FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Jung-Hynes, B Nihal, M Zhong, WX Ahmad, N AF Jung-Hynes, Brittney Nihal, Minakshi Zhong, Weixiong Ahmad, Nihal TI Role of Sirtuin Histone Deacetylase SIRT1 in Prostate Cancer A TARGET FOR PROSTATE CANCER MANAGEMENT VIA ITS INHIBITION? SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FORKHEAD TRANSCRIPTION FACTOR; PROMOTES CELL-SURVIVAL; ANDROGEN RECEPTOR; LIFE-SPAN; FOXO; EXPRESSION; GROWTH; P53; LONGEVITY; DISEASE AB Prostate cancer (PCa) is a major age-related malignancy, and according to estimates from the American Cancer Society, a man's chance of developing this cancer significantly increases with increasing age, from 1 in 10,149 by age 39 to 1 in 38 by age 59 to 1 in 7 by age 70. Therefore, it is important to identify the causal connection between mechanisms of aging and PCa. Employing in vitro and in vivo approaches, in this study, we tested the hypothesis that SIRT1, which belongs to the Sir2 (silent information regulator 2) family of sirtuin class III histone deacetylases, is overexpressed in PCa, and its inhibition will have antiproliferative effects in human PCa cells. Our data demonstrated that SIRT1 was significantly overexpressed in human PCa cells (DU145, LNCaP, 22Rv1, and PC3) compared with normal prostate epithelial cells (PrEC) at protein, mRNA, and enzymatic activity levels. SIRT1 was also found to be overexpressed in human PCa tissues compared with adjacent normal prostate tissue. Interestingly, our data demonstrated that SIRT1 inhibition via nicotinamide and sirtinol (at the activity level) as well as via short hairpin RNA-mediated RNA interference (at the genetic level) resulted in a significant inhibition in the growth and viability of human PCa cells while having no effect on normal prostate epithelial cells. Further, we found that inhibition of SIRT1 caused an increase in FOXO1 acetylation and transcriptional activation in PCa cells. Our data suggested that SIRT1, via inhibiting FOXO1 activation, could contribute to the development of PCa. We suggest that SIRT1 could serve as a target toward developing novel strategies for PCa management. C1 [Ahmad, Nihal] Univ Wisconsin, Med Sci Ctr, Dept Dermatol, Madison, WI 53706 USA. [Jung-Hynes, Brittney; Ahmad, Nihal] Univ Wisconsin, Mol & Environm Toxicol Ctr, Madison, WI 53706 USA. [Nihal, Minakshi; Zhong, Weixiong] Univ Wisconsin, William S Middleton Mem Vet Hosp, Madison, WI 53706 USA. [Zhong, Weixiong] Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53706 USA. [Zhong, Weixiong; Ahmad, Nihal] Univ Wisconsin, Ctr Comprehens Canc, Madison, WI 53706 USA. RP Ahmad, N (reprint author), Univ Wisconsin, Med Sci Ctr, Dept Dermatol, 1300 Univ Ave, Madison, WI 53706 USA. EM nahmad@wisc.edu FU National Institutes of Health; NIEHS; Molecular and Environmental Toxicology Center Training [T32ES007015] FX This work was supported, in whole or in part, by National Institutes of Health, NIEHS, Molecular and Environmental Toxicology Center Training Grant T32ES007015 (predoctoral traineeship to B.J.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. NR 62 TC 91 Z9 97 U1 1 U2 12 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 6 PY 2009 VL 284 IS 6 BP 3823 EP 3832 DI 10.1074/jbc.M807869200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 400MO UT WOS:000262872500051 PM 19075016 ER PT J AU Luo, BH Karanicolas, J Harmacek, LD Baker, D Springer, TA AF Luo, Bing-Hao Karanicolas, John Harmacek, Laura D. Baker, David Springer, Timothy A. TI Rationally Designed Integrin beta 3 Mutants Stabilized in the High Affinity Conformation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MURINE MONOCLONAL-ANTIBODY; CD11B A-DOMAIN; CRYSTAL-STRUCTURE; STRUCTURAL BASIS; I-DOMAIN; EXTRACELLULAR SEGMENT; GLYCOPROTEIN-IIIA; HYBRID DOMAIN; OUTSIDE-IN; PROTEIN AB Integrins are important cell surface receptors that transmit bidirectional signals across the membrane. It has been shown that a conformational change of the integrin beta-subunit head-piece (i.e. the beta I domain and the hybrid domain) plays a critical role in regulating integrin ligand binding affinity and function. Previous studies have used coarse methods (a glycan wedge, mutations in transmembrane contacts) to force the beta-subunit into either the open or closed conformation. Here, we demonstrate a detailed understanding of this conformational change by applying computational design techniques to select five amino acid side chains that play an important role in the energetic balance between the open and closed conformations of alpha(IIb)beta(3). Eight single-point mutants were designed at these sites, of which five bound ligands much better than wild type. Further, these mutants were found to be in a more extended conformation than wild type, suggesting that the conformational change at the ligand binding headpiece was propagated to the legs of the integrin. This detailed understanding of the conformational change will assist in the development of allosteric drugs that either stabilize or destabilize specific integrin conformations without occluding the ligand-binding site. C1 [Luo, Bing-Hao; Harmacek, Laura D.; Springer, Timothy A.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Luo, Bing-Hao; Harmacek, Laura D.; Springer, Timothy A.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Luo, Bing-Hao] Louisiana State Univ, Dept Biol Sci, Baton Rouge, LA 70803 USA. [Karanicolas, John; Baker, David] Univ Washington, Dept Biochem, Seattle, WA 98195 USA. [Karanicolas, John; Baker, David] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA. RP Springer, TA (reprint author), Harvard Univ, Sch Med, Immune Dis Inst, 200 Longwood Ave, Boston, MA 02115 USA. EM SpringerOffice@idi.harvard.edu RI Baker, David/K-8941-2012 OI Baker, David/0000-0001-7896-6217 FU National Institutes of Health [HL48675] FX This work was supported, in whole or in part, by National Institutes of Health Grant HL48675 (to T.A.S.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. NR 37 TC 24 Z9 25 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 6 PY 2009 VL 284 IS 6 BP 3917 EP 3924 DI 10.1074/jbc.M806312200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 400MO UT WOS:000262872500060 PM 19019827 ER PT J AU Offner, H Vandenbark, AA Hurn, PD AF Offner, H. Vandenbark, A. A. Hurn, P. D. TI EFFECT OF EXPERIMENTAL STROKE ON PERIPHERAL IMMUNITY: CNS ISCHEMIA INDUCES PROFOUND IMMUNOSUPPRESSION SO NEUROSCIENCE LA English DT Review DE stroke; spleen; Treg cells; macrophages; immunosuppression ID REGULATORY T-CELLS; FOCAL CEREBRAL-ISCHEMIA; CENTRAL-NERVOUS-SYSTEM; MONOCYTE CHEMOATTRACTANT PROTEIN-1; INTERFERON-INDUCIBLE PROTEIN-10; CHEMOKINE RECEPTOR ANTAGONIST; MESSENGER-RNA EXPRESSION; INDUCED IMMUNODEPRESSION; TRANSCRIPTION FACTOR; LYMPHOCYTE SUBSETS AB The profound damage to the CNS caused by ischemic lesions has been well documented. Yet, relatively little is known about the contribution to and effects on the immune system during stroke. We have focused on both early and late events in the peripheral immune system during stroke in mice and have observed an early activation of splenocytes that conceivably could result in immune-mediated damage in the developing CNS lesion, followed by global immunosuppression that affects the spleen, thymus, lymph nodes and circulation. While this second immunosuppressive phase may not directly enhance infarction size, it without doubt leads to an inability to respond to antigenic challenges, thereby enhancing the risk for crippling systemic infection and septicemia in stroke survivors. These novel findings advocate the need to develop or effectively utilize agents that can block early neural splenic activation and modulate immune cells specific for brain antigens as a means to prevent mobilization of T and B cells carrying a cytokine death warrant to the brain. Equally important for the recovering stroke patient are approaches that can derail the second phase of immune dysfunction and restore the ability to mount a defense against systemic infectious insults. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved. C1 [Offner, H.; Vandenbark, A. A.] Portland VA Med Ctr, Portland, OR 97239 USA. [Offner, H.; Vandenbark, A. A.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Offner, H.; Hurn, P. D.] Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97239 USA. [Vandenbark, A. A.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97239 USA. RP Offner, H (reprint author), Portland VA Med Ctr, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM offnerva@ohsu.edu FU US Public Health Service NIH [NS33668, NR03521, NS49210, RR00163]; Biomedical Laboratoty R&D Service, Department of Veterans Affairs FX The authors wish to thank Ms. Eva Niehaus for assistance in preparing and submitting the manuscript and Dr. Wenri Zhang and Ms. Susan Parker for the preparation of cerebral blood flow autoradiography in the SCID mice. This work was supported by US Public Health Service NIH grants NS33668, NR03521, NS49210, RR00163, and the Biomedical Laboratoty R&D Service, Department of Veterans Affairs. NR 62 TC 101 Z9 110 U1 1 U2 10 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 FEB 6 PY 2009 VL 158 IS 3 BP 1098 EP 1111 DI 10.1016/j.neuroscience.2008.05.033 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 409TW UT WOS:000263529700013 PM 18597949 ER PT J AU Wang, ZX Chen, F Zhai, RH Zhang, LS Su, L Lin, XH Thompson, T Christiani, DC AF Wang, Zhaoxi Chen, Feng Zhai, Rihong Zhang, Lingsong Su, Li Lin, Xihong Thompson, Taylor Christiani, David C. TI Plasma Neutrophil Elastase and Elafin Imbalance Is Associated with Acute Respiratory Distress Syndrome (ARDS) Development SO PLOS ONE LA English DT Article AB Background: We conducted an exploratory study of genome-wide gene expression in whole blood and found that the expression of neutrophil elastase inhibitor (PI3, elafin) was down-regulated during the early phase of ARDS. Further analyses of plasma PI3 levels revealed a rapid decrease during early ARDS development. PI3 and secretory leukocyte proteinase inhibitor (SLPI) are important low-molecular-weight proteinase inhibitors produced locally at neutrophil infiltration site in the lung. In this study, we tested the hypothesis that an imbalance between neutrophil elastase (HNE) and its inhibitors in blood is related to the development of ARDS. Methodology/Principal Findings: PI3, SLPI, and HNE were measured in plasma samples collected from 148 ARDS patients and 63 critical ill patients at risk for ARDS (controls). Compared with the controls, the ARDS patients had higher HNE, but lower PI3, at the onset of ARDS, resulting in increased HNE/PI3 ratio (mean = 14.5; 95% CI, 10.9-19.4, P<0.0001), whereas plasma SLPI was not associated with the risk of ARDS development. Although the controls had elevated plasma PI3 and HNE, their HNE/PI3 ratio (mean = 6.5; 95% CI, 4.9-8.8) was not significantly different from the healthy individuals (mean = 3.9; 95% CI, 2.7-5.9). Before the onset (7-days period prior to ARDS diagnosis), we only observed significantly elevated HNE, but the HNE-PI3 balance remained normal. With the progress from prior to the onset of ARDS, the plasma level of PI3 declined, whereas HNE was maintained at a higher level, tilting the balance toward more HNE in the circulation as characterized by an increased HNE/PI3 ratio. In contrast, three days after ICU admission, there was a significant drop of HNE/PI3 ratio in the at-risk controls. Conclusions/Significance: Plasma profiles of PI3, HNE, and HNE/PI3 may be useful clinical biomarkers in monitoring the development of ARDS. C1 [Wang, Zhaoxi; Chen, Feng; Zhai, Rihong; Su, Li; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Zhang, Lingsong; Lin, Xihong] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Thompson, Taylor; Christiani, David C.] Massachusetts Gen Hosp, Pulmon & Critical Care Unit, Boston, MA 02114 USA. [Christiani, David C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Wang, ZX (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. EM mikewang@hsph.harvard.edu FU National Institute of Health [HL60710, ES00002] FX This study was supported by grants from National Institute of Health (HL60710, ES00002). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 37 TC 24 Z9 31 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD FEB 6 PY 2009 VL 4 IS 2 AR e4380 DI 10.1371/journal.pone.0004380 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 437JM UT WOS:000265483700005 PM 19197381 ER PT J AU Yang, JJ Cohen, A Hersh, W AF Yang, Jianji Cohen, Aaron Hersh, William TI Evaluation of a gene information summarization system by users during the analysis process of microarray datasets SO BMC BIOINFORMATICS LA English DT Article CT 1st Summit on Translational Bioinformatics CY MAR 10-12, 2008 CL San Francisco, CA SP Amer Med Informat Assoc, Int Soc Computat Biol ID BIOMEDICAL LITERATURE AB Background: Summarization of gene information in the literature has the potential to help genomics researchers translate basic research into clinical benefits. Gene expression microarrays have been used to study biomarkers for disease and discover novel types of therapeutics and the task of finding information in journal articles on sets of genes is common for translational researchers working with microarray data. However, manually searching and scanning the literature references returned from PubMed is a time-consuming task for scientists. We built and evaluated an automatic summarizer of information on genes studied in microarray experiments. The Gene Information Clustering and Summarization System (GICSS) is a system that integrates two related steps of the microarray data analysis process: functional gene clustering and gene information gathering. The system evaluation was conducted during the process of genomic researchers analyzing their own experimental microarray datasets. Results: The clusters generated by GICSS were validated by scientists during their microarray analysis process. In addition, presenting sentences in the abstract provided significantly more important information to the users than just showing the title in the default PubMed format. Conclusion: The evaluation results suggest that GICSS can be useful for researchers in genomic area. In addition, the hybrid evaluation method, partway between intrinsic and extrinsic system evaluation, may enable researchers to gauge the true usefulness of the tool for the scientists in their natural analysis workflow and also elicit suggestions for future enhancements. Availability: GICSS can be accessed online at: http://ir.ohsu.edu/jianji/index.html C1 [Yang, Jianji; Cohen, Aaron; Hersh, William] Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Portland, OR 97239 USA. [Yang, Jianji] Portland VA Med Ctr, Portland Ctr Evaluat Clin Serv, Portland, OR 97239 USA. RP Yang, JJ (reprint author), Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Portland, OR 97239 USA. EM jianji.yang2@va.gov; cohenaa@ohsu.edu; hersh@ohsu.edu OI Hersh, William/0000-0002-4114-5148 FU NLM NIH HHS [1T15 LM009461] NR 17 TC 3 Z9 3 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD FEB 5 PY 2009 VL 10 AR S5 DI 10.1186/1471-2105-10-S2-S5 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 439BS UT WOS:000265602500006 PM 19208193 ER PT J AU de Leon, DC Perez-Montiel, D Villavicencio, V Carranca, AG Betancourt, AM Acuna-Alonzo, V Lopez-Tello, A Vargas-Alarcon, G Barquera, R Yu, N Yunis, EJ Granados, J AF Cantu de Leon, David Perez-Montiel, Delia Villavicencio, Veronica Garcia Carranca, Alejandro Mohar Betancourt, Alejandro Acuna-Alonzo, Victor Lopez-Tello, Alberto Vargas-Alarcon, Gilberto Barquera, Rodrigo Yu, Neng Yunis, Edmond J. Granados, Julio TI High resolution human leukocyte antigen (HLA) class I and class II allele typing in Mexican mestizo women with sporadic breast cancer: case-control study SO BMC CANCER LA English DT Article ID RISK-FACTORS; UNITED-STATES; EXPRESSION; CARCINOMA; TUMOR; SUSCEPTIBILITY; ASSOCIATION; PROGNOSIS; DISEASE; CELLS AB Background: The development of breast cancer is multifactorial. Hormonal, environmental factors and genetic predisposition, among others, could interact in the presentation of breast carcinoma. Human leukocyte antigen (HLA) alleles play an important role in immunity (cellular immunity) and may be important genetic traits. HLAAllele-specific interaction has not been well established. Recently, several studies had been conducted in order to do so, but the results are controversial and in some instances contradictory. Methods: We designed a case-control study to quantify the association of HLA class I and II genes and breast cancer. HLA typing was performed by high resolution sequence-specific oligotyping after DNA amplification (PCR-SSOP) of 100 breast cancer Mexican mestizo patients and 99 matched healthy controls. Results: HLA-A frequencies that we were able to observe that there was no difference between both groups from the statistical viewpoint. HLA-B*1501 was found three times more common in the case group (OR, 3.714; p = 0.031). HLA-Cw is not a marker neither for risk, nor protection for the disease, because we did not find significant statistical differences between the two groups. DRB1*1301, which is expressed in seven cases and in only one control, observing an risk increase of up to seven times and DRB1*1602, which behaves similarly in being present solely in the cases (OR, 16.701; 95% CI, 0.947-294.670). DQ*0301-allele expression, which is much more common in the control group and could be protective for the presentation of the disease (OR, 0.078; 95% CI, 0.027-0.223, p = 0.00001). Conclusion: Our results reveal the role of the MHC genes in the pathophysiology of breast cancer, suggesting that in the development of breast cancer exists a disorder of immune regulation. The triggering factor seems to be restricted to certain ethnic groups and certain geographical regions since the relevant MHC alleles are highly diverse. This is the first study in Mexican population where high resolutions HLA typing has been performed in order to try to establish an association with malignancy. C1 [Cantu de Leon, David] Inst Nacl Cancerol Mexico, Dept Gynecol Oncol, Mexico City, DF, Mexico. [Perez-Montiel, Delia] Inst Nacl Cancerol, Dept Pathol, Mexico City, DF, Mexico. [Villavicencio, Veronica] Inst Nacl Cancerol, Div Surg, Mexico City, DF, Mexico. [Garcia Carranca, Alejandro] Univ Nacl Autonoma Mexico, Inst Invest Biomed, Lab Virus & Canc, Mexico City 04510, DF, Mexico. [Mohar Betancourt, Alejandro] Inst Nacl Cancerol, Unidad Invest Biomed, Mexico City, DF, Mexico. [Acuna-Alonzo, Victor; Barquera, Rodrigo] ENAH, Mol Genet Lab, Mexico City, DF, Mexico. [Lopez-Tello, Alberto; Granados, Julio] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Immunol & Rheumatol, Mexico City, DF, Mexico. [Vargas-Alarcon, Gilberto] Inst Nacl Cardiol Ignacio Chavez, Dept Physiol, Mexico City, DF, Mexico. [Yu, Neng] Amer Red Cross Blood Serv, Dedham, MA USA. [Yunis, Edmond J.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP de Leon, DC (reprint author), Inst Nacl Cancerol Mexico, Dept Gynecol Oncol, Mexico City, DF, Mexico. EM dcantude@yahoo.com; madeliapmg@hotmail.com; verovilla67@hotmail.com; carranca@biomedicas.unam.mx; amohar@incan.edu.mx; acunaav@gmail.com; lopeztelloa@gmeil.com; gvargas63@yahoo.com; jrockdrigo@excite.com; yun@usa.redcross.org; Edmond_Yunis@dfci.harvard.edu; julgrate@yahoo.com RI Acuna Alonzo, Victor/E-2312-2013 OI Acuna Alonzo, Victor/0000-0003-2205-7625 NR 36 TC 7 Z9 7 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD FEB 5 PY 2009 VL 9 AR 48 DI 10.1186/1471-2407-9-48 PG 9 WC Oncology SC Oncology GA 417HH UT WOS:000264066600001 ER PT J AU Mayer, RJ AF Mayer, Robert J. TI Targeted Therapy for Advanced Colorectal Cancer-More Is Not Always Better SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID CETUXIMAB C1 [Mayer, Robert J.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Mayer, RJ (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 10 TC 48 Z9 49 U1 0 U2 1 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 FEB 5 PY 2009 VL 360 IS 6 BP 623 EP 625 DI 10.1056/NEJMe0809343 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 402QS UT WOS:000263028800011 PM 19196680 ER PT J AU Wen, XH Shen, LX Brush, RS Michaud, N Al-Ubaidi, MR Gurevich, VV Hamm, HE Lem, J DiBenedetto, E Anderson, RE Makino, CL AF Wen, Xiao-Hong Shen, Lixin Brush, Richard S. Michaud, Norman Al-Ubaidi, Muayyad R. Gurevich, Vsevolod V. Hamm, Heidi E. Lem, Janis DiBenedetto, Emmanuele Anderson, Robert E. Makino, Clint L. TI Overexpression of Rhodopsin Alters the Structure and Photoresponse of Rod Photoreceptors SO BIOPHYSICAL JOURNAL LA English DT Article ID LEBER CONGENITAL AMAUROSIS; OUTER SEGMENT MEMBRANES; DEEP-SEA FISHES; RETINAL RODS; ELECTRON-MICROSCOPY; MOUSE RETINA; VERTEBRATE PHOTOTRANSDUCTION; VISUAL PIGMENTS; DISC MEMBRANES; KNOCKOUT MICE AB Rhodopsins are densely packed in rod outer-segment membranes to maximize photon absorption, but this arrangement interferes with transducin activation by restricting the mobility of both proteins. We attempted to explore this phenomenon in transgenic mice that overexpressed rhodopsin in their rods. Photon capture was improved, and, for a given number of photoisomerizations, bright-flash responses rose more gradually with a reduction in amplification-but not because rhodopsins were more tightly packed in the membrane. Instead, rods increased their outer-segment diameters, accommodating the extra rhodopsins without changing the rhodopsin packing density. Because the expression of other phototransduction proteins did not increase, transducin and its effector phosphodiesterase were distributed over a larger surface area. That feature, as well as an increase in cytosolic volume, was responsible for delaying the onset of the photoresponse and for attenuating its amplification. C1 [Wen, Xiao-Hong; Michaud, Norman; Makino, Clint L.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Wen, Xiao-Hong; Michaud, Norman; Makino, Clint L.] Harvard Univ, Sch Med, Boston, MA USA. [Shen, Lixin; Gurevich, Vsevolod V.; Hamm, Heidi E.] Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA. [Brush, Richard S.; Al-Ubaidi, Muayyad R.; Anderson, Robert E.] Univ Oklahoma, Hlth Sci Ctr, Dept Cell Biol, Oklahoma City, OK USA. [Brush, Richard S.; Al-Ubaidi, Muayyad R.; Anderson, Robert E.] Univ Oklahoma, Hlth Sci Ctr, Dept Ophthalmol, Oklahoma City, OK USA. [Lem, Janis] Tufts Univ, Sch Med, Dept Ophthalmol, Program Genet,Program Neurosci, Boston, MA 02111 USA. [Lem, Janis] Tufts Univ, Sch Med, Dept Ophthalmol, Program Cell Mol & Dev Biol, Boston, MA 02111 USA. [DiBenedetto, Emmanuele] Vanderbilt Univ, Dept Math, Nashville, TN USA. RP Wen, XH (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. EM wenx@meei.harvard.edu RI Gurevich, Vsevolod/A-3236-2008; Hamm, Heidi/G-2374-2014; OI Gurevich, Vsevolod/0000-0002-3950-5351; Hamm, Heidi/0000-0001-5437-5287; Makino, Clint/0000-0002-6005-9069 FU Lions of Massachusetts for the Massachusens Eye and Ear Infirmary; Tufts University School of Medicine; New England Eye Center at Tufts University School of Medicine; National Center for Research Resources; Presbyterian Health Foundation Research to Prevent Blindness; Foundation Fighting Blindness, Inc.; National Institutes of Health [GM068953]; National Eye Institute [EY011358, EY014104, EY12008, EY04149, EY00871, EY12190, EY14052, EY11500, EY006062] FX This research was supported by the Lions of Massachusetts for the Massachusens Eye and Ear Infirmary and for the Tufts University School of Medicine; a Research to Prevent Blindness Challenge Grant to the New England Eye Center at Tufts University School of Medicine; the National Center for Research Resources: the Presbyterian Health Foundation Research to Prevent Blindness; the Foundation Fighting Blindness, Inc.; the National Institutes of Health (GM068953); and the National Eye Institute (EY011358, EY014104, EY12008, EY04149, EY00871, EY12190, EY14052, EY11500 and EY006062). NR 65 TC 38 Z9 38 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB 4 PY 2009 VL 96 IS 3 BP 939 EP 950 DI 10.1016/j.bpj.2008.10.016 PG 12 WC Biophysics SC Biophysics GA 450CB UT WOS:000266377500016 PM 19186132 ER PT J AU Mick, E Wozniak, J Wilens, TE Biederman, J Faraone, SV AF Mick, Eric Wozniak, Janet Wilens, Timothy E. Biederman, Joseph Faraone, Stephen V. TI Family-based association study of the BDNF, COMT and serotonin transporter genes and DSM-IV bipolar-I disorder in children SO BMC PSYCHIATRY LA English DT Article ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; EARLY ADOLESCENT BIPOLARITY; GENOME-WIDE ASSOCIATION; POPULATION-ASCERTAINED SUBSAMPLES; SUBSTANCE USE DISORDERS; PILOT SWEDISH TWIN; LINKAGE DISEQUILIBRIUM; DOPAMINE TRANSPORTER; GLUTAMATE DECARBOXYLASES AB Background: Over the past decade pediatric bipolar disorder has gained recognition as a potentially more severe and heritable form of the disorder. In this report we test for association with genes coding brain-derived neurotrophic factor (BDNF), the serotonin transporter (SLC6A4), and catechol-O-methyltransferase (COMT). Methods: Bipolar-I affected offspring triads (N = 173) were drawn from 522 individuals with 2 parents in 332 nuclear families recruited for genetic studies of pediatric psychopathology at the Clinical and Research Program in Pediatric Psychopharmacology and Adult ADHD at Massachusetts General Hospital. Results: We failed to identify an association with the val66 allele in BDNF (OR = 1.23, p = 0.36), the COMT-I allele (OR = 1.27, p = 0.1), or the HTTLPR short allele (OR = 0.87, p = 0.38). Conclusion: Our study suggests that the markers examined thus far in COMT and SLC6A4 are not associated with pediatric bipolar disorder and that if the val66met marker in BDNF is associated with pediatric bipolar disorder the magnitude of the association is much smaller than first reported. C1 [Mick, Eric; Wozniak, Janet; Wilens, Timothy E.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Mick, Eric; Wozniak, Janet; Wilens, Timothy E.; Biederman, Joseph] Harvard Univ, Sch Med, Boston, MA USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY USA. RP Mick, E (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. EM mick@helix.mgh.harvard.edu; wozniak@helix.mgh.harvard.edu; twilens@partners.org; biederman@helix.mgh.harvard.edu; faraones@upstate.edu OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 FU NICHD NIH HHS [R01 HD036317, R01 HD037694, R01HD036317, R01HD37694]; NIDA NIH HHS [R01 DA012945, R01DA012945]; NIMH NIH HHS [R01 MH066877, K01 MH065523, K01MH065523, K08MH001503, R01 MH050657, R01 MH057934, R01 MH066237, R01MH050657, R01MH066237, R01MH066877, R01MH57934] NR 53 TC 13 Z9 13 U1 4 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-244X J9 BMC PSYCHIATRY JI BMC Psychiatry PD FEB 4 PY 2009 VL 9 AR 2 DI 10.1186/1471-244X-9-2 PG 6 WC Psychiatry SC Psychiatry GA 406BU UT WOS:000263270800001 PM 19193231 ER PT J AU Higgs, MH Spain, WJ AF Higgs, Matthew H. Spain, William J. TI Conditional Bursting Enhances Resonant Firing in Neocortical Layer 2-3 Pyramidal Neurons SO JOURNAL OF NEUROSCIENCE LA English DT Article DE burst; resonance; oscillator; frequency; cortex; pyramidal cell ID HIGH-FREQUENCY OSCILLATIONS; CAT SENSORIMOTOR CORTEX; WHITE-NOISE ANALYSIS; IN-VITRO; CORTICAL-NEURONS; SUBTHRESHOLD OSCILLATIONS; SYNAPTIC-TRANSMISSION; COINCIDENCE DETECTION; EXCITATORY NETWORKS; DYNAMIC PROPERTIES AB The frequency response properties of neurons are critical for signal transmission and control of network oscillations. At subthreshold membrane potential, some neurons show resonance caused by voltage-gated channels. During action potential firing, resonance of the spike output may arise from subthreshold mechanisms and/or spike-dependent currents that cause afterhyperpolarizations (AHPs) and afterdepolarizations (ADPs). Layer 2-3 pyramidal neurons (L2-3 PNs) have a fast ADP that can trigger bursts. The present study investigated what stimuli elicit bursting in these cells and whether bursts transmit specific frequency components of the synaptic input, leading to resonance at particular frequencies. We found that two-spike bursts are triggered by step onsets, sine waves in two frequency bands, and noise. Using noise adjusted to elicit firing at similar to 10 Hz, we measured the gain for modulation of the time-varying firing rate as a function of stimulus frequency, finding a primary peak (7-16 Hz) and a high-frequency resonance (250-450 Hz). Gain was also measured separately for single and burst spikes. For a given spike rate, bursts provided higher gain at the primary peak and lower gain at intermediate frequencies, sharpening the high-frequency resonance. Suppression of bursting using automated current feedback weakened the primary and high-frequency resonances. The primary resonance was also influenced by the SK channel-mediated medium AHP (mAHP), because the SK blocker apamin reduced the sharpness of the primary peak. Our results suggest that resonance in L2-3 PNs depends on burst firing and the mAHP. Bursting enhances resonance in two distinct frequency bands. C1 [Higgs, Matthew H.; Spain, William J.] Vet Affairs Puget Sound Hlth Care Syst, Neurol Sect, Seattle, WA 98018 USA. [Higgs, Matthew H.; Spain, William J.] Univ Washington, Dept Physiol & Biophys, Seattle, WA 98195 USA. [Spain, William J.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. RP Spain, WJ (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Neurol Sect, Mail Stop 127,1660 S Columbian Way, Seattle, WA 98018 USA. EM spain@u.washington.edu FU BLRD VA [I01 BX000386] NR 82 TC 39 Z9 40 U1 0 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD FEB 4 PY 2009 VL 29 IS 5 BP 1285 EP 1299 DI 10.1523/JNEUROSCI.3728-08.2009 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 403GZ UT WOS:000263072400005 PM 19193876 ER PT J AU Little, J Higgins, JPT Ioannidis, JPA Moher, D Gagnon, F von Elm, E Khoury, MJ Cohen, B Davey-Smith, G Grimshaw, J Scheet, P Gwinn, M Williamson, RE Zou, GY Hutchings, K Johnson, CY Tait, V Wiens, M Golding, J van Duijn, C McLaughlin, J Paterson, A Wells, G Fortier, I Freedman, M Zecevic, M King, R Infante-Rivard, C Stewart, AFR Birkett, N AF Little, Julian Higgins, Julian P. T. Ioannidis, John P. A. Moher, David Gagnon, France von Elm, Erik Khoury, Muin J. Cohen, Barbara Davey-Smith, George Grimshaw, Jeremy Scheet, Paul Gwinn, Marta Williamson, Robin E. Zou, Guang Yong Hutchings, Kim Johnson, Candice Y. Tait, Valerie Wiens, Miriam Golding, Jean van Duijn, Cornelia McLaughlin, John Paterson, Andrew Wells, George Fortier, Isabel Freedman, Matthew Zecevic, Maja King, Richard Infante-Rivard, Claire Stewart, Alex F. R. Birkett, Nick TI STrengthening the REporting of Genetic Association Studies (STREGA): An Extension of the STROBE Statement SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID GENOME-WIDE ASSOCIATION; HARDY-WEINBERG EQUILIBRIUM; SINGLE-NUCLEOTIDE POLYMORPHISMS; POPULATION STRATIFICATION; RANDOMIZED-TRIALS; DISEASE ASSOCIATIONS; GENOTYPING ERRORS; COMPLEX DISEASES; PROSTATE-CANCER; LINKAGE-DISEQUILIBRIUM AB Making sense of rapidly evolving evidence on genetic associations is crucial to making genuine advances in human genomics and the eventual integration of this information into the practice of medicine and public health. Assessment of the strengths and weaknesses of this evidence, and hence the ability to synthesize it, has been limited by inadequate reporting of results. The STrengthening the REporting of Genetic Association studies (STREGA) initiative builds on the STrengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement and provides additions to 12 of the 22 items on the STROBE checklist. The additions concern population stratification, genotyping errors, modeling haplotype variation, Hardy-Weinberg equilibrium, replication, selection of participants, rationale for choice of genes and variants, treatment effects in studying quantitative traits, statistical methods, relatedness, reporting of descriptive and outcome data, and issues of data volume that are important to consider in genetic association studies. The STREGA recommendations do not prescribe or dictate how a genetic association study should be designed but seek to enhance the transparency of its reporting, regardless of choices made during design, conduct, or analysis. C1 [Little, Julian] Univ Ottawa, Ottawa, ON K1H 8M5, Canada. Univ Toronto, Toronto, ON, Canada. Univ Western Ontario, London, ON, Canada. Robarts Res Inst, Toronto, ON, Canada. Canc Care Ontario, Toronto, ON, Canada. Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. McGill Univ, Montreal, PQ, Canada. Genome Quebec Innovat Ctr, Montreal, PQ, Canada. Tufts Univ, Sch Med, Boston, MA 02111 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Cell Press, Cambridge, MA USA. Lancet Publishing Grp, New York, NY USA. Amer Coll Med Genet, Bethesda, MD USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Univ Texas Houston, Houston, TX USA. MRC, Cambridge, England. Univ Bristol & Blackwell Publishing, Bristol, Avon, England. Springer Netherlands, Rotterdam, Netherlands. German Cochrane Ctr, Freiburg, Germany. Univ Bern, Bern, Switzerland. Univ Ioannina, Sch Med, GR-45110 Ioannina, Greece. RP Little, J (reprint author), Univ Ottawa, 451 Smyth Rd, Ottawa, ON K1H 8M5, Canada. EM jlittle@uottawa.ca RI Ioannidis, John/G-9836-2011; Higgins, Julian/H-4008-2011; McLaughlin, John/E-4577-2013; Paterson, Andrew/A-4088-2011; Davey Smith, George/A-7407-2013; OI Higgins, Julian/0000-0002-8323-2514; Paterson, Andrew/0000-0002-9169-118X; Davey Smith, George/0000-0002-1407-8314; von Elm, Erik/0000-0002-7412-0406; Stewart, Alexandre/0000-0003-2673-9164; Grimshaw, Jeremy/0000-0001-8015-8243; Moher , David /0000-0003-2434-4206 FU Institutes of Genetics and of Nutrition, Metabolism and Diabetes; Canadian Institutes of Health Research; Genome Canada; Biotechnology, Genomics and Population Health Branch, Public Health Agency of Canada; Affymetrix; DNA Genotek; TrialStat!; GeneSens FX Grant Support: By the Institutes of Genetics and of Nutrition, Metabolism and Diabetes, Canadian Institutes of Health Research; Genome Canada; Biotechnology, Genomics and Population Health Branch, Public Health Agency of Canada; Affymetrix; DNA Genotek; TrialStat!; and GeneSens. NR 154 TC 55 Z9 58 U1 1 U2 5 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD FEB 3 PY 2009 VL 150 IS 3 BP 206 EP + PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 402RA UT WOS:000263029600008 PM 19189911 ER PT J AU Krumholz, HM Ross, JS AF Krumholz, Harlan M. Ross, Joseph S. TI Relationships with the drug industry: More regulation, greater transparency SO BRITISH MEDICAL JOURNAL LA English DT Editorial Material C1 [Krumholz, Harlan M.] Yale Univ, Sch Med, Sect Cardiovasc Med, New Haven, CT 06520 USA. [Krumholz, Harlan M.] Yale Univ, Sch Med, Robert Wood Johnson Clin Scholars Program, Dept Med,Sect Hlth Policy & Adm,Sch Publ Hlth, New Haven, CT 06520 USA. [Krumholz, Harlan M.] Yale New Haven Med Ctr, Ctr Outcomes Res & Evaluat, New Haven, CT 06504 USA. [Ross, Joseph S.] Mt Sinai Sch Med, Dept Geriatr & Adult Dev, New York, NY USA. [Ross, Joseph S.] James J Peters VA Med Ctr, Bronx, NY USA. RP Krumholz, HM (reprint author), Yale Univ, Sch Med, Sect Cardiovasc Med, POB 208088, New Haven, CT 06520 USA. EM harlan.krumholz@yale.edu NR 7 TC 5 Z9 5 U1 1 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-8146 J9 BRIT MED J JI