induced by RF ablation to the left atrium as seen by EGD and evaluate the association of these descriptions with the time elapsed until complete healing. METHODS This study analyzed 219 patients undergoing RF ablation for atrial fibrillation. Esophageal temperature probes were used during each ablation, and EGD was performed in cases with intraesophageal temperature >= 39 degrees C. Repeat EGD was obtained at 10 days to evaluate for healing in all cases demonstrating esophageal injury. Serial endoscopies were repeated every 2 weeks until complete healing was documented. Lesions were classified according to severity as superficial or deep ulceration; size and shape were also noted. RESULTS We found 37.4% of patients (82 of 219) with esophageal intraluminal temperatures >= 39 degrees C. Of these, 22 patients (27%) were identified with esophageal injury, with 68% being superficial ulcerations and 32% deep. On repeat EGD at 10 days, only 29% of deep ulcerations were healed, as compared with 87% of the superficial injuries (P = .0136). No difference in healing was found when analyzed for size or shape. CONCLUSIONS The macroscopic severity of esophageal lesions detected on endoscopy the day after RF ablation can predict the time to resolution, with severe, deep ulcerations requiring a longer time to heal. C1 [Contreras-Valdes, Fernando M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Heist, E. Kevin; Danik, Stephan B.; Barrett, Conor D.; Blendea, Dan; Ptaszek, Leon; Ruskin, Jeremy N.; Mansour, Moussa] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Heart Ctr,Cardiac Arrhythmia Serv, Boston, MA USA. [Brugge, William R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Endoscopy Unit, Boston, MA USA. RP Mansour, M (reprint author), 55 Fruit St,GRB-109, Boston, MA 02114 USA. EM mmansour@partners.org FU Biotronik; Boston Scientific; St. Jude Medical; Biosense Webster; MC 10; Voyage Medical; Rhythmia Medical; CardioFocus; Medtronic FX E. Kevin Heist has the following potential conflicts of interest: Biotronik (Research Grant, Honoraria-modest); Boston Scientific (Research Grant, Consultant, Honoraria-modest); Medtronic (Honoraria-modest); Sorin (Consultant, Honoraria-modest); St. Jude Medical (Research Grant, Consultant, Honoraria-modest); Jeremy N. Ruskin has the following potential conflicts of interest: Biosense Webster (Consultant-modest; Fellowship Support-significant); Boston Scientific (Fellowship Support-significant); CardioFocus (Clinical Oversight Committee-no compensation); CardioInsight (Scientific Advisory Board-modest); CryoCath (Scientific Steering Committee-no compensation); Medtronic (Consultant-modest; Fellowship Grant-significant); St. Jude Medical (Fellowship Support-significant), and Moussa Mansour has the following potential conflicts of interest: Biosense Webster (Consultant, Research Grant); Boston Scientific (Consultant, Research Grant); St. Jude Medical (Consultant, Research Grant); Medtronic (Consultant); MC 10 (Research Grant); Voyage Medical (Research Grant); Rhythmia Medical (Research Grant); CardioFocus (Research Grant). NR 35 TC 13 Z9 13 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD DEC PY 2011 VL 8 IS 12 BP 1862 EP 1868 DI 10.1016/j.hrthm.2011.07.022 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 863CE UT WOS:000298139600008 PM 21782773 ER PT J AU Larsen, GK Evans, J Lambert, WE Chen, YY Raitt, MH AF Larsen, Gail K. Evans, John Lambert, William E. Chen, Yiyi Raitt, Merritt H. TI Shocks burden and increased mortality in implantable cardioverter-defibrillator patients SO HEART RHYTHM LA English DT Article DE Implantable cardioverter-defibrillator; Shocks; Antitachycardia pacing; Ventricular arrhythmia; Death ID SUDDEN CARDIAC DEATH; HEART-FAILURE; VENTRICULAR-ARRHYTHMIA; MADIT-II; THERAPY; CARDIOMYOPATHY; PREVENTION; SURVIVAL AB BACKGROUND Implantable cardioverter-defibrillator (ICD) shocks are associated with an increased risk of death. It is unclear whether ICD shocks are detrimental per se or a marker of higher risk patients. OBJECTIVE We aimed to assess the association between ICD shocks and time to death after correction for baseline mortality based on the Seattle Heart Failure Model (SHFM). METHODS The primary analysis compared time-to-death between patients receiving no shocks and patients receiving shocks of any type adjusted for SHFM score at time of implantation and other comorbidities. Subgroup analyses were performed to further describe the relationship between shocks and mortality risk. RESULTS Over a median follow-up of 41 months (interquartile range 23-64), one or more shock episodes occurred in 59% of 425 patients and 40% of the patients died. Patients receiving shocks of any type had increased risk of death (hazard ratio 1.55; 95% confidence interval 1.07-2.23; P = .02) versus patients receiving no shocks. While patients with 1-5 days with shock (shock days) did not show evidence of increased risk of death (1.30 [0.88-.94]; P = 0.19), those with 6-10 shock days (2.22 [1.21-4.08]; P <.01) and >10 shock days (3.66 [1.86 -7.19]; P <.01) had increasingly higher risk. There was no increased hazard for death (0.73 [0.34 -1.57]; P = .41) in patients treated only with antitachycardia pacing (ATP). CONCLUSION ICD shocks were associated with increased mortality risk after adjustment for SHFM-predicted mortality, and the burden of shocks played a role in this association. ATP did not increase mortality risk, suggesting that shocks may themselves be detrimental. C1 [Raitt, Merritt H.] Portland VA Med Ctr, Portland, OR 97239 USA. [Larsen, Gail K.; Lambert, William E.; Chen, Yiyi; Raitt, Merritt H.] Oregon Hlth & Sci Univ, Sch Med, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. [Evans, John] Stanford Univ, Sch Med, Stanford, CA 94305 USA. RP Raitt, MH (reprint author), Portland VA Med Ctr, 3710 SW US Vet Rd, Portland, OR 97239 USA. EM merritt.raitt@va.gov OI Raitt, Merritt/0000-0001-5638-7732 NR 18 TC 48 Z9 49 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD DEC PY 2011 VL 8 IS 12 BP 1881 EP 1886 DI 10.1016/j.hrthm.2011.07.036 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 863CE UT WOS:000298139600011 PM 21816127 ER PT J AU Burstein, HJ AF Burstein, Harold J. TI Avastin for Breast Cancer, 2005-2011: Requiescat in Pacem? SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Editorial Material C1 [Burstein, Harold J.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Burstein, Harold J.] Dana Farber Canc Inst, Boston, MA USA. [Burstein, Harold J.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Burstein, HJ (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 2 TC 3 Z9 5 U1 0 U2 0 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD DEC PY 2011 VL 9 IS 12 BP 1321 EP 1323 PG 3 WC Oncology SC Oncology GA 861BS UT WOS:000297994500002 PM 22157551 ER PT J AU Shaw, AT Solomon, B Mino-Kenudson, M AF Shaw, Alice T. Solomon, Benjamin Mino-Kenudson, Mari TI Crizotinib and Testing for ALK SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article DE ALK; crizotinib; lung cancer; targeted therapy ID CELL LUNG-CANCER; EML4-ALK FUSION GENE; TRANSBRONCHIAL NEEDLE ASPIRATION; IN-SITU-HYBRIDIZATION; INHIBITOR; IMMUNOHISTOCHEMISTRY; ADENOCARCINOMAS; IDENTIFICATION; FEATURES AB Crizotinib was recently approved by the US FDA for the treatment of advanced non-small cell lung cancer (NSCLC) harboring the ALK (anaplastic lymphoma kinase) gene rearrangement. To ensure identification of patients most likely to benefit, the FDA approved crizotinib concurrently with a companion diagnostic test-the Vysis ALK Break Apart FISH Probe Kit. This kit was used in 1 of the 2 pivotal trials leading to the FDA approval of crizotinib and has become the gold standard for detecting ALK rearrangement in NSCLC. Although ALK FISH is clinically validated, the assay can be technically challenging and costly. Therefore, other diagnostic modalities are being explored, including immunohistochemistry (IHC) and reverse transcriptase-polymerase chain reaction. This article provides an overview of the diagnostic assays available for detecting ALK rearrangement. Each assay, including ALK FISH, has its strengths and weaknesses. Recent work with commercially available ALK antibodies suggests that IHC-based tests may represent a reliable and cost-effective screening strategy; however, large multicenter studies comparing IHC with FISH are needed to validate ALK IHC. While ALK FISH remains the current standard for diagnosing ALK positivity, large-scale screening of patients with newly diagnosed advanced NSCLC, as recommended by NCCN, may require development and validation of alternative screening strategies, such as combination IHC and FISH. (JNCCN 2011; 9: 1335-1341) C1 [Shaw, Alice T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Shaw, Alice T.; Mino-Kenudson, Mari] Harvard Univ, Sch Med, Boston, MA USA. [Shaw, Alice T.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Solomon, Benjamin] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Shaw, AT (reprint author), MGH Canc Ctr Yawkey 7B, 32 Fruit St, Boston, MA 02114 USA. EM ashaw1@partners.org FU V Foundation for Cancer Research; Pfizer Inc. FX Dr. Shaw is supported by a translational grant from the V Foundation for Cancer Research and is the Charles W. and Jennifer C. Johnson Koch Institute Clinical Investigator at MIT. Dr. Shaw also receives clinical research support from Pfizer Inc.; and is a consultant for Pfizer Inc., ARIAD Pharmaceuticals, Inc., Chugai Pharmaceutical Co., Ltd., and Novartis AG. Dr. Solomon receives clinical research support from Pfizer Inc., and serves on the advisory board for Pfizer Inc. Dr. Mino-Kenudson has disclosed that she has no financial interests, arrangements, or affiliations with the manufacturers of any products discussed in this article or their competitors. NR 26 TC 59 Z9 62 U1 1 U2 9 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD DEC PY 2011 VL 9 IS 12 BP 1335 EP 1341 PG 7 WC Oncology SC Oncology GA 861BS UT WOS:000297994500005 PM 22157554 ER PT J AU Ettinger, DS Agulnik, M Cates, JMM Cristea, M Denlinger, CS Eaton, KD Fidias, PM Gierada, D Gockerman, JP Handorf, CR Iyer, R Lenzi, R Phay, J Rashid, A Saltz, L Shulman, LN Smerage, JB Varadhachary, GR Zager, JS Zhen, WN AF Ettinger, David S. Agulnik, Mark Cates, Justin M. M. Cristea, Mihaela Denlinger, Crystal S. Eaton, Keith D. Fidias, Panagiotis M. Gierada, David Gockerman, Jon P. Handorf, Charles R. Iyer, Renuka Lenzi, Renato Phay, John Rashid, Asif Saltz, Leonard Shulman, Lawrence N. Smerage, Jeffrey B. Varadhachary, Gauri R. Zager, Jonathan S. Zhen, Weining (Ken) TI Occult Primary Clinical Practice Guidelines in Oncology SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review DE NCCN Clinical Practice Guidelines; NCCN Guidelines; occult primary; carcinoma of unknown primary; metastatic; chemotherapy ID UNKNOWN PRIMARY SITE; PHASE-II TRIAL; CANCER-RESEARCH-NETWORK; POSITRON-EMISSION-TOMOGRAPHY; SQUAMOUS-CELL CARCINOMA; POORLY DIFFERENTIATED ADENOCARCINOMA; COMBINATION-CHEMOTHERAPY REGIMENS; CHAIN-REACTION ASSAY; PRIMARY TUMORS; METASTATIC CARCINOMA C1 [Ettinger, David S.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD 21231 USA. [Agulnik, Mark] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Cates, Justin M. M.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Cristea, Mihaela] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Denlinger, Crystal S.] Fox Chase Canc Ctr, Philadelphia, PA USA. [Eaton, Keith D.] Seattle Canc Care Alliance, Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [Fidias, Panagiotis M.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Gierada, David] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Gierada, David] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO 63110 USA. [Gockerman, Jon P.] Duke Canc Inst, Durham, NC USA. [Handorf, Charles R.] Univ Tennessee, Inst Canc, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Iyer, Renuka] Roswell Pk Canc Inst, Buffalo, NY USA. [Lenzi, Renato; Rashid, Asif; Varadhachary, Gauri R.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Phay, John] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Phay, John] Solove Res Inst, Columbus, OH USA. [Saltz, Leonard] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Shulman, Lawrence N.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Smerage, Jeffrey B.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Zager, Jonathan S.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Zhen, Weining (Ken)] Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE USA. RP Ettinger, DS (reprint author), Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD 21231 USA. NR 107 TC 6 Z9 6 U1 0 U2 6 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD DEC PY 2011 VL 9 IS 12 BP 1358 EP 1395 PG 38 WC Oncology SC Oncology GA 861BS UT WOS:000297994500007 PM 22157556 ER PT J AU Crowley, WF AF Crowley, William F., Jr. TI Commentary: The Year in Endocrine Genetics for Basic Scientists SO MOLECULAR ENDOCRINOLOGY LA English DT Editorial Material ID IDIOPATHIC HYPOGONADOTROPIC HYPOGONADISM; GONADOTROPIN-RELEASING-HORMONE; GENOME-WIDE ASSOCIATION; OF-FUNCTION MUTATIONS; KALLMANN-SYNDROME; LUTEINIZING-HORMONE; PROKINETICIN-2 GENE; LOCI; PUBERTY; DEFICIENCY AB During the past several years, one of the most interesting and challenging issues in endocrine genetics is determining how to integrate the findings and approaches traditionally used to understand the powerful, single-gene mutations causing endocrine syndromes with those newer techniques used to dissect the complex genetic architecture of polygenic conditions. With this overriding consideration in mind, it makes sense to begin these considerations with recent novel findings derived from the study of a particularly prismatic monogenic disorder, isolated GnRH deficiency, in defining an area of neuroendocrinology and development. Careful study of this human disease model has been employed successfully by several groups to provide unique windows through which to gain an improved understanding of the challenging issues of the developmental biology of the GnRH neurons where previous nonhuman approaches have had significant technical limitations. For example, study of this disorder has provided the field of neuroendocrinology with several unique insights into the surprising origins and early development of the GnRH neuronal network. Its associated clinical phenotypes have helped to unearth a growing list of genes responsible for GnRH neuronal specification, migration, and neuroendocrine function. Finally, this human genetic model is beginning to provide increasing evidence of interactions between these single genes, clearly demonstrating that an oligogenic genetic architecture underlies this condition. (Molecular Endocrinology 25:1989-2002, 2011) C1 [Crowley, William F., Jr.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Crowley, William F., Jr.] Harvard Univ, Sch Med, Ctr Excellence Reprod Endocrinol, NICHHD, Boston, MA 02114 USA. RP Crowley, WF (reprint author), Care of Haworth M, Endocrine Society Journals Dept, 8401 Connecticut Ave,Suite 900, Chevy Chase, MD 20815 USA. EM molendo@endo-society.org FU NICHD NIH HHS [R01 HD015788, U54 HD028138] NR 49 TC 2 Z9 2 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD DEC PY 2011 VL 25 IS 12 BP 1989 EP 2002 DI 10.1210/me.2011-1247 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 861YB UT WOS:000298055800002 PM 22108799 ER PT J AU El-Shewy, HM Abdel-Samie, SA Al Qalam, AM Lee, MH Kitatani, K Anelli, V Jaffa, AA Obeid, LM Luttrell, LM AF El-Shewy, Hesham M. Abdel-Samie, Souzan A. Al Qalam, Abdelmohsen M. Lee, Mi-Hye Kitatani, Kazuyuki Anelli, Viviana Jaffa, Ayad A. Obeid, Lina M. Luttrell, Louis M. TI Phospholipase C and Protein Kinase C-beta 2 Mediate Insulin-Like Growth Factor II-Dependent Sphingosine Kinase 1 Activation SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID HETEROTRIMERIC G-PROTEINS; G-ALPHA-Q; FACTOR-II/MANNOSE-6-PHOSPHATE RECEPTOR; RECYCLING ENDOSOMES; PLASMA-MEMBRANE; ADULT-RAT; CELLS; EXPRESSION; TRANSLOCATION; PKC AB We recently reported that IGF-II binding to the IGF-II/mannose-6-phosphate (M6P) receptor activates the ERK1/2 cascade by triggering sphingosine kinase 1 (SK1)-dependent transactivation of G protein-coupled sphingosine 1-phosphate (S1P) receptors. Here, we investigated the mechanism of IGF-II/M6P receptor-dependent sphingosine kinase 1 (SK1) activation in human embryonic kidney 293 cells. Pretreating cells with protein kinase C (PKC) inhibitor, bisindolylmaleimide-I, abolished IGF-II-stimulated translocation of green fluorescent protein (GFP)-tagged SK1 to the plasma membrane and activation of endogenous SK1, implicating PKC as an upstream regulator of SK1. Using confocal microscopy to examine membrane translocation of GFP-tagged PKC alpha, beta 1, beta 2, delta, and zeta, we found that IGF-II induced rapid, transient, and isoform-specific translocation of GFP-PKC beta 2 to the plasma membrane. Immunoblotting of endogenous PKC phosphorylation confirmed PKC beta 2 activation in response to IGF-II. Similarly, IGF-II stimulation caused persistent membrane translocation of the kinase-deficient GFP-PKC beta 2 (K371R) mutant, which does not dissociate from the membrane after translocation. IGF-II stimulation increased diacylglycerol (DAG) levels, the established activator of classical PKC. Interestingly, the polyunsaturated fraction of DAG was increased, indicating involvement of phosphatidyl inositol/phospholipase C (PLC). Pretreating cells with the PLC inhibitor, U73122, attenuated IGF-II-dependent DAG production and PKC beta 2 phosphorylation, blocked membrane translocation of the kinase-deficient GFP-PKC beta 2 (K371R) mutant, and reduced sphingosine 1-phosphate production, suggesting that PLC/PKC beta 2 are upstream regulators of SK1 in the pathway. Taken together, these data provide evidence that activation of PLC and PKC beta 2 by the IGF-II/M6P receptor are required for the activation of SK1. (Molecular Endocrinology 25:2144-2156, 2011) C1 [El-Shewy, Hesham M.] Med Univ S Carolina, Div Endocrinol Diabet & Med Genet, Dept Med, Charleston, SC 29425 USA. [Abdel-Samie, Souzan A.; Kitatani, Kazuyuki; Anelli, Viviana; Luttrell, Louis M.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Obeid, Lina M.; Luttrell, Louis M.] Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC 29401 USA. RP El-Shewy, HM (reprint author), Med Univ S Carolina, Div Endocrinol Diabet & Med Genet, Dept Med, 114 Doughty St,MSC 776, Charleston, SC 29425 USA. EM elshewy@musc.edu FU South Carolina Center for Biomedical Research Excellence in Lipidomics and Pathology; National Institutes of Health (NIH) [DK55524]; NIH/NCRR [P20 RR17677, HL087986, HL077192]; Department of Veterans Affairs; Veteran Affairs Merit Award FX This work was supported by a grant from South Carolina Center for Biomedical Research Excellence in Lipidomics and Pathology (to H. M. E.), National Institutes of Health (NIH) Grants DK55524 (to L.M.L.) and NIH/NCRR P20 RR17677 (to L.M.O.), HL087986 and HL077192 (to A.A.J.), Department of Veterans Affairs Research Enhancement Award (L.M.L.), and Veteran Affairs Merit Award (to L.M.O.). NR 44 TC 11 Z9 11 U1 0 U2 16 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD DEC PY 2011 VL 25 IS 12 BP 2144 EP 2156 DI 10.1210/me.2011-0101 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 861YB UT WOS:000298055800015 PM 22016563 ER PT J AU Basha, G Novobrantseva, TI Rosin, N Tam, YYC Hafez, IM Wong, MK Sugo, T Ruda, VM Qin, J Klebanov, B Ciufolini, M Akinc, A Tam, YK Hope, MJ Cullis, PR AF Basha, Genc Novobrantseva, Tatiana I. Rosin, Nicole Tam, Yuen Yi C. Hafez, Ismail M. Wong, Matthew K. Sugo, Tsukasa Ruda, Vera M. Qin, June Klebanov, Boris Ciufolini, Marco Akinc, Akin Tam, Ying K. Hope, Michael J. Cullis, Pieter R. TI Influence of Cationic Lipid Composition on Gene Silencing Properties of Lipid Nanoparticle Formulations of siRNA in Antigen-Presenting Cells SO MOLECULAR THERAPY LA English DT Article ID SMALL INTERFERING RNA; IN-VIVO; DENDRITIC CELLS; ALLOGRAFT-REJECTION; LIPOSOME CLEARANCE; NUCLEIC-ACID; DELIVERY; EFFICIENT; LIVER; MICE AB Lipid nanoparticles (LNPs) are currently the most effective in vivo delivery systems for silencing target genes in hepatocytes employing small interfering RNA. Antigen-presenting cells (APCs) are also potential targets for LNP siRNA. We examined the uptake, intracellular trafficking, and gene silencing potency in primary bone marrow macrophages (bmMF) and dendritic cells of siRNA formulated in LNPs containing four different ionizable cationic lipids namely DLinDAP, DLinDMA, DLinK-DMA, and DLinKC2-DMA. LNPs containing DLinKC2-DMA were the most potent formulations as determined by their ability to inhibit the production of GAPDH target protein. Also, LNPs containing DLinKC2-DMA were the most potent intracellular delivery agents as indicated by confocal studies of endosomal versus cytoplamic siRNA location using fluorescently labeled siRNA. DLinK-DMA and DLinKC2-DMA formulations exhibited improved gene silencing potencies relative to DLinDMA but were less toxic. In vivo results showed that LNP siRNA systems containing DLinKC2-DMA are effective agents for silencing GAPDH in APCs in the spleen and peritoneal cavity following systemic administration. Gene silencing in APCs was RNAi mediated and the use of larger LNPs resulted in substantially reduced hepatocyte silencing, while similar efficacy was maintained in APCs. These results are discussed with regard to the potential of LNP siRNA formulations to treat immunologically mediated diseases. Received 2 February 2011; accepted 21 July 2011; published online 04 October 2011. doi:10.1038/mt.2011.190 C1 [Basha, Genc; Rosin, Nicole; Tam, Yuen Yi C.; Hafez, Ismail M.; Cullis, Pieter R.] Univ British Columbia, Dept Biochem & Mol Biol, Inst Life Sci, NanoMed Res Grp, Vancouver, BC V6T 1Z3, Canada. [Novobrantseva, Tatiana I.; Sugo, Tsukasa; Qin, June; Klebanov, Boris; Akinc, Akin] Alnylam Pharmaceut, Cambridge, MA USA. [Wong, Matthew K.] Univ British Columbia, Ctr Drug Res & Dev, Vancouver, BC V6T 1Z3, Canada. [Ruda, Vera M.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Ruda, Vera M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Ruda, Vera M.] Harvard Univ, Sch Med, Boston, MA USA. [Ciufolini, Marco] Univ British Columbia, Dept Chem, Vancouver, BC V6T 1Z3, Canada. [Tam, Ying K.; Hope, Michael J.] AlCana Technol Inc, Vancouver, BC, Canada. RP Basha, G (reprint author), Univ British Columbia, Dept Biochem & Mol Biol, Inst Life Sci, NanoMed Res Grp, 2350 Hlth Sci Mall, Vancouver, BC V6T 1Z3, Canada. EM gbasha@mail.ubc.ca FU Canadian Institutes for Health Research (CIHR) under UOP [FRN 59836]; Tekmira Pharmaceuticals; Alnylam Pharmaceuticals; Alnylam FX The authors would like to acknowledge support from the Canadian Institutes for Health Research (CIHR) under UOP grant FRN 59836, as well as support from Tekmira Pharmaceuticals and Alnylam Pharmaceuticals. P. R. C. has a financial interest in Tekmira and receives grant support from Alnylam. NR 50 TC 50 Z9 52 U1 0 U2 28 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD DEC PY 2011 VL 19 IS 12 BP 2186 EP 2200 DI 10.1038/mt.2011.190 PG 15 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 861SK UT WOS:000298039300013 PM 21971424 ER PT J AU De, S Michor, F AF De, Subhajyoti Michor, Franziska TI DNA replication timing and long-range DNA interactions predict mutational landscapes of cancer genomes SO NATURE BIOTECHNOLOGY LA English DT Article ID COPY-NUMBER; GENES; REPAIR; RECOMBINATION; CHECKPOINT; EVOLUTION; DISEASE; POOLS; CELLS AB Somatic copy-number alterations (SCNA) are a hallmark of many cancer types, but the mechanistic basis underlying their genome-wide patterns remains incompletely understood. Here we integrate data on DNA replication timing, long-range interactions between genomic material, and 331,724 SCNAs from 2,792 cancer samples classified into 26 cancer types. We report that genomic regions of similar replication timing are clustered spatially in the nucleus, that the two boundaries of SCNAs tend to be found in such regions, and that regions replicated early and late display distinct patterns of frequencies of SCNA boundaries, SCNA size and a preference for deletions over insertions. We show that long-range interaction and replication timing data alone can identify a significant proportion of SCNAs in an independent test data set. We propose a model for the generation of SCNAs in cancer, suggesting that data on spatial proximity of regions replicating at the same time can be used to predict the mutational landscapes of cancer genomes. C1 [De, Subhajyoti; Michor, Franziska] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [De, Subhajyoti; Michor, Franziska] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP De, S (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. EM subho@jimmy.harvard.edu; michor@jimmy.harvard.edu FU National Cancer Institute's initiative to found Physical Science-Oncology Centers [U54CA143798]; Human Frontier Science Program long-term fellowship FX We would like to thank K. Polyak, A. Melnick, K.J. Patel, A. Chakravarti and R. Beroukhim for comments and discussions. S. D. is a recipient of Human Frontier Science Program long-term fellowship and is a Research Fellow at King's College, Cambridge. This work was funded by the National Cancer Institute's initiative to found Physical Science-Oncology Centers (U54CA143798). NR 32 TC 84 Z9 86 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD DEC PY 2011 VL 29 IS 12 BP 1103 EP U119 DI 10.1038/nbt.2030 PG 7 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 861SE UT WOS:000298038700019 PM 22101487 ER PT J AU Fudenberg, G Getz, G Meyerson-, M Mirny, LA AF Fudenberg, Geoff Getz, Gad Meyerson-, Matthew Mirny, Leonid A. TI High order chromatin architecture shapes the landscape of chromosomal alterations in cancer SO NATURE BIOTECHNOLOGY LA English DT Article ID SEQUENCING REVEALS; COPY-NUMBER; GENOME; REARRANGEMENTS; TRANSLOCATIONS; MECHANISMS; PROXIMITY; MUTATION; CELLS; LOCI AB The accumulation of data on structural variation in cancer genomes provides an opportunity to better understand the mechanisms of genomic alterations and the forces of selection that act upon these alterations in cancer. Here we test evidence supporting the influence of two major forces, spatial chromosome structure and purifying (or negative) selection, on the landscape of somatic copy-number alterations (SCNAs) in cancer(1). Using a maximum likelihood approach, we compare SCNA maps and three-dimensional genome architecture as determined by genome-wide chromosome conformation capture (HiC) and described by the proposed fractal-globule model(2,3). This analysis suggests that the distribution of chromosomal alterations in cancer is spatially related to three-dimensional genomic architecture and that purifying selection, as well as positive selection, influences SCNAs during somatic evolution of cancer cells. C1 [Getz, Gad; Meyerson-, Matthew; Mirny, Leonid A.] Broad Inst Massachusetts Inst Technol & Harvard, Cambridge, MA USA. [Fudenberg, Geoff] Harvard Univ, Program Biophys, Boston, MA 02115 USA. [Meyerson-, Matthew] Harvard Univ, Sch Med, Boston, MA USA. [Meyerson-, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Meyerson-, Matthew] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Mirny, Leonid A.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Mirny, Leonid A.] MIT, Dept Phys, Cambridge, MA 02139 USA. RP Mirny, LA (reprint author), Broad Inst Massachusetts Inst Technol & Harvard, Cambridge, MA USA. EM leonid@mit.edu RI Meyerson, Matthew/E-7123-2012; OI , /0000-0001-5905-6517 FU US National Institutes of Health/National Cancer Institute Physical Sciences Oncology Center at MIT [U54CA143874]; TCGA (NIH) [U24CA143845, U24CA144025, U24CA143867] FX We thank members of the Mirny Lab for helpful conversations, in particular with C. McFarland regarding purifying selection and M. Imakaev regarding fractal globules. We thank C. Mermel for an introduction to SCNA data. We thank V. Agarwala, J. Engrietz, R. McCord and J. Dekker for helpful comments and suggestions. This work was supported by the US National Institutes of Health/National Cancer Institute Physical Sciences Oncology Center at MIT (U54CA143874). G. G. and M. M. are TCGA-funded investigators (NIH U24CA143845, U24CA144025 and U24CA143867). NR 27 TC 81 Z9 83 U1 0 U2 19 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD DEC PY 2011 VL 29 IS 12 BP 1109 EP U75 DI 10.1038/nbt.2049 PG 6 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 861SE UT WOS:000298038700020 PM 22101486 ER PT J AU Kim, K Zhao, R Doi, A Ng, K Unternaehrer, J Cahan, P Huo, HG Loh, YH Aryee, MJ Lensch, MW Li, H Collins, JJ Feinberg, AP Daley, GQ AF Kim, Kitai Zhao, Rui Doi, Akiko Ng, Kitwa Unternaehrer, Juli Cahan, Patrick Huo Hongguang Loh, Yuin-Han Aryee, Martin J. Lensch, M. William Li, Hu Collins, James J. Feinberg, Andrew P. Daley, George Q. TI Donor cell type can influence the epigenome and differentiation potential of human induced pluripotent stem cells SO NATURE BIOTECHNOLOGY LA English DT Article ID METHYLATION; MEMORY; LINES AB We compared bona fide human induced pluripotent stem cells (iPSCs) derived from umbilical cord blood (CB) cells and neonatal keratinocytes (K). As a consequence of both incomplete erasure of tissue-specific methylation and aberrant de novo methylation, CB-iPSCs and K-iPSCs were distinct in genome-wide DNA methylation profiles and differentiation potential. Extended passage of some iPSC clones in culture did not improve their epigenetic resemblance to embryonic stem cells, implying that some human iPSCs retain a residual 'epigenetic memory' of their tissue of origin. C1 [Kim, Kitai; Zhao, Rui; Ng, Kitwa; Unternaehrer, Juli; Cahan, Patrick; Huo Hongguang; Loh, Yuin-Han; Lensch, M. William; Daley, George Q.] Childrens Hosp, Howard Hughes Med Inst, Stem Cell Transplantat Program, Div Pediat Hematol Oncol,Manton Ctr Orphan Dis Re, Boston, MA 02115 USA. [Kim, Kitai; Zhao, Rui; Ng, Kitwa; Unternaehrer, Juli; Cahan, Patrick; Huo Hongguang; Loh, Yuin-Han; Lensch, M. William; Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kim, Kitai; Zhao, Rui; Unternaehrer, Juli; Cahan, Patrick; Loh, Yuin-Han; Lensch, M. William; Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Kim, Kitai; Zhao, Rui; Ng, Kitwa; Unternaehrer, Juli; Cahan, Patrick; Huo Hongguang; Loh, Yuin-Han; Lensch, M. William; Daley, George Q.] Harvard Stem Cell Inst, Cambridge, MA USA. [Doi, Akiko; Feinberg, Andrew P.] Johns Hopkins Univ, Sch Med, Ctr Epigenet, Baltimore, MD USA. [Doi, Akiko; Feinberg, Andrew P.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Aryee, Martin J.] Johns Hopkins Univ, Dept Oncol, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Li, Hu; Collins, James J.] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Li, Hu; Collins, James J.] Boston Univ, Ctr BioDynam, Boston, MA 02215 USA. [Collins, James J.] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA. [Daley, George Q.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. RP Daley, GQ (reprint author), Childrens Hosp, Howard Hughes Med Inst, Stem Cell Transplantat Program, Div Pediat Hematol Oncol,Manton Ctr Orphan Dis Re, Boston, MA 02115 USA. EM afeinberg@jhu.edu; george.daley@childrens.harvard.edu RI Loh, Yuin-Han/E-1096-2014; OI Loh, Yuin-Han/0000-0002-4715-6454; Cahan, Patrick/0000-0003-3652-2540 FU US National Institutes of Health (NIH) [DK70055, DK59279, RC2-HL102815, K99HL093212-01, R37CA054358, P50HG003233]; Leukemia and Lymphoma Society [3567-07]; Cooley's Anemia Foundation FX G.Q.D. was funded by US National Institutes of Health (NIH) grants DK70055 and DK59279, special funds received by the NIH under the American Recovery and Reinvestment Act (RC2-HL102815). K. K. was supported by NIH (K99HL093212-01), Leukemia and Lymphoma Society (3567-07), and Cooley's Anemia Foundation. A. P. F. was funded by NIH grants R37CA054358 and P50HG003233. NR 13 TC 233 Z9 244 U1 3 U2 31 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD DEC PY 2011 VL 29 IS 12 BP 1117 EP 1119 DI 10.1038/nbt.2052 PG 3 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 861SE UT WOS:000298038700022 PM 22119740 ER PT J AU Amps, K Andrews, PW Anyfantis, G Armstrong, L Avery, S Baharvand, H Baker, J Baker, D Munoz, MB Beil, S Benvenisty, N Ben-Yosef, D Biancotti, JC Bosman, A Brena, RM Brison, D Caisander, G Camarasa, MV Chen, JM Chiao, E Choi, YM Choo, ABH Collins, D Colman, A Crook, JM Daley, GQ Dalton, A De Sousa, PA Denning, C Downie, J Dvorak, P Montgomery, KD Feki, A Ford, A Fox, V Fraga, AM Frumkin, T Ge, L Gokhale, PJ Golan-Lev, T Gourabi, H Gropp, M Lu, GX Hampl, A Harron, K Healy, L Herath, W Holm, F Hovatta, O Hyllner, J Inamdar, MS Irwanto, AK Ishii, T Jaconi, M Jin, Y Kimber, S Kiselev, S Knowles, BB Kopper, O Kukharenko, V Kuliev, A Lagarkova, MA Laird, PW Lako, M Laslett, AL Lavon, N Lee, DR Lee, JE Li, CL Lim, LS Ludwig, TE Ma, Y Maltby, E Mateizel, I Mayshar, Y Mileikovsky, M Minger, SL Miyazaki, T Moon, SY Moore, H Mummery, C Nagy, A Nakatsuji, N Narwani, K Oh, SKW Oh, SK Olson, C Otonkoski, T Pan, F Park, IH Pells, S Pera, MF Pereira, LV Qi, O Raj, GS Reubinoff, B Robins, A Robson, P Rossant, J Salekdeh, GH Schulz, TC Sermon, K Mohamed, JS Shen, H Sherrer, E Sidhu, K Sivarajah, S Skottman, H Spits, C Stacey, GN Strehl, R Strelchenko, N Suemori, H Sun, BW Suuronen, R Takahashi, K Tuuri, T Venu, P Verlinsky, Y Ward-van Oostwaard, D Weisenberger, DJ Wu, Y Yamanaka, S Young, L Zhou, Q AF Amps, Katherine Andrews, Peter W. Anyfantis, George Armstrong, Lyle Avery, Stuart Baharvand, Hossein Baker, Julie Baker, Duncan Munoz, Maria B. Beil, Stephen Benvenisty, Nissim Ben-Yosef, Dalit Biancotti, Juan-Carlos Bosman, Alexis Brena, Romulo Martin Brison, Daniel Caisander, Gunilla Camarasa, Maria V. Chen, Jieming Chiao, Eric Choi, Young Min Choo, Andre B. H. Collins, Daniel Colman, Alan Crook, Jeremy M. Daley, George Q. Dalton, Anne De Sousa, Paul A. Denning, Chris Downie, Janet Dvorak, Petr Montgomery, Karen D. Feki, Anis Ford, Angela Fox, Victoria Fraga, Ana M. Frumkin, Tzvia Ge, Lin Gokhale, Paul J. Golan-Lev, Tamar Gourabi, Hamid Gropp, Michal Lu Guangxiu Hampl, Ales Harron, Katie Healy, Lyn Herath, Wishva Holm, Frida Hovatta, Outi Hyllner, Johan Inamdar, Maneesha S. Irwanto, Astrid Kresentia Ishii, Tetsuya Jaconi, Marisa Jin, Ying Kimber, Susan Kiselev, Sergey Knowles, Barbara B. Kopper, Oded Kukharenko, Valeri Kuliev, Anver Lagarkova, Maria A. Laird, Peter W. Lako, Majlinda Laslett, Andrew L. Lavon, Neta Lee, Dong Ryul Lee, Jeoung Eun Li, Chunliang Lim, Linda S. Ludwig, Tenneille E. Ma, Yu Maltby, Edna Mateizel, Ileana Mayshar, Yoav Mileikovsky, Maria Minger, Stephen L. Miyazaki, Takamichi Moon, Shin Yong Moore, Harry Mummery, Christine Nagy, Andras Nakatsuji, Norio Narwani, Kavita Oh, Steve K. W. Oh, Sun Kyung Olson, Cia Otonkoski, Timo Pan, Fei Park, In-Hyun Pells, Steve Pera, Martin F. Pereira, Lygia V. Qi, Ouyang Raj, Grace Selva Reubinoff, Benjamin Robins, Alan Robson, Paul Rossant, Janet Salekdeh, Ghasem H. Schulz, Thomas C. Sermon, Karen Mohamed, Jameelah Sheik Shen, Hui Sherrer, Eric Sidhu, Kuldip Sivarajah, Shirani Skottman, Heli Spits, Claudia Stacey, Glyn N. Strehl, Raimund Strelchenko, Nick Suemori, Hirofumi Sun, Bowen Suuronen, Riitta Takahashi, Kazutoshi Tuuri, Timo Venu, Parvathy Verlinsky, Yuri Ward-van Oostwaard, Dorien Weisenberger, Daniel J. Wu, Yue Yamanaka, Shinya Young, Lorraine Zhou, Qi CA Int Stem Cell Initiative TI Screening ethnically diverse human embryonic stem cells identifies a chromosome 20 minimal amplicon conferring growth advantage SO NATURE BIOTECHNOLOGY LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; COPY NUMBER VARIATION; HUMAN ES CELLS; DNA-SEQUENCE; IN-VIVO; CULTURE; LINES; TUMORS; PLURIPOTENCY; GENES AB The International Stem Cell Initiative analyzed 125 human embryonic stem (ES) cell lines and 11 induced pluripotent stem (iPS) cell lines, from 38 laboratories worldwide, for genetic changes occurring during culture. Most lines were analyzed at an early and late passage. Single-nucleotide polymorphism (SNP) analysis revealed that they included representatives of most major ethnic groups. Most lines remained karyotypically normal, but there was a progressive tendency to acquire changes on prolonged culture, commonly affecting chromosomes 1, 12, 17 and 20. DNA methylation patterns changed haphazardly with no link to time in culture. Structural variants, determined from the SNP arrays, also appeared sporadically. No common variants related to culture were observed on chromosomes 1, 12 and 17, but a minimal amplicon in chromosome 20q11.21, including three genes expressed in human ES cells, ID1, BCL2L1 and HM13, occurred in >20% of the lines. Of these genes, BCL2L1 is a strong candidate for driving culture adaptation of ES cells. C1 [Amps, Katherine; Andrews, Peter W.; Ford, Angela; Gokhale, Paul J.; Moore, Harry] Univ Sheffield, Dept Biomed Sci, Ctr Stem Cell Biol, Sheffield S10 2TN, S Yorkshire, England. [Anyfantis, George; Armstrong, Lyle; Lako, Majlinda] Int Ctr Life, NE England Stem Cell Inst Life, Newcastle Upon Tyne, Tyne & Wear, England. [Avery, Stuart; Colman, Alan; Crook, Jeremy M.; Knowles, Barbara B.] ASTAR, Inst Med Biol, Immunos, Singapore. [Baharvand, Hossein; Gourabi, Hamid] Royan Inst Reprod Biomed, Dept Genet, Tehran, Iran. [Baker, Julie; Chiao, Eric] Stanford Univ, Stanford, CA 94305 USA. [Baker, Duncan; Dalton, Anne; Maltby, Edna] Sheffield Childrens NHS Trust, Sheffield Diagnost Genet Serv, Sheffield, S Yorkshire, England. [Munoz, Maria B.; Denning, Chris; Young, Lorraine] Univ Nottingham, Ctr Biomol Sci, Wolfson Ctr Stem Cells Tissue Engn & Modelling ST, Nottingham NG7 2RD, England. [Beil, Stephen; Fox, Victoria] Univ So Calif, Keck Sch Med, USC Stem Cell Core Facil, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Los Angeles, CA 90033 USA. [Benvenisty, Nissim; Golan-Lev, Tamar; Kopper, Oded; Mayshar, Yoav] Hebrew Univ Jerusalem, Dept Genet, Alexander Silberman Inst Life Sci, Stem Cell Unit, IL-91904 Jerusalem, Israel. [Ben-Yosef, Dalit; Frumkin, Tzvia] Lis Matern Hosp, Tel Aviv Sourasky Med Ctr, Racine IVF Unit, Tel Aviv, Israel. [Ben-Yosef, Dalit] Tel Aviv Univ, Sackler Fac Med, Dept Cell Dev Biol, IL-69978 Tel Aviv, Israel. [Biancotti, Juan-Carlos; Lavon, Neta; Narwani, Kavita] Cedars Sinai Med Inst, Regenerat Med Inst, Los Angeles, CA USA. [Bosman, Alexis; Jaconi, Marisa] Univ Geneva, Fac Med, Dept Pathol & Immunol, Geneva, Switzerland. [Brena, Romulo Martin; Laird, Peter W.; Pan, Fei; Shen, Hui; Weisenberger, Daniel J.] Univ So Calif, Keck Sch Med, USC Epigenome Ctr, Los Angeles, CA 90033 USA. [Brison, Daniel] Cent Manchester NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, St Maryss Hosp, Dept Reprod Med, Manchester, Lancs, England. [Caisander, Gunilla; Hyllner, Johan; Strehl, Raimund] Cellartis AB, Gothenburg, Sweden. [Camarasa, Maria V.; Kimber, Susan] Univ Manchester, Fac Life Sci, Manchester, Lancs, England. [Chen, Jieming; Herath, Wishva; Irwanto, Astrid Kresentia; Lim, Linda S.; Robson, Paul; Mohamed, Jameelah Sheik] Genome Inst Singapore, Singapore, Singapore. [Chiao, Eric] Hoffmann LaRoche, Nutley, NJ USA. [Choi, Young Min; Moon, Shin Yong] Seoul Natl Univ, Coll Med, Dept Obstet & Gynaecol, Seoul, South Korea. [Choo, Andre B. H.; Oh, Steve K. W.] Bioproc Technol Inst, Singapore, Singapore. [Collins, Daniel; De Sousa, Paul A.; Downie, Janet] Roslin Cells Ltd, Roslin Bioctr, Roslin, Midlothian, Scotland. [Colman, Alan; Crook, Jeremy M.; Raj, Grace Selva; Sivarajah, Shirani] ASTAR, Singapore Stem Cell Consortium, Singapore, Singapore. [Crook, Jeremy M.; Sivarajah, Shirani] Univ Melbourne, Ctr Neural Engn, Parkville, Vic 3052, Australia. [Crook, Jeremy M.; Sivarajah, Shirani] Univ Melbourne, Opt & Nanoelect Res Grp, NICTA Victorian Res Lab, Parkville, Vic 3052, Australia. [Crook, Jeremy M.] Univ Melbourne, St Vincents Hosp, Dept Surg, Fitzroy, Vic 3065, Australia. [Daley, George Q.] Childrens Hosp, Howard Hughes Med Inst, Stem Cell Transplantat Program, Div Pediat Hematol Oncol,Manton Ctr Orphan Dis Re, Boston, MA 02115 USA. [Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Daley, George Q.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. [Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Daley, George Q.] Harvard Stem Cell Inst, Boston, MA USA. [De Sousa, Paul A.; Pells, Steve] Univ Edinburgh, MRC, Ctr Regenerat Med, Edinburgh, Midlothian, Scotland. [Dvorak, Petr] Masaryk Univ, Dept Biol, Fac Med, Brno, Czech Republic. [Montgomery, Karen D.; Ludwig, Tenneille E.] WiCell Res Inst, Madison, WI USA. [Feki, Anis] Hop Cantonal Fribourgois, Dept Obstet & Gynecol, Freibourg, Switzerland. [Fraga, Ana M.; Pereira, Lygia V.] Univ Sao Paulo, Dept Genet & Evolutionary Biol, Natl Lab Embryon Stem Cell Res LaNCE, Sao Paulo, Brazil. [Ge, Lin; Lu Guangxiu; Qi, Ouyang] Cent S Univ, Inst Reprod & Stem Cell Engn, Reprod & Genet Hosp CITIC XIANGYA, Changsha, Hunan, Peoples R China. [Gropp, Michal; Reubinoff, Benjamin] Hadassah Univ, Med Ctr, Goldyne Savad Inst Gene Therapy, Hadassah Human Embryon Stem Cell Res Ctr, Jerusalem, Israel. [Hampl, Ales] Masaryk Univ, Fac Med, Dept Histol & Embryol, Brno, Czech Republic. [Hampl, Ales] Inst Expt Med ASCR, Prague, Czech Republic. [Harron, Katie] UCL, Inst Child Hlth, MRC Ctr Epidemiol Child Hlth, London, England. [Healy, Lyn; Stacey, Glyn N.] Natl Inst Biol Stand & Controls, Div Cell Biol & Imaging, UK Stem Cell Bank, S Mimms, Herts, England. [Holm, Frida; Hovatta, Outi] Karolinska Univ, Huddinge Hosp, Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden. [Inamdar, Maneesha S.; Venu, Parvathy] Indian Inst Sci, Jawaharlal Nehru Ctr Adv Sci Res, Bangalore 560012, Karnataka, India. [Ishii, Tetsuya; Takahashi, Kazutoshi; Yamanaka, Shinya] Kyoto Univ, Ctr iPS Cell Res & Applicat CiRA, Kyoto, Japan. [Jin, Ying] CAS Shanghai Jiao Tong Univ, Shanghai Inst Biol Sci, Key Lab Stem Cell Biol, Inst Hlth Sci,Sch Med, Shanghai, Peoples R China. [Kiselev, Sergey] NRC Kurchatov Inst, Stem Cell Dept, Moscow, Russia. [Kiselev, Sergey; Lagarkova, Maria A.] Vavilov Inst Gen Genet, Moscow, Russia. [Kukharenko, Valeri; Kuliev, Anver; Strelchenko, Nick; Verlinsky, Yuri] Illinois Masonic Med Ctr, Inst Reprod Genet, Chicago, IL 60657 USA. [Laslett, Andrew L.; Zhou, Qi] CSIRO Mat Sci & Engn, Clayton, Vic, Australia. [Laslett, Andrew L.] Monash Univ, Dept Anat & Dev Biol, Clayton, Vic, Australia. [Lee, Dong Ryul] CHA Univ, CHA Stem Cell Inst, Dept Biomed Sci, Seoul, South Korea. [Li, Chunliang; Ma, Yu; Sun, Bowen] Shanghai Jiao Tong Univ, Sch Med, Shanghai Stem Cell Inst, Shanghai 200030, Peoples R China. [Mateizel, Ileana; Sermon, Karen; Spits, Claudia] Vrije Univ Brussel, Dept Embryol & Genet, Brussels, Belgium. [Mileikovsky, Maria; Nagy, Andras] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Minger, Stephen L.; Wu, Yue] Kings Coll London, Wolfson Ctr Age Related Dis, London WC2R 2LS, England. [Minger, Stephen L.; Wu, Yue] GE Healthcare, Cardiff, S Glam, Wales. [Miyazaki, Takamichi; Suemori, Hirofumi] Kyoto Univ, Inst Frontier Med Sci, Stem Cell Res Ctr, Lab Embryon Stem Cell Res, Kyoto, Japan. [Mummery, Christine; Ward-van Oostwaard, Dorien] Leiden Univ, Med Ctr, Dept Anat & Embryol, Leiden, Netherlands. [Nakatsuji, Norio; Yamanaka, Shinya] Kyoto Univ, Inst Integrated Cell Mat Sci, Sakyo Ku, Kyoto, Japan. [Oh, Sun Kyung] Seoul Natl Univ, Med Res Ctr, Inst Reprod Med & Populat, Seoul, South Korea. [Olson, Cia; Otonkoski, Timo; Tuuri, Timo] Univ Helsinki, Res Programs Unit, Biomedicum Stem Cell Ctr, FIN-00014 Helsinki, Finland. [Otonkoski, Timo] Univ Helsinki, Childrens Hosp, FIN-00014 Helsinki, Finland. [Otonkoski, Timo] Univ Helsinki, Cent Hosp, FIN-00014 Helsinki, Finland. [Park, In-Hyun] Yale Univ, Sch Med, Dept Genet, Yale Stem Cell Ctr, New Haven, CT 06510 USA. [Robins, Alan; Schulz, Thomas C.; Sherrer, Eric] Viacyte, Athens, GA USA. [Rossant, Janet] Hosp Sick Children, Program Dev Biol, Toronto, ON M5G 1X8, Canada. [Salekdeh, Ghasem H.] ACECR, Royan Inst Stem Cell Biol & Technol, Cell Sci Res Ctr, Dept Mol Syst Biol, Tehran, Iran. [Sidhu, Kuldip] Univ New S Wales, Fac Med, Stem Cell Lab, Sydney, NSW 2052, Australia. [Skottman, Heli; Suuronen, Riitta] Univ Tampere, Inst Regenerat Med, FIN-33101 Tampere, Finland. [Yamanaka, Shinya] Japan Sci & Technol Agcy, Yamanaka iPS Cell Special Project, Kawaguchi, Saitama, Japan. [Yamanaka, Shinya] Gladstone Inst Cardiovasc Dis, San Francisco, CA USA. RP Amps, K (reprint author), Univ Sheffield, Dept Biomed Sci, Ctr Stem Cell Biol, Sheffield S10 2TN, S Yorkshire, England. RI Dvorak, Petr/G-2509-2013; Nagy, Andras/G-6465-2013; Robson, Paul/A-3464-2009; PERA, MARTIN/A-9812-2012; Pereira, Lygia/C-1049-2012; Vopenkova, Katerina/C-7133-2012; Salekdeh, Ghasem Hosseini/E-4198-2012; Laird, Peter/G-8683-2012; Choi, Young Min/J-2794-2012; Moon, Shin-Yong/J-5467-2012; Lako, Majlinda/B-6297-2013; Armstrong, Lyle/B-7812-2013; Laslett, Andrew/A-9760-2011; De Sousa, Paul/H-7416-2013; Celulas tronco, Inct/I-1921-2013; denning, chris/D-4777-2013; Spits, Claudia/J-1964-2014; Jaconi, Marisa/J-4392-2013; Hampl, Ales/N-1632-2016; Dvorak, Petr/N-8936-2016; Salekdeh, Ghasem Hosseini/R-8716-2016; OI Dvorak, Petr/0000-0002-3229-140X; Robson, Paul/0000-0002-0191-3958; PERA, MARTIN/0000-0001-6239-0428; Pereira, Lygia/0000-0002-0002-725X; Laslett, Andrew/0000-0003-4729-8193; De Sousa, Paul/0000-0003-0745-2504; Dvorak, Petr/0000-0002-3229-140X; Kimber, Susan/0000-0002-0568-6342; Anyfantis, George/0000-0001-5647-3841; Chen, Jieming/0000-0003-3767-9486; Gokhale, Paul/0000-0001-7225-4403; kiselev, sergey/0000-0001-7921-6987; Pells, Stephen/0000-0001-5866-5759; Ishii, Tetsuya/0000-0002-7085-7750; Harron, Katie/0000-0002-3418-2856; Denning, Chris/0000-0003-0802-8617 FU International Stem Cell Forum; Ministry of Science and Technology of China [2006AA02A102]; Japan Society for the Promotion of Science (JSPS); MEXT; Swiss National Science Foundation [4046-114410]; North West Science Fund, UK; One North East Regional Developmental Agency; Medical Research Council, UK; Newcastle University; Australian Stem Cell Centre; Netherlands Proteomics Consortium [T4-3]; Stem Cell Network, Canada; MEXT, Japan; Singapore Stem Cell Consortium (SSCC); Agency for Science Technology and Research (AstarSTAR); Genome Institute of Singapore Core Genotyping Lab; Academy of Finland [218050]; Sigrid Juselius Foundation; Conselho Nacional de Desenvolvimento Cientifico e Tecnologico/Departamento de Ciencia e Tecnologia do Ministerio da Saude (CNPq/MS/DECIT); Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP); Judy; Sidney Swartz; Faculty of Medicine; University of New South Wales (UNSW); National Health and Medical Research Council (NHMRC) [568969]; South Eastern Sydney and Illawarra Area Health Service (SEIAHS); Tampere University Hospital [9F217] FX The International Stem Cell Initiative is funded by The International Stem Cell Forum. The authors would like to acknowledge the following: Medical Research Council, UK (P. W. A., H. M.); Mohammad Pakzad & Adeleh Taei, Royan Institute (H. B., G. H. S.); California Institute for Regenerative Medicine (CIRM) (E. C., P. W. L.); Institute of Medical Biology, AstarSTAR, Singapore (J.M.C.); Ministry of Education, Youth and Sports of the Czech Republic (P. D., A. H.); Stem Cell Research Center of the 21st Century Frontier Research Program, Ministry of Education, Science & Technology, Republic of Korea (SC-1140) (D. R. L., S.K.O.); Ministry of Science and Technology of China (863 program 2006AA02A102) (L. G.); Swedish Research Council, Cellartis (O.H.); Department of Biotechnology, Government of India, UK-India Education and Research Initiative and the Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, India (M. I.); Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation, Leading Project of the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST Program) of the Japan Society for the Promotion of Science (JSPS), Grants in-Aid for Scientific Research of JSPS and MEXT (T. I., S.Y., K. T.); Swiss National Science Foundation (grant no. 4046-114410) (M.J.); Shanghai Science and Technology Developmental Foundation (06DJ14001), Chinese Ministry of Science and Technology (2007CB948004) (Y.J.); funding from the North West Science Fund, UK (S. K.); One North East Regional Developmental Agency, Medical Research Council, UK, Newcastle University (M. L.); research funding from the Australian Stem Cell Centre (A. L. L.); The Netherlands Proteomics Consortium grant T4-3 (C. M.); Stem Cell Network, Canada (A.N.); National BioResource Project, MEXT, Japan (N.N.); Singapore Stem Cell Consortium (SSCC) & the Agency for Science Technology and Research (AstarSTAR) (S. K. W.O., P. R.) and the Genome Institute of Singapore Core Genotyping Lab (P. R.); Academy of Finland, Sigrid Juselius Foundation (T.O.); Conselho Nacional de Desenvolvimento Cientifico e Tecnologico/Departamento de Ciencia e Tecnologia do Ministerio da Saude (CNPq/MS/DECIT), and Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) (L. V. P.); supported by the kind donation of Judy and Sidney Swartz (B. R.); financial support from the Faculty of Medicine, University of New South Wales (UNSW) and the National Health and Medical Research Council (NHMRC) Program Grant no. 568969 (Perminder Sachdev), South Eastern Sydney and Illawarra Area Health Service (SEIAHS) for making hES cell line Endeavour-2 available for this study, and H. Chung and J. Kim for their help in preparing the samples (K. S.); Academy of Finland (grant 218050), the Competitive Research Funding of the Tampere University Hospital (grant 9F217) (H. Skottman). NR 69 TC 183 Z9 188 U1 7 U2 106 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 EI 1546-1696 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD DEC PY 2011 VL 29 IS 12 BP 1132 EP U113 DI 10.1038/nbt.2051 PG 15 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 861SE UT WOS:000298038700025 ER PT J AU Amit, I Regev, A Hacohen, N AF Amit, Ido Regev, Aviv Hacohen, Nir TI Strategies to discover regulatory circuits of the mammalian immune system SO NATURE REVIEWS IMMUNOLOGY LA English DT Article ID GENE-EXPRESSION; NONCODING RNAS; TRANSCRIPTIONAL NETWORK; DNA-DAMAGE; T-CELLS; BIOLOGY; CHROMATIN; DYNAMICS; DIFFERENTIATION; SIGNATURE AB Recent advances in technologies for genome- and proteome-scale measurements and perturbations promise to accelerate discovery in every aspect of biology and medicine. Although such rapid technological progress provides a tremendous opportunity, it also demands that we learn how to use these tools effectively. One application with great potential to enhance our understanding of biological systems is the unbiased reconstruction of genetic and molecular networks. Cells of the immune system provide a particularly useful model for developing and applying such approaches. Here, we review approaches for the reconstruction of signalling and transcriptional networks, with a focus on applications in the mammalian innate immune system. C1 [Amit, Ido; Regev, Aviv; Hacohen, Nir] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Amit, Ido] Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel. [Regev, Aviv] MIT, Dept Biol, Howard Hughes Med Inst, Cambridge, MA 02142 USA. [Hacohen, Nir] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. [Hacohen, Nir] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Amit, I (reprint author), Broad Inst MIT & Harvard, 7 Cambridge Ctr, Cambridge, MA 02142 USA. EM ido.amit@weizmann.ac.il; aregev@broadinstitute.org; nhacohen@partners.org FU US National Institutes of Health; Howard Hughes Medical Institute; Human Frontier Science Program and the Broad Institute FX The authors would like to thank the US National Institutes of Health, the Howard Hughes Medical Institute, the Human Frontier Science Program and the Broad Institute for funding the work presented here. NR 66 TC 35 Z9 35 U1 0 U2 13 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD DEC PY 2011 VL 11 IS 12 BP 873 EP 880 DI 10.1038/nri3109 PG 8 WC Immunology SC Immunology GA 861XU UT WOS:000298054800006 PM 22094988 ER PT J AU Nabors, LB Supko, JG Rosenfeld, M Chamberlain, M Phuphanich, S Batchelor, T Desideri, S Ye, X Wright, J Gujar, S Grossman, SA AF Nabors, L. B. Supko, J. G. Rosenfeld, M. Chamberlain, M. Phuphanich, S. Batchelor, T. Desideri, S. Ye, X. Wright, J. Gujar, S. Grossman, S. A. CA New Approaches Brain Tumor Therapy TI Phase I trial of sorafenib in patients with recurrent or progressive malignant glioma SO NEURO-ONCOLOGY LA English DT Article DE angiogenesis; glioma; pharmacokinetics; proliferation; targeted therapy ID REFRACTORY SOLID TUMORS; ENDOTHELIAL GROWTH-FACTOR; FACTOR RECEPTOR INHIBITOR; RENAL-CELL CARCINOMA; DAYS ON/7 DAYS; RAF KINASE; COGNITIVE FUNCTION; ANTITUMOR-ACTIVITY; GRADE GLIOMA; BAY-43-9006 AB Sorafenib is an inhibitor of multiple kinases that has demonstrated antiproliferative and antiangiogenic activity in a number of in vitro and in vivo model systems. A phase I study was conducted to determine the maximum tolerated dose (MTD) of sorafenib in patients with recurrent malignant glioma. Sorafenib was given orally, twice a day (BID), continuously in 28-day cycles. The dose was escalated in 2 groups of patients stratified by use of enzyme-inducing antiseizure drugs (+/- EIASDs). Dose-limiting toxicity (DLT) was defined as any grades 3-4 nonhematological toxicity, grade 4 hematological toxicity, and febrile neutropenia. The number of evaluable patients enrolled in the + EIASD and -EIASD arms were 23 and 24, respectively. DLTs were predominantly dermatological and gastrointestinal effects, as observed in previous clinical trials of sorafenib. The MTD was 600 mg BID for patients receiving EIASDs and 800 mg BID for those who were not. The plasma pharmacokinetics of sorafenib were not significantly affected by the concurrent administration of EIASDs. The MTD of sorafenib given orally BID on a continuous basis was established as 600 mg BID in patients with malignant glioma who were concurrently receiving EIASDs and 800 mg BID in those who were not. Further evaluation is warranted of sorafenib at the recommended MTD against recurrent or progressive malignant glioma in combination with other molecularly targeted drugs or in the newly diagnosed setting concurrent with chemoradiation. C1 [Nabors, L. B.] Univ Alabama, Birmingham, AL 35294 USA. [Supko, J. G.; Batchelor, T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. [Rosenfeld, M.] Hosp Univ Penn, Philadelphia, PA 19104 USA. [Chamberlain, M.] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle Canc Care Alliance, Seattle, WA 98195 USA. [Phuphanich, S.] Cedar Sinai Med Ctr, Los Angeles, CA USA. [Wright, J.] NCI, Bethesda, MD 20892 USA. [Desideri, S.; Ye, X.; Gujar, S.; Grossman, S. A.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. RP Nabors, LB (reprint author), Univ Alabama, Birmingham, AL 35294 USA. OI Rosenfeld, Myrna/0000-0001-5095-2534 FU National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland [U01-CA62475, U01-CA105689] FX This study was supported by grants U01-CA62475 and U01-CA105689 from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland. Preliminary results of this study were presented at the 2004 annual meeting of the Society of Neuro-Oncology. NR 27 TC 23 Z9 23 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD DEC PY 2011 VL 13 IS 12 BP 1324 EP 1330 DI 10.1093/neuonc/nor145 PG 7 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 860GH UT WOS:000297936300008 PM 21954442 ER PT J AU Johnson, KA Dickerson, BC AF Johnson, K. A. Dickerson, B. C. TI A tale of two tracers The age of wisdom for dementia diagnosis? SO NEUROLOGY LA English DT Editorial Material C1 [Johnson, K. A.; Dickerson, B. C.] Massachusetts Gen Hosp, Dept Neurol, Frontotemporal Dementia Unit, Boston, MA 02114 USA. [Johnson, K. A.] Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Dept Imaging, Boston, MA 02114 USA. [Dickerson, B. C.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Johnson, K. A.; Dickerson, B. C.] Harvard Univ, Sch Med, Dept Neurol, Brigham & Womens Hosp, Boston, MA USA. [Johnson, K. A.; Dickerson, B. C.] Massachusetts Alzheimers Dis Res Ctr, Boston, MA USA. RP Johnson, KA (reprint author), White 427 MGH,33 Fruit St, Boston, MA 02114 USA. EM kajohnson@pet.mgh.harvard.edu NR 7 TC 0 Z9 0 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC PY 2011 VL 77 IS 23 BP 2008 EP 2009 DI 10.1212/WNL.0b013e31823b9c9f PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 861TP UT WOS:000298042400007 PM 22131545 ER PT J AU Louis, DN Virgin, HW Asa, SL AF Louis, David N. Virgin, Herbert W. Asa, Sylvia L. TI "Next-Generation" Pathology and Laboratory Medicine Diagnosis SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Editorial Material C1 [Louis, David N.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Louis, David N.] Harvard Univ, Sch Med, Boston, MA USA. [Virgin, Herbert W.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA. [Asa, Sylvia L.] Univ Hlth Network, Lab Med Program, Toronto, ON, Canada. [Asa, Sylvia L.] Univ Toronto, Toronto, ON, Canada. RP Louis, DN (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. EM dlouis@partners.org NR 1 TC 7 Z9 9 U1 0 U2 3 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD DEC PY 2011 VL 135 IS 12 BP 1531 EP 1532 DI 10.5858/arpa.2011-0414-ED PG 2 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 860HF UT WOS:000297938700007 PM 22129178 ER PT J AU Evans, KK Tambouret, RH Evered, A Wilbur, DC Wolfe, JM AF Evans, Karla K. Tambouret, Rosemary H. Evered, Andrew Wilbur, David C. Wolfe, Jeremy M. TI Prevalence of Abnormalities Influences Cytologists' Error Rates in Screening for Cervical Cancer SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID PROGRAM; NUMBERS; SMEARS; BREAST AB Context.-Medical screening tasks are often difficult, visual searches with low target prevalence (low rates of disease). Under laboratory conditions, when targets are rare, nonexpert searchers show decreases in false-positive results and increases in false-negative results compared with results when targets are common. This prevalence effect is not due to vigilance failures or target unfamiliarity. Objective.-To determine whether prevalence effects could be a source of elevated false-negative errors in medical experts. Design.-We studied 2 groups of cytologists involved in cervical cancer screening (Boston, Massachusetts, and South Wales, UK). Cytologists evaluated photomicrographs of cells at low (2% or 5%) or higher (50%) rates of abnormality prevalence. Two versions of the experiment were performed. The Boston, Massachusetts, group made decisions of normal or abnormal findings using a 4-point rating scale. Additionally, the group from South Wales localized apparent abnormalities. Results.-In both groups, there is evidence for prevalence effects. False-negative errors were 17% (higher prevalence), rising to 30% (low prevalence) in the Boston, Massachusetts, group. The error rate was 27% (higher prevalence), rising to 42% (low prevalence) in the South Wales group. (Comparisons between the 2 groups are not meaningful because the stimulus sets were different.) Conclusions.-These results provide the first evidence, to our knowledge, that experts are not immune to the effects of prevalence even with stimuli from their domain of expertise. Prevalence is a factor to consider in screening for disease by human observers and has significant implications for cytology-based cervical cancer screening in the post-human papillomavirus vaccine era, when prevalence rates of high-grade lesions in the population are expected to decline. (Arch Pathol Lab Med. 2011; 135:1557-1560; doi:10.5858/arpa.2010-0739-OA) C1 [Evans, Karla K.; Wolfe, Jeremy M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Ophthalmol,Visual Attent Lab, Cambridge, MA 02139 USA. [Tambouret, Rosemary H.; Wilbur, David C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Evered, Andrew] Univ Wales Coll Cardiff, Inst Cardiff, Dept Pathol, Cardiff CF1 3NS, S Glam, Wales. RP Evans, KK (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Ophthalmol,Visual Attent Lab, 64 Sidney St,Ste 170, Cambridge, MA 02139 USA. EM kevans@search.bwh.harvard.edu RI Wolfe, Jeremy/C-1621-2012; Wolfe, Jeremy/A-9248-2016 OI Wolfe, Jeremy/0000-0002-6475-1984; Wolfe, Jeremy/0000-0002-6475-1984 FU NIH [EY017001]; ONR MURI [N000141010278]; NIH/NEI [1F32EY019819-01]; Research Capacity Building Collaboration Wales; British Society for Clinical Cytology; National Association of Cytologists FX This work was supported by NIH EY017001 and ONR MURI N000141010278 to J.M.W.; K. K. E. was supported by NIH/NEI 1F32EY019819-01; and A. E. was supported by Research Capacity Building Collaboration Wales and British Society for Clinical Cytology and the National Association of Cytologists. NR 13 TC 35 Z9 35 U1 1 U2 8 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD DEC PY 2011 VL 135 IS 12 BP 1557 EP 1560 DI 10.5858/arpa.2010-0739-OA PG 4 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 860HF UT WOS:000297938700012 PM 22129183 ER PT J AU Tse, SM Kinane, TB Mark, EJ Haver, KE AF Tse, Sze Man Kinane, T. Bernard Mark, Eugene J. Haver, Kenan E. TI An 11-Year-Old Boy With Respiratory Failure and Massive Pleural Fluid Drainage SO CHEST LA English DT Article ID THORACIC LYMPHANGIOMATOSIS; CHYLOTHORAX; CHILD; WALL C1 [Tse, Sze Man; Kinane, T. Bernard; Mark, Eugene J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Haver, Kenan E.] Childrens Hosp, Boston, MA 02115 USA. RP Tse, SM (reprint author), Massachusetts Gen Hosp, 5th Floor,175 Cambridge St, Boston, MA 02114 USA. EM stse@partners.org NR 9 TC 0 Z9 0 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD DEC PY 2011 VL 140 IS 6 BP 1659 EP 1661 DI 10.1378/chest.11-1097 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 860RX UT WOS:000297966500040 PM 22147826 ER PT J AU McGrath, MM Isakova, T Rennke, HG Mottoa, AM Laliberte, KA Niles, JL AF McGrath, Martina M. Isakova, Tamara Rennke, Helmut G. Mottoa, Ann M. Laliberte, Karen A. Niles, John L. TI Contaminated Cocaine and Antineutrophil Cytoplasmic Antibody-Associated Disease SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID MIDLINE DESTRUCTIVE LESIONS; LEVAMISOLE-TAINTED COCAINE; CEREBRAL VASCULITIS; CIRCULATING AUTOANTIBODIES; BILATERAL NECROSIS; AGRANULOCYTOSIS; NEUTROPENIA; PREVALENCE; ADULTERANT; ABUSE AB Background and objectives Approximately 70% of illicit cocaine consumed in the United States is contaminated with levamisole. Most commonly used as a veterinary antihelminthic agent, levamisole is a known immunomodulating agent. Prolonged use in humans has been associated with cutaneous vasculitis and agranulocytosis. We describe the development of a systemic autoimmune disease associated with antineutrophil cytoplasmic antibodies (ANCA) in cocaine users. This complication appears to be linked to combined cocaine and levamisole exposure. Design, setting, participants, & measurements Cases were identified between March 2009 and November 2010 at Massachusetts General Hospital's ANCA laboratory. Cocaine exposure was identified from patient history in all cases. Medical records were reviewed for clinical presentation and for laboratory and diagnostic evaluation. Results Thirty cases of ANCA positivity associated with cocaine ingestion were identified. All had antimyeloperoxidase antibodies and 50% also had antiproteinase 3 antibodies. Complete clinical and laboratory data were available for 18 patients. Arthralgia (83%) and skin lesions (61%) were the most frequent complaints at presentation. Seventy-two percent of patients reported constitutional symptoms, including fever, night sweats, weight loss, or malaise. Four patients had biopsy-proven vasculitis. Two cases of acute kidney injury and three cases of pulmonary hemorrhage occurred. From the entire cohort of 30, two cases were identified during the first 3 months of our study period and nine cases presented during the last 3 months. Conclusions We describe an association between the ingestion of levamisole-contaminated cocaine and ANCA-associated systemic autoimmune disease. Our data suggest that this is a potentially life-threatening complication of cocaine use. Clin J Am Soc Nephrol 6: 2799-2805, 2011. doi: 10.2215/CJN.03440411 C1 [Niles, John L.] Massachusetts Gen Hosp, Dept Med, Renal Unit, Boston, MA 02114 USA. [Mottoa, Ann M.; Niles, John L.] Massachusetts Gen Hosp, ANCA Lab, Boston, MA 02114 USA. [McGrath, Martina M.] Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. [Isakova, Tamara] Univ Miami, Miller Sch Med, Div Nephrol & Hypertens, Dept Med, Miami, FL 33136 USA. [Rennke, Helmut G.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Niles, JL (reprint author), Massachusetts Gen Hosp, Dept Med, Renal Unit, Boston, MA 02114 USA. EM jlniles@partners.org NR 47 TC 34 Z9 35 U1 0 U2 1 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD DEC PY 2011 VL 6 IS 12 BP 2799 EP 2805 DI 10.2215/CJN.03440411 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 860LD UT WOS:000297948900012 PM 21980179 ER PT J AU Capelli, J Kantarci, A Haffajee, A Teles, RP Fidel, R Figueredo, CM AF Capelli Junior, Jonas Kantarci, Alpdogan Haffajee, Anne Teles, Ricardo Palmier Fidel, Rivail, Jr. Figueredo, Carlos Marcelo TI Matrix metalloproteinases and chemokines in the gingival crevicular fluid during orthodontic tooth movement SO EUROPEAN JOURNAL OF ORTHODONTICS LA English DT Article ID NECROSIS-FACTOR-ALPHA; PERIODONTAL-LIGAMENT; TISSUE INHIBITORS; IN-VITRO; EXPRESSION; COLLAGEN; VIVO; DOGS; RATS AB Matrix metalloproteinases (MMPs) and monocyte chemoattractants are key modulators of the biological mechanisms triggered in the periodontium by mechanical forces. The gingival crevicular fluid (GCF) provides a non-invasive method to assess longitudinally the release of inflammatory mediators during orthodontic tooth movement. The goal of this study was to examine the GCF levels of MMP3, MMP-9, and MMP-13 and of the chemokines macrophage inflammatory protein (MIP)-1 beta, monocyte chemoattractant protein (MCP)-1, and regulated on activation normal T cells expressed and secreted (RANTES) at different time points during orthodontic tooth movement. Fourteen subjects (three males and 11 females, 18.8 +/- 4.8 years of age; range from 12 to 28 years) had their maxillary canines retracted. Thirty-second GCF samples were collected from the tension and pressure sides 7 days prior to the activation of the orthodontic appliance, on the day of activation, and after 1 and 24 hours, and 14, 21, and 80 days of constant force application. The volume of GCF was measured and samples analysed using a multiplexed bead immunoassay for the content of the six target molecules. Differences in the mean GFC volumes and mean level for each analyte over time were assessed using the Friedman test, and differences between the tension and pressure sides at each time point with the Mann-Whitney test. The mean levels of the three MMPs changed significantly over time but only at the compression side (P < 0.05, Friedman test). The GCF levels of the three chemokines were not affected by the application of mechanical stress. The levels of MMPs in GCF at the pressure side are modulated by the application of orthodontic force. C1 [Capelli Junior, Jonas; Fidel, Rivail, Jr.; Figueredo, Carlos Marcelo] Univ Estado Rio De Janeiro, Dept Orthodont, BR-20551030 Rio De Janeiro, Brazil. [Capelli Junior, Jonas; Fidel, Rivail, Jr.; Figueredo, Carlos Marcelo] Univ Estado Rio De Janeiro, Dept Periodontol, BR-20551030 Rio De Janeiro, Brazil. [Kantarci, Alpdogan] Boston Univ, Goldman Sch Dent Med, Dept Periodontol & Oral Biol, Boston, MA USA. [Haffajee, Anne; Teles, Ricardo Palmier] Boston Univ, Forsyth Inst, Dept Periodontol, Boston, MA USA. RP Capelli, J (reprint author), Univ Estado Rio De Janeiro, Dept Orthodont, Rua 28 Setembro,157 Vila Isabel, BR-20551030 Rio De Janeiro, Brazil. EM jonascapelli@gmail.com RI Figueredo, Carlos Marcelo/H-3356-2013 OI Figueredo, Carlos Marcelo/0000-0003-0222-9231 NR 25 TC 10 Z9 12 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0141-5387 J9 EUR J ORTHODONT JI Eur. J. Orthodont. PD DEC PY 2011 VL 33 IS 6 BP 705 EP 711 DI 10.1093/ejo/cjq148 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 851ZM UT WOS:000297311400018 PM 21389074 ER PT J AU Sherman, KE Thomas, DL Chung, RT AF Sherman, Kenneth E. Thomas, David L. Chung, Raymond T. TI Human Immunodeficiency Virus and Liver Disease Forum 2010: Conference Proceedings SO HEPATOLOGY LA English DT Article ID HEPATITIS-C VIRUS; HIV-INFECTED PATIENTS; NONCIRRHOTIC PORTAL-HYPERTENSION; ANTIRETROVIRAL THERAPY; FIBROSIS PROGRESSION; COINFECTED PATIENTS; HEPATOCELLULAR-CARCINOMA; MICROBIAL TRANSLOCATION; GENETIC-VARIATION; HEPATOCYTES AB Liver disease continues to represent a critical mediator of morbidity and mortality in those with human immunodeficiency virus (HIV) infection. The frequent presence and overlap of concomitant injurious processes, including hepatitis C virus and hepatitis B virus infections, hepatoxicity associated with antiretroviral therapeutic agents, alcohol, and other toxins, in the setting of immunosuppression lead to rapid fibrotic progression and early development of end-stage liver disease. This conference summary describes the proceedings of a state-of-the-art gathering of international experts designed to highlight the status of current research in epidemiology, natural history, pathogenesis, and treatment of HIV and liver disease. (HEPATOLOGY 2011; 54: 2245-2253) C1 [Sherman, Kenneth E.] Univ Cincinnati, Coll Med, Div Digest Dis, Cincinnati, OH 45267 USA. [Thomas, David L.] Johns Hopkins Univ, Med Ctr, Div Infect Dis, Baltimore, MD 21218 USA. [Chung, Raymond T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chung, Raymond T.] Harvard Univ, Sch Med, Boston, MA USA. RP Sherman, KE (reprint author), Univ Cincinnati, Coll Med, Div Digest Dis, 231 Albert Sabin Way, Cincinnati, OH 45267 USA. EM Kenneth.sherman@uc.edu FU Genentech, Inc.; Gilead Sciences, Inc.; Merck Co.; Merck; Vertex; SciClone; Roche; Gilead; Boehringer Ingelheim; Siemens; Anadys; National Institute of Allergy and Infectious Diseases (NIAID) [R13 AI 071925]; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National Institute on Alcohol Abuse and Alcoholism (NIAAA) FX Potential conflict of interest: Unrestricted educational grants from pharmaceutical sponsors to support this meeting were provided by Genentech, Inc., Gilead Sciences, Inc., Merck & Co., Three Rivers Pharmaceuticals, LLC, and Vertex Pharmaceuticals, Inc. Continuing Medical Education credit and content oversight were provided by Medical Education Resources, Inc. Dr. Sherman advises and received grants from Merck, Vertex, SciClone, and Roche. He advises Bristol-Myers Squibb, GlaxoSmithKline, Baxter, and Regulus. He received grants from Gilead, Boehringer Ingelheim, Siemens, and Anadys. He holds other interests with Pfizer, Tibotec, and Medpace.; The project described was supported by Award Number R13 AI 071925 from the National Institute of Allergy and Infectious Diseases (NIAID) and was cofunded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the National Institute on Alcohol Abuse and Alcoholism (NIAAA). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIAID, NIDDK, NIAAA, or the National Institutes of Health. NR 52 TC 7 Z9 9 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD DEC PY 2011 VL 54 IS 6 BP 2245 EP 2253 DI 10.1002/hep.24651 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 860VB UT WOS:000297974900036 PM 21898501 ER PT J AU Nair, G Pardue, MT Kim, M Duong, TQ AF Nair, Govind Pardue, Machelle T. Kim, Moon Duong, Timothy Q. TI Manganese-Enhanced MRI Reveals Multiple Cellular and Vascular Layers in Normal and Degenerated Retinas SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE magnetic resonance imaging; MEMRI; retinal degeneration; high resolution imaging; MRI microscopy; RCS ID OPTICAL COHERENCE TOMOGRAPHY; VISUAL PATHWAY; FUNCTIONAL MRI; RAT RETINA; RCS RAT; BRAIN; RESOLUTION; CLEARANCE; TRANSPORT; CONTRAST AB Purpose: To use manganese-enhanced magnetic resonance imaging (MEMRI) at 25 x 25 x 800 mu m(3) to image different retinal and vascular layers in the rat retinas. Materials and Methods: Manganese-chloride was injected intraocularly in normal (n = 5) and Royal College of Surgeons (RCS, an model of photoreceptor degeneration) (n = 5) rats at postnatal day 90. MEMRI at 4.7 T was performed 24 hours later. MRI was repeated following intravenous Gd-DTPA in the same animals to highlight the vasculatures. Layer assignment and thickness were compared to histology. Results: MEMRI 24 hours after intravitreal manganese-chloride injection revealed seven bands of alternating hyper- and hypointensities, corresponding histologically to the ganglion cell layer, inner plexiform layer, inner nuclear layer, outer plexiform layer, outer nuclear layer, photoreceptor-segment layer, and choroidal vascular layer. Intravenous Gd-DTPA-which does not cross the blood-retinal barrier and the retinal pigment epithelium-further enhanced the two layers bounding the retina, corresponding to the retinal and choroidal vascular layers, but not the avascular outer nuclear layer and the photoreceptor-segment layer. MEMRI of the RCS retinas revealed the loss of the outer plexiform layer, outer nuclear layer, and photoreceptor-segment layer. Histological analysis corroborated the MRI laminar assignments and thicknesses. Conclusion: Lamina-specific retinal structures neurodegenerative changes to structure in retinal diseases can be detected using MEMRI. C1 [Duong, Timothy Q.] UTHSCSA, Res Imaging Inst, Dept Ophthalmol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] UTHSCSA, Res Imaging Inst, Dept Physiol, San Antonio, TX 78229 USA. [Nair, Govind] Univ Massachusetts, Sch Med, Grad Sch Biomed Sci, Worcester, MA USA. [Nair, Govind] Worcester Polytech Inst, Worcester, MA 01609 USA. [Nair, Govind] Emory Univ, Yerkes Imaging Ctr, Neurosci Div, Atlanta, GA 30322 USA. [Pardue, Machelle T.; Kim, Moon] Atlanta Vet Affairs Med Ctr, Atlanta, GA USA. [Pardue, Machelle T.] Emory Univ, Dept Ophthalmol, Atlanta, GA 30322 USA. [Duong, Timothy Q.] S Texas Vet Hlth Care Syst, Dept Vet Affairs, San Antonio, TX USA. RP Duong, TQ (reprint author), UTHSCSA, Res Imaging Inst, Dept Ophthalmol, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA. EM duongt@uthscsa.edu RI Duong, Timothy/B-8525-2008 FU NEI NIH HHS [R01 EY018855, R01 EY014211] NR 33 TC 12 Z9 12 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD DEC PY 2011 VL 34 IS 6 BP 1422 EP 1429 DI 10.1002/jmri.22719 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 851VG UT WOS:000297298800020 PM 21964629 ER PT J AU Winer, JH Raut, CP AF Winer, Joshua H. Raut, Chandrajit P. TI Management of Recurrent Gastrointestinal Stromal Tumors SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Review DE recurrent gastrointestinal stromal tumor; imatinib mesylate; sunitinib malate; surgery; neoadjuvant therapy; blood level testing ID PHASE-II TRIAL; IMATINIB MESYLATE; SURGICAL RESECTION; KINASE INHIBITOR; RESIDUAL DISEASE; TYROSINE-KINASE; DOSE IMATINIB; GIST; THERAPY; SURGERY AB Recurrence after resection of primary gastrointestinal stromal tumor (GIST) is an unfortunately all-too-common phenomenon. The principal treatment for recurrent GIST is the first-line tyrosine kinase inhibitor (TKI) imatinib mesylate. Those who progress on, or are intolerant of imatinib, are treated with second-line TKI sunitinib malate. Cytoreductive surgery may be considered as an "adjuvant" therapy for patients with disease stabilized on imatinib, and, on an individual basis, sunitinib. J. Surg. Oncol. 2011;104:915-920. (C) 2011 Wiley Periodicals, Inc. C1 [Winer, Joshua H.; Raut, Chandrajit P.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Winer, Joshua H.; Raut, Chandrajit P.] Harvard Univ, Sch Med, Boston, MA USA. [Raut, Chandrajit P.] Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. RP Raut, CP (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. EM craut@partners.org NR 45 TC 5 Z9 6 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-4790 EI 1096-9098 J9 J SURG ONCOL JI J. Surg. Oncol. PD DEC PY 2011 VL 104 IS 8 SI SI BP 915 EP 920 DI 10.1002/jso.21890 PG 6 WC Oncology; Surgery SC Oncology; Surgery GA 860FX UT WOS:000297935300010 PM 21337345 ER PT J AU Pappo, AS Janeway, K Laquaglia, M Kim, SY AF Pappo, Alberto S. Janeway, Katherine Laquaglia, Michael Kim, Su Young TI Special Considerations in Pediatric Gastrointestinal Tumors SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Review DE pediatric; GIST; IGF1 ID FINE-NEEDLE-ASPIRATION; GASTRIC STROMAL TUMORS; V600E BRAF MUTATIONS; CARNEY TRIAD; WILD-TYPE; IMATINIB; MANAGEMENT; DIAGNOSIS AB Pediatric gastrointestinal tumors are rare in children but are being increasingly recognized. These tumors have distinct biologic and clinical feature that are different from those observed in adults. This review highlights the biological and clinical characteristics of pediatric GIST and provides diagnostic and therapeutic guidelines for the management these unique and challenging group of tumors. J. Surg. Oncol. 2011;104:928-932. (C) 2011 Wiley Periodicals, Inc. C1 [Pappo, Alberto S.] St Jude Childrens Hosp, Memphis, TN 38105 USA. [Janeway, Katherine] Dana Farber Canc Inst, Div Hematol Oncol, Boston, MA 02115 USA. [Laquaglia, Michael] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Kim, Su Young] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Pappo, AS (reprint author), St Jude Childrens Hosp, 262 Danny Thomas Pl, Memphis, TN 38105 USA. EM alberto.pappo@stjude.org FU ALSAC (American Lebanese Syrian Associated Charities) FX Grant sponsor: ALSAC (American Lebanese Syrian Associated Charities). NR 25 TC 13 Z9 15 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-4790 J9 J SURG ONCOL JI J. Surg. Oncol. PD DEC PY 2011 VL 104 IS 8 SI SI BP 928 EP 932 DI 10.1002/jso.21868 PG 5 WC Oncology; Surgery SC Oncology; Surgery GA 860FX UT WOS:000297935300012 PM 22069178 ER PT J AU Lum, G AF Lum, Gifford TI Falsely Elevated Parathyroid Hormone-Related Protein (PTH-RP) in a Patient With Hypercalcemia and Renal Failure SO LABMEDICINE LA English DT Article DE PTH-RP; hypercalcemia; false elevation; renal faliure; malignancy; C-terminal PTH-RP; N-terminal PTH-RP ID CANCER AB Humoral hypercalcemia of malignancy (HHM) is the cause of hypercalcemia in the majority of patients with hypercalcemia and cancer. Parathyroid hormone-related protein (PTH-RP) has been identified as the circulating factor that mediates HHM. An N-terminal and a C-terminal PTH-RP are clinically useful assays for screening patients for HHM, and both assays are elevated in such patients. C-terminal PTH-RP depends on glomerular filtration and accumulates in patients with renal failure without malignancy, resulting in falsely-elevated levels, whereas N-terminal PTH-RP is low or undetectable in such patients. We present a case of a patient with renal failure and hypercalcemia who did not have an obvious malignancy and who presented with an elevated C-terminal PTH-RP level and a normal N-terminal PTH-RP. In patients with renal failure and hypercalcemia without cancer, C-terminal PTH-RP may be falsely elevated, especially if the eGFR is <20 mL/minute, and in such patients, N-terminal PTH-RP, because it is less affected by renal function, is the preferred test. C1 VA Boston Healthcare Syst, Pathol & Lab Med Serv, Boston, MA USA. RP Lum, G (reprint author), VA Boston Healthcare Syst, Pathol & Lab Med Serv, Boston, MA USA. EM gifford.lum@med.va.gov NR 10 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0007-5027 J9 LABMEDICINE JI Labmedicine PD DEC PY 2011 VL 42 IS 12 BP 726 EP 728 DI 10.1309/LM23TD4IUTAJBJMG PG 3 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 853PN UT WOS:000297438300004 ER PT J AU Growdon, WB AF Growdon, Whitfield B. TI Age and postmenopausal bleeding risk factors for malignant changes in endometrial polyps SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Editorial Material ID CANCER; METAANALYSIS; WOMEN C1 Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Growdon, WB (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. NR 13 TC 2 Z9 4 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD DEC PY 2011 VL 18 IS 12 BP 1267 EP 1267 DI 10.1097/gme.0b013e3182357995 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 859ZO UT WOS:000297914800003 PM 22089182 ER PT J AU Weinstein, MM AF Weinstein, Milena M. TI Urine leakage: menopause or normal aging? SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Editorial Material ID ESTROGEN; INCONTINENCE; TRACT; RECEPTORS; SYMPTOMS; WOMEN C1 Massachusetts Gen Hosp, Vincent Obstet & Gynecol Serv, Boston, MA 02114 USA. RP Weinstein, MM (reprint author), Massachusetts Gen Hosp, Vincent Obstet & Gynecol Serv, Boston, MA 02114 USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD DEC PY 2011 VL 18 IS 12 BP 1268 EP 1269 DI 10.1097/gme.0b013e318238e157 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 859ZO UT WOS:000297914800004 PM 22138571 ER PT J AU Tilly, JL AF Tilly, Jonathan L. TI Ovarian Aging: Can Science Turn Back the Clock? SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Meeting Abstract CT 22nd Annual Meeting of the North-American-Menopause-Society (NAMS) CY SEP 21-24, 2011 CL Washington, DC SP N Amer Menopause Soc (NAMS) C1 [Tilly, Jonathan L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD DEC PY 2011 VL 18 IS 12 BP 1337 EP 1338 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 859ZO UT WOS:000297914800021 ER PT J AU Joffe, H AF Joffe, Hadine TI Menopause, Depression & Hormones: What's the Connection? SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Meeting Abstract CT 22nd Annual Meeting of the North-American-Menopause-Society (NAMS) CY SEP 21-24, 2011 CL Washington, DC SP N Amer Menopause Soc (NAMS) C1 [Joffe, Hadine] Massachusetts Gen Hosp, Div Sleep Med, Dept Psychiat, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD DEC PY 2011 VL 18 IS 12 BP 1338 EP 1338 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 859ZO UT WOS:000297914800023 ER PT J AU Joffe, H Guthrie, KA Cohen, L Carpenter, J Larson, J LaCroix, A Freeman, EW AF Joffe, Hadine Guthrie, Katherine A. Cohen, Lee Carpenter, Janet Larson, Joseph LaCroix, Andrea Freeman, Ellen W. TI Hot Flashes Recur Rapidly After Discontinuation of the SSRI Escitalopram: Results from the MsFLASH Research Network SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Meeting Abstract CT 22nd Annual Meeting of the North-American-Menopause-Society (NAMS) CY SEP 21-24, 2011 CL Washington, DC SP N Amer Menopause Soc (NAMS) C1 [Joffe, Hadine; Cohen, Lee] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Guthrie, Katherine A.; Larson, Joseph; LaCroix, Andrea] Univ Washington, Fred Hutchinson Canc Res Ctr, Sch Publ Hlth, Seattle, WA 98195 USA. [Carpenter, Janet] Indiana Univ, Sch Nursing, Indianapolis, IN 46204 USA. [Freeman, Ellen W.] Univ Penn, Dept Obstet Gynecol, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD DEC PY 2011 VL 18 IS 12 BP 1347 EP 1347 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 859ZO UT WOS:000297914800056 ER PT J AU Gibson, C Joffe, H Bromberger, J Thurston, RC Lewis, T Khalil, N Matthews, K AF Gibson, Carolyn Joffe, Hadine Bromberger, Joyce Thurston, Rebecca C. Lewis, Tene Khalil, Nails Matthews, Karen TI Anxiety and Depressive Symptoms Following Natural Menopause, Hysterectomy with Ovarian Conservation, and Hysterectomy with Bilateral Oophorectomy SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Meeting Abstract CT 22nd Annual Meeting of the North-American-Menopause-Society (NAMS) CY SEP 21-24, 2011 CL Washington, DC SP N Amer Menopause Soc (NAMS) C1 [Gibson, Carolyn; Bromberger, Joyce; Thurston, Rebecca C.; Matthews, Karen] Univ Pittsburgh, Pittsburgh, PA USA. [Joffe, Hadine] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Lewis, Tene] Yale Univ, Sch Med, New Haven, CT USA. [Khalil, Nails] Wright State Univ, Dayton, OH 45435 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD DEC PY 2011 VL 18 IS 12 BP 1359 EP 1360 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 859ZO UT WOS:000297914800106 ER PT J AU Looby, S Joffe, H Rope, AM Shifren, JL Grinspoon, S AF Looby, Sara Joffe, Hadine Rope, Alison M. Shifren, Jan L. Grinspoon, Steven TI Assessment of Menopause-Related Symptoms among Perimenopausal Women with HIV SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Meeting Abstract CT 22nd Annual Meeting of the North-American-Menopause-Society (NAMS) CY SEP 21-24, 2011 CL Washington, DC SP N Amer Menopause Soc (NAMS) C1 [Looby, Sara; Rope, Alison M.; Grinspoon, Steven] Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. [Looby, Sara; Rope, Alison M.; Grinspoon, Steven] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Looby, Sara; Joffe, Hadine; Rope, Alison M.; Shifren, Jan L.; Grinspoon, Steven] Harvard Univ, Sch Med, Boston, MA USA. [Joffe, Hadine] Massachusetts Gen Hosp, Ctr Womens Mental Hlth, Boston, MA 02114 USA. [Shifren, Jan L.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD DEC PY 2011 VL 18 IS 12 BP 1363 EP 1363 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 859ZO UT WOS:000297914800119 ER PT J AU Marsh, W Bromberger, J Crawford, S Randolph, J Joffe, H Kravitz, H Soares, CN AF Marsh, Wendy Bromberger, Joyce Crawford, Sybil Randolph, John Joffe, Hadine Kravitz, Howard Soares, Claudio N. TI Lifetime Estradiol Exposure and Risk of Depression during the Menopausal Transition: The Study of Women's Health Across the Nation SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Meeting Abstract CT 22nd Annual Meeting of the North-American-Menopause-Society (NAMS) CY SEP 21-24, 2011 CL Washington, DC SP N Amer Menopause Soc (NAMS) C1 [Marsh, Wendy] Univ Massachusetts, Dept Psychiat, Worcester, MA 01605 USA. [Bromberger, Joyce] Univ Pittsburgh, Pittsburgh, PA USA. [Randolph, John] Univ Michigan, Ann Arbor, MI 48109 USA. [Joffe, Hadine] Massachusetts Gen Hosp, Ctr Womens Mental Hlth, Boston, MA 02114 USA. [Kravitz, Howard] Rush Univ, Chicago, IL 60612 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD DEC PY 2011 VL 18 IS 12 BP 1364 EP 1364 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 859ZO UT WOS:000297914800121 ER PT J AU Liang, HY Ward, WF Jang, YC Bhattacharya, A Bokov, AF Li, Y Jernigan, A Richardson, A Van Remmen, H AF Liang, Huiyun Ward, Walter F. Jang, Youngmok C. Bhattacharya, Arunabh Bokov, Alex F. Li, Yan Jernigan, Amanda Richardson, Arlan Van Remmen, Holly TI PGC-1 alpha PROTECTS NEURONS AND ALTERS DISEASE PROGRESSION IN AN AMYOTROPHIC LATERAL SCLEROSIS MOUSE MODEL SO MUSCLE & NERVE LA English DT Article DE amyotrophic lateral sclerosis; excitatory amino acid transporter protein 2 (EAAT2); motor neuron; neuromuscular junction; PGC-1 alpha transgenic mice ID CU,ZN SUPEROXIDE-DISMUTASE; OXYGEN SPECIES PRODUCTION; ACETYLCHOLINE-RECEPTOR; MITOCHONDRIAL BIOGENESIS; CALORIC RESTRICTION; SKELETAL-MUSCLE; TRANSGENIC MICE; TRANSCRIPTIONAL COACTIVATOR; NEUROMUSCULAR-JUNCTION; RADICAL GENERATION AB Introduction: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease. We sought to determine whether peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1 alpha) would have a beneficial effect on this disease. Methods: PGC-1 alpha transgenic mice were crossed with SOD1 mutant G93A DL mice. Results: We observed a moderate but non-significant increase in average lifespan in PGC-1 alpha/G93A DL mice, as compared with G93A DL mice (292 +/- 3 days vs. 274 +/- 7 days). Although the onset of ALS was not altered, progression of the disease was significantly slower (similar to 34% increase in duration) in the PGC-1 alpha/G93A DL mice. These mice also exhibited markedly improved performance on the rotarod test, and the improved motor activity was associated with a decreased loss of motor neurons and less degeneration of neuromuscular junctions. Conclusion: A sustained level of excitatory amino acid transporter protein 2 (EAAT2) in astrocytes of the PGC-1 alpha/G93A DL mice may contribute to neuronal protection. Muscle Nerve 44: 947-956, 2011 C1 [Liang, Huiyun; Ward, Walter F.; Jang, Youngmok C.; Bhattacharya, Arunabh; Bokov, Alex F.; Li, Yan; Jernigan, Amanda; Richardson, Arlan; Van Remmen, Holly] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Ward, Walter F.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Bokov, Alex F.] Univ Texas Hlth Sci Ctr San Antonio, Dept Biostat & Epidemiol, San Antonio, TX 78229 USA. [Bhattacharya, Arunabh; Richardson, Arlan; Van Remmen, Holly] Univ Texas San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Richardson, Arlan; Van Remmen, Holly] S Texas Vet Hlth Care Syst, GRECC, San Antonio, TX USA. RP Van Remmen, H (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. EM vanremmen@uthscsa.edu FU Muscular Dystrophy Association [MDA 69814, 10047]; VA Merit grant FX The authors thank Dr. Florian Muller for his helpful input for this study. This work was supported by Muscular Dystrophy Association grants MDA 69814 (to H.L.) and 10047 (to H.v.R.), and a VA Merit grant (to H.v.R.). NR 59 TC 39 Z9 39 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0148-639X J9 MUSCLE NERVE JI Muscle Nerve PD DEC PY 2011 VL 44 IS 6 BP 947 EP 956 DI 10.1002/mus.22217 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 860HG UT WOS:000297938800017 PM 22102466 ER PT J AU Haiman, CA Chen, GK Vachon, CM Canzian, F Dunning, A Millikan, RC Wang, XS Ademuyiwa, F Ahmed, S Ambrosone, CB Baglietto, L Balleine, R Bandera, EV Beckmann, MW Berg, CD Bernstein, L Blomqvist, C Blot, WJ Brauch, H Buring, JE Carey, LA Carpenter, JE Chang-Claude, J Chanock, SJ Chasman, DI Clarke, CL Cox, A Cross, SS Deming, SL Diasio, RB Dimopoulos, AM Driver, WR Dunnebier, T Durcan, L Eccles, D Edlund, CK Ekici, AB Fasching, PA Feigelson, HS Flesch-Janys, D Fostira, F Forsti, A Fountzilas, G Gerty, SM Giles, GG Godwin, AK Goodfellow, P Graham, N Greco, D Hamann, U Hankinson, SE Hartmann, A Hein, R Heinz, J Holbrook, A Hoover, RN Hu, JJ Hunter, DJ Ingles, SA Irwanto, A Ivanovich, J John, EM Johnson, N Jukkola-Vuorinen, A Kaaks, R Ko, YD Kolonel, LN Konstantopoulou, I Kosma, VM Kulkarni, S Lambrechts, D Lee, AM Le Marchand, L Lesnick, T Liu, JJ Lindstrom, S Mannermaa, A Margolin, S Martin, NG Miron, P Montgomery, GW Nevanlinna, H Nickels, S Nyante, S Olswold, C Palmer, J Pathak, H Pectasides, D Perou, CM Peto, J Pharoah, PDP Pooler, LC Press, MF Pylkas, K Rebbeck, TR Rodriguez-Gil, JL Rosenberg, L Ross, E Rudiger, T Silva, ID Sawyer, E Schmidt, MK Schulz-Wendtland, R Schumacher, F Severi, G Sheng, X Signorello, LB Sinn, HP Stevens, KN Southey, MC Tapper, WJ Tomlinson, I Hogervorst, FBL Wauters, E Weaver, J Wildiers, H Winqvist, R Van Den Berg, D Wan, P Xia, LY Yannoukakos, D Zheng, W Ziegler, RG Siddiq, A Slager, SL Stram, DO Easton, D Kraft, P Henderson, BE Couch, FJ AF Haiman, Christopher A. Chen, Gary K. Vachon, Celine M. Canzian, Federico Dunning, Alison Millikan, Robert C. Wang, Xianshu Ademuyiwa, Foluso Ahmed, Shahana Ambrosone, Christine B. Baglietto, Laura Balleine, Rosemary Bandera, Elisa V. Beckmann, Matthias W. Berg, Christine D. Bernstein, Leslie Blomqvist, Carl Blot, William J. Brauch, Hiltrud Buring, Julie E. Carey, Lisa A. Carpenter, Jane E. Chang-Claude, Jenny Chanock, Stephen J. Chasman, Daniel I. Clarke, Christine L. Cox, Angela Cross, Simon S. Deming, Sandra L. Diasio, Robert B. Dimopoulos, Athanasios M. Driver, W. Ryan Duennebier, Thomas Durcan, Lorraine Eccles, Diana Edlund, Christopher K. Ekici, Arif B. Fasching, Peter A. Feigelson, Heather S. Flesch-Janys, Dieter Fostira, Florentia Foersti, Asta Fountzilas, George Gerty, Susan M. Giles, Graham G. Godwin, Andrew K. Goodfellow, Paul Graham, Nikki Greco, Dario Hamann, Ute Hankinson, Susan E. Hartmann, Arndt Hein, Rebecca Heinz, Judith Holbrook, Andrea Hoover, Robert N. Hu, Jennifer J. Hunter, David J. Ingles, Sue A. Irwanto, Astrid Ivanovich, Jennifer John, Esther M. Johnson, Nicola Jukkola-Vuorinen, Arja Kaaks, Rudolf Ko, Yon-Dschun Kolonel, Laurence N. Konstantopoulou, Irene Kosma, Veli-Matti Kulkarni, Swati Lambrechts, Diether Lee, Adam M. Le Marchand, Loic Lesnick, Timothy Liu, Jianjun Lindstrom, Sara Mannermaa, Arto Margolin, Sara Martin, Nicholas G. Miron, Penelope Montgomery, Grant W. Nevanlinna, Heli Nickels, Stephan Nyante, Sarah Olswold, Curtis Palmer, Julie Pathak, Harsh Pectasides, Dimitrios Perou, Charles M. Peto, Julian Pharoah, Paul D. P. Pooler, Loreall C. Press, Michael F. Pylkas, Katri Rebbeck, Timothy R. Rodriguez-Gil, Jorge L. Rosenberg, Lynn Ross, Eric Ruediger, Thomas Silva, Isabel dos Santos Sawyer, Elinor Schmidt, Marjanka K. Schulz-Wendtland, Ruediger Schumacher, Fredrick Severi, Gianluca Sheng, Xin Signorello, Lisa B. Sinn, Hans-Peter Stevens, Kristen N. Southey, Melissa C. Tapper, William J. Tomlinson, Ian Hogervorst, Frans B. L. Wauters, Els Weaver, JoEllen Wildiers, Hans Winqvist, Robert Van Den Berg, David Wan, Peggy Xia, Lucy Y. Yannoukakos, Drakoulis Zheng, Wei Ziegler, Regina G. Siddiq, Afshan Slager, Susan L. Stram, Daniel O. Easton, Douglas Kraft, Peter Henderson, Brian E. Couch, Fergus J. CA Gene Environm Interaction Breast C TI A common variant at the TERT-CLPTM1L locus is associated with estrogen receptor-negative breast cancer SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; PROSTATE-CANCER; IDENTIFIES 5; RISK AB Estrogen receptor (ER)-negative breast cancer shows a higher incidence in women of African ancestry compared to women of European ancestry. In search of common risk alleles for ER-negative breast cancer, we combined genome-wide association study (GWAS) data from women of African ancestry (1,004 ER-negative cases and 2,745 controls) and European ancestry (1,718 ER-negative cases and 3,670 controls), with replication testing conducted in an additional 2,292 ER-negative cases and 16,901 controls of European ancestry. We identified a common risk variant for ER-negative breast cancer at the TERT-CLPTM1L locus on chromosome 5p15 (rs10069690: per-allele odds ratio (OR) = 1.18 per allele, P = 1.0 x 10(-10)). The variant was also significantly associated with triple-negative (ER-negative, progesterone receptor (PR)-negative and human epidermal growth factor-2 (HER2)-negative) breast cancer (OR = 1.25, P = 1.1 x 10(-9)), particularly in younger women (<50 years of age) (OR = 1.48, P = 1.9 x 10(-9)). Our results identify a genetic locus associated with estrogen receptor negative breast cancer subtypes in multiple populations. C1 [Haiman, Christopher A.; Chen, Gary K.; Edlund, Christopher K.; Holbrook, Andrea; Ingles, Sue A.; Pooler, Loreall C.; Schumacher, Fredrick; Sheng, Xin; Van Den Berg, David; Wan, Peggy; Xia, Lucy Y.; Stram, Daniel O.; Henderson, Brian E.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. [Vachon, Celine M.; Lesnick, Timothy; Olswold, Curtis; Stevens, Kristen N.; Slager, Susan L.; Couch, Fergus J.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Canzian, Federico] DKFZ, Genom Epidemiol Grp, Heidelberg, Germany. [Dunning, Alison; Ahmed, Shahana; Pharoah, Paul D. P.; Easton, Douglas] Strangeways Lab, Ctr Canc Genet Epidemiol, Cambridge, England. [Wang, Xianshu; Couch, Fergus J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Ademuyiwa, Foluso] Roswell Pk Canc Inst, Dept Med, Buffalo, NY 14263 USA. [Ambrosone, Christine B.] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA. [Baglietto, Laura; Giles, Graham G.; Severi, Gianluca] Univ Melbourne, Canc Epidemiol Ctr, Canc Council Victoria, Melbourne, Vic 3010, Australia. [Baglietto, Laura; Giles, Graham G.; Severi, Gianluca] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic 3010, Australia. [Balleine, Rosemary] Western Sydney Local Hlth Network, Westmead Hosp, Dept Translat Oncol, Westmead, NSW, Australia. [Bandera, Elisa V.] Canc Inst New Jersey, New Brunswick, NJ USA. [Beckmann, Matthias W.; Fasching, Peter A.] Univ Erlangen Nurnberg, Dept Gynecol & Obstet, Univ Hosp Erlangen, D-91054 Erlangen, Germany. [Berg, Christine D.] NCI, Canc Prevent Div, US Natl Inst Hlth, Bethesda, MD 20892 USA. [Bernstein, Leslie] Beckman Res Inst, Dept Populat Sci, Div Canc Etiol, City Of Hope, CA USA. [Blomqvist, Carl] Univ Helsinki, Cent Hosp, Dept Oncol, Helsinki, Finland. [Blot, William J.; Deming, Sandra L.; Signorello, Lisa B.; Zheng, Wei] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Nashville, TN 37212 USA. [Blot, William J.; Deming, Sandra L.; Signorello, Lisa B.; Zheng, Wei] Vanderbilt Univ, Sch Med, Div Epidemiol, Dept Med,Vanderbilt Epidemiol Ctr, Nashville, TN 37212 USA. [Blot, William J.; Signorello, Lisa B.] Int Epidemiol Inst, Rockville, MD USA. [Brauch, Hiltrud] Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-7000 Stuttgart, Germany. [Brauch, Hiltrud] Univ Tubingen, Tubingen, Germany. [Buring, Julie E.; Chasman, Daniel I.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Carey, Lisa A.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Med, Chapel Hill, NC 27599 USA. [Carpenter, Jane E.; Clarke, Christine L.] Univ Sydney, Australian Breast Canc Tissue Bank, Westmead Millennium Inst, Westmead, NSW 2145, Australia. [Chang-Claude, Jenny; Hein, Rebecca; Nickels, Stephan] German Canc Res Ctr, Div Canc Epidemiol, D-6900 Heidelberg, Germany. [Chanock, Stephen J.; Hoover, Robert N.; Ziegler, Regina G.] NCI, Div Canc Epidemiol & Genet, US Natl Inst Hlth, Bethesda, MD 20892 USA. [Cox, Angela] Univ Sheffield, Inst Canc Studies, Dept Oncol, Fac Med Dent & Hlth, Sheffield, S Yorkshire, England. [Cross, Simon S.] Univ Sheffield, Acad Unit Pathol, Dept Neurosci, Fac Med Dent & Hlth, Sheffield, S Yorkshire, England. [Diasio, Robert B.; Lee, Adam M.] Mayo Clin, Dept Pharmacol, Rochester, MN USA. [Dimopoulos, Athanasios M.] Univ Athens, Sch Med, Dept Clin Therapeut, Alexandra Hosp, GR-11527 Athens, Greece. [Driver, W. Ryan] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Durcan, Lorraine; Eccles, Diana; Gerty, Susan M.; Graham, Nikki; Tapper, William J.] Princess Anne Hosp, Wessex Clin Genet Serv, Southampton, Hants, England. [Ekici, Arif B.] Univ Erlangen Nurnberg, Inst Human Genet, Erlangen, Germany. [Fasching, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA. [Feigelson, Heather S.] Kaiser Permanente Colorado, Denver, CO USA. [Flesch-Janys, Dieter; Heinz, Judith] Univ Clin Hamburg Eppendorf, Inst Med Biometr & Epidemiol, Hamburg, Germany. [Fostira, Florentia; Konstantopoulou, Irene; Yannoukakos, Drakoulis] Natl Ctr Sci Res Demokritos, Mol Diagnost Lab, Inst Radioisotopes & Radiodiagnost Prod, Athens, Greece. [Foersti, Asta] DKFZ, Div Mol Genet Epidemiol, Heidelberg, Germany. [Foersti, Asta] Lund Univ, Ctr Primary Hlth Care Res, Malmo, Sweden. [Fountzilas, George] Aristotle Univ Thessaloniki, Dept Med Oncol, Papageorgiou Hosp, GR-54006 Thessaloniki, Greece. [Godwin, Andrew K.] Univ Kansas, Dept Pathol & Lab Med, Med Ctr, Lawrence, KS 66045 USA. [Goodfellow, Paul; Ivanovich, Jennifer] Washington Univ, Sch Med, Barnes Jewish Hosp, St Louis, MO USA. [Goodfellow, Paul; Ivanovich, Jennifer] Siteman Canc Ctr, St Louis, MO USA. [Greco, Dario; Nevanlinna, Heli] Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, FIN-00290 Helsinki, Finland. [Hankinson, Susan E.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Hankinson, Susan E.] Harvard Univ, Sch Med, Boston, MA USA. [Hankinson, Susan E.; Hunter, David J.; Lindstrom, Sara; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Hartmann, Arndt; Schulz-Wendtland, Ruediger] Univ Erlangen Nurnberg, Inst Pathol, Univ Hosp Erlangen, Erlangen, Germany. [Hu, Jennifer J.; Rodriguez-Gil, Jorge L.] Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA. [Hu, Jennifer J.; Rodriguez-Gil, Jorge L.] Univ Miami, Miller Sch Med, Dept Epidemiol & Publ Hlth, Miami, FL 33136 USA. [Hunter, David J.; Lindstrom, Sara; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. [Irwanto, Astrid; Liu, Jianjun] Genome Inst Singapore, Div Human Genet, Singapore, Singapore. [John, Esther M.] Canc Prevent Inst Calif, Fremont, CA USA. [John, Esther M.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [John, Esther M.] Stanford Univ, Stanford Canc Ctr, Stanford, CA 94305 USA. [Johnson, Nicola] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England. [Jukkola-Vuorinen, Arja] Univ Oulu, Dept Oncol, Oulu Univ Hosp, Oulu, Finland. [Kaaks, Rudolf] DKFZ, Div Canc Epidemiol, Heidelberg, Germany. [Ko, Yon-Dschun] Evangel Kliniken Johanniter & Waldkrankenhaus Bon, Dept Internal Med, Bonn, Germany. [Kolonel, Laurence N.; Le Marchand, Loic] Univ Hawaii, Canc Res Ctr, Program Epidemiol, Honolulu, HI 96813 USA. [Kosma, Veli-Matti; Mannermaa, Arto] Kuopio Univ Hosp, Imaging Ctr, Dept Pathol, SF-70210 Kuopio, Finland. [Kulkarni, Swati] Roswell Pk Canc Inst, Dept Surg Oncol, Buffalo, NY 14263 USA. [Lambrechts, Diether; Wauters, Els] Vlaams Inst Biotechnol, Vesalius Res Ctr, Louvain, Belgium. [Lambrechts, Diether; Wauters, Els] Univ Leuven, Vesalius Res Ctr, Louvain, Belgium. [Mannermaa, Arto] Univ Eastern Finland, Bioctr Kuopio, Dept Pathol, Inst Clin Med, Kuopio, Finland. [Margolin, Sara] Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden. [Martin, Nicholas G.; Montgomery, Grant W.] Queensland Inst Med Res QIMR Genome Wide Assoc St, Brisbane, Qld, Australia. [Miron, Penelope] Dana Farber Canc Inst, Boston, MA 02115 USA. [Palmer, Julie; Rosenberg, Lynn] Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA. [Pathak, Harsh; Weaver, JoEllen] Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA. [Pectasides, Dimitrios] Hippokrateion Hosp, Dept Internal Med, Oncol Sect, Athens, Greece. [Perou, Charles M.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Genet, Chapel Hill, NC 27599 USA. [Perou, Charles M.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Pathol, Chapel Hill, NC 27599 USA. [Peto, Julian; Silva, Isabel dos Santos] London Sch Hyg & Trop Med, Dept Epidemiol & Populat Hlth, London WC1, England. [Press, Michael F.] Univ So Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA 90033 USA. [Pylkas, Katri; Winqvist, Robert] Univ Oulu, Canc Genet Lab, Dept Clin Genet, Oulu Univ Hosp, Oulu, Finland. [Pylkas, Katri; Winqvist, Robert] Univ Oulu, Bioctr Oulu, Oulu Univ Hosp, Oulu, Finland. [Rebbeck, Timothy R.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Ross, Eric] Fox Chase Canc Ctr, Dept Biostat, Philadelphia, PA 19111 USA. [Ruediger, Thomas] Stadt Klinikum Karlsruhe, Inst Pathol, Karlsruhe, Germany. [Sawyer, Elinor] Guys & St Thomas Natl Hlth Serv Fdn Trust, Natl Inst Hlth Res Comprehens Biomed Res Ctr, London, England. [Schmidt, Marjanka K.] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Div Epidemiol, Amsterdam, Netherlands. [Schmidt, Marjanka K.] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Div Expt Therapy & Mol Pathol, Amsterdam, Netherlands. [Sinn, Hans-Peter] Univ Heidelberg Hosp, Dept Pathol, Heidelberg, Germany. [Southey, Melissa C.] Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Melbourne, Vic, Australia. [Tomlinson, Ian] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Tomlinson, Ian] Univ Oxford, Oxford Biomed Res Ctr, Oxford, England. [Hogervorst, Frans B. L.] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Family Canc Clin, Amsterdam, Netherlands. [Wildiers, Hans] Univ Hosp Gasthuisberg, Multidisciplinary Breast Ctr, B-3000 Louvain, Belgium. [Siddiq, Afshan] Univ London Imperial Coll Sci Technol & Med, London, England. [Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Haiman, CA (reprint author), Univ So Calif, Keck Sch Med, Dept Prevent Med, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. EM haiman@usc.edu; couch.fergus@mayo.edu RI Verdrengh, Evelien/H-4571-2012; Ekici, Arif/C-3971-2013; Berg , Christine/K-1047-2014; Bandera, Elisa/M-4169-2014; Montgomery, Grant/B-7148-2008; OI Dunning, Alison Margaret/0000-0001-6651-7166; Perou, Charles/0000-0001-9827-2247; Bandera, Elisa/0000-0002-8789-2755; Montgomery, Grant/0000-0002-4140-8139; Konstantopoulou, Irene/0000-0002-0470-0309; Nevanlinna, Heli/0000-0002-0916-2976; dos Santos Silva, Isabel/0000-0002-6596-8798; Yannoukakos, Drakoulis/0000-0001-7509-3510 FU US Department of Defense [W81XWH-08-1-0383]; Norris Foundation; Mayo Clinic College of Medicine; Breast Cancer Research Foundation; US National Institutes of Health [CA128978, CA122340, CA148065]; Komen Foundation for the Cure FX This work was supported by a US Department of Defense Breast Cancer Research Program Era of Hope Scholar Award to C.A.H. (W81XWH-08-1-0383), the Norris Foundation, the Mayo Clinic College of Medicine, Komen Foundation for the Cure, the Breast Cancer Research Foundation and US National Institutes of Health grants CA128978, CA122340 and CA148065. Study specific acknowledgments are listed in the Supplementary Note. NR 15 TC 140 Z9 140 U1 2 U2 20 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD DEC PY 2011 VL 43 IS 12 BP 1210 EP U61 DI 10.1038/ng.985 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 860EK UT WOS:000297931400013 PM 22037553 ER PT J AU Raychaudhuri, S Iartchouk, O Chin, K Tan, PL Tai, AK Ripke, S Gowrisankar, S Vemuri, S Montgomery, K Yu, Y Reynolds, R Zack, DJ Campochiaro, B Campochiaro, P Katsanis, N Daly, MJ Seddon, JM AF Raychaudhuri, Soumya Iartchouk, Oleg Chin, Kimberly Tan, Perciliz L. Tai, Albert K. Ripke, Stephan Gowrisankar, Sivakumar Vemuri, Soumya Montgomery, Kate Yu, Yi Reynolds, Robyn Zack, Donald J. Campochiaro, Betsy Campochiaro, Peter Katsanis, Nicholas Daly, Mark J. Seddon, Johanna M. TI A rare penetrant mutation in CFH confers high risk of age-related macular degeneration SO NATURE GENETICS LA English DT Article ID HEMOLYTIC-UREMIC SYNDROME; GENOME-WIDE ASSOCIATION; FACTOR-H POLYMORPHISM; GENE; VARIANTS; SUSCEPTIBILITY; INDIVIDUALS; HAPLOTYPE; LINKAGE; DISEASE AB Two common variants in the gene encoding complement factor H (CFH), the Y402H substitution (rs1061170, c.1204C>T)(1-4) and the intronic rs1410996 SNP(5,6), explain 17% of age-related macular degeneration (AMD) liability. However, proof for the involvement of CFH, as opposed to a neighboring transcript, and knowledge of the potential mechanism of susceptibility alleles are lacking. Assuming that rare functional variants might provide mechanistic insights, we used genotype data and high-throughput sequencing to discover a rare, high-risk CFH haplotype with a c.3628C>T mutation that resulted in an R1210C substitution. This allele has been implicated previously in atypical hemolytic uremic syndrome, and it abrogates C-terminal ligand binding(7,8). Genotyping R1210C in 2,423 AMD cases and 1,122 controls demonstrated high penetrance (present in 40 cases versus 1 control, P = 7.0 x 10(-6)) and an association with a 6-year-earlier onset of disease (P = 2.3 x 10(-6)). This result suggests that loss-of-function alleles at CFH are likely to drive AMD risk. This finding represents one of the first instances in which a common complex disease variant has led to the discovery of a rare penetrant mutation. C1 [Raychaudhuri, Soumya] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. [Raychaudhuri, Soumya] Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. [Raychaudhuri, Soumya; Iartchouk, Oleg; Gowrisankar, Sivakumar; Vemuri, Soumya; Montgomery, Kate] Partners HealthCare Ctr Personalized Genet Med, Boston, MA USA. [Raychaudhuri, Soumya; Ripke, Stephan; Daly, Mark J.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Chin, Kimberly; Yu, Yi; Reynolds, Robyn; Seddon, Johanna M.] Tufts Med Ctr, Ophthalm Epidemiol & Genet Serv, New England Eye Ctr, Boston, MA USA. [Tan, Perciliz L.; Katsanis, Nicholas] Duke Univ, Ctr Human Dis Modeling, Dept Cell Biol, Durham, NC USA. [Tan, Perciliz L.; Katsanis, Nicholas] Duke Univ, Dept Pediat, Durham, NC 27706 USA. [Tai, Albert K.] Tufts Univ, Sch Med, Dept Pathol, Study Ctr Immunogenet Infect Dis, Boston, MA 02111 USA. [Ripke, Stephan; Daly, Mark J.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Zack, Donald J.; Campochiaro, Betsy; Campochiaro, Peter] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, McKusick Nathans Inst Genet Med,Dept Ophthalmol, Baltimore, MD 21205 USA. [Seddon, Johanna M.] Tufts Univ, Sch Med, Dept Ophthalmol, Boston, MA 02111 USA. RP Raychaudhuri, S (reprint author), Brigham & Womens Hosp, Div Genet, 75 Francis St, Boston, MA 02115 USA. EM soumya@broadinstitute.org; jseddon@tuftsmedicalcenter.org RI Katsanis, Nicholas/E-1837-2012; OI Zack, Don/0000-0002-7966-1973; Katsanis, Nicholas/0000-0002-2480-0171 FU US National Institutes of Health (NIH) [RO1-EY11309, K08AR055688-01A1, U01 MH085520-01]; Massachusetts Lions Eye Research Fund, Inc.; American Macular Degeneration Research Fund; Foundation Fighting Blindness; Macular Vision Research Foundation; Research to Prevent Blindness Challenge Grant; Department of Ophthalmology; Tufts University School of Medicine; Ophthalmic Epidemiology and Genetics Service; New England Eye Center; Tufts Medical Center; NIH National Heart, Lung, and Blood Institute (NLBI) [R01HL087676]; NIH National Center for Research Resources (NCRR) FX We appreciate the contribution to the research of J.M.S. of an anonymous donor. This research was supported in part by grants RO1-EY11309 (J.M.S.), K08AR055688-01A1 (S. Raychaudhuri) and U01 MH085520-01 (S. Ripke) from the US National Institutes of Health (NIH), and by the Massachusetts Lions Eye Research Fund, Inc., the American Macular Degeneration Research Fund, the Foundation Fighting Blindness, the Macular Vision Research Foundation, a Research to Prevent Blindness Challenge Grant to the New England Eye Center, Department of Ophthalmology, Tufts University School of Medicine, and the Macular Degeneration Research Fund of the Ophthalmic Epidemiology and Genetics Service, New England Eye Center, Tufts Medical Center, Tufts University School of Medicine. N.K. is a Distinguished Brumley Professor. The MIGen study was funded by grants from the NIH National Heart, Lung, and Blood Institute (NLBI) (R01HL087676) and the NIH National Center for Research Resources (NCRR). We acknowledge informal and helpful discussions from our colleagues B. Neale, R. Plenge, P. de Bakker, D. Reich, E. Stahl, B. Stranger and B. Voight. NR 45 TC 138 Z9 142 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD DEC PY 2011 VL 43 IS 12 BP 1232 EP U91 DI 10.1038/ng.976 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 860EK UT WOS:000297931400018 PM 22019782 ER PT J AU Reece-Hoyes, JS Barutcu, AR McCord, RP Jeong, JS Jiang, LZ MacWilliams, A Yang, XP Salehi-Ashtiani, K Hill, DE Blackshaw, S Zhu, H Dekker, J Walhout, AJM AF Reece-Hoyes, John S. Barutcu, A. Rasim McCord, Rachel Patton Jeong, Jun Seop Jiang, Lizhi MacWilliams, Andrew Yang, Xinping Salehi-Ashtiani, Kourosh Hill, David E. Blackshaw, Seth Zhu, Heng Dekker, Job Walhout, Albertha J. M. TI Yeast one-hybrid assays for gene-centered human gene regulatory network mapping SO NATURE METHODS LA English DT Article ID TRANSCRIPTION-FACTOR-BINDING; DNA INTERACTION NETWORK; OPEN READING FRAMES; PROTEIN-DNA; SYSTEM; MODULARITY; RESOURCE; DATABASE; GENOME AB Gateway-compatible yeast one-hybrid (Y1H) assays provide a convenient gene-centered (DNA to protein) approach to identify transcription factors that can bind a DNA sequence of interest. We present Y1H resources, including clones for 988 of 1,434 (69%) predicted human transcription factors, that can be used to detect both known and new interactions between human DNA regions and transcription factors. C1 [Reece-Hoyes, John S.; McCord, Rachel Patton; Dekker, Job; Walhout, Albertha J. M.] Univ Massachusetts, Sch Med, Program Syst Biol, Worcester, MA 01605 USA. [Reece-Hoyes, John S.; Barutcu, A. Rasim; McCord, Rachel Patton; Dekker, Job; Walhout, Albertha J. M.] Univ Massachusetts, Sch Med, Program Gene Funct & Express, Worcester, MA USA. [Reece-Hoyes, John S.; Walhout, Albertha J. M.] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA USA. [Barutcu, A. Rasim; McCord, Rachel Patton; Dekker, Job] Univ Massachusetts, Sch Med, Dept Mol Pharmacol & Biochem, Worcester, MA USA. [Jeong, Jun Seop; Jiang, Lizhi; Blackshaw, Seth; Zhu, Heng] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA. [Jeong, Jun Seop; Jiang, Lizhi; Blackshaw, Seth; Zhu, Heng] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD 21205 USA. [Jeong, Jun Seop; Jiang, Lizhi; Blackshaw, Seth; Zhu, Heng] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Jeong, Jun Seop; Jiang, Lizhi; Blackshaw, Seth; Zhu, Heng] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA. [Jeong, Jun Seop; Jiang, Lizhi; Blackshaw, Seth; Zhu, Heng] Johns Hopkins Univ, Sch Med, Ctr High Throughput Biol, Baltimore, MD 21205 USA. [Jeong, Jun Seop; Jiang, Lizhi; Blackshaw, Seth; Zhu, Heng] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Baltimore, MD 21205 USA. [MacWilliams, Andrew; Yang, Xinping; Salehi-Ashtiani, Kourosh; Hill, David E.; Dekker, Job; Walhout, Albertha J. M.] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. [MacWilliams, Andrew; Yang, Xinping; Salehi-Ashtiani, Kourosh; Hill, David E.; Dekker, Job; Walhout, Albertha J. M.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [MacWilliams, Andrew; Yang, Xinping; Salehi-Ashtiani, Kourosh; Hill, David E.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. RP Walhout, AJM (reprint author), Univ Massachusetts, Sch Med, Program Syst Biol, Worcester, MA 01605 USA. EM john.reece-hoyes@umassmed.edu; marian.walhout@umassmed.edu RI Hill, David/B-6617-2011; OI Barutcu, Ahmet Rasim/0000-0002-4838-8695; Salehi-Ashtiani, Kourosh/0000-0002-6521-5243; Walhout, Marian/0000-0001-5587-3608 FU US National Institutes of Health (NIH) [DK068429, GM082971]; NIH [HG003143, GM076102]; W.M. Keck Foundation; Ellison Foundation; Dana Farber Cancer Institute; Ruth and Milton Steinbach Fund FX We thank members of the Walhout lab for discussions and critical reading of the manuscript. Research in the Walhout lab is supported by US National Institutes of Health (NIH) grants DK068429 and GM082971. This work was supported by NIH grant HG003143 and a W.M. Keck Foundation Distinguished Young scholar award to J.D., an Ellison Foundation grant and Dana Farber Cancer Institute Sponsored Research funds awarded to Center for Cancer Systems Biology. Research in the Blackshaw lab is funded by a W.M. Keck Foundation Distinguished Young scholar award and a grant from the Ruth and Milton Steinbach Fund. H.Z. is supported by NIH grant GM076102. NR 25 TC 19 Z9 19 U1 0 U2 16 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 J9 NAT METHODS JI Nat. Methods PD DEC PY 2011 VL 8 IS 12 BP 1050 EP + DI 10.1038/NMETH.1764 PG 5 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 860EN UT WOS:000297931700016 PM 22037702 ER PT J AU Colwell, AS Damjanovic, B Zahedi, B Medford-Davis, L Hertl, C Austen, WG AF Colwell, Amy S. Damjanovic, Branimir Zahedi, Bita Medford-Davis, Laura Hertl, Catherine Austen, William G., Jr. TI Retrospective Review of 331 Consecutive Immediate Single-Stage Implant Reconstructions with Acellular Dermal Matrix: Indications, Complications, Trends, and Costs SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID BREAST RECONSTRUCTION; TISSUE MATRIX; ALLODERM; MASTECTOMY; EXPERIENCE; COVERAGE AB Background: Immediate single-stage direct-to-implant breast reconstruction with acellular dermal matrix optimizes aesthetics by preserving the mastectomy skin envelope. The authors report trends, early complications, and costs. Methods: A retrospective review of three surgeons' experience was performed for immediate single-stage implant reconstruction with acellular dermal matrix and tissue expander reconstruction without it at Massachusetts General Hospital. Results: Two hundred eleven patients had 331 direct-to-implant reconstructions using AlloDerm following nipple-sparing (n = 66) or skin-sparing (n = 265) mastectomy for cancer (n = 216) or prophylaxis (n = 115). The number of single-stage implant reconstructions increased from seven in 2006 to 116 in 2009. The percentage performed for prophylaxis increased from 29 percent to 41 percent. Fifty-one patients underwent preoperative (n = 33) or postoperative (n = 18) irradiation. Total complications included 10 infections (3.0 percent), five seromas (1.5 percent), four hematomas (1.2 percent), and 30 reconstructions (9.1 percent), with skin necrosis leading to five implant losses (1.5 percent). Tissue expander reconstruction without AlloDerm had a similar total complication rate (158 reconstructions) (p = 0.18), including nine infections (5.7 percent), three seromas (1.9 percent), three hematomas (1.9 percent), and 16 reconstructions (10.1 percent), with skin necrosis leading to 11 implant losses (7.0 percent). A higher complication rate occurred in the surgeons' combined first year performing single-stage implant reconstruction (21.4 percent) compared with subsequent years (10.9 percent) (p < 0.02) and in one-or two-stage reconstruction patients undergoing irradiation (p = 0.005). There was no significant difference in total overall costs (p = 0.8). Conclusions: Immediate single-stage implant reconstruction using acellular dermal matrix offers a cost-effective reconstruction with a low complication rate. This may be the procedure of choice in select patients. (Plast. Reconstr. Surg. 128: 1170, 2011.) C1 [Colwell, Amy S.; Damjanovic, Branimir; Zahedi, Bita; Medford-Davis, Laura; Hertl, Catherine; Austen, William G., Jr.] Harvard Univ, Div Plast Surg, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Colwell, AS (reprint author), Harvard Univ, Div Plast Surg, Massachusetts Gen Hosp, Sch Med, 15 Parkman St,WACC 435, Boston, MA 02114 USA. EM acolwell@partners.org NR 23 TC 95 Z9 97 U1 3 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD DEC PY 2011 VL 128 IS 6 BP 1170 EP 1178 DI 10.1097/PRS.0b013e318230c2f6 PG 9 WC Surgery SC Surgery GA 852DU UT WOS:000297329700046 PM 22094736 ER PT J AU Baddley, JW Pappas, PG AF Baddley, John W. Pappas, Peter G. TI Pulmonary Fungal Infections PREFACE SO SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Editorial Material C1 [Baddley, John W.; Pappas, Peter G.] Univ Alabama, Dept Med, Div Infect Dis, Birmingham, AL 35294 USA. [Baddley, John W.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Baddley, JW (reprint author), Univ Alabama, Dept Med, Div Infect Dis, Tinsley Harrison Tower 229,1530 3rd Ave S, Birmingham, AL 35294 USA. EM jbaddley@uab.edu NR 0 TC 1 Z9 1 U1 0 U2 1 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1069-3424 J9 SEMIN RESP CRIT CARE JI Semin. Respir. Crit. Care Med. PD DEC PY 2011 VL 32 IS 6 BP 661 EP 662 DI 10.1055/s-0031-1295713 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 860OZ UT WOS:000297958900001 PM 22167393 ER PT J AU Thompson, GR Patterson, TF AF Thompson, George R., III Patterson, Thomas F. TI Pulmonary Aspergillosis: Recent Advances SO SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Review DE Aspergillosis; chronic cavitary aspergillosis; aspergilloma ID STEM-CELL TRANSPLANTATION; CRITICALLY-ILL PATIENTS; BETA-GLUCAN RECEPTOR; INVASIVE MOLD INFECTION; AMPHOTERICIN-B THERAPY; ANTIFUNGAL THERAPY; NEUTROPENIC PATIENTS; CANCER-PATIENTS; FUMIGATUS; POSACONAZOLE AB Aspergillosis remains a significant cause of morbidity and mortality. The spectrum of disease is diverse and ranges from noninvasive disease with an excessive immune response, such as in allergic bronchopulmonary aspergillosis (ABPA), to a lack of an immune response as seen in patients with quantitative or qualitative granulocyte deficits and subsequent invasive pulmonary aspergillosis. Noninvasive diagnostic testing has improved the time to initiation of effective antifungal therapy, and numerous agents in different therapeutic classes are now available as treatment options. Voriconazole remains the preferred agent in the treatment of invasive pulmonary aspergillosis, and recent data have increased interest in the potential of combination therapy against this often lethal infection. The role of host genetics in selecting patients that may benefit from more aggressive antifungal prophylaxis or treatment practices remains unclear but is likely to guide therapeutic choices as newer data become available. C1 [Thompson, George R., III] Univ Calif Davis, Dept Internal Med, Div Infect Dis, Davis, CA 95616 USA. [Thompson, George R., III] Univ Calif Davis, Dept Med Microbiol & Immunol, Davis, CA 95616 USA. [Patterson, Thomas F.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Patterson, Thomas F.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Thompson, GR (reprint author), Univ Calif Davis, Dept Internal Med, Div Infect Dis, 1 Shields Ave,Tupper Hall,Rm 3146, Davis, CA 95616 USA. EM grthompson@ucdavis.edu NR 74 TC 18 Z9 18 U1 1 U2 5 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1069-3424 EI 1098-9048 J9 SEMIN RESP CRIT CARE JI Semin. Respir. Crit. Care Med. PD DEC PY 2011 VL 32 IS 6 BP 673 EP 681 DI 10.1055/s-0031-1295715 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 860OZ UT WOS:000297958900003 PM 22167395 ER PT J AU Brizendine, KD Baddley, JW Pappas, PG AF Brizendine, Kyle D. Baddley, John W. Pappas, Peter G. TI Pulmonary Cryptococcosis SO SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Review DE Cryptococcus; pulmonary; cryptococcosis; cryptococcal; pneumonia ID HUMAN-IMMUNODEFICIENCY-VIRUS; INVASIVE FUNGAL-INFECTIONS; ACTIVE ANTIRETROVIRAL THERAPY; BRONCHOALVEOLAR LAVAGE FLUID; ORGAN TRANSPLANT RECIPIENTS; NECROSIS-FACTOR-ALPHA; NEOFORMANS INFECTION; IMMUNOCOMPETENT PATIENTS; MAINTENANCE THERAPY; NEGATIVE PATIENTS AB Cryptococcosis is an invasive fungal infection (IFI), caused predominantly by Cryptococcus neoformans or Cryptococcus gattii, that affects both immunocompromised (IC) and non-IC patients. Although the most serious disease manifestation is meningoencephalitis, cryptococcal pneumonia is underdiagnosed and may disseminate to the central nervous system (CNS) and other sites depending upon host defenses and administration of appropriate antifungal therapy. The clinical presentation of pulmonary cryptococcosis varies along a spectrum from asymptomatic infection to severe pneumonia and respiratory failure, and the radiological presentation can be characterized by an array of findings, including nodules, consolidation, cavitary lesions, and a diffuse interstitial pattern. Diagnosis most often relies upon isolation of Cryptococcus from a pulmonary specimen in the appropriate clinical and radiological context. Treatment recommendations include induction therapy with an amphotericin B preparation and flucytosine for IC patients and those with severe disease and fluconazole for mild-to-moderate, localized disease. Knowledge of the pathophysiology, epidemiology, clinical presentation, and treatment of pulmonary cryptococcosis may lead to greater recognition of this underdiagnosed IFI and improved outcomes. C1 [Brizendine, Kyle D.; Baddley, John W.; Pappas, Peter G.] Univ Alabama, Dept Med, Div Infect Dis, Birmingham, AL 35294 USA. [Baddley, John W.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Pappas, PG (reprint author), Univ Alabama, Dept Med, Div Infect Dis, Tinsley Harrison Tower 229,1530 3rd Ave S, Birmingham, AL 35294 USA. EM pappas@uab.edu NR 71 TC 18 Z9 21 U1 1 U2 10 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1069-3424 J9 SEMIN RESP CRIT CARE JI Semin. Respir. Crit. Care Med. PD DEC PY 2011 VL 32 IS 6 BP 727 EP 734 DI 10.1055/s-0031-1295720 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 860OZ UT WOS:000297958900008 PM 22167400 ER PT J AU Thacker, EL Psaty, BM McKnight, B Heckbert, SR Longstreth, WT Mukamal, KJ Meigs, JB de Boer, IH Boyko, EJ Carnethon, MR Kizer, JR Tracy, RP Smith, NL Siscovick, DS AF Thacker, Evan L. Psaty, Bruce M. McKnight, Barbara Heckbert, Susan R. Longstreth, W. T., Jr. Mukamal, Kenneth J. Meigs, James B. de Boer, Ian H. Boyko, Edward J. Carnethon, Mercedes R. Kizer, Jorge R. Tracy, Russell P. Smith, Nicholas L. Siscovick, David S. TI Fasting and Post-Glucose Load Measures of Insulin Resistance and Risk of Ischemic Stroke in Older Adults SO STROKE LA English DT Article DE nondiabetic older adults; cohort study; Gutt insulin sensitivity index ID CORONARY-HEART-DISEASE; CARDIOVASCULAR HEALTH; ATHEROSCLEROSIS AB Background and Purpose-Few studies have assessed post-glucose load measures of insulin resistance and ischemic stroke risk, and data are sparse for older adults. We investigated whether fasting and post-glucose load measures of insulin resistance were related to incident ischemic stroke in nondiabetic, older adults. Methods-Participants were men and women in the Cardiovascular Health Study, age 65+ years and without prevalent diabetes or stroke at baseline, followed for 17 years for incident ischemic stroke. The Gutt insulin sensitivity index was calculated from baseline body weight and from fasting and 2-hour postload insulin and glucose; a lower Gutt index indicates higher insulin resistance. Results-Analyses included 3442 participants (42% men) with a mean age of 73 years. Incidence of ischemic stroke was 9.8 strokes per 1000 person-years. The relative risk (RR) for lowest quartile versus highest quartile of Gutt index was 1.64 (95% CI, 1.24-2.16), adjusted for demographics and prevalent cardiovascular and kidney disease. Similarly, the adjusted RR for highest quartile versus lowest quartile of 2-hour glucose was 1.84 (95% CI, 1.39-2.42). In contrast, the adjusted RR for highest quartile versus lowest quartile of fasting insulin was 1.10 (95% CI, 0.84-1.46). Conclusions-In nondiabetic, older adults, insulin resistance measured by Gutt index or 2-hour glucose, but not by fasting insulin, was associated with risk of incident ischemic stroke. (Stroke. 2011;42:3347-3351.) C1 [Thacker, Evan L.; Psaty, Bruce M.; McKnight, Barbara; Heckbert, Susan R.; Smith, Nicholas L.; Siscovick, David S.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Thacker, Evan L.; Psaty, Bruce M.; Heckbert, Susan R.; Longstreth, W. T., Jr.; Boyko, Edward J.; Smith, Nicholas L.; Siscovick, David S.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Psaty, Bruce M.; Longstreth, W. T., Jr.; de Boer, Ian H.; Boyko, Edward J.; Siscovick, David S.] Univ Washington, Dept Med, Seattle, WA USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [McKnight, Barbara] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Longstreth, W. T., Jr.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Psaty, Bruce M.; Heckbert, Susan R.; Smith, Nicholas L.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Mukamal, Kenneth J.] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Meigs, James B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Boyko, Edward J.; Smith, Nicholas L.] Vet Affairs Off Res & Dev, Epidemiol Res & Informat Ctr, Seattle, WA USA. [Carnethon, Mercedes R.] Northwestern Univ, Dept Prevent Med, Chicago, IL 60611 USA. [Kizer, Jorge R.] Weill Cornell Med Coll, Dept Med, New York, NY USA. [Tracy, Russell P.] Univ Vermont, Dept Pathol & Lab Med, Burlington, VT USA. RP Thacker, EL (reprint author), 1730 Minor Ave,Ste 1360, Seattle, WA 98101 USA. EM ethacker@uw.edu OI Thacker, Evan/0000-0002-3813-0885 FU National Heart, Lung, and Blood Institute (NHLBI) [N01-HC-85239, N01-HC-85079, N01-HC-85086, N01-HC-35129, N01-HC-15103, N01-HC-55222, N01-HC-75150, N01-HC-45133, HL-080295, HL-094555]; National Institute of Neurological Disorders and Stroke (NINDS); National Institute on Aging (NIA) [AG-023629, AG-15928, AG-20098, AG-027058]; NHLBI [T32-HL007902]; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [K24-DK080140, P30-DK17047]; Veterans Affairs Puget Sound Health Care System FX The research reported in this article was supported by contracts N01-HC-85239, N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01-HC-15103, N01-HC-55222, N01-HC-75150, N01-HC-45133, and grants HL-080295 and HL-094555 from the National Heart, Lung, and Blood Institute (NHLBI), with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided through AG-023629, AG-15928, AG-20098, and AG-027058 from the National Institute on Aging (NIA). EL Thacker was supported by NHLBI training grant T32-HL007902 (PI: Siscovick). JB Meigs was supported by grant K24-DK080140 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). EJ Boyko was supported by NIDDK grant P30-DK17047 and by the Veterans Affairs Puget Sound Health Care System. NR 16 TC 15 Z9 17 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD DEC PY 2011 VL 42 IS 12 BP 3347 EP U57 DI 10.1161/STROKEAHA.111.620773 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 860IH UT WOS:000297941500013 PM 21998054 ER PT J AU Howard, G Cushman, M Kissela, BM Kleindorfer, DO McClure, LA Safford, MM Rhodes, JD Soliman, EZ Moy, CS Judd, SE Howard, VJ AF Howard, George Cushman, Mary Kissela, Brett M. Kleindorfer, Dawn O. McClure, Leslie A. Safford, Monika M. Rhodes, J. David Soliman, Elsayed Z. Moy, Claudia S. Judd, Suzanne E. Howard, Virginia J. CA REGARDS Investigators TI Traditional Risk Factors as the Underlying Cause of Racial Disparities in Stroke Lessons From the Half-Full (Empty?) Glass SO STROKE LA English DT Article DE stroke; risk factors; hypertension; diabetes mellitus; mediation analysis ID SOUTHEASTERN UNITED-STATES; CARDIOVASCULAR-DISEASES; BLOOD-PRESSURE; FOLLOW-UP; HYPERTENSION; AWARENESS; ASSOCIATION; PREVALENCE; MORTALITY; REASONS AB Background and Purpose-Black/white disparities in stroke incidence are well documented, but few studies have assessed the contributions to the disparity. Here we assess the contribution of "traditional" risk factors. Methods-A total of 25 714 black and white men and women, aged >= 45 years and stroke-free at baseline, were followed for an average of 4.4 years to detect stroke. Mediation analysis using proportional hazards analysis assessed the contribution of traditional risk factors to racial disparities. Results-At age 45 years, incident stroke risk was 2.90 (95% CI: 1.72-4.89) times more likely in blacks than in whites and 1.66 (95% CI: 1.34-2.07) times at age 65 years. Adjustment for risk factors attenuated these excesses by 40% and 45%, respectively, resulting in relative risks of 2.14 (95% CI: 1.25-3.67) and 1.35 (95% CI: 1.08-1.71). Approximately one half of this mediation is attributable to systolic blood pressure. Further adjustment for socioeconomic factors resulted in total mediation of 47% and 53% to relative risks of 2.01 (95% CI: 1.16-3.47) and 1.30 (1.03-1.65), respectively. Conclusions-Between ages 45 to 65 years, approximately half of the racial disparity in stroke risk is attributable to traditional risk factors (primarily systolic blood pressure) and socioeconomic factors, suggesting a critical need to understand the disparity in the development of these traditional risk factors. Because half of the excess stroke risk in blacks is not attributable to traditional risk factors and socioeconomic factors, differential impact of risk factors, residual confounding, or nontraditional risk factors may also play a role. (Stroke. 2011;42:3369-3375.) C1 [Howard, George; McClure, Leslie A.; Rhodes, J. David; Judd, Suzanne E.] Univ Alabama, Sch Publ Hlth, Dept Biostat, Birmingham, AL 35294 USA. [Howard, Virginia J.] Univ Alabama, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA. [Safford, Monika M.] Univ Alabama, Deep S Ctr Effectiveness, Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Safford, Monika M.] Univ Alabama, Dept Med, Div Prevent Med, Birmingham, AL 35294 USA. [Cushman, Mary] Univ Vermont, Coll Med, Dept Med, Burlington, VT 05405 USA. [Kissela, Brett M.; Kleindorfer, Dawn O.] Univ Cincinnati, Dept Neurol, Cincinnati, OH USA. [Soliman, Elsayed Z.] Wake Forest Univ, Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC 27109 USA. [Moy, Claudia S.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA. RP Howard, G (reprint author), Univ Alabama, Sch Publ Hlth, Dept Biostat, 1665 Univ Blvd, Birmingham, AL 35294 USA. EM ghoward@uab.edu RI McClure, Leslie/P-2929-2015; OI Kissela, Brett/0000-0002-9773-4013 FU National Institute of Neurological Disorders and Stroke [NS 041588] FX The research reported in this article was supported by cooperative agreement NS 041588 from the National Institute of Neurological Disorders and Stroke. NR 29 TC 56 Z9 57 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD DEC PY 2011 VL 42 IS 12 BP 3369 EP 3375 DI 10.1161/STROKEAHA.111.625277 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 860IH UT WOS:000297941500017 PM 21960581 ER PT J AU Kim, DE Kim, JY Nahrendorf, M Lee, SK Ryu, JH Kim, K Kwon, IC Schellingerhout, D AF Kim, Dong-Eog Kim, Jeong-Yeon Nahrendorf, Matthias Lee, Su-Kyoung Ryu, Ju Hee Kim, Kwangmeyung Kwon, Ick Chan Schellingerhout, Dawid TI Direct Thrombus Imaging as a Means to Control the Variability of Mouse Embolic Infarct Models The Role of Optical Molecular Imaging SO STROKE LA English DT Article DE thrombus imaging; embolic cerebral infarction; molecular imaging; optical imaging ID ACTIVATED FACTOR-XIII; CEREBRAL-ISCHEMIA; FIBRINOLYTIC RESISTANCE; STROKE; RAT; OCCLUSION; MICE AB Background and Purpose-High experimental variability in mouse embolic stroke models could mask the effects of experimental treatments. We hypothesized that imaging thrombus directly would allow this variability to be controlled. Methods-We optically labeled thrombi with a near-infrared fluorescent (NIRF) probe C15 that is covalently linked to fibrin by factor-XIIIa. Labeled thrombus was injected into the left distal internal carotid artery (ICA) of C57/BL6 mice (n=47), near its bifurcation, and laser-Doppler cerebral-blood-flow (CBF) was assessed for 30 minutes. NIRF thrombus imaging was done ex vivo at 24 hours. Results-CBF variably decreased to 43.9 +/- 17.3% at 5 minutes (rCBF; 11.2 similar to 80.4%). NIRF thrombus imaging at 24 hours showed variability in distribution (ICA bifurcation, adjacent and/or remote areas) and burden (2279 +/- 1270 pixels; 0 similar to 5940 pixels). Final infarct size was also variable (21.0 +/- 10.3%; 4.7 similar to 60.3% of the bihemispheric volume). Despite this heterogeneity, a strong thrombus-infarct correlation was maintained. The left hemispheric target infarct size (% of the hemisphere) correlated with thrombus burden, as a stronger predictor of infarct volume (P<0.001, r=0.50) than rCBF (P=0.02, r=-0.34). The infarct size was best predicted by a combination of thrombus imaging and CBF: left-hemispheric big-thrombi (>1865 pixels)/low-rCBF (<= 42%) had an infarct volume of 56.9 +/- 10.4% (n=12), big-thrombi/high-rCBF had 45.9 +/- 23.5% (n=11), small-thrombi/low-rCBF 35.7 +/- 17.3% (n=11) and small-thrombi/ high-rCBF 27.3 +/- 16.4% (n=12). Conclusions-This is the first study to demonstrate that the highly heterogeneous nature of the mouse embolic stroke model can be characterized and managed by using near-infrared fluorescent thrombus imaging combined with CBF monitoring to stratify animals into useful subgroups. (Stroke. 2011;42:3566-3573.) C1 [Kim, Dong-Eog; Kim, Jeong-Yeon; Lee, Su-Kyoung] Dongguk Univ, Coll Med, Mol Imaging & Neurovasc Res MINER Lab, Goyang, South Korea. [Nahrendorf, Matthias] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol, Cambridge, MA 02138 USA. [Ryu, Ju Hee; Kim, Kwangmeyung; Kwon, Ick Chan] Korea Inst Sci & Technol, Biomed Res Ctr, Seoul, South Korea. [Schellingerhout, Dawid] Univ Texas MD Anderson Canc Ctr, Dept Radiol, Houston, TX 77030 USA. [Schellingerhout, Dawid] Univ Texas MD Anderson Canc Ctr, Dept Expt Diagnost Imaging, Houston, TX 77030 USA. RP Kim, DE (reprint author), Dongguk Univ, Ilsan Hosp, Dept Neurol, MINER Lab, 814 Siksa Dong, Goyang, South Korea. EM kdongeog@duih.org FU National Research Foundation; Korean government [2010-0019862] FX This work was supported by the Bio & Medical Technology Development Program of the National Research Foundation funded by the Korean government (2010-0019862). NR 20 TC 10 Z9 10 U1 2 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD DEC PY 2011 VL 42 IS 12 BP 3566 EP 3573 DI 10.1161/STROKEAHA.111.629428 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 860IH UT WOS:000297941500048 PM 22020025 ER PT J AU Chou, SHY Lee, PS Konigsberg, RG Gallacci, D Chiou, T Arai, K Simmons, S Bauer, D Feske, SK Lo, EH Ning, MM AF Chou, Sherry H. -Y. Lee, Po-Shun Konigsberg, Rachael G. Gallacci, Dana Chiou, Terry Arai, Ken Simmons, Suzanne Bauer, David Feske, Steven K. Lo, Eng H. Ning, MingMing TI Plasma-Type Gelsolin Is Decreased in Human Blood and Cerebrospinal Fluid After Subarachnoid Hemorrhage SO STROKE LA English DT Article DE biomarker; gelsolin; matrix metalloproteinases; subarachnoid hemorrhage ID BRAIN-INJURY; ACTIN AB Background and Purpose-Subarachnoid hemorrhage (SAH) pathophysiology involves neurovascular proteolysis and inflammation. How these 2 phenomena are related remains unclear. We hypothesize that matrix metalloproteinases (MMPs) mediate the depletion of anti-inflammatory plasma-type gelsolin (pGSN). Methods-We enrolled 42 consecutive SAH subjects and sampled cerebrospinal fluid (CSF) and blood on post-SAH Days 2 to 3, 4 to 5, 6 to 7, and 10 to 14. Control subjects were 20 consecutive non-SAH hydrocephalus patients with lumbar drains. Enzyme-linked immunosorbent assay, Western blotting, and zymography were used to quantify pGSN and MMP-9. Results-In CSF, pGSN was lower in SAH compared with control subjects on post-SAH Days 2 to 3 (P = 0.0007), 4 to 5 (P = 0.041), and 10 to 14 (P = 0.007). In blood, pGSN decreased over time (P = 0.001) and was lower in SAH compared with control subjects on post-SAH Days 4 to 5 (P = 0.037), 6 to 7 (P = 0.006), and 10 to 14 (P = 0.006). Western blots demonstrated that SAH CSF had novel bands at 52 and 46 kDa, representing cleaved pGSN fragments. Gelatin zymography showed that CSF MMP-9 was elevated in SAH compared with control subjects. Higher CSF MMP-9 correlated with lower CSF pGSN on post-SAH Day 7 (r = -0.38; P = 0.05). Conclusions-SAH is associated with decreased CSF and blood pGSN and elevated CSF MMP-9. Novel cleaved pGSN fragments are present in CSF of SAH subjects, consistent with pGSN cleavage by MMPs. Because pGSN is known to inhibit inflammatory mediators, these findings suggest that MMPs may reduce pGSN and exacerbate inflammation after SAH. Further studies are warranted to investigate the mechanisms underlying MMP-pGSN signaling in SAH. (Stroke. 