Br. Med. J. PD FEB 3 PY 2009 VL 338 AR b211 DI 10.1136/bmj.b211 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 414OX UT WOS:000263876200004 PM 19193612 ER PT J AU Benjamin, EJ Chen, PS Bild, DE Mascette, AM Albert, CM Alonso, A Calkins, H Connolly, SJ Curtis, AB Darbar, D Ellinor, PT Go, AS Goldschlager, NF Heckbert, SR Jalife, J Kerr, CR Levy, D Lloyd-Jones, DM Massie, BM Nattel, S Olgin, JE Packer, DL Po, SS Tsang, TSM Van Wagoner, DR Waldo, AL Wyse, DG AF Benjamin, Emelia J. Chen, Peng-Sheng Bild, Diane E. Mascette, Alice M. Albert, Christine M. Alonso, Alvaro Calkins, Hugh Connolly, Stuart J. Curtis, Anne B. Darbar, Dawood Ellinor, Patrick T. Go, Alan S. Goldschlager, Nora F. Heckbert, Susan R. Jalife, Jose Kerr, Charles R. Levy, Daniel Lloyd-Jones, Donald M. Massie, Barry M. Nattel, Stanley Olgin, Jeffrey E. Packer, Douglas L. Po, Sunny S. Tsang, Teresa S. M. Van Wagoner, David R. Waldo, Albert L. Wyse, D. George TI Prevention of Atrial Fibrillation Report From a National Heart, Lung, and Blood Institute Workshop SO CIRCULATION LA English DT Article DE atrial fibrillation; atrium; epidemiology; prevention; risk factors; National Heart, Lung and Blood Institute ID OF-FUNCTION MUTATION; PULMONARY VEINS; RISK-FACTORS; RHYTHM-CONTROL; FAMILIAL AGGREGATION; CARDIAC-ARRHYTHMIAS; CHANNEL MUTATIONS; RANDOMIZED-TRIAL; SECULAR TRENDS; LIFETIME RISK AB The National Heart, Lung, and Blood Institute convened an expert panel April 28 to 29, 2008, to identify gaps and recommend research strategies to prevent atrial fibrillation (AF). The panel reviewed the existing basic scientific, epidemiological, and clinical literature about AF and identified opportunities to advance AF prevention research. After discussion, the panel proposed the following recommendations: (1) enhance understanding of the epidemiology of AF in the population by systematically and longitudinally investigating symptomatic and asymptomatic AF in cohort studies; (2) improve detection of AF by evaluating the ability of existing and emerging methods and technologies to detect AF; (3) improve noninvasive modalities for identifying key components of cardiovascular remodeling that promote AF, including genetic, fibrotic, autonomic, structural, and electrical remodeling markers; (4) develop additional animal models reflective of the pathophysiology of human AF; (5) conduct secondary analyses of already-completed clinical trials to enhance knowledge of potentially effective methods to prevent AF and routinely include AF as an outcome in ongoing and future cardiovascular studies; and (6) conduct clinical studies focused on secondary prevention of AF recurrence, which would inform future primary prevention investigations. (Circulation. 2009; 119: 606-618.) C1 [Benjamin, Emelia J.; Levy, Daniel] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Boston, MA 02118 USA. [Chen, Peng-Sheng] Indiana Univ, Krannert Inst Cardiol, Indianapolis, IN 46204 USA. [Bild, Diane E.; Mascette, Alice M.] NHLBI, NIH, Bethesda, MD 20892 USA. [Albert, Christine M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Alonso, Alvaro] Univ Minnesota, Minneapolis, MN USA. [Calkins, Hugh] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Connolly, Stuart J.] McMaster Univ, Hamilton, ON, Canada. [Curtis, Anne B.] Univ S Florida, Tampa, FL USA. [Darbar, Dawood] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [Ellinor, Patrick T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Go, Alan S.] Kaiser Permanente No Calif, Oakland, CA USA. [Go, Alan S.; Goldschlager, Nora F.; Massie, Barry M.; Olgin, Jeffrey E.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Heckbert, Susan R.] Univ Washington, Seattle, WA 98195 USA. [Jalife, Jose] Univ Michigan, Ann Arbor, MI 48109 USA. [Kerr, Charles R.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Kerr, Charles R.] St Pauls Hosp, Vancouver, BC V6Z 1Y6, Canada. [Lloyd-Jones, Donald M.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Massie, Barry M.] San Francisco VA Med Ctr, San Francisco, CA USA. [Packer, Douglas L.; Tsang, Teresa S. M.] Mayo Clin Rochester, Rochester, MN USA. [Nattel, Stanley] Univ Montreal, Montreal, PQ, Canada. [Nattel, Stanley] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. [Po, Sunny S.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Van Wagoner, David R.] Cleveland Clin, Cleveland, OH 44106 USA. [Waldo, Albert L.] Case Western Reserve Univ, Univ Hosp Case Med Ctr, Cleveland, OH 44106 USA. [Wyse, D. George] Univ Calgary, Libin Cardiovasc Inst Alberta, Calgary, AB, Canada. RP Benjamin, EJ (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM emelia@bu.edu RI Lloyd-Jones, Donald/C-5899-2009; Van Wagoner, David/C-6783-2008; Alonso, Alvaro/A-4917-2010; Darbar, Dawood/C-9079-2015; Jalife, Jose/L-4833-2015; OI Van Wagoner, David/0000-0001-8250-9828; Alonso, Alvaro/0000-0002-2225-8323; Darbar, Dawood/0000-0002-4103-5977; Jalife, Jose/0000-0003-0080-3500; Benjamin, Emelia/0000-0003-4076-2336 FU NHGRI NIH HHS [U01 HG004402, U01 HG004402-01]; NHLBI NIH HHS [R01 HL070074-01, K23 HL075266, K23 HL075266-01A1, K23 HL075266-04, N01 HC055015, N01 HC055016, N01 HC055018, N01 HC055019, N01 HC055020, N01 HC055021, N01 HC055022, P01 HL039707, P01 HL039707-18, P01 HL087226, P01 HL087226-01, R01 HL059367, R01 HL059367-02, R01 HL068986, R01 HL068986-01A1, R01 HL070074, R01 HL071140, R01 HL071140-01, R01 HL075431, R01 HL075431-01A1, R01 HL076784, R01 HL076784-01, R01 HL078932, R01 HL078932-01, R01 HL085690, R01 HL085690-01A2, R01 HL086694, R01 HL086694-01A1, R01 HL087641, R01 HL087641-01, R01 HL090620, R01 HL090620-01A1, R01 HL092577, R01 HL092577-01A1, R01 HL104156]; NIA NIH HHS [R01 AG028321, R01 AG028321-01]; NIDA NIH HHS [R21 DA027021] NR 92 TC 247 Z9 252 U1 1 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 3 PY 2009 VL 119 IS 4 BP 606 EP 618 DI 10.1161/CIRCULATIONAHA.108.825380 PG 13 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 402RV UT WOS:000263031700015 PM 19188521 ER PT J AU Horton, ES AF Horton, Edward S. TI Defining the Role of Basal and Prandial Insulin for Optimal Glycemic Control SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID TYPE-2 DIABETES-MELLITUS; CORONARY HEART-DISEASE; CARDIOVASCULAR EVENTS; MYOCARDIAL-INFARCTION; BLOOD-GLUCOSE; HYPERGLYCEMIA; ROSIGLITAZONE; ASSOCIATION; MORTALITY; THERAPY AB Type 2 diabetes mellitus is a progressive disease characterized by early impairment of beta-cell function and ultimately loss of beta-cell mass. Hence, a single daily injection of a long-acting insulin is commonly initiated after intensification of oral antihyperglycemic therapy. Hemoglobin A1C should be measured every 3 months and therapy adjusted if the target is not met. As beta-cell function continues to decline, it is often necessary to add exogenous bolus insulin therapy, using short-acting insulin analogs or regular insulin. Alternatively, the use of pre-mixed insulin preparations, combining both long-acting and short-acting insulins, may be used. (J Am Coll Cardiol 2009;53:S21-7) (C) 2009 by the American College of Cardiology Foundation C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Horton, ES (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM edward.horton@joslin.harvard.edu NR 31 TC 6 Z9 6 U1 0 U2 1 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 FEB 3 PY 2009 VL 53 IS 5 BP S21 EP S27 DI 10.1016/j.jacc.2008.11.008 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 400DK UT WOS:000262848000005 PM 19179213 ER PT J AU Driver, JA Logroscino, G Gaziano, JM Kurth, T AF Driver, Jane A. Logroscino, Giancarlo Gaziano, J. Michael Kurth, Tobias TI Incidence and remaining lifetime risk of Parkinson disease in advanced age SO NEUROLOGY LA English DT Article ID CARDIOVASCULAR-DISEASE; ALZHEIMERS-DISEASE; PHYSICIANS HEALTH; HEART-DISEASE; BETA-CAROTENE; MORTALITY; CANCER; MEN; POPULATION; PREVENTION AB Objective: To estimate the incidence and lifetime risk (LTR) of Parkinson disease (PD) in a large cohort of men. Background: Age is the strongest risk factor for PD, but whether its incidence continues to increase after age 80 years remains unclear. Methods: Prospective cohort of 21,970 US male physicians aged 40-84 years at baseline who did not report PD before study entry. Participants self-reported PD on yearly follow-up questionnaires, and all deaths were confirmed. We calculated incidence rates and cumulative incidence using a modified Kaplan-Meier analysis. LTR was estimated by adjusting cumulative incidence for competing risks of death. Results: Five hundred sixty-three cases of PD were identified over 23 years of follow-up. The crude incidence rate of PD was 121 cases/100,000 person-years. Age-specific incidence rates increased sharply beginning at age 60 years, peaked in those aged 85-89 years, and declined beginning at age 90 years. Cumulative incidence substantially overestimated the long-term risk of PD, particularly in those aged 80 years and older. Cumulative incidence was 9.9% (95% confidence interval [CI] 8.48%-11.30%) from ages 45 to 100 years, whereas LTR for the same period was 6.7% (95% CI 6.01%-7.43%). The incidence and LTR of PD decreased with increasing exposure to smoking. Conclusions: Our study provides evidence that the incidence of Parkinson disease (PD) in men increases through age 89 years. Whether the subsequent decline represents a true decrease in risk remains to be established. A history of smoking substantially decreased the incidence and lifetime risk of PD. Incidence studies that do not adjust for competing risks of death may overestimate the true risk of PD in the elderly. Neurology (R) 2009;72:432-438 C1 [Driver, Jane A.; Gaziano, J. Michael; Kurth, Tobias] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Aging,Dept Med, Boston, MA 02120 USA. [Gaziano, J. Michael; Kurth, Tobias] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Prevent Med, Boston, MA 02120 USA. [Logroscino, Giancarlo] Univ Bari, Sch Med, Dept Neurol & Psychiat, I-70121 Bari, Italy. [Kurth, Tobias] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02120 USA. [Gaziano, J. Michael] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res Informat Ctr, Boston, MA USA. RP Driver, JA (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Aging,Dept Med, 1620 Tremont St, Boston, MA 02120 USA. EM jdriver@partners.org RI Kurth, Tobias/A-9243-2012; LOGROSCINO, GIANCARLO/K-5148-2016 OI Kurth, Tobias/0000-0001-7169-2620; LOGROSCINO, GIANCARLO/0000-0003-0423-3242 FU NCI NIH HHS [R01 CA097193-03, CA-097193, CA-34944, CA-40360, R01 CA034944, R01 CA034944-03, R01 CA040360, R01 CA040360-14, R01 CA040360-15, R01 CA040360-16, R01 CA040360-17, R01 CA097193, R01 CA097193-01, R01 CA097193-02, R01 CA097193-04, R01 CA097193-05, R01 CA097193-06A1, R01 CA097193-07]; NHLBI NIH HHS [HL-26490, HL-34595, R01 HL026490, R01 HL026490-03, R01 HL034595, R01 HL034595-07] NR 34 TC 52 Z9 55 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD FEB 3 PY 2009 VL 72 IS 5 BP 432 EP 438 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 404YF UT WOS:000263188200008 PM 19188574 ER PT J AU Lewis, RF Traish, AS Lessell, S AF Lewis, Richard F. Traish, Aisha S. Lessell, Simmons TI ATYPICAL VOLUNTARY NYSTAGMUS SO NEUROLOGY LA English DT Editorial Material C1 [Lewis, Richard F.] Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA. [Lewis, Richard F.