2011; 42: 3624-3627.) C1 [Ning, MingMing] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Clin Prote Res Ctr,Dept Neurol, Boston, MA 02114 USA. [Chou, Sherry H. -Y.; Konigsberg, Rachael G.; Simmons, Suzanne; Bauer, David; Feske, Steven K.] Harvard Univ, Sch Med, Dept Neurol, Brigham & Womens Hosp, Boston, MA 02115 USA. [Lee, Po-Shun; Gallacci, Dana; Chiou, Terry] Harvard Univ, Sch Med, Translat Med Div, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Ning, MM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Clin Prote Res Ctr,Dept Neurol, Boston, MA 02114 USA. EM ning@hms.harvard.edu RI Chou, Sherry/G-5779-2015 FU American Heart Association [10CRP2610341]; Harvard Clinical and Translational Science Center/National Institutes of Health [5KL2RR025757]; National Institute of Neurological Disorders and Stroke [K23-NS073806, R21-NS52498, R01-NS48422, R37-NS37074, P01-NS55104] FX Supported by the American Heart Association (10CRP2610341), Harvard Clinical and Translational Science Center/National Institutes of Health (5KL2RR025757), and the National Institute of Neurological Disorders and Stroke (K23-NS073806, R21-NS52498, R01-NS48422, R37-NS37074, P01-NS55104). NR 12 TC 18 Z9 18 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD DEC PY 2011 VL 42 IS 12 BP 3624 EP 3627 DI 10.1161/STROKEAHA.111.631135 PG 4 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 860IH UT WOS:000297941500060 PM 21940962 ER PT J AU Zaganas, I Halpin, AP Oleinik, A Alegakis, A Kotzamani, D Zafiris, S Chlapoutaki, C Tsimoulis, D Giannakoudakis, E Chochlidakis, N Ntailiani, A Valatsou, C Papadaki, E Vakis, A Furie, KL Greenberg, SM Plaitakis, A AF Zaganas, Ioannis Halpin, Amy P. Oleinik, Alexandra Alegakis, Athanasios Kotzamani, Dimitra Zafiris, Spiros Chlapoutaki, Chryssanthi Tsimoulis, Dimitris Giannakoudakis, Emmanouil Chochlidakis, Nikolaos Ntailiani, Aikaterini Valatsou, Christina Papadaki, Efrosini Vakis, Antonios Furie, Karen L. Greenberg, Steven M. Plaitakis, Andreas TI A Comparison of Acute Hemorrhagic Stroke Outcomes in 2 Populations The Crete-Boston Study SO STROKE LA English DT Article DE dexamethasone; ICH; stroke management ID SUPRATENTORIAL INTRACEREBRAL HEMORRHAGE; DEXAMETHASONE AB Background and Purpose-Although corticosteroid use in acute hemorrhagic stroke is not widely adopted, management with intravenous dexamethasone has been standard of care at the University Hospital of Heraklion, Crete with observed outcomes superior to those reported in the literature. To explore this further, we conducted a retrospective, multivariable-adjusted 2-center study. Methods-We studied 391 acute hemorrhagic stroke cases admitted to the University Hospital of Heraklion, Crete between January 1997 and July 2010 and compared them with 510 acute hemorrhagic stroke cases admitted to Massachusetts General Hospital, Boston, from January 2003 to September 2009. Of the Cretan cases, 340 received a tapering scheme of intravenous dexamethasone, starting with 16 to 32 mg/day, whereas the Boston patients were managed without steroids. Results-The 2 cohorts had comparable demographics and stroke severity on admission, although anticoagulation was more frequent in Boston. The in-hospital mortality was significantly lower on Crete (23.8%, n = 340) than in Boston (38.0%, n = 510; P < 0.001) as was the 30-day mortality (Crete: 25.4%, n = 307; Boston: 39.4%, n = 510; P < 0.001). Exclusion of patients on anticoagulants showed even greater differences (30-day mortality: Crete 20.8%; n = 259; Boston 37.0%; n = 359; P < 0.001). The improved survival on Crete was observed 3 days after initiation of intravenous dexamethasone and was pronounced for deep-seated hemorrhages. After adjusting for acute hemorrhagic stroke volume/location, Glasgow Coma Scale, hypertension, diabetes mellitus, smoking, coronary artery disease and statin, antiplatelet, and anticoagulant use, intravenous dexamethasone treatment was associated with better functional outcomes and significantly lower risk of death at 30 days (OR, 0.357; 95% CI, 0.174-0.732). Conclusions-This study suggests that intravenous dexamethasone improves outcome in acute hemorrhagic stroke and supports a randomized clinical trial using this approach. (Stroke. 2011; 42: 3640-3642.) C1 [Zaganas, Ioannis; Kotzamani, Dimitra; Zafiris, Spiros; Chlapoutaki, Chryssanthi; Tsimoulis, Dimitris; Giannakoudakis, Emmanouil; Plaitakis, Andreas] Univ Hosp Herakl, Dept Neurol, Iraklion 71021, Crete, Greece. [Alegakis, Athanasios] Univ Hosp Herakl, Dept Toxicol, Iraklion 71021, Crete, Greece. [Chochlidakis, Nikolaos; Vakis, Antonios] Univ Hosp Herakl, Dept Neurosurg, Iraklion 71021, Crete, Greece. [Ntailiani, Aikaterini; Valatsou, Christina; Papadaki, Efrosini] Univ Hosp Herakl, Dept Radiol, Iraklion 71021, Crete, Greece. [Halpin, Amy P.; Oleinik, Alexandra; Furie, Karen L.; Greenberg, Steven M.] Massachusetts Gen Hosp, Stroke Serv, Boston, MA 02114 USA. RP Plaitakis, A (reprint author), Univ Hosp Herakl, Dept Neurol, Iraklion 71021, Crete, Greece. EM plaitakis@yahoo.com OI Alegakis, Athanasios/0000-0001-6507-8691 FU Association for Research and Treatment of Neurologic Disorders of Crete "EY ZHN"; National Institutes of Health [2R01 AG26484] FX Supported by the Association for Research and Treatment of Neurologic Disorders of Crete "EY ZHN" (I.Z., A.P.) and grant 2R01 AG26484 from the National Institutes of Health (S.M.G.). NR 10 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD DEC PY 2011 VL 42 IS 12 BP 3640 EP U495 DI 10.1161/STROKEAHA.111.632174 PG 14 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 860IH UT WOS:000297941500065 PM 22020030 ER PT J AU Prevost, TP Jin, G de Moya, MA Alam, HB Suresh, S Socrate, S AF Prevost, Thibault P. Jin, Guang de Moya, Marc A. Alam, Hasan B. Suresh, Subra Socrate, Simona TI Dynamic mechanical response of brain tissue in indentation in vivo, in situ and in vitro SO ACTA BIOMATERIALIA LA English DT Article DE Brain indentation; Porcine; Viscoelasticity; Constitutive properties; Brain injury ID MAGNETIC-RESONANCE ELASTOGRAPHY; VISCOELASTIC PROPERTIES; DURA-MATER; BEHAVIOR; SHEAR; BIOMECHANICS; INJURY; DEFORMATION; COMPRESSION; ELASTICITY AB Characterizing the dynamic mechanical properties of brain tissue is deemed important for developing a comprehensive knowledge of the mechanisms underlying brain injury. The results gathered to date on the tissue properties have been mostly obtained in vitro. Learning how these results might differ quantitatively from those encountered in vivo is a critical step towards the development of biofidelic brain models. The present study provides novel and unique experimental results on, and insights into, brain biorheology in vivo, in situ and in vitro, at large deformations, in the quasi-static and dynamic regimes. The nonlinear dynamic response of the cerebral cortex was measured in indentation on the exposed frontal and parietal lobes of anesthetized porcine subjects. Load-unload cycles were applied to the tissue surface at sinusoidal frequencies of 10, 1, 0.1 and 0.01 Hz. Ramp-relaxation tests were also conducted to assess the tissue viscoelastic behavior at longer times. After euthanasia, the indentation test sequences were repeated in situ on the exposed cortex maintained in its native configuration within the cranium. Mixed gray and white matter samples were subsequently excised from the superior cortex to be subjected to identical indentation test segments in vitro within 6-7 h post mortem. The main response features (e.g. nonlinearities, rate dependencies, hysteresis and conditioning) were measured and contrasted in vivo, in situ and in vitro. The indentation response was found to be significantly stiffer in situ than in vivo. The consistent, quantitative set of mechanical measurements thereby collected provides a preliminary experimental database, which may be used to support the development of constitutive models for the study of mechanically mediated pathways leading to traumatic brain injury. (C) 2011 Acts Materialia Inc. Published by Elsevier Ltd. All rights reserved. C1 [Socrate, Simona] MIT, Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Prevost, Thibault P.; Suresh, Subra] MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA. [Jin, Guang; de Moya, Marc A.; Alam, Hasan B.] Massachusetts Gen Hosp, Dept Surg, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. RP Socrate, S (reprint author), MIT, Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. EM ssocrate@mit.edu FU US Army Research Office; Joint Improvised Explosive Devices Defeat Organization [W911NF-07-1-0035]; US Army Medical Research Material Command [GRANTT00521959]; MIT Institute for Soldier Nanotechnologies [W911NF-07-D-0004]; Ecole Nationale des Ponts et Chaussees (Universite Paris-Est, France); Singapore-MIT Alliance (SMA); Interdisciplinary Research Group on Infectious Diseases at the Singapore-MIT Alliance for Research and Technology (SMART) FX This work was supported by the US Army Research Office and Joint Improvised Explosive Devices Defeat Organization, under Contract No. W911NF-07-1-0035; the US Army Medical Research Material Command GRANTT00521959 (to HBA); the MIT Institute for Soldier Nanotechnologies, under contract number W911NF-07-D-0004; Ecole Nationale des Ponts et Chaussees (Universite Paris-Est, France); the Computational Systems Biology Programme of the Singapore-MIT Alliance (SMA); and the Interdisciplinary Research Group on Infectious Diseases at the Singapore-MIT Alliance for Research and Technology (SMART). The authors are grateful to Dr. Asha Balakrishnan for designing the testing frame used in the in vivo experiments. NR 54 TC 36 Z9 37 U1 5 U2 37 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1742-7061 J9 ACTA BIOMATER JI Acta Biomater. PD DEC PY 2011 VL 7 IS 12 BP 4090 EP 4101 DI 10.1016/j.actbio.2011.06.032 PG 12 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 853OV UT WOS:000297436500001 PM 21742064 ER PT J AU Colbert, AP Spaulding, KP Ahn, AC Cutro, JA AF Colbert, Agatha P. Spaulding, Keith P. Ahn, Andrew C. Cutro, Janet A. TI Clinical utility of electrodermal activity at acupuncture points: a narrative review SO ACUPUNCTURE IN MEDICINE LA English DT Review ID DOUBLE-BLIND; SKIN AB Objectives To provide an in-depth analysis of seven well-reported studies that examined electrodermal activity (EDA) at acupuncture points with regard to three commonly held tenets of acupuncture: (1) EDA at pathology-related acupuncture points is distinguishable from non-pathology-related acupuncture points; (2) EDA at acupuncture points can assist in diagnosing and monitoring therapeutic progress; and (3) EDA at acupuncture points is able to identify substances that are either therapeutically beneficial or toxic to an individual. Methods Seven of 29 studies that scored >50% on their quality of reporting 54 essential technical and clinical details of EDA testing in human patients were identified from a previous literature review. Fourteen categories of data were extracted from these seven studies for further discussion. Results Two studies compared EDA at pathology-related auricular acupuncture points to non-pathology-related sites. Two studies correlated EDA measurements at sites other than auricular acupuncture points with the presence of specific medical conditions. The final three studies assessed changes in EDA at acupuncture points on the fingers and toes when different substances were placed in the electrical circuit with the patient. Conclusions This review highlights the heterogeneity of approaches to EDA assessments and the discrepancies between common clinical practice and the scientific evidence to support that practice. It also provides pilot data that suggest EDA testing at auricular acupuncture points may distinguish pathology-related acupuncture points from non-pathology-related points; decreased skin conductance correlates with tiredness or low energy; and EDA testing at the Jing-Well acupuncture points, on the tips of the fingers and toes, may assist in monitoring effectiveness of acupuncture treatment. The evidence does not support the use of VEGA testing for allergic status. C1 [Colbert, Agatha P.] Natl Coll Nat Med, Helfgott Res Inst, Portland, OR 97201 USA. [Spaulding, Keith P.] New England Sch Acupuncture, Newton, MA USA. [Ahn, Andrew C.] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Ahn, Andrew C.] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. [Cutro, Janet A.] Northeastern Univ, Dept Phys, Boston, MA 02115 USA. RP Colbert, AP (reprint author), Natl Coll Nat Med, Helfgott Res Inst, 049 SW Porter St, Portland, OR 97201 USA. EM acolbert@ncnm.edu RI cmu, library/L-1810-2013 NR 20 TC 2 Z9 2 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0964-5284 J9 ACUPUNCT MED JI Acupunct. Med. PD DEC PY 2011 VL 29 IS 4 BP 270 EP 275 DI 10.1136/acupmed-2011-010021 PG 6 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 857CJ UT WOS:000297691600006 PM 22002962 ER PT J AU Green, SM Selzer, F Mulukutla, SR Tadajweski, EJ Green, JA Wilensky, RL Laskey, WK Cohen, HA Rao, SV Weisbord, SD Lee, JS Reis, SE Kip, KE Kelsey, SF Williams, DO Marroquin, OC AF Green, Sandy M. Selzer, Faith Mulukutla, Suresh R. Tadajweski, Edward J. Green, Jamie A. Wilensky, Robert L. Laskey, Warren K. Cohen, Howard A. Rao, Sunil V. Weisbord, Steven D. Lee, Joon S. Reis, Steven E. Kip, Kevin E. Kelsey, Sheryl F. Williams, David O. Marroquin, Oscar C. TI Comparison of Bare-Metal and Drug-Eluting Stents in Patients with Chronic Kidney Disease (from the NHLBI Dynamic Registry) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID PERCUTANEOUS CORONARY INTERVENTION; GLOMERULAR-FILTRATION-RATE; RENAL-INSUFFICIENCY; ARTERY-DISEASE; CARDIOVASCULAR OUTCOMES; MYOCARDIAL-INFARCTION; THROMBOSIS; ANGIOPLASTY; EVENTS; ERA AB Patients with chronic kidney disease (CKD) have a disproportionate burden of coronary artery disease and commonly undergo revascularization. The role and safety of percutaneous coronary intervention (PCI) using drug-eluting stents (DESs) verses bare-metal stents in patients with CKD not on renal replacement therapy has not been fully evaluated. This study investigated the efficacy and safety of DES in patients with CKD not on renal replacement therapy. Patients were drawn from the National Heart, Lung, and Blood Institute Dynamic Registry and were stratified by renal function based on estimated glomerular filtration rate (GFR). Of the 4,157 participants, 1,108 had CKD ("low GFR" <60 ml/min/1.73 m(2)), whereas 3,049 patients had normal renal function ("normal GFR" >= 60 ml/min/1.73 m(2)). For each stratum of renal function we compared risk of death, myocardial infarction, or repeat revascularization between subjects who received DESs and bare-metal stents at the index procedure. Patients with low GFR had higher 1-year rates of death and myocardial infarction and a decreased rate of repeat revascularization compared to patients with normal GFR. Use of DESs was associated with a decreased need for repeat revascularization in the normal-GFR group (adjusted hazard ratio 0.63, 95% confidence interval 0.50 to 0.79, p <0.001) but not in the low-GFR group (hazard ratio 0.69, 95% confidence interval 0.45 to 1.06, p = 0.09). Risks of death and myocardial infarction were not different between the 2 stents in either patient population. In conclusion, presence of CKD predicted poor outcomes after PCI with high rates of mortality regardless of stent type. The effect of DES in decreasing repeat revascularization appeared to be attenuated in these patients. (C) 2011 Elsevier Inc. All rights reserved. (Am J Cardiol 2011;108:1658-1664) C1 [Green, Sandy M.; Mulukutla, Suresh R.; Tadajweski, Edward J.; Green, Jamie A.; Weisbord, Steven D.; Lee, Joon S.; Reis, Steven E.; Marroquin, Oscar C.] Univ Pittsburgh, Med Ctr, Inst Heart & Vasc, Pittsburgh, PA 15260 USA. [Wilensky, Robert L.] Univ Penn Hlth Syst, Philadelphia, PA USA. [Laskey, Warren K.] Univ New Mexico, Albuquerque, NM USA. [Cohen, Howard A.] Lenox Hill Heart & Vasc Inst, New York, NY USA. [Rao, Sunil V.] Duke Univ, Med Ctr, Durham, NC USA. [Weisbord, Steven D.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Kip, Kevin E.] Univ S Florida, Tampa, FL USA. [Williams, David O.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Selzer, Faith; Mulukutla, Suresh R.; Kelsey, Sheryl F.; Marroquin, Oscar C.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. RP Marroquin, OC (reprint author), Univ Pittsburgh, Med Ctr, Inst Heart & Vasc, Pittsburgh, PA 15260 USA. EM marroquinoc@upmc.edu RI Reis, Steven/J-3957-2014; Marroquin, Oscar/F-2214-2015 OI Marroquin, Oscar/0000-0002-0909-0319 FU National Heart, Lung, and Blood Institute, Bethesda, Maryland [HL033292] FX This study was supported in part by Grant HL033292 from the National Heart, Lung, and Blood Institute, Bethesda, Maryland. NR 30 TC 10 Z9 10 U1 1 U2 4 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD DEC 1 PY 2011 VL 108 IS 11 BP 1658 EP 1664 DI 10.1016/j.amjcard.2011.07.029 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 859MH UT WOS:000297880000022 PM 21890077 ER PT J AU Au, DH AF Au, David H. TI Health Care Reform and Comparative Effectiveness Research in Critical Care Medicine SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Editorial Material ID COSTS C1 [Au, David H.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. [Au, David H.] Univ Washington, Div Pulm & Crit Care Med, Seattle, WA 98195 USA. RP Au, DH (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. NR 15 TC 0 Z9 0 U1 0 U2 2 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD DEC 1 PY 2011 VL 184 IS 11 BP 1219 EP 1220 DI 10.1164/rccm.201107-1354ED PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 855NU UT WOS:000297572100003 PM 22162878 ER PT J AU Haspel, JA Choi, AMK AF Haspel, Jeffrey A. Choi, Augustine M. K. TI Autophagy A Core Cellular Process with Emerging Links to Pulmonary Disease SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Review DE autophagy; macroautophagy; lung; disease; chronic obstructive pulmonary disease ID CHAPERONE-MEDIATED AUTOPHAGY; ENDOPLASMIC-RETICULUM; MYCOBACTERIUM-TUBERCULOSIS; ELECTRON-MICROSCOPY; MAMMALIAN AUTOPHAGY; IN-VIVO; INTRACELLULAR MYCOBACTERIA; TISSUE TRANSGLUTAMINASE; MONITORING AUTOPHAGY; REGULATES AUTOPHAGY AB Autophagy is a highly conserved homeostatic pathway by which cells transport damaged proteins and organelles to lysosomes for degradation. Dysregulation of autophagy contributes to the pathogenesis of clinically important disorders in a variety of organ systems but, until recently, little was known about its relationship to diseases of the lung. However, there is now growing evidence at the basic research level that autophagy is linked to the pathogenesis of important pulmonary disorders such as chronic obstructive pulmonary disease, cystic fibrosis, and tuberculosis. In this review, we provide an introduction to the field of autophagy research geared to clinical and research pulmonologists. We focus on the best-studied autophagic mechanism, macroautophagy, and summarize studies that link the regulation of this pathway to pulmonary disease. Last, we offer our perspective on how a better understanding of macroautophagy might be used for designing novel therapies for pulmonary disorders. C1 [Haspel, Jeffrey A.; Choi, Augustine M. K.] Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care Med, Boston, MA 02115 USA. [Haspel, Jeffrey A.] Vet Affairs Boston Healthcare Syst, Pulm & Crit Care Med Sect, Boston, MA USA. RP Choi, AMK (reprint author), Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care Med, 75 Francis St, Boston, MA 02115 USA. EM amchoi@rics.bwh.harvard.edu FU NIH [T32 HL007633, R03 HL097005] FX Supported by NIH T32 HL007633 and R03 HL097005. NR 122 TC 26 Z9 26 U1 0 U2 6 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD DEC 1 PY 2011 VL 184 IS 11 BP 1237 EP 1246 DI 10.1164/rccm.201106-0966CI PG 10 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 855NU UT WOS:000297572100013 PM 21836133 ER PT J AU Sim, JA Gadikota, HR Li, JS Li, GA Gill, TJ AF Sim, Jae Ang Gadikota, Hemanth R. Li, Jing-Sheng Li, Guoan Gill, Thomas J. TI Biomechanical Evaluation of Knee Joint Laxities and Graft Forces After Anterior Cruciate Ligament Reconstruction by Anteromedial Portal, Outside-In, and Transtibial Techniques SO AMERICAN JOURNAL OF SPORTS MEDICINE LA English DT Article DE anterior cruciate ligament reconstruction; anteromedial portal; outside-in; transtibial; knee kinematics ID FEMORAL TUNNEL PLACEMENT; 2-INCISION TECHNIQUE; ACL RECONSTRUCTION; TIBIAL TUNNEL; TENDON AB Background: Recently, anatomic anterior cruciate ligament (ACL) reconstruction is emphasized to improve joint laxity and to potentially avert initiation of cartilage degeneration. There is a paucity of information on the efficacy of ACL reconstructions by currently practiced tunnel creation techniques in restoring normal joint laxity. Study Design: Controlled laboratory study. Hypothesis: Anterior cruciate ligament reconstruction by the anteromedial (AM) portal technique, outside-in (OI) technique, and modified transtibial (TT) technique can equally restore the normal knee joint laxity and ACL forces. Methods: Eight fresh-frozen human cadaveric knee specimens were tested using a robotic testing system under an anterior tibial load (134 N) at 0 degrees, 30 degrees, 60 degrees, and 90 degrees of flexion and combined torques (10-N.m valgus and 5-N.m internal tibial torques) at 0 degrees and 30 degrees of flexion. Knee joint kinematics, ACL, and ACL graft forces were measured in each knee specimen under 5 different conditions (ACL-intact knee, ACL-deficient knee, ACL-reconstructed knee by AM portal technique, ACL-reconstructed knee by OI technique, and ACL-reconstructed knee by TT technique). Results: Under anterior tibial load, no significant difference was observed between the 3 reconstructions in terms of restoring anterior tibial translation (P > .05). However, none of the 3 ACL reconstruction techniques could completely restore the normal anterior tibial translations (P < .05). Under combined tibial torques, both AM portal and OI techniques closely restored the normal knee anterior tibial translation (P > .05) at 0 degrees of flexion but could not do so at 30 degrees of flexion (P < .05). The ACL reconstruction by the TT technique was unable to restore normal anterior tibial translations at both 0 degrees and 30 degrees of flexion under combined tibial torques (P < .05). Forces experienced by the ACL grafts in the 3 reconstruction techniques were lower than those experienced by normal ACL under both the loading conditions. Conclusion: Anterior cruciate ligament reconstructions by AM portal, OI, and modified TT techniques are biomechanically comparable with each other in restoring normal knee joint laxity and in situ ACL forces. Clinical Relevance: Anterior cruciate ligament reconstructions by AM portal, OI, and modified TT techniques result in similar knee joint laxities. Technical perils and pearls should be carefully considered before choosing a tunnel creating technique. C1 [Sim, Jae Ang; Gadikota, Hemanth R.; Li, Jing-Sheng; Li, Guoan; Gill, Thomas J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Bioengn Lab,Dept Orthopaed Surg, Boston, MA 02114 USA. RP Li, GA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Bioengn Lab,Dept Orthopaed Surg, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM gli1@partners.org FU National Research Foundation of Korea; Korean Government [NRF-2011-013-E00029]; National Institutes of Health [R01AR055612] FX One or more of the authors has declared the following potential conflict of interest or source of funding: This work was supported by the National Research Foundation of Korea Grant funded by the Korean Government (NRF-2011-013-E00029) and by the National Institutes of Health (R01AR055612). NR 23 TC 23 Z9 26 U1 0 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0363-5465 J9 AM J SPORT MED JI Am. J. Sports Med. PD DEC PY 2011 VL 39 IS 12 BP 2604 EP 2610 DI 10.1177/0363546511420810 PG 7 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 857GA UT WOS:000297704300011 PM 21908717 ER PT J AU Rosso, C Kovtun, K Dow, W McKenzie, B Nazarian, A DeAngelis, JP Ramappa, AJ AF Rosso, Claudio Kovtun, Konstantin Dow, William McKenzie, Brett Nazarian, Ara DeAngelis, Joseph P. Ramappa, Arun J. TI Comparison of All-Inside Meniscal Repair Devices With Matched Inside-Out Suture Repair SO AMERICAN JOURNAL OF SPORTS MEDICINE LA English DT Article DE meniscus repair; all-inside; initial displacement; biomechanics ID BIOMECHANICAL ANALYSIS; FIXATION STRENGTH; HORIZONTAL SUTURE; FAILURE STRENGTH; MEDIAL MENISCUS; IN-VITRO; ARROW; ANCHORS; SYSTEM AB Background: All-inside meniscal repairs are performed with increasing frequency because of the availability of newly developed devices. A comparison of their biomechanical characteristics may aid physicians in selecting a method of meniscal repair. Hypothesis: All-inside meniscal repairs will be superior to their inside-out controls in response to cyclic loading and load-to-failure testing. Study Design: Controlled laboratory study. Methods: Sixty-six bucket-handle tears in matched porcine menisci were repaired using the Ultra FasT-Fix, Meniscal Cinch, Ultrabraid No. 0, and FiberWire 2-0 sutures. Initial displacement, cyclic loading (100, 300, and 500 cycles), and load-to-failure testing were performed. The displacement, response to cyclic loading, and mode of failure were recorded. The stiffness was calculated. Results: The Meniscal Cinch demonstrated a significantly higher initial displacement than the other methods tested (P = .04). No significant difference was found among the methods in response to cyclic loading. The inside-out FiberWire repair demonstrated the highest load to failure (120.8 +/- 23.5 N) and was significantly higher than both the Meniscal Cinch (64.8 +/- 24.1 N, P < .001) and the Ultra FasT-Fix (88.3 +/- 14.3 N, P = .002). It was not significantly higher than the inside-out Ultrabraid suture repair (98.8 +/- 29.2 N). The inside-out FiberWire repair had the highest stiffness (28.7 +/- 7.8 N/mm). It was significantly higher than the Meniscal Cinch (18.0 +/- 8.8 N/mm, P = .01). The most common mode of failure in all methods was suture failure. Conclusion: An inside-out suture repair affords surgeons the best overall biomechanical characteristics of the devices tested (initial displacement, response to cyclic loading, and load to failure). For an all-inside repair, the Ultra FasT-Fix reproduces the characteristics of its matched inside-out suture repair more closely than the Meniscal Cinch. Clinical Relevance: Inside-out sutures and all-inside devices have similar responses to cyclic loading. C1 [Ramappa, Arun J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Ctr Adv Orthopaed Studies,BIDMC Dept Orthopaed, Boston, MA 02215 USA. RP Ramappa, AJ (reprint author), BIDMC Dept Orthopaed, 330 Brookline Ave,ST 10, Boston, MA 02215 USA. EM aramappa@bidmc.harvard.edu RI DeAngelis, Joseph/N-8002-2014; OI DeAngelis, Joseph/0000-0001-6617-9697; Rosso, Claudio/0000-0003-2846-6999 FU Swiss National Science Foundation SNF; Swiss Society for Orthopaedic Surgery and Traumatology; Arthrex and Smith Nephew FX One or more of the authors has declared the following potential conflict of interest or source of funding: Materials for this study were received from Arthrex and Smith & Nephew. Dr DeAngelis is a consultant to Connective Orthopaedics (Woburn, Massachusetts). Funding from the Swiss National Science Foundation SNF (to C. R.) and the Swiss Society for Orthopaedic Surgery and Traumatology (to C. R.) supported this project. NR 26 TC 12 Z9 16 U1 0 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0363-5465 J9 AM J SPORT MED JI Am. J. Sports Med. PD DEC PY 2011 VL 39 IS 12 BP 2634 EP 2639 DI 10.1177/0363546511424723 PG 6 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 857GA UT WOS:000297704300015 PM 21997730 ER PT J AU Yamada, K Hirakata, A Tchipashvili, V Shimizu, A Iwaki, H Griesemer, A Vallabhajosyula, P Moran, S Sachs, DH AF Yamada, K. Hirakata, A. Tchipashvili, V. Shimizu, A. Iwaki, H. Griesemer, A. Vallabhajosyula, P. Moran, S. Sachs, D. H. TI Composite Islet-Kidneys From Single Baboon Donors Cure Diabetes Across Fully Allogenic Barriers SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Islet transplantation; kidney allograft; nonhuman primate; vascularization ID MINIATURE SWINE; CELL TRANSPLANTATION; RECIPIENTS; TOLERANCE; PANCREAS; ACTIVATION; ALLOGRAFTS; INDUCTION; SURVIVAL; THERAPY AB We have previously reported that transplantation (Tx) of prevascularized donor islets as composite islet-kidneys (IK) reverses diabetic hyperglycemia in miniature swine. In order to test the potential clinical applicability of this strategy, we have extended it to a fully allogeneic nonhuman primate model. IKs were prepared in baboons by isolating islets from 50% to 70% partial pancreatectomies and injecting them under the autologous renal capsule, allowing vascularization before allogeneic Tx. Baboons with diabetes induced by stereptozotocin or total pancreatectomy, received composite IKs (n = 3) or free islets under the renal capsule or intraportally (n = 3), across fully allogeneic barriers with an immunosuppressive regimen consisting of ATG followed by MMF and tacrolimus. FBS of two of IK recipients decreased immediately after Tx and no insulin therapy was required throughout the experimental period (225 and 301 days). In contrast, all recipients of allogeneic free islets showed unstable FBS levels and required insulin within 2 months. We conclude that in addition to maintaining creatinine in the normal range, fully allogeneic IKs from single primate donors can achieve glucose regulation without insulin therapy, while free islets do not. These results support the feasibility of composite allogeneic IK Tx as a potential cure for end-stage diabetic nephropathy. C1 [Yamada, K.; Hirakata, A.; Shimizu, A.; Iwaki, H.; Griesemer, A.; Vallabhajosyula, P.; Moran, S.; Sachs, D. H.] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. [Tchipashvili, V.] Joslin Diabet Ctr, Boston, MA 02215 USA. RP Yamada, K (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. EM kaz.yamada@tbrc.mgh.harvard.edu FU NIH NIDDK [U01AI074634-01] FX This work was supported by NIH NIDDK U01AI074634-01. NR 26 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD DEC PY 2011 VL 11 IS 12 BP 2603 EP 2612 DI 10.1111/j.1600-6143.2011.03733.x PG 10 WC Surgery; Transplantation SC Surgery; Transplantation GA 853FO UT WOS:000297411800012 PM 21929644 ER PT J AU Savitski, MM Sweetman, G Askenazi, M Marto, JA Lang, MJ Zinn, N Bantscheff, M AF Savitski, Mikhail M. Sweetman, Gavain Askenazi, Manor Marto, Jarrod A. Lang, Manja Zinn, Nico Bantscheff, Marcus TI Delayed Fragmentation and Optimized Isolation Width Settings for Improvement of Protein Identification and Accuracy of Isobaric Mass Tag Quantification on Orbitrap-Type Mass Spectrometers SO ANALYTICAL CHEMISTRY LA English DT Article ID QUANTITATIVE PROTEOMIC ANALYSIS; ABSOLUTE PROTEIN; MIXTURES; ITRAQ; PEPTIDES; PHOSPHORYLATION; DISSOCIATION; ACQUISITION; INHIBITORS; COMPLEXES AB Fragmentation of multiple peptides in a single tandem mass scan impairs accuracy of isobaric mass tag based quantification. Consequently, practitioners aim at fragmenting peptide ions with the highest possible purity without compromising on sensitivity and coverage achieved in the experiment. Here we report the first systematic study optimizing delayed fragmentation options on Orbitrap instruments. We demonstrate that by delaying peptide fragmentation to occur closer to the apex of the chromatographic peak in liquid chromatography-tandem mass spectrometry (LC-MS/MS) experiments cofragmentation is reduced by 2-fold and peptides are fragmented with 2.8-fold better signal-to-noise ratios. This results in significantly improved accuracy of isobaric mass tag quantification. Further, we measured cofragmentation dependence on isolation width. In comparison to Orbitrap XL instruments the reduced space charging in the Orbitrap Velos enables isolation widths as narrow as 1 Th without impairing coverage, thus substantially reducing cofragmentation. When delayed peptide fragmentation and narrow isolation cofragmentation-induced ratio compression could be reduced by 32% on a log2 scale under width settings were both applied, otherwise identical conditions. C1 [Savitski, Mikhail M.; Sweetman, Gavain; Lang, Manja; Zinn, Nico; Bantscheff, Marcus] Cellzome AG, D-69117 Heidelberg, Germany. [Askenazi, Manor; Marto, Jarrod A.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Askenazi, Manor; Marto, Jarrod A.] Dana Farber Canc Inst, Blais Prote Ctr, Boston, MA 02115 USA. [Askenazi, Manor; Marto, Jarrod A.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Askenazi, Manor] Hebrew Univ Jerusalem, Sudarsky Ctr Computat Biol, Dept Biol Chem, IL-91905 Jerusalem, Israel. RP Bantscheff, M (reprint author), Cellzome AG, Meyerhofstr 1, D-69117 Heidelberg, Germany. EM marcus.bantscheff@cellzome.com NR 42 TC 41 Z9 41 U1 3 U2 19 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD DEC 1 PY 2011 VL 83 IS 23 BP 8959 EP 8967 DI 10.1021/ac201760x PG 9 WC Chemistry, Analytical SC Chemistry GA 854FZ UT WOS:000297481700021 PM 22017476 ER PT J AU Charnin, JE Bateman, BT Bittner, EA AF Charnin, Jonathan E. Bateman, Brian T. Bittner, Edward A. TI Pus in the Ventricles of a Patient with a Lumbar Cerebrospinal Fluid Drain for a Thoracoabdominal Aneurysm Repair SO ANESTHESIOLOGY LA English DT Editorial Material ID EXTRACORPOREAL-CIRCULATION; SAFETY C1 [Charnin, Jonathan E.; Bateman, Brian T.; Bittner, Edward A.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Charnin, JE (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM jcharnin@partners.org NR 5 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD DEC PY 2011 VL 115 IS 6 BP 1302 EP 1302 DI 10.1097/ALN.0b013e3182267c30 PG 1 WC Anesthesiology SC Anesthesiology GA 855RL UT WOS:000297581800023 PM 21709541 ER PT J AU Lech, M Kantner, C Kulkarni, OP Ryu, M Vlasova, E Heesemann, J Anz, D Endres, S Kobayashi, KS Flavell, RA Martin, J Anders, HJ AF Lech, Maciej Kantner, Claudia Kulkarni, Onkar P. Ryu, Mi Vlasova, Ekaterina Heesemann, Juergen Anz, David Endres, Stefan Kobayashi, Koichi S. Flavell, Richard A. Martin, Javier Anders, Hans-Joachim TI Interleukin-1 receptor-associated kinase-M suppresses systemic lupus erythematosus SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID TOLL-LIKE RECEPTORS; MURINE LUPUS; AUTOIMMUNE-DISEASE; IRAK-M; INNATE IMMUNITY; INFLAMMATORY DISEASE; MICE; GLOMERULONEPHRITIS; TOLERANCE; PATHOGENESIS AB Objectives Interleukin-1 receptor-associated kinase (IRAK)-M suppresses Toll-like receptor (TLR)-mediated activation of innate immunity during infection. A similar role was hypothesised for IRAK-M in autoimmunity. Methods Irak-m-deficient mice were crossed with autoimmune C57BL/6-lpr/lpr mice and detailed phenotype analysis was performed. Results Irak-m deficiency converted the mild autoimmune phenotype of C57BL/6-lpr/lpr mice into a massive lymphoproliferative syndrome with lethal autoimmune lung disease and lupus nephritis. Irak-m deficiency induced a number of interferon-related genes, cytokines and plasma cell survival factors in spleen cells of these mice. Irak-m-deficient C57BL/6-lpr/lpr mice showed expansion of autoreactive T cells, dysfunctional regulatory T cells and plasma cells which was associated with increased lupus autoantibody production. TLR7 antagonism almost completely abrogated this phenotype consistent with IRAK-M-mediated suppression of TLR7 signalling in vitro. Conclusions These data identify a previously unknown function of IRAK-M-namely, suppression of TLR7-mediated autoimmunity-and mutant IRAK-M as a previously unknown genetic risk for murine SLE. C1 [Lech, Maciej; Kantner, Claudia; Kulkarni, Onkar P.; Ryu, Mi; Anders, Hans-Joachim] Klinikum Univ Munchen LMU, Med Poliklin, Munich, Germany. [Vlasova, Ekaterina; Heesemann, Juergen] Univ Munich, Max von Pettenkofer Inst Hyg & Med Microbiol, D-80336 Munich, Germany. [Anz, David; Endres, Stefan] Univ Munich, Dept Clin Pharmacol, D-80336 Munich, Germany. [Kobayashi, Koichi S.; Flavell, Richard A.] Yale Univ, Sch Med, Howard Hughes Med Inst, Sect Immunobiol, New Haven, CT 06510 USA. [Kobayashi, Koichi S.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Martin, Javier] CSIC, Inst Parasitol & Biomed Lopez Neyra, Granada, Spain. RP Anders, HJ (reprint author), Univ Munich, Med Poliklin, Pettenkoferstr 8A, D-80336 Munich, Germany. EM hjanders@med.uni-muenchen.de RI Martin, Javier/B-8141-2008 FU Deutsche Forschungsgemeinschaft [AN372/10-1, GRK 1202]; Medical Faculty, University of Munich FX This work was supported by a grant from the Deutsche Forschungsgemeinschaft (AN372/10-1 and GRK 1202) to H-JA. CK was funded by the FoFoLe program of the Medical Faculty, University of Munich. NR 45 TC 18 Z9 18 U1 0 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD DEC PY 2011 VL 70 IS 12 BP 2207 EP 2217 DI 10.1136/ard.2011.155515 PG 11 WC Rheumatology SC Rheumatology GA 855NS UT WOS:000297571900026 PM 21875872 ER PT J AU Monach, PA Tomasson, G Specks, U Stone, JH Cuthbertson, D Krischer, J Ding, LN Fervenza, FC Fessler, BJ Hoffman, GS Ikle, D Kallenberg, CGM Langford, CA Mueller, M Seo, P St Clair, EW Spiera, R Tchao, N Ytterberg, SR Gu, YZ Snyder, RD Merkel, PA AF Monach, Paul A. Tomasson, Gunnar Specks, Ulrich Stone, John H. Cuthbertson, David Krischer, Jeffrey Ding, Linna Fervenza, Fernando C. Fessler, Barri J. Hoffman, Gary S. Ikle, David Kallenberg, Cees G. M. Langford, Carol A. Mueller, Mark Seo, Philip St Clair, E. William Spiera, Robert Tchao, Nadia Ytterberg, Steven R. Gu, Yi-Zhong Snyder, Ronald D. Merkel, Peter A. TI Circulating markers of vascular injury and angiogenesis in antineutrophil cytoplasmic antibody-associated vasculitis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID MICROVASCULAR ENDOTHELIAL-CELLS; C-REACTIVE PROTEIN; WEGENERS-GRANULOMATOSIS; MATRIX METALLOPROTEINASES; KAWASAKI-DISEASE; RENAL-DISEASE; SERUM-LEVELS; FOLLOW-UP; EXPRESSION; GENE AB Objective To identify biomarkers that distinguish between active antineutrophil cytoplasmic antibody (ANCA)associated vasculitis (AAV) and remission in a manner superior or complementary to established markers of systemic inflammation. Methods. Markers of vascular injury and angiogenesis were measured before and after treatment in a large clinical trial in AAV: 163 subjects enrolled in the Rituximab in ANCA-Associated Vasculitis trial were screened for the present study. Serum levels of E-selectin, intercellular adhesion molecule 3 matrix metalloproteinase protein 1 (MMP-1), MMP-3, MMP-9, P-selectin, thrombomodulin, and vascular endothelial growth factor were measured at study screening (time of active disease) and at month 6. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels had been measured at the time of the clinical visit. The primary outcome measure was the difference in marker level between screening and month 6 among patients whose disease was in remission (Birmingham Vasculitis Activity Score for Wegener's granulomatosis [BVAS/WG] score of 0) at month 6. Results. All patients had severe active vasculitis at screening (mean +/- SD BVAS/WG score 8.6 +/- 3.2). Among the 123 patients whose disease was clinically in remission at month 6, levels of all markers except E-selectin showed significant declines. MMP-3 levels were also higher among the 23 patients with active disease at month 6 than among the 123 patients whose disease was in remission. MMP-3 levels correlated weakly with ESR and CRP levels. Conclusion. Many markers of vascular injury and angiogenesis are elevated in severe active AAV and decline with treatment, but MMP-3 appears to distinguish active AAV from remission better than the other markers studied. Further study of MMP-3 is warranted to determine its clinical utility in combination with conventional markers of inflammation and ANCA titers. C1 [Merkel, Peter A.] Boston Univ, Sch Med, Rheumatol Sect, Vasculitis Ctr, Boston, MA 02118 USA. [Specks, Ulrich; Fervenza, Fernando C.; Ytterberg, Steven R.] Mayo Clin, Coll Med, Rochester, MN USA. [Stone, John H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cuthbertson, David; Krischer, Jeffrey] Univ S Florida, Coll Med, Tampa, FL USA. [Ding, Linna] NIAID, NIH, Bethesda, MD 20892 USA. [Fessler, Barri J.] Univ Alabama Birmingham, Birmingham, AL USA. [Hoffman, Gary S.; Langford, Carol A.] Cleveland Clin, Cleveland, OH 44106 USA. [Ikle, David] Rho, Chapel Hill, NC USA. [Kallenberg, Cees G. M.] Univ Groningen, Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands. [Mueller, Mark] Immune Tolerance Network, Bethesda, MD USA. [Seo, Philip] Johns Hopkins Univ, Baltimore, MD USA. [St Clair, E. William] Duke Univ, Durham, NC USA. [Spiera, Robert] Hosp Special Surg, New York, NY 10021 USA. [Tchao, Nadia] Immune Tolerance Network, San Francisco, CA USA. [Gu, Yi-Zhong; Snyder, Ronald D.] Merck Res Labs, Summit, NJ USA. RP Merkel, PA (reprint author), Boston Univ, Sch Med, Rheumatol Sect, Vasculitis Ctr, 72 E Concord St,E533, Boston, MA 02118 USA. EM pmerkel@bu.edu FU Vasculitis Clinical Research Consortium; NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases) [U54-AR-057319, 1-RC1-AR-058303]; NIH (National Center for Research Resources) [U54-RR-019497]; NIH (National Institute of Neurological Disorders and Stroke) [NS-064808]; NIH Office of Rare Diseases Research; NIH (National Institute of Allergy and Infectious Diseases) [N01-AI-15416]; Juvenile Diabetes Research Foundation; Genentech; Biogen Idec; NIH (Mayo Clinic and Foundation: National Center for Research Resources); NIH (Johns Hopkins University: National Center for Research Resources) [RR-025005, K24-AR-049185, K23-AR-052820]; NIH (Boston University: National Center for Research Resources) [RR-025771, M01-RR-00533, K24-AR-02224]; Arthritis Foundation FX This work was sponsored by the Vasculitis Clinical Research Consortium, which received support from the NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases grants U54-AR-057319 and 1-RC1-AR-058303, National Center for Research Resources grant U54-RR-019497, and National Institute of Neurological Disorders and Stroke grant NS-064808) and the NIH Office of Rare Diseases Research. The Rituximab in ANCA-Associated Vasculitis (RAVE) trial was performed with the support of the Immune Tolerance Network, an international clinical research consortium supported by the NIH (National Institute of Allergy and Infectious Diseases contract N01-AI-15416) and the Juvenile Diabetes Research Foundation. Genentech and Biogen Idec provided the study medications and partial funding for the RAVE trial. At the Mayo Clinic and Foundation, Johns Hopkins University, and Boston University, the RAVE trial was supported by the NIH (Mayo Clinic and Foundation: National Center for Research Resources Clinical and Translational Science award RR-024150-01; Johns Hopkins University: National Center for Research Resources Clinical and Translational Science grant RR-025005 and career development awards K24-AR-049185 to Dr. Stone and K23-AR-052820 to Dr. Seo; Boston University: National Center for Research Resources Clinical and Translational Science award RR-025771, grant M01-RR-00533, and career development award K24-AR-02224 to Dr. Merkel). Dr. Monach's work was supported by the Arthritis Foundation (Arthritis Investigator award). NR 32 TC 21 Z9 23 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD DEC PY 2011 VL 63 IS 12 BP 3988 EP 3997 DI 10.1002/art.30615 PG 10 WC Rheumatology SC Rheumatology GA 853XH UT WOS:000297458500040 PM 21953143 ER PT J AU Cannon, GW Mikuls, TR Hayden, CL Ying, J Curtis, JR Reimold, AM Caplan, L Kerr, GS Richards, JS Johnson, DS Sauer, BC AF Cannon, Grant W. Mikuls, Ted R. Hayden, Candace L. Ying, Jian Curtis, Jeffrey R. Reimold, Andreas M. Caplan, Liron Kerr, Gail S. Richards, J. Steuart Johnson, Dannette S. Sauer, Brian C. TI Merging Veterans Affairs rheumatoid arthritis registry and pharmacy data to assess methotrexate adherence and disease activity in clinical practice SO ARTHRITIS CARE & RESEARCH LA English DT Article ID MODIFYING ANTIRHEUMATIC DRUGS; HEALTH-ASSESSMENT QUESTIONNAIRE; MEDICATION ADHERENCE; PREDICTORS; NONADHERENCE; PATIENT; CARE; PERSISTENCE; MANAGEMENT; DATABASES AB Objective The Veterans Affairs (VA) Rheumatoid Arthritis (VARA) registry and the VA Pharmacy Benefits Management database were linked to determine the association of methotrexate (MTX) adherence with rheumatoid arthritis (RA) disease activity. Methods. For each patient, the medication possession ratio (MPR) was calculated for the first episode of MTX exposure of a duration of > 12 weeks for both new and established MTX users. High MTX adherence was defined as an MPR > 0.80 and low MTX adherence was defined as an MPR < 0.80. For each patient, the mean Disease Activity Score with 28 joints (DAS28) score, erythrocyte sedimentation rate (ESR), and C-reaction protein (CRP) level observed during registry followup were compared in high-versus low-adherence groups. Results. In 455 RA patients, the prescribed doses of MTX (mean +/- SD 16 +/- 4 mg versus 16 +/- 4 mg; P = 0.6) were similar in high-adherence patients (n = 370) in comparison to low-adherence patients (n = 85). However, the actual observed MTX doses taken by patients were significantly higher in the high-adherence group (mean +/- SD 16 +/- 5 mg versus 11 +/- 3 mg; P < 0.001). DAS28 (mean +/- SD 3.6 +/- 1.2 versus 3.9 +/- 1.5; P < 0.02), ESR (mean +/- SD 24 +/- 18 versus 29 +/- 24 mm/hour; P = 0.05), and CRP level (mean +/- SD 1.2 +/- 1.3 versus 1.6 +/- 1.5 mg/dl; P < 0.03) were lower in the high-adherence group compared to those with low MTX adherence. These variances were not explained by differences in baseline demographic features, concurrent treatments, or whether MTX was initiated before or after VARA enrollment. Conclusion. High MTX adherence was associated with improved clinical outcomes in RA patients treated with MTX. Adjustment for potential confounders did not alter the estimated effect of adherence. These results demonstrate the advantages of being able to merge clinical observations with pharmacy databases to evaluate antirheumatic drugs in clinical practice. C1 [Cannon, Grant W.; Hayden, Candace L.; Sauer, Brian C.] George E Wahlen VA Med Ctr, Salt Lake City, UT 84148 USA. [Cannon, Grant W.; Hayden, Candace L.; Ying, Jian; Sauer, Brian C.] Univ Utah, Salt Lake City, UT USA. [Mikuls, Ted R.] Omaha VA Med Ctr, Omaha, NE USA. [Mikuls, Ted R.] Univ Nebraska Med Ctr, Omaha, NE USA. [Curtis, Jeffrey R.] Univ Alabama Birmingham, Birmingham, AL USA. [Reimold, Andreas M.] VA Med Ctr, Dallas, TX USA. [Reimold, Andreas M.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Caplan, Liron] Denver VA Med Ctr, Aurora, CO USA. [Caplan, Liron] Univ Colorado, Aurora, CO USA. [Kerr, Gail S.] Georgetown Univ, VA Med Ctr, Washington, DC USA. [Kerr, Gail S.] Howard Univ, Washington, DC 20059 USA. [Johnson, Dannette S.] Montgomery VA Med Ctr, Jackson, VA USA. [Johnson, Dannette S.] Univ Mississippi, Jackson, MS 39216 USA. RP Cannon, GW (reprint author), George E Wahlen VA Med Ctr, 500 Foothill Blvd, Salt Lake City, UT 84148 USA. EM grant.cannon@va.gov FU VA Health Services [SHP-08-172]; VA; NIH [K23, AR053351]; Agency for Healthcare Research and Quality [R01-HS-018517]; VA Career Development Awards [RCD-06-300-2, CDA-07-221] FX Supported by a VA Health Services Research & Development grant (SHP-08-172). Dr. Mikuls's work was supported by a VA Clinical Science Research & Development Merit award. Dr. Curtis's work was supported by the NIH (grants K23 and AR053351) and the Agency for Healthcare Research and Quality (grant R01-HS-018517). Drs. Caplan and Sauer's work was supported by VA Career Development Awards (RCD-06-300-2 and CDA-07-221). NR 40 TC 26 Z9 26 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2151-464X J9 ARTHRIT CARE RES JI Arthritis Care Res. PD DEC PY 2011 VL 63 IS 12 BP 1680 EP 1690 DI 10.1002/acr.20629 PG 11 WC Rheumatology SC Rheumatology GA 853WV UT WOS:000297457300006 PM 21905260 ER PT J AU Clowse, MEB Copland, SC Hsieh, TC Chow, SC Hoffman, GS Merkel, PA Spiera, RF Davis, JC McCune, WJ Ytterberg, SR St Clair, EW Allen, NB Specks, U Stone, JH AF Clowse, Megan E. B. Copland, Susannah C. Hsieh, Tsung-Cheng Chow, Shein-Chung Hoffman, Gary S. Merkel, Peter A. Spiera, Robert F. Davis, John C., Jr. McCune, W. Joseph Ytterberg, Steven R. St Clair, E. William Allen, Nancy B. Specks, Ulrich Stone, John H. CA WGET Res Grp TI Ovarian reserve diminished by oral cyclophosphamide therapy for granulomatosis with polyangiitis (Wegener's) SO ARTHRITIS CARE & RESEARCH LA English DT Article ID ANTI-MULLERIAN HORMONE; INTRAVENOUS CYCLOPHOSPHAMIDE; CHEMOTHERAPY; FERTILITY; WOMEN; PRESERVATION; VASCULITIS; FAILURE; MARKER; PULSE AB Objective Standard treatment for severe granulomatosis with polyangiitis (Wegener's) (GPA) is daily oral cyclophosphamide (CYC), a cytotoxic agent associated with ovarian failure. In this study, we assessed the rate of diminished ovarian reserve in women with GPA who received CYC versus methotrexate (MTX). Methods. Patients in the Wegener's Granulomatosis Etanercept Trial received either daily CYC or weekly MTX and were randomized to etanercept or placebo. For all women ages <50 years, plasma samples taken at baseline or early in the study were evaluated against samples taken later in the study to compare levels of anti- Mullerian hormone (AMH) and follicle- stimulating hormone (FSH), endocrine markers of remaining egg supply. Diminished ovarian reserve was defined as an AMH level of < 1.0 ng/ml. Results. Of 42 women in this analysis (mean age 35 years), 24 had CYC exposure prior to enrollment and 28 received the drug during the study. At study entry, women with prior CYC exposure had significantly lower AMH, higher FSH, and a higher rate of early menstruation cessation. For women with normal baseline ovarian function, 6 of 8 who received CYC during the trial developed diminished ovarian reserve, compared to 0 of 4 who did not receive CYC (P < 0.05). Changes in AMH correlated inversely with cumulative CYC dose (P < 0.01), with a 0.74 ng/ml decline in AMH level for each 10 gm of CYC. Conclusion. Daily oral CYC, even when administered for less than 6 months, causes diminished ovarian reserve, as indicated by low AMH levels. These data highlight the need for alternative treatments for GPA in women of childbearing age. C1 [Clowse, Megan E. B.; Copland, Susannah C.; Hsieh, Tsung-Cheng; Chow, Shein-Chung; St Clair, E. William; Allen, Nancy B.] Duke Univ, Med Ctr, Durham, NC USA. [Hoffman, Gary S.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Merkel, Peter A.] Boston Univ, Boston, MA 02215 USA. [Spiera, Robert F.] Hosp Special Surg, New York, NY 10021 USA. [Davis, John C., Jr.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [McCune, W. Joseph] Univ Michigan, Ann Arbor, MI 48109 USA. [Ytterberg, Steven R.; Specks, Ulrich] Mayo Clin, Rochester, MN USA. [Stone, John H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Clowse, MEB (reprint author), Box 3535,Trent Dr, Durham, NC 27710 USA. EM megan.clowse@duke.edu FU Amgen; NIH National Institute of Arthritis and Musculoskeletal and Skin Diseases [N01-AR-9-2240]; FDA Office of Orphan Products [FD-R-001652-01]; NIH National Center for Research Resources [M01-RR0-2719]; Boston University [M01-RR0-00533]; University of Michigan [M01-RR-0042]; Duke University [M01-RR-30]; Duke University Medical Center's Department of Obstetrics and Gynecology; Genentech FX Supported by Amgen; a contract with the NIH National Institute of Arthritis and Musculoskeletal and Skin Diseases (N01-AR-9-2240); a grant from the FDA Office of Orphan Products (FD-R-001652-01); General Clinical Research Center grants from the NIH National Center for Research Resources to Johns Hopkins University School of Medicine (M01-RR0-2719), Boston University (M01-RR0-00533), University of Michigan (M01-RR-0042), and Duke University (M01-RR-30); and the Charles Hammond Research Fund of Duke University Medical Center's Department of Obstetrics and Gynecology.; Dr. Allen has received consultant fees, speaking fees, and/or honoraria (less than $10,000) from Genentech. NR 14 TC 24 Z9 25 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 2151-464X J9 ARTHRIT CARE RES JI Arthritis Care Res. PD DEC PY 2011 VL 63 IS 12 BP 1777 EP 1781 DI 10.1002/acr.20605 PG 5 WC Rheumatology SC Rheumatology GA 853WV UT WOS:000297457300019 PM 22127969 ER PT J AU LaBode, V Sher, L AF LaBode, Vanessa Sher, Leo TI Suicide prevention in older men: do medical professionals know enough? SO AUSTRALIAN AND NEW ZEALAND JOURNAL OF PSYCHIATRY LA English DT Letter C1 [LaBode, Vanessa] James J Peters Vet Adm Med Ctr, New York, NY USA. Mt Sinai Sch Med, New York, NY USA. RP LaBode, V (reprint author), James J Peters Vet Adm Med Ctr, New York, NY USA. NR 5 TC 1 Z9 1 U1 0 U2 3 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0004-8674 J9 AUST NZ J PSYCHIAT JI Aust. N. Z. J. Psych. PD DEC PY 2011 VL 45 IS 12 BP 1094 EP 1094 DI 10.3109/00048674.2011.613066 PG 1 WC Psychiatry SC Psychiatry GA 854BK UT WOS:000297469300014 PM 22014105 ER PT J AU Hijiya, N Thomson, B Isakoff, MS Silverman, LB Steinherz, PG Borowitz, MJ Kadota, R Cooper, T Shen, V Dahl, G Thottassery, JV Jeha, S Maloney, K Paul, JA Barry, E Carroll, WL Gaynon, PS AF Hijiya, Nobuko Thomson, Blythe Isakoff, Michael S. Silverman, Lewis B. Steinherz, Peter G. Borowitz, Michael J. Kadota, Richard Cooper, Todd Shen, Violet Dahl, Gary Thottassery, Jaideep V. Jeha, Sima Maloney, Kelly Paul, Jo-Anne Barry, Elly Carroll, William L. Gaynon, Paul S. TI Phase 2 trial of clofarabine in combination with etoposide and cyclophosphamide in pediatric patients with refractory or relapsed acute lymphoblastic leukemia SO BLOOD LA English DT Article ID FLUDARABINE; EXPRESSION; CHILDREN; CELLS; SENSITIVITY; CLADRIBINE; RESISTANCE; ANALOG; MODEL; DNA AB The outcomes in children with refractory/relapsed (R/R) acute lymphoblastic leukemia (ALL) are dismal. The efficacy and safety of intravenous clofarabine 40 mg/m(2) per day, cyclophosphamide 440 mg/m(2) per day, and etoposide 100 mg/m(2) per day for 5 consecutive days in pediatric patients with R/R ALL was evaluated in this phase 2 study. The primary endpoint was overall response rate (complete remission [CR] plus CR without platelet recovery [CRp]). Among the 25 patients (median age, 14 years; pre-B cell ALL, 84%; >= 2 prior regimens: 84%; refractory to previous regimen: 60%), the overall response rate was 44% (7 CR, 4 CRp) with a 67.3-week median duration or remission censored at last follow-up. Most patients proceeded to alternative therapy, and 10 patients (40%) received hematopoietic stem cell transplantation. Six patients (24%) died because of treatment-related adverse events associated with infection, hepatotoxicity, and/or multiorgan failure. The study protocol was amended to exclude patients with prior hematopoietic stem cell transplantation after 4 of the first 8 patients developed severe hepatotoxicity suggestive of veno-occlusive disease. No additional cases of veno-occlusive disease occurred. The regimen offered encouraging response rates and sustained remission in R/R patients. Future investigation should include exploration of patient selection, dosing, and supportive care. This trial was registered at www.clinicaltrials.gov as #NCT00315705. (Blood. 2011;118(23):6043-6049) C1 [Hijiya, Nobuko] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60614 USA. [Thomson, Blythe] Seattle Childrens Hosp, Seattle, WA USA. [Isakoff, Michael S.] Connecticut Childrens Med Ctr, Hartford, CT USA. [Silverman, Lewis B.] Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Steinherz, Peter G.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Borowitz, Michael J.] Johns Hopkins Univ, Baltimore, MD USA. [Kadota, Richard; Paul, Jo-Anne; Barry, Elly] Genzyme Corp, Cambridge, MA USA. [Kadota, Richard] Childrens Hosp, San Diego, CA USA. [Cooper, Todd] Childrens Healthcare Atlanta, Atlanta, GA USA. [Shen, Violet] Childrens Hosp Orange Cty, Orange, CA 92668 USA. [Dahl, Gary] Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. [Thottassery, Jaideep V.] So Res Inst, Birmingham, AL 35255 USA. [Jeha, Sima] St Jude Childrens Hosp, Memphis, TN 38105 USA. [Maloney, Kelly] Univ Colorado, Sch Med, Aurora, CO USA. [Maloney, Kelly] Childrens Hosp Colorado, Aurora, CO USA. [Carroll, William L.] NYU, Inst Canc, New York, NY USA. [Gaynon, Paul S.] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. RP Hijiya, N (reprint author), Northwestern Univ, Dept Pediat Hematol Oncol, Childrens Mem Hosp, Feinberg Sch Med, 2300 Childrens Plaza,Box 30, Chicago, IL 60614 USA. EM nhijiya@childrensmemorial.org FU Genzyme Corporation; Genzyme FX This work was supported by Genzyme Corporation.; Conflict-of-interest disclosure: N.H. and P.G.S. have participated as members of a Genzyme advisory board and received honoraria and research support for clinical studies. S.J., P.S.G., and J.V.T. have received research support for clinical studies from Genzyme. B.T. has participated as a member of a Genzyme advisory board. E.B., J.-A.P., and R.K. are employees of Genzyme Corporation. The remaining authors declare no competing financial interests. NR 17 TC 44 Z9 44 U1 1 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 1 PY 2011 VL 118 IS 23 BP 6043 EP 6049 DI 10.1182/blood-2011-08-374710 PG 7 WC Hematology SC Hematology GA 857XI UT WOS:000297757700013 PM 21967976 ER PT J AU Schwarz, D Schwarz, R Gauchan, B Andrews, J Sharma, R Karelas, G Rajbhandari, R Acharya, B Mate, K Bista, A Bista, MG Sox, C Maru, DSR AF Schwarz, Dan Schwarz, Ryan Gauchan, Bikash Andrews, Jason Sharma, Ranju Karelas, Gregory Rajbhandari, Ruma Acharya, Bibhav Mate, Kedar Bista, Amir Bista, Megha Giri Sox, Colin Maru, Duncan Smith-Rohrberg TI Implementing a systems-oriented morbidity and mortality conference in remote rural Nepal for quality improvement SO BMJ QUALITY & SAFETY LA English DT Article ID DEPARTMENTS; AUDIT; ERROR AB Problem: In hospitals in rural, resource-limited settings, there is an acute need for simple, strategies to improve healthcare quality. Setting: A district hospital in remote western Key measures for improvement: To provide a mechanism for systems-level reflection so that can identify targets for quality improvement in healthcare delivery. Strategies for change: To develop a morbidity and mortality conference (M&M) quality improvement initiative that aims to facilitate structured analysis patient care and identify barriers to providing care, which can subsequently be improved. Design: The authors designed an M&M involving clinical and non-clinical staff in conducting root-cause analyses of healthcare delivery at their hospital. Weekly conferences focus on seven domains of analysis: operations, supply chain, equipment, personnel, outreach, societal, and structural. Each conference focuses on assessing the care provided, and identifying ways in which services can be improved in the future. Effects of change: Staff reception of the M&Ms positive. In these M&Ms, staff identified problem in healthcare delivery and steps for improvement. Subsequently, changes were made in hospital workflow, supply procurement, and on-site training. Lessons learnt: While widely practiced throughout the world, M&Ms typically do not involve both and non-clinical staff members and do not take a systems-level approach. The authors' experience suggests that the adapted M&M conference is a simple, feasible tool for quality improvement in resource-limited settings. Senior managerial commitment is crucial to ensure successful implementation of M&Ms, given the challenging logistics of implementing these programmes in resource-limited health facilities. C1 [Schwarz, Dan; Schwarz, Ryan; Gauchan, Bikash; Andrews, Jason; Sharma, Ranju; Karelas, Gregory; Rajbhandari, Ruma; Acharya, Bibhav; Bista, Amir; Bista, Megha Giri; Maru, Duncan Smith-Rohrberg] Nyaya Hlth Bayalpata Hosp, Achham, Nepal. [Schwarz, Dan] Brown Univ, Sch Med, Providence, RI 02912 USA. [Schwarz, Dan] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Schwarz, Ryan; Rajbhandari, Ruma; Mate, Kedar; Maru, Duncan Smith-Rohrberg] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Schwarz, Ryan; Maru, Duncan Smith-Rohrberg] Childrens Hosp, Dept Med, Boston, MA 02115 USA. [Andrews, Jason] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Acharya, Bibhav] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Mate, Kedar] Inst Healthcare Improvement, Cambridge, MA USA. [Mate, Kedar] Weill Cornell Med Coll, Dept Med, New York, NY USA. [Sox, Colin; Maru, Duncan Smith-Rohrberg] Boston Med Ctr, Boston, MA USA. RP Maru, DSR (reprint author), 42 Union Ave, Boston, MA 02130 USA. EM duncansr@post.harvard.edu OI Rajbhandari, Ruma/0000-0001-8281-550X; Mate, Kedar/0000-0001-7579-6697 FU Frederick Lovejoy Foundation at Children's Hospital Boston; Brigham and Women's Hospital Center of Expertise on Quality and Safety FX Financial support for the programme was provided by grants to DM from the Frederick Lovejoy Foundation at Children's Hospital Boston and the Brigham and Women's Hospital Center of Expertise on Quality and Safety. NR 18 TC 10 Z9 10 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-5415 J9 BMJ QUAL SAF JI BMJ Qual. Saf. PD DEC PY 2011 VL 20 IS 12 BP 1082 EP 1088 DI 10.1136/bmjqs-2011-000273 PG 7 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 856ED UT WOS:000297619300013 PM 21949441 ER PT J AU Zhang, XH Giovannucci, EL Smith-Warner, SA Wu, K Fuchs, CS Pollak, M Willett, WC Ma, J AF Zhang, Xuehong Giovannucci, Edward L. Smith-Warner, Stephanie A. Wu, Kana Fuchs, Charles S. Pollak, Michael Willett, Walter C. Ma, Jing TI A prospective study of intakes of zinc and heme iron and colorectal cancer risk in men and women SO CANCER CAUSES & CONTROL LA English DT Article DE Colorectal cancer; Zinc; Iron; Heme iron; Cohort study ID FOOD FREQUENCY QUESTIONNAIRE; COLON-CANCER; ALCOHOL-CONSUMPTION; RED MEAT; REPRODUCIBILITY; VALIDITY; DIET; SUPPLEMENTATION; BIOAVAILABILITY; ASSOCIATION AB Although laboratory studies linked zinc and heme iron to colorectal cancer, epidemiologic evidence is limited. We prospectively examined these associations in the Nurses' Health Study and Health Professionals Followup Study. We used Cox proportional hazards regression analyses to calculate cohort-specific relative risks (RRs) and pooled results using a fixed-effects model. We documented 2,114 incident colorectal cancer cases during up to 22 years of follow-up. Compared highest to lowest quintile of dietary zinc intake, the pooled multivariable RRs (95% CIs) were 0.86 (0.73, 1.02) for colorectal cancer, 0.92 (0.76, 1.11) for colon cancer, and 0.68 (0.47, 0.99) for rectal cancer. The significant inverse association between dietary zinc intake and risk of rectal cancer was mainly driven by data in women, although the difference in the sex-specific results was not statistically significant. For the same comparison, the pooled multivariable RRs (95% CIs) for heme iron were 1.10 (0.93, 1.30) for colorectal cancer, 1.06 (0.88, 1.29) for colon cancer, and 1.20 (0.83, 1.75) for rectal cancer. These associations were not significantly modified by alcohol consumption, body mass index, physical activity, menopausal status, or postmenopausal hormone use. Total zinc intake, total iron intake, dietary iron intake, and zinc or iron supplement uses were largely not associated with colorectal cancer risk. Our study does not support strong roles of zinc and heme iron intake in colorectal cancer risk; however, a suggestive inverse association of dietary zinc intake with rectal cancer risk in women requires further study. C1 [Zhang, Xuehong; Giovannucci, Edward L.; Fuchs, Charles S.; Willett, Walter C.; Ma, Jing] Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab Landmark Ctr W Wing,Dept Med, Boston, MA 02115 USA. [Giovannucci, Edward L.; Smith-Warner, Stephanie A.; Wu, Kana; Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Giovannucci, Edward L.; Smith-Warner, Stephanie A.; Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Fuchs, Charles S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Pollak, Michael] McGill Univ, Dept Oncol, Montreal, PQ H3T 1E2, Canada. [Pollak, Michael] Lady Davis Res Inst, Montreal, PQ H3T 1E2, Canada. RP Zhang, XH (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab Landmark Ctr W Wing,Dept Med, 401 Pk Dr, Boston, MA 02115 USA. EM xuehong.zhang@channing.harvard.edu RI Zhang, Xuehong/E-6219-2012; Pollak, Michael/G-9094-2011 OI Pollak, Michael/0000-0003-3047-0604 FU NIH [CA87969, CA55075] FX We are grateful for all participants in the Nurses' Health Study and Health Professionals Follow-up Study for their continuous contribution and support. This work was supported by the NIH grants CA87969 and CA55075. NR 45 TC 21 Z9 21 U1 0 U2 10 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD DEC PY 2011 VL 22 IS 12 BP 1627 EP 1637 DI 10.1007/s10552-011-9839-z PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 858LO UT WOS:000297799200002 PM 21909950 ER PT J AU McCormack, VA Hung, RJ Brenner, DR Bickeboller, H Rosenberger, A Muscat, JE Lazarus, P Tjonneland, A Friis, S Christiani, DC Chun, EM Le Marchand, L Rennert, G Rennert, HS Andrew, AS Orlow, I Park, B Boffetta, P Duell, EJ AF McCormack, Valerie A. Hung, Rayjean J. Brenner, Darren R. Bickeboeller, Heike Rosenberger, Albert Muscat, Joshua E. Lazarus, Philip Tjonneland, Anne Friis, Soren Christiani, David C. Chun, Eun-mi Le Marchand, Loic Rennert, Gad Rennert, Hedy S. Andrew, Angeline S. Orlow, Irene Park, Bernard Boffetta, Paolo Duell, Eric J. TI Aspirin and NSAID use and lung cancer risk: a pooled analysis in the International Lung Cancer Consortium (ILCCO) SO CANCER CAUSES & CONTROL LA English DT Article DE NSAIDs; Aspirin; Lung cancer ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; PRIMARY PREVENTION; COLORECTAL-CANCER; RANDOMIZED-TRIAL; EXPRESSION; COHORT; WOMEN; POLYMORPHISMS; POPULATION; CARCINOMA AB Purpose To investigate the hypothesis that non-steroidal anti-inflammatory drugs (NSAIDs) lower lung cancer risk. Methods We analysed pooled individual-level data from seven case-control and one cohort study in the International Lung Cancer Consortium (ILCCO). Relative risks for lung cancer associated with self-reported history of aspirin and other NSAID use were estimated within individual studies using logistic regression or proportional hazards models, adjusted for packyears of smoking, age, calendar period, ethnicity and education and were combined using random effects meta-analysis. Results A total of 4,309 lung cancer cases (mean age at diagnosis 65 years, 45% adenocarcinoma and 22% squamous-cell carcinoma) and 58,301 non-cases/controls were included. Amongst controls, 34% had used NSAIDs in the past (81% of them used aspirin). After adjustment for negative confounding by smoking, ever-NSAID use (affirmative answer to the study-specific question on NSAID use) was associated with a 26% reduction (95% confidence interval 8 to 41%) in lung cancer risk in men, but not in women (3% increase (-11% to 30%)). In men, the association was stronger in current and former smokers, and for squamous-cell carcinoma than for adenocarcinomas, but there was no trend with duration of use. No differences were found in the effects on lung cancer risk of aspirin and non-aspirin NSAIDs. Conclusions Evidence from ILCCO suggests that NSAID use in men confers a modest protection for lung cancer, especially amongst ever-smokers. Additional investigation is needed regarding the possible effects of age, duration, dose and type of NSAID and whether effect modification by smoking status or sex exists. C1 [McCormack, Valerie A.] Int Agcy Res Canc, Sect Environm & Radiat, F-69008 Lyon, France. [Hung, Rayjean J.; Brenner, Darren R.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Hung, Rayjean J.; Brenner, Darren R.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada. [Bickeboeller, Heike; Rosenberger, Albert] Univ Gottingen, Sch Med, Dept Genet Epidemiol, Gottingen, Germany. [Muscat, Joshua E.; Lazarus, Philip] Penn State Coll Med, Penn State Canc Inst, Hershey, PA USA. [Tjonneland, Anne; Friis, Soren] Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark. [Christiani, David C.; Chun, Eun-mi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Sch Publ Hlth, Boston, MA USA. [Le Marchand, Loic] Univ Hawaii, Canc Res Ctr Hawaii, Honolulu, HI 96813 USA. [Rennert, Gad; Rennert, Hedy S.] Carmel Hosp, Dept Community Med & Epidemiol, Haifa, Israel. [Rennert, Gad; Rennert, Hedy S.] Technion Israel Inst Technol, Bruce Rappaport Fac Med, IL-31096 Haifa, Israel. [Rennert, Gad; Rennert, Hedy S.] Natl Canc Control Ctr, Clalit Hlth Serv, Haifa, Israel. [Andrew, Angeline S.] Dartmouth Med Sch, Norris Cotton Canc Ctr, Dept Community & Family Med, Lebanon, NH USA. [Orlow, Irene; Park, Bernard] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Park, Bernard] Hackensack Univ, Med Ctr, Hackensack, NJ USA. [Boffetta, Paolo] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA. [Boffetta, Paolo] Mt Sinai Sch Med, Inst Translat Epidemiol, New York, NY USA. [Boffetta, Paolo] Int Prevent Res Inst, Lyon, France. [Duell, Eric J.] Bellvitge Biomed Res Inst IDIBELL, Catalan Inst Oncol, Canc Epidemiol Res Program, Unit Nutr Environm & Canc, Barcelona, Spain. RP McCormack, VA (reprint author), Int Agcy Res Canc, Sect Environm & Radiat, 150 Cours Albert Thomas, F-69008 Lyon, France. EM mccormackv@iarc.fr RI Hung, Rayjean/A-7439-2013; OI Duell, Eric J/0000-0001-5256-0163; Orlow, Irene/0000-0001-6234-6961 FU Canadian Cancer Society [020214]; Cancer Care Ontario Research Chair Award; National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) [P20RR018787]; MSKCC: Steps for Breath and the Labrecque Foundation; Society of Memorial Sloan-Kettering Cancer Center FX The ILCCO data management is supported by Canadian Cancer Society (CCSRI no. 020214) and Cancer Care Ontario Research Chair Award. Individual ILCCO studies were funded or supported by various institutions and organisations. NEL-CS: Grant Number P20RR018787 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH); MSKCC: Steps for Breath and the Labrecque Foundation, the Society of Memorial Sloan-Kettering Cancer Center. The authors would like to thank the following for their contribution with data management: Urvi Mujumdar and Radhai Rastogi (MSKCC) and Katja Boll (DDCHS). NR 31 TC 14 Z9 15 U1 1 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 EI 1573-7225 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD DEC PY 2011 VL 22 IS 12 BP 1709 EP 1720 DI 10.1007/s10552-011-9847-z PG 12 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 858LO UT WOS:000297799200010 PM 21987079 ER PT J AU Bertrand, KA Chang, ET Abel, GA Zhang, SM Spiegelman, D Qureshi, AA Laden, F AF Bertrand, Kimberly A. Chang, Ellen T. Abel, Gregory A. Zhang, Shumin M. Spiegelman, Donna Qureshi, Abrar A. Laden, Francine TI Sunlight exposure, vitamin D, and risk of non-Hodgkin lymphoma in the Nurses' Health Study SO CANCER CAUSES & CONTROL LA English DT Article DE Non-Hodgkin lymphoma; Sunlight; Ultraviolet radiation; Vitamin D; Epidemiology ID ULTRAVIOLET-RADIATION EXPOSURE; SUN EXPOSURE; UNITED-STATES; POOLED ANALYSIS; PIGMENTARY CHARACTERISTICS; 25-HYDROXYVITAMIN D; MALIGNANT-LYMPHOMA; CANCER INCIDENCE; EPIDEMIOLOGY; MORTALITY AB Purpose Case-control studies suggest increased sun exposure reduces non-Hodgkin lymphoma (NHL) risk. Evidence from prospective cohort studies, however, is limited and inconsistent. We evaluated the association between ambient ultraviolet radiation (UV) exposure and NHL in a nationwide cohort of women, the Nurses' Health Study (NHS). Methods Between 1976 and 2006, we identified 1064 incident NHL cases among 115,482 women in the prospective NHS. Exposures assessed included average annual UV-B flux based on residence at various times during life, vitamin D intake, and predicted plasma 25-hydroxyvitamin D levels. We estimated incidence rate ratios (RRs) and 95% confidence intervals (CIs) for risk of all NHL and histologic subtypes using Cox proportional hazards models. Results NHL risk was increased for women residing in areas of high ambient UV radiation (UV-B flux >113 R-B count x 10(-4)) compared to those with lower exposure (<113), with positive linear trends at all time points. The multivariable-adjusted RR for high UV area at age 15 was 1.21 (95% CI: 1.00, 1.47; p-trend < 0.01). There was no evidence of statistical heterogeneity by subtype, although power was limited for subtype analyses. We observed no association between vitamin D measures and risk of NHL overall or by subtype. Conclusions Our findings do not support the hypothesis of a protective effect of UV radiation exposure on NHL risk. We found no association between vitamin D and NHL risk. C1 [Bertrand, Kimberly A.; Spiegelman, Donna; Laden, Francine] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Bertrand, Kimberly A.; Qureshi, Abrar A.; Laden, Francine] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Chang, Ellen T.] Canc Prevent Inst Calif, Fremont, CA USA. [Chang, Ellen T.] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Div Epidemiol, Stanford, CA 94305 USA. [Abel, Gregory A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Outcomes & Policy Res,Dept Med Oncol, Boston, MA 02115 USA. [Zhang, Shumin M.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. [Spiegelman, Donna] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Dermatol, Clin Res Program, Boston, MA 02115 USA. [Laden, Francine] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. RP Bertrand, KA (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA. EM kbertran@hsph.harvard.edu FU National Institutes of Health [CA87969, CA098122]; Training Program in Environmental Health Sciences [T32 ES007155]; Nutritional Epidemiology of Cancer Education and Career Development Program [R25 CA098566] FX This work was supported by the National Institutes of Health (CA87969 and CA098122). K. A. B. was supported by the Training Program in Environmental Health Sciences (T32 ES007155) and the Nutritional Epidemiology of Cancer Education and Career Development Program (R25 CA098566). NR 55 TC 18 Z9 18 U1 0 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD DEC PY 2011 VL 22 IS 12 BP 1731 EP 1741 DI 10.1007/s10552-011-9849-x PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 858LO UT WOS:000297799200012 PM 21987081 ER PT J AU Sacks, HS Fain, JN AF Sacks, Harold S. Fain, John N. TI Human epicardial fat: what is new and what is missing? SO CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY LA English DT Article DE adipokines; coronary atherosclerosis; epicardial fat; genes; inflammation ID CORONARY-ARTERY-DISEASE; PERIVASCULAR ADIPOSE-TISSUE; PERICARDIAL FAT; CARDIOVASCULAR-DISEASE; NONDIABETIC PATIENTS; COMPUTED-TOMOGRAPHY; SURROUNDING TISSUE; INSULIN-RESISTANCE; METABOLIC SYNDROME; BARIATRIC SURGERY AB 1. Putative physiological functions of human epicardial adipose tissue (EAT) include: (i) lipid storage for the energy needs of the myocardium; (ii) thermoregulation, whereby brown fat components of EAT generate heat by non-shivering thermogenesis in response to core cooling; (iii) neuroprotection of the cardiac autonomic ganglia and nerves; and (iv) regulation of vasomotion and luminal size of the coronary arteries. Under pathophysiological circumstances, EAT may play an adverse paracrine role in cardiac arrhythmias and in lipotoxic cardiomyopathy, but of major current interest is its hypothetical role as an immunological organ contributing to inflammation around coronary artery disease (CAD). C1 [Sacks, Harold S.] VA Greater Los Angeles Healthcare Syst, Endocrinol & Diabet Div 111D, Los Angeles, CA 90073 USA. [Fain, John N.] Univ Tennessee, Dept Mol Sci, Hlth Sci Ctr, Memphis, TN USA. RP Sacks, HS (reprint author), VA Greater Los Angeles Healthcare Syst, Endocrinol & Diabet Div, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM hsacks@hotmail.com FU van Vleet Chair of Excellence (University of Tennessee); Baptist Heart Institute and Foundation (Memphis, TN, USA); Cardiometabolic Disease Research Foundation (Memphis, TN, USA) FX The authors' work reported herein was supported by the van Vleet Chair of Excellence (University of Tennessee), The Baptist Heart Institute and Foundation (Memphis, TN, USA) and The Cardiometabolic Disease Research Foundation (Memphis, TN, USA). Both authors contributed equally to this work and the authors have no conflicts of interest to declare. NR 75 TC 37 Z9 39 U1 1 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0305-1870 J9 CLIN EXP PHARMACOL P JI Clin. Exp. Pharmacol. Physiol. PD DEC PY 2011 VL 38 IS 12 BP 879 EP 887 DI 10.1111/j.1440-1681.2011.05601.x PG 9 WC Pharmacology & Pharmacy; Physiology SC Pharmacology & Pharmacy; Physiology GA 853GE UT WOS:000297413400015 PM 21895738 ER PT J AU Leung, FW AF Leung, Felix W. TI Water Exchange May Be Superior to Water Immersion for Colonoscopy SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Editorial Material ID US VETERANS; SEDATION; IMPACT C1 [Leung, Felix W.] Vet Affairs Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr, North Hills, CA USA. [Leung, Felix W.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Leung, FW (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr, North Hills, CA USA. NR 15 TC 18 Z9 18 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD DEC PY 2011 VL 9 IS 12 BP 1012 EP 1014 DI 10.1016/j.cgh.2011.09.007 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 857WJ UT WOS:000297754100009 PM 21946120 ER PT J AU Coleman, R Costa, L Saad, F Cook, R Hadji, P Terpos, E Garnero, P Brown, J Body, JJ Smith, M Lee, KA Major, P Dimopoulos, M Lipton, A AF Coleman, Robert Costa, Luis Saad, Fred Cook, Richard Hadji, Peyman Terpos, Evangelos Garnero, Patrick Brown, Janet Body, Jean-Jacques Smith, Matthew Lee, Ker-Ai Major, Pierre Dimopoulos, Meletios Lipton, Allan TI Consensus on the utility of bone markers in the malignant bone disease setting SO CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY LA English DT Review DE Antiresorptive; Bisphosphonate; Bone marker; Bone metastasis; Bone turnover; Cancer; Osteolysis ID BREAST-CANCER PATIENTS; ANDROGEN-DEPRIVATION THERAPY; MULTIPLE-MYELOMA PATIENTS; RESISTANT ACID-PHOSPHATASE; METASTATIC PROSTATE-CANCER; AMINO-TERMINAL PROPEPTIDE; COMPOSITE END-POINTS; COLLAGEN TYPE-I; RENAL-CELL CARCINOMA; BIOCHEMICAL MARKERS AB Biochemical markers of bone turnover provide insight into ongoing rates of skeletal metabolism and tumor-bone interactions in patients with malignant bone disease. This article reviews the available recent evidence assessing the potential of bone markers for detecting and monitoring malignant bone lesions in patients with advanced cancers, and for assessing overall skeletal health and response to antiresorptive therapies in patients at all stages of cancer progression. Most data thus far are for urinary N-terminal cross-linked telopeptide of type I collagen (NTX) in predicting risks of skeletal morbidity and death and monitoring response to zoledronic acid in patients with bone metastases. Ongoing studies are evaluating such correlations for other markers and therapies. Emerging evidence suggests that bone markers may help identify patients at high risk for bone metastasis or bone lesion progression, thereby allowing improved follow-up. Results from ongoing clinical trials evaluating such potential applications of bone markers are awaited. (C) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Coleman, Robert] Univ Sheffield, Weston Pk Hosp, Acad Unit Clin Oncol, Canc Res Ctr, Sheffield S10 2S, S Yorkshire, England. [Costa, Luis] Hosp Santa Maria, Lisbon, Portugal. [Saad, Fred] Univ Montreal, Ctr Hosp, Montreal, PQ, Canada. [Cook, Richard; Lee, Ker-Ai] Univ Waterloo, Waterloo, ON N2L 3G1, Canada. [Hadji, Peyman] Univ Marburg, Marburg, Germany. [Terpos, Evangelos; Dimopoulos, Meletios] Univ Athens, Sch Med, GR-11527 Athens, Greece. [Garnero, Patrick] INSERM, Res Unit 664, F-69008 Lyon, France. [Garnero, Patrick] Cisbio Bioassays, Bagnol Ceze, France. [Brown, Janet] Univ Leeds, Canc Res UK Clin Ctr Leeds, Leeds, W Yorkshire, England. [Body, Jean-Jacques] Univ Libre Brussels, CHU Brugmann, Brussels, Belgium. [Smith, Matthew] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Major, Pierre] McMaster Univ, Juravinski Canc Ctr, Hamilton, ON, Canada. [Lipton, Allan] Penn State Milton S Hershey Med Ctr, Hershey, PA USA. RP Coleman, R (reprint author), Univ Sheffield, Weston Pk Hosp, Acad Unit Clin Oncol, Canc Res Ctr, Whitham Rd, Sheffield S10 2S, S Yorkshire, England. EM r.e.coleman@sheffield.ac.uk OI Costa, Luis/0000-0002-4782-7318 FU Novartis; Amgen; Pfizer; Roche; AstraZeneca; Novartis Oncology; Amgen Oncology; GTx Incorporated; Janssen-Cilag; GlaxoSmithKline; Monogram Biosciences; Oncogene Science; Novartis Pharmaceuticals Corporation; Novartis Pharmaceuticals FX Dr. Coleman has received consultancy fees from Novartis, Amgen, and Pfizer; speaker fees from Novartis, Roche, Pfizer, AstraZeneca, and Amgen; and research funding from Novartis. He has given expert testimony on behalf of Novartis.; Dr. Major has received consultancy fees from Novartis Oncology and Amgen Oncology. He is currently a member of the data monitoring committees for Amgen and for the Austrian Breast and Colorectal Cancer Study Group (ABCSG).; Dr. Smith has received research funding and/or served as a consultant to Amgen, Novartis, and GTx Incorporated.; Dr. Terpos has received honoraria and research funding from Novartis, Janssen-Cilag, and Amgen.; Dr. Cook has received honoraria and consulting fees from Abbott, Amgen, GlaxoSmithKline, and Novartis.; Dr. Lipton has participated as a consultant for Amgen, Novartis, Acceleron Pharmaceuticals, and Monogram Biosciences; received honoraria from Amgen and Novartis; and received research funding from Novartis, Monogram Biosciences, and Oncogene Science. Dr. Lipton has given expert testimony for Novartis.; Financial support for medical editorial assistance was provided by Novartis Pharmaceuticals Corporation.; The manuscript was initiated on the basis of discussions by the authors at various medical meetings. The authors thank Shalini Murthy, PhD, ProEd Communications, Inc., for her assistance with this manuscript. She helped draft the initial manuscript and handled the various revisions submitted by all authors. The sponsor (Novartis Pharmaceuticals) has had no influence in any phase of the development or submission of this manuscript. NR 188 TC 32 Z9 34 U1 1 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1040-8428 EI 1879-0461 J9 CRIT REV ONCOL HEMAT JI Crit. Rev. Oncol./Hematol. PD DEC PY 2011 VL 80 IS 3 BP 411 EP 432 DI 10.1016/j.critrevonc.2011.02.005 PG 22 WC Oncology; Hematology SC Oncology; Hematology GA 859SF UT WOS:000297895400006 PM 21411334 ER PT J AU Foster, T Hon, HM Kanwal, F Han, S Spiegel, B AF Foster, Temitope Hon, Huiming Kanwal, Fasiha Han, Steven Spiegel, Brennan TI Screening High Risk Individuals for Hepatitis B: Physician Knowledge, Attitudes, and Beliefs SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Hepatitis B; Vaccines; Screening; Guideline adherence ID ACUTE VIRAL-HEPATITIS; VIRUS INFECTION; UNITED-STATES; RECOMMENDATIONS; PREVENTION; IMMUNIZATION; SURVEILLANCE; IMMUNITY; ADULTS AB Background Although the overall incidence of hepatitis B virus (HBV) has declined since the introduction of universal vaccine guidelines, the incidence remains elevated in high risk groups. Recent guidelines from the Centers for Disease Control (CDC) have underscored the importance of vaccination against HBV in high risk individuals. However, the incidence of HBV in this group remains elevated, suggesting underuse of vaccinations by healthcare providers. Aim The purpose of this study was to measure practice patterns of HBV vaccination, and identify predictors of vaccination underuse. Methods We created a survey with four vignettes describing patients at high risk for contracting HBV, followed by questions regarding knowledge, attitudes, and beliefs (KAB) of HBV screening and vaccination. A random sample of 1,000 physicians, including internists, family medicine, OB/GYN, gastroenterologists, and experts in HBV epidemiology were surveyed. Regression analysis on composite guideline adherence scores identified KAB profiles that predict scores. Results On average, responders endorsed 71% of the CDC HBV vaccination guidelines. There were three predictors of diminished screening proclivity: (1) younger provider age (P = 0.028), (2) lower awareness that adult HBV is contracted primarily through heterosexual sex (P = 0.023), and (3) being a provider other than a gastroenterologist (P = 0.009). Conclusions Respondents endorsed most-but not all-CDC supported HBV screening practices. Lower adherence was predicted by specific and modifiable KAB profiles, and by younger age. Future efforts to improve adherence should target trainees, emphasize the importance of obtaining sexual histories in high risk patients, and inform that HBV is predominantly a heterosexually transmitted infection. C1 [Foster, Temitope; Hon, Huiming] Emory Univ, Sch Med, Div Digest Dis, Atlanta, GA 30303 USA. [Kanwal, Fasiha] St Louis Univ, St Louis, MO 63103 USA. [Han, Steven; Spiegel, Brennan] Univ Calif Los Angeles, Los Angeles, CA USA. [Spiegel, Brennan] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Spiegel, Brennan] CURE Digest Dis Res Ctr, Los Angeles, CA USA. [Spiegel, Brennan] UCLA VA Ctr Outcomes Res & Educ CORE, Los Angeles, CA USA. RP Foster, T (reprint author), Emory Univ, Sch Med, Div Digest Dis, 49 Jesse Hill Jr Dr SE,Rm 437, Atlanta, GA 30303 USA. EM tyfoste@emory.edu FU Ruth L. Kirschstein-National Service [T32 DK 07180-34]; Bristol-Meyers Squibb FX Dr. Foster was supported by a Ruth L. Kirschstein-National Service Research Award (T32 DK 07180-34). This study was supported by an investigator-initiated research grant by Bristol-Meyers Squibb. NR 20 TC 4 Z9 4 U1 1 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD DEC PY 2011 VL 56 IS 12 BP 3471 EP 3487 DI 10.1007/s10620-011-1928-z PG 17 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 857UM UT WOS:000297747300010 PM 22001940 ER PT J AU Faquin, WC Bongiovanni, M Sadow, PM AF Faquin, William C. Bongiovanni, Massimo Sadow, Peter M. TI Update in Thyroid Fine Needle Aspiration SO ENDOCRINE PATHOLOGY LA English DT Article DE Thyroid; FNA; Cytology; Follicular-patterned lesions; Bethesda; Poorly differentiated carcinoma ID SOCIETY-OF-CYTOPATHOLOGY; UNDETERMINED SIGNIFICANCE; INSULAR CARCINOMA; FOLLICULAR CARCINOMAS; SCIENCE CONFERENCE; FOLLOW-UP; DIAGNOSIS; CYTOLOGY; CANCER; NODULES AB Thyroid fine needle aspiration (FNA) is a safe, cost effective, and relatively accurate method for guiding the initial management of a thyroid nodule. The popularity of thyroid FNA is reflected in the fact that over 350,000 thyroid FNAs are performed each year in the USA. As we move into the next decade, several issues pertaining to thyroid FNA are being addressed including: how to better apply thyroid FNA as a differential test for follicular-patterned thyroid tumors, how to manage the atypical thyroid FNA, and how to use thyroid FNA in the evaluation of poorly differentiated thyroid carcinomas. C1 [Faquin, William C.; Sadow, Peter M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Faquin, William C.; Sadow, Peter M.] Harvard Univ, Sch Med, Boston, MA USA. [Bongiovanni, Massimo] Inst Pathol, Locarno, Switzerland. RP Faquin, WC (reprint author), Massachusetts Gen Hosp, Dept Pathol, WRN 219,55 Fruit St, Boston, MA 02114 USA. EM WFaquin@Partners.org RI Bongiovanni, Massimo/C-3144-2017 OI Bongiovanni, Massimo/0000-0001-9846-6682 NR 46 TC 7 Z9 9 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1046-3976 J9 ENDOCR PATHOL JI Endocr. Pathol. PD DEC PY 2011 VL 22 IS 4 BP 178 EP 183 DI 10.1007/s12022-011-9182-7 PG 6 WC Endocrinology & Metabolism; Pathology SC Endocrinology & Metabolism; Pathology GA 857UV UT WOS:000297748800003 PM 21997833 ER PT J AU Storey, RF Becker, RC Harrington, RA Husted, S James, SK Cools, F Steg, PG Khurmi, NS Emanuelsson, H Cooper, A Cairns, R Cannon, CP Wallentin, L AF Storey, Robert F. Becker, Richard C. Harrington, Robert A. Husted, Steen James, Stefan K. Cools, Frank Steg, Philippe Gabriel Khurmi, Nardev S. Emanuelsson, Hakan Cooper, Anna Cairns, Richard Cannon, Christopher P. Wallentin, Lars TI Characterization of dyspnoea in PLATO study patients treated with ticagrelor or clopidogrel and its association with clinical outcomes SO EUROPEAN HEART JOURNAL LA English DT Article DE Platelet; Platelet inhibitor; Clopidogrel; Ticagrelor; P2Y(12) receptor; Coronary artery disease ID ACUTE CORONARY SYNDROMES; P2Y(12) RECEPTOR ANTAGONIST; AZD6140; INHIBITION; ADENOSINE; SAFETY; TRIAL AB Aims To describe the incidence of dyspnoea and its associations with demographic characteristics and clinical outcomes in patients with acute coronary syndromes (ACS) treated with ticagrelor or clopidogrel in the PLATelet inhibition and patient Outcomes (PLATO) study. Methods and results In the PLATO study, 18 624 patients were randomized to receive either clopidogrel [300-600 mg loading dose (LD), 75 mg daily] or ticagrelor (180 mg LD, 90 mg b.i.d.). The occurrence of reported dyspnoea adverse events (AEs) was analysed in the 18 421 patients who received at least one dose of study medication in relation to demographic characteristics, clinical outcomes and other associations of patients with and without dyspnoea. A total of 1339 ticagrelor-treated patients (14.5%) and 798 clopidogrel-treated patients (8.7%) had a dyspnoea AE following randomization, with respectively 39 (0.4%) and 24 (0.3%) classified as severe in intensity. Excluding dyspnoea AEs occurring after the secondary endpoint of myocardial infarction (MI), the yearly rates of the efficacy endpoints in dyspnoea AE patients in the ticagrelor and clopidogrel groups were: for the primary composite of CV death, MI, and stroke, 8.8 and 10.4% (unadjusted P = 0.25; adjusted P = 0.54); for CV death, 3.1 and 4.8% (unadjusted P = 0.024; adjusted P = 0.18); and for total death 3.7 and 6.2% (unadjusted P = 0.004; adjusted P = 0.06), respectively. Conclusions Ticagrelor-related dyspnoea is usually mild or moderate in intensity and does not appear to be associated with differences concerning any efficacy or safety outcomes with ticagrelor compared with clopidogrel therapy in ACS patients. C1 [Storey, Robert F.] Univ Sheffield, Dept Cardiovasc Sci, Sheffield S10 2RX, S Yorkshire, England. [Becker, Richard C.; Harrington, Robert A.] Duke Clin Res Inst, Durham, NC USA. [Husted, Steen] Arhus Univ Hosp, Aarhus, Denmark. [James, Stefan K.; Wallentin, Lars] Univ Hosp, Uppsala Clin Res Ctr, Uppsala, Sweden. [James, Stefan K.; Wallentin, Lars] Univ Hosp, Dept Med Sci, Uppsala, Sweden. [Cools, Frank] Gen Hosp Klina, Brasschaat, Belgium. [Steg, Philippe Gabriel] Univ Paris, INSERM, U698, F-75252 Paris, France. [Steg, Philippe Gabriel] Hop La Pitie Salpetriere, AP HP, Paris, France. [Khurmi, Nardev S.; Emanuelsson, Hakan] AstraZeneca, Wilmington, DE USA. [Emanuelsson, Hakan] AstraZeneca, Molndal, Sweden. [Cooper, Anna; Cairns, Richard] Worldwide Clin Trials, Nottingham, England. [Cannon, Christopher P.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. RP Storey, RF (reprint author), Univ Sheffield, Dept Cardiovasc Sci, Beech Hill Rd, Sheffield S10 2RX, S Yorkshire, England. EM r.f.storey@sheffield.ac.uk FU AstraZeneca; Dynabyte; Eli Lilly/Daiichi Sankyo alliance; Schering-Plough/Merck; Accumetrics; Merck; Novartis; Sanofi-Aventis/Bristol-Myers Squibb; Eisai; Regado Biosciences; Johnson and Johnson; Bayer; Bristol-Myers Squibb; Daiichi Sankyo; Boehringer Ingelheim; Portola; Sanofi-Aventis; Eli Lilly; Pfizer; Servier; Astellas; GlaxoSmithKline; Medtronic; Otsuka Pharmaceutical; Roche; Intekrin Therapeutics; Takeda; Bristol-Myers Squibb/Sanofi; Regado Biotechnologies; Athera Biotechnologies; The Medicines Company FX R.F.S.: research/educational grants from AstraZeneca, Dynabyte, Eli Lilly/Daiichi Sankyo alliance, Schering-Plough/Merck, and Accumetrics; honoraria from AstraZeneca, Eli Lilly/Daiichi Sankyo alliance, Medscape, Novartis, GlaxoSmithKline, and Schering-Plough/Merck; consultant fees from AstraZeneca, Eli Lilly/Daiichi Sankyo alliance, Merck, Novartis, Sanofi-Aventis/Bristol-Myers Squibb, Eisai. The Medicines Company and Accumetrics; travel support from AstraZeneca, Eli Lilly/Daiichi Sankyo alliance, and Schering-Plough/Merck. R.C.B.: research grants from AstraZeneca, Regado Biosciences, Johnson and Johnson, Bayer, and Bristol-Myers Squibb; consultant fees from Daiichi Sankyo, Boehringer Ingelheim, and AstraZeneca. R.A.H.: consulting fees from AstraZeneca, Bristol-Myers Squibb, Schering Plough/Merck, Novartis, Portola, Sanofi-Aventis, and The Medicines Company; honoraria/lecture fees from Eli Lilly, AstraZeneca; grant support from AstraZeneca, Bristol-Myers Squibb, Portola, Schering-Plough/Merck. S.H.: research grants from AstraZeneca, Bristol-Myers Squibb, Pfizer, and Bayer; consultant fees from Sanofi-Aventis, Pfizer, and AstraZeneca. S.K.J.: research grants from AstraZeneca, Bristol-Myers Squibb, and Eli Lilly; honoraria and advisory board compensation from AstraZeneca, Merck, Sanofi-Aventis and Eli Lilly. P.G.S.: research grants from Servier; consultant fees/advisory board membership; Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi/Sankyo/Eli Lilly alliance, GlaxoSmithKline, Medtronic, Merck, Otsuka Pharmaceutical, Roche, Sanofi-Aventis, Servier, and The Medicines Company; and having equity ownership in Aterovax. N.S.K. and H.E.: employees of AstraZeneca and having equity ownerships in AstraZeneca. F.C. and A.C.: no conflicts of interest declared. C.P.C.: research grants from Accumetrics, AstraZeneca, GlaxoSmithKline, Intekrin Therapeutics, Merck, and Takeda; advisory board participation with Alnylam, Novartis and Bristol-Myers Squibb/Sanofi (but funds donated to charity); being a clinical advisor and having equity ownership interest in Automedics. L.W.: research grants from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, and Schering-Plough; honoraria from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Schering-Plough, and Eli Lilly; consultant fees from Regado Biotechnologies, Athera Biotechnologies, Boehringer Ingelheim, AstraZeneca, GlaxoSmithKline, and Eli Lilly; lecture fees from AstraZeneca, Boehringer Ingelheim, and Eli Lilly. NR 10 TC 69 Z9 77 U1 1 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD DEC PY 2011 VL 32 IS 23 BP 2945 EP 2953 DI 10.1093/eurheartj/ehr231 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 856MX UT WOS:000297647400009 PM 21804104 ER PT J AU Caetano, BC Biswas, A Lima, DS Benevides, L Mineo, TWP Horta, CV Lee, KH Silva, JS Gazzinelli, RT Zamboni, DS Kobayashi, KS AF Caetano, Braulia C. Biswas, Amlan Lima-Junior, Djalma S. Benevides, Luciana Mineo, Tiago W. P. Horta, Catarina V. Lee, Kyoung-Hee Silva, Joao S. Gazzinelli, Ricardo T. Zamboni, Dario S. Kobayashi, Koichi S. TI Intrinsic expression of Nod2 in CD4(+) T lymphocytes is not necessary for the development of cell-mediated immunity and host resistance to Toxoplasma gondii SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE Nod2; Nucleotide-binding domain leucine-rich repeat proteins (NLR); Toxoplasma gondii ID PANETH CELLS; INNATE; PEPTIDOGLYCAN; DISEASE; GENE AB Nod2 belongs to the nucleotide-binding domain leucine-rich repeat family of proteins and senses bacterial cell wall components to initiate innate immune responses against various pathogens. Recently, it has been reported that T-cell-intrinsic expression of Nod2 promotes host defense against Toxoplasma gondii infection by inducing type 1 immunity. Here, we present results that demonstrate that Nod2 does not play a role in the defense against T. gondii infection. Nod2-deficient mice were fully capable of inducing Th1 immune responses and did not show enhanced susceptibility to infection. Upon TCR stimulation in vitro, Nod2-deficient CD4(+) T cells showed normal activation, IL-2 production, proliferation, and Th1/2 differentiation. Nod2 mRNA and protein were expressed in CD4(+) T and CD8(+) T cells at substantial levels. Therefore, Nod2, although expressed in CD4(+) T cells, does not have an intrinsic function in T-cell activation and differentiation. C1 [Kobayashi, Koichi S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA. [Caetano, Braulia C.; Gazzinelli, Ricardo T.] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA USA. [Biswas, Amlan; Lee, Kyoung-Hee; Kobayashi, Koichi S.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Lima-Junior, Djalma S.; Horta, Catarina V.; Zamboni, Dario S.] Dept Cell Biol, Sao Paulo, Brazil. [Benevides, Luciana; Mineo, Tiago W. P.; Silva, Joao S.] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Biochem & Immunol, Sao Paulo, Brazil. RP Kobayashi, KS (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Dana 1420A,450 Brookline Ave, Boston, MA 02215 USA. EM Ricardo.Gazzinelli@umassmed.edu; dszamboni@fmrp.usp.br; Koichi_Kobayashi@dfci.harvard.edu RI Silva, Joao/A-4484-2008; Benevides, Luciana/D-2715-2012; Zamboni, Dario/D-3024-2012; Mineo, Tiago/B-4153-2009; Vacinas, Inct/J-9431-2013; Lima-Junior, Djalma/H-4833-2013 OI Zamboni, Dario/0000-0002-7856-7512; Mineo, Tiago/0000-0002-2339-2743; Lima-Junior, Djalma/0000-0002-2092-8047 FU NIH [R01DK074738, R01AI071319, U01AI077887]; FAPESP [10/50959-4]; INCTV-CNPq; Cancer Research Institute; Claudia Adams Barr Award FX The authors thank Torsten Meissner for helpful discussions; Andrea Dearth, Yuen-Joyce Liu, Bianca Carmo, and Maira Nakamura for technical assistance; Amy Li for critical reading. This work was supported by a grant from the NIH (R01DK074738) to K. S. K.; from the NIH (R01AI071319 and U01AI077887) to R. T. G.; from FAPESP (10/50959-4) to D. S. Z.; and INCTV-CNPq to J. S. S., R. T. G. and D. S. Z. J. S. S., R. T. G. and D. S. Z. are Research Fellows from CNPq; and K. S. K. is a recipient of the Investigator Award from the Cancer Research Institute and the Claudia Adams Barr Award. NR 19 TC 22 Z9 22 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD DEC PY 2011 VL 41 IS 12 BP 3627 EP 3631 DI 10.1002/eji.201141876 PG 5 WC Immunology SC Immunology GA 853ZU UT WOS:000297465000027 PM 22002196 ER PT J AU Cuenca, AG Maier, RV Cuschieri, J Moore, EE Moldawer, LL Tompkins, RG AF Cuenca, A. G. Maier, R. V. Cuschieri, J. Moore, E. E. Moldawer, L. L. Tompkins, R. G. CA Large Scale Collaborative Res TI The Glue Grant experience: characterizing the post injury genomic response SO EUROPEAN JOURNAL OF TRAUMA AND EMERGENCY SURGERY LA English DT Article DE Polytrauma; Protocols; Critical care; Inflammation ID SCALE COLLABORATIVE PROJECT; ORIENTED RESEARCH CORE; STANDARD OPERATING PROCEDURES; MESSENGER-RNA EXPRESSION; HOST RESPONSE; CLINICAL CARE; TRAUMA PATIENT; SEVERE SEPSIS; SEPTIC SHOCK; IMPROVES SURVIVAL AB Despite ongoing improvements in resuscitation, care, and outcomes, traumatic injury remains a significant health care and economic burden. The causes are multifactorial, but our approach to the clinical management of these patients remains limited by our current understanding of the pathobiology of the disease. A multicenter, multidisciplinary program known as the "Inflammation and the Host Response to Injury" Large Scale Collaborative Research Program was created by the National Institute of General Medical Sciences (NIGMS, U54 GM062119-10) in 2001 in a 10-year effort to address some of these issues. Its primary goal is to describe the human genomic response to severe trauma and burns, and to examine changes in gene expression in the context of different clinical outcomes. The Program has not only successfully implemented clinical care guidelines for managing the severe trauma patient based on the best available evidence to minimize iatrogenic variability, but it has also examined the genome-wide, immune-inflammatory response in total and isolated blood leukocyte populations. This review will address current milestones as well as future directions for the Program. C1 [Maier, R. V.; Cuschieri, J.] Univ Washington, Harborview Med Ctr, Dept Surg, Seattle, WA 98104 USA. [Cuenca, A. G.; Moldawer, L. L.] Univ Florida, Coll Med, Dept Surg, Gainesville, FL 32610 USA. [Moore, E. E.] Univ Colorado, Hlth Sci Ctr, Denver, CO 80262 USA. [Moore, E. E.] Denver Gen Hosp, Dept Surg, Denver, CO 80262 USA. [Tompkins, R. G.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02215 USA. RP Maier, RV (reprint author), Univ Washington, Harborview Med Ctr, Dept Surg, 325 Ninth Ave,Box 359796, Seattle, WA 98104 USA. EM alex.cuenca@surgery.ufl.edu; ronmaier@u.washington.edu FU NRSA from National Institute of General Medical Sciences (NIGMS) [F32 GM-093665-01]; [U54 GM-062119-10]; [T32 GM-08721-11] FX Supported in part by grant U54 GM-062119-10. A.G.C. was supported by a T32 training grant in burns and trauma (T32 GM-08721-11). A.G.C. was also supported by an individual NRSA award (F32 GM-093665-01) from the National Institute of General Medical Sciences (NIGMS). NR 45 TC 2 Z9 2 U1 0 U2 1 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1863-9933 J9 EUR J TRAUMA EMERG S JI Eur. J. Trauma Emerg. Surg. PD DEC PY 2011 VL 37 IS 6 BP 549 EP 558 DI 10.1007/s00068-011-0148-8 PG 10 WC Emergency Medicine SC Emergency Medicine GA 858QW UT WOS:000297818500003 PM 26815465 ER PT J AU Zacharias, N Blank, R Bittner, EA Joyce, S Kondili, D Fisher, D Eikermann, M Velmahos, GC Schmidt, U AF Zacharias, N. Blank, R. Bittner, E. A. Joyce, S. Kondili, D. Fisher, D. Eikermann, M. Velmahos, G. C. Schmidt, U. TI Introduction of guidelines to facilitate enteral nutrition in a surgical intensive care unit is associated with earlier enteral feeding SO EUROPEAN JOURNAL OF TRAUMA AND EMERGENCY SURGERY LA English DT Article DE Tube feedings; Nutrition; Surgical intensive care unit ID CRITICALLY-ILL PATIENT; CLINICAL-PRACTICE GUIDELINES; PARENTERAL-NUTRITION; AMERICAN SOCIETY; SUPPORT THERAPY; ADULT PATIENTS; METAANALYSIS; INFECTIONS; PROVISION; MEDICINE AB Patients treated postoperatively in surgical intensive care units often receive delayed enteral nutrition. We hypothesized that the introduction of guidelines promoting early enteral nutrition is associated with earlier enteral feeding. Enteral nutrition guidelines were created by the consensus of a multidisciplinary team consisting of intensivists, nurses, nutritionists, and surgeons. The guidelines were implemented through repeated staff education. We prospectively compared data on nutritional support in the surgical intensive care unit of a tertiary care center before (pre-intervention period, from January 27 to April 30, 2008) and after (post-intervention period, from May 1st to August 15th, 2008) implementation of the guidelines. The primary outcome was time to enteral feeding (oral or tube feeding). 146 patients were evaluated during the pre-period and 141 patients during the post-period. Patients during the two time periods had similar demographics and clinical characteristics. None of the patients were without nutrition for longer than 7 days. Oral or feeding tube nutrition was started earlier in the post-period (median 1 vs. 2 days, p < 0.001). There was no difference in the percentages of patients receiving parenteral nutrition (7.4 vs. 10%, p = 0.360). There was no increase in aspiration events in the post-period (8 vs. 9.4%, p = 0.606). Introduction of guidelines to facilitate enteral nutrition in a surgical intensive care unit was associated with earlier enteral feeding. C1 [Blank, R.; Bittner, E. A.; Kondili, D.; Eikermann, M.; Schmidt, U.] Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Zacharias, N.; Velmahos, G. C.] Div Trauma Emergency Surg & Surg Crit Care, Boston, MA USA. [Joyce, S.] Massachusetts Gen Hosp, Dept Patient Care Serv, Boston, MA 02114 USA. [Fisher, D.] Massachusetts Gen Hosp, Dept Resp Therapy, Boston, MA 02114 USA. RP Schmidt, U (reprint author), Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM uschmidt@partners.org NR 21 TC 1 Z9 1 U1 1 U2 4 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1863-9933 J9 EUR J TRAUMA EMERG S JI Eur. J. Trauma Emerg. Surg. PD DEC PY 2011 VL 37 IS 6 BP 605 EP 608 DI 10.1007/s00068-011-0085-6 PG 4 WC Emergency Medicine SC Emergency Medicine GA 858QW UT WOS:000297818500010 PM 26815472 ER PT J AU Kolbe, JJ Revell, LJ Szekely, B Brodie, ED Losos, JB AF Kolbe, Jason J. Revell, Liam J. Szekely, Brian Brodie, Edmund D., III Losos, Jonathan B. TI CONVERGENT EVOLUTION OF PHENOTYPIC INTEGRATION AND ITS ALIGNMENT WITH MORPHOLOGICAL DIVERSIFICATION IN CARIBBEAN ANOLIS ECOMORPHS SO EVOLUTION LA English DT Article DE Adaptive radiation; common principal components analysis; convergent evolution; genetic constraint; Mantel test; phenotypic variance-covariance matrices; random skewers ID QUANTITATIVE GENETIC-ANALYSIS; G-MATRIX; NATURAL-SELECTION; CORRELATIONAL SELECTION; PHYLOGENETIC ANALYSIS; HABITAT USE; BODY-SIZE; CONTINUOUS CHARACTERS; POLYGENIC CHARACTERS; COVARIANCE STRUCTURE AB The adaptive landscape and the G-matrix are keys concepts for understanding how quantitative characters evolve during adaptive radiation. In particular, whether the adaptive landscape can drive convergence of phenotypic integration (i.e., the pattern of phenotypic variation and covariation summarized in the P-matrix) is not well studied. We estimated and compared P for 19 morphological traits in eight species of Caribbean Anolis lizards, finding that similarity in P among species was not correlated with phylogenetic distance. However, greater similarity in P among ecologically similar Anolis species (i.e., the trunk-ground ecomorph) suggests the role of convergent natural selection. Despite this convergence and relatively deep phylogenetic divergence, a large portion of eigenstructure of P is retained among our eight focal species. We also analyzed P as an approximation of G to test for correspondence with the pattern of phenotypic divergence in 21 Caribbean Anolis species. These patterns of covariation were coincident, suggesting that either genetic constraint has influenced the pattern of among-species divergence or, alternatively, that the adaptive landscape has influenced both G and the pattern of phenotypic divergence among species. We provide evidence for convergent evolution of phenotypic integration for one class of Anolis ecomorph, revealing yet another important dimension of evolutionary convergence in this group. C1 [Kolbe, Jason J.; Losos, Jonathan B.] Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA. [Revell, Liam J.] Natl Evolutionary Synth Ctr, Durham, NC 27705 USA. [Szekely, Brian] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Brodie, Edmund D., III] Univ Virginia, Mt Lake Biol Stn, Charlottesville, VA 22904 USA. [Brodie, Edmund D., III] Univ Virginia, Dept Biol, Charlottesville, VA 22904 USA. [Kolbe, Jason J.; Losos, Jonathan B.] Harvard Univ, Museum Comparat Zool, Cambridge, MA 02138 USA. RP Kolbe, JJ (reprint author), Harvard Univ, Dept Organism & Evolutionary Biol, 26 Oxford St, Cambridge, MA 02138 USA. EM jjkolbe@gmail.com RI Brodie III, Edmund/B-2335-2013 FU National Evolutionary Synthesis Center (NSF) [EF-0423641]; National Science Foundation [DEB-0519777, DEB-0519658] FX We thank the following individuals and institutions for help obtaining museum specimens: J. Simmons and L. Trueb, University of Kansas Natural History Museum; J. Rosado and J. Hanken, Harvard University Museum of Comparative Zoology; R. Powell, Avila University; and R. Glor, University of Rochester. We thank M. Alfaro, S. Arnold, J. McGlothlin, and an anonymous reviewer for comments. LJR was supported by the National Evolutionary Synthesis Center (NSF #EF-0423641) during the preparation of this manuscript. This work is supported by the National Science Foundation (DEB-0519777 & DEB-0519658). NR 95 TC 31 Z9 32 U1 2 U2 49 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0014-3820 J9 EVOLUTION JI Evolution PD DEC PY 2011 VL 65 IS 12 BP 3608 EP 3624 DI 10.1111/j.1558-5646.2011.01416.x PG 17 WC Ecology; Evolutionary Biology; Genetics & Heredity SC Environmental Sciences & Ecology; Evolutionary Biology; Genetics & Heredity GA 857PW UT WOS:000297732000020 PM 22133229 ER PT J AU Yan, W Ding, P Geng, Z Zhou, XH AF Yan, Wei Ding, Peng Geng, Zhi Zhou, Xiaohua TI Identifiability of causal effects on a binary outcome within principal strata SO FRONTIERS OF MATHEMATICS IN CHINA LA English DT Article DE Causal inference; identifiability; principal effect; multi-component intervention ID INFERENCE; STRATIFICATION; STATISTICS AB Principal strata are defined by the potential values of a post-treatment variable, and a principal effect is a causal effect within a principal stratum. Identifying the principal effect within every principal stratum is quite challenging. In this paper, we propose an approach for identifying principal effects on a binary outcome via a pre-treatment covariate. We prove the identifiability with single post-treatment intervention under the monotonicity assumption. Furthermore, we discuss the local identifiability with multicomponent intervention. Simulations are performed to evaluate our approach. We also apply it to a real data set from the Improving Mood-Promoting Access to Collaborate Treatment program. C1 [Yan, Wei; Ding, Peng; Geng, Zhi] Peking Univ, Sch Math Sci, Beijing 100871, Peoples R China. [Zhou, Xiaohua] Peking Univ, Beijing Int Ctr Math Res, Beijing 100871, Peoples R China. [Zhou, Xiaohua] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Zhou, Xiaohua] VA Puget Sound Hlth Care Syst, HSR&D Ctr Excellence, Biostat Unit, Seattle, WA 98101 USA. RP Geng, Z (reprint author), Peking Univ, Sch Math Sci, Beijing 100871, Peoples R China. EM zgeng@math.pku.edu.cn FU NIH [R03 TW007197]; National Natural Science Foundation of China [10721403, 10931002] FX The authors would like to thank the referees for their valuable comments and suggestions. The authors are grateful to Dr. Unutzer and the IMPACT study team for making their data available. This work was supported by NIH R03 TW007197 and the National Natural Science Foundation of China (Grant Nos. 10721403, 10931002). NR 10 TC 1 Z9 1 U1 0 U2 6 PU HIGHER EDUCATION PRESS PI BEIJING PA SHATANHOU ST 55, BEIJING 100009, PEOPLES R CHINA SN 1673-3452 J9 FRONT MATH CHINA JI Front. Math. China PD DEC PY 2011 VL 6 IS 6 BP 1249 EP 1263 DI 10.1007/s11464-011-0127-8 PG 15 WC Mathematics SC Mathematics GA 856MT UT WOS:000297647000013 ER PT J AU Moskvina, V O'Dushlaine, C Purcell, S Craddock, N Holmans, P O'Donovan, MC AF Moskvina, Valentina O'Dushlaine, Colm Purcell, Shaun Craddock, Nick Holmans, Peter O'Donovan, Michael C. TI Evaluation of an approximation method for assessment of overall significance of multiple-dependent tests in a genomewide association study SO GENETIC EPIDEMIOLOGY LA English DT Article DE GWAS; set-based analysis; multiple-dependent tests ID COMBINING INDEPENDENT TESTS; P-VALUES; ASYMPTOTIC OPTIMALITY; TRUNCATED PRODUCT; WIDE ASSOCIATION; FISHERS METHOD; SCHIZOPHRENIA AB We describe implementation of a set-based method to assess the significance of findings from genomewide association study data. Our method, implemented in PLINK, is based on theoretical approximation of Fisher's statistics such that the combination of P-vales at a gene or across a pathway is carried out in a manner that accounts for the correlation structure, or linkage disequilibrium, between single nucleotide polymorphisms. We compare our method to a permutation-based product of P-values approach and show a typical correlation in excess of 0.98 for a number of comparisons. The method gives Type I error rates that are less than or equal to the corresponding nominal significance levels, making it robust to the effects of false positives. We show that in broadly similar populations, reference data sets of markers are an appropriate substrate for deriving marker-marker linkage disequilibrium (LD), negating the need to access individual level genotypes, greatly facilitating its generic applicability. We show that the method is thus robust to LD-associated bias and has equivalent performance to permutation-based methods, with a significantly shorter runtime. This is particularly relevant at a time of increasing public availability of significantly larger genetic data sets and should go a long way to assist in the rapid analysis of these data sets. Genet. Epidemiol. 2011. (C) 2011 Wiley Periodicals, Inc.35:861-866, 2011 C1 [Moskvina, Valentina; Craddock, Nick; Holmans, Peter; O'Donovan, Michael C.] Cardiff Univ, Sch Med, MRC Ctr Neuropsychiat Genet & Genom, Cardiff CF14 4XN, S Glam, Wales. [O'Dushlaine, Colm; Purcell, Shaun] Massachusetts Gen Hosp, Dept Psychiat, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [O'Dushlaine, Colm; Purcell, Shaun] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [O'Dushlaine, Colm; Purcell, Shaun] Harvard Univ, Sch Med, Boston, MA USA. [O'Dushlaine, Colm; Purcell, Shaun] MIT, Stanley Ctr Psychiat Res, Cambridge, MA 02139 USA. RP Moskvina, V (reprint author), Cardiff Univ, Sch Med, MRC Ctr Neuropsychiat Genet & Genom 8, Cardiff CF14 4XN, S Glam, Wales. EM MoskvinaV1@cf.ac.uk RI Holmans, Peter/F-4518-2015; OI Holmans, Peter/0000-0003-0870-9412; O'Donovan, Michael/0000-0001-7073-2379; Escott-Price, Valentina/0000-0003-1784-5483 FU MRC (UK); NIMH (USA) CONTE [2 P50 MH066392-05A1] FX Contract grant sponsors: MRC (UK); NIMH (USA) CONTE; Contract grant number: 2 P50 MH066392-05A1. NR 16 TC 19 Z9 19 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD DEC PY 2011 VL 35 IS 8 BP 861 EP 866 DI 10.1002/gepi.20636 PG 6 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 854BD UT WOS:000297468600012 PM 22006681 ER PT J AU Viswanathan, AN Macklin, EA Berkowitz, R Matulonis, U AF Viswanathan, Akita N. Macklin, Eric A. Berkowitz, Ross Matulonis, Ursula TI The importance of chemotherapy and radiation in uterine papillary serous carcinoma SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Uterine papillary serous cancer; Chemotherapy; Radiation therapy ID GYNECOLOGIC-ONCOLOGY-GROUP; PLATINUM-BASED CHEMOTHERAPY; RISK ENDOMETRIAL CANCER; PHASE-III TRIAL; WHOLE ABDOMINOPELVIC IRRADIATION; LONG-TERM SURVIVAL; ADJUVANT CHEMOTHERAPY; CLEAR-CELL; ABDOMINAL RADIOTHERAPY; PELVIC RADIOTHERAPY AB Purpose. To identify prognostic and predictive factors of overall survival (OS), relapse-free survival (RFS) and toxicity for patients with uterine papillary serous carcinoma (UPSC). Materials and methods. Patient, tumor, treatment and relapse characteristics of 135 women with Stages I-IVA UPSC treated between 1980 and 2006 at Dana-Farber/Brigham and Women's Cancer Center (DF/BWCC) were analyzed using Cox regression models to determine prognostic and predictive factors for OS. RFS and toxicity. Results. Mean follow-up was 5.5 years (range, 0.01-25.2). Median 5-year OS was 52%, and RFS was 42% for all patients. On Cox regression analysis, increasing age, stage, and myometrial invasion were prognostic factors associated with shorter OS and RFS. A paclitaxel-platinum chemotherapy regimen was significantly associated with longer OS (hazard ratio [HR] = 0.34, 95% confidence interval [CI] 0.15-0.74, p = 0.007) and RFS (HR = 0.45, 95% CI 0.22-0.92, p = 0.03). RFS was improved for patients treated with RT (HR = 0.44, 95% CI 0.25-0.77, p = 0.004). The 5-year grade 3+ toxicity rate was 3.5% for those who received RT and was 2.9% for those who did not (p = NS). Conclusion. Uterine papillary serous cancer can be an aggressive tumor type with a poor prognosis. RFS was improved by radiation and chemotherapy with few grade 3 or higher complications. Using radiation and paclitaxel-platinum chemotherapy should be attempted whenever feasible for patients with UPSC who do not have distant metastases at diagnosis. (C) 2011 Elsevier Inc. All rights reserved. C1 [Viswanathan, Akita N.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol,Med Sch, Boston, MA 02115 USA. [Macklin, Eric A.] Harvard Univ, Massachusetts Gen Hosp, Ctr Biostat, Sch Med, Boston, MA 02115 USA. [Berkowitz, Ross] Harvard Univ, Brigham & Womens Hosp, Div Gynecol Oncol, Sch Med, Boston, MA 02115 USA. [Matulonis, Ursula] Harvard Univ, Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA. RP Viswanathan, AN (reprint author), Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol,Med Sch, 75 Francis St,ASB 1,L2, Boston, MA 02115 USA. EM aviswanathan@lroc.harvard.edu RI Macklin, Eric/E-2955-2013 OI Macklin, Eric/0000-0003-1618-3502 FU NIH [5-K07-CA117979-02] FX Dr. Viswanathan receives support through NIH grant 5-K07-CA117979-02. NR 53 TC 22 Z9 24 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD DEC PY 2011 VL 123 IS 3 BP 542 EP 547 DI 10.1016/j.ygyno.2011.09.005 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 856CA UT WOS:000297613000018 PM 21963091 ER PT J AU Smith, KE Kang, Y Freeman, GJ O'Callaghan, C Klenerman, P Willberg, CB AF Smith, K. E. Kang, Y. Freeman, G. J. O'Callaghan, C. Klenerman, P. Willberg, C. B. TI Probing the function of PILAR/KACL, a novel C type lectin SO IMMUNOLOGY LA English DT Meeting Abstract CT Annual Congress of the British-Society-for-Immunology CY DEC 05-08, 2011 CL Liverpool, ENGLAND SP British Soc Immunol C1 [Smith, K. E.; O'Callaghan, C.; Klenerman, P.; Willberg, C. B.] Univ Oxford, Nuffield Dept Med, Oxford, England. [Kang, Y.; Freeman, G. J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD DEC PY 2011 VL 135 SU 1 SI SI BP 100 EP 100 PG 1 WC Immunology SC Immunology GA 854PQ UT WOS:000297507100293 ER PT J AU Biswas, S Chang, H Sarkis, PTN Fikrig, E Zhu, Q Marasco, WA AF Biswas, Subhabrata Chang, Hong Sarkis, Phuong T. N. Fikrig, Erol Zhu, Quan Marasco, Wayne A. TI Humoral immune responses in humanized BLT mice immunized with West Nile virus and HIV-1 envelope proteins are largely mediated via human CD5(+) B cells SO IMMUNOLOGY LA English DT Article DE BLT; HIVgp140; humanized mice; IC31; West Nile virus envelope ID SCID IL2R-GAMMA(NULL) MICE; HEMATOPOIETIC STEM-CELLS; IMMUNODEFICIENT MICE; HUMAN-BLOOD; T-CELLS; INFECTION; TRANSMISSION; ANTIBODIES; TRANSPLANTATION; RECONSTITUTION AB BLT mice, constructed by surgical implantation of human fetal thymus-liver tissues and intravenous delivery of autologous CD34(+) haematopoietic stem cells into adult non-obese diabetic/severe combined immunodeficiency mice, were evaluated for vaccine-induced humoral immune responses. Following engraftment, these mice developed a human lymphoid system; however, the majority of the peripheral human B lymphocytes displayed an immature phenotype as evidenced by surface CD10 expression. Over 50% of the human B cells in the periphery but not in the bone marrow also expressed the CD5 antigen, which is found only infrequently on mature follicular B cells in humans. A single intramuscular immunization with recombinant viral envelope antigens, e. g. HIV-gp140 and West Nile Virus envelope proteins, together with the immune stimulatory IC31 (R) adjuvant resulted in seroconversion characterized by antigen-specific human antibodies predominantly of the IgM isotype. However, repeated booster immunizations did not induce secondary immune responses as evidenced by the lack of class switching and specific IgM levels remaining relatively unchanged. Interestingly, the peripheral CD19(+) CD5(+) but not the CD19(+) CD5(-) human B lymphocytes displayed a late developing CD27(+) IgM(+) memory phenotype, suggesting that the CD5(+) B-cell subset, previously implicated in 'natural antibody' production, may play a role in the vaccine-induced antibody response. Furthermore, human T lymphocytes from these mice demonstrated suboptimal proliferative responses and loss of co-stimulatory surface proteins ex vivo that could be partially reversed with human interleukin-2 and interleukin-7. Therefore, vaccine-induced immune responses in BLT mice resemble a T-cell-independent pathway that can potentially be modulated in vivo by the exogenous delivery of human cytokines/growth factors. C1 [Biswas, Subhabrata; Chang, Hong; Sarkis, Phuong T. N.; Zhu, Quan; Marasco, Wayne A.] Harvard Univ, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Sch Med, Boston, MA 02215 USA. [Biswas, Subhabrata; Chang, Hong; Sarkis, Phuong T. N.; Zhu, Quan; Marasco, Wayne A.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. [Fikrig, Erol] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. RP Marasco, WA (reprint author), Harvard Univ, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Sch Med, 450 Brookline Ave,JFB824, Boston, MA 02215 USA. EM wayne_marasco@dfci.harvard.edu FU NIAID [UO1 AI0703431, 5U01 AI061318, 1R21 AI091557]; National Foundation of Cancer Research FX The authors are grateful to Michel Ledizet (L2 Diagnostics, LLC, New Haven, CT) and Erol Fikrig (Yale University School of Medicine) for generously providing the recombinant WNV-E antigen and to Xingzhen Yang (DFCI) for providing the plasmid DNA construct expressing the HIVgp140 trimer. The monoclonal antibodies to HIV-1 gp41 (4E10 from Hermann Katinger) and gp120 (b12 from Dennis Burton) were obtained through the AIDS Research and Reference Reagent Program, Division of AIDS, National Institute of Allergic and Infectious Diseases (NIAID; National Institutes of Health, Germantown, MD). The authors also thank the staff of the Animal Research Facility at DFCI for excellent animal care and housing. This work was supported by NIAID grants UO1 AI0703431 to E.F., 5U01 AI061318 and 1R21 AI091557 to W.A.M. E.F. is an Investigator of the Howard Hughes Medical Institute. Financial assistance from the National Foundation of Cancer Research is also acknowledged. NR 50 TC 32 Z9 32 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD DEC PY 2011 VL 134 IS 4 BP 419 EP 433 DI 10.1111/j.1365-2567.2011.03501.x PG 15 WC Immunology SC Immunology GA 853XS UT WOS:000297459600007 PM 22044090 ER PT J AU Lemonovich, TL Haynes, K Lautenbach, E Amorosa, VK AF Lemonovich, T. L. Haynes, K. Lautenbach, E. Amorosa, V. K. TI Combination therapy with an aminoglycoside for Staphylococcus aureus endocarditis and/or persistent bacteremia is associated with a decreased rate of recurrent bacteremia: a cohort study SO INFECTION LA English DT Article ID ANTIMICROBIAL THERAPY; RISK-FACTORS; PROSPECTIVE MULTICENTER; INFECTIVE ENDOCARDITIS; BACTERIAL-ENDOCARDITIS; GENTAMICIN; MORTALITY; CARE; PREDICTORS; DIAGNOSIS AB Purpose Although limited data exist on the efficacy and potential risk of synergistic aminoglycoside therapy for persistent Staphylococcus aureus bacteremia and endocarditis, aminoglycosides are frequently used in clinical practice. Methods As our study population, we included subjects fulfilling the modified Duke criteria for S. aureus endocarditis and/or having greater than 72 h of S. aureus bacteremia. Among these subjects, we compared patients who did and did not receive aminoglycoside therapy for their S. aureus bloodstream infection. These groups were compared for the primary outcome of recurrent bacteremia, as well as for the duration of bacteremia, mortality, complication rate, and incident renal failure. Results Eighty-seven subjects fulfilled the inclusion criteria. Of these, 49 received aminoglycoside therapy, whereas 38 did not. There were no significant differences in the baseline characteristics when comparing groups who did or did not receive aminoglycoside therapy. Four (8.2%) subjects treated with aminoglycoside therapy experienced recurrent bacteremia versus nine (23.7%) who did not receive aminoglycoside therapy [relative risk and 95% confidence interval [RR (95% CI)] = 0.51 (0.22-1.17), p = 0.04]. In multivariable analyses, aminoglycoside use remained significantly associated with a decrease in recurrent bacteremia [adjusted odds ratio (OR) (95% CI) = 0.26 (0.07-0.98), p = 0.046]. No significant differences were seen between groups treated with and without an aminoglycoside in terms of the 6-month all-cause mortality (51.0 vs. 42.1%, p = 0.41), complication rate (71.4 vs. 73.7%, p = 0.82), or incident renal failure (54.5 vs. 46.9%, p = 0.54). Conclusions The use of combination therapy with an aminoglycoside in persistent S. aureus bacteremia and/or endocarditis may be associated with a lower rate of recurrent bacteremia without significant differences in the incident renal failure. C1 [Lemonovich, T. L.] Case Western Reserve Univ, Div Infect Dis & HIV Med, Dept Med, Cleveland, OH 44106 USA. [Haynes, K.; Lautenbach, E.] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Lautenbach, E.; Amorosa, V. K.] Univ Penn, Sch Med, Div Infect Dis, Dept Med, Philadelphia, PA 19104 USA. [Lautenbach, E.] Univ Penn, Sch Med, Ctr Educ, Philadelphia, PA 19104 USA. [Lautenbach, E.] Univ Penn, Sch Med, Ctr Res Therapeut, Philadelphia, PA 19104 USA. [Amorosa, V. K.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Lemonovich, TL (reprint author), Case Western Reserve Univ, Div Infect Dis & HIV Med, Dept Med, 11100 Euclid Ave, Cleveland, OH 44106 USA. EM tracy.lemonovich@UHhospitals.org FU Merck; Ortho-McNeil; AstraZeneca FX Ebbing Lautenbach has received research funding from Merck, Ortho-McNeil, and AstraZeneca. All other authors have no conflicts. NR 32 TC 4 Z9 4 U1 0 U2 1 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0300-8126 EI 1439-0973 J9 INFECTION JI Infection PD DEC PY 2011 VL 39 IS 6 BP 549 EP 554 DI 10.1007/s15010-011-0189-2 PG 6 WC Infectious Diseases SC Infectious Diseases GA 855RX UT WOS:000297583200009 PM 21898120 ER PT J AU Sidhu, M Cotoner, CA Guleng, B Arihiro, S Chang, SY Duncan, KW Ajami, AM Chau, M Reinecker, HC AF Sidhu, Maninder Cotoner, Carmen Alonso Guleng, Bayasi Arihiro, Seiji Chang, Sunyoung Duncan, Kenneth W. Ajami, Alfred M. Chau, MyDoanh Reinecker, Hans-Christian TI Small Molecule Tyrosine Kinase Inhibitors for the Treatment of Intestinal Inflammation SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE Flt3 receptor tyrosine kinase inhibitors; inflammatory bowel diseases; Crohn's disease; ulcerative colitis; novel treatment; mucosal recovery; dendritic cells; TNF-alpha; IL-10 ID RECOMBINANT HUMAN INTERLEUKIN-10; ACTIVE CROHNS-DISEASE; BOWEL-DISEASE; INNATE IMMUNITY; DENDRITIC CELLS; RECEPTOR; LIGAND; THERAPIES; EXPANSION; NOD2 AB Background: We developed a series of dendritic cell autoimmune modulators (DCAMs) based on small molecule Flt3 receptor tyrosine kinase inhibitors (TKIs) for the inhibition of intestinal inflammation and oral delivery. Methods: DCAMs were administered orally during and after induction of dextran sodium sulfate (DSS)-induced colitis. Dendritic cell recruitment and inflammatory responses were determined in the mucosal immune system during acute intestinal inflammatory responses and mucosal recovery. Bone marrow-derived macrophages were utilized to define the mechanisms by which DCAMs can modify responses to microbial signals. Results: Oral doses of DCAMs prevented severe weight loss and mucosal inflammation associated with DSS colitis in mice. The presence of DCAMs increased the number of CD11c(+)PDCA1(+) dendritic cells, induced interleukin (IL)-10 expression, and reduced inflammatory cytokine expression in the mucosal immune system. Surprisingly, DCAMs regulated innate immune responses in macrophages resulting in the inhibition of tumor necrosis factor alpha (TNF-alpha) production and the induction of IL-10 expression during Toll-like receptor-mediated signaling. Conclusions: We identified two new imidazoacridinone derivatives that protect mice from severe colitis and promote mucosal recovery by enhancing protective cytokine production while inhibiting proinflammatory stimuli during microbial recognition. These compounds are promising candidates for further development into potent orally available drugs for the prevention of colitis and promotion of mucosal recovery. (Inflamm Bowel Dis 2011; 17:2416-2426) C1 [Reinecker, Hans-Christian] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Dept Med, Gastroenterol Unit, Boston, MA 02114 USA. [Reinecker, Hans-Christian] Harvard Univ, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. [Duncan, Kenneth W.; Ajami, Alfred M.; Chau, MyDoanh] Antisoma Inc, Cambridge, MA USA. RP Reinecker, HC (reprint author), Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Dept Med, Gastroenterol Unit, Jackson Bldg R711,Fruit St, Boston, MA 02114 USA. EM hans-christian_reinecker@hms.harvard.edu RI Alonso-Cotoner, Carmen/N-7057-2014 OI Alonso-Cotoner, Carmen/0000-0002-3483-2919 FU NIDDK (National Institute of Diabetes and Digestive and Kidney Diseases) [DK068181, DK033506, DK043351]; Antisoma, Inc. FX Supported by grants NIDDK (National Institute of Diabetes and Digestive and Kidney Diseases) DK068181, DK033506, DK043351 and a research grant from Antisoma, Inc. NR 44 TC 7 Z9 7 U1 1 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD DEC PY 2011 VL 17 IS 12 BP 2416 EP 2426 DI 10.1002/ibd.21646 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 857QP UT WOS:000297734000009 PM 21438094 ER PT J AU Sonnenberg, A Melton, SD Genta, RM Lewis, AD AF Sonnenberg, Amnon Melton, Shelby D. Genta, Robert M. Lewis, Anne D. TI Absence of Focally Enhanced Gastritis in Macaques with Idiopathic Colitis SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE etiology of inflammatory bowel disease; focally enhanced gastritis; gastritis; idiopathic chronic colitis of macaques; infectious organisms in inflammatory bowel disease; rhesus macaques (Macaca mulatta) ID RHESUS MACAQUES; CROHNS-DISEASE; HELICOBACTER-PYLORI; CHRONIC DIARRHEA; MACACA-MULATTA; MONKEYS; BIOPSIES; MODEL AB Background: Focally enhanced gastritis has been described in association with Crohn's disease and ulcerative colitis, but is rare in the general population. The study aim was to test whether idiopathic colitis in macaques was associated with any characteristic changes of the gastric mucosa resembling similar changes in humans. Methods: The presence or absence of idiopathic colitis was established by gross and microscopic examination of the colons of rhesus macaques (Macaca mulatta), which died at the Oregon National Primate Research Center. Gastric tissue specimens were compared between a case population of 26 macaques with idiopathic colitis and a control population of 21 macaques without colitis. The specimens were histologically assessed by two independent pathologists blinded to the presence or absence of idiopathic colitis. Differences between cases and controls were compared using a two-sided Fisher's exact test. Results: Of the 26 cases of macaques with colitis, 11 animals (42%) harbored signs of chronic gastritis. Of the 21 control macaques without colitis, nine animals (43%) harbored signs of chronic gastritis, P = 1.0000. Of all animals with gastritis, 1/11 animals with colitis and 2/9 control animals showed rare active gastritis as evidenced by the presence of neutrophils, P = 0.5658. Lymphocytic infiltrates of the gastric mucosa were seen in 4/11 colitis cases and 0/9 controls, P = 0.0942. No gastric specimens with focally enhanced gastritis were found among any of the case or control animals. Conclusions: Unlike chronic inflammatory bowel disease in humans, idiopathic colitis in macaques is not associated with focally enhanced gastritis or any other type of specific gastritis. (Inflamm Bowel Dis 2011;17:2456-2461) C1 [Sonnenberg, Amnon] Portland VA Med Ctr, Portland, OR USA. [Sonnenberg, Amnon; Lewis, Anne D.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Melton, Shelby D.; Genta, Robert M.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Melton, Shelby D.; Genta, Robert M.] Caris Diagnost, Dallas, TX USA. [Melton, Shelby D.; Genta, Robert M.] Dallas VA Med Ctr, Dallas, TX USA. [Lewis, Anne D.] Oregon Natl Primate Res Ctr, Portland, OR USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr P3 GI, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu FU Takeda Pharmaceuticals; Oregon National Primate Research Center NCRR [RR000163] FX The authors have no potential conflicts of interest to declare. Amnon Sonnenberg has been supported by a grant from Takeda Pharmaceuticals. Anne D. Lewis has been supported by the Oregon National Primate Research Center NCRR base grant RR000163. NR 17 TC 3 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD DEC PY 2011 VL 17 IS 12 BP 2456 EP 2461 DI 10.1002/ibd.21696 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 857QP UT WOS:000297734000013 PM 21425215 ER PT J AU Boden, E Goettel, J Ahmed, O Moran, C Nguyen, D Dunkin, D Mayer, L Snapper, S AF Boden, Elisa Goettel, Jeremy Ahmed, Osub Moran, Christopher Nguyen, Deanna Dunkin, David Mayer, Lloyd Snapper, Scott TI The Wiskott Aldrich Syndrome protein (WASp) reduces T cell proliferation and regulatory T cell induction via increased sensitivity to TGF beta SO INFLAMMATORY BOWEL DISEASES LA English DT Meeting Abstract C1 [Boden, Elisa] Benaroya Res Inst, Seattle, WA USA. [Moran, Christopher; Nguyen, Deanna] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Dunkin, David; Mayer, Lloyd] Mt Sinai Hosp, New York, NY 10029 USA. [Goettel, Jeremy; Ahmed, Osub; Snapper, Scott] Childrens Hosp Boston, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD DEC PY 2011 VL 17 SU 2 BP S74 EP S74 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 857RB UT WOS:000297735300243 ER PT J AU Chen, XH Yang, GX Song, JH Xu, H Li, D Zeng, HY Parsons-Wingerter, P Reinecker, HC Kelly, C AF Chen, Xinhua Yang, Guoxun Song, Joo Hye Xu, Hua Li, Dan Zeng, Huiyan Parsons-Wingerter, Patricia Reinecker, Hans-Christian Kelly, Ciaran TI Probiotic Yeast Inhibits VEGFR Signaling and Angiogenesis in Colonic Inflammation SO INFLAMMATORY BOWEL DISEASES LA English DT Meeting Abstract C1 [Chen, Xinhua; Yang, Guoxun; Xu, Hua; Li, Dan; Zeng, Huiyan; Kelly, Ciaran] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Song, Joo Hye; Reinecker, Hans-Christian] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Parsons-Wingerter, Patricia] John Glenn NASA Res Ctr, Cleveland, OH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD DEC PY 2011 VL 17 SU 2 BP S76 EP S77 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 857RB UT WOS:000297735300251 ER PT J AU Essers, J Ripke, S Neale, B Xavier, R Targan, S Vu, M Rotter, J Dubinsky, M McGovern, D Daly, M AF Essers, Jonah Ripke, Stephan Neale, Benjamin Xavier, Ramnik Targan, Stephan Vu, Michelle Rotter, Jerome Dubinsky, Marla McGovern, Dermot Daly, Mark TI An accurate and reproducible discrimination tool for inflammatory bowel disease subtype using genetics, serologies, and smoking status SO INFLAMMATORY BOWEL DISEASES LA English DT Meeting Abstract C1 [Essers, Jonah; Targan, Stephan] Childrens Hosp, Boston, MA 02115 USA. [Essers, Jonah; Ripke, Stephan; Neale, Benjamin; Xavier, Ramnik; Daly, Mark] Massachussetts Gen Hosp, Boston, MA USA. [Ripke, Stephan; Neale, Benjamin] Broad Inst, Cambridge, MA USA. [Vu, Michelle; Rotter, Jerome; Dubinsky, Marla; McGovern, Dermot] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD DEC PY 2011 VL 17 SU 2 BP S1 EP S1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 857RB UT WOS:000297735300003 ER PT J AU Hagin, S Lobato, DJ Sands, BE Korzenik, JR Merrick, M Shah, SA Bancroft, B Bright, R Law, M Durfee, H LeLeiko, NS AF Hagin, Sarah Lobato, Debra J. Sands, Bruce E. Korzenik, Joshua R. Merrick, Marjorie Shah, Samir A. Bancroft, Barbara Bright, Renee Law, Meaghan Durfee, Heather LeLeiko, Neal S. TI Nutrition and dietary behaviors in pediatric Inflammatory Bowel Disease SO INFLAMMATORY BOWEL DISEASES LA English DT Meeting Abstract C1 [Hagin, Sarah; Lobato, Debra J.; Shah, Samir A.; Bancroft, Barbara; Bright, Renee; Law, Meaghan; Durfee, Heather; LeLeiko, Neal S.] Rhode Isl Hosp, Providence, RI USA. [Lobato, Debra J.; Shah, Samir A.; LeLeiko, Neal S.] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA. [Sands, Bruce E.] Mt Sinai Sch Med, New York, NY USA. [Korzenik, Joshua R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Merrick, Marjorie] Crohns & Colitis Fdn Amer, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD DEC PY 2011 VL 17 SU 2 BP S32 EP S32 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 857RB UT WOS:000297735300100 ER PT J AU Tran, H Barnich, N Lau, C Mizoguchi, A Darfeuille-Michaud, A Mizoguchi, E AF Hoa Tran Barnich, Nicola Lau, Cindy Mizoguchi, Atsushi Darfeuille-Michaud, Arlette Mizoguchi, Emiko TI Glycosylated chitinase 3-like 1 protein and chitin-binding motif of potentially pathogenic E. coli play a critical role in host-microbial interactions SO INFLAMMATORY BOWEL DISEASES LA English DT Meeting Abstract C1 [Hoa Tran; Lau, Cindy; Mizoguchi, Atsushi; Mizoguchi, Emiko] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Barnich, Nicola; Darfeuille-Michaud, Arlette] Univ Auvergne, Clermont Ferrand, France. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD DEC PY 2011 VL 17 SU 2 BP S80 EP S80 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 857RB UT WOS:000297735300262 ER PT J AU Hou, J Chang, MM Nguyen, T Kramer, J Richardson, P Sansgiry, S D'Avolio, L El-Serag, H AF Hou, Jason Chang, Mimi Thien Nguyen Kramer, Jennifer Richardson, Peter Sansgiry, Shubhada D'Avolio, Leonard El-Serag, Hashem TI Automated document-level classification of surveillance and diagnostic colonoscopy for Inflammatory Bowel Disease: An application of natural language processing SO INFLAMMATORY BOWEL DISEASES LA English DT Meeting Abstract C1 [Hou, Jason; Kramer, Jennifer; Richardson, Peter; Sansgiry, Shubhada; El-Serag, Hashem] Michael E DeBakey VA Med Ctr, Houston VA HSR&D Ctr Excellence, Houston, TX USA. [Hou, Jason; Chang, Mimi; Kramer, Jennifer; Richardson, Peter; Sansgiry, Shubhada; El-Serag, Hashem] Baylor Coll Med, Houston, TX 77030 USA. [Thien Nguyen; D'Avolio, Leonard] VA Boston Healthcare Syst, Cooperat Studies Coordinating Ctr, Massachusetts Vet Epidemiol Res & Informat Ctr MA, Jamaica Plain, MA USA. [D'Avolio, Leonard] Harvard Univ, Sch Med, Div Aging, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD DEC PY 2011 VL 17 SU 2 BP S37 EP S38 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 857RB UT WOS:000297735300115 ER PT J AU Khalili, H Huang, E Ananthakrishnan, A Higuchi, L Richter, J Fuchs, C Chan, A AF Khalili, Hamed Huang, Edward Ananthakrishnan, Ashwin Higuchi, Leslie Richter, James Fuchs, Charles Chan, Andrew TI Geographic variation and the incidence of inflammatory bowel disease among US women SO INFLAMMATORY BOWEL DISEASES LA English DT Meeting Abstract C1 [Khalili, Hamed; Huang, Edward; Ananthakrishnan, Ashwin; Richter, James; Chan, Andrew] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Higuchi, Leslie] Childrens Hosp, Boston, MA 02115 USA. [Fuchs, Charles] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD DEC PY 2011 VL 17 SU 2 BP S15 EP S15 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 857RB UT WOS:000297735300048 ER PT J AU Mukhopadhyay, S Paidassi, H Acharya, M Kwon, M Chow, C Lacy-Hulbert, A AF Mukhopadhyay, Subhankar Paidassi, Helena Acharya, Mridu Kwon, Manjae Chow, Camille Lacy-Hulbert, Adam TI Innate and adaptive immune cross-talk regulates intestinal macrophage activation and drives colitis in mice SO INFLAMMATORY BOWEL DISEASES LA English DT Meeting Abstract C1 [Mukhopadhyay, Subhankar; Paidassi, Helena; Acharya, Mridu; Kwon, Manjae; Chow, Camille; Lacy-Hulbert, Adam] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Acharya, Mridu; Kwon, Manjae; Chow, Camille; Lacy-Hulbert, Adam] Harvard Univ, Sch Med, Boston, MA USA. [Mukhopadhyay, Subhankar] Univ Oxford, Oxford, England. [Paidassi, Helena] Univ Edinburgh, Edniburgh, Scotland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD DEC PY 2011 VL 17 SU 2 BP S81 EP S81 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 857RB UT WOS:000297735300266 ER PT J AU Nguyen, DD Goettel, JA Ahmed, O Horwitz, BH Snapper, SB AF Nguyen, Deanna D. Goettel, Jeremy A. Ahmed, Osub Horwitz, Bruce H. Snapper, Scott B. TI Colitis in mice with WASP-Deficient myleoid cells is associated with defects in IL-10 secretion and can be rescued with exogenous IL-10 SO INFLAMMATORY BOWEL DISEASES LA English DT Meeting Abstract C1 [Nguyen, Deanna D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Nguyen, Deanna D.; Goettel, Jeremy A.; Ahmed, Osub; Horwitz, Bruce H.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Goettel, Jeremy A.; Ahmed, Osub; Snapper, Scott B.] Childrens Hosp, Div Gastroenterol Nutr, Boston, MA 02115 USA. [Horwitz, Bruce H.] Brigham & Womens Hosp, Div Pathol, Boston, MA 02115 USA. [Snapper, Scott B.] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD DEC PY 2011 VL 17 SU 2 BP S74 EP S75 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 857RB UT WOS:000297735300244 ER PT J AU Tse, WKF Lai, KP Takei, Y AF Tse, William K. F. Lai, K. P. Takei, Y. TI Medaka osmotic stress transcription factor 1b (Ostf1b/TSC22D3-2) triggers hyperosmotic responses of different ion transporters in medaka gill and human embryonic kidney cells via the JNK signalling pathway SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY LA English DT Article DE Ion transporters; JNK pathway; Medaka; Osmoregulation ID TILAPIA OREOCHROMIS-MOSSAMBICUS; HYPERTONICITY-INDUCED AQUAPORIN-1; PROTEIN-KINASE; FRESH-WATER; GENE-EXPRESSION; MESSENGER-RNA; ANGUILLA-JAPONICA; PAVEMENT CELLS; NA+/K+-ATPASE; JAPANESE EEL AB Eukaryotic cells undergo rapid regulatory processes to maintain cellular homeostasis upon osmotic stress. In fishes, gill epithelial cells play main roles in these processes. Although osmoregulatory functions of fish gills have been well studied, little is known about the underlying mechanisms, particularly the hypertonic-induced signalling pathways during osmotic stress. This study reports for the first time on the osmo-sensing signal cascade that related to the medaka osmotic stress transcription factor 1 (Ostf1), a hypertonic induced immediate early gene, under hypertonic stress. Quantitative real-time PCR showed the rapid increase of Ostf1 in gill after transfer of medaka from fresh water to 50% seawater; particularly Ostf1b whose mRNA expression increased to 4 folds at 0.5 h and reached to 10 folds at 6 h after the transfer. The in vivo knockdown of Ostf1b profoundly inhibited SEK and JNK phosphorylation, but not p38 and ERK phosphorylation in the medaka gill tissue. To further investigate the possible role of Ostf1b in the JNK pathway, Ostf1b was ectopically expressed in HEK293 cells. Results indicated that Ostf1b is a downstream target of SEK and JNK and exerts a positive feedback loop on the JNK signalling pathway via activation of GCK and/or MLK3 proteins. Additionally, MAPK inhibitors experiments suggested that activation of the JNK pathway by hypertonicity is involved in the maintenance of Ostf1b stability, which in turn provides continuous stimulation of GCK for JNK phosphorylation. Lastly, changes in transcription levels of different water/ion transporters were found in knockdown or ecoptic over-expression of Ostf1b in medaka gills and human embryonic kidney cells, suggesting the role of Ostf1b in modulation of critical water channel/ion transporters during osmotic stress. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Tse, William K. F.; Takei, Y.] Univ Tokyo, Physiol Lab, Atmosphere & Ocean Res Inst, Tokyo 1138654, Japan. [Lai, K. P.] Chinese Univ Hong Kong, Dept Anat & Cellular Pathol, Hong Kong, Hong Kong, Peoples R China. RP Tse, WKF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med, Room 4450,185 Cambridge St, Boston, MA 02114 USA. EM kftse@aori.u-tokyo.ac.jp RI TSE, KA FAI WILLIAM/C-9384-2012; Lai, Keng Po/F-2045-2013; OI TSE, KA FAI WILLIAM/0000-0002-3738-0460; LAI, Keng Po/0000-0001-8135-6030 FU Japan Society for the Promotion of Science (JSPS) FX This work was supported by the Grants-in-Aid for JSPS Fellows, Japan Society for the Promotion of Science (JSPS) to Y. Takei and W.K.F. Tse. NR 53 TC 13 Z9 13 U1 0 U2 16 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1357-2725 J9 INT J BIOCHEM CELL B JI Int. J. Biochem. Cell Biol. PD DEC PY 2011 VL 43 IS 12 BP 1764 EP 1775 DI 10.1016/j.biocel.2011.08.013 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 854JV UT WOS:000297491700015 PM 21907305 ER PT J AU Houbballah, R Robaldo, A Albadawi, H Titus, J LaMuraglia, GM AF Houbballah, Rabih Robaldo, Alessandro Albadawi, Hassan Titus, James LaMuraglia, Glenn M. TI A novel model of accelerated intimal hyperplasia in the pig iliac artery SO INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY LA English DT Article DE animal model; intimal hyperplasia; restenosis ID PORCINE CORONARY-ARTERIES; BALLOON ANGIOPLASTY; NATURAL-HISTORY; ANIMAL-MODEL; INJURY; RESTENOSIS; STENTS; SWINE; PROLIFERATION AB There is no good animal model of large artery injury-induced intimal hyperplasia (IH). Those available are reproducible, providing only a few layers of proliferating cells or have the disadvantage of the presence of a metallic stent that complicates histology evaluation. This study was designed to develop a new, simple model of accelerated IH based on balloon injury in conjunction with disruption of the Internal Elastic Lamina (IEL) in pig external iliac arteries. Iliac artery injury (n = 24) was performed in 12 Yorkshire pigs divided in two groups: Group I (n = 10), overdistention injury induced by an oversized non-compliant balloon; Group II (n = 14), arterial wall disruption by pulling back an isometric cutting balloon (CB) followed by stretching with a compliant Fogarty Balloon (FB). At two weeks, arteries were processed for morphometric analysis and immunohistochemistry (IHC) for smooth muscle cells (SMC) and proliferating cell nuclear antigen (PCNA). When comparing the two groups, at 2 weeks, arteries of group II had a higher incidence of IH (100% vs. 50%, P = 0.0059), increased intimal areas (2.54 +/- 0.33 mm(2) vs. 0.93 +/- 0.36 mm(2), P = 0.004), increased intimal area/Media area ratios (0.95 +/- 0.1 vs. 0.28 +/- 0.05; P < 0.0001) and decreased lumen areas (6.24 +/- 0.44 vs. 9.48 +/- 1.56, P = 0.026). No thrombosis was noticed in Group II. Neointima was composed by proliferating SMC located with the highest concentration in the area of IEL disruption (IHC). Arterial injury by pulling back CB and FB induces significant IH in pig iliac arteries by two weeks without thrombosis. This model is superior to the classical overdistention non-compliant model and should be useful and cost-effective for preclinical testing of procedures designed to inhibit IH in large peripheral arteries. C1 [Houbballah, Rabih; Robaldo, Alessandro; Albadawi, Hassan; Titus, James; LaMuraglia, Glenn M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc & Endovasc Surg,Gen Surg Serv, Boston, MA 02114 USA. RP Houbballah, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc & Endovasc Surg,Gen Surg Serv, 55 Fruit St, Boston, MA 02114 USA. EM docrabih@gmail.com NR 22 TC 4 Z9 4 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0959-9673 J9 INT J EXP PATHOL JI Int. J. Exp. Pathol. PD DEC PY 2011 VL 92 IS 6 BP 422 EP 427 DI 10.1111/j.1365-2613.2011.00790.x PG 6 WC Pathology SC Pathology GA 854PC UT WOS:000297505700069 PM 22050434 ER PT J AU Ameresekere, M Borg, R Frederick, J Vragovic, O Saia, K Raj, A AF Ameresekere, Maithri Borg, Ryan Frederick, Jamie Vragovic, Olivera Saia, Kelley Raj, Anita TI Somali immigrant women's perceptions of cesarean delivery and patient-provider communication surrounding female circumcision and childbirth in the USA SO INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS LA English DT Article DE Cesarean delivery; Female circumcision; Female genital mutilation; Somali immigrant women ID GENITAL MUTILATION; REFUGEE WOMEN; PREGNANCY; EXPERIENCES; CARE; COUNTRIES; OUTCOMES; SECTION; NORWAY AB Objective: To explore perceptions of cesarean delivery and patient-provider communication surrounding female circumcision and childbirth through interviews with Somali women residing in the USA. Methods: Semistructured in-depth interviews were conducted with 23 Somali immigrant women living in Boston who had given birth in the USA and Africa. Interviews asked about birth experiences in the USA and Africa, as well as norms and attitudes surrounding childbirth practices. Interview transcripts were coded and themes identified through an iterative process. Results: Participants were aged 25-52 years and had been living in the USA for an average of 7 years. All women had experienced circumcision. Five women had undergone a cesarean delivery. Women feared having a cesarean because of their perception that it could result in death or disability. Women also highlighted that providers in the USA rarely discussed female circumcision or how it could affect childbirth experiences. Conclusions: Previous experiences and cultural beliefs can affect how Somali immigrant women understand labor and delivery practices in the USA and can explain why some women are wary of cesarean delivery. Educating providers and encouraging patient-provider communication about cesarean delivery and female circumcision can ease fears, increase trust, and improve birth experiences for Somali immigrant women in the USA. (C) 2011 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved. C1 [Ameresekere, Maithri] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Borg, Ryan] Boston Univ, Sch Publ Hlth, Dept Community Hlth Sci, Boston, MA USA. [Frederick, Jamie] Boston Univ, Sch Publ Hlth, Dept Int Hlth, Boston, MA USA. [Vragovic, Olivera; Saia, Kelley] Boston Univ, Sch Med, Div Obstet & Gynecol, Boston, MA 02118 USA. [Raj, Anita] Univ Calif San Diego, Sch Med, Div Global Publ Hlth, Dept Med, San Diego, CA 92103 USA. RP Ameresekere, M (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St,Wang 812, Boston, MA 02114 USA. EM maithri@post.harvard.edu OI Saia, Kelley/0000-0001-9198-5295; Vragovic, Olivera/0000-0002-3385-2686 FU Tufts University School of Medicine; Obstetrics and Gynecology Department of Boston Medical Center FX Funding for this study was provided by the Harold Williams Fellowship awarded by Tufts University School of Medicine and the Obstetrics and Gynecology Department of Boston Medical Center. NR 21 TC 15 Z9 15 U1 3 U2 14 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0020-7292 J9 INT J GYNECOL OBSTET JI Int. J. Gynecol. Obstet. PD DEC PY 2011 VL 115 IS 3 BP 227 EP 230 DI 10.1016/j.ijgo.2011.07.019 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 859PV UT WOS:000297889200006 PM 21937037 ER PT J AU Bourgier, C Pichenot, C Verstraet, R El Nemr, M Heymann, S Biron, B Delaloge, S Mathieu, MC Garbay, JR Bourhis, J Taghian, AG Marsiglia, H AF Bourgier, Celine Pichenot, Charlotte Verstraet, Rodolfe El Nemr, Mohamed Heymann, Steve Biron, Bruno Delaloge, Suzette Mathieu, Marie-Christine Garbay, Jean-Remy Bourhis, Jean Taghian, Alphonse G. Marsiglia, Hugo TI EARLY SIDE EFFECTS OF THREE-DIMENSIONAL CONFORMAL EXTERNAL BEAM ACCELERATED PARTIAL BREAST IRRADIATION TO A TOTAL DOSE OF 40 GY IN ONE WEEK (A PHASE II TRIAL) SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE 3D-Conformal accelerated partial breast irradiation; 40 Gy in 1 week; Toxicities ID INTENSITY-MODULATED RADIOTHERAPY; BRACHYTHERAPY REGISTRY TRIAL; INITIAL CLINICAL-EXPERIENCE; 20-YEAR FOLLOW-UP; RANDOMIZED-TRIAL; CONSERVING SURGERY; RADIATION-THERAPY; INTERSTITIAL BRACHYTHERAPY; UK STANDARDIZATION; AMERICAN SOCIETY AB Purpose: Several accelerated partial breast irradiation (APBI) techniques are described in the literature, and apparently, the three-dimensional (3D)-conformal technique is being used increasingly. Nonetheless, the optimal radiation dose is not yet known. Here, we report feasibility and early toxicities of APBI delivering 40 Gy over 5 days, in a phase II trial. Methods and Materials: From October 2007 to September 2008, 25 patients with pT1N0 cancer received 3D-conformal APBI. The prescribed radiation dose was 40 Gy in 4-Gy fractions given twice daily. This technique used two minitangents and an "en face" electron field. Toxicities were systematically assessed at 1, 2, and 6 months and then once every 6 months. Results: The planning tumor volume for evaluation (PTV_EVAL) coverage was adequate: the mean dose to the PTV_EVAL was 41.8 Gy (range, 41-42.4 Gy). Mean doses to the ipsilateral lung and heart were 1.6 Gy (range, 1.0-2.3 Gy) and 1.2 Gy (range, 1.0-1.6 Gy), respectively. One and two months after completion of APBI, most patients had no or mild erythema (n = 16 patients at 1 month; n = 25 patients at 2 months); none of these patients developed moist desquamation. After a median follow-up of 12 months, only 1 patient had a significant moderate field contracture (grade 2). Other reported late toxicities were grade 1. Conclusions: 3D-conformal APBI (with two minitangents and an "en face" electron field) using a total dose of 40 Gy in 10 fractions twice daily over 5 days achieved appropriate PTV_EVAL coverage and offered significant sparing of normal tissue. Early tolerance was excellent. (C) 2011 Elsevier Inc. C1 [Bourgier, Celine; El Nemr, Mohamed; Heymann, Steve; Bourhis, Jean; Marsiglia, Hugo] Inst Gustave Roussy, Dept Radiat Oncol, F-94800 Villejuif, France. [Pichenot, Charlotte; Verstraet, Rodolfe; Biron, Bruno] Inst Gustave Roussy, Dept Phys, F-94800 Villejuif, France. [Delaloge, Suzette] Inst Gustave Roussy, Dept Breast Oncol, F-94800 Villejuif, France. [Mathieu, Marie-Christine] Inst Gustave Roussy, Dept Pathol, F-94800 Villejuif, France. [Garbay, Jean-Remy] Inst Gustave Roussy, Dept Breast Surg, F-94800 Villejuif, France. [Taghian, Alphonse G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. [Marsiglia, Hugo] Univ Florence, Radiotherapy Unit, Florence, Italy. RP Bourgier, C (reprint author), Inst Gustave Roussy, Dept Radiotherapie, 39 Rue Camille Desmoulins, F-94800 Villejuif, France. EM bourgier@igr.fr NR 54 TC 13 Z9 13 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD DEC 1 PY 2011 VL 81 IS 5 BP 1228 EP 1235 DI 10.1016/j.ijrobp.2010.07.040 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 855YO UT WOS:000297602400005 PM 20932662 ER PT J AU Cotter, SE Herrup, DA Friedmann, A Macdonald, SM Pieretti, RV Robinson, G Adams, J Tarbell, NJ Yock, TI AF Cotter, Shane E. Herrup, David A. Friedmann, Alison Macdonald, Shannon M. Pieretti, Raphael V. Robinson, Gregoire Adams, Judith Tarbell, Nancy J. Yock, Torunn I. TI PROTON RADIOTHERAPY FOR PEDIATRIC BLADDER/PROSTATE RHABDOMYOSARCOMA: CLINICAL OUTCOMES AND DOSIMETRY COMPARED TO INTENSITY-MODULATED RADIATION THERAPY SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 51st Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY NOV 01-05, 2009 CL Chicago, IL SP Amer Soc Radiat Oncol (ASTRO) DE Proton; Pediatrics; Rhabdomyosarcoma; Bladder; Prostate ID INTERGROUP RHABDOMYOSARCOMA; PHOTON RADIOTHERAPY; CHILDHOOD-CANCER; HODGKINS-DISEASE; BLADDER FUNCTION; 2ND CANCERS; RISK; IRRADIATION; CHILDREN; PRESERVATION AB Purpose: In this study, we report the clinical outcomes of 7 children with bladder/prostate rhabdomyosarcoma (RMS) treated with proton radiation and compare proton treatment plans with matched intensity-modulated radiation therapy (IMRT) plans, with an emphasis on dose savings to reproductive and skeletal structures. Methods and Materials: Follow-up consisted of scheduled clinic appointments at our institution or direct communication with the treating physicians for referred patients. Each proton radiotherapy plan used for treatment was directly compared to an BIRT plan generated for the study. Clinical target volumes and normal tissue volumes were held constant to facilitate dosimetric comparisons. Each plan was optimized for target coverage and normal tissue sparing. Results: Seven male patients were treated with proton radiotherapy for bladder/prostate RMS at the Massachusetts General Hospital between 2002 and 2008. Median age at treatment was 30 months (11-70 months). Median follow-up was 27 months (10-90 months). Four patients underwent a gross total resection prior to radiation, and all patients received concurrent chemotherapy. Radiation doses ranged from 36 cobalt Gray equivalent (CGE) to 50.4 CGE. Five of 7 patients were without evidence of disease and with intact bladders at study completion. Target volume dosimetry was equivalent between the two modalities for all 7 patients. Proton radiotherapy led to a significant decrease in mean organ dose to the bladder (25.1 CGE vs. 33.2 Gy; p = 0.03), testes (0.0 CGE vs. 0.6 Gy; p = 0.016), femoral heads (1.6 CGE vs. 10.6 Gy; p = 0.016), growth plates (21.7 CGE vs. 32.4 Gy; p = 0.016), and pelvic bones (8.8 CGE vs. 13.5 Gy; p = 0.016) compared to IMRT. Conclusions: This study provides evidence of significant dose savings to normal structures with proton radiotherapy compared to IMRT and is well tolerated in this patient population. The long-term impact of these reduced doses can be tested in future studies incorporating extended follow-up, objective outcome measures, and quality-of-life analyses. (C) 2011 Elsevier Inc. C1 [Herrup, David A.; Macdonald, Shannon M.; Robinson, Gregoire; Adams, Judith; Tarbell, Nancy J.; Yock, Torunn I.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Cotter, Shane E.] Harvard Radiat Oncol Program, Boston, MA USA. [Friedmann, Alison] Massachusetts Gen Hosp, Dept Pediat Hematol Oncol, Boston, MA 02114 USA. [Pieretti, Raphael V.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Yock, TI (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St, Boston, MA 02114 USA. EM tyock@partners.org NR 31 TC 27 Z9 29 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD DEC 1 PY 2011 VL 81 IS 5 BP 1367 EP 1373 DI 10.1016/j.ijrobp.2010.07.1989 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 855YO UT WOS:000297602400023 PM 20934266 ER PT J AU Nghiemphu, PL Wen, PY Lamborn, KR Drappatz, J Robins, HI Fink, K Malkin, MG Lieberman, FS DeAngelis, LM Torres-Trejo, A Chang, SM Abrey, L Fine, HA Demopoulos, A Lassman, AB Kesari, S Mehta, MP Prados, MD Cloughesy, TF AF Nghiemphu, Phioanh Leia Wen, Patrick Y. Lamborn, Kathleen R. Drappatz, Jan Robins, H. Ian Fink, Karen Malkin, Mark G. Lieberman, Frank S. DeAngelis, Lisa M. Torres-Trejo, Alejandro Chang, Susan M. Abrey, Lauren Fine, Howard A. Demopoulos, Alexis Lassman, Andrew B. Kesari, Santosh Mehta, Minesh P. Prados, Michael D. Cloughesy, Timothy F. CA N Amer Brain Tumor Consortium TI A PHASE I TRIAL OF TIPIFARNIB WITH RADIATION THERAPY, WITH AND WITHOUT TEMOZOLOMIDE, FOR PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Tipifarnib; Newly diagnosed glioblastoma; Radiation; Farnesyltransferase inhibitor; Temozolomide ID BRAIN-TUMOR CONSORTIUM; PROTEIN TRANSFERASE INHIBITOR; RECURRENT MALIGNANT GLIOMA; FARNESYLTRANSFERASE INHIBITOR; GUANOSINE TRIPHOSPHATE; ANTIEPILEPTIC DRUGS; RAS; R115777; RADIOTHERAPY; GROWTH AB Purpose: To determine the maximum tolerated dose (MTD) of tipifarnib in combination with conventional radiotherapy for patients with newly diagnosed glioblastoma. The MTD was evaluated in three patient cohorts, stratified based on concurrent use of enzyme-inducing antiepileptic drugs (EIAED) or concurrent treatment with temozolomide (TMZ): Group A: patients not receiving EIAED and not receiving TMZ; Group A-TMZ: patients not receiving EIAED and receiving treatment with TMZ; Group B: any patients receiving EIAED but not TMZ. Patients and Methods: After diagnostic surgery or biopsy, treatment with tipifarnib started 5 to 9 days before initiating radiotherapy, twice daily, in 4-week cycles using discontinuous dosing (21 out of 28 days), until toxicity or progression. For Group A-TMZ, patients also received TMZ daily during radiotherapy and then standard 5/28 days dosing after radiotherapy. Dose-limiting toxicity (DLT) was determined over the first 10 weeks of therapy for all cohorts. Results: Fifty-one patients were enrolled for MTD determination: 10 patients in Group A, 21 patients in Group A-TMZ, and 20 patients in Group B. In the Group A and Group A-TMZ cohorts, patients achieved the intended MTD of 300 mg twice daily (bid) with DLTs including rash and fatigue. For Group B, the MTD was determined as 300 mg bid, half the expected dose. The DLTs included rash and one intracranial hemorrhage. Thirteen of the 20 patients evaluated in Group A-TMZ were alive at 1 year. Conclusion: Tipifarnib is well tolerated at 300 mg bid given discontinuously (21/28 days) in 4-week cycles, concurrently with standard chemo/radiotherapy. A Phase II study should evaluate the efficacy of tipifarnib with radiation and TMZ in patients with newly diagnosed glioblastoma and not receiving EIAED. (C) 2011 Elsevier Inc. C1 [Nghiemphu, Phioanh Leia; Cloughesy, Timothy F.] Univ Calif Los Angeles, Los Angeles, CA USA. [Wen, Patrick Y.; Drappatz, Jan; Kesari, Santosh] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Lamborn, Kathleen R.; Chang, Susan M.; Prados, Michael D.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Robins, H. Ian; Mehta, Minesh P.] Univ Wisconsin, Madison, WI USA. [Fink, Karen] Univ Texas Dallas, Dallas, TX 75230 USA. [Malkin, Mark G.; DeAngelis, Lisa M.; Abrey, Lauren; Demopoulos, Alexis; Lassman, Andrew B.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Lieberman, Frank S.; Torres-Trejo, Alejandro] Univ Pittsburgh, Pittsburgh, PA USA. [Fine, Howard A.] NCI, Neurooncol Branch, NIH, Bethesda, MD 20892 USA. RP Nghiemphu, PL (reprint author), 710 Westwood Plaza,Reed 1-230, Los Angeles, CA 90095 USA. EM leian@ucla.edu RI Kesari, Santosh/E-8461-2013; OI mehta, minesh/0000-0002-4812-5713 FU NCATS NIH HHS [UL1 TR000124, UL1 TR000005]; NCI NIH HHS [U01 CA062399, U01 CA062399-14, U01 CA105695, U01 CA105695-05]; NCRR NIH HHS [UL1 RR033176] NR 33 TC 12 Z9 13 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD DEC 1 PY 2011 VL 81 IS 5 BP 1422 EP 1427 DI 10.1016/j.ijrobp.2010.07.1997 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 855YO UT WOS:000297602400031 PM 20934264 ER PT J AU Halasz, LM Bussiere, MR Dennis, ER Niemierko, A Chapman, PH Loeffler, JS Shih, HA AF Halasz, Lia M. Bussiere, Marc R. Dennis, Elizabeth R. Niemierko, Andrzej Chapman, Paul H. Loeffler, Jay S. Shih, Helen A. TI PROTON STEREOTACTIC RADIOSURGERY FOR THE TREATMENT OF BENIGN MENINGIOMAS SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 50th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 21-28, 2008 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) DE Benign meningioma; Stereotactic radiosurgery; Proton radiation; Radiation therapy ID SKULL BASE MENINGIOMAS; LINEAR-ACCELERATOR RADIOSURGERY; CAVERNOUS SINUS MENINGIOMAS; GAMMA-KNIFE RADIOSURGERY; INTRACRANIAL MENINGIOMAS; TUMOR-CONTROL; DOSE DISTRIBUTIONS; RADIATION-THERAPY; RADIOTHERAPY; MANAGEMENT AB Purpose: Given the excellent prognosis for patients with benign meningiomas, treatment strategies to minimize late effects are important. One strategy is proton radiation therapy (RT), which allows less integral dose to normal tissue and greater homogeneity than photon RT. Here, we report the first series of proton stereotactic radiosurgery (SRS) used for the treatment of meningiomas. Methods and Materials: We identified 50 patients with 51 histologically proven or image- defined, presumed-benign meningiomas treated at our institution between 1996 and 2007. Tumors of < 4 cm in diameter and located >= 2 mm from the optic apparatus were eligible for treatment. Indications included primary treatment (n = 32), residual tumor following surgery (n = 8), and recurrent tumor following surgery (n = 10). The median dose delivered was 13 Gray radiobiologic equivalent (Gy[RBE]) (range, 10.0-15.5 Gy[RBE]) prescribed to the 90% isodose line. Results: Median follow-up was 32 months (range, 6-133 months). Magnetic resonance imaging at the most recent follow-up or time of progression revealed 33 meningiomas with stable sizes, 13 meningiomas with decreased size, and 5 meningiomas with increased size. The 3-year actuarial tumor control rate was 94% (95% confidence interval, 77%-98%). Symptoms were improved in 47% (16/34) of patients, unchanged in 44% (15/34) of patients, and worse in 9% (3/34) of patients. The rate of potential permanent adverse effects after SRS was 5.9% (3/51 patients). Conclusions: Proton SRS is an effective therapy for small benign meningiomas, with a potentially lower rate of long-term treatment-related morbidity. Longer follow-up is needed to assess durability of tumor control and late effects. (C) 2011 Elsevier Inc. C1 [Halasz, Lia M.] Massachusetts Gen Hosp, Dept Radiat Oncol, Harvard Radiat Oncol Program, Boston, MA 02114 USA. [Chapman, Paul H.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Halasz, Lia M.; Chapman, Paul H.; Loeffler, Jay S.; Shih, Helen A.] Harvard Univ, Sch Med, Boston, MA USA. RP Halasz, LM (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Harvard Radiat Oncol Program, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM lhalasz@partners.org NR 40 TC 16 Z9 16 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD DEC 1 PY 2011 VL 81 IS 5 BP 1428 EP 1435 DI 10.1016/j.ijrobp.2010.07.1991 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 855YO UT WOS:000297602400032 PM 20934263 ER PT J AU Garofalo, K Penno, A Schmidt, BP Lee, HJ Frosch, MP von Eckardstein, A Brown, RH Hornemann, T Eichler, FS AF Garofalo, Kevin Penno, Anke Schmidt, Brian P. Lee, Ho-Joon Frosch, Matthew P. von Eckardstein, Arnold Brown, Robert H. Hornemann, Thorsten Eichler, Florian S. TI Oral L-serine supplementation reduces production of neurotoxic deoxysphingolipids in mice and humans with hereditary sensory autonomic neuropathy type 1 SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID SPHINGOLIPID METABOLISM; CERAMIDE SYNTHASE; HSAN-I; PALMITOYLTRANSFERASE; MUTATIONS; SPTLC1; DISEASE; ACCUMULATION; DEFICIENCY; INHIBITOR AB Hereditary sensory and autonomic neuropathy type 1 (HSAN1) causes sensory loss that predominantly affects the lower limbs, often preceded by hyperpathia and spontaneous shooting or lancinating pain. It is caused by several missense mutations in the genes encoding 2 of the 3 subunits of the enzyme serine palmitoyltransferase (SPT). The mutant forms of the enzyme show a shift from their canonical substrate L-serine to the alternative substrate L-alanine. This shift leads to increased formation of neurotoxic deoxysphingolipids (dSLs). Our initial analysis showed that in HEK cells transfected with SPTLC1 mutants, dSL generation was modulated in vitro in the presence of various amino acids. We therefore examined whether in vivo specific amino acid substrate supplementation influenced dSL levels and disease severity in HSAN1. In mice bearing a transgene expressing the C133W SPTLC1 mutant linked to HSAN1, a 10% L-serine-enriched diet reduced dSL levels. L-serine supplementation also improved measures of motor and sensory performance as well as measures of male fertility. In contrast, a 10% L-alanine-enriched diet increased dSL levels and led to severe peripheral neuropathy. In a pilot study with 14 HSAN1 patients, L-serine supplementation similarly reduced dSL levels. These observations support: the hypothesis that an altered substrate selectivity of the mutant SPT is key to the pathophysiology of HSAN1 and raise the prospect of L-serine supplementation as a first treatment option for this disorder. C1 [Garofalo, Kevin; Schmidt, Brian P.; Eichler, Florian S.] Harvard Univ, Sch Med, Dept Neurol, MGH Neurosci Ctr, Boston, MA 02115 USA. [Penno, Anke; von Eckardstein, Arnold; Hornemann, Thorsten] Univ Zurich Hosp, Inst Clin Chem, CH-8091 Zurich, Switzerland. [Lee, Ho-Joon] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol, Boston, MA USA. [Frosch, Matthew P.] Harvard Univ, Sch Med, Dept Pathol, CS Kubik Lab Neuropathol,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Brown, Robert H.] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA USA. RP Eichler, FS (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St,ACC 708, Boston, MA 02114 USA. EM feichler@partners.org OI Schmidt, Brian/0000-0003-3460-0605; Schmidt, Brian/0000-0001-6589-1287 FU NIH [K08NS52550, R01 NS072446]; Dearer Foundation; European Union [LSHM-CT-2006-037631]; Zurich Center for Integrative Human Physiology (ZIHP); Gebert-Ruf Foundation [GRS-047/09] FX We thank Cotton Widdicombe and Martin Selig for their assistance in the rodent studies and Ourania Giannikopoulos for her assistance in the human studies. The work was supported by the NIH (grants K08NS52550 and R01 NS072446) and the Dearer Foundation (to F.S. Eichler); by the European Union (grant LSHM-CT-2006-037631; to T. Hornemann and A. von Eckardstein); and by the Zurich Center for Integrative Human Physiology (ZIHP) and the Gebert-Ruf Foundation (grant GRS-047/09; to T. Hornemann). NR 30 TC 55 Z9 56 U1 1 U2 13 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 2011 VL 121 IS 12 BP 4735 EP 4745 DI 10.1172/JCI57549 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 855XL UT WOS:000297599500023 PM 22045570 ER PT J AU Buijze, GA Lozano-Calderon, SA Strackee, SD Blankevoort, L Jupiter, JB AF Buijze, Geert A. Lozano-Calderon, Santiago A. Strackee, Simon D. Blankevoort, Leendert Jupiter, Jesse B. TI Osseous and Ligamentous Scaphoid Anatomy: Part I. A Systematic Literature Review Highlighting Controversies SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Review DE Anatomy; scaphoid; ligaments; systematic review; controversy ID SCAPHOLUNATE INTEROSSEOUS LIGAMENT; TRANSVERSE CARPAL LIGAMENT; RADIOSCAPHOLUNATE LIGAMENT; HUMAN WRIST; MULTIPLANAR RECONSTRUCTIONS; FLEXOR RETINACULUM; NORMAL APPEARANCE; DORSAL LIGAMENTS; JOINT; GROSS AB Purpose The interpretation of scaphoid anatomy and kinematics is confusing and controversial. This results from a lack of consensus on the anatomy of the ligaments attaching to the scaphoid and an overwhelming variety of substantially different anatomic descriptions and classification systems of the wrist joint in the literature. The present study systemically reviews the consistencies or inconsistencies of the various scaphoid ligament descriptions and aims to clarify and unify different concepts and classification systems. Methods We performed a systematic search of the medical literature from 1950 to 2010. We included all descriptive reports of the anatomy or morphology of the scaphoid, ligaments, or both. With the aim to describe the best available evidence, we considered all anatomical descriptions but emphasized a selection of the most frequently cited articles. Results The literature search resulted in 555 potentially eligible descriptive reports, 58 of which met the inclusion criteria and were included in the review. Variations in the anatomic descriptions appear to be mostly due to the difficulty of identifying individual interdigitating ligaments or bundles by macroscopic dissections, as well as the interindividual variability in ligament anatomy. The most important areas of controversy in the scaphoid ligament attachments include the radial collateral ligament, dorsal radiocarpal ligament, dorsal intercarpal ligament, volar scaphotriquetral ligament, and scaphotrapezium-trapezoid ligament. Conclusions None of the scaphoid ligaments other than the scaphocapitate ligament have been described consistently. Future research is required to verify the ligament attachments that currently have the most controversial descriptions, while addressing the interindividual variability of ligament insertions and morphology. Clinical relevance Thorough knowledge of the anatomy will enhance our understanding of the kinematics of the scaphoid. (J Hand Surg 2011;36A:1926-1935. Copyright (C) 2011 by the American Society for Surgery of the Hand. All rights reserved.) C1 [Buijze, Geert A.] Acad Med Ctr, Dept Orthopaed Surg, Orthopaed Res Ctr Amsterdam, NL-1100 DD Amsterdam, Netherlands. Acad Med Ctr, Dept Plast Reconstruct & Hand Surg, NL-1100 DD Amsterdam, Netherlands. Massachusetts Gen Hosp, Hand & Upper Extrem Serv, Boston, MA 02114 USA. New York Med Coll, Westchester Med Ctr, Dept Orthopaed Surg, Valhalla, NY 10595 USA. RP Buijze, GA (reprint author), Acad Med Ctr, Dept Orthopaed Surg, Orthopaed Res Ctr Amsterdam, Meibergdreef 9, NL-1100 DD Amsterdam, Netherlands. EM g.a.buijze@amc.uva.nl FU Netherlands Organisation for Scientific Research (NWO) FX G.A.B. thanks the Netherlands Organisation for Scientific Research (NWO) for support to this research. NR 73 TC 14 Z9 14 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD DEC PY 2011 VL 36A IS 12 BP 1926 EP 1935 DI 10.1016/j.jhsa.2011.09.012 PG 10 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 858DX UT WOS:000297777200005 PM 22051230 ER PT J AU Mondal, S Ghosh-Roy, S Loison, F Li, YT Jia, YH Harris, C Williams, DA Luo, HBR AF Mondal, Subhanjan Ghosh-Roy, Saurabh Loison, Fabien Li, Yitang Jia, Youghui Harris, Chad Williams, David A. Luo, Hongbo R. TI PTEN Negatively Regulates Engulfment of Apoptotic Cells by Modulating Activation of Rae GTPase SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-SUPPRESSOR PTEN; IN-VIVO; PHOSPHATIDYLSERINE RECEPTOR; TYROSINE PHOSPHORYLATION; NEUTROPHIL TRAFFICKING; CYTOKINE PRODUCTION; GENE-EXPRESSION; HOST-DEFENSE; KINASE-AKT; MACROPHAGES AB Efficient clearance of apoptotie cells by phagocytes (efferocytosis) is critical for normal tissue homeostasis and regulation of the immune system. Apoptotic cells are recognized by a vast repertoire of receptors on macrophage that lead to transient formation of phosphatidylinosito1-3,4,5-trisphosphate [PtdIns(3,4,5)P3] and subsequent cytoskeletal reorganization necessary for engulfment. Certain P13K isoforms are required for engulfment of apoptotic cells, but relatively little is known about the role of lipid phosphatases in this process. In this study, we report that the activity of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a phosphatidylinositol 3-phosphatase, is elevated upon efferocytosis. Depletion of PTEN in macrophage results in elevated PtdIns(3,4,5)P3 production and enhanced phagocytic ability both in vivo and in vitro, whereas overexpression of wild-type.PTEN abrogates this process. Loss of PTEN in macrophage leads to activation of the pleckstrin homology domain-containing guanine-nucleotide exchange factor Vav1 and subsequent activation of Racl GTPase, resulting in increased amounts of F-actin upon engulfment of apoptotic cells. PTEN disruption also leads to increased production of anti-inflammatory cytokine IL-10 and decreased production of proinflammatory IL-6 and TNF-et upon engulfment of apoptotic cells. These data suggest that PTEN exerts control over efferocytosis potentially by regulating PtdIns(3,4,5)P3 levels that modulate Rac GTPase and F-actin reorganization through Vavl exchange factor and enhancing apoptotic cell-induced anti-inflammatory response. The Journal of Immunology, 2011, 187: 5783-5794. C1 [Mondal, Subhanjan; Ghosh-Roy, Saurabh; Loison, Fabien; Li, Yitang; Jia, Youghui; Luo, Hongbo R.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Mondal, Subhanjan; Ghosh-Roy, Saurabh; Loison, Fabien; Li, Yitang; Jia, Youghui; Luo, Hongbo R.] Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA. [Harris, Chad; Williams, David A.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Harris, Chad; Williams, David A.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Luo, HBR (reprint author), Harvard Univ, Sch Med, Dept Pathol, Karp Family Res Bldg,Room 10214, Boston, MA 02115 USA. EM Hongbo.Luo@childrens.harvard.edu FU National Institutes of Health [HL-085100, A1076471, HL092020, GM076084]; Deutscheforschungsgemeinshaft FX The work was supported by National Institutes of Health Grants HL-085100, A1076471, HL092020, and GM076084 (to H.R.L.) and by a postdoctoral fellowship from the Deutscheforschungsgemeinshaft (to S.M.). NR 63 TC 10 Z9 10 U1 1 U2 6 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 2011 VL 187 IS 11 BP 5783 EP 5794 DI 10.4049/jimmunol.1100484 PG 12 WC Immunology SC Immunology GA 853UA UT WOS:000297450000039 PM 22043008 ER PT J AU Fachin, F Chen, GD Toner, M Wardle, BL AF Fachin, Fabio Chen, Grace Dongqing Toner, Mehmet Wardle, Brian L. TI Integration of Bulk Nanoporous Elements in Microfluidic Devices With Application to Biomedical Diagnostics SO JOURNAL OF MICROELECTROMECHANICAL SYSTEMS LA English DT Article DE Carbon nanotube (CNT) forest; functionalization; microfluidics; multiscale bioparticle isolation; nanoporosity; permeability ID DARCY-FORCHHEIMER DRAG; CARBON NANOTUBES; DRUG-DELIVERY; PERMEABILITY; CATALYST; FABRICATION; GROWTH; BLOOD; CELLS; CHROMATOGRAPHY AB We demonstrate integration of ultraporous (99% porous) elements composed of nanoporous forests of vertically aligned carbon nanotubes (VA-CNTs, or VACNTs) in microelectromechanical systems (MEMS), illustrating their use in fluidic applications for biomedical diagnostics. Our method enables definition of high-aspect-ratio (similar to 10(4), heights similar to 100 mu m, and pore spacings similar to 10 nm) nanoporous elements and preserves the VACNT elements' shapes even under flowthrough conditions. The fluid permeability of the VACNT elements is measured experimentally and shown to be comparable to that of much larger micro-and macroscopic porous materials. Permeability tailoring of VACNT elements through manipulation of both material and CNT growth process parameters is also experimentally demonstrated. Distinct from solid designs (e. g., Si and polydimethylsiloxane), our approach enables fluid flow both around and through the nanoporous microfluidic elements, hence enhancing isolation efficiency by increased physical interaction between the particles in the flow and the functional elements. Simultaneous multiphysics (chemical and mechanical) and multiscale (several orders of magnitude in size) isolation of bioparticles using microfluidic devices with nanoporous elements is demonstrated as well. C1 [Fachin, Fabio; Wardle, Brian L.] MIT, Dept Aeronaut & Astronaut, Cambridge, MA 02139 USA. [Chen, Grace Dongqing; Toner, Mehmet] Massachusetts Gen Hosp, BioMEMS Resource Ctr, Charlestown, MA 02129 USA. [Chen, Grace Dongqing; Toner, Mehmet] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Chen, Grace Dongqing; Toner, Mehmet] Harvard Massachusetts Inst Technol, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Fachin, F (reprint author), MIT, Dept Aeronaut & Astronaut, Cambridge, MA 02139 USA. EM ffachin@mit.edu; gracec@mit.edu; mehmet_toner@hms.harvard.edu; wardle@mit.edu FU U.S. Department of State; Massachusetts Institute of Technology; National Institute of Biomedical Imaging and Bioengineering [P41 EB002503] FX This work was supported in part by the U.S. Department of State's Fulbright Science and Technology Award, in part by the Massachusetts Institute of Technology's Whitaker Health Sciences Fund Fellowship, and in part by the National Institute of Biomedical Imaging and Bioengineering under Grant P41 EB002503 (BioMEMS Resource Center). Subject Editor D. DeVoe. NR 49 TC 15 Z9 15 U1 1 U2 21 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1057-7157 J9 J MICROELECTROMECH S JI J. Microelectromech. Syst. PD DEC PY 2011 VL 20 IS 6 BP 1428 EP 1438 DI 10.1109/JMEMS.2011.2167669 PG 11 WC Engineering, Electrical & Electronic; Nanoscience & Nanotechnology; Instruments & Instrumentation; Physics, Applied SC Engineering; Science & Technology - Other Topics; Instruments & Instrumentation; Physics GA 855TZ UT WOS:000297589200022 ER PT J AU Harris, JP Capadona, JR Miller, RH Healy, BC Shanmuganathan, K Rowan, SJ Weder, C Tyler, DJ AF Harris, J. P. Capadona, J. R. Miller, R. H. Healy, B. C. Shanmuganathan, K. Rowan, S. J. Weder, C. Tyler, D. J. TI Mechanically adaptive intracortical implants improve the proximity of neuronal cell bodies SO JOURNAL OF NEURAL ENGINEERING LA English DT Article ID SILICON MICROELECTRODE ARRAYS; BRAIN-TISSUE RESPONSE; SPINAL-CORD-INJURY; ADULT-RAT BRAIN; GLIAL SCAR; POLYMER NANOCOMPOSITES; REACTIVE ASTROGLIOSIS; NEURITE OUTGROWTH; NEURAL PROBES; CNS AB The hypothesis is that the mechanical mismatch between brain tissue and microelectrodes influences the inflammatory response. Our unique, mechanically adaptive polymer nanocomposite enabled this study within the cerebral cortex of rats. The initial tensile storage modulus of 5 GPa decreases to 12 MPa within 15 min under physiological conditions. The response to the nanocomposite was compared to surface-matched, stiffer implants of traditional wires (411 GPa) coated with the identical polymer substrate and implanted on the contralateral side. Both implants were tethered. Fluorescent immunohistochemistry labeling examined neurons, intermediate filaments, macrophages, microglia and proteoglycans. We demonstrate, for the first time, a system that decouples the mechanical and surface chemistry components of the neural response. The neuronal nuclei density within 100 mu m of the device at four weeks post-implantation was greater for the compliant nanocomposite compared to the stiff wire. At eight weeks post-implantation, the neuronal nuclei density around the nanocomposite was maintained, but the density around the wire recovered to match that of the nanocomposite. The glial scar response to the compliant nanocomposite was less vigorous than it was to the stiffer wire. The results suggest that mechanically associated factors such as proteoglycans and intermediate filaments are important modulators of the response of the compliant nanocomposite. C1 [Harris, J. P.; Capadona, J. R.; Rowan, S. J.; Tyler, D. J.] CWRU, Dept Biomed Engn, Cleveland, OH 44106 USA. [Harris, J. P.; Capadona, J. R.; Rowan, S. J.; Tyler, D. J.] L Stokes Cleveland VA Med Ctr, Cleveland, OH 44106 USA. [Miller, R. H.] CWRU, Dept Neurosci, Cleveland, OH 44106 USA. [Healy, B. C.] Harvard Univ, Dept Neurol, Brigham & Womens Hosp, Partners MS Ctr,Med Sch, Boston, MA 02445 USA. [Healy, B. C.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Shanmuganathan, K.; Rowan, S. J.; Weder, C.] CWRU, Dept Macromol Sci & Engn, Cleveland, OH 44106 USA. [Weder, C.] Univ Fribourg, Adolphe Merkle Inst, CH-1723 Marly 1, Switzerland. [Weder, C.] Univ Fribourg, Fribourg Ctr Nanomat, CH-1723 Marly 1, Switzerland. RP Tyler, DJ (reprint author), CWRU, Dept Biomed Engn, 2071 Martin Luther King Jr Dr,Wickenden Bldg, Cleveland, OH 44106 USA. EM dustin.tyler@case.edu RI Tyler, Dustin/C-7995-2015; OI Tyler, Dustin/0000-0002-2298-8510; Merkle Institute, Adolphe/0000-0002-6220-424X FU National Institute of Neurological Disorders and Stroke [R21-NS053798, F31-NS063640, T32-EB004314-06]; Veteran's Affairs [C3819C, F4827H, B6344W] FX This work was supported by grant numbers R21-NS053798 and F31-NS063640 from the National Institute of Neurological Disorders and Stroke and T32-EB004314-06 for the National Institute of Biomedical Imaging and Bioengineering. Additional support was from Veteran's Affairs grants C3819C, F4827H and B6344W. The authors acknowledge the support of Anne DeChant and Dr Horst von Recum. None of the funding sources aided in the collection, analysis and interpretation of data, in the writing of the report, or in the decision to submit the paper for publication. The authors have no conflicts of interest related to this work to disclose. NR 58 TC 62 Z9 64 U1 3 U2 16 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 1741-2560 J9 J NEURAL ENG JI J. Neural Eng. PD DEC PY 2011 VL 8 IS 6 AR 066011 DI 10.1088/1741-2560/8/6/066011 PG 13 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA 856ZW UT WOS:000297684400024 PM 22049097 ER PT J AU Lin, NU Eierman, W Greil, R Campone, M Kaufman, B Steplewski, K Lane, SR Zembryki, D Rubin, SD Winer, EP AF Lin, Nancy U. Eierman, Wolfgang Greil, Richard Campone, Mario Kaufman, Bella Steplewski, Klaudia Lane, Stephen R. Zembryki, Denise Rubin, Stephen D. Winer, Eric P. TI Randomized phase II study of lapatinib plus capecitabine or lapatinib plus topotecan for patients with HER2-positive breast cancer brain metastases SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Lapatinib; Capecitabine; Topotecan; Brain metastases; Breast cancer ID NERVOUS-SYSTEM METASTASES; CEREBROSPINAL-FLUID; TRASTUZUMAB; SURVIVAL; THERAPY; COMBINATION; CARCINOMA; TUMORS; TRIAL AB Approximately one-third of patients with advanced, HER2-positive breast cancer develop brain metastases. A significant proportion of women experience central nervous system (CNS) progression after standard radiation therapy. The optimal treatment in the refractory setting is undefined. This study evaluated the toxicity and efficacy of lapatinib in combination with chemotherapy among patients with HER2-positive, progressive brain metastases. Patients with HER2-positive breast cancer with progressive brain metastases after trastuzumab and cranial radiotherapy were included. The primary endpoint was CNS objective response, defined as a >= 50% volumetric reduction of CNS lesion(s) in the absence of new or progressive CNS or non-CNS lesions, or increasing steroid requirements. The study was closed early after 22 of a planned 110 patients were enrolled due to excess toxicity and lack of efficacy in the lapatinib plus topotecan arm. The objective response rate (ORR) in the lapatinib plus capecitabine arm was 38% (exact 95% confidence interval [CI] 13.9-68.4). No responses were observed in the lapatinib plus topotecan arm. Although the study was stopped prior to full enrollment, some promising indications of CNS activity were noted for lapatinib plus capecitabine. The combination of lapatinib plus topotecan was not active and was associated with excess toxicity. C1 [Lin, Nancy U.; Winer, Eric P.] Dana Farber Canc Inst, Dept Med Oncol, Div Womens Canc, Boston, MA 02215 USA. [Eierman, Wolfgang] Frauen Klin Vom Roten Kreuz, Munich, Germany. [Greil, Richard] Private Med Univ Hosp, Med Dept Hematol & Med Oncol 3, Salzburg, Austria. [Campone, Mario] Ctr Rene Gauducheau, St Herblain, France. [Kaufman, Bella] Sheba Med Ctr, Tel Hashomer, Israel. [Steplewski, Klaudia; Lane, Stephen R.; Zembryki, Denise; Rubin, Stephen D.] GlaxoSmithKline Inc, Collegeville, PA USA. RP Lin, NU (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Div Womens Canc, 450 Brookline Ave, Boston, MA 02215 USA. EM nlin@partners.org RI Greil, Richard/C-7673-2017 OI Greil, Richard/0000-0002-4462-3694 FU Breast Cancer Research Foundation; American Society of Clinical Oncology Cancer Foundation; GlaxoSmithKline FX The authors would like to acknowledge the work of Trinity Urban and Gordon J. Harris, M. D. (Tumor Imaging Metrics Core, Dana-Farber/Harvard Cancer Center) for independent radiology review including volumetric analyses of brain MRIs. The authors would also like to acknowledge the following investigators and study sites for their contributions to the study: Steve Chui, Oregon Health and Science University, Portland, OR; Catherine Doyle, Hopital du Saint Sacrement du CHAUQ-Quebec-Canada; Gabrielle Doering, Praxis fuer Haematologie und Onkologie, Bremen, Germany; Ella Evron, Assaf Harofeh MC, Zrifin, Israel; Karen Gelmon, BC Cancer Agency, Vancouver Centre, Vancouver, Canada; Henrik Lindman, Akademiska Sjukhuset, Uppsala, Sweden; Minetta Liu, Georgetown University Hospital, Washington, D. C.; Rafael Lopez, Clinico de Santiago-Santiago de Compostela-Spain; Franco Nole, Instituto Europeo di Oncologia (IRCCS) di Milano, Milan, Italy; Anna Maria Storniolo, Indiana University, Indianapolis, IN. The study was supported by the Breast Cancer Research Foundation (to E. P. W. and N.U.L.), American Society of Clinical Oncology Cancer Foundation (Career Development Award to N.U.L.), and GlaxoSmithKline. NR 24 TC 63 Z9 63 U1 1 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD DEC PY 2011 VL 105 IS 3 BP 613 EP 620 DI 10.1007/s11060-011-0629-y PG 8 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 858MR UT WOS:000297803100018 PM 21706359 ER PT J AU Croen, LA Connors, SL Matevia, M Qian, YG Newschaffer, C Zimmerman, AW AF Croen, Lisa A. Connors, Susan L. Matevia, Marilyn Qian, Yinge Newschaffer, Craig Zimmerman, Andrew W. TI Prenatal exposure to beta 2-adrenergic receptor agonists and risk of autism spectrum disorders SO JOURNAL OF NEURODEVELOPMENTAL DISORDERS LA English DT Article DE Asthma; Beta 2 adrenergic agonist; B2AR agonists; Autistic; Perinatal risk factors; Terbutaline ID PRETERM LABOR; BRAIN-REGIONS; TERBUTALINE; NEUROINFLAMMATION; ABNORMALITIES; SENSITIZATION; ACTIVATION; RITODRINE; TOCOLYSIS; ASTHMA AB This study aims to investigate the association between prenatal exposure to terbutaline and other beta 2 adrenergic receptor (B2AR) agonists and autism spectrum disorders (ASDs). The methodology used is a case-control study among children born from 1995 to 1999 at Kaiser Permanente Northern California hospitals. Cases (n=291) were children with an ASD diagnosis; controls (n=284) were children without ASDs, randomly sampled and frequency-matched to cases on sex, birth year, and delivery hospital. Exposure to B2AR agonists during 30 days prior to conception and each trimester of pregnancy was ascertained from prenatal medical records and health plan databases. The frequency of exposure to any B2AR agonist during pregnancy was similar for mothers of children with ASD and mothers of controls (18.9% vs. 14.8%, P=0.19). Exposure to B2AR agonists other than terbutaline was not associated with an increased risk for ASDs. However, terbutaline exposure for >2 days during the third trimester was associated with more than a fourfold increased risk for ASDs independent of indication although the limited sample size resulted in an imprecise and nonsignificant effect estimate (OR(adj)=4.4; 95% confidence interval, 0.8-24.6). This analysis does not offer evidence linking B2AR exposure in pregnancy with autism risk. However, exposure to terbutaline during the third trimester for >2 days may be associated with an increased risk of autism. Should this result be confirmed in larger samples, it would point to late pregnancy as an etiologic window of interest in autism risk factor research. C1 [Croen, Lisa A.; Matevia, Marilyn; Qian, Yinge] Kaiser Permanente No Calif, Div Res, Oakland, CA 94612 USA. [Connors, Susan L.; Zimmerman, Andrew W.] Kennedy Krieger Inst, Dept Neurol & Dev Med, Baltimore, MD 21205 USA. [Connors, Susan L.] Massachusetts Gen Hosp, LADDERS Clin, Dept Med, Cambridge, MA 02142 USA. [Connors, Susan L.] Massachusetts Gen Hosp, LADDERS Clin, Dept Pediat, Cambridge, MA 02142 USA. [Newschaffer, Craig] Drexel Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Philadelphia, PA 19102 USA. [Zimmerman, Andrew W.] Kennedy Krieger Inst, Ctr Autism & Related Disorders, Baltimore, MD 21205 USA. [Zimmerman, Andrew W.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Zimmerman, Andrew W.] Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA. [Zimmerman, Andrew W.] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA. [Zimmerman, Andrew W.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. RP Croen, LA (reprint author), Kaiser Permanente No Calif, Div Res, 2000 Broadway, Oakland, CA 94612 USA. EM lisa.a.croen@kp.org FU Centers for Disease Control and Prevention [U10/CCU920392]; Kaiser Foundation Research Institute; Autism Speaks FX We thank Dorothy E. Crowell for bringing the issue of terbutaline exposure to our attention, Theodore A. Slotkin, PhD, for his extensive work on the B2AR and valuable advice; James P. Reichmann, MBA, American Home Patient, Brentwood, TN; and Kaht Dorward, MD, Kaiser Permanente Northern California, for helpful historical insights concerning the use of terbutaline for tocolysis. We also thank Roxana Odouli, MSPH, for her help with project coordination; Darmell Brown and Martha Estrada for performing all medical record review and abstraction; and Cathleen Yoshida, MS, for preparing and managing all study data files. This study was funded by grants from the Centers for Disease Control and Prevention, U10/CCU920392, Kaiser Foundation Research Institute and Autism Speaks. NR 39 TC 13 Z9 13 U1 3 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1866-1947 J9 J NEURODEV DISORD JI J. Neurodev. Disord. PD DEC PY 2011 VL 3 IS 4 SI SI BP 307 EP 315 DI 10.1007/s11689-011-9093-4 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 858JW UT WOS:000297794000002 PM 21874331 ER PT J AU Hage, FG Dean, P Iqbal, F Heo, J Iskandrian, AE AF Hage, Fadi G. Dean, Phillip Iqbal, Fahad Heo, Jaekyeong Iskandrian, Ami E. TI A blunted heart rate response to regadenoson is an independent prognostic indicator in patients undergoing myocardial perfusion imaging SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Article DE Regadenoson; heart rate response; myocardial perfusion imaging; risk stratification ID DIABETES-MELLITUS; ADENOSINE; STRESS; RECLASSIFICATION; PREDICTOR; MORTALITY; AGONIST; TRIAL; AGE AB Regadenoson myocardial perfusion imaging (MPI) is a useful method for risk assessment. We hypothesized that the heart rate response (HRR) to regadenoson carries incremental prognostic information to that derived from perfusion pattern and left ventricular (LV) ejection fraction (EF). The study population included 1,156 (60 +/- A 13 years, 46% women, 40% diabetes mellitus, 53% chronic kidney disease) patients. During a follow-up period of 22 +/- A 5 months, 103 patients died (9%). Independent determinants of the HRR included age, gender, race, diabetes mellitus, coronary revascularization, LVEF, use of insulin and aldosterone antagonists. Decreasing HRR was associated with stepwise increase in mortality (log-rank P < .0001). In a Cox proportional model for mortality that adjusted for age, gender, diabetes mellitus, renal disease, and MPI findings, HRR in the lowest quartile was independently associated with fivefold increase in mortality compared to the highest quartile [HR 5.2, 95% CI 2.3-12.0, P < .0001]. Patients with a normal HRR had a relatively low annualized total mortality despite the presence of risk factors. The addition of HRR to traditional MPI findings had a net reclassification improvement of 15%, P = .02. A blunted HRR to regadenoson is an independent predictor of poor outcome, adds incremental value to MPI, and helps in better risk stratification. C1 [Hage, Fadi G.; Iqbal, Fahad; Heo, Jaekyeong; Iskandrian, Ami E.] Univ Alabama, Div Cardiovasc Dis, Birmingham, AL 35294 USA. [Dean, Phillip] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. [Hage, Fadi G.] Birmingham Vet Affairs Med Ctr, Div Cardiol, Birmingham, AL USA. RP Hage, FG (reprint author), Univ Alabama, Div Cardiovasc Dis, ZRB 1024,1530 3rd AVE S, Birmingham, AL 35294 USA. EM fadihage@uab.edu OI Hage, Fadi/0000-0002-1397-4942 FU Astellas FX Ami Iskandrian has received research funds from Astellas and served as consultant for Gilead. NR 25 TC 24 Z9 24 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-3581 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD DEC PY 2011 VL 18 IS 6 BP 1086 EP 1094 DI 10.1007/s12350-011-9429-1 PG 9 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 856GK UT WOS:000297626600016 PM 21785922 ER PT J AU Zhang, DF Cheriyan, T Martin, SD Gomoll, AH Schmid, TM Spector, M AF Zhang, Dafang Cheriyan, Thomas Martin, Scott D. Gomoll, Andreas H. Schmid, Thomas M. Spector, Myron TI Lubricin Distribution in the Torn Human Anterior Cruciate Ligament and Meniscus SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE lubricin; torn ACL; torn meniscus; intact ACL; intact meniscus ID SUPERFICIAL ZONE PROTEIN; ARTICULAR-CARTILAGE; SYNOVIAL-FLUID; FLEXOR TENDON; EXPRESSION; KNEE; PROTEOGLYCAN-4; METABOLISM; REPAIR; CHONDROCYTES AB The objective of this study was to: (1) determine the distribution of lubricin in the human torn anterior cruciate ligament (ACL) and meniscus; (2) determine the distribution of lubricin in the human intact ACL and meniscus; (3) and identify potential cellular sources of lubricin in these tissues. Ten torn ACLs and six torn menisci were obtained from surgeries; for comparison, 11 intact ACLs and 13 intact menisci were obtained from total knee replacements. Samples were formalin fixed and processed for immunohistochemical staining with a monoclonal antibody for lubricin. In torn ACLs and menisci, lubricin was generally found as a discrete layer covering the torn surface. No surface lubricin staining was found on the transected edges produced during excision. Lubricin was also found on the native surfaces of intact ACLs and menisci. In all tissues, lubricin was found in the matrix and intracellularly. The surface layer of lubricin coating torn edges of ACLs and menisci may interfere with the integrative healing process needed for repair. (C) 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29: 1916-1922, 2011. C1 [Zhang, Dafang; Cheriyan, Thomas; Martin, Scott D.; Gomoll, Andreas H.; Spector, Myron] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Zhang, Dafang; Spector, Myron] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Zhang, Dafang; Cheriyan, Thomas; Spector, Myron] VA Boston Healthcare Syst, Tissue Engn Labs, Boston, MA 02130 USA. [Zhang, Dafang; Cheriyan, Thomas; Martin, Scott D.; Gomoll, Andreas H.; Spector, Myron] Brigham & Womens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. [Schmid, Thomas M.] Rush Univ, Med Ctr, Dept Biochem, Chicago, IL 60612 USA. RP Spector, M (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM mspector@rics.bwh.harvard.edu FU U.S. Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service FX This work was supported in part by the U.S. Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service. NR 28 TC 11 Z9 11 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0736-0266 J9 J ORTHOP RES JI J. Orthop. Res. PD DEC PY 2011 VL 29 IS 12 BP 1916 EP 1922 DI 10.1002/jor.21473 PG 7 WC Orthopedics SC Orthopedics GA 859ZC UT WOS:000297913500018 PM 21647956 ER PT J AU Badizadegan, K Thompson, KM AF Badizadegan, Kamran Thompson, Kimberly M. TI Value of Information in Nonfocal Colonic Biopsies SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article DE colonoscopy; inflammatory bowel disease; pathology; value of information ID CHRONIC DIARRHEA; DIAGNOSTIC-VALUE; IF COLONOSCOPY; ILEOSCOPY AB Objectives: Pediatric gastrointestinal (GI) biopsies represent a disproportionately large fraction of the mucosal biopsies submitted for pathology evaluation relative to the fraction of pediatric endoscopies performed. We sought to explore the rationale for this large sample volume and identify its diagnostic value. Patients and Methods: Conceptual value-of-information analysis of 100 sequential colonoscopies, including 770 total biopsy specimens. The diagnostic value of each biopsy was evaluated based on its order of appearance in the model and overall contribution to the pathological classification of the disease. Results: Current practice standards for pediatric GI biopsies provide no guidance on sampling strategy for nonfocal biopsy of suspected inflammatory diseases, resulting in the collection of a nonstandardized number of individual samples and sampling sites that may vary significantly by clinician and institution. We find that this practice adds little to no diagnostic value over more cost-effective protocols, such as a fewer biopsies overall, or fewer specimens with pooled regional biopsies. Conclusions: In the absence of clear guidance, pediatric GI clinicians and institutions should explore alternative strategies such as the left-right pooled biopsy protocol (common in adult GI practice), or preferably, a more conservative 4-region protocol covering major anatomical landmarks in the colon for nonfocal pediatric colonic biopsies. This will allow individual practitioners and clinical centers to test the hypothesis, supported by our analysis, that such a reduction in resource utilization will have no measurable impact on the quality of care. C1 [Badizadegan, Kamran] Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. [Thompson, Kimberly M.] Kid Risk Inc, Newton, MA USA. RP Badizadegan, K (reprint author), Massachusetts Gen Hosp, James Homer Wright Pathol Labs, 55 Fruit St,WRN219, Boston, MA 02114 USA. EM kbadizadegan@partners.org NR 11 TC 2 Z9 3 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD DEC PY 2011 VL 53 IS 6 BP 679 EP 683 DI 10.1097/MPG.0b013e31822862d9 PG 5 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 855DB UT WOS:000297542700019 PM 21681109 ER PT J AU Luo, S Sepehr, A Tsao, H AF Luo, Su Sepehr, Alireza Tsao, Hensin TI Spitz nevi and other Spitzoid lesions Part I. Background and diagnoses SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE atypical Spitz tumor management; natural history; Spitz nevus ID LYMPH-NODE BIOPSY; EPITHELIOID CELL NEVUS; COPY NUMBER CHANGES; MALIGNANT-MELANOMA; MELANOCYTIC TUMORS; DIFFERENTIAL-DIAGNOSIS; NEVOID MELANOMA; SPINDLE-CELL; BRAF GENE; CUTANEOUS MELANOMA AB Spitz nevi are melanocytic proliferations that are characterized by spindled and/or epithelioid nevomelanocytes. First interpreted as juvenile melanoma, these lesions were later characterized as benign and were observed to affect all age groups. Today, contrasting opinions persist regarding the fundamental benignancy versus malignancy within the spectrum of Spitz tumors. Beyond clinical outcome, this controversy has also been fueled by complex and sometimes convoluted classification schemes based on pathologic characteristics. More recently, immunophenotypic and molecular analyses have begun to clarify the etiologic nature of these tumors. Recent evidence suggests that histopathologic features that suggest more aggressiveness in Spitz tumors relate to mitoses and inflammation. (J Am Acad Dermatol 2011;65:1073-84.) C1 [Luo, Su; Tsao, Hensin] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Luo, Su; Tsao, Hensin] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Tsao, Hensin] Massachusetts Gen Hosp, MGH Canc Ctr, Boston, MA 02114 USA. [Luo, Su] Univ Miami, Miami, FL USA. [Sepehr, Alireza] Beth Israel Deaconess, Dermatopathol, Boston, MA USA. [Sepehr, Alireza] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Tsao, H (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Bartlett 622,48 Blossom St, Boston, MA 02114 USA. EM htsao@partners.org FU American Medical Association; National Institutes of Health [K24 CA149202-01]; American Cancer Society [RSG MGO-112970] FX Supported by a grant from the American Medical Association (Dr Luo), the National Institutes of Health (K24 CA149202-01 to Dr Tsao), the American Cancer Society (RSG MGO-112970 to Dr Tsao) and generous donors to the MGH Millennium Melanoma Fund. NR 80 TC 21 Z9 21 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD DEC PY 2011 VL 65 IS 6 BP 1073 EP 1084 DI 10.1016/j.jaad.2011.04.040 PG 12 WC Dermatology SC Dermatology GA 857KK UT WOS:000297717200001 PM 22082838 ER PT J AU Luo, S Sepehr, A Tsao, H AF Luo, Su Sepehr, Ahreza Tsao, Hensin TI Spitz nevi and other Spitzoid lesions Part II. Natural history and management SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE atypical Spitz tumor management; natural history; Spitz nevus ID LYMPH-NODE BIOPSY; MELANOCYTIC LESIONS; MALIGNANT-MELANOMA; TUMORS; DIAGNOSIS; PROPOSAL; CHILDHOOD; DIFFICULT; FEATURES; PATIENT AB For dermatologists, evidence-based management guidelines for Spitz tumors have not been established. Despite the lack of a standardized approach, most dermatologists recommend the excision of Spitz tumors occurring in adults and adopt more conservative measures towards pediatric cases. The histopathologic attributes and the clinical scenario are factored into management in each case. While the metastatic behavior of certain Spitz tumors is well known, the malignant potential of these lesions remains unclear because they only rarely result in negative outcomes. The risks and benefits of adjunctive measures, such as sentinel lymph node biopsy and interferon use, remain untested and are subjects of ongoing controversy. (In part II of this continuing medical education article, we will continue to use the terminology defined in part I for purposes of continuity. "Spitz tumor" is used as the umbrella term for the entire category of lesions, "common Spitz nevi" refers to only the most typical lesions seen in pediatric cases, and "atypical Spitz tumors" encompass the "all other" category, which continues to cause debate.) (J Am Acad Dermatol 2011;65:1087-92.) C1 [Luo, Su; Tsao, Hensin] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Luo, Su; Tsao, Hensin] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Tsao, Hensin] Massachusetts Gen Hosp, MGH Canc Ctr, Boston, MA 02114 USA. [Luo, Su] Univ Miami, Miami, FL USA. [Sepehr, Ahreza] Beth Israel Deaconess, Dermatopathol, Boston, MA USA. [Sepehr, Ahreza] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Tsao, H (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Bartlett 622,48 Blossom St, Boston, MA 02114 USA. EM htsao@partners.org FU American Medical Association; National Institutes of Health [K24 CA149202-01]; American Cancer Society [RSG MGO-112970] FX Supported by a grant from the American Medical Association (Dr Luo), the National Institutes of Health (K24 CA149202-01 and to Dr Tsao), the American Cancer Society (RSG MGO-112970 to Dr Tsao) and generous donors to the MGH Millennium Melanoma Fund. NR 28 TC 32 Z9 32 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD DEC PY 2011 VL 65 IS 6 BP 1087 EP 1092 DI 10.1016/j.jaad.2011.06.045 PG 6 WC Dermatology SC Dermatology GA 857KK UT WOS:000297717200002 PM 22082839 ER PT J AU Goreshi, R Chock, M Foering, K Feng, R Okawa, J Rose, M Fiorentino, D Werth, V AF Goreshi, Renato Chock, Monika Foering, Kristen Feng, Rui Okawa, Joyce Rose, Matt Fiorentino, David Werth, Victoria TI Quality of life in dermatomyositis SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE autoimmune disease; clinical research; connective tissue disease; cutaneous lupus; dermatomyositis; itch; pruritus; quality of life ID HEALTH SURVEY SF-36; PSYCHIATRIC-DISORDERS; SKIN-DISEASE; DERMATOLOGICAL OUTPATIENTS; PSYCHOLOGICAL DISTRESS; VALIDITY; RELIABILITY; MORBIDITY; PSORIASIS; PRURITUS AB Background: Quality of life (QoL) for patients with inflammatory skin disease can he significant, but has been evaluated in just one study in dermatomyositis (DM). Objective: We sought to examine the relationship between the Cutaneous Dermatomyositis Area (CDASI) and Severity Index, a DM-specific cutaneous severity instrument. and various QoL study instruments and to determine the impact of DM on QoL. Methods: Skin-specific QoL instruments, the Skindex and the Dermatology Life Quality Index, and global medical QoL instruments, the Short Form 36 and the Health Assessment Questionnaire-Disability Index, were used. Pruritus was evaluated by a visual analog scale and a 0-to-10 scale in DM and cutaneous lupus erythematosus (CLE) populations, respectively. Results: There was a significant correlation between the CDASI and all skin-specific QoL scores (lowest P = .0377). Using the Short Form 36, DM population was found to have significantly worse QoL scores than the general population with the exception of bodily pain (all subscore P values < .01). Furthermore, DM had a significantly lower vitality score, representing energy level, compared with CLE, hypertension, diabetes, and recent myocardial infarction scores (lowest P = .003). There was a significantly lower mental health score, representing overall mood, to all compared diseases except CLE and clinical depression (P values < .01 when significant). We found that DM produces more pruritus than CLE (P < .0001). Limitations: A larger patient population needs to be studied to further assess QoL in patients with DM. Conclusion: We conclude that DM has a large impact on QoL, even when compared with other diseases, and that DM skin disease activity correlates with a poorer QoL. (J Am Acad Dermatol 2011;65:1107-16.) C1 [Goreshi, Renato; Foering, Kristen; Okawa, Joyce; Rose, Matt; Werth, Victoria] Philadelphia Dept Vet Affairs Med Ctr, Philadelphia, PA USA. [Goreshi, Renato; Foering, Kristen; Okawa, Joyce; Rose, Matt; Werth, Victoria] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Chock, Monika; Fiorentino, David] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Feng, Rui] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. RP Werth, V (reprint author), Perelman Ctr Adv Med, Dept Dermatol, Suite 1-330A,3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM werth@mail.med.upenn.edu OI Fiorentino, David/0000-0001-7951-3674 FU National Institutes of Health (NIH) [NIH K24-AR 02207, NIH 5-R25-HL084665-04]; Department of Veterans Affairs Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development; Centocor; Abbott Laboratories; Amgen FX This material is based on work supported by the National Institutes of Health (NIH), including NIH K24-AR 02207 (Dr Werth) and training grant NIH 5-R25-HL084665-04 (Dr Goreshi). This work was also partially supported by a Merit Review Grant from the Department of Veterans Affairs Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development.; Dr Fiorentino received honoraria from Amgen, Centocor, Chemocentryx, and MedImmune; received grants from Centocor, Abbott Laboratories, and Amgen; and filed a patent (US patent application serial number 12/694,980 for "Profiling for Determination of Response to Treatment for Inflammatory Disease" filed on January 27, 2010). Drs Goreshi, Chock, Feng, and Werth, Ms Foering, Ms Okawa, and Mr Rose have no conflicts of interest to declare. NR 53 TC 22 Z9 23 U1 2 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD DEC PY 2011 VL 65 IS 6 BP 1107 EP 1116 DI 10.1016/j.jaad.2010.10.016 PG 10 WC Dermatology SC Dermatology GA 857KK UT WOS:000297717200004 PM 21722989 ER PT J AU Asgari, MM Chren, MM Warton, EM Friedman, GD White, E AF Asgari, Maryam M. Chren, Mary-Margaret Warton, E. Margaret Friedman, Gary D. White, Emily TI Supplement use and risk of cutaneous squamous cell carcinoma SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE antioxidant; epidemiology; skin cancer; squamous cell carcinoma; supplement; vitamin ID NONMELANOMA SKIN-CANCER; ORAL VITAMIN-E; GRAPE SEED; ALPHA-TOCOPHEROL; CONTROLLED-TRIAL; BETA-CAROTENE; BASAL-CELL; IN-VITRO; POLYPHENOLIC FRACTION; DIETARY FACTORS AB Background: Laboratory and epidemiologic studies suggest that certain dietary supplements may alter risk of cutaneous squamous cell carcinoma (SCC). Objective: We sought to examine the association between supplement use and SCC risk. Methods: Cases (n = 415) were defined as Kaiser Permanente Northern California members with a pathology-verified SCC in 2004 and control subjects (n = 415) were age-, sex-, and race-matched members with no history of skin cancer. Supplement use and SCC risk factors were ascertained by questionnaire. Associations of SCC with use of multivitamins; vitamins A, C, D, and E; and grape seed extract were estimated as odds ratios and 95% confidence intervals using conditional logistic regression. Models were adjusted for SCC risk factors and other supplement use. Results: Grape seed extract users had a significantly decreased risk of cutaneous SCC (adjusted odds ratio 0.26, confidence interval 0.08-0.89, P = .031). Multivitamin use was associated with a borderline significant reduction in SCC risk (adjusted odds ratio 0.71, confidence interval 0.51-1.00, P = .049). Use of vitamins A, C, 0, and E was not associated with SCC risk. Limitations: The data may be prone to recall and selection bias because of the case-control design. No information was obtained on dose or duration of supplement use. Conclusions: Use of grape seed extract may be associated with a decreased risk of cutaneous SCC. The other supplements included in our study did not reveal clear associations with SCC risk. (J Am Acad Dermatol 2011;65:1145-51.) C1 [Asgari, Maryam M.; Warton, E. Margaret; Friedman, Gary D.] Kaiser Permanente No Calif, Div Res, Oakland, CA 94612 USA. [Asgari, Maryam M.; Chren, Mary-Margaret] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [Chren, Mary-Margaret] San Francisco VA Med Ctr, Hlth Serv Res Enhancement Award Program, San Francisco, CA USA. [Friedman, Gary D.] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA. [White, Emily] Univ Washington, Med Ctr, Dept Epidemiol, Seattle, WA 98195 USA. [White, Emily] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98104 USA. RP Asgari, MM (reprint author), Kaiser Permanente No Calif, Div Res, 2000 Broadway, Oakland, CA 94612 USA. EM maryam.m.asgari@kp.org RI Asgari, Maryam/O-4947-2016 FU National Institute of Arthritis and Musculoskeletal and Skin Diseases [K23 AR 051037, K24 AR 052667]; National Cancer Institute [R01 CA 098838, K05CA154337] FX Supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (K23 AR 051037 to Dr Asgari, K24 AR 052667 to Dr Chren) and by the National Cancer Institute (R01 CA 098838 to Dr Friedman, K05CA154337 to Dr White). NR 47 TC 6 Z9 6 U1 1 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD DEC PY 2011 VL 65 IS 6 BP 1145 EP 1151 DI 10.1016/j.jaad.2010.09.009 PG 7 WC Dermatology SC Dermatology GA 857KK UT WOS:000297717200008 PM 21664718 ER PT J AU Troianos, CA Hartman, GS Glas, KE Skubas, NJ Eberhardt, RT Walker, JD Reeves, ST AF Troianos, Christopher A. Hartman, Gregg S. Glas, Kathryn E. Skubas, Nikolaos J. Eberhardt, Robert T. Walker, Jennifer D. Reeves, Scott T. CA Amer Soc Echocardiography TI Guidelines for Performing Ultrasound Guided Vascular Cannulation: Recommendations of the American Society of Echocardiography and the Society of Cardiovascular Anesthesiologists SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Editorial Material DE Anatomy; Artery; Cannulation; Femoral; Guidelines; Internal jugular; Pediatric; Peripheral; Subclavian; Ultrasound; Vascular; Venous ID INTERNAL JUGULAR-VEIN; CENTRAL VENOUS CATHETERIZATION; RADIAL ARTERY CANNULATION; PERIPHERAL INTRAVENOUS ACCESS; RANDOMIZED CONTROLLED-TRIAL; CONTROLLED CLINICAL-TRIAL; COMMON FEMORAL-ARTERY; CROSS-SECTIONAL AREA; ANATOMIC RELATIONSHIP; HEAD ROTATION C1 [Troianos, Christopher A.] W Penn Allegheny Hlth Syst, Dept Anesthesiol, Pittsburgh, PA USA. [Hartman, Gregg S.] Dartmouth Hitchcock Med Ctr, Dept Anesthesiol, Lebanon, NH 03766 USA. [Glas, Kathryn E.] Emory Univ, Dept Anesthesiol, Atlanta, GA 30322 USA. [Skubas, Nikolaos J.] Weill Cornell Med Coll, Dept Anesthesiol, New York, NY USA. [Eberhardt, Robert T.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Walker, Jennifer D.] Massachusetts Gen Hosp, Dept Cardiothorac Surg, Boston, MA 02114 USA. [Reeves, Scott T.] Med Univ S Carolina, Dept Anesthesiol, Charleston, SC 29425 USA. RP Troianos, CA (reprint author), 2100 Gateway Ctr Blvd,Suite 310, Morrisville, NC 27560 USA. OI Eberhardt, Robert/0000-0002-5076-7416 NR 96 TC 74 Z9 83 U1 0 U2 8 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD DEC PY 2011 VL 24 IS 12 BP 1291 EP 1318 DI 10.1016/j.echo.2011.09.021 PG 28 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 857DZ UT WOS:000297697300001 PM 22115322 ER PT J AU Baskin, KM Hogan, MJ Sidhu, MK Connolly, BL Towbin, RB Saad, WEA Dubois, J Heran, MKS Marshalleck, FE Miller, DL Roebuck, D Temple, MJ Walker, TG Cardella, JF AF Baskin, Kevin M. Hogan, Mark J. Sidhu, Manrita K. Connolly, Bairbre L. Towbin, Richard B. Saad, Wael E. A. Dubois, Josee Heran, Manraj K. S. Marshalleck, Francis E. Miller, Donald L. Roebuck, Derek Temple, Michael J. Walker, T. Gregory Cardella, John F. TI Developing a Clinical Pediatric Interventional Practice: A Joint Clinical Practice Guideline from the Society of Interventional Radiology and the Society for Pediatric Radiology SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID RADIATION-EXPOSURE; MANAGEMENT; SAFETY; SUITE; STRATEGIES; EQUIPMENT; QUALITY C1 [Baskin, Kevin M.] Univ Pittsburgh, Childrens Hosp Pittsburgh, Med Ctr, Dept Radiol, Pittsburgh, PA 15213 USA. [Cardella, John F.] Geisinger Hlth Syst, Dept Radiol, Danville, PA USA. [Hogan, Mark J.] Ohio State Univ, Nationwide Childrens Hosp, Sect Vasc & Intervent Radiol, Dept Radiol, Columbus, OH 43210 USA. [Sidhu, Manrita K.] Univ Washington, Dept Radiol, Seattle Childrens Hosp, Seattle, WA 98195 USA. [Connolly, Bairbre L.; Temple, Michael J.] Univ Toronto, Hosp Sick Children, Ctr Image Guided Therapy, Toronto, ON M5G 1X8, Canada. [Dubois, Josee] Ctr Hosp Univ St Justine, Dept Med Imaging, Montreal, PQ, Canada. [Heran, Manraj K. S.] British Columbia Childrens Hosp, Dept Radiol, Vancouver, BC, Canada. [Heran, Manraj K. S.] Vancouver Gen Hosp, Dept Radiol, Vancouver, BC, Canada. [Towbin, Richard B.] Phoenix Childrens Hosp, Dept Radiol, Phoenix, AZ USA. [Saad, Wael E. A.] Univ Virginia Hlth Syst, Dept Radiol, Charlottesville, VA USA. [Marshalleck, Francis E.] Indiana Univ Sch Med, Riley Hosp Children, Dept Radiol, Indianapolis, IN USA. [Miller, Donald L.] Uniformed Serv Univ Hlth Sci, Dept Radiol, Bethesda, MD 20814 USA. [Miller, Donald L.] Natl Naval Med Ctr, Dept Radiol, Bethesda, MD USA. [Roebuck, Derek] Great Ormond St Hosp Sick Children, Dept Radiol, London, England. [Walker, T. Gregory] Massachusetts Gen Hosp, Div Vasc Imaging & Intervent, Boston, MA 02114 USA. RP Baskin, KM (reprint author), 3975 Fair Ridge Dr,Suite 400 N, Fairfax, VA 22033 USA. EM kevin.baskin@chp.eclu RI Temple, Michael/E-4082-2013; OI Temple, Michael/0000-0002-5843-0519; Baskin, Kevin/0000-0001-8928-9688; Roebuck, Derek/0000-0003-1734-2536 FU Siemens (Forchheim, Germany) FX W.E.A.S. is a paid consultant for Boston Scientific (Natick, Massachusetts), has research funded by Siemens (Forchheim, Germany), and serves on the Speaker's Bureau for Atrium (Hudson, New Hampshire). None of the other authors have identified a conflict of interest. NR 55 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD DEC PY 2011 VL 22 IS 12 BP 1647 EP 1655 DI 10.1016/j.jvir.2011.07.010 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 858VB UT WOS:000297830200001 PM 21963252 ER PT J AU Anselmetti, GC Manca, A Hirsch, J Montemurro, F Isaia, G Osella, G Chiara, G Iussich, G Debernardi, F Regge, D AF Anselmetti, Giovanni Carlo Manca, Antonio Hirsch, Joshua Montemurro, Filippo Isaia, Giancarlo Osella, Giangiacomo Chiara, Gabriele Iussich, Gabriella Debernardi, Felicino Regge, Daniele TI Percutaneous Vertebroplasty in Osteoporotic Patients: An Institutional Experience of 1,634 Patients with Long-Term Follow-Up SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID VERTEBRAL COMPRESSION FRACTURES; POSTMENOPAUSAL WOMEN; RANDOMIZED-TRIAL; SINGLE-CENTER; RISK; PAIN; VERTOS; EPIDEMIOLOGY AB Purpose: To assess long-term clinical outcome of percutaneous vertebroplasty (PV). Materials and Methods: PV was performed in 1,634 patients (1,387 women; median age 73 years +/- 9.3) with painful osteoporotic vertebral compression fractures (VCFs). All patients had back pain that persisted for >= 2 months with a concordant magnetic resonance imaging study. After PV, medical therapy for osteoporosis was continued, and patients were prospectively evaluated (follow-up 11.8-44.9 months, mean 25.0 months). Visual analog scale (VAS), Oswestry Disability Index (ODI), analgesic drug use, and use of external brace support were recorded at baseline and during follow-up. New occurrences of symptomatic vertebral fractures were recorded. Results: The mean VAS score of 7.94 significantly improved to 1.12 at the primary endpoint (P < .001). Differences in patterns of analgesic usage compared with baseline values were highly statistically significant (marginal homogeneity test, P < .001). Median ODI values of 82% before treatment significantly decreased to 6% (P < .001). Before intervention, 1,279 patients wore a brace; 1,167 (91.2%) patients did not wear a brace after PV (chi(2) = 31.005, P < .0001). A new painful fracture with a significant higher proportion of contiguous vertebrae (63.6%) occurred in 214 (13.1%) patients (z = 7.59, P = .025). Conclusions: PV can provide durable pain relief and improvement in ambulation in patients with VCFs. C1 [Anselmetti, Giovanni Carlo; Manca, Antonio; Chiara, Gabriele] IRCC, Intervent Radiol Unit, I-10060 Turin, Italy. [Montemurro, Filippo] IRCC, Internal Med Unit, I-10060 Turin, Italy. [Iussich, Gabriella; Regge, Daniele] IRCC, Radiol Unit, I-10060 Turin, Italy. [Debernardi, Felicino] IRCC, Anesthesiol Unit, I-10060 Turin, Italy. [Hirsch, Joshua] Massachusetts Gen Hosp, Dept Intervent Neuroradiol, Boston, MA 02114 USA. [Isaia, Giancarlo] Azienda Osped S Giovanni Battista, Dept Internal Med, Turin, Italy. [Osella, Giangiacomo] Azienda Osped San Luigi, SCDU Med Interna 1, Turin, Italy. RP Anselmetti, GC (reprint author), IRCC, Intervent Radiol Unit, Str Provinciale 142 Km 3,95, I-10060 Turin, Italy. EM giovanni.sanselmetti@ircc.it OI Manca, Antonio/0000-0002-8193-5208 NR 30 TC 19 Z9 27 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD DEC PY 2011 VL 22 IS 12 BP 1714 EP 1720 DI 10.1016/j.jvir.2011.09.001 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 858VB UT WOS:000297830200009 PM 22019853 ER PT J AU Kwolek, CJ Malek, J Conrad, M AF Kwolek, Christopher J. Malek, Junaid Conrad, Mark TI A New Tool for Extreme IVC Filter Removal SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract CT Annual Meeting of the Southern-Association-for-Vascular-Surgery CY 2012 CL Scottsdale, AZ SP So Assoc Vasc Surg C1 [Kwolek, Christopher J.; Malek, Junaid; Conrad, Mark] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD DEC PY 2011 VL 54 IS 6 BP 1855 EP 1856 PG 2 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 858SQ UT WOS:000297823400062 ER PT J AU Johnson, LL Verioti, C Gelber, J Spector, M D'Lima, D Pittsley, A AF Johnson, Lanny L. Verioti, Christopher Gelber, Jonathan Spector, Myron D'Lima, Darryl Pittsley, Andrew TI The pathology of the end-stage osteoarthritic lesion of the knee: Potential role in cartilage repair SO KNEE LA English DT Article DE Pathology; Osteoarthritis; Cartilage repair ID HIGH TIBIAL OSTEOTOMY; ARTICULAR-CARTILAGE; SUBCHONDRAL BONE; HIP; REGENERATION; DEGENERATION; ARTHRITIS; CELLS AB The purpose was to explore whether there were any pathological characteristics of the end-stage osteoarthritic sclerotic lesion that have potential to participate in cartilage repair. Specimens harvested following total knee surgery were examined for gross pathology including staining with Safranin O. Multiple small sections of the lesion were placed in tissue culture for 6 weeks. Gross examination and photographic documentation was made at 3 and 6 weeks. At 6 weeks the specimens from culture were subject to histological examination. The pathology of the end-stage osteoarthritic lesion showed sclerotic bone, dead osteons, hypervascularity and scattered cartilaginous aggregates. Additional observations showed multiple pitting on the sclerotic surface, which histologically was related to three events; fragmentation of dead bone, ruptured blood vessels, and eroded aggregates. There were no pathological or biological changes in the specimens following the time in tissue culture. The in-depth pathological evaluation showed the end-stage osteoarthritic lesion to have certain features with potential to facilitate cartilage repair. The cartilaginous aggregates may be a participant in cartilage repair following surgery. The cartilaginous aggregates remained unchanged in the tissue culture absent the normal synovial joint chemical and physical environment and therefore further testing with a different experimental model would be necessary to establish these aggregates as a source of cartilage regeneration. The multiple small depressions in this lesion may have potential to be a "home" for therapeutics. (C) 2010 Elsevier B.V. All rights reserved. C1 [Verioti, Christopher; Gelber, Jonathan; D'Lima, Darryl] Scripps Clin, Shiley Ctr Orthopaed Res & Educ SCORE, La Jolla, CA 92037 USA. [Spector, Myron] Harvard Univ, Sch Med, Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02130 USA. RP Johnson, LL (reprint author), 4658 Chippewa Dr, Okemos, MI 48864 USA. EM LLJMD@aol.com; cverioti@gmail.com; Jonathon.gelber@mssm.edu; mspector@rics.bwh.harvard.edu; DLima.Darryl@scrippshealth.org; Andrew@drymud.com OI D'Lima, Darryl/0000-0002-8707-1455 FU Lanny L Johnson FX The authors thank and appreciate the expertise and attention to detail that Lilo Creighton provided with the histology. This study is funded in its entirety by Lanny L Johnson, M.D. Dr. Johnson participated in the analysis and interpretation of data, in the writing of the manuscript, and in the decision to submit the manuscript for publication. The work was done independently at Scripps Clinic's SCORE under a work for hire agreement NR 21 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0968-0160 J9 KNEE JI Knee PD DEC PY 2011 VL 18 IS 6 BP 402 EP 406 DI 10.1016/j.knee.2010.07.012 PG 5 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 853NK UT WOS:000297432800010 PM 20934341 ER PT J AU Warner, EA Kotz, KT Ungaro, RF Abouhamze, AS Lopez, MC Cuenca, AG Kelly-Scumpia, KM Moreno, C O'Malley, KA Lanz, JD Baker, HV Martin, LC Toner, M Tompkins, RG Efron, PA Moldawer, LL AF Warner, Elizabeth A. Kotz, Kenneth T. Ungaro, Ricardo F. Abouhamze, Amer S. Lopez, M. Cecilia Cuenca, Alex G. Kelly-Scumpia, Kindra M. Moreno, Claudia O'Malley, Kerri A. Lanz, Jennifer D. Baker, Henry V. Martin, Larry C. Toner, Mehmet Tompkins, Ronald G. Efron, Philip A. Moldawer, Lyle L. TI Microfluidics-based capture of human neutrophils for expression analysis in blood and bronchoalveolar lavage SO LABORATORY INVESTIGATION LA English DT Article DE dextran; Ficoll; genomics; microfluidics; neutrophil isolation ID BREAST-CANCER; WHOLE-BLOOD; LEUKOCYTES; GENOMICS; DEXTRAN; CELL AB Gene expression analysis can be a powerful tool in predicting patient outcomes and identifying patients who may benefit from targeted therapies. However, isolating human blood polymorphonuclear cells (PMNs) for genomic analysis has been challenging. We used a novel microfluidic technique that isolates PMNs by capturing CD66b(+) cells and compared it with dextran-Ficoll gradient isolation. We also used microfluidic isolation techniques for blood and bronchoalveolar lavage (BAL) samples of patients with acute respiratory distress syndrome (ARDS) to evaluate PMN genomic alterations secondary to pulmonary sequestration. PMNs obtained from ex vivo lipopolysaccharide (LPS)-stimulated or -unstimulated whole blood from five healthy volunteers were isolated by either dextran-Ficoll gradient, microfluidics capture, or a combination of the two techniques. Blood and BAL fluid PMNs were also isolated using microfluidics from seven hospitalized patients with ARDS. Gene expression was inferred from extracted RNA using Affymetrix U133 Plus 2.0 GeneChips. All methods of PMN isolation produced similar quantities of high-quality RNA, when adjusted for recovered cell number. Unsupervised analysis and hierarchical clustering indicated that LPS stimulation was the primary factor affecting gene expression patterns among all ex vivo samples. Patterns of gene expression from blood and BAL PMNs differed significantly from each other in the patients with ARDS. Isolation of PMNs by microfluidics can be applied to both blood and BAL specimens from critically ill, hospitalized patients. Unique genomic expression patterns are obtained from the blood and BAL fluid of critically ill patients with ARDS, and these differ significantly from genomic patterns seen after ex vivo LPS stimulation. Laboratory Investigation (2011) 91, 1787-1795; doi:10.1038/labinvest.2011.94; published online 19 September 2011 C1 [Warner, Elizabeth A.; Ungaro, Ricardo F.; Abouhamze, Amer S.; Cuenca, Alex G.; Kelly-Scumpia, Kindra M.; Moreno, Claudia; O'Malley, Kerri A.; Lanz, Jennifer D.; Martin, Larry C.; Efron, Philip A.; Moldawer, Lyle L.] Univ Florida, Coll Med, Dept Surg, Gainesville, FL 32610 USA. [Kotz, Kenneth T.; Toner, Mehmet; Tompkins, Ronald G.] Massachusetts Gen Hosp, Dept Surg, MGH BioMEMS Resource Ctr, Boston, MA 02114 USA. [Lopez, M. Cecilia; Baker, Henry V.] Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Gainesville, FL 32610 USA. RP Moldawer, LL (reprint author), Univ Florida, Coll Med, Dept Surg, Room 6116,POB 100019,1600 SW Archer Rd, Gainesville, FL 32610 USA. EM moldawer@surgery.ufl.edu OI Baker, Henry/0000-0002-8273-5320 FU National Institutes of Health, USPHS [R01 GM-40586, R01 GM-81923, P41 EB-002503]; National Institute of General Medical Sciences [GM-008721, F32 NRSA GM-093665-01] FX Supported in part by grants R01 GM-40586, R01 GM-81923 and P41 EB-002503, awarded by the National Institutes of Health, USPHS, KMK-S, AGC, and CM were supported by a National Institute of General Medical Sciences training grant in burns and trauma (GM-008721). AGC was supported by F32 NRSA GM-093665-01, awarded by the National Institute of General Medical Sciences. Development of the microfluidics cassette was supported by the Inflammation and Host Response to Injury Large Scale Collaborative Research Program (Glue Grant; U54 GM062119-9), awarded to Dr Ronald G Tompkins, Massachusetts General Hospital by the National Institute of General Medical Sciences. This work represents a secondary product of the Program, and although the completed manuscript has been seen by the leadership of the Program, the conclusions and discussion are ours, and do not necessarily represent the views of either the Program, Massachusetts General Hospital, or the National Institute of General Medical Sciences. NR 21 TC 13 Z9 13 U1 0 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD DEC PY 2011 VL 91 IS 12 BP 1787 EP 1795 DI 10.1038/labinvest.2011.94 PG 9 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 856HC UT WOS:000297628500010 PM 21931299 ER PT J AU Barnighausen, T Chaiyachati, K Chimbindi, N Peoples, A Haberer, J Newell, ML AF Baernighausen, Till Chaiyachati, Krisda Chimbindi, Natsayi Peoples, Ashleigh Haberer, Jessica Newell, Marie-Louise TI Interventions to increase antiretroviral adherence in sub-Saharan Africa: a systematic review of evaluation studies SO LANCET INFECTIOUS DISEASES LA English DT Review ID HIV-INFECTED PATIENTS; IMMUNODEFICIENCY-VIRUS-INFECTION; DIRECTLY OBSERVED THERAPY; RANDOMIZED CONTROLLED-TRIAL; LESS-THAN 95-PERCENT; IMPROVE ADHERENCE; MEDICATION ADHERENCE; VIROLOGICAL RESPONSE; PROTEASE INHIBITORS; MANAGEMENT PROGRAM AB The success of potent antiretroviral treatment for HIV infection is primarily determined by adherence. We systematically review the evidence of effectiveness of interventions to increase adherence to antiretroviral treatment in sub-Saharan Africa. We identified 27 relevant reports from 26 studies of behavioural, cognitive, biological, structural, and combination interventions done between 2003 and 2010. Despite study diversity and limitations, evidence suggests that treatment supporters, directly observed therapy, mobile-phone text messages, diary cards, and food rations can effectively increase adherence in sub-Saharan Africa. However, some interventions are unlikely to have large or lasting effects, and others are effective only in specific settings. These findings emphasise the need for more research, particularly for randomised controlled trials, to examine the effect of context and specific features of intervention content on effectiveness. Future work should assess intervention targeting and selection of interventions based on behavioural theories relevant to sub-Saharan Africa. C1 [Baernighausen, Till; Chaiyachati, Krisda] Harvard Univ, Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA 02115 USA. [Baernighausen, Till; Chimbindi, Natsayi; Newell, Marie-Louise] Univ KwaZulu Natal, Africa Ctr Hlth & Populat Studies, Mtubatuba, South Africa. [Chaiyachati, Krisda] Univ Michigan, Sch Med, Ann Arbor, MI USA. [Peoples, Ashleigh] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Haberer, Jessica] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Newell, Marie-Louise] UCL Inst Child Hlth, Ctr Paediat Epidemiol & Biostat, London, England. RP Barnighausen, T (reprint author), Harvard Univ, Sch Publ Hlth, Dept Global Hlth & Populat, 665 Huntington Ave, Boston, MA 02115 USA. EM tbaernig@hsph.harvard.edu RI Emchi, Karma/Q-1952-2016; OI Newell, Marie-Louise/0000-0002-1074-7699 FU National Institute of Child Health and Human Development (NICHD) [1R01-HD058482-01]; National Institute of Mental Health [1R01MG083539-01, K23087228]; Wellcome Trust; World Bank FX TB is supported by grant 1R01-HD058482-01 from the National Institute of Child Health and Human Development (NICHD) and by grant 1R01MG083539-01 from the National Institute of Mental Health and the Wellcome Trust. The funding organisation had no role in the design and conduct of the study, in the collection, analysis, and interpretation of the data, or in the preparation, review, or approval of the report. TB has been paid by UNITAID for consultancy work and has received grant funding for HIV modelling from the World Bank. JH is supported by National Institute of Mental Health grant K23087228. M-LN is supported by the Wellcome Trust. NR 113 TC 112 Z9 113 U1 1 U2 16 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1473-3099 J9 LANCET INFECT DIS JI Lancet Infect. Dis. PD DEC PY 2011 VL 11 IS 12 BP 942 EP 951 DI 10.1016/S1473-3099(11)70181-5 PG 10 WC Infectious Diseases SC Infectious Diseases GA 854KV UT WOS:000297494300021 PM 22030332 ER PT J AU Stock, W Douer, D DeAngelo, DJ Arellano, M Advani, A Damon, L Kovacsovics, T Litzow, M Rytting, M Borthakur, G Bleyer, A AF Stock, Wendy Douer, Dan DeAngelo, Daniel J. Arellano, Martha Advani, Anjali Damon, Lloyd Kovacsovics, Tibor Litzow, Mark Rytting, Michael Borthakur, Gautam Bleyer, Archie TI Prevention and management of asparaginase/pegasparaginase-associated toxicities in adults and older adolescents: recommendations of an expert panel SO LEUKEMIA & LYMPHOMA LA English DT Review DE Asparaginase; pegasparaginase; toxicities; guidelines; adults ID ACUTE LYMPHOBLASTIC-LEUKEMIA; ASPARAGINASE-ASSOCIATED PANCREATITIS; ESCHERICHIA-COLI-ASPARAGINASE; CONJUGATED L-ASPARAGINASE; ANTITHROMBIN-III DEFICIENCY; REGIONAL ARTERIAL INFUSION; RECEIVING L-ASPARAGINASE; CHILDRENS ONCOLOGY GROUP; THROMBOTIC COMPLICATIONS; PEGYLATED ASPARAGINASE AB The rapidly increasing use of pegasparaginase (pegASNase) in adults, after a half century of use of asparaginase (ASNase) in children, has prompted a need for guidelines in the management and prevention of toxicities of asparagine depletion in adults. Accordingly, an initial set of recommendations are provided herein. Major advantages of pegASNase are its 2-3-week duration of action, in contrast to less than 3 days with native ASNase, and the flexibility of intravenous or intramuscular administration of pegASNase and associated patient and physician convenience. The most frequent toxicities of both types of ASNase are hepatic and pancreatic, with pancreatitis being the most serious. Other toxicities are hypersensitivity reactions, thrombosis, nausea/vomiting, and fatigue. Whether or not the replacement of one dose of pegASNase for 6-9 doses of native ASNase can be achieved in adults with similar efficacy and acceptable toxicities to those achieved in children remains to be established. C1 [Stock, Wendy] Univ Chicago, Chicago, IL 60637 USA. [Douer, Dan] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [DeAngelo, Daniel J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [DeAngelo, Daniel J.] Harvard Univ, Boston, MA 02115 USA. [Arellano, Martha] Emory Univ, Atlanta, GA 30322 USA. [Advani, Anjali] Cleveland Clin, Cleveland, OH 44106 USA. [Damon, Lloyd] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Kovacsovics, Tibor] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Litzow, Mark] Mayo Clin, Rochester, MN USA. [Rytting, Michael; Borthakur, Gautam] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Bleyer, Archie] St Charles Hlth Syst, Bend, OR USA. [Bleyer, Archie] Univ Texas Med Sch Houston, Houston, TX USA. RP Bleyer, A (reprint author), Pediat & Young Adult Oncol, 2884 NW Horizon Dr, Bend, OR 97701 USA. EM ableyer@gmail.com FU NCI NIH HHS [P30 CA016672] NR 125 TC 49 Z9 50 U1 1 U2 10 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD DEC PY 2011 VL 52 IS 12 BP 2237 EP 2253 DI 10.3109/10428194.2011.596963 PG 17 WC Oncology; Hematology SC Oncology; Hematology GA 857FD UT WOS:000297700900007 PM 21827361 ER PT J AU Siegel, D Jagannath, S Vesole, DH Borello, I Mazumder, A Mitsiades, C Goddard, J Dunbar, J Normant, E Adams, J Grayzel, D Anderson, KC Richardson, P AF Siegel, David Jagannath, Sundar Vesole, David H. Borello, Ivan Mazumder, Amitabha Mitsiades, Constantine Goddard, Jill Dunbar, Joi Normant, Emmanuel Adams, Julian Grayzel, David Anderson, Kenneth C. Richardson, Paul TI A phase 1 study of IPI-504 (retaspimycin hydrochloride) in patients with relapsed or relapsed and refractory multiple myeloma SO LEUKEMIA & LYMPHOMA LA English DT Article DE Multiple myeloma; HSP90; IPI-504; phase 1; relapsed/refractory ID UNFOLDED PROTEIN RESPONSE; ADVANCED CANCER; I TRIAL; HSP90; CHAPERONE; CELLS; INHIBITORS; 17-ALLYLAMINO-17-DEMETHOXYGELDANAMYCIN; HEAT-SHOCK-PROTEIN-90; GELDANAMYCIN AB A phase 1 study of IPI-504 (retaspimycin hydrochloride) administered intravenously twice weekly for 2 weeks at 22.5, 45, 90, 150, 225, 300 or 400 mg/m(2) followed by 10 days off-treatment was conducted to determine the safety and maximum tolerated dose (MTD) of IPI-504 in patients with relapsed or relapsed/refractory multiple myeloma (MM). Anti-tumor activity and pharmacokinetics were also evaluated. Eighteen patients (mean age 60.5 years; median 9 prior therapies) were enrolled. No dose-limiting toxicities (DLTs) were reported for IPI-504 doses up to 400 mg/m(2). The most common treatment-related adverse event was grade 1 infusion site pain (four patients). All other treatment-related events were assessed as grade 1 or 2 in severity. The area under the curve (AUC) increased with increasing dose, and the mean half-life was approximately 2-4 h for IPI-504 and its metabolites. Four patients had stable disease, demonstrating modest single-agent activity in relapsed or relapsed/refractory MM. C1 [Siegel, David; Jagannath, Sundar; Vesole, David H.; Mazumder, Amitabha] Hackensack Univ Med Ctr, Hackensack, NJ 07601 USA. [Borello, Ivan] Johns Hopkins, Sydney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Mitsiades, Constantine; Anderson, Kenneth C.; Richardson, Paul] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Goddard, Jill; Dunbar, Joi; Normant, Emmanuel; Adams, Julian; Grayzel, David] Infin Pharmaceut Inc, Cambridge, MA USA. RP Siegel, D (reprint author), Hackensack Univ Med Ctr, 360 Essex St, Hackensack, NJ 07601 USA. EM DSiegel@humed.com FU Infinity Pharmaceuticals, Inc. FX David Siegel, Sundar Jagannath, David H. Vesole, Ivan Borello, Amitabha Mazumder, Constantine Mitsiades, Kenneth C. Anderson and Paul Richardson received research funding from Infinity Pharmaceuticals, Inc. to support the conduct of this trial. NR 29 TC 11 Z9 11 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD DEC PY 2011 VL 52 IS 12 BP 2308 EP 2315 DI 10.3109/10428194.2011.600481 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA 857FD UT WOS:000297700900016 PM 21851215 ER PT J AU Loberiza, FR Swore-Fletcher, BA Block, SD Back, AL Goldman, RE Tulsky, JA Lee, SJ AF Loberiza, Fausto R., Jr. Swore-Fletcher, Barbara A. Block, Susan D. Back, Anthony L. Goldman, Roberta E. Tulsky, James A. Lee, Stephanie J. TI Coping styles, health status and advance care planning in patients with hematologic malignancies SO LEUKEMIA & LYMPHOMA LA English DT Article DE Advance care planning; coping; health status; hematological cancer ID CELL TRANSPLANTATION; DECISION-MAKING; OUTCOMES; CANCER; DIRECTIVES; ANXIETY; DEATH; WANT; NEED AB This study evaluated whether measures of psychological well-being, including coping style, are associated with advance care planning (ACP). Data were from the Hematology Communications Study (HEMA-COMM), a prospective observational study of physician-patient communication in patients with hematologic malignancies. ACP was defined as having a living will, having a health care proxy, discussing life support with family or friends and discussing life support with a doctor or nurse. A total of 293 patients participated: only 45 (15%) had all the elements of ACP; 215 (73%) had at least one element of ACP, while 33 (11%) did not engage in ACP. In multi-variate analysis, specific coping styles but not other measures of psychosocial well-being were associated with having written ACP. Verbal ACP was associated with patient-reported health and physician estimate of life expectancy. Our study suggests that tailoring ACP discussions to a patient's coping style may increase engagement in ACP. C1 [Loberiza, Fausto R., Jr.; Swore-Fletcher, Barbara A.] Univ Nebraska Med Ctr, Omaha, NE USA. [Block, Susan D.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Block, Susan D.] Harvard Univ, Sch Med, Boston, MA USA. [Back, Anthony L.; Lee, Stephanie J.] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. [Goldman, Roberta E.] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA. [Goldman, Roberta E.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Tulsky, James A.] Duke Univ, Sch Med, Durham, NC USA. RP Loberiza, FR (reprint author), 987680 Nebraska Med Ctr, Omaha, NE 68198 USA. EM floberiza@unmc.edu FU National Cancer Institute (NCI) [CA098486] FX This study received funding from the National Cancer Institute (NCI CA098486). NR 22 TC 8 Z9 8 U1 0 U2 4 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD DEC PY 2011 VL 52 IS 12 BP 2342 EP 2348 DI 10.3109/10428194.2011.601474 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA 857FD UT WOS:000297700900021 PM 21851220 ER PT J AU Sacks, HS Fain, JN Cheema, P Bahouth, SW Garrett, E Wolf, RY Wolford, D Samaha, J AF Sacks, Harold S. Fain, John N. Cheema, Paramjeet Bahouth, Suleiman W. Garrett, Edward Wolf, Rodney Y. Wolford, David Samaha, Joseph TI Depot-Specific Overexpression of Proinflammatory, Redox, Endothelial Cell, and Angiogenic Genes in Epicardial Fat Adjacent to Severe Stable Coronary Atherosclerosis SO METABOLIC SYNDROME AND RELATED DISORDERS LA English DT Article ID ADIPOSE-TISSUE; ARTERY-DISEASE; CARDIOVASCULAR-DISEASE; INSULIN-RESISTANCE; OXIDATIVE STRESS; EXPRESSION; MEDIATORS AB Background: Pro- and antiinflammatory genes are expressed in epicardial adipose tissue (EAT). Our objectives were to characterize genes in EAT that may contribute specifically to coronary atherogenesis and to measure circulating adipokines matched to their messenger RNAs (mRNAs) in EAT. We hypothesized that severe coronary atherosclerosis (CAD) would preferentially affect gene expression in EAT as compared to substernal fat or subcutaneous thoracic adipose tissue (SAT), as well as circulating levels of adipokines. Methods: Fat mRNA was quantified using reverse transcription polymerase chain reaction (RT-PCR), and circulating adipokines were measured by enzyme-linked immunosorbent assays (ELISAs) in patients with severe stable CAD and controls without severe CAD undergoing open heart surgery. Results: A total of 39 of 70 mRNAs in EAT were significantly increased in CAD. Only 4 and 3 of these mRNAs were increased in substernal fat and SAT, respectively. Of the mRNAs increased in EAT, 17 were either inflammatory adipokines or proteins known to be involved in inflammatory processes, 7 were involved in oxidative stress and or oxygen species regulation, whereas 15 were proteins involved in metabolism and regulation of gene transcription or proteins unique to fat cells. The largest increases, over three-fold, were seen in GPX3, gp91 phox, p47phox, heme oxygenase, and interleukin-8 (IL-8). Tpl2 mRNA was uniquely elevated in all three fat depots from CAD patients, and its expression in SAT, but not in EAT or substernal fat, was directly correlated with homeostasis model assessment of insulin resistance (HOMA-IR) values. Compared to controls, there were no associations between circulating levels of IL-8, lipocalin-2, nerve growth factor (NGF), RANTES, CD-163, GPX-3, monocyte chemotactic protein-1 (MCP-1)/CCL2, leptin, soluble vascular endothelial growth factor receptor-1 (sFLT1), fatty acid binding protein-4 (FABP-4), and plasminogen activator inhibitor-1 (PAI-1) and increases in their gene expression in EAT adjacent to CAD. Conclusions: Expression of proinflammatory, redox, endothelial cell, and angiogenic genes in EAT is depot specific and supports the hypothesis that pathophysiologically EAT contributes locally to CAD. CAD links with these fat depots might involve Tpl2 as a primary response indicator. C1 [Sacks, Harold S.] Univ Tennessee, Hlth Sci Ctr, Coll Med, Dept Med, Memphis, TN USA. [Fain, John N.; Cheema, Paramjeet] Univ Tennessee, Hlth Sci Ctr, Coll Med, Dept Mol Sci, Memphis, TN USA. [Bahouth, Suleiman W.] Univ Tennessee, Hlth Sci Ctr, Coll Med, Dept Pharmacol, Memphis, TN USA. [Sacks, Harold S.; Garrett, Edward; Wolf, Rodney Y.; Wolford, David; Samaha, Joseph] Baptist Mem Hosp, Baptist Heart Inst, Memphis, TN 38146 USA. RP Sacks, HS (reprint author), VA Greater Angeles Healthcare Syst, Endocrinol & Diabet Div, 111D,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM hsacks@hotmail.com FU Van Vleet Chair of Excellence, University of Tennessee; Baptist Heart Institute and Foundation, Memphis, TN; Cardiometabolic Disease Research Foundation, Memphis, TN FX This study was supported by the Van Vleet Chair of Excellence, University of Tennessee; the Baptist Heart Institute and Foundation, Memphis, TN; and the Cardiometabolic Disease Research Foundation, Memphis, TN. NR 28 TC 17 Z9 17 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-4196 J9 METAB SYNDR RELAT D JI Metab. Syndr. Relat. Disord. PD DEC PY 2011 VL 9 IS 6 BP 433 EP 439 DI 10.1089/met.2011.0024 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 859BL UT WOS:000297849000004 PM 21679057 ER PT J AU Vassy, JL Shrader, P Yang, QH Liu, TB Yesupriya, A Chang, MH Dowling, NF Ned, RM Dupuis, J Florez, JC Khoury, MJ Meigs, JB AF Vassy, Jason L. Shrader, Peter Yang, Quanhe Liu, Tiebin Yesupriya, Ajay Chang, Man-huei Dowling, Nicole F. Ned, Renee M. Dupuis, Josee Florez, Jose C. Khoury, Muin J. Meigs, James B. TI Genetic Associations with Metabolic Syndrome and Its Quantitative Traits by Race/Ethnicity in the United States SO METABOLIC SYNDROME AND RELATED DISORDERS LA English DT Article ID GENOME-WIDE ASSOCIATION; NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; BODY-MASS INDEX; INSULIN-RESISTANCE; CARDIOVASCULAR-DISEASE; FTO GENE; SUSCEPTIBILITY LOCI; COMMON VARIANTS; ADULT OBESITY AB Background: Elevated insulin resistance (IR), triglycerides (TG), body mass index (BMI), and waist circumference (WC) are features of the metabolic syndrome. Although several single- nucleotide polymorphisms (SNPs) associated with these traits have been reported, no study has reported their risk allele frequencies and effect sizes among the major U.S. race/ethnic groups in a nationally representative sample. Methods: We compared the risk allele frequencies of eight SNPs previously associated with IR, TG, BMI, or WC by race/ethnicity (non-Hispanic white, non-Hispanic black, Mexican American) in 3,030 participants of the National Health and Nutrition Examination Study III (NHANES III). In regression models predicting IR, TG, BMI, WC, and metabolic syndrome, we tested whether the SNP effect sizes on these traits varied by race/ ethnicity. Results: Risk allele frequencies varied by race/ethnicity for all eight loci (P < 0.0001). The directionality of effects of the variants on IR, TG, WC, and BMI was generally consistent with previous observations and did not differ by race/ethnicity (P > 0.001), although our study had low power for this test. No SNP predicted metabolic syndrome in any of the three groups (P > 0.05). Conclusions: The significance of racial/ethnic differences in risk allele frequencies merits consideration if genetic discoveries are to have clinical and public health applicability. C1 [Vassy, Jason L.; Shrader, Peter; Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Yang, Quanhe; Liu, Tiebin; Yesupriya, Ajay; Chang, Man-huei; Dowling, Nicole F.; Ned, Renee M.; Khoury, Muin J.] Ctr Dis Control & Prevent, Off Publ Hlth Genom, CDC, Atlanta, GA USA. [Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Florez, Jose C.; Meigs, James B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Vassy, JL (reprint author), Massachusetts Gen Hosp, Div Gen Med, 50 Staniford St, Boston, MA 02114 USA. EM jvassy@partners.org OI Dupuis, Josee/0000-0003-2871-3603 FU National Institutes of Health (NIH) National Research Service Health Resources and Services Administration [T32 HP12706]; NIH FX We thank Dana Crawford, Ph. D., and Matthew Oetjens, B.S., for sharing their NHANES III ancestry analyses. Dr. Vassy is supported by National Institutes of Health (NIH) National Research Service Award grant T32 HP12706 from the Health Resources and Services Administration and the NIH Loan Repayment Program (National Institute of Diabetes and Digestive and Kidney Diseases, NIDDK). The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. NR 42 TC 4 Z9 4 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-4196 J9 METAB SYNDR RELAT D JI Metab. Syndr. Relat. Disord. PD DEC PY 2011 VL 9 IS 6 BP 475 EP 482 DI 10.1089/met.2011.0021 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 859BL UT WOS:000297849000009 PM 21848424 ER PT J AU Foo, JP Mantzoros, CS AF Foo, Joo-Pin Mantzoros, Christos S. TI The quest for the perfect biomarker of long-term glycemia: new studies, new trials and tribulations SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Editorial Material ID SERUM FRUCTOSAMINE CONCENTRATION; DEPENDENT DIABETES-MELLITUS; HEMOGLOBIN A(1C) LEVELS; CHRONIC KIDNEY-DISEASE; BLOOD-GLUCOSE CONTROL; GLYCATED ALBUMIN; PLASMA-GLUCOSE; INTENSIVE TREATMENT; ASSOCIATION; 1,5-ANHYDROGLUCITOL C1 [Foo, Joo-Pin; Mantzoros, Christos S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab,Dept Internal Med, Boston, MA 02215 USA. [Mantzoros, Christos S.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Mantzoros, Christos S.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Dept Internal Med,Sect Endocrinol, Boston, MA USA. RP Foo, JP (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab,Dept Internal Med, Boston, MA 02215 USA. EM cmantzor@bidmc.harvard.edu NR 36 TC 1 Z9 1 U1 1 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD DEC PY 2011 VL 60 IS 12 BP 1651 EP 1654 DI 10.1016/j.metabol.2011.06.016 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 854XP UT WOS:000297528400002 PM 21820137 ER PT J AU Lee, YH Magkos, F Mantzoros, CS Kang, ES AF Lee, Yong-ho Magkos, Faidon Mantzoros, Christos S. Kang, Eun Seok TI Effects of leptin and adiponectin on pancreatic beta-cell function SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Review ID ACTIVATED PROTEIN-KINASE; STIMULATED INSULIN-SECRETION; RECOMBINANT HUMAN LEPTIN; SENSITIVE K+ CHANNELS; C-REACTIVE PROTEIN; GENE-EXPRESSION; IN-VIVO; DIABETES-MELLITUS; PLASMA LEPTIN; HUMAN ISLETS AB Leptin and adiponectin are hormones secreted from adipocytes that have important roles in metabolism and energy homeostasis. This review evaluates the effects of leptin and adiponectin on beta-cell function by analyzing and compiling results from human clinical trials and epidemiologic studies as well as in vitro and in vivo experiments. Leptin has been shown to inhibit ectopic fat accumulation and thereby prevent beta-cell dysfunction and protect the beta-cell from cytokine- and fatty acid-induced apoptosis. However, leptin suppresses insulin gene expression and secretion as well as glucose transport into the beta-cell. Adiponectin stimulates insulin secretion by enhancing exocytosis of insulin granules and upregulating the expression of the insulin gene; however, this effect depends on the prevailing glucose concentration and status of insulin resistance. In addition, adiponectin has antiapoptotic properties in beta-cells. Available evidence concerning the role of these adipokines on insulin secretion, insulin gene expression, and apoptosis is not always entirely consistent; and many fundamental questions remain to be answered by future studies. (C) 2011 Elsevier Inc. All rights reserved. C1 [Magkos, Faidon; Mantzoros, Christos S.; Kang, Eun Seok] Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. [Lee, Yong-ho; Kang, Eun Seok] Yonsei Univ, Coll Med, Dept Internal Med, Seoul, South Korea. [Lee, Yong-ho; Kang, Eun Seok] Yonsei Univ, Grad Sch, Dept Med, Seoul 120749, South Korea. [Magkos, Faidon] Harokopio Univ, Dept Nutr & Dietet, Athens, Greece. [Mantzoros, Christos S.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02215 USA. [Mantzoros, Christos S.] VA Boston Healthcare Syst, Endocrinol Sect, Boston, MA USA. [Kang, Eun Seok] Yonsei Univ, Coll Med, Inst Endocrine Res, Seoul, South Korea. [Kang, Eun Seok] Yonsei Univ, Coll Med, Brain Korea Med Sci 21, Seoul, South Korea. RP Kang, ES (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. EM ekang@bidmc.harvard.edu FU National Research Foundation of Korea; Korean Government MEST [NRF-2010-013-E0008] FX This work was supported by the National Research Foundation of Korea Grant funded by the Korean Government MEST, Basic Research Promotion Fund, NRF-2010-013-E0008. NR 80 TC 43 Z9 46 U1 0 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD DEC PY 2011 VL 60 IS 12 BP 1664 EP 1672 DI 10.1016/j.metabol.2011.04.008 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 854XP UT WOS:000297528400004 PM 21632069 ER PT J AU Blum, K Chen, TJH Bailey, J Bowirrat, A Femino, J Chen, ALC Simpatico, T Morse, S Giordano, J Damle, U Kerner, M Braverman, ER Fornari, F Downs, BW Rector, C Barh, D Oscar-Berman, M AF Blum, Kenneth Chen, Thomas J. H. Bailey, John Bowirrat, Abdalla Femino, John Chen, Amanda L. C. Simpatico, Thomas Morse, Siobhan Giordano, John Damle, Uma Kerner, Mallory Braverman, Eric R. Fornari, Frank Downs, B. William Rector, Cynthia Barh, Debmayla Oscar-Berman, Marlene TI Can the Chronic Administration of the Combination of Buprenorphine and Naloxone Block Dopaminergic Activity Causing Anti-reward and Relapse Potential? SO MOLECULAR NEUROBIOLOGY LA English DT Article DE Buprenorphine; Dopamine; Naloxone; Opioid dependence; Relapse; Suboxone; Subutex ID POSITRON-EMISSION-TOMOGRAPHY; DORSAL ANTERIOR CINGULATE; HUMAN-BRAIN; SUBLINGUAL BUPRENORPHINE; DEFICIENCY-SYNDROME; OPIOID DEPENDENCE; OPIATE ADDICTION; HEROIN-ADDICTION; DRUG-ADDICTION; RECEPTOR GENE AB Opiate addiction is associated with many adverse health and social harms, fatal overdose, infectious disease transmission, elevated health care costs, public disorder, and crime. Although community-based addiction treatment programs continue to reduce the harms of opiate addiction with narcotic substitution therapy such as methadone maintenance, there remains a need to find a substance that not only blocks opiate-type receptors (mu, delta, etc.) but also provides agonistic activity; hence, the impetus arose for the development of a combination of narcotic antagonism and mu receptor agonist therapy. After three decades of extensive research, the federal Drug Abuse Treatment Act 2000 (DATA) opened a window of opportunity for patients with addiction disorders by providing increased access to options for treatment. DATA allows physicians who complete a brief specialty-training course to become certified to prescribe buprenorphine and buprenorphine/naloxone (Subutex, Suboxone) for treatment of patients with opioid dependence. Clinical studies indicate that buprenorphine maintenance is as effective as methadone maintenance in retaining patients in substance abuse treatment and in reducing illicit opioid use. With that stated, we must consider the long-term benefits or potential toxicity attributed to Subutex or Suboxone. We describe a mechanism whereby chronic blockade of opiate receptors, in spite of only partial opiate agonist action, may ultimately block dopaminergic activity causing anti-reward and relapse potential. While the direct comparison is not as yet available, toxicity to buprenorphine can be found in the scientific literature. In considering our cautionary note in this commentary, we are cognizant that, to date, this is what we have available, and until such a time when the real magic bullet is discovered, we will have to endure. However, more than anything else this commentary should at least encourage the development of thoughtful new strategies to target the specific brain regions responsible for relapse prevention. C1 [Blum, Kenneth; Bailey, John] Univ Florida, Coll Med, Dept Psychiat, Gainesville, FL 32610 USA. [Chen, Thomas J. H.] Chang Jung Christian Univ, Dept Occupat Safety & Hlth, Tainan, Taiwan. [Bowirrat, Abdalla] EMMS Nazareth Nazareth Hosp, Dept Neurosci & Populat Genet, Nazareth, Israel. [Femino, John] Meadows Edge Recovery Ctr, N Kingstown, RI 02852 USA. [Chen, Amanda L. C.] Chang Jung Christian Univ, Dept Engn & Management Adv Technol, Tainan, Taiwan. [Simpatico, Thomas] Univ Vermont, Coll Med, Dept Psychiat, Burlington, VT 05401 USA. [Simpatico, Thomas] Univ Vermont, Community Mental Hlth Inst, Ctr Clin & Translat Sci, Burlington, VT 05401 USA. [Blum, Kenneth; Morse, Siobhan; Giordano, John] Natl Inst Holist Addict Studies NIFHAS, N Miami Beach, FL 33162 USA. [Blum, Kenneth; Morse, Siobhan; Giordano, John] G&G Holist Addict Treatment Ctr, N Miami Beach, CA 33162 USA. [Blum, Kenneth; Damle, Uma; Kerner, Mallory; Braverman, Eric R.] Path Fdn, Dept Clin Neurol, New York, NY 10010 USA. [Braverman, Eric R.] Weill Cornell Coll Med, Dept Neurol Surg, New York, NY 10010 USA. [Blum, Kenneth; Fornari, Frank] Dominion Diagnost Lab, N Kingstown, RI 02852 USA. [Blum, Kenneth; Downs, B. William] LifeGen Inc, Dept Nutrigenom, San Diego, CA 92101 USA. [Rector, Cynthia] Amer Behav Consultants, Dept Child & Adult Psychiat, Lebanon, TN 37087 USA. [Blum, Kenneth; Barh, Debmayla] IIOAB, Ctr Genom & Appl Gene Therapy, Purba Medinipur, W Bengal, India. [Oscar-Berman, Marlene] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Oscar-Berman, Marlene] Boston VA Healthcare Syst, Boston, MA 02118 USA. [Oscar-Berman, Marlene] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. [Blum, Kenneth; Bailey, John] Univ Florida, Coll Med, McKnight Brain Inst, Gainesville, FL 32610 USA. RP Blum, K (reprint author), Univ Florida, Coll Med, Dept Psychiat, Gainesville, FL 32610 USA. EM drd2gene@aol.com RI Barh, Debmalya/O-4246-2015 OI Barh, Debmalya/0000-0002-2557-7768 FU NIAAA [R01-AA07112, K05-AA00219]; LifeGen, Inc., San Diego, CA, USA FX We thank the staff of PATH Foundation NY. The writing of this article was funded in part by LifeGen, Inc., San Diego, CA, USA. Other support came from NIAAA grants R01-AA07112 and K05-AA00219 and the Medical Research Service of the US Department of Veterans Affairs (to MO-B). NR 115 TC 7 Z9 7 U1 10 U2 23 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0893-7648 J9 MOL NEUROBIOL JI Mol. Neurobiol. PD DEC PY 2011 VL 44 IS 3 BP 250 EP 268 DI 10.1007/s12035-011-8206-0 PG 19 WC Neurosciences SC Neurosciences & Neurology GA 857OH UT WOS:000297727500003 PM 21948099 ER PT J AU Vogel, KS Perez, M Momand, JR Acevedo-Torres, K Hildreth, K Garcia, RA Torres-Ramos, CA Ayala-Torres, S Prihoda, TJ McMahan, CA Walter, CA AF Vogel, Kristine S. Perez, Marissa Momand, Jamila R. Acevedo-Torres, Karina Hildreth, Kim Garcia, Rebecca A. Torres-Ramos, Carlos A. Ayala-Torres, Sylvette Prihoda, Thomas J. McMahan, C. Alex Walter, Christi A. TI Age-Related Instability in Spermatogenic Cell Nuclear and Mitochondrial DNA Obtained From Apex1 Heterozygous Mice SO MOLECULAR REPRODUCTION AND DEVELOPMENT LA English DT Article ID BASE EXCISION-REPAIR; HUMAN APURINIC ENDONUCLEASE; INDUCED SPECIFIC-LOCUS; POLYMERASE-BETA; OXIDATIVE STRESS; MAMMALIAN-CELLS; HUMAN SPERM; OLD MICE; SPERMATOZOAL CHROMATIN; SPONTANEOUS MUTATION AB The prevalence of spontaneous mutations increases with age in the male germline; consequently, older men have an increased risk of siring children with genetic disease due to de novo mutations. The lacI transgenic mouse can be used to study paternal age effects, and in this system, the prevalence of de novo mutations increases in the male germline at old ages. Mutagenesis is linked with DNA repair capacity, and base excision repair (BER), which can ameliorate spontaneous DNA damage, decreases in nuclear extracts of spermatogenic cells from old mice. Mice heterozygous for a null allele of the Apex1 gene, which encodes apurinic/apyrimidinic endonuclease I (APEN), an essential BER enzyme, display an accelerated increase in spontaneous germline mutagenesis early in life. Here, the consequences of lifelong reduction of APEN on genetic instability in the male germline were examined, for the first time, at middle and old ages. Mutant frequency increased earlier in spermatogenic cells from Apex1(+/-) mice (by 6 months of age). Nuclear DNA damage increased with age in the spermatogenic lineage for both wild-type and Apex1(+/-) mice. By old age, mutant frequencies were similar for wild-type and APEN-deficient mice. Mitochondrial genome-repair also depends on APEN, and novel analysis of mitochondrial-DNA(mtDNA) damage revealed an increase in the Apex1(+/-) spermatogenic cells by middle age. Thus, Apex1 heterozygosity results in accelerated damage to mtDNA and spontaneous mutagenesis, consistent with an essential role for APEN in maintaining nuclear and mtDNA integrity in spermatogenic cells throughout life. C1 [Vogel, Kristine S.; Perez, Marissa; Momand, Jamila R.; Hildreth, Kim; Garcia, Rebecca A.; Walter, Christi A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Acevedo-Torres, Karina; Torres-Ramos, Carlos A.] Univ Puerto Rico, Dept Physiol, San Juan, PR 00936 USA. [Ayala-Torres, Sylvette] Univ Puerto Rico, Dept Pharmacol, San Juan, PR 00936 USA. [Prihoda, Thomas J.; McMahan, C. Alex] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Walter, Christi A.] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Walter, Christi A.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Walter, CA (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM walter@uthscsa.edu FU NIH-NIA [AG0211663, AG024364]; NIH-NCI [CCSG CA054174]; NIH-NINDS [5U54NS039408]; NIH-NIGMS [NIH-NCRR-G12RR03051, 5SC3GM084759, 5R25GM061838] FX The authors would like to thank Roderick Haesevoets, DNA Sequencing Facility, Centre for Biomedical Research at the University of Victoria, for lacI sequencing and mutation spectrum data. This work was supported by grants AG0211663 and AG024364 (NIH-NIA) to C.A.W., the CCSG CA054174 (NIH-NCI) to UTHSCSA, and by grants 5U54NS039408 (NIH-NINDS), NIH-NCRR-G12RR03051, 5SC3GM084759 (NIH-NIGMS), and 5R25GM061838 (NIH-NIGMS) to C.A.T.-R. NR 68 TC 10 Z9 10 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1040-452X J9 MOL REPROD DEV JI Mol. Reprod. Dev. PD DEC PY 2011 VL 78 IS 12 BP 906 EP 919 DI 10.1002/mrd.21374 PG 14 WC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology SC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology GA 855EU UT WOS:000297547400004 PM 21919107 ER PT J AU Kim, E Cameron, M Lovera, J Schaben, L Bourdette, D Whitham, R AF Kim, E. Cameron, M. Lovera, J. Schaben, L. Bourdette, D. Whitham, R. TI American ginseng does not improve fatigue in multiple sclerosis: a single center randomized double-blind placebo-controlled crossover pilot study SO MULTIPLE SCLEROSIS JOURNAL LA English DT Article DE clinical trial; complementary therapies; fatigue; ginseng; Panax; multiple sclerosis ID MODAFINIL; IMPACT; SCALE AB This study examined the safety and efficacy of an escalating dose (100 mg, 200 mg, 400 mg/day) of American ginseng over 6 weeks in a single-center, randomized, double-blind, placebo-controlled, crossover trial with 56 subjects with multiple sclerosis and fatigue. There were no serious adverse events but fatigue on ginseng, as assessed by the Fatigue Severity Scale, was not significantly different from fatigue on placebo. C1 [Kim, E.; Cameron, M.; Bourdette, D.; Whitham, R.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Kim, E.; Cameron, M.; Bourdette, D.; Whitham, R.] Portland VA Med Ctr, Neurol Serv, Portland, OR USA. [Kim, E.; Cameron, M.; Bourdette, D.; Whitham, R.] Portland VA Med Ctr, MS Ctr Excellence W, Portland, OR USA. [Lovera, J.] Louisiana State Univ, Hlth Sci Ctr, Dept Neurol, New Orleans, LA USA. [Schaben, L.] Bend Neurol Associates, Bend, OR USA. RP Cameron, M (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, 3181 SW Sam Jackson Pk Rd,CR120, Portland, OR 97239 USA. EM cameromi@ohsu.edu FU Department of Veterans Affairs; Department of Veterans Affairs, Rehabilitation Research and Development Service; National MS Society [PP1307, CA 1055-A-3]; PHS [5 M01 RR000334]; Medical Research Foundation; Nancy Davis Center without Walls; Oregon Clinical and Translational Research Institute (OCTRI); National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) [UL1 RR024140]; NIH Roadmap for Medical Research FX Dr Kim and Dr Schaben were Multiple Sclerosis Fellows supported by the Department of Veterans Affairs. Dr Cameron was supported by a Career Development Award from the Department of Veterans Affairs, Rehabilitation Research and Development Service. Ginseng and placebo products were donated by Afexa Life Sciences Inc. (Edmonton, Canada).; This study was supported by National MS Society grants PP1307 (Pilot Project Award) and CA 1055-A-3 (Collaborative MS Research Center Award); PHS Grant 5 M01 RR000334; the Medical Research Foundation; and the Nancy Davis Center without Walls. This publication was made possible with support from the Oregon Clinical and Translational Research Institute (OCTRI), grant number UL1 RR024140 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. NR 10 TC 5 Z9 5 U1 0 U2 8 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 J9 MULT SCLER J JI Mult. Scler. J. PD DEC PY 2011 VL 17 IS 12 BP 1523 EP 1526 DI 10.1177/1352458511412062 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 854UZ UT WOS:000297521400018 PM 21803872 ER PT J AU Xia, ZD Kwon, YM Mehmood, S Downing, C Jurkschat, K Murray, DW AF Xia, Zhidao Kwon, Young-Min Mehmood, Shahid Downing, Clive Jurkschat, Kerstin Murray, David W. TI Characterization of metal-wear nanoparticles in pseudotumor following metal-on-metal hip resurfacing SO NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE LA English DT Article DE Metal-on-metal hip resurfacing; Metal wear nanoparticles; Cobalt; Chromium; Macrophages ID INFLAMMATORY PSEUDOTUMOR; IN-VITRO; ARTHROPLASTY; PARTICLES; REPLACEMENTS; FAILURE AB Biopsies from a typical case of pseudotumor following metal-on-metal hip resurfacing (MoMHR) were analyzed using light and transmission electron microscopy, backscatter scanning electron microscopy and energy dispersive x-ray spectrometry (EDS). Heavy macrophage infiltration was observed in all black pigmented specimens. Metal nanoparticles (NPs) were observed exclusively within phagosomes of living macrophages and fragments of dead macrophages. Although dead fibroblasts were found to be juxtaposed with dead and disintegrated macrophages, the NPs were not seen within either live or dead fibroblasts. Chromium (Cr) but not cobalt (Co) was the predominant component of the remaining wear NPs in tissue. The current study finding suggests that corrosion of Co in phagosomes of macrophages and resultant Co ion release lead to tissue necrosis and adverse soft tissue reactions (pseudotumors). Further studies are required to elucidate the precise mechanism of intracellular corrosion of metal NPs and the long-term toxicity of the Cr remaining in the peri-prosthetic tissues. From the Clinical Editor: In this study of metal-on-metal hip resurfacing-related tissue necrosis and pseudotumor formation, corrosion and decomposition of metallic cobalt in phagosomes of macrophages and resultant cobalt ion release were demonstrated to be the key elements of pathogenesis. (C) 2011 Elsevier Inc. All rights reserved. C1 [Xia, Zhidao] Swansea Univ, Sch Med, Ctr Nanohlth, Swansea SA2 8PP, W Glam, Wales. [Xia, Zhidao; Mehmood, Shahid; Murray, David W.] Univ Oxford, Nuffield Dept Orthopaed Rheumatol & Musculoskelet, Botnar Res Ctr, Oxford, England. [Kwon, Young-Min; Jurkschat, Kerstin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthoped Surg, Boston, MA USA. [Downing, Clive] Univ Oxford, Dept Mat, Oxford OX1 3PH, England. RP Xia, ZD (reprint author), Swansea Univ, Sch Med, Ctr Nanohlth, Singleton Pk, Swansea SA2 8PP, W Glam, Wales. EM z.xia@swansea.ac.uk FU NIHR Musculoskeletal Biomedical Research Unit; Botnar Research Fellowship FX This project was partly supported by the NIHR Musculoskeletal Biomedical Research Unit and Botnar Research Fellowship. No conflict of interest was reported by the authors of this article. NR 20 TC 26 Z9 26 U1 1 U2 15 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1549-9634 J9 NANOMED-NANOTECHNOL JI Nanomed.-Nanotechnol. Biol. Med. PD DEC PY 2011 VL 7 IS 6 BP 674 EP 681 DI 10.1016/j.nano.2011.08.002 PG 8 WC Nanoscience & Nanotechnology; Medicine, Research & Experimental SC Science & Technology - Other Topics; Research & Experimental Medicine GA 857EV UT WOS:000297699900002 PM 21856277 ER PT J AU Mroz, P Xia, YM Asanuma, D Konopko, A Zhiyentayev, T Huang, YY Sharma, SK Dai, TH Khan, UJ Wharton, T Hamblin, MR AF Mroz, Pawel Xia, Yumin Asanuma, Daisuke Konopko, Aaron Zhiyentayev, Timur Huang, Ying-Ying Sharma, Sulbha K. Dai, Tianhong Khan, Usman J. Wharton, Tim Hamblin, Michael R. TI Intraperitoneal photodynamic therapy mediated by a fullerene in a mouse model of abdominal dissemination of colon adenocarcinoma SO NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE LA English DT Article DE Photodynamic therapy; Functionalized fullerene; Disseminated abdominal cancer; Micellar formulation; Hydroxyl radicals ID PHASE-II TRIAL; PERITONEAL CARCINOMATOSIS; FUNCTIONALIZED FULLERENES; OXYGEN; C-60; KERATINOCYTES; SENSITIZERS; GENERATION; MECHANISM; MICELLES AB Functionalized fullerenes represent a new class of photosensitizer (PS) that is being investigated for photodynamic therapy (PDT) of various diseases, including cancer. We tested the hypothesis that fullerenes could be used to mediate PDT of intraperitoneal (IP) carcinomatosis in a mouse model. In humans this form of cancer responds poorly to standard treatment and manifests as a thin covering of tumor nodules on intestines and on other abdominal organs. We used a colon adenocarcinoma cell line (CT26) stably expressing luciferase to allow monitoring of IP tumor burden in BALB/c mice by noninvasive real-time optical imaging using a sensitive low-light camera. IP injection of a preparation of N-methylpyrrolidinium-fullerene formulated in Cremophor-EL micelles, followed by white-light illumination delivered through the peritoneal wall (after creation of a skin flap), produced a statistically significant reduction in bioluminescence and a survival advantage in mice. From the Clinical Editor: This team of investigators report on functionalized fullerenes, to be used as photosensitizer for photodynamic therapy and demonstrate the efficacy of this method in an intraperitoneal carcinomatosis mouse model. (C) 2011 Elsevier Inc. All rights reserved. C1 [Mroz, Pawel; Xia, Yumin; Asanuma, Daisuke; Konopko, Aaron; Zhiyentayev, Timur; Huang, Ying-Ying; Sharma, Sulbha K.; Dai, Tianhong; Khan, Usman J.; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Mroz, Pawel; Huang, Ying-Ying; Dai, Tianhong; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Xia, Yumin] Wuhan Univ, Renmin Hosp, Dept Dermatol, Wuhan 430072, Peoples R China. [Asanuma, Daisuke] Univ Tokyo, Grad Sch Pharmaceut Sci, Tokyo, Japan. [Konopko, Aaron; Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Zhiyentayev, Timur] CALTECH, Div Chem & Chem Engn, Pasadena, CA 91125 USA. [Huang, Ying-Ying] Guangxi Med Univ, Aesthet & Plast Ctr, Nanning, Peoples R China. [Khan, Usman J.] Univ Cent Florida, Orlando, FL 32816 USA. [Wharton, Tim] Lynntech Inc, College Stn, TX USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu RI Huang, Ying-ying/G-3153-2011; OI Huang, Ying-ying/0000-0003-3066-6981; Hamblin, Michael/0000-0001-6431-4605 FU US NIH [R43AI68400, R01AI050875]; US Air Force Medical Free Electron Laser Program [FA9550-04-1-0079]; Genzyme; NIH; Bullock Wellman Postdoctoral Fellowship; Airlift Research Foundation [109421]; SBIR FX Conflict of Interest Statement: At the time of the research Tim Wharton was an employee of Lynntech Inc. Pawel Mroz, Tim Wharton and Michael R Hamblin are inventors on a patent describing the use of fullerenes as photosensitizers for PDT that has been licensed by Lynntech. The Hamblin laboratory has received funding in Phase 1 and 2 SBIR grants awarded to Lynntech.; This work was supported by US NIH grants R43AI68400 to Lynntech Inc and R01AI050875 to M.R.H. and by the US Air Force Medical Free Electron Laser Program (FA9550-04-1-0079). P.M. was partly supported by a Genzyme-Partners Translational Research Grant and NIH Training Grant. T. D. was supported by the Bullock Wellman Postdoctoral Fellowship and an Airlift Research Foundation grant (grant #109421). NR 48 TC 24 Z9 25 U1 1 U2 25 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1549-9634 J9 NANOMED-NANOTECHNOL JI Nanomed.-Nanotechnol. Biol. Med. PD DEC PY 2011 VL 7 IS 6 BP 965 EP 974 DI 10.1016/j.nano.2011.04.007 PG 10 WC Nanoscience & Nanotechnology; Medicine, Research & Experimental SC Science & Technology - Other Topics; Research & Experimental Medicine GA 857EV UT WOS:000297699900033 PM 21645643 ER PT J AU Yokoyama, S Woods, SL Boyle, GM Aoude, LG MacGregor, S Zismann, V Gartside, M Cust, AE Haq, R Harland, M Taylor, JC Duffy, DL Holohan, K Dutton-Regester, K Palmer, JM Bonazzi, V Stark, MS Symmons, J Law, MH Schmidt, C Lanagan, C O'Connor, L Holland, EA Schmid, H Maskiell, JA Jetann, J Ferguson, M Jenkins, MA Kefford, RF Giles, G Armstrong, BK Aitken, JF Hopper, JL Whiteman, DC Pharoah, PD Easton, DF Dunning, AM Newton-Bishop, JA Montgomery, GW Martin, NG Mann, GJ Bishop, DT Tsao, H Trent, JM Fisher, DE Hayward, NK Brown, KM AF Yokoyama, Satoru Woods, Susan L. Boyle, Glen M. Aoude, Lauren G. MacGregor, Stuart Zismann, Victoria Gartside, Michael Cust, Anne E. Haq, Rizwan Harland, Mark Taylor, John C. Duffy, David L. Holohan, Kelly Dutton-Regester, Ken Palmer, Jane M. Bonazzi, Vanessa Stark, Mitchell S. Symmons, Judith Law, Matthew H. Schmidt, Christopher Lanagan, Cathy O'Connor, Linda Holland, Elizabeth A. Schmid, Helen Maskiell, Judith A. Jetann, Jodie Ferguson, Megan Jenkins, Mark A. Kefford, Richard F. Giles, GrahamG. Armstrong, Bruce K. Aitken, Joanne F. Hopper, John L. Whiteman, David C. Pharoah, Paul D. Easton, Douglas F. Dunning, Alison M. Newton-Bishop, Julia A. Montgomery, Grant W. Martin, Nicholas G. Mann, Graham J. Bishop, D. Timothy Tsao, Hensin Trent, Jeffrey M. Fisher, David E. Hayward, Nicholas K. Brown, Kevin M. TI A novel recurrent mutation in MITF predisposes to familial and sporadic melanoma SO NATURE LA English DT Article ID GENOME-WIDE ASSOCIATION; CUTANEOUS MELANOMA; TRANSCRIPTION FACTOR; PHENOTYPIC CHARACTERISTICS; GERMLINE MUTATIONS; MALIGNANT-MELANOMA; MELANOCYTIC NEVI; SUN EXPOSURE; CANCER-RISK; VARIANTS AB So far, two genes associated with familial melanoma have been identified, accounting for a minority of genetic risk in families. Mutations in CDKN2A account for approximately 40% of familial cases(1), and predisposing mutations in CDK4 have been reported in a very small number of melanoma kindreds(2). Here we report the whole-genome sequencing of probands from several melanoma families, which we performed in order to identify other genes associated with familial melanoma. We identify one individual carrying a novel germline variant (coding DNA sequence c. G1075A; protein sequence p. E318K; rs149617956) in the melanoma-lineage-specific oncogene microphthalmia-associated transcription factor (MITF). Although the variant co-segregated with melanoma in some but not all cases in the family, linkage analysis of 31 families subsequently identified to carry the variant generated a log of odds (lod) score of 2.7 under a dominant model, indicating E318K as a possible intermediate risk variant. Consistent with this, the E318K variant was significantly associated with melanoma in a large Australian case-control sample. Likewise, it was similarly associated in an independent case-control sample from the United Kingdom. In the Australian sample, the variant allele was significantly over-represented in cases with a family history of melanoma, multiple primary melanomas, or both. The variant allele was also associated with increased naevus count and non-blue eye colour. Functional analysis of E318K showed that MITF encoded by the variant allele had impaired sumoylation and differentially regulated several MITF targets. These data indicate that MITF is a melanoma-predisposition gene and highlight the utility of whole-genome sequencing to identify novel rare variants associated with disease susceptibility. C1 [Zismann, Victoria; Trent, Jeffrey M.; Brown, Kevin M.] Translat Genom Res Inst, Phoenix, AZ 85004 USA. [Yokoyama, Satoru; Haq, Rizwan; Fisher, David E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr,Dept Dermatol, Boston, MA 02114 USA. [Woods, Susan L.; Boyle, Glen M.; Aoude, Lauren G.; MacGregor, Stuart; Gartside, Michael; Duffy, David L.; Holohan, Kelly; Dutton-Regester, Ken; Palmer, Jane M.; Bonazzi, Vanessa; Stark, Mitchell S.; Symmons, Judith; Law, Matthew H.; Schmidt, Christopher; Lanagan, Cathy; O'Connor, Linda; Whiteman, David C.; Montgomery, Grant W.; Martin, Nicholas G.; Hayward, Nicholas K.] Queensland Inst Med Res, Brisbane, Qld 4029, Australia. [Cust, Anne E.; Armstrong, Bruce K.] Univ Sydney, Sydney Med Sch, Sydney Sch Publ Hlth, Sydney, NSW 2006, Australia. [Harland, Mark; Taylor, John C.; Newton-Bishop, Julia A.; Bishop, D. Timothy] St James Univ Hosp, Canc Res UK Clin Ctr Leeds, Leeds Inst Mol Med, Epidemiol & Biostat Sect, Leeds LS9 7TF, W Yorkshire, England. [Holland, Elizabeth A.; Schmid, Helen; Kefford, Richard F.; Mann, Graham J.] Univ Sydney, Westmead Millennium Inst, Westmead Inst Canc Res, Westmead, NSW 2145, Australia. [Holland, Elizabeth A.; Schmid, Helen; Kefford, Richard F.; Mann, Graham J.] Melanoma Inst Australia, Westmead, NSW 2145, Australia. [Maskiell, Judith A.; Jenkins, Mark A.; Hopper, John L.] Univ Melbourne, Sch Populat Hlth, Ctr Mol Environm Genet & Analyt Epidemiol, Parkville, Vic 3052, Australia. [Jetann, Jodie; Ferguson, Megan; Aitken, Joanne F.] Canc Council Queensland, Viertel Ctr Res Canc Control, Brisbane, Qld 4004, Australia. [Giles, GrahamG.] Canc Council Victoria, Canc Epidemiol Ctr, Carlton, Vic 3053, Australia. [Pharoah, Paul D.; Easton, Douglas F.; Dunning, Alison M.] Univ Cambridge, Cambridge CB1 8RN, England. [Tsao, Hensin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. [Brown, Kevin M.] NCI, Div Canc Epidemiol & Genet, NIH, Gaithersburg, MD 20892 USA. RP Brown, KM (reprint author), Translat Genom Res Inst, Phoenix, AZ 85004 USA. EM brownkm2@mail.nih.gov RI Macgregor, Stuart/C-6442-2009; Boyle, Glen/G-1347-2013; Mann, Graham/G-4758-2014; Aoude, Lauren/C-7484-2014; hayward, nicholas/C-1367-2015; Armstrong, Bruce/K-9464-2015; Montgomery, Grant/B-7148-2008; Duffy, David/B-7392-2013; Whiteman, David/P-2728-2014; Jenkins, Mark/P-7803-2015; Stark, Mitchell/E-3542-2010; OI Macgregor, Stuart/0000-0001-6731-8142; Boyle, Glen/0000-0002-1385-529X; Mann, Graham/0000-0003-1301-405X; Aoude, Lauren/0000-0003-1448-3923; hayward, nicholas/0000-0003-4760-1033; Armstrong, Bruce/0000-0001-8940-7525; Montgomery, Grant/0000-0002-4140-8139; Duffy, David/0000-0001-7227-632X; Whiteman, David/0000-0003-2563-9559; Woods, Susan/0000-0002-8955-2017; Jenkins, Mark/0000-0002-8964-6160; Stark, Mitchell/0000-0002-4510-2161; Bonazzi, Vanessa/0000-0002-2574-0334; Dunning, Alison Margaret/0000-0001-6651-7166; Bishop, Tim/0000-0002-8752-8785; Newton Bishop, Julia/0000-0001-9147-6802; Giles, Graham/0000-0003-4946-9099; Martin, Nicholas/0000-0003-4069-8020 FU Melanoma Research Alliance; American Cancer Society [RSG-08-200-01]; National Institutes of Health (NIH) [AR043369-14, CA88363, K24CA149202, P50CA93683, R01 CA83115, CA-83115-01A2]; Doris Duke Medical Foundation; Dr Miriam and Sheldon G. Adelson Medical Research Foundation; US-Israel Binational Science Foundation; Division of Cancer Epidemiology and Genetics of the National Cancer Institute; National Health and Medical Research Council of Australia (NHMRC); Cancer Australia [1011143]; Cancer Research UK [C8216/A6129, C588/A4994, C588/A10589, C490/A11021, C8197/A10123]; NHMRC [566946, 107359, 211172, 402761, 520018]; Cancer Council New South Wales [77/00, 06/10]; Cancer Council Victoria; Cancer Council Queensland [371]; Cancer Institute NSW [10/ECF/2-06]; University of Sydney Medical Foundation FX This work was supported by team science awards by the Melanoma Research Alliance (J.M.T., N.K.H., H. T. and D. E. F.), the American Cancer Society (K. M. B., RSG-08-200-01), the National Institutes of Health (NIH; D. E. F., AR043369-14; N.K.H., CA88363; H. T., K24CA149202 and P50CA93683), Doris Duke Medical Foundation (D. E. F.), Dr Miriam and Sheldon G. Adelson Medical Research Foundation (D. E. F.), US-Israel Binational Science Foundation (D. E. F.), and the Division of Cancer Epidemiology and Genetics of the National Cancer Institute (K. M. B.). N.K.H., D. L. D., S. M. and G. W. M. are supported by National Health and Medical Research Council of Australia (NHMRC) research fellowships. M. H. L. is supported by Cancer Australia grant 1011143. The collection of samples in the Leeds-based case-control study (the Melanoma Cohort Study) was funded by Cancer Research UK (Project Grant C8216/A6129 and Programme awards C588/A4994 and C588/A10589) and by the NIH (R01 CA83115). Recruitment was facilitated by the UK National Cancer Research Network. We thank S. Leake, S. Haynes, S. Waseem for Leeds case-control data collection; and H. Snowdon and C. Taylor from the Leeds Cancer Research UK Cancer Centre Genomics Facility for the genotyping of the UK samples. AMFS was supported by the NHMRC (project grants 566946, 107359, 211172 and program grant number 402761 to G.J.M. and R. F. K.); the Cancer Council New South Wales (project grant 77/00, 06/10), the Cancer Council Victoria and the Cancer Council Queensland (project grant 371); and the NIH (via RO1 grant CA-83115-01A2 to the international Melanoma Genetics Consortium-GenoMEL). The University of Cambridge SEARCH study was supported by Cancer Research UK Programme awards (C490/A11021 and C8197/A10123). A. E. C. is the recipient of an NHMRC public health postdoctoral fellowship (520018) and a Cancer Institute NSW Early Career Development Fellowship (10/ECF/2-06). B. K. A. is supported by a University of Sydney Medical Foundation Program Grant and J.L.H. is an Australia Fellow of the NHMRC. We gratefully acknowledge all of the participants, the work and dedication of the research coordinators, interviewers, examiners and data management staff, including J. Arbuckle, S. Columbus, M. Lang, H. Rodais, C. Ellis (Centre for MEGA Epidemiology); E. A. Holland, C. Agha-Hamilton, C. El Hayek, L. Morgan, J. Roland, E. Tyler, J. Barton, C. Watts and L. Porter (Westmead Institute of Cancer Research); M. Hillcoat, K. Holland, P. Saunders, J. Roberts and S. Tait (Viertel Centre for Research in Cancer Control); A. Kurien, C. Patterson, C. Thoo, S. de Zwaan, A. Sklavos, S. Manoharan, J. Cahill and S. Brennand (skin examiners). NR 46 TC 160 Z9 164 U1 0 U2 28 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD DEC 1 PY 2011 VL 480 IS 7375 BP 99 EP U266 DI 10.1038/nature10630 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 861PO UT WOS:000298031900042 PM 22080950 ER PT J AU Orvedahl, A Sumpter, R Xiao, GH Ng, A Zou, ZJ Tang, Y Narimatsu, M Gilpin, C Sun, QH Roth, M Forst, CV Wrana, JL Zhang, YE Luby-Phelps, K Xavier, RJ Xie, Y Levine, B AF Orvedahl, Anthony Sumpter, Rhea, Jr. Xiao, Guanghua Ng, Aylwin Zou, Zhongju Tang, Yi Narimatsu, Masahiro Gilpin, Christopher Sun, Qihua Roth, Michael Forst, Christian V. Wrana, Jeffrey L. Zhang, Ying E. Luby-Phelps, Katherine Xavier, Ramnik J. Xie, Yang Levine, Beth TI Image-based genome-wide siRNA screen identifies selective autophagy factors SO NATURE LA English DT Article ID UBIQUITIN LIGASE; DEGRADATION; P62/SQSTM1; MITOPHAGY; PROTEIN; SYSTEM; PARKIN; VDAC1 AB Selective autophagy involves the recognition and targeting of specific cargo, such as damaged organelles, misfolded proteins, or invading pathogens for lysosomal destruction(1-4). Yeast genetic screens have identified proteins required for different forms of selective autophagy, including cytoplasm-to-vacuole targeting, pexophagy and mitophagy, and mammalian genetic screens have identified proteins required for autophagy regulation(5). However, there have been no systematic approaches to identify molecular determinants of selective autophagy in mammalian cells. Here, to identify mammalian genes required for selective autophagy, we performed a high-content, image-based, genome-wide small interfering RNA screen to detect genes required for the colocalization of Sindbis virus capsid protein with autophagolysosomes. We identified 141 candidate genes required for viral autophagy, which were enriched for cellular pathways related to messenger RNA processing, interferon signalling, vesicle trafficking, cytoskeletal motor function and metabolism. Ninety-six of these genes were also required for Parkin-mediated mitophagy, indicating that common molecular determinants may be involved in autophagic targeting of viral nucleocapsids and autophagic targeting of damaged mitochondria. Murine embryonic fibroblasts lacking one of these gene products, the C2-domain containing protein, SMURF1, are deficient in the autophagosomal targeting of Sindbis and herpes simplex viruses and in the clearance of damaged mitochondria. Moreover, SMURF1-deficient mice accumulate damaged mitochondria in the heart, brain and liver. Thus, our study identifies candidate determinants of selective autophagy, and defines SMURF1 as a newly recognized mediator of both viral autophagy and mitophagy. C1 [Orvedahl, Anthony; Sumpter, Rhea, Jr.; Zou, Zhongju; Sun, Qihua; Levine, Beth] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA. [Orvedahl, Anthony; Levine, Beth] Univ Texas SW Med Ctr Dallas, Dept Microbiol, Dallas, TX 75390 USA. [Sumpter, Rhea, Jr.; Zou, Zhongju; Sun, Qihua; Levine, Beth] Univ Texas SW Med Ctr Dallas, Ctr Autophagy Res, Dallas, TX 75390 USA. [Xiao, Guanghua; Forst, Christian V.; Xie, Yang] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA. [Ng, Aylwin; Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Ng, Aylwin; Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. [Ng, Aylwin; Xavier, Ramnik J.] Broad Inst Harvard, Cambridge, MA 02142 USA. [Ng, Aylwin; Xavier, Ramnik J.] MIT, Cambridge, MA 02142 USA. [Zou, Zhongju; Levine, Beth] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA. [Tang, Yi; Zhang, Ying E.] NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Narimatsu, Masahiro; Wrana, Jeffrey L.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Ctr Syst Biol, Toronto, ON M5G 1X5, Canada. [Gilpin, Christopher; Luby-Phelps, Katherine] Univ Texas SW Med Ctr Dallas, Dept Cell Biol, Dallas, TX 75390 USA. [Roth, Michael] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA. [Roth, Michael; Xie, Yang; Levine, Beth] Univ Texas SW Med Ctr Dallas, Harold C Simmons Comprehens Canc Ctr, Dallas, TX 75390 USA. [Wrana, Jeffrey L.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 3E1, Canada. RP Levine, B (reprint author), Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA. EM beth.levine@utsouthwestern.edu RI Wrana, Jeffrey/F-8857-2013; Zhang, Ying/G-3657-2015; OI Zhang, Ying/0000-0003-2753-7601; Roth, Michael/0000-0002-9056-332X FU NIH [AI109617, CA84254, UL1 RR024982, AI062773, DK83756, DK086502, DK043351]; NSF [DMS-0907562]; Center for Cancer Research, National Cancer Institute FX We thank M. Vishwanath, S. Wei and B. Posner for assistance with high-throughput siRNA screening; W. Sun for information technology support; K. Scudder for assistance with image analysis algorithms; A. Diehl for expert medical illustration; V. Stollar, M. McDonald, R. Kuhn and R. Youle for helpful discussions and providing reagents; A. Bugde for assistance in the UTSW Live Cell Imaging Facility; and L. Mueller and T. Januszewski for assistance with electron microscopy. This work was supported by NIH grants AI109617 (B. L.), CA84254 (B. L.), UL1 RR024982 (G. X., Y.X.), AI062773 (R.J.X.), DK83756 (R.J.X.), DK086502 (R.J.X.) and DK043351 (R.J.X. and A.N.); NSF grant DMS-0907562 (G. X.); and the Center for Cancer Research, National Cancer Institute Intramural Research Program (Y.E.Z.). NR 25 TC 179 Z9 181 U1 6 U2 51 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD DEC 1 PY 2011 VL 480 IS 7375 BP 113 EP 117 DI 10.1038/nature10546 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 861PO UT WOS:000298031900045 PM 22020285 ER PT J AU Cudkowicz, M Bozik, ME Ingersoll, EW Miller, R Mitsumoto, H Shefner, J Moore, DH Schoenfeld, D Mather, JL Archibald, D Sullivan, M Amburgey, C Moritz, J Gribkoff, VK AF Cudkowicz, Merit Bozik, Michael E. Ingersoll, Evan W. Miller, Robert Mitsumoto, Hiroshi Shefner, Jeremy Moore, Dan H. Schoenfeld, David Mather, James L. Archibald, Donald Sullivan, Mary Amburgey, Craig Moritz, Juliet Gribkoff, Valentin K. TI The effects of dexpramipexole (KNS-760704) in individuals with amyotrophic lateral sclerosis SO NATURE MEDICINE LA English DT Article ID PREDICTS SURVIVAL-TIME; ALS CLINICAL-TRIALS; QUALITY-OF-LIFE; MITOCHONDRIAL DYSFUNCTION; RANDOMIZED-TRIAL; EARLY PHASE; PROGRESSION; DESIGN AB Amyotrophic lateral sclerosis (ALS) is characterized by upper and lower motor neuron dysfunction and loss, rapidly progressive muscle weakness, wasting and death(1-3). Many factors, including mitochondrial dysfunction, may contribute to ALS pathogenesis(4-9). Riluzole, which has shown only modest benefits in a measure of survival time without demonstrated effects on muscle strength or function, is the only approved treatment for ALS(10,11). We tested the putative mitochondrial modulator dexpramipexole (KNS-760704; (6R)-4,5,6,7-tetrahydro-N6-propyl-2,6-benzothiazole-diamine)(12-14) in subjects with ALS in a two-part, double-blind safety and tolerability study, with a preliminary assessment of its effects on functional decline and mortality. In part 1, the effects of dexpramipexole (50, 150 or 300 mg d(-1)) versus placebo were assessed over 12 weeks. In part 2, after a 4-week, single-blind placebo washout, continuing subjects were re-randomized to dexpramipexole at 50 mg d(-1) or 300 mg d(-1) as double-blind active treatment for 24 weeks. Dexpramipexole was safe and well tolerated. Trends showing a dose-dependent attenuation of the slope of decline of the ALS Functional Rating Scale-Revised (ALSFRS-R) in part 1 and a statistically significant (P = 0.046) difference between groups in a joint rank test of change from baseline in ALSFRS-R and mortality in part 2 strongly support further testing of dexpramipexole in ALS. C1 [Bozik, Michael E.; Ingersoll, Evan W.; Mather, James L.; Archibald, Donald; Sullivan, Mary; Amburgey, Craig; Moritz, Juliet; Gribkoff, Valentin K.] Knopp Biosci, Pittsburgh, PA USA. [Cudkowicz, Merit] Massachusetts Gen Hosp, Neurol Clin Trial Unit, Boston, MA 02114 USA. [Miller, Robert; Moore, Dan H.] Calif Pacific Med Ctr, San Francisco, CA USA. [Mitsumoto, Hiroshi] Columbia Univ, Med Ctr, New York, NY USA. [Shefner, Jeremy] SUNY Upstate Med Univ, Syracuse, NY USA. RP Gribkoff, VK (reprint author), Knopp Biosci, Pittsburgh, PA USA. EM gribkoffv@aol.com NR 37 TC 81 Z9 82 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD DEC PY 2011 VL 17 IS 12 BP 1652 EP U169 DI 10.1038/nm.2579 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 860WC UT WOS:000297978000038 PM 22101764 ER PT J AU Yoo, H Kim, JW Shishkov, M Namati, E Morse, T Shubochkin, R McCarthy, JR Ntziachristos, V Bouma, BE Jaffer, FA Tearney, GJ AF Yoo, Hongki Kim, Jin Won Shishkov, Milen Namati, Eman Morse, Theodore Shubochkin, Roman McCarthy, Jason R. Ntziachristos, Vasilis Bouma, Brett E. Jaffer, Farouc A. Tearney, Guillermo J. TI Intra-arterial catheter for simultaneous microstructural and molecular imaging in vivo SO NATURE MEDICINE LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; DRUG-ELUTING STENTS; ATHEROSCLEROSIS; REPRODUCIBILITY; IMPLANTATION; MICROSCOPY; THROMBOSIS; ADVANTAGE; SYSTEM AB Advancing understanding of human coronary artery disease requires new methods that can be used in patients for studying atherosclerotic plaque microstructure in relation to the molecular mechanisms that underlie its initiation, progression and clinical complications, including myocardial infarction and sudden cardiac death. Here we report a dual-modality intra-arterial catheter for simultaneous microstructural and molecular imaging in vivo using a combination of optical frequency domain imaging (OFDI) and near-infrared fluorescence (NIRF) imaging. By providing simultaneous molecular information in the context of the surrounding tissue microstructure, this new catheter could provide new opportunities for investigating coronary atherosclerosis and stent healing and for identifying high-risk biological and structural coronary arterial plaques in vivo. C1 [Kim, Jin Won; Jaffer, Farouc A.] Harvard Univ, Sch Med, Cardiovasc Res Ctr, Boston, MA 02115 USA. [Yoo, Hongki; Shishkov, Milen; Namati, Eman; Bouma, Brett E.] Harvard Univ, Sch Med, Wellman Ctr Photomed, Boston, MA USA. [Yoo, Hongki; Kim, Jin Won; Shishkov, Milen; Namati, Eman; McCarthy, Jason R.; Bouma, Brett E.; Tearney, Guillermo J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kim, Jin Won; Jaffer, Farouc A.] Harvard Univ, Sch Med, Div Cardiol, Boston, MA USA. [Kim, Jin Won] Korea Univ, Guro Hosp, Ctr Cardiovasc, Seoul, South Korea. [Morse, Theodore; Shubochkin, Roman] Boston Univ, Photon Ctr, Boston, MA 02215 USA. [McCarthy, Jason R.] Harvard Univ, Sch Med, Ctr Syst Biol, Boston, MA USA. [Ntziachristos, Vasilis] Helmholtz Zentrum Munchen, Inst Biol & Med Imaging, Munich, Germany. [Ntziachristos, Vasilis] Tech Univ Munich, Munich, Germany. [Bouma, Brett E.; Tearney, Guillermo J.] Harvard Massachusetts Inst Technol Hlth Sci & Tec, Cambridge, MA USA. [Tearney, Guillermo J.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Jaffer, FA (reprint author), Harvard Univ, Sch Med, Cardiovasc Res Ctr, Boston, MA 02115 USA. EM fjaffer@mgh.harvard.edu; gtearney@partners.org RI Yoo, Hongki/B-6421-2013; OI Yoo, Hongki/0000-0001-9819-3135; Jaffer, Farouc/0000-0001-7980-384X FU US National Institutes of Health [R01HL076398, R01HL093717, R01HL108229-01A1]; Center for Integration of Medicine and Innovative Technology [DAMD17-02-2-0006]; American Heart Association [0830352N]; Howard Hughes Medical Institute; Cardio Vascular Research Foundation (CVRF) FX We thank J. Gardecki for preparation of the cadaver coronary artery and CVPath for pathology of the stented artery. We also thank A. Rosenthal and G. Mallas for their technical support and A. Mauskapf for preparing and assisting in animal procedures. We thank Y. Iwamoto, Y. Yagi and E. Salomatina for assistance in histopathology. This research was supported in part by the US National Institutes of Health (R01HL076398 and R01HL093717 to G.J.T. and R01HL108229-01A1 to F.A.J.), the Center for Integration of Medicine and Innovative Technology (DAMD17-02-2-0006 to G.J.T. and F.A.J.), an American Heart Association Scientist Development grant (#0830352N to F.A.J.), a Howard Hughes Medical Institute Early Career Award (F.A.J.) and the Cardio Vascular Research Foundation (CVRF, J.W.K.). NR 26 TC 105 Z9 106 U1 1 U2 20 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD DEC PY 2011 VL 17 IS 12 BP 1680 EP U202 DI 10.1038/nm.2555 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 860WC UT WOS:000297978000043 PM 22057345 ER PT J AU Corless, CL Barnett, CM Heinrich, MC AF Corless, Christopher L. Barnett, Christine M. Heinrich, Michael C. TI Gastrointestinal stromal tumours: origin and molecular oncology SO NATURE REVIEWS CANCER LA English DT Review ID FACTOR-RECEPTOR-ALPHA; C-KIT GENE; OF-FUNCTION MUTATIONS; POSITRON-EMISSION-TOMOGRAPHY; CYCLE REGULATORY PROTEINS; TYROSINE KINASE INHIBITOR; V600E BRAF MUTATIONS; TERM-FOLLOW-UP; IMATINIB MESYLATE; INTERSTITIAL-CELLS AB Gastrointestinal stromal tumours (GISTs) are a paradigm for the development of personalized treatment for cancer patients. The nearly simultaneous discovery of a biomarker that is reflective of their origin and the presence of gain-of-function kinase mutations in these tumours set the stage for more accurate diagnosis and the development of kinase inhibitor therapy. Subsequent studies of genotype and phenotype have led to a molecular classification of GIST and to treatment optimization on the basis of molecular subtype. The study of drug-resistant tumours has advanced our understanding of kinase biology, enabling the development of novel kinase inhibitors. Further improvements in GIST treatment may require targeting GIST stem cell populations and/or additional genomic events. C1 [Heinrich, Michael C.] Oregon Hlth & Sci Univ, Knight Canc Inst, Div Haematol & Oncol, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Pathol, Portland VA Med Ctr, Portland, OR 97239 USA. RP Heinrich, MC (reprint author), Oregon Hlth & Sci Univ, Knight Canc Inst, Div Haematol & Oncol, Portland, OR 97239 USA. EM heinrich@ohsu.edu FU GIST; BP Lester Foundation; LifeRaft Group; Department of Veterans Affairs FX The authors wish to acknowledge all of the members of their laboratories for their continuing efforts on gastrointestinal stromal tumour (GIST) research. Some of the work referenced in this article was supported by generous donations from the GIST Cancer Research Fund and the BP Lester Foundation, and by grant support from the LifeRaft Group. In addition, M. C. H. received research grant funding from the Department of Veterans Affairs (Merit Review Award). NR 194 TC 237 Z9 252 U1 5 U2 32 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD DEC PY 2011 VL 11 IS 12 BP 865 EP 878 DI 10.1038/nrc3143 PG 14 WC Oncology SC Oncology GA 859DC UT WOS:000297853900013 PM 22089421 ER PT J AU Khandekar, MJ Cohen, P Spiegelman, BM AF Khandekar, Melin J. Cohen, Paul Spiegelman, Bruce M. TI Molecular mechanisms of cancer development in obesity SO NATURE REVIEWS CANCER LA English DT Review ID TUMOR-NECROSIS-FACTOR; GROWTH-FACTOR-I; BODY-MASS INDEX; PLASMINOGEN-ACTIVATOR INHIBITOR-1; HUMAN BREAST-CANCER; FATTY-ACID SYNTHASE; INDUCED INSULIN-RESISTANCE; GASTRIC BYPASS-SURGERY; MESENCHYMAL STEM-CELLS; PLASMA C-PEPTIDE AB The increasing incidence of obesity and its co-morbid conditions poses a great challenge to global health. In addition to cardiovascular disease and diabetes, epidemiological data demonstrate a link between obesity and multiple types of cancer. The molecular mechanisms underlying how obesity causes an increased risk of cancer are poorly understood. Obesity disrupts the dynamic role of the adipocyte in energy homeostasis, resulting in inflammation and alteration of adipokine (for example, leptin and adiponectin) signalling. Additionally, obesity causes secondary changes that are related to insulin signalling and lipid deregulation that may also foster cancer development. Understanding these molecular links may provide an avenue for preventive and therapeutic strategies to reduce cancer risk and mortality in an increasingly obese population. C1 [Khandekar, Melin J.; Cohen, Paul; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Khandekar, Melin J.; Cohen, Paul; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Khandekar, Melin J.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Cohen, Paul] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. RP Spiegelman, BM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM bruce_spiegelman@dfci.harvard.edu NR 172 TC 278 Z9 281 U1 8 U2 72 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD DEC PY 2011 VL 11 IS 12 BP 886 EP 895 DI 10.1038/nrc3174 PG 10 WC Oncology SC Oncology GA 859DC UT WOS:000297853900015 PM 22113164 ER PT J AU Lee, JT AF Lee, Jeannie T. TI Gracefully ageing at 50, X-chromosome inactivation becomes a paradigm for RNA and chromatin control SO NATURE REVIEWS MOLECULAR CELL BIOLOGY LA English DT Review ID PREIMPLANTATION MOUSE EMBRYOS; PRIMORDIAL GERM-CELLS; LONG NONCODING RNAS; FACULTATIVE HETEROCHROMATIN FORMATION; XIST RNA; DOSAGE COMPENSATION; TSIX TRANSCRIPTION; STEM-CELLS; DNA METHYLATION; SEX-CHROMOSOMES AB The discovery of X-chromosome inactivation (XCI) celebrated its golden anniversary this year. Originally offered as an explanation for the establishment of genetic equality between males and females, 50 years on, XCI presents more than a curious gender-based phenomenon that causes silencing of sex chromosomes. How have the mysteries of XCI unfolded? And what general lessons can be extracted? Several of the cell biological mechanisms that are used to establish the inactive X chromosome, including regulatory networks of non-coding RNAs and unusual nuclear dynamics, are now suspected to hold true for processes occurring on a genome-wide scale. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Howard Hughes Med Inst,Dept Mol Biol,Dept Genet, Boston, MA 02114 USA. RP Lee, JT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Howard Hughes Med Inst,Dept Mol Biol,Dept Genet, Boston, MA 02114 USA. EM lee@molbio.mgh.harvard.edu FU Howard Hughes Medical Institute FX I am greatly indebted to members of the laboratory, past and present, for their valuable intellectual and experimental contributions. I also thank A. Riggs, B. Payer and Y. Jeon for critical reading of the manuscript, and the Howard Hughes Medical Institute for providing ongoing support. NR 201 TC 85 Z9 90 U1 3 U2 34 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0072 J9 NAT REV MOL CELL BIO JI Nat. Rev. Mol. Cell Biol. PD DEC PY 2011 VL 12 IS 12 BP 815 EP 826 DI 10.1038/nrm3231 PG 12 WC Cell Biology SC Cell Biology GA 856TM UT WOS:000297666300013 PM 22108600 ER PT J AU Coumans, JVCE Walcott, BP AF Coumans, Jean-Valery C. E. Walcott, Brian P. TI Incidental vertebral lesions SO NEUROSURGICAL FOCUS LA English DT Article DE incidental finding; vertebra; congenital; os odontoideum ID SPINA-BIFIDA OCCULTA; URINARY-TRACT DYSFUNCTION; KLIPPEL-FEIL SYNDROME; LOW-BACK-PAIN; CERVICAL-SPINE; LUMBAR SPINE; DISK DISEASE; BONE; FRACTURES; MARROW AB Incidental vertebral lesions on imaging of the spine are commonly encountered in clinical practice. Contributing factors include the aging population, the increasing prevalence of back pain, and increased usage of MR imaging. Additionally, refinements in CT and MR imaging have increased the number of demonstrable lesions. The management of incidental findings varies among practitioners and commonly depends more on practice style than on data or guidelines. In this article we review incidental findings within the vertebral column and review management of these lesions, based on available Class III data. (DOI: 10.3171/2011.9.FOCUS11207) C1 [Walcott, Brian P.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Walcott, BP (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 55 Fruit St,White Bldg,Room 502, Boston, MA 02114 USA. EM walcott.brian@mgh.harvard.edu NR 58 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 1092-0684 J9 NEUROSURG FOCUS JI Neurosurg. Focus PD DEC PY 2011 VL 31 IS 6 AR E17 DI 10.3171/2011.9.FOCUS11207 PG 9 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 857TL UT WOS:000297743200019 PM 22133170 ER PT J AU Tregellas, JR Wylie, KP Rojas, DC Tanabe, J Martin, J Kronberg, E Cordes, D Cornier, MA AF Tregellas, Jason R. Wylie, Korey P. Rojas, Donald C. Tanabe, Jody Martin, Jesse Kronberg, Eugene Cordes, Dietmar Cornier, Marc-Andre TI Altered Default Network Activity in Obesity SO OBESITY LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; VISUAL FOOD CUES; HUMAN BRAIN; RESTING STATE; NEURONAL RESPONSE; NEURAL RESPONSES; FUNCTIONAL MRI; LIQUID-MEAL; REWARD; FMRI AB The regulation of energy intake is a complex process involving the integration of homeostatic signals and both internal and external sensory inputs. To better understand the neurobiology of this process and how it may be dysfunctional in obesity, this study examined activity of the brain's "default network" in reduced-obese (RO) as compared to lean individuals. The default network is a group of functionally connected brain regions thought to play an important role in internally directed cognitive activity and the interplay between external and internal sensory processing. Functional magnetic resonance imaging was performed in 24 lean and 18 RO individuals in the fasted state after 2 days of eucaloric energy intake and after 2 days of 30% overfeeding in a counterbalanced design. Scanning was performed while subjects passively viewed images of food and nonfood objects. Independent component analysis was used to identify the default network component. In the eucaloric state, greater default network activity was observed in RO compared to lean individuals in the lateral inferior parietal and posterior cingulate cortices. Activity was positively correlated with appetite. Overfeeding resulted in increased default network activity in lean but not RO individuals. These findings suggest that the function of the default network, a major contributor to intrinsic neuronal activity, is altered in obesity and/or obese-prone individuals. Future studies of the network's function and its relationship to other brain networks may improve our understanding of the mechanisms and treatment of obesity. C1 [Tregellas, Jason R.; Wylie, Korey P.; Rojas, Donald C.; Tanabe, Jody; Martin, Jesse; Kronberg, Eugene; Cordes, Dietmar] Denver VA Med Ctr, Dept Psychiat, Aurora, CO USA. [Cornier, Marc-Andre] Univ Colorado Denver, Div Endocrinol, Dept Med, Aurora, CO USA. [Tanabe, Jody; Cordes, Dietmar] Univ Colorado, Dept Radiol, Denver, CO 80202 USA. RP Tregellas, JR (reprint author), Denver VA Med Ctr, Dept Psychiat, Aurora, CO USA. EM Jason.tregellas@ucdenver.edu RI Rojas, Don/F-4296-2012; Tregellas, Jason/J-3637-2015; OI Rojas, Don/0000-0001-6560-9616 FU NIH/NCRR Colorado CTSI [UL1 RR025780]; NIH/NIDDK Clinical Nutrition Research Unit [DK48520]; NIH/NCRR [RR016185, R01DK072174, R01DK089095] FX This study was supported by NIH/NCRR Colorado CTSI Grant Number UL1 RR025780, NIH/NIDDK Clinical Nutrition Research Unit Grant Number DK48520, and NIH/NCRR Grant Numbers RR016185, R01DK072174 and R01DK089095. NR 46 TC 29 Z9 29 U1 1 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1930-7381 EI 1930-739X J9 OBESITY JI Obesity PD DEC PY 2011 VL 19 IS 12 BP 2316 EP 2321 DI 10.1038/oby.2011.119 PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 853EM UT WOS:000297409000005 PM 21633398 ER PT J AU Baskin, KM Hogan, MJ Sidhu, MK Connolly, BL Towbin, RB Saad, WEA Dubois, J Heran, MKS Marshalleck, FE Miller, DL Roebuck, D Temple, MJ Walker, TG Cardella, JF AF Baskin, Kevin M. Hogan, Mark J. Sidhu, Manrita K. Connolly, Bairbre L. Towbin, Richard B. Saad, Wael E. A. Dubois, Josee Heran, Manraj K. S. Marshalleck, Francis E. Miller, Donald L. Roebuck, Derek Temple, Michael J. Walker, T. Gregory Cardella, John F. TI Developing a clinical pediatric interventional practice: a joint clinical practice guideline from the Society of Interventional Radiology and the Society for Pediatric Radiology SO PEDIATRIC RADIOLOGY LA English DT Article ID RADIATION-EXPOSURE; MANAGEMENT; SAFETY; SUITE; STRATEGIES; EQUIPMENT; QUALITY C1 [Baskin, Kevin M.] SIR, Fairfax, VA 22033 USA. [Baskin, Kevin M.] Univ Pittsburgh, Childrens Hosp Pittsburgh, Dept Radiol, Med Ctr, Pittsburgh, PA 15213 USA. [Sidhu, Manrita K.] Univ Washington, Dept Radiol, Seattle Childrens Hosp, Seattle, WA 98195 USA. [Connolly, Bairbre L.; Temple, Michael J.] Univ Toronto, Hosp Sick Children, Ctr Image Guided Therapy, Toronto, ON M5G 1X8, Canada. [Towbin, Richard B.] Phoenix Childrens Hosp, Dept Radiol, Phoenix, AZ USA. [Hogan, Mark J.] Ohio State Univ, Dept Radiol, Sect Vasc & Intervent Radiol, Nationwide Childrens Hosp, Columbus, OH 43210 USA. [Saad, Wael E. A.] Univ Virginia Hlth Syst, Dept Radiol, Charlottesville, VA USA. [Dubois, Josee] Univ Sainte Justine, Ctr Hosp, Dept Med Imaging, Montreal, PQ, Canada. [Miller, Donald L.] Uniformed Serv Univ Hlth Sci, Dept Radiol, Bethesda, MD 20814 USA. [Heran, Manraj K. S.] British Columbia Childrens Hosp, Dept Radiol, Vancouver, BC V6H 3V4, Canada. [Miller, Donald L.] Natl Naval Med Ctr, Dept Radiol, Bethesda, MD USA. [Roebuck, Derek] Great Ormond St Hosp Sick Children, Dept Radiol, London, England. [Heran, Manraj K. S.] Vancouver Gen Hosp, Dept Radiol, Vancouver, BC V5Z 1M9, Canada. [Walker, T. Gregory] Massachusetts Gen Hosp, Div Vasc Imaging & Intervent, Boston, MA 02114 USA. [Marshalleck, Francis E.] Indiana Univ Sch Med, Dept Radiol, Riley Hosp Children, Indianapolis, IN USA. [Cardella, John F.] Geisinger Hlth Syst, Dept Radiol, Danville, PA USA. RP Baskin, KM (reprint author), SIR, 3975 Fair Ridge Dr,Suite 400 N, Fairfax, VA 22033 USA. EM kevin.baskin@chp.edu OI Baskin, Kevin/0000-0001-8928-9688; Temple, Michael/0000-0002-5843-0519; Roebuck, Derek/0000-0003-1734-2536 FU Siemens (Forchheim, Germany) FX W.E.A.S. is a paid consultant for Boston Scientific (Natick, MA, USA), has research funded by Siemens (Forchheim, Germany) and serves on the Speaker's Bureau for Atrium (Hudson, NH, USA). None of the other authors has identified a conflict of interest. The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Department of the Navy, Army, Department of Defense or the United States Government. NR 55 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0301-0449 J9 PEDIATR RADIOL JI Pediatr. Radiol. PD DEC PY 2011 VL 41 IS 12 BP 1600 EP 1612 DI 10.1007/s00247-011-2247-4 PG 13 WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging GA 856EY UT WOS:000297621800017 ER PT J AU Mullarky, E Mattaini, KR Heiden, MGV Cantley, LC Locasale, JW AF Mullarky, Edouard Mattaini, Katherine R. Heiden, Matthew G. Vander Cantley, Lewis C. Locasale, Jason W. TI PHGDH amplification and altered glucose metabolism in human melanoma SO PIGMENT CELL & MELANOMA RESEARCH LA English DT Article DE PHGDH; serine; biosynthesis; cancer; metabolism; 3-phosphoglycerate; glycolysis ID SUCCINATE-DEHYDROGENASE; CELL-GROWTH; CANCER; SERINE; TET2; DIFFERENTIATION; ONCOGENESIS; AUTOPHAGY; CULTURES; ENZYMES AB The metabolic requirements of cancer cells differ from that of their normal counterparts. To support their proliferation, cancer cells switch to a fermentative metabolism that is thought to support biomass production. Instances where metabolic enzymes promote tumorigenesis remain rare. However, an enzyme involved in the de novo synthesis of serine, 3-phosphoglycerate dehydrogenase (PHGDH), was recently identified as a putative oncogene. The potential mechanisms by which PHGDH promotes cancer are discussed. C1 [Mullarky, Edouard; Cantley, Lewis C.; Locasale, Jason W.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02215 USA. [Mullarky, Edouard; Cantley, Lewis C.; Locasale, Jason W.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02215 USA. [Mattaini, Katherine R.; Heiden, Matthew G. Vander] MIT, Dept Biol, Kock Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Heiden, Matthew G. Vander] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. RP Locasale, JW (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02215 USA. EM jlocasal@bidmc.harvard.edu RI Cantley, Lewis/D-1800-2014; OI Cantley, Lewis/0000-0002-1298-7653; Locasale, Jason/0000-0002-7766-3502 NR 32 TC 28 Z9 28 U1 0 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1755-1471 J9 PIGM CELL MELANOMA R JI Pigment Cell Melanoma Res. PD DEC PY 2011 VL 24 IS 6 BP 1112 EP 1115 DI 10.1111/j.1755-148X.2011.00919.x PG 4 WC Oncology; Cell Biology; Dermatology SC Oncology; Cell Biology; Dermatology GA 859AD UT WOS:000297845100010 PM 21981974 ER PT J AU Yang, H Magpayo, N Rusek, A Chiang, IH Sivertz, M Held, KD AF Yang, H. Magpayo, N. Rusek, A. Chiang, I-H. Sivertz, M. Held, K. D. TI Effects of Very Low Fluences of High-Energy Protons or Iron Ions on Irradiated and Bystander Cells SO RADIATION RESEARCH LA English DT Article ID DOUBLE-STRAND BREAKS; MEDIATED INTERCELLULAR COMMUNICATION; HUMAN FIBROBLASTS; ALPHA-PARTICLES; IN-VIVO; RADIATION ONCOGENESIS; IONIZING-RADIATION; MICRONUCLEUS ASSAY; GAMMA-IRRADIATION; SPACE EXPLORATION AB Yang, H., Magpayo, N., Rusek, A., Chiang, I-H., Sivertz, M. and Held, K. D. Effects of Very Low Fluences of High-Energy Protons or Iron Ions on Irradiated and Bystander Cells. Radiat. Res. 176, 695-705 (2011). In space, astronauts are exposed to radiation fields consisting of energetic protons and high atomic number, high-energy (HZE) particles at very low dose rates or fluences. Under these conditions, it is likely that, in addition to cells in an astronaut's body being traversed by ionizing radiation particles, unirradiated cells can also receive intercellular bystander signals from irradiated cells. Thus this study was designed to determine the dependence of DNA damage induction on dose at very low fluences of charged particles. Novel techniques to quantify particle fluence have been developed at the NASA Space Radiation Biology Laboratory (NSRL) at Brookhaven National Laboratory (BNL). The approach uses a large ionization chamber to visualize the radiation beam coupled with a scintillation counter to measure fluence. This development has allowed us to irradiate cells with 1 GeV/nucleon protons and iron ions at particle fluences as low as 200 particles/cm(2) and quantify biological responses. Our results show an increased fraction of cells with DNA damage in both the irradiated population and bystander cells sharing medium with irradiated cells after low fluences. The fraction of cells with damage, manifest as micronucleus formation and 53BP1 focus induction, is about 2-fold higher than background at doses as low as similar to 0.47 mGy iron ions (similar to 0.02 iron ions/cell) or similar to 70 mu Gy protons (similar to 2 protons/cell). In the irradiated population, irrespective of radiation type, the fraction of damaged cells is constant from the lowest damaging fluence to about 1 cGy, above which the fraction of damaged cells increases with dose. In the bystander population, the level of damage is the same as in the irradiated population up to 1 cGy, but it does not increase above that plateau level with increasing dose. The data suggest that at fluences of high-energy protons or iron ions less than about 5 cGy, the response in irradiated cell populations may be dominated by the bystander response. (C) 2011 by Radiation Research Society C1 [Yang, H.; Magpayo, N.; Held, K. D.] Harvard Univ, Dept Radiat Oncol, Massachusetts Gen Hosp, Sch Med,COX 302, Boston, MA 02114 USA. [Rusek, A.; Chiang, I-H.; Sivertz, M.] NASA, Space Radiat Biol Lab, Brookhaven Natl Lab, Upton, NY 11973 USA. RP Held, KD (reprint author), Harvard Univ, Dept Radiat Oncol, Massachusetts Gen Hosp, Sch Med,COX 302, 55 Fruit St, Boston, MA 02114 USA. EM kheld@partners.org FU NASA [NNX07AE40G] FX The authors acknowledge the excellent assistance from the support personnel in the Medical and Biology Departments of Brookhaven National Laboratory. The authors thank Drs. Kevin M. Prise, Howard L. Liber and Robert W. Redmond for many helpful discussions. This research was supported by NASA grant no. NNX07AE40G. NR 56 TC 15 Z9 15 U1 1 U2 6 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD DEC PY 2011 VL 176 IS 6 BP 695 EP 705 DI 10.1667/RR2674.1 PG 11 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 859VN UT WOS:000297904000001 PM 21988573 ER PT J AU Ngwa, W Korideck, H Chin, LM Makrigiorgos, GM Berbeco, RI AF Ngwa, Wilfred Korideck, Houari Chin, Lee M. Makrigiorgos, G. Mike Berbeco, Ross I. TI MOSFET Assessment of Radiation Dose Delivered to Mice Using the Small Animal Radiation Research Platform (SARRP) SO RADIATION RESEARCH LA English DT Article ID CONFORMAL IRRADIATOR; HIGH-RESOLUTION; DOSIMETRY; RADIOTHERAPY; SYSTEM; DETECTORS; GUIDANCE; BUILDUP AB Ngwa, W., Korideck, H., Chin, L. M., Makrigiorgos, G. M. and Berbeco, R. I. MOSFET Assessment of Radiation Dose Delivered to Mice Using the Small Animal Radiation Research Platform (SARRP). Radiat. Res. 176, 816-820 (2011). The Small Animal Radiation Research Platform (SARRP) is a novel isocentric irradiation system that enables state-of-the-art image-guided radiotherapy research to be performed with animal models. This paper reports the results obtained from investigations assessing the radiation dose delivered by the SARRP to different anatomical target volumes in mice. Surgically implanted metal oxide semiconductor field effect transistors (MOSFET) dosimeters were employed for the dose assessment. The results reveal differences between the calculated and measured dose of -3.5 to 0.5%, -5.2 to -0.7%, -3.9 to 0.5%, -5.9 to 2.5%, -5.5 to 0.5%, and -4.3 to 0% for the left kidney, liver, pancreas, prostate, left lung, and brain, respectively. Overall, the findings show less than 6% difference between the delivered and calculated dose, without tissue heterogeneity corrections. These results provide a useful assessment of the need for tissue heterogeneity corrections in SARRP dose calculations for clinically relevant tumor model sites. (C) 2011 by Radiation Research Society C1 [Berbeco, Ross I.] Brigham & Womens Hosp, Dept Radiat Oncol, Div Med Phys & Biophys, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Berbeco, RI (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, Div Med Phys & Biophys, Dana Farber Canc Inst, 75 Francis St,ASBI-L2, Boston, MA 02115 USA. EM rberbeco@lroc.harvard.edu NR 27 TC 3 Z9 3 U1 0 U2 2 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD DEC PY 2011 VL 176 IS 6 BP 816 EP 820 DI 10.1667/RR2536.1 PG 5 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 859VN UT WOS:000297904000014 PM 21962005 ER PT J AU Daniel, C von Boehmer, H AF Daniel, Carolin von Boehmer, Harald TI Extra-thymically induced regulatory T cells: Do they have potential in disease prevention? SO SEMINARS IN IMMUNOLOGY LA English DT Review DE Regulatory T cells; Foxp3; Conversion; Vaccination; Autoimmune disease ID FOXP3 GENE-EXPRESSION; LIGASE CBL-B; IN-VIVO; TGF-BETA; DENDRITIC CELLS; NOD MICE; RETINOIC-ACID; CUTTING EDGE; LINEAGE COMMITMENT; EPITHELIAL-CELLS AB Fopx3(+) Treg safeguard against autoimmune diseases and immune pathology. The extrathymic conversion of naive T cells into Foxp3(+) regulatory T cells can be achieved in vivo by the delivery of strong-agonist ligands under subimmunogenic conditions. Tolerogenic vaccination with strong-agonist mimetopes of self-antigen to promote self-antigen specific tolerance may represent the most specific and safest means of preventing autoimmunity. This review discusses the requirements for induction of dominant tolerance exerted by Foxp3(+) Tregs in autoimmunity with special emphasis on their impact to interfere with T1D. The future goals are the understanding of self-non-self discrimination at the cellular and molecular level, which should then enable investigators to develop clinical vaccination protocols that specifically interfere with unwanted immune responses. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Daniel, Carolin; von Boehmer, Harald] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Lab Lymphocyte Biol, Boston, MA 02215 USA. [Daniel, Carolin] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [von Boehmer, Harald] Harvard Univ, Harvard Fac Arts & Sci, Cambridge, MA 02138 USA. RP von Boehmer, H (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Lab Lymphocyte Biol, 450 Brookline Ave,Smith 736, Boston, MA 02215 USA. EM harald_von_boehmer@dfci.harvard.edu RI Daniel, Carolin/M-4624-2014 OI Daniel, Carolin/0000-0003-4698-7069 FU National Institutes of Health [NIH-AI-53102]; Leopoldina research fellowship [BMBF-LPD 9901/8-184]; Federal State of Hessen, Germany FX The studies were supported by National Institutes of Health Grant NIH-AI-53102 (to H.v.B.). C.D. was supported by a Leopoldina research fellowship (BMBF-LPD 9901/8-184) and by the LOEWE (LipidSignaling Forschungszentrum Frankfurt) program of the Federal State of Hessen, Germany. NR 129 TC 8 Z9 9 U1 0 U2 6 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-5323 J9 SEMIN IMMUNOL JI Semin. Immunol. PD DEC PY 2011 VL 23 IS 6 BP 410 EP 417 DI 10.1016/j.smim.2011.06.004 PG 8 WC Immunology SC Immunology GA 859XU UT WOS:000297909900003 PM 21724411 ER PT J AU Kim, HJ Cantor, H AF Kim, Hye-Jung Cantor, Harvey TI Regulation of self-tolerance by Qa-1-restricted CD8(+) regulatory T cells SO SEMINARS IN IMMUNOLOGY LA English DT Review DE CD8(+) regulatory T cells; Qa-1; HLA-E; IL-15; autoimmunity ID PEPTIDE-BINDING-SPECIFICITY; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; CLASS IB MOLECULES; HLA-E BINDS; POSITIVE SELECTION; CUTTING EDGE; INHIBITORY RECEPTORS; AUTOIMMUNE-DISEASE; ADAPTIVE IMMUNITY; HELPER-CELLS AB Mounting an efficient immune response to pathogens while avoiding damage to host tissues is the central task of the immune system. Emerging evidence has highlighted the contribution of the CD8(+) lineage of regulatory T cells to the maintenance of self-tolerance. Specific recognition of the MHC class Ib molecule Qa-1 complexed to peptides expressed by activated CD4(+) T cells by regulatory CD8(+) T cells triggers an inhibitory interaction that prevents autoimmune responses. Conversely, defective Qa-1-restricted CD8(+). regulatory activity can result in development of systemic autoimmune disease. Here, we review recent research into the cellular and molecular basis of these regulatory T cells, their mechanism of suppressive activity and the potential application of these insights into new treatments for autoimmune disease and cancer. (C) 2011 Published by Elsevier Ltd. C1 [Cantor, Harvey] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02215 USA. RP Cantor, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 450 Brookline Ave, Boston, MA 02215 USA. EM Harvey_Cantor@dfci.harvard.edu FU NIH [AI 037562]; National Multiple Sclerosis Foundation; Lupus Research Institute; NRSA [DFCI/NCI T32 CA070083] FX This work was supported in part by grants from the NIH (AI 037562), National Multiple Sclerosis Foundation, Lupus Research Institute, and a gift from the LeRoy Schecter Research Foundation to HC and NRSA Fellowship (DFCI/NCI T32 CA070083) to H-JK. The authors wish to thank LB. Goodman for critical reading and A. Angel for editorial assistance. NR 89 TC 31 Z9 32 U1 2 U2 10 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-5323 J9 SEMIN IMMUNOL JI Semin. Immunol. PD DEC PY 2011 VL 23 IS 6 BP 446 EP 452 DI 10.1016/j.smim.2011.06.001 PG 7 WC Immunology SC Immunology GA 859XU UT WOS:000297909900008 PM 22136694 ER PT J AU Martin, JL Fiorentino, L Jouldjian, S Mitchell, M Josephson, KR Alessi, CA AF Martin, Jennifer L. Fiorentino, Lavinia Jouldjian, Stella Mitchell, Michael Josephson, Karen R. Alessi, Cathy A. TI Poor Self-Reported Sleep Quality Predicts Mortality within One Year of Inpatient Post-Acute Rehabilitation among Older Adults SO SLEEP LA English DT Article DE Aging; rehabilitation; mortality ID ILLNESS RATING-SCALE; FOLLOW-UP; DAYTIME SLEEPINESS; POPULATION; DISTURBANCES; VALIDATION; RECOVERY; DISEASE; PEOPLE; MODEL AB Study Objective: To evaluate the association between self-reported sleep quality among older adults during inpatient post-acute rehabilitation and one-year survival. Design: Prospective, observational cohort study. Setting: Two inpatient post-acute rehabilitation sites (one community and one Veterans Administration). Participants: Older patients (aged >= 65 years, n = 245) admitted for inpatient post-acute rehabilitation. Interventions: None. Measurements and Results: Within one year of post-acute rehabilitation, 57 participants (23%) were deceased. Cox proportional hazards models showed that worse Pittsburgh Sleep Quality Index (PSQI) total scores during the post-acute care stay were associated with increased mortality risk when controlling for amount of rehabilitation therapy received, comorbidities, and cognitive functioning (Hazard ratio [95% CI] = 1.11 [1.02-1.20]). Actigraphically estimated sleep was unrelated to mortality risk. Conclusions: Poorer self-reported sleep quality, but not objectively estimated sleep parameters, during post-acute rehabilitation was associated with shorter survival among older adults. This suggests self-reported poor sleep may be an important and potentially modifiable risk factor for negative outcomes in these vulnerable older adults. Studies of interventions to improve sleep quality during inpatient rehabilitation should therefore be undertaken, and the long-term health benefits of improved sleep should be explored. C1 [Martin, Jennifer L.; Alessi, Cathy A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Martin, Jennifer L.; Jouldjian, Stella; Mitchell, Michael; Josephson, Karen R.; Alessi, Cathy A.] VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, Los Angeles, CA USA. [Fiorentino, Lavinia] Univ Calif San Diego, Dept Psychiat, Div Geriatr Mental Hlth, San Diego, CA 92103 USA. RP Martin, JL (reprint author), VA GRECC 11E, 16111 Plummer St, North Hills, CA 91007 USA. EM Jennifer.Martin@va.gov FU NIA [K23 AG028452]; VA HSRD [IIR-01-053-1, IIR 04-321-2, AIA-03-047]; NIMH [T32 MH 019925-11, T32 MH019934]; VA Greater Los Angeles Healthcare System Geriatric Research, Education and Clinical Center (GRECC) FX The authors thank the participating facilities and their staff, and the members of the research team who made this study possible. In particular, the authors thank Terry Vandenberg, MA, Sergio Martinez, Maryanne Devereaux, Christina Kurtz, RN, Rebecca Saia, Crystal Barker, RN, Jae Lee, MD, David Kim, PA, and Adam Webber, BSc(Hons), MRCP (UK). This study was supported by NIA K23 AG028452; VA HSR&D (IIR-01-053-1; IIR 04-321-2; AIA-03-047), NIMH T32 MH 019925-11, NIMH T32 MH019934, and VA Greater Los Angeles Healthcare System Geriatric Research, Education and Clinical Center (GRECC). NR 28 TC 17 Z9 17 U1 2 U2 6 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD DEC 1 PY 2011 VL 34 IS 12 BP 1715 EP 1721 DI 10.5665/sleep.1444 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 857BT UT WOS:000297689800018 PM 22131610 ER PT J AU Barton, C Morris, R Rothlind, J Yaffe, K AF Barton, Cynthia Morris, Rebecca Rothlind, Johannes Yaffe, Kristine TI Video-Telemedicine in a Memory Disorders Clinic: Evaluation and Management of Rural Elders with Cognitive Impairment SO TELEMEDICINE AND E-HEALTH LA English DT Article DE telemedicine; telehealth; telecommunications ID DEMENTIA; DIAGNOSIS; TELEHEALTH; CONSULTATION; ASSESSMENTS AB Objective: Telemedicine is increasingly being used to provide consultation for healthcare in rural areas. Little work has been done with dementia although preliminary research suggests that clinical diagnosis performed via telemedicine consultation is valid. We implemented a program to provide multidisciplinary, state-of-the-art diagnosis of cognitive impairment by video-telemedicine (VTM) integrated into a clinical setting. Methods: Patients at a rural veteran's community clinic were referred by their local provider for evaluation of memory complaints by the multidisciplinary team of the San Francisco Veterans Administration (SFVA) Memory Disorders Clinic (MDC). The evaluation was integrated into the usual clinic structure and included a neurological evaluation and neuropsychological testing by the MDC team via video assisted by a remote clinician at the community clinic. Results: We evaluated 15 new patients referred to our multidisciplinary clinic. In each case, the VTM format permitted the MDC team to arrive at a working diagnosis; 12 patients with dementia, two with mild cognitive impairment, and one cognitively normal. Relevant treatment recommendations were made to the patients and caregivers. The evaluation results were discussed with providers who joined the MDC postclinic conference via VTM. In the majority of cases, recommendations were followed and there was satisfaction with VTM by providers and patients. Conclusions: VTM is emerging as an effective way to provide consultation and care to rural residents who may not have access to specialty services and can be integrated into current clinical settings. C1 [Barton, Cynthia; Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Barton, Cynthia; Rothlind, Johannes; Yaffe, Kristine] San Francisco Vet Adm Med Ctr, San Francisco, CA USA. [Morris, Rebecca] Vet Adm Community Based Clin, Eureka, CA USA. [Rothlind, Johannes; Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. RP Barton, C (reprint author), San Francisco VAMC Memory Disorders Clin, UCSF Memory & Aging Ctr, 4150 Clement St,Box 127, San Francisco, CA 94121 USA. EM cbarton@memory.ucsf.edu NR 23 TC 14 Z9 15 U1 1 U2 5 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1530-5627 J9 TELEMED E-HEALTH JI Telemed. e-Health PD DEC PY 2011 VL 17 IS 10 BP 789 EP 793 DI 10.1089/tmj.2011.0083 PG 5 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 860BD UT WOS:000297919800008 PM 22023458 ER PT J AU Li, HK Horton, M Bursell, SE Cavallerano, J Zimmer-Galler, I Tennant, M Abramoff, M Chaum, E DeBuc, DC Leonard-Martin, T Winchester, M AF Li, Helen K. Horton, Mark Bursell, Sven-Erik Cavallerano, Jerry Zimmer-Galler, Ingrid Tennant, Mathew Abramoff, Michael Chaum, Edward DeBuc, Debra Cabrera Leonard-Martin, Tom Winchester, Marc TI Telehealth Practice Recommendations for Diabetic Retinopathy, Second Edition SO TELEMEDICINE AND E-HEALTH LA English DT Article ID COLOR FUNDUS PHOTOGRAPHS; AUTOMATED DETECTION; MACULAR EDEMA; SCREENING-PROGRAM; FLUORESCEIN ANGIOGRAMS; COMPLICATIONS TRIAL; INTENSIVE THERAPY; QUALITY-ASSURANCE; COMPUTER-PROGRAM; VASCULAR CHANGES C1 [Li, Helen K.] Methodist Hosp, Dept Ophthalmol, Weill Cornell Med Coll, Houston, TX 77030 USA. [Li, Helen K.] Univ Texas Hlth Sci Ctr, Sch Biomed Informat, Houston, TX USA. [Li, Helen K.] Thomas Jefferson Univ, Jefferson Med Coll, Dept Ophthalmol, Philadelphia, PA 19107 USA. [Horton, Mark] Phoenix Indian Med Ctr, Phoenix, AZ 85016 USA. [Bursell, Sven-Erik] Univ Hawaii, John A Burns Sch Med, Telehlth Res Inst, Honolulu, HI 96822 USA. [Cavallerano, Jerry] Beetham Eye Inst, Joslin Diabet Ctr, Boston, MA USA. [Zimmer-Galler, Ingrid] Johns Hopkins Med Inst, Wilmer Eye Inst, Baltimore, MD 21205 USA. [Tennant, Mathew] Univ Alberta, Dept Ophthalmol, Edmonton, AB, Canada. [Abramoff, Michael] Univ Iowa Hosp & Clin, Dept Ophthalmol & Visual Sci, Iowa City, IA 52242 USA. [Chaum, Edward] Univ Tennessee, Hlth Sci Ctr, Hamilton Eye Inst, Memphis, TN USA. [DeBuc, Debra Cabrera] Univ Miami, Bascom Palmer Eye Inst, Miami, FL USA. [Leonard-Martin, Tom] Insight Diagnost Inc, Oklahoma City, OK USA. [Winchester, Marc] Digital Healthcare Inc, Wake Forest, NC USA. RP Li, HK (reprint author), Community Retina Grp, 6550 Fannin St,Smith 2317, Houston, TX 77030 USA. EM hli@communityretina.com; mark.horton@ihs.gov RI Abramoff, Michael/A-5836-2009 OI Abramoff, Michael/0000-0002-3490-0037 NR 155 TC 32 Z9 33 U1 1 U2 4 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1530-5627 EI 1556-3669 J9 TELEMED E-HEALTH JI Telemed. e-Health PD DEC PY 2011 VL 17 IS 10 BP 814 EP 837 DI 10.1089/tmj.2011.0075 PG 24 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 860BD UT WOS:000297919800013 PM 21970573 ER PT J AU Badr, CE Tannous, BA AF Badr, Christian E. Tannous, Bakhos A. TI Bioluminescence imaging: progress and applications SO TRENDS IN BIOTECHNOLOGY LA English DT Review ID MESENCHYMAL STEM-CELLS; PROTEIN-PROTEIN INTERACTIONS; TRANSCRIPTIONAL AMPLIFICATION STRATEGY; LUCIFERASE-FRAGMENT COMPLEMENTATION; REPORTER GENE-EXPRESSION; IN-VIVO; FIREFLY LUCIFERASE; LIVING SUBJECTS; T-CELLS; GAUSSIA LUCIFERASE AB Application of bioluminescence imaging has increased tremendously in the past decade and has significantly contributed to core conceptual advances in biomedical research. This technology provides valuable means for monitoring of different biological processes in immunology, oncology, virology and neuroscience. In this review, we discuss current trends in bioluminescence and its application in different fields with an emphasis on cancer research. C1 [Badr, Christian E.; Tannous, Bakhos A.] Massachusetts Gen Hosp, Dept Neurol, Ctr Neurosci, Boston, MA 02114 USA. [Tannous, Bakhos A.] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA. [Badr, Christian E.; Tannous, Bakhos A.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. RP Badr, CE (reprint author), Massachusetts Gen Hosp, Dept Neurol, Ctr Neurosci, Boston, MA 02114 USA. EM badr.christian@mgh.harvard.edu; btannous@hms.harvard.edu FU NINDS NIH HHS [R01 NS064983] NR 85 TC 80 Z9 82 U1 8 U2 62 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0167-7799 J9 TRENDS BIOTECHNOL JI Trends Biotechnol. PD DEC PY 2011 VL 29 IS 12 BP 624 EP 633 DI 10.1016/j.tibtech.2011.06.010 PG 10 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 859LN UT WOS:000297878000005 PM 21788092 ER PT J AU Hynes, BG Ruggiero, NJ Hirsch, JA Rosenfield, K AF Hynes, Brian G. Ruggiero, Nicholas J. Hirsch, Joshua A. Rosenfield, Kenneth TI Carotid stent fracture and restenosis management SO VASCULAR MEDICINE LA English DT Article DE angioplasty; balloon; carotid arteries; carotid artery diseases; stents ID ARTERY AB We report an unusual case of asymptomatic accelerated right carotid artery in-stent restenosis in a patient referred for revascularization of a de novo stenosis of her left internal carotid artery. C1 [Hynes, Brian G.] Massachusetts Gen Hosp, Div Cardiol, Dept Cardiol, Sect Vasc Med & Peripheral Intervent, Boston, MA 02114 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept Intervent Neuroradiol, Boston, MA 02114 USA. RP Hynes, BG (reprint author), Massachusetts Gen Hosp, Div Cardiol, Dept Cardiol, Sect Vasc Med & Peripheral Intervent, 55 Fruit St, Boston, MA 02114 USA. EM bghynes@hotmail.com FU Abbott Vascular; Bard Peripheral Vascular; Medtronic/Invatec; Atrium; Boston Scientific Corp; Complete Conference Management; Harvard Clinical Research Institute; Contego; Micell; Becker Ventures FX Dr Rosenfield reports receiving research grants from Abbott Vascular, Bard Peripheral Vascular, Medtronic/Invatec, and Atrium; receiving consulting/advisory board fees from Abbott Vascular, Boston Scientific Corp, Complete Conference Management, Harvard Clinical Research Institute, Contego, Micell, and Becker Ventures; having equity in Lumen Biomedical, Medical Stimulation Corp, Angioguard (Cordis), and Micell; and serving on the board of directors for VIVA Physicians (501C3). The other authors report no conflicts. NR 5 TC 1 Z9 1 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1358-863X J9 VASC MED JI Vasc. Med. PD DEC PY 2011 VL 16 IS 6 BP 436 EP 442 DI 10.1177/1358863X11422563 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 854FJ UT WOS:000297480100004 PM 21967889 ER PT J AU Yachimski, P Mino-Kenudson, M Sherwood, ME Puricelli, WP Nishioka, NS Lauwers, GY AF Yachimski, Patrick Mino-Kenudson, Mari Sherwood, Margaret E. Puricelli, William P. Nishioka, Norman S. Lauwers, Gregory Y. TI Cyclooxygenase-2 expression in esophageal epithelium before and after photodynamic therapy for Barrett's esophagus with high-grade dysplasia or intramucosal carcinoma SO VIRCHOWS ARCHIV LA English DT Article DE Barrett's esophagus; Photodynamic therapy; Cyclooxygenase; High-grade dysplasia; Esophageal adenocarcinoma ID GENE-EXPRESSION; TUMOR RESPONSE; ADENOCARCINOMA; BEVACIZUMAB; CANCER; CELLS AB Cyclooxygenase-2 expression is upregulated in Barrett's esophagus and esophageal adenocarcinoma. Photodynamic therapy using porfimer sodium can result in ablation of dysplasia and intramucosal carcinoma, eradication of Barrett's esophagus, and restitution of squamous epithelium. The aim of this study was to determine the effect of photodynamic therapy on cyclooxygenase-2 expression in esophageal epithelium. Paired pre- and post-photodynamic therapy biopsy samples from the same anatomical levels of 20 individuals who had undergone photodynamic therapy for Barrett's esophagus with high-grade dysplasia and/or intramucosal carcinoma were immunostained using a cyclooxygenase-2 monoclonal antibody. Cyclooxygenase-2 expression was graded in squamous epithelium, Barrett's esophagus, and neoplasia (if present) as follows: grade 0 (no staining), grade 1 (staining in 1-10% of cells), grade 2 (staining in 11-90% of cells), and grade 3 (staining in > 90% of cells). Pre-photodynamic therapy median cyclooxygenase-2 expression was grade 2 (range 1-3) in neoplastic foci and grade 1 (range 1-3) in nondysplastic Barrett's esophagus (P = 0.0009 for pairwise comparison). With the exception of a few cells staining in the basal epithelial layers, median cyclooxygenase-2 expression was graded as 0 (similar to controls) in both pre-photodynamic therapy squamous epithelium and post-photodynamic therapy neosquamous epithelium. This was significantly lower when compared to either neoplastic foci (P < 0.0001) or nondysplastic Barrett's esophagus (P < 0.0001) pre-photodynamic therapy. Notably, in four patients with post-photodynamic therapy recurrent neoplasia, cyclooxygenase-2 expression returned to elevated levels. Cyclooxygenase-2 expression is elevated in Barrett's esophagus with high-grade dysplasia or intramucosal carcinoma prior to photodynamic therapy. Following successful photodynamic therapy, cyclooxygenase-2 expression in neosquamous epithelium returns to a low baseline level similar to that observed in native esophageal squamous epithelium. Post-photodynamic therapy neoplastic recurrence is associated with elevated cyclooxygenase-2 expression. Prospective studies should determine whether cyclooxygenase inhibitors have a role as adjuvant therapy to prevent recurrence of Barrett's esophagus following endoscopic therapy. C1 [Yachimski, Patrick] Vanderbilt Univ, Med Ctr, Div Gastroenterol Hepatol & Nutr, Nashville, TN 37232 USA. [Yachimski, Patrick; Puricelli, William P.; Nishioka, Norman S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. [Yachimski, Patrick; Sherwood, Margaret E.; Puricelli, William P.; Nishioka, Norman S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. [Mino-Kenudson, Mari; Lauwers, Gregory Y.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. RP Yachimski, P (reprint author), Vanderbilt Univ, Med Ctr, Div Gastroenterol Hepatol & Nutr, 1660 Vanderbilt Clin, Nashville, TN 37232 USA. EM patrick.yachimski@vanderbilt.edu NR 29 TC 0 Z9 0 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0945-6317 J9 VIRCHOWS ARCH JI Virchows Arch. PD DEC PY 2011 VL 459 IS 6 BP 581 EP 586 DI 10.1007/s00428-011-1167-x PG 6 WC Pathology SC Pathology GA 854TL UT WOS:000297517300004 PM 22081106 ER PT J AU Fortier, CB Leritz, EC Salat, DH Venne, JR Maksimovskiy, AL Williams, V Milberg, WP McGlinchey, RE AF Fortier, Catherine B. Leritz, Elizabeth C. Salat, David H. Venne, Jonathan R. Maksimovskiy, Arkadiy L. Williams, Victoria Milberg, William P. McGlinchey, Regina E. TI Reduced Cortical Thickness in Abstinent Alcoholics and Association with Alcoholic Behavior SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Adult; Humans; Magnetic Resonance Imaging; Cortical Thickness; Alcoholism ID SURFACE-BASED ANALYSIS; HUMAN CEREBRAL-CORTEX; WHITE-MATTER; COORDINATE SYSTEM; SEX-DIFFERENCES; BRAIN-DAMAGE; SEGMENTATION; RELIABILITY; DRINKING; ATROPHY AB Background: Chronic misuse of alcohol results in widespread damage to the brain. Prior morphometric studies have examined cortical atrophy in individuals with alcoholism; however, no previous studies have examined alcohol-associated atrophy using cortical thickness measurements to obtain regional mapping of tissue loss across the full cortical surface. Methods: We compared cortical thickness measures from 31 abstinent individuals with a history of prior alcohol abuse to 34 healthy nonalcoholic control participants (total sample size = 65). Cortical surface models were created from high-resolution T1-weighted images, and cortical thickness was then estimated as the distance between the gray matter / white matter boundary and the outer cortical surface. Results: Abstinent alcoholics showed reduced whole-brain thickness as compared to nonalcoholic participants. Decreases in thickness were found bilaterally in (i) superior frontal, (ii) precentral, (iii) postcentral, (iv) middle frontal, (v) middle / superior temporal, (vi) middle temporal, and (vii) lateral occipital cortical regions. Decreased cortical thickness in the alcoholic group was associated with severity of alcohol abuse. Conclusions: These findings demonstrate widespread reduction in cortical thickness as a consequence of chronic alcoholism, with most severe reductions in frontal and temporal brain regions. C1 [Fortier, Catherine B.; Leritz, Elizabeth C.; Salat, David H.; Venne, Jonathan R.; Maksimovskiy, Arkadiy L.; Williams, Victoria; Milberg, William P.; McGlinchey, Regina E.] VA Boston Healthcare Syst, GRECC, Boston, MA 02130 USA. [Fortier, Catherine B.; Venne, Jonathan R.; Milberg, William P.; McGlinchey, Regina E.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Fortier, Catherine B.; Leritz, Elizabeth C.; Salat, David H.; Milberg, William P.; McGlinchey, Regina E.] VA Boston Healthcare Syst, Neuroimaging Res Ctr Vet, Boston, MA 02130 USA. [Leritz, Elizabeth C.; Salat, David H.; Williams, Victoria] Anthinoula A Martinos Ctr Biomed Imaging, Boston, MA USA. [Leritz, Elizabeth C.] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. RP Fortier, CB (reprint author), VA Boston Healthcare Syst, GRECC, 182,150 S Huntington Ave, Boston, MA 02130 USA. EM Catherine_Fortier@hms.harvard.edu RI Maksimovskiy, Arkadiy/M-3700-2013; McGlinchey, Regina/R-1971-2016 OI Maksimovskiy, Arkadiy/0000-0001-6696-7853; FU NIH NIAAA [14205]; NIH [AG08796, MH 53673]; NIH NINR [R01NR010827]; NIH NIA [K01AG024898]; VA Merit Review Awards FX This research was supported by NIH NIAAA 14205, NIH AG08796, NIH MH 53673, NIH NINR R01NR010827, NIH NIA K01AG024898, and VA Merit Review Awards to CBF and REM. NR 47 TC 27 Z9 29 U1 3 U2 14 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD DEC PY 2011 VL 35 IS 12 BP 2193 EP 2201 DI 10.1111/j.1530-0277.2011.01576.x PG 9 WC Substance Abuse SC Substance Abuse GA 849WZ UT WOS:000297157400010 PM 21919920 ER PT J AU Fitch, K Grinspoon, S AF Fitch, Kathleen Grinspoon, Steven TI Nutritional and metabolic correlates of cardiovascular and bone disease in HIV-infected patients SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID CORONARY-HEART-DISEASE; REVERSE-TRANSCRIPTASE INHIBITORS; POTENT ANTIRETROVIRAL THERAPY; MYOCARDIAL-INFARCTION RATES; RANDOMIZED CONTROLLED-TRIAL; HORMONE-RELEASING FACTOR; EXCESS ABDOMINAL FAT; HEALTH-CARE-SYSTEM; POSTMENOPAUSAL WOMEN; PROTEASE INHIBITORS AB The treatment of HIV infection has dramatically reduced the incidence of AIDS-related illnesses. At the same time, non-AIDS-related illnesses such as cardiovascular and bone disease are becoming more prevalent in this population. The mechanisms of these illnesses are complex and are related in part to the HIV virus, antiretroviral medications prescribed for HIV infection, traditional risk factors exacerbated by HIV, and lifestyle and nutritional factors. Further prospective research is needed to clarify the mechanisms by which HIV, antiretroviral medications, and nutritional abnormalities contribute to bone and cardiovascular disease in the HIV population. Increasingly, it is being recognized that optimizing the treatment of HIV infection to improve immune function and reduce viral load may also benefit the development of non-AIDS-related illnesses such as cardiovascular and bone disease. Am J Clin Nutr 2011;94 (suppl):1721S-8S. C1 [Fitch, Kathleen; Grinspoon, Steven] Massachusetts Gen Hosp, Program Nutrit Metab, Boston, MA 02114 USA. RP Grinspoon, S (reprint author), Massachusetts Gen Hosp, Program Nutrit Metab, Boston, MA 02114 USA. EM sgrinspoon@partners.org FU NIH [K24 DK064545, NIH R01 049302, NIH T32 HD 052961, NIH M01 RR01066,]; Mary Fisher Clinical AIDS Research and Education (CARE) Fund; Theratechnologies; Bristol Myers Squibb FX Supported in part by NIH K24 DK064545, NIH R01 049302, NIH T32 HD 052961, and NIH M01 RR01066, and the Mary Fisher Clinical AIDS Research and Education (CARE) Fund.; The authors' responsibilities were as follows-SG: originated the project and presented the material at the NIH and WHO conference; and KF and SG: reviewed the published literature to provide the structure for the article and wrote, read, and edited the text, including references. The funding sources exercised no influence on the manuscript. SG has received research funding from Theratechnologies and Bristol Myers Squibb and served as a consultant for Theratechnologies and EMD Serono. KF had no disclosures to make. NR 64 TC 9 Z9 9 U1 0 U2 5 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD DEC PY 2011 VL 94 IS 6 BP 1721S EP 1728S DI 10.3945/ajcn.111.012120 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 852PA UT WOS:000297368700049 PM 22089442 ER PT J AU Weiser, SD Young, SL Cohen, CR Kushel, MB Tsai, AC Tien, PC Hatcher, AM Frongillo, EA Bangsberg, DR AF Weiser, Sheri D. Young, Sera L. Cohen, Craig R. Kushel, Margot B. Tsai, Alexander C. Tien, Phyllis C. Hatcher, Abigail M. Frongillo, Edward A. Bangsberg, David R. TI Conceptual framework for understanding the bidirectional links between food insecurity and HIV/AIDS SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-INFECTED INDIVIDUALS; NUTRITION EXAMINATION SURVEY; AIDS-RELATED MORTALITY; RISK-SHARING NETWORKS; INJECTION-DRUG USERS; AGE ADULT MORTALITY; BODY-MASS INDEX; DISEASE PROGRESSION AB Food insecurity, which affects >1 billion people worldwide, is inextricably linked to the HIVepidemic. We present a conceptual framework of the multiple pathways through which food insecurity and HIV/AIDS may be linked at the community, household, and individual levels. Whereas the mechanisms through which HIV/AIDS can cause food insecurity have been fairly well elucidated, the ways in which food insecurity can lead to HIV are less well understood. We argue that there are nutritional, mental health, and behavioral pathways through which food insecurity leads to HIV acquisition and disease progression. Specifically, food insecurity can lead to macronutrient and micronutrient deficiencies, which can affect both vertical and horizontal transmission of HIV, and can also contribute to immunologic decline and increased morbidity and mortality among those already infected. Food insecurity can have mental health consequences, such as depression and increased drug abuse, which, in turn, contribute to HIV transmission risk and incomplete HIV viral load suppression, increased probability of AIDS-defining illness, and AIDS-related mortality among HIV-infected individuals. As a result of the inability to procure food in socially or personally acceptable ways, food insecurity also contributes to risky sexual practices and enhanced HIV transmission, as well as to antiretroviral therapy nonadherence, treatment interruptions, and missed clinic visits, which are strong determinants of worse HIV health outcomes. More research on the relative importance of each of these pathways is warranted because effective interventions to reduce food insecurity and HIV depend on a rigorous understanding of these multifaceted relationships. Am J Clin Nutr 2011;94(suppl):1729S-39S. C1 [Weiser, Sheri D.; Hatcher, Abigail M.] San Francisco Gen Hosp, Div HIV AIDS, San Francisco, CA 94110 USA. [Weiser, Sheri D.; Hatcher, Abigail M.] San Francisco Gen Hosp, Ctr AIDS Prevent Studies, San Francisco, CA 94110 USA. [Kushel, Margot B.] San Francisco Gen Hosp, Div Gen Internal Med, San Francisco, CA 94110 USA. [Young, Sera L.; Cohen, Craig R.; Hatcher, Abigail M.] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA USA. [Tien, Phyllis C.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Tsai, Alexander C.] Harvard Univ, Robert Wood Johnson Hlth & Soc Scholars Program, Cambridge, MA 02138 USA. [Tien, Phyllis C.] San Francisco VA Med Ctr, San Francisco, CA USA. [Frongillo, Edward A.] Univ S Carolina, Arnold Sch Publ Hlth, Dept Hlth Promot Educ & Behav, Columbia, SC 29208 USA. [Young, Sera L.] Cornell Univ, Div Nutrit Sci, Ithaca, NY 14853 USA. [Bangsberg, David R.] Mbarara Univ Sci & Technol, Mbarara, Uganda. [Bangsberg, David R.] Harvard Univ, Sch Med, MIT & Harvard,Ragon Inst MGH, Massachusetts Gen Hosp,Ctr Global Hlth, Cambridge, MA 02138 USA. RP Weiser, SD (reprint author), UCSF, Posit Hlth Program, POB 0874, San Francisco, CA 94143 USA. EM sheri.weiser@ucsf.edu RI Hatcher, Abigail/G-9128-2011; OI Hatcher, Abigail/0000-0002-4150-1405; Tsai, Alexander/0000-0001-6397-7917 FU National Institute of Mental Health (NIMH) [79713-01, 54907, 87227]; University of California, San Francisco, AIDS Research Institute; Burke Global Health Faculty Award; California HIV/AIDS Research Program [ID08-SF-054]; Robert Wood Johnson Health and Society FX Supported by National Institute of Mental Health (NIMH) 79713-01; the University of California, San Francisco, AIDS Research Institute; The Burke Global Health Faculty Award; and the California HIV/AIDS Research Program ID08-SF-054 (SDW); by Robert Wood Johnson Health and Society Scholars Program (ACT); and by NIMH 54907 and NIMH 87227 (DRB). NR 193 TC 83 Z9 83 U1 2 U2 19 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD DEC PY 2011 VL 94 IS 6 BP 1729S EP 1739S DI 10.3945/ajcn.111.012070 PG 11 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 852PA UT WOS:000297368700050 PM 22089434 ER PT J AU Lee, JS Primack, BA Mor, MK Stone, RA Obrosky, DS Yealy, DM Fine, MJ AF Lee, Jonathan S. Primack, Brian A. Mor, Maria K. Stone, Roslyn A. Obrosky, D. Scott Yealy, Donald M. Fine, Michael J. TI Processes of Care and Outcomes for Community-Acquired Pneumonia SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Pneumonia; Processes of care; Quality of care ID CHI-SQUARED TESTS; QUALITY-OF-CARE; MYOCARDIAL-INFARCTION; ELDERLY-PATIENTS; RISK PATIENTS; GUIDELINES; MANAGEMENT; THERAPY; IMPROVEMENT; MORTALITY AB BACKGROUND: Although processes of care are common proxies for health care quality, their associations with medical outcomes remain uncertain. METHODS: For 2076 patients hospitalized with pneumonia from 32 emergency departments, we used multilevel logistic regression modeling to assess independent associations between patient outcomes and the performance of 4 individual processes of care (assessment of oxygenation, blood cultures, and rapid initiation [<4 hours] and appropriate selection of antibiotic therapy) and the cumulative number of processes of care performed. RESULTS: Overall, 141 patients (6.8%) died. Mortality was 0.3% to 1.7% lower for patients who had each of the individual processes of care performed (P >= .13 for each comparison); mortality was 7.5% for patients who had 0 to 2 processes of care, 7.2% for those with 3 processes of care, and 5.8% for those with all 4 processes of care performed (P = .39). Mortality was not significantly associated with either individual or cumulative process measures in multivariable models. CONCLUSION: Neither the individual processes of care nor the cumulative number performed is associated with short-term mortality for pneumonia. Published by Elsevier Inc. The American Journal of Medicine (2011) 124, 1175.e9-1175.e17 C1 [Lee, Jonathan S.; Primack, Brian A.; Fine, Michael J.] Univ Pittsburgh, Sch Med, Dept Med, Div Gen Internal Med, Pittsburgh, PA USA. [Primack, Brian A.; Stone, Roslyn A.; Fine, Michael J.] Univ Pittsburgh, Sch Med, Ctr Res Hlth Care, Pittsburgh, PA USA. [Primack, Brian A.] Univ Pittsburgh, Sch Med, Dept Pediat, Div Adolescent Med, Pittsburgh, PA 15261 USA. [Yealy, Donald M.] Univ Pittsburgh, Sch Med, Dept Emergency Med, Pittsburgh, PA USA. [Mor, Maria K.; Stone, Roslyn A.; Obrosky, D. Scott; Fine, Michael J.] VA Pittsburgh Healthcare Syst, VA Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Mor, Maria K.; Stone, Roslyn A.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. RP Fine, MJ (reprint author), Vet Adm Pittsburgh Healthcare Syst 151 C H, Ctr Hlth Equ Res & Promot, 7180 Highland Dr,Room 4059E, Pittsburgh, PA 15206 USA. EM Michael.Fine@va.gov FU Agency for Healthcare Research and Quality [R01-HS10049]; National Institute of Allergy and Infectious Diseases [K24-AI001769]; Robert Wood Johnson Foundation; National Cancer Institute [K07-CA114315] FX Grant R01-HS10049 from the Agency for Healthcare Research and Quality. Dr Fine was supported in part from a career development award from the National Institute of Allergy and Infectious Diseases (Grant Number K24-AI001769). Dr Primack was supported in part by a Physician Faculty Scholar Award from the Robert Wood Johnson Foundation and a career development award from the National Cancer Institute (K07-CA114315). NR 32 TC 6 Z9 6 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD DEC PY 2011 VL 124 IS 12 AR 1175.e9 DI 10.1016/j.amjmed.2011.05.029 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 853CZ UT WOS:000297405100027 PM 22000624 ER PT J AU Boruta, DM Growdon, WB McCann, CK Garrett, LA del Carmen, MG Goodman, A Schorge, JO AF Boruta, David M., II Growdon, Whitfield B. McCann, Christopher K. Garrett, Leslie A. del Carmen, Marcela G. Goodman, Annekathryn Schorge, John O. TI Evolution of surgical management of early-stage endometrial cancer SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 39th Global Congress of Minimally Invasive Gynecology of the American-Association-of-Gynecologic-Laparoscopists (AAGL) CY NOV 08-12, 2010 CL Las Vegas, NV SP Amer Assoc Gynecol Laparoscopists (AAGL) DE endometrial cancer; laparoscopy; surgical staging ID LYMPHADENECTOMY; HYSTERECTOMY; EXPERIENCE; SURGERY; TRIAL; OBESE AB OBJECTIVE: We sought to examine the evolution of surgical care for early-stage endometrial cancers and factors affecting use of laparoscopy. STUDY DESIGN: Women with surgically managed early-stage endometrial cancer were divided into 2 groups corresponding to before and after addition of faculty with formal fellowship training in laparoscopic staging and access to a robotic surgery platform. RESULTS: In all, 502 women were identified. Laparoscopic management increased from 24-69% between time periods (P < .0001). Performance of comprehensive surgical staging, and lymph node counts, increased (P < .0001) despite an increase in median body mass index (P = .001). A traditional "straight stick" technique was performed in 72% of laparoscopic cases during the later period. Laparoscopy patients had lower estimated blood losses and shorter hospital stays (each P < .0001) compared to laparotomy patients. CONCLUSION: Addition of faculty with formal fellowship training in laparoscopic staging and access to a robotic surgery platform shifted management of early-stage endometrial cancer toward laparoscopy. C1 [Boruta, David M., II] Massachusetts Gen Hosp, Vincent Obstet & Gynecol Serv, Gillette Ctr Gynecol Oncol, Div Gynecol Oncol,Dept Obstet & Gynecol,Yawkey Ct, Boston, MA 02114 USA. RP Boruta, DM (reprint author), Massachusetts Gen Hosp, Vincent Obstet & Gynecol Serv, Gillette Ctr Gynecol Oncol, Div Gynecol Oncol,Dept Obstet & Gynecol,Yawkey Ct, Suite 9E,55 Fruit St, Boston, MA 02114 USA. EM dboruta@partners.org NR 25 TC 2 Z9 2 U1 1 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2011 VL 205 IS 6 AR 565.e1 DI 10.1016/j.ajog.2011.06.081 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 852DR UT WOS:000297329200031 PM 21855843 ER PT J AU Berquist, TH Uppot, RN AF Berquist, Thomas H. Uppot, Raul N. TI Preview of 2012 SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Editorial Material ID ONLINE; IPAD; PRINT; FUTURE C1 [Berquist, Thomas H.; Uppot, Raul N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Berquist, TH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. EM ajrsubmit@arrs.org; ruppot@partners.org NR 18 TC 1 Z9 1 U1 0 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD DEC PY 2011 VL 197 IS 6 BP 1283 EP 1284 DI 10.2214/AJR.11.7843 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 852PM UT WOS:000297369900037 ER PT J AU Javery, O Krajewski, K O'Regan, K Kis, B Giardino, A Jagannathan, J Ramaiya, NH AF Javery, Omar Krajewski, Katherine O'Regan, Kevin Kis, Bela Giardino, Angela Jagannathan, Jyothi Ramaiya, Nikhil H. TI A to Z of Extraskeletal Ewing Sarcoma Family of Tumors in Adults: Imaging Features of Primary Disease, Metastatic Patterns, and Treatment Responses SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE adults; Ewing sarcoma; extraskeletal disease; primitive neuroectodermal tumor ID PRIMITIVE NEUROECTODERMAL TUMORS; SINGLE INSTITUTION; CT AB OBJECTIVE. Though classically thought of as an osseous-based sarcoma of children and adolescents, it is important to recognize that approximately 20% of all cases of Ewing sarcoma family of tumors (ESFT) occur in patients older than 18 years, often with extraskeletal disease. Understanding the specific imaging features, manners of presentation, and patterns of behavior of ESFT is therefore important in all settings. CONCLUSION. This article presents the imaging findings of ESFT in the adult, with specific attention to extraskeletal manifestations. C1 [Javery, Omar; Kis, Bela] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Krajewski, Katherine; O'Regan, Kevin; Giardino, Angela; Jagannathan, Jyothi; Ramaiya, Nikhil H.] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. RP Javery, O (reprint author), Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. EM ojavery@partners.org NR 15 TC 17 Z9 18 U1 1 U2 5 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD DEC PY 2011 VL 197 IS 6 BP W1015 EP W1022 DI 10.2214/AJR.11.6667 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 852PM UT WOS:000297369900008 PM 22109315 ER PT J AU Shinagare, AB Giardino, AA Jagannathan, JP Van den Abbeele, AD Ramaiya, NH AF Shinagare, Atul B. Giardino, Angela A. Jagannathan, Jyothi P. Van den Abbeele, Annick D. Ramaiya, Nikhil H. TI Hereditary Cancer Syndromes: A Radiologist's Perspective SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE colorectal cancer; familial adenomatous polyposis; hereditary cancer syndromes; Li-Fraumeni cancer syndrome; multiple endocrine neoplasia; neurofibromatosis; von Hippel-Lindau syndrome ID EMISSION TOMOGRAPHY/COMPUTED TOMOGRAPHY; COLORECTAL-CANCER; DESMOID TUMORS; APPEARANCES; FAMILY AB OBJECTIVE. The purpose of this article is to present the important malignancies associated with the most common hereditary cancer syndromes. CONCLUSION. Hereditary cancer syndromes comprise 5% of all cancers and have an increased risk of early onset and of multiple or bilateral malignancies. Radiologists should be familiar with various hereditary cancer syndromes and their common associations because early detection of these neoplasms may help decrease patient morbidity and mortality. C1 [Shinagare, Atul B.; Giardino, Angela A.; Jagannathan, Jyothi P.; Van den Abbeele, Annick D.; Ramaiya, Nikhil H.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Imaging, Boston, MA 02215 USA. [Shinagare, Atul B.; Giardino, Angela A.; Jagannathan, Jyothi P.; Van den Abbeele, Annick D.; Ramaiya, Nikhil H.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02215 USA. RP Shinagare, AB (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02215 USA. EM ashinagare@partners.org NR 12 TC 5 Z9 6 U1 0 U2 4 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD DEC PY 2011 VL 197 IS 6 BP W1001 EP W1007 DI 10.2214/AJR.11.6465 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 852PM UT WOS:000297369900006 PM 22109313 ER PT J AU Shinagare, AB Ramaiya, NH Jagannathan, JP Krajewski, KM Giardino, AA Butrynski, JE Raut, CP AF Shinagare, Atul B. Ramaiya, Nikhil H. Jagannathan, Jyothi P. Krajewski, Katherine M. Giardino, Angela A. Butrynski, James E. Raut, Chandrajit P. TI A to Z of Desmoid Tumors SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE complications; deep fibromatosis; desmoid tumors; extraabdominal desmoids; treatment-related changes ID FIBROMATOSIS; THERAPY; FEATURES AB OBJECTIVE. The purpose of this article is to illustrate the common locations of desmoid tumors (deep fibromatosis), complications of intra-and extraabdominal desmoids, and treatment-related changes in their imaging appearance. CONCLUSION. Desmoids are locally aggressive fibrous tumors with a tendency to recur. Desmoids can be intraabdominal, in the abdominal wall, or extraabdominal. Complications, such as compression or invasion of adjacent structures, and abscess formation can occur. Treatment options include observation, local treatment (surgery, radiotherapy), or systemic therapy (conventional chemotherapy, molecular targeted agents). C1 [Shinagare, Atul B.; Ramaiya, Nikhil H.; Jagannathan, Jyothi P.; Krajewski, Katherine M.; Giardino, Angela A.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Imaging, Boston, MA 02215 USA. [Shinagare, Atul B.; Ramaiya, Nikhil H.; Jagannathan, Jyothi P.; Krajewski, Katherine M.; Giardino, Angela A.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02215 USA. [Butrynski, James E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Raut, Chandrajit P.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Shinagare, AB (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02215 USA. EM ashinagare@partners.org NR 16 TC 20 Z9 20 U1 1 U2 6 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD DEC PY 2011 VL 197 IS 6 BP W1008 EP W1014 DI 10.2214/AJR.11.6657 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 852PM UT WOS:000297369900007 PM 22109314 ER PT J AU Zhang, J Dong, YL Xu, ZP Zhang, YY Pan, CX McAuliffe, S Ichinose, F Yue, Y Liang, WM Xie, ZC AF Zhang, Jun Dong, Yuanlin Xu, Zhipeng Zhang, Yiying Pan, Chuxiong McAuliffe, Sayre Ichinose, Fumito Yue, Yun Liang, Weimin Xie, Zhongcong TI 2-Deoxy-D-Glucose Attenuates Isoflurane-Induced Cytotoxicity in an In Vitro Cell Culture Model of H4 Human Neuroglioma Cells SO ANESTHESIA AND ANALGESIA LA English DT Article ID AMYLOID PROTEIN-LEVELS; ALZHEIMERS-DISEASE; CASPASE ACTIVATION; INDUCED APOPTOSIS; OXIDATIVE STRESS; TRANSGENIC MICE; BETA-PEPTIDE; ANESTHESIA; EXPOSURE; NEUROTOXICITY AB BACKGROUND: beta-Amyloid protein (A beta) accumulation and caspase activation have been shown to contribute to Alzheimer disease neuropathogenesis. A beta is produced from amyloid precursor protein through proteolytic processing by aspartyl protease beta-site amyloid precursor protein-cleaving enzyme (BACE). The inhaled anesthetic isoflurane has been shown to induce caspase activation and increase levels of BACE and A beta. However, the underlying mechanisms and interventions of the isoflurane-induced neurotoxicity remain largely to be determined. The glucose analog 2-deoxy-D-glucose (2-DG) has neuroprotective effects. Therefore, we sought to determine whether 2-DG can reduce caspase-3 activation and the increase in the levels of BACE and reactive oxygen species (ROS) induced by isoflurane. METHODS: H4 human neuroglioma cells were treated with saline or 2-DG (5 mM) for 1 hour followed by a control condition or 2% isoflurane for 6 hours. The levels of caspase-3 cleavage (activation), BACE, cytosolic calcium, and ROS were determined. Two-way analysis of variance was used to assess the interactions of 2-DG and isoflurane on caspase-3 activation, and levels of BACE and ROS. RESULTS: In H4 human neuroglioma cells, 2-DG reduced the caspase-3 activation (477% vs 186%, F = 8.68; P = 0.019) and the increase in BACE levels (345% vs 123%, F = 42.24; P = 0.0002) induced by isoflurane. 2-DG decreased the levels of cytosolic calcium and ROS (100% vs 66%, F = 1.94; P = 0.014). CONCLUSIONS: These results suggest that 2-DG may decrease oxidative stress and increase cytosolic calcium levels, thus attenuating isoflurane-induced neurotoxicity. (Anesth Analg 2011;113:1468-75) C1 [Xie, Zhongcong] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Geriatr Anesthesia Res Unit, Charlestown, MA 02129 USA. [Ichinose, Fumito] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Yue, Yun] Capital Med Univ, Beijing Chaoyang Hosp, Dept Anesthesia, Beijing, Peoples R China. [Liang, Weimin] Fudan Univ, Huashan Hosp, Dept Anesthesiol, Shanghai 200433, Peoples R China. RP Xie, ZC (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Geriatr Anesthesia Res Unit, 149 13th St,Room 4310, Charlestown, MA 02129 USA. EM zxie@partners.org FU National Institutes of Health [K08NS048140, R21AG029856, R01 GM088801, R01GM079360]; American Geriatrics Society; Alzheimer's Association; China National Science Foundation [NSF30928026] FX Supported by K08NS048140, R21AG029856, and R01 GM088801 (National Institutes of Health), Jahnigen Career Development Award (American Geriatrics Society), Investigator Initiated Research Grant (Alzheimer's Association) (to ZX), R01GM079360 (National Institutes of Health) (to FI), and China National Science Foundation Overseas Young Scholar Collaboration Research Award NSF30928026 (to YY and ZX). NR 41 TC 10 Z9 11 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD DEC PY 2011 VL 113 IS 6 BP 1468 EP 1475 DI 10.1213/ANE.0b013e31822e913c PG 8 WC Anesthesiology SC Anesthesiology GA 852RP UT WOS:000297375500028 PM 21965367 ER PT J AU Wu, Y Amonkar, MM Sherrill, BH O'Shaughnessy, J Ellis, C Baselga, J Blackwell, KL Burstein, HJ AF Wu, Y. Amonkar, M. M. Sherrill, B. H. O'Shaughnessy, J. Ellis, C. Baselga, J. Blackwell, K. L. Burstein, H. J. TI Impact of lapatinib plus trastuzumab versus single-agent lapatinib on quality of life of patients with trastuzumab-refractory HER2+metastatic breast cancer SO ANNALS OF ONCOLOGY LA English DT Article DE breast cancer; health-related quality of life; HER2; lapatinib; metastatic; trastuzumab ID 1ST-LINE TREATMENT; PHASE-II; THERAPY; COMBINATION; MONOTHERAPY; SURVIVAL; PROGRESSION; PACLITAXEL; SAFETY AB Background: Progression-free survival (PFS) was significantly longer for the lapatinib plus trastuzumab (L+T) arm than for L alone in a phase III, randomized, open-label study of women with human epidermal growth factor receptor 2 positive metastatic breast cancer who had documented progression on at least one T-containing regimen in the metastatic setting. This analysis focused on impact of treatments on health-related quality of life (HRQOL). Methods: HRQOL was assessed using the Functional Assessment of Cancer Therapy-Breast (FACT-B) questionnaire. Changes from baseline and time to deterioration were analyzed in the intent-to-treat population. Results: Differences between the treatment arms in adjusted mean change from baseline favored the L+T arm, ranging from 0.0 to 4.1 (FACT-B), 1.0-4.0 [Functional Assessment of Cancer Therapy-General (FACT-G)], and 0.5-2.7 (Trial Outcome Index). Most differences were not statistically significant, except for FACT-G at week 12 (delta = 4.0, P = 0.037). Similar results were found in a sensitivity analysis that included HRQOL records up to patient withdrawal from original randomized treatment. The longer time to HRQOL deterioration in the L+T arm was not statistically significant (FACT-B hazard ratio, 0.82; 95% confidence interval 0.56-1.20). Conclusion: The addition of lapatinib to trastuzumab prolonged PFS while improving or maintaining near-term HRQOL, suggesting a meaningful clinical benefit to patients. C1 [Wu, Y.; Sherrill, B. H.] Res Triangle Inst Hlth Solut, Biometr Dept, Res Triangle Pk, NC 27709 USA. [Amonkar, M. M.; Ellis, C.] GlaxoSmithKline Inc, Global Hlth Outcomes, Oncol, Collegeville, PA USA. [O'Shaughnessy, J.] US Oncol, Baylor Sammons Canc Ctr, Texas Oncol, Dallas, TX USA. [Baselga, J.] Vall dHebron Univ Hosp, Med Oncol Serv, Barcelona, Spain. [Blackwell, K. L.] Duke Univ, Med Ctr, Durham, NC 27706 USA. [Burstein, H. J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Wu, Y (reprint author), Res Triangle Inst Hlth Solut, Biometr Dept, 3040 Cornwallis Rd,POB 12194, Res Triangle Pk, NC 27709 USA. EM ywu@rti.org FU GSK FX This work and the EGF104900 study were supported by GSK. NR 25 TC 14 Z9 15 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD DEC PY 2011 VL 22 IS 12 BP 2582 EP 2590 DI 10.1093/annonc/mdr014 PG 9 WC Oncology SC Oncology GA 852IR UT WOS:000297351700008 PM 21406472 ER PT J AU Sequist, LV Heist, RS Shaw, AT Fidias, P Rosovsky, R Temel, JS Lennes, IT Digumarthy, S Waltman, BA Bast, E Tammireddy, S Morrissey, L Muzikansky, A Goldberg, SB Gainor, J Channick, CL Wain, JC Gaissert, H Donahue, DM Muniappan, A Wright, C Willers, H Mathisen, DJ Choi, NC Baselga, J Lynch, TJ Ellisen, LW Mino-Kenudson, M Lanuti, M Borger, DR Iafrate, AJ Engelman, JA Dias-Santagata, D AF Sequist, L. V. Heist, R. S. Shaw, A. T. Fidias, P. Rosovsky, R. Temel, J. S. Lennes, I. T. Digumarthy, S. Waltman, B. A. Bast, E. Tammireddy, S. Morrissey, L. Muzikansky, A. Goldberg, S. B. Gainor, J. Channick, C. L. Wain, J. C. Gaissert, H. Donahue, D. M. Muniappan, A. Wright, C. Willers, H. Mathisen, D. J. Choi, N. C. Baselga, J. Lynch, T. J. Ellisen, L. W. Mino-Kenudson, M. Lanuti, M. Borger, D. R. Iafrate, A. J. Engelman, J. A. Dias-Santagata, D. TI Implementing multiplexed genotyping of non-small-cell lung cancers into routine clinical practice SO ANNALS OF ONCOLOGY LA English DT Article DE carcinoma; non-small cell; genotype; molecular targeted therapy ID NEVER-SMOKERS; SOMATIC MUTATIONS; MYELOID-LEUKEMIA; KRAS MUTATIONS; BETA-CATENIN; PHASE-III; GEFITINIB; GENE; ADENOCARCINOMA; CHEMOTHERAPY AB Background: Personalizing non-small-cell lung cancer (NSCLC) therapy toward oncogene addicted pathway inhibition is effective. Hence, the ability to determine a more comprehensive genotype for each case is becoming essential to optimal cancer care. Methods: We developed a multiplexed PCR-based assay (SNaPshot) to simultaneously identify > 50 mutations in several key NSCLC genes. SNaPshot and FISH for ALK translocations were integrated into routine practice as Clinical Laboratory Improvement Amendments-certified tests. Here, we present analyses of the first 589 patients referred for genotyping. Results: Pathologic prescreening identified 552 (95%) tumors with sufficient tissue for SNaPshot; 51% had >= 1 mutation identified, most commonly in KRAS (24%), EGFR (13%), PIK3CA (4%) and translocations involving ALK (5%). Unanticipated mutations were observed at lower frequencies in IDH and beta-catenin. We observed several associations between genotypes and clinical characteristics, including increased PIK3CA mutations in squamous cell cancers. Genotyping distinguished multiple primary cancers from metastatic disease and steered 78 (22%) of the 353 patients with advanced disease toward a genotype-directed targeted therapy. Conclusions: Broad genotyping can be efficiently incorporated into an NSCLC clinic and has great utility in influencing treatment decisions and directing patients toward relevant clinical trials. As more targeted therapies are developed, such multiplexed molecular testing will become a standard part of practice. C1 [Sequist, L. V.; Heist, R. S.; Shaw, A. T.; Fidias, P.; Rosovsky, R.; Temel, J. S.; Lennes, I. T.; Bast, E.; Tammireddy, S.; Morrissey, L.; Goldberg, S. B.; Baselga, J.; Ellisen, L. W.; Borger, D. R.; Engelman, J. A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Sequist, L. V.; Heist, R. S.; Shaw, A. T.; Fidias, P.; Rosovsky, R.; Temel, J. S.; Lennes, I. T.; Digumarthy, S.; Waltman, B. A.; Muzikansky, A.; Goldberg, S. B.; Gainor, J.; Channick, C. L.; Wain, J. C.; Gaissert, H.; Donahue, D. M.; Muniappan, A.; Wright, C.; Willers, H.; Mathisen, D. J.; Choi, N. C.; Baselga, J.; Ellisen, L. W.; Mino-Kenudson, M.; Lanuti, M.; Borger, D. R.; Iafrate, A. J.; Engelman, J. A.; Dias-Santagata, D.] Harvard Univ, Sch Med, Boston, MA USA. [Digumarthy, S.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Muzikansky, A.] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. [Gainor, J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Channick, C. L.] Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA. [Wain, J. C.; Gaissert, H.; Donahue, D. M.; Muniappan, A.; Wright, C.; Mathisen, D. J.; Lanuti, M.] Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. [Willers, H.; Choi, N. C.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Lynch, T. J.] Yale Univ, Sch Med, New Haven, CT USA. [Lynch, T. J.] Yale Canc Ctr, New Haven, CT USA. [Mino-Kenudson, M.; Iafrate, A. J.; Dias-Santagata, D.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Sequist, LV (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,Profess Off Bldg Room 212, Boston, MA 02114 USA. EM lvsequist@partners.org; ddiassantagata@partners.org FU NCI NIH HHS [P50 CA090578, P50 CA090578-09] NR 42 TC 175 Z9 179 U1 1 U2 13 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD DEC PY 2011 VL 22 IS 12 BP 2616 EP 2624 DI 10.1093/annonc/mdr489 PG 9 WC Oncology SC Oncology GA 852IR UT WOS:000297351700013 PM 22071650 ER PT J AU Ruhnke, GW Warshaw, AL AF Ruhnke, Gregory W. Warshaw, Andrew L. TI A Most Unusual Patient at the Massachusetts General Hospital SO ANNALS OF SURGERY LA English DT Article ID CARMINE AB This year marks 200 years of patient care at the Massachusetts General Hospital (MGH). In celebration of this milestone, a unique Grand Rounds case is presented. A 450-year-old rotund man admitted 60 times presents with a classic triad of periumbilical pain, bilateral plantar burns, and a frozen scalp. Although this triad may at first strike a cord of familiarity among seasoned clinicians, the disease mechanism is truly noteworthy, being clarified only after a detailed occupational history. Ergo, the lessons hark back to the days of yesteryear, when the history and physical served as the cornerstone of Yuletide clinical diagnosis. A discussion of epidemiology and prognosis accompanies a detailed examination of the pathophysiholiday. Although some consider this patient uncouth, as you will see, he is quite a medical sleuth. The long-standing relationship between this patient and the MGH prompted his family to write a letter of appreciation, which will remind the reader of the meaning that our care brings to patients and their families. Harvey Cushing, who completed his internship at the MGH in 1895, professed "A physician is obligated to consider more than a diseased organ, more even than the whole man-he must view the man in his world." We hope this unusual Grand Rounds case intrigues you as it reminds you of Cushing's lesson and wishes you a joyous holiday season. C1 [Ruhnke, Gregory W.] Univ Chicago, Med Ctr, Dept Med, Chicago, IL 60637 USA. [Warshaw, Andrew L.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Warshaw, Andrew L.] Harvard Univ, Sch Med, Boston, MA USA. RP Ruhnke, GW (reprint author), Univ Chicago, Med Ctr, Dept Med, 5841 S Maryland Ave,MC 5000, Chicago, IL 60637 USA. EM gruhnke@medicine.bsd.uchicago.edu FU University of Chicago FX Supported by Gregory Ruhnke's development funds at the University of Chicago for travel to Boston for data collection. No funding was received from any other organization. NR 9 TC 0 Z9 0 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD DEC PY 2011 VL 254 IS 6 BP 845 EP 849 DI 10.1097/SLA.0b013e31823a9a36 PG 5 WC Surgery SC Surgery GA 852RM UT WOS:000297375200001 PM 22107737 ER PT J AU Finlayson, E Wang, L Landefeld, CS Dudley, RA AF Finlayson, Emily Wang, Li Landefeld, C. Seth Dudley, R. Adams TI Major Abdominal Surgery in Nursing Home Residents A National Study SO ANNALS OF SURGERY LA English DT Article ID ACUTE APPENDICITIS; SURGICAL OUTCOMES; OLDER; OCTOGENARIANS; CANCER AB Objective: To determine surgical risk in nursing home residents undergoing major abdominal surgery. Background: Recent studies suggest that surgery can be performed safely in the very old. Surgical risk in nursing home residents is poorly understood. Methods: We used national Medicare claims and the nursing home Minimum Data Set (1999-2006) to identify nursing home residents undergoing surgery (surgery for bleeding duodenal ulcer, cholecystectomy, appendectomy, and colectomy, n = 70,719). We compared operative mortality and use of invasive interventions (mechanical ventilation, intravascular hemodynamic monitoring, feeding tube placement, tracheostomy, and vena cava filters) among nursing home residents to rates among noninstitutionalized Medicare enrollees age 65 and older undergoing the same procedures. (n = 1,060,389). We adjusted for patient characteristics using logistic regression. Results: Operative mortality among nursing home residents was substantially higher than among noninstitutionalized Medicare enrollees for all procedures (surgery for bleeding duodenal ulcer, 42% versus 26%, adjusted odds ratio (AOR) 1.79; colectomy, 32% versus 13%, AOR 2.06; appendectomy, 12% versus 2%, AOR 3.27; cholecystectomy, 11% versus 3%, AOR 2.65; P < 0.001 for all comparisons). Overall, invasive interventions were more common among nursing home residents than controls (ranging from 18% and 5%, respectively, for cholecystectomy to 55% and 43%, respectively, for surgery for bleeding duodenal ulcer, P < 0.0001 for all comparisons). Conclusions: Nursing home residents experience substantially higher rates of mortality and invasive interventions after major surgery than other Medicare beneficiaries that are independent of age and measured comorbidities. Our data suggest that the risks of major surgery are substantially higher in nursing home residents and this information should inform decisions of physicians and patients and their families. C1 [Finlayson, Emily; Dudley, R. Adams] Univ Calif San Francisco, Philip R Lee Inst Hlth Policy Studies, San Francisco, CA 94118 USA. [Finlayson, Emily] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94118 USA. [Wang, Li] StatinMed, Ann Arbor, MI USA. [Landefeld, C. Seth] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94118 USA. [Landefeld, C. Seth] San Francisco VA Med Ctr, San Francisco, CA USA. [Dudley, R. Adams] Univ Calif San Francisco, Dept Med, San Francisco, CA 94118 USA. RP Finlayson, E (reprint author), Univ Calif San Francisco, Philip R Lee Inst Hlth Policy Studies, 3333 Calif St,Suite 265, San Francisco, CA 94118 USA. EM emily.finlayson@ucsfmedctr.org FU National Institute on Aging [5K08AG028965]; Robert Wood Johnson Foundation FX Supported by a National Institute on Aging/Paul B. Beeson Clinical Scientist Development Award in Aging (5K08AG028965). Dr. Dudley's work was supported by an Investigator Award in Health Policy from the Robert Wood Johnson Foundation. NR 15 TC 14 Z9 14 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD DEC PY 2011 VL 254 IS 6 BP 921 EP 926 DI 10.1097/SLA.0b013e3182383a78 PG 6 WC Surgery SC Surgery GA 852RM UT WOS:000297375200013 PM 22020197 ER PT J AU Genevay, M Mino-Kenudson, M Yaeger, K Konstantinidis, IT Ferrone, CR Thayer, S Fernandez-del Castillo, C Sahani, D Bounds, B Forcione, D Brugge, WR Pitman, MB AF Genevay, Muriel Mino-Kenudson, Mari Yaeger, Kurt Konstantinidis, Ioannis T. Ferrone, Cristina R. Thayer, Sarah Fernandez-del Castillo, Carlos Sahani, Dushyant Bounds, Brenna Forcione, David Brugge, William R. Pitman, Martha Bishop TI Cytology Adds Value to Imaging Studies for Risk Assessment of Malignancy in Pancreatic Mucinous Cysts SO ANNALS OF SURGERY LA English DT Article ID FINE-NEEDLE-ASPIRATION; ENDOSCOPIC ULTRASOUND; CLINICOPATHOLOGICAL CHARACTERISTICS; SYMPTOMATIC PATIENTS; SEROUS-CYSTADENOMA; FLUID ANALYSIS; NEOPLASMS; MANAGEMENT; LESIONS; DIAGNOSIS AB Objective: Evaluate the value of cytology relative to imaging features in risk assessment for malignancy as defined in the Sendai Guidelines. Background: The Sendai Guidelines list symptoms, cyst size > 30 mm, dilated main pancreatic duct (MPD) > 6 mm, mural nodule (MN) and "positive" cytology as high risk stigmata for malignancy warranting surgical triage. Methods: We reviewed clinical, radiological and cytological data of 112 patients with histologically confirmed mucinous cysts of the pancreas evaluated in a single tertiary medical center. Cytology slides were blindly rereviewed and epithelial cells grouped as either benign or high-grade atypia (HGA) [>= high-grade dysplasia]. Histologically, neoplasms were grouped as benign (low-grade and moderate dysplasia) and malignant (in situ and invasive carcinoma). Performance characteristics of cytology relative to other risk factors were evaluated. Results: Dilated MPD, MN, and HGA were independent predictors of malignancy (p < 0.0001), but not symptoms (p = 0.29) or cyst size > 30 mm (p = 0.51). HGA was the most sensitive predictor of malignancy in all cysts (72%) and in small (<= 30 mm) branch-duct intraductal papillary mucinous neoplasm (BD IPMN; 67%), whereas also being specific (85 and 88%, respectively). MN and dilated MPD were highly specific (> 90%), but insensitive (39%-44%). Cytology detected 30% more cancers in small cysts than dilated MPD or MN and half of the cancers without either of these high-risk imaging features. Conclusions: Cytology adds value to the radiological assessment of predicting malignancy in mucinous cysts, particularly in small BD IPMN. C1 [Genevay, Muriel; Mino-Kenudson, Mari; Yaeger, Kurt; Pitman, Martha Bishop] Harvard Univ, Dept Pathol, James Homer Wright Labs, Massachusetts Gen Hosp,Sch Med, Boston, MA 02114 USA. [Konstantinidis, Ioannis T.; Ferrone, Cristina R.; Thayer, Sarah; Fernandez-del Castillo, Carlos] Harvard Univ, Dept Surg, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Sahani, Dushyant] Harvard Univ, Dept Radiol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Bounds, Brenna; Forcione, David; Brugge, William R.] Harvard Univ, Div Gastroenterol, Massachusetts Gen Hosp, Sch Med,Dept Med, Boston, MA 02114 USA. RP Pitman, MB (reprint author), Harvard Univ, Dept Pathol, James Homer Wright Labs, Massachusetts Gen Hosp,Sch Med, Warren 105-D,55 Fruit St, Boston, MA 02114 USA. EM mpitman@partners.org FU Foundation pour la Recherche Nuovo-Soldati FX Dr. Genevay was a visiting fellow from the Service of Clinical Pathology, University Hospitals of Geneva and supported by the Foundation pour la Recherche Nuovo-Soldati. NR 61 TC 60 Z9 63 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD DEC PY 2011 VL 254 IS 6 BP 977 EP 983 DI 10.1097/SLA.0b013e3182383118 PG 7 WC Surgery SC Surgery GA 852RM UT WOS:000297375200022 PM 22041510 ER PT J AU Goldfarb, M Perry, Z Hodin, RA Parangi, S AF Goldfarb, Melanie Perry, Zvi Hodin, Richard A. Parangi, Sareh TI Medical and Surgical Risks in Thyroid Surgery: Lessons from the NSQIP SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID GENERAL-ANESTHESIA; COMPLICATIONS; OUTCOMES; PARATHYROIDECTOMY; MANAGEMENT; PATIENT; DISEASE; SAFETY; COST AB To assess whether perioperative surgical outcomes associated with thyroid operations were different in those with benign or malignant conditions, we queried the NSQIP, a multi-institutional, risk-adjusted, prospective U.S. database. A total of 10,838 patients who underwent initial thyroid surgery as their principal operation during 2005-2007 were analyzed. Analysis focused on demographics, preoperative risk factors, operative details, postoperative complications, return to the operating room, and length of surgical stay. Thirty-three percent of patients had a postoperative diagnosis of malignancy. Mean operating time was 121.8 min (119.3 min benign, 123.0 min malignant, P = .004) and average length of stay 1.16 days (1.12 days benign, vs. 1.21 days malignant, P = .007). Overall morbidity (return to the operating room plus medical complications) was 3.8% for the entire cohort, significantly higher in patients with malignant disease (4.9 vs. 3.3%, respectively, P < .001). On multivariate analysis, American Society of Anesthesiologists class, congestive heart failure (odds ratio [OR] 6.83, 95% confidence interval [CI] 1.81-25.80), dyspnea, and return to the operating room (OR 5.41, 95% CI 3.1-9.45) were significant risk factors for complications, while malignant disease (OR 2.25, 95% CI 1.75-2.9), outpatient status (OR 3.16, 95% CI 2.4-4.17), and other complications (OR 6.46, 95% CI 3.61-11.54) were risk factors for returning to the operating room. Patients undergoing thyroid surgery for malignancy have a longer length of stay (1.21 days), longer operation times, and return to the operating room at higher rates compared to those with benign disease. Malignancy itself is only an independent risk factor for return to the operating room and not other complications; surgeons may consider keeping those patients overnight for observation. C1 [Goldfarb, Melanie] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Goldfarb, Melanie] Univ So Calif, Keck Sch Med, Div Breast Endocrine & Soft Tissue Surg, Los Angeles, CA 90033 USA. [Hodin, Richard A.; Parangi, Sareh] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Endocrine Surg,Thyroid Canc Res Lab, Boston, MA USA. [Perry, Zvi] Tufts Med Ctr, Surg Res Lab, Boston, MA USA. RP Goldfarb, M (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. EM Melanie.Goldfarb@med.usc.edu OI Perry, Zvi/0000-0002-1131-5230 NR 30 TC 9 Z9 10 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD DEC PY 2011 VL 18 IS 13 BP 3551 EP 3558 DI 10.1245/s10434-011-1938-2 PG 8 WC Oncology; Surgery SC Oncology; Surgery GA 852LH UT WOS:000297358900006 PM 21769463 ER PT J AU Coopey, S Smith, BL Hanson, S Buckley, J Hughes, KS Gadd, M Specht, MC AF Coopey, Suzanne Smith, Barbara L. Hanson, Stephanie Buckley, Julliette Hughes, Kevin S. Gadd, Michele Specht, Michelle C. TI The Safety of Multiple Re-excisions after Lumpectomy for Breast Cancer SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID SURGICAL MARGIN STATUS; 20-YEAR FOLLOW-UP; CONSERVING SURGERY; CONSERVATION SURGERY; POSITIVE MARGINS; LOCAL RECURRENCE; SYSTEMIC THERAPY; RESIDUAL DISEASE; MASTECTOMY; PREDICTORS AB Background. Breast cancer patients may undergo multiple re-excisions after lumpectomy in an attempt to obtain clear margins and avoid mastectomy. We sought to determine the overall local recurrence rate and surgical outcome of patients undergoing two or more re-excisions and to identify predictors of success in attaining clear margins. Methods. Retrospective review of breast cancer patients who underwent lumpectomy for invasive cancer or ductal carcinoma in situ (DCIS) from 1997 to 2007. Patients who underwent two or more re-excisions were identified and analyzed. Results. We identified 3,737 patients who underwent lumpectomy over this 10-year period. 875 (23.4%) had close or positive margins requiring a second procedure; 797 (91.1%) had a re-excision; and 78 (8.9%) went directly to mastectomy. Seventy patients underwent multiple re-excisions; 66 patients had 2 re-excisions, 3 patients had 3 re-excisions, and 1 patient had 4 re-excisions. 70% (49/70) of multiple re-excision patients achieved clear margins (26 DCIS, 35 T1, 8 T2, and 1 T3 tumors). All 49 patients who successfully treated with multiple re-excisions received radiation. At a median follow-up of 64 months, 1 of 49 (2.0%) patients had an in-breast recurrence, and 1 of 49 (2.0%) patients had a distant recurrence. Statistically significant risk factors for persistently involved margins after two re-excisions included multifocality and positive lymph node status. Conclusion. Multiple re-excisions to obtain clear margins are a safe alternative to mastectomy for women with invasive cancer or DCIS. There is an acceptably low risk of local and systemic failure when negative margins are ultimately achieved. C1 [Coopey, Suzanne; Smith, Barbara L.; Hanson, Stephanie; Buckley, Julliette; Hughes, Kevin S.; Gadd, Michele; Specht, Michelle C.] Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02114 USA. RP Coopey, S (reprint author), Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02114 USA. EM scoopey@partners.org OI Hughes, Kevin/0000-0003-4084-6484 NR 19 TC 21 Z9 21 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD DEC PY 2011 VL 18 IS 13 BP 3797 EP 3801 DI 10.1245/s10434-011-1802-4 PG 5 WC Oncology; Surgery SC Oncology; Surgery GA 852LH UT WOS:000297358900041 PM 21630123 ER PT J AU Pascual-Figal, DA Garrido, IP Blanco, R Minguela, A Lax, A Ordonez-Llanos, J Bayes-Genis, A Valdes, M Moore, SA Januzzi, JL AF Pascual-Figal, Domingo A. Garrido, Iris P. Blanco, Rosa Minguela, Alfredo Lax, Antonio Ordonez-Llanos, Jordi Bayes-Genis, Antoni Valdes, Mariano Moore, Stephanie A. Januzzi, James L. TI Soluble ST2 Is a Marker for Acute Cardiac Allograft Rejection SO ANNALS OF THORACIC SURGERY LA English DT Article ID RECEPTOR FAMILY-MEMBER; NATRIURETIC PEPTIDE LEVELS; MYOCARDIAL-INFARCTION; HEART-FAILURE; SERUM-LEVELS; EXPRESSION; TRANSPLANTATION; MORTALITY; SURVEILLANCE; RECIPIENTS AB Background. Soluble ST2 (sST2), an interleukin (IL)-1 receptor family member, has a role in immunologic tolerance and has also emerged as a biomarker of cardiac stretch and remodeling. The sST2 role in heart transplantation is still unknown. Methods. From the heart transplantation population at our institution (n = 74), we selected a subset of 26 patients who had an acute rejection episode in the first year after transplantation (35%; 52 +/- 14 years; 76% men). Endomyocardial biopsy (EMB) results obtained at the time of the first rejection episode represented the rejection cohort (n = 26). Each patient served as a control to himself or herself, with EMB without rejection obtained before and after the rejection episode (n = 52). All laboratory measurements and blood samples were obtained at the time of EMB. Results. sST2 concentrations rose significantly in the context of acute rejection (130 [60 to 238] versus 51 ng/mL [28 to 80]; p = 0.002). Tertile analyses of sST2 concentrations revealed a graded association with rejection (p = 0.002) and repeated measurement analyses showed that sST2 concentrations were significantly modulated by the presence of rejection (p = 0.001). In receiver operator characteristic (ROC) analysis, sST2 had an area under the curve (AUC) of 0.72; the optimal cutoff point was 68 ng/mL (positive predictive value of 53%, negative predictive value of 83%), which predicted acute cellular rejection (odds ratio [OR] 4.9; 95% confidence interval [CI], 1.7 to 14.5; p = 0.004). The addition of sST2 values to those for the N-terminal pro B-type natriuretic peptide (NT-proBNP) resulted in a significant improvement on the integrated discrimination index (IDI) for rejection (relative improvement of 24%; p = 0.021). Conclusions. sST2 concentrations are modulated by the presence of acute rejection and provide complementary predictive ability to NT-proBNP for the biochemical identification of rejection. (Ann Thorac Surg 2011;92:2118-24) (C) 2011 by The Society of Thoracic Surgeons C1 Virgen de la Arrixaca Hosp, Serv Cardiol, Murcia, Spain. Univ Murcia, Dept Med, Murcia, Spain. Virgen de la Arrixaca Hosp, Inmunol Serv, Murcia, Spain. St Pau Hosp, Serv Biochem, Barcelona, Spain. UAB, Dept Biochem & Mol Biol, Barcelona, Spain. Hosp Badalona Germans Trias & Pujol, Serv Cardiol, Barcelona, Spain. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Pascual-Figal, DA (reprint author), Virgen de la Arrixaca Univ Hosp, Dept Cardiol, Heart Failure & Heart Transplantat Unit, Ctra Madrid Cartagena S-N, Murcia 30120, Spain. EM dapascual@servicam.com RI Ordonez-Llanos, Jorge/A-9335-2010; Ordonez-Llanos, Jordi/B-4961-2011; Pascual Figal, Domingo /B-3794-2008; Bayes-Genis, Antoni/C-4002-2015 OI Ordonez-Llanos, Jordi/0000-0003-4896-5832; Pascual Figal, Domingo /0000-0002-4993-9540; Bayes-Genis, Antoni/0000-0002-3044-197X FU Red Nacional de Investigacion en Insuficiencia Cardiaca (REDINSCOR) [RD06/0003]; Instituto de Salud Carlos III; Ministry of Health, Madrid, Spain; Balson Cardiac Scholar Fund FX This work was supported by Red Nacional de Investigacion en Insuficiencia Cardiaca (REDINSCOR) (RD06/0003), Instituto de Salud Carlos III, Ministry of Health, Madrid, Spain. Dr Januzzi is supported in part by the Balson Cardiac Scholar Fund. The authors wish to thank Critical Diagnostics Inc. for providing sST2 reagents and technical assistance required for the study. NR 31 TC 13 Z9 14 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD DEC PY 2011 VL 92 IS 6 BP 2118 EP 2124 DI 10.1016/j.athoracsur.2011.07.048 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 852EL UT WOS:000297333300035 PM 22035779 ER PT J AU Chu, D Bakaeen, FG AF Chu, Danny Bakaeen, Faisal G. TI Hypoalbuminemia as a Contributor to the Progression of Cardiovascular Diseases Reply SO ANNALS OF THORACIC SURGERY LA English DT Letter C1 [Chu, Danny; Bakaeen, Faisal G.] Baylor Coll Med, Div Cardiothorac Surg, Texas Heart Inst, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Chu, D (reprint author), Baylor Coll Med, Div Cardiothorac Surg, Texas Heart Inst, Michael E DeBakey Vet Affairs Med Ctr, 2002 Holcombe Blvd,OCL 112, Houston, TX 77030 USA. EM dchu@bcm.edu NR 2 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD DEC PY 2011 VL 92 IS 6 BP 2305 EP 2306 PG 4 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 852EL UT WOS:000297333300080 ER PT J AU Cella, D Wang, ML Wagner, L Miller, K AF Cella, David Wang, Molin Wagner, Lynne Miller, Kathy TI Survival-adjusted health-related quality of life (HRQL) among patients with metastatic breast cancer receiving paclitaxel plus bevacizumab versus paclitaxel alone: results from Eastern Cooperative Oncology Group Study 2100 (E2100) SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Health-related quality of life; Metastatic breast cancer; Survival-adjusted quality of life; Patient-reported outcomes ID TRIAL AB The purpose of this study was to examine health-related quality of life (HRQL) among women with metastatic breast cancer treated on E2100 with paclitaxel or paclitaxel plus bevacizumab. Trial participants (N = 670) completed the Functional Assessment of Cancer Therapy-Breast (FACT-B) pre-treatment and following 4 and 8 cycles of treatment to assess HRQL and breast cancer-specific concerns. A significantly higher proportion of missing FACT-B assessments was observed among patients receiving paclitaxel only, due to faster time to death. To account for this non-ignorable pattern of missing data, we conducted a survival-adjusted HRQL analysis by jointly modeling the longitudinal HRQL outcome and time to non-ignorable dropout using a two-stage model. FACT scores assessing HRQL did not differ following 4 and 8 cycles of treatment; however mean scores on the 9-item Breast Cancer Scale were significantly higher after 4 and 8 cycles of treatment among patients receiving paclitaxel plus bevacizumab. No differences were observed between treatment arms on FACT-B total scores. The addition of bevacizumab was not associated with additional side effect burden from the patient perspective and was associated with a greater reduction in breast cancer-specific concerns. No other differences were noted. C1 [Cella, David; Wagner, Lynne] Northwestern Univ, Feinberg Med Sch, Dept Med Social Sci, Chicago, IL 60611 USA. [Cella, David; Wagner, Lynne] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [Wang, Molin] Harvard Univ, Sch Publ Hlth, Boston, MA USA. [Wang, Molin] Dana Farber Canc Inst, Boston, MA 02115 USA. [Miller, Kathy] Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN USA. RP Wagner, L (reprint author), Northwestern Univ, Feinberg Med Sch, Dept Med Social Sci, 625 N Michigan Ave,Suite 2700, Chicago, IL 60611 USA. EM lwagner@northwestern.edu FU Public Health Service from the National Cancer Institute [CA23318, CA66636, CA21115, CA49883, CA16116]; National Institutes of Health; Department of Health and Human Services; Genentech, Inc. FX This study was supported in part by Public Health Service Grants (Grant numbers CA23318, CA66636, CA21115, CA49883, and CA16116) from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services, and by Genentech, Inc. David Cella, Ph.D. consulting honoraria received research funding from Genentech, Inc. Kathy Miller, M. D. consulting honoraria and speaker's bureau from Genentech, Inc. No other authors have disclosures to report. NR 10 TC 18 Z9 18 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2011 VL 130 IS 3 BP 855 EP 861 DI 10.1007/s10549-011-1725-6 PG 7 WC Oncology SC Oncology GA 850US UT WOS:000297225600014 PM 21874312 ER PT J AU Brewster, AM Etzel, C Zhou, R Wong, Y Edge, S Blayney, DW Wilson, J Hudis, C Ottesen, R Hughes, ME Weeks, JC Theriault, RL AF Brewster, A. M. Etzel, C. Zhou, R. Wong, Y. Edge, S. Blayney, D. W. Wilson, J. Hudis, C. Ottesen, R. Hughes, M. E. Weeks, J. C. Theriault, R. L. TI The impact of obesity on receipt of adjuvant chemotherapy for breast cancer in the National Comprehensive Cancer Network (NCCN) centers SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Obesity; Breast neoplasms; Chemotherapy; Adjuvant; Standard-of-care; Healthcare Disparities ID OLDER WOMEN; DISPARITIES; CARCINOMA; SURVIVAL; THERAPY; HEALTH; CARE; DETERMINANTS; ETHNICITY; MORTALITY AB Disparities in the receipt of adjuvant chemotherapy for early stage breast cancer is an important factor influencing mortality. We investigated whether greater body mass index (BMI) decreases receipt of adjuvant chemotherapy among women with operable breast cancer. In the NCCN breast cancer outcomes database, we identified women aged a parts per thousand currency sign70 with newly diagnosed stage I, II, or III breast cancer between 1997 and 2007, for whom use of adjuvant chemotherapy was classified as either standard-of-care or discretionary based on their clinical characteristics. Body mass index was assessed in categories (< 18.5 kg/m(2) [underweight], 18.5 to < 25 kg/m(2) [normal], 25 to < 30 kg/m(2) [overweight], 30-39 kg/m(2) [obese], a parts per thousand yen40 kg/m(2) [extreme obese]). Multivariable logistic regression analysis was used to examine the association between BMI and receipt of chemotherapy in each classification group. 9,527 women were eligible for the study; 40% normal weight or less; 31% overweight; 24% obese; and 5% extremely obese. In multivariable analysis, there was no significant association between BMI and receipt of chemotherapy in either classification group. Among women for whom chemotherapy would be considered standard-of-care, older age (P < 0.001), comorbidity (P < 0.001), and non-Hispanic black ethnicity (P = 0.002) were associated with a lower likelihood of receipt of chemotherapy; however, the effect of ethnicity was not modified by obesity. Among women treated for operable breast cancer in the NCCN centers, BMI had no impact on receipt of adjuvant chemotherapy and did not modify the lower likelihood of chemotherapy among non-Hispanic black patients. Further investigation is needed into other factors that contribute to patient disparities in the receipt of chemotherapy in major academic centers. C1 [Brewster, A. M.; Etzel, C.; Zhou, R.; Theriault, R. L.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77230 USA. [Wong, Y.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Edge, S.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Blayney, D. W.] Stanford Canc Ctr, Stanford, CA USA. [Wilson, J.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Hudis, C.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Ottesen, R.] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Hughes, M. E.; Weeks, J. C.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Brewster, AM (reprint author), Univ Texas MD Anderson Canc Ctr, POB 301439, Houston, TX 77230 USA. EM abrewster@mdanderson.org FU National Cancer Institute [CA089393]; National Comprehensive Cancer Network FX This work was Supported in part by Grant No. CA089393 from the National Cancer Institute to Dana-Farber Cancer Institute and by the National Comprehensive Cancer Network. NR 33 TC 7 Z9 8 U1 2 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2011 VL 130 IS 3 BP 897 EP 904 DI 10.1007/s10549-011-1516-0 PG 8 WC Oncology SC Oncology GA 850US UT WOS:000297225600018 PM 21809116 ER PT J AU Nikolaou, V Kang, X Stratigos, A Gogas, H Latorre, MC Gabree, M Plaka, M Njauw, CN Kypreou, K Mirmigi, I Stefanaki, I Tsao, H AF Nikolaou, V. Kang, X. Stratigos, A. Gogas, H. Latorre, M. C. Gabree, M. Plaka, M. Njauw, C. N. Kypreou, K. Mirmigi, I. Stefanaki, I. Tsao, H. TI Comprehensive mutational analysis of CDKN2A and CDK4 in Greek patients with cutaneous melanoma SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article ID GERMLINE MUTATIONS; CARRIER PROBABILITY; MALIGNANT-MELANOMA; FAMILIAL MELANOMA; RISK; INDIVIDUALS; PREVALENCE; VARIANTS AB Background The penetrance of CDKN2A mutations is subject to geographical and latitudinal variation and is presumably dictated by ultraviolet radiation exposure and possibly other co-inherited genetic factors. The frequency of mutations increases with the number of family members affected and the number of primary tumours, and also fluctuates with geography. To date, little is known about the prevalence of CDKN2A mutations in patients with melanoma from Greece. Objective To characterize the frequency of CDKN2A and CDK4 mutations in a hospital- based population of Greek patients with melanoma. Methods Three hundred and four consecutive single primary melanoma (SPM), nine familial melanoma (FM) and seven multiple primary melanoma cases (MPM) were assessed for sequence variants in exons 1a, 1b and 2 of CDKN2A and exon 2 of CDK4. Results Germline CDKN2A mutations were detected in 10 of 304 SPM (3.3%), in four of seven MPM (57%) and in two of nine FM (22%) cases. The most common mutation was a Northern European allele (p16 p. R24P) detected in eight individuals. Five previously unreported CDKN2A variants were also identified:) -34G> C, c. 41_ 43delins20bp, c. 301G>C (p. G101R), c.301G> A (p.G101E) and c. 296_297insGACC. We also describe the first report of a CDK4 p. R24H substitution in a Greek family. Conclusions The Greek population appears to harbour a higher prevalence of the CDKN2A mutation than other reported cohorts. This supports the notion that genetic susceptibility may play a stronger influence in a country with a relatively low incidence of melanoma. Furthermore, the identification of Northern European alleles suggests that gene migration may be responsible, in part, for the observed cases in Greece. C1 [Nikolaou, V.; Stratigos, A.; Plaka, M.; Kypreou, K.; Mirmigi, I.; Stefanaki, I.; Tsao, H.] Univ Athens, Sch Med, Dept Dermatol, A Sygros Hosp, Athens 16121, Greece. [Kang, X.; Latorre, M. C.; Gabree, M.; Njauw, C. N.] Massachusetts Gen Hosp, Dept Dermatol, Wellman Ctr Photomed, MGH Canc Ctr, Boston, MA 02114 USA. [Gogas, H.] Univ Athens, Laikon Hosp, Dept Internal Med, Athens 11527, Greece. RP Tsao, H (reprint author), Univ Athens, Sch Med, Dept Dermatol, A Sygros Hosp, I Dragoumi 5, Athens 16121, Greece. EM htsao@partners.org FU NIH [K24 CA149202-01]; American Cancer Society [RSG-07-085-01-MGO] FX This activity was supported in part by the NIH (K24 CA149202-01 to H. T.), the American Cancer Society (RSG-07-085-01-MGO to H. T.) and the generous donors to the MGH Millennium Melanoma Fund. NR 14 TC 22 Z9 22 U1 1 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-0963 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD DEC PY 2011 VL 165 IS 6 BP 1219 EP 1222 DI 10.1111/j.1365-2133.2011.10551.x PG 4 WC Dermatology SC Dermatology GA 852BM UT WOS:000297320000110 PM 21801156 ER PT J AU Asato, R Kita, T Kawahara, S Arita, R Mochizuki, Y Aiello, LP Ishibashi, T AF Asato, Ryo Kita, Takeshi Kawahara, Shuhei Arita, Ryoichi Mochizuki, Yasutaka Aiello, Lloyd Paul Ishibashi, Tatsuro TI Vitreous levels of soluble vascular endothelial growth factor receptor (VEGFR)-1 in eyes with vitreoretinal diseases SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID PROLIFERATIVE DIABETIC-RETINOPATHY; RETINAL VEIN OCCLUSION; MACULAR DEGENERATION; GENE-TRANSFER; ERYTHROPOIETIN; INHIBITION; NEOVASCULARIZATION; PATHOGENESIS; FLUID; EDEMA AB Background/aims To determine the vitreous levels of soluble vascular endothelial growth factor receptor (sVEGFR)-1 in patients with various vitreoretinal diseases, and to investigate its correlation with patients' age and the activity of proliferative diabetic retinopathy (PDR). Methods Vitreous fluid samples were obtained from 187 eyes of 170 patients who underwent vitrectomy for the treatment of idiopathic macular hole (MH, n=30), branch retinal vein occlusion (BRVO, n=37), central retinal vein occlusion (CRVO, n=27), diabetic macular oedema (DME, n=42) and PDR (n=51). The levels of sVEGFR-1 in the vitreous were measured by ELISA. Results The levels of sVEGFR-1 (pg/ml) were not significantly different among each disease examined (MH 3900.1+/-1188.9, BRVO 3969.7+/-1741.6, CRVO 4897.7+/-1717.7, DME 3856.21+/-1374.7, PDR 4212.3+/-1474.9). There was a significant positive correlation between vitreous concentrations of sVEGFR-1 and patients' age (r=0.430, p<0.01). The sVEGFR-1 concentration in subjects with active PDR was significantly lower than in those with quiescent PDR (p<0.0001), even after being adjusted for age (p<0.0001). Conclusions Vitreous concentrations of sVEGFR-1 increase with advancing age and are associated with quiescent rather than active PDR even after adjustment for age. C1 [Kita, Takeshi] Kyushu Univ, Dept Ophthalmol, Grad Sch Med Sci, Higashi Ku, Fukuoka 8128582, Japan. [Aiello, Lloyd Paul] Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. [Aiello, Lloyd Paul] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Kita, T (reprint author), Kyushu Univ, Dept Ophthalmol, Grad Sch Med Sci, Higashi Ku, 3-1-1 Maidashi, Fukuoka 8128582, Japan. EM kita@eye.med.kyushu-u.ac.jp FU Ministry of Education, Science, Sports and Culture, Japan [21592233] FX This study was supported in part by grants from the Ministry of Education, Science, Sports and Culture, Japan (Grant-in-Aid for Scientific Research #21592233). NR 23 TC 4 Z9 4 U1 0 U2 3 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD DEC PY 2011 VL 95 IS 12 BP 1745 EP 1748 DI 10.1136/bjophthalmol-2011-300139 PG 4 WC Ophthalmology SC Ophthalmology GA 851IM UT WOS:000297261700027 PM 21719570 ER PT J AU Bhargava, P Vaidya, S Kolokythas, O Katz, DS Dighe, M AF Bhargava, P. Vaidya, S. Kolokythas, O. Katz, D. S. Dighe, M. TI Hepatic vascular shunts: embryology and imaging appearances SO BRITISH JOURNAL OF RADIOLOGY LA English DT Review ID HEREDITARY HEMORRHAGIC TELANGIECTASIA; PORTOSYSTEMIC VENOUS SHUNT; HEPATOCELLULAR-CARCINOMA; CT; SONOGRAPHY; CIRRHOSIS AB The purpose of this pictorial review is to understand the embryological basis of the development of congenital hepatic vascular shunts and to review the multimodality imaging appearances of congenital and acquired hepatic vascular shunts. Hepatic vascular shunts are commonly seen in imaging. Familiarity with their characteristic appearances is important in order to accurately characterise these shunts and diagnose the underlying disorders. C1 [Bhargava, P.] Univ Washington, Vet Affairs Puget Sound Hlth Care Ctr, Sch Med, Dept Radiol, Seattle, WA 98108 USA. [Bhargava, P.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Katz, D. S.] Winthrop Univ Hosp, Dept Radiol, Mineola, NY 11501 USA. RP Bhargava, P (reprint author), Univ Washington, Vet Affairs Puget Sound Hlth Care Ctr, Sch Med, Dept Radiol, Mail Box 358280,1660 S Columbian Way, Seattle, WA 98108 USA. EM bhargp@uw.edu OI Bhargava, Puneet/0000-0002-3849-9666 NR 17 TC 4 Z9 5 U1 0 U2 2 PU BRITISH INST RADIOLOGY PI LONDON PA 36 PORTLAND PLACE, LONDON W1N 4AT, ENGLAND SN 0007-1285 J9 BRIT J RADIOL JI Br. J. Radiol. PD DEC PY 2011 VL 84 IS 1008 BP 1142 EP 1152 DI 10.1259/bjr/82649468 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 851IZ UT WOS:000297263000018 PM 22101582 ER PT J AU Karaosmanoglu, AD Arellano, R Baker, G AF Karaosmanoglu, A. D. Arellano, R. Baker, G. TI Peripancreatic intranodal haemangioma mimicking pancreatic neuroendocrine tumour: imaging and pathological findings SO BRITISH JOURNAL OF RADIOLOGY LA English DT Article ID LYMPH-NODE AB Haemangiomas are common benign tumours that are generally detected within the skin, mucosal surfaces and soft tissues. However, intranodal haemangiomas are extremely rare and are among the benign primary vascular abnormalities of the lymph nodes that include lymphangioma, haemangioendothelioma, angiomyomatous hamartoma and haemangiomas. In this case report, we present the imaging and pathological findings of an intranodal haemangioma in the pancreatic head simulating a pancreatic neuroendocrine tumour. To the best of our knowledge, this is the first report of an intranodal haemangioma in this location. C1 [Karaosmanoglu, A. D.; Arellano, R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Abdominal Imaging & Intervent,Dept Radiol, Boston, MA 02114 USA. [Baker, G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Karaosmanoglu, AD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Abdominal Imaging & Intervent,Dept Radiol, 55 Fruit St,White 2, Boston, MA 02114 USA. EM alidevrim76@yahoo.com RI Karaosmanoglu, Ali/D-8624-2015 OI Karaosmanoglu, Ali/0000-0003-0027-9593 NR 6 TC 0 Z9 0 U1 0 U2 2 PU BRITISH INST RADIOLOGY PI LONDON PA 36 PORTLAND PLACE, LONDON W1N 4AT, ENGLAND SN 0007-1285 J9 BRIT J RADIOL JI Br. J. Radiol. PD DEC PY 2011 VL 84 IS 1008 BP E236 EP E239 DI 10.1259/bjr/77657029 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 851IZ UT WOS:000297263000004 PM 22101590 ER PT J AU LoRusso, P Shapiro, GI Hurwitz, H Pilat, MJ Chemidlin, J Kollia, G Syed, S Fischer, B Masson, E AF LoRusso, Patricia Shapiro, Geoffrey I. Hurwitz, Herbert Pilat, Mary Jo Chemidlin, Janice Kollia, Georgia Syed, Shariq Fischer, Bruce Masson, Eric TI Lack of food effect on single-dose pharmacokinetics of brivanib, and safety and efficacy following multiple doses in subjects with advanced or metastatic solid tumors SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE Pharmacokinetics; Exposure; Food; Safety; Brivanib alaninate; Solid tumors ID RENAL-CELL CARCINOMA; ANGIOGENESIS INHIBITOR BEVACIZUMAB; GROWTH-FACTOR RECEPTOR; HEPATOCELLULAR-CARCINOMA; CANCER-PATIENTS; DUAL INHIBITOR; SORAFENIB; METAANALYSIS; KINASES; MODELS AB Brivanib alaninate, an orally available prodrug of brivanib, is currently under evaluation for the treatment of several malignancies. This study aimed to (1) investigate effects of a high-fat meal on single-dose pharmacokinetics of brivanib in subjects with advanced/metastatic solid tumors and (2) assess the safety and preliminary efficacy of single and multiple doses of brivanib alaninate in this population. A two-part study was conducted consisting of a single-dose phase (Part A) and a multiple-dose phase (Part B). In Part A, subjects received a single dose of brivanib alaninate (800 mg) either in a fasting state or following ingestion of a high-fat meal (approximately 951 kcal [15% protein, 33% carbohydrate, 52% fat]); serial blood samples were collected for pharmacokinetic analysis up to 48 h post-dosing. In Part B, subjects received brivanib alaninate (800 mg) once daily until discontinuation. Throughout both phases, subjects were evaluated for adverse events (AEs) and best clinical response. No clinically significant differences in brivanib exposure were observed between fed and fasting subjects in Part A; C (max) was unchanged and AUC(INF) decreased marginally when administered in a fed versus fasted state. In Part A, the incidence of treatment-emergent AEs was broadly similar in a fed or fasted state. Brivanib alaninate was generally well tolerated throughout the study and showed preliminary evidence of antitumor activity. Consumption of a high-fat meal had no significant effect on brivanib pharmacokinetics. The study further demonstrates the acceptable safety/tolerability profile and antitumor potential of brivanib in patients with advanced malignancies. C1 [LoRusso, Patricia; Pilat, Mary Jo] Karmanos Canc Inst, Detroit, MI 48201 USA. [Shapiro, Geoffrey I.