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Cambridge, MA 02138 USA. [Traish, Aisha S.; Lessell, Simmons] Harvard Univ, Sch Med, Dept Ophthalmol, Cambridge, MA 02138 USA. RP Lewis, RF (reprint author), Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02114 USA. EM richard_lewis@meei.harvard.edu NR 5 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD FEB 3 PY 2009 VL 72 IS 5 BP 467 EP 469 DI 10.1212/01.wnl.0000341876.76523.99 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 404YF UT WOS:000263188200014 PM 19188580 ER PT J AU Sheikh, SI AF Sheikh, Sarah I. TI International Issues: Of saints and sickness A neurology elective in India SO NEUROLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Sheikh, SI (reprint author), Massachusetts Gen Hosp, WACC 835,55 Fruit St, Boston, MA 02114 USA. EM sisheikh@partners.org NR 0 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD FEB 3 PY 2009 VL 72 IS 5 BP E24 EP E26 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 404YF UT WOS:000263188200024 PM 19188566 ER PT J AU Iacob, RE Pene-Dumitrescu, T Zhang, J Gray, NS Smithgall, TE Engen, JR AF Iacob, Roxana E. Pene-Dumitrescu, Teodora Zhang, Jianming Gray, Nathanael S. Smithgall, Thomas E. Engen, John R. TI Conformational disturbance in Abl kinase upon mutation and deregulation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE allosteric interactions; chronic mylogenous leukemia; hydrogen exchange; mass spectrometry ID CHRONIC MYELOID-LEUKEMIA; TYROSINE KINASE; C-ABL; BCR-ABL; CRYSTAL-STRUCTURE; SRC; BINDING; AUTOINHIBITION; ACTIVATION; RESISTANCE AB Protein dynamics are inextricably linked to protein function but there are few techniques that allow protein dynamics to be conveniently interrogated. For example, mutations and translocations give rise to aberrant proteins such as Bcr-Abl where changes in protein conformation and dynamics are believed to result in deregulated kinase activity that provides the oncogenic signal in chronic myelogeous leukemia. Although crystal structures of the down-regulated c-Abl kinase core have been reported, the conformational impact of mutations that render Abl resistant to small-molecule kinase inhibitors are largely unknown as is the allosteric interplay of the various regulatory elements of the protein. Hydrogen exchange mass spectrometry (HX MS) was used to compare the conformations of wild-type Abl with a nonmyristoylated form and with 3 clinically relevant imatinib resistance mutants (T315I, Y253H and E255V). A HX-resistant core localized to the interface between the SH2 and kinase domains, a region known to be important for maintaining the down-regulated state. Conformational differences upon demyristoylation were consistent with the SH2 domain moving to the top of the small lobe of the kinase domain as a function of activation. There were conformational changes in the T315I mutant but, surprisingly, no major changes in conformation were detected in either the Y253H or the E255V mutants. Taken together, these results provide evidence that allosteric interactions and conformational changes play a major role in Abl kinase regulation in solution. Similar analyses could be performed on any protein to provide mechanistic details about conformational changes and protein function. C1 [Iacob, Roxana E.; Engen, John R.] Northeastern Univ, Barnett Inst, Boston, MA 02115 USA. [Engen, John R.] Northeastern Univ, Dept Chem & Chem Biol, Boston, MA 02115 USA. [Pene-Dumitrescu, Teodora; Smithgall, Thomas E.] Univ Pittsburgh, Sch Med, Dept Microbiol & Mol Genet, Pittsburgh, PA 15261 USA. [Zhang, Jianming; Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Zhang, Jianming; Gray, Nathanael S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Engen, JR (reprint author), Northeastern Univ, Barnett Inst, Boston, MA 02115 USA. EM j.engen@neu.edu FU National Institutes of Health [GM070590, CA101828]; Novartis Institute of Biomedical Research; Waters Corporation FX We thank T.E. Wales and D.J. Houde for technical assistance. This work was supported by National Institutes of Health Grants GM070590 (to J.R.E.) and CA101828 (to T.E.S.), the Novartis Institute of Biomedical Research (N.S.G.), and Waters Corporation (J.R.E.). This is Barnett Institute contribution no. 931. NR 28 TC 48 Z9 48 U1 0 U2 10 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 3 PY 2009 VL 106 IS 5 BP 1386 EP 1391 DI 10.1073/pnas.0811912106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 403HV UT WOS:000263074600020 PM 19164531 ER PT J AU Machida, K Tsukamoto, H Mkrtchyan, H Duan, L Dynnyk, A Liu, HM Asahina, K Govindarajan, S Raye, R Ou, JJ Seki, E Deshaies, R Miyake, K Lai, MMC AF Machida, Keigo Tsukamoto, Hidekazu Mkrtchyan, Hasmik Duan, Lewei Dynnyk, Alla Liu, Helene Minyi Asahina, Kinji Govindarajan, Sugantha Raye, Ratna Ou, Jing-hsiung James Seki, Ekihiro Deshaies, Raymond Miyake, Kensuke Lai, Michael M. -C. TI Toll-like receptor 4 mediates synergism between alcohol and HCV in hepatic oncogenesis involving stem cell marker Nanog SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID VIRUS CORE PROTEIN; NONSTRUCTURAL 5A PROTEIN; C VIRUS; HEPATOCELLULAR-CARCINOMA; OXIDATIVE STRESS; VIRAL-HEPATITIS; TRANSGENIC MICE; UP-REGULATION; LIVER; ACTIVATION AB Alcohol synergistically enhances the progression of liver disease and the risk for liver cancer caused by hepatitis C virus (HCV). However, the molecular mechanism of this synergy remains unclear. Here, we provide the first evidence that Toll-like receptor 4 (TLR4) is induced by hepatocyte-specific transgenic (Tg) expression of the HCV nonstructural protein NS5A, and this induction mediates synergistic liver damage and tumor formation by alcohol-induced endotoxemia. We also identify Nanog, the stem/progenitor cell marker, as a novel downstream gene up-regulated by TLR4 activation and the presence of CD133/Nanog-positive cells in liver tumors of alcohol-fed NS5A Tg mice. Transplantation of p53-deficient hepatic progenitor cells transduced with TLR4 results in liver tumor development in mice following repetitive LPS injection, but concomitant transduction of Nanog short-hairpin RNA abrogates this outcome. Taken together, our study demonstrates a TLR4-dependent mechanism of synergistic liver disease by HCV and alcohol and an obligatory role for Nanog, a TLR4 downstream gene, in HCV-induced liver oncogenesis enhanced by alcohol. C1 [Machida, Keigo; Tsukamoto, Hidekazu; Mkrtchyan, Hasmik; Dynnyk, Alla; Asahina, Kinji; Govindarajan, Sugantha; Ou, Jing-hsiung James] Univ So Calif, Keck Sch Med, So Calif Res Ctr Alcohol Liver & Pancreat Dis & C, Los Angeles, CA 90033 USA. [Machida, Keigo; Duan, Lewei; Liu, Helene Minyi; Ou, Jing-hsiung James; Lai, Michael M. -C.] Univ So Calif, Keck Sch Med, Dept Mol Microbiol & Immunol, Los Angeles, CA 90033 USA. [Tsukamoto, Hidekazu; Govindarajan, Sugantha] Univ So Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA 90033 USA. [Tsukamoto, Hidekazu] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90033 USA. [Raye, Ratna] St Louis Univ, Dept Pathol, St Louis, MO 63103 USA. [Seki, Ekihiro] Univ Calif San Diego, La Jolla, CA 92093 USA. [Deshaies, Raymond] CALTECH, Howard Hughes Med Inst, Pasadena, CA 91125 USA. [Deshaies, Raymond] CALTECH, Div Biol, Pasadena, CA 91125 USA. [Miyake, Kensuke] Univ Tokyo, Inst Med Sci, Tokyo 1088639, Japan. [Lai, Michael M. -C.] Natl Cheng Kung Univ, Dept Microbiol Immunol, Tainan 701, Taiwan. RP Machida, K (reprint author), Univ So Calif, Keck Sch Med, So Calif Res Ctr Alcohol Liver & Pancreat Dis & C, 2011 Zonal Ave, Los Angeles, CA 90033 USA. EM kmachida@usc.edu RI Lai, Michael Ming-Chao/I-7001-2012; Deshaies, Raymond/B-8354-2014; Seki, Ekihiro/K-2481-2016; OI Deshaies, Raymond/0000-0002-3671-9354; LIU, HELENE MINYI/0000-0003-4837-5373 FU pilot project; National Institute on Alcohol Abuse and Alcoholism/National Institutes of Health (NIAAA/NIH) [P50 AA011999, AI 40038, CA123328, CA108302]; Medical Research Service of the Veterans Administration FX We thank Qing-gao Deng, Jiaohong Wang, Sean Vorah, and Jeffrey Huang (University of Southern California) for mouse experiments; Michael Karin (University of California at San Diego) for discussions; Paul Robson (Genome Institute of Singapore, Immunos, Singapore) for Nanog-promoter luciferase construct; Steven Weinman (University of Texas) for suggestions; and Moli Chen and Alex Trana for histological service. The study was supported by pilot project funding; the Animal and Morphology Cores of the Southern California Research Center for ALPD & Cirrhosis (P50 AA011999) funded by the National Institute on Alcohol Abuse and Alcoholism/National Institutes of Health (NIAAA/NIH); NIH Grants AI 40038, CA123328, and CA108302; and the Medical Research Service of the Veterans Administration. NR 34 TC 117 Z9 129 U1 1 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 3 PY 2009 VL 106 IS 5 BP 1548 EP 1553 DI 10.1073/pnas.0807390106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 403HV UT WOS:000263074600048 PM 19171902 ER PT J AU Tsai, CL Camargo, CA AF Tsai, Chu-Lin Camargo, Carlos A., Jr. TI Racial and Ethnic Differences in Emergency Care for Acute Exacerbation of Chronic Obstructive Pulmonary Disease SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE chronic obstructive pulmonary disease; exacerbation; ethnicity; quality of care; race ID QUALITY-OF-CARE; RACE/ETHNICITY; MANAGEMENT; ASTHMA; TRENDS; COPD; MULTICENTER; DEPARTMENTS; DISPARITIES; ANALGESIA AB The objective was to investigate racial and ethnic differences in emergency care for patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD). The authors performed a prospective multicenter cohort study involving 24 emergency departments (EDs) in 15 U.S. states. Using a standard protocol, consecutive ED patients with AECOPD were interviewed, their charts reviewed, and 2-week telephone follow-ups were completed. Among 330 patients, 218 (66%) were white, 84 (25%) were African American, and 28 (8%) were Hispanic. A quarter of the 24 EDs cared for 59% of all minority patients. Compared with white patients, African American and Hispanic patients were more likely to be uninsured or with Medicaid (19, 49, and 52%, respectively; p < 0.001), were less likely to have a primary care provider (93, 81, and 82%, respectively; p = 0.005), and had more frequent ED visits in the past year (medians = 1, 2, and 3, respectively; p = 0.002). In the unadjusted analyses, minority patients were less likely to receive diagnostic procedures, more likely to receive systemic corticosteroids in the ED, less likely to be admitted, and more likely to have a relapse. After adjustment for patient and ED characteristics, these many racial and ethnic differences in quality of care were nearly completely eliminated. Despite pronounced racial and ethnic differences in stable COPD, all racial and ethnic groups received comparable quality of emergency care for AECOPD and had similar short-term outcomes. C1 [Tsai, Chu-Lin; Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02115 USA. RP Tsai, CL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02115 USA. EM cltsai@post.harvard.edu OI TSAI, CHU-LIN/0000-0003-4639-1513 FU Boehringer Ingelheim (Ridgefield, CT); Altana; AstraZeneca; Aventis; Aventis Pasteur; Boehringer Ingelheim; Dey; GlaxoSmithKline; MedImmune; Merck; Novartis; Pfizer; Respironics; Schering Plough FX Conduct of the two cohort studies was supported by an unrestricted grant from Boehringer Ingelheim (Ridgefield, CT). Dr. Camargo has received financial support (research grants, consulting, lectures) in the past 5 years from Altana, AstraZeneca, Aventis, Aventis Pasteur, Boehringer Ingelheim, Dey, GlaxoSmithKline, MedImmune, Merck, Novartis, Pfizer, Respironics, and Schering Plough. Dr. Tsai has no conflicts of interest to disclose. NR 39 TC 7 Z9 7 U1 2 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD FEB PY 2009 VL 16 IS 2 BP 108 EP 115 DI 10.1111/j.1553-2712.2008.00319.x PG 8 WC Emergency Medicine SC Emergency Medicine GA 399DR UT WOS:000262781100002 PM 19076100 ER PT J AU Roedl, JB Prabhakar, HB Mueller, PR Colen, RR Blake, MA AF Roedl, Johannes B. Prabhakar, Hima B. Mueller, Peter R. Colen, Rivka R. Blake, Michael A. TI Prediction of Metastatic Disease and Survival in Patients with Gastric and Gastroesophageal Junction Tumors: The Incremental Value of PET-CT over PET and the Clinical Role of Primary Tumor Volume Measurements SO ACADEMIC RADIOLOGY LA English DT Article DE Esophageal carcinoma; tumor volume; positron emission tomography; computed tomography; metastasis ID POSITRON-EMISSION-TOMOGRAPHY; ESOPHAGEAL CANCER; COMPUTED-TOMOGRAPHY; DISTANT METASTASES; F-18-FDG PET; CARCINOMA; ADENOCARCINOMA; RADIOTHERAPY; DELINEATION; UTILITY AB Rationale and Objectives. To investigate the accuracy of M staging (staging of metastatic disease) in esophageal carcinoma based on a visual interpretation and based on tumor volume measurements on positron emission tomography (PET) computed tomography (CT). Materials and Methods. Fifty-nine untreated patients with gastroesophageal junction tumors were enrolled, including 36 subcardial gastric tumors (type III according to Siewert classification) and 23 adenocarcinomas of the cardia (AEG, type 11 Siewert). Patients were grouped in metastasis free (MO stage, n = 34) and metastatic stages (MI stage, n = 25). Tumor volume and mean and maximum standardized uptake value were measured on PET-CT. The accuracy of these quantitative tumor volume parameters in distinguishing metastasis-free tumors (MO stage) from metastatic stages (MI stage) was compared to the accuracy of a visual analysis with fused PET-CT. Furthermore, accuracy of PET-CT was compared to PET reviewed side by side with CT in a lesion-based analysis of 84 distant metastatic sites. Results. In the visual interpretation, PET-CT (accuracy 88%, 74/84) was more accurate than PET (accuracy 78%, 66/84; P=.008) in characterizing the 84 potential metastatic sites in the 59 patients. Among the tumor parameters. the PET-CT tumor volume was the most accurate predictor of M I stage and overall survival. With a threshold of 39 mL, PET-CT volume was able to predict M I stage disease with a sensitivity of 96% and a specificity of 85%. The accuracy of M-staging was increased further when combining tumor volume measurements with the results from the visual analysis (combined results: sensitivity 96%, specificity 94%). Conclusions. PET-CT was more accurate than PET (reviewed side by side with CT) in characterizing distant metastatic sites of gastroesophageal junction carcinomas. The highest accuracy for M-staging was obtained when combining the results of the visual analysis with the results from primary tumor volume measurements. Primary tumor volume was shown to be an independent prognostic factor. C1 [Roedl, Johannes B.; Prabhakar, Hima B.; Mueller, Peter R.; Colen, Rivka R.; Blake, Michael A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Div Abdominal & Intervent Radiol, Boston, MA 02114 USA. [Roedl, Johannes B.; Colen, Rivka R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Div Nucl Med, Boston, MA 02114 USA. RP Roedl, JB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Div Abdominal & Intervent Radiol, Boston, MA 02114 USA. EM johannes.roedl@gmail.com NR 21 TC 7 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD FEB PY 2009 VL 16 IS 2 BP 218 EP 226 DI 10.1016/j.acra.2008.06.004 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 395PR UT WOS:000262536500015 PM 19124108 ER PT J AU Cruz-Gonzalez, I Dejoseph-Gauthier, D Chia, S Raffel, OC Jang, IK AF Cruz-Gonzalez, Ignacio Dejoseph-Gauthier, Denise Chia, Stanley Raffel, Owen C. Jang, Ik-Kyung TI Non-invasive assessment of myocardial ischaemia by using low amplitude oscillations of the conventional ECG signals (ECG dispersion mapping) during percutaneous coronary intervention SO ACTA CARDIOLOGICA LA English DT Article DE ECG dispersion map; myocardial ischoemia; percutaneous coronary intervention ID ANGIOGRAPHY AB Objective - The HeartVue (TM) 6S System is a recently developed novel technology that may provide non-invasive assessment of myocardial ischaemia by analysing low amplitude oscillations of the conventional ECG signals (ECG dispersion mapping). The available data to validate this new technology is limited. Therefore we performed a prospective study to assess the HeortVueTM 6S System for the detection of myocardial ischaemia during coronary occlusion in patients undergoing percutaneous coronary intervention (PCI). Methods - A total of 101 patients undergoing cardiac catheterization were prospectively enrolled. HeartVueTM 6S System ECG dispersion mapping was obtained at baseline, and during the first balloon inflation and at the end of the procedure if PCI was performed. Parameters provided by the HeartVueTM 6S System were analysed. Results - Fifty patients who underwent PCI comprised the final study population. The mean age was 63.7 +/- 10 years and 58% were men. In 58% of cases the indication was acute coronary syndrome. In 98% of patients, PCI was successful. There were significant differences in the G7+G9 values between the first inflation and the end of the procedure, which reflect changes in ventricular depolarization (P = 0.02 by Wilcoxon signed rank test). Conclusions - The HeartVueTM 6S System may have potential for a non-invasive assessment of ischaemia in patients with suspected coronary artery disease. Larger studies are warranted to confirm these preliminary findings. C1 [Cruz-Gonzalez, Ignacio; Dejoseph-Gauthier, Denise; Chia, Stanley; Raffel, Owen C.; Jang, Ik-Kyung] Harvard Univ, Div Cardiol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Jang, IK (reprint author), Harvard Univ, Div Cardiol, Massachusetts Gen Hosp, Sch Med, Gray Bigelow 800,55 Fruit St, Boston, MA 02114 USA. EM ijang@partners.org RI 2009, Secribsal/A-1266-2012 NR 9 TC 4 Z9 5 U1 0 U2 0 PU ACTA CARDIOLOGICA PI BRUSSELS PA AVENUE CIRCULAIRE 138A, 1180 BRUSSELS, BELGIUM SN 0001-5385 J9 ACTA CARDIOL JI Acta Cardiol. PD FEB PY 2009 VL 64 IS 1 BP 11 EP 15 DI 10.2143/AC.64.1.2034355 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 415XZ UT WOS:000263971100002 PM 19317291 ER PT J AU Rigotti, NA Gonzales, D Dale, LC Lawrence, D Chang, Y AF Rigotti, Nancy A. Gonzales, David Dale, Lowell C. Lawrence, Daniel Chang, Yuchiao CA CIRRUS Study Grp TI A randomized controlled trial of adding the nicotine patch to rimonabant for smoking cessation: efficacy, safety and weight gain SO ADDICTION LA English DT Article DE Nicotine patch; randomized controlled trial; rimonabant; smoking cessation ID SUSTAINED-RELEASE BUPROPION; CANNABINOID-1 RECEPTOR BLOCKER; RISK-FACTORS; OVERWEIGHT PATIENTS; PARTIAL AGONIST; SMOKERS; PLACEBO; REPLACEMENT; VARENICLINE; DEPENDENCE AB Because smoking cessation rates might be improved by combining drugs and by reducing post-cessation weight gain, we tested the smoking cessation efficacy, safety and effect on body weight of adding the nicotine patch to rimonabant, a cannabanoid type-1 receptor antagonist that reduces body weight. Randomized double-blind placebo-controlled trial. Fifteen US research centers. A total of 755 smokers (>= 15 cigarettes/day). Rimonabant (20 mg daily) was given open-label for 9 weeks. The 735 participants completing week 1 were randomized at day 8 (target quit day) to add a nicotine patch (n = 369) or placebo patch (n = 366) for 10 weeks (21 mg daily for 8 weeks plus a 2-week taper). Participants received weekly smoking counseling and were followed for 24 weeks. Biochemically validated 4-week continuous abstinence at end-of-treatment (weeks 6-9; primary end-point); 7-day point prevalence abstinence at weeks 9 and 24; sustained abstinence (weeks 6-24); change in body weight; and adverse events. Rimonabant plus nicotine patch was superior to rimonabant plus placebo in validated continuous abstinence at weeks 6-9 (39.0% versus 21.3%; odds ratio 2.36, 95% confidence interval: 1.71-2.37; P < 0.01) and in all other efficacy measures. Mean end-of-treatment weight gain among quitters did not differ between groups (0.04 kg for combination versus 0.49 kg for rimonabant only, P = 0.15) and was similar in weight-concerned smokers. Serious adverse event rates did not differ between groups. Depression- and anxiety-related adverse events occurred in 32 (4.2%) and 44 (5.8%) subjects, respectively; eight (1.1%) and nine (1.2%) subjects stopped the drug due to depression and anxiety, respectively. Adding a nicotine patch to rimonabant was well tolerated and increased smoking cessation rates over rimonabant alone. There was little post-cessation weight gain in either group, even among weight-concerned smokers, during drug treatment. C1 [Rigotti, Nancy A.] Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. [Rigotti, Nancy A.; Chang, Yuchiao] Harvard Univ, Sch Med, Boston, MA USA. [Gonzales, David] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Dale, Lowell C.] Mayo Clin, Rochester, MN USA. [Lawrence, Daniel] Univ Wisconsin, Sch Med, Madison, WI USA. RP Rigotti, NA (reprint author), Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, 50 Staniford St,9th floor, Boston, MA 02114 USA. EM nrigotti@partners.org OI Gonzales, David/0000-0002-4323-198X NR 32 TC 35 Z9 36 U1 1 U2 5 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0965-2140 J9 ADDICTION JI Addiction PD FEB PY 2009 VL 104 IS 2 BP 266 EP 276 DI 10.1111/j.1360-0443.2008.02454.x PG 11 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 394MK UT WOS:000262450600019 PM 19149823 ER PT J AU Raw, M Regan, S Rigotti, NA McNeill, A AF Raw, Martin Regan, Susan Rigotti, Nancy A. McNeill, Ann TI A survey of tobacco dependence treatment services in 36 countries SO ADDICTION LA English DT Article DE Tobacco dependence treatment; survey AB This paper reports the results of a survey of national tobacco dependence treatment services in 36 countries. The objective was to describe the services and discuss the results in the context of Article 14 of the Framework Convention on Tobacco Control, which asks countries to promote adequate treatment for tobacco dependence. A questionnaire on tobacco dependence treatment services was e-mailed to a convenience sample of contacts in 2007. Completed questionnaires were received from contacts in 36 countries. The survey instrument was a 10-item questionnaire asking about treatment policy and practice, including medications. According to our informants, fewer than half the countries in our survey had an official written policy on (44%), or a government official responsible for (49%), treatment. Only 19% had a specialized national treatment system and only 24% said help was easily available in general practice. Most countries (94%) allowed the sale of nicotine replacement therapy (NRT), bupropion (75%) and varenicline (69%) but only 40% permitted NRT on 'general sale'. Very few countries responding to the question fully reimbursed any of the medications. Fewer than half (45%) fully reimbursed brief advice and only 29% fully reimbursed intensive specialist support. Only 31% of countries said that their official treatment policy included the mandatory recording of patients' smoking status in medical notes. Taken together, our findings show that few countries have well-developed tobacco dependence treatment services and that, at a national level, treatment is not yet a priority in most countries. C1 [Raw, Martin; McNeill, Ann] Univ Nottingham, Div Epidemiol & Publ Hlth, Nottingham NG7 2RD, England. [Regan, Susan; Rigotti, Nancy A.] Harvard Univ, Sch Med, Boston, MA USA. [Rigotti, Nancy A.] Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Div Gen Med, Boston, MA 02114 USA. RP Raw, M (reprint author), City Hosp Nottingham, Clin Sci Bldg, Nottingham NG5 1PB, England. EM martin@martinraw.com OI Regan, Susan/0000-0003-0940-2017 FU Society for the Study of Addiction; Doreen McIntyre and the Global Treatment Partnership FX We gratefully acknowledge the Society for the Study of Addiction for financial support for the data analysis and writing-up of this report, Doreen McIntyre and the Global Treatment Partnership for financial support of the survey and Catherine Slevin for research assistance with the survey. We thank the following for advice on various aspects of the project including developing the questionnaire: Mira Aghi, Peter Anderson, Linda Bailey, Rick Botelho, David Graham, Joe Gitchell, Paul Hooper, John Hughes, Natasha Jategaonkar, Luk Joossens, Hayden McRobbie, Yumiko Mochizukiy, Hana Ross, Peter Selby, Karen Slama, Fran Stillman, Ken Wassum, Robert West and Heather Wipfli. Finally, we sincerely thank the many country contacts who filled in the questionnaire and without whom this survey could not have happened. The Society for the Study of Addiction is a learned society based in Britain. The Global Treatment Partnership is a project funded by Pfizer and other organizations hosted by the International Non-Governmental Coalition Against Tobacco (INGCAT), whose director is Doreen McIntyre. NR 17 TC 29 Z9 29 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0965-2140 J9 ADDICTION JI Addiction PD FEB PY 2009 VL 104 IS 2 BP 279 EP 287 DI 10.1111/j.1360-0443.2008.02443.x PG 9 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 394MK UT WOS:000262450600021 PM 19149825 ER PT J AU Rigotti, NA Bitton, A Richards, AE Reyen, M Wassum, K Raw, M AF Rigotti, Nancy A. Bitton, Asaf Richards, Ann E. Reyen, Michele Wassum, Kenneth Raw, Martin TI An international survey of training programs for treating tobacco dependence SO ADDICTION LA English DT Article DE Tobacco use cessation; training; world health ID SMOKING AB The World Health Organization (WHO) Framework Convention on Tobacco Control (FCTC) requires countries to implement tobacco dependence treatment programs. To provide treatment effectively, a country needs trained individuals to deliver these services. We report on the global status of programs that train individuals to provide tobacco dependence treatment. Cross-sectional web-based survey of tobacco treatment training programs in a stratified convenience sample of countries chosen to vary by WHO geographic region and World Bank income level. Key informants in 48 countries; 70% of 69 countries who were sent surveys responded. Program prevalence, frequency, duration and size; background of trainees; content (adherence to pre-defined core competencies); funding sources; challenges. We identified 61 current tobacco treatment training programs in 37 (77%) of 48 countries responding to the survey. Three-quarters of them began in 2000 or later, and 40% began after 2003, when the FCTC was adopted. Programs estimated training 14 194 individuals in 2007. Training was offered to a variety of professionals and paraprofessionals, but most often to physicians and nurses. Median program duration was 16 hours, but programs' duration, intensity and size varied widely. Most programs used evidence-based guidelines and reported adherence to core tobacco treatment competencies. Training programs were less frequent in low-income countries and in Africa. Securing funding was the major challenge for most programs; current funding sources were government (58%), non-government organizations (23%), pharmaceutical companies (17%) and, in one case, the tobacco industry. Training programs for tobacco treatment providers are diverse and growing. Most upper- and middle-income countries have programs, and most programs appear to be evidence-based. However, funding is a major challenge. In particular, more programs are needed for non-physicians and for low-income countries. C1 [Rigotti, Nancy A.; Richards, Ann E.; Reyen, Michele] Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. [Rigotti, Nancy A.; Richards, Ann E.; Reyen, Michele] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Bitton, Asaf] Brigham & Womens Hosp, Div Gen Med & Primary Care, Boston, MA 02115 USA. [Rigotti, Nancy A.; Bitton, Asaf] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Wassum, Kenneth] Free & Clear Inc, Seattle, WA USA. [Raw, Martin] Univ Nottingham, Div Epidemiol & Publ Hlth, Nottingham NG7 2RD, England. RP Rigotti, NA (reprint author), Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, 50 Staniford St,Room 914, Boston, MA 02114 USA. EM nrigotti@partners.org FU Association for the Treatment of Tobacco Use and Dependence (ATTUD); Global Treatment Partnership; National Heart Lung and Blood Institute [K24-HL04440] FX We are grateful to our External Advisory Board (Gregory Connolly, Thomas Glynn and Harry Lando) for their guidance, to all the individuals around the world who took the time to respond to our survey, and to Susan Regan PhD for assistance with the data analysis. This study was supported by a funding grant from the Association for the Treatment of Tobacco Use and Dependence (ATTUD), with funds provided by the Global Treatment Partnership. N. Rigotti's time was funded by a grant from the National Heart Lung and Blood Institute (no. K24-HL04440). NR 16 TC 10 Z9 10 U1 1 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0965-2140 J9 ADDICTION JI Addiction PD FEB PY 2009 VL 104 IS 2 BP 288 EP 296 DI 10.1111/j.1360-0443.2008.02442.x PG 9 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 394MK UT WOS:000262450600022 PM 19149826 ER PT J AU Perez, VI Van Remmen, H Bokov, A Epstein, CJ Vijg, J Richardson, A AF Perez, Viviana I. Van Remmen, Holly Bokov, Alex Epstein, Charles J. Vijg, Jan Richardson, Arlan TI The overexpression of major antioxidant enzymes does not extend the lifespan of mice SO AGING CELL LA English DT Editorial Material DE aging; antioxidant enzymes; transgenic and knockout mice ID MANGANESE SUPEROXIDE-DISMUTASE; ADULT DROSOPHILA-MELANOGASTER; UBIQUITOUS OVEREXPRESSION; TRANSGENIC MICE; EXPRESSION; CATALASE AB We evaluated the effect of overexpressing antioxidant enzymes on the lifespans of transgenic mice that overexpress copper zinc superoxide dismutase (CuZnSOD), catalase, or combinations of either CuZnSOD and catalase or CuZnSOD and manganese superoxide dismutase (MnSOD). Our results show that the overexpression of these major antioxidant enzymes, which are known to scavenge superoxide and hydrogen peroxide in the cytosolic and mitochondrial compartments, is insufficient to extend lifespan in mice. C1 [Perez, Viviana I.; Van Remmen, Holly; Bokov, Alex; Richardson, Arlan] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Perez, Viviana I.; Van Remmen, Holly; Richardson, Arlan] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Van Remmen, Holly; Bokov, Alex] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Van Remmen, Holly; Richardson, Arlan] S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78229 USA. [Epstein, Charles J.] Univ Calif San Francisco, Inst Human Genet, Sch Med, San Francisco, CA 94143 USA. [Epstein, Charles J.] Univ Calif San Francisco, Dept Pediat, Sch Med, San Francisco, CA 94143 USA. [Vijg, Jan] Albert Einstein Coll Med, Dept Genet, Bronx, NY 10461 USA. RP Richardson, A (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, Texas Res Pk Campus,15355 Lambda Dr, San Antonio, TX 78245 USA. EM richardsona@uthscsa.edu FU NIA NIH HHS [1P30-AG-13319, P01 AG019316, P01-AG-19316, P30 AG013319, R37 AG026557, R37-AG026557] NR 18 TC 144 Z9 144 U1 0 U2 12 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1474-9718 J9 AGING CELL JI Aging Cell PD FEB PY 2009 VL 8 IS 1 BP 73 EP 75 DI 10.1111/j.1474-9726.2008.00449.x PG 3 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 400ON UT WOS:000262877900008 PM 19077044 ER PT J AU Applebaum, AJ Richardson, MA Brady, SM Brief, DJ Keane, TM AF Applebaum, Allison J. Richardson, Mark A. Brady, Stephen M. Brief, Deborah J. Keane, Terence M. TI Gender and Other Psychosocial Factors as Predictors of Adherence to Highly Active Antiretroviral Therapy (HAART) in Adults with Comorbid HIV/AIDS, Psychiatric and Substance-related Disorder SO AIDS AND BEHAVIOR LA English DT Article DE Adherence; HIV/AIDS; Gender; HAART ID QUALITY-OF-LIFE; DEPRESSION; WOMEN AB This study assessed adherence to HAART among 67 HIV-infected adults, and the degree to which gender and psychological factors-including depression, drug and alcohol use, quality of life, and medication side effects-influenced adherence. Although overall adherence was greater than rates reported in similar studies, no significant difference in adherence was observed between men and women in the present sample. Medication side effects were a significant predictor of non-adherence in the sample at large and among women in particular, while alcohol dependence was a significant predictor of non-adherence only in women. Possible explanations are explored. C1 [Applebaum, Allison J.; Richardson, Mark A.; Keane, Terence M.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Richardson, Mark A.; Brady, Stephen M.; Brief, Deborah J.; Keane, Terence M.] Boston Univ, Sch Med, Div Psychiat, Boston, MA 02215 USA. [Brief, Deborah J.] VA Boston Healthcare Syst, Dept Psychol, Boston, MA USA. [Keane, Terence M.] VA Boston Healthcare Syst, Res Serv, Boston, MA USA. RP Applebaum, AJ (reprint author), Boston Univ, Dept Psychol, 648 Beacon St,2nd Floor, Boston, MA 02215 USA. EM aja231@bu.edu OI Brady, Stephen/0000-0002-8379-0903; Richardson, Mark/0000-0003-4730-3431 NR 12 TC 22 Z9 26 U1 1 U2 2 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 J9 AIDS BEHAV JI AIDS behav. PD FEB PY 2009 VL 13 IS 1 BP 60 EP 65 DI 10.1007/s10461-008-9441-x PG 6 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 387FE UT WOS:000261936300008 PM 18690532 ER PT J AU Arya, M Behforouz, HL Viswanath, K AF Arya, Monisha Behforouz, Heidi L. Viswanath, Kasisomayajula TI African American Women and HIV/AIDS: A National Call for Targeted Health Communication Strategies to Address a Disparity SO AIDS READER LA English DT Article DE HIV/AIDS; Women; African American; Health disparities; Media/communication strategies ID RISK-REDUCTION; HIV-INFECTION; INFORMATION; PERSPECTIVE; PREVENTION; BEHAVIOR; ADULTS; VIDEO AB African American women are disproportionately affected by the HIV/AIDS epidemic in the United States. To address this disparity, the CDC released a call for targeted communication campaigns in African American communities. The mass media is an HIV/AIDS information source used by African Americans, and media initiatives can be cost-effective for delivering HIV prevention messages. Needed is research ill communities at risk to determine the messages needed and the preferred formats and channels with which to deliver the messages so that targeted communication campaigns can be part of the multifaceted approach to ending the HIV/AIDS disparity affecting African American women. [AIDS Reader. 