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hurwitz, Herbert] Duke Univ, Med Ctr, Durham, NC 27710 USA. [Chemidlin, Janice; Kollia, Georgia; Syed, Shariq; Fischer, Bruce; Masson, Eric] Bristol Myers Squibb Co, Lawrenceville, NJ 08540 USA. RP LoRusso, P (reprint author), Karmanos Canc Inst, 4100 John R, Detroit, MI 48201 USA. EM lorussop@karmanos.org FU Bristol-Myers Squibb [CA182022]; GlaxoSmithKline FX The authors would like to acknowledge the contributions of the enrolled patients and their families, as well as the nursing and data management staff who worked on this study. Additional bioanalytical support was provided by Janice Pursley (Bristol-Myers Squibb). In the development of this manuscript, editorial support was provided by Richard Daniel, PhD, of PAREXEL and was funded by Bristol-Myers Squibb. Grant support: Supported by research funding from Bristol-Myers Squibb (Study No. CA182022).; Patricia LoRusso: Declares the receipt of funding from GlaxoSmithKline. NR 26 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD DEC PY 2011 VL 68 IS 6 BP 1377 EP 1385 DI 10.1007/s00280-011-1603-2 PG 9 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 852GJ UT WOS:000297344300002 PM 21461891 ER PT J AU Aggarwal, NR Knickelbine, T Tande, A Stoltzfus, L Lesser, JR Schwartz, RS AF Aggarwal, Niti R. Knickelbine, Thomas Tande, Aaron Stoltzfus, Luke Lesser, John R. Schwartz, Robert S. TI Noncalcified plaque: Relationship between results of multislice computed tomography, risk factors, and late clinical outcome SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE CT angiography; noncalcified plaque; risk factors; coronary artery disease; cardiac imaging; cardiac CT ID CORONARY-ARTERY-DISEASE; ATHEROSCLEROTIC PLAQUE; INTRAVASCULAR ULTRASOUND; CT ANGIOGRAPHY; CALCIUM SCORE; NONINVASIVE ASSESSMENT; MYOCARDIAL-INFARCTION; PROGNOSTIC VALUE; STABLE ANGINA; CALCIFICATION AB Background: Contrast-enhanced multislice computed tomographic angiography (MSCTA) detects noncalcified plaque (NCP) in coronary arteries and associated coronary stenoses. However, the clinical relevance of NCP is poorly defined. Objectives: Our goal was to examine the relationship NCP, risk factors (RFs), and clinical follow-up in unselected outpatients undergoing MSCTA. Methods: Five hundred six patients undergoing contrast MSCTA were evaluated for NCP (intraluminal density 25 < Hounsfield units < 130). One hundred twenty-four patients (24.5%) had calcium scores (CAC) of zero. Of these, 111 patients were examined for RFs and followed clinically for a mean of 34 months. Results: Of 124 patients with zero CAC, 111 (89.5%) included 52 (46.8%) with no NCP, 40 (36.0%) with NCP, and mild luminal stenosis, 14 (12.6%) and 5 (4.5%) with NCP causing significant and severe stenosis, respectively. Patients in each group were similar in age but differed significantly in number of RFs. Current or former smokers, hypertensive, and obese patients had more NCP and associated stenosis. At a mean of 34 months, there were no events in the no NCP group, 2/54 (3.7%) events in the NCP without severe stenosis group (one sudden cardiac death and one ventricular tachycardia), and 2/5 (40.0%) patients had revascularization in the NCP with severe stenosis group. Conclusions: (1) In patients with zero CAC, presence of NCP on MSCTA was associated with more RFs, especially smoking, obesity, and hypertension. (2) NCP can result in severe coronary stenosis. (3) NCP detected by MSCTA in patients with zero CAC may identify patients with late cardiac events. (c) 2011 Wiley Periodicals, Inc. C1 [Knickelbine, Thomas; Stoltzfus, Luke; Lesser, John R.; Schwartz, Robert S.] Minneapolis Heart Inst Fdn, Minneapolis, MN USA. [Aggarwal, Niti R.] Mayo Clin, Div Cardiovasc Dis, Rochester, MN USA. [Tande, Aaron] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Schwartz, RS (reprint author), Minneapolis Heart Inst, 920 E 28th St,Suite 620, Minneapolis, MN 55407 USA. EM rss@rsschwartz.com NR 46 TC 5 Z9 5 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD DEC 1 PY 2011 VL 78 IS 7 BP 1116 EP 1124 DI 10.1002/ccd.23138 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 850NW UT WOS:000297203000027 PM 21542104 ER PT J AU Marks, G Gardner, LI Craw, J Giordano, TP Mugavero, MJ Keruly, JC Wilson, TE Metsch, LR Drainoni, ML Malitz, F AF Marks, Gary Gardner, Lytt I. Craw, Jason Giordano, Thomas P. Mugavero, Michael J. Keruly, Jeanne C. Wilson, Tracey E. Metsch, Lisa R. Drainoni, Mari-Lynn Malitz, Faye TI The Spectrum of Engagement in HIV Care: Do More Than 19% of HIV-Infected Persons in the US Have Undetectable Viral Load? SO CLINICAL INFECTIOUS DISEASES LA English DT Letter C1 [Marks, Gary; Gardner, Lytt I.; Craw, Jason] Ctr Dis Control & Prevent, Div HIV AIDS Prevent, Atlanta, GA 30333 USA. [Giordano, Thomas P.] Baylor Coll Med, Thomas St Hlth Ctr, Houston, TX 77030 USA. [Giordano, Thomas P.] DeBakey VA Med Ctr, Houston, TX USA. [Mugavero, Michael J.] Univ Alabama Birmingham UAB, UAB Ctr AIDS Res, Birmingham, AL USA. [Mugavero, Michael J.] UAB 1917 Clin, Birmingham, AL USA. [Keruly, Jeanne C.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA. [Wilson, Tracey E.] Suny Downstate Med Ctr, Sch Publ Hlth, Brooklyn, NY 11203 USA. [Metsch, Lisa R.] Univ Miami, Miller Sch Med, Dev Ctr AIDS Res, Coral Gables, FL 33124 USA. [Drainoni, Mari-Lynn] Boston Univ, Dept Hlth Policy & Management, Sch Publ Hlth, Sect Infect Dis,Dept Med,Sch Med, Boston, MA 02215 USA. [Malitz, Faye] Hlth Resources & Serv Adm, HIV AIDS Bur, Rockville, MD USA. RP Marks, G (reprint author), Ctr Dis Control & Prevent, Div HIV AIDS Prevent, Atlanta, GA 30333 USA. EM gmarks@cdc.gov NR 4 TC 16 Z9 16 U1 0 U2 11 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC 1 PY 2011 VL 53 IS 11 BP 1168 EP U154 DI 10.1093/cid/cir678 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 851OH UT WOS:000297279900025 PM 21976466 ER PT J AU Celik, S Giannitsis, E Wollert, KC Schwobel, K Lossnitzer, D Hilbel, T Lehrke, S Zdunek, D Hess, A Januzzi, JL Katus, HA AF Celik, S. Giannitsis, E. Wollert, K. C. Schwoebel, K. Lossnitzer, D. Hilbel, T. Lehrke, S. Zdunek, D. Hess, A. Januzzi, J. L. Katus, H. A. TI Cardiac troponin T concentrations above the 99th percentile value as measured by a new high-sensitivity assay predict long-term prognosis in patients with acute coronary syndromes undergoing routine early invasive strategy SO CLINICAL RESEARCH IN CARDIOLOGY LA English DT Article DE High-sensitivity cardiac troponin T; Acute coronary syndrome; Prognosis; Early diagnosis ID ELEVATION MYOCARDIAL-INFARCTION; MEDICINE PRACTICE GUIDELINES; EARLY-DIAGNOSIS; ADVERSE EVENTS; I ASSAY; NATIONAL ACADEMY; HEART-FAILURE; ULTRA ASSAY; POPULATION; ABILITY AB Objective A recently developed immunoassay for high-sensitivity measurement of cardiac troponin T (hsTnT) allows measurement at the 99th percentile for a normal population with an assay imprecision < 10%. It is unclear whether such a low cutpoint (14 ng/L) is helpful for long-term risk stratification of patients with an acute coronary syndrome (ACS) undergoing routine early invasive strategy. Patients and main outcome measures Consecutive patients with ACS admitted to a chest pain unit were studied. The usefulness of hsTnT for early diagnosis of myocardial infarction (MI) and prediction of all-cause death or death/MI over a median of 271 days following presentation was compared against the fourth generation cTnT at the 99th percentile cutpoint. Results Of 1,384 patients with ACS enrolled, 47.8% had non-ST-segment elevation MI (NSTEMI), 26.4% unstable angina, 21.8% STEMI and 4% had non-ACS. Adjusted risk for all-cause death [adjusted HR 8.26 (95%CI: 1.13-66.33), p = 0.038] and death/MI [adjusted HR 2.71 (95% CI: 1.15-6.38), p = 0.023] were significantly higher with hsTnT above the 99th percentile. In particular, among patients with a standard fourth generation cTnT result below the 99th percentile cutoff (0.01 ng/mL), hsTnT improved risk assessment. Mortality risk associated with an elevated hsTnT was present across the spectrum of ACS, as well as in conditions with hsTnT elevations not related to ACS. Conclusion hsTnT at the 99th percentile cutoff is useful for the diagnostic evaluation of patients with ACS, and provides strong and independent predictive power for adverse long-term outcomes even after early invasive strategy. C1 [Celik, S.; Giannitsis, E.; Schwoebel, K.; Lossnitzer, D.; Hilbel, T.; Lehrke, S.; Katus, H. A.] Univ Klinikum Heidelberg, Med Klin, Abt Innere Med 3, D-69120 Heidelberg, Germany. [Wollert, K. C.] Hannover Med Sch, Klin Kardiol & Angiol, D-30625 Hannover, Germany. [Zdunek, D.; Hess, A.] Roche Diagnost GmbH, Penzberg, Germany. [Januzzi, J. L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Giannitsis, E (reprint author), Univ Klinikum Heidelberg, Med Klin, Abt Innere Med 3, Neuenheimer Feld 410, D-69120 Heidelberg, Germany. EM evangelos_giannitsis@med.uni-heidelberg.de RI Katus, Hugo/P-1712-2016 FU Roche Diagnostics, Germany; Roche Diagnostics FX We thank Mr. Oliver Hartmann, a biostatistician from BRAHMS Biomarkers (clinical diagnostics division of Thermo Fisher Scientific) for support regarding statistical analyses. EG has received financial support for clinical trials from Roche Diagnostics, Germany. He is consultant to Roche Diagnostics and receives honoraria for lectures from Roche Diagnostics. JLJ has received grant support from Roche Diagnostics, and has received honoraria for lectures from Roche Diagnostics. HAK has developed the cTnT assay and holds a patent jointly with Roche Diagnostics. He has received grants and research support from several companies, and has received honoraria for lectures from Roche Diagnostics. DZ and GH are employees of Roche Diagnostics responsible for the preclinical testing of hsTnT. The investigations were supported by Roche Diagnostics, Germany providing assays for hsTnT assay. NR 31 TC 24 Z9 27 U1 0 U2 7 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1861-0684 J9 CLIN RES CARDIOL JI Clin. Res. Cardiol. PD DEC PY 2011 VL 100 IS 12 BP 1077 EP 1085 DI 10.1007/s00392-011-0344-x PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 852NF UT WOS:000297364000004 PM 21792561 ER PT J AU Desseilles, M Dang-Vu, TT Sterpenich, V Schwartz, S AF Desseilles, Martin Thien Thanh Dang-Vu Sterpenich, Virginie Schwartz, Sophie TI Cognitive and emotional processes during dreaming: A neuroimaging view SO CONSCIOUSNESS AND COGNITION LA English DT Article DE Dreaming; Sleep; Rapid eye movement (REM); Functional neuroimaging; Neuropsychology; Cognitive neuroscience; Brain; Amygdala ID EYE-MOVEMENT SLEEP; POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL-BLOOD-FLOW; HUMAN REM-SLEEP; POSTTRAUMATIC-STRESS-DISORDER; THREAT SIMULATION THEORY; BRAIN-MIND STATES; PARADOXICAL SLEEP; WAKE CYCLE; MEMORY CONSOLIDATION AB Dream is a state of consciousness characterized by internally-generated sensory, cognitive and emotional experiences occurring during sleep. Dream reports tend to be particularly abundant, with complex, emotional, and perceptually vivid experiences after awakenings from rapid eye movement (REM) sleep. This is why our current knowledge of the cerebral correlates of dreaming, mainly derives from studies of REM sleep. Neuroimaging results show that REM sleep is characterized by a specific pattern of regional brain activity. We demonstrate that this heterogeneous distribution of brain activity during sleep explains many typical features in dreams. Reciprocally, specific dream characteristics suggest the activation of selective brain regions during sleep. Such an integration of neuroimaging data of human sleep, mental imagery, and the content of dreams is critical for current models of dreaming; it also provides neurobiological support for an implication of sleep and dreaming in some important functions such as emotional regulation. (C) 2010 Elsevier Inc. All rights reserved. C1 [Desseilles, Martin] Univ Geneva, Dept Neurosci, Geneva Ctr Neurosci, CH-1211 Geneva 4, Switzerland. [Desseilles, Martin] Univ Geneva, Dept Psychiat, CH-1211 Geneva 4, Switzerland. [Desseilles, Martin; Thien Thanh Dang-Vu] Univ Liege, Cyclotron Res Ctr, B-4000 Liege, Belgium. [Thien Thanh Dang-Vu] Harvard Univ, Sch Med, Div Sleep Med, Boston, MA USA. [Thien Thanh Dang-Vu] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Sterpenich, Virginie; Schwartz, Sophie] Univ Geneva, Swiss Ctr Affect Sci, CH-1211 Geneva 4, Switzerland. RP Desseilles, M (reprint author), Univ Geneva, Dept Neurosci, Geneva Ctr Neurosci, Michel Servet 1, CH-1211 Geneva 4, Switzerland. EM martin.desseilles@unige.ch; sophie.schwartz@unige.ch OI Dang Vu, Thien Thanh/0000-0002-7235-2721 NR 134 TC 39 Z9 42 U1 5 U2 49 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8100 J9 CONSCIOUS COGN JI Conscious. Cogn. PD DEC PY 2011 VL 20 IS 4 SI SI BP 998 EP 1008 DI 10.1016/j.concog.2010.10.005 PG 11 WC Psychology, Experimental SC Psychology GA 851NP UT WOS:000297278100004 PM 21075010 ER PT J AU Mendez, MF Shapira, JS AF Mendez, Mario F. Shapira, Jill S. TI Loss of emotional insight in behavioral variant frontotemporal dementia or "frontal anosodiaphoria" SO CONSCIOUSNESS AND COGNITION LA English DT Article DE Insight; Anosognosia; Anosodiaphoria; Dementia; Frontotemporal dementia; Alzheimer's disease ID ALZHEIMERS-DISEASE; SELF-AWARENESS; COGNITIVE IMPAIRMENT; DIAGNOSTIC-CRITERIA; PREFRONTAL CORTEX; ANOSOGNOSIA; DEFICITS; UNAWARENESS; DEGENERATION; RECOGNITION AB Loss of insight is a prominent clinical manifestation of behavioral variant frontotemporal dementia (bvFTD), but its characteristics are poorly understood. Twelve bvFTD patients were compared with 12 Alzheimer's disease (AD) patients on a structured insight interview of cognitive insight (awareness of having a disorder) and emotional insight (concern over having a disorder). Compared to the AD patients, the bvFTD patients were less aware and less concerned about their disorder, and they had less appreciation of its effects on themselves and on others. After corrective feedback ("updating"), the bvFTD patients were just as aware of their disorder as the AD patients but remained unconcerned and unappreciative of its effects. These findings suggest that lack of insight in bvFTD is not due to "anosognosia," or impaired cognitive and executive awareness of disease, but to "frontal anosodiaphoria," or lack of emotional concern over having bvFTD and its impact on themselves and others. Published by Elsevier Inc. C1 [Mendez, Mario F.] VA Greater Los Angeles Healthcare Ctr, Neurobehav Unit 691 116AF, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. RP Mendez, MF (reprint author), VA Greater Los Angeles Healthcare Ctr, Neurobehav Unit 691 116AF, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM mmendez@UCLA.edu FU NIA NIH HHS [R01 AG034499, R01 AG034499-03, R01AG034499-02] NR 66 TC 22 Z9 23 U1 1 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8100 J9 CONSCIOUS COGN JI Conscious. Cogn. PD DEC PY 2011 VL 20 IS 4 SI SI BP 1690 EP 1696 DI 10.1016/j.concog.2011.09.005 PG 7 WC Psychology, Experimental SC Psychology GA 851NP UT WOS:000297278100066 PM 21959203 ER PT J AU Wilens, TE Adler, LA Tanaka, Y Xiao, F D'Souza, DN Gutkin, SW Upadhyaya, HP AF Wilens, Timothy E. Adler, Lenard A. Tanaka, Yoko Xiao, Feng D'Souza, Deborah N. Gutkin, Stephen W. Upadhyaya, Himanshu P. TI Correlates of alcohol use in adults with ADHD and comorbid alcohol use disorders: exploratory analysis of a placebo-controlled trial of atomoxetine SO CURRENT MEDICAL RESEARCH AND OPINION LA English DT Article DE Adult; Alcohol; Atomoxetine; Attention-deficit/hyperactivity disorder; Drug therapy; Treatment outcomes ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; SUBSTANCE USE DISORDERS; DEFICIT HYPERACTIVITY DISORDER; COMPULSIVE DRINKING SCALE; CONDUCT DISORDER; PSYCHIATRIC COMORBIDITY; RATING-SCALE; DRIVING PERFORMANCE; SOCIAL DRINKERS; COCAINE ABUSERS AB Background: Attention-deficit/hyperactivity disorder (ADHD) and substance use disorder are often comorbid in adults. The effects of ADHD treatment on comorbid alcohol use disorder have not been extensively studied. Objective: To assess correlates of ADHD and alcohol use outcomes in ADHD with comorbid alcohol use disorders, via a post-hoc exploratory subgroup analysis of a previously conducted, randomized, double-blind, placebo-controlled study of recently abstinent adults. Methods: Adults who had ADHD and alcohol use disorders and were abstinent for 4-30 days were randomized to daily atomoxetine 25-100 mg (mean final dose = 89.9 mg) or placebo for 12 weeks. Changes in ADHD symptoms from baseline to endpoint were assessed using the ADHD Investigator Symptom Rating Scale (AISRS) total score, alcohol use by the timeline followback method, and alcohol cravings by the Obsessive Compulsive Drinking Scale. Results: Of 147 subjects receiving atomoxetine (n = 72) or placebo (n = 75) in the primary study, 80 (54%) completed 12 weeks (n = 32 atomoxetine; n = 48 placebo). Improvements in ADHD symptoms on the AISRS correlated significantly with decreases in alcohol cravings (Pearson's r = 0.28; 95% confidence interval [CI] = 0.11-0.43; p = 0.002), and the correlation was most notable with atomoxetine (r = 0.29; CI [0.04-0.51]; p = 0.023) rather than with placebo (r = 0.24; CI [0.00-0.46]; p = 0.055). On-treatment drinking levels correlated with AISRS scores (r = 0.12; CI [0.05-0.19]; p = 0.001). Relapse to alcohol abuse significantly correlated with worse ADHD symptoms on 15 of 18 items of the AISRS in the placebo group (p<0.05 for each). Conclusions: No baseline predictor (other than degree of sobriety) of alcohol use or ADHD outcomes emerged. ADHD symptom improvements correlated significantly with reductions in alcohol cravings, and relapse to alcohol abuse correlated significantly with worsening of most ADHD symptoms in the placebo group, but not in the atomoxetine group. This post-hoc subgroup analysis is of a hypothesis-generating nature, and the generalizability of the findings may be limited by exclusion of adults with common ADHD comorbidities from the base study. Further, prospective clinical trials in larger and more heterogeneous patient populations are warranted to confirm or reject these preliminary associations. C1 [Wilens, Timothy E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Adler, Lenard A.] NYU, Sch Med, New York, NY USA. [Adler, Lenard A.] VA New York Harbor Healthcare Serv, New York, NY USA. [Tanaka, Yoko; Upadhyaya, Himanshu P.] Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. [Xiao, Feng; D'Souza, Deborah N.] i3 Statprobe, Cary, NC USA. [Gutkin, Stephen W.] Rete Biomed Commun Corp, Wyckoff, NJ USA. RP Wilens, TE (reprint author), Massachusetts Gen Hosp, 55 Fruit St,YAW 6A, Boston, MA 02114 USA. EM twilens@partners.org OI Adler, Len/0000-0002-9812-8234 FU Eli Lilly and Co. (Indianapolis, IN, USA); National Institute on Drug Abuse [K24 DA016264]; Abbott; McNeil; Lilly; Nextwave; National Institutes of Health/National Institute of Drug Addiction (NIH/NIDA); Merck; Shire; Bristol-Myers Squibb; Novartis; Pfizer; Ortho-McNeil/Janssen/Johnson Johnson; New River Pharmaceuticals; Cephalon; NIDA; Chelsea Therapeutics; Organon; Eli Lilly and Co. FX This study and the present communication were supported by Eli Lilly and Co. (Indianapolis, IN, USA) and a National Institute on Drug Abuse grant to T.E.W. (#K24 DA016264).; T.E.W. has disclosed that he receives or has received grant support from the following sources: Abbott, McNeil, Lilly, Nextwave, National Institutes of Health/National Institute of Drug Addiction (NIH/NIDA), Merck, and Shire; has been a speaker for Lilly, McNeil, Novartis, and Shire; and is or has been a consultant for Abbott, AstraZeneca, McNeil, Lilly, Nextwave, NIH, Novartis, Merck, and Shire. T.E.W. has a published book with Guilford Press: Straight Talk About Psychiatric Medications for Kids. L. A. A. has disclosed that, in the past 3 years, he has received grant/research support from Abbott, Bristol-Myers Squibb, Merck, Novartis, Pfizer, Shire, Lilly, Ortho-McNeil/Janssen/Johnson & Johnson, New River Pharmaceuticals, Cephalon, NIDA, Chelsea Therapeutics, and Organon; served on advisory boards and as a consultant to Abbott, Cortex Pharmaceuticals, Novartis, Pfizer, Shire, Lilly, Ortho McNeil/Janssen/Johnson & Johnson, Merck, Organon, sanofi-aventis, Psychogenics, Mindsite (uncompensated), AstraZeneca, Major League Baseball, and i3 Research; and has served as a consultant to Epi-Q, INC Research, United BioSource, Otsuka, and the Major League Baseball Players Association. L. A. A. has served on speakers bureaus for Shire, Ortho-McNeil/Janssen/Johnson & Johnson, and Lilly (but does not currently serve on any speakers bureaus) and has received royalty payments (as inventor) from NYU for license of adult ADHD scales and training materials. He has no stock ownership. Y.T. and H. P. U. are employees of and shareholders in Lilly. F. X. and D.N.D. are paid consultants to Lilly and/or its affiliates. When the study was conducted and early drafts of the manuscript prepared, D.N.D. was an employee of, and minor shareholder in, the study sponsor. S. W. G. is a paid consultant to Lilly (and its affiliates) and BioBehavioral Diagnostics (Westford, MA, and Plymouth Meeting, PA, USA).; Editorial assistance was provided by Ann C. Sherwood, PhD, and Lauren Baker, PhD, Rete Biomedical Communications Corp. (Wyckoff, NJ), with financial support from Eli Lilly and Co. NR 76 TC 19 Z9 19 U1 4 U2 9 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0300-7995 J9 CURR MED RES OPIN JI Curr. Med. Res. Opin. PD DEC PY 2011 VL 27 IS 12 BP 2309 EP 2320 DI 10.1185/03007995.2011.628648 PG 12 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 852GC UT WOS:000297343100011 PM 22029549 ER PT J AU Motyckova, G Stone, RM AF Motyckova, Gabriela Stone, Richard M. TI Treatment of Elderly Acute Myeloid Leukemia Patients SO CURRENT TREATMENT OPTIONS IN ONCOLOGY LA English DT Article ID ACUTE MYELOGENOUS LEUKEMIA; RISK MYELODYSPLASTIC SYNDROME; LOW-DOSE CYTARABINE; HEMATOPOIETIC-CELL TRANSPLANTATION; MICRORNA-EXPRESSION SIGNATURES; ACUTE NONLYMPHOCYTIC LEUKEMIA; INTERNAL TANDEM DUPLICATION; CONVENTIONAL CARE REGIMENS; SOUTHWEST-ONCOLOGY-GROUP; 1ST COMPLETE REMISSION AB Older patients with acute myelogenous leukemia (AML) fare much less well than younger patients with the same disease due to a combination of comorbidities and intrinsic disease resistance. Likely due to aging of the US population, the median age of AML patients at diagnosis has increased from 68 to 72 years. AML is a heterogeneous disease, particularly in older patients, making therapeutic decisions challenging. Older patients who are 'fit' for intensive chemotherapy and would have a reasonable chance to benefit based on host and disease characteristics should receive standard induction chemotherapy with 7 days of continuous infusion of cytarabine and at least 60 mg/m(2) daunorubicin daily for 3 days. Therapeutic options for patients who are not candidates for or are not likely to respond to intensive therapy include clofarabine, low intensity chemotherapy such as low dose cytarabine, hypomethylating agents, or investigational agents. For older AML patients in complete remission, post-remission or consolidation chemotherapy with repeat induction or modified high dose cytarabine may offer a small chance for long term disease-free survival. Selected older patients who achieve remission by any means should be considered for reduced-intensity stem cell transplantation which may offer improved chances of cure and survival compared with standard post-remission chemotherapy. C1 [Motyckova, Gabriela; Stone, Richard M.] Dana Farber Canc Inst, Boston, MA 02215 USA. RP Motyckova, G (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM gmotyckova@partners.org; rstone@partners.org NR 62 TC 4 Z9 4 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1527-2729 J9 CURR TREAT OPTION ON JI Curr. Treat. Options Oncol. PD DEC PY 2011 VL 12 IS 4 BP 341 EP 353 DI 10.1007/s11864-011-0162-4 PG 13 WC Oncology SC Oncology GA 849HY UT WOS:000297117800004 PM 21901552 ER PT J AU Cannizzo, E Carulli, G Del Vecchio, L Ottaviano, V Bellio, E Zenari, E Azzara, A Petrini, M Preffer, F AF Cannizzo, E. Carulli, G. Del Vecchio, L. Ottaviano, V. Bellio, E. Zenari, E. Azzara, A. Petrini, M. Preffer, F. TI THE ROLE OF CD19 AND CD27 IN THE DIAGNOSIS OF MULTIPLE MYELOMA BY FLOW CYTOMETRY: A NEW STATISTICAL MODEL SO CYTOMETRY PART A LA English DT Meeting Abstract CT 29th National Conference of the Italian-Society-of-Cytometry GIC CY OCT 05-08, 2011 CL Salerno, ITALY SP Italian Soc Cytometry C1 [Cannizzo, E.; Carulli, G.; Ottaviano, V.; Bellio, E.; Zenari, E.; Azzara, A.; Petrini, M.] Univ Pisa, Sect Hematol, Dept Oncol Transplants & Adv Med, Pisa, Italy. [Del Vecchio, L.] Univ Naples Federico 2, CEINGE Inst, Dept Biochem & Med Biotechnol, Naples, Italy. [Preffer, F.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Preffer, F.] Harvard Univ, Sch Med, Boston, MA USA. EM elisacannizzo@libero.it NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4922 J9 CYTOM PART A JI Cytom. Part A PD DEC PY 2011 VL 79A IS 12 BP 1044 EP 1045 PG 2 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 851FP UT WOS:000297254100058 ER PT J AU Petrelli, A Carvello, M Vergani, A Lee, KM Tezza, S Du, M Kleffel, S Liu, CW Mfarrej, BG Hwu, P Secchi, A Leonard, WJ Young, D Sayegh, MH Markmann, JF Zajac, AJ Fiorina, P AF Petrelli, Alessandra Carvello, Michele Vergani, Andrea Lee, Kang Mi Tezza, Sara Du, Ming Kleffel, Sonja Liu Chengwen Mfarrej, Bechara G. Hwu, Patrick Secchi, Antonio Leonard, Warren J. Young, Deborah Sayegh, Mohamed H. Markmann, James F. Zajac, Allan J. Fiorina, Paolo TI IL-21 Is an Antitolerogenic Cytokiine of the Late-Phase Alloimmune Response SO DIABETES LA English DT Article ID REGULATORY T-CELLS; MEDIATED SUPPRESSION; ISLET TRANSPLANTATION; REJECTION; GENERATION; TOLERANCE; DIFFERENTIATION; COSTIMULATION; PATHWAYS; DISEASE AB OBJECTIVE-Interleukin-21 (IL-21) is a proinflanimatory cytokine that has been shown to affect Treg/Teff balance. However, the mechanism by which IL-21 orchestrates alloimmune response and interplays with Tregs is still unclear. RESEARCH DESIGN AND METHODS-The interplay between IL-21/IL-21R signaling, FoxP3 expression, and Treg survival and function was evaluated in vitro in immunologically relevant assays and in vivo in allogenic and autoimmune models of islet transplantation. RESULTS-IL-21R expression decreases on T cells and B cells in vitro and increases in the graft in vivo, while IL-21 levels increase in vitro and in vivo during anti-CD3/anti-CD28 stimulation/allostimulation in the late phase of the alloimmune response. In vitro, IL-21/IL-21R signaling (by using rmIL-21 or genetically modified CD4(+) T cells [IL-21 pOrf plasmid-treated or hIL-21-Tg mice]) enhances the T-cell response during anti-CD3/anti-CD28 stimulation/allostimulation, prevents Treg generation, inhibits Treg function, induces Treg apoptosis, and reduces FoxP3 and FoxP3-dependent gene transcripts without affecting FoxP3 methylation status. In vivo targeting of IL-21/IL-21R expands intragraft and peripheral Tregs, promotes Treg neogenesis, and regulates the antidonor immune response, whereas IL-21/IL-21R signaling in Doxa-inducible ROSA-rtTA-IL-21-Tg mice expands Teffs and FoxP3(-) cells. Treatment with a combination of mIL-21R.Fc and CTLA4-Ig (an inhibitor of the early alloimmune response) leads to robust graft tolerance in a purely alloimmune setting and prolonged islet graft survival in NOD mice. CONCLUSIONS-IL-21 interferes with different checkpoints of the FoxP3 Treg chain in the late phase of alloimmune response and, thus, acts as an antitolerogenic cytokine. Blockade of the IL-21/IL-21R pathway could be a precondition for tolerogenic protocols in transplantation. Diabetes 60:3223-3234, 2011 C1 [Petrelli, Alessandra; Vergani, Andrea; Tezza, Sara; Kleffel, Sonja; Mfarrej, Bechara G.; Sayegh, Mohamed H.; Fiorina, Paolo] Harvard Univ, Childrens Hosp, Transplantat Res Ctr, Sch Med, Boston, MA 02115 USA. [Petrelli, Alessandra; Vergani, Andrea; Secchi, Antonio; Fiorina, Paolo] Ist Sci San Raffaele, Dept Med, I-20132 Milan, Italy. [Carvello, Michele; Lee, Kang Mi; Markmann, James F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Du, Ming; Zajac, Allan J.] Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. [Liu Chengwen; Hwu, Patrick] Univ Texas MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Ctr Canc Immunol Res, Houston, TX 77030 USA. [Leonard, Warren J.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. [Young, Deborah] Pfizer, Immunol & Inflammat, Cambridge, MA USA. RP Fiorina, P (reprint author), Harvard Univ, Childrens Hosp, Transplantat Res Ctr, Sch Med, Boston, MA 02115 USA. EM paolo.fiorina@childrens.harvard.edu RI Petrelli, Alessandra/M-7004-2015 OI Petrelli, Alessandra/0000-0002-5639-9415 FU National Institutes of Health [U01-AI-082966]; Juvenile Diabetes Research Foundation; American Society of Nephrology; National Heart, Lung, and Blood Institute, National Institutes of Health FX A.J.Z. has received National Institutes of Health Grant U01-AI-082966. P.F. has received a Juvenile Diabetes Research Foundation Career Development Award and the American Society of Nephrology Career Development Award. W.J.L. is supported by the Intramural Research Program, National Heart, Lung, and Blood Institute, National Institutes of Health. NR 40 TC 15 Z9 15 U1 0 U2 7 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD DEC PY 2011 VL 60 IS 12 BP 3223 EP 3234 DI 10.2337/db11-0880 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 857JP UT WOS:000297715100017 PM 22013017 ER PT J AU Bolo, NR Musen, G Jacobson, AM Weinger, K McCartney, RL Flores, V Renshaw, PF Simonson, DC AF Bolo, Nicolas R. Musen, Gail Jacobson, Alan M. Weinger, Katie McCartney, Richard L. Flores, Veronica Renshaw, Perry F. Simonson, Donald C. TI Brain Activation During Working Memory Is Altered in Patients With Type 1 Diabetes During Hypoglycemia SO DIABETES LA English DT Article ID MILD COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; MODERATE HYPOGLYCEMIA; DEFAULT MODE; MELLITUS; REGIONS; METABOLISM; CORTEX; SCHIZOPHRENIA; CONNECTIVITY AB OBJECTIVE-To investigate the effects of acute hypoglycemia on working memory and brain function in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS-Using blood oxygen level-dependent (BOLD) functional magnetic resonance imaging during euglycemic (5.0 nunol/L) and hypoglycemic (2.8 mmol/L) hyperinsulinemic clamps, we compared brain activation response to a working-memory task (WMT) in type 1 diabetic subjects (n = 16) with that in age-matched nondiabetic control subjects (n = 16). Behavioral performance was assessed by percent correct responses. RESULTS-During euglycemia, the WMT activated the bilateral frontal and parietal cortices, insula, thalamus, and cerebellum in both groups. During hypoglycemia, activation decreased in both groups but remained 80% larger in type 1 diabetic versus control subjects (P < 0.05). In type 1 diabetic subjects, higher HbA(1c) was associated with lower activation in the right parahippocampal gyrus and amygdala (R(2) = 0.45, P < 0.002). Deactivation of the default-mode network (DMN) also was seen in both groups during euglycemia. However, during hypoglycemia, type 1 diabetic patients deactivated the DMN 70% less than control subjects (P < 0.05). Behavioral performance did not differ between glycemic conditions or groups. CONCLUSIONS-BOLD activation was increased and deactivation was decreased in type 1 diabetic versus control subjects during hypoglycemia. This higher level of brain activation required by type 1 diabetic subjects to attain the same level of cognitive performance as control subjects suggests reduced cerebral efficiency in type 1 diabetes. Diabetes 60:3256-3264, 2011 C1 [Bolo, Nicolas R.; Renshaw, Perry F.] McLean Hosp, Brain Imaging Ctr, Belmont, MA 02178 USA. [Bolo, Nicolas R.] Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02215 USA. [Bolo, Nicolas R.; Musen, Gail; Jacobson, Alan M.; Weinger, Katie; Renshaw, Perry F.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Musen, Gail; Jacobson, Alan M.; Weinger, Katie; McCartney, Richard L.; Flores, Veronica] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Jacobson, Alan M.] Winthrop Univ Hosp, Res Inst, Mineola, NY 11501 USA. [Renshaw, Perry F.] Univ Utah, Dept Psychiat, Salt Lake City, UT USA. [Simonson, Donald C.] Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. [Simonson, Donald C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Bolo, NR (reprint author), McLean Hosp, Brain Imaging Ctr, 115 Mill St, Belmont, MA 02178 USA. EM nbolo@bidmc.harvard.edu FU National Institutes of Health [5R01-DK073843-03, DK-60754, DK-62218-01A1, P30-DK-36836]; Herbert Graetz Fund; [5M01-RR001032-32] FX This study was supported in part by National Institutes of Health grants 5R01-DK073843-03, DK-60754, DK-62218-01A1, and P30-DK-36836 (Joslin Diabetes and Endocrinology Research Center); the Herbert Graetz Fund; and grant 5M01-RR001032-32 to the Beth Israel Deaconess General Clinical Research Center. NR 50 TC 21 Z9 24 U1 2 U2 10 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD DEC PY 2011 VL 60 IS 12 BP 3256 EP 3264 DI 10.2337/db11-0506 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 857JP UT WOS:000297715100020 PM 21984582 ER PT J AU Cohen-Kfir, E Artsi, H Levin, A Abramowitz, E Bajayo, A Gurt, I Zhong, L D'Urso, A Toiber, D Mostoslavsky, R Dresner-Pollak, R AF Cohen-Kfir, Einav Artsi, Hanna Levin, Avi Abramowitz, Eva Bajayo, Alon Gurt, Irina Zhong, Lei D'Urso, Agustina Toiber, Debra Mostoslavsky, Raul Dresner-Pollak, Rivka TI Sirt1 Is a Regulator of Bone Mass and a Repressor of Sost Encoding for Sclerostin, a Bone Formation Inhibitor SO ENDOCRINOLOGY LA English DT Article ID DECREASES ADIPOCYTE FORMATION; MESENCHYMAL STEM-CELLS; VAN-BUCHEM-DISEASE; PARATHYROID-HORMONE; OSTEOBLAST DIFFERENTIATION; CALORIE RESTRICTION; BMP ANTAGONIST; PPAR-GAMMA; LIFE-SPAN; GENE AB Sirt1, the mammalian ortholog of the yeast Sir2 (silent information regulator 2), was shown to play an important role in metabolism and in age-associated diseases, but its role in skeletal homeostasis and osteoporosis has yet not been studied. Using 129/Sv mice with a germline mutation in the Sirt1 gene, we demonstrate that Sirt1 haplo-insufficient (Sirt1(+/-)) female mice exhibit a significant reduction in bone mass characterized by decreased bone formation and increased marrow adipogenesis. Importantly, we identify Sost, encoding for sclerostin, a critical inhibitor of bone formation, as a novel target of Sirt1. Using chromatin immunoprecipitation analysis, we reveal that Sirt1 directly and negatively regulates Sost gene expression by deacetylating histone 3 at lysine 9 at the Sost promoter. Sost down-regulation by small interfering RNA and the administration of a sclerostin-neutralizing antibody restore gene expression of osteocalcin and bone sialoprotein as well as mineralized nodule formation in Sirt1(+/-) marrow-derived mesenchymal stem cells induced to osteogenesis. These findings reveal a novel role for Sirt1 in bone as a regulator of bone mass and a repressor of sclerostin, and have potential implications suggesting that Sirt1 is a target for promoting bone formation as an anabolic approach for treatment of osteoporosis. (Endocrinology 152: 4514-4524, 2011) C1 [Cohen-Kfir, Einav; Artsi, Hanna; Levin, Avi; Abramowitz, Eva; Gurt, Irina; Dresner-Pollak, Rivka] Hadassah Hebrew Univ Med Ctr, Endocrinol & Metab Serv, Dept Med, IL-91120 Jerusalem, Israel. [Bajayo, Alon] Hebrew Univ Jerusalem, Bone Lab, IL-91120 Jerusalem, Israel. [Zhong, Lei; D'Urso, Agustina; Toiber, Debra; Mostoslavsky, Raul] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA. RP Dresner-Pollak, R (reprint author), Hadassah Hebrew Univ Med Ctr, Endocrinol & Metab Serv, Dept Med, POB 12000, IL-91120 Jerusalem, Israel. EM rivkap@hadassah.org.il FU Israel Science Foundation [1230/07]; Ministry of Health, Israel [3_3926]; Hadassah Zionist Women Organization of America; American Federation of Aging Research FX This work was supported by the Israel Science Foundation Grant 1230/07 (to R.D.-P.), the Chief Scientist, Ministry of Health, Israel Grant 3_3926 (to R.D.-P.), Hadassah Zionist Women Organization of America Research Fund for Women's Health (to R.D.-P.). R.M. is a Kimmel Scholar and is the recipient of a Young Investigator Award from the American Federation of Aging Research. NR 46 TC 51 Z9 56 U1 1 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 2011 VL 152 IS 12 BP 4514 EP 4524 DI 10.1210/en.2011-1128 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 852RZ UT WOS:000297376500008 PM 21952235 ER PT J AU Karagiannides, I Bakirtzi, K Kokkotou, E Stavrakis, D Margolis, KG Thomou, T Giorgadze, N Kirkland, JL Pothoulakis, C AF Karagiannides, Iordanes Bakirtzi, Kyriaki Kokkotou, Efi Stavrakis, Dimitris Margolis, Kara Gross Thomou, Thomas Giorgadze, Nino Kirkland, James L. Pothoulakis, Charalabos TI Role of Substance P in the Regulation of Glucose Metabolism via Insulin Signaling-Associated Pathways SO ENDOCRINOLOGY LA English DT Article ID ENDOPLASMIC-RETICULUM STRESS; HIGH-FAT DIET; ADIPOSE-TISSUE; ENDOCRINE ORGAN; OBESE SUBJECTS; TNF-ALPHA; IKK-BETA; RESISTANCE; RECEPTOR; PREADIPOCYTES AB Substance P (SP), encoded by the tachykinin 1 (Tac1) gene, is the most potent tachykinin ligand for the high-affinity neurokinin-1 receptor (NK-1R). We previously reported that NK-1R-deficient mice show less weight gain and reduced circulating levels of leptin and insulin in response to a high-fat diet (HFD) and demonstrated the presence of functional NK-1R in isolated human preadipocytes. Here we assessed the effects of SP on weight gain in response to HFD and determined glucose metabolism in Tac1-deficient (Tac1(-/-)) mice. The effect of SP on the expression of molecules that may predispose to reduced glucose uptake was also determined in isolated human mesenteric, omental, and sc preadipocytes. We show that although weight accumulation in response to HFD was similar between Tac1(-/-) mice and wild-type littermates, Tac1(-/-) mice demonstrated lower glucose and leptin and increased adiponectin blood levels and showed improved responses to insulin challenge after HFD. SP stimulated phosphorylation of c-Jun N-terminal kinase, protein kinase C theta, mammalian target of rapamycin, and inhibitory serine insulin receptor substrate-1 phosphorylation in human preadipocytes in vitro. Preincubation of human mesenteric preadipocytes with the protein kinase C theta pseudosubstrate inhibitor reduced insulin receptor substrate 1 phosphorylation in response to SP. Lastly, SP also induced insulin receptor substrate-1 phosphorylation in mature human sc adipocytes. Our results demonstrate an important role for SP in adipose tissue responses and obesity-associated pathologies. These novel SP effects on molecules that enhance insulin resistance at the adipocyte level may reflect an important role for this peptide in the pathophysiology of type 2 diabetes. (Endocrinology 152: 4571-4580, 2011) C1 [Karagiannides, Iordanes; Bakirtzi, Kyriaki; Stavrakis, Dimitris; Pothoulakis, Charalabos] Univ Calif Los Angeles, David Geffen Sch Med, Ctr Inflammatory Bowel Dis, Div Digest Dis, Los Angeles, CA 90095 USA. [Kokkotou, Efi] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Gastroenterol, Boston, MA 02215 USA. [Thomou, Thomas] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. [Margolis, Kara Gross] Columbia Univ, Med Ctr, Dept Pediat, New York, NY 10032 USA. [Giorgadze, Nino; Kirkland, James L.] Mayo Clin, Robert & Arlene Kogod Ctr Aging, Rochester, MN 55905 USA. RP Pothoulakis, C (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Ctr Inflammatory Bowel Dis, Div Digest Dis, 675 Charles E Young Dr,S MRL Bldg 1240, Los Angeles, CA 90095 USA. EM ikaragiannidis@mednet.ucla.edu; cpothoulakis@mdenet.ucla.edu RI Kirkland, James/F-9159-2016 FU National Institutes of Health [DK 47343, 1RC1 DK 086150-01, AG13925, AG031736]; Crohn's and Colitis Foundation of America, Inc.; Noaber Foundation; Ted Nash Foundation; Broad Medical Foundation FX This work was supported by Grants DK47343 and 1RC1 DK 086150-01 (to C.P.) and AG13925 and AG031736 (to J.L.K.) from the National Institutes of Health. This work was also supported by the Eli and Edythe Broad Chair (to C.P.), a Research Fellowship Award from the Crohn's and Colitis Foundation of America, Inc. (to I.K.), the Noaber Foundation (to J.L.K.), the Ted Nash Foundation (to J.L.K.), and the Broad Medical Foundation (to I.K.). NR 49 TC 11 Z9 11 U1 2 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 2011 VL 152 IS 12 BP 4571 EP 4580 DI 10.1210/en.2011-1170 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 852RZ UT WOS:000297376500013 PM 22009727 ER PT J AU Samuvel, DJ Jin, JF Sundararaj, KP Li, YC Zhang, XM Lopes-Virella, MF Huang, Y AF Samuvel, Devadoss J. Jin, Junfei Sundararaj, Kamala P. Li, Yanchun Zhang, Xiaoming Lopes-Virella, Maria F. Huang, Yan TI TLR4 Activation and IL-6-Mediated Cross Talk between Adipocytes and Mononuclear Cells Synergistically Stimulate MMP-1 Expression SO ENDOCRINOLOGY LA English DT Article ID ADIPOSE-TISSUE DEVELOPMENT; LOW-GRADE INFLAMMATION; DIET-INDUCED OBESITY; NF-KAPPA-B; INSULIN-RESISTANCE; MATRIX METALLOPROTEINASES; TRANSCRIPTION FACTOR; ACID; ANGIOGENESIS; INHIBITION AB Obesity is associated with increased monocyte infiltration into adipose tissue and hence increased interaction between adipocytes and monocytes. Although it has been shown that matrix metalloproteinases (MMP) play a critical role in adipose tissue development, the effect of adipocyte and monocyte interaction on MMP production remains largely unknown. Furthermore, although it has been shown that Toll-like receptor 4 (TLR4), a receptor mediating innate immune response, plays an important role in the obesity-associated inflammation and insulin resistance, the effect of TLR4 activation in coculture of adipocytes and monocytes on MMP production has not been investigated. In this study, we cocultured adipocytes with U937 mononuclear cells in a Transwell coculture system and activated TLR4 with lipopolysaccharide or palmitic acid. We found that TLR4 activation and the coculture had a synergistic effect on MMP-1 production. In our further investigation on the underlying mechanisms, it was indicated that adipocyte-derived IL-6 and TLR4 activation acted in concert to synergistically stimulate MMP-1 expression by U937 cells. Taken together, this study has uncovered a novel mechanism potentially involved in MMP-1 up-regulation in adipose tissue, which may facilitate adipose tissue development and obesity. (Endocrinology 152: 4662-4671, 2011) C1 [Lopes-Virella, Maria F.; Huang, Yan] Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. [Samuvel, Devadoss J.; Jin, Junfei; Sundararaj, Kamala P.; Li, Yanchun; Zhang, Xiaoming; Lopes-Virella, Maria F.; Huang, Yan] Med Univ S Carolina, Div Endocrinol Diabet & Med Genet, Charleston, SC 29425 USA. [Samuvel, Devadoss J.; Jin, Junfei; Sundararaj, Kamala P.; Li, Yanchun; Zhang, Xiaoming; Lopes-Virella, Maria F.; Huang, Yan] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. RP Huang, Y (reprint author), Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, 114 Doughty St, Charleston, SC 29403 USA. EM huangyan@musc.edu FU Department of Veterans Affairs; National Institutes of Health [DE16353] FX This work was supported by a Merit Review Grant from Department of Veterans Affairs and National Institutes of Health Grant DE16353 (to Y.H.). NR 36 TC 6 Z9 6 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 2011 VL 152 IS 12 BP 4662 EP 4671 DI 10.1210/en.2011-1026 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 852RZ UT WOS:000297376500022 PM 21952248 ER PT J AU Gahete, MD Cordoba-Chacon, J Anadumaka, CV Lin, Q Bruning, JC Kahn, CR Luque, RM Kineman, RD AF Gahete, Manuel D. Cordoba-Chacon, Jose Anadumaka, Chike V. Lin, Qing Bruening, Jens C. Kahn, C. Ronald Luque, Raul M. Kineman, Rhonda D. TI Elevated GH/IGF-I, Due to Somatotrope-Specific Loss of Both IGF-I and Insulin Receptors, Alters Glucose Homeostasis and Insulin Sensitivity in a Diet-Dependent Manner SO ENDOCRINOLOGY LA English DT Article ID HORMONE-TRANSGENIC MICE; GROWTH-FACTOR-I; HIGH-FAT DIET; BODY-COMPOSITION; FUSION GENES; ENERGY-EXPENDITURE; PROTEIN-METABOLISM; BINDING-PROTEINS; INDUCED OBESITY; ADIPOSE-TISSUE AB A unique mouse model was developed with elevated endogenous GH (2- to 3-fold) and IGF-I (1.2- to 1.4-fold), due to somatotrope-specific Cre-mediated inactivation of IGF-I receptor (IgfIr) and insulin receptor (Insr) genes (IgfIr, Insr(rGHpCre), referred to as HiGH mice). We demonstrate that the metabolic phenotype of HiGH mice is diet dependent and differs from that observed in other mouse models of GH excess due to ectopic heterologous transgene expression or pituitary tumor formation. Elevated endogenous GH promotes lean mass and whole-body lipid oxidation but has minimal effects on adiposity, even in response to diet-induced obesity. When caloric intake is moderated, elevated GH improves glucose clearance, despite low/normal insulin sensitivity, which may be explained in part by enhanced IGF-I and insulin output. However, when caloric intake is in excess, elevated GH promotes hepatic lipid accumulation, insulin resistance, hyperglycemia, and ketosis. The HiGH mouse model represents a useful tool to study the role endogenous circulating GH levels play in regulating health and disease. (Endocrinology 152: 4825-4837, 2011) C1 [Gahete, Manuel D.; Cordoba-Chacon, Jose; Anadumaka, Chike V.; Lin, Qing; Kineman, Rhonda D.] Univ Illinois, Jesse Brown Vet Affairs Med Ctr, Div Res & Dev, Chicago, IL 60612 USA. [Gahete, Manuel D.; Cordoba-Chacon, Jose; Anadumaka, Chike V.; Lin, Qing; Kineman, Rhonda D.] Univ Illinois, Sect Endocrinol Diabet & Metab, Dept Med, Chicago, IL 60612 USA. [Bruening, Jens C.] Univ Hosp, Inst Genet, D-50924 Cologne, Germany. [Bruening, Jens C.] Univ Hosp, Ctr Mol Med Mouse Genet & Metab, D-50924 Cologne, Germany. [Bruening, Jens C.] Univ Hosp, Max Planck Inst Neurol Res, D-50924 Cologne, Germany. [Bruening, Jens C.] Univ Hosp, Ctr Endocrinol Diabet & Prevent Med, D-50924 Cologne, Germany. [Kahn, C. Ronald] Joslin Diabet Ctr, Sect Obes & Hormone Act, Boston, MA 02215 USA. [Luque, Raul M.] Univ Cordoba, Inst Maimonides Invest Biomed Cordoba IMIBIC, Dept Cell Biol Physiol & Immunol, Cordoba 14014, Spain. [Luque, Raul M.] Ctr Invest Biomed Red Fisiopatol Obesidad & Nutr, Cordoba 14014, Spain. RP Kineman, RD (reprint author), Univ Illinois, Jesse Brown Vet Affairs Med Ctr, Div Res & Dev, 820 S Damen Ave,Bldg 11A,Suite 6215,MP151, Chicago, IL 60612 USA. EM kineman@uic.edu RI Gahete, Manuel/C-4969-2009; Kineman, Rhonda/H-2221-2011 OI Gahete, Manuel/0000-0002-4578-2179; Kineman, Rhonda/0000-0001-7322-1152 FU Department of Veterans Affairs; Veterans Health Administration; Office of Research and Development; National Institutes of Health [R21AG031465, R01DK088133]; Fundacion Caja Madrid; Ministerio de Ciencia e Innovacion [RYC-2007-00186, BFU2008-01136/BFI]; Ministerio de Educacion [JC2008-00220] FX This work was supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development Merit Award, National Institutes of Health Grants R21AG031465 and R01DK088133 (to R.D.K.), Fundacion Caja Madrid, Postdoctoral Grant (M.D.G.), Ministerio de Ciencia e Innovacion Grants RYC-2007-00186 and BFU2008-01136/BFI and Ministerio de Educacion Grant JC2008-00220 (to R.M.L.). NR 64 TC 15 Z9 15 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 2011 VL 152 IS 12 BP 4825 EP 4837 DI 10.1210/en.2011-1447 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 852RZ UT WOS:000297376500036 PM 21990313 ER PT J AU Carrithers, LM Hulseberg, P Sandor, M Carrithers, MD AF Carrithers, Lisette M. Hulseberg, Paul Sandor, Matyas Carrithers, Michael D. TI The human macrophage sodium channel NaV1.5 regulates mycobacteria processing through organelle polarization and localized calcium oscillations SO FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY LA English DT Article DE macrophage; phagocytosis; voltage-gated sodium channel; calcium signaling ID INTRACELLULAR CA2+ STORES; HUMAN NEUTROPHILS; PHAGOCYTOSIS; PROTEIN; CELLS; TUBERCULOSIS; INHIBITION; PHAGOSOME; DYNAMICS; RELEASE AB Phagocytosis and intracellular processing of mycobacteria by macrophages are complex cellular processes that require spatial and temporal coordination of particle uptake, organelle movement, activation of signaling pathways, and channel-mediated ionic flux. Recent work demonstrated that human macrophage NaV1.5, an intracellular voltage-gated sodium channel expressed on late endosomes, enhances endosomal acidification and phagocytosis. Here, using bacillus Camille-Guerin (BCG) as a model of mycobacterial infection, we examined how this channel regulates phagocytosis and phagosome maturation in human macrophages. Knockdown of NaV1.5 reduced high capacity uptake of labeled BCG. BCG-containing, NaV1.5-expressing cells demonstrated localization of NaV1.5 and Rab-7 positive endosomes and mitochondria to periphagosome regions that was not observed in NaV1.5-deficient cells. Knockdown of the channel reduced the initial calcium response following bacterial challenge and prevented the generation of prolonged and localized calcium oscillations during phagosome maturation. Inhibition of the mitochondrial Na+/Ca2+ exchanger also prevented prolonged calcium oscillations during phagosome maturation. These results suggest that NaV1.5 and mitochondrial-dependent calcium signaling regulate mycobacteria phagocytosis and phagosome maturation in human macrophages through spatial-temporal coordination of calcium signaling within a unique subcellular region. C1 [Carrithers, Lisette M.; Carrithers, Michael D.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Neurol, Madison, WI 53706 USA. [Hulseberg, Paul; Sandor, Matyas] Univ Wisconsin, Sch Med & Publ Hlth, Dept Pathol, Madison, WI 53706 USA. Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Carrithers, Michael D.] William S Middleton Mem Vet Adm Med Ctr, Neurol Serv, Madison, WI USA. RP Carrithers, MD (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Dept Neurol, 1300 Univ Ave,Room 2679, Madison, WI 53706 USA. EM carrithers@neurology.wisc.edu FU University of Wisconsin; VA Merit Award (BLRD) FX This work is supported by the University of Wisconsin and a VA Merit Award (BLR&D) to M.D.C. NR 27 TC 23 Z9 23 U1 0 U2 10 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0928-8244 J9 FEMS IMMUNOL MED MIC JI FEMS Immunol. Med. Microbiol. PD DEC PY 2011 VL 63 IS 3 BP 319 EP 327 DI 10.1111/j.1574-695X.2011.00853.x PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 850PH UT WOS:000297207200002 PM 22092558 ER PT J AU Cassani, B Villablanca, EJ Quintana, FJ Love, PE Lacy-Hulbert, A Blaner, WS Sparwasser, T Snapper, SB Weiner, HL Mora, JR AF Cassani, Barbara Villablanca, Eduardo J. Quintana, Francisco J. Love, Paul E. Lacy-Hulbert, Adam Blaner, William S. Sparwasser, Tim Snapper, Scott B. Weiner, Howard L. Mora, J. Rodrigo TI Gut-Tropic T Cells That Express Integrin alpha 4 beta 7 and CCR9 Are Required for Induction of Oral Immune Tolerance in Mice SO GASTROENTEROLOGY LA English DT Article DE Immune Regulation; Autoimmunity; Allergy; Intestine; Peyer's Patch ID PLASMACYTOID DENDRITIC CELLS; RETINOIC-ACID; SMALL-INTESTINE; SUPPRESSION; COLITIS; ABSENCE; IL-10; TH17; INFLAMMATION; LYMPHOCYTES AB BACKGROUND & AIMS: Induction of oral immune tolerance (OT) blocks proinflammatory responses to orally administered antigens and might be used to treat autoimmune conditions. We investigated whether gut-tropic T cells that express the integrin alpha 4 beta 7 and the chemokine receptor CCR9 are required for OT. METHODS: Skin delayed-type hypersensitivity and experimental autoimmune encephalomyelitis were used to monitor OT in mice. To assess the role of receptors that mediate localization of lymphocytes to the gut (gut-homing receptors) in induction of OT, we studied CCR9(-/-) and beta 7(-/-) mice and also blocked the alpha 4 beta 7 ligand MAdCAM-1 in wild-type mice. We used DEREG and Scurfy mice to assess the role of Foxp3(+) regulatory T cells (Treg) and IL-10(-/-) and IL-10R beta(-/-) mice to examine the role of interleukin (IL)-10 in induction of OT. RESULTS: OT could not be induced in CCR9(-/-) or beta 7(-/-) mice, or when MAdCAM-1 was blocked in wild-type mice, indicating that gut-homing receptors are required for oral tolerization. Consistent with the role of all-trans retinoic acid in inducing gut-homing T cells, OT could not be induced in mice depleted of vitamin A. OT was rescued in CCR9(-/-) mice following adoptive transfer of wild-type T cells, but not CCR9(-/-) or beta 7(-/-) T cells. Gut-homing T cells are therefore necessary and sufficient to induce OT. Wild-type Treg and IL-10 were required to restore OT to CCR9-/- mice, indicating that homing and functional differentiation of IL-10-producing Treg in the gut is required for OT. Conversely, transfer of CCR9(-/-) or beta 7(-/-) T cells to wild-type mice partially inhibited OT. CONCLUSIONS: Expression of CCR9 and alpha 4 beta 7 on T cells and their subsequent localization to the gut is required for induction of OT in mice. Therapies designed to block gut-homing receptors might, under some conditions, interfere with normal tolerogenic mechanisms in the intestinal mucosa. C1 [Cassani, Barbara; Villablanca, Eduardo J.; Mora, J. Rodrigo] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Snapper, Scott B.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Snapper, Scott B.] Childrens Hosp, Gastrointestinal Unit, Boston, MA 02115 USA. [Quintana, Francisco J.; Weiner, Howard L.] Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. [Love, Paul E.; Lacy-Hulbert, Adam] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Blaner, William S.] Columbia Univ, Dept Med, New York, NY USA. [Sparwasser, Tim] Ctr Expt & Clin Infect Res, Inst Infect Immunol, Hannover, Germany. RP Mora, JR (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. EM j_rodrigo_mora@hms.harvard.edu RI Villablanca, Eduardo/E-1380-2016; Cassani, Barbara/K-3871-2016; OI Villablanca, Eduardo/0000-0001-9522-9729; Cassani, Barbara/0000-0002-4115-8109; Lacy-Hulbert, Adam/0000-0003-2162-0156 FU EMBO; Crohn's & Colitis Foundation of America; National Institutes of Health [R00 AI075285-02, AI435801, NS38037, P30 AR042689, DP2 2009A054301]; National Multiple Sclerosis Society [RG4111A1]; Boston Area Diabetes Endocrinology Research Center; Cancer Research Institute; Massachusetts Life Science Center FX B.C. was supported by an EMBO postdoctoral fellowship. E.J.V. was supported by a postdoctoral fellowship from the Crohn's & Colitis Foundation of America. F.J.Q. was supported by grants from the National Institutes of Health (R00 AI075285-02), National Multiple Sclerosis Society (RG4111A1), and Boston Area Diabetes Endocrinology Research Center. H.L.W. was supported by National Institutes of Health grants AI435801 and NS38037. J.R.M. was supported by grants from the Crohn's & Colitis Foundation of America, Cancer Research Institute, Massachusetts Life Science Center, National Institutes of Health Pilot Feasibility Award P30 AR042689, and National Institutes of Health Director's New Innovator Award DP2 2009A054301. NR 44 TC 74 Z9 76 U1 0 U2 9 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD DEC PY 2011 VL 141 IS 6 BP 2109 EP 2118 DI 10.1053/j.gastro.2011.09.015 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 852DQ UT WOS:000297329000032 PM 21925467 ER PT J AU Rowland, KJ Trivedi, S Lee, D Wan, K Kulkarni, RN Holzenberger, M Brubaker, PL AF Rowland, Katherine J. Trivedi, Shivangi Lee, Daiyoon Wan, Ken Kulkarni, Rohit N. Holzenberger, Martin Brubaker, Patricia L. TI Loss of Glucagon-Like Peptide-2-Induced Proliferation Following Intestinal Epithelial Insulin-Like Growth Factor-1-Receptor Deletion SO GASTROENTEROLOGY LA English DT Article DE Enteroendocrine L Cell; Growth; Signaling; Mouse Model ID FACTOR-I; IGF-I; MESENCHYMAL CELLS; ENTERIC NEURONS; BLOOD-FLOW; MICE; GLP-2; EXPRESSION; LOCALIZATION; HORMONE AB BACKGROUND & AIMS: Glucagon-like peptide-2 (GLP-2) is an intestinal hormone that promotes growth of the gastrointestinal tract. Although insulin-like growth factor (IGF)-1 and the IGF-1 receptor (IGF-1R) are required for GLP-2-induced proliferation of crypt cells, little is known about localization of the IGF-1R which mediates the intestinotropic actions of GLP-2. METHODS: We examined intestinal growth and proliferative responses in mice with conditional deletion of IGF-1R from intestinal epithelial cells (IE-igf1rKO) after acute administration (30-90 min) of GLP-2, in response to 24-hour fasting and re-feeding (to induce GLP-2-dependent adaptation), and after chronic exposure (10 days) to GLP-2. RESULTS: IE-igf1rKO mice had normal small intestinal weight, morphometric parameters, proliferative indices, and distribution of differentiated epithelial cell lineages. Acute administration of GLP-2 increased nuclear translocation of beta-catenin in non-Paneth crypt cells and stimulated the crypt-cell proliferative marker c-Myc in control but not IE-igf1rKO mice. Small intestinal weight, crypt depth, villus height, and crypt-cell proliferation were decreased in control and IE-igf1rKO mice after 24-hour fasting. Although re-feeding control mice restored all of these parameters, re-fed IE-igf1rKO mice had reductions in adaptive regrowth of the villi and crypt-cell proliferation. Control mice that were given chronic GLP-2 had increases in small intestinal weight, mucosal cross-sectional area, crypt depth, villus height, and crypt-cell proliferation. However, the GLP-2-induced increase in crypt-cell proliferation was not observed in IE-igf1rKO mice, and growth of the crypt-villus axis was reduced. CONCLUSIONS: The proliferative responses of the intestinal epithelium to exogenous GLP-2 administration and conditions of GLP-2-dependent adaptive re-growth require the intestinal epithelial IGF-1R. C1 [Rowland, Katherine J.; Trivedi, Shivangi; Lee, Daiyoon; Wan, Ken; Brubaker, Patricia L.] Univ Toronto, Dept Physiol, Toronto, ON M5S 1A8, Canada. [Kulkarni, Rohit N.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Brubaker, Patricia L.] Univ Toronto, Fac Med, Dept Med, Toronto, ON M5S 1A8, Canada. [Holzenberger, Martin] Univ Paris 06, Fac Med, UPMC UMR938, St Antoine Hosp, Paris, France. [Holzenberger, Martin] INSERM, Paris, France. RP Brubaker, PL (reprint author), Univ Toronto, Dept Physiol, Med Sci Bldg,Room 3366,1 Kings Coll Circle, Toronto, ON M5S 1A8, Canada. EM p.brubaker@utoronto.ca FU Canadian Institutes of Health Research [MOP-9940]; Canadian Digestive Health Foundation; Banting and Best Diabetes Centre, University of Toronto; Canadian Association of Gastroenterology; Canada Research Chairs Program; National Institutes of Health [DK67536]; Glaxo-Smith-Kline; Regeneron FX Katherine Rowland was supported by a Doctoral Research Award from the Canadian Institutes of Health Research in partnership with the Canadian Digestive Health Foundation, and by a Banting and Best Diabetes Centre Graduate Studentship, University of Toronto; Shivangi Trivedi and Ken Wan were supported by Canadian Association of Gastroenterology Summer Studentships; and Patricia Brubaker was supported by the Canada Research Chairs Program. These studies were supported by an operating grant from the Canadian Institutes of Health Research (#MOP-9940 to PLB); and by the National Institutes of Health (RO1 #DK67536; to RNK).; This author discloses the following: Patricia Brubaker has received consulting fees from Glaxo-Smith-Kline and Regeneron. The remaining authors disclose no conflicts. NR 41 TC 26 Z9 26 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD DEC PY 2011 VL 141 IS 6 BP 2166 EP U330 DI 10.1053/j.gastro.2011.09.014 PG 17 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 852DQ UT WOS:000297329000037 PM 21925122 ER PT J AU Foulkes, WD Bahubeshi, A Hamel, N Pasini, B Asioli, S Baynam, G Choong, CS Charles, A Frieder, RP Dishop, MK Graf, N Ekim, M Bouron-Dal Soglio, D Arseneau, J Young, RH Sabbaghian, N Srivastava, A Tischkowitz, MD Priest, JR AF Foulkes, William D. Bahubeshi, Amin Hamel, Nancy Pasini, Barbara Asioli, Sofia Baynam, Gareth Choong, Catherine S. Charles, Adrian Frieder, Richard P. Dishop, Megan K. Graf, Nicole Ekim, Mesiha Bouron-Dal Soglio, Dorothee Arseneau, Jocelyne Young, Robert H. Sabbaghian, Nelly Srivastava, Archana Tischkowitz, Marc D. Priest, John R. TI Extending the phenotypes associated with DICER1 mutations SO HUMAN MUTATION LA English DT Article DE DICER1; sarcoma; cPNET; Wilms tumor; congenital cardiac defects ID LEYDIG CELL TUMOR; PLEUROPULMONARY BLASTOMA; SARCOMA BOTRYOIDES; CYSTIC NEPHROMA; CERVIX AB DICER1 is crucial for embryogenesis and early development. Forty different heterozygous germline DICER1 mutations have been reported worldwide in 42 probands that developed as children or young adults, pleuropulmonary blastoma (PPB), cystic nephroma (CN), ovarian sex cord-stromal tumors (especially Sertoli-Leydig cell tumor [SLCT]), and/or multinodular goiter (MNG). We report DICER1 mutations in seven additional families that manifested uterine cervix embryonal rhabdomyosarcoma (cERMS, four cases) and primitive neuroectodermal tumor (cPNET, one case), Wilms tumor (WT, three cases), pulmonary sequestration (PS, one case), and juvenile intestinal polyp (one case). One carrier developed (age 25 years) a pleomorphic sarcoma of the thigh; another carrier had transposition of great arteries (TGA). These observations show that cERMS, cPNET, WT, PS, and juvenile polyps fall within the spectrum of DICER1-related diseases. DICER1 appears to be the first gene implicated in the etiology of cERMS, cPNET, and PS. Young adulthood sarcomas and perhaps congenital malformations such as TGA may also be associated. 32:13811384, 2011. (C) 2011 Wiley Periodicals, Inc. C1 [Foulkes, William D.] McGill Univ, Program Canc Genet, Dept Oncol, Gerald Bronfman Ctr Clin Res Oncol, Montreal, PQ H2W 1S6, Canada. [Foulkes, William D.; Bahubeshi, Amin; Sabbaghian, Nelly; Srivastava, Archana; Tischkowitz, Marc D.] McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Segal Canc Ctr, Montreal, PQ H3T 1E2, Canada. [Foulkes, William D.; Hamel, Nancy] McGill Univ, Res Inst, Ctr Hlth, Montreal, PQ H2W 1S6, Canada. [Pasini, Barbara] Univ Turin, Dept Genet Biol & Biochem, I-10124 Turin, Italy. [Baynam, Gareth; Choong, Catherine S.] Univ Western Australia, Sch Paediat & Child Hlth, Nedlands, WA 6009, Australia. [Charles, Adrian] Univ Western Australia, Sch Pathol, Nedlands, WA 6009, Australia. [Frieder, Richard P.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90095 USA. [Frieder, Richard P.] Canc Risk Assessment & Prevent, Santa Monica, CA USA. [Dishop, Megan K.] Childrens Hosp Colorado, Dept Pathol, Aurora, CO USA. [Dishop, Megan K.] Univ Colorado Denver, Sch Med, Aurora, CO USA. [Graf, Nicole] Childrens Hosp Westmead, Dept Pathol, Sydney, NSW, Australia. [Ekim, Mesiha] Ankara Univ, Dept Pediat Nephrol, Sch Med, TR-06100 Ankara, Turkey. [Bouron-Dal Soglio, Dorothee] CHU St Justine, Dept Pathol, Montreal, PQ, Canada. [Arseneau, Jocelyne] McGill Univ, Dept Pathol, Montreal, PQ H2W 1S6, Canada. [Young, Robert H.] Harvard Univ, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Priest, John R.] Childrens Hosp & Clin Minnesota, Int Pleuropulm Blastoma Registry, Minneapolis, MN USA. [Foulkes, William D.; Bahubeshi, Amin; Hamel, Nancy; Sabbaghian, Nelly; Srivastava, Archana; Tischkowitz, Marc D.] McGill Univ, Program Canc Genet, Dept Human Genet, Montreal, PQ H2W 1S6, Canada. [Asioli, Sofia] Univ Turin, Dept Biomed Sci & Human Oncol, I-10124 Turin, Italy. RP Foulkes, WD (reprint author), McGill Univ, Program Canc Genet, Dept Oncol, Gerald Bronfman Ctr Clin Res Oncol, 546 Pine Ave W, Montreal, PQ H2W 1S6, Canada. EM william.foulkes@mcgill.ca RI Ekim, Mesiha/L-9398-2014; OI Charles, Adrian/0000-0002-3193-1065; foulkes, william/0000-0001-7427-4651 FU Fonds de recherche du Quebec-Sante; The Weekend the End Women's Cancer; Susan G. Komen for the Cure; Marsha Rivkin Centre for Ovarian Cancer Research; Turner Cancer Research Fund; Mendon F Schutt Foundation; Pine Tree Apple Tennis Classic; Theodora H. Lang Charitable Trust FX Contract grant sponsors: Fonds de recherche du Quebec-Sante; The Weekend the End Women's Cancer; Susan G. Komen for the Cure; Marsha Rivkin Centre for Ovarian Cancer Research; Turner Cancer Research Fund; Mendon F Schutt Foundation; Pine Tree Apple Tennis Classic; Theodora H. Lang Charitable Trust. NR 21 TC 65 Z9 66 U1 1 U2 13 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD DEC PY 2011 VL 32 IS 12 BP 1381 EP 1384 DI 10.1002/humu.21600 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 851CV UT WOS:000297246800009 PM 21882293 ER PT J AU Stricker, CT Jacobs, LA Risendal, B Jones, A Panzer, S Ganz, PA Syrjala, KL McCabe, MS Baker, KS Miller, K Casillas, J Rosenstein, DL Campbell, M Palmer, SC AF Stricker, Carrie Tompkins Jacobs, Linda A. Risendal, Betsy Jones, Alison Panzer, Sarahlena Ganz, Patricia A. Syrjala, Karen L. McCabe, Mary S. Baker, K. Scott Miller, Kenneth Casillas, Jacqueline Rosenstein, Donald L. Campbell, Marci Palmer, Steven C. TI Survivorship care planning after the Institute of Medicine recommendations: how are we faring? SO JOURNAL OF CANCER SURVIVORSHIP-RESEARCH AND PRACTICE LA English DT Article DE Treatment summaries; Survivorship care plans/planning; Breast cancer survivorship ID CANCER SURVIVORS; BREAST-CANCER; FOLLOW-UP; PHYSICIAN WORKFORCE; EXCELLENCE NETWORK; PATIENT; PLANS; CENTERS; VIEWS AB This study evaluates the concordance of treatment summaries (TSs) and survivorship care plans (SCPs) delivered to breast cancer survivors within the LIVESTRONG (TM) Network of Survivorship Centers of Excellence with Institute of Medicine (IOM) recommendations and describes additional structure/process variables. Seven NCI-designated comprehensive cancer centers and six community-based centers participated. TS/SCPs for 65 patients were rated against IOM recommendations using a study-derived checklist, and surveys were administered to better understand the structure and process of delivering TSs/SCPs. On average, fewer than half of IOM content recommendations were met for TSs (M = 46%) and less than two thirds for SCPs (M = 59%). No sites achieved a parts per thousand yen75% overall concordance with IOM recommendations for TSs and only two of 13 met this criterion for SCPs. Content domain scores across sites varied widely, as did the number of sites addressing domain content with a parts per thousand yen75% concordance. Nonetheless, resources required for document preparation and delivery were substantial. Gaps in concordance with IOM recommendations exist even in dedicated survivorship centers. A substantial time burden was also noted. Further research is needed to determine which informational elements are essential, to develop and test strategies for improving efficiency and reach, and to determine if outcomes of survivorship care planning warrant the resources required in their preparation and delivery. TSs and SCPs have been recommended for all cancer survivors. Essential elements must be determined, approaches made more efficient, outcome improvements demonstrated, and cost-benefit analyses determined before survivors should expect widespread implementation of this recommendation for survivorship care. C1 [Stricker, Carrie Tompkins; Jacobs, Linda A.; Panzer, Sarahlena; Palmer, Steven C.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Risendal, Betsy; Jones, Alison] Univ Colorado, Ctr Canc, Aurora, CO 80045 USA. [Ganz, Patricia A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Sch Med, Los Angeles, CA 90095 USA. [Ganz, Patricia A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Sch Publ Hlth, Los Angeles, CA 90095 USA. [Syrjala, Karen L.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Survivorship Program, Seattle, WA 98109 USA. [Baker, K. Scott] Fred Hutchinson Canc Res Ctr, Pediat Blood & Marrow Transplantat Program, Seattle, WA 98109 USA. [McCabe, Mary S.] Mem Sloan Kettering Canc Ctr, Survivorship Program, New York, NY 10065 USA. [Miller, Kenneth] Dana Farber Canc Inst, Boston, MA 02215 USA. [Casillas, Jacqueline] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Div Hematol Oncol, Los Angeles, CA 90095 USA. [Rosenstein, Donald L.] Univ N Carolina, N Carolina Canc Hosp, Comprehens Canc Support Program, Dept Psychiat, Chapel Hill, NC 27514 USA. [Rosenstein, Donald L.] Univ N Carolina, N Carolina Canc Hosp, Comprehens Canc Support Program, Dept Med, Chapel Hill, NC 27514 USA. [Rosenstein, Donald L.; Campbell, Marci] Univ N Carolina, Lineberger Canc Ctr, Chapel Hill, NC 27514 USA. RP Stricker, CT (reprint author), Univ Penn, Abramson Canc Ctr, 3400 Civ Ctr Blvd,3rd Floor W, Philadelphia, PA 19104 USA. EM carrie.stricker@uphs.upenn.edu; linda.jacobs@uphs.upenn.edu; Betsy.Risendal@ucdenver.edu; alison.jones@uch.edu; sarahlena.panzer@uphs.upenn.edu; pganz@ucla.edu; ksyrjala@fhcrc.org; McCabeM@mskcc.org; ksbaker@fhcrc.org; kenneth_miller@dfci.harvard.edu; jcasillas@mednet.ucla.edu; Donald_rosenstein@med.enc.edu; Campbel7@email.unc.edu; stpalmer@mail.med.upenn.edu FU LIVESTRONG(TM) Foundation FX The authors would like to acknowledge contributions of both Donna Pucci and Alison Taggi, research coordinators at the University of Pennsylvania who were instrumental in conducting this study. We are also grateful to all of the clinical and research staff at each of the LIVESTRONG (TM) Survivorship Centers of Excellence and community-based affiliates who participated in and helped collect data for this study. This research was supported by funding from the LIVESTRONG (TM) Foundation. NR 52 TC 70 Z9 70 U1 1 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1932-2259 J9 J CANCER SURVIV JI J. Cancer Surviv.-Res. Pract. PD DEC PY 2011 VL 5 IS 4 BP 358 EP 370 DI 10.1007/s11764-011-0196-4 PG 13 WC Oncology; Social Sciences, Biomedical SC Oncology; Biomedical Social Sciences GA 852PL UT WOS:000297369800005 PM 21968543 ER PT J AU Casillas, J Syrjala, KL Ganz, PA Hammond, E Marcus, AC Moss, KM Crespi, CM Lu, PY McCabe, MS Ford, JS Jacobs, LA Pucci, D Palmer, SC Termuhlen, AM Diller, L Campbell, M Jones, B Friedman, DL AF Casillas, Jacqueline Syrjala, Karen L. Ganz, Patricia A. Hammond, Emy Marcus, Alfred C. Moss, Kerry M. Crespi, Catherine M. Lu, Peiyun McCabe, Mary S. Ford, Jennifer S. Jacobs, Linda A. Pucci, Donna Palmer, Steven C. Termuhlen, Amanda M. Diller, Lisa Campbell, Marci Jones, Barbara Friedman, Debra L. TI How confident are young adult cancer survivors in managing their survivorship care? A report from the LIVESTRONG (TM) Survivorship Center of Excellence Network SO JOURNAL OF CANCER SURVIVORSHIP-RESEARCH AND PRACTICE LA English DT Article DE Neoplasm; Young adult; Cancer survivors; Delivery of health care; Survivorship care plan ID RANDOMIZED CONTROLLED-TRIAL; QUALITY-OF-CARE; CHILDHOOD-CANCER; HEALTH-CARE; DELPHI PANEL; COMMUNICATION; ADOLESCENT; PATIENT; REPRODUCTION; PERCEPTIONS AB This study examined the association between sociodemographic, cancer treatment, and care delivery factors on young adult cancer survivors' confidence in managing their survivorship care. Survivors aged 18-39 years (n = 376) recruited from the LIVESTRONG (TM) Survivorship Center of Excellence Network sites completed a survey assessing self-reported receipt of survivorship care planning, expectations of their providers, and confidence in managing their survivorship care. Multivariate logistic regression identified characteristics of those reporting low confidence in managing their survivorship care. Mean age was 28 years; mean interval from diagnosis was 9 +/- 8 years. Seventy-one percent reported currently attending an oncology survivorship clinic. Regarding survivorship care planning, 33% did not have copies of their cancer-related medical records, 48% did not have a treatment summary, and 55% had not received a survivorship care plan. Seventy percent identified the oncologist as the most important health care provider for decisions regarding test and treatment decisions while 10% reported using a "shared-care model" involving both primary care providers and oncologists. Forty-one percent were classified as having low confidence in managing survivorship care. In multivariate analysis, low confidence was associated with non-white ethnicity and lack of a survivorship care plan (both p < 0.05). Findings suggest that provision of survivorship care plans for young adult cancer survivors can be used to improve confidence in managing survivorship care, particularly for ethnic minorities. Survivors should consider advocating for receipt of a survivorship care plan as it may facilitate confidence as a consumer of survivorship care. C1 [Casillas, Jacqueline] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Div Hematol Oncol, Los Angeles, CA 90095 USA. [Casillas, Jacqueline; Ganz, Patricia A.; Crespi, Catherine M.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Div Canc Prevent & Control Res, Los Angeles, CA 90095 USA. [Syrjala, Karen L.; Hammond, Emy] Fred Hutchinson Canc Res Ctr, Biobehav Sci Dept, Seattle, WA 98104 USA. [Marcus, Alfred C.] Univ Colorado, Ctr Canc, Denver, CO 80262 USA. [Diller, Lisa] Dana Farber Canc Inst, Boston, MA 02115 USA. [Termuhlen, Amanda M.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Termuhlen, Amanda M.] Miller Childrens Hosp, Jonathan Jacques Canc Ctr, Los Angeles, CA USA. [Jacobs, Linda A.; Pucci, Donna; Palmer, Steven C.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [McCabe, Mary S.; Ford, Jennifer S.] Mem Sloan Kettering Canc Ctr, Survivorship Program, New York, NY 10021 USA. [Crespi, Catherine M.] Univ Calif Los Angeles, Dept Biostat, Sch Publ Hlth, Los Angeles, CA 90095 USA. [Moss, Kerry M.] Connecticut Childrens Med Ctr, Hartford, CT USA. [Campbell, Marci] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Jones, Barbara] Univ Texas Austin, Sch Social Work, Austin, TX 78712 USA. [Friedman, Debra L.] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Dept Pediat, Nashville, TN 37212 USA. RP Casillas, J (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Div Hematol Oncol, 10833 Le Conte Ave,Room A2-410 MDCC, Los Angeles, CA 90095 USA. EM jcasillas@mednet.ucla.edu FU Lance Armstrong Foundation for the COE Network; Jonsson Comprehensive Cancer Center Foundation; American Society for Clinical Oncology; NIH [CA 16042, CA112631] FX This work was supported by grants from the Lance Armstrong Foundation for the COE Network, the Jonsson Comprehensive Cancer Center Foundation's STOP Cancer Research Career Development Award, and American Society for Clinical Oncology's Career Development Award. C. Crespi was supported by NIH CA 16042. K. Syrjala was also supported by NIH grant CA112631. NR 65 TC 18 Z9 18 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1932-2259 J9 J CANCER SURVIV JI J. Cancer Surviv.-Res. Pract. PD DEC PY 2011 VL 5 IS 4 BP 371 EP 381 DI 10.1007/s11764-011-0199-1 PG 11 WC Oncology; Social Sciences, Biomedical SC Oncology; Biomedical Social Sciences GA 852PL UT WOS:000297369800006 PM 22042661 ER PT J AU Judge, DP Markwald, RR Hagege, AA Levine, RA AF Judge, Daniel P. Markwald, Roger R. Hagege, Albert A. Levine, Robert A. TI Translational Research on the Mitral Valve: from Developmental Mechanisms to New Therapies SO JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH LA English DT Editorial Material ID CARDIAC VALVULAR DYSTROPHY; MARFAN-SYNDROME; MOUSE MODEL; FILAMIN-A; PROLAPSE; GENE C1 [Judge, Daniel P.] Johns Hopkins Univ, Sch Med, Div Cardiol, Baltimore, MD 21218 USA. [Judge, Daniel P.; Hagege, Albert A.] Univ Paris 05, Paris, France. [Markwald, Roger R.] Med Univ S Carolina, Dept Regenerat Med & Cell Biol, Charleston, SC 29425 USA. [Hagege, Albert A.] INSERM, U633, Paris, France. [Hagege, Albert A.] Paris Cardiovasc Res Ctr, Paris, France. [Hagege, Albert A.] Hop Europeen Georges Pompidou, Dept Cardiol, Assistance Publ Hop Paris, Paris, France. [Levine, Robert A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, Boston, MA USA. RP Judge, DP (reprint author), Johns Hopkins Univ, Sch Med, Div Cardiol, Ross 1049,720 Rutland Ave, Baltimore, MD 21218 USA. EM djudge@jhmi.edu FU NHLBI NIH HHS [R01 HL072265, R01 HL072265-06] NR 12 TC 5 Z9 5 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1937-5387 J9 J CARDIOVASC TRANSL JI J. Cardiovasc. Transl. Res. PD DEC PY 2011 VL 4 IS 6 SI SI BP 699 EP 701 DI 10.1007/s12265-011-9320-0 PG 3 WC Cardiac & Cardiovascular Systems; Medicine, Research & Experimental SC Cardiovascular System & Cardiology; Research & Experimental Medicine GA 851DM UT WOS:000297248600001 PM 21901526 ER PT J AU Peal, DS Lynch, SN Milan, DJ AF Peal, David S. Lynch, Stacey N. Milan, David J. TI Patterning and Development of the Atrioventricular Canal in Zebrafish SO JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH LA English DT Article DE Atrioventricular canal; Zebrafish ID CARDIAC-VALVE FORMATION; HEART TUBE; MORPHOGENESIS; GENE; TRANSFORMATION; CUSHION; PATHWAY; DISEASE; SYSTEM AB Proper atrioventricular canal (AVC) patterning and subsequent valvulogenesis is a complex process, and defects can result in disease or early death. The zebrafish Danio rerio has become a useful model system for studying AVC development, and much progress has been made in dissecting out the critical steps. Here, we review the recent advances in the field and highlight the cellular and molecular changes observed during zebrafish AVC development. C1 [Peal, David S.; Lynch, Stacey N.; Milan, David J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA 02129 USA. [Peal, David S.; Lynch, Stacey N.; Milan, David J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, Boston, MA 02129 USA. [Milan, David J.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP Milan, DJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, 149 13th St, Boston, MA 02129 USA. EM dmilan@partners.org FU NHLBI NIH HHS [T32 HL007208-33, T32 HL007208] NR 31 TC 4 Z9 4 U1 1 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1937-5387 J9 J CARDIOVASC TRANSL JI J. Cardiovasc. Transl. Res. PD DEC PY 2011 VL 4 IS 6 SI SI BP 720 EP 726 DI 10.1007/s12265-011-9313-z PG 7 WC Cardiac & Cardiovascular Systems; Medicine, Research & Experimental SC Cardiovascular System & Cardiology; Research & Experimental Medicine GA 851DM UT WOS:000297248600004 PM 21948390 ER PT J AU Hagege, AA Bruneval, P Levine, RA Desnos, M Neamatalla, H Judge, DP AF Hagege, Albert A. Bruneval, Patrick Levine, Robert A. Desnos, Michel Neamatalla, Hany Judge, Daniel P. TI The Mitral Valve in Hypertrophic Cardiomyopathy SO JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH LA English DT Article DE Mitral valve; Hypertrophic cardiomyopathy; Mitral regurgitation ID SYSTOLIC ANTERIOR MOTION; OUTFLOW TRACT OBSTRUCTION; ECHOCARDIOGRAPHIC FEATURES; INFECTIVE ENDOCARDITIS; GENERAL-POPULATION; AORTIC-STENOSIS; HEART-VALVES; REGURGITATION; LEAFLET; MECHANISM AB Elongation and pathological thickening of the mitral valve (MV) is commonly seen in hypertrophic cardiomyopathy (HCM), and its pathogenic basis is poorly understood. Associated features include mal-positioning of the papillary muscles and MV, as well as systolic anterior motion (SAM) of the MV leaflets, which can worsen the turbulence and dynamic left ventricular outflow tract (LVOT) gradient. Coaptation of the MV leaflets depends on both anterior and posterior leaflet length and position, and failure of either to optimally adapt in this setting can result in mitral regurgitation or worsened LVOT obstruction. The cause of MV enlargement in HCM is not currently understood, and several different hypotheses may be relevant. The lack of correlation between MV size and the severity of left ventricular hypertrophy, as well as the early findings in genetically predisposed individuals with sarcomere mutations, suggest that it may be an intrinsic aspect of HCM in certain individuals. Other evidence points to a reactive process in the setting of excess production of paracrine growth factors in diseased myocardium that may influence valve overgrowth. Improved understanding of the responsible adaptive mechanisms will pave the way for studies targeted on the prevention and treatment of MV disease in HCM. C1 [Hagege, Albert A.; Desnos, Michel; Neamatalla, Hany] Hop Europeen Georges Pompidou, Dept Cardiol, Assistance Publ Hop Paris, F-75015 Paris, France. [Judge, Daniel P.] Johns Hopkins Univ, Ctr Inherited Heart Dis, Baltimore, MD USA. [Levine, Robert A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, Boston, MA USA. [Bruneval, Patrick] Hop Europeen Georges Pompidou, Assistance Publ Hop Paris, Dept Pathol, F-75015 Paris, France. [Hagege, Albert A.; Bruneval, Patrick; Desnos, Michel; Judge, Daniel P.] Univ Paris 05, Fac Med, Paris, France. [Hagege, Albert A.; Desnos, Michel; Neamatalla, Hany] Paris Cardiovasc Res Ctr PARCC, INSERM, U633, Paris, France. RP Hagege, AA (reprint author), Hop Europeen Georges Pompidou, Dept Cardiol, Assistance Publ Hop Paris, 20 Rue Leblanc, F-75015 Paris, France. EM albert.hagege@egp.aphp.fr FU Leducq Foundation, Paris, France [07CVD04] FX This research project was funded by grant 07CVD04 from the Leducq Foundation, Paris, France, for the Leducq MITRAL Transatlantic Network. NR 60 TC 16 Z9 17 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1937-5387 J9 J CARDIOVASC TRANSL JI J. Cardiovasc. Transl. Res. PD DEC PY 2011 VL 4 IS 6 SI SI BP 757 EP 766 DI 10.1007/s12265-011-9319-6 PG 10 WC Cardiac & Cardiovascular Systems; Medicine, Research & Experimental SC Cardiovascular System & Cardiology; Research & Experimental Medicine GA 851DM UT WOS:000297248600008 PM 21909825 ER PT J AU Wiren, KM Hashimoto, JG Zhang, XW AF Wiren, Kristine M. Hashimoto, Joel G. Zhang, Xiao-Wei TI Stem Cell Activation in Adults Can Reverse Detrimental Changes in Body Composition to Reduce Fat and Increase Lean Mass in Both Sexes SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE STEM CELL; AGING; TESTOSTERONE; ANDROGEN RECEPTOR; LEAN MASS; FAT MASS; NEURAL CREST ID ANDROGEN REPLACEMENT THERAPY; BONE-MINERAL DENSITY; POSTMENOPAUSAL WOMEN; TRANSDERMAL TESTOSTERONE; METABOLIC SYNDROME; HYPOGONADAL MEN; SEXUAL FUNCTION; DOUBLE-BLIND; RECEPTOR; MICE AB Detrimental changes in body composition are often associated with declining levels of testosterone. Here, we evaluated the notion that multipotent mesenchymal stem cells, that give rise to both fat and muscle tissue, can play a significant role to alter existing body composition in the adult. Transgenic mice with targeted androgen receptor (AR) overexpression in stem cells were employed. Wild-type littermate and AR-transgenic male and female mice were gonadectomized and left untreated for 2 months. After the hypogonadal period, mice were then treated with 5 alpha-dihydrotestosterone (DHT) for 6 weeks. After orchidectomy (ORX), wild-type males have reduced lean mass and increased fat mass compared to shams. DHT treatment was beneficial to partially restore body composition. In wild-type females, ovariectomy (OVX) produced a similar change but there was no improvement with DHT. In targeted AR transgenic mice, DHT treatment increased lean and reduced fat mass to sham levels. In contrast to wild-type females, DHT treatment in female transgenic mice significantly ameliorated the increased fat and decreased lean mass changes that result after OVX. Our results show that DHT administration reduces fat mass and increases lean mass in wildtype males but not females, indicating that wild-type females are not as sensitive to androgen treatment. Because both male and female transgenic mice are more responsive than wild-type, results suggest that body composition remains linked to stem cell fate in the adult and that targeted androgen signaling in stem cells can play a significant role to reverse detrimental changes in body composition in both sexes. J. Cell. Biochem. 112: 3638-3647, 2011. (C) 2011 Wiley Periodicals, Inc. C1 [Wiren, Kristine M.] Oregon Hlth & Sci Univ, Dept Med, Portland VA Med Ctr, Res Serv P3 R&D39, Portland, OR 97239 USA. [Wiren, Kristine M.; Hashimoto, Joel G.; Zhang, Xiao-Wei] Vet Affairs Med Ctr, Res Serv, Portland, OR 97239 USA. [Wiren, Kristine M.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland VA Med Ctr, Res Serv P3 R&D39, Portland, OR 97239 USA. RP Wiren, KM (reprint author), Oregon Hlth & Sci Univ, Dept Med, Portland VA Med Ctr, Res Serv P3 R&D39, 3710 SW Vet Hosp Rd, Portland, OR 97239 USA. EM wirenk@ohsu.edu OI Wiren, Kristine/0000-0002-6159-4450 FU National Institute of Diabetes, Digestive and Kidney Disease [R01 DK067541]; Department of Defense; United States Army [W81XWH-05-1-0086] FX Grant sponsor: National Institute of Diabetes, Digestive and Kidney Disease; Grant number: R01 DK067541; Grant sponsor: Department of Defense; United States Army Research Acquisition Activity Award No.; Grant number: W81XWH-05-1-0086. NR 48 TC 2 Z9 2 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD DEC PY 2011 VL 112 IS 12 BP 3638 EP 3647 DI 10.1002/jcb.23288 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 851YV UT WOS:000297309600018 PM 21793043 ER PT J AU Carvalho, AR Ichinose, F Schettino, IA Hess, D Rojas, J Giannella-Neto, A Agnihotri, A Walker, J MacGillivray, TE Melo, MFV AF Carvalho, Alysson R. Ichinose, Fumito Schettino, Ivany A. Hess, Dean Rojas, Javier Giannella-Neto, Antonio Agnihotri, Arvind Walker, Jennifer MacGillivray, Thomas E. Vidal Melo, Marcos F. TI Tidal Lung Recruitment and Exhaled Nitric Oxide During Coronary Artery Bypass Grafting in Patients With and Without Chronic Obstructive Pulmonary Disease SO LUNG LA English DT Article DE Acute lung injury; Pulmonary disease; Chronic obstructive; Coronary artery bypass surgery; Nitric oxide; Perioperative period ID END-EXPIRATORY PRESSURE; VENTILATION-PERFUSION INEQUALITY; CARDIAC-SURGERY; CARDIOPULMONARY BYPASS; GAS-EXCHANGE; MECHANICAL VENTILATION; INFLAMMATORY RESPONSE; RESPIRATORY MECHANICS; AIRWAY INFLAMMATION; EXTUBATION FAILURE AB We studied the occurrence of intraoperative tidal alveolar recruitment/derecruitment, exhaled nitric oxide (eNO), and lung dysfunction in patients with and without chronic obstructive pulmonary disease (COPD) undergoing coronary artery bypass grafting (CABG). We performed a prospective observational physiological study at a university hospital. Respiratory mechanics, shunt, and eNO were assessed in moderate COPD patients undergoing on-pump (n = 12) and off-pump (n = 8) CABG and on-pump controls (n = 8) before sternotomy (baseline), after sternotomy and before cardiopulmonary bypass (CPB), and following CPB before and after chest closure. Respiratory system resistance (R (rs)), elastance (E (rs)), and stress index (to quantify tidal recruitment) were estimated using regression analysis. eNO was measured with chemiluminescence. Mechanical evidence of tidal recruitment/derecruitment (stress index < 1.0) was observed in all patients, with stress index < 0.8 in 29% of measurements. Rrs in on-pump COPD was larger than in controls (p < 0.05). Ers increased in controls from baseline to end of surgery (19.4 +/- A 5.5 to 27.0 +/- A 8.5 ml cm H(2)O(-1), p < 0.01), associated with increased shunt (p < 0.05). Neither Ers nor shunt increased significantly in the COPD on-pump group. eNO was comparable in the control (11.7 +/- A 7.0 ppb) and COPD on-pump (9.9 +/- A 6.8 ppb) groups at baseline, and decreased similarly by 29% at end of surgery(p < 0.05). Changes in eNO were not correlated to changes in lung function. Tidal recruitment/derecruitment occurs frequently during CABG and represents a risk for ventilator-associated lung injury. eNO changes are consistent with small airway injury, including that from tidal recruitment injury. However, those changes are not correlated with respiratory dysfunction. Controls have higher susceptibility to develop complete lung derecruitment. C1 [Ichinose, Fumito; Schettino, Ivany A.; Hess, Dean; Rojas, Javier; Vidal Melo, Marcos F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Carvalho, Alysson R.] Carlos Chagas Filho Inst Biophys, Lab Respirat Physiol, Rio De Janeiro, Brazil. [Giannella-Neto, Antonio] Univ Fed Rio de Janeiro, Biomed Engn Program, Rio De Janeiro, Brazil. [Agnihotri, Arvind; Walker, Jennifer; MacGillivray, Thomas E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. RP Melo, MFV (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM mvidalmelo@partners.org RI Fisiologia, Ciencias Biologicas/C-2407-2012; Inbeb, Inct/K-2317-2013 NR 71 TC 3 Z9 3 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0341-2040 J9 LUNG JI Lung PD DEC PY 2011 VL 189 IS 6 BP 499 EP 509 DI 10.1007/s00408-011-9325-0 PG 11 WC Respiratory System SC Respiratory System GA 852IC UT WOS:000297350000009 PM 21952833 ER PT J AU Bolar, DS Rosen, BR Sorensen, AG Adalsteinsson, E AF Bolar, D. S. Rosen, B. R. Sorensen, A. G. Adalsteinsson, E. TI QUantitative Imaging of eXtraction of Oxygen and TIssue Consumption (QUIXOTIC) Using Venular-Targeted Velocity-Selective Spin Labeling SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE cerebral metabolic rate of oxygen; arterial spin labeling; velocity selective; oxygen extraction fraction ID CEREBRAL METABOLIC-RATE; IN-VIVO MEASUREMENT; BLOOD-VOLUME; RELAXATION-TIME; BRAIN; MRI; QUANTIFICATION; FLOW; PET; VALIDATION AB While oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO(2)) are fundamental parameters of brain health and function, a robust MRI-based mapping of OEF and CMRO(2) amenable to functional MRI (fMRI) has not been established. To address this issue, a novel method called QUantitative Imaging of eXtraction of Oxygen and TIssue Consumption, or QUIXOTIC, is introduced. The key innovation in QUIXOTIC is the use of velocity-selective spin labeling to isolate MR signal exclusively from postcapillary venular blood on a voxel-by-voxel basis. Measuring the T(2) of this venular-targeted blood allows calibration to venular oxygen saturation (Y(v)) via theoretical and experimental T(2) versus blood oxygen saturation relationships. Y(v) is converted to OEF, and baseline CMRO(2) is subsequently estimated from OEF and additional cerebral blood flow and hematocrit measurements. Theory behind the QUIXOTIC technique is presented, and implications of cutoff velocity (V(CUTOFF)) and outflow time parameters are discussed. Cortical gray matter values obtained with QUIXOTIC in 10 healthy volunteers are Y(v) = 0.73 +/- 0.02, OEF 5 0.26 +/- 0.02, and CMRO(2) = 125 +/- 15 mu mol/100 g min. Results are compared to global measures obtained with the T(2) relaxation under spin tagging (TRUST) technique. The preliminary data presented suggest that QUIXOTIC will be useful for mapping Y(v), OEF, and CMRO(2), in both clinical and functional MRI settings. Magn Reson Med 66:1550-1562, 2011. (C) 2011 Wiley Periodicals, Inc. C1 [Bolar, D. S.; Adalsteinsson, E.] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Bolar, D. S.; Rosen, B. R.; Sorensen, A. G.; Adalsteinsson, E.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Bolar, D. S.; Rosen, B. R.; Sorensen, A. G.; Adalsteinsson, E.] Harvard Univ, MIT, Harvard Mit Div Hlth Sci & Technol, Sch Med, Cambridge, MA 02139 USA. RP Bolar, DS (reprint author), MIT, Dept Elect Engn & Comp Sci, Bldg 36-792,77 Massachusetts Ave, Cambridge, MA 02139 USA. EM dbolar@nmr.mgh.harvard.edu FU Siemens Medical Solutions; Division of Health Sciences and Technology; Advanced Multimodal Neuroimaging Training Program; NIH [RO1 EB007942, T32-GM07753, 5-T32-EB001680, 5-R01-EB002066-20]; Center for Functional Neuroimaging Technologies [P41RR14075S10RR023401] FX Grant sponsor: Siemens Medical Solutions; Grant sponsor: Division of Health Sciences and Technology Martinos Catalyst Fund; Grant sponsor: Advanced Multimodal Neuroimaging Training Program Grant; Grant sponsor: NIH; Grant number: RO1 EB007942; Grant sponsor: NIH Medical Scientist Training Program Fellowship; Grant number: T32-GM07753; Grant sponsor: NIH Neuroimaging Training Program Grant; Grant numbers: 5-T32-EB001680, 5-R01-EB002066-20; Grant sponsor: Center for Functional Neuroimaging Technologies; Grant number: P41RR14075S10RR023401. NR 42 TC 44 Z9 45 U1 0 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD DEC PY 2011 VL 66 IS 6 BP 1550 EP 1562 DI 10.1002/mrm.22946 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 851QC UT WOS:000297285000009 PM 21674615 ER PT J AU Keil, B Alagappan, V Mareyam, A Mcnab, JA Fujimoto, K Tountcheva, V Triantafyllou, C Dilks, DD Kanwisher, N Lin, WL Grant, PE Wald, LL AF Keil, Boris Alagappan, Vijay Mareyam, Azma Mcnab, Jennifer A. Fujimoto, Kyoko Tountcheva, Veneta Triantafyllou, Christina Dilks, Daniel D. Kanwisher, Nancy Lin, Weili Grant, P. Ellen Wald, Lawrence L. TI Size-optimized 32-Channel Brain Arrays for 3 T Pediatric Imaging SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE magnetic resonance imaging; phased-array coil; pediatric imaging; parallel imaging ID PHASED-ARRAY; NIH MRI; HEAD CIRCUMFERENCE; NOISE; TESLA; COIL; CHILDREN; DESIGN; SENSE; BIRTH AB Size-optimized 32-channel receive array coils were developed for five age groups, neonates, 6 months old, 1 year old, 4 years old, and 7 years old, and evaluated for pediatric brain imaging. The array consisted of overlapping circular surface coils laid out on a close-fitting coil-former. The two-section coil former design was obtained from surface contours of aligned three-dimensional MRI scans of each age group. Signal-to-noise ratio and noise amplification for parallel imaging were evaluated and compared to two coils routinely used for pediatric brain imaging; a commercially available 32-channel adult head coil and a pediatric-sized birdcage coil. Phantom measurements using the neonate, 6-month-old, 1-year-old, 4-year-old, and 7-year-old coils showed signal-to-noise ratio increases at all locations within the brain over the comparison coils. Within the brain cortex the five dedicated pediatric arrays increased signal-to-noise ratio by up to 3.6-, 3.0-, 2.6-, 2.3-, and 1.7-fold, respectively, compared to the 32-channel adult coil, as well as improved G-factor maps for accelerated imaging. This study suggests that a size-tailored approach can provide significant sensitivity gains for accelerated and unaccelerated pediatric brain imaging. Magn Reson Med 66:1777-1787, 2011. (C) 2011 Wiley Periodicals, Inc. C1 [Keil, Boris; Alagappan, Vijay; Mcnab, Jennifer A.; Triantafyllou, Christina; Grant, P. Ellen; Wald, Lawrence L.] Harvard Univ, Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Dept Radiol,Med Sch, Charlestown, MA 02129 USA. [Triantafyllou, Christina; Dilks, Daniel D.; Kanwisher, Nancy] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. [Lin, Weili] Univ N Carolina, Dept Radiol, Chapel Hill, NC USA. [Lin, Weili] Univ N Carolina, BRIC, Chapel Hill, NC USA. [Grant, P. Ellen] Childrens Hosp, Div Newborn Med, Boston, MA 02115 USA. [Wald, Lawrence L.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Grant, P. Ellen] Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Keil, B (reprint author), Harvard Univ, Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Dept Radiol,Med Sch, 149 13th St, Charlestown, MA 02129 USA. EM keil@nmr.mgh.harvard.edu RI Keil, Boris/P-1411-2014; Wald, Lawrence/D-4151-2009; OI Fujimoto, Kyoko/0000-0002-0087-1397 FU National Institutes of Health [U01MH093765, P41RR14075, R21EB008547, R21HD058725, R01EB009756, R01NS055754]; Ellison Medical Foundation FX Grant sponsor: National Institutes of Health; Grant numbers: U01MH093765, P41RR14075, R21EB008547, R21HD058725, R01EB009756, R01NS055754; Grant sponsor: Ellison Medical Foundation. NR 25 TC 29 Z9 29 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD DEC PY 2011 VL 66 IS 6 BP 1777 EP 1787 DI 10.1002/mrm.22961 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 851QC UT WOS:000297285000033 PM 21656548 ER PT J AU Shackelton-Piccolo, R McKinlay, JB Marceau, LD Goroll, AH Link, CL AF Shackelton-Piccolo, Rebecca McKinlay, John B. Marceau, Lisa D. Goroll, Allan H. Link, Carol L. TI Differences Between Internists and Family Practitioners in the Diagnosis and Management of the Same Patient With Coronary Heart Disease SO MEDICAL CARE RESEARCH AND REVIEW LA English DT Article DE primary care; disease models; coronary heart disease ID CLINICAL DECISION-MAKING; STANDARDIZED PATIENTS; FACTORIAL EXPERIMENT; MEDICAL SPECIALTIES; CARE; VIGNETTES; PHYSICIANS; QUALITY; GUIDELINES; OUTCOMES AB It has been suggested that internists and family practitioners have somewhat different "disease" perspectives, which may be generated by use of different explanatory models during medical training (pathophysiological vs. biopsychosocial, respectively). This article explores differences between internists and family practitioners in their suggested diagnoses, level of diagnostic certainty, test and prescription ordering, when encountering exactly the same "patient" with coronary heart disease (CHD). Internists were more certain of a CHD diagnosis than family practitioners and were more likely to act on this diagnosis. Family practitioners were more likely to diagnose (and were more certain of) a mental health condition. While many physicians simultaneously entertain several alternate diagnoses, diagnostic certainty has shown to have an important influence on subsequent clinical actions, such as stress testing and prescription of beta blockers. These results may inform future educational strategies designed to reduce diagnostic uncertainty in the face of life-threatening conditions, such as CHD. C1 [Shackelton-Piccolo, Rebecca; McKinlay, John B.; Marceau, Lisa D.; Link, Carol L.] New England Res Inst Inc, Watertown, MA 02472 USA. [Goroll, Allan H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Shackelton-Piccolo, R (reprint author), New England Res Inst Inc, 9 Galen St, Watertown, MA 02472 USA. EM rpiccolo@neriscience.com FU National Institutes of Health, National Institute on Aging [R01 AG016747]; National Heart, Lung and Blood Institute [R01 HL079174] FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by grants from the National Institutes of Health, National Institute on Aging (Grant R01 AG016747, John B. McKinlay, PI) and National Heart, Lung and Blood Institute (Grant R01 HL079174, John B. McKinlay, PI). NR 39 TC 4 Z9 5 U1 1 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1077-5587 J9 MED CARE RES REV JI Med. Care Res. Rev. PD DEC PY 2011 VL 68 IS 6 BP 650 EP 666 DI 10.1177/1077558711409047 PG 17 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 850UR UT WOS:000297225500002 PM 21680578 ER PT J AU Qureshi, AI Palesch, YY Martin, R Novitzke, J Cruz-Flores, S Ehtisham, A Ezzeddine, MA Goldstein, JN Kirmani, JF Hussein, HM Suri, MFK Tariq, N Liu, Y AF Qureshi, Adnan I. Palesch, Yuko Y. Martin, Renee Novitzke, Jill Cruz-Flores, Salvador Ehtisham, Asad Ezzeddine, Mustapha A. Goldstein, Joshua N. Kirmani, Jawad F. Hussein, Haitham M. Suri, M. Fareed K. Tariq, Nauman Liu, Yuan CA ATACH Investigators TI Association of Serum Glucose Concentrations During Acute Hospitalization with Hematoma Expansion, Perihematomal Edema, and Three Month Outcome Among Patients with Intracerebral Hemorrhage SO NEUROCRITICAL CARE LA English DT Article DE Intracerebral hemorrhage; Hyperglycemia; Hematoma expansion; Modified Rankin scale; Edema ID ACUTE CEREBRAL-HEMORRHAGE; CRITICALLY-ILL PATIENTS; AMERICAN-STROKE-ASSOCIATION; INTENSIVE INSULIN THERAPY; TIGHT GLYCEMIC CONTROL; HEART-ASSOCIATION; HYPERGLYCEMIA; MANAGEMENT; MORTALITY; TRIAL AB There is some evidence that hyperglycemia increases the rate of poor outcomes in patients with intracerebral hemorrhage (ICH). We explored the relationship between various parameters of serum glucose concentrations measured during acute hospitalization and hematoma expansion, perihematomal edema, and three month outcome among subjects with ICH. A post-hoc analysis of a multicenter prospective study recruiting subjects with ICH and elevated systolic blood pressure (SBP) a parts per thousand yen170 mmHg who presented within 6 h of symptom onset was performed. The serum glucose concentration was measured repeatedly up to 5 times over 3 days after admission and change over time was characterized using a summary statistic by fitting the linear regression model for each subject. The admission glucose, glucose change between admission and 24 hour glucose concentration, and estimated parameters (slope and intercept) were entered in the logistic regression model separately to predict the functional outcome as measured by modified Rankin scale (mRS) at 90 days (0-3 vs. 4-6); hematoma expansion at 24 h (a parts per thousand currency sign33 vs. > 33%); and relative perihematomal edema expansion at 24 h (a parts per thousand currency sign40 vs. > 40%). A total of 60 subjects were recruited (aged 62.0 +/- 15.1 years; 56.7% men). The mean of initial glucose concentration (+/- standard deviation) was 136.7 mg/dl (+/- 58.1). Thirty-five out of 60 (58%) subjects had a declining glucose over time (negative slope). The risk of poor outcome (mRS 4-6) in those with increasing serum glucose levels was over two-fold relative to those who had declining serum glucose levels (RR = 2.64, 95% confidence interval [CI]: 1.03, 6.75). The RRs were 2.59 (95% CI: 1.27, 5.30) for hematoma expansion > 33%; and 1.25 (95% CI: 0.73, 2.13) for relative edema expansion > 40%. Decline in serum glucose concentration correlated with reduction in proportion of subjects with hematoma expansion and poor clinical outcome. These results provide a justification for a randomized controlled clinical trial to evaluate the efficacy of aggressive serum glucose reduction in reducing death and disability among patients with ICH. C1 [Qureshi, Adnan I.; Novitzke, Jill; Ezzeddine, Mustapha A.; Hussein, Haitham M.; Suri, M. Fareed K.; Tariq, Nauman] Univ Minnesota, Zeenat Qureshi Stroke Res Ctr, Dept Neurol, Minneapolis, MN 55455 USA. [Palesch, Yuko Y.; Martin, Renee] Med Univ S Carolina, Div Biostat & Epidemiol, Charleston, SC 29425 USA. [Cruz-Flores, Salvador] St Louis Univ Hlth Sci Ctr, St Louis, MO USA. [Ehtisham, Asad] Univ Kansas, Sch Med, Neurosci Crit Care Unit, Wichita, KS 67214 USA. [Goldstein, Joshua N.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Kirmani, Jawad F.] John F Kennedy Med Ctr, Neurosci Inst, Edison, NJ USA. [Liu, Yuan] Emory Univ, Atlanta, GA 30322 USA. RP Qureshi, AI (reprint author), Univ Minnesota, Zeenat Qureshi Stroke Res Ctr, Dept Neurol, 12-100 PWB,516 Delaware St SE, Minneapolis, MN 55455 USA. EM aiqureshi@hotmail.com RI Goldstein, Joshua/H-8953-2016 NR 44 TC 16 Z9 16 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1541-6933 J9 NEUROCRIT CARE JI Neurocrit. Care PD DEC PY 2011 VL 15 IS 3 BP 428 EP 435 DI 10.1007/s12028-011-9541-8 PG 8 WC Critical Care Medicine; Clinical Neurology SC General & Internal Medicine; Neurosciences & Neurology GA 852NT UT WOS:000297365400011 PM 21573860 ER PT J AU Anderson, CD Bartscher, JF Scripko, PD Biffi, A Chase, D Guanci, M Greer, DM AF Anderson, Christopher D. Bartscher, James F. Scripko, Patricia D. Biffi, Alessandro Chase, Deborah Guanci, Mary Greer, David M. TI Neurologic Examination and Extubation Outcome in the Neurocritical Care Unit SO NEUROCRITICAL CARE LA English DT Article DE Neurocritical care; Extubation failure; Mechanical ventilation; Neurology; Neurosurgery; Weaning ID SPONTANEOUS BREATHING TRIAL; LARYNGEAL EDEMA; RISK-FACTORS; MECHANICAL VENTILATION; TRACHEAL EXTUBATION; CUFF-LEAK; FAILURE; PREVENTION; PARAMETERS; PREDICTORS AB Extubation failure in the neurocritical care unit (NCCU) is difficult to predict, and is an important source of prolonged intensive care, exposure to morbidity, and increased cost. In this observational cohort study in the NCCU of a tertiary care hospital, we examined patients undergoing extubation or tracheostomy with > 6 h of intubation. Observational data were collected at the time of the decision to extubate or pursue tracheostomy. The primary end-point was extubation failure within 72 h. A total of 378 tracheostomy versus extubation decisions were made on 339 individuals, resulting in 93 tracheostomies and 285 extubations. The extubation failure rate was 48/285 (16.8%). Individuals who underwent extubation had similar GCS scores [median 10T (IQR 10-11), P = 0.21]. Extubation failures had similar rates of pneumonia and fever, chest X-ray (CXR) findings, and admission diagnoses (P = NS). Factors associated with success in univariate analysis included intact gag reflex, normal eye movements, ability to close eyes to command, and ability to cough to command (all P < 0.05). In multivariate analysis, the ability to follow four commands (close eyes, show two fingers, wiggle toes, cough to command) was associated with success (P = 0.01). ROC analysis identified a significant difference in favor of a multivariate model incorporating four commands over GCS alone (P = 0.007). The ability to follow four commands and other examination criteria were strongly associated with extubation success in this observational study. Modeling suggests that specific neurologic examination parameters provide additional predictive information over GCS alone. A prospective, protocol-driven trial is needed to test and expand these findings. C1 [Anderson, Christopher D.] CZPN 6818, Boston, MA 02114 USA. [Anderson, Christopher D.; Bartscher, James F.; Greer, David M.] Massachusetts Gen Hosp, Neurocrit Care Serv, Boston, MA 02114 USA. [Anderson, Christopher D.; Biffi, Alessandro] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Anderson, Christopher D.; Bartscher, James F.; Biffi, Alessandro; Greer, David M.] Massachusetts Gen Hosp, Stroke Serv, Boston, MA 02114 USA. [Scripko, Patricia D.] Case Western Reserve Univ, Cleveland Clin, Lerner Coll Med, Cleveland, OH 44106 USA. [Chase, Deborah] Massachusetts Gen Hosp, Resp Care Serv, Boston, MA 02114 USA. [Guanci, Mary] Massachusetts Gen Hosp, Neurosci Intens Care Unit, Boston, MA 02114 USA. RP Anderson, CD (reprint author), CZPN 6818, 185 Cambridge St, Boston, MA 02114 USA. EM cdanderson@partners.org OI Anderson, Christopher/0000-0002-0053-2002 NR 16 TC 11 Z9 12 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1541-6933 J9 NEUROCRIT CARE JI Neurocrit. Care PD DEC PY 2011 VL 15 IS 3 BP 490 EP 497 DI 10.1007/s12028-010-9369-7 PG 8 WC Critical Care Medicine; Clinical Neurology SC General & Internal Medicine; Neurosciences & Neurology GA 852NT UT WOS:000297365400020 PM 20428967 ER PT J AU Gold, AL Shin, LM Orr, SP Carson, MA Rauch, SL Macklin, ML Lasko, NB Metzger, LJ Dougherty, DD Alpert, NM Fischman, AJ Pitman, RK AF Gold, A. L. Shin, L. M. Orr, S. P. Carson, M. A. Rauch, S. L. Macklin, M. L. Lasko, N. B. Metzger, L. J. Dougherty, D. D. Alpert, N. M. Fischman, A. J. Pitman, R. K. TI Decreased regional cerebral blood flow in medial prefrontal cortex during trauma-unrelated stressful imagery in Vietnam veterans with post-traumatic stress disorder SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Anterior cingulate cortex; anxiety; emotion; neuroimaging; positron emission tomography; post-traumatic stress disorder; script-driven imagery ID SCRIPT-DRIVEN IMAGERY; CHILDHOOD SEXUAL-ABUSE; POSITRON-EMISSION-TOMOGRAPHY; FUNCTIONAL MRI; PSYCHOPHYSIOLOGICAL ASSESSMENT; SYMPTOM PROVOCATION; COMBAT VETERANS; PTSD; RESPONSES; AMYGDALA AB Background. Neuroimaging research has demonstrated medial prefrontal cortex (mPFC) hyporesponsivity and amygdala hyperresponsivity to trauma-related or emotional stimuli in post-traumatic stress disorder (PTSD). Relatively few studies have examined brain responses to the recollection of stressful, but trauma-unrelated, personal events in PTSD. In the current study, we sought to determine whether regional cerebral blood flow (rCBF) abnormalities in mPFC and amygdala in PTSD could be observed during the recollection of trauma-unrelated stressful personal events. Method. Participants were 35 right-handed male combat veterans (MCVs) and female nurse veterans (FNVs) who served in Vietnam: 17 (seven male, 10 female) with current military-related PTSD and 18 (nine male, nine female) with no current or lifetime PTSD. We used positron emission tomography (PET) and script-driven imagery to study rCBF during the recollection of trauma-unrelated stressful versus neutral and traumatic events. Results. Voxelwise tests revealed significant between-group differences for the trauma-unrelated stressful versus neutral comparison in mPFC, specifically in the anterior cingulate cortex (ACC). Functional region of interest (ROI) analyses demonstrated that this interaction in mPFC represented greater rCBF decreases in the PTSD group during trauma-unrelated stressful imagery relative to neutral imagery compared to the non-PTSD group. No differential amygdala activation was observed between groups or in either group separately. Conclusions. Veterans with PTSD, compared to those without PTSD, exhibited decreased rCBF in mPFC during mental imagery of trauma-unrelated stressful personal experiences. Functional neuroanatomical models of PTSD must account for diminished mPFC responses that extend to emotional stimuli, including stressful personal experiences that are not directly related to PTSD. C1 [Gold, A. L.; Shin, L. M.; Orr, S. P.; Lasko, N. B.; Metzger, L. J.; Dougherty, D. D.; Pitman, R. K.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Shin, L. M.] Tufts Univ, Dept Psychol, Medford, MA 02155 USA. [Orr, S. P.; Macklin, M. L.; Lasko, N. B.; Metzger, L. J.] Vet Affairs Res Serv, Manchester, NH USA. [Carson, M. A.] St Anselm Coll, Dept Nursing, Manchester, NH 03102 USA. [Gold, A. L.; Shin, L. M.; Orr, S. P.; Rauch, S. L.; Lasko, N. B.; Metzger, L. J.; Dougherty, D. D.; Alpert, N. M.; Fischman, A. J.; Pitman, R. K.] Harvard Univ, Sch Med, Boston, MA USA. [Rauch, S. L.] McLean Hosp, Dept Psychiat, Belmont, MA 02178 USA. [Alpert, N. M.; Fischman, A. J.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Gold, AL (reprint author), Yale Univ, Dept Psychol, POB 208205, New Haven, CT 06520 USA. EM andrea.gold@yale.edu RI Schueter, nicos/A-3625-2014; OI Gold, Andrea/0000-0003-4447-776X FU Veterans Affairs Medical Research Service; National Alliance for Research on Schizophrenia and Depression, Great Neck, NY; National Institute of Mental Health, Bethesda, MD [MH60219]; Medtronics, Inc. through MGH for Brain Stimulation Therapy; Cyberonics through MGH for VNS; Cephalon through MGH on anxiolytic action; Medtronic; Eli Lilly; Brand Ideas; McNeil; Reed Elsevier; Cyberonics; Jazz Pharmaceuticals; Bristol-Myers Squibb; Northstar Neuroscience; Forest; Trancept Pharmaceuticals; Cephalon; JK Associates, Inc.; American Psychiatric Publishing, Inc.; Advocate Health and Hospitals Corporation; DHHS/NIH; Leerink Swann LLC; Oxford University Press; Professional Practice Group/Psychiatry Syracuse; Y&R Inc. DBA Sudler Henessy FX This study was supported by Merit Review grants from the Veterans Affairs Medical Research Service (Drs Pitman, Carson and Orr); an Award from the National Alliance for Research on Schizophrenia and Depression, Great Neck, NY (Dr Shin); and grant MH60219 from the National Institute of Mental Health, Bethesda, MD (Dr Rauch). We are grateful to the participants. We also thank S. Barrow, A. Loring and S. Weise for technical assistance, and J. C. Britton for comments on a previous version of this manuscript.; Dr Rauch received funded research through MGH for Brain Stimulation Therapy from Medtronics, Inc.; funded research through MGH for VNS from Cyberonics; and funded research through MGH on anxiolytic action from Cephalon. He also received honoraria from Novartis for consultation on emerging treatments; Neurogen for his participation as a consultant on emerging trends in anxiety associated with insomnia; Sepracor for his consultation on fear/conditioning/extinction; Primedia for his participation in developing a CE activity; and Medtronics, Inc for his attendance of the Advisory Board meeting on the Anatomy and Neuroscience of anxiety and depression. The financial disclosures for Dr Dougherty are as follows: Current: Medtronic (Research and Consulting/Honoraria - significant); Eli Lilly (Research and Consulting/Honoraria - significant); Brand Ideas (Consulting/Honoraria - modest); McNeil (Research and Consulting/Honoraria - significant); Reed Elsevier (Consulting/Honoraria - modest); Cyberonics (Research - significant); More than 1 year ago: Jazz Pharmaceuticals (Consulting/Honoraria - modest); Wyeth (Consulting/Honoraria - modest); Bristol-Myers Squibb (Consulting/Honoraria - modest); Northstar Neuroscience (Research and Consulting/Honoraria - significant); Forest (previous Research significant); Trancept Pharmaceuticals (Consulting/Honoraria - modest); Cephalon (previous Research modest); Cyberonics (Consulting/Honoraria - significant); Trancept Pharmaceuticals (Consulting/Honoraria - modest); JK Associates, Inc. (Consulting/Honoraria - modest); American Psychiatric Publishing, Inc. (Consulting/Honoraria - modest); Advocate Health and Hospitals Corporation (Consulting/Honoraria - modest); DHHS/NIH (Consulting/Honoraria modest); Leerink Swann LLC (Consulting/Honoraria modest); Oxford University Press (Consulting/Honoraria - modest); Professional Practice Group/Psychiatry Syracuse (Consulting/Honoraria - modest); Y&R Inc. DBA Sudler & Henessy (Consulting/Honoraria - modest). NR 47 TC 16 Z9 16 U1 3 U2 8 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD DEC PY 2011 VL 41 IS 12 BP 2563 EP 2572 DI 10.1017/S0033291711000730 PG 10 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 851TA UT WOS:000297292600010 PM 21733221 ER PT J AU Gazelle, GS Kessler, L Lee, DW McGinn, T Menzin, J Neumann, PJ van Amerongen, D White, LA AF Gazelle, G. Scott Kessler, Larry Lee, David W. McGinn, Thomas Menzin, Joseph Neumann, Peter J. van Amerongen, Derek White, Leigh Ann CA Working Grp Comparative Effectiven TI A Framework for Assessing the Value of Diagnostic Imaging in the Era of Comparative Effectiveness Research SO RADIOLOGY LA English DT Editorial Material ID COST-EFFECTIVENESS; COLORECTAL-CANCER; CT COLONOGRAPHY; TECHNOLOGY-ASSESSMENT; MEDICARE POPULATION; COMPUTED-TOMOGRAPHY; OUTCOMES C1 [Gazelle, G. Scott] Massachusetts Gen Hosp, Dept Radiol, Inst Technol Assessment, Boston, MA 02114 USA. [Kessler, Larry] Univ Washington, Dept Hlth Serv, Sch Publ Hlth, Seattle, WA 98195 USA. [Lee, David W.] GE Healthcare, Wauwatosa, WI USA. [McGinn, Thomas] N Shore Univ Hosp, Dept Med, Manhasset, NY USA. [Menzin, Joseph; White, Leigh Ann] Boston Hlth Econ, Waltham, MA USA. [Neumann, Peter J.] Tufts Univ, Sch Med, Inst Clin Res & Hlth Policy Studies, Boston, MA 02111 USA. [van Amerongen, Derek] Humana Hlth Plans Ohio, Cincinnati, OH USA. RP Gazelle, GS (reprint author), Massachusetts Gen Hosp, Dept Radiol, Inst Technol Assessment, 101 Merrimac St,10th Floor, Boston, MA 02114 USA. EM scott@mgh-ita.org NR 29 TC 22 Z9 22 U1 0 U2 4 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD DEC PY 2011 VL 261 IS 3 BP 692 EP 698 DI 10.1148/radiol.11110155 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 849PR UT WOS:000297138100006 PM 22095993 ER PT J AU Gahramanov, S Muldoon, LL Li, X Neuwelt, EA AF Gahramanov, Seymur Muldoon, Leslie L. Li, Xin Neuwelt, Edward A. TI Improved Perfusion MR Imaging Assessment of Intracerebral Tumor Blood Volume and Antiangiogenic Therapy Efficacy in a Rat Model with Ferumoxytol SO RADIOLOGY LA English DT Article ID CONTRAST-ENHANCED MR; BRAIN-TUMORS; GLIOBLASTOMA-MULTIFORME; GLIOMA MODEL; GRADE; PROGRESSION; SURVIVAL; AGENT; MAPS; BEVACIZUMAB AB Purpose: To evaluate the consistency of tumor blood volume measurements and antiangiogenic therapy efficacy assessments with a low-molecular-weight gadolinium-based contrast agent (GBCA, gadodiamide) versus an iron oxide nanoparticle (ferumoxytol) in the presence or absence of a loading dose of contrast agent before perfusion magnetic resonance (MR) imaging (preload method). Materials and Methods: The protocol was approved by the institutional animal care and use committee. U87MG tumor cells were implanted intracerebrally in 13 rats. All 13 rats underwent 11.75-T MR imaging with gadodiamide (60 mu L) 13 days after tumor implantation. The next day, nine rats underwent MR imaging with ferumoxytol (60 mu L). Immediately after ferumoxytol imaging, six rats received bevacizumab (45 mg/kg). MR imaging was repeated 48 hours after bevacizumab treatment with gadodiamide and 72 hours after treatment with ferumoxytol. Each study included three consecutive dynamic susceptibility-weighted contrast material-enhanced (DSC) MR acquisitions, which were performed without preload, with single-dose preload, and with double-dose preload. Tumor relative cerebral blood volume (rCBV) was estimated from each DSC MR acquisition. Two-way repeated measures analysis of variance was performed to test for differences between groups with both contrast agents. Results: DSC MR imaging with gadodiamide and without preload showed low rCBV (<= 1.75) in nine of the 13 tumors; estimated rCBV increased progressively with both single- and double-dose preloads (P < .001). Conversely, rCBVs obtained with ferumoxytol were high (>1.75) and remained constant with all three acquisitions. The magnitude of rCBV decrease after bevacizumab administration was dependent: on the dose of gadodiamide preload, whereas the magnitude of rCBV decrease with ferumoxytol was constant regardless of whether contrast agent preload was used. Conclusion: With GBCA, tumor rCBV can be underestimated without preload and becomes dose dependent with preload correction. Conversely, ferumoxytol provides consistent assessment of tumor rCBV and antiangiogenic therapy efficacy. (C) RSNA, 2011 C1 [Gahramanov, Seymur; Muldoon, Leslie L.; Neuwelt, Edward A.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Neuwelt, Edward A.] Oregon Hlth & Sci Univ, Dept Neurosurg, Portland, OR 97239 USA. [Li, Xin] Oregon Hlth & Sci Univ, Adv Imaging Res Ctr, Portland, OR 97239 USA. [Neuwelt, Edward A.] Portland VA Med Ctr, Portland, OR USA. RP Neuwelt, EA (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, 3181 SW Sam Jackson Pk Rd,Room L603, Portland, OR 97239 USA. EM neuwelte@ohsu.edu FU Veterans Administration; National Institutes of Health [NS053468, CA137488, NS044687]; AMAG Pharmaceuticals FX Supported by a Veterans Administration Merit Review grant.; This study was supported by the National Institutes of Health (grants NS053468, CA137488, and NS044687).; Disclosures of Potential Conflicts of Interest: S.G. No potential conflicts of interest to disclose. L.L.M. No potential conflicts of interest to disclose. X.I.. No potential conflicts of interest, to disclose. E.A.N. Financial activities related to the present article: ferumoxytol ultrasmall superparamagnetic iron oxide nanoparticles were donated by AMAG Pharmaceuticals. Financial activities not, related to the present article: has a sponsored research agreement with AMAG Pharmaceuticals. Other relationships: none to disclose. NR 38 TC 24 Z9 24 U1 0 U2 10 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD DEC PY 2011 VL 261 IS 3 BP 796 EP 804 DI 10.1148/radiol.11103503 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 849PR UT WOS:000297138100016 PM 21940504 ER PT J AU Hsiao, EM Cao, XH Zurakowski, D Zukotynski, KA Drubach, LA Grant, FD Yahil, A Vija, AH Davis, RT Fahey, FH Treves, ST AF Hsiao, Edward M. Cao, Xinhua Zurakowski, David Zukotynski, Katherine A. Drubach, Laura A. Grant, Frederick D. Yahil, Amos Vija, A. Hans Davis, Royal T. Fahey, Frederic H. Treves, S. Ted TI Reduction in Radiation Dose in Mercaptoacetyltriglycerine Renography with Enhanced Planar Processing SO RADIOLOGY LA English DT Article ID DIFFERENTIAL RENAL-FUNCTION; RECONSTRUCTION; CHILDREN AB Purpose: To determine the minimum close of technetium 99m ((99m)Tc) mercaptoacetyltriglycerine (MAG3) needed to perform dynamic renal scintigraphy in the pediatric population without loss of diagnostic quality or accurate quantification of renal function and to investigate whether adaptive noise reduction could help further reduce the minimum close required. Materials and Methods: Approval for this retrospective study was obtained from the institutional review board, with waiver of informed consent:. A retrospective review was conducted in 33 pediatric patients consecutively referred for a (99m)Tc-MAG3 study. In each each patient, a 20-minute dynamic study was performed after administration of 7.4 MBq/kg. Binomial subsampling was used to simulate studies performed with 50%, 30%, 20%, and 10% of the administered dose. Four nuclear medicine physicians independently reviewed the original and subsampled images, with and without noise reduction, for image quality. Two observers independently performed a quantitative analysis of renal function. Subjective rater confidence was analyzed by using a logistic regression model, and the quantitative analysis was performed by using the paired Student t. test. Results: Reducing the administered close to 30% did not substantially affect image quality, with or without noise reduction. When the dose was reduced to 20%, there was a slight but: significant decrease (P = .0074) in image quality, which resolved with noise reduction. Reducing the dose to 10% caused a decrease in image quality (P = .0003) that was not corrected with noise reduction. However, the dose could be reduced to 10% without a substantial change in the quantitative evaluation of renal function independent of the application of noise reduction. Conclusion: Decreasing the close of (99m)Tc-MAG3 from 7.4 to 2.2 MBq/kg did not compromise image quality. With noise reduction, the dose can be reduced to 1.5 MBq/kg without subjective loss in image quality. The quantitative evaluation of renal function was not substantially altered, even with a theoretical close as low as 0.74 MBq/kg. (C) RSNA, 2011 C1 [Hsiao, Edward M.; Cao, Xinhua; Drubach, Laura A.; Grant, Frederick D.; Davis, Royal T.; Fahey, Frederic H.; Treves, S. Ted] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Nucl Med & Mol Imaging, Boston, MA 02115 USA. [Zurakowski, David] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Anesthesia, Boston, MA 02115 USA. [Hsiao, Edward M.; Zukotynski, Katherine A.; Drubach, Laura A.; Grant, Frederick D.; Fahey, Frederic H.; Treves, S. Ted] Harvard Univ, Sch Med, Joint Program Nucl Med, Boston, MA 02115 USA. [Zukotynski, Katherine A.] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. [Yahil, Amos] Pixon LLC, Stony Brook, NY USA. [Vija, A. Hans] Siemens Med Solut USA Inc, Mol Imaging, Malvern, PA USA. RP Treves, ST (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Div Nucl Med & Mol Imaging, 300 Longwood Ave, Boston, MA 02115 USA. EM treves@childrens.harvard.edu FU ImageRecon LLC; Pixon LLC; ImageRecon FX E.M.H. Financial activities related to the present. article: none to disclose. Financial activities not related to the present. article: employed as staff radiologist by University Hospitals Health System. Other relationships: none to disclose. X.C. No potential conflicts of interest to disclose. D.Z. No potential conflicts of interest to disclose. K.A.Z. No potential conflicts of interest to disclose. L.A.D. No potential conflicts of interest to disclose. F.D.G. No potential conflicts of interest to disclose. A.Y. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: received payment for patents from ImageRecon LLC and Pixon LLC and institution received payment for royalties from ImageRecon Other relationships: none to disclose. A.H.V. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: employed by Siemens Medical Solutions USA. Other relationships: none to disclose. R.T.D. No potential conflicts of interest to disclose. F.H.F: No potential conflicts of interest to disclose. S.T.T. No potential conflicts of interest to disclose. NR 14 TC 12 Z9 12 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD DEC PY 2011 VL 261 IS 3 BP 907 EP 915 DI 10.1148/radiol.11110602 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 849PR UT WOS:000297138100028 PM 21900613 ER PT J AU Tucker, JD Yin, YP Wang, BX Chen, XS Cohen, MS AF Tucker, Joseph D. Yin, Yue-Ping Wang, Baoxi Chen, Xiang-Sheng Cohen, Myron S. TI An expanding syphilis epidemic in China: epidemiology, behavioural risk and control strategies with a focus on low-tier female sex workers and men who have sex with men SO SEXUALLY TRANSMITTED INFECTIONS LA English DT Article ID ENTERTAINMENT WORKERS; HEPATITIS-B; HIV; INFECTIONS; PREVALENCE; PREDICTORS; PROVINCE; COHORT; VIRUS C1 [Tucker, Joseph D.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. [Tucker, Joseph D.; Cohen, Myron S.] UNC Chapel Hill Sch Med, Dept Med, Div Infect Dis, Chapel Hill, NC USA. [Yin, Yue-Ping; Wang, Baoxi; Chen, Xiang-Sheng] Chinese Acad Med Sci, Natl Ctr STD Control, Nanjing, Peoples R China. [Yin, Yue-Ping; Wang, Baoxi; Chen, Xiang-Sheng] Peking Union Med Coll, Inst Dermatol, Nanjing, Peoples R China. RP Chen, XS (reprint author), 12 Jiangwangmiao St, Nanjing 210042, Peoples R China. EM chenxs@ncstdlc.org FU Mega Project of China National Science Research for the 11th Five-Year Plan [2008ZX10001-005]; NIH [US NIH 1K01TW008200-01A1]; UNC Social Science Research on HIV/AIDS in China [NIH NICHD R24 HD056670-01]; UNC Center for AIDS Research; China-Australia Health and HIV/AIDS Facility Project [HIV 04]; WHO [CHN/10/HS/003353, Unicef/UNDP/World Bank/WHO A70577] FX Financial support for this research came from the Mega Project of China National Science Research for the 11th Five-Year Plan (2008ZX10001-005), theNIH Fogarty K01 Award (US NIH 1K01TW008200-01A1), the UNC Social Science Research on HIV/AIDS in China (NIH NICHD R24 HD056670-01), the UNC Center for AIDS Research, the China-Australia Health and HIV/AIDS Facility Project (HIV 04), WHO Country Project (CHN/10/HS/003353) and the WHO Rapid Syphilis Test Project (Unicef/UNDP/World Bank/WHO A70577). NR 32 TC 7 Z9 9 U1 0 U2 3 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1368-4973 J9 SEX TRANSM INFECT JI Sex. Transm. Infect. PD DEC PY 2011 VL 87 SU 2 BP II16 EP II18 DI 10.1136/sti.2010.048314 PG 3 WC Infectious Diseases SC Infectious Diseases GA 852BQ UT WOS:000297320700006 PM 22110145 ER PT J AU Lee, HY Kaneki, M Andreas, J Tompkins, RG Martyn, JAJ AF Lee, Hyung-yul Kaneki, Masao Andreas, Jonathan Tompkins, Ronald G. Martyn, J. A. Jeevendra TI NOVEL MITOCHONDRIA-TARGETED ANTIOXIDANT PEPTIDE AMELIORATES BURN-INDUCED APOPTOSIS AND ENDOPLASMIC RETICULUM STRESS IN THE SKELETAL MUSCLE OF MICE SO SHOCK LA English DT Article DE SS-31 peptide; burn injury; reactive oxygen species; insulin resistance ID INSULIN-RESISTANCE; OXIDATIVE STRESS; DELIVERY-SYSTEM; ER STRESS; INJURY; INFLAMMATION; DYSFUNCTION; TRAUMA; RATS; ACTIVATION AB This study tested the hypothesis that a novel mitochondria-targeted SS-31 peptide attenuates the burn injury-induced apoptosis and endoplasmic reticulum stress and improves insulin sensitivity in the skeletal muscle. Following 30% total body surface area burn or sham burn, mice were injected daily with SS-31 peptide (5 mg/kg body weight), and the rectus abdominis muscles collected on postburn days 1, 3, and 7. The tissues were subjected to various biochemical and immunohistochemical analyses. Treatment with SS-31 peptide prevented burn-induced increases in the caspase 3 activity (P < 0.05) and apoptosis (P < 0.01) on postburn day 7. The SS-31 peptide treatment also prevented the increase in the expression levels of phosphatase and tensin homolog on postburn days 3 and 7. Burn injury-induced increases in the levels of two endoplasmic reticulum stress markers, binding immunoglobulin protein and protein disulfide isomerase, were significantly decreased by the SS-31 peptide treatments on postburn day 7 and on day 3 for binding immunoglobulin protein as well (P < 0.05). The effects of SS-31 appear to be, in part, due to its ability to reduce oxidative stress in burned mice, evidenced by reduced expression of oxidized proteins that were clearly evident on postburn day 7. Our results demonstrate a possible therapeutic potential of SS-31 peptide to ameliorate the adverse effects of burn injury in skeletal muscle. C1 Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Martyn, JAJ (reprint author), 51 Blossom St,Room 206, Boston, MA 02114 USA. EM jmartyn@partners.org FU Shriners Hospitals for Children; National Institutes of Health [GM055082, GM 25000] FX This study was supported, in part, by grants from Shriners Hospitals for Children (research grants to J.A.J.M. and fellowship grant to H.L.) and from National Institutes of Health grants (GM055082 and GM 25000 Project IV to J.A.J.M.). NR 35 TC 20 Z9 22 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1073-2322 J9 SHOCK JI Shock PD DEC PY 2011 VL 36 IS 6 BP 580 EP 585 DI 10.1097/SHK.0b013e3182366872 PG 6 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA 850OB UT WOS:000297203800009 PM 21937949 ER PT J AU Cullen, G Kroshinsky, D Cheifetz, AS Korzenik, JR AF Cullen, G. Kroshinsky, D. Cheifetz, A. S. Korzenik, J. R. TI Psoriasis associated with anti-tumour necrosis factor therapy in inflammatory bowel disease: a new series and a review of 120 cases from the literature SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Review ID CROHNS-DISEASE; CERTOLIZUMAB PEGOL; FACTOR-ALPHA; MAINTENANCE THERAPY; ULCERATIVE-COLITIS; INFLIXIMAB; TRIAL; TNF; ADALIMUMAB; INDUCTION AB Background Anti-tumour necrosis factor (TNF) antibodies are used to treat both psoriasis and inflammatory bowel disease. The seemingly paradoxical occurrence of psoriasis in patients treated with anti-TNF antibodies is increasingly recognised, but the distinct features associated with inflammatory bowel disease have been incompletely characterised. Aim To identify inflammatory bowel disease patients who developed psoriasis while receiving an anti-TNF antibody at two academic medical centres between 2000 and 2009 and review all published cases of this phenomenon in inflammatory bowel disease. Methods We identified retrospectively all cases of anti-TNF-induced psoriasis in inflammatory bowel disease patients attending two North American healthcare centres. We analysed these cases alongside the published reports of anti-TNF-induced psoriasis. Results We identified 30 subjects who developed a psoriatic rash while receiving anti-TNF therapy for inflammatory bowel disease. Forty-seven per cent (14/30) responded to topical therapy and 23% (7/30) ultimately discontinued the anti-TNF. The new data were combined with those from 120 published cases of anti-TNF-induced psoriasis in inflammatory bowel disease. Anti-TNF-induced psoriasis in inflammatory bowel disease was more common in women (70%). The most common distributions were palmoplantar (43%) and scalp (42%). Complete follow-up in 148 cases showed that 41% responded to topical therapy but 43% required definitive withdrawal of anti-TNF therapy due to the rash. A second anti-TNF was tried in 27 cases with recurrence or persistence of the rash in 14 (52%). Conclusions In this analysis, psoriasiform lesions related to anti-TNF therapy in inflammatory bowel disease occurred most commonly in women. Approximately 41% of those who developed psoriasis while on anti-TNFs responded to topical therapy and were able to continue the drug, while 52% of those treated with an alternate anti-TNF had recurrence of the rash. C1 [Cullen, G.; Cheifetz, A. S.] Beth Israel Deaconess Med Ctr, Div Gastroenterol, Boston, MA 02215 USA. [Cullen, G.; Korzenik, J. R.] Massachusetts Gen Hosp, Crohns & Colitis Ctr, Boston, MA 02114 USA. [Kroshinsky, D.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Cullen, G.; Kroshinsky, D.; Cheifetz, A. S.; Korzenik, J. R.] Harvard Univ, Sch Med, Boston, MA USA. RP Cullen, G (reprint author), Beth Israel Deaconess Med Ctr, Div Gastroenterol, Boston, MA 02215 USA. EM gcullen@bidmc.harvard.edu FU Warner Chilcott; UCB FX Adam S Cheifetz has served as an advisory board member for UCB, Warner Chilcott and Abbott. Joshua R Korzenik has served as an advisory board member for Elan and received research support from Warner Chilcott and UCB. NR 36 TC 75 Z9 79 U1 0 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0269-2813 J9 ALIMENT PHARM THER JI Aliment. Pharmacol. Ther. PD DEC PY 2011 VL 34 IS 11-12 BP 1318 EP 1327 DI 10.1111/j.1365-2036.2011.04866.x PG 10 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 849BO UT WOS:000297100300006 PM 21957906 ER PT J AU Tinsley, A Macklin, EA Korzenik, JR Sands, BE AF Tinsley, A. Macklin, E. A. Korzenik, J. R. Sands, B. E. TI Validation of the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) in patients with inflammatory bowel disease SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID QUALITY-OF-LIFE; HEALTH-RELATED QUALITY; MEASUREMENT SYSTEM; SCALE; PREVALENCE; ANEMIA; QUESTIONNAIRES; TRANSLATION; POPULATION; ARTHRITIS AB Background Many patients with ulcerative colitis (UC) and Crohns disease (CD) complain of significant fatigue. To date, no instrument to measure fatigue has been validated in a US inflammatory bowel disease (IBD) population. Aim To determine the reliability and validity of the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale in IBD. Methods A total of 209 patients with IBD completed the 13 items of the FACIT-F, alongside laboratory testing and disease activity assessment. Internal consistency was measured by Cronbachs alpha; testretest reliability by the intraclass correlation coefficient (ICC); validity by the correlation of the FACIT-F score with C-reactive protein (CRP) erythrocyte sedimentation rate (ESR), haematocrit (HCT) and disease activity as measured by the Harvey-Bradshaw Index (HBI; CD) and Simple Clinical Colitis Activity Index (SCCAI; UC). Results The mean +/- SD FACIT-F score was 38.9 +/- 11.0 overall (CD 38.6 +/- 11.3; UC 39.4 +/- 10.6). Cronbachs alpha was 0.94. The ICC for first and repeat FACIT-F scores assessed within 180 days without change in disease state was 0.81 (CD 0.78; UC 0.87). FACIT-F scores were lower in patients with active symptoms (CD 4.6 points, 95% CI 2.46.9, P < 0.001; UC 8.5 points, 95% CI 5.511.4, P < 0.001). In UC, FACIT-F scores were correlated with ESR (-0.76, 95% CI -0.89 to -0.50), CRP (-0.72, 95% CI -0.88 to -0.43) and HCT (0.53, 95% CI 0.220.74). Conclusion The FACIT-F scale is a reliable and valid instrument for measuring fatigue in IBD. C1 [Tinsley, A.; Sands, B. E.] Mt Sinai Sch Med, Dr Henry D Janowitz Div Gastroenterol, New York, NY 10029 USA. [Macklin, E. A.] Massachusetts Gen Biostat Ctr, Boston, MA USA. [Korzenik, J. R.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Sands, BE (reprint author), Mt Sinai Sch Med, Dr Henry D Janowitz Div Gastroenterol, 1 Gustave L Levy Pl,Box 1069, New York, NY 10029 USA. EM bruce.sands@mssm.edu RI Macklin, Eric/E-2955-2013 OI Macklin, Eric/0000-0003-1618-3502 FU Celgene; UCB; Warner-Chilcott FX The authors thank David Cella PhD, for his permission to use the FACIT-F in this study and subsequent publication. Declaration of personal interests: Dr Bruce E Sands has served as a consultant or advisor for Abbot Immunology, Axcan Pharma, Avaxia Biologics, Bristol-Myers Squib, Centocor, Elan Pharmaceuticals, Flaxo SmithKline Welcome, Millenium Pharmaceuticals, Novartis Pharmaceuticals, Pfizer and Marina Biotech, and has received research funding from Celgene and UCB. Dr Joshua R Korzenik has served as a speaker, a consultant and an advisory board member for Elan Pharmaceuticals and received research funding from Warner-Chilcott. Declaration of funding interests: None. NR 39 TC 24 Z9 25 U1 1 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0269-2813 J9 ALIMENT PHARM THER JI Aliment. Pharmacol. Ther. PD DEC PY 2011 VL 34 IS 11-12 BP 1328 EP 1336 DI 10.1111/j.1365-2036.2011.04871.x PG 9 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 849BO UT WOS:000297100300007 PM 21999576 ER PT J AU Bourgier, C Taghian, A Marsiglia, H AF Bourgier, Celine Taghian, Alphonse Marsiglia, Hugo TI Three-field Electron/Minitangent Photon Technique Offer Dosimetric Advantages to a Multifield, Photon-only Technique for Accelerated Partial Breast Irradiation if Well Implemented SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Letter C1 [Bourgier, Celine; Marsiglia, Hugo] Inst Gustave Roussy, Dept Radiat Therapy, Breast Unit, Paris, France. [Taghian, Alphonse] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Marsiglia, Hugo] Univ Florence, Florence, Italy. RP Bourgier, C (reprint author), Inst Gustave Roussy, Dept Radiat Therapy, Breast Unit, Paris, France. NR 7 TC 2 Z9 2 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3732 J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD DEC PY 2011 VL 34 IS 6 BP 648 EP 648 DI 10.1097/COC.0b013e31820059a2 PG 1 WC Oncology SC Oncology GA 851HK UT WOS:000297258800009 PM 22101390 ER PT J AU Hinney, A Scherag, A Jarick, I Albayrak, O Putter, C Pechlivanis, S Dauvermann, MR Beck, S Weber, H Scherag, S Nguyen, TT Volckmar, AL Knoll, N Faraone, SV Neale, BM Franke, B Cichon, S Hoffmann, P Nothen, MM Schreiber, S Jockel, KH Wichmann, HE Freitag, C Lempp, T Meyer, J Gilsbach, S Herpertz-Dahlmann, B Sinzig, J Lehmkuhl, G Renner, TJ Warnke, A Romanos, M Lesch, KP Reif, A Schimmelmann, BG Hebebrand, J AF Hinney, Anke Scherag, Andre Jarick, Ivonne Albayrak, Oezguer Puetter, Carolin Pechlivanis, Sonali Dauvermann, Maria R. Beck, Sebastian Weber, Heike Scherag, Susann Nguyen, Trang T. Volckmar, Anna-Lena Knoll, Nadja Faraone, Stephen V. Neale, Benjamin M. Franke, Barbara Cichon, Sven Hoffmann, Per Noethen, Markus M. Schreiber, Stefan Joeckel, Karl-Heinz Wichmann, H. -Erich Freitag, Christine Lempp, Thomas Meyer, Jobst Gilsbach, Susanne Herpertz-Dahlmann, Beate Sinzig, Judith Lehmkuhl, Gerd Renner, Tobias J. Warnke, Andreas Romanos, Marcel Lesch, Klaus-Peter Reif, Andreas Schimmelmann, Benno G. Hebebrand, Johannes CA Psychiat GWAS Consortium ADHD Subg TI Genome-Wide Association Study in German Patients With Attention Deficit/Hyperactivity Disorder SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE psychiatric; children; early onset; homogeneous ID DEFICIT HYPERACTIVITY DISORDER; RESTLESS-LEGS-SYNDROME; MOLECULAR-GENETICS; BIPOLAR DISORDER; COMMON VARIANTS; ADHD; LINKAGE; GENES; METAANALYSIS; LOCI AB The heritability of attention deficit hyperactivity disorder (ADHD) is approximately 0.8. Despite several larger scale attempts, genome-wide association studies (GWAS) have not led to the identification of significant results. We performed a GWAS based on 495 German young patients with ADHD (according to DSM-IV criteria; Human660W-Quadv1; Illumina, San Diego, CA) and on 1,300 population-based adult controls (HumanHap550v3; Illumina). Some genes neighboring the single nucleotide polymorphisms (SNPs) with the lowest P-values (best P-value: 8.38 x 10(-7)) have potential relevance for ADHD (e. g., glutamate receptor, metabotropic 5 gene, GRM5). After quality control, the 30 independent SNPs with the lowest P-values (P-values <= 7.57 x 10(-5)) were chosen for confirmation. Genotyping of these SNPs in up to 320 independent German families comprising at least one child with ADHD revealed directionally consistent effect-size point estimates for 19 (10 not consistent) of the SNPs. In silico analyses of the 30 SNPs in the largest meta-analysis so far (2,064 trios, 896 cases, and 2,455 controls) revealed directionally consistent effect-size point estimates for 16 SNPs (11 not consistent). None of the combined analyses revealed a genome-wide significant result. SNPs in previously described autosomal candidate genes did not show significantly lower P-values compared to SNPs within random sets of genes of the same size. We did not find genome-wide significant results in a GWAS of German children with ADHD compared to controls. The second best SNP is located in an intron of GRM5, a gene located within a recently described region with an infrequent copy number variation in patients with ADHD. (C) 2011 Wiley Periodicals, Inc. C1 [Hinney, Anke; Albayrak, Oezguer; Dauvermann, Maria R.; Beck, Sebastian; Scherag, Susann; Schimmelmann, Benno G.; Hebebrand, Johannes] Univ Duisburg Essen, Dept Child & Adolescent Psychiat, D-45147 Essen, Germany. [Scherag, Andre; Puetter, Carolin; Pechlivanis, Sonali; Joeckel, Karl-Heinz] Univ Duisburg Essen, IMIBE, D-45147 Essen, Germany. [Jarick, Ivonne; Nguyen, Trang T.] Univ Marburg, Inst Med Biometrie & Epidemiol, Marburg, Germany. [Dauvermann, Maria R.; Schimmelmann, Benno G.] Univ Bern, Univ Hosp Child & Adolescent Psychiat, Bern, Switzerland. [Weber, Heike; Renner, Tobias J.; Warnke, Andreas] Univ Wurzburg, Dept Child & Adolescent Psychiat, Wurzburg, Germany. [Faraone, Stephen V.] SUNY Upstate Med Univ, Syracuse, NY USA. [Neale, Benjamin M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Neale, Benjamin M.] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA USA. [Franke, Barbara] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands. [Franke, Barbara] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Psychiat, NL-6525 ED Nijmegen, Netherlands. [Cichon, Sven] Res Ctr Juelich, Inst Neurosci & Med INM 1, Julich, Germany. [Cichon, Sven; Hoffmann, Per; Noethen, Markus M.] Univ Bonn, Inst Human Genet, D-5300 Bonn, Germany. [Cichon, Sven; Hoffmann, Per; Noethen, Markus M.] Univ Bonn, Dept Genom, Life & Brain Ctr, D-5300 Bonn, Germany. [Schreiber, Stefan] Univ Hosp Schleswig Holstein, Inst Clin Mol Biol, Kiel, Germany. [Wichmann, H. -Erich] German Res Ctr Environm Hlth, Helmholtz Ctr Munich, Inst Epidemiol, Munich, Germany. [Freitag, Christine; Lempp, Thomas] Goethe Univ Frankfurt, Dept Child & Adolescent Psychiat Psychosomat & Ps, Frankfurt, Germany. [Meyer, Jobst] Univ Trier, Inst Psychobiol, Dept Neurobehav Genet, Trier, Germany. [Gilsbach, Susanne; Herpertz-Dahlmann, Beate] Rhein Westfal TH Aachen, Univ Clin, Dept Child & Adolescent Psychiat Psychosomat & Ps, Aachen, Germany. [Sinzig, Judith; Lehmkuhl, Gerd] Univ Cologne, Dept Child & Adolescent Psychiat, Cologne, Germany. [Sinzig, Judith] LVR Clin Bonn, Dept Child & Adolescent Psychiat & Psychotherapy, Bonn, Germany. [Romanos, Marcel] Univ Hosp Munich, Dept Child & Adolescent Psychiat Psychosomat & Ps, Munich, Germany. [Lesch, Klaus-Peter; Reif, Andreas] Univ Wurzburg, Dept Psychiat Psychosomat & Psychotherapy, Wurzburg, Germany. RP Hinney, A (reprint author), Univ Duisburg Essen, Dept Child & Adolescent Psychiat, D-45147 Essen, Germany. EM anke.hinney@uni-due.de RI Franke, Barbara/D-4836-2009; Cichon, Sven/B-9618-2014; Schreiber, Stefan/B-6748-2008; Lesch, Klaus-Peter/J-4906-2013; Romanos, Marcel/D-7695-2017; Buitelaar, Jan/E-4584-2012; Hinney, Anke/D-6953-2011; Renner, Tobias/I-2120-2013; Cichon, Sven/H-8803-2013; OI Kent, Lindsey/0000-0002-5315-3399; Scherag, Andre/0000-0002-9406-4704; Anney, Richard/0000-0002-6083-407X; Nothen, Markus/0000-0002-8770-2464; Thapar, Anita/0000-0002-3689-737X; Hoffmann, Per/0000-0002-6573-983X; Faraone, Stephen/0000-0002-9217-3982; Franke, Barbara/0000-0003-4375-6572; Cichon, Sven/0000-0002-9475-086X; Schreiber, Stefan/0000-0003-2254-7771; Lesch, Klaus-Peter/0000-0001-8348-153X; Sinzig, Judith/0000-0002-3693-3318; Weber, Heike/0000-0002-9421-1292; Buitelaar, Jan/0000-0001-8288-7757; Hinney, Anke/0000-0001-5659-0706; Cichon, Sven/0000-0002-9475-086X; Langley, Kate/0000-0002-2033-2657 FU German Research Association (DFG) [He1446/9-1, KFO 125, SFB 581, GRK 1156, ME 1923/5-1, ME 1923/5-3, GRK 1389, SCHA 542/10-3]; Bundesministerium fur Bildung und Forschung [BMBF 01GV0605]; Medical Faculty, RWTH Aachen, Germany [EK 119/05]; US National of Institute of Health [R13MH059126, R01MH62873, R01MH081803, K23MH066275]; University of Pennsylvania CTR [UL1-RR-024134]; Children's Hospital of Philadelphia; Affymetrix Power Award; NHMRC (Australia); Sidney Sax Public Health Fellowship [443036]; UMC Utrecht Genvlag Grant; Radboud University Nijmegen Medical Centre FX We thank the children and their families for their participation. We thank the German Research Association (DFG) who funded the GWAS analyses and confirmatory studies (He1446/9-1 to J. Hebebrand, K.-P. Lesch, A. Hinney and T. Renner, KFO 125, SFB 581, GRK 1156 to K. P. Lesch; ME 1923/5-1, ME 1923/5-3 to J. Meyer and C. M. Freitag, GRK 1389 to J. Meyer, SCHA 542/10-3 to H. Schafer) and the Bundesministerium fur Bildung und Forschung (BMBF 01GV0605 to K.P. Lesch). We thank the START Program EK 119/05 of the Medical Faculty, RWTH Aachen, Germany. We thank the Cardiff group of IMAGE2 for providing summary statistics for the 30 best SNPs; the group comprises Anita Thapar, Michael C O'Donovan, Michael J. Owen, Kate Langley, Nigel Williams, Peter Holmans at the MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, UK. The ADHD meta-analysis was supported by the following grants: US National of Institute of Health Grants R13MH059126, R01MH62873 and R01MH081803 to S.V.Faraone and K23MH066275 to J. Elia, The University of Pennsylvania CTR grant UL1-RR-024134 to J. Elia and H. Hakonarson and Institutional Development Award to the Center for Applied Genomics from the Children's Hospital of Philadelphia to H. Hakonarson; Affymetrix Power Award, 2007 to B. Franke; NHMRC (Australia) and Sidney Sax Public Health Fellowship (443036) to S.E. Medland; Wellcome Trust, UK for sample collection to L Kent. MH58277 to S. Smalley. UMC Utrecht Genvlag Grant, an Internal Grant of Radboud University Nijmegen Medical Centre to J. Buitelaar. NR 52 TC 40 Z9 40 U1 1 U2 13 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD DEC PY 2011 VL 156B IS 8 BP 888 EP 897 DI 10.1002/ajmg.b.31246 PG 10 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 850TP UT WOS:000297222700002 PM 22012869 ER PT J AU Landers, SJ Mimiaga, MJ Conron, KJ AF Landers, Stewart J. Mimiaga, Matthew J. Conron, Kerith J. TI Sexual Orientation Differences in Asthma Correlates in a Population-Based Sample of Adults SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID HEALTH; INDIVIDUALS; LESBIANS; GAY; WOMEN; MEN AB To understand what conditions may correlate with asthma diagnoses in the lesbian, gay, and bisexual (LGB) population, we used Massachusetts Behavioral Risk Factor Surveillance System data to construct multivariable logistic regression models separately for LGB individuals and heterosexuals. Current or former smoking and obesity were positively associated with history of an asthma diagnosis among both LGB individuals and heterosexuals. Being underweight (negative correlation) and overweight and reporting frequent symptoms of depression in the preceding 30 days also predicted a history of asthma diagnosis among heterosexuals. (Am J Public Health. 2011;101:2233-2244. doi:10.2105/AJPH.2011.300305) C1 [Landers, Stewart J.] John Snow Inc, Boston, MA 02210 USA. [Mimiaga, Matthew J.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Mimiaga, Matthew J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Conron, Kerith J.] Northeastern Univ, Inst Urban Hlth Res, Boston, MA 02115 USA. RP Landers, SJ (reprint author), John Snow Inc, 44 Farnsworth St, Boston, MA 02210 USA. EM landers@jsi.com FU Williams Institute at the University of California, Los Angeles, School of Law; Massachusetts Department of Public Health (DPH) FX The Williams Institute at the University of California, Los Angeles, School of Law and the Massachusetts Department of Public Health (DPH) provided financial support for the analyses reported here. NR 16 TC 9 Z9 9 U1 1 U2 5 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 2011 VL 101 IS 12 BP 2238 EP 2241 DI 10.2105/AJPH.2011.300305 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 849QT UT WOS:000297140900013 PM 22021292 ER PT J AU Alley, DE Lloyd, J Pagan, JA Pollack, CE Shardell, M Cannuscio, C AF Alley, Dawn E. Lloyd, Jennifer Pagan, Jose A. Pollack, Craig E. Shardell, Michelle Cannuscio, Carolyn TI Mortgage Delinquency and Changes in Access to Health Resources and Depressive Symptoms in a Nationally Representative Cohort of Americans Older Than 50 Years SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID US ELDERLY PERSONS; SOCIOECONOMIC DISPARITIES; FOOD INSECURITY; UNITED-STATES; MORTALITY; HOME; PEOPLE; CONSEQUENCES; ASSOCIATION; COMMUNITY AB Objectives. We evaluated associations between mortgage delinquency and changes in health and health-relevant resources over 2 years, with data from the Health and Retirement Study, a longitudinal survey representative of US adults older than 50 years. Methods. In 2008, participants reported whether they had fallen behind on mortgage payments since 2006 (n=2474). We used logistic regression to compare changes in health (incidence of elevated depressive symptoms, major declines in self-rated health) and access to health-relevant resources (food, prescription medications) between participants who fell behind on their mortgage payments and those who did not. Results. Compared with nondelinquent participants, the mortgage-delinquent group had worse health status and less access to health-relevant resources at baseline. They were also significantly more likely to develop incident depressive symptoms (odds ratio [OR]=8.60; 95% confidence interval [CI]=3.38, 21.85), food insecurity (OR=7.53; 95% CI=3.01, 18.84), and cost-related medication nonadherence (OR=8.66; 95% CI=3.72, 20.16) during follow-up. Conclusions. Mortgage delinquency was associated with significant elevations in the incidence of mental health impairments and health-relevant material disadvantage. Widespread mortgage default may have important public health implications. (Am J Public Health. 2011;101:2293-2298. doi:10.2105/AJPH.2011.300245) C1 [Alley, Dawn E.; Lloyd, Jennifer; Shardell, Michelle] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA. [Pagan, Jose A.] Univ N Texas Hlth Sci Ctr, Sch Publ Hlth, Dept Hlth Management & Policy, Ft Worth, TX USA. [Pollack, Craig E.] Johns Hopkins Sch Med, Dept Med, Baltimore, MD USA. [Cannuscio, Carolyn] Dept Vet Affairs Med Ctr, Vet Affairs Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA. RP Alley, DE (reprint author), 660 W Redwood St,221B, Baltimore, MD 21201 USA. EM dalley@epi.umaryland.edu RI Cannuscio, Carolyn/A-1123-2007 FU National Institutes of Health [T32AG000262, K12HC043489]; Philadelphia Veterans Affairs Medical Center; Organized Research Center on Aging at the University of Maryland, Baltimore FX This study was supported by the National Institutes of Health (grants T32AG000262 and K12HC043489). It was conducted with support, resources, and use of facilities from the Philadelphia Veterans Affairs Medical Center in conjunction with the Organized Research Center on Aging at the University of Maryland, Baltimore NR 38 TC 31 Z9 31 U1 2 U2 11 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 2011 VL 101 IS 12 BP 2293 EP 2298 DI 10.2105/AJPH.2011.300245 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 849QT UT WOS:000297140900022 PM 22021301 ER PT J AU Tsuchiya, K Banks, AS Liang, CP Tabas, I Tall, AR Accili, D AF Tsuchiya, Kyoichiro Banks, Alexander S. Liang, Chien-Ping Tabas, Ira Tall, Alan R. Accili, Domenico TI Homozygosity for an Allele Encoding Deacetylated FoxO1 Protects Macrophages From Cholesterol-Induced Inflammation Without Increasing Apoptosis SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE apoptosis; diabetes mellitus; insulin resistance; lipids; macrophages ID NF-KAPPA-B; ADVANCED ATHEROSCLEROTIC LESIONS; ENDOPLASMIC-RETICULUM STRESS; TRANSCRIPTION FACTOR FOXO1; SMOOTH-MUSCLE-CELLS; MAP KINASE; INSULIN-RESISTANCE; ACTIVATION; AKT; PHOSPHORYLATION AB Objective-Insulin resistance renders macrophages more prone to cholesterol-induced apoptosis by promoting nuclear localization of transcription factor forkhead box transcription factor (Fox) O1. However, FoxO1 also decreases macrophage inflammation, raising the question of how the balance between proapoptotic and antiinflammatory effects is determined. We sought to identify the mechanism whereby FoxO1 dampens inflammation without promoting apoptosis. We hypothesized that nutrient-dependent FoxO1 acetylation plays a role in this process. Methods and Results-We generated knock-in mice bearing alleles that encode constitutively deacetylated FoxO1 and studied the ex vivo response of primary peritoneal macrophages. We show that macrophages derived from mice homozygous for constitutively deacetylated FoxO1 alleles retain antiinflammatory properties in response to free cholesterol loading, without increasing apoptosis. Deacetylated FoxO1 inhibits free cholesterol-induced Akt phosphorylation and increases levels of the nuclear factor-kappa B precursor p105, decreasing nuclear translocation of nuclear factor-kappa B p65 subunit and dampening mitogen-activated protein/extracellular signal-regulated kinase activation to prevent inflammation. Conclusion-Deacetylated FoxO1 regulates p105 to prevent macrophage inflammation without causing apoptosis, suggesting a potential novel therapeutic approach to atherosclerosis through FoxO1 deacetylation. (Arterioscler Thromb Vasc Biol. 2011;31:2920-2928.) C1 [Tsuchiya, Kyoichiro; Liang, Chien-Ping; Tabas, Ira; Tall, Alan R.; Accili, Domenico] Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY USA. [Tabas, Ira; Tall, Alan R.] Columbia Univ, Coll Phys & Surg, Dept Anat & Cell Biol, New York, NY USA. [Tabas, Ira; Tall, Alan R.] Columbia Univ, Coll Phys & Surg, Dept Physiol & Cellular Biophys, New York, NY USA. [Banks, Alexander S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Accili, D (reprint author), 1150 St Nicholas Ave, New York, NY 10032 USA. EM da230@columbia.edu RI Banks, Alexander/B-4832-2012 OI Banks, Alexander/0000-0003-1787-6925 FU Uehara Memorial Foundation of Tokyo; National Institutes of Health [P01-HL087123, R01-HL054591, F32DK79496, DK63608] FX Dr Tsuchiya is the recipient of a research fellowship from the Uehara Memorial Foundation of Tokyo. This work was supported by National Institutes of Health Grants P01-HL087123, R01-HL054591 (to I. T.), F32DK79496 (to A. S. B.), and DK63608 (Columbia Diabetes and Endocrinology Research Center). NR 51 TC 7 Z9 7 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD DEC PY 2011 VL 31 IS 12 BP 2920 EP 2928 DI 10.1161/ATVBAHA.110.219477 PG 9 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 851CK UT WOS:000297245700029 PM 21940942 ER PT J AU Wilhelm, S Phillips, KA Fama, JM Greenberg, JL Steketee, G AF Wilhelm, Sabine Phillips, Katharine A. Fama, Jeanne M. Greenberg, Jennifer L. Steketee, Gail TI Modular Cognitive-Behavioral Therapy for Body Dysmorphic Disorder SO BEHAVIOR THERAPY LA English DT Article DE body dysmorphic disorder; BDD; cognitive-behavioral therapy; body image; treatment ID POPULATION-BASED SURVEY; SKIN PICKING; RESPONSE PREVENTION; CLINICAL-FEATURES; PREVALENCE; SUICIDE; INDIVIDUALS; RELIABILITY; EXPOSURE; VALIDITY AB This study pilot tested a newly developed modular cognitive behavioral therapy (CBT) treatment manual for body dysmorphic disorder (BDD). We tested feasibility, acceptability, and treatment outcome in a sample of 12 adults with primary BDD. Treatment was delivered in weekly individual sessions over 18 or 22 weeks. Standardized clinician ratings and self-report measures were used to assess BDD and related symptoms pre- and posttreatment and at 3- and 6-month follow-ups. At posttreatment, BDD and related symptoms (e.g., mood) were significantly improved. Treatment gains were maintained at follow-up. A relatively low drop-out rate, high patient satisfaction ratings, and patient feedback indicated that the treatment was highly acceptable to patients. To our knowledge, this represents the first test of a broadly applicable, individual psychosocial treatment for BDD. C1 [Wilhelm, Sabine; Fama, Jeanne M.; Greenberg, Jennifer L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wilhelm, Sabine; Fama, Jeanne M.; Greenberg, Jennifer L.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Phillips, Katharine A.] Rhode Isl Hosp, Providence, RI 02903 USA. [Phillips, Katharine A.] Butler Hosp, Providence, RI 02906 USA. [Phillips, Katharine A.] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA. [Steketee, Gail] Boston Univ, Boston, MA 02215 USA. RP Wilhelm, S (reprint author), Massachusetts Gen Hosp, Simches Res Bldg,185 Cambridge St,Suite 2282, Boston, MA 02114 USA. EM wilhelm@psych.mgh.harvard.edu FU NIMH NIH HHS [R34 MH070490, R34 MH070490-01] NR 58 TC 29 Z9 29 U1 2 U2 15 PU ASSOC ADV BEHAVIOR THERAPY PI NEW YORK PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 USA SN 0005-7894 J9 BEHAV THER JI Behav. Therapy PD DEC PY 2011 VL 42 IS 4 BP 624 EP 633 PG 10 WC Psychology, Clinical SC Psychology GA 848EH UT WOS:000297032600007 PM 22035991 ER PT J AU Balboni, T Balboni, M Paulk, ME Phelps, A Wright, A Peteet, J Block, S Lathan, C VanderWeele, T Prigerson, H AF Balboni, Tracy Balboni, Michael Paulk, M. Elizabeth Phelps, Andrea Wright, Alexi Peteet, John Block, Susan Lathan, Chris VanderWeele, Tyler Prigerson, Holly TI Support of cancer patients' spiritual needs and associations with medical care costs at the end of life SO CANCER LA English DT Article DE spiritual care; palliative care; medical costs; end of life; spirituality; religion; supportive care ID QUALITY-OF-LIFE; TREATMENT PREFERENCES; PALLIATIVE CARE; NEAR-DEATH; ETHNIC-DIFFERENCES; TERMINAL ILLNESS; UNIT; ACKNOWLEDGMENT; RELIGIOUSNESS; QUESTIONNAIRE AB BACKGROUND: Although spiritual care is associated with less aggressive medical care at the end of life (EOL), it remains infrequent. It is unclear if the omission of spiritual care impacts EOL costs. METHODS: A prospective, multisite study of 339 advanced cancer patients accrued subjects from September 2002 to August 2007 from an outpatient setting and followed them until death. Spiritual care was measured by patients' reports that the health care team supported their religious/spiritual needs. EOL costs in the last week were compared among patients reporting that their spiritual needs were inadequately supported versus those who reported that their needs were well supported. Analyses were adjusted for confounders (eg, EOL discussions). RESULTS: Patients reporting that their religious/spiritual needs were inadequately supported by clinic staff were less likely to receive a week or more of hospice (54% vs 72.8%; P=.01) and more likely to die in an intensive care unit (ICU) (5.1% vs 1.0%, P=.03). Among minorities and high religious coping patients, those reporting poorly supported religious/spiritual needs received more ICU care (11.3% vs 1.2%, P=.03 and 13.1% vs 1.6%, P=.02, respectively), received less hospice (43.% vs 75.3% >= 1 week of hospice, P=.01 and 45.3% vs 73.1%, P=.007, respectively), and had increased ICU deaths (11.2% vs 1.2%, P=.03 and 7.7% vs 0.6%, P=.009, respectively). EOL costs were higher when patients reported that their spiritual needs were inadequately supported ($4947 vs $2833, P=.03), particularly among minorities ($6533 vs $2276, P=.02) and high religious copers ($6344 vs $2431, P=.005). CONCLUSIONS: Cancer patients reporting that their spiritual needs are not well supported by the health care team have higher EOL costs, particularly among minorities and high religious coping patients. Cancer 2011; 117: 5383-91. (C) 2011 American Cancer Society. C1 [Balboni, Tracy; Balboni, Michael; Phelps, Andrea; Wright, Alexi; Peteet, John; Block, Susan; Prigerson, Holly] Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, Boston, MA 02115 USA. [Balboni, Tracy; Balboni, Michael; Phelps, Andrea; Wright, Alexi; Peteet, John; Block, Susan; Prigerson, Holly] Dana Farber Canc Inst, Dept Palliat Care, Boston, MA 02115 USA. [Balboni, Tracy] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Paulk, M. Elizabeth] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA. [Wright, Alexi; Prigerson, Holly] Dana Farber Canc Inst, Div Womens Canc, Dept Med Oncol, Boston, MA 02115 USA. [Peteet, John; Block, Susan] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [VanderWeele, Tyler] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [VanderWeele, Tyler] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Balboni, Tracy; Balboni, Michael; Phelps, Andrea; Wright, Alexi; Peteet, John; Block, Susan; Prigerson, Holly] Harvard Univ, Sch Med, Ctr Palliat Care, Boston, MA USA. RP Balboni, T (reprint author), 44 Binney St, Boston, MA 01225 USA. EM tbalboni@lroc.harvard.edu FU National Institute of Mental Health [MHJ63892]; National Cancer Institute [CA 106370]; Fetzer Foundation; ASCO FX Supported by grant No. MHJ63892 from the National Institute of Mental Health, grant No. CA 106370 from the National Cancer Institute (H. P.), the Fetzer Foundation (H. P., M. E. P.), and an ASCO Young Investigator Award (T. B.). The funding organizations had no role in the design and conduct of the study; collection, analysis, or preparation of the data; or preparation, review, or approval of the manuscript. NR 44 TC 69 Z9 72 U1 3 U2 15 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD DEC 1 PY 2011 VL 117 IS 23 BP 5383 EP 5391 DI 10.1002/cncr.26221 PG 9 WC Oncology SC Oncology GA 849YH UT WOS:000297161000018 PM 21563177 ER PT J AU Agbor, TA Demma, ZC Mumy, KL Bien, JD McCormick, BA AF Agbor, Terence A. Demma, Zachary C. Mumy, Karen L. Bien, Jeffrey D. McCormick, Beth A. TI The ERM protein, Ezrin, regulates neutrophil transmigration by modulating the apical localization of MRP2 in response to the SipA effector protein during Salmonella Typhimurium infection SO CELLULAR MICROBIOLOGY LA English DT Article ID INTESTINAL EPITHELIAL-CELLS; TRANSEPITHELIAL MIGRATION; NHE3 TRANSLOCATION; HEPOXILIN A(3); RADIXIN; IDENTIFICATION; FAMILY; ORGANIZATION; ACTIVATION; EXPRESSION AB In human disease induced by Salmonella enterica serovar Typhimurium (S. Typhimurium), transepithelial migration of neutrophils rapidly follows attachment of the bacteria to the epithelial apical membrane. We have previously shown that during S. Typhimurium infection the multidrug resistance-associated protein 2 (MRP2) is highly expressed at the apical surface of the intestinal epithelia, and that it functions as an efflux pump for the potent neutrophil chemoattractant hepoxilin A3. However, the molecular mechanisms regulating its apical localization during active states of inflammation remain unknown. Thus, our objective was to determine the mechanistic basis for the translocation of MRP2 to the apical surface of intestinal epithelial cells during S. Typhimurium infection. We show that suppression of ezrin, through either RNAi or truncation of the C-terminus, results not only in a decrease in S. Typhimurium-induced neutrophil transmigration but also significantly attenuates the apical membrane expression of MRP2 during Salmonella infection. In addition, we determined that S. Typhimurium induces the activation of ezrin via a PKC-a-dependent pathway and that ezrin activation is coupled to apical localization of MRP2. Based on these results we propose that activation of ezrin is required for the apical localization of MRP2 during S. Typhimurium infection. C1 [Agbor, Terence A.; Demma, Zachary C.; Mumy, Karen L.; McCormick, Beth A.] Univ Massachusetts, Sch Med, Dept Microbiol & Physiol Syst, Worcester, MA 01655 USA. [Bien, Jeffrey D.] Massachusetts Gen Hosp, Dept Pediat Gastroenterol & Nutr, Mucosal Immunol Labs, Charlestown, MA 02129 USA. [Bien, Jeffrey D.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP McCormick, BA (reprint author), Univ Massachusetts, Sch Med, Dept Microbiol & Physiol Syst, 55 Lake Ave N, Worcester, MA 01655 USA. EM beth.mccormick@umassmed.edu FU Crohn's and Colitis Foundation of America; National Institutes of Health [DK56754] FX The research was supported by grants from the Crohn's and Colitis Foundation of America and the National Institutes of Health (DK56754) to B.A.M. The use of human volunteers in this study was in accordance with appropriate guidelines and was approved by the University of Massachusetts Medical School Review Board for the Protection of Human Subjects (approval #13006). Dr Jerrold R. Turner, University of Chicago School of Medicine, is thanked for generous gift of the ezrin mutant constructs. NR 31 TC 14 Z9 14 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1462-5814 J9 CELL MICROBIOL JI Cell Microbiol. PD DEC PY 2011 VL 13 IS 12 BP 2007 EP 2021 DI 10.1111/j.1462-5822.2011.01693.x PG 15 WC Cell Biology; Microbiology SC Cell Biology; Microbiology GA 849GY UT WOS:000297115000001 PM 21899702 ER PT J AU Kim, E Bird, JA Kulis, M Laubach, S Shreffler, W Steele, P Kamilaris, J Vickery, BP Burks, AW AF Kim, E. Bird, J. A. Kulis, M. Laubach, S. Shreffler, W. Steele, P. Kamilaris, J. Vickery, B. P. Burks, A. W. TI Evidence of desensitization in a study of sublingual immunotherapy for peanut allergy SO CLINICAL AND EXPERIMENTAL ALLERGY LA English DT Meeting Abstract CT Annual Meeting of the British-Society-for-Allergy-and-Clinical-Immunology (BSACI) CY JUL 11-13, 2011 CL Nottingham, ENGLAND SP British Soc Allergy & Clin Immunol (BSACI) C1 [Kim, E.; Bird, J. A.; Kulis, M.; Laubach, S.; Steele, P.; Kamilaris, J.; Vickery, B. P.; Burks, A. W.] Duke Univ, Med Ctr, Durham, NC USA. [Shreffler, W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0954-7894 J9 CLIN EXP ALLERGY JI Clin. Exp. Allergy PD DEC PY 2011 VL 41 IS 12 BP 1823 EP 1824 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA 851PR UT WOS:000297283800025 ER PT J AU Pujari, S Siddique, SS Dohlman, CH Chodosh, J AF Pujari, Siddharth Siddique, Sana S. Dohlman, Claes H. Chodosh, James TI The Boston Keratoprosthesis Type II: The Massachusetts Eye and Ear Infirmary Experience SO CORNEA LA English DT Article DE Boston keratoprosthesis; mucous membrane pemphigoid; Stevens-Johnson syndrome; long-term outcomes ID STEVENS-JOHNSON-SYNDROME; TOXIC EPIDERMAL NECROLYSIS; INTRAVENOUS IMMUNOGLOBULIN; COMPLICATIONS; PREVENTION AB Purpose: To report the long-term outcomes of Boston keratoprosthesis type II implantation in the management of severe ocular surface disease and corneal blindness through a retrospective interventional case series. Methods: This retrospective review included medical records of patients who underwent Boston keratoprosthesis type II implantation at the Massachusetts Eye and Ear Infirmary from January 1, 2000 through December 31, 2009. The main outcome measures analyzed were visual acuity, keratoprosthesis retention, and postoperative complications. Results: A total of 29 eyes of 26 patients received a Boston keratoprosthesis type II during the study period. Patients undergoing operation had corneal blindness because of mucous membrane pemphigoid (51.7%), Stevens-Johnson syndrome/toxic epidermal necrolysis (41.4%), or other ocular surface disease (6.9%). Visual acuity after surgery improved to 20/200 or better in 23 eyes (79.3%) and to 20/30 or better in 10 eyes (34.5%). In patients with at least 1 year of follow-up (n = 21), visual acuity of 20/200 or better was maintained in 12 eyes (57.1%). Of 13 eyes followed-up for more than 5 years, 6 eyes (46.2%) had visual acuity of 20/200 or better at the last follow-up examination. Eyes that did not improve to 20/200 or lost vision during the follow-up had end-stage glaucoma, previous retinal detachment, or age-related macular degeneration. Of the total of 29 eyes, 17 devices (58.6%) were retained without extrusion or replacement during a total follow-up time of 107.9 person-years. Conclusions: The Boston keratoprosthesis type II is a viable option for corneal blindness from severe autoimmune ocular surface diseases. C1 [Pujari, Siddharth; Siddique, Sana S.; Dohlman, Claes H.; Chodosh, James] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Chodosh, J (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM james_chodosh@meei.harvard.edu FU Research to Prevent Blindness, New York, NY FX Supported in part by an unrestricted grant to the Department of Ophthalmology, Harvard Medical School from the Research to Prevent Blindness, New York, NY. NR 19 TC 29 Z9 30 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 J9 CORNEA JI Cornea PD DEC PY 2011 VL 30 IS 12 BP 1298 EP 1303 DI 10.1097/ICO.0b013e318215207c PG 6 WC Ophthalmology SC Ophthalmology GA 849GC UT WOS:000297112600003 PM 21963861 ER PT J AU Cade, F Grosskreutz, CL Tauber, A Dohlman, CH AF Cade, Fabiano Grosskreutz, Cynthia L. Tauber, Allyson Dohlman, Claes H. TI Glaucoma in Eyes With Severe Chemical Burn, Before and After Keratoprosthesis SO CORNEA LA English DT Article DE keratoprosthesis; glaucoma; chemical burn ID BOSTON TYPE-1 KERATOPROSTHESIS; RISK-FACTORS; ENDOPHTHALMITIS; COMPLICATIONS; MANAGEMENT; INJURIES; SURGERY AB Purpose: The purpose of this study was to evaluate the incidence of glaucoma in eyes with severe chemical burn, before and after keratoprosthesis. Methods: A retrospective chart review of 28 eyes of 23 patients with severe ocular chemical burns who had undergone Boston Keratoprosthesis (BKPro) surgery at the Massachusetts Eye and Ear Infirmary, between 1990 and 2010. The incidence and severity of the outcome of glaucoma, preoperatively and postoperatively, were reviewed. Related issues, such as type of chemical burn; visual acuity (VA); device retention rate; number and nature of previous, concomitant, and subsequent procedures; and incidence of other postoperative complications, were reviewed for a median follow-up time of 57 months. Results: The number of eyes with a preoperative history or signs of glaucoma was 21, 9 of which had glaucoma progression after BKPro implantation. In addition, 2 more eyes developed glaucoma postoperatively. Preoperative vision was counting fingers or worse in all eyes. Best-corrected postoperative VA ranged from no light perception to 20/20. Seventeen eyes (61%) achieved 20/60 or better VA at some point during their follow-up, but only 9 (32%) maintained 20/60 at the last follow-up. Of the 28 eyes, 6 had the BKPro replaced once and 1 had it replaced twice. Superimposed, 8 of the most severely burned patients developed retinal detachment postoperatively. Conclusions: Glaucoma is very common in eyes with severe chemical burns. A keratoprosthesis can rehabilitate vision, but postoperative glaucoma can be difficult to manage. C1 [Cade, Fabiano; Grosskreutz, Cynthia L.; Tauber, Allyson; Dohlman, Claes H.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. RP Dohlman, CH (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02114 USA. EM claes_dohlman@meei.harvard.edu FU Massachusetts Eye and Ear Infirmary FX Supported by Keratoprosthesis Fund, Massachusetts Eye and Ear Infirmary. NR 27 TC 14 Z9 14 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 J9 CORNEA JI Cornea PD DEC PY 2011 VL 30 IS 12 BP 1322 EP 1327 DI 10.1097/ICO.0b013e31821eead6 PG 6 WC Ophthalmology SC Ophthalmology GA 849GC UT WOS:000297112600007 PM 22001817 ER PT J AU Beyer, J Todani, A Dohlman, C AF Beyer, Jill Todani, Amit Dohlman, Claes TI Prevention of Visually Debilitating Deposits on Soft Contact Lenses in Keratoprosthesis Patients SO CORNEA LA English DT Article DE keratoprosthesis; bandage contact lens; deposits; hybrid contact lens AB Purpose: To describe visually debilitating deposit formation on hydrogel contact lenses routinely used for protection in eyes with keratoprosthesis and to present different types of contact lenses that provide improved deposit resistance. Methods: Seven keratoprosthesis eyes with a history of rapid and severe deposit formation on their hydrogel lenses were evaluated and documented. The Schirmer values and blink rate of each patient were additionally analyzed. These patients were then subsequently refitted with varying types of contact lenses. Results: When soft hydrogel lenses were replaced with lenses with water-impermeable centers, dramatically fewer deposits accumulated. Deposit formation on hydrogel lenses did not seem to correlate with low Schirmer values but rather with an insufficient blink rate. Conclusion: Excellent deposit resistance can be achieved in these patients with the use of hybrid contact lenses with rigid centers or large-diameter entirely rigid contact lenses. C1 [Beyer, Jill] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Contact Lens Dept, Boston, MA 02114 USA. [Todani, Amit; Dohlman, Claes] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Cornea & External Dis, Boston, MA 02114 USA. RP Beyer, J (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Contact Lens Dept, 243 Charles St, Boston, MA 02114 USA. EM jill_beyer@meei.harvard.edu FU Massachusetts Eye and Ear Infirmary FX Supported by the Keratoprosthesis Manufacturing Fund, Massachusetts Eye and Ear Infirmary. NR 5 TC 4 Z9 4 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 J9 CORNEA JI Cornea PD DEC PY 2011 VL 30 IS 12 BP 1419 EP 1422 DI 10.1097/ICO.0b013e31821f183a PG 4 WC Ophthalmology SC Ophthalmology GA 849GC UT WOS:000297112600024 PM 21993471 ER PT J AU Lee, HS Chauhan, SK Okanobo, A Nallasamy, N Dana, R AF Lee, Hyun Soo Chauhan, Sunil K. Okanobo, Andre Nallasamy, Nambi Dana, Reza TI Therapeutic Efficacy of Topical Epigallocatechin Gallate in Murine Dry Eye SO CORNEA LA English DT Article DE cornea; dry eye disease; epigallocatechin gallate; lymphangiogenesis ID NF-KAPPA-B; GREEN TEA; OCULAR SURFACE; EPITHELIAL-CELLS; DISEASE; GROWTH; ANGIOGENESIS; EXPRESSION; MODEL; VEGF AB Objective: To study the efficacy of topical epigallocatechin gallate (EGCG) for the treatment of dry eye disease (DED). Methods: Seven-to 8-week-old female C57BL/6 mice were housed in the controlled environment chamber to induce DED. Topical 0.01% or 0.1% EGCG, or vehicle, was applied to the eyes of DED mice. Corneal fluorescein staining and the number of corneal CD11b+ cells were assessed in the different groups. Expression of interleukin-1 beta, tumor necrosis factor-a, chemokine ligand 2, and vascular endothelial growth factor (VEGF)-A/C/D was evaluated by real-time polymerase chain reaction in the corneas at day 9. Corneas were stained for lymphatic vessel endothelial hyaluronan receptor (LYVE)-1 to evaluate lymphangiogenesis, and the terminal transferase dUTP nick end labeling (TUNEL) assay was used to evaluate apoptosis of corneal epithelial cells. Results: Treatment with 0.1% EGCG showed a significant decrease in corneal fluorescein staining compared with the vehicle (24.6%, P = 0.001) and untreated controls (41.9%, P < 0.001). A significant decrease in the number of CD11b+ cells was observed in 0.1% EGCG-treated eyes, compared with the vehicle in the peripheral (23.3%, P = 0.001) and central (26.1%, P = 0.009) corneas. Treatment with 0.1% EGCG was associated with a significant decrease in the corneal expression of interleukin-1 beta (P = 0.029) and chemokine ligand 2 (P = 0.001) compared with the vehicle and in VEGF-A and VEGF-D levels compared with the untreated group (P = 0.007 and P = 0.048, respectively). EGCG 0.01% also showed a decrease in inflammation at the molecular level but no significant changes in the clinical signs of DED. No cellular toxicity to the corneal epithelium was observed with 0.01% or 0.1% EGCG. Conclusions: Topical EGCG treatment is able to reduce the clinical signs and inflammatory changes in DED by suppressing the inflammatory cytokine expression and infiltration of CD11b+ cells in the cornea. C1 [Dana, Reza] Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. Harvard Univ, Dept Ophthalmol, Sch Med, Boston, MA 02114 USA. RP Dana, R (reprint author), Harvard Univ, Sch Med, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM reza.dana@schepens.harvard.edu FU National Institutes of Health [EY-19098]; Research to Prevent Blindness Lew R. Wasserman Merit Award FX Supported in part by the National Institutes of Health Grant EY-19098 and a Research to Prevent Blindness Lew R. Wasserman Merit Award. NR 33 TC 16 Z9 16 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 J9 CORNEA JI Cornea PD DEC PY 2011 VL 30 IS 12 BP 1465 EP 1472 DI 10.1097/ICO.0b013e31821c9b5a PG 8 WC Ophthalmology SC Ophthalmology GA 849GC UT WOS:000297112600032 PM 21993466 ER PT J AU Brown, LM Calfee, CS Matthay, MA Brower, RG Thompson, BT Checkley, W AF Brown, Lisa M. Calfee, Carolyn S. Matthay, Michael A. Brower, Roy G. Thompson, B. Taylor Checkley, William CA Natl Inst Hlth Acute Resp Distress TI A simple classification model for hospital mortality in patients with acute lung injury managed with lung protective ventilation SO CRITICAL CARE MEDICINE LA English DT Article DE acute lung injury; outcomes; classification ID RESPIRATORY-DISTRESS-SYNDROME; CRITICALLY-ILL PATIENTS; POTENTIALLY INEFFECTIVE CARE; DEAD-SPACE FRACTION; INTENSIVE-CARE; MECHANICAL VENTILATION; CONDITIONAL INFERENCE; MULTIVARIATE-ANALYSIS; PROGNOSTIC-FACTORS; CLINICAL-TRIAL AB Objective: Despite improvements in the care of critically ill patients, hospital mortality rate for acute lung injury remains high at approximately 40%. We developed a classification rule to stratify mechanically ventilated patients with acute lung injury according to hospital mortality and compared this rule with the Acute Physiology and Chronic Health Evaluation III prediction. Patients: We used data of 2,022 participants in Acute Respiratory Distress Syndrome Network trials to build a classification rule based on 54 variables collected before randomization. Design: We used a classification tree approach to stratify patients according to hospital mortality using a training subset of 1800 participants and estimated expected prediction errors using tenfold crossvalidation. We validated our classification tree using a subset of 222 participants not included in model building and calculated areas under the receiver operating characteristic curves. Measurements and Main Results: We identified combinations of age (>63 yrs), blood urea nitrogen (>15 mg/dL), shock, respiratory rate (>21 breaths/min), and minute ventilation (>13.9 L/min) as important predictors of hospital mortality at 90 days. The classification tree had a similar expected prediction error in the training set (28% vs. 26%; p = .18) and areas under the receiver operating characteristic curve in the validation set (0.71 vs. 0.73; p = .71) as did a model based on Acute Physiology and Chronic Health Evaluation III. Conclusions: Our tree-based classification rule performed similarly to Acute Physiology and Chronic Health Evaluation III in stratifying patients according to hospital mortality, is simpler to use, contains risk factors that may be specific to acute lung injury, and identified minute ventilation as a potential novel predictor of death in patients with acute lung injury. (Crit Care Med 2011; 39:2645-2651) C1 [Brower, Roy G.; Checkley, William] Johns Hopkins Univ, Sch Med, Div Pulm & Crit Care, Baltimore, MD 21218 USA. [Thompson, B. Taylor] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Checkley, William] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Int Hlth, Program Global Dis Epidemiol & Control, Baltimore, MD USA. [Brown, Lisa M.] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. [Brown, Lisa M.; Matthay, Michael A.] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. [Calfee, Carolyn S.; Matthay, Michael A.] Univ Calif San Francisco, Dept Med, Pulm & Crit Care Div, San Francisco, CA 94143 USA. RP Checkley, W (reprint author), Johns Hopkins Univ, Sch Med, Div Pulm & Crit Care, Baltimore, MD 21218 USA. EM wcheckl1@jhmi.edu FU National Heart, Lung, and Blood Institute (NHLBI) [N01-HR-46054-46064, N01-HR 56165-56179, HL090833, HL51856, K99HL096955]; National Institutes of Health, National Heart, Lung, and Blood Institute; National Institutes of Health [T32GM008258-21]; Flight Attendant Medical Research Institute; Johns Hopkins University FX Supported by National Heart, Lung, and Blood Institute (NHLBI) contracts N01-HR-46054-46064 and N01-HR 56165-56179 with the National Institutes of Health, National Heart, Lung, and Blood Institute. L.M.B. was supported by a National Institutes of Health Training Grant (T32GM008258-21). C.S.C. was supported by NHLBI grant HL090833 and by a grant of the Flight Attendant Medical Research Institute. M.A.M. was supported by NHLBI HL51856. W.C. was supported by a Clinician Scientist Award of the Johns Hopkins University and a Pathway to Independence Award from the NHLBI (K99HL096955). NR 48 TC 9 Z9 10 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2011 VL 39 IS 12 BP 2645 EP 2651 DI 10.1097/CCM.0b013e3182266779 PG 7 WC Critical Care Medicine SC General & Internal Medicine GA 851FO UT WOS:000297254000008 PM 21725235 ER PT J AU Liu, KD Thompson, BT Ancukiewicz, M Steingrub, JS Douglas, IS Matthay, MA Wright, P Peterson, MW Rock, P Hyzy, RC Anzueto, A Truwit, JD AF Liu, Kathleen D. Thompson, B. Taylor Ancukiewicz, Marek Steingrub, Jay S. Douglas, Ivor S. Matthay, Michael A. Wright, Patrick Peterson, Michael W. Rock, Peter Hyzy, Robert C. Anzueto, Antonio Truwit, Jonathon D. CA Natl Inst Hlth Natl Heart Lung and TI Acute kidney injury in patients with acute lung injury: Impact of fluid accumulation on classification of acute kidney injury and associated outcomes SO CRITICAL CARE MEDICINE LA English DT Article DE acute kidney injury; acute lung injury; acute respiratory distress syndrome; fluid balance; creatinine; mortality ID RESPIRATORY-DISTRESS-SYNDROME; CRITICALLY-ILL PATIENTS; ACUTE-RENAL-FAILURE; BIOMARKERS; VENTILATION; MORTALITY; PRESSURE AB Objective: It has been suggested that fluid accumulation may delay recognition of acute kidney injury. We sought to determine the impact of fluid balance on the incidence of nondialysis requiring acute kidney injury in patients with acute lung injury and to describe associated outcomes, including mortality. Design: Analysis of the Fluid and Catheter Treatment Trial, a factorial randomized clinical trial of conservative vs. liberal fluid management and of management guided by a central venous vs. pulmonary artery catheter. Setting: Acute Respiratory Distress Syndrome Network hospitals. Patients: One thousand patients. Interventions: None. Measurements and Main Results: The incidence of acute kidney injury, defined as an absolute rise in creatinine of >= 0.3 mg/dL or a relative change of >50% over 48 hrs, was examined before and after adjustment of serum creatinine for fluid balance. The incidence of acute kidney injury before adjustment for fluid balance was greater in those managed with the conservative fluid protocol (57% vs. 51%, p = .04). After adjustment for fluid balance, the incidence of acute kidney injury was greater in those managed with the liberal fluid protocol (66% vs. 58%, p = .007). Patients who met acute kidney injury criteria after adjustment of creatinine for fluid balance (but not before) had a mortality rate that was significantly greater than those who did not meet acute kidney injury criteria both before and after adjustment for fluid balance (31% vs. 12%, p < .001) and those who had acute kidney injury before but not after adjustment for fluid balance (31% vs. 11%, p = .005). The mortality of those patients meeting acute kidney injury criteria after but not before adjustment for fluid balance was similar to patients with acute kidney injury both before and after adjustment for fluid balance (31% vs. 38%, p = .18). Conclusions: Fluid management influences serum creatinine and therefore the diagnosis of acute kidney injury using creatinine-based definitions. Patients with "unrecognized" acute kidney injury that is identified after adjusting for positive fluid balance have higher mortality rates, and patients who have acute kidney injury before but not after adjusting for fluid balance have lower mortality rates. Future studies of acute kidney injury should consider potential differences in serum creatinine caused by changes in fluid balance and the impact of these differences on diagnosis and prognosis. (Crit Care Med 2011; 39:2665-2671) C1 [Truwit, Jonathon D.] Univ Virginia, Div Pulm & Crit Care Med, Charlottesville, VA 22903 USA. [Liu, Kathleen D.] Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94143 USA. [Liu, Kathleen D.] Univ Calif San Francisco, Div Crit Care Med, San Francisco, CA 94143 USA. [Matthay, Michael A.] Univ Calif San Francisco, Div Pulm & Crit Care Med, San Francisco, CA 94143 USA. [Thompson, B. Taylor] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Ancukiewicz, Marek] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Ancukiewicz, Marek] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. [Steingrub, Jay S.] Baystate Med Ctr, Div Crit Care Med, Springfield, MA USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. [Douglas, Ivor S.] Univ Colorado, Div Pulm Sci & Crit Care Med, Denver, CO 80202 USA. Denver Hlth Med Ctr, Denver, CO USA. [Wright, Patrick] Moses Cone Hosp, Greensboro, NC USA. [Peterson, Michael W.] Univ Calif San Francisco, Dept Med, Fresno, CA USA. [Rock, Peter] Univ Maryland, Dept Anesthesiol, Baltimore, MD 21201 USA. [Hyzy, Robert C.] Univ Michigan, Ann Arbor, MI 48109 USA. [Anzueto, Antonio] S Texas Vet Hlth Care Syst, Pulm & Crit Care Med, San Antonio, TX USA. Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. RP Truwit, JD (reprint author), Univ Virginia, Div Pulm & Crit Care Med, Charlottesville, VA 22903 USA. EM truwit@virginia.edu OI Douglas, Ivor/0000-0002-4541-1431 FU National Heart, Lung, and Blood Institute, National Institutes of Health [N01-HR-46046-64, N01-HR-16146-54]; National Institutes of Health/National Center for Research Resources/OD University of California-San Francisco-CTSI [KL2 RR024130]; GlaxoSmithKline FX All authors were supported by contracts N01-HR-46046-64 and N01-HR-16146-54 with the National Heart, Lung, and Blood Institute, National Institutes of Health. K.D.L. was supported by National Institutes of Health/National Center for Research Resources/OD University of California-San Francisco-CTSI Grant Number KL2 RR024130.; Dr. Wright received honoraria/speaking fees from GlaxoSmithKline. The remaining authors have not disclosed any potential conflicts of interest. NR 23 TC 98 Z9 101 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2011 VL 39 IS 12 BP 2665 EP 2671 DI 10.1097/CCM.0b013e318228234b PG 7 WC Critical Care Medicine SC General & Internal Medicine GA 851FO UT WOS:000297254000011 PM 21785346 ER PT J AU Alleyn, CR Laffel, LMB Volkening, LK Anderson, BJ Nansel, TR Wysocki, T Weissberg-Benchell, J AF Alleyn, C. R. Laffel, L. M. B. Volkening, L. K. Anderson, B. J. Nansel, T. R. Wysocki, T. Weissberg-Benchell, J. TI Comparison of longitudinal point-of-care and high-performance liquid chromatography HbA1c measurements in a multi-centre trial SO DIABETIC MEDICINE LA English DT Article DE children; HbA1c; point-of-care; Type 1 diabetes ID DEPENDENT DIABETES-MELLITUS; INTENSIVE TREATMENT; HEMOGLOBIN A1C; COMPLICATIONS; CHILDREN; THERAPY; GLUCOSE AB Aims Point-of-care HbA1c is routine in clinical practice. Comparison of point-of-care HbA1c against laboratory measurements across sites and over time is warranted. Methods One hundred and twenty-one young persons with Type 1 diabetes from four centres provided 450 paired samples collected over 10 months for point-of-care HbA1c and central laboratory-based high-performance liquid chromatography (HPLC) HbA1c determinations. Change in HbA1c over time was assessed by difference from initial to final HbA1c and by growth modelling with annualized slope calculation. Change in HbA1c was categorized as improved (decrease of = 0.5% or negative slope), no change (+/- 0.4% of initial HbA1c or slope = 0) or worsened (increase of = 0.5% or positive slope). Results The 450 paired samples (median of four pairs/patient) were highly correlated (r = 0.97, P < 0.0001), as were time-specific and site-specific pairs (r = 0.94 to 0.98, P < 0.0001). Initial-to-final point-of-care HbA1c and HPLC HbA1c changes were 0.3 +/- 1.1% (range -2.7 to 4.1) and 0.4 +/- 1.2% (-3.9 to 4.5), respectively, with 21% of patients (n = 26) discordant for change categories. ?HbA1c by point-of-care HbA1c vs. HPLC HbA1c differed across the HbA1c range and by = 0.5% absolute difference in ?HbA1c in 14 (54%) of the 26 patients discordant for HbA1c change categories. Mean annual HbA1c slope was 0.4 +/- 1.5% (-5.4 to 4.8) for point-of-care HbA1c and 0.4 +/- 1.6% (-6.9 to 5.2) for HPLC HbA1c, with 18% (n = 22 pairs) discordant for change categories. Conclusions Assessment of absolute HbA1c change may not be different for point-of-care HbA1c compared with HPLC HbA1c; however, misclassification of patients by discrete cut-off values may occur with point-of-care HbA1c compared with HPLC HbA1c determinations. C1 [Alleyn, C. R.; Laffel, L. M. B.; Volkening, L. K.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Anderson, B. J.] Texas Childrens Hosp, Houston, TX 77030 USA. [Nansel, T. R.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Wysocki, T.] Nemours Childrens Clin, Jacksonville, FL USA. [Weissberg-Benchell, J.] Childrens Mem Hosp, Chicago, IL 60614 USA. RP Laffel, LMB (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM lori.laffel@joslin.harvard.edu FU National Institute of Child Health and Human Development (NICHD), NIH [P30DK036836, T32DK007260]; Maria Griffin Drury Pediatric Fund; Katherine Adler Astrove Youth Education Fund; Charles H. Hood Foundation; Children's Memorial Hospital, Chicago [N01-HD-4-3363]; Texas Children's Hospital, Houston [N01-HD-4-3362]; Nemours Children's Clinic, Jacksonville, FL [N01-HD-4-3361]; Joslin Diabetes Center, Boston, MA [N01-HD-4-3364]; James Bell Associates, Arlington, VA [N01-HD-3-3360] FX This work was supported by the intramural research programme of the National Institute of Child Health and Human Development (NICHD), NIH grants P30DK036836 and T32DK007260, the Maria Griffin Drury Pediatric Fund, the Katherine Adler Astrove Youth Education Fund and the Charles H. Hood Foundation. The following investigators and institutions made up the steering committee of the Family Management of Childhood Diabetes multi-site trial: Jill Weissberg-Benchell PhD, Grayson Holmbeck PhD (Children's Memorial Hospital, Chicago, Contract N01-HD-4-3363); Barbara Anderson PhD (Texas Children's Hospital, Houston, Contract N01-HD-4-3362); Tim Wysocki PhD, Amanda Lochrie PhD (Nemours Children's Clinic, Jacksonville, FL, Contract N01-HD-4-3361); Lori Laffel MD MPH, Deborah Butler MSW, Lisa Volkening MA (Joslin Diabetes Center, Boston, MA, Contract N01-HD-4-3364); Tonja Nansel PhD, Ronald Iannotti PhD (NICHD, Bethesda, MD); Cheryl McDonnell PhD, MaryAnn D'Elio (James Bell Associates, Arlington, VA, Contract N01-HD-3-3360). Portions of this manuscript were presented at the 70th Scientific Sessions of the American Diabetes Association (2010). NR 18 TC 2 Z9 2 U1 2 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0742-3071 J9 DIABETIC MED JI Diabetic Med. PD DEC PY 2011 VL 28 IS 12 BP 1525 EP 1529 DI 10.1111/j.1464-5491.2011.03404.x PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 849IE UT WOS:000297118400015 PM 21824185 ER PT J AU Yeh, DD Lonergan, KL Fu, D Yeh, RW Echt, DS Foster, E AF Yeh, Doreen DeFaria Lonergan, Katy Lease Fu, David Yeh, Robert W. Echt, Debra S. Foster, Elyse TI Clinical factors and echocardiographic techniques related to the presence, size, and location of acoustic windows for leadless cardiac pacing SO EUROPACE LA English DT Article DE Leadless pacing; Cardiac resynchronization therapy; Heart failure; Echocardiography; Acoustic window ID RESYNCHRONIZATION THERAPY; HEART-FAILURE; IMPLANTATION; GUIDELINES; DEVICES AB Aims Temporary leadless cardiac pacing using ultrasound energy is feasible in patients. An implantable left ventricular stimulation system being developed for cardiac resynchronization therapy transfers energy from a subcutaneous transmitter to an endocardial receiver through tissue free of interfering lung or rib ('acoustic window'). The aim was to use transthoracic echocardiography to evaluate acoustic window (AW) locations and sizes to determine the implant site for a transmitter, and to investigate clinical predictors of AW location and size. Methods and results Inclusion criteria were ejection fraction <= 35%, and New York Heart Association functional class III or IV. Acoustic windows were evaluated in intercostal spaces (ICSs) measured in the supine, right lateral, sitting, and standing position during normal respiration and held inspiration. Among 42 patients, at least one adequate AW (>= 2 cm(2)) was identified in 41, 19 patients had adequate AWs in 2 ICSs and 20 patients had adequate AWs in 3. Acoustic window areas were generally smallest in the lateral position with held inspiration and largest in the standing position with normal respiration. Patients with ischaemic cardiomyopathy compared with non-ischaemic cardiomyopathy had smaller heart size [left ventricular end-systolic volume index (LVESVI) 78 +/- 38 mL/m(2) vs. 104 +/- 46 mL/m(2), P = 0.03] but larger AWs in the right lateral position (11.4 +/- 6.5 cm(2) vs. 7.3 +/- 3.4 cm(2), P = 0.01) and standing position (14.0 +/- 7.2 cm(2) vs. 9.4 +/- 3.3 cm(2), P = 0.02). Conclusions Adequate AWs were present in nearly all patients. Despite smaller hearts, ischaemic cardiomyopathy patients had adequate AWs. A simple procedure performed as an adjunct to pre-implant echocardiography can screen patients and identify transmitter implant locations for an ultrasound-mediated leadless pacing system. C1 [Lonergan, Katy Lease; Fu, David; Foster, Elyse] Univ Calif San Francisco, Echocardiog Sect, Div Cardiol, San Francisco, CA 94143 USA. [Yeh, Doreen DeFaria; Yeh, Robert W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Echt, Debra S.] EBR Syst Inc, Sunnyvale, CA 94085 USA. RP Foster, E (reprint author), Univ Calif San Francisco, Echocardiog Sect, Div Cardiol, 505 Parnassus Ave,M14, San Francisco, CA 94143 USA. EM foster@medicine.ucsf.edu FU Boston Scientific; Evalve; EBR Systems FX E. F. has received grant support from Boston Scientific, Evalve, and EBR Systems. NR 9 TC 1 Z9 1 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1099-5129 J9 EUROPACE JI Europace PD DEC PY 2011 VL 13 IS 12 BP 1760 EP 1765 DI 10.1093/europace/eur199 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 850VT UT WOS:000297228300016 ER PT J AU Doherty-King, B Bowers, B AF Doherty-King, Barbara Bowers, Barbara TI How Nurses Decide to Ambulate Hospitalized Older Adults: Development of a Conceptual Model SO GERONTOLOGIST LA English DT Article DE Conceptual development; Grounded theory; Hospital; ambulatory care; Nursing studies; Function (physical; mental) ID FUNCTIONAL DECLINE; LOW MOBILITY; CARE; OUTCOMES AB Adults over the age of 65 years account for 60% of all hospital admissions and experience consequential negative outcomes directly related to hospitalization. Negative outcomes include falls, delirium, loss in ability to perform basic activities of daily living, and new walking dependence. New walking dependence, defined as the loss in ability to walk independently, occurs in 16%--59% of hospitalized older patients. Nurses are pivotal in promoting functional walking independence in hospitalized patients. However, little is known about how nurses make decisions about whether, when, and how to ambulate older patients. A qualitative study using grounded dimensional analysis was conducted to further explore how nurses make decisions about ambulating hospitalized older adults. Twenty-five registered nurses participated in in-depth interviews lasting 30--60 min. Open, axial, and selective coding was used during the analysis. A conceptual model, which is grounded in how nurses experience ambulating patients, was developed. Multiple categories and dimensions interact and produce an action by the nurse to either restrict mobilization to the level of the bed or progress the patient to ambulation in the hallway. Factors that seemed to have a greater impact on nurses' decisions on whether, when, and how to ambulate were the risk/opportunity assessment, preventing complications, and the presence of a unit expectation to ambulate patients. C1 [Doherty-King, Barbara] William S Middleton Mem Vet Adm Med Ctr, GRECC, Geriatr Educ Res & Clin Ctr, Madison, WI 53705 USA. [Doherty-King, Barbara; Bowers, Barbara] Univ Wisconsin, Sch Nursing, Madison, WI 53706 USA. RP Doherty-King, B (reprint author), William S Middleton Mem Vet Adm Med Ctr, GRECC, Geriatr Educ Res & Clin Ctr, 2500 Overlook Terrace G11, Madison, WI 53705 USA. EM Barbara.king4@va.gov OI King, Barbara/0000-0003-0577-9028; Bowers, Barbara/0000-0002-3226-0718 NR 20 TC 13 Z9 13 U1 0 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD DEC PY 2011 VL 51 IS 6 BP 786 EP 797 DI 10.1093/geront/gnr044 PG 12 WC Gerontology SC Geriatrics & Gerontology GA 851BD UT WOS:000297242400007 PM 22024979 ER PT J AU Davis, MM Bond, LA Howard, A Sarkisian, CA AF Davis, Melinda M. Bond, Lynne A. Howard, Alan Sarkisian, Catherine A. TI Primary Care Clinician Expectations Regarding Aging SO GERONTOLOGIST LA English DT Article DE Attitudes toward aging; Successful aging; Expectations regarding aging ID OLDER-ADULTS; SELF-PERCEPTIONS; HEALTH; DEPRESSION; ATTITUDES; AGEISM AB Purpose: Expectations regarding aging (ERA) in community-dwelling older adults are associated with personal health behaviors and health resource usage. Clinicians' age expectations likely influence patients' expectations and care delivery patterns; yet, limited research has explored clinicians' age expectations. The Expectations Regarding Aging Survey (ERA-12) was used to assess (a) age expectations in a sample of primary care clinicians practicing in the United States and (b) clinician characteristics associated with ERA-12 scores. Design and Methods: This study was a cross-sectional survey of primary care clinicians affiliated with 5 practice-based research networks, October 2008 to June 2009. A total of 374 of the 1,510 distributed surveys were returned (24.8% response rate); 357 analyzed. Mean respondent age was 48.6 years (SD = 11.6; range 23-87 years); 88.0% physicians, 96.0% family medicine, 94.9% White, and 61.9% male. Results: Female clinicians reported higher ERA-12 scores; clinicians' age expectations decreased with greater years in practice. Among the clinicians, higher ERA-12 scores were associated with higher clinician ratings of the importance of and personal skill in administering preventive counseling and the importance of delivering preventive services. Agreement with individual ERA-12 items varied widely. Implications: Unrealistically high or low ERA could negatively influence the quality of care provided to patients and patients' own age expectations. Research should examine the etiology of clinicians' age expectations and their association with older adult diagnoses and treatment. Medical education must incorporate strategies to promote clinician attitudes that facilitate successful patient aging. C1 [Davis, Melinda M.] Oregon Hlth & Sci Univ, Dept Family Med, Oregon Rural Practice Based Res Network, Portland, OR 97239 USA. [Bond, Lynne A.] Univ Vermont, Dept Psychol, Burlington, VT 05405 USA. [Howard, Alan] Univ Vermont, Acad Comp Serv, Burlington, VT 05405 USA. [Sarkisian, Catherine A.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Sarkisian, Catherine A.] Univ Calif Los Angeles, Dept Med, Div Geriatr, Geriatr Res Educ Clin Ctr, Los Angeles, CA USA. RP Davis, MM (reprint author), Oregon Hlth & Sci Univ, Dept Family Med, Oregon Rural Practice Based Res Network, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM davismel@ohsu.edu FU NCRR NIH HHS [1U1 RR02414-01] NR 39 TC 5 Z9 5 U1 1 U2 10 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD DEC PY 2011 VL 51 IS 6 BP 856 EP 866 DI 10.1093/geront/gnr017 PG 11 WC Gerontology SC Geriatrics & Gerontology GA 851BD UT WOS:000297242400013 PM 21430129 ER PT J AU Deo, R Katz, R Shlipak, MG Sotoodehnia, N Psaty, BM Sarnak, MJ Fried, LF Chonchol, M de Boer, IH Enquobahrie, D Siscovick, D Kestenbaum, B AF Deo, Rajat Katz, Ronit Shlipak, Michael G. Sotoodehnia, Nona Psaty, Bruce M. Sarnak, Mark J. Fried, Linda F. Chonchol, Michel de Boer, Ian H. Enquobahrie, Daniel Siscovick, David Kestenbaum, Bryan TI Vitamin D, Parathyroid Hormone, and Sudden Cardiac Death Results From the Cardiovascular Health Study SO HYPERTENSION LA English DT Article DE sudden cardiac death; vitamin D; parathyroid hormone; elderly; risk factors ID SMOOTH-MUSCLE-CELLS; D DEFICIENCY; MYOCARDIAL-INFARCTION; CORONARY-ANGIOGRAPHY; SEASONAL-VARIATION; RISK; HYPERTROPHY; MORTALITY; POPULATION; 25-HYDROXYVITAMIN-D AB Recent studies have demonstrated greater risks of cardiovascular events and mortality among persons who have lower 25-hydroxyvitamin D (25-OHD) and higher parathyroid hormone (PTH) levels. We sought to evaluate the association between markers of mineral metabolism and sudden cardiac death (SCD) among the 2312 participants from the Cardiovascular Health Study who were free of clinical cardiovascular disease at baseline. We estimated associations of baseline 25-OHD and PTH concentrations individually and in combination with SCD using Cox proportional hazards models after adjustment for demographics, cardiovascular risk factors, and kidney function. During a median follow-up of 14 years, there were 73 adjudicated SCD events. The annual incidence of SCD was greater among subjects who had lower 25-OHD concentrations, 2 events per 1000 for 25-OHD >= 20 ng/mL and 4 events per 1000 for 25-OHD <20 ng/mL. Similarly, SCD incidence was greater among subjects who had higher PTH concentrations, 2 events per 1000 for PTH <65 pg/mL and 4 events per 1000 for PTH >= 65 pg/mL. Multivariate adjustment attenuated associations of 25-OHD and PTH with SCD. Finally, 267 participants (11.7% of the cohort) had high PTH and low 25-OHD concentrations. This combination was associated with a >2-fold risk of SCD after adjustment (hazard ratio: 2.19 [95% CI: 1.17-4.10]; P=0.017) compared with participants with normal levels of PTH and 25-OHD. The combination of lower 25-OHD and higher PTH concentrations appears to be associated independently with SCD risk among older adults without cardiovascular disease. (Hypertension. 2011;58:1021-1028.) C1 [Deo, Rajat] Univ Penn, Sect Electrophysiol, Div Cardiovasc Med, Philadelphia, PA 19104 USA. [Katz, Ronit] Univ Washington, Collaborat Hlth Studies Coordinating Ctr, Seattle, WA 98195 USA. [Sotoodehnia, Nona] Univ Washington, Div Cardiol, Seattle, WA 98195 USA. [Psaty, Bruce M.; Enquobahrie, Daniel; Siscovick, David] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Psaty, Bruce M.; Enquobahrie, Daniel; Siscovick, David] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Psaty, Bruce M.; Enquobahrie, Daniel; Siscovick, David] Univ Washington, Dept Hlth Serv, Cardiovasc Hlth Res Unit, Seattle, WA USA. [de Boer, Ian H.; Kestenbaum, Bryan] Univ Washington, Div Nephrol, Seattle, WA 98195 USA. [de Boer, Ian H.; Kestenbaum, Bryan] Univ Washington, Kidney Res Inst, Seattle, WA 98195 USA. [Shlipak, Michael G.] Vet Affairs Med Ctr, Gen Internal Med Sect, San Francisco, CA 94121 USA. [Shlipak, Michael G.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Shlipak, Michael G.] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. [Shlipak, Michael G.] Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA. [Sarnak, Mark J.] Tufts Med Ctr, Div Nephrol, Boston, MA USA. [Fried, Linda F.] Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Pittsburgh, PA USA. [Fried, Linda F.] Vet Affairs Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. [Chonchol, Michel] Univ Colorado Denver & Hlth Sci Ctr, Div Renal Dis & Hypertens, Aurora, CO USA. RP Deo, R (reprint author), Univ Penn, Sect Electrophysiol, Div Cardiovasc Med, 3400 Spruce St,9 Founders Cardiol, Philadelphia, PA 19104 USA. EM Rajat.Deo@uphs.upenn.edu FU National Institute on Aging at the National Institutes of Health [AG-023629]; National Heart, Lung, and Blood Institute at the National Institutes of Health [N01-HC-80007, N01-HC-85079, N01-HC-85086, N01-HC-35129, N01-HC-15103, N01-HC-55222, N01-HC-75150, N01-HC-45133, U01-HL-080295]; National Institute on Aging [R01 AG-15928, R01 AG-20098, AG-027058]; National Heart, Lung, and Blood Institute [R01 HL-075366]; University of Pittsburgh Claude D. Pepper Older Americans Independence Center [P30-AG-024827]; National Institutes of Health [R01 HL084443, R01 HL088456]; [K23DK089118] FX This work was supported by the National Institute on Aging at the National Institutes of Health (grant AG-023629). The CHS was supported by contracts N01-HC-80007, N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01-HC-15103, N01-HC-55222, N01-HC-75150, N01-HC-45133, and U01-HL-080295 from the National Heart, Lung, and Blood Institute at the National Institutes of Health, with additional contribution from the National Institute of Neurological Disorders and Stroke at the National Institutes of Health. Additional support was provided through grants R01 AG-15928, R01 AG-20098, and AG-027058 from the National Institute on Aging; R01 HL-075366 from the National Heart, Lung, and Blood Institute; and the University of Pittsburgh Claude D. Pepper Older Americans Independence Center P30-AG-024827. R.D. was supported by K23DK089118. Additional grant support includes National Institutes of Health grants R01 HL084443 and R01 HL088456. NR 38 TC 48 Z9 49 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD DEC PY 2011 VL 58 IS 6 BP 1021 EP 1028 DI 10.1161/HYPERTENSIONAHA.111.179135 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 850TI UT WOS:000297221900015 PM 22068871 ER PT J AU Oikonen, M Tikkanen, E Juhola, J Tuovinen, T Seppala, I Juonala, M Taittonen, L Mikkila, V Kahonen, M Ripatti, S Viikari, J Lehtimaki, T Havulinna, AS Kee, F Newton-Cheh, C Peltonen, L Schork, NJ Murray, SS Berenson, GS Chen, W Srinivasan, SR Salomaa, V Raitakari, OT AF Oikonen, Mervi Tikkanen, Emmi Juhola, Jonna Tuovinen, Tarja Seppala, Ilkka Juonala, Markus Taittonen, Leena Mikkila, Vera Kahonen, Mika Ripatti, Samuli Viikari, Jorma Lehtimaki, Terho Havulinna, Aki S. Kee, Frank Newton-Cheh, Christopher Peltonen, Leena Schork, Nicholas J. Murray, Sarah S. Berenson, Gerald S. Chen, Wei Srinivasan, Sathanur R. Salomaa, Veikko Raitakari, Olli T. TI Genetic Variants and Blood Pressure in a Population-Based Cohort The Cardiovascular Risk in Young Finns Study SO HYPERTENSION LA English DT Article DE epidemiological study; genetic risk score; blood pressure; cardiovascular disease ID GENOME-WIDE ASSOCIATION; ESSENTIAL-HYPERTENSION; CHILDHOOD; POLYMORPHISMS; PHENOTYPES; MORTALITY; DISCOVERY; ADULTHOOD; THICKNESS; DISEASE AB Clinical relevance of a genetic predisposition to elevated blood pressure was quantified during the transition from childhood to adulthood in a population-based Finnish cohort (N=2357). Blood pressure was measured at baseline in 1980 (age 3-18 years) and in follow-ups in 1983, 1986, 2001, and 2007. Thirteen single nucleotide polymorphisms associated with blood pressure were genotyped, and 3 genetic risk scores associated with systolic and diastolic blood pressures and their combination were derived for all of the participants. Effects of the genetic risk score were 0.47 mm Hg for systolic and 0.53 mm Hg for diastolic blood pressures (both P<0.01). The combination genetic risk score was associated with diastolic blood pressure from age 9 years onward (beta=0.68 mm Hg; P=0.015). Replications in 1194 participants of the Bogalusa Heart Study showed essentially similar results. The participants in the highest quintile of the combination genetic risk score had a 1.82-fold risk of hypertension in adulthood (P<0.0001) compared with the lowest quintile, independent of a family history of premature hypertension. These findings show that genetic variants are associated with preclinical blood pressure traits in childhood; individuals with several susceptibility alleles have, on average, a 0.5-mm Hg higher blood pressure, and this trajectory continues from childhood to adulthood. (Hypertension. 2011;58:1079-1085.) . Online Data Supplement C1 [Oikonen, Mervi; Juhola, Jonna; Raitakari, Olli T.] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, FI-20521 Turku, Finland. [Tikkanen, Emmi; Tuovinen, Tarja; Ripatti, Samuli] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland. [Mikkila, Vera] Univ Helsinki, Dept Food & Environm Sci, Helsinki, Finland. [Seppala, Ilkka; Lehtimaki, Terho] Tampere Univ Hosp, Dept Clin Chem, FIN-33521 Tampere, Finland. [Kahonen, Mika] Tampere Univ Hosp, Dept Clin Physiol, FIN-33521 Tampere, Finland. Univ Tampere, FIN-33101 Tampere, Finland. [Juonala, Markus; Viikari, Jorma] Turku Univ Hosp, Dept Med, FIN-20520 Turku, Finland. [Raitakari, Olli T.] Turku Univ Hosp, Dept Clin Physiol, FIN-20520 Turku, Finland. [Taittonen, Leena] Univ Oulu, Dept Pediat, SF-90100 Oulu, Finland. [Taittonen, Leena] Vaasa Cent Hosp, Dept Pediat, Vaasa, Finland. [Tikkanen, Emmi; Tuovinen, Tarja; Ripatti, Samuli; Havulinna, Aki S.; Salomaa, Veikko] Natl Inst Hlth & Welf, Helsinki, Finland. [Kee, Frank] Queens Univ Belfast, United Kingdom Clin Res Collaborat Ctr Excellence, Belfast BT7 1NN, Antrim, North Ireland. [Newton-Cheh, Christopher] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Newton-Cheh, Christopher] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Newton-Cheh, Christopher] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Peltonen, Leena] Wellcome Trust Sanger Inst, Hinxton, England. [Schork, Nicholas J.; Murray, Sarah S.] Scripps Genom Med & Scripps Translat Sci Inst, La Jolla, CA USA. [Berenson, Gerald S.; Chen, Wei; Srinivasan, Sathanur R.] Tulane Univ, Dept Epidemiol, New Orleans, LA 70118 USA. RP Oikonen, M (reprint author), Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, POB 52, FI-20521 Turku, Finland. EM mervi.oikonen@utu.fi RI Ripatti, Samuli/H-9446-2014; OI Ripatti, Samuli/0000-0002-0504-1202; Oikonen, Mervi/0000-0001-6509-996X FU Academy of Finland [126925, 121584, 124282, 129494, 139635]; Social Insurance Institution of Finland; Tampere University Hospital; Kuopio University Hospital; Turku University Hospital; Juho Vainio Foundation; Paavo Nurmi Foundation; Emil Aaltonen Foundation; Finnish Foundation of Cardiovascular Research; Finnish Cultural Foundation; Burroughs Wellcome Fund; Doris Duke Charitable Foundation; National Institutes of Health; Academy of Finland Center of Excellence for Complex Disease Genetics [213506, 129680]; Wellcome Trust; American Heart Association [0855082E]; Eunice Kennedy Shriver National Institute of Child Health and Human Development [HD-061437, HD-062783]; National Institute on Aging [AG-16592] FX The Young Finns Study has been financially supported by the Academy of Finland (grants 126925, 121584, and 124282), the Social Insurance Institution of Finland, the Tampere (to T.L. and M.K.), Kuopio and Turku University Hospital Medical Funds, Juho Vainio Foundation, Paavo Nurmi Foundation, Emil Aaltonen Foundation (to T.L.), Finnish Foundation of Cardiovascular Research, and Finnish Cultural Foundation. C.N.-C. is supported by grants from the Burroughs Wellcome Fund, Doris Duke Charitable Foundation, and the National Institutes of Health. V.S. was supported by grants 129494 and 139635 from the Academy of Finland. S.R. and L.P. were supported by the Academy of Finland Center of Excellence for Complex Disease Genetics (grants 213506 and 129680). Genotyping was done with the support of the Wellcome Trust. The Bogalusa Heart Study was supported by grants 0855082E from the American Heart Association, HD-061437 and HD-062783 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and AG-16592 from the National Institute on Aging. NR 39 TC 21 Z9 21 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD DEC PY 2011 VL 58 IS 6 BP 1079 EP U228 DI 10.1161/HYPERTENSIONAHA.111.179291 PG 18 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 850TI UT WOS:000297221900023 PM 22025373 ER PT J AU Woodham, PC Brittain, JE Baker, AM Long, DL Haeri, S Camargo, CA Boggess, KA Stuebe, AM AF Woodham, Padmashree Chaudhury Brittain, Julia E. Baker, Arthur M. Long, D. Leann Haeri, Sina Camargo, Carlos A., Jr. Boggess, Kim A. Stuebe, Alison M. TI Midgestation Maternal Serum 25-Hydroxyvitamin D Level and Soluble Fms-Like Tyrosine Kinase 1/Placental Growth Factor Ratio as Predictors of Severe Preeclampsia SO HYPERTENSION LA English DT Article DE 25-hydroxyvitamin D; angiogenic factors; preeclampsia; sFLT-1/PlGF ratio; VEGF ID CIRCULATING ANGIOGENIC FACTORS; VITAMIN-D; WOMEN; RISK; PREGNANCY; STORAGE AB Recent studies have shown that low serum 25-hydroxyvitamin D (25[OH] D) level is a risk factor for preeclampsia. The clinical significance of in vitro findings that vitamin D regulates vascular endothelial growth factor production is unclear. We sought to determine whether there is an association between midgestation serum 25(OH)D levels and angiogenic factor activity and to compare their predictive value for the development of severe preeclampsia. We conducted a nested case-control study of women with severe preeclampsia (n = 41) versus women with uncomplicated term birth (n = 123) who had second trimester genetic screening (15-20 weeks). Using banked frozen serum, we measured levels of 25(OH)D, vascular endothelial growth factor, soluble fms-like tyrosine kinase 1, and placental growth factor and compared their correlations and predictive values. We found no correlation between serum 25(OH)D and angiogenic factors levels. 25(OH)D alone was comparable to vascular endothelial growth factor and soluble fms-like tyrosine kinase 1/placental growth factor ratio as a predictive marker for severe preeclampsia. A composite of both 25(OH)D level and soluble fms-like tyrosine kinase 1/placental growth factor ratio was more predictive than either alone (area under curve: 0.83 versus 0.74 and 0.67, respectively). In conclusion, combining midpregnancy 25(OH)D level with soluble fms-like tyrosine kinase 1/placental growth factor ratio provides a better prediction for the development of severe preeclampsia. (Hypertension. 2011;58:1120-1125.) C1 [Woodham, Padmashree Chaudhury; Boggess, Kim A.; Stuebe, Alison M.] Univ N Carolina, Dept Obstet, Chapel Hill, NC 27599 USA. [Woodham, Padmashree Chaudhury; Boggess, Kim A.; Stuebe, Alison M.] Univ N Carolina, Dept Gynecol, Chapel Hill, NC 27599 USA. [Brittain, Julia E.] Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA. [Long, D. Leann] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Biostat, Chapel Hill, NC 27599 USA. [Baker, Arthur M.] Savannah Perinatol Associates Inc, Savannah, GA USA. [Haeri, Sina] Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA. [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Woodham, PC (reprint author), Univ N Carolina, Dept Obstet, 3010 Old Clin Bldg,CB 7516, Chapel Hill, NC 27599 USA. EM pchaudh@gmail.com FU North Carolina Translational and Clinical Sciences Institution [2KR70904]; Massachusetts General Hospital Center for D-receptor Activation Research; National Institute of Environmental Health Sciences [T32ES007018] FX This study was supported by the North Carolina Translational and Clinical Sciences Institution grant (2KR70904). C.A.C. was supported, in part, by the Massachusetts General Hospital Center for D-receptor Activation Research. Finally, this work was supported in part by National Institute of Environmental Health Sciences grant T32ES007018. NR 26 TC 16 Z9 16 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0194-911X EI 1524-4563 J9 HYPERTENSION JI Hypertension PD DEC PY 2011 VL 58 IS 6 BP 1120 EP 1125 DI 10.1161/HYPERTENSIONAHA.111.179069 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 850TI UT WOS:000297221900028 PM 21986503 ER PT J AU Lavender, JM De Young, KP Franko, DL Eddy, KT Kass, AE Sears, MS Herzog, DB AF Lavender, Jason M. De Young, Kyle P. Franko, Debra L. Eddy, Kamryn T. Kass, Andrea E. Sears, Meredith S. Herzog, David B. TI An Investigation of the Joint Longitudinal Trajectories of Low Body Weight, Binge Eating, and Purging in Women with Anorexia Nervosa and Bulimia Nervosa SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article DE anorexia nervosa; bulimia nervosa; symptom trajectories; course; longitudinal ID FOLLOW-UP; DIAGNOSTIC CROSSOVER; DISORDER PHENOTYPES; NATURAL-HISTORY; PREDICTORS; ADOLESCENTS; PATTERNS; RECOVERY; CLASSIFICATION; STABILITY AB Objectives: To describe the longitudinal course of three core eating disorder symptoms-low body weight, binge eating, and purging-in women with anorexia nervosa (AN) and bulimia nervosa (BN) using a novel statistical approach. Method: Treatment-seeking women with AN (n = 136) or BN (n = 110) completed the Eating Disorders Longitudinal Interval Follow-Up Evaluation interview every 6 months, yielding weekly eating disorder symptom data for a 5-year period. Semiparametric mixture modeling was used to identify longitudinal trajectories for the three core symptoms. Results: Four individual trajectories were identified for each eating disorder symptom. The number and general shape of the individual trajectories was similar across symptoms, with each model including trajectories depicting stable absence and stable presence of symptoms as well as one or more trajectories depicting the declining presence of symptoms. Unique trajectories were found for low body weight (fluctuating presence) and purging (increasing presence). Conjunction analyses yielded the following joint trajectories: low body weight and binge eating, low body weight and purging, and binge eating and purging. Discussion: The course of individual eating disorder symptoms among patients with AN and BN is highly variable. Future research identifying clinical predictors of trajectory membership may inform treatment and nosological research. (C) 2010 by Wiley Periodicals, Inc. C1 [Franko, Debra L.; Eddy, Kamryn T.; Kass, Andrea E.; Sears, Meredith S.; Herzog, David B.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Lavender, Jason M.; De Young, Kyle P.] SUNY Albany, Dept Psychol, Albany, NY 12222 USA. [Franko, Debra L.] Northeastern Univ, Dept Counseling & Appl Educ Psychol, Boston, MA 02115 USA. [Eddy, Kamryn T.; Herzog, David B.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Herzog, DB (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 2 Longfellow Pl,Suite 200, Boston, MA 02114 USA. EM dherzog@partners.org FU NIMH NIH HHS [R01 MH038333] NR 34 TC 4 Z9 4 U1 0 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD DEC PY 2011 VL 44 IS 8 BP 679 EP 686 DI 10.1002/eat.20880 PG 8 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 851YS UT WOS:000297309300002 PM 22072404 ER PT J AU Linville, D Stice, E Gau, J O'Neil, M AF Linville, Deanna Stice, Eric Gau, Jeff O'Neil, Maya TI Predictive Effects of Mother and Peer Influences on Increases in Adolescent Eating Disorder Risk Factors and Symptoms: A 3-Year Longitudinal Study SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article DE maternal and peer; eating disorders; predictive effects ID DUAL-PATHWAY MODEL; BODY DISSATISFACTION; BULIMIC PATHOLOGY; WEIGHT-LOSS; DIAGNOSTIC SCALE; GIRLS; BEHAVIORS; DEPRESSION; IMAGE; BOYS AB Objective: To investigate the relation of maternal and peer attitudes and behaviors to changes in eating disorder risk factors and symptoms in adolescent females. Method: We tested whether maternal and peer eating attitudes, behaviors, and deficits in social support at baseline predicted subsequent increases in eating disorder risk factors and symptoms among 483 late adolescent females followed over 3 years. Results: Data provide partial support for hypotheses, as eating disorder risk factors and symptoms increased over time and maternal thin ideal internalization significantly predicted a future increases in adolescent bulimic symptoms. There were no significant predictors of adolescent thin ideal internalization or body dissatisfaction. Discussion: Findings only partially support the hypothesis that unhealthy attitudes and behaviors of mothers increase risk for eating disorder symptoms in their late adolescent daughters. These results underscore why eating disorder prevention programs should be based on risk factor research that has used prospective and rigorous designs. (C) 2011 by Wiley Periodicals, Inc. C1 [Linville, Deanna] Univ Oregon, Dept Counseling Psychol & Human Serv, Eugene, OR 97403 USA. [Stice, Eric] Univ Texas Austin, Dept Psychol, Austin, TX 78712 USA. [Gau, Jeff] Oregon Res Inst, Eugene, OR 97403 USA. [O'Neil, Maya] Portland VA Med Ctr, Hlth Serv Res & Dev Serv, Portland, OR USA. RP Linville, D (reprint author), Univ Oregon, Dept Counseling Psychol & Human Serv, 5251 Univ Oregon, Eugene, OR 97403 USA. EM Linville@uoregon.edu FU National Institutes of Health [MH01708, MH/DK61957] FX Supported by MH01708, MH/DK61957 from National Institutes of Health. NR 50 TC 10 Z9 11 U1 2 U2 19 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD DEC PY 2011 VL 44 IS 8 BP 745 EP 751 DI 10.1002/eat.20907 PG 7 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 851YS UT WOS:000297309300013 PM 21344465 ER PT J AU Robinson, EB Munir, K McCormick, MC Koenen, KC Santangelo, SL AF Robinson, Elise B. Munir, Kerim McCormick, Marie C. Koenen, Karestan C. Santangelo, Susan L. TI Brief Report: No Association Between Parental Age and Extreme Social-Communicative Autistic Traits in the General Population SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorders; Autistic traits; Parental age; ALSPAC ID ASPERGER-SYNDROME TEST; PATERNAL AGE; SPECTRUM DISORDERS; MATERNAL AGE; RISK; CHILDHOOD; RELIABILITY; VALIDITY; OUTCOMES; CAST AB This is the first investigation of the relationship between parental age and extreme social-communicative autistic traits in the general population. The parents of 5,246 children in the Avon Longitudinal Study of Parents and Children (ALSPAC) completed the Social and Communication Disorders Checklist (SCDC). The association between parental age and SCDC scores was assessed in the full sample and among high scoring individuals (e.g. top 5%, 1%). There was no association between parental age and social-communicative autistic traits in the general population. Neither maternal nor paternal age was associated with extreme scores. These findings suggest that advanced parental age does not confer increased risk for extreme social and communication impairment assessed quantitatively. C1 [Robinson, Elise B.; Koenen, Karestan C.; Santangelo, Susan L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02114 USA. [Robinson, Elise B.; Santangelo, Susan L.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, Boston, MA 02114 USA. [Robinson, Elise B.; Munir, Kerim] Childrens Hosp Boston, Div Dev Med, Boston, MA USA. [Munir, Kerim; Santangelo, Susan L.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02114 USA. [McCormick, Marie C.; Koenen, Karestan C.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02114 USA. [Koenen, Karestan C.] Harvard Ctr Dev Child, Cambridge, MA USA. RP Robinson, EB (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Simches Res Bldg,185 Cambridge St,6th Floor, Boston, MA 02114 USA. EM erobinso@hsph.harvard.edu RI Munir, Kerim/D-6910-2015; Koenen, Karestan/K-5402-2014 OI Munir, Kerim/0000-0002-2404-1806; Robinson, Elise/0000-0003-2314-2792; Koenen, Karestan/0000-0003-3293-4281 FU Medical Research Council [74882, G0400085, G9815508]; NIMH NIH HHS [MH71286, R25 MH071286, R25 MH071286-03, R25 MH071286-04, T32 MH017119, T32 MH017119-25, T32MH017119]; Wellcome Trust [076467, 092731] NR 21 TC 2 Z9 2 U1 1 U2 5 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD DEC PY 2011 VL 41 IS 12 BP 1733 EP 1737 DI 10.1007/s10803-011-1202-4 PG 5 WC Psychology, Developmental SC Psychology GA 850BB UT WOS:000297168300015 PM 21350918 ER PT J AU Tsai, AC Bangsberg, DR AF Tsai, Alexander C. Bangsberg, David R. TI The Importance of Social Ties in Sustaining Medication Adherence in Resource-Limited Settings SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material ID SUB-SAHARAN AFRICA; PRIMARY-HEALTH-CARE; ANTIRETROVIRAL THERAPY; HIV-INFECTION; METAANALYSIS; VARIABLES; LESSONS; DISEASE; DICHOTOMIZATION; CONSEQUENCES C1 [Tsai, Alexander C.] Harvard Univ, Robert Wood Johnson Hlth & Soc Scholars Program, Cambridge, MA 02138 USA. [Bangsberg, David R.] Mbarara Univ Sci & Technol, Mbarara, Uganda. [Bangsberg, David R.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Bangsberg, David R.] Brigham & Womens Hosp, Div Global Hlth Equ, Boston, MA 02115 USA. [Bangsberg, David R.] Massachusetts Gen Hosp, Massachusetts Inst Technol, Phillip T & Susan M Ragon Inst, Boston, MA 02114 USA. [Bangsberg, David R.] Harvard Univ, Sch Med, Boston, MA USA. RP Tsai, AC (reprint author), Harvard Univ, Robert Wood Johnson Hlth & Soc Scholars Program, Cambridge, MA 02138 USA. EM atsai@hsph.harvard.edu OI Tsai, Alexander/0000-0001-6397-7917 FU NIMH NIH HHS [K24 MH087227, R01 MH054907] NR 37 TC 8 Z9 8 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD DEC PY 2011 VL 26 IS 12 BP 1391 EP 1393 DI 10.1007/s11606-011-1841-3 PG 3 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 849ST UT WOS:000297146100002 PM 21879369 ER PT J AU Olson, DM Constable, M Britz, GW Lin, CB Zimmer, LO Schwamm, LH Fonarow, GC Peterson, ED AF Olson, DaiWai M. Constable, Mark Britz, Gavin W. Lin, Cheryl B. Zimmer, Louise O. Schwamm, Lee H. Fonarow, Gregg C. Peterson, Eric D. TI A Qualitative Assessment of Practices Associated With Shorter Door-to-Needle Time for Thrombolytic Therapy in Acute Ischemic Stroke SO JOURNAL OF NEUROSCIENCE NURSING LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; AMERICAN-HEART-ASSOCIATION; ORGANIZATIONAL CULTURE; EMERGENCY-DEPARTMENT; SCIENTIFIC STATEMENT; OF-CARE; GUIDELINES; OUTCOMES; TEAM; IMPROVEMENT AB Early treatment with intravenous (IV) recombinant tissue plasminogen activator/alteplase (tPA) is associated with improved outcomes for patients with an acute ischemic stroke. Thus, rapid triage and treatment of stroke patients are essential, with a goal of door-to-needle time of no more than 60 minutes. We sought to identify best practices associated with faster treatment among hospitals participating in Get With the Guidelines-Stroke. Qualitative telephone interviews were conducted to elicit strategies being used by these centers to assess, treat, and monitor stroke patients treated with IV tPA. We sequentially carried out these interviews until we no longer identified novel factors. Interviews were conducted with 13 personnel at 7 top-performing U. S. hospitals. With the use of a hermeneutic-phenomenological framework, 5 distinct domains associated with rapid IV tPA delivery were identified. These included (a) communication and teamwork, (b) process, (c) organizational culture, (d) performance monitoring and feedback, and (e) overcoming barriers. C1 [Olson, DaiWai M.; Britz, Gavin W.] Duke Univ, Med Ctr, Dept Neurol, Durham, NC 27706 USA. [Lin, Cheryl B.; Zimmer, Louise O.; Peterson, Eric D.] Duke Clin Res Inst, Durham, NC USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Div Cardiol, Los Angeles, CA USA. RP Olson, DM (reprint author), Duke Univ, Med Ctr, Dept Neurol, Durham, NC 27706 USA. EM Olson006@mc.duke.edu OI Schwamm, Lee/0000-0003-0592-9145 FU Agency for Healthcare Research and Quality [U18HS016964] FX This project was supported by cooperative agreement number U18HS016964 from the Agency for Healthcare Research and Quality. NR 35 TC 13 Z9 13 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0888-0395 J9 J NEUROSCI NURS JI J. Neurosci. Nurs. PD DEC PY 2011 VL 43 IS 6 BP 329 EP 336 DI 10.1097/JNN.0b013e318234e7fb PG 8 WC Clinical Neurology; Nursing SC Neurosciences & Neurology; Nursing GA 850PL UT WOS:000297207700007 PM 22089410 ER PT J AU Nosho, K Ogino, S AF Nosho, Katsuhiko Ogino, Shuji TI Reply to letter entitled 'How dense, how intense? Role of tumour-infiltrating lymphocytes across colorectal cancer stages'. Re: Nosho et al. Tumour-infiltrating T-cell subsets, molecular changes in colorectal cancer, and prognosis: cohort study and literature review. J Pathol 2010; 222: 350-366 SO JOURNAL OF PATHOLOGY LA English DT Letter ID COLON-CANCER; SURVIVAL C1 [Ogino, Shuji] Dana Farber Harvard Canc Ctr, Canc Epidemiol Program, Boston, MA USA. [Ogino, Shuji] Dana Farber Harvard Canc Ctr, Gastrointestinal Malignancies Program, Boston, MA USA. [Ogino, Shuji] Harvard Univ, Brigham & Womens Hosp, Dept Pathol, Dana Farber Canc Inst,Dept Med Oncol,Sch Med, Boston, MA 02115 USA. [Nosho, Katsuhiko] Sapporo Med Univ, Dept Internal Med 1, Sapporo, Hokkaido, Japan. RP Ogino, S (reprint author), Dana Farber Harvard Canc Ctr, Canc Epidemiol Program, Boston, MA USA. EM shuji_ogino@dfci.harvard.edu NR 16 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3417 J9 J PATHOL JI J. Pathol. PD DEC PY 2011 VL 225 IS 4 BP 629 EP 630 DI 10.1002/path.2956 PG 2 WC Oncology; Pathology SC Oncology; Pathology GA 851VN UT WOS:000297299500017 ER PT J AU Yang, W Yamada, M Tamura, Y Chang, KH Mao, J Zou, L Feng, Y Kida, K Scherrer-Crosbie, M Chao, W Ichinose, F Yu, YM Fischman, AJ Tompkins, RG Yao, SL Kaneki, M AF Yang, Wen Yamada, Marina Tamura, Yoshiaki Chang, Kyungho Mao, Ji Zou, Lin Feng, Yan Kida, Kotaro Scherrer-Crosbie, Marielle Chao, Wei Ichinose, Fumito Yu, Yong-Ming Fischman, Alan J. Tompkins, Ronald G. Yao, Shanglong Kaneki, Masao TI Farnesyltransferase Inhibitor FTI-277 Reduces Mortality of Septic Mice along with Improved Bacterial Clearance SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID REGULATORY T-CELLS; COA REDUCTASE INHIBITOR; NITRIC-OXIDE SYNTHASE; SEVERE SEPSIS; STATIN THERAPY; MURINE MODEL; IN-VIVO; PROTEIN; SURVIVAL; ATORVASTATIN AB Treatment with statins, inhibitors of HMG-CoA reductase, extends the survival of septic mice. However, the molecular mechanisms underlying the cholesterol-lowering, independent beneficial effects of statins in sepsis are poorly understood. The inhibition of protein isoprenylation, namely farnesylation and geranylgeranylation, has been proposed as a mediator of the pleiotropic protective effects of statins, although direct evidence is lacking. Major features of sepsis-induced immune suppression include T-cell dysfunction, which is characterized by apoptosis of splenic T cells, increased CD4(+)Foxp3(+) regulatory T cells (Tregs), and suppression of type 1 helper T-cell response [e.g., interferon-gamma (IFN-gamma) secretion] in mice. Here, we show that the induction of sepsis by cecal ligation and puncture (CLP) resulted in increases in farnesyltransferase activity and farnesylated proteins in the spleen relative to sham operation. Treatment with farnesyltransferase inhibitor N-[4-[2(R)-amino-3-mercaptopropyl]amino-2-phenylbenzoyl]methionine methyl ester trifluoroacetate salt (FTI-277) (25 mg/kg b.wt. i.p.) at 2 h after CLP blocked the increase in farnesylated proteins and improved survival and bacterial clearance of septic mice. FTI-277 reverted to or mitigated sepsis-induced apoptosis in spleen and thymus, increased splenic CD4(+)Foxp3(+) Tregs, and suppressed IFN-gamma secretion and proliferation of splenocytes in response to anti-CD3+CD28 antibodies in mice. Moreover, FTI-277 promoted macrophage phagocytotic activity in septic mice. These results indicate that elevation in protein farnesylation plays a role in derangements in immune function and mortality of septic mice. These findings suggest that prevention of immune dysfunction might contribute to FTI-277-induced improvement in survival of septic mice. These data highlight protein farnesyltransferase as a novel potential molecular target to reduce the mortality of patients with sepsis. C1 [Yang, Wen; Yamada, Marina; Tamura, Yoshiaki; Chang, Kyungho; Mao, Ji; Zou, Lin; Feng, Yan; Kida, Kotaro; Chao, Wei; Ichinose, Fumito; Kaneki, Masao] Harvard Univ, Sch Med, Dept Anesthesia Crit Care & Pain Med, Massachusetts Gen Hosp, Charlestown, MA USA. [Yu, Yong-Ming; Tompkins, Ronald G.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Yamada, Marina; Tamura, Yoshiaki; Mao, Ji; Yu, Yong-Ming; Fischman, Alan J.; Tompkins, Ronald G.; Kaneki, Masao] Shriners Hosp Children, Boston, MA USA. [Scherrer-Crosbie, Marielle] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab,Cardiol Div,Dept Med, Boston, MA USA. [Yang, Wen; Yao, Shanglong] Huazhong Univ Sci & Technol, Dept Anesthesia, Union Hosp, Wuhan 430074, Peoples R China. RP Kaneki, M (reprint author), 149 13th St,Rm 6604, Charlestown, MA 02129 USA. EM mkaneki@helix.mgh.harvard.edu RI Feng, Yan/H-5808-2012 FU National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [R01-DK05827]; National Institutes of Health National Institute of General Medical Sciences [R01-GM079360, R01-GM08096]; National Institutes of Health National Heart, Lung, and Blood Institute [NHLB-I1S10-RR022586]; Shriners Hospitals for Children [85400, 71000]; American Heart Association [0755890T] FX This work was supported by the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [Grant R01-DK05827] (to M.K.); the National Institutes of Health National Institute of General Medical Sciences [Grants R01-GM079360, R01-GM08096] (to F.I. and W.C., respectively); the National Institutes of Health National Heart, Lung, and Blood Institute [Grant NHLB-I1S10-RR022586 (to M.S.-C.)]; Shriners Hospitals for Children [Research Grants 85400, 71000] (to M.K.); and the American Heart Association [Grant 0755890T] (to W.C.). NR 41 TC 12 Z9 12 U1 3 U2 6 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD DEC PY 2011 VL 339 IS 3 BP 832 EP 841 DI 10.1124/jpet.111.183558 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 851KM UT WOS:000297267800011 PM 21873557 ER PT J AU Granier, M Jensen, MO Honge, JL Bel, A Menasche, P Nielsen, SL Carpentier, A Levine, RA Hagege, AA AF Granier, Mathieu Jensen, Morten O. Honge, Jesper L. Bel, Alain Menasche, Philippe Nielsen, Sten L. Carpentier, Alain Levine, Robert A. Hagege, Albert A. TI Consequences of mitral valve prolapse on chordal tension: Ex vivo and in vivo studies in large animal models SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Editorial Material ID REGURGITATION C1 [Hagege, Albert A.] Hop Europeen Georges Pompidou, Assistance Publ Hop Paris, Dept Cardiol, F-75015 Paris, France. [Granier, Mathieu; Bel, Alain; Menasche, Philippe; Carpentier, Alain] Fdn Alain Carpentier, Lab Biosurg Res, Paris, France. [Granier, Mathieu; Bel, Alain; Menasche, Philippe; Carpentier, Alain; Hagege, Albert A.] Paris Cardiovasc Res Ctr, INSERM, U633, Paris, France. [Granier, Mathieu; Bel, Alain; Menasche, Philippe; Carpentier, Alain; Hagege, Albert A.] Univ Paris 05, Paris, France. [Jensen, Morten O.] Engn Coll Aarhus, Dept Biomed Engn, Aarhus, Denmark. [Jensen, Morten O.; Honge, Jesper L.; Nielsen, Sten L.] Aarhus Univ Hosp, Dept Cardiothorac & Vasc Surg, DK-8000 Aarhus, Denmark. [Bel, Alain; Menasche, Philippe; Carpentier, Alain] Hop Europeen Georges Pompidou, Assistance Publ Hop Paris, Dept Cardiovasc Surg, F-75015 Paris, France. [Levine, Robert A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, Boston, MA USA. RP Hagege, AA (reprint author), Hop Europeen Georges Pompidou, Assistance Publ Hop Paris, Dept Cardiol, 20 Rue Leblanc, F-75015 Paris, France. EM albert.hagege@egp.aphp.fr FU NHLBI NIH HHS [R01 HL072265, K24 HL067434-10, K24 HL67434, K24 HL067434] NR 5 TC 8 Z9 8 U1 1 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD DEC PY 2011 VL 142 IS 6 BP 1585 EP 1587 DI 10.1016/j.jtcvs.2011.08.035 PG 3 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 850RC UT WOS:000297214200045 PM 21955468 ER PT J AU Shwartz, M Pekoz, EA Labonte, A Heineke, J Restuccia, JD AF Shwartz, Michael Pekoez, Erol A. Labonte, Alan Heineke, Janelle Restuccia, Joseph D. TI Bringing Responsibility for Small Area Variations in Hospitalization Rates Back to the Hospital The Propensity to Hospitalize Index and a Test of the Roemer's Law SO MEDICAL CARE LA English DT Article DE small area variations; hospitals; Roemer's Law ID ADMISSION RATES; GEOGRAPHIC-VARIATION; CARE; HEALTH; POPULATION; DELIVERY AB Objective: To assign responsibility for variations in small area hospitalization rates to specific hospitals and to evaluate the Roemer's Law in a way that does not artificially induce correlation between bed supply and utilization. Data Sources/Study Setting: We used data on hospitalizations and outpatient treatment for 15 medical conditions of nonmanaged care Part B eligible Medicare enrollees of 65 years and older in Massachusetts in 2000. Study Design: We used a Bayesian model to estimate each hospital's pool of potential patients and the fraction of the pool hospitalized (its propensity to hospitalize, PTH). To evaluate the Roemer's Law, we calculated the correlation between hospitals' PTH and beds per potential patient. Patient severity was measured using All Patient Refined Diagnosis Related Groups. Results: We show that our approach does not artificially induce a correlation between beds and utilization whereas the traditional approach does. Nevertheless, our approach indicates a strong relationship between PTH and beds (r = 0.56). Eighteen (of 66) hospitals had a high PTH that differed significantly from 16 hospitals with a low PTH. Average patient severity in the high PTH hospitals was lower than in the low PTH hospitals. Although the difference was not statistically significant (P = 0.12), there was a medium effect size (0.58). Discussion: Variation across hospitals in the PTH index, the strong relationship between beds and the PTH, and the lack of relationship between severity and the PTH suggest the importance of policies that limit bed growth of high PTH hospitals and create incentives for high PTH hospitals to reduce hospitalizations. C1 [Shwartz, Michael; Labonte, Alan; Restuccia, Joseph D.] VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, Boston, MA 02215 USA. [Shwartz, Michael; Pekoez, Erol A.; Heineke, Janelle; Restuccia, Joseph D.] Boston Univ, Sch Management, Boston, MA 02215 USA. RP Shwartz, M (reprint author), VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, 595 Commonwealth Ave, Boston, MA 02215 USA. EM mshwartz@bu.edu FU Agency for Healthcare Research and Quality FX Supported in part by the Agency for Healthcare Research and Quality. NR 28 TC 4 Z9 4 U1 2 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD DEC PY 2011 VL 49 IS 12 BP 1062 EP 1067 DI 10.1097/MLR.0b013e3182353907 PG 6 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 850TN UT WOS:000297222500004 PM 22002646 ER PT J AU Carney, BJ Shah, K AF Carney, B. J. Shah, K. TI MIGRATION AND FATE OF THERAPEUTIC STEM CELLS IN DIFFERENT BRAIN DISEASE MODELS SO NEUROSCIENCE LA English DT Review DE stem cell; pathotropic migration; differentiation; therapeutics ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; HEPATOCYTE GROWTH-FACTOR; NEURAL PROGENITOR CELLS; PROMOTES FUNCTIONAL RECOVERY; FOCAL CEREBRAL-ISCHEMIA; CENTRAL-NERVOUS-SYSTEM; BONE-MARROW; RAT-BRAIN; IN-VITRO; CHEMOKINE RECEPTOR AB Stem cells have a number of properties, which make them excellent candidates for the treatment of various neurologic disorders, the most important of which being their ability to migrate to and differentiate predictably at sites of pathology in the brain. The disease-directed migration and well-characterized differentiation patterns of stem cells may eventually provide a powerful tool for the treatment of both localized and diffuse disease processes within the human brain. A thorough understanding of the molecular mechanisms governing their migratory properties and their choice between different differentiation programs is essential if these cells are to be used therapeutically in humans. This review focuses on summarizing the migration and differentiation of therapeutic neural and mesenchymal stem cells in different disease models in the brain and also discusses the promise of these cells to eventually treat various forms of neurologic disease. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved. C1 [Carney, B. J.; Shah, K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Neurotherapy & Imaging Lab,Dept Radiol & Neur, Boston, MA 02115 USA. RP Shah, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Neurotherapy & Imaging Lab,Dept Radiol & Neur, Boston, MA 02115 USA. EM kshah@mgh.harvard.edu FU NINDS NIH HHS [R01 NS071197] NR 101 TC 20 Z9 20 U1 0 U2 22 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD DEC 1 PY 2011 VL 197 BP 37 EP 47 DI 10.1016/j.neuroscience.2011.08.063 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 849QR UT WOS:000297140700005 PM 21946010 ER PT J AU Dworak, M McCarley, RW Kim, T Basheer, R AF Dworak, M. McCarley, R. W. Kim, T. Basheer, R. TI DELTA OSCILLATIONS INDUCED BY KETAMINE INCREASE ENERGY LEVELS IN SLEEP-WAKE RELATED BRAIN REGIONS SO NEUROSCIENCE LA English DT Article DE ATP; brain energy metabolism; ketamine-xylazine; slow-wave-activity; Na(+)-K(+)-ATPase; NREM sleep ID CYTOCHROME-C-OXIDASE; BASAL FOREBRAIN; CEREBRAL-CORTEX; RAT-BRAIN; SYNAPTIC-TRANSMISSION; GENERAL-ANESTHESIA; HZ OSCILLATION; ATP CHANGES; ADENOSINE; DEPRIVATION AB Neuronal signaling consumes much of the brain energy, mainly through the restoration of the membrane potential (MP) by ATP-consuming ionic pumps. We have reported that, compared with waking, ATP levels increase during the initial hours of natural slow-wave sleep, a time with prominent electroencephalogram (EEG) delta oscillations (0.5-4.5 Hz). We have hypothesized that there is a delta oscillation-ATP increase coupling, since, during delta waves, neurons exhibit a prolonged hyperpolarizing phase followed by a very brief phase of action potentials. However, direct proof of this hypothesis is lacking, and rapid changes in EEG/neuronal activity preclude measurement in the naturally sleeping brain. Thus, to induce a uniform state with pure delta oscillations and one previously shown to be accompanied by a similar pattern of neuronal activity during delta waves as natural sleep, we used ketamine-xylazine treatment in rats. We here report that, with this treatment, the high-energy molecules ATP and ADP increased in frontal and cingulate cortices, basal forebrain, and hippocampus compared with spontaneous waking. Moreover, the degree of ATP increase positively and significantly correlated with the degree of EEG delta activity. Supporting the hypothesis of decreased ATP consumption during delta activity, the ATP-consuming Na(+)-K(+)-ATPase mRNA levels were significantly decreased, whereas the mRNAs for the ATP-producing cytochrome c oxidase (COX) subunits COX III and COX IVa were unchanged. Taken together, these data support the hypothesis of a cortical delta oscillation-dependent reduction in ATP consumption, thus providing the brain with increased ATP availability, and likely occurring because of reduced Na(+)-K(+)-ATPase related energy consumption. Published by Elsevier Ltd on behalf of IBRO. C1 [Basheer, R.] VA Boston Healthcare Syst, Dept Psychiat, Neurosci Lab, W Roxbury, MA USA. Harvard Univ, Sch Med, W Roxbury, MA USA. RP Basheer, R (reprint author), VA Boston Healthcare Syst, Dept Psychiat, Neurosci Lab, W Roxbury, MA USA. EM radhika_basheer@hms.harvard.edu RI McCarley, Robert/N-5562-2014 OI McCarley, Robert/0000-0001-5705-7495 FU Department of Veterans Affairs Medical Research Service; Deutsche Forschungsgemeinschaft [DW66/1-1]; National Institute of Mental Health [NIMH39683] FX We gratefully acknowledge Farzana Pervin Nipa for technical assistance, and Diane Ghera and Dewayne Williams for help with animal care. This work was supported by awards from the Department of Veterans Affairs Medical Research Service Award to R.B., a Deutsche Forschungsgemeinschaft fellowship (DW66/1-1) to M.D., and the National Institute of Mental Health (NIMH39683) to R.W.M. NR 65 TC 4 Z9 4 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD DEC 1 PY 2011 VL 197 BP 72 EP 79 DI 10.1016/j.neuroscience.2011.09.027 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 849QR UT WOS:000297140700008 PM 21958867 ER PT J AU Kalkonde, YV Shelton, R Villarreal, M Sigala, J Mishra, PK Ahuja, SS Barea-Rodriguez, E Moretti, P Ahuja, SK AF Kalkonde, Y. V. Shelton, R. Villarreal, M. Sigala, J. Mishra, P. K. Ahuja, S. S. Barea-Rodriguez, E. Moretti, P. Ahuja, S. K. TI THE CC CHEMOKINE RECEPTOR 5 REGULATES OLFACTORY AND SOCIAL RECOGNITION IN MICE SO NEUROSCIENCE LA English DT Article DE chemokine; CC-chemokine receptor 5; CC-chemokine ligand 3; behavior; social recognition; N-methyl D-aspartate receptor 1 ID LONG-TERM-MEMORY; MOUSE MODEL; NERVOUS-SYSTEM; BRAIN; EXPRESSION; OXYTOCIN; BEHAVIOR; NEURONS; DISEASE; GENE AB Chemokines are chemotactic cytokines that regulate cell migration and are thought to play an important role in a broad range of inflammatory diseases. The availability of chemokine receptor blockers makes them an important therapeutic target. In vitro, chemokines are shown to modulate neurotransmission. However, it is not very clear if chemokines play a role in behavior and cognition. Here we evaluated the role of CC chemokine receptor 5 (CCR5) in various behavioral tasks in mice using Wt (Ccr5(+/+)) and Ccr5-null (Ccr5(-/-)) mice. Ccr5(-/-) mice showed enhanced social recognition. Administration of CC chemokine ligand 3 (CCL3), one of the CCR5-ligands, impaired social recognition. Since the social recognition task is dependent on the sense of olfaction, we tested olfactory recognition for social and non-social scents in these mice. Ccr5(-/-) mice had enhanced olfactory recognition for both these scents indicating that enhanced performance in social recognition task could be due to enhanced olfactory recognition in these mice. Spatial memory and aversive memory were comparable in Wt and Ccr5(-/-) mice. Collectively, these results suggest that chemokines/chemokine receptors might play an important role in olfactory recognition tasks in mice and to our knowledge represents the first direct demonstration of an in vivo role of CCR5 in modulating social behavior in mice. These studies are important as CCR5 blockers are undergoing clinical trials and can potentially modulate behavior. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved. C1 [Kalkonde, Y. V.; Shelton, R.; Sigala, J.; Ahuja, S. S.; Ahuja, S. K.] S Texas Vet Hlth Care Syst, Vet Adm Res Ctr AIDS & HIV Infect 1, San Antonio, TX USA. [Kalkonde, Y. V.; Shelton, R.; Sigala, J.; Ahuja, S. S.; Ahuja, S. K.] S Texas Vet Hlth Care Syst, Ctr Personalized Med, San Antonio, TX USA. [Kalkonde, Y. V.; Shelton, R.; Sigala, J.; Ahuja, S. S.; Ahuja, S. K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Villarreal, M.; Mishra, P. K.; Barea-Rodriguez, E.] Univ Texas San Antonio, Dept Biol, San Antonio, TX USA. [Moretti, P.] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. RP Kalkonde, YV (reprint author), SEARCH, PO Gadchiroli, Gadchiroli 442605, Maharashtra, India. EM yvkalkonde@gmail.com FU Veterans Administration Center on AIDS and HIV infection of the South Texas Veterans Health Care System; MERIT [R37046326]; NIH [AI043279, MH069270]; Elizabeth Glaser Scientist Award; Burroughs Wellcome Clinical Scientist Award in Translational Research FX We thank William Kuziel for providing Ccr5-/- mice on C57BL6/J background, Timothy Freeman and Carlo Condello for help with experiments and Ivan Becerra, William Pate and Harjeet Singh for help with illustrations. This work was supported by the Veterans Administration Center on AIDS and HIV infection of the South Texas Veterans Health Care System, and a MERIT (R37046326) and other awards (AI043279 and MH069270) from the NIH to S.K.A. S.K.A. is a recipient of the Elizabeth Glaser Scientist Award and the Burroughs Wellcome Clinical Scientist Award in Translational Research. The funding sources had no role NR 46 TC 6 Z9 7 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD DEC 1 PY 2011 VL 197 BP 153 EP 161 DI 10.1016/j.neuroscience.2011.09.039 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 849QR UT WOS:000297140700016 PM 21963866 ER PT J AU Xi, M Fung, SJ Sampogna, S Chase, MH AF Xi, M. Fung, S. J. Sampogna, S. Chase, M. H. TI EXCITATORY PROJECTIONS FROM THE AMYGDALA TO NEURONS IN THE NUCLEUS PONTIS ORALIS IN THE RAT: AN INTRACELLULAR STUDY SO NEUROSCIENCE LA English DT Article DE amygdala; electrical stimulation; REM sleep; synaptic potentials; nucleus pontis oralis ID EYE-MOVEMENT SLEEP; TERM SYNAPTIC PLASTICITY; REM-SLEEP; ELECTRICAL-STIMULATION; RETICULAR-FORMATION; PONTOGENICULOOCCIPITAL WAVES; PARADOXICAL SLEEP; BRAIN-STEM; FUNCTIONAL NEUROANATOMY; LUMBAR MOTONEURONS AB There is a consensus that active (REM) sleep (AS) is controlled by cholinergic projections from the laterodorsal and pedunculopontine tegmental nuclei (LDT/PPT) to neurons in the nucleus pontis oralis (NPO) that generate AS (i.e. AS-Generator neurons). The present study was designed to provide evidence that other projections to the NPO, such as those from the amygdala, are also capable of inducing AS. Accordingly, the responses of neurons, recorded intracellularly in the NPO, were examined following stimulation of the ipsilateral central nucleus of the amygdala (CNA) in urethane-anesthetized rats. Single pulse stimulation in the CNA produced an early, fast depolarizing potential (EPSP) in neurons within the NPO. The mean latency to the onset of these excitatory postsynaptic potentials (EPSPs) was 3.6 +/- 0.2 ms. A late, small-amplitude inhibitory synaptic potential (IPSP) was present following EPSPs in a portion of the NPO neurons. Following stimulation of the CNA with a train of 8-10 pulses, NPO neurons exhibited a sustained depolarization (5-10 my) of their resting membrane potential. When single subthreshold intracellular depolarizing current pulses were delivered to NPO neurons, CNA-induced EPSPs were sufficient to promote the discharge of these cells. Stimulation of the CNA with a short train of stimuli induced potent temporal facilitation of EPSPs in NPO neurons. Two forms of synaptic plasticity were revealed by the patterns of response of NPO neurons following stimulation of the CNA: paired-pulse facilitation (PPF) and post-tetanic potentiation (PIP). Six of recorded NPO neurons were identified morphologically with neurobiotin. They were medium to large, multipolar cells with diameters >20 mu M, which resemble AS-on cells in the NPO. The present results demonstrate that amygdalar projections are capable of exerting a powerful excitatory postsynaptic drive that activates NPO neurons. Therefore, we suggest that the amygdala is capable of inducing AS via direct projections to AS-Generator neurons in the NPO. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved. C1 [Xi, M.; Fung, S. J.; Sampogna, S.; Chase, M. H.] WebSci Int, Los Angeles, CA 90024 USA. [Xi, M.; Fung, S. J.; Chase, M. H.] VA Greater Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Chase, M. H.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90025 USA. RP Xi, M (reprint author), WebSci Int, 1251 Westwood Blvd, Los Angeles, CA 90024 USA. EM mxi@websciences.org FU NIH [NS 60917] FX This research was supported by NIH grant NS 60917. We are grateful to Mr. Vincent Lim. Ms. Nichole Stevens and Mr. Daniel Bronson for their excellent technical assistance. NR 61 TC 8 Z9 8 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD DEC 1 PY 2011 VL 197 BP 181 EP 190 DI 10.1016/j.neuroscience.2011.09.029 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 849QR UT WOS:000297140700019 PM 21955600 ER PT J AU Koreth, J Matsuoka, K Kim, HT McDonough, SM Bindra, B Alyea, EP Armand, P Cutler, C Ho, VT Treister, NS Bienfang, DC Prasad, S Tzachanis, D Joyce, RM Avigan, DE Antin, JH Ritz, J Soiffer, RJ AF Koreth, John Matsuoka, Ken-ichi Kim, Haesook T. McDonough, Sean M. Bindra, Bhavjot Alyea, Edwin P., III Armand, Philippe Cutler, Corey Ho, Vincent T. Treister, Nathaniel S. Bienfang, Don C. Prasad, Sashank Tzachanis, Dmitrios Joyce, Robin M. Avigan, David E. Antin, Joseph H. Ritz, Jerome Soiffer, Robert J. TI Interleukin-2 and Regulatory T Cells in Graft-versus-Host Disease SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID BONE-MARROW-TRANSPLANTATION; CONSENSUS DEVELOPMENT PROJECT; LOW-DOSE INTERLEUKIN-2; WORKING GROUP-REPORT; CLINICAL-TRIALS; TOLERANCE; EXPRESSION; INFUSION; THERAPY; IL-2 AB Background Dysfunction of regulatory T (Treg) cells has been detected in diverse inflammatory disorders, including chronic graft-versus-host disease (GVHD). Interleukin-2 is critical for Treg cell growth, survival, and activity. We hypothesized that low-dose interleukin-2 could preferentially enhance Treg cells in vivo and suppress clinical manifestations of chronic GVHD. Methods In this observational cohort study, patients with chronic GVHD that was refractory to glucocorticoid therapy received daily low-dose subcutaneous interleukin-2 (0.3x10(6), 1x10(6), or 3x10(6) IU per square meter of body-surface area) for 8 weeks. The end points were safety and clinical and immunologic response. After a 4-week hiatus, patients with a response could receive interleukin-2 for an extended period. Results A total of 29 patients were enrolled. None had progression of chronic GVHD or relapse of a hematologic cancer. The maximum tolerated dose of interleukin-2 was 1x106 IU per square meter. The highest dose level induced unacceptable constitutional symptoms. Of the 23 patients who could be evaluated for response, 12 had major responses involving multiple sites. The numbers of CD4+ Treg cells were preferentially increased in all patients, with a peak median value, at 4 weeks, that was more than eight times the baseline value (P<0.001), without affecting CD4+ conventional T (Tcon) cells. The Treg: Tcon ratio increased to a median of more than five times the baseline value (P<0.001). The Treg cell count and Treg: Tcon ratio remained elevated at 8 weeks (P<0.001 for both comparisons with baseline values), then declined when the patients were not receiving interleukin-2. The increased numbers of Treg cells expressed the transcription factor forkhead box P3 (FOXP3) and could inhibit autologous Tcon cells. Immunologic and clinical responses were sustained in patients who received interleukin-2 for an extended period, permitting the glucocorticoid dose to be tapered by a mean of 60% (range, 25 to 100). Conclusions Daily low-dose interleukin-2 was safely administered in patients with active chronic GVHD that was refractory to glucocorticoid therapy. Administration was associated with preferential, sustained Treg cell expansion in vivo and amelioration of the manifestations of chronic GVHD in a substantial proportion of patients. (Funded by a Dana-Farber Dunkin' Donuts Rising Star award and others.) C1 [Koreth, John; Matsuoka, Ken-ichi; McDonough, Sean M.; Bindra, Bhavjot; Alyea, Edwin P., III; Armand, Philippe; Cutler, Corey; Ho, Vincent T.; Antin, Joseph H.; Ritz, Jerome; Soiffer, Robert J.] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02215 USA. [Kim, Haesook T.] Dana Farber Canc Inst, Div Biostat & Computat Biol, Boston, MA 02215 USA. [Treister, Nathaniel S.] Brigham & Womens Hosp, Div Oral Med & Dent, Boston, MA 02115 USA. [Bienfang, Don C.; Prasad, Sashank] Brigham & Womens Hosp, Neurol Ophthalmol Sect, Boston, MA 02215 USA. [Tzachanis, Dmitrios; Joyce, Robin M.; Avigan, David E.] Beth Israel Deaconess Med Ctr, Hematol Oncol Div, Boston, MA 02215 USA. RP Koreth, J (reprint author), Dana Farber Canc Inst, Div Hematol Malignancies, 450 Brookline Ave, Boston, MA 02215 USA. EM john_koreth@dfci.harvard.edu OI Ritz, Jerome/0000-0001-5526-4669 FU Dana-Farber Dunkin' Donuts Rising Star award; American Society of Blood; Marrow Transplantation/Pharmion New Investigator award; National Cancer Institute [P01 CA142106]; Jock and Bunny Adams Research and Education Endowment; National Institute of Allergy and Infectious Diseases [AI29530] FX Supported in part by a Dana-Farber Dunkin' Donuts Rising Star award and an American Society of Blood and Marrow Transplantation/Pharmion New Investigator award (to Dr. Koreth); a grant from the National Cancer Institute (P01 CA142106, to Dr. Antin); and grants from the Jock and Bunny Adams Research and Education Endowment and the National Institute of Allergy and Infectious Diseases (AI29530, to Dr. Soiffer). NR 41 TC 346 Z9 353 U1 2 U2 21 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 1 PY 2011 VL 365 IS 22 BP 2055 EP 2066 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 854MO UT WOS:000297499000006 PM 22129252 ER PT J AU O'Donnell, CJ Nabel, EG AF O'Donnell, Christopher J. Nabel, Elizabeth G. TI GENOMIC MEDICINE Genomics of Cardiovascular Disease SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID CORONARY-ARTERY-DISEASE; SCALE ASSOCIATION ANALYSIS; ABDOMINAL AORTIC-ANEURYSM; WIDE ASSOCIATION; HEART-FAILURE; MYOCARDIAL-INFARCTION; INTRACRANIAL ANEURYSM; SUSCEPTIBILITY LOCI; ATRIAL-FIBRILLATION; CHARGE CONSORTIUM C1 [Nabel, Elizabeth G.] Brigham & Womens Hosp, Boston, MA 02115 USA. [O'Donnell, Christopher J.] NHLBI, NIH, Bethesda, MD 20892 USA. [O'Donnell, Christopher J.] NIH, Framingham Heart Study, Bethesda, MD 20892 USA. [O'Donnell, Christopher J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [O'Donnell, Christopher J.; Nabel, Elizabeth G.] Harvard Univ, Sch Med, Boston, MA USA. RP Nabel, EG (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM enabel@partners.org NR 80 TC 64 Z9 73 U1 2 U2 8 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 1 PY 2011 VL 365 IS 22 BP 2098 EP 2109 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 854MO UT WOS:000297499000010 PM 22129254 ER PT J AU Kapoor, R Johnson, RA AF Kapoor, Roger Johnson, Richard A. TI Polydactyly SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Kapoor, Roger; Johnson, Richard A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kapoor, R (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM rogerkapoor@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 1 PY 2011 VL 365 IS 22 BP 2122 EP 2122 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 854MO UT WOS:000297499000012 PM 22129256 ER PT J AU Oron, Y Roth, Y Levine, RA AF Oron, Yahav Roth, Yehudah Levine, Robert A. TI Sudden Brief Unilateral Tapering Tinnitus: Prevalence and Properties SO OTOLOGY & NEUROTOLOGY LA English DT Article DE Paroxysmal; Survey; Tinnitus ID BRAIN-STEM AB Objective: To systematically characterize unilateral tinnitus typically lasting less than a minute. Study Design: Observational study. Setting: Outpatient clinic in a tertiary referral hospital. Patients: Study I: 62 unselected adults. Study II: 74 adults with sudden brief unilateral tapering tinnitus (SBUTT). Interventions: Study I: Structured interview regarding SBUTTs and other types of tinnitus. Study II: Maintaining an SBUTT log for 4 consecutive months. Main Outcome Measures: Study I: Retrospective prevalence of SBUTTs. Study II: Prospective frequency and characteristics of SBUTTs. Results: Study I: 76% of the participants recalled having at least one SBUTT in the past. There was no significant difference in the incidence of SBUTTs with respect to handedness, age, sex, the presence or absence of chronic tinnitus, whether tinnitus could be brought on by exposure to loud sounds, or whether auditory perception could be modulated with strong muscle contractions of the neck or jaw. Study II: SBUTTs mean rate was 1.2 per month ( range, 0-11.5). The rate in people with chronic tinnitus was twice that of those without chronic tinnitus. Right ear SBUTTs predominated nearly 2 to 1. Pitch estimates ranged between 0.1 and 4.4 kHz; 75% of SBUTTs lasted 25 seconds or less. A quarter occurred with simultaneous ear fullness. Conclusion: In the 76% of adults with SBUTTs, the average rate of occurrence was about once a month. SBUTTs are twice as common for the right ear as the left. One of 4 SBUTTs occurs with ear fullness. A quarter of adults never recalled ever having an SBUTT. C1 [Oron, Yahav; Roth, Yehudah] Tel Aviv Univ, Dept Otolaryngol Head & Neck Surg, Sackler Sch Med, Edith Wolfson Med Ctr, IL-58100 Holon, Israel. [Roth, Yehudah] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada. [Levine, Robert A.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Oron, Y (reprint author), Tel Aviv Univ, Dept Otolaryngol Head & Neck Surg, Sackler Sch Med, Edith Wolfson Med Ctr, POB 5, IL-58100 Holon, Israel. EM oron.yahav@gmail.com NR 13 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD DEC PY 2011 VL 32 IS 9 BP 1409 EP 1414 DI 10.1097/MAO.0b013e3182355626 PG 6 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 850SH UT WOS:000297217700006 PM 21970850 ER PT J AU Rosowski, JJ Cheng, JT Merchant, SN Harrington, E Furlong, C AF Rosowski, John J. Cheng, Jeffrey Tao Merchant, Saumil N. Harrington, Ellery Furlong, Cosme TI New Data on the Motion of the Normal and Reconstructed Tympanic Membrane SO OTOLOGY & NEUROTOLOGY LA English DT Article; Proceedings Paper CT 144th Annual Meeting of the American-Otological-Society CY APR 30-MAY 01, 2011 CL Chicago, IL SP Amer Otol Soc DE Middle ear function; Tympanic membrane; Tympano-ossicular sound conduction ID HUMAN MIDDLE-EAR; TIME-AVERAGED HOLOGRAPHY; DOPPLER VIBROMETER LDV; FINITE-ELEMENT MODEL; HUMAN TEMPORAL BONES; STROBOSCOPIC HOLOGRAPHY; SOUND-TRANSMISSION; CAT EARDRUM; WAVE MODEL; MECHANICS AB Hypothesis: The sound-induced motion of the tympanic membrane has features that are most consistent with modal responses to a uniform stimulus. Background: Conceptual models of the coupling of tympanic membrane motion to the ossicular chain can be classified as either modal responses to a uniform stimulation of the entire membrane or traveling wave models in which sound energy is captured at the membrane's rim and travels along the surface to the umbo. The stroboscopic holography technique we use can separate strongly modal or traveling wave-dominated motions of the tympanic membrane surface. Methods: We use computer-aided optoelectronic holography with stroboscopic illumination to measure the magnitude and phase of the sound-induced motion of more than 40,000 points on the surface of the tympanic membrane in cadaveric human temporal bones. Our techniques are sensitive to motions of the membrane as small as 0.01 mu m and allow determinations of membrane displacement at frequencies as large as 20 kHz. Results: We report clear signs of both modal tympanic membrane responses and traveling waves on the human tympanic membrane. Modal responses are seen throughout the frequency range, whereas the traveling waves are most apparent between 2 and 8 kHz. In general, the magnitudes of the traveling waves are small compared with the modal magnitudes. Conclusion: Much of the motion of the tympanic membrane is well approximated by modal motions of the tympanic membrane surface. This conclusion has implications for eardrum pathology and its treatment. C1 [Rosowski, John J.; Cheng, Jeffrey Tao; Merchant, Saumil N.; Furlong, Cosme] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. [Rosowski, John J.; Cheng, Jeffrey Tao; Merchant, Saumil N.; Furlong, Cosme] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Harrington, Ellery; Furlong, Cosme] Worcester Polytech Inst, Ctr Holog Studies & Laser MicromechaTron, Worcester, MA 01609 USA. [Harrington, Ellery; Furlong, Cosme] Worcester Polytech Inst, Dept Mech Engn, Worcester, MA 01609 USA. RP Rosowski, JJ (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM John_Rosowski@meei.harvard.edu FU NIDCD NIH HHS [R01 DC008642, F32 DC009949-02, R03 DC011617-02, R03 DC011617-01, F32 DC009949-01, F32DC009949, F32 DC009949, R01 DC008642-05] NR 45 TC 14 Z9 14 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD DEC PY 2011 VL 32 IS 9 BP 1559 EP 1567 DI 10.1097/MAO.0b013e31822e94f3 PG 9 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 850SH UT WOS:000297217700033 PM 21956597 ER PT J AU Sher, L LaBode, V AF Sher, Leo LaBode, Vanessa TI TEACHING HEALTH CARE PROFESSIONALS ABOUT SUICIDE SAFETY PLANNING SO PSYCHIATRIA DANUBINA LA English DT Article DE suicide; training; public health AB The suicide safety plan is a plan of action created by the clinician and patient that essentially charts the course of what the patient should do if he/she begins to experience suicidal urges. It is important for clinicians to learn how to implement a safety plan so that they can offer this service to their patients and teach their colleagues and associates about suicide safety planning. The safety plan is a great tool employed to help patients with suicidal urges, but trainees-clinicians and clinician associates alike - should fully understand that it is not a form of treatment. However, since an effective treatment for suicidality does not exist, practitioners should definitely use suicide safety planning. Although more resources are now being provided to individuals with suicidal behavior, more research needs to be done to develop new, effective methods of treatment and prevention of suicidal behavior. C1 [Sher, Leo; LaBode, Vanessa] James J Peters Vet Adm Med Ctr, New York, NY USA. RP Sher, L (reprint author), Mt Sinai Sch Med, Dept Psychiat, Med Ctr, James J Peters Vet Adm, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM Leo.Sher@mssm.edu NR 12 TC 4 Z9 4 U1 0 U2 2 PU MEDICINSKA NAKLADA PI ZAGREB PA VLASKA 69, HR-10000 ZAGREB, CROATIA SN 0353-5053 J9 PSYCHIAT DANUB JI Psychiatr. Danub. PD DEC PY 2011 VL 23 IS 4 BP 396 EP 397 PG 2 WC Psychiatry SC Psychiatry GA 850YZ UT WOS:000297236800010 PM 22075742 ER PT J AU Evans, WS Caplan, D Waters, G AF Evans, William S. Caplan, David Waters, Gloria TI Effects of concurrent arithmetical and syntactic complexity on self-paced reaction times and eye fixations SO PSYCHONOMIC BULLETIN & REVIEW LA English DT Article DE Dual-task performance; Eye movements and reading; Working memory; Language comprehension ID WORKING-MEMORY; SENTENCE COMPREHENSION; RELATIVE CLAUSES AB Two dual-task experiments (replications of Experiments 1 and 2 in Fedorenko, Gibson, & Rohde, Journal of Memory and Language, 56, 246-269 2007) were conducted to determine whether syntactic and arithmetical operations share working memory resources. Subjects read object- or subject-extracted relative clause sentences phrase by phrase in a self-paced task while simultaneously adding or subtracting numbers. Experiment 2 measured eye fixations as well as self-paced reaction times. In both experiments, there were main effects of syntax and of mathematical operation on self-paced reading times, but no interaction of the two. In the Experiment 2 eye-tracking results, there were main effects of syntax on first-pass reading time and total reading time and an interaction between syntax and math in total reading time on the noun phrase within the relative clause. The findings point to differences in the ways individuals process sentences under these dual-task conditions, as compared with viewing sentences during "normal" reading conditions, and do not support the view that arithmetical and syntactic integration operations share a working memory system. C1 [Caplan, David] Massachusetts Gen Hosp, Dept Neurol, Neuropsychol Lab, Boston, MA 02114 USA. [Evans, William S.; Waters, Gloria] Boston Univ, Dept Speech Language & Hearing Sci, Sargent Coll, Boston, MA 02215 USA. RP Caplan, D (reprint author), Massachusetts Gen Hosp, Dept Neurol, Neuropsychol Lab, Boston, MA 02114 USA. EM dcaplan@partners.org FU NIA NIH HHS [AG09661] NR 13 TC 2 Z9 3 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1069-9384 J9 PSYCHON B REV JI Psychon. Bull. Rev. PD DEC PY 2011 VL 18 IS 6 BP 1203 EP 1211 DI 10.3758/s13423-011-0159-9 PG 9 WC Psychology, Mathematical; Psychology, Experimental SC Psychology GA 850VL UT WOS:000297227500024 PM 21956381 ER PT J AU Sawyer, AM Gooneratne, NS Marcus, CL Ofer, D Richards, KC Weaver, TE AF Sawyer, Amy M. Gooneratne, Nalaka S. Marcus, Carole L. Ofer, Dafna Richards, Kathy C. Weaver, Terri E. TI A systematic review of CPAP adherence across age groups: Clinical and empiric insights for developing CPAP adherence interventions SO SLEEP MEDICINE REVIEWS LA English DT Review DE Obstructive sleep apnea; Continuous positive airway pressure; Patient compliance ID POSITIVE AIRWAY PRESSURE; OBSTRUCTIVE-SLEEP-APNEA; QUALITY-OF-LIFE; LONG-TERM COMPLIANCE; APNOEA/HYPOPNOEA SYNDROME; NASAL CPAP; APNEA/HYPOPNEA SYNDROME; HYPOPNEA-SYNDROME; RANDOMIZED-TRIAL; BREATHING DISORDERS AB Continuous positive airway pressure (CPAP) is a highly efficacious treatment for obstructive sleep apnea (OSA) but adherence to the treatment limits its overall effectiveness across all age groups of patients. Factors that influence adherence to CPAP include disease and patient characteristics, treatment titration procedures, technological device factors and side effects, and psychological and social factors. These influential factors have guided the development of interventions to promote CPAP adherence. Various intervention strategies have been described and include educational, technological, psychosocial, pharmacological, and multi-dimensional approaches. Though evidence to date has led to innovative strategies that address adherence in CPAP-treated children, adults, and older adults, significant opportunities exist to develop and test interventions that are clinically applicable, specific to sub-groups of patients likely to demonstrate poor adherence, and address the multi-factorial nature of CPAP adherence. The translation of CPAP adherence promotion interventions to clinical practice is imperative to improve health and functional outcomes in all persons with,CPAP-treated OSA. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Gooneratne, Nalaka S.] Univ Penn, Sch Med, Div Geriatr Med, Philadelphia, PA 19104 USA. [Sawyer, Amy M.; Richards, Kathy C.] Univ Penn, Sch Nursing, Biobehav Hlth Sci Div, Philadelphia, PA 19104 USA. [Gooneratne, Nalaka S.; Marcus, Carole L.; Ofer, Dafna] Univ Penn, Sch Med, Ctr Sleep & Circadian Neurobiol, Philadelphia, PA 19104 USA. [Richards, Kathy C.] Univ Penn, Sch Nursing, Ctr Integrat Sci Aging, Philadelphia, PA 19104 USA. [Sawyer, Amy M.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Marcus, Carole L.; Ofer, Dafna] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Weaver, Terri E.] Univ Illinois, Coll Nursing, Chicago, IL 60612 USA. RP Sawyer, AM (reprint author), Penn State Univ, Sch Nursing, 201 HHD Bldg E, University Pk, PA 16802 USA. EM ams24@psu.edu; ngoonera@mail.med.upenn.edu; Dafna.ofer@uphs.upenn.edu; kathyr@nursing.upenn.edu; teweaver@uic.edu FU National Institutes of Health, National Institute of Nursing Research [K99NR011173] FX This work was supported by a grant from National Institutes of Health, National Institute of Nursing Research K99NR011173 (Sawyer AM). NR 94 TC 129 Z9 134 U1 1 U2 16 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1087-0792 J9 SLEEP MED REV JI Sleep Med. Rev. PD DEC PY 2011 VL 15 IS 6 BP 343 EP 356 DI 10.1016/j.smrv.2011.01.003 PG 14 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 850WT UT WOS:000297231000002 PM 21652236 ER PT J AU Guirand, AS Dicianno, BE Mahajan, H Cooper, RA AF Guirand, Alcinto S. Dicianno, Brad E. Mahajan, Harshal Cooper, Rory A. TI Tuning Algorithms for Control Interfaces for Users with Upper-Limb Impairments SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE Assistive Technology; Isometric Joystick; Rehabilitation; Movement Disorders; Wheelchairs ID ELECTRIC-POWERED WHEELCHAIRS; ISOMETRIC JOYSTICKS; POSITION; INDIVIDUALS AB Guirand AS, Dicianno BE, Mahajan H, Cooper RA: Tuning algorithms for control interfaces for users with upper-limb impairments. Am J Phys Med Rehabil 2011;90:992-998. Objective: Approximately 40% of Americans with disabilities cannot operate wheeled mobility devices and computers adequately because of diminished upper-limb motor control, sensory limitations, and cognitive impairments. We developed tuning software that can customize control interfaces for individuals with upper-limb impairments. This study compared the differences in each parameter among different diagnostic groups. Design: The age of the subjects ranged from 18 to 80 yrs. The participants were classified into the following groups: athetoid cerebral palsy, spastic cerebral palsy, multiple sclerosis, upper-limb spasticity, and control. We used a validated tuning software protocol to customize an isometric joystick before a virtual tracing or driving task. Tuning parameters were then compared across groups. Results: Seventy-five subjects were included. Gain, the parameter responsible for force-to-output ratios, in each directional axis (leftward gain: P = 0.018; rightward gain: P = 0.003; reverse gain: P = 0.007; forward gain: P = 0.014) was significantly different across the diagnostic groups. Post hoc analyses showed that the control group required smaller leftward gain than spastic cerebral palsy, multiple sclerosis and upper-limb spasticity groups and smaller gain in all other directions compared with spastic cerebral palsy. Conclusions: Gain may be a useful parameter in tuning by clinicians, and efforts aimed at gain customization may aid the development of commercially available tuning software packages. C1 [Guirand, Alcinto S.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Guirand, Alcinto S.; Dicianno, Brad E.; Mahajan, Harshal; Cooper, Rory A.] Highland Drive VA Med Ctr, Human Engn Res Labs, Pittsburgh, PA USA. [Dicianno, Brad E.; Mahajan, Harshal; Cooper, Rory A.] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. [Dicianno, Brad E.; Mahajan, Harshal; Cooper, Rory A.] Univ Pittsburgh, Med Ctr, Dept Phys Med & Rehabil PM&R, Pittsburgh, PA USA. [Dicianno, Brad E.; Mahajan, Harshal; Cooper, Rory A.] VA Pittsburgh Healthcare Syst, Ctr Excellence Wheelchairs & Associated Rehabil E, Pittsburgh, PA USA. RP Dicianno, BE (reprint author), UPMC Dept PM&R, 3471 5th Ave,Suite 202, Pittsburgh, PA 15213 USA. OI Dicianno, Brad/0000-0003-0738-0192 FU NIH [K12 HD001097-09]; VA Center of Excellence for Wheelchairs and Associated Rehabilitation Engineering [B3142C]; VA Merit Review [B3287R]; University of Pittsburgh School of Medicine FX Funded by the Rehabilitation Medicine Scientist Training Program NIH: K12 HD001097-09, the VA Center of Excellence for Wheelchairs and Associated Rehabilitation Engineering (B3142C), VA Merit Review (B3287R), and the University of Pittsburgh School of Medicine Dean's Summer Research Stipend. NR 20 TC 4 Z9 4 U1 3 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD DEC PY 2011 VL 90 IS 12 BP 992 EP 998 DI 10.1097/PHM.0b013e318228ca9f PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 846RX UT WOS:000296922000004 PM 22019961 ER PT J AU Cadena, J Nair, S Henao-Martinez, AF Jorgensen, JH Patterson, JE Sreeramoju, PV AF Cadena, Jose Nair, Shalini Henao-Martinez, Andres F. Jorgensen, James H. Patterson, Jan E. Sreeramoju, Pranavi V. TI Dose of Trimethoprim-Sulfamethoxazole To Treat Skin and Skin Structure Infections Caused by Methicillin-Resistant Staphylococcus aureus SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID SOFT-TISSUE INFECTIONS; CLINDAMYCIN; THERAPY; CEPHALEXIN; TRIAL AB We undertook this study to investigate whether treatment with a higher dose of trimethoprim-sulfamethoxazole (TMP/SMX) led to greater clinical resolution in patients with skin and soft tissue infections (SSTIs) caused by methicillin-resistant Staphylococcus aureus (MRSA). A prospective, observational cohort with nested case-control study was performed at a public tertiary health system. Among patients with MRSA SSTIs during the period from May 2008 to September 2008 who received oral monotherapy with TMP/SMX and whose clinical outcome was known, the clinical characteristics and outcomes were compared between patients treated with a high dose of TMP/SMX (320 mg/1,600 mg twice daily) for 7 to 15 days and patients treated with the standard dose of TMP/SMX (160 mg/800 mg twice daily) for 7 to 15 days. In patients with MRSA SSTIs, those treated with the high dose of TMP/SMX (n = 121) had clinical characteristics similar to those of patients treated with the standard dose of TMP/SMX (n = 170). The only exception was a higher proportion of patients with a history of trauma upon admission among the patients treated with the higher dose. The proportion of patients with clinical resolution of infection was not different in the two groups (88/121 [73%] versus 127/170 [75%]; P = 0.79). The lack of significance remained in patients with abscess upon stratified analysis by whether surgical drainage was performed. The study found that patients with MRSA SSTIs treated with the higher dose of TMP/SMX (320/1,600 mg twice daily) for 7 to 15 days had a similar rate of clinical resolution as patients treated with the standard dose of TMP/SMX (160/800 mg twice daily) for 7 to 15 days. C1 [Sreeramoju, Pranavi V.] Univ Texas SW Med Ctr Dallas, Dept Med Infect Dis, Dallas, TX 75390 USA. [Cadena, Jose; Patterson, Jan E.] S Texas Vet Healthcare Syst, San Antonio, TX USA. [Cadena, Jose; Patterson, Jan E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med Infect Dis, San Antonio, TX 78229 USA. [Nair, Shalini; Henao-Martinez, Andres F.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Jorgensen, James H.; Patterson, Jan E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. RP Sreeramoju, PV (reprint author), Univ Texas SW Med Ctr Dallas, Dept Med Infect Dis, 5323 Harry Hines Blvd,MC 9113, Dallas, TX 75390 USA. EM pranavi.sreeramoju@utsouthwestern.edu RI Henao-Martinez, Andres/E-1488-2012 OI Henao-Martinez, Andres/0000-0001-7363-8652 NR 12 TC 6 Z9 7 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD DEC PY 2011 VL 55 IS 12 BP 5430 EP 5432 DI 10.1128/AAC.00706-11 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 846RJ UT WOS:000296920600002 PM 21930870 ER PT J AU Dai, TH de Arce, VJB Tegos, GP Hamblin, MR AF Dai, Tianhong de Arce, Vida J. Bil Tegos, George P. Hamblin, Michael R. TI Blue Dye and Red Light, a Dynamic Combination for Prophylaxis and Treatment of Cutaneous Candida albicans Infections in Mice SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID PHOTODYNAMIC THERAPY; STAPHYLOCOCCUS-AUREUS; METHYLENE-BLUE; IN-VITRO; PHOTOBACTERICIDAL ACTIVITY; 5-AMINOLEVULINIC ACID; PHENOTHIAZINIUM DYES; INACTIVATION; PHOTOTOXICITY; RESISTANCE AB The objective of this study was to investigate photodynamic therapy (PDT), using blue dye and red light, for prophylaxis and treatment of cutaneous Candida albicans infections in mice. A mouse model of skin abrasion infected with C. albicans was developed by inoculating wounds measuring 1.2 cm by 1.2 cm with 10(6) or 10(7) CFU. The use of a luciferase-expressing strain of C. albicans allowed real-time monitoring of the extent of infection in mice noninvasively through bioluminescence imaging. The phenothiazinium salts toluidine blue O (TBO), methylene blue (MB), and new methylene blue (NMB) were compared as photosensitizers (PS) for the photodynamic inactivation of C. albicans in vitro. PDT in vivo was initiated either at 30 min or at 24 h after fungal inoculation to investigate the efficacies of PDT for both prophylaxis and treatment of infections. Light at 635 +/- 15 nm or 660 +/- 15 nm was delivered with a light dose of 78 J/cm(2) (for PDT at 30 min postinfection) or 120 J/cm(2) (for PDT at 24 h postinfection) in multiple exposures with bioluminescence imaging taking place after each exposure of light. In vitro studies showed that NMB was superior to TBO and MB as the PS in the photodynamic inactivation of C. albicans. The efficacy of PDT was related to the ratio of PS concentration to fungal cell density. PDT in vivo initiated either at 30 min or at 24 h postinfection significantly reduced C. albicans burden in the infected mouse skin abrasion wounds. These data suggest that PDT is a viable approach for prophylaxis and treatment of cutaneous C. albicans infections. C1 [Dai, Tianhong; de Arce, Vida J. Bil; Tegos, George P.; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Dai, Tianhong; Tegos, George P.; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Tegos, George P.] Univ New Mexico, Sch Med, Dept Pathol, Albuquerque, NM 87131 USA. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, 40 Blossom St, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu OI Hamblin, Michael/0000-0001-6431-4605 FU NIH [RO1 AI050875, 5U54MH084690-02]; Airlift Research Foundation [109421] FX This work was supported by the NIH (grant RO1 AI050875 to M.R.H. and grant 5U54MH084690-02 to G.P.T.) and an Airlift Research Foundation Extremity Trauma research grant (grant 109421 to T.D.). NR 36 TC 35 Z9 38 U1 0 U2 12 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD DEC PY 2011 VL 55 IS 12 BP 5710 EP 5717 DI 10.1128/AAC.05404-11 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 846RJ UT WOS:000296920600039 PM 21930868 ER PT J AU Miller, AK Brannon, MK Stevens, L Johansen, HK Selgrade, SE Miller, SI Hoiby, N Moskowitz, SM AF Miller, Amanda K. Brannon, Mark K. Stevens, Laurel Johansen, Helle Krogh Selgrade, Sara E. Miller, Samuel I. Hoiby, Niels Moskowitz, Samuel M. TI PhoQ Mutations Promote Lipid A Modification and Polymyxin Resistance of Pseudomonas aeruginosa Found in Colistin-Treated Cystic Fibrosis Patients SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID 2-COMPONENT REGULATORY SYSTEM; ANTIMICROBIAL PEPTIDE RESISTANCE; ENTERICA SEROVAR TYPHIMURIUM; GRAM-NEGATIVE BACTERIA; ESCHERICHIA-COLI; PMRA-PMRB; ACINETOBACTER-BAUMANNII; OPPORTUNISTIC PATHOGEN; CHRONIC INFECTION; EPIDEMIC STRAIN AB Pseudomonas aeruginosa can develop resistance to polymyxin and other cationic antimicrobial peptides. Previous work has shown that mutations in the PmrAB and PhoPQ regulatory systems can confer low to moderate levels of polymyxin resistance (MICs of 8 to 64 mg/liter) in laboratory and clinical strains of this organism. To explore the role of PhoPQ in high-level clinical polymyxin resistance, P. aeruginosa strains with colistin MICs > 512 mg/liter that had been isolated from cystic fibrosis patients treated with inhaled colistin (polymyxin E) were analyzed. Probable loss-of-function phoQ alleles found in these cystic fibrosis strains conferred resistance to polymyxin. Partial and complete suppressor mutations in phoP were identified in some cystic fibrosis strains with resistance-conferring phoQ mutations, suggesting that additional loci can be involved in polymyxin resistance in P. aeruginosa. Disruption of chromosomal phoQ in the presence of an intact phoP allele stimulated 4-amino-L-arabinose addition to lipid A and induced transcription from the promoter of the pmrH (arnB) operon, consistent with the known role of this lipid A modification in polymyxin resistance. These results indicate that phoQ loss-of-function mutations can contribute to high-level polymyxin resistance in clinical strains of P. aeruginosa. C1 [Moskowitz, Samuel M.] Massachusetts Gen Hosp, Div Pediat Pulm Med, Dept Pediat, Boston, MA 02114 USA. [Miller, Amanda K.; Brannon, Mark K.; Stevens, Laurel; Moskowitz, Samuel M.] Univ Washington, Dept Pediat, Seattle, WA 98195 USA. [Johansen, Helle Krogh; Hoiby, Niels] Copenhagen CF Ctr, Dept Clin Microbiol, Copenhagen, Denmark. [Selgrade, Sara E.; Miller, Samuel I.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Miller, Samuel I.] Univ Washington, Dept Med, Seattle, WA USA. [Miller, Samuel I.] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. [Moskowitz, Samuel M.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Moskowitz, SM (reprint author), Massachusetts Gen Hosp, Div Pediat Pulm Med, Dept Pediat, 175 Cambridge St, Boston, MA 02114 USA. EM smoskowitz@partners.org FU National Heart Lung and Blood Institute [K08HL067903, R01AI067653]; National Institute of Allergy and Infectious Diseases [R01AI030479]; National Institute of Allergy and Infectious Diseases; CF Foundation [MOSKOW01A1] FX This work was supported by Public Health Service grants K08HL067903 to S.M.M. from the National Heart Lung and Blood Institute, R01AI067653 to S.M.M. from the National Institute of Allergy and Infectious Diseases, and R01AI030479 to S.I.M. from the National Institute of Allergy and Infectious Diseases. This work was also supported by grant MOSKOW01A1 to S.M.M. from the CF Foundation. NR 61 TC 52 Z9 52 U1 1 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD DEC PY 2011 VL 55 IS 12 BP 5761 EP 5769 DI 10.1128/AAC.05391-11 PG 9 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 846RJ UT WOS:000296920600046 PM 21968359 ER PT J AU Okumura, R Liao, CH Gavin, M Jacoby, GA Hooper, DC AF Okumura, Ryo Liao, Chun-Hsing Gavin, Mariah Jacoby, George A. Hooper, David C. TI Quinolone Induction of qnrVS1 in Vibrio splendidus and Plasmid-Carried qnrS1 in Escherichia coli, a Mechanism Independent of the SOS System SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID GENE-EXPRESSION; RESISTANCE DETERMINANTS; TRANSCRIPTION; ANTIBIOTICS; EXPOSURE AB Plasmid-carried qnrS1 is derived from Vibrio splendidus chromosomal qnrVS1. qnrVS1 transcripts increased 21- to 34-fold with subinhibitory concentrations of ciprofloxacin but much less with mitomycin. No LexA binding sites were upstream of qnrS1 or qnrVS1, and similar induction levels were observed in lexA-positive and lexA-negative Escherichia coli strains with native qnrS1 plasmid pMG306 but not with pUC18-cloned qnrS1 or qnrVS1. Thus, qnrS1 induction by quinolones is independent of the SOS system and requires sequence besides that of the structural gene. C1 [Okumura, Ryo; Liao, Chun-Hsing; Gavin, Mariah; Hooper, David C.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Okumura, Ryo; Liao, Chun-Hsing; Gavin, Mariah; Hooper, David C.] Harvard Univ, Sch Med, Boston, MA USA. [Okumura, Ryo] Daiichi Sankyo Co Ltd, Biol Res Labs, Tokyo, Japan. [Liao, Chun-Hsing] Far Eastern Mem Hosp, Taipei, Taiwan. [Jacoby, George A.] Lahey Clin Fdn, Burlington, MA USA. RP Hooper, DC (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. EM dhooper@partners.org FU Daiichi Sankyo Co., Ltd., Tokyo, Japan; National Institutes of Health, U.S. Public Health Service [R01 AI057576] FX This work was supported in part by salary support for R.O. from Daiichi Sankyo Co., Ltd., Tokyo, Japan, and by grant R01 AI057576 (to D.C.H. and G.A.J.) from the National Institutes of Health, U.S. Public Health Service. NR 31 TC 7 Z9 7 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD DEC PY 2011 VL 55 IS 12 BP 5942 EP 5945 DI 10.1128/AAC.05142-11 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 846RJ UT WOS:000296920600072 PM 21930884 ER PT J AU Chauhan, D Bandi, M Singh, AV Ray, A Raje, N Richardson, P Anderson, KC AF Chauhan, Dharminder Bandi, Madhavi Singh, Ajita V. Ray, Arghya Raje, Noopur Richardson, Paul Anderson, Kenneth C. TI Preclinical evaluation of a novel SIRT1 modulator SRT1720 in multiple myeloma cells SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE multiple myeloma; apoptosis; microenvironment ID NF-KAPPA-B; VIVO SYNERGISTIC CYTOTOXICITY; DNA-DAMAGE RESPONSE; IN-VIVO; BONE-MARROW; THERAPEUTIC TARGETS; ANTITUMOR-ACTIVITY; CANCER-CELLS; COLON-CANCER; INHIBITOR AB SIRT1 belongs to the silent information regulator 2 (Sir2) protein family of enzymes and functions as a NAD(+)-dependent class III histone deacetylase. Here, we examined the anti-multiple myeloma (MM) activity of a novel oral agent, SRT1720, which targets SIRT1. Treatment of MM cells with SRT1720 inhibited growth and induced apoptosis in MM cells resistant to conventional and bortezomib therapies without significantly affecting the viability of normal cells. Mechanistic studies showed that anti-MM activity of SRT1720 is associated with: (i) activation of caspase-8, caspase-9, caspase-3, poly(ADP) ribose polymerase; (ii) increase in reactive oxygen species; (iii) induction of phosphorylated ataxia telangiectasia mutated/checkpoint kinase 2 signalling; (iv) decrease in vascular endothelial growth factor-induced migration of MM cells and associated angiogenesis; and (v) inhibition of nuclear factor-kappa B. Blockade of ATM attenuated SRT1720-induced MM cell death. In animal tumour model studies, SRT1720 inhibited MM tumour growth. Finally, SRT1720 enhanced the cytotoxic activity of bortezomib or dexamethasone. Our preclinical studies provide the rationale for novel therapeutics targeting SIRT1 in MM. C1 [Chauhan, Dharminder] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. RP Chauhan, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, Mayer Bldg,Room 561,44 Binney St, Boston, MA 02115 USA. EM Dharminder_Chauhan@dfci.harvard.edu; Kenneth_Anderson@dfci.harvard.edu FU National Institutes of Health [SPORE-P50100707, PO1-CA078378, RO1CA050947] FX This investigation was supported by National Institutes of Health grants SPORE-P50100707, PO1-CA078378 and RO1CA050947. KCA is an ACS Clinical Research Professor. NR 57 TC 21 Z9 25 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD DEC PY 2011 VL 155 IS 5 BP 588 EP 598 DI 10.1111/j.1365-2141.2011.08888.x PG 11 WC Hematology SC Hematology GA 848KC UT WOS:000297049500007 PM 21950728 ER PT J AU Sherif, S Susarla, SM Hwang, JW Weber, HP Wright, RF AF Sherif, Sami Susarla, Srinivas M. Hwang, Jae-Woong Weber, Hans-Peter Wright, Robert F. TI Clinician- and patient-reported long-term evaluation of screw- and cement-retained implant restorations: a 5-year prospective study SO CLINICAL ORAL INVESTIGATIONS LA English DT Article DE Dental implant; Screw-retained restoration; Cement-retained restoration; Peri-implant soft-tissue health ID METAL-CERAMIC CROWNS; DENTAL IMPLANTS; MARGINAL DISCREPANCY; TISSUE INTEGRATION; IN-VITRO; SOFT; RETENTION; SYSTEM; SATISFACTION; MULTICENTER AB The purpose of this study was to evaluate the survival and success of screw- versus cement-retained implant crowns over a 5-year period. This was a multi-center prospective cohort study, consisting of patients who had a parts per thousand yen1 dental implant placed and restored in the anterior maxilla over a 5-year period. The primary predictor variable was the type of restoration (screw- versus cement-retained). The outcome variables were clinician- or patient-reported measures related to soft tissue and restoration quality. Descriptive and bivariate statistics were computed to compare the screw- versus cement-retained groups. Kaplan-Meier statistics were computed for implant survival. Information was collected for 102 patients who had 214 implants placed during the study period. Complete data, amenable to analysis, were available for 99 (97.1%) patients and 193 (90.2%) implants. The restorations were approximately evenly divided between screw- (53.4%) and cement-retained (46.6%). Approximately 49% of patients in the sample were female; the sample's mean age was 47.3 +/- 13.9 years; each patient had an average of 2.0 +/- 1.0 implants placed and restored. The mean time from prosthesis placement (definitive) to study endpoint was 61.9 +/- 10.6 months. The overall implant survival rate was 96.4%, with no statistically significant difference in survival between the screw- and cement-retained groups (p = 0.45). The majority of clinician- and patient-assessed outcomes were similar. The results of this study indicate that for the majority of clinician- and patient-assessed success parameters screw- and cement-retained restorations are equivalent in the anterior maxilla. C1 [Susarla, Srinivas M.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Sherif, Sami; Hwang, Jae-Woong; Weber, Hans-Peter; Wright, Robert F.] Harvard Univ, Sch Dent Med, Dept Restorat Dent & Biomat Sci, Boston, MA 02115 USA. RP Susarla, SM (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, WACC230, Boston, MA 02114 USA. EM ssusarla1@partners.org OI Susarla, Srinivas/0000-0003-0155-8260 FU Massachusetts General Hospital Department of Oral and Maxillofacial Surgery FX This study was completed, in part, with the generous support of the Oral and Maxillofacial Surgery Foundation (SMS), the Massachusetts General Hospital Department of Oral and Maxillofacial Surgery Education and Research Fund (SMS) and the Harvard Medical School Office of Enrichment Programs (SS, SMS). NR 37 TC 19 Z9 19 U1 0 U2 11 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1432-6981 J9 CLIN ORAL INVEST JI Clin. Oral Investig. PD DEC PY 2011 VL 15 IS 6 BP 993 EP 999 DI 10.1007/s00784-010-0460-4 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 846EK UT WOS:000296879800018 PM 20809428 ER PT J AU Buijze, GA Mallee, WH Beeres, FJP Hanson, TE Johnson, WO Ring, D AF Buijze, Geert A. Mallee, Wouter H. Beeres, Frank J. P. Hanson, Timothy E. Johnson, Wesley O. Ring, David TI Diagnostic Performance Tests for Suspected Scaphoid Fractures Differ with Conventional and Latent Class Analysis SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID BONE-SCINTIGRAPHY; GOLD STANDARD; COMPUTED-TOMOGRAPHY; SENSITIVITY; RADIOGRAPHY; SPECIFICITY; ACCURACY; ABSENCE; TRAUMA; WRIST AB Evaluation of the diagnostic performance characteristics of radiographic tests for diagnosing a true fracture among suspected scaphoid fractures is hindered by the lack of a consensus reference standard. Latent class analysis is a statistical method that takes advantage of unobserved, or latent, classes in the data that can be used to determine diagnostic performance characteristics when there is no consensus reference (gold) standard. We therefore compared the diagnostic performance characteristics of MRI, CT, bone scintigraphy, and physical examination to identify true fractures among suspected scaphoid fractures. We used data from two studies, one that prospectively studied 34 patients who had MRI and CT of the wrist, and a second that studied 78 patients who had MRI, bone scintigraphy, and structured physical examination. We compared the diagnostic performance characteristics calculated by latent class analysis with those calculated using formulas based on a reference standard. In the first cohort, the calculated sensitivity and specificity with latent class analysis were different than those with traditional reference standard-based calculations for the CT in the scaphoid planes (sensitivity, 0.78 versus 0.67; specificity, 1.0 versus 0.96) and the MRI (sensitivity, 0.80 versus 0.67; specificity, 0.93 versus 0.89). In the second cohort, the greatest differences were in the sensitivity of MRI (0.84 versus 0.75) and the sensitivities of physical examination maneuvers (range, 0.63-0.73 versus 1.0). The diagnostic performance characteristics calculated using latent class analysis may differ from those calculated according to formulas based on a reference standard. We believe latent class analysis merits further study as an option for assessing diagnostic performance characteristics for orthopaedic conditions when there is no consensus reference standard. Level II, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence. C1 [Buijze, Geert A.; Ring, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand & Upper Extrem Serv,Yawkey Ctr, Boston, MA 02114 USA. [Buijze, Geert A.; Mallee, Wouter H.] Univ Amsterdam, Acad Med Ctr, Orthopaed Res Ctr Amsterdam, NL-1105 AZ Amsterdam, Netherlands. [Beeres, Frank J. P.] Med Ctr Haaglanden, Dept Gen Surg, The Hague, Netherlands. [Hanson, Timothy E.] Univ Minnesota, Div Biostat, Minneapolis, MN USA. [Johnson, Wesley O.] Univ Calif Irvine, Dept Stat, Irvine, CA USA. RP Ring, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand & Upper Extrem Serv,Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org RI Hanson, Timothy/A-9127-2016; OI Beeres, Frank/0000-0002-7277-3438 FU Netherlands Organisation for Scientific Research (NWO) FX One author (GAB) received funding from the Netherlands Organisation for Scientific Research (NWO). NR 38 TC 10 Z9 10 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD DEC PY 2011 VL 469 IS 12 BP 3400 EP 3407 DI 10.1007/s11999-011-2074-9 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 844FP UT WOS:000296733400019 PM 21960154 ER PT J AU Bedair, H Ting, N Bozic, KJ Della Valle, CJ Sporer, SM AF Bedair, Hany Ting, Nicholas Bozic, Kevin J. Della Valle, Craig J. Sporer, Scott M. TI Treatment of Early Postoperative Infections after THA: A Decision Analysis SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID TOTAL HIP-ARTHROPLASTY; ONE-STAGE REVISION; TOTAL JOINT ARTHROPLASTY; COST-EFFECTIVENESS; PERIPROSTHETIC INFECTION; UNCEMENTED REVISION; KNEE ARTHROPLASTY; DEEP INFECTION; OPERATING ROOM; FOLLOW-UP AB Background The treatment for an early postoperative periprosthetic infection after cementless THA that results in the highest quality of life after the control of infection is unknown. Although common treatments include irrigation and d,bridement with component retention, a one-stage exchange, or a two-stage exchange, it is unclear whether any of these provides a higher quality of life after the control of infection. Questions/purposes We projected, through decision-analysis modeling, the possible estimated final health states defined as health-related quality of life based on quality-of-life studies of an early postoperative periprosthetic infection after cementless THA treated by irrigation and d,bridement, one-stage exchange, or two-stage exchange. Methods Publications addressing early postoperative infections after THA were analyzed for the estimated rate of infection control and quality-of-life measures after a specific treatment. Decision analysis was used to model the different treatments and describe which, if any, treatment results in the greatest quality of life after early THA infection. Results In the model, a one-stage exchange was the treatment for early THA infection that maximized quality-of-life outcomes if the probability of controlling the infection exceeded 66% with this procedure. If the probability of infection control of a one-stage exchange was less than 66% or that of irrigation and d,bridement was greater than 60%, then irrigation and d,bridement appeared to result in the greatest quality-of-life outcome. Conclusions A decision analysis using estimates of infection control rate and quality-of-life outcomes after different treatments for an early postoperative infection after THA showed possible outcomes for each treatment. C1 [Bedair, Hany] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02115 USA. [Ting, Nicholas; Della Valle, Craig J.; Sporer, Scott M.] Rush Univ, Med Ctr, Dept Orthopaed Surg, Chicago, IL 60612 USA. [Bozic, Kevin J.] Univ Calif San Francisco, Dept Orthopaed Surg, Philip R Lee Inst Hlth Policy, San Francisco, CA USA. RP Bedair, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02115 USA. EM hbedair@gmail.com NR 37 TC 9 Z9 9 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD DEC PY 2011 VL 469 IS 12 BP 3477 EP 3485 DI 10.1007/s11999-011-2119-0 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 844FP UT WOS:000296733400029 PM 21997783 ER PT J AU Bachoura, A Guitton, TG Smith, RM Vrahas, MS Zurakowski, D Ring, D AF Bachoura, Abdo Guitton, Thierry G. Smith, R. Malcolm Vrahas, Mark S. Zurakowski, David Ring, David TI Infirmity and Injury Complexity are Risk Factors for Surgical-site Infection after Operative Fracture Care (vol 469, pg 2621, 2011) SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Correction C1 [Ring, David] Massachusetts Gen Hosp, Yawkey Ctr, Boston, MA 02114 USA. [Bachoura, Abdo; Guitton, Thierry G.; Ring, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand & Upper Extrem Serv, Boston, MA USA. [Smith, R. Malcolm; Vrahas, Mark S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed, Boston, MA USA. [Zurakowski, David] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Anesthesia, Boston, MA USA. [Zurakowski, David] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Surg, Boston, MA USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 1 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD DEC PY 2011 VL 469 IS 12 BP 3513 EP 3514 DI 10.1007/s11999-011-2103-8 PG 2 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 844FP UT WOS:000296733400037 ER PT J AU Liu, J Matulonis, UA AF Liu, Joyce Matulonis, Ursula A. TI Anti-angiogenic Agents in Ovarian Cancer: Dawn of a New Era? SO CURRENT ONCOLOGY REPORTS LA English DT Article DE Ovarian cancer; Anti-angiogenic therapy; VEGF; Bevacizumab; Cediranib; Tyrosine kinase inhibitor (TKI) ID ENDOTHELIAL GROWTH-FACTOR; RECURRENT EPITHELIAL OVARIAN; FALLOPIAN-TUBE CANCER; PHASE-II TRIAL; PERITONEAL CARCINOMA; SERUM VEGF; BEVACIZUMAB; STAGE; PACLITAXEL; SUNITINIB AB Epithelial ovarian cancer is a leading cause of cancer-related death for women both in the United States and worldwide, and the effectiveness of cytotoxic chemotherapy has plateaued. Angiogenesis plays an important role in ovarian cancer biology, and exploration of anti-angiogenic agents in this disease has demonstrated anti-tumor activity both as monotherapy and in combination with cytotoxic chemotherapy. However, key questions remain regarding the use of these drugs in ovarian cancer, such as where in treatment should they be used, should these drugs be used as single agents or combined with chemotherapy, can and which biomarkers predict efficacy, are there efficacy and toxicity differences amongst the various agents, what are the cost-benefit ratios of these therapies, and are the patient outcome improvements observed in completed studies significant enough to warrant widespread use of these drugs? Here, we review recent progress and discuss ongoing controversies regarding the use of anti-angiogenic therapies in ovarian cancer. C1 [Liu, Joyce; Matulonis, Ursula A.] Dana Farber Canc Inst, Boston, MA 02215 USA. RP Liu, J (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM joyce_liu@dfci.harvard.edu; ursula_matulonis@dfci.harvard.edu NR 54 TC 9 Z9 9 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3790 EI 1534-6269 J9 CURR ONCOL REP JI Curr. Oncol. Rep. PD DEC PY 2011 VL 13 IS 6 BP 450 EP 458 DI 10.1007/s11912-011-0194-8 PG 9 WC Oncology SC Oncology GA 846FB UT WOS:000296881500005 PM 21993845 ER PT J AU Schneider, L Giordano, S Zelickson, BR Johnson, MS Benavides, GA Ouyang, XS Fineberg, N Darley-Usmar, VM Zhang, JH AF Schneider, Lonnie Giordano, Samantha Zelickson, Blake R. Johnson, Michelle S. Benavides, Gloria A. Ouyang, Xiaosen Fineberg, Naomi Darley-Usmar, Victor M. Zhang, Jianhua TI Differentiation of SH-SY5Y cells to a neuronal phenotype changes cellular bioenergetics and the response to oxidative stress SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE HNE; DMNQ; Oxidative stress; Cellular bioenergetics; SH-SY5Y; Free radicals ID LIPID-PEROXIDATION PRODUCTS; SPARE RESPIRATORY CAPACITY; CYTOCHROME-C-OXIDASE; IN-VITRO MODEL; HUMAN NEUROBLASTOMA; PARKINSONS-DISEASE; MITOCHONDRIAL RESPIRATION; GLUTAMATE EXCITOTOXICITY; COMPLEX-I; MEMBRANE AB Cell differentiation is associated with changes in metabolism and function. Understanding these changes during differentiation is important in the context of stem cell research, cancer, and neurodegenerative diseases. An early event in neurodegenerative diseases is the alteration of mitochondrial function and increased oxidative stress. Studies using both undifferentiated and differentiated SH-SY5Y neuroblastoma cells have shown distinct responses to cellular stressors; however, the mechanisms remain unclear. We hypothesized that because the regulation of glycolysis and oxidative phosphorylation is modulated during cellular differentiation, this would change bioenergetic function and the response to oxidative stress. To test this, we used retinoic acid (RA) to induce differentiation of SH-SY5Y cells and assessed changes in cellular bioenergetics using extracellular flux analysis. After exposure to RA, the SH-SY5Y cells had an increased mitochondrial membrane potential, without changing mitochondria! number. Differentiated cells exhibited greater stimulation of mitochondrial respiration with uncoupling and an increased bioenergetic reserve capacity. The increased reserve capacity in the differentiated cells was suppressed by the inhibitor of glycolysis 2-deoxy-D-glucose. Furthermore, we found that differentiated cells were substantially more resistant to cytotoxicity and mitochondrial dysfunction induced by the reactive lipid species 4-hydroxynonenal or the reactive oxygen species generator 2,3-dimethoxy-1,4-naphthoquinone. We then analyzed the levels of selected mitochondrial proteins and found an increase in complex IV subunits, which we propose contributes to the increase in reserve capacity in the differentiated cells. Furthermore, we found an increase in MnSOD that could, at least in part, account for the increased resistance to oxidative stress. Our findings suggest that profound changes in mitochondrial metabolism and antioxidant defenses occur upon differentiation of neuroblastoma cells to a neuron-like phenotype. (C) 2011 Elsevier Inc. All rights reserved. C1 [Schneider, Lonnie; Giordano, Samantha; Zelickson, Blake R.; Johnson, Michelle S.; Benavides, Gloria A.; Ouyang, Xiaosen; Darley-Usmar, Victor M.; Zhang, Jianhua] Univ Alabama Birmingham, Dept Pathol, Sch Publ Hlth, Birmingham, AL 35294 USA. [Schneider, Lonnie; Giordano, Samantha; Zelickson, Blake R.; Johnson, Michelle S.; Benavides, Gloria A.; Darley-Usmar, Victor M.; Zhang, Jianhua] Univ Alabama Birmingham, Sch Publ Hlth, Ctr Free Rad Biol, Birmingham, AL 35294 USA. [Ouyang, Xiaosen; Zhang, Jianhua] Birmingham VA Med Ctr, Dept Vet Affairs, Birmingham, AL 35233 USA. [Fineberg, Naomi] Univ Alabama Birmingham, Dept Biostat, Sch Publ Hlth, Birmingham, AL 35294 USA. RP Zhang, JH (reprint author), Univ Alabama Birmingham, Dept Pathol, Sch Publ Hlth, Birmingham, AL 35294 USA. EM zhanja@uab.edu RI zhang, jianhua/D-3404-2009; OI Zhang, Jianhua/0000-0002-2128-9574 FU Michael J. Fox Foundation; NIH [R01-NS064090]; VA merit award; [ES/HL10167]; [DK75865] FX We thank members of Dr. Zhang's and Dr. Darley-Usmar's laboratories for technical help and discussions. We thank Dr. Balu Chacko for help with confocal imaging. This work was supported by ES/HL10167 and DK75865 (to V.M.D.U.), the Michael J. Fox Foundation, NIHR01-NS064090, and a VA merit award (to J.Z.). NR 57 TC 60 Z9 60 U1 2 U2 18 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD DEC 1 PY 2011 VL 51 IS 11 BP 2007 EP 2017 DI 10.1016/j.freeradbiomed.2011.08.030 PG 11 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 848FR UT WOS:000297036500007 PM 21945098 ER PT J AU Wiggs, JL Kang, JH Yaspan, BL Mirel, DB Laurie, C Crenshaw, A Brodeur, W Gogarten, S Olson, LM Abdrabou, W DelBono, E Loomis, S Haines, JL Pasquale, LR AF Wiggs, Janey L. Kang, Jae Hee Yaspan, Brian L. Mirel, Daniel B. Laurie, Cathy Crenshaw, Andrew Brodeur, Wendy Gogarten, Stephanie Olson, Lana M. Abdrabou, Wael DelBono, Elizabeth Loomis, Stephanie Haines, Jonathan L. Pasquale, Louis R. CA Geneva Consortium TI Common variants near CAV1 and CAV2 are associated with primary open-angle glaucoma in Caucasians from the USA SO HUMAN MOLECULAR GENETICS LA English DT Article ID HORMONE REPLACEMENT THERAPY; FEMALE REPRODUCTIVE FACTORS; NITRIC-OXIDE SYNTHASE; INTRAOCULAR-PRESSURE; TRABECULAR MESHWORK; 17-BETA-ESTRADIOL; HERITABILITY; ENDOTHELIUM; ROTTERDAM; MENOPAUSE AB Primary open-angle glaucoma (POAG) is a genetically complex common disease characterized by progressive optic nerve degeneration that results in irreversible blindness. Recently, a genome-wide association study (GWAS) for POAG in an Icelandic population identified significant associations with single nucleotide polymorphisms (SNPs) between the CAV1 and CAV2 genes on chromosome 7q31. In this study, we confirm that the identified SNPs are associated with POAG in our Caucasian US population and that specific haplotypes located in the CAV1/CAV2 intergenic region are associated with the disease. We also present data suggesting that associations with several CAV1/CAV2 SNPs are significant mostly in women. C1 [Wiggs, Janey L.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Kang, Jae Hee] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02114 USA. [Yaspan, Brian L.; Olson, Lana M.; Haines, Jonathan L.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [Mirel, Daniel B.; Crenshaw, Andrew; Brodeur, Wendy] Broad Inst, Boston, MA USA. [Gogarten, Stephanie] Univ Washington, Seattle, WA 98195 USA. RP Wiggs, JL (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM janey_wiggs@meei.harvard.edu RI Haines, Jonathan/C-3374-2012; OI Gogarten, Stephanie/0000-0002-7231-9745 FU NIH GEI [U01HG04424]; [NHGRI U01HG004728]; [NEI R01EY015473]; [NCI CA87969]; [CA49449]; [CA055075]; [R01EY015872] FX This project was supported by grants to Pasquale (NHGRI U01HG004728; NEI R01EY015473; NCI CA87969, CA49449, CA055075; Research to Prevent Blindness Physician Scientist Award; the Margolis Fund (shared with J.L.W.) and J.L.W. (NEI R01EY015872). Genotyping was performed at the Broad Institute of MIT and Harvard, with funding support from the NIH GEI (U01HG04424). The GENEVA Coordinating Center (U01HG004446) provided assistance with genotype cleaning. NR 36 TC 77 Z9 77 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD DEC 1 PY 2011 VL 20 IS 23 BP 4707 EP 4713 DI 10.1093/hmg/ddr382 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 848KD UT WOS:000297049600016 PM 21873608 ER PT J AU Cox, DG Simard, J Sinnett, D Hamdi, Y Soucy, P Ouimet, M Barjhoux, L Verny-Pierre, C McGuffog, L Healey, S Szabo, C Greene, MH Mai, PL Andrulis, IL Thomassen, M Gerdes, AM Caligo, MA Friedman, E Laitman, Y Kaufman, B Paluch, SS Borg, A Karlsson, P Askmalm, MS Bustinza, GB Nathanson, KL Domchek, SM Rebbeck, TR Benitez, J Hamann, U Rookus, MA van den Ouweland, AMW Ausems, MGEM Aalfs, CM van Asperen, CJ Devilee, P Gille, HJJP Peock, S Frost, D Evans, DG Eeles, R Izatt, L Adlard, J Paterson, J Eason, J Godwin, AK Remon, MA Moncoutier, V Gauthier-Villars, M Lasset, C Giraud, S Hardouin, A Berthet, P Sobol, H Eisinger, F de Paillerets, BB Caron, O Delnatte, C Goldgar, D Miron, A Ozcelik, H Buys, S Southey, MC Terry, MB Singer, CF Dressler, AC Tea, MK Hansen, TVO Johannsson, O Piedmonte, M Rodriguez, GC Basil, JB Blank, S Toland, AE Montagna, M Isaacs, C Blanco, I Gayther, SA Moysich, KB Schmutzler, RK Wappenschmidt, B Engel, C Meindl, A Ditsch, N Arnold, N Niederacher, D Sutter, C Gadzicki, D Fiebig, B Caldes, T Laframboise, R Nevanlinna, H Chen, XQ Beesley, J Spurdle, AB Neuhausen, SL Ding, YC Couch, FJ Wang, XS Peterlongo, P Manoukian, S Bernard, L Radice, P Easton, DF Chenevix-Trench, G Antoniou, AC Stoppa-Lyonnet, D Mazoyer, S Sinilnikova, OM AF Cox, David G. Simard, Jacques Sinnett, Daniel Hamdi, Yosr Soucy, Penny Ouimet, Manon Barjhoux, Laure Verny-Pierre, Carole McGuffog, Lesley Healey, Sue Szabo, Csilla Greene, Mark H. Mai, Phuong L. Andrulis, Irene L. Thomassen, Mads Gerdes, Anne-Marie Caligo, Maria A. Friedman, Eitan Laitman, Yael Kaufman, Bella Paluch, Shani S. Borg, Ake Karlsson, Per Askmalm, Marie Stenmark Bustinza, Gisela Barbany Nathanson, Katherine L. Domchek, Susan M. Rebbeck, Timothy R. Benitez, Javier Hamann, Ute Rookus, Matti A. van den Ouweland, Ans M. W. Ausems, Margreet G. E. M. Aalfs, Cora M. van Asperen, Christi J. Devilee, Peter Gille, Hans J. J. P. Peock, Susan Frost, Debra Evans, D. Gareth Eeles, Ros Izatt, Louise Adlard, Julian Paterson, Joan Eason, Jacqueline Godwin, Andrew K. Remon, Marie-Alice Moncoutier, Virginie Gauthier-Villars, Marion Lasset, Christine Giraud, Sophie Hardouin, Agnes Berthet, Pascaline Sobol, Hagay Eisinger, Francois de Paillerets, Brigitte Bressac Caron, Olivier Delnatte, Capucine Goldgar, David Miron, Alex Ozcelik, Hilmi Buys, Saundra Southey, Melissa C. Terry, Mary Beth Singer, Christian F. Dressler, Anne-Catharina Tea, Muy-Kheng Hansen, Thomas V. O. Johannsson, Oskar Piedmonte, Marion Rodriguez, Gustavo C. Basil, Jack B. Blank, Stephanie Toland, Amanda E. Montagna, Marco Isaacs, Claudine Blanco, Ignacio Gayther, Simon A. Moysich, Kirsten B. Schmutzler, Rita K. Wappenschmidt, Barbara Engel, Christoph Meindl, Alfons Ditsch, Nina Arnold, Norbert Niederacher, Dieter Sutter, Christian Gadzicki, Dorothea Fiebig, Britta Caldes, Trinidad Laframboise, Rachel Nevanlinna, Heli Chen, Xiaoqing Beesley, Jonathan Spurdle, Amanda B. Neuhausen, Susan L. Ding, Yuan C. Couch, Fergus J. Wang, Xianshu Peterlongo, Paolo Manoukian, Siranoush Bernard, Loris Radice, Paolo Easton, Douglas F. Chenevix-Trench, Georgia Antoniou, Antonis C. Stoppa-Lyonnet, Dominique Mazoyer, Sylvie Sinilnikova, Olga M. CA Ontario Canc Genetics Network SWE-BRCA Collaborators HEBON EMBRACE GEMO Study Collaborators Breast Canc Family Registry Consortium Investigators Modifiers TI Common variants of the BRCA1 wild-type allele modify the risk of breast cancer in BRCA1 mutation carriers SO HUMAN MOLECULAR GENETICS LA English DT Article ID OVARIAN-CANCER; GENE-EXPRESSION; MUTAGEN SENSITIVITY; CHROMOSOMAL RADIOSENSITIVITY; SUSCEPTIBILITY GENES; ASSOCIATION; PROMOTER; PREDISPOSITION; TRANSCRIPTION; SUBSTITUTIONS AB Mutations in the BRCA1 gene substantially increase a woman's lifetime risk of breast cancer. However, there is great variation in this increase in risk with several genetic and non-genetic modifiers identified. The BRCA1 protein plays a central role in DNA repair, a mechanism that is particularly instrumental in safeguarding cells against tumorigenesis. We hypothesized that polymorphisms that alter the expression and/or function of BRCA1 carried on the wild-type (non-mutated) copy of the BRCA1 gene would modify the risk of breast cancer in carriers of BRCA1 mutations. A total of 9874 BRCA1 mutation carriers were available in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) for haplotype analyses of BRCA1. Women carrying the rare allele of single nucleotide polymorphism rs16942 on the wild-type copy of BRCA1 were at decreased risk of breast cancer (hazard ratio 0.86, 95% confidence interval 0.77-0.95, P = 0.003). Promoter in vitro assays of the major BRCA1 haplotypes showed that common polymorphisms in the regulatory region alter its activity and that this effect may be attributed to the differential binding affinity of nuclear proteins. In conclusion, variants on the wild-type copy of BRCA1 modify risk of breast cancer among carriers of BRCA1 mutations, possibly by altering the efficiency of BRCA1 transcription. C1 [Cox, David G.; Barjhoux, Laure; Verny-Pierre, Carole; Mazoyer, Sylvie; Sinilnikova, Olga M.] Univ Lyon 1, Canc Res Ctr Lyon, CNRS UMR5286, INSERM,U1052, F-69365 Lyon, France. [Cox, David G.] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England. [Simard, Jacques; Hamdi, Yosr; Soucy, Penny] Ctr Hosp Univ Quebec, Canc Genom Lab, Quebec City, PQ, Canada. [Simard, Jacques; Hamdi, Yosr; Soucy, Penny; Laframboise, Rachel] Univ Laval, Quebec City, PQ, Canada. [Sinnett, Daniel; Ouimet, Manon] St Justine Univ Hlth Ctr, Div Hematol Oncol, Res Ctr, Montreal, PQ, Canada. [Sinnett, Daniel] Univ Montreal, Dept Pediat, Fac Med, Montreal, PQ H3C 3J7, Canada. [McGuffog, Lesley; Peock, Susan; Frost, Debra; Easton, Douglas F.; Antoniou, Antonis C.; EMBRACE] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge CB2 1TN, England. [Healey, Sue; Chen, Xiaoqing; Beesley, Jonathan; Spurdle, Amanda B.; Chenevix-Trench, Georgia] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Szabo, Csilla] Univ Delaware, Newark, DE USA. [Greene, Mark H.; Mai, Phuong L.] US Natl Canc Inst, Clin Genet Branch, Rockville, MD USA. [Andrulis, Irene L.] Univ Toronto, Dept Mol Genet & Lab Med & Pathobiol, Toronto, ON M5S 1A1, Canada. [Andrulis, Irene L.; Ozcelik, Hilmi] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Fred A Litwin Ctr Canc Genet, Toronto, ON M5G 1X5, Canada. [Thomassen, Mads] Odense Univ Hosp, Dept Clin Genet, Odense, Denmark. [Gerdes, Anne-Marie] Copenhagen Univ Hosp, Dept Clin Genet, Copenhagen, Denmark. [Hansen, Thomas V. O.] Copenhagen Univ Hosp, Ctr Genom Med, Rigshosp, Copenhagen, Denmark. [Caligo, Maria A.] Univ Hosp Pisa, Sect Genet Oncol, Pisa, Italy. [Friedman, Eitan; Laitman, Yael] Chaim Sheba Med Ctr, Susanne Levy Gertner Oncogenet Unit, IL-52621 Tel Hashomer, Israel. [Kaufman, Bella] Chaim Sheba Med Ctr, Inst Oncol, IL-52621 Tel Hashomer, Israel. [Friedman, Eitan; Kaufman, Bella; Paluch, Shani S.] Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel. [Borg, Ake] Univ Lund Hosp, Dept Oncol, S-22185 Lund, Sweden. [Karlsson, Per] Sahlgrens Univ Hosp, Dept Oncol, Gothenburg, Sweden. [Askmalm, Marie Stenmark] Linkoping Univ Hosp, Dept Oncol, S-58185 Linkoping, Sweden. [Bustinza, Gisela Barbany] Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden. [Nathanson, Katherine L.; Domchek, Susan M.; Rebbeck, Timothy R.] Univ Penn, Abramson Canc Ctr, Perelman Sch Med, Philadelphia, PA 19104 USA. [Benitez, Javier] Spanish Natl Canc Res Ctr, Human Canc Genet Programme, Human Genet Grp & Genotyping Unit, Madrid, Spain. [Benitez, Javier] Spanish Natl Canc Res Ctr, Spanish Network Rare Dis CIBERER, Madrid, Spain. [Hamann, Ute] Deutsch Krebsforschungszentrum, D-6900 Heidelberg, Germany. [Rookus, Matti A.] Netherlands Canc Inst, Dept Epidemiol, Amsterdam, Netherlands. [van den Ouweland, Ans M. W.] Erasmus Univ, Med Ctr, Dept Clin Genet, Family Canc Clin, Rotterdam, Netherlands. [Ausems, Margreet G. E. M.] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands. [Aalfs, Cora M.] Univ Amsterdam, Acad Med Ctr, Dept Clin Genet, NL-1105 AZ Amsterdam, Netherlands. [van Asperen, Christi J.] Leiden Univ, Med Ctr, Dept Clin Genet, Leiden, Netherlands. [Devilee, Peter] Leiden Univ, Med Ctr, Dept Human Genet, Leiden, Netherlands. [Devilee, Peter] Leiden Univ, Med Ctr, Dept Pathol, Leiden, Netherlands. [Gille, Hans J. J. P.] Vrije Univ Amsterdam Med Ctr, Dept Clin Genet, Amsterdam, Netherlands. [Evans, D. Gareth] Cent Manchester Univ Hosp NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England. [Eeles, Ros] Inst Canc Res, Oncogenet Team, Surrey, England. [Eeles, Ros] Royal Marsden NHS Fdn Trust, Surrey, England. [Izatt, Louise] Guys & St Thomas NHS Fdn Trust, London, England. [Adlard, Julian] Yorkshire Reg Genet Serv, Leeds, W Yorkshire, England. [Paterson, Joan] Addenbrookes Hosp, Dept Clin Genet, E Anglian Reg Genet Serv, Cambridge, England. [Eason, Jacqueline] Nottingham Univ Hosp NHS Trust, Nottingham Clin Genet Serv, Nottingham, England. [Godwin, Andrew K.] Fox Chase Canc Ctr, Womens Canc Program, Philadelphia, PA 19111 USA. [Remon, Marie-Alice; Moncoutier, Virginie; Gauthier-Villars, Marion; Stoppa-Lyonnet, Dominique] Inst Curie, Serv Genet Oncol, Paris, France. [Stoppa-Lyonnet, Dominique] Inst Curie, Unite INSERM U830, Paris, France. [Lasset, Christine] Univ Lyon 1, CNRS UMR5558, F-69365 Lyon, France. [Lasset, Christine] Ctr Leon Berard, Unite Prevent & Epidemiol Genet, F-69373 Lyon, France. [Giraud, Sophie; Sinilnikova, Olga M.] Ctr Leon Berard, Ctr Hosp Univ Lyon, Unite Mixte Genet Constitut Canc Frequents, F-69373 Lyon, France. [Hardouin, Agnes; Berthet, Pascaline] Ctr Francois Baclesse, Caen, France. [Sobol, Hagay] Univ Aix Marseille 2, Dept Oncol Genet Prevent & Depistage, Inst Paoli Calmettes, INSERM CIC P9502, F-13284 Marseille 07, France. [Eisinger, Francois] Inst Paoli Calmettes, Canc Control Dept, Marseille, France. [Caron, Olivier] Inst Cancerol Gustave Roussy, Dept Med, Villejuif, France. [de Paillerets, Brigitte Bressac] Inst Cancerol Gustave Roussy, Dept Genet, Villejuif, France. [de Paillerets, Brigitte Bressac] Fdn Jean Dausset, INSERM U946, Paris, France. [Delnatte, Capucine] Ctr Rene Gauducheau, Serv Oncol Med, F-44035 Nantes, France. [Goldgar, David] Univ Utah, Sch Med, Dept Dermatol, Salt Lake City, UT USA. [Miron, Alex] Dana Farber Canc Inst, Boston, MA 02115 USA. [Buys, Saundra] Univ Utah, Hlth Sci Ctr, Huntsman Canc Inst, Salt Lake City, UT USA. [Southey, Melissa C.] Univ Melbourne, Dept Pathol, Melbourne, Vic 3010, Australia. [Terry, Mary Beth] Columbia Univ, Dept Epidemiol, New York, NY USA. [Breast Canc Family Registry] Med Univ Vienna, Breast Canc Family Registry, Vienna, Austria. [Singer, Christian F.; Dressler, Anne-Catharina; Tea, Muy-Kheng] Med Univ Vienna, Dept OB GYN, Vienna, Austria. [Singer, Christian F.; Dressler, Anne-Catharina; Tea, Muy-Kheng] Med Univ Vienna, Ctr Comprehens Canc, Vienna, Austria. [Johannsson, Oskar] Univ Iceland, Dept Oncol, Landspitali Univ Hosp, Reykjavik, Iceland. [Johannsson, Oskar] Univ Iceland, Fac Med, Reykjavik, Iceland. [Piedmonte, Marion] Roswell Pk Canc Inst, Stat & Data Ctr, Buffalo, NY 14263 USA. [Moysich, Kirsten B.] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA. [Rodriguez, Gustavo C.] Univ Chicago, Dept Obstet & Gynecol, Northshore Univ Healthsyst, Chicago, IL 60637 USA. [Basil, Jack B.] Good Samaritan Hosp, Dept Obstet & Gynecol, Cincinnati, OH USA. [Blank, Stephanie] NYU, Sch Med, Dept Obstet & Gynecol, New York, NY USA. [Toland, Amanda E.] Ohio State Univ, Dept Mol Virol, Columbus, OH 43210 USA. [Toland, Amanda E.] Ohio State Univ, Dept Immunol & Med Genet, Columbus, OH 43210 USA. [Toland, Amanda E.] Ohio State Univ, Dept Internal Med, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Montagna, Marco] Inst Oncol Veneto IOV IRCCS, Immunol & Mol Oncol Unit, Padua, Italy. [Isaacs, Claudine] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. [Blanco, Ignacio] Catalan Inst Oncol, Hereditary Canc Program, Genet Counseling Unit, Barcelona, Spain. [Gayther, Simon A.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Schmutzler, Rita K.; Wappenschmidt, Barbara] Univ Hosp Cologne, Dept Obstet & Gynaecol, Ctr Familial Breast & Ovarian Canc, Cologne, Germany. [Schmutzler, Rita K.; Wappenschmidt, Barbara] Univ Hosp Cologne, Ctr Integrated Oncol, Cologne, Germany. [Engel, Christoph] Univ Leipzig, Inst Med Informat Stat & Epidemiol, Leipzig, Germany. [Meindl, Alfons] Tech Univ Munich, Klinikum Rechts Isar, Div Tumor Genet, Dept Obstet & Gynaecol, D-8000 Munich, Germany. [Ditsch, Nina] Univ Munich, Dept Obstet & Gynaecol, Munich, Germany. [Arnold, Norbert] Univ Kiel, Univ Hosp Schleswig Holstein, Dept Obstet & Gynaecol, D-24098 Kiel, Germany. [Niederacher, Dieter] Univ Dusseldorf, Univ Hosp Dusseldorf, Dept Obstet & Gynaecol, D-4000 Dusseldorf, Germany. [Sutter, Christian] Univ Heidelberg, Div Mol Genet, Inst Human Genet, D-6900 Heidelberg, Germany. [Gadzicki, Dorothea] Hannover Med Sch, Inst Cell & Mol Pathol, D-3000 Hannover, Germany. [Fiebig, Britta] Univ Regensburg, Inst Human Genet, D-8400 Regensburg, Germany. [Caldes, Trinidad] Hosp Clin San Carlos, Mol Oncol Lab, Madrid, Spain. [Laframboise, Rachel] Ctr Hosp Univ Quebec, Div Med Genet, Quebec City, PQ, Canada. [Nevanlinna, Heli] Helsinki Univ Cent Hosp, Dept Obstet & Gynecol, Helsinki, Finland. [Neuhausen, Susan L.; Ding, Yuan C.] Beckman Res Inst City Hope, Dept Populat Sci, Duarte, CA USA. [Couch, Fergus J.; Wang, Xianshu] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Peterlongo, Paolo; Radice, Paolo] Fdn IRCCS Ist Nazl Tumori INT, Unit Mol Bases Genet Risk & Genet Testing, Milan, Italy. [Manoukian, Siranoush] Fdn IRCCS Ist Nazl Tumori INT, Unit Med Genet, Dept Prevent & Predicted Med, Milan, Italy. [Peterlongo, Paolo; Radice, Paolo] Fdn Ist FIRC Oncol Mol, Milan, Italy. [Bernard, Loris] Ist Europeo Oncol IEO, Div Expt Oncol, Milan, Italy. [Bernard, Loris] Cogentech, Consortium Genom Technol, Milan, Italy. [Stoppa-Lyonnet, Dominique] Univ Paris 05, Fac Med, Paris, France. RP Sinilnikova, OM (reprint author), Univ Lyon 1, Canc Res Ctr Lyon, CNRS UMR5286, INSERM,U1052, F-69365 Lyon, France. EM olga.sinilnikova@lyon.unicancer.fr RI Ligtenberg, Marjolijn/N-9666-2013; manoukian, siranoush/E-7132-2017; Rahman, Nazneen/D-2802-2013; Spurdle, Amanda/A-4978-2011; Cox, David/A-2023-2009; Arnold, Norbert/E-3012-2010; Toland, Amanda/E-4202-2011; Hoogerbrugge, Nicoline/O-1016-2013; Radice, Paolo/O-3119-2013; Blanco, Ignacio/D-2565-2013; Ditsch, Nina/F-6267-2014; Oosterwijk, Jan C./G-5770-2011; Bernard, Loris/K-5953-2014; Ehrencrona, Hans/M-5619-2014; GLADIEFF, Laurence/O-5129-2014; montagna, marco/E-2225-2012; Andrulis, Irene/E-7267-2013 OI Nevanlinna, Heli/0000-0002-0916-2976; Jacobs, Chris/0000-0002-9557-9080; VENAT-BOUVET, Laurence/0000-0002-0716-2550; Evans, Gareth/0000-0002-8482-5784; Ligtenberg, Marjolijn/0000-0003-1290-1474; manoukian, siranoush/0000-0002-6034-7562; Nordling, Margareta/0000-0002-4047-4994; Nathanson, Katherine/0000-0002-6740-0901; Rahman, Nazneen/0000-0003-4376-0440; Barton, David E/0000-0002-2031-9719; Eeles, Rosalind/0000-0002-3698-6241; Spurdle, Amanda/0000-0003-1337-7897; Cox, David/0000-0002-2152-9259; Arnold, Norbert/0000-0003-4523-8808; Blanco, Ignacio/0000-0002-7414-7481; Ehrencrona, Hans/0000-0002-5589-3622; GLADIEFF, Laurence/0000-0002-6980-9719; montagna, marco/0000-0002-4929-2150; FU US National Cancer Institute; Westat, Inc., Rockville, MD [NO2-CP-11019-50, N02-CP-65504]; Cancer Care Ontario; Fundacion Mutua Madrilena; Asociacion Espanola Contra el Cancer; Spanish Ministry of Science and Innovation [FIS PI08 1120]; DKFZ; Dutch Cancer Society [NKI1998-1854, NKI2004-3088, NKI2007-3756]; ZonMW [91109024]; Cancer Research UK [C1287/A10118, C1287/A11990, C5047/A8385]; NIHR; Royal Marsden NHS Foundation Trust; Eileen Stein Jacoby Fund; Ligue National Contre le Cancer; Association for International Cancer Research [AICR-07-0454]; Association 'Le cancer du sein, parlons-en!'; National Cancer Institute, National Institutes of Health [RFA-CA-06-503]; BCFR; Cancer Care Ontario [U01 CA69467]; Columbia University [U01 CA69398]; Fox Chase Cancer Center [U01 CA69631]; Huntsman Cancer Institute [U01 CA69446]; Northern California Cancer Center [U01 CA69417]; University of Melbourne [U01 CA69638]; Georgetown University Informatics Support Center (RFP) [N02PC45022-46]; NEYE; NCI; GOG's Cancer Prevention and Control Committee; OSU Comprehensive Cancer Center; Ministero dell'Universitae della Ricerca (MIUR); Ministero della Salute (P.I.O. V and 'Progetto Tumori Femminili'); Alleanza Contro il Cancro; CRUK; German Cancer Aid [107054]; Helsinki University; Academy of Finland [132473]; Finnish Cancer Society; Sigrid Juselius Foundation; National Health and Medical Research Council (NHMRC) [145684, 288704, 454508]; National Breast Cancer Foundation; Queensland Cancer Fund; Cancer Councils of New South Wales, Victoria, Tasmania and South Australia; Cancer Foundation of Western Australia; Breast Cancer Research Foundation (BCRF); Komen Foundation for the Cure; Department of Defense [W81XWH-10-1-0341]; US National Cancer Institute, National Institutes of Health [CA128978]; Familial Cancer Registry; Tissue Culture Shared Registry at Georgetown University (NIH/NCI) [P30-CA051008]; Cancer Genetics Network [HHSN261200744000C]; Swing Fore the Cure; Breast Cancer Research Foundation; Susan G. Komen Foundation; Instituto de Salud Carlos III [RD06/0020/0021]; European Community [223175 (HEALTH-F2-2009-223175)]; INSERM/INCa; LIGUE CONTRE LE CANCER; Canadian Institutes of Health Research; Canadian Breast Cancer Research Alliance [019511]; [R01CA140323]; [U01CA69631]; [5U01CA113916]; [NIH CA74415]; [R01-CA083855]; [R01-CA102776] FX National Cancer Institute (NCI): The research of Drs PL Mai and MH Greene was supported by the Intramural Research Program of the US National Cancer Institute, and by support services contracts NO2-CP-11019-50 and N02-CP-65504 with Westat, Inc., Rockville, MD.; Ontario Cancer Genetics Network (OCGN): We wish to thank Gord Glendon, Teresa Selander, Nayana Weerasooriya and members of the Ontario Cancer Genetics Network for their contributions to the study. The OCGN is supported by Cancer Care Ontario.; Spanish National Cancer Centre (CNIO): This study was partially supported by Fundacion Mutua Madrilena, Asociacion Espanola Contra el Cancer and the Spanish Ministry of Science and Innovation (FIS PI08 1120).; Deutsches Krebsforschungszentrum (DKFZ): The DKFZ study was supported by the DKFZ. We thank Diana Torres and Muhammad U. Rashid for providing DNA samples and supplying data. We thank Antje Seidel-Renkert for expert technical assistance.; The Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON): HEBON Collaborating Centers: Coordinating center: Netherlands Cancer Institute, Amsterdam, NL: F. B. L. Hogervorst, S. Verhoef, M. Verheus, L.J. van't Veer, F. E. van Leeuwen, M. A. Rookus; Erasmus Medical Center, Rotterdam, NL: M. Collee, A. M. W. van den Ouweland, A. Jager, M.J. Hooning, M. M. A. Tilanus-Linthorst, C. Seynaeve; Leiden University Medical Center, NL, Leiden: C.J. van Asperen, J.T. Wijnen, M. P. Vreeswijk, R. A. Tollenaar, P. Devilee; Radboud University Nijmegen Medical Center, Nijmegen, NL: M.J. Ligtenberg, N. Hoogerbrugge; University Medical Center Utrecht, Utrecht, NL: M. G. Ausems, R. B. van der Luijt; Amsterdam Medical Center, NL: C. M. Aalfs, T. A. van Os; VU University Medical Center, Amsterdam, NL: J.J.P. Gille, Q. Waisfisz, H.E.J. Meijers-Heijboer; University Hospital Maastricht, Maastricht, NL: E. B. Gomez-Garcia, C. E. van Roozendaal, Marinus J. Blok, B. Caanen; University Medical Center Groningen University, NL: J. C. Oosterwijk, A. H. van der Hout, M. J. Mourits; The Netherlands Foundation for the Detection of Hereditary Tumours, Leiden, NL: H. F. Vasen. The HEBON study is supported by the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756 and the ZonMW grant 91109024.; Epidemiological study of BRCA1 & BRCA2 mutation carriers (EMBRACE): Douglas F. Easton is the PI of the study. EMBRACE Collaborating Centers are: Coordinating Centre, Cambridge: Susan Peock, Margaret Cook, Debra Frost, Radka Platte. North of Scotland Regional Genetics Service, Aberdeen: Zosia Miedzybrodzka, Helen Gregory. Northern Ireland Regional Genetics Service, Belfast: Patrick Morrison, Lisa Jeffers. West Midlands Regional Clinical Genetics Service, Birmingham: Trevor Cole, Kai-ren Ong, Jonathan Hoffman. South West Regional Genetics Service, Bristol: Alan Donaldson, Margaret James. East Anglian Regional Genetics Service, Cambridge: Joan Paterson, Sarah Downing, Amy Taylor. Medical Genetics Services for Wales, Cardiff: Alexandra Murray, Mark T. Rogers, Emma McCann. St James's Hospital, Dublin & National Centre for Medical Genetics, Dublin: M. John Kennedy, David Barton. South East of Scotland Regional Genetics Service, Edinburgh: Mary Porteous, Sarah Drummond. Peninsula Clinical Genetics Service, Exeter: Carole Brewer, Emma Kivuva, Anne Searle, Selina Goodman, Kathryn Hill. West of Scotland Regional Genetics Service, Glasgow: Rosemarie Davidson, Victoria Murday, Nicola Bradshaw, Lesley Snadden, Mark Longmuir, Catherine Watt, Sarah Gibson, Eshika Haque, Ed Tobias, Alexis Duncan. South East Thames Regional Genetics Service, Guy's Hospital London: Louise Izatt, Chris Jacobs, Caroline Langman, Anna Whaite. North West Thames Regional Genetics Service, Harrow: Huw Dorkins. Leicestershire Clinical Genetics Service, Leicester: Julian Barwell. Yorkshire Regional Genetics Service, Leeds: Julian Adlard, Carol Chu, Julie Miller. Merseyside & Cheshire Clinical Genetics Service, Liverpool: Ian Ellis, Catherine Houghton. Manchester Regional Genetics Service, Manchester: D Gareth Evans, Fiona Lalloo, Jane Taylor. North East Thames Regional Genetics Service, NE Thames, London: Lucy Side, Alison Male, Cheryl Berlin. Nottingham Centre for Medical Genetics, Nottingham: Jacqueline Eason, Rebecca Collier. Northern Clinical Genetics Service, Newcastle: Fiona Douglas, Oonagh Claber, Irene Jobson. Oxford Regional Genetics Service, Oxford: Lisa Walker, Diane McLeod, Dorothy Halliday, Sarah Durell, Barbara Stayner. The Institute of Cancer Research and Royal Marsden NHS Foundation Trust: Ros Eeles, Susan Shanley, Nazneen Rahman, Richard Houlston, Elizabeth Bancroft, Lucia D'Mello, Elizabeth Page, Audrey Ardern-Jones, Kelly Kohut, Jennifer Wiggins, Elena Castro, Anita Mitra, Lisa Robertson. North Trent Clinical Genetics Service, Sheffield: Jackie Cook, Oliver Quarrell, Cathryn Bardsley. South West Thames Regional Genetics Service, London: Shirley Hodgson, Sheila Goff, Glen Brice, Lizzie Winchester, Charlotte Eddy, Vishakha Tripathi, Virginia Attard. Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton: Diana Eccles, Anneke Lucassen, Gillian Crawford, Donna McBride, Sarah Smalley. EMBRACE is supported by Cancer Research UK Grants C1287/A10118 and C1287/A11990. D. Gareth Evans and Fiona Lalloo are supported by an NIHR grant to the Biomedical Research Centre, Manchester. The Investigators at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust are supported by an NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. Ros Eeles, Elizabeth Bancroft and Lucia D'Mello are also supported by Cancer Research UK Grant C5047/A8385.; Fox Chase Cancer Centre (FCCC): University of Kansas Medical Center (KUMC): A. K. G. was funded by R01CA140323, U01CA69631, 5U01CA113916, and the Eileen Stein Jacoby Fund.; Genetic Modifiers of cancer risk in BRCA1/2 mutation carriers (GEMO) study: Cancer Genetics Network 'Groupe Geneetique et Cancer', Federation Nationale des Centres de Lutte Contre le Cancer, France. The study was supported by the Ligue National Contre le Cancer; Association for International Cancer Research Grant (AICR-07-0454); and the Association 'Le cancer du sein, parlons-en!' Award. We wish to thank all the GEMO collaborating groups for their contribution to this study. GEMO Collaborating Centers are: Coordinating Centres, Unite Mixte de Genetique Constitutionnelle des Cancers Frequents, Centre Hospitalier Universitaire de Lyon/Centre Leon Berard, & Equipe "Genetique du cancer du sein", Centre de Recherche en Cancerologie de Lyon, Lyon: Olga Sinilnikova, Laure Barjhoux, Carole Verny-Pierre, Sophie Giraud, Melanie Leone, Sylvie Mazoyer; and Service de Genetique Oncologique, Institut Curie, Paris: Dominique Stoppa-Lyonnet, Marion Gauthier-Villars, Bruno Buecher, Claude Houdayer, Virginie Moncoutier, Muriel Belotti, Carole Tirapo, Antoine de Pauw. Institut Gustave Roussy, Villejuif: Brigitte Bressac-de-Paillerets, Audrey Remenieras, Veronique Byrde, Olivier Caron, Gilbert Lenoir. Centre Jean Perrin, Clermont-Ferrand: Yves-Jean Bignon, Nancy Uhrhammer. Centre Leon Berard, Lyon: Christine Lasset, Valerie Bonadona. Centre Francois Baclesse, Caen: Agnes Hardouin, Pascaline Berthet. Institut Paoli Calmettes, Marseille: Hagay Sobol, Violaine Bourdon, Tetsuro Noguchi, Francois Eisinger. Groupe Hospitalier Pitie-Salpetriere, Paris: Florence Coulet, Chrystelle Colas, Florent Soubrier. CHU de Arnaud-de-Villeneuve, Montpellier: Isabelle Coupier, Pascal Pujol. Centre Oscar Lambret, Lille: JeanPhilippe Peyrat, Joelle Fournier, Francoise Revillion, Philippe Vennin, Claude Adenis. Hopital Rene Huguenin/Institut Curie, St Cloud: Etienne Rouleau, Rosette Lidereau, Liliane Demange, Catherine Nogues. Centre Paul Strauss, Strasbourg: Daniele Muller, Jean-Pierre Fricker. Institut Bergonie, Bordeaux: Michel Longy, Nicolas Sevenet. Institut Claudius Regaud, Toulouse: Christine Toulas, Rosine Guimbaud, Laurence Gladieff, Viviane Feillel. CHU de Grenoble: Dominique Leroux, Helene Dreyfus, Christine Rebischung. CHU de Dijon: Fanny Coron, Laurence Faivre. CHU de St-Etienne: Fabienne Prieur, Marine Lebrun. Hotel Dieu Centre Hospitalier, Chambery: Sandra Fert Ferrer. Centre Antoine Lacassagne, Nice: Marc Frenay. CHU de Limoges: Laurence Venat-Bouvet. CHU de Nantes: Capucine Delnatte. CHU Bretonneau, Tours: Isabelle Mortemousque. Creighton University, Omaha, USA: Henry T. Lynch, Carrie L. Snyder.; The Breast Cancer Family Registry (BCFR): BCFR is supported by the National Cancer Institute, National Institutes of Health under RFA-CA-06-503 and through cooperative agreements with members of the BCFR and Principal Investigators, including Cancer Care Ontario (U01 CA69467), Columbia University (U01 CA69398), Fox Chase Cancer Center (U01 CA69631), Huntsman Cancer Institute (U01 CA69446), Northern California Cancer Center (U01 CA69417), University of Melbourne (U01 CA69638) and the Georgetown University Informatics Support Center (RFP No. N02PC45022-46). Samples from the NCCC, FCCC and HCI were processed and distributed by the Coriell Institute for Medical Research. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the BCFR, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government or the BCFR.; Copenhagen Breast Cancer Study (CBCS): We would like to thank Bent Ejlertsen, Mette K. Andersen, and Susanne Kjaergaard for clinical data. Moreover, we thank the NEYE Foundation for financial support.; Gynecologic Oncology Group (GOG): GOG's participation was supported through funding provided by both intramural (Clinical Genetics Branch, DCEG) and extramural (Community Oncology and Prevention Trials Program, COPTRG) NCI programs, as well as by GOG's Cancer Prevention and Control Committee.; Ohio State University Clinical Cancer Center (OSU CCG): We thank Leigha Senter and Kevin Sweet for accrual of study participants and Michelle O'Connor and Caroline Craven for database entry. The OSU Human Genetics Sample Bank processed DNA samples and the OSU CCC Nucleic Acids Shared Resource performed the Taqman Plate Reads. This work was supported by funds from the OSU Comprehensive Cancer Center.; Istituto Oncologico Veneto-Hereditary Breast Ovarian Cancer Study (IOVHBOCS): The study was supported by the Ministero dell'Universitae della Ricerca (MIUR), Ministero della Salute (P.I.O. V and 'Progetto Tumori Femminili') and Alleanza Contro il Cancro.; UK and Gilda Radner Familial Ovarian Cancer Registries (UKGRFOCR): UKFOCR was supported by a project grant from CRUK to Paul Pharoah. We thank Paul Pharoah, Susan Ramus, Carole Pye, Patricia Harrington and Eva Wozniak for their contributions towards the UKFOCR. We'd like to acknowledge the Roswell Park Alliance Foundation for their continued support of the Gilda Radner Ovarian Family Cancer Registry. GRFOCR would like to acknowledge Lara Sucheston (Department of Cancer Prevention and Control) and Kunle Odunsi (Departments Gynecologic Oncology and Immunology).; The German Consortium of Hereditary Breast and Ovarian Cancer (GC-HBOC): GC- HBOC is supported by a grant of the German Cancer Aid (grant 107054). We thank Raymonda Varon-Mateeva (Center Berlin), Karin Kast (Center Dresden), Sabine Preisler-Adams (Center Munster), Helmut Deissler (Center Ulm), Ines Schonbuchner (Center Wurzburg), Wolfram Heinritz (Center Leipzig) and Dieter Schafer (Center Frankfurt) for providing samples and clinical data and Juliane Kohler for her excellent technical assistance.; Helsinki Breast Cancer Study (HEBCS): The HEBCS study has been financially supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (132473), the Finnish Cancer Society and the Sigrid Juselius Foundation. HEBCS thanks Drs Kristiina Aittomaki, Carl Blomqvist and Tuomas Heikkinen and RN Irja Erkkila for their help with the patient data and samples.; Kathleen Cuningham Foundation Consortium for research into Familial Breast cancer (kConFab): We wish to thank Heather Thorne, Eveline Niedermayr, all the kConFab research nurses and staff, the heads and staff of the Family Cancer Clinics and the Clinical Follow Up Study (funded by NHMRC grants 145684, 288704 and 454508) for their contributions to this resource, and the many families who contribute to kConFab. kConFab is supported by grants from the National Breast Cancer Foundation, the National Health and Medical Research Council (NHMRC) and by the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. A. B. S. and G.C.-T. are supported by a NHMRC Senior Research and Principal Research Fellowships, respectively; University of California Irvine (UCI) (now the Beckman Research Institute of City of Hope): Genotyping at UCI was funded by grant NIH CA74415.; Mayo Clinic (MAYO): This work was supported by grants from the Breast Cancer Research Foundation (BCRF), Komen Foundation for the Cure, Department of Defense ovarian cancer research award (W81XWH-10-1-0341) and US National Cancer Institute, National Institutes of Health grant CA128978.; Georgetown University (GEORGETOWN): C. I. received support from the Familial Cancer Registry and the Tissue Culture Shared Registry at Georgetown University (NIH/NCI grant P30-CA051008), the Cancer Genetics Network (HHSN261200744000C), and Swing Fore the Cure.; University of Pennsylvania (UPENN): We acknowledge support by the Breast Cancer Research Foundation to K.L.N., by the Susan G. Komen Foundation to S. M. D., and by R01-CA083855 and R01-CA102776 to T. R. R. for the MAGIC consortium.; Hospital Clinico San Carlos (HCSC): The HCSC study was partially supported by Instituto de Salud Carlos III: RD06/0020/0021. We wish to thank Dr Miguel de la Hoya and Pedro Perez-Segura for their contribution to this study.; This work was supported by the European Community's Seventh Framework Programme under grant agreement no. 223175 (HEALTH-F2-2009-223175). D. G. C. received a grant from the INSERM/INCa. J.S. is Chairholder of the Canada Research Chair in Oncogenetics. This work was supported by the LIGUE CONTRE LE CANCER (S. M. and O.M.S.) and by the Canadian Institutes of Health Research for the 'CIHR Team in Familial Risks of Breast Cancer' program and by the Canadian Breast Cancer Research Alliance-grant #019511. D. S. holds the Francois-Karl Viau Chair in Pediatric Oncogenomics and is a scholar of the Fonds de la Recherche en Sante du Quebec (FRSQ). A. C. A. is a CR-UK Senior Cancer Research Fellow, D. F. E. is CR-UK Principal Research Fellow and G. C. T. is a NHMRC Senior Principal Research Fellow. NR 52 TC 7 Z9 8 U1 1 U2 20 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD DEC 1 PY 2011 VL 20 IS 23 BP 4732 EP 4747 DI 10.1093/hmg/ddr388 PG 16 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 848KD UT WOS:000297049600019 PM 21890493 ER PT J AU Villar, J Blanco, J Anon, JM Santos-Bouza, A Blanch, L Ambros, A Gandia, F Carriedo, D Mosteiro, F Basaldua, S Fernandez, RL Kacmarek, RM AF Villar, Jesus Blanco, Jesus Manuel Anon, Jose Santos-Bouza, Antonio Blanch, Lluis Ambros, Alfonso Gandia, Francisco Carriedo, Demetrio Mosteiro, Fernando Basaldua, Santiago Lidia Fernandez, Rosa Kacmarek, Robert M. CA ALIEN Network TI The ALIEN study: incidence and outcome of acute respiratory distress syndrome in the era of lung protective ventilation SO INTENSIVE CARE MEDICINE LA English DT Article DE Incidence; Acute respiratory distress syndrome; Lung protective mechanical ventilation; Prognosis ID END-EXPIRATORY PRESSURE; RANDOMIZED CONTROLLED-TRIAL; INTENSIVE-CARE UNITS; TIDAL VOLUMES; INJURY; MORTALITY; FAILURE; EPIDEMIOLOGY; DEFINITIONS; SEVERITY AB While our understanding of the pathogenesis and management of acute respiratory distress syndrome (ARDS) has improved over the past decade, estimates of its incidence have been controversial. The goal of this study was to examine ARDS incidence and outcome under current lung protective ventilatory support practices before and after the diagnosis of ARDS. This was a 1-year prospective, multicenter, observational study in 13 geographical areas of Spain (serving a population of 3.55 million at least 18 years of age) between November 2008 and October 2009. Subjects comprised all consecutive patients meeting American-European Consensus Criteria for ARDS. Data on ventilatory management, gas exchange, hemodynamics, and organ dysfunction were collected. A total of 255 mechanically ventilated patients fulfilled the ARDS definition, representing an incidence of 7.2/100,000 population/year. Pneumonia and sepsis were the most common causes of ARDS. At the time of meeting ARDS criteria, mean PaO2/FiO(2) was 114 +/- A 40 mmHg, mean tidal volume was 7.2 +/- A 1.1 ml/kg predicted body weight, mean plateau pressure was 26 +/- A 5 cmH(2)O, and mean positive end-expiratory pressure (PEEP) was 9.3 +/- A 2.4 cmH(2)O. Overall ARDS intensive care unit (ICU) and hospital mortality was 42.7% (95%CI 37.7-47.8) and 47.8% (95%CI 42.8-53.0), respectively. This is the first study to prospectively estimate the ARDS incidence during the routine application of lung protective ventilation. Our findings support previous estimates in Europe and are an order of magnitude lower than those reported in the USA and Australia. Despite use of lung protective ventilation, overall ICU and hospital mortality of ARDS patients is still higher than 40%. C1 [Kacmarek, Robert M.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 01460 USA. [Villar, Jesus; Blanco, Jesus; Blanch, Lluis; Basaldua, Santiago; Lidia Fernandez, Rosa] Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain. [Villar, Jesus; Lidia Fernandez, Rosa] Hosp Univ Dr Negrin, Multidisciplinary Organ Dysfunct Evaluat Res Netw, Res Unit, Las Palmas Gran Canaria, Spain. [Blanco, Jesus] Hosp Univ Rio Hortega, Intens Care Unit, Valladolid, Spain. [Manuel Anon, Jose] Hosp Virgen Luz, Intens Care Unit, Cuenca, Spain. [Santos-Bouza, Antonio] Univ Santiago, Complejo Hosp, Intens Care Unit, Santiago De Compostela, Spain. [Blanch, Lluis] Corp Sanitaria Parc Tauli, Crit Care Ctr, Sabadell, Spain. [Ambros, Alfonso] Hosp Gen Ciudad Real, Intens Care Unit, Ciudad Real, Spain. [Gandia, Francisco] Univ Valladolid, Hosp Clin, Intens Care Unit, Valladolid, Spain. [Carriedo, Demetrio] Hosp Gen Leon, Intens Care Unit, Leon, Spain. [Mosteiro, Fernando] Univ A Coruna, Complejo Hosp, Intens Care Unit, La Coruna, Spain. [Basaldua, Santiago] Hosp Univ NS Candelaria, Res Unit, Tenerife, Spain. [Kacmarek, Robert M.] Harvard Univ, Dept Anesthesia, Boston, MA USA. [Villar, Jesus] Hosp Univ Dr Negrin, Res Unit, Las Palmas Gran Canaria 35010, Spain. RP Kacmarek, RM (reprint author), Massachusetts Gen Hosp, Dept Resp Care, 55 Fruit St, Boston, MA 01460 USA. EM jesus.villar54@gmail.com; rkacmarek@partners.org FU Instituto de Salud Carlos III, Spain [PI 07/0113, CB06/06/1088] FX Supported in part by grants from the Instituto de Salud Carlos III, Spain (PI 07/0113, CB06/06/1088). NR 42 TC 168 Z9 190 U1 0 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD DEC PY 2011 VL 37 IS 12 BP 1932 EP 1941 DI 10.1007/s00134-011-2380-4 PG 10 WC Critical Care Medicine SC General & Internal Medicine GA 849WF UT WOS:000297155300006 PM 21997128 ER PT J AU Estrada, CA Safford, MM Salanitro, AH Houston, TK Curry, W Williams, JH Ovalle, F Kim, Y Foster, P Allison, JJ AF Estrada, Carlos A. Safford, Monika M. Salanitro, Amanda H. Houston, Thomas K. Curry, William Williams, Jessica H. Ovalle, Fernando Kim, Yongin Foster, Pamela Allison, Jeroan J. TI A web-based diabetes intervention for physician: a cluster-randomized effectiveness trial SO INTERNATIONAL JOURNAL FOR QUALITY IN HEALTH CARE LA English DT Article DE internet; translational research; diabetes mellitus; rural health services; education; medical; continuing process assessment (Health Care) ID CONTINUING MEDICAL-EDUCATION; PRACTICE IMPROVEMENT MODULE; RE-AIM FRAMEWORK; SELF-ASSESSMENT; CARE; CME; BENEFICIARIES; MANAGEMENT; QUALITY; IMPACT AB To determine the effectiveness of a provider-based education and implementation intervention for improving diabetes control. Cluster-randomized trial with baseline and follow-up cross sections of diabetes patients in each participating physicians practice. Eleven US Southeastern states, 200608. Two hundred and five rural primary care physicians. Multi-component interactive intervention including Web-based continuing medical education, performance feedback and quality improvement tools. oAcceptable control' [hemoglobin A1c 9, blood pressure (BP) 140/90 mmHg, low-density lipoprotein cholesterol (LDL) 130 mg/dl] and ooptimal control' (A1c 7, BP 130/80 mmHg, LDL 100 mg/dl). Of 364 physicians attempting to register, 205 were randomized to the intervention (n 102) or control arms (n 103). Baseline and follow-up data were provided by 95 physicians (2127 patients). The proportion of patients with A1c 9 was similar at baseline and follow-up in both the control [adjusted odds ratio (AOR): 0.94; 95 confidence interval (CI): 0.61, 1.47] and intervention arms [AOR: 1.16 (95 CI: 0.80, 1.69)]; BP 140/90 mmHg and LDL 130 mg/dl were also similar at both measurement points (P 0.66, P 0.46; respectively). We observed no significant effect on diabetes control attributable to the intervention for any of the primary outcome measures. Intervention physicians engaged with the Website over a median of 64.7 weeks [interquartile range (IQR): 45.481.8) for a median total of 37 min (IQR: 1666). A wide-reach, low-intensity, Web-based interactive multi-component intervention did not improve control of glucose, BP or lipids for patients with diabetes of physicians practicing in the rural Southeastern US. C1 [Estrada, Carlos A.; Curry, William] Birmingham Vet Affairs Med Ctr, Birmingham, AL 35294 USA. [Estrada, Carlos A.] Vet Affairs Natl Qual Scholars Program, Birmingham, AL USA. [Estrada, Carlos A.; Safford, Monika M.; Curry, William; Williams, Jessica H.; Ovalle, Fernando; Kim, Yongin] Univ Alabama, Birmingham, AL USA. [Salanitro, Amanda H.; Houston, Thomas K.] VA Tennessee Valley Healthcare Geriatr Res Educ C, Nashville, TN USA. [Salanitro, Amanda H.; Houston, Thomas K.] Vanderbilt Univ, Nashville, TN USA. [Houston, Thomas K.] Bedford Vet Affairs Med Ctr, Bedford, MA USA. [Foster, Pamela] Univ Alabama, Tuscaloosa, AL USA. [Allison, Jeroan J.] Univ Massachusetts, Sch Med, Worcester, MA USA. RP Estrada, CA (reprint author), Birmingham Vet Affairs Med Ctr, Birmingham, AL 35294 USA. EM cestrada@uab.edu RI Houston, Thomas/F-2469-2013; OI Allison, Jeroan/0000-0003-4472-2112 FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [5R18DK065001]; Veterans Affairs National Quality Scholars Program FX Awards by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) 5R18DK065001 to Dr J.J.A. Drs A. H. S and C. A. E. were supported by the Veterans Affairs National Quality Scholars Program. NR 28 TC 7 Z9 7 U1 2 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1353-4505 J9 INT J QUAL HEALTH C JI Int. J. Qual. Health Care PD DEC PY 2011 VL 23 IS 6 BP 682 EP 689 DI 10.1093/intqhc/mzr053 PG 8 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 848QL UT WOS:000297067900009 PM 21831967 ER PT J AU Shera, CA Olson, ES Guinan, JJ AF Shera, Christopher A. Olson, Elizabeth S. Guinan, John J., Jr. TI On Cochlear Impedances and the Miscomputation of Power Gain SO JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY LA English DT Article DE cochlea; cochlear amplifier; power gain; impedance ID MODEL; EAR AB In their article, "Measurement of cochlear power gain in the sensitive gerbil ear," Ren et al. (Nat Commun 2:216, 2011) claim to provide "the first direct experimental evidence of power amplification in the sensitive living cochlea." While we recognize the technical challenges of the experiments and appreciate the beauty of the data, the authors' analysis and interpretation of the measurements are invalid. We review the concept of impedance (i.e., the ratio of pressure to velocity) as it applies to cochlear mechanics and show that Ren et al. mistakenly equate the impedances near the basilar membrane and stapes with the impedance characteristic of an infinite, uniform tube of fluid. As a consequence of this error, Ren et al.'s measurements and analysis provide no evidence for power amplification in the cochlea. Compelling evidence for power amplification has, however, been previously provided by others. C1 [Shera, Christopher A.; Guinan, John J., Jr.] Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, Boston, MA 02114 USA. [Olson, Elizabeth S.] Columbia Univ, Dept Otolaryngol Head & Neck Surg, New York, NY 10032 USA. RP Shera, CA (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, 243 Charles St, Boston, MA 02114 USA. EM shera@epl.meei.harvard.edu FU NIDCD, National Institutes of Health [R01 DC003687, DC003130, DC00235] FX This work was supported by grants R01 DC003687 (CAS), DC003130 (ESO), and DC00235 (JJG) from the NIDCD, National Institutes of Health. NR 24 TC 1 Z9 1 U1 2 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1525-3961 J9 JARO-J ASSOC RES OTO JI JARO PD DEC PY 2011 VL 12 IS 6 BP 671 EP 676 DI 10.1007/s10162-011-0287-y PG 6 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 849OW UT WOS:000297135900001 PM 21947765 ER PT J AU Makary, CA Shin, J Kujawa, SG Liberman, MC Merchant, SN AF Makary, Chadi A. Shin, Jennifer Kujawa, Sharon G. Liberman, M. Charles Merchant, Saumil N. TI Age-Related Primary Cochlear Neuronal Degeneration in Human Temporal Bones SO JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY LA English DT Article DE spiral ganglion; cochlear neurons; histopathology; otopathology ID HAIR CELL LOSS; INDUCED HEARING-LOSS; GUINEA-PIG COCHLEA; SPIRAL GANGLION; RETROGRADE DEGENERATION; INNER-EAR; NERVE; INNERVATION; POPULATIONS; SURVIVAL AB In cases of acquired sensorineural hearing loss, death of cochlear neurons is thought to arise largely as a result of sensory-cell loss. However, recent studies of acoustic overexposure report massive degeneration of the cochlear nerve despite complete hair cell survival (Kujawa and Liberman, J Neurosci 29:14077-14085, 2009). To assess the primary loss of spiral ganglion cells (SGCs) in human ears, neuronal counts were performed in 100 temporal bones from 100 individuals, aged newborn to 100 years, selected to include only cases with a normal population of inner and outer hair cells. Ganglion cell counts declined at a mean rate of 100 cells per year of life. There were no significant gender or inter-aural differences, and a slight increase in degeneration in the basal turn re upper turns was not statistically significant. The age-related decline in SGCs was significantly less than that in prior studies that included ears with hair cell loss (Otte et al., Laryngoscope 88:1231-1246, 1978), but significantly more than for analogous data on vestibular ganglion cells in cases without vestibular hair cell loss (Velazquez-Villasenor et al., Ann Otol Rhinol Laryngol Suppl 181:14-19, 2000). The age-related decline in SGC counts may contribute to the well-known decline in hearing-in-noise performance, and the data will help in interpretation of histopathological findings from temporal bones with known otologic disease. C1 [Makary, Chadi A.; Shin, Jennifer; Kujawa, Sharon G.; Liberman, M. Charles; Merchant, Saumil N.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Makary, Chadi A.; Shin, Jennifer; Kujawa, Sharon G.; Liberman, M. Charles; Merchant, Saumil N.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Kujawa, Sharon G.; Liberman, M. Charles; Merchant, Saumil N.] Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, Boston, MA 02114 USA. RP Merchant, SN (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM Saumil_merchant@meei.harvard.edu RI Shin, Jennifer/A-3169-2016 FU NIH [U24 DC008559, R01 DC0188, R01 DC8577] FX We thank Jon Pack for the photomicrographs. This work was supported by NIH grants U24 DC008559 (SNM), R01 DC0188 (MCL) and R01 DC8577 (SGK). NR 37 TC 81 Z9 82 U1 3 U2 24 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1525-3961 J9 JARO-J ASSOC RES OTO JI JARO PD DEC PY 2011 VL 12 IS 6 BP 711 EP 717 DI 10.1007/s10162-011-0283-2 PG 7 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 849OW UT WOS:000297135900005 PM 21748533 ER PT J AU Phipatanakul, W Bailey, A Hoffman, EB Sheehan, WJ Lane, JP Baxi, S Rao, D Permaul, P Gaffin, JM Rogers, CA Muilenberg, ML Gold, DR AF Phipatanakul, Wanda Bailey, Anne Hoffman, Elaine B. Sheehan, William J. Lane, Jeffrey P. Baxi, Sachin Rao, Devika Permaul, Perdita Gaffin, Jonathan M. Rogers, Christine A. Muilenberg, Michael L. Gold, Diane R. TI The School Inner-City Asthma Study: Design, Methods, and Lessons Learned SO JOURNAL OF ASTHMA LA English DT Article DE asthma; inner-city; school ID URBAN ELEMENTARY-SCHOOLS; ION-CHARGING DEVICE; FEL-D-I; ALLERGEN LEVELS; ENVIRONMENTAL ALLERGENS; COCKROACH ALLERGENS; AIRBORNE ALLERGENS; INDOOR ALLERGENS; PUBLIC PLACES; DUST AB Background. Children spend a significant amount of time in school. Little is known about the role of allergen exposure in school environments and asthma morbidity. Objectives. The School Inner-City Asthma Study (SICAS) is a National Institutes of Health (NIH)-funded prospective study evaluating the school/classroom-specific risk factors and asthma morbidity among urban children. Methods/results. This article describes the design, methods, and important lessons learned from this extensive investigation. A single center is recruiting 500 elementary school-aged children, all of whom attend inner-city metropolitan schools. The primary hypothesis is that exposure to common indoor allergens in the classroom will increase the risk of asthma morbidity in children with asthma, even after controlling for home allergen exposures. The protocol includes screening surveys of entire schools and baseline eligibility assessments obtained in the spring prior to the academic year. Extensive baseline clinical visits are being conducted among eligible children with asthma during the summer prior to the academic school year. Environmental classroom/school assessments including settled dust and air sampling for allergen, mold, air pollution, and inspection data are collected twice during the academic school year and one home dust sample linked to the enrolled student. Clinical outcomes are measured every 3 months during the academic school year. Conclusion. The overall goal of SICAS is to complete the first study of its kind to better understand school-specific urban environmental factors on childhood asthma morbidity. We also discuss the unique challenges related to school-based urban research and lessons being learned from recruiting such a cohort. C1 [Phipatanakul, Wanda; Sheehan, William J.; Baxi, Sachin] Childrens Hosp, Dept Pediat, Div Allergy & Immunol, Boston, MA 02115 USA. [Phipatanakul, Wanda; Bailey, Anne; Gold, Diane R.] Brigham & Womens Hosp, Dept Med, Channing Lab, Div Resp Epidemiol, Boston, MA USA. [Phipatanakul, Wanda; Sheehan, William J.; Baxi, Sachin; Rao, Devika; Permaul, Perdita; Gaffin, Jonathan M.; Gold, Diane R.] Harvard Univ, Sch Med, Boston, MA USA. [Hoffman, Elaine B.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Lane, Jeffrey P.] Facil Management, Boston, MA USA. [Rao, Devika; Gaffin, Jonathan M.] Childrens Hosp, Dept Pediat, Div Pediat Pulmonol, Boston, MA 02115 USA. [Permaul, Perdita] Massachusetts Gen Hosp, Div Pediat Allergy & Immunol, Boston, MA 02114 USA. [Rogers, Christine A.; Muilenberg, Michael L.] Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Div Environm Hlth Sci, Amherst, MA 01003 USA. RP Phipatanakul, W (reprint author), Childrens Hosp, Dept Pediat, Div Allergy & Immunol, 300 Longwood Ave, Boston, MA 02115 USA. EM wanda.phipatanakul@childrens.harvard.edu RI Rogers, Christine/A-2189-2008 OI Rogers, Christine/0000-0003-0887-9606 FU National Institutes of Health [R01 AI 073964, R01 AI 073964-02S1]; Harvard Catalyst \ The Harvard Clinical and Translational Science Center [UL1 RR 025758]; Harvard University FX This study was supported by grants R01 AI 073964 and R01 AI 073964-02S1 from the National Institutes of Health. All authors do not have any financial and personal relationships with other people or organizations that could influence (bias) their work. We have no disclosures of any affiliation with any organization with a financial interest, direct or indirect, in the subject matter or materials discussed in the manuscript (such as consultancies, employment, paid expert testimony, honoraria, speakers bureaus, retainers, stock options or ownership, patents or patent applications, or travel grants) that may affect the conduct or reporting of the work submitted. This work was conducted with support from Harvard Catalyst vertical bar The Harvard Clinical and Translational Science Center (NIH Award #UL1 RR 025758 and financial contributions from Harvard University and its affiliated academic health care centers). The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic health care centers, the National Center for Research Resources, or the National Institutes of Health. NR 36 TC 20 Z9 20 U1 2 U2 7 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0277-0903 J9 J ASTHMA JI J. Asthma PD DEC PY 2011 VL 48 IS 10 BP 1007 EP 1014 DI 10.3109/02770903.2011.624235 PG 8 WC Allergy; Respiratory System SC Allergy; Respiratory System GA 850BI UT WOS:000297169000005 PM 22010992 ER PT J AU Smith, MR Saad, F Egerdie, B Sieber, P Tammela, TLJ Leder, BZ Ke, CL Goessl, C AF Smith, Matthew R. Saad, Fred Egerdie, Blair Sieber, Paul Tammela, Teuvo L. J. Leder, Benjamin Z. Ke, Chunlei Goessl, Carsten TI Denosumab and Changes in Bone Turnover Markers During Androgen Deprivation Therapy for Prostate Cancer SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE DENOSUMAB; ANDROGEN DEPRIVATION THERAPY; BONE TURNOVER MARKERS; PROSTATE CANCER ID POSTMENOPAUSAL WOMEN; ZOLEDRONIC ACID; CLINICAL-TRIAL; MEN; OSTEOPOROSIS; DENSITY AB Androgen deprivation therapy (ADT) for prostate cancer increases fracture risk, decreases bone mineral density, and increases bone turnover markers (BTMs) including serum type 1 C-telopeptide (sCTX), tartrate-resistant alkaline phosphatase 5b (TRAP-5b), and procollagen-1 N-terminal telopeptide (P1NP). In a prespecified exploratory analysis of a phase 3, multicenter, double-blind study, we evaluated the effects of denosumab (60 mg subcutaneously every 6 months for 3 years) versus placebo (1468 patients, 734 in each group) on BTM values. BTMs were measured at baseline, month 1, and predose at months 6, 12, 24, and 36 in the overall population. BTMs at month 1 are also reported for subgroups based on age (< 70 years versus >= 70 years), prior duration of ADT (<= 6 months versus >6 months), and baseline BTM (<= median versus > median BTM values). Treatment with denosumab provided a rapid and sustained decrease of BTM values compared with placebo. The median change in sCTX levels at month 1 was -90% in the denosumab group and -3% in the placebo group (p < 0.0001). The median change in TRAP-5b levels at month 1 was -55% in the denosumab group and -3% in the placebo group (p < 0.0001). The maximal median change in P1NP was -64% in the denosumab group and -11% in the placebo group, (p < 0.0001). Significantly greater decreases in BTM for denosumab were also seen in subgroup analyses based on age, prior ADT treatment, and baseline BTM values. Suppression of bone turnover markers was consistent with marked increases in bone mineral density reported previously. (C) 2011 American Society for Bone and Mineral Research. C1 [Smith, Matthew R.] Massachusetts Gen Hosp, Ctr Canc, Genitourinary Oncol Program, Boston, MA 02114 USA. [Saad, Fred] Ctr Hosp Univ Montreal, Dept Urol, Montreal, PQ, Canada. [Egerdie, Blair] Urol Associates Urol Med Res, Kitchener, ON, Canada. [Sieber, Paul] Urol Associates Lancaster Ltd, Lancaster, PA USA. [Tammela, Teuvo L. J.] Tampere Univ Hosp, Dept Surg, Tampere, Finland. [Leder, Benjamin Z.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Ke, Chunlei] Amgen Inc, Global Biostat Sci, Thousand Oaks, CA 91320 USA. [Goessl, Carsten] Amgen Inc, Clin Dev, Thousand Oaks, CA 91320 USA. RP Smith, MR (reprint author), Massachusetts Gen Hosp, Ctr Canc, Genitourinary Oncol Program, Yawkey 7030,55 Fruit St, Boston, MA 02114 USA. EM smith.matthew@mgh.harvard.edu FU Amgen; Amgen Inc.; NIH [5K24CA121990]; Prostate Cancer Foundation FX We thank the patients and investigators at all participating sites who made important contributions to this study. We also thank Sue Hudson and Geoffrey Smith, PhD, supported by Amgen, for medical writing assistance in preparing this manuscript. Funding for the study and financial support for the preparation of the manuscript was provided by Amgen Inc. This study is registered with ClinicalTrials.gov, with the identifier NCT00089674. Dr. Smith is supported by an NIH Midcareer Investigator Award (5K24CA121990) and competitive research awards from the Prostate Cancer Foundation. NR 21 TC 10 Z9 11 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD DEC PY 2011 VL 26 IS 12 BP 2827 EP 2833 DI 10.1002/jbmr.492 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 849QB UT WOS:000297139100006 PM 21898590 ER PT J AU Dvorak-Ewell, MM Chen, TH Liang, N Garvey, C Liu, B Tu, CL Chang, WH Bikle, DD Shoback, DM AF Dvorak-Ewell, Melita M. Chen, Tsui-Hua Liang, Nathan Garvey, Caitlin Liu, Betty Tu, Chialing Chang, Wenhan Bikle, Daniel D. Shoback, Dolores M. TI Osteoblast Extracellular Ca2+-Sensing Receptor Regulates Bone Development, Mineralization, and Turnover SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE EXTRACELLULAR Ca2+-SENSING RECEPTOR; OSTEOBLASTS; BONE DEVELOPMENT; OSTEOBLAST DIFFERENTIATION ID CALCIUM-SENSING RECEPTOR; ALKALINE-PHOSPHATASE; CANCELLOUS BONE; SKELETAL PHENOTYPE; MC3T3-E1 CELLS; DEFICIENT MICE; MURINE BONE; DIFFERENTIATION; CASR; OSTEOPROTEGERIN AB The extracellular Ca2+-sensing receptor (CaR), a G protein-coupled receptor responsible for maintenance of calcium homeostasis, is implicated in regulation of skeletal metabolism. To discern the role of the osteoblast CaR in regulation of bone development and remodeling, we generated mice in which the CaR is excised in a broad population of osteoblasts expressing the 3.6-kb a(1)(I) collagen promoter. Conditional knockouts had abnormal skeletal histology at birth and developed progressively reduced mineralization secondary to retarded osteoblast differentiation, evident by significantly reduced numbers of osteoblasts and decreased expression of collagen I, osteocalcin, and sclerostin mRNAs. Elevated expression of ankylosis protein, ectonucleotide pyrophosphatase/phospho-diesterase 1, and osteopontin mRNAs in the conditional knockout indicate altered regulation of genes important in mineralization. Knockout of the osteoblast CaR also resulted in increased expression of the receptor activator of NF-kappa B ligand (RANKL), the major stimulator of osteoclast differentiation and function, consistent with elevated osteoclast numbers in vivo. Osteoblasts from the conditional knockouts exhibited delayed differentiation, reduced mineralizing capacity, altered expression of regulators of mineralization, and increased ability to promote osteoclastogenesis in coculture experiments. We conclude that CaR signaling in a broad population of osteoblasts is essential for bone development and remodeling and plays an important role in the regulation of differentiation and expression of regulators of bone resorption and mineralization. (C) 2011 American Society for Bone and Mineral Research. C1 [Shoback, Dolores M.] Univ Calif San Francisco, San Francisco VA Med Ctr, Endocrine Res Unit, Dept Vet Affairs Med Ctr,Dept Med, San Francisco, CA 94121 USA. RP Shoback, DM (reprint author), Univ Calif San Francisco, San Francisco VA Med Ctr, Endocrine Res Unit, Dept Vet Affairs Med Ctr,Dept Med, 111N,4150 Clement St, San Francisco, CA 94121 USA. EM dolores.shoback@ucsf.edu FU Veterans Affairs Merit Review; Department of Veterans Research Enhancement; NIH [RO1 AG21353, RO1 AR055888, RO1 DK054793] FX We gratefully acknowledge Dr Barbara Kream for the gift of the Col 3.6-Cre mice, as well as the technical help of Hashem Elalieh and Michelle Buttler. This work was supported by a Veterans Affairs Merit Review (DS), a Department of Veterans Research Enhancement Award Program in Bone Disease (DS, DB), NIH RO1 AG21353 (WC), NIH RO1 AR055888 (DS), and NIH RO1 DK054793 (DB). NR 39 TC 36 Z9 38 U1 0 U2 13 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD DEC PY 2011 VL 26 IS 12 BP 2935 EP 2947 DI 10.1002/jbmr.520 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 849QB UT WOS:000297139100016 PM 21956637 ER PT J AU McDonald, CC Deatrick, JA Kassam-Adams, N Richmond, TS AF McDonald, Catherine C. Deatrick, Janet A. Kassam-Adams, Nancy Richmond, Therese S. TI Community Violence Exposure and Positive Youth Development in Urban Youth SO JOURNAL OF COMMUNITY HEALTH LA English DT Article DE Community violence; Family functioning; Positive youth development; Urban ID INNER-CITY ADOLESCENTS; MENTAL-HEALTH; POSTTRAUMATIC STRESS; PROTECTIVE FACTORS; SOCIAL SUPPORT; SYMPTOMS; TRAJECTORIES; BEHAVIORS; 4-H; STRATEGIES AB Youth in urban environments are exposed to community violence, yet some do well and continue on a positive developmental trajectory. This study investigated the relationships between lifetime community violence exposure (including total, hearing about, witnessing, and victimization), family functioning, and positive youth development (PYD) among 110 urban youth ages 10-16 years (54% female) using a paper and pen self-report survey. This cross-sectional study was part of an interdisciplinary community-based participatory research effort in West/Southwest Philadelphia. Almost 97% of the sample reported some type of community violence exposure. Controlling for presence of mother in the home and presence of father in the home, separate linear regression models for PYD by each type of community violence exposure indicated that gender and family functioning were significantly associated with PYD. None of the types of community violence exposure were significant in the models. Significant interactions between gender and presence of mother in the home and gender and family functioning helped better explain these relationships for some of the types of community violence exposure. Presence of mother was associated with higher PYD for girls, but not for boys. Boys with poor family functioning had lower PYD than girls with poor family functioning. This study helps to better delineate relationships between CVE and PYD by adding new knowledge to the literature on the role of family functioning. Points of intervention should focus on families, with attention to parental figures in the home and overall family functioning. C1 [McDonald, Catherine C.; Deatrick, Janet A.] Univ Penn, Sch Nursing, Ctr Hlth Equ Res, Philadelphia, PA 19104 USA. [McDonald, Catherine C.; Kassam-Adams, Nancy; Richmond, Therese S.] Philadelphia Collaborat Violence Prevent Ctr, Philadelphia, PA 19104 USA. [Kassam-Adams, Nancy] Childrens Hosp Philadelphia, Ctr Injury Res & Prevent, Philadelphia, PA 19104 USA. [Richmond, Therese S.] Univ Penn, Sch Nursing, Div Biobehav & Hlth Sci, Philadelphia, PA 19104 USA. RP McDonald, CC (reprint author), Univ Penn, Sch Nursing, Ctr Hlth Equ Res, 2L,418 Curie Blvd, Philadelphia, PA 19104 USA. EM mcdonalc@nursing.upenn.edu RI Kassam-Adams, Nancy/C-4091-2009 FU NCIPC CDC HHS [U49 CE001093, 5 U49 CE001093]; NINR NIH HHS [F31 NR011107, F31 NR011107-02, F31NR011107] NR 48 TC 5 Z9 5 U1 3 U2 15 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0094-5145 J9 J COMMUN HEALTH JI J. Community Health PD DEC PY 2011 VL 36 IS 6 BP 925 EP 932 DI 10.1007/s10900-011-9391-5 PG 8 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 838NV UT WOS:000296300400005 PM 21461763 ER PT J AU Drubach, LA Palmer, EL Connolly, LP Baker, A Zurakowski, D Cypess, AM AF Drubach, Laura A. Palmer, Edwin L., III Connolly, Leonard P. Baker, Amanda Zurakowski, David Cypess, Aaron M. TI Pediatric Brown Adipose Tissue: Detection, Epidemiology, and Differences from Adults SO JOURNAL OF PEDIATRICS LA English DT Article ID BODY-MASS INDEX; F-18-FDG PET/CT; USA-FAT; HUMANS; CHILDREN; THERMOGENESIS; AGE AB Objectives To evaluate the prevalence and factors affecting the detection of active brown adipose tissue (BAT) in children and adolescents using 18 F-fluorodeoxyglucose positron emission tomography. Study design A total of 385 positron emission tomography scans performed for various oncologic indications in 172 patients aged 5-21 years were reviewed. BAT activity was detected by visual inspection as present or absent in the neck, thorax, and abdomen based on its well-characterized and typical appearance and then quantified by comparing the 18 F-fluorodeoxyglucose activity in the cervical-supraclavicular depots with that measured in the liver. Clinical indices were recorded. Results The BAT detection rate was not significantly different between boys and girls (43.3% vs 45.3%). BAT activity was found most often in the cervical-supraclavicular depots. The highest percentage of patients with detectable BAT and the highest BAT/liver activity were in the 13-to 14.99-year age group in both males and females (P = .005). Body mass index percentile correlated inversely with BAT activity (P = .012). BAT activity did not correlate with outdoor temperature or clinical diagnosis. Conclusion Under typical clinical imaging conditions, BAT is detected more frequently in children than in adults. BAT activity increases from childhood into adolescence, when it is detected in almost half of patients, and it correlates inversely with obesity, suggesting that BAT may play a prominent role in pediatric metabolism. (J Pediatr 2011;159:939-44). C1 [Drubach, Laura A.; Baker, Amanda; Zurakowski, David] Childrens Hosp, Dept Radiol, Boston, MA 02466 USA. [Palmer, Edwin L., III; Connolly, Leonard P.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Cypess, Aaron M.] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Drubach, Laura A.; Palmer, Edwin L., III; Connolly, Leonard P.; Baker, Amanda; Zurakowski, David; Cypess, Aaron M.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. RP Drubach, LA (reprint author), Childrens Hosp, Dept Radiol, 300 Longwood Ave, Boston, MA 02466 USA. EM laura.drubach@childrens.harvard.edu FU Eli Lilly Foundation; National Institutes of Health [DK046200, DK081604, DK087317, RR025757]; National Institute of Diabetes and Digestive and Kidney Diseases [P30 DK036836] FX Supported by the Eli Lilly Foundation, the National Institutes of Health (grants DK046200, DK081604, DK087317, and RR025757, to A. C.), and the National Institute of Diabetes and Digestive and Kidney Diseases (grant P30 DK036836). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the National Institute of Diabetes and Digestive and Kidney Diseases. The authors declare no conflicts of interest. NR 27 TC 30 Z9 32 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 J9 J PEDIATR-US JI J. Pediatr. PD DEC PY 2011 VL 159 IS 6 BP 939 EP 944 DI 10.1016/j.jpeds.2011.06.028 PG 6 WC Pediatrics SC Pediatrics GA 845UQ UT WOS:000296849400014 PM 21839465 ER PT J AU Brewster, LP Hall, DE Joehl, RJ AF Brewster, Luke P. Hall, Dan E. Joehl, Raymond J. TI Assessing Residents in Surgical Ethics: We Do It a Lot; We Only Know a Little SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE surgical ethics; resident education; clinical ethics ID EDUCATION; FUTURE AB Background. PGY-1 year of surgical residency brings together many persons of disparate experiences and educational backgrounds, including their exposure to ethics. We hypothesized that surgical PGY-1s would have a similar exposure to ethical scenarios but lack the confidence in practice and understanding of ethical principles compared with more senior residents. Materials and Methods. Surgical residents were invited to resident-initiated surgical ethics workshops utilizing a standardized text. Here a survey and multiple choice tests were administered to participants. The survey determined prior exposure to ethics curricula, the frequency of exposure to various ethics topics, and their comfort with these scenarios. A multiple choice test then quantified the knowledge base of participating residents. The results were collected and compared between surgical PGY-1s and more senior residents. Results. Eighteen PGY-1s and 12 senior residents completed this curriculum. Resident exposure to ethical concepts was common. Resident confidence in these topics was ranked moderate or higher for both groups. Despite frequent clinical exposure and strong confidence in their skills of addressing these topics, performance on the test was poor, with an average score of 59% for PGY-1s and 47% for more senior residents (P = 0.03). Conclusions. Despite clinical exposure to and confidence in their management of ethical topics, their knowledge base was poor and worse for more senior residents. Given the overall interest in a formal ethics curriculum and the knowledge deficit demonstrated, educational intervention and professional ethics support should be provided for surgical residents even with the current educational time constraints. (c) 2011 Elsevier Inc. All rights reserved. C1 [Brewster, Luke P.] Emory Univ Hosp, Dept Surg, Atlanta, GA 30022 USA. [Hall, Dan E.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Hall, Dan E.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA. [Joehl, Raymond J.] Edward J Hines Jr VA Hosp, Hines, IL USA. [Joehl, Raymond J.] Loyola Univ, Med Ctr, Maywood, IL 60153 USA. RP Brewster, LP (reprint author), Emory Univ Hosp, Dept Surg, 1364 Clifton Rd, Atlanta, GA 30022 USA. EM lukebrewst@aol.com RI Hall, Daniel/H-4843-2013; OI Hall, Daniel/0000-0001-6382-0522 NR 7 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD DEC PY 2011 VL 171 IS 2 BP 395 EP 398 DI 10.1016/j.jss.2011.04.008 PG 4 WC Surgery SC Surgery GA 847FS UT WOS:000296957900018 PM 21601880 ER PT J AU Johnson, GD Sendler, E Lalancette, C Hauser, R Diamond, MP Krawetz, SA AF Johnson, G. D. Sendler, E. Lalancette, C. Hauser, R. Diamond, M. P. Krawetz, S. A. TI Cleavage of rRNA ensures translational cessation in sperm at fertilization SO MOLECULAR HUMAN REPRODUCTION LA English DT Article DE next generation sequencing; rRNA; sperm; spermiogenesis ID MATURE HUMAN SPERMATOZOA; MESSENGER-RNA; AMPLIFICATION-FREE; SECONDARY STRUCTURE; LIBRARY PREPARATION; CELLS; SPERMATOGENESIS; TRANSCRIPTS; EXPRESSION; PROFILES AB Intact ribosomal RNAs (rRNAs) comprise the majority of somatic transcripts, yet appear conspicuously absent in spermatozoa, perhaps reflecting cytoplasmic expulsion during spermatogenesis. To discern their fate, total RNA retained in mature spermatozoa from three fertile donors was characterized by Next Generation Sequencing. In all samples, >75% of total sequence reads aligned to rRNAs. The distribution of reads along the length of these transcripts exhibited a high degree of non-uniformity that was reiterated between donors. The coverage of sequencing reads was inversely correlated with guanine-cytosine (GC)-richness such that sequences greater than similar to 70% GC were virtually absent in all sperm RNA samples. To confirm the loss of sequence, the relative abundance of specific regions of the 28S transcripts in sperm was established by 7-Deaza-2'-deoxy-guanosine-5'-triphosphate RT-PCR. The inability to amplify specific regions of the 28S sequence from sperm despite the abundant representation of this transcript in the sequencing libraries demonstrates that approximately three-quarters of RNA retained in the mature male gamete are products of rRNA fragmentation. Hence, cleavage (not expulsion of the RNA component of the translational machinery) is responsible for preventing spurious translation following spermiogenesis. These results highlight the potential importance of those transcripts, including many mRNAs, which evade fragmentation and remain intact when sperm are delivered at fertilization. Sequencing data are deposited in GEO as: GSE29160. C1 [Johnson, G. D.; Sendler, E.; Lalancette, C.; Krawetz, S. A.] Wayne State Univ, Sch Med, CS Mott Ctr Human Growth & Dev, Ctr Mol Med & Genet, Detroit, MI 48201 USA. [Sendler, E.; Lalancette, C.; Diamond, M. P.; Krawetz, S. A.] Wayne State Univ, Sch Med, CS Mott Ctr Human Growth & Dev, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Hauser, R.] Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Boston, MA 02114 USA. [Hauser, R.] Harvard Univ, Sch Med, Dept Environm Hlth, Boston, MA USA. [Hauser, R.] Harvard Univ, Sch Med, Dept Epidemiol, Boston, MA 02115 USA. RP Krawetz, SA (reprint author), Wayne State Univ, Sch Med, CS Mott Ctr Human Growth & Dev, Ctr Mol Med & Genet, Detroit, MI 48201 USA. EM steve@compbio.med.wayne.edu RI Lalancette, Claudia/K-2502-2013; OI Diamond, Michael/0000-0001-6353-4489 FU Harvard School of Public Health; National Institutes of Health [ES017285]; National Institute of Environmental Health Sciences [ES009718]; Presidential Research Enhancement Program in Computational Biology; Charlotte B. Failing Professorship FX This work was supported, in part, by a pilot grant to SAK and RH from Harvard School of Public Health; National Institutes of Health (grant number ES017285); National Institute of Environmental Health Sciences (grant number ES009718); the Presidential Research Enhancement Program in Computational Biology and the Charlotte B. Failing Professorship (S.A.K.). NR 39 TC 32 Z9 32 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1360-9947 J9 MOL HUM REPROD JI Mol. Hum. Reprod. PD DEC PY 2011 VL 17 IS 12 BP 721 EP 726 DI 10.1093/molehr/gar054 PG 6 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA 848IO UT WOS:000297045400001 PM 21831882 ER PT J AU Hammer, GE Turer, EE Taylor, KE Fang, CJ Advincula, R Oshima, S Barrera, J Huang, EJ Hou, B Malynn, BA Reizis, B DeFranco, A Criswell, LA Nakamura, MC Ma, A AF Hammer, Gianna Elena Turer, Emre E. Taylor, Kimberly E. Fang, Celia J. Advincula, Rommel Oshima, Shigeru Barrera, Julio Huang, Eric J. Hou, Baidong Malynn, Barbara A. Reizis, Boris DeFranco, Anthony Criswell, Lindsey A. Nakamura, Mary C. Ma, Averil TI Expression of A20 by dendritic cells preserves immune homeostasis and prevents colitis and spondyloarthritis SO NATURE IMMUNOLOGY LA English DT Article ID TOLL-LIKE RECEPTORS; NF-KAPPA-B; SYSTEMIC-LUPUS-ERYTHEMATOSUS; PATTERN-RECOGNITION RECEPTORS; GENOME-WIDE ASSOCIATION; INFLAMMATORY DISEASE; IN-VIVO; ANKYLOSING-SPONDYLITIS; PERIPHERAL TOLERANCE; ADAPTIVE IMMUNITY AB Dendritic cells (DCs), which are known to support immune activation during infection, may also regulate immune homeostasis in resting animals. Here we show that mice lacking the ubiquitin-editing molecule A20 specifically in DCs spontaneously showed DC activation and population expansion of activated T cells. Analysis of DC-specific epistasis in compound mice lacking both A20 and the signaling adaptor MyD88 specifically in DCs showed that A20 restricted both MyD88-independent signals, which drive activation of DCs and T cells, and MyD88-dependent signals, which drive population expansion of T cells. In addition, mice lacking A20 specifically in DCs spontaneously developed lymphocyte-dependent colitis, seronegative ankylosing arthritis and enthesitis, conditions stereotypical of human inflammatory bowel disease (IBD). Our findings indicate that DCs need A20 to preserve immune quiescence and suggest that A20-dependent DC functions may underlie IBD and IBD-associated arthritides. C1 [Hammer, Gianna Elena; Turer, Emre E.; Taylor, Kimberly E.; Fang, Celia J.; Advincula, Rommel; Oshima, Shigeru; Barrera, Julio; Huang, Eric J.; Malynn, Barbara A.; Criswell, Lindsey A.; Nakamura, Mary C.; Ma, Averil] Univ Calif San Francisco, Dept Med, San Francisco, CA 94080 USA. [Fang, Celia J.] San Francisco VA Med Ctr, San Francisco, CA USA. [Huang, Eric J.; Nakamura, Mary C.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94140 USA. [Huang, Eric J.; Nakamura, Mary C.] VA Med Ctr, Pathol Serv, San Francisco, CA USA. [Hou, Baidong; DeFranco, Anthony] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA. [Reizis, Boris] Columbia Univ, Dept Microbiol & Immunol, New York, NY USA. RP Ma, A (reprint author), Univ Calif San Francisco, Dept Med, San Francisco, CA 94080 USA. EM averil.ma@ucsf.edu RI Oshima, Shigeru/C-9865-2015; OI Oshima, Shigeru/0000-0003-1186-9177; Huang, Eric/0000-0002-5381-3801; Reizis, Boris/0000-0003-1140-7853 FU US National Institutes of Health; Crohn's and Colitis Foundation of America; Damon Runyon Cancer Research Foundation; Kenneth Rainin Foundation; UCSF Liver Center; Wellcome Trust [076113, 085475] FX This work was supported by the US National Institutes of Health (A. M.), The Crohn's and Colitis Foundation of America (A. M. and S.O.), The Damon Runyon Cancer Research Foundation (G. E. H.), the Kenneth Rainin Foundation and the UCSF Liver Center and the Wellcome Trust (076113 and 085475 to the Wellcome Trust Case-Control Consortium). A full list of investigators who contributed to this work is available from the Wellcome Trust Case-Control Consortium website. NR 56 TC 102 Z9 104 U1 0 U2 15 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD DEC PY 2011 VL 12 IS 12 BP 1184 EP U77 DI 10.1038/ni.2135 PG 11 WC Immunology SC Immunology GA 850NT UT WOS:000297202700013 PM 22019834 ER PT J AU Karageorgiou, E Schulz, SC Gollub, RL Andreasen, NC Ho, BC Lauriello, J Calhoun, VD Bockholt, HJ Sponheim, SR Georgopoulos, AP AF Karageorgiou, Elissaios Schulz, S. Charles Gollub, Randy L. Andreasen, Nancy C. Ho, Beng-Choon Lauriello, John Calhoun, Vince D. Bockholt, H. Jeremy Sponheim, Scott R. Georgopoulos, Apostolos P. TI Neuropsychological Testing and Structural Magnetic Resonance Imaging as Diagnostic Biomarkers Early in the Course of Schizophrenia and Related Psychoses SO NEUROINFORMATICS LA English DT Article DE Schizophrenia; Schizophreniform; Schizoaffective; PCA; LDA; Biomarkers; Neuropsychology; MRI; Cross-validation; Diagnosis; MCIC ID 1ST-EPISODE SCHIZOPHRENIA; MATTER VOLUME; BRAIN; CLASSIFICATION; ABNORMALITIES; SCHIZOTYPAL; DISORDERS; ILLNESS; GRAY AB Making an accurate diagnosis of schizophrenia and related psychoses early in the course of the disease is important for initiating treatment and counseling patients and families. In this study, we developed classification models for early disease diagnosis using structural MRI (sMRI) and neuropsychological (NP) testing. We used sMRI measurements and NP test results from 28 patients with recent-onset schizophrenia and 47 healthy subjects, drawn from the larger sample of the Mind Clinical Imaging Consortium. We developed diagnostic models based on Linear Discriminant Analysis (LDA) following two approaches; namely, (a) stepwise (STP) LDA on the original measurements, and (b) LDA on variables created through Principal Component Analysis (PCA) and selected using the Humphrey-Ilgen parallel analysis. Error estimation of the modeling algorithms was evaluated by leave-one-out external cross-validation. These analyses were performed on sMRI and NP variables separately and in combination. The following classification accuracy was obtained for different variables and modeling algorithms. sMRI only: (a) STP-LDA: 64.3% sensitivity and 76.6% specificity, (b) PCA-LDA: 67.9% sensitivity and 72.3% specificity. NP only: (a) STP-LDA: 71.4% sensitivity and 80.9% specificity, (b) PCA-LDA: 78.5% sensitivity and 91.5% specificity. Combined sMRI-NP: (a) STP-LDA: 64.3% sensitivity and 83.0% specificity, (b) PCA-LDA: 89.3% sensitivity and 93.6% specificity. (i) Maximal diagnostic accuracy was achieved by combining sMRI and NP variables. (ii) NP variables were more informative than sMRI, indicating that cognitive deficits can be detected earlier than volumetric structural abnormalities. (iii) PCA-LDA yielded more accurate classification than STP-LDA. As these sMRI and NP tests are widely available, they can increase accuracy of early intervention strategies and possibly be used in evaluating treatment response. C1 [Karageorgiou, Elissaios; Sponheim, Scott R.; Georgopoulos, Apostolos P.] Vet Affairs Med Ctr, Brain Sci Ctr 11B, Minneapolis, MN 55417 USA. [Karageorgiou, Elissaios; Georgopoulos, Apostolos P.] Univ Minnesota, Sch Med, Dept Neurosci, Minneapolis, MN 55455 USA. [Karageorgiou, Elissaios; Georgopoulos, Apostolos P.] Univ Minnesota, Sch Med, Dept Neurol, Minneapolis, MN 55455 USA. [Karageorgiou, Elissaios; Georgopoulos, Apostolos P.] Univ Minnesota, Sch Med, Ctr Cognit Sci, Minneapolis, MN 55455 USA. [Schulz, S. Charles; Sponheim, Scott R.; Georgopoulos, Apostolos P.] Univ Minnesota, Sch Med, Dept Psychiat, Minneapolis, MN 55455 USA. [Schulz, S. Charles; Calhoun, Vince D.; Bockholt, H. Jeremy] Mind Res Network, Albuquerque, NM USA. [Gollub, Randy L.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. [Gollub, Randy L.] Harvard Univ, Sch Med, Charlestown, MA USA. [Andreasen, Nancy C.; Ho, Beng-Choon] Univ Iowa, Dept Psychiat, Carver Coll Med, Iowa City, IA 52242 USA. [Lauriello, John] Univ New Mexico, Dept Psychiat, Albuquerque, NM 87131 USA. [Calhoun, Vince D.] Univ New Mexico, Dept Elect & Comp Engn, Albuquerque, NM 87131 USA. [Sponheim, Scott R.] Vet Affairs Med Ctr, Mental Hlth Patient Serv Line, Minneapolis, MN 55417 USA. [Sponheim, Scott R.] Univ Minnesota, Sch Med, Dept Psychol, Minneapolis, MN 55455 USA. RP Georgopoulos, AP (reprint author), Vet Affairs Med Ctr, Brain Sci Ctr 11B, 1 Vet Dr, Minneapolis, MN 55417 USA. EM karag001@umn.edu; scs@umn.edu; rgollub@partners.org; nancy-andreasen@uiowa.edu; beng-ho@uiowa.edu; JLauriello@salud.unm.edu; vcalhoun@unm.edu; jbockholt@mrn.org; sponh001@umn.edu; omega@umn.edu RI Ho, Beng-Choon/D-6959-2011; Calhoun, Vince/H-7146-2013; OI Ho, Beng-Choon/0000-0003-3976-1555; Calhoun, Vince/0000-0001-9058-0747; Karageorgiou, Elissaios/0000-0001-9628-6370; Gollub, Randy L./0000-0002-9434-4044 FU United States Department of Energy [DE-FG02-99ER62764]; Department of Veterans Affairs; American Legion Brain Sciences Chair; Stanley Medical Research Institute FX Supported by the United States Department of Energy under Award Number DE-FG02-99ER62764 to The Mind Research Network (formerly The Mental Illness and Neuroscience Discovery [MIND] Institute), the Department of Veterans Affairs, the American Legion Brain Sciences Chair, and the Stanley Medical Research Institute. NR 48 TC 18 Z9 18 U1 1 U2 6 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1539-2791 J9 NEUROINFORMATICS JI Neuroinformatics PD DEC PY 2011 VL 9 IS 4 BP 321 EP 333 DI 10.1007/s12021-010-9094-6 PG 13 WC Computer Science, Interdisciplinary Applications; Neurosciences SC Computer Science; Neurosciences & Neurology GA 849UE UT WOS:000297150000002 PM 21246418 ER PT J AU Ropper, AE Cahill, KS Hanna, JW McCarthy, EF Gokaslan, ZL Chi, JH AF Ropper, Alexander E. Cahill, Kevin S. Hanna, John W. McCarthy, Edward F. Gokaslan, Ziya L. Chi, John H. TI Primary Vertebral Tumors: A Review of Epidemiologic, Histological, and Imaging Findings, Part I: Benign Tumors SO NEUROSURGERY LA English DT Review DE Aneurysmal bone cyst; Bone tumors; Eosinophilic granuloma; Hemangioma; Osteoid osteoma; Primary vertebral tumor; Spinal malignancies ID ANEURYSMAL BONE-CYST; OF-THE-LITERATURE; LANGERHANS CELL HISTIOCYTOSIS; PEDIATRIC CERVICAL-SPINE; EOSINOPHILIC GRANULOMA; FIBROUS DYSPLASIA; OSTEOID OSTEOMA; NATURAL-HISTORY; MOBILE SPINE; FLUID LEVELS AB Primary vertebral tumors, although less common than metastases to the spine, make up a heterogeneous group of neoplasms that can pose diagnostic and treatment challenges. They affect both the adult and the pediatric population and may be benign, locally aggressive, or malignant. An understanding of typical imaging findings will aid in accurate diagnosis and help neurosurgeons appreciate anatomic subtleties that may increase their effective resection. An understanding of the histological similarities and differences between these tumors is imperative for all members of the clinical team caring for these patients. In this first review of 2 parts, we discuss the epidemiological, histological, and imaging features of the most common benign primary vertebral tumors-aneurysmal bone cyst, chondroma and enchondroma, hemangioma, osteoid osteoma, and osteoblastoma-and lesions related to eosinophilic granuloma and fibrous dysplasia. In addition, we discuss the basic management paradigms for each of these diagnoses. In combination with part II of the review, which focuses on locally aggressive and malignant tumors, this article provides a comprehensive review of primary vertebral tumors. C1 [Ropper, Alexander E.; Cahill, Kevin S.; Chi, John H.] Harvard Univ, Brigham & Womens Hosp, Dept Neurosurg, Dana Farber Canc Inst,Sch Med, Boston, MA 02115 USA. [Hanna, John W.] Harvard Univ, Brigham & Womens Hosp, Dept Pathol, Dana Farber Canc Inst,Sch Med, Boston, MA 02115 USA. [McCarthy, Edward F.] Johns Hopkins Univ, Sch Med, Dept Pathol, Johns Hopkins Hosp, Baltimore, MD 21205 USA. [Gokaslan, Ziya L.] Johns Hopkins Univ, Sch Med, Dept kNeurosurg, Johns Hopkins Hosp, Baltimore, MD 21205 USA. RP Chi, JH (reprint author), Brigham & Womens Hosp, Dept Neurosurg, 15 Francis St, Boston, MA 02115 USA. EM jchi@partners.org NR 73 TC 25 Z9 25 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD DEC PY 2011 VL 69 IS 6 BP 1171 EP 1180 DI 10.1227/NEU.0b013e31822b8107 PG 10 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 845AF UT WOS:000296794500021 PM 21725252 ER PT J AU Falowski, SM Sharan, A Reyes, BAS Sikkema, C Szot, P Van Bockstaele, EJ AF Falowski, Steven M. Sharan, Ashwini Reyes, Beverly A. S. Sikkema, Carl Szot, Patricia Van Bockstaele, Elisabeth J. TI An Evaluation of Neuroplasticity and Behavior After Deep Brain Stimulation of the Nucleus Accumbens in an Animal Model of Depression SO NEUROSURGERY LA English DT Article DE DBS; Deep brain stimulation; Dendritic plasticity; Depression; Neuroplasticity; Nucleus accumbens ID MEDIAL PREFRONTAL CORTEX; WISTAR-KYOTO RATS; NEUROPSYCHIATRIC DISORDERS; STRAIN DIFFERENCES; STRESS; SHELL; THALAMUS; ANTIDEPRESSANT; EPIDEMIOLOGY; CONVERGENCE AB BACKGROUND: Recent interest has demonstrated the nucleus accumbens (NAcc) as a potential target for the treatment of depression with deep brain stimulation (DBS). OBJECTIVE: To demonstrate that DBS of the NAcc is an effective treatment modality for depression and that chemical and structural changes associated with these behavioral changes are markers of neuroplasticity. METHODS: A deep brain stimulator was placed in the NAcc of male Wistar-Kyoto rats. Groups were divided into sham (no stimulation), intermittent (3 h/d for 2 weeks), or continuous (constant stimulation for 2 weeks). Exploratory and anxietylike behaviors were evaluated with the open-field test before and after stimulation. Tissue samples of the prefrontal cortex (PFC) were processed with Western blot analysis of markers of noradrenergic activity that included the noradrenergic synthesizing enzyme tyrosine hydroxylase. Analysis of tissue levels for catecholamines was achieved with high-performance liquid chromatography. Morphological properties of cortical pyramidal neurons were assessed with Golgi-Cox staining. RESULTS: Subjects undergoing intermittent and continuous stimulation of the NAcc exhibited an increase in exploratory behavior and reduced anxietylike behaviors. Tyrosine hydroxylase expression levels were decreased in the PFC after intermittent and continuous DBS, and dopamine and norepinephrine levels were decreased after continuous stimulation. Golgi-Cox staining indicated that DBS increased the length of apical and basilar dendrites in pyramidal neurons of the PFC. CONCLUSION: Deep brain stimulation induces behavioral improvement in and neurochemical and morphological alterations of the PFC that demonstrate changes within the circuitry of the brain different from the target area of stimulation. This observed dendritic plasticity may underlie the therapeutic efficacy of this treatment. C1 [Falowski, Steven M.; Sharan, Ashwini] Thomas Jefferson Univ, Dept Neurosurg, Philadelphia, PA 19107 USA. [Reyes, Beverly A. S.; Van Bockstaele, Elisabeth J.] Thomas Jefferson Univ, Dept Neurosci, Farber Inst Neurosci, Philadelphia, PA 19107 USA. [Sikkema, Carl; Szot, Patricia] VA Puget Sound Hlth Care Syst, MIRECC, Seattle, WA USA. RP Falowski, SM (reprint author), Thomas Jefferson Univ, Dept Neurosurg, 909 Walnut St, Philadelphia, PA 19107 USA. EM sfalowski@gmail.com FU NIDA NIH HHS [R01 DA009082] NR 50 TC 29 Z9 30 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD DEC PY 2011 VL 69 IS 6 BP 1281 EP 1290 DI 10.1227/NEU.0b013e3182237346 PG 10 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 845AF UT WOS:000296794500033 PM 21566538 ER PT J AU Proctor, SP Heaton, KJ Smith, KW Rodrigues, ER Widing, DE Herrick, R Vasterling, JJ McClean, MD AF Proctor, Susan P. Heaton, Kristin J. Smith, Kristen W. Rodrigues, Ema R. Widing, Drew E. Herrick, Robert Vasterling, Jennifer J. McClean, Michael D. TI The Occupational JP8 Exposure Neuroepidemiology Study (OJENES): Repeated workday exposure and central nervous system functioning among US Air Force personnel SO NEUROTOXICOLOGY LA English DT Article DE JP8; Jet fuel; Central nervous system; Exposure assessment; Military ID VOLATILE ORGANIC-COMPOUNDS; CLINICAL BALANCE TESTS; TRUNK SWAY MEASURES; S-TRANSFERASE M1; JET FUEL JP-8; POSTURAL STABILITY; MASS-SPECTROMETRY; DERMAL EXPOSURE; BENZENE; WORKERS AB One of the most prevalent workplace chemical exposures historically and currently confronting the global military and civilian workforce is jet propellant (JP) fuel (e.g., JP4, JP5, JP8, jet A1), a complex mixture of numerous hydrocarbon compounds and additives. To date, numerous protective and preventive strategies (e.g., federal exposure limits, workplace procedure protocols, protective gear such as goggles, respirator use, gloves, and coveralls) have been put in place to minimize acutely toxic exposure levels. However, questions remain regarding the effect of repeated exposures at lower (than regulated) levels of JP fuel. The Occupational JP8 Exposure Neuroepidemiology Study (OJENES) was designed to examine the relationships between occupational JP8 exposure over multiple, repeated workdays and specific aspects of central nervous system (CNS) functioning among Air Force (AF) personnel. In this report, we present the OJENES methodology, descriptive findings related to participant characteristics, JP8 exposure levels observed over a work week among higher and lower exposure groups, and neuropsychological task performances at the first study assessment. Results indicated minimal differences between participants in the high and lower exposure groups in terms of descriptive characteristics, other than daily JP8 exposure levels (p < 0.001). In addition, neuropsychological task performances for most task measures were not found to be significantly different from reported reference ranges. These findings demonstrated that confounding and misclassification of exposure and outcome status are not major concerns for the study. Therefore, future OJENES analyses targeting the more focused research questions regarding associations between JP8 exposure and CNS functioning are likely to provide valid conclusions, as they will be less influenced by these research biases. (C) 2011 Elsevier Inc. All rights reserved. C1 [Proctor, Susan P.; Heaton, Kristin J.] USA, Mil Performance Div, Environm Med Res Inst, Natick, MA 01760 USA. [Proctor, Susan P.] VA Boston Healthcare Syst, Res Serv, Boston, MA 02130 USA. [Proctor, Susan P.; Heaton, Kristin J.; Smith, Kristen W.; Rodrigues, Ema R.; McClean, Michael D.] Boston Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02118 USA. [Widing, Drew E.] USAF, Res Lab, Wright Patterson AFB, OH 45433 USA. [Herrick, Robert] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Vasterling, Jennifer J.] VA Boston Healthcare Syst, Psychol Serv, Boston, MA 02130 USA. [Vasterling, Jennifer J.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. RP Proctor, SP (reprint author), USA, Mil Performance Div, Environm Med Res Inst, Kansas St,Bldg 42, Natick, MA 01760 USA. EM susan.proctor@us.army.mil RI Heaton, Kristin/E-3660-2013; McClean, Michael/J-2934-2015; OI McClean, Michael/0000-0002-3902-8823 FU U.S. Air Force; US Army Medical Research [W81XWH-06-1-0105] FX We thank the U.S. Air Force personnel for their support and generous participation in the project. We are grateful to LTC Theresa Brininger, along with additional Boston area study team personnel (N. Longcore, E. Kryskow, K. Merchant-Borna, H. MacDonald, and A. Graefe) and other personnel from local universities for their assistance in Study 2 data collection process at the respective US Air Force base locations. We acknowledge and appreciate the personnel at the Organic Chemistry Analytical Laboratory at the Harvard School of Public Health (HSPH), Centers for Disease Control and Prevention (CDC, Combustion Products and Persistent Pollutants Biomonitoring Laboratory, VOC and Perchlorate Laboratory, and Tobacco Exposure Biomarkers Laboratory), and Brown University (Center for Environmental Health and Technology) for the timely analyses of collected environmental and personal samples. We appreciate the assistance of Ms. Alexis Maule in helping to prepare this manuscript for submission. This work was supported by the US Army Medical Research and Materiel Command/Neurotoxin Exposure Treatment Program (NETRP) through a grant award (W81XWH-06-1-0105: PI: S. P. Proctor) to the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. NR 70 TC 4 Z9 4 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD DEC PY 2011 VL 32 IS 6 BP 799 EP 808 DI 10.1016/j.neuro.2011.06.010 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 847VK UT WOS:000297000400014 PM 21824494 ER PT J AU Chao, LDL Abadjian, L Hlavin, J Meyerhoff, DJ Weiner, MW AF Chao, Linda L. Abadjian, Linda Hlavin, Jennifer Meyerhoff, Deiter J. Weiner, Michael W. TI Effects of low-level sarin and cyclosarin exposure and Gulf War Illness on Brain Structure and Function: A study at 4 T SO NEUROTOXICOLOGY LA English DT Article DE Magnetic resonance imaging; Morphometric analysis; Brain; Central nervous system; Cognitive functioning; Chemical warfare agents; Sarin; Cyclosarin; Gulf War veterans ID US ARMY VETERANS; NEUROBEHAVIORAL DEFICITS; PARKINSONS-DISEASE; RISK-FACTORS; MULTISYMPTOM ILLNESS; ALZHEIMER-DISEASE; MR SPECTROSCOPY; INJURY; KHAMISIYAH; DEMENTIA AB Background: More than 100,000 US troops were potentially exposed to chemical warfare agents sarin (GB) and cyclosarin (GF) when an ammunition dump at Khamisiyah, Iraq was destroyed during the 1991 Persian Gulf War (GW). We previously found reduced total gray matter (GM) volume in 40 GW veterans with suspected GB/GF exposure relative to 40 matched, unexposed GW veterans on a 1.5 T MR scanner. In this study, we reexamine the relationship between GB/GF exposure and volumetric measurements of gross neuroanatomical structures in a different cohort of GW veterans on a 4 T MR scanner. Methods: Neuropsychological and magnetic resonance imaging (MRI) data from a cross sectional study on Gulf War Illness performed between 2005 and 2010 were used in this study. 4T MRI data were analyzed using automated image processing techniques that produced volumetric measurements of gray matter (GM), white matter (WM) and cerebrospinal fluid (CSF). Results: Binary comparisons of 64 GB/GF exposed veterans and 64 'matched', unexposed veterans revealed reduced GM (p = 0.03) and WM (p = 0.03) volumes in the exposed veterans. Behaviorally, exposed veterans committed more errors of omission (p = 0.02) and tended to have slower responses (p = 0.05) than unexposed veterans on the Continuous Performance Test (CPT), a measure sustained and selective attention. Regression analyses confirmed that GB/GF exposure status predicted GM (beta = -0.11, p = 0.02) and WM (beta = -0.14, p = 0.03) volumes, and number of CPT omission errors (beta = 0.22, p = 0.02) over and above potentially confounding demographic, clinical, and psychosocial variables. There was no dose-response relationship between estimated levels of GB/GF exposure and brain volume. However, we did find an effect of Gulf War Illness/Chronic Mulitsymptom Illness on both GM and WM volume in the GB/GF exposed veterans. Conclusions: These findings confirm previous reports by our group and others of central nervous system pathology in GW veterans with suspected exposure to low levels of GB/GF two decades after the exposure. (C) 2011 Elsevier Inc. All rights reserved. C1 [Chao, Linda L.; Abadjian, Linda; Hlavin, Jennifer; Meyerhoff, Deiter J.; Weiner, Michael W.] San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA USA. [Chao, Linda L.; Weiner, Michael W.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Chao, Linda L.; Meyerhoff, Deiter J.; Weiner, Michael W.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. RP Chao, LDL (reprint author), 4150 Clement St,114M, San Francisco, CA 94121 USA. EM linda.chao@ucsf.edu FU NIH/NCRR UCSF-CTSI [UL1 RR024131]; Department of Defense [DAMD17-01-1-0764]; US Army Medical Research and Materiel Command and a Department of Veterans Affairs [B3776]; Department of Veteran's Affairs FX This publication was supported by NIH/NCRR UCSF-CTSI Grant Number UL1 RR024131. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. This study was also supported by Department of Defense grant DAMD17-01-1-0764 entitled 'Magnetic Resonance and Spectroscopy of the Human Brain in Gulf War Illness', awarded to the Northern California Institute for Research and Education from the Department of Defense Gulf War Illnesses Research Program, US Army Medical Research and Materiel Command and a Department of Veterans Affairs grant VA GWI No. B3776 entitled 'Effects of Gulf War Illness on Brain Structure Function and Metabolism: MRI/MRS at 4 T', awarded to Dr. Michael Weiner. This material is the result of work supported with resources and the use of facilities at the San Francisco Veterans Affairs Medical Center. The authors acknowledge Col. Karl Friedl, US Army Medical Research and Materiel Command, Derek Flenniken for managing the database, Diana Truran Sacrey and her staff for scanning the subjects and processing the MRI data, Larry Sippos, Executive Officer to the Deputy Assistant Secretary of Defense for Force Health Protection and Readiness for providing information about the presence or absence of the research participants' units in the modeled hazard areas and the cumulative estimated GB/GF exposure levels, and the Gulf War veterans who participated in these studies.; The opinions or assertions contained herein are the private views of the author(s) and are not to be construed as official or reflecting the views of the Army, Department of Defense, or Department of Veterans Affairs. Drs. Chao, Meyerhoff, and Weiner have received grant support from the Department of Defense and Dr. Weiner receives grant support from the Department of Veteran's Affairs. NR 49 TC 19 Z9 19 U1 2 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD DEC PY 2011 VL 32 IS 6 BP 814 EP 822 DI 10.1016/j.neuro.2011.06.006 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 847VK UT WOS:000297000400016 PM 21741405 ER PT J AU Han, LP Geng, LN Liu, XR Shi, HR He, W Wu, MX AF Han, Liping Geng, Lina Liu, Xiangrong Shi, Huirong He, Wei Wu, Mei X. TI Clinical Significance of IEX-1 Expression in Ovarian Carcinoma SO ULTRASTRUCTURAL PATHOLOGY LA English DT Article DE apoptosis; IEX-1; ovarian carcinoma; prognosis ID EARLY-RESPONSE GENE; NF-KAPPA-B; IMMEDIATE-EARLY GENE; P53 TUMOR-SUPPRESSOR; CELL-DEATH; APOPTOSIS; CANCER; IDENTIFICATION; ACTIVATION; KERATINOCYTES AB Background: The stress-inducible immediate early response gene X-1 (IEX-1) regulates cell proliferation and apoptosis in a cell type and stimulus-dependent manner. The aim of this study was to investigate IEX-1 expression and its role in apoptosis of ovarian epithelial tumors for potential use in clinical diagnosis and therapy. Methods: IEX-1 expression was examined in paraffin-embedded specimens from 77 patients with epithelial ovarian tumors using immunohistochemistry. Correlation between IEX-1 expression and other clinicopathological parameters was evaluated. Apoptosis of tumor cells was detected by terminal deoxynucleotide transferase-mediated dUTP nick end labeling (TUNEL). Results: IEX-1 expression was significantly lower in ovarian cancers compared to cystadenomas and borderline tumors (p < .05). The expression was significantly associated with FIGO stage and histological grade (p < .05), but not with age, histological type, or residual tumor (p > .05). A positive correlation was also observed between IEX-1 expression and apoptotic index (p < .01) or survival (p = .005). Conclusion: With the development of epithelial ovarian tumors from benign to malignant, IEX-1 expression is decreased, concomitant with a decreased rate of cell apoptosis. Thus, IEX-1 is pro-apoptotic in the development of epithelial ovarian cancer. The pro-apoptotic activity may take part in restraining tumor growth at the early stage of ovarian epithelial cancer, whereas its decreased expression probably contributes to the abnormal survival advantage for malignant cancer. Altered IEX-1 expression can potentially be a new predictor of the malignant transformation and a prognostic indicator for cancer therapy. C1 [Han, Liping; Geng, Lina; Liu, Xiangrong; Shi, Huirong] Zhengzhou Univ, Dept Obstet & Gynaecol, Affiliated Hosp 1, Zhengzhou, Henan, Peoples R China. [He, Wei] Zhengzhou Univ, Continuing Educ Sch, Zhengzhou, Henan, Peoples R China. [Wu, Mei X.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. RP Han, LP (reprint author), Zhengzhou Univ, Dept Obstet & Gynaecol, Affiliated Hosp 1, Zhengzhou, Henan, Peoples R China. EM hanlp0825@yahoo.com.cn NR 34 TC 12 Z9 12 U1 0 U2 3 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0191-3123 J9 ULTRASTRUCT PATHOL JI Ultrastruct. Pathol. PD DEC PY 2011 VL 35 IS 6 BP 260 EP 266 DI 10.3109/01913123.2011.608916 PG 7 WC Microscopy; Pathology SC Microscopy; Pathology GA 848PD UT WOS:000297062600005 PM 22085302 ER PT J AU Schwartzman, A Gavrilov, Y Adler, RJ AF Schwartzman, Armin Gavrilov, Yulia Adler, Robert J. TI MULTIPLE TESTING OF LOCAL MAXIMA FOR DETECTION OF PEAKS IN 1D SO ANNALS OF STATISTICS LA English DT Article DE False discovery rate; Gaussian process; kernel smoothing; matched filter; topological inference ID FALSE DISCOVERY RATE; RANDOM-FIELD THEORY; BIOMARKER DISCOVERY; MASS-SPECTROMETRY; PROTEOMIC DATA; DECONVOLUTION; INFERENCE; SIGNALS; ACTIVATION; SPIKES AB A topological multiple testing scheme for one-dimensional domains is proposed where, rather than testing every spatial or temporal location for the presence of a signal, tests are performed only at the local maxima of the smoothed observed sequence. Assuming unimodal true peaks with finite support and Gaussian stationary ergodic noise, it is shown that the algorithm with Bonferroni or Benjamini-Hochberg correction provides asymptotic strong control of the family wise error rate and false discovery rate, and is power consistent, as the search space and the signal strength get large, where the search space may grow exponentially faster than the signal strength. Simulations show that error levels are maintained for nonasymptotic conditions, and that power is maximized when the smoothing kernel is close in shape and bandwidth to the signal peaks, akin to the matched filter theorem in signal processing. The methods are illustrated in an analysis of electrical recordings of neuronal cell activity. C1 [Schwartzman, Armin; Gavrilov, Yulia] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02446 USA. [Schwartzman, Armin; Gavrilov, Yulia] Dana Farber Canc Inst, Boston, MA 02446 USA. [Adler, Robert J.] Technion Israel Inst Technol, Dept Elect Engn, IL-32000 Haifa, Israel. RP Schwartzman, A (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 450 Brookline Ave,CLS 11007, Boston, MA 02446 USA. EM armins@hsph.harvard.edu; yuliagavrilov@gmail.com; robert@ee.technion.ac.il OI Schwartzman, Armin/0000-0001-5335-1611 FU Claudia Adams Barr Program in Cancer Research; William F. Milton Fund; NIH [P01-CA134294]; US-Israel Binational Science Foundation [2008262]; Israel Science Foundation [853/10] FX Supported in part by the Claudia Adams Barr Program in Cancer Research, the William F. Milton Fund and NIH Grant P01-CA134294.; Supported in part by US-Israel Binational Science Foundation, 2008262 and Israel Science Foundation, 853/10. NR 36 TC 14 Z9 14 U1 0 U2 7 PU INST MATHEMATICAL STATISTICS PI CLEVELAND PA 3163 SOMERSET DR, CLEVELAND, OH 44122 USA SN 0090-5364 J9 ANN STAT JI Ann. Stat. PD DEC PY 2011 VL 39 IS 6 BP 3290 EP 3319 DI 10.1214/11-AOS943 PG 30 WC Statistics & Probability SC Mathematics GA 044RD UT WOS:000311639700006 PM 23576826 ER PT J AU Yang, PL Gao, M Lin, K Liu, QS Villareal, VA AF Yang, Priscilla L. Gao, Min Lin, Kai Liu, Qingsong Villareal, Valerie A. TI Anti-HCV drugs in the pipeline SO CURRENT OPINION IN VIROLOGY LA English DT Article ID HEPATITIS-C-VIRUS; TREATMENT-NAIVE PATIENTS; DEPENDENT RNA-POLYMERASE; REPLICATION IN-VITRO; NS5A INHIBITOR BMS-790052; CYCLOPHILIN INHIBITOR; ANTIVIRAL ACTIVITY; GENOTYPE 1; CRYSTAL-STRUCTURE; NONNUCLEOSIDE POLYMERASE AB Several directly acting and host targeting antivirals that inhibit hepatitis C virus replication have entered clinical trials. Among the most advanced of these are RG7128, an inhibitor of the NS5B polymerase; BMS-790052, an inhibitor of NS5A; and alisporivir, an inhibitor of human cyclophilins. These agents have potent antiviral activity in chronic HCV patients, act additively or synergistically with inhibitors of the HCV NS3/4A protease, and improve the rate of virologic response produced by traditional pegylated interferon plus ribavirin therapy. No cross resistance has been observed; moreover, nucleoside NS5B and cyclophilin inhibitors appear to suppress resistance to non-nucleoside NS5B and NS3/4A inhibitors. Several recent reports of virologic responses produced by combinations of agents that inhibit HCV replication in the absence of interferon provide optimism that eradication of HCV will be possible without interferon in the future. C1 [Yang, Priscilla L.; Villareal, Valerie A.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. [Gao, Min] Bristol Myers Squibb Co, Dept Virol, Wallingford, CT 06492 USA. [Lin, Kai] Novartis Inst Biomed Res Inc, Cambridge, MA 01239 USA. [Liu, Qingsong] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Liu, Qingsong] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Yang, PL (reprint author), Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, 200 Longwood Ave, Boston, MA 02115 USA. EM Priscilla_yang@hms.harvard.edu OI liu, qing song/0000-0002-7829-2547 FU Bristol Myers Squibb Company; Novartis; Research Enabling Grant from the Harvard Office of Faculty Development and Diversity, a John and Virginia Kaneb Fellowship; National Institutes of Health [AI068999, AI076442]; Diversity Supplement [AI076442] FX Min Gao is a full-time employee of the Bristol Myers Squibb Company, which is the sponsor developing BMS-790052. Kai Lin is a full-time employee of Novartis, which is the sponsor developing alisorivir for the treatment of hepatitis C.; PLY was supported by a Research Enabling Grant from the Harvard Office of Faculty Development and Diversity, a John and Virginia Kaneb Fellowship, and National Institutes of Health grant awards AI068999 and AI076442. VAV was supported by a Diversity Supplement to NIH AI076442. NR 90 TC 29 Z9 29 U1 3 U2 10 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1879-6257 J9 CURR OPIN VIROL JI Curr. Opin. Virol. PD DEC PY 2011 VL 1 IS 6 BP 607 EP 616 DI 10.1016/j.coviro.2011.10.019 PG 10 WC Virology SC Virology GA 051FV UT WOS:000312112500020 PM 22440918 ER PT J AU Khosroshahi, A Deshpande, V Stone, JH AF Khosroshahi, Arezou Deshpande, Vikram Stone, John H. TI The Clinical and Pathological Features of IgG(4)-Related Disease SO CURRENT RHEUMATOLOGY REPORTS LA English DT Article DE IgG(4); IgG(4)-related disease; Autoimmune pancreatitis; Chronic sclerosing sialadenitis; Riedel's thyroiditis; Sclerosing cholangitis; Lymphoplasmacytic aortitis; Retroperitoneal fibrosis; Tubulointerstitial nephritis; Orbital pseudotumor; Dacryoadenitis; Dacrocystitis; Lacrimal gland; Mikulicz's syndrome; Lymphadenopathy; Pachymeningitis; Storiform fibrosis; Obliterative phlebitis; Eosinophilia; Hypophysitis; Hepatopathy; Rituximab; Vasculitis AB The rapidly emerging disorder now known as IgG(4)-related disease (IgG(4)-RD) includes a variety of clinical entities once regarded as being entirely separate diseases. Manifestations of IgG(4)-RD have now been reported in essentially all organ systems. Regardless of which organ is involved, tissue biopsies reveal striking histopathological similarities. The hallmark pathology findings are diffuse lymphoplasmacytic infiltrates, abundant IgG(4)-positive plasma cells, modest tissue eosinophilia, and extensive fibrosis. Tumorous swelling and obliterative phlebitis are other frequently observed features. Polyclonal elevations of serum IgG(4) are found in approximately 70% of patients. Many questions pertaining to the etiology, pathophysiology, epidemiology, clinical features, therapy, disease monitoring, and long-term outcomes remain to be addressed. This paper focuses on the clinical and pathological features of IgG(4)-RD. C1 [Khosroshahi, Arezou; Stone, John H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Rheumatol Unit, Boston, MA 02114 USA. [Deshpande, Vikram] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Stone, JH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Rheumatol Unit, Boston, MA 02114 USA. EM jhstone@partners.org NR 91 TC 8 Z9 8 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3774 EI 1534-6307 J9 CURR RHEUMATOL REP JI Curr. Rheumatol. Rep. PD DEC PY 2011 VL 13 IS 6 BP 473 EP 481 DI 10.1007/s11926-011-0213-7 PG 9 WC Rheumatology SC Rheumatology GA V29TU UT WOS:000208771500002 PM 21964954 ER PT J AU Michelson, AD AF Michelson, Alan D. TI Advances in Antiplatelet Therapy SO HEMATOLOGY-AMERICAN SOCIETY HEMATOLOGY EDUCATION PROGRAM LA English DT Article AB Because of the central role of platelets in cardiovascular atherothrombosis, there is a well-established therapeutic role for antiplatelet therapy that includes aspirin (a cyclooxygenase 1 [COX1] inhibitor), clopidogrel (an antagonist of the ADP P2Y(12) receptor), and the GPIIb-GPIIIa (alpha IIb beta 3) antagonists. However, there remains a significant incidence of arterial thrombosis in patients treated with currently available antiplatelet therapy. Novel P2Y(12) antagonists such as the recently US Food and Drug Administration (FDA)-approved prasugrel, along with ticagrelor, cangrelor, and elinogrel, have advantages over clopidogrel, including more rapid, less variable, and more complete inhibition of platelet function. Currently ongoing phase 3 studies will determine whether these new P2Y(12) antagonists will result in better and/or more rapid antithrombotic effects than clopidogrel, without an unacceptable increase in hemorrhagic or other side effects, as has been recently reported in some clinical settings for prasugrel and ticagrelor. Antagonists of the thrombin receptor protease-activated receptor 1 (PAR1) are also undergoing phase 3 trials, and many other novel antiplatelet agents are under investigation as antithrombotic agents. C1 [Michelson, Alan D.] Harvard Univ, Sch Med, Dana Farber Canc Inst,Childrens Hosp Boston, Ctr Platelet Res Studies,Div Hematol Oncol, Boston, MA 02115 USA. RP Michelson, AD (reprint author), Childrens Hosp, Ctr Platelet Res Studies, Karp 08213,300 Longwood Ave, Boston, MA 02115 USA. EM alan.michelson@childrens.harvard.edu FU Lilly/Daiichi Sankyo; Takeda; GLSynthesis FX The author has received research funding from Lilly/Daiichi Sankyo, Takeda, and GLSynthesis, and has served on a data-monitoring committee for a clinical trial for Lilly/Daiichi Sankyo. Off-label drug use: None disclosed. NR 40 TC 18 Z9 19 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 1520-4391 J9 HEMATOL-AM SOC HEMAT JI Hematol.-Am. Soc. Hematol. Educ. Program PD DEC PY 2011 BP 62 EP 69 DI 10.1182/asheducation-2011.1.62 PG 8 WC Education, Scientific Disciplines; Hematology SC Education & Educational Research; Hematology GA V29PG UT WOS:000208759700009 ER PT J AU Guinan, EC AF Guinan, Eva C. TI Diagnosis and Management of Aplastic Anemia SO HEMATOLOGY-AMERICAN SOCIETY HEMATOLOGY EDUCATION PROGRAM LA English DT Article AB Aplastic anemia remains a diagnosis of exclusion. Our ability to reliably diagnose, and therefore exclude, a variety of inherited or acquired diseases with similar phenotypes has improved markedly. An efficient diagnostic plan is important because time from diagnosis to treatment is related to outcome regardless of the therapeutic option chosen. HSCT remains the mainstay of therapy for those with matched sibling donors, and results have improved even further in recent years. For those without a sibling donor, the high response and overall survival rates of combined immunosuppressive therapy (IST) have proven robust. Nonetheless, incomplete response, relapse, and progression to myelodysplasia/leukemia have more clearly emerged as significant long-term issues. Improvements in outcome of alternative donor transplantation and the use of established and novel immunosuppressive agents provide multiple alternatives for treating refractory or relapsed patients. Best practices in this regard are not yet clearly established and may vary by a variety of demographic and treatment-specific factors. Regardless of the type of therapeutic approach, patients require ongoing monitoring for occurrence of disease and/or therapy-related side effects. C1 Dana Farber Canc Inst, Boston, MA 02215 USA. RP Guinan, EC (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM eva_guinan@dfci.harvard.edu NR 50 TC 15 Z9 15 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 1520-4391 J9 HEMATOL-AM SOC HEMAT JI Hematol.-Am. Soc. Hematol. Educ. Program PD DEC PY 2011 BP 76 EP 81 DI 10.1182/asheducation-2011.1.76 PG 6 WC Education, Scientific Disciplines; Hematology SC Education & Educational Research; Hematology GA V29PG UT WOS:000208759700011 ER PT J AU DeZern, AE Guinan, EC AF DeZern, Amy E. Guinan, Eva C. TI Therapy for Aplastic Anemia SO HEMATOLOGY-AMERICAN SOCIETY HEMATOLOGY EDUCATION PROGRAM LA English DT Article AB A 24-year-old man from Ecuador presents to your clinic with dyspnea on exertion, bruising, and petechiae. He is noted to be pancytopenic with ANC 430, hemoglobin 7.4 g/dL(reticulocyte count 0.9%), and platelets 18 000. His BM biopsy is hypocellular for age. Ultimately, he is diagnosed with severe aplastic anemia. He is the only child of 2 South American parents without any matches in the unrelated donor registry, including cord blood. He is red cell-and platelet transfusion-dependent. He has been recommended therapy with antithymocyte globulin and cyclosporine but declined it. He seeks recommendations about new alternatives to this regimen to improve his chance of response. C1 [DeZern, Amy E.] Johns Hopkins Univ, Dept Oncol, Baltimore, MD 21205 USA. [Guinan, Eva C.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP DeZern, AE (reprint author), Johns Hopkins Univ, Sch Med, Dept Oncol, CRB 1,Room 186, Baltimore, MD 21205 USA. EM adezern1@jhmi.edu NR 12 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 1520-4391 J9 HEMATOL-AM SOC HEMAT JI Hematol.-Am. Soc. Hematol. Educ. Program PD DEC PY 2011 BP 82 EP 83 DI 10.1182/asheducation-2011.1.82 PG 2 WC Education, Scientific Disciplines; Hematology SC Education & Educational Research; Hematology GA V29PG UT WOS:000208759700012 ER PT J AU Arnason, JE Brown, JR AF Arnason, Jon E. Brown, Jennifer R. TI Alemtuzumab Use In Relapsed and Refractory Chronic Lymphocytic Leukemia SO HEMATOLOGY-AMERICAN SOCIETY HEMATOLOGY EDUCATION PROGRAM LA English DT Article AB A 62-year-old woman with chronic lymphocytic leukemia (CLL) who initially presented with lymphocytosis and 13q deletion in 1996 now presents to the clinic for recommendations regarding relapsed disease. The patient has received multiple prior therapies, including single-agent fludarabine, fludarabine and rituximab, and bendamustine and rituximab. She now has recurrent lymphocytosis with a WBC count that has increased from 13 000 2 months ago to 115 000 today and a platelet count of 55 000 but no lymphadenopathy. In addition, your evaluation finds that she has acquired a 17p deletion. C1 [Arnason, Jon E.; Brown, Jennifer R.] Harvard Univ, Sch Med, Boston, MA USA. [Arnason, Jon E.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Brown, Jennifer R.] DFCI, CLL Ctr, Boston, MA USA. RP Arnason, JE (reprint author), Beth Israel Deaconess Med Ctr, 330 Brookline Ave,KS 121, Boston, MA 02215 USA. EM jarnason@bidmc.harvard.edu FU Calistoga; Celgene; Genzyme; GSK FX J.A. declares no competing financial interests. J.B. has consulted for Calistoga; has received honoraria from Celgene; and has received research funding from Calistoga, Celgene, Genzyme, and GSK. Off-label drug use: Alemtuzumab given subcutaneously. NR 13 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 1520-4391 J9 HEMATOL-AM SOC HEMAT JI Hematol.-Am. Soc. Hematol. Educ. Program PD DEC PY 2011 BP 119 EP 120 DI 10.1182/asheducation-2011.1.119 PG 2 WC Education, Scientific Disciplines; Hematology SC Education & Educational Research; Hematology GA V29PG UT WOS:000208759700018 ER PT J AU Anderson, KC AF Anderson, Kenneth C. TI New Insights into Therapeutic Targets in Myeloma SO HEMATOLOGY-AMERICAN SOCIETY HEMATOLOGY EDUCATION PROGRAM LA English DT Article AB Patient outcome in multiple myeloma (MM) has been remarkably improved due to the use of combination therapies including proteasome inhibitors and immunomodulatory drugs, which target the tumor in its BM microenvironment. Ongoing efforts to improve the treatment paradigm even further include using oncogenomics to better characterize molecular pathogenesis and to develop refined patient stratification and personalized medicine in MM; using models of MM in its BM milieu to identify novel targets and to validate next-generation therapeutics directed at these targets; developing immune-based therapies including mAbs, immunotoxins targeting MM cells and cytokines, and novel vaccine strategies; and using functional oncogenomics to inform the design of novel combination therapies. With continued rapid evolution of progress in these areas, MM will be a chronic illness with sustained complete response in a significant number of patients. C1 Dana Farber Canc Inst, Boston, MA 02215 USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,Mayer 557, Boston, MA 02215 USA. EM kenneth_anderson@dfci.harvard.edu NR 68 TC 20 Z9 21 U1 0 U2 6 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 1520-4391 J9 HEMATOL-AM SOC HEMAT JI Hematol.-Am. Soc. Hematol. Educ. Program PD DEC PY 2011 BP 184 EP 190 DI 10.1182/asheducation-2011.1.184 PG 7 WC Education, Scientific Disciplines; Hematology SC Education & Educational Research; Hematology GA V29PG UT WOS:000208759700028 ER PT J AU Bernt, KM Armstrong, SA AF Bernt, Kathrin M. Armstrong, Scott A. TI Targeting Epigenetic Programs in MLL-Rearranged Leukemias SO HEMATOLOGY-AMERICAN SOCIETY HEMATOLOGY EDUCATION PROGRAM LA English DT Article AB Rearrangements of the Mixed-Lineage Leukemia (MLL) gene are found in > 70% of infant leukemia, similar to 10% of adult acute myelogenous leukemia (AML), and many cases of secondary acute leukemias. The presence of an MLL rearrangement generally confers a poor prognosis. There are more than 60 known fusion partners of MLL having some correlation with disease phenotype and prognosis. The most common fusion proteins induce the inappropriate expression of homeotic (Hox) genes, which, during normal hematopoiesis, are maintained by wild-type MLL. MLL-rearranged leukemias display remarkable genomic stability, with very few gains or losses of chromosomal regions. This may be explained by recent studies suggesting that MLL-rearranged leukemias are largely driven by epigenetic dysregulation. Several epigenetic regulators that modify DNA or histones have been implicated in MLL-fusion driven leukemogenesis, including DNA methylation, histone acetylation, and histone methylation. The histone methyltransferase DOT1L has emerged as an important mediator of MLL-fusion-mediated leukemic transformation. The clinical development of targeted inhibitors of these epigenetic regulators may therefore hold promise for the treatment of MLL-rearranged leukemia. C1 [Bernt, Kathrin M.; Armstrong, Scott A.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02215 USA. [Bernt, Kathrin M.; Armstrong, Scott A.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Armstrong, Scott A.] Harvard Stem Cell Inst, Boston, MA USA. RP Armstrong, SA (reprint author), Childrens Hosp, Karp Family Res Labs, 1 Blackfan Cir, Boston, MA 02215 USA. EM Scott.Armstrong@childrens.harvard.edu RI Bernt, Kathrin/L-1826-2016 OI Bernt, Kathrin/0000-0002-5400-0482 NR 86 TC 23 Z9 23 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 1520-4391 J9 HEMATOL-AM SOC HEMAT JI Hematol.-Am. Soc. Hematol. Educ. Program PD DEC PY 2011 BP 354 EP 360 DI 10.1182/asheducation-2011.1.354 PG 7 WC Education, Scientific Disciplines; Hematology SC Education & Educational Research; Hematology GA V29PG UT WOS:000208759700053 ER PT J AU Brown, JR AF Brown, Jennifer R. TI The Treatment of Relapsed Refractory Chronic Lymphocytic Leukemia SO HEMATOLOGY-AMERICAN SOCIETY OF HEMATOLOGY EDUCATION PROGRAM LA English DT Article AB Despite the widespread use of highly effective chemoimmunotherapy (CIT), fludarabine-refractory chronic lymphocytic leukemia (CLL) remains a challenging clinical problem associated with poor overall survival (OS). The traditional definition, which includes those patients with no response or relapse within 6 months of fludarabine, is evolving with the recognition that even patients with longer remissions of up to several years after CIT have poor subsequent treatment response and survival. Approved therapeutic options for these patients remain limited, and the goal of therapy for physically fit patients is often to achieve adequate cytoreduction to proceed to allogeneic stem cell transplantation (alloSCT). Fortunately, several novel targeted therapeutics in clinical trials hold promise of significant benefit for this patient population. This review discusses the activity of available and novel therapeutics in fludarabine-refractory or fludarabine-resistant CLL as well as recently updated data on alloSCT in CLL. C1 [Brown, Jennifer R.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Brown, Jennifer R.] Dana Farber Canc Inst, CLL Ctr, Boston, MA 02215 USA. RP Brown, JR (reprint author), Harvard Univ, Sch Med, 450 Brookline Ave,Mayer 226, Boston, MA 02215 USA. EM jbrown2@partners.org FU Celgene; Genzyme FX J.R.B. has served as a consultant for Calistoga Pharmaceuticals, Pharmacyclics, and Celgene and has received research funding from Celgene, and Genzyme. Off-label drug use: Off-label use of lenalidomide is discussed herein. NR 67 TC 18 Z9 18 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 1520-4391 EI 1520-4383 J9 HEMATOL-AM SOC HEMAT JI Hematol.-Am. Soc. Hematol. Educ. Program PD DEC PY 2011 BP 110 EP 118 DI 10.1182/asheducation-2011.1.110 PG 9 WC Education, Scientific Disciplines; Hematology SC Education & Educational Research; Hematology GA V29PG UT WOS:000208759700017 ER PT J AU Eagan, MJ Bluth, BE Zhao, KW Brinkmann, EJ Wu, BM McAllister, DR AF Eagan, Michael J. Bluth, Benjamin E. Zhao, Ke-Wei Brinkmann, Elyse J. Wu, Benjamin M. McAllister, David R. TI The Effect of Growth and Differentiation Factor-5 on Two-Dimensional Cultures of Mouse Bone Marrow Stromal Cells SO JOURNAL OF BIOMATERIALS AND TISSUE ENGINEERING LA English DT Article DE GDF-5; Ligament Engineering; BMSCs; ACL ID ANTERIOR CRUCIATE LIGAMENT; MESENCHYMAL STEM-CELLS; MEDIAL COLLATERAL LIGAMENT; TGF-BETA-SUPERFAMILY; ACHILLES-TENDON; IN-VITRO; SILK SCAFFOLD; RABBIT MODEL; YOUNG-ADULTS; FIBROBLASTS AB Rupture of the anterior cruciate ligament (ACL) is one of the most common sports-related injuries. However, with its poor healing capacity, surgical reconstruction is currently required to restore its function. Due to serious complications associated with these reconstructions, the use of tissue engineering as an alternative has grown in appeal. Engineering approaches using ligament-derived fibroblasts have been promising but their slow growth rate may limit their practical application. More promising results have been being achieved using stem cells, in combination with appropriate growth factors. As a growth factor, GDF-5 has been shown to play a role in ligament and tendon formation, while bone marrow stem cells have shown promise in their repair. Combining these two parameters, previous work by our group has shown that a combination of GDF-5 and bone marrow stem cells in a 3D environment results in increased expression of several ligament tissue markers. In this study, we continue this work to explore if a dose-response relationship exists between GDF-5 and the stem cell. For this, murine bone marrow stem cells (D1 cells) were exposed to increasing doses of GDF-5 in a standard monolayer culture system and the expression of several ligament genes quantified. In contrast to our previous 3D system, exposing D1 cells to increasing doses of GDF-5 in a 2D culture system did not significantly affect the expression of these markers. Therefore, a more appropriate system for determining the effect of growth factors on stem cells may be a 3D culture system. C1 [Eagan, Michael J.; McAllister, David R.] Univ Calif Los Angeles, David Geffen Sch Med, Ctr Hlth Sci, Dept Orthopaed Surg, Los Angeles, CA 90095 USA. [Bluth, Benjamin E.; Brinkmann, Elyse J.] Univ Calif Los Angeles, David Geffen Sch Med, Div Plast Surg, Dept Surg,Ctr Hlth Sci, Los Angeles, CA 90095 USA. [Zhao, Ke-Wei; McAllister, David R.] VA Greater Los Angeles Healthcare Syst, W Los Angeles Healthcare Ctr, Orthopaed Tissue Engn Lab Los Angeles, Los Angeles, CA 90073 USA. [Brinkmann, Elyse J.; Wu, Benjamin M.] Univ Calif Los Angeles, Henry Samueli Sch Engn & Appl Sci, Dept Biomed Engn, Los Angeles, CA 90095 USA. RP McAllister, DR (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Ctr Hlth Sci, Dept Orthopaed Surg, Los Angeles, CA 90095 USA. FU VA Rehabilitation RRD FX This study was supported by a VA Rehabilitation RR&D grant. NR 40 TC 1 Z9 1 U1 0 U2 2 PU AMER SCIENTIFIC PUBLISHERS PI VALENCIA PA 26650 THE OLD RD, STE 208, VALENCIA, CA 91381-0751 USA SN 2157-9083 J9 J BIOMATER TISS ENG JI J. Biomater. Tissue Eng. PD DEC PY 2011 VL 1 IS 2 BP 210 EP 214 DI 10.1166/jbt.2011.1025 PG 5 WC Cell & Tissue Engineering SC Cell Biology GA 057NP UT WOS:000312570600010 ER PT J AU Singh, H Classen, DC Sittig, DF AF Singh, Hardeep Classen, David C. Sittig, Dean F. TI Creating an Oversight Infrastructure for Electronic Health Record-Related Patient Safety Hazards SO JOURNAL OF PATIENT SAFETY LA English DT Article DE electronic health record; patient safety; surveillance AB Electronic health records (EHRs) have potential quality and safety benefits. However, reports of EHR-related safety hazards are now emerging. The Office of the National Coordinator for Health Information Technology recently sponsored an Institute of Medicine committee to evaluate how health information technology use affects patient safety. In this article, we propose the creation of a national EHR oversight program to provide dedicated surveillance of EHR-related safety hazards and to promote learning from identified errors, close calls, and adverse events. The program calls for data gathering, investigation/analysis, and regulatory components. The first 2 functions will depend on institution-level EHR safety committees that will investigate all known EHR-related adverse events and near-misses and report them nationally using standardized methods. These committees should also perform routine safety self-assessments to proactively identify new risks. Nationally, we propose the long-term creation of a centralized, nonpartisan board with an appropriate legal and regulatory infrastructure to ensure the safety of EHRs. We discuss the rationale of the proposed oversight program and its potential organizational components and functions. These include mechanisms for robust data collection and analyses of all safety concerns using multiple methods that extend beyond reporting, multidisciplinary investigation of selected high-risk safety events, and enhanced coordination with other national agencies to facilitate broad dissemination of hazards information. Implementation of this proposed infrastructure can facilitate identification of EHR-related adverse events and errors and potentially create a safer and more effective EHR-based health care delivery system. C1 [Singh, Hardeep] Houston VA Hlth Serv Res & Dev Ctr Excellence, Houston, TX USA. [Singh, Hardeep] Baylor Coll Med, Houston VA Patient Safety Ctr Inquiry, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Singh, Hardeep] Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. [Classen, David C.] Univ Utah, Salt Lake City, UT USA. [Classen, David C.] CSC, Salt Lake City, UT USA. [Sittig, Dean F.] Univ Texas Hlth Sci Ctr, Sch Biomed Informat, Univ Texas Mem Hermann Ctr Healthcare Qual & Safe, Houston, TX USA. RP Sittig, DF (reprint author), Univ Texas Sch Hlth Informat Sci Houston, UT Mem Hermann Ctr Healthcare Qual & Safety, 6410 Fannin St,UTPB 1100-13, Houston, TX 77030 USA. EM Dean.F.Sittig@uth.tmc.edu FU National Institutes of Health K23 career development award [K23CA125585]; VA National Center of Patient Safety, Agency for Health Care Research and Quality; Office of the National Coordinator for Health Information Technology (ONC) [10510592]; Houston VA Health Services Research and Development Service Center of Excellence [HFP90-020]; National Library of Medicine [R01-LM006942] FX Dr Singh is supported by a National Institutes of Health K23 career development award (K23CA125585), the VA National Center of Patient Safety, Agency for Health Care Research and Quality, a SHARP contract from the Office of the National Coordinator for Health Information Technology (ONC no. 10510592), and in part by the Houston VA Health Services Research and Development Service Center of Excellence (HFP90-020). Dr Sittig is supported in part by a grant from the National Library of Medicine R01-LM006942 and by a SHARP contract from the Office of the National Coordinator for Health Information Technology (ONC no. 10510592). Dr Classen is an employee of CSC, a technology services company. These sources had no role in the preparation, review, or approval of the article. NR 72 TC 17 Z9 17 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1549-8417 J9 J PATIENT SAF JI J. Patient Saf. PD DEC PY 2011 VL 7 IS 4 BP 169 EP 174 DI 10.1097/PTS.0b013e31823d8df0 PG 6 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA V27KQ UT WOS:000208612500001 PM 22080284 ER PT J AU Baeuml, J Bose-O'Reilly, S Gothe, RM Lettmeier, B Roider, G Drasch, G Siebert, U AF Baeuml, Jennifer Bose-O'Reilly, Stephan Gothe, Raffaella Matteucci Lettmeier, Beate Roider, Gabriele Drasch, Gustav Siebert, Uwe TI Human Biomonitoring Data from Mercury Exposed Miners in Six Artisanal Small-Scale Gold Mining Areas in Asia and Africa SO MINERALS LA English DT Article DE artisanal small-scale gold mining; human biomonitoring; mercury vapor AB Objectives: In artisanal small-scale gold mining (ASGM) areas in many developing countries, mercury (Hg) is used to extract gold from ore. Data of 1250 participants from Indonesia, Mongolia, Philippines, Tanzania, and Zimbabwe were combined to analyze the relation between exposure in ASGM areas and body burden. Methods: Four groups were selected relating to their intensity of contact with mercury: (i) a non-exposed control group; (ii) a low exposed group with participants only living in mining areas, but not working as miners; (iii) a medium exposed group, miners living in exposed areas and working with mercury without smelting amalgam; and (iv) a high exposed group, miners living in exposed areas and smelting amalgam. Results: Compared to the non-exposed control group, participants living and/or miners working in highly exposed areas have significantly higher concentration of total mercury in urine, hair and blood (p-value < 0.001). The median mercury value in urine in the control group is < 0.2 mu g/L. In the high exposed group of amalgam smelters, the median in urine is 12.0 mu g/L. The median in blood in the control group is < 0.93 mu g/L. The median level in blood of the high exposed group is 7.56 mu g/L. The median for mercury in hair samples from the control group is 0.21 mu g/g. In the high exposed group the median hair concentration is 2.4 mu g/g hair. Mercury levels also differ considerably between the countries, reflecting a diverse background burden due to different fish eating habits and different work place methods. Conclusions: A high percentage of exposed individuals had levels above threshold values. These high levels of mercury are likely to be related with serious health problems. C1 [Baeuml, Jennifer; Bose-O'Reilly, Stephan; Gothe, Raffaella Matteucci; Lettmeier, Beate; Siebert, Uwe] Hlth & Life Sci Univ UMIT, Inst Publ Hlth Med Decis Making & Hlth Technol As, A-6060 Hall In Tirol, Austria. [Bose-O'Reilly, Stephan] WHO, Collaborating Ctr Occupat Hlth, Univ Hosp Munich, Inst & Outpatient Clin Occupat Social & Environm, D-80336 Munich, Germany. [Roider, Gabriele; Drasch, Gustav] LMU Univ Munich, Inst Forens Med, D-80336 Munich, Germany. [Siebert, Uwe] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Inst Technol Assessment,cardiovasc Res Program, Boston, MA 02115 USA. [Siebert, Uwe] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02115 USA. [Siebert, Uwe] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Ctr Hlth Decis Sci, Boston, MA 02115 USA. RP Bose-O'Reilly, S (reprint author), Hlth & Life Sci Univ UMIT, Inst Publ Hlth Med Decis Making & Hlth Technol As, Eduard Wallnoefer Ctr 1, A-6060 Hall In Tirol, Austria. EM jennifer.baeuml@umit.at; stephan.boeseoreilly@umit.at; raffaella.gothe@umit.at; beate.lettmeier@umit.at; Gabriele.Roider@med.uni-muenchen.de; Gustav.Drasch@med.uni-muenchen.de; uwe.siebert@umit.at FU UNIDO-United Nations Industrial Development Organization; LMU; WHO-World Health Organization; Ministry of Health of Mongolia FX This paper consists of differently funded projects: UNIDO-United Nations Industrial Development Organization funded the projects in Indonesia, Philippines, Tanzania and Zimbabwe (2004), LMU funded the project Zimbabwe 2006 and WHO-World Health Organization funded the project Mongolia together with the Ministry of Health of Mongolia. NR 35 TC 10 Z9 10 U1 3 U2 11 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 2075-163X J9 MINERAL-BASEL JI Minerals PD DEC PY 2011 VL 1 IS 1 BP 122 EP 143 DI 10.3390/min1010122 PG 22 WC Mineralogy; Mining & Mineral Processing SC Mineralogy; Mining & Mineral Processing GA V34LH UT WOS:000209087400007 ER PT J AU Lyles, CR Karter, AJ Young, BA Spigner, C Grembowski, D Schillinger, D Adler, N AF Lyles, Courtney R. Karter, Andrew J. Young, Bessie A. Spigner, Clarence Grembowski, David Schillinger, Dean Adler, Nancy TI Provider factors and patient-reported healthcare discrimination in the Diabetes Study of California (DISTANCE) SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE Race/ethnicity; Discrimination; Provider factors; Diabetes care; Managed care AB Objective: We examined provider-level factors and reported discrimination in the healthcare setting. Methods: With data from the Diabetes Study of Northern California (DISTANCE) - a race-stratified survey of diabetes patients in Kaiser Permanente Northern California - we analyzed patient-reported racial/ethnic discrimination from providers. Primary exposures were characteristics of the primary care provider (PCP, who coordinates care in this system), including specialty/type, and patient-provider relationship variables, including racial concordance. Results: Subjects (n = 12,151) included 20% black, 20% Latino, 23% Asian, 30% white, and 6% other patients, with 2-8% reporting discrimination by racial/ethnic group. Patients seeing nurse practitioners as their PCP (OR = 0.09; 95% CI: 0.01-0.67) and those rating their provider higher on communication (OR = 0.70; 95% CI: 0.66-0.74) were less likely to report discrimination, while those with more visits (OR = 1.10; 95% CI: 1.03-1.18) were more likely to report discrimination. Racial concordance was not significant once adjusting for patient race/ethnicity. Conclusions: Among diverse diabetes patients in managed care, provider type and communication were significantly related to patient-reported discrimination. Practice implications: Given potential negative impacts on patient satisfaction and treatment decisions, future studies should investigate which interpersonal aspects of the provider-patient relationship reduce patient perceptions of unfair treatment. (C) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Lyles, Courtney R.; Karter, Andrew J.; Young, Bessie A.; Spigner, Clarence; Grembowski, David] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Karter, Andrew J.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Young, Bessie A.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Schillinger, Dean; Adler, Nancy] UCSF, Dept Med Psychol, San Francisco, CA USA. [Schillinger, Dean; Adler, Nancy] UCSF, Dept Psychiat, San Francisco, CA USA. [Schillinger, Dean; Adler, Nancy] UCSF, Dept Pediat, San Francisco, CA USA. [Schillinger, Dean] UCSF, Dept Med, San Francisco, CA USA. [Schillinger, Dean] San Francisco Gen Hosp, Ctr Vulnerable Populat, San Francisco, CA 94110 USA. RP Lyles, CR (reprint author), Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Box 359455, Seattle, WA 98195 USA. EM crees@u.washington.edu FU National Research Service Award from the Agency for Healthcare Research and Quality [HS013853]; National Institute of Diabetes, Digestive and Kidney Diseases [R01 DK65664]; National Institute of Child Health and Human Development [R01 HD46113] FX This project was supported by a National Research Service Award, grant number HS013853 from the Agency for Healthcare Research and Quality, and funds were provided by National Institute of Diabetes, Digestive and Kidney Diseases R01 DK65664 and National Institute of Child Health and Human Development R01 HD46113. None of the authors had conflicts of interest, and the funders had no role in the design and conduct of the study; collection, management, analysis, or interpretation of the data; or preparation, review, or approval of the manuscript. NR 64 TC 7 Z9 7 U1 1 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD DEC PY 2011 VL 85 IS 3 BP E216 EP E224 DI 10.1016/j.pec.2011.04.031 PG 9 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA V41JR UT WOS:000209543000007 PM 21605956 ER PT J AU Saha, S Sanders, DS Korthuis, PT Cohn, JA Sharp, VL Haidet, P Moore, RD Beach, MC AF Saha, Somnath Sanders, David S. Korthuis, Philip Todd Cohn, Jonathan A. Sharp, Victoria L. Haidet, Paul Moore, Richard D. Beach, Mary Catherine TI The role of cultural distance between patient and provider in explaining racial/ethnic disparities in HIV care SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE Physician-patient relations; Culture; HIV AB Objective: We sought to evaluate whether cultural distance between patients and providers was associated with quality of care for people living with HIV/AIDS, and whether cultural distance helped explain racial/ethnic disparities in HIV care. Methods: We surveyed 437 patients and 45 providers at 4 HIV clinics in the U.S. We examined the association of patients' perceived cultural distance from their providers with patient ratings of healthcare quality, trust in provider, receipt of antiretroviral therapy, medication adherence, and viral suppression. We also examined whether racial/ethnic disparities in these aspects of HIV care were mediated by cultural distance. Results: Greater cultural distance was associated with lower patient ratings of healthcare quality and less trust in providers. Compared to white patients, nonwhites had significantly lower levels of trust, adherence, and viral suppression. Adjusting for patient-provider cultural distance did not significantly affect any of these disparities (p-values for mediation >.10). Conclusion: Patient-provider cultural distance was negatively associated with perceived quality of care and trust but did not explain racial/ethnic disparities in HIV care. Practice implications: Bridging cultural differences may improve patient-provider relationships but may have limited impact in reducing racial/ethnic disparities, unless coupled with efforts to address other sources of unequal care. Published by Elsevier Ireland Ltd. C1 [Saha, Somnath] Portland VA Med Ctr, Gen Internal Med Sect, Portland, OR 97239 USA. [Saha, Somnath; Korthuis, Philip Todd] Oregon Hlth & Sci Univ, Div Gen Internal Med & Geriatr, Portland, OR 97201 USA. [Sanders, David S.] Oregon Hlth & Sci Univ, Sch Med, Portland, OR 97201 USA. [Cohn, Jonathan A.] Wayne State Univ, Dept Med, Detroit, MI 48202 USA. [Sharp, Victoria L.] St Lukes Roosevelt Hosp, Ctr Comprehens Care, New York, NY USA. [Haidet, Paul] Penn State Univ, Coll Med, Hershey, PA USA. [Moore, Richard D.; Beach, Mary Catherine] Johns Hopkins Univ, Dept Med, Baltimore, MD USA. RP Saha, S (reprint author), Portland VA Med Ctr, Gen Internal Med Sect, 3710 SW US Vet Hosp Rd P3HSRD, Portland, OR 97239 USA. EM sahas@ohsu.edu FU Agency for Healthcare Research and Quality [AHRQ 290-01-0012, K08 HS013903-05]; Robert Wood Johnson Foundation Generalist Physician Faculty Scholar Awards; National Institute on Drug Abuse [K23DA019809]; Department of Veterans Affairs FX This research was supported by a contract from the Agency for Healthcare Research and Quality (AHRQ 290-01-0012). Dr. Beach was supported by the Agency for Healthcare Research and Quality (K08 HS013903-05) and both Drs. Beach and Saha were supported by Robert Wood Johnson Foundation Generalist Physician Faculty Scholar Awards. Dr. Korthuis was supported by the National Institute on Drug Abuse (K23DA019809). Dr. Saha was supported by the Department of Veterans Affairs. NR 39 TC 21 Z9 21 U1 2 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD DEC PY 2011 VL 85 IS 3 BP E278 EP E284 DI 10.1016/j.pec.2011.01.012 PG 7 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA V41JR UT WOS:000209543000016 PM 21310581 ER PT J AU Guanci, MM AF Guanci, Mary McKenna TI Why does the QT interval become prolonged when a patient is under hypothermia? SO THERAPEUTIC HYPOTHERMIA AND TEMPERATURE MANAGEMENT LA English DT Letter C1 Massachusetts Gen Hosp, Neurosci ICU, Boston, MA 02114 USA. RP Guanci, MM (reprint author), Massachusetts Gen Hosp, Neurosci ICU, Boston, MA 02114 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 2153-7658 EI 2153-7933 J9 THER HYPOTHERMIA TEM JI Ther. Hypothermia Temp. Manag. PD DEC 1 PY 2011 VL 1 IS 4 BP 222 EP 222 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA V38QD UT WOS:000209357000005 ER PT J AU Vick, CC Graham, LA Henderson, WG Houston, TK Hawn, MT AF Vick, Catherine C. Graham, Laura A. Henderson, William G. Houston, Thomas K., II Hawn, Mary T. TI Translating preoperative smoking cessation interventions into routine clinical care of veterans: provider beliefs SO TRANSLATIONAL BEHAVIORAL MEDICINE LA English DT Article DE Smoking cessation; Counseling; Preoperative; Advise; Assess; Postoperative surgical complications; Primary care clinic; Anesthesia; Smoking status AB Smoking among veterans undergoing surgery is estimated to be 36%. Smoking has been linked to postoperative surgical complications including ischemia and cardiac arrhythmias, pneumonia, deep venous thrombosis, pulmonary embolism, and surgical site infection. Preoperative smoking cessation interventions, in which smokers quit at least 6weeks prior to surgery, have been shown to be effective both in smoking cessation and reduction of postoperative complications; however, little is known about physician beliefs regarding the optimal location and the responsible provider for intervention, or whether surgery should be postponed or delayed based on smoking status. Within the routine coordination from medical to surgical care, how should cessation interventions best be implemented? To better inform the translation of preoperative best practices for smoking cessation into clinical care in VA, a survey regarding preoperative smoking cessation beliefs and practices was administered to primary care physicians, surgeons, and anesthesia providers. Chi-square tests were used to examine differences in proportions by provider type. Most providers agreed that the primary care clinic is the best location for intervention, with preoperative and surgical clinics ranked by few as the optimal location (13% and 11%, respectively); most respondents (82%) reported that they would refuse or delay surgery in some cases based on smoking status. There were no differences in either beliefs on location or delay based on provider type. Primary care providers were most likely to advise (86.7%) and assess (80.0%) while anesthesia providers were least likely (59.1% and 22.7%, respectively). Taking time to counsel and the belief that dedicated resources would improve quit rates were associated with advising patients to quit smoking, while being uncomfortable with counseling, the belief that acute health takes precedence and the belief that there is not always time to counsel were identified as barriers to assessing patients for smoking cessation intervention. Primary care providers were more optimistic (100%) that patients would quit if counseled, more often (73.3%) reported having time to counsel, and were less likely to report that acute health takes precedence. Most providers believe that smoking cessation would reduce postoperative complications, with the ideal location for the intervention being the primary care clinic, and that some surgical cases should be delayed for this intervention. C1 [Vick, Catherine C.; Graham, Laura A.; Hawn, Mary T.] Birmingham VAMC, Ctr Surg Med Acute Care Res & Transit, Birmingham, AL 35233 USA. [Henderson, William G.] Univ Colorado, Hlth Outcomes Program, Aurora, CO USA. [Houston, Thomas K., II] Bedford VAMC, VA eHlth Qual Enhancement Res Initiat, Bedford, MA USA. [Houston, Thomas K., II] Univ Massachusetts, Sch Med, Div Hlth Informat & Implementat Sci Quantitat Hlt, Worcester, MA USA. [Hawn, Mary T.] Univ Alabama Birmingham, Sch Med, Dept Surg, Sect Gastrointestinal Surg, Birmingham, AL 35294 USA. RP Vick, CC (reprint author), Birmingham VAMC, Ctr Surg Med Acute Care Res & Transit, Birmingham, AL 35233 USA. EM catherine.vick@va.gov FU United States Department of Veterans' Affairs Health Services Research and Development grant [IAB 06-038] FX The authors would like to acknowledge Heather Coley, MPH, for assistance in development of the survey instrument and data collection. The authors would like to acknowledge Jasvinder Singh, MD, for critical revision of the manuscript. This research was funded by the United States Department of Veterans' Affairs Health Services Research and Development grant IAB 06-038. NR 25 TC 2 Z9 2 U1 1 U2 2 PU SPRINGER INTERNATIONAL PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 1869-6716 EI 1613-9860 J9 TRANSL BEHAV MED JI Transl. Behav. Med. PD DEC PY 2011 VL 1 IS 4 BP 604 EP 608 DI 10.1007/s13142-011-0096-1 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA V39LJ UT WOS:000209412200016 PM 24073083 ER PT J AU Gershman, B Kulkarni, N Sahani, DV Eisner, BH AF Gershman, Boris Kulkarni, Naveen Sahani, Dushyant V. Eisner, Brian H. TI Causes of renal forniceal rupture SO BJU INTERNATIONAL LA English DT Article DE calyceal rupture; forniceal rupture; kidney; obstruction ID POSTERIOR URETHRAL VALVES; PERIRENAL URINOMA; CALYCEAL RUPTURE; URINARY ASCITES; PELVIS; HYDRONEPHROSIS; OBSTRUCTION; CARCINOMA; PREGNANCY; SECONDARY AB OBJECTIVE To perform a retrospective review aiming to identify causes of renal forniceal rupture. PATIENTS AND METHODS A retrospective review was performed of the longitudinal medical record and CT records for patients identified as having renal 'forniceal rupture' or 'calyceal rupture' using a radiological database. RESULTS In total, 108 patients were identified with the CT diagnosis of renal 'forniceal' or 'calyceal' rupture. Forniceal rupture was caused by ureteric stones in 80 cases (74.1%), malignant extrinsic ureteric compression in nine cases (8.3%), benign extrinsic ureteric compression in two cases (1.9%), pelvic-ureteric junction obstruction in two cases (1.9%), vesicoureteric junction (VUJ) obstruction in one case (0.9%), bladder outlet obstruction in one case (0.9%) and iatrogenic causes in four cases (3.7%). No definitive cause was found in nine cases (8.3%). For patients in whom a ureteric stone was the cause of forniceal rupture, the level of obstruction was proximal ureter in 24.3% of cases, distal ureter in 17.6% of cases and VUJ in 58.1% of cases. Mean (SD) stone size was 4.09 (2.0) mm. Mean (SD) stone size was 5.34 (1.87) mm for proximal stones, 4.08 (1.69) mm for distal stones and 3.53 (1.96) mm for VUJ stones (P = 0.005). Urinary tract infection was present in five out of 97 patients (5.2%) in whom data were available for analysis. CONCLUSION The most common aetiology of renal forniceal rupture is obstruction caused by distal ureteric stones followed by malignant extrinsic ureteric compression. C1 [Gershman, Boris; Eisner, Brian H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02114 USA. [Kulkarni, Naveen; Sahani, Dushyant V.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Eisner, BH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, GRB 1102,55 Fruit St, Boston, MA 02114 USA. EM beisner@partners.org NR 19 TC 15 Z9 16 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 EI 1464-410X J9 BJU INT JI BJU Int. PD DEC PY 2011 VL 108 IS 11 BP 1909 EP 1911 DI 10.1111/j.1464-410X.2011.10164.x PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 849CM UT WOS:000297103100041 PM 21736690 ER PT J AU Nakabayashi, M Werner, L Oh, WK Regan, MM Kantoff, PW Taplin, ME AF Nakabayashi, Mari Werner, Lillian Oh, William K. Regan, Meredith M. Kantoff, Philip W. Taplin, Mary-Ellen TI Secondary Hormonal Therapy in Men With Castration-Resistant Prostate Cancer SO CLINICAL GENITOURINARY CANCER LA English DT Article DE Androgen deprivation therapy; Androgen resistance; Castration-resistant prostate cancer; Natural history; Secondary hormonal therapy ID ANDROGEN-DEPRIVATION THERAPY; LEUKEMIA GROUP-B; PHASE-II; RECEPTOR MUTATIONS; PROGNOSTIC FACTORS; ADRENAL ANDROGENS; NATURAL-HISTORY; KETOCONAZOLE; EFFICACY; BICALUTAMIDE AB A retrospective cohort of 436 men with CRPC was used to evaluate the profile of secondary hormonal therapy response in CRPC. Longer duration of primary androgen deprivation therapy was associated with longer duration of secondary hormonal therapy. Men who received the first secondary hormonal treatment for longer than 6 months were more likely to respond to subsequent secondary hormonal therapies. Background: Androgen receptor (AR) signaling remains important in castration-resistant prostate cancer (CRPC) and sequential responses to hormonal therapies are observed. Little is known about the factors associated with responsiveness to secondary hormone therapy (HT). Methods: We retrospectively identified patients with CRPC who were treated with secondary HT. Patient characteristics and types and duration of secondary HT were analyzed. Selected clinical characteristics and their association with duration of secondary HT were evaluated. Results: Of 436 eligible patients, 321 (74%) and 87 (20%) received at least two or four secondary HT regimens, respectively. Median duration of time on primary androgen deprivation therapy alone (ADT) and secondary HT were 24.0 months (range, 1.5 to 171.8 months) and 30.3 months (range, 0.6 to 156.1+ months), respectively. Patients who received primary ADT >= 24 months received secondary HT for a median duration of 40.0 months, whereas men who received ADT < 24 months had a median duration of 18.4 months on secondary HT (P < .0001). Metastatic disease at secondary HT initiation was associated with a shorter time on secondary HT (P = .0001). Patients who received the first secondary HT for >= 6 months were more likely to have a longer duration on subsequent secondary HT compared with the men who received the first secondary HT < 6 months (P = .0001). Conclusions: Treatment durations of secondary HT are variable. Longer duration of primary ADT was associated with longer duration of secondary HT. These results imply that AR signaling remains an important therapeutic target in CRPC. C1 [Nakabayashi, Mari; Kantoff, Philip W.; Taplin, Mary-Ellen] Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Dept Med Oncol, Boston, MA 02115 USA. [Nakabayashi, Mari; Werner, Lillian; Regan, Meredith M.; Kantoff, Philip W.; Taplin, Mary-Ellen] Harvard Univ, Sch Med, Boston, MA USA. [Werner, Lillian; Regan, Meredith M.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Oh, William K.] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA. RP Taplin, ME (reprint author), Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM mary_taplin@dfei.harvard.edu RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 FU Fairweather Fund for Prostate Cancer Research FX We thank our CRIS team for their excellent data entry work and the Gelb Center for maintaining the operation of the Prostate CRIS. Support was provided by the Fairweather Fund for Prostate Cancer Research (MET). NR 41 TC 11 Z9 12 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1558-7673 J9 CLIN GENITOURIN CANC JI Clin. Genitourin. Cancer PD DEC PY 2011 VL 9 IS 2 BP 95 EP 103 DI 10.1016/j.clgc.2011.06.006 PG 9 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 847TC UT WOS:000296994400004 PM 21958520 ER PT J AU Sneag, DB Ramaiya, N O'Regan, KN Jagannathan, JP Hornick, JL Ho, VT Hayes, JH AF Sneag, Darryl B. Ramaiya, Nikhil O'Regan, Kevin N. Jagannathan, Jyothi P. Hornick, Jason L. Ho, Vincent T. Hayes, Julia H. TI Peritoneal Relapse of Testicular Seminomatous Germ Cell Tumor Treated Successfully With Salvage Chemotherapy and Autologous Stem Cell Transplantation SO CLINICAL GENITOURINARY CANCER LA English DT Article DE Autologous stem cell transplantation; Retroperitoneal lymph node dissection; Salvage chemotherapy; Testicular seminomatous germ cell tumor ID HIGH-DOSE CHEMOTHERAPY; POSITRON-EMISSION-TOMOGRAPHY; INTRAPERITONEAL METASTASES; STAGE-I; CANCER; MANAGEMENT; DIAGNOSIS; CARCINOMATOSIS; ETOPOSIDE; CONSENSUS AB This case report describes a 47-year-old man who developed peritoneal relapse of a testicular seminomatous GCT, without prior RPLND. Only several cases of peritoneal spread of testicular GOT have been published, most that involved nonseminomatous tumors in patients with prior RPLND. In addition, most of these peritoneal relapses have resulted in death. Our case study is alive today after treatment with salvage HDC as well as ASCT and has complete remission based on recent imaging and laboratory serum markers. C1 [Sneag, Darryl B.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol,Mellins Lib, Boston, MA 02115 USA. [Ramaiya, Nikhil; O'Regan, Kevin N.; Jagannathan, Jyothi P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. [Hornick, Jason L.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Ho, Vincent T.; Hayes, Julia H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Sneag, DB (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol,Mellins Lib, 75 Francis St, Boston, MA 02115 USA. EM dsneag@partners.org NR 23 TC 0 Z9 0 U1 0 U2 1 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1558-7673 J9 CLIN GENITOURIN CANC JI Clin. Genitourin. Cancer PD DEC PY 2011 VL 9 IS 2 BP 124 EP 129 DI 10.1016/j.clgc.2011.05.006 PG 6 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 847TC UT WOS:000296994400008 PM 21723796 ER PT J AU Guancial, EA Taplin, ME AF Guancial, Elizabeth A. Taplin, Mary-Ellen TI Case Report: Responses to Cabazitaxel in Metastatic Castration-Resistant Prostate Cancer After Extensive Docetaxel Treatment SO CLINICAL GENITOURINARY CANCER LA English DT Article DE Cabazitaxel; Disseminated intravascular coagulation; Docetaxel; Metastatic castration-resistant prostate cancer ID DISSEMINATED INTRAVASCULAR COAGULATION; MITOXANTRONE PLUS PREDNISONE; EVERY 3 WEEKS; PHASE-II; ESTRAMUSTINE; KETOCONAZOLE; SURVIVAL; TAXANE; MEN AB Cabazitaxel is the first FDA-approved agent for second-line chemotherapy in metastatic castration-resistant prostate cancer (mCRPC) after treatment with docetaxel. Cabazitaxel can safely be administered to patients with mCRPC, including those with advanced visceral disease and tumor-related disseminated intravascular coagulation (DIC), who are heavily pretreated with docetaxel-containing chemotherapy regimens. Treatment with cabazitaxel can reverse mCRPC-related DIC and produce objective prostate-specific antigen responses and stabilization of visceral disease. C1 [Guancial, Elizabeth A.; Taplin, Mary-Ellen] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Guancial, EA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,Smith 353, Boston, MA 02115 USA. EM eguancial@partners.org FU NCI NIH HHS [T32 CA009172] NR 21 TC 0 Z9 0 U1 0 U2 1 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1558-7673 J9 CLIN GENITOURIN CANC JI Clin. Genitourin. Cancer PD DEC PY 2011 VL 9 IS 2 BP 130 EP 132 DI 10.1016/j.clgc.2011.06.001 PG 3 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 847TC UT WOS:000296994400009 PM 21816687 ER PT J AU Tafti, BA Shaba, W Li, YX Yevdayev, E Berenji, GR Glass, E AF Tafti, Bashir Akhavan Shaba, Wisam Li, Yuxin Yevdayev, Ella Berenji, Gholam Reza Glass, Edwin TI Detection of a Sinus of Valsalva Aneurysm by F-18 FDG PET/CT Imaging SO CLINICAL NUCLEAR MEDICINE LA English DT Editorial Material DE sinus of Valsalva; aneurysm; positron emission tomography/CT AB An echocardiographic examination performed on a 72-year-old man for assessment of left ventricular hypertrophy revealed a right atrial mass, approximately 4 cm in size, attached to the interatrial septum. Given his history of leiomyosarcoma with vascular invasion, the patient was referred for PET/CT to assess the possibility of metastatic involvement. The results suggested an aneurysmal mass of the aortic noncoronary cusp consistent with a sinus of Valsalva aneurysm. A subsequent CT angiogram and surgery confirmed the diagnosis. To the best of our knowledge, this is the first reported case of a sinus of Valsalva aneurysm detected in PET/CT images. C1 [Tafti, Bashir Akhavan; Shaba, Wisam; Li, Yuxin; Yevdayev, Ella; Berenji, Gholam Reza; Glass, Edwin] Vet Adm Greater Los Angeles Hlth Care Syst, Nucl Med Sect, Dept Radiol, Los Angeles, CA 90073 USA. RP Glass, E (reprint author), Vet Adm Greater Los Angeles Hlth Care Syst, Nucl Med Sect, Dept Radiol, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM edwin.glass@va.gov NR 11 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-9762 J9 CLIN NUCL MED JI Clin. Nucl. Med. PD DEC PY 2011 VL 36 IS 12 BP 1144 EP 1145 DI 10.1097/RLU.0b013e3182335f4d PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 845BC UT WOS:000296796800040 PM 22064097 ER PT J AU Toepker, M Mahabadi, AA Heinzle, G Hofmann, W Mathies, R Schuster, A Cejna, M AF Toepker, M. Mahabadi, A. A. Heinzle, G. Hofmann, W. Mathies, R. Schuster, A. Cejna, M. TI Accuracy of MDCT in the determination of supraaortic artery stenosis using DSA as the reference standard SO EUROPEAN JOURNAL OF RADIOLOGY LA English DT Article DE CTA; DSA; Supraaortic vessels; Stenosis quantification ID AMERICAN-HEART-ASSOCIATION; HEALTH-CARE PROFESSIONALS; INTERNAL CAROTID-ARTERY; STROKE COUNCIL; CT ANGIOGRAPHY; DISEASE; ENDARTERECTOMY; STATEMENT; RISK; PREVENTION AB Purpose: Accurate stenosis quantification in the carotid arteries is of great clinical importance. We aimed to compare the diagnostic accuracy of multi-slice computed tomography angiography (CTA) to digital subtraction angiography (DSA) for the detection and grading of atherosclerotic lesions involving the supraaortic arteries. Materials and methods: We retrospectively analyzed 30 patients (10 women; mean age, 67 years). CTA was performed after administration of 100 ml Ultravist 370 (Bayer Schering, Germany), at a flow of 5 ml/s, using a Philips Brilliance 16MDCT scanner (Philips, Best, Netherland) at a collimation of 16 mm x 0.75 mm prior to DSA. The supraaortic arteries were divided into 17 segments, and, within each segment, the presence and severity of stenotic or occlusive lesions was determined, based on a four-point scale (0-49%, 50-69%, 70-99%, occlusion), by four independent readers using the NASCET criteria. Sensitivity and specificity of MDCT was calculated for the detection of moderate (50-69%) versus significant stenoses (70-99%) and occlusion. Results: There were 291 segments assessed with both methods. Thirteen lesions were "not assessable" on CTA. DSA identified 53 significant lesions, and CTA 56 significant lesions. With regard to significant lesions, CTA overrated six lesions and underestimated six lesions, resulting in a sensitivity, specificity, and accuracy of 86.4%, 97.6%, and 95.9%, respectively. For the detection of stenoses greater than 50%, sensitivity, specificity, and accuracy were 90.2%, 95.8%, and 94.8%, respectively. Conclusions: Compared to DSA, CTA shows high accuracy in the detection and grading of lesions involving the supraaortic arteries enabling its use in the detection and treatment planning for stenoses of the supraaortic vessels. (C) 2010 Elsevier Ireland Ltd. All rights reserved. C1 [Toepker, M.] Med Univ Vienna, Vienna Gen Hosp, Dept Radiol, A-1090 Vienna, Austria. [Mahabadi, A. A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac MR PET CT Program, Boston, MA USA. [Toepker, M.; Heinzle, G.; Schuster, A.; Cejna, M.] LKH Feldkirch, Dept Radiol, Feldkirch, Austria. [Hofmann, W.] LKH Feldkirch, Dept Vasc Surg, Feldkirch, Austria. [Mathies, R.] LKH Feldkirch, Dept Internal Med, Feldkirch, Austria. RP Toepker, M (reprint author), Med Univ Vienna, Vienna Gen Hosp, Dept Radiol, Waehringer Guertel 18-20, A-1090 Vienna, Austria. EM michael.toepker@meduniwien.ac.at NR 28 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0720-048X J9 EUR J RADIOL JI Eur. J. Radiol. PD DEC PY 2011 VL 80 IS 3 BP E351 EP E355 DI 10.1016/j.ejrad.2010.11.031 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 844QV UT WOS:000296763300029 PM 21156342 ER PT J AU Mino-Kenudson, M Fernandez-del Castillo, C Baba, Y Valsangkar, NP Liss, AS Hsu, M Correa-Gallego, C Ingkakul, T Johnston, RP Turner, BG Androutsopoulos, V Deshpande, V McGrath, D Sahani, DV Brugge, WR Ogino, S Pitman, MB Warshaw, AL Thayer, SP AF Mino-Kenudson, Mari Fernandez-del Castillo, Carlos Baba, Yoshifumi Valsangkar, Nakul P. Liss, Andrew S. Hsu, Maylee Correa-Gallego, Camilo Ingkakul, Thun Johnston, Rocio Perez Turner, Brian G. Androutsopoulos, Vasiliki Deshpande, Vikram McGrath, Deborah Sahani, Dushyant V. Brugge, William R. Ogino, Shuji Pitman, Martha B. Warshaw, Andrew L. Thayer, Sarah P. TI Prognosis of invasive intraductal papillary mucinous neoplasm depends on histological and precursor epithelial subtypes SO GUT LA English DT Article ID PANCREATIC DUCTAL ADENOCARCINOMA; CLINICOPATHOLOGICAL FEATURES; UPDATED EXPERIENCE; INTESTINAL PATHWAY; SURGICAL RESECTION; COLORECTAL-CANCER; EXPRESSION; SURVIVAL; TUMOR; CARCINOMA AB Objective Invasive cancers arising from intraductal papillary mucinous neoplasm (IPMN) are recognised as a morphologically and biologically heterogeneous group of neoplasms. Less is known about the epithelial subtypes of the precursor IPMN from which these lesions arise. The authors investigate the clinicopathological characteristics and the impact on survival of both the invasive component and its background IPMN. Design and patients The study cohort comprised 61 patients with invasive IPMN (study group) and 570 patients with pancreatic ductal adenocarcinoma (PDAC, control group) resected at a single institution. Multivariate analyses were performed using a stage-matched Cox proportional hazard model. Results The histology of invasive components of the IPMN cohort was tubular in 38 (62%), colloid in 16 (26%), and oncocytic in seven (12%). Compared with PDAC, invasive IPMNs were associated with a lower incidence of adverse pathological features and improved mortality by multivariate analysis (HR 0.58; 95% CI 0.39 to 0.86). In subtype analysis, this favourable outcome remained only for colloid and oncocytic carcinomas, while tubular adenocarcinoma was associated with worse overall survival, not significantly different from that of PDAC (HR 0.85; 95% CI 0.53 to 1.36). Colloid and oncocytic carcinomas arose only from intestinal- and oncocytic-type IPMNs, respectively, and were mostly of the main-duct type, whereas tubular adenocarcinomas primarily originated in the gastric background, which was often associated with branch-duct IPMN. Overall survival of patients with invasive adenocarcinomas arising from gastric-type IPMN was significantly worse than that of patients with non-gastric-type IPMN (p=0.016). Conclusions Tubular, colloid and oncocytic invasive IPMNs have varying prognosis, and arise from different epithelial subtypes. Colloid and oncocytic types have markedly improved biology, whereas the tubular type has a course that resembles PDAC. Analysis of these subtypes indicates that the background epithelium plays an equally, if not more, important role in defining the biology and prognosis of invasive IPMNs. C1 [Mino-Kenudson, Mari; Hsu, Maylee; Deshpande, Vikram; Pitman, Martha B.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Mino-Kenudson, Mari; Fernandez-del Castillo, Carlos; Baba, Yoshifumi; Valsangkar, Nakul P.; Liss, Andrew S.; Hsu, Maylee; Correa-Gallego, Camilo; Ingkakul, Thun; Johnston, Rocio Perez; Turner, Brian G.; Androutsopoulos, Vasiliki; Deshpande, Vikram; McGrath, Deborah; Sahani, Dushyant V.; Brugge, William R.; Ogino, Shuji; Pitman, Martha B.; Warshaw, Andrew L.; Thayer, Sarah P.] Harvard Univ, Sch Med, Boston, MA USA. [Fernandez-del Castillo, Carlos; Valsangkar, Nakul P.; Liss, Andrew S.; Correa-Gallego, Camilo; Ingkakul, Thun; Androutsopoulos, Vasiliki; McGrath, Deborah; Warshaw, Andrew L.; Thayer, Sarah P.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Baba, Yoshifumi; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Johnston, Rocio Perez; Sahani, Dushyant V.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Turner, Brian G.; Brugge, William R.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Mino-Kenudson, M (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren 122, Boston, MA 02114 USA. EM mminokenudson@partners.org FU NCI NIH HHS [P50 CA127003, P01 CA117969, P01 CA117969-04, P01 CA117969-04S1, P01 CA117969-05, P50 CA127003-04, P50 CA127003-05]; NIDDK NIH HHS [K08 DK071329, K08 DK071329-05] NR 47 TC 98 Z9 100 U1 0 U2 5 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD DEC PY 2011 VL 60 IS 12 BP 1712 EP 1720 DI 10.1136/gut.2010.232272 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 844UQ UT WOS:000296774500015 PM 21508421 ER PT J AU Kasperkovitz, PV Khan, NS Tam, JM Mansour, MK Davids, PJ Vyas, JM AF Kasperkovitz, Pia V. Khan, Nida S. Tam, Jenny M. Mansour, Michael K. Davids, Peter J. Vyas, Jatin M. TI Toll-Like Receptor 9 Modulates Macrophage Antifungal Effector Function during Innate Recognition of Candida albicans and Saccharomyces cerevisiae SO INFECTION AND IMMUNITY LA English DT Article ID MYELOID DENDRITIC CELLS; ASPERGILLUS-FUMIGATUS; PROTEOLYTIC CLEAVAGE; PATTERN-RECOGNITION; DEOXYNUCLEIC ACIDS; HOST-DEFENSE; PATHOGENS; IMMUNITY; TLR9; ACTIVATION AB Phagocytic responses are critical for effective host defense against opportunistic fungal pathogens. Macrophages sample the phagosomal content and orchestrate the innate immune response. Toll-like receptor 9 (TLR9) recognizes unmethylated CpG DNA and is activated by fungal DNA. Here we demonstrate that specific triggering of TLR9 recruitment to the macrophage phagosomal membrane is a conserved feature of fungi of distinct phylogenetic origins, including Candida albicans, Saccharomyces cerevisiae, Malassezia furfur, and Cryptococcus neoformans. The capacity to trigger phagosomal TLR9 recruitment was not affected by a loss of fungal viability or cell wall integrity. TLR9 deficiency has been linked to increased resistance to murine candidiasis and to restriction of fungal growth in vivo. Macrophages lacking TLR9 demonstrate a comparable capacity for phagocytosis and normal phagosomal maturation compared to wild-type macrophages. We now show that TLR9 deficiency increases macrophage tumor necrosis factor alpha (TNF-alpha) production in response to C. albicans and S. cerevisiae, independent of yeast viability. The increase in TNF-alpha production was reversible by functional complementation of the TLR9 gene, confirming that TLR9 was responsible for negative modulation of the cytokine response. Consistently, TLR9 deficiency enhanced the macrophage effector response by increasing macrophage nitric oxide production. Moreover, microbicidal activity against C. albicans and S. cerevisiae was more efficient in TLR9 knockout (TLR9KO) macrophages than in wild-type macrophages. In conclusion, our data demonstrate that TLR9 is compartmentalized selectively to fungal phagosomes and negatively modulates macrophage antifungal effector functions. Our data support a model in which orchestration of antifungal innate immunity involves a complex interplay of fungal ligand combinations, host cell machinery rearrangements, and TLR cooperation and antagonism. C1 [Kasperkovitz, Pia V.; Khan, Nida S.; Tam, Jenny M.; Mansour, Michael K.; Davids, Peter J.; Vyas, Jatin M.] Massachusetts Gen Hosp, Div Infect Dis, Dept Med, Boston, MA 02114 USA. [Kasperkovitz, Pia V.; Tam, Jenny M.; Mansour, Michael K.; Vyas, Jatin M.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Vyas, JM (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Dept Med, Room 504, Boston, MA 02114 USA. EM jvyas@partners.org RI Vyas, Jatin/Q-1627-2016 OI Vyas, Jatin/0000-0002-9985-9565 FU Boston Area Diabetes and Endocrinology Research Center [DK57521]; MGH Department of Medicine; MGH ECOR; NIAID, NIH [1R01AI092084-01A1]; [DK43351] FX Electron microscopy was performed by Mary McKee in the Microscopy Core of the Center for Systems Biology/Program in Membrane Biology, Massachusetts General Hospital, Boston, MA, which is partially supported by an Inflammatory Bowel Disease grant (DK43351) and a Boston Area Diabetes and Endocrinology Research Center award (DK57521). J.M.V. was supported in part by MGH Department of Medicine internal funds, MGH ECOR funds, and the NIAID, NIH (1R01AI092084-01A1). NR 35 TC 24 Z9 25 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD DEC PY 2011 VL 79 IS 12 BP 4858 EP 4867 DI 10.1128/IAI.05626-11 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 846RL UT WOS:000296920800011 PM 21947771 ER PT J AU Grady, BJ Samuels, DC Robbins, GK Selph, D Canter, JA Pollard, RB Haas, DW Shafer, R Kalams, SA Murdock, DG Ritchie, MD Hulgan, T AF Grady, Benjamin J. Samuels, David C. Robbins, Gregory K. Selph, Doug Canter, Jeffrey A. Pollard, Richard B. Haas, David W. Shafer, Robert Kalams, Spyros A. Murdock, Deborah G. Ritchie, Marylyn D. Hulgan, Todd CA ACTG 384 Study Teams DACS 250 Study Team TI Mitochondrial Genomics and CD4 T-Cell Count Recovery After Antiretroviral Therapy Initiation in AIDS Clinical Trials Group Study 384 SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article; Proceedings Paper CT 60th Annual Meeting of the American-Society-of-Human-Genetics CY NOV 02-06, 2010 CL Washington, DC SP Amer Soc Human Genet DE antiretroviral therapy; CD4 count; HIV; mitochondrial DNA; pharmacogenetics ID PERIPHERAL NEUROPATHY; DNA HAPLOGROUPS; VIROLOGICAL RESPONSE; HIV-1 INFECTION; APOPTOSIS; POLYMORPHISMS; DISEASE; GENE; ENCEPHALOMYOPATHIES; POPULATION AB Background: Mitochondrial DNA (mtDNA) variation has been associated with time to progression to AIDS and adverse effects from antiretroviral therapy (ART). In this study, full mitochondrial DNA (mtDNA) sequence data from US-based adult participants in the AIDS Clinical Trials Group study 384 was used to assess associations between mtDNA variants and CD4 T-cell recovery with ART. Methods: Full mtDNA sequence was determined using chip-based array sequencing. Sequence and CD4 cell count data was available at baseline and after ART initiation for 423 subjects with HIV RNA levels <400 copies per milliliter plasma. The primary outcome was change in CD4 count of >= 100 cells per cubic millimeter from baseline. Analyses were adjusted for baseline age, CD4 cell count, HIV RNA, and naive: memory CD4 cell ratio. Results: Race-stratified analysis of mtDNA variants with a minor allele frequency >1% revealed multiple mtDNA variants marginally associated (P < 0.05 before Bonferroni correction) with CD4 cell recovery. The most significant single nucleotide polymorphism associations were those tagging the African L2 haplogroup, which was associated with a decreased likelihood of >= 100 cells per cubic millimeter CD4 count increase at week 48 in non-Hispanic blacks (adjusted odds ratio = 0.17; 95% confidence interval = 0.06 to 0.53; P = 0.002). Conclusions: An African mtDNA haplogroup was associated with CD4 cell recovery after ART in this clinical trial population. These initial findings warrant replication and further investigation to confirm the role of mtDNA variation in CD4 cell recovery during ART. C1 [Haas, David W.; Kalams, Spyros A.; Hulgan, Todd] Vanderbilt Univ, Sch Med, Nashville, TN 37232 USA. [Grady, Benjamin J.; Samuels, David C.; Selph, Doug; Canter, Jeffrey A.; Murdock, Deborah G.; Ritchie, Marylyn D.] Vanderbilt Univ, Ctr Human Genet Res, Nashville, TN 37232 USA. [Robbins, Gregory K.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA USA. [Pollard, Richard B.] Univ Calif Davis, Sacramento, CA 95817 USA. [Shafer, Robert] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. RP Hulgan, T (reprint author), Vanderbilt Univ, Sch Med, A2200 MCN,1161 21st Ave S, Nashville, TN 37232 USA. EM todd.hul-gan@vanderbilt.edu RI Samuels, David/A-5393-2008; Samuels, David/C-1365-2012; Murdock, Deborah/C-3483-2012; Ritchie, Marylyn/C-1114-2012; Hulgan, Todd/B-3947-2014; Vella, Stefano/D-4912-2015 OI Samuels, David/0000-0003-3529-7791; Hulgan, Todd/0000-0002-3339-067X; Vella, Stefano/0000-0003-2347-5984 FU NCRR NIH HHS [KL2 RR024977, TL1 RR024978, UL1 RR024975, UL1 RR024975-05]; NHLBI NIH HHS [HL087726, R21 HL087726, R21 HL087726-02]; NIAID NIH HHS [U01 AI069424, AI062435, AI069415, AI069419, AI069423, AI069424, AI069428, AI069432, AI069434, AI069450, AI069452, AI069465, AI069471, AI069472, AI069474, AI069477, AI069484, AI069495, AI069501, AI069502, AI069511, AI069513, AI069532, AI069556, AI077505, AI25859, AI27661, AI34835, AI34853, AI38844, AI38858, AI46370, AI54999, AI69467, AI69495, K01 AI062435, K01 AI062435-05, P30 AI054999, P30 AI054999-08, R01 AI077505, R01 AI077505-04, U01 AI025859, U01 AI025859-18, U01 AI027661, U01 AI027661-19, U01 AI032782-13, U01 AI034835-07, U01 AI034853, U01 AI034853-12, U01 AI038844-04, U01 AI038858, U01 AI038858-09, U01 AI046370, U01 AI046370-05, U01 AI068636, U01 AI068636-01, U01 AI069415, U01 AI069415-06, U01 AI069419, U01 AI069419-06, U01 AI069423, U01 AI069423-01, U01 AI069423-06, U01 AI069424-06, U01 AI069428, U01 AI069428-06, U01 AI069432, U01 AI069432-01, U01 AI069432-06, U01 AI069434, U01 AI069434-06, U01 AI069450, U01 AI069450-06, U01 AI069452, U01 AI069452-06, U01 AI069465, U01 AI069465-06, U01 AI069467, U01 AI069467-06, U01 AI069471, U01 AI069471-06, U01 AI069472, U01 AI069472-06, U01 AI069474, U01 AI069474-06, U01 AI069477, U01 AI069477-06, U01 AI069484, U01 AI069484-06, U01 AI069495, U01 AI069495-06, U01 AI069501, U01 AI069501-06, U01 AI069502, U01 AI069502-06, U01 AI069511, U01 AI069511-06, U01 AI069513, U01 AI069513-02, U01 AI069513-06, U01 AI069532, U01 AI069532-06, U01 AI069556, U01 AI069556-06, U01AI068636, UM1 AI069415, UM1 AI069419, UM1 AI069423, UM1 AI069424, UM1 AI069428, UM1 AI069432, UM1 AI069434, UM1 AI069450, UM1 AI069452, UM1 AI069465, UM1 AI069467, UM1 AI069471, UM1 AI069472, UM1 AI069474, UM1 AI069477, UM1 AI069484, UM1 AI069495, UM1 AI069501, UM1 AI069502, UM1 AI069511, UM1 AI069513, UM1 AI069532, UM1 AI069556]; NIGMS NIH HHS [5T32GM80178, T32 GM080178, T32 GM080178-05]; NINDS NIH HHS [NS059330, R21 NS059330, R21 NS059330-01]; PHS HHS [AL32782] NR 35 TC 10 Z9 10 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD DEC 1 PY 2011 VL 58 IS 4 BP 363 EP 370 DI 10.1097/QAI.0b013e31822c688b PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 846RM UT WOS:000296920900012 PM 21792066 ER PT J AU Dunn, EC Uddin, M Subramanian, SV Smoller, JW Galea, S Koenen, KC AF Dunn, Erin C. Uddin, Monica Subramanian, S. V. Smoller, Jordan W. Galea, Sandro Koenen, Karestan C. TI Research Review: Gene-environment interaction research in youth depression - a systematic review with recommendations for future research SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Review DE Depression; children; adolescents; youth; gene; environment; interaction ID SEROTONIN TRANSPORTER GENE; STRESSFUL LIFE EVENTS; GENOME-WIDE ASSOCIATION; SOCIOECONOMIC-STATUS; URBAN/RURAL RESIDENCY; ADOLESCENT DEPRESSION; PHYSICAL MALTREATMENT; 5-HTTLPR GENOTYPE; MENTAL-ILLNESS; NO INTERACTION AB Background: Depression is a major public health problem among youth, currently estimated to affect as many as 9% of US children and adolescents. The recognition that both genes (nature) and environments (nurture) are important for understanding the etiology of depression has led to a rapid growth in research exploring gene-environment interactions (GxE). However, there has been no systematic review of GxE in youth depression to date. Methods: The goal of this article was to systematically review evidence on the contribution of GxE to the risk of child and adolescent depression. Through a search of PubMed and PsycINFO databases to 1 April 2010, we identified 20 candidate gene-environment interaction studies focused on depression in youth (up to age 26) and compared each study in terms of the following characteristics: research design and sample studied; measure of depression and environment used; genes explored; and GxE findings in relation to these factors. Results: In total, 80% of studies (n = 16) found at least one significant GxE association. However, there was wide variation in methods and analyses adopted across studies, especially with respect to environmental measures used and tests conducted to estimate GxE. This heterogeneity made it difficult to compare findings and evaluate the strength of the evidence for GxE. Conclusions: The existing body of GxE research on depression in youth contains studies that are conceptually and methodologically quite different, which contributes to mixed findings and makes it difficult to assess the current state of the evidence. To decrease this heterogeneity, we offer 20 recommendations that are focused on: (a) reporting GxE research; (b) testing and reporting GxE effects; (c) conceptualizing, measuring and analyzing depression; (d) conceptualizing, measuring and analyzing environment; (e) increasing power to test for GxE; and (f) improving the quality of genetic data used. Although targeted to GxE research on depression, these recommendations can be adopted by GxE researchers focusing on other mental health outcomes. C1 [Dunn, Erin C.; Subramanian, S. V.; Koenen, Karestan C.] Harvard Univ, Dept Soc Human Dev & Hlth, Sch Publ Hlth, Boston, MA 02115 USA. [Dunn, Erin C.; Koenen, Karestan C.] Harvard Univ, Ctr Developing Child, Cambridge, MA 02138 USA. [Uddin, Monica] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. [Uddin, Monica] Wayne State Univ, Dept Psychiat & Behav Neurosci, Detroit, MI USA. [Smoller, Jordan W.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Galea, Sandro; Koenen, Karestan C.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. RP Dunn, EC (reprint author), Harvard Univ, Dept Soc Human Dev & Hlth, Sch Publ Hlth, 677 Huntington Ave,7th Floor, Boston, MA 02115 USA. EM erindunn@hsph.harvard.edu RI Koenen, Karestan/K-5402-2014 OI Koenen, Karestan/0000-0003-3293-4281 FU National Institute of Mental Health [MH088074]; Center on the Developing Child at Harvard University; National Institute of Health [DA022720, DA022720-S1, MH088283-01, HL081275, MH079799, MH078152, MH082729, MH070627, MH078928] FX Erin C. Dunn was supported by a predoctoral training grant from the National Institute of Mental Health (MH088074) and a fellowship from the Center on the Developing Child at Harvard University. This work was also supported by National Institute of Health grants DA022720, DA022720-S1 (S. G. and M. U.), MH088283-01 (M. U.), HL081275 (S. V. S.), MH079799 (J.W.S.), MH078152 and MH082729 (S. G.), and MH070627 and MH078928 (K. C. K.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental Health or the National Institutes of Health. The authors thank Carol Mita for her assistance in conducting the literature search and Felton Earls, MD, Stephanie M. Jones, PhD, Laura Kubzansky, PhD, and Kate McLaughlin, PhD for their insights on conceptualizing 'environment'. NR 89 TC 39 Z9 42 U1 5 U2 39 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0021-9630 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry PD DEC PY 2011 VL 52 IS 12 BP 1223 EP 1238 DI 10.1111/j.1469-7610.2011.02466.x PG 16 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA 840EW UT WOS:000296422100002 PM 21954964 ER PT J AU Guyatt, GH Oxman, AD Kunz, R Woodcock, J Brozek, J Helfand, M Alonso-Coello, P Glasziou, P Jaeschke, R Akl, EA Norris, S Vist, G Dahm, P Shukla, VK Higgins, J Falck-Ytter, Y Schunemann, HJ AF Guyatt, Gordon H. Oxman, Andrew D. Kunz, Regina Woodcock, James Brozek, Jan Helfand, Mark Alonso-Coello, Pablo Glasziou, Paul Jaeschke, Roman Akl, Elie A. Norris, Susan Vist, Gunn Dahm, Philipp Shukla, Vijay K. Higgins, Julian Falck-Ytter, Yngve Schuenemann, Holger J. CA GRADE Working Grp TI GRADE guidelines: 7. Rating the quality of evidence-inconsistency SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE GRADE; Inconsistency; Heterogeneity; Variability; Sub-group analysis; Interaction ID CLINICAL-TRIALS; METAANALYSIS; EPINEPHRINE; VASOPRESSIN AB This article deals with inconsistency of relative (rather than absolute) treatment effects in binary/dichotomous outcomes. A body of evidence is not rated up in quality if studies yield consistent results, but may be rated down in quality if inconsistent. Criteria for evaluating consistency include similarity of point estimates, extent of overlap of confidence intervals, and statistical criteria including tests of heterogeneity and I(2). To explore heterogeneity, systematic review authors should generate and test a small number of a priori hypotheses related to patients, interventions, outcomes, and methodology. When inconsistency is large and unexplained, rating down quality for inconsistency is appropriate, particularly if some studies suggest substantial benefit, and others no effect or harm (rather than only large vs. small effects). Apparent subgroup effects may be spurious. Credibility is increased if subgroup effects are based on a small number of a priori hypotheses with a specified direction; subgroup comparisons come from within rather than between studies; tests of interaction generate low P-values; and have a biological rationale. (C) 2011 Elsevier Inc. All rights reserved. C1 [Guyatt, Gordon H.] McMaster Univ, Dept Clin Epidemiol & Biostat, CLARITY Res Grp, W Hamilton, ON L8N 3Z5, Canada. [Guyatt, Gordon H.; Jaeschke, Roman; Schuenemann, Holger J.] McMaster Univ, Dept Med, W Hamilton, ON L8N 3Z5, Canada. [Oxman, Andrew D.; Vist, Gunn] Norwegian Knowledge Ctr Hlth Serv, N-0130 Oslo, Norway. [Kunz, Regina] Univ Basel Hosp, Basel Inst Clin Epidemiol, CH-4031 Basel, Switzerland. [Woodcock, James] London Sch Hyg & Trop Med, London WC1, England. [Helfand, Mark] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Oregon Evidence Based Practice Ctr, Portland, OR 97201 USA. [Alonso-Coello, Pablo] Univ Autonoma Barcelona, Serv Epidemiol Clin & Salud Publ, Iberoamer Cochrane Ctr, Barcelona 08041, Spain. [Alonso-Coello, Pablo] Univ Autonoma Barcelona, Hosp St Pau, CIBERESP, Barcelona 08041, Spain. [Glasziou, Paul] Bond Univ, Fac Hlth Sci, Ctr Res Evidence Based Practice, Gold Coast, Qld 4229, Australia. [Akl, Elie A.] SUNY Buffalo, Dept Med, Buffalo, NY 14260 USA. [Norris, Susan] Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Portland, OR 97239 USA. [Dahm, Philipp] Univ Florida, Coll Med, Dept Urol, Gainesville, FL USA. [Shukla, Vijay K.] CADTH, Ottawa, ON K1S 5S8, Canada. [Higgins, Julian] MRC Biostat Unit, Cambridge, England. [Falck-Ytter, Yngve] Case Western Reserve Univ, Div Gastroenterol, Case Med Ctr & VA, Cleveland, OH 44106 USA. RP Guyatt, GH (reprint author), McMaster Univ, Dept Clin Epidemiol & Biostat, CLARITY Res Grp, Room 2C12,1200 Main St, W Hamilton, ON L8N 3Z5, Canada. EM guyatt@mcmaster.ca RI Higgins, Julian/H-4008-2011; Glasziou, Paul/A-7832-2008 OI Higgins, Julian/0000-0002-8323-2514; Glasziou, Paul/0000-0001-7564-073X FU Medical Research Council [MC_U105285807] NR 18 TC 457 Z9 469 U1 3 U2 17 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD DEC PY 2011 VL 64 IS 12 BP 1294 EP 1302 DI 10.1016/j.jclinepi.2011.03.017 PG 9 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 847TI UT WOS:000296995000007 PM 21803546 ER PT J AU Guyatt, GH Oxman, AD Kunz, R Woodcock, J Brozek, J Helfand, M Alonso-Coello, P Falck-Ytter, Y Jaeschke, R Vist, G Akl, EA Post, PN Norris, S Meerpohl, J Shukla, VK Nasser, M Schunemann, HJ AF Guyatt, Gordon H. Oxman, Andrew D. Kunz, Regina Woodcock, James Brozek, Jan Helfand, Mark Alonso-Coello, Pablo Falck-Ytter, Yngve Jaeschke, Roman Vist, Gunn Akl, Elie A. Post, Piet N. Norris, Susan Meerpohl, Joerg Shukla, Vijay K. Nasser, Mona Schuenemann, Holger J. CA GRADE Working Group TI GRADE guidelines: 8. Rating the quality of evidence-indirectness SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE GRADE; Quality of evidence; Indirectness; Indirect comparisons; Applicability; Generalizability ID RANDOMIZED CONTROLLED-TRIALS; METAANALYSIS; INTERVENTIONS; THERAPY; CANCER AB Direct evidence comes from research that directly compares the interventions in which we are interested when applied to the populations in which we are interested and measures outcomes important to patients. Evidence can be indirect in one of four ways. First, patients may differ from those of interest (the term applicability is often used for this form of indirectness). Secondly, the intervention tested may differ from the intervention of interest. Decisions regarding indirectness of patients and interventions depend on an understanding of whether biological or social factors are sufficiently different that one might expect substantial differences in the magnitude of effect. Thirdly, outcomes may differ from those of primary interest-for instance, surrogate outcomes that are not themselves important, but measured in the presumption that changes in the surrogate reflect changes in an outcome important to patients. A fourth type of indirectness, conceptually different from the first three, occurs when clinicians must choose between interventions that have not been tested in head-to-head comparisons. Making comparisons between treatments under these circumstances requires specific statistical methods and will be rated down in quality one or two levels depending on the extent of differences between the patient populations, co-interventions, measurements of the outcome, and the methods of the trials of the candidate interventions. (C) 2011 Elsevier Inc. All rights reserved. C1 [Guyatt, Gordon H.] McMaster Univ, Dept Clin Epidemiol & Biostat, CLARITY Res Grp, W Hamilton, ON L8N 3Z5, Canada. [Guyatt, Gordon H.; Jaeschke, Roman; Schuenemann, Holger J.] McMaster Univ, Dept Med, W Hamilton, ON L8N 3Z5, Canada. [Oxman, Andrew D.; Vist, Gunn] Norwegian Knowledge Ctr Hlth Serv, N-0130 Oslo, Norway. [Kunz, Regina] Univ Basel Hosp, Acad Swiss Insurance Med, CH-4031 Basel, Switzerland. [Kunz, Regina] Univ Basel Hosp, Basel Inst Clin Epidemiol, CH-4031 Basel, Switzerland. [Woodcock, James] London Sch Hyg & Trop Med, London WC1, England. [Helfand, Mark] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Oregon Evidence Based Practice Ctr, Portland, OR 97201 USA. [Alonso-Coello, Pablo] Univ Autonoma Barcelona, Iberoamer Cochrane Ctr, Serv Epidemiol Clin & Salud Publ, Barcelona 08041, Spain. [Alonso-Coello, Pablo] Univ Autonoma Barcelona, Hosp St Pau, CIBERESP, Barcelona 08041, Spain. [Falck-Ytter, Yngve] Case Western Reserve Univ, Case & VA Med Ctr, Div Gastroenterol, Cleveland, OH 44106 USA. [Falck-Ytter, Yngve] Univ Oxford, Oxford, England. [Akl, Elie A.] SUNY Buffalo, Dept Med, Buffalo, NY 14260 USA. [Post, Piet N.] Dutch Inst Healthcare Improvement CBO, Utrecht, Netherlands. [Norris, Susan] Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Portland, OR 97239 USA. [Meerpohl, Joerg] Univ Med Ctr Freiburg, Inst Med Biometry & Med Informat, German Cochrane Ctr, D-79104 Freiburg, Germany. [Meerpohl, Joerg] Univ Med Ctr Freiburg, Dept Pediat & Adolescent Med, Div Pediat Hematol & Oncol, D-79106 Freiburg, Germany. [Shukla, Vijay K.] CADTH, Ottawa, ON K1S 5S8, Canada. [Nasser, Mona] Inst Qual & Efficiency Hlth Care IQWiG, Dept Hlth Informat, Cologne, Germany. RP Guyatt, GH (reprint author), McMaster Univ, Dept Clin Epidemiol & Biostat, CLARITY Res Grp, Room 2C12,1200 Main St, W Hamilton, ON L8N 3Z5, Canada. EM guyatt@mcmaster.ca RI Nasser, Mona/J-3601-2013; Meerpohl, Joerg/J-4224-2013 OI Meerpohl, Joerg/0000-0002-1333-5403 NR 21 TC 304 Z9 316 U1 1 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD DEC PY 2011 VL 64 IS 12 BP 1303 EP 1310 DI 10.1016/j.jclinepi.2011.04.014 PG 8 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 847TI UT WOS:000296995000008 PM 21802903 ER PT J AU Chopra, MP Trevino, KM Kowall, NW AF Chopra, Mohit P. Trevino, Kelly M. Kowall, Neil W. TI Memantine for Posttraumatic Stress Disorder in an Older Veteran SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Letter ID AGGRESSION; PRAZOSIN C1 [Chopra, Mohit P.] Boston Univ, Sch Med, VA Boston Healthcare Syst, Dept Psychiat, Boston, MA 02118 USA. [Trevino, Kelly M.] Harvard Univ, Sch Med, Dept Psychiat, Dana Farber Canc Inst, Boston, MA 02115 USA. [Kowall, Neil W.] Boston Univ, Sch Med, VA Boston Healthcare Syst, Dept Neurol,Geriat Res Educ & Clin Ctr, Boston, MA 02118 USA. RP Chopra, MP (reprint author), Boston Univ, Sch Med, VA Boston Healthcare Syst, Dept Psychiat, Boston, MA 02118 USA. EM mpchopra@hotmail.com RI Kowall, Neil/G-6364-2012; Chopra, Mohit P/F-7250-2013 OI Kowall, Neil/0000-0002-6624-0213; Chopra, Mohit P/0000-0002-9208-7224 NR 12 TC 2 Z9 2 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD DEC PY 2011 VL 31 IS 6 BP 787 EP 788 DI 10.1097/JCP.0b013e31823657bf PG 2 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 844IX UT WOS:000296742000022 PM 22051925 ER PT J AU Hayes, SM Buchler, N Stokes, J Kragel, J Cabeza, R AF Hayes, Scott M. Buchler, Norbou Stokes, Jared Kragel, James Cabeza, Roberto TI Neural Correlates of Confidence during Item Recognition and Source Memory Retrieval: Evidence for Both Dual-process and Strength Memory Theories SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID MEDIAL TEMPORAL-LOBE; EPISODIC MEMORY; PARIETAL CORTEX; PREFRONTAL CORTEX; RECOLLECTION; FAMILIARITY; FMRI; LESIONS; DISSOCIATION; INFORMATION AB Although the medial-temporal lobes (MTL), PFC, and parietal cortex are considered primary nodes in the episodic memory network, there is much debate regarding the contributions of MTL, PFC, and parietal subregions to recollection versus familiarity (dual-process theory) and the feasibility of accounts on the basis of a single memory strength process (strength theory). To investigate these issues, the current fMRI study measured activity during retrieval of memories that differed quantitatively in terms of strength (high vs. low-confidence trials) and qualitatively in terms of recollection versus familiarity (source vs. item memory tasks). Support for each theory varied depending on which node of the episodic memory network was considered. Results from MTL best fit a dual-process account, as a dissociation was found between a right hippocampal region showing high-confidence activity during the source memory task and bilateral rhinal regions showing high-confidence activity during the item memory task. Within PFC, several left-lateralized regions showed greater activity for source than item memory, consistent with recollective orienting, whereas a right-lateralized ventrolateral area showed low-confidence activity in both tasks, consistent with monitoring processes. Parietal findings were generally consistent with strength theory, with dorsal areas showing low-confidence activity and ventral areas showing high-confidence activity in both tasks. This dissociation fits with an attentional account of parietal functions during episodic retrieval. The results suggest that both dual-process and strength theories are partly correct, highlighting the need for an integrated model that links to more general cognitive theories to account for observed neural activity during episodic memory retrieval. C1 [Hayes, Scott M.] VA Boston Healthcare Syst, Memory Disorders Res Ctr, Boston, MA 02130 USA. [Hayes, Scott M.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. [Hayes, Scott M.] VA Boston Healthcare Syst, Neuroimaging Res Ctr, Boston, MA 02130 USA. [Buchler, Norbou] USA, Res Lab, Aberdeen Proving Ground, MD USA. [Stokes, Jared; Kragel, James; Cabeza, Roberto] Duke Univ, Ctr Cognit Neurosci, Durham, NC 27706 USA. [Cabeza, Roberto] Duke Univ, Med Ctr, Brain Imaging & Anal Ctr, Durham, NC 27706 USA. [Cabeza, Roberto] Duke Univ, Med Ctr, Ctr Study Aging & Human Dev, Durham, NC 27706 USA. RP Hayes, SM (reprint author), VA Boston Healthcare Syst, Memory Disorders Res Ctr 151A, 150 S Huntington Ave, Boston, MA 02130 USA. EM smhayes@bu.edu FU National Institutes of Health; National Institute on Aging (NIA) [R01 AG019731, R56 AG23770, F32 AG029738]; Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research & Development Service [E7822W] FX The authors thank Michael White and Micah Adams for assistance with data collection and Allen Song for providing technical assistance with MRI data acquisition. We would also like to thank two anonymous reviewers for their helpful comments. This work was supported by the National Institutes of Health, the National Institute on Aging (NIA; grants R01 AG019731 and R56 AG23770 awarded to R. C. and grant F32 AG029738 awarded to S. M. H.) and the Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research & Development Service (grant E7822W awarded to S. M. H.). The content is solely the responsibility of the authors and does not necessarily represent the official views of NIH or NIA. NR 64 TC 22 Z9 22 U1 2 U2 11 PU MIT PRESS PI CAMBRIDGE PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD DEC PY 2011 VL 23 IS 12 BP 3959 EP 3971 PG 13 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 844PB UT WOS:000296758500023 PM 21736454 ER PT J AU Nishikawa-Torikai, S Osawa, M Nishikawa, S AF Nishikawa-Torikai, Satomi Osawa, Masatake Nishikawa, Shin-ichi TI Functional Characterization of Melanocyte Stem Cells in Hair Follicles SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID TISSUE-ENGINEERED SKIN; IN-VITRO EXPANSION; EX-VIVO EXPANSION; SURFACE MARKER; DIFFERENTIATION; GROWTH; PROLIFERATION; MELANOBLASTS; POPULATIONS; CULTURES AB In mice, coat pigmentation requires a stem cell (SC) system in which the survival, proliferation, and differentiation of melanocytes (MCs) are regulated by microenvironments in hair follicles (HFs). In vitro systems are required to analyze the behavior of single melanocyte stem cells (MCSCs) and their potential to form SC systems in vivo. We describe here an experimental system for the isolation, self-renewal, and differentiation of MCSCs, as well as an in vivo reconstitution assay for assessing their potential. Using Dct(tm1(Cre)Bee)/CAG-CAT-GFP mice, we show that, in the presence of stem cell factor and basic fibroblast growth factor and the XB2 feeder cell line, purified MCSCs can undergo clonogenic proliferation, resulting in c-Kit(low) side scatter(low) cells. In culture, these cells maintain their capacity to differentiate and reconstitute an MCSC system in HFs. As these cells are present in the upper part of the HF near the bulge region, express only low levels of housekeeping genes, and are resistant to neonatal treatment with ACK2, it is likely that only MCSCs that are quiescent in vivo have clonogenic activity in vitro. We also found that MCSCs can be purified from wild-type mice by fluorescent cell sorting and can be characterized in vitro. C1 [Nishikawa-Torikai, Satomi] RIKEN Ctr Dev Biol, Lab Stem Cell Biol, Chou Ku, Kobe, Hyogo, Japan. [Osawa, Masatake] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. RP Nishikawa-Torikai, S (reprint author), RIKEN Ctr Dev Biol, Lab Stem Cell Biol, Chou Ku, 2-2-3 Minatojima Minamimachi, Kobe, Hyogo, Japan. EM torikai@cdb.riken.jp NR 43 TC 20 Z9 22 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD DEC PY 2011 VL 131 IS 12 BP 2358 EP 2367 DI 10.1038/jid.2011.195 PG 10 WC Dermatology SC Dermatology GA 847ON UT WOS:000296982400006 PM 21753783 ER PT J AU Tarr, RW Albuquerque, F Hirsh, J Prestigiacomo, C AF Tarr, Robert W. Albuquerque, Felipe Hirsh, Joshua Prestigiacomo, Charles TI The SAMMPRIS trial: the end or just the beginning SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Editorial Material ID INTRACRANIAL ARTERIAL-STENOSIS; WINGSPAN STENT C1 [Tarr, Robert W.] Univ Hosp Case Med Ctr, Cleveland, OH 44102 USA. [Albuquerque, Felipe] Barrow Neurol Inst, Phoenix, AZ 85013 USA. [Hirsh, Joshua] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Prestigiacomo, Charles] Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. RP Tarr, RW (reprint author), Univ Hosp Case Med Ctr, Cleveland, OH 44102 USA. EM robert.tarr@uhhospitals.org NR 6 TC 4 Z9 6 U1 0 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD DEC PY 2011 VL 3 IS 4 BP 310 EP 311 DI 10.1136/neurintsurg-2011-010144 PG 2 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 844ZU UT WOS:000296793400002 PM 21993494 ER PT J AU Leslie-Mazwi, TM Chandra, RV Oh, DC Nogueira, RG AF Leslie-Mazwi, Thabele M. Chandra, Ronil V. Oh, Daniel C. Nogueira, Raul G. TI Novel use of prasugrel for intracranial stent thrombosis SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Article ID PLATELET REACTIVITY; CLOPIDOGREL; ASPIRIN; ANTIPLATELET; VARIABILITY; INHIBITION; PLACEMENT; IMPACT AB Dual antiplatelet therapy is established for prevention of stent thrombosis in cardiac patients, and widely utilized in neurointerventional stent cases. Aspirin and clopidogrel are typically synergistic. We present a case of clopidogrel resistance due to genetic polymorphism resulting in acute stent thrombosis during elective stent-assisted coiling, with novel use of prasugrel as an alternative platelet inhibitor in the neurovascular setting. C1 [Leslie-Mazwi, Thabele M.; Chandra, Ronil V.; Oh, Daniel C.] Massachusetts Gen Hosp, Dept Intervent Neuroradiol Endovasc Neurosurg, Boston, MA 02114 USA. [Nogueira, Raul G.] Emory Univ, Sch Med, Grady Mem Hosp, Marcus Stroke & Neurosci Ctr, Atlanta, GA USA. RP Leslie-Mazwi, TM (reprint author), Massachusetts Gen Hosp, Dept Intervent Neuroradiol Endovasc Neurosurg, 2-214 Gray Bigelow,55 Fruit St, Boston, MA 02114 USA. EM tleslie-mazwi@partners.org NR 18 TC 7 Z9 7 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD DEC PY 2011 VL 3 IS 4 BP 358 EP 360 DI 10.1136/jnis.2010.004382 PG 3 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 844ZU UT WOS:000296793400014 PM 21990454 ER PT J AU Manchikanti, L Hirsch, JA AF Manchikanti, Laxmaiah Hirsch, Joshua A. TI Medicare physician payment rules for 2011: a primer for the neurointerventionalist SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Article ID HEALTH-CARE AB Physicians generally have been affected by significant changes in the patterns of medical practice evolving over the past several decades. The Patient Protection and Affordable Care Act of 2010, also called ACA for short, impacts physician professional practice dramatically. Physicians are paid in the USA for their personal services. The payment system is highly variable in the private insurance market; however, governmental systems have a formula based payment, mostly based on the Medicare payment system. Physician services are billed under part B. The Neurointerventional practice is typically performed in a hospital setting. The VA system is a frequently cited successful implementation of a government supported health care program. Availability of neurointerventional services at many VA medical centers is limited. Since the inception of the Medicare program in 1965, several methods have been used to determine the amounts paid to physicians for each covered service. Initially, the payment systems compensated physicians on the basis of their charges. In 1975, just over 10 years after the inception of the Medicare program, payments changed so as not to exceed the increase in medical economic index. The involvement of medical economic index failed to curb increases in costs, leading to the determination of a yearly change in fees by legislation from 1984 to 1991. In 1992, the fee schedule essentially replaced the prior payment system that was based on the physician's charges, which also failed to curb the growth in spending. Thus, in 1998, the sustainable growth rate system was introduced. In 2009, multiple unsuccessful attempts were made by Congress to repeal the formula. The mechanism of the sustainable growth rate includes three components that are incorporated into a statutory formula: expenditure targets, growth rate period and annual adjustments of payment rates for physician services. C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY 42003 USA. [Manchikanti, Laxmaiah] Univ Louisville, Dept Anesthesiol & Perioperat Med, Louisville, KY 40292 USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Manchikanti, L (reprint author), Pain Management Ctr Paducah, 2831 Lone Oak Rd, Paducah, KY 42003 USA. EM drlm@thepainmd.com NR 21 TC 20 Z9 20 U1 0 U2 2 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 EI 1759-8486 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD DEC PY 2011 VL 3 IS 4 BP 399 EP 402 DI 10.1136/jnis.2011.004937 PG 4 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 844ZU UT WOS:000296793400026 PM 21990479 ER PT J AU Mitin, T Chen, MH Zhang, YY Moran, BJ Dosoretz, DE Katin, MJ Braccioforte, MH Salenius, SA D'Amico, AV AF Mitin, Timur Chen, Ming-Hui Zhang, Yuanye Moran, Brian J. Dosoretz, Daniel E. Katin, Michael J. Braccioforte, Michelle H. Salenius, Sharon A. D'Amico, Anthony V. TI Diabetes Mellitus, Race and the Odds of High Grade Prostate Cancer in Men Treated With Radiation Therapy SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatic neoplasms; diabetes mellitus; African Americans; risk ID STAGE RENAL-DISEASE; RADICAL PROSTATECTOMY; MEXICAN-AMERICANS; RISK; METAANALYSIS; DEATH AB Purpose: Black men present more frequently with high grade prostate cancer and are more likely to have diabetes mellitus. We evaluated whether there is an independent association between diabetes mellitus and the risk of high grade prostate cancer in men diagnosed with prostate cancer and treated with radiation therapy. Materials and Methods: A polychotomous logistic regression analysis was performed to evaluate whether a diagnosis of diabetes mellitus was associated with the odds of Gleason score 7 or 8-10 prostate cancer in a cohort of 16,286 men, adjusting for black race, advancing age, prostate specific antigen and digital rectal examination findings. Results: Black men (adjusted OR 1.84, 95% CI 1.08-3.13, p = 0.024) and non-black men (adjusted OR 1.59, 95% CI 1.33-1.89, p <0.001) with diabetes were more likely to have Gleason score 8-10 vs 6 or less prostate cancer than nondiabetic men. However, this was not true for Gleason score 7 vs 6 or less prostate cancer. Black race was significantly associated with Gleason score 7 vs 6 or less prostate cancer in men without and with diabetes (adjusted OR 1.38, 95% CI 1.17-1.63, p <0.001 and 1.61, 95% CI 1.17-2.21, p = 0.003, respectively). Black race was also associated with Gleason score 8-10 vs 6 or less prostate cancer in men without and with diabetes (adjusted OR 1.36, 95% CI 1.01-1.83, p = 0.04 and 1.58, 95% CI 0.98-2.53, p = 0.06, respectively). Conclusions: In a cohort of men undergoing radiotherapy for prostate cancer the diagnosis of diabetes mellitus was significantly associated with an increased risk of being diagnosed with Gleason score 8-10 prostate cancer independent of black race. C1 [Mitin, Timur] Brigham & Womens Hosp, Harvard Radiat Oncol Program, Dept Radiat Oncol, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. Prostate Canc Fdn Chicago, Westmont, IL USA. 21st Century Oncol Inc, Dept Radiat Oncol, Ft Myers, FL USA. RP Mitin, T (reprint author), Brigham & Womens Hosp, Harvard Radiat Oncol Program, Dept Radiat Oncol, 75 Francis St,L-2 Level, Boston, MA 02215 USA. EM tmitin@partners.org RI zhang, yuanye/H-6315-2013 NR 27 TC 18 Z9 18 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD DEC PY 2011 VL 186 IS 6 BP 2233 EP 2237 DI 10.1016/j.juro.2011.07.072 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 844PC UT WOS:000296758600024 PM 22019035 ER PT J AU Smith, MR Malkowicz, SB Brawer, MK Hancock, ML Morton, RA Steiner, MS AF Smith, Matthew R. Malkowicz, S. Bruce Brawer, Michael K. Hancock, Michael L. Morton, Ronald A. Steiner, Mitchell S. TI Toremifene Decreases Vertebral Fractures in Men Younger Than 80 Years Receiving Androgen Deprivation Therapy for Prostate Cancer SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatic neoplasms; toremifene; thromboembolism; fractures, bone ID PREVENTION; DISEASE; RISK; TRIAL AB Purpose: Androgen deprivation therapy is associated with an increased fracture risk. In a recent phase III trial toremifene significantly decreased vertebral fractures in men on androgen deprivation therapy. Similar to other selective estrogen receptor modulators, toremifene was associated with an increase in venous thromboembolic events with the greatest risk in men 80 years old or older. In this post hoc analysis we evaluated the efficacy and safety of toremifene in men younger than 80 years. Materials and Methods: This analysis included 847 men younger than 80 years, of whom 430 received toremifene 80 mg by mouth daily and 417 received placebo for up to 24 months. The primary end point was new vertebral fractures. Secondary end points included fragility fractures, bone mineral density and safety. Results: Compared with placebo, toremifene decreased the relative risk of new vertebral fractures by 79.5% (95% CI 29.8-94.0, p <0.005). The new vertebral fracture incidence was 1.0% for toremifene and 4.8% for placebo (absolute risk reduction 3.8%). Compared with placebo, toremifene significantly decreased the incidence of nontraumatic fracture or greater than 7% bone loss by 24 months (p <0.0001). Toremifene also significantly increased bone mineral density at all measured sites (all comparisons p <0.001). The incidence of venous thromboembolic events was similar in the toremifene and placebo groups (2.1% and 1.0%, respectively, p = 0.26). The rates of other adverse events were also similar between the groups. Conclusions: Toremifene significantly decreased new vertebral fractures in men younger than 80 years receiving androgen deprivation therapy for prostate cancer. The risk of venous thromboembolic events was lower than in the overall study population, suggesting an improved risk-benefit profile in younger men. C1 [Smith, Matthew R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Malkowicz, S. Bruce] Univ Penn, Philadelphia, PA 19104 USA. [Brawer, Michael K.; Hancock, Michael L.; Morton, Ronald A.; Steiner, Mitchell S.] GTx Inc, Memphis, TN USA. RP Smith, MR (reprint author), Massachusetts Gen Hosp, Ctr Canc, Yawkey 7030,55 Fruit St, Boston, MA 02114 USA. EM smith.matthew@mgh.harvard.edu FU GTx, Inc.; National Institutes of Health [K24CA121990]; Prostate Cancer Foundation FX Supported by GTx, Inc., National Institutes of Health K24 Midcareer Investigator Award K24CA121990 (MRS) and Prostate Cancer Foundation research awards (MRS). NR 23 TC 14 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD DEC PY 2011 VL 186 IS 6 BP 2239 EP 2244 DI 10.1016/j.juro.2011.07.090 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 844PC UT WOS:000296758600027 PM 22014807 ER PT J AU Watkins, JD Diaz-Rodriguez, J Siddappa, NB Corti, D Ruprecht, RM AF Watkins, Jennifer D. Diaz-Rodriguez, Juan Siddappa, Nagadenahalli B. Corti, Davide Ruprecht, Ruth M. TI Efficiency of Neutralizing Antibodies Targeting the CD4-Binding Site: Influence of Conformational Masking by the V2 Loop in R5-Tropic Clade C Simian-Human Immunodeficiency Virus SO JOURNAL OF VIROLOGY LA English DT Article ID MONOCLONAL-ANTIBODIES; ENVELOPE GLYCOPROTEIN; HIV-1; MACAQUES; PROTECTION; GP120; CD4; GLYCOSYLATION; CHALLENGE; INFECTION AB In R5-tropic clade C simian-human immunodeficiency viruses (SHIV-Cs), we identified a 3-asparagine (3N) deletion mutation in the V2 loop stem of gp120 as the major determinant of neutralization escape of the anti-CD4-binding site (anti-CD4-bs) neutralizing monoclonal antibody (nMAb) b12. However, the more potent anti-CD4-bs nMAbs VRC01 and VRC03 were not sensitive to this mutation. Using isogenic tier 1 or tier 2 proviruses differing only in the 3N mutation, we showed that this mutation might result in selective conformational b12 epitope masking. Therefore, human immunodeficiency virus (HIV) Env immunogens targeting the CD4-bs and designed to neutralize tier 2 viruses should take conformational masking by the V2 loop into account. C1 [Watkins, Jennifer D.; Diaz-Rodriguez, Juan; Siddappa, Nagadenahalli B.; Ruprecht, Ruth M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Watkins, Jennifer D.; Siddappa, Nagadenahalli B.; Ruprecht, Ruth M.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Corti, Davide] Humabs SAGL, Bellinzona, Switzerland. RP Ruprecht, RM (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM ruth_ruprecht@dfci.harvard.edu OI Byrareddy, Siddappa /0000-0002-7423-1763 FU NIH [R37 AI034266, P01 AI048240] FX This study was supported by NIH grants R37 AI034266 and P01 AI048240. NR 27 TC 9 Z9 9 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2011 VL 85 IS 23 BP 12811 EP 12814 DI 10.1128/JVI.05994-11 PG 4 WC Virology SC Virology GA 843WU UT WOS:000296708100067 PM 21957314 ER PT J AU Wu, C So, J Davis-Dusenbery, BN Qi, HH Bloch, DB Shi, Y Lagna, G Hata, A AF Wu, Connie So, Jessica Davis-Dusenbery, Brandi N. Qi, Hank H. Bloch, Donald B. Shi, Yang Lagna, Giorgio Hata, Akiko TI Hypoxia Potentiates MicroRNA-Mediated Gene Silencing through Posttranslational Modification of Argonaute2 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MAMMALIAN STRESS GRANULES; PROLYL 4-HYDROXYLASE; PULMONARY-HYPERTENSION; SKELETAL-MUSCLE; MESSENGER-RNA; EXPRESSION; COLLAGEN; BIOGENESIS; PROTEINS; CANCER AB Hypoxia contributes to the pathogenesis of various human diseases, including pulmonary artery hypertension (PAH), stroke, myocardial or cerebral infarction, and cancer. For example, acute hypoxia causes selective pulmonary artery (PA) constriction and elevation of pulmonary artery pressure. Chronic hypoxia induces structural and functional changes to the pulmonary vasculature, which resembles the phenotype of human PAH and is commonly used as an animal model of this disease. The mechanisms that lead to hypoxia-induced phenotypic changes have not been fully elucidated. Here, we show that hypoxia increases type I collagen prolyl-4-hydroxylase [C-P4H(I)], which leads to prolyl-hydroxylation and accumulation of Argonaute2 (Ago2), a critical component of the RNA-induced silencing complex (RISC). Hydroxylation of Ago2 is required for the association of Ago2 with heat shock protein 90 (Hsp90), which is necessary for the loading of microRNAs (miRNAs) into the RISC, and translocation to stress granules (SGs). We demonstrate that hydroxylation of Ago2 increases the level of miRNAs and increases the endonuclease activity of Ago2. In summary, this study identifies hypoxia as a mediator of the miRNA-dependent gene silencing pathway through posttranslational modification of Ago2, which might be responsible for cell survival or pathological responses under low oxygen stress. C1 [Lagna, Giorgio; Hata, Akiko] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94158 USA. [So, Jessica; Davis-Dusenbery, Brandi N.; Lagna, Giorgio; Hata, Akiko] Tufts Med Ctr, Mol Cardiol Res Inst, Boston, MA 02111 USA. [Qi, Hank H.; Shi, Yang] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Newborn Med & Epigenet Program,Dept Med, Boston, MA 02115 USA. [Qi, Hank H.; Shi, Yang] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Qi, Hank H.] Univ Iowa, Carver Coll Med, Dept Anat & Cell Biol, Iowa City, IA 52242 USA. [Bloch, Donald B.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. [Wu, Connie; Hata, Akiko] Tufts Univ, Sackler Sch Grad Biomed Sci, Grad Program Biochem, Boston, MA 02111 USA. [Wu, Connie; Hata, Akiko] Tufts Univ, Sch Med, Dept Biochem, Boston, MA 02111 USA. RP Hata, A (reprint author), Univ Calif San Francisco, Cardiovasc Res Inst, 555 Mission Bay Blvd S,Room 252T, San Francisco, CA 94158 USA. EM akiko.hata@ucsf.edu RI Davis-Dusenbery, Brandi/N-2798-2013 OI Davis-Dusenbery, Brandi/0000-0001-7811-8613 FU NHLBI [HL093154]; LeDucq Foundation; American Heart Association FX This work was supported by grants from the NHLBI (HL093154), LeDucq Foundation, and American Heart Association (to A.H.). NR 51 TC 56 Z9 57 U1 1 U2 13 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 2011 VL 31 IS 23 BP 4760 EP 4774 DI 10.1128/MCB.05776-11 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 844ZF UT WOS:000296791900009 PM 21969601 ER PT J AU Carneiro, HA Mavrakis, A Mylonakis, E AF Carneiro, Herman Anthony Mavrakis, Anastasios Mylonakis, Eleftherios TI Candida Peritonitis: An Update on the Latest Research and Treatments SO WORLD JOURNAL OF SURGERY LA English DT Article ID INTENSIVE-CARE-UNIT; INVASIVE FUNGAL-INFECTIONS; CRITICALLY-ILL PATIENTS; COMPLICATED INTRAABDOMINAL INFECTIONS; POLYMERASE-CHAIN-REACTION; RISK SURGICAL-PATIENTS; BETA-D-GLUCAN; ESCHERICHIA-COLI; STAPHYLOCOCCUS-AUREUS; BACTEROIDES-FRAGILIS AB The incidence of Candida peritonitis is increasing and the mortality rate remains high. Candida albicans is the most common yeast causing Candida peritonitis, but a shift to more drug-resistant non-albicans strains has been observed. Major risk factors for developing Candida peritonitis include hollow viscus perforation, abdominal and thoracic surgery, surgical drains in situ, intravenous and urinary catheters, total parenteral nutrition, severe sepsis, antibiotic therapy (a parts per thousand yen48 h before peritonitis), immunosuppression, diabetes mellitus, and extensive Candida colonization. Polymicrobial peritoneal infections with Candida spp. and enteric bacteria (such as E. coli and B. fragilis) have been associated with higher mortality. Laboratory detection of Candida is still based on histopathological diagnosis and culture-based methods. Isolated Candida spp. must be treated as a pathogen contributing to peritonitis. Prompt diagnosis, effective antifungal therapy, and skilled surgical management are essential components of treatment. Treatment includes removal of all foreign bodies, such as intravenous and urinary catheters and drains, whereas abscesses usually require surgical or radiological drainage. Antifungal therapy should be chosen based on sensitivity profiles. Fluconazole is still appropriate for most severe community-acquired or nosocomial infections. Echinocandins are used as first-line in critically ill patients, those with prior azole exposure, and those with fluconazole-resistant candidiasis. Peritoneal lavage can be used in combination with other antifungal agents to treat refractory infections. Risk factors must be weighed to decide on prophylaxis (usually with fluconazole) to limit antifungal resistance. C1 [Carneiro, Herman Anthony] Imperial Coll Healthcare NHS Trust, W London Renal & Transplant Ctr, Hammersmith Hosp, London W12 0HS, England. [Mavrakis, Anastasios] UCSF Fresno Hosp, Div Gastroenterol, Fresno, CA USA. [Carneiro, Herman Anthony; Mylonakis, Eleftherios] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA. RP Carneiro, HA (reprint author), Imperial Coll Healthcare NHS Trust, W London Renal & Transplant Ctr, Hammersmith Hosp, Cane Rd, London W12 0HS, England. EM herman.carneiro@doctors.org.uk; anmavrakis@msn.com; emylonakis@partners.org FU Astellas Pharma, Inc.; T2 Biosystems, Inc. FX EM has received research funding from Astellas Pharma, Inc. and T2 Biosystems, Inc. NR 121 TC 15 Z9 17 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2313 J9 WORLD J SURG JI World J.Surg. PD DEC PY 2011 VL 35 IS 12 BP 2650 EP 2659 DI 10.1007/s00268-011-1305-2 PG 10 WC Surgery SC Surgery GA 846DZ UT WOS:000296878700010 PM 21976010 ER PT J AU Santry, HP Janjua, S Chang, YC Petrovick, L Velmahos, GC AF Santry, Heena P. Janjua, Sumbal Chang, Yuchiao Petrovick, Laurie Velmahos, George C. TI Interhospital Transfers of Acute Care Surgery Patients: Should Care for Nontraumatic Surgical Emergencies be Regionalized? SO WORLD JOURNAL OF SURGERY LA English DT Article ID GENERAL-SURGERY; TRAUMA SURGEONS; UNITED-STATES; FUTURE; MODEL; SERVICE; APPENDICITIS; PERSPECTIVE; MORTALITY; SYSTEMS AB Patients with major nontraumatic surgical emergencies (NTSEs) are commonly transferred from small hospitals to tertiary care centers. We hypothesized that transferred patients (TRANS) have worse outcomes than patients with similar diagnoses admitted directly to a tertiary center (DIRECT). We reviewed all patients admitted to the acute care surgery service of our tertiary center (September 1, 2006-October 31, 2009) with one of eight diagnoses indicating a major NTSE. Patients transferred for reasons other than the severity of illness were excluded. Univariate and multivariable analyses compared TRANS and DIRECT patients. Of 319 patients eligible for analysis, 103 (34%) were TRANS and averaged 3.8 days in the referring hospital before transfer. Compared to DIRECT patients, TRANS patients were more likely to be obese (18.5 vs. 8.0%, P = 0.006) and have cardiac (24 vs. 14%, P = 0.022) or pulmonary (25 vs. 12%, P = 0.003) co-morbidities. TRANS patients were also more likely to present to the tertiary center with hypotension (9 vs. 2%, P = 0.021), tachycardia (20 vs. 13%, P = 0.036), anemia (83 vs. 58%, P < 0.001), and hypoalbuminemia (50 vs. 14%, P < 0.001). TRANS patients had higher mortality (4.9 vs. 0.9%, P = 0.038) and longer hospital stay (8 with 5-13 days vs. 5 with 3-8 days, P < 0.001). TRANS patients comprised a significant portion of the population with major NTSEs admitted to the acute care surgery service of our tertiary center. They presented with greater physiologic derangement and had worse outcomes than DIRECT patients. As is currently established for trauma care, regionalization of care for NTSEs should be considered. C1 [Santry, Heena P.] Univ Massachusetts, UMass Mem Med Ctr, Div Trauma & Crit Care, Worcester, MA 01655 USA. [Janjua, Sumbal] St Elizabeths Med Ctr, Dept Internal Med, Brighton, MA 02135 USA. [Chang, Yuchiao] Massachusetts Gen Hosp, Dept Med, Clin Epidemiol Unit, Boston, MA 02114 USA. [Petrovick, Laurie; Velmahos, George C.] Massachusetts Gen Hosp, Dept Surg, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. RP Santry, HP (reprint author), Univ Massachusetts, UMass Mem Med Ctr, Div Trauma & Crit Care, 55 Lake Ave N, Worcester, MA 01655 USA. EM Heena.Santry@umassmemorial.org; sumbaljanjua@hotmail.com; ychang@partners.org; lpetrovick@partners.org; gvelmahos@partners.org NR 25 TC 21 Z9 21 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2313 J9 WORLD J SURG JI World J.Surg. PD DEC PY 2011 VL 35 IS 12 BP 2660 EP 2667 DI 10.1007/s00268-011-1292-3 PG 8 WC Surgery SC Surgery GA 846DZ UT WOS:000296878700011 PM 22002495 ER PT J AU Upadhyay, J Anderson, J Schwarz, AJ Coimbra, A Baumgartner, R Pendse, G George, E Nutile, L Wallin, D Bishop, J Neni, S Maier, G Iyengar, S Evelhoch, JL Bleakman, D Hargreaves, R Becerra, L Borsook, D AF Upadhyay, Jaymin Anderson, Julie Schwarz, Adam J. Coimbra, Alexandre Baumgartner, Richard Pendse, G. George, Edward Nutile, Lauren Wallin, Diana Bishop, James Neni, Saujanya Maier, Gary Iyengar, Smriti Evelhoch, Jeffery L. Bleakman, David Hargreaves, Richard Becerra, Lino Borsook, David TI Imaging Drugs with and without Clinical Analgesic Efficacy SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE phMRI; evoked fMRI; analgesia; buprenorphine; fosaprepitant ID OPIOID RECEPTOR AVAILABILITY; ROSTRAL VENTROMEDIAL MEDULLA; HEROIN-DEPENDENT VOLUNTEERS; NOXIOUS THERMAL STIMULI; CHRONIC PAIN; SUBSTANCE-P; HUMAN BRAIN; FUNCTIONAL CONNECTIVITY; PERIAQUEDUCTAL GRAY; HEALTHY-VOLUNTEERS AB The behavioral response to pain is driven by sensory and affective components, each of which is mediated by the CNS. Subjective pain ratings are used as readouts when appraising potential analgesics; however, pain ratings alone cannot enable a characterization of CNS pain circuitry during pain processing or how this circuitry is modulated pharmacologically. Having a more objective readout of potential analgesic effects may allow improved understanding and detection of pharmacological efficacy for pain. The pharmacological/functional magnetic resonance imaging (phMRI/fMRI) methodology can be used to objectively evaluate drug action on the CNS. In this context, we aimed to evaluate two drugs that had been developed as analgesics: one that is efficacious for pain (buprenorphine (BUP)) and one that failed as an analgesic in clinical trials aprepitant (APREP). Using phMRI, we observed that activation induced solely by BUP was present in regions with mu-opioid receptors, whereas APREP-induced activation was seen in regions expressing NK(1) receptors. However, significant pharmacological modulation of functional connectivity in pain-processing pathways was only observed following BUP administration. By implementing an evoked pain fMRI paradigm, these drugs could also be differentiated by comparing the respective fMRI signals in CNS circuits mediating sensory and affective components of pain. We report a correlation of functional connectivity and evoked pain fMRI measures with pain ratings as well as peak drug concentration. This investigation demonstrates how CNS-acting drugs can be compared, and how the phMRI/fMRI methodology may be used with conventional measures to better evaluate candidate analgesics in small subject cohorts. Neuropsychopharmacology (2011) 36, 2659-2673; doi: 10.1038/npp.2011.156; published online 17 August 2011 C1 [Borsook, David] Harvard Univ, Sch Med, McLean Hosp, Brain Imaging Ctr,PAIN Grp, Belmont, MA 02478 USA. [Upadhyay, Jaymin; Anderson, Julie; Schwarz, Adam J.; Coimbra, Alexandre; Baumgartner, Richard; Pendse, G.; George, Edward; Nutile, Lauren; Wallin, Diana; Bishop, James; Neni, Saujanya; Maier, Gary; Iyengar, Smriti; Evelhoch, Jeffery L.; Bleakman, David; Hargreaves, Richard; Becerra, Lino; Borsook, David] Imaging Consortium Drug Dev, Belmont, MA USA. [Schwarz, Adam J.; Iyengar, Smriti; Bleakman, David] Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. [Coimbra, Alexandre; Baumgartner, Richard; Evelhoch, Jeffery L.; Hargreaves, Richard] Merck Res Labs, West Point, PA USA. [Neni, Saujanya; Maier, Gary] Sunovion Inc, Marlborough, MA USA. [Becerra, Lino; Borsook, David] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Borsook, D (reprint author), Harvard Univ, Sch Med, McLean Hosp, Brain Imaging Ctr,PAIN Grp, 115 Mill St Belmont, Belmont, MA 02478 USA. EM dborsook@partners.org OI Wallin, Diana/0000-0003-4244-0314 FU Imaging Consortium for Drug Development; Glaxo SmithKline; Merck and Company FX We thank Dr Brigitte Robertson and Ms Margaret Grant for assistance in preparing this manuscript. This study was funded by the Imaging Consortium for Drug Development.; Adam J Schwarz, Smriti Iyengar, and David Bleakman are employed by Eli Lilly and Company. Alexandre Coimbra, Richard Baumgartner, Jeffery L Evelhoch, and Richard Hargreaves are employed by Merck and Company. Soujanya Neni, Gary Maier, and Brigitte Robertson are employed by Sunovion Incorporated. David Borsook and Lino Becerra currently receive research grants from Glaxo SmithKline and Merck and Company. NR 75 TC 26 Z9 26 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2011 VL 36 IS 13 BP 2659 EP 2673 DI 10.1038/npp.2011.156 PG 15 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 845YJ UT WOS:000296863600008 PM 21849979 ER PT J AU Hunt, KJ Gonzalez, ME Lopez, R Haffner, SM Stern, MP Gonzalez-Villalpando, C AF Hunt, Kelly J. Elena Gonzalez, Maria Lopez, Ruy Haffner, Steve M. Stern, Michael P. Gonzalez-Villalpando, Clicerio TI Diabetes is More Lethal in Mexicans and Mexican-Americans Compared to Non-Hispanic Whites SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE World Health; Epidemiology; Mortality ID CARDIOVASCULAR RISK-FACTORS; IMPAIRED GLUCOSE-TOLERANCE; SAN-ANTONIO; MYOCARDIAL-INFARCTION; DISEASE MORTALITY; PLASMA-GLUCOSE; US ADULTS; ALL-CAUSE; CITY; PREVALENCE AB PURPOSE: To examine the mortality risk associated with diabetes in the Mexico City Diabetes Study (MCDS) and the San Antonio Heart Study (SAHS). METHODS: Prospective cohorts conducted 1990-2007 in MCDS and 1979-2000 in SAHS. Mortality risk was examined using Cox proportional hazard models in 1402 non-Hispanic whites (NHW), 1907 U.S.-born Mexican-Americans (MA), 444 Mexican-horn MA, and 2281 Mexico City residents (MCR) between the ages of 35-64. RESULTS: Age- and sex-adjusted mortality hazard ratios (FIR) comparing U.S.-born MA, Mexican-born MA, and MCR to NHW were 1.09(95% confidence interval [CI]: 0.86, 1.37), 1.23 (95% Cl: 0.86, 1.76), and 0.97 (95% Cl: 0.77, 1.23), respectively, in nondiabetic individuals; in contrast, mortality risk varied in diabetic individuals with respective HRs of 1.77 (95% Cl: 1.20, 2.61), 1.08 (95% Cl: 0.59, 1.97), and 2.27 (95% Cl: 1.53, 3.35) (interaction p = .0003). Excluding Mexican-born MA and nondiabetic individuals, controlling for medication use, insulin use, fasting glucose levels, and duration of diabetes explained a significant proportion of the mortality differential (HRs relative to NHW were 1.31 [95% Cl: 0.87, 1.981 in U.S.-born MA and 1.38(95% CI: 0.89, 2.121 in MCR). CONCLUSIONS: This study provides evidence that diabetes is more lethal in U.S.-born MA and MCR than in NHW. Ann Epidemiol 201121:899-906. (C) 2011 Elsevier Inc. All rights reserved. C1 [Hunt, Kelly J.] Med Univ S Carolina, Charleston, SC 29425 USA. [Hunt, Kelly J.] Ralph H Johnson Dept Vet Affairs Med Ctr, Ctr Dis Prevent & Hlth Intervent Diverse Populat, Charleston, SC USA. [Elena Gonzalez, Maria; Lopez, Ruy; Gonzalez-Villalpando, Clicerio] Unidad Invest Diabet, Mexico City, DF, Mexico. [Elena Gonzalez, Maria; Lopez, Ruy; Gonzalez-Villalpando, Clicerio] Riesgo Cardiovasc Inst Nacl Salud Publ, Mexico City, DF, Mexico. [Elena Gonzalez, Maria; Lopez, Ruy; Gonzalez-Villalpando, Clicerio] Ctr Estudios Diabet, Mexico City, DF, Mexico. [Haffner, Steve M.] Baylor Coll Med, Houston, TX 77030 USA. [Stern, Michael P.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. RP Hunt, KJ (reprint author), Med Univ S Carolina, 135 Cannon St,Suite 302,POB 250835, Charleston, SC 29425 USA. EM huntke@musc.edu FU Consejo Nacional de Ciencia y Tecnologia Apoyo [14502]; National Heart Lung and Blood Institute [R01-HL24799, R01-HL36820]; National Institute of Diabetes and Digestive and Kidney Diseases [K01-DK064867]; National Center on Minority Health and Health Disparities [R01-MD004251]; Office of Research and Development, Department of Veterans Affairs; Ralph H. Johnson VAMC; VA HSRD [IIR-06-219] FX This work was supported by grants from the Consejo Nacional de Ciencia y Tecnologia Apoyo (14502), the National Heart Lung and Blood Institute (R01-HL24799 and R01-HL36820), the National Institute of Diabetes and Digestive and Kidney Diseases (K01-DK064867), the National Center on Minority Health and Health Disparities (R01-MD004251), the Office of Research and Development, Department of Veterans Affairs, and the Ralph H. Johnson VAMC,. Further support was provided through VA HSR&D REAP Award (grant IIR-06-219). The funding agencies did not participate in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the U.S. Department of Veterans Affairs. NR 27 TC 8 Z9 9 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD DEC PY 2011 VL 21 IS 12 BP 899 EP 906 DI 10.1016/j.annepidem.2011.07.003 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 844NX UT WOS:000296755400005 PM 21840730 ER PT J AU Inslicht, SS Otte, C McCaslin, SE Apfel, BA Henn-Haase, C Metzler, T Yehuda, R Neylan, TC Marmar, CR AF Inslicht, Sabra S. Otte, Christian McCaslin, Shannon E. Apfel, Brigitte A. Henn-Haase, Clare Metzler, Thomas Yehuda, Rachel Neylan, Thomas C. Marmar, Charles R. TI Cortisol Awakening Response Prospectively Predicts Peritraumatic and Acute Stress Reactions in Police Officers SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Acute stress disorder; cortisol; peritraumatic dissociation; police stress; posttraumatic stress disorder ID VEHICLE ACCIDENT VICTIMS; POSTTRAUMATIC-STRESS; SALIVARY CORTISOL; SLEEP QUALITY; PTSD SYMPTOMS; PSYCHOMETRIC PROPERTIES; TRAUMA VICTIMS; HPA AXIS; DISORDER; ADULTS AB Background: The hypothalamic-pituitary-adrenal axis is a major stress response system hypothesized to be involved in the pathogenesis of posttraumatic stress disorder (PTSD). However, few studies have prospectively examined the relationships among pre-exposure hypothalamic-pituitary-adrenal activity, acute stress reactions and PTSD. Methods: Two hundred ninety-six police recruits were assessed during academy training before critical incident exposure and provided salivary cortisol at first awakening and after 30 minutes. A measure of cortisol awakening response (CAR) was computed as the change in cortisol level from the first to the second collection. At 12, 24, and 36 months following the start of active police service, officers were assessed for peritraumatic distress, peritraumatic dissociation, acute stress disorder (ASD) symptoms, and PTSD symptoms to their self-identified worst duty-related critical incident. Mixed models for repeated measures were used to analyze the effects of CAR on the outcome variables pooled across the three follow-up assessments. Results: After controlling for time of awakening, first awakening cortisol levels, and cumulative critical incident stress exposure, CAR during academy training was associated with greater peritraumatic dissociation, beta = .14, z = 3.49, p < .0001, and greater ASD symptoms during police service assessed at 12, 24, and 36 months, beta = .09, Z = 2.03, p < .05, but not with peritraumatic distress, beta = .03, z = .81, p = .42, or PTSD symptoms, beta = -.004, z = -.09, p = .93. Conclusions: These findings suggest that greater cortisol response to awakening is a pre-exposure risk factor for peritraumatic dissociation and ASD symptoms during police service. C1 [Inslicht, Sabra S.; McCaslin, Shannon E.; Apfel, Brigitte A.; Metzler, Thomas; Neylan, Thomas C.] San Francisco VA Med Ctr, PTSD Res Program, San Francisco, CA USA. [Inslicht, Sabra S.; McCaslin, Shannon E.; Apfel, Brigitte A.; Neylan, Thomas C.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Metzler, Thomas] No Calif Inst Res & Educ, San Francisco, CA USA. [Otte, Christian] Charite, Dept Psychiat & Psychotherapy, Ctr Berlin, D-13353 Berlin, Germany. [Henn-Haase, Clare; Marmar, Charles R.] NYU, Sch Med, Dept Psychiat, New York, NY USA. [Yehuda, Rachel] Mt Sinai Sch Med, Traumat Stress Div, Bronx, NY USA. James J Peters Vet Affairs Med Ctr, Bronx, NY USA. RP Inslicht, SS (reprint author), Vet Affairs Med Ctr, PTSD Res Program, 4150 Clement St,116P, San Francisco, CA 94121 USA. EM Sabra.Inslicht@ucsf.edu FU National Institute of Mental Health [R01 - MH056350-06]; Veterans Affairs Clinical Science Research and Development [CDA-2-037-07F, CDA-2-032-06F] FX This research was supported by National Institute of Mental Health Grant (R01 - MH056350-06) to CRM. SSI and SEM were supported by Veterans Affairs Clinical Science Research and Development, Career Development Awards (CDA-2-037-07F and CDA-2-032-06F, respectively). NR 67 TC 20 Z9 21 U1 1 U2 21 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD DEC 1 PY 2011 VL 70 IS 11 BP 1055 EP 1062 DI 10.1016/j.biopsych.2011.06.030 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 842FL UT WOS:000296578800010 PM 21906725 ER PT J AU Schulz-Heik, RJ Schaer, M Eliez, S Hallmayer, JF Lin, XY Kaloupek, DG Woodward, SH AF Schulz-Heik, R. Jay Schaer, Marie Eliez, Stephan Hallmayer, Joachim F. Lin, Xiaoyan Kaloupek, Danny G. Woodward, Steven H. TI Catechol-O-Methyltransferase Val158Met Polymorphism Moderates Anterior Cingulate Volume in Posttraumatic Stress Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Anterior cingulate cortex; catechol-o-methyltransferase; genetics; neuroimaging; posttraumatic stress disorder; Val158Met ID MEDIAL PREFRONTAL CORTEX; HUMAN CEREBRAL-CORTEX; CORTICAL THICKNESS; GENETIC-VARIATION; DOPAMINE RELEASE; HUMAN BRAIN; PTSD; COMT; RELIABILITY; EXPOSURE AB Background: Posttraumatic stress disorder (PTSD) is associated with structural and functional compromise of the anterior cingulate cortex (ACC), which may in turn be associated with impairment of its ability to regulate the amygdala. The Val158Met polymorphism in the catechol-O-methyltransferase gene, which substantially influences dopamine inactivation in the frontal lobe in general and in ACC in particular, may moderate ACC integrity in PTSD. Methods: Wetested this hypothesis in a sample of Vietnam and Persian Gulf War veterans who experienced substantial military operational stress, including 51 who met criteria for PTSD and 48 matched controls who did not. Results: Participants with PTSD were previously reported to have smaller ACC volumes than controls in this sample. A novel repeated measures analysis of variance was conducted with PTSD diagnosis, Val158Met genotype, and their interaction predicting left and right ACC volume. Genotype was not directly related to ACC volume, but it did significantly interact with the PTSD diagnosis. The difference in ACC volume between the participants without PTSD and participants with PTSD was greater among individuals homozygous for the Val allele than among carriers of the Met allele. This finding was driven largely by the right ACC. Analyses of Caucasian-only, non-Caucasian-only, and male-only subsamples indicated similar patterns. Conclusions: Our findings suggest Val158Met genotype moderates the effect of PTSD-related processes on right ACC volume. C1 [Schulz-Heik, R. Jay] Vet Affairs Palo Alto Hlth Care Syst, Psychol Serv 116B, Natl Ctr PTSD, Palo Alto, CA 94304 USA. [Schaer, Marie; Eliez, Stephan] Univ Geneva, Sch Med, Dept Psychiat, Off Med Pedag, CH-1211 Geneva, Switzerland. [Hallmayer, Joachim F.; Lin, Xiaoyan] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Kaloupek, Danny G.] Vet Affairs Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. RP Schulz-Heik, RJ (reprint author), Vet Affairs Palo Alto Hlth Care Syst, Psychol Serv 116B, Natl Ctr PTSD, 3801 Miranda Ave, Palo Alto, CA 94304 USA. EM jay.schulz-heik@va.gov RI Schueter, nicos/A-3625-2014; OI Kaloupek, Danny/0000-0002-0795-593X FU Veterans Affairs/Department of Defense FX We thank Christelle Martinez, M.A., Wendy K. Stegman, B.A., Catherine J. Kutter, Ph.D., Lorraine P. Stewart, M.A., Rebecca S. Prestel, B.A., and Ned J. Arsenault, B.A., for their technical assistance and also Rachel Kimerling, Ph.D., for her financial support for genotyping participants. Major funding for this work was provided under a Veterans Affairs/Department of Defense assistance agreement to Drs. Woodward and Kaloupek from the U.S. Army Medical Research and Materiel Command (Department of Defense) administered through the Institute for Medical Research (Veterans Affairs). NR 57 TC 12 Z9 12 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD DEC 1 PY 2011 VL 70 IS 11 BP 1091 EP 1096 DI 10.1016/j.biopsych.2011.06.012 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 842FL UT WOS:000296578800014 PM 21783175 ER PT J AU Nguyen, AD Pelavin, PE Shenton, ME Chilakamarri, P McCarley, RW Nestor, PG Levitt, JJ AF Nguyen, An D. Pelavin, Paula E. Shenton, Martha E. Chilakamarri, Priyanka McCarley, Robert W. Nestor, Paul G. Levitt, James J. TI Olfactory sulcal depth and olfactory bulb volume in patients with schizophrenia: an MRI study SO BRAIN IMAGING AND BEHAVIOR LA English DT Article DE Olfactory sulcus; Olfactory bulb; Schizophrenia; Smell identification; Olfaction; Neuroimaging ID NEUROLEPTIC-NAIVE PATIENTS; IDENTIFICATION ABILITY; DEFICITS; DYSFUNCTION; IMPAIRMENT; DEPRESSION; UNPLEASANT; DISORDERS; RELATIVES; PLEASANT AB The current report used structural magnetic resonance imaging (MRI) to objectively measure olfactory bulb volume and olfactory sulcal depth in patients diagnosed with chronic schizophrenia and healthy controls. Additional measures were obtained to assess olfactory function. The olfactory bulb and sulcus were manually traced on structural 3T MRIs for 25 right-handed male patients diagnosed with chronic schizophrenia and 25 matched male healthy controls. A sub-set of subjects received the University of Pennsylvania Smell Identification Test (UPSIT). Olfactory bulb volume was significantly decreased in patients with schizophrenia compared to healthy controls, as was their performance on the UPSIT. Additionally, a positive correlation was seen in patients between right bulb volume and UPSIT scores. Overall, our findings support earlier research studies showing morphometric and functional changes in the olfactory system in patients with schizophrenia. C1 [Nguyen, An D.; Shenton, Martha E.; McCarley, Robert W.; Levitt, James J.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Dept Psychiat, Brockton, MA 02301 USA. [Nguyen, An D.; Pelavin, Paula E.; Shenton, Martha E.; Chilakamarri, Priyanka; McCarley, Robert W.; Nestor, Paul G.; Levitt, James J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Psychiat Neuroimaging Lab,Dept Psychiat, Boston, MA 02115 USA. RP Levitt, JJ (reprint author), Harvard Univ, Sch Med, VA Boston Healthcare Syst, Dept Psychiat, Brockton Campus,116A4,940 Belmont St, Brockton, MA 02301 USA. EM james_levitt@hms.harvard.edu RI McCarley, Robert/N-5562-2014 OI McCarley, Robert/0000-0001-5705-7495 FU VA Merit Awards; VA Schizophrenia Center; National Institute of Mental Health [MH 070047, MH 50740]; NIH Mental Health Center for Clinical Interventional Development and Applied Research [P50 11P50 MH 080272] FX This work was supported in part by VA Merit Awards (JJL, MES, RWM), by a VA Schizophrenia Center Grant (RWM, MES), by a K05 Award supported by the National Institute of Mental Health (MH 070047 to MES), by an R01 Award supported by the National Institute of Mental Health (MH 50740 to MES), and by support from an NIH Mental Health Center for Clinical Interventional Development and Applied Research (P50 11P50 MH 080272; RWM, MES). NR 55 TC 20 Z9 22 U1 2 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1931-7557 J9 BRAIN IMAGING BEHAV JI Brain Imaging Behav. PD DEC PY 2011 VL 5 IS 4 BP 252 EP 261 DI 10.1007/s11682-011-9129-0 PG 10 WC Neuroimaging SC Neurosciences & Neurology GA 842XQ UT WOS:000296635600002 PM 21728040 ER PT J AU Horowitz, NS AF Horowitz, Neil S. TI Management of Adnexal Masses in Pregnancy SO CLINICAL OBSTETRICS AND GYNECOLOGY LA English DT Article DE adnexal mass; pregnancy; surgical management ID OVARIAN-TUMORS; LAPAROSCOPIC MANAGEMENT; CHEMOTHERAPY; PACLITAXEL; CARCINOMA; DIAGNOSIS; CANCER; 2ND AB The identification of a pelvic mass during pregnancy can often change a time of happiness and exciting anticipation to 1 of anxiety and fearful unknown. Although diagnosed more commonly with the implementation of ultrasonography as part of routine prenatal care, discovering an adnexal mass during pregnancy remains a rare event. Fortunately, the majority of masses are benign and rarely negatively impact pregnancy outcomes; however, no specific protocols exist for the appropriate management of these women. This study will review the most current incidence, management, and outcomes for women diagnosed with an adnexal mass during pregnancy. C1 Brigham & Womens Hosp, Div Gynecol Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Horowitz, NS (reprint author), Brigham & Womens Hosp, Div Gynecol Oncol, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. EM nhorowitz@partners.org NR 31 TC 6 Z9 6 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-9201 J9 CLIN OBSTET GYNECOL JI Clin. Obstet. Gynecol. PD DEC PY 2011 VL 54 IS 4 BP 519 EP 527 DI 10.1097/GRF.0b013e318236c583 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 842FO UT WOS:000296579300002 PM 22031242 ER PT J AU Ritholz, MD Beverly, EA Weinger, K AF Ritholz, Marilyn D. Beverly, Elizabeth A. Weinger, Katie TI Digging Deeper: The Role of Qualitative Research in Behavioral Diabetes SO CURRENT DIABETES REPORTS LA English DT Article DE Qualitative research; Qualitative methodology; Behavioral diabetes; Type 1 diabetes; Type 2 diabetes; Psychosocial experiences ID AFRICAN-AMERICAN WOMEN; SELF-MANAGEMENT; OLDER-ADULTS; PATIENTS PERSPECTIVES; PSYCHOSOCIAL FACTORS; INSULIN PUMP; OF-LIFE; TYPE-2; PERCEPTIONS; PARENTS AB Qualitative research methodology is more recognized and valued in diabetes behavioral research in recent years. Qualitative methods help clinicians answer questions that quantitative research may not be able to answer, such as exploring patients' motivations, perceptions, and expectations. This paper reviews recent (2005-present) rigorous qualitative studies of children, adolescents, and adult patients with type 1 and type 2 diabetes with the aim of answering the following research question: How has qualitative research contributed to our understanding of behavioral diabetes care? We focus on studies exploring patients', health care providers', and families' interpersonal experiences of diabetes as well as patients' psychosocial experiences of diagnosis and treatment, self-care, complications, and cultural factors. After reviewing the research in each area, we conclude by discussing how qualitative research contributes to our increased understanding of behavioral diabetes. C1 [Ritholz, Marilyn D.] Joslin Diabet Ctr, MH Unit, Boston, MA 02115 USA. [Ritholz, Marilyn D.; Beverly, Elizabeth A.; Weinger, Katie] Harvard Univ, Sch Med, Boston, MA USA. [Ritholz, Marilyn D.] Childrens Hosp, Boston, MA 02115 USA. RP Ritholz, MD (reprint author), Joslin Diabet Ctr, MH Unit, Off 212,1 Joslin Pl, Boston, MA 02115 USA. EM marilyn.ritholz@joslin.harvard.edu; elizabeth.beverly@joslin.harvard.edu; katie.weinger@joslin.harvard.edu NR 75 TC 12 Z9 14 U1 1 U2 13 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1534-4827 J9 CURR DIABETES REP JI Curr. Diabetes Rep. PD DEC PY 2011 VL 11 IS 6 BP 494 EP 502 DI 10.1007/s11892-011-0226-7 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 841LA UT WOS:000296512600007 PM 21932032 ER EF