2009;19:79-84, C3] C1 [Arya, Monisha] Baylor Coll Med, Infect Dis Sect, Houston, TX 77030 USA. [Arya, Monisha] Houston Ctr Qual Care & Utilizat, Houston, TX USA. [Behforouz, Heidi L.] Harvard Univ, Sch Med, Boston, MA USA. [Behforouz, Heidi L.] Prevent & Access Care & Treatment Project, Boston, MA USA. [Behforouz, Heidi L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Viswanath, Kasisomayajula] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Viswanath, Kasisomayajula] Dana Farber Harvard Canc Ctr, Boston, MA USA. RP Arya, M (reprint author), Baylor Coll Med, Infect Dis Sect, Houston, TX 77030 USA. FU Harvard University Center for AIDS Research (CFAR); NIH-funded program [P30 A1060354] FX This article resulted in part from research support to Dr Arya by the Harvard University Center for AIDS Research (CFAR), an NIH-funded program (P30 A1060354) NR 29 TC 1 Z9 1 U1 1 U2 3 PU CLIGGOTT PUBLISHING CO PI DARIEN PA 330 BOSTON POST RD, DARIEN, CT 06820 USA SN 1053-0894 J9 AIDS READ JI Aids Read. PD FEB PY 2009 VL 19 IS 2 BP 79 EP 84 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 404YQ UT WOS:000263189300004 PM 19271331 ER PT J AU Simpson, TL Saxon, AJ Meredith, CW Malte, CA McBride, B Ferguson, LC Gross, CA Hart, KL Raskind, M AF Simpson, Tracy L. Saxon, Andrew J. Meredith, Charles W. Malte, Carol A. McBride, Brittney Ferguson, Laura C. Gross, Christopher A. Hart, Kim L. Raskind, Murray TI A Pilot Trial of the Alpha-1 Adrenergic Antagonist, Prazosin, for Alcohol Dependence SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Noradrenergic; Prazosin; Alcohol Dependence; Human Clinical Trial ID RANDOMIZED CONTROLLED-TRIAL; POSTTRAUMATIC-STRESS-DISORDER; PLACEBO-CONTROLLED TRIAL; DISULFIRAM TREATMENT; DOUBLE-BLIND; GENDER-DIFFERENCES; DRINKING; ETHANOL; NOREPINEPHRINE; ABSTINENCE AB Current medications for alcohol dependence (AD) show only modest efficacy. None target brain noradrenergic pathways. Theory and preclinical evidence suggest that noradrenergic circuits may be involved in alcohol reinforcement and relapse. We therefore tested the alpha-1 adrenergic receptor antagonist, prazosin, as a pharmacotherapy for AD. We randomized 24 participants with AD but without posttraumatic stress disorder to receive either prazosin or placebo in a 6-week, double-blind pilot study. Medication was titrated to a target dose of 4 mg QAM, 4 mg QPM, and 8 mg QHS by the end of week 2. Participants received 5 medical management treatment sessions. Participants were reminded 3 times each day via a text pager to take medications and to call a telephone monitoring system once daily to provide self-reports of alcohol consumption and craving, the primary outcome measures. Results were analyzed using mixed linear regression adjusted for drinking days per week at baseline and week number. Twenty of the 24 (83%) subjects completed. Among the completers, the prazosin group reported fewer drinking days per week than the placebo group during the final 3 weeks of the study. Since only 1 woman was randomized to placebo and only three women completed the trial, the following results focus on the 17 male completers. The prazosin group reported fewer drinking days per week and fewer drinks per week during the final 3 weeks of the study; average total number of drinking days for the placebo group 5.7 (SEM 1.9) versus 0.9 (SEM 0.5) for the prazosin group, and average total number of drinks 20.8 (SEM 6.5) for the placebo group versus 2.6 (SEM 1.3) for the prazosin group. Rates of adverse events were equivalent across conditions. Prazosin holds promise as a pharmacologic treatment for AD and deserves further evaluation in a larger controlled trial. C1 [Simpson, Tracy L.; Saxon, Andrew J.; Malte, Carol A.; McBride, Brittney] Univ Washington, Ctr Excellence Substance Abuse Treatment Educ, Seattle, WA 98195 USA. [Simpson, Tracy L.; Meredith, Charles W.; Ferguson, Laura C.; Gross, Christopher A.; Hart, Kim L.; Raskind, Murray] Univ Washington, Mental Illness Res Educ & Clin Ctr, Seattle, WA 98195 USA. Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Simpson, Tracy L.; Saxon, Andrew J.; Meredith, Charles W.; Ferguson, Laura C.; Gross, Christopher A.; Raskind, Murray] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Simpson, TL (reprint author), 1660 S Columbian Way,116-ATC-S, Seattle, WA 98108 USA. EM Tracy.Simpson@va.gov FU University of Washington's Alcohol and Drug Abuse Institute FX The funding for this study was provided by the VA Puget Sound Health Care System, Seattle, Washington Center of Excellence in Substance Abuse Treatment and Education and by a grant from the University of Washington's Alcohol and Drug Abuse Institute. The authors wish to thank the following individuals for the invaluable assistance with this project: Lynne Hyerle, M.A., Norah Sullivan, ARNP, David Hoff, PA, Craig Jaffe, MD, and Kathleen Ang Lee, MD. NR 63 TC 72 Z9 73 U1 1 U2 6 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD FEB PY 2009 VL 33 IS 2 BP 255 EP 263 DI 10.1111/j.1530-0277.2008.00807.x PG 9 WC Substance Abuse SC Substance Abuse GA 397KS UT WOS:000262662200007 PM 18945226 ER PT J AU Finn, AV Oh, JS Hendricks, M Daher, M Cagliero, E Byrne, RM Nadelson, J Crimins, J Kastrati, A Schomig, A Bruskina, O Palacios, I John, MC Gold, HK AF Finn, Aloke V. Oh, Jae S. Hendricks, Michael Daher, Maureen Cagliero, Enrico Byrne, Raphael M. Nadelson, Jeffrey Crimins, Johanna Kastrati, Adnan Schoemig, Albert Bruskina, Olga Palacios, Igor John, Michael C. Gold, Herman K. TI Predictive factors for in-stent late loss and coronary lesion progression in patients with type 2 diabetes mellitus randomized to rosiglitazone or placebo SO AMERICAN HEART JOURNAL LA English DT Article AB Background Type 2 diabetics (DM2) are at increased risk for restenosis as well as nonculprit coronary artery lesion (NCCL) progression. Rosiglitozone (RSG) favorably modifies many of the altered biologic processes in DM2, although recent reports have questioned its safety. We conducted a double-blind randomized trial to assess the effects of RSG versus placebo on in-stent late lumen loss (LL) and angiographic progression of NCCL. Methods A total of 65 DM2 were randomized to RSG 14 mg/d) (n = 32) or placebo (n = 33) at the time of stenting and underwent clinical and laboratory analysis at 1 and 4 months and 8-month angiography (n = 46 patients). Rapid angiographic progression (RAP) was defined as >= 20% diameter reduction of preexisting NCCL by quantitative coronary angiography, or a new narrowing >= 30%. Results Mean LL in RSG (n = 33 lesions) was not different from that of placebo (0.62 +/- 0.59 vs 0.70 +/- 0.67, P = NS). Seven (13.5%) of 52 NCCLs have RAP in RSG versus 9 (16.1%) of 56 in placebo (P = NS). High-sensitivity C-reactive protein (hs-CRP) was the only predictor of RAP. Patients with a 120-day hs-CRP >= 75th percentile had an OR of 7.35 (95% Cl 2.35-23) for RAP versus those below. Although RSG treatment also lowered log (hs-CRP) at 4 months (RSG 0.10 +/- 0.37 vs placebo 0.26 +/- 0,49, P =.06), it did not decrease the likelihood of plaque progression while also raising LDL and N-terminal brain naturetic peptide. Conclusions Rosiglitazone appears not to lower LL or reduce angiographic progression of NCCL in DM2 and had complex effects on markers of cardiac risk. (Am Heart J 2009; 1 57:383.e 1-383.e8.) C1 [Finn, Aloke V.; Oh, Jae S.; Hendricks, Michael; Daher, Maureen; Cagliero, Enrico; Byrne, Raphael M.; Nadelson, Jeffrey; Crimins, Johanna; Palacios, Igor; John, Michael C.; Gold, Herman K.] Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. [Kastrati, Adnan; Schoemig, Albert; Bruskina, Olga] Tech Univ Munich, Deutsch Herzzentrum, Munich, Germany. RP Finn, AV (reprint author), Emory Univ, Sch Med, Emory Crawford Long Hosp, 550 Peachtree St NE, Atlanta, GA 30308 USA. EM avfinn@emory.edu FU HKG from Abbott Vascular (Santa Cloro, CA) FX The study was funded in part by a research grant to HKG from Abbott Vascular (Santa Cloro, CA). NR 0 TC 1 Z9 1 U1 1 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD FEB PY 2009 VL 157 IS 2 DI 10.1016/j.ahj.2008.11.013 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 409DL UT WOS:000263486300025 ER PT J AU Olenchock, BA Fonarow, GG Pan, WQ Hernandez, A Cannon, CP AF Olenchock, Benjamin A. Fonarow, Gregg G. Pan, Wenqin Hernandez, Adrian Cannon, Christopher P. CA Get GuidelinessSM Steering Comm TI Current Use of Beta Blockers in Patients With Reactive Airway Disease Who Are Hospitalized With Acute Coronary Syndromes SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; ACUTE MYOCARDIAL-INFARCTION; ISCHEMIC-HEART-DISEASE; THERAPY; ASTHMA; INITIATION; SAFETY; COPD AB Beta blockers have a proven benefit in the management of patients with acute coronary syndromes (ACS) and for secondary prevention of coronary events. Current guidelines list such reactive airway diseases (RADs) such as asthma and chronic obstructive pulmonary disease as relative contraindications to beta-blocker use. However, the co-morbid burden of RAD and coronary heart disease is substantial, and data suggest that the treatment benefit of beta blockers is shared by patients with RAD. The Get with the Guidelines(SM) (GWTG) database was used to evaluate use of beta blockers within 24 hours of admission and at discharge in patients with ACS with (n = 12,967) and without (n = 81,140) a history of RAD. Data were collected in 435 hospitals between January 2000 and September 2006. A multivariable logistic regression model was used to determine predictors of beta-blocker treatment. In patients with no RAD history, P-blocker prescription rates were 78.3% at admission and 88.7% at discharge; in patients with a RAD history, rates were 65.6% at admission and 77.2% at discharge. Compared with patients with no history of RAD, patients with a history of RAD were 42% less likely (odds ratio 0.58, confidence interval 0.54 to 0.62, p <0.0001) to receive a beta blocker upon admission and 55% less likely (odds ratio 0.45, confidence interval 0.41 to 0.48, p <0.0001) to receive a beta blocker at discharge in multivariable analysis. Among all other clinical factors, RAD history was the most significant predictor of likelihood of not receiving a beta blocker at admission or discharge. Receipt of R blockers within 24 hours after admission was associated with a lower in-hospital mortality rate for patients with RAD (odds ratio = 0.52, p <0.601) and for patients without RAD (odds ratio = 0.38, p <0.001). Careful assessment of beta-blocker safety and RAD severity by physicians is needed to improve P-blocker prescription rates in this large group of patients with ACS. (C) 2009 Elsevier Inc. (Am J Cardiol 2009;103: 295-300) C1 [Olenchock, Benjamin A.; Cannon, Christopher P.] Harvard Univ, Brigham & Womens Hosp, Sch Med, TIMI Study Grp,Cardiovasc Div,Dept Med, Boston, MA 02115 USA. [Fonarow, Gregg G.] Univ Calif Los Angeles, Div Cardiol, Los Angeles, CA USA. [Pan, Wenqin; Hernandez, Adrian] Duke Clin Res Inst, Durham, NC USA. RP Cannon, CP (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, TIMI Study Grp,Cardiovasc Div,Dept Med, Boston, MA 02115 USA. EM cpcannon@partners.org RI Hernandez, Adrian F./A-7818-2016 OI Hernandez, Adrian F./0000-0003-3387-9616 FU American Heart Association FX This study was supported by Get With The GuidelinesSM-CAD, sponsored by the American Heart Association with funding in part from an unrestricted education grant from the Merck-Schering Plough Partnership. NR 19 TC 33 Z9 34 U1 0 U2 1 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 FEB 1 PY 2009 VL 103 IS 3 BP 295 EP 300 DI 10.1016/j.amjcard.2008.09.081 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 406DR UT WOS:000263275700001 PM 19166678 ER PT J AU Syed, Z Scirica, BM Mohanavelu, S Sung, P Michelson, EL Cannon, CP Stone, PH Stultz, CM Guttag, JV AF Syed, Zeeshan Scirica, Benjamin M. Mohanavelu, Satishkumar Sung, Phil Michelson, Eric L. Cannon, Christopher P. Stone, Peter H. Stultz, Collin M. Guttag, John V. TI Relation of Death Within 90 Days of Non-ST-Elevation Acute Coronary Syndromes to Variability in Electrocardiographic Morphology SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID T-WAVE MORPHOLOGY; RISK STRATIFICATION AB Electrocardiographic measures can facilitate the identification of patients at risk of death after acute coronary syndromes. This study evaluates a new risk metric, morphologic variability (MV), which measures beat-to-beat variability in the shape of the entire heart beat signal. This metric is analogous to heart rate variability (HRV) approaches, which focus on beat-to-beat changes in the heart rate. MV was calculated using a dynamic time-warping technique in 764 patients from the DISPERSE2 (TIMI 33) trial for whom 24-hour continuous electrocardiograph was recorded within 48 hours of non-ST-elevation acute coronary syndrome. The patients were evaluated during a 90-day follow-up for the end point of death. Patients with high MV showed an increased risk of death during follow-up (hazard ratio 8.46; p <0.001). The relationship between high MV and death could be observed even after adjusting for baseline clinical characteristics and HRV measures (adjusted hazard ratio 6.91; p = 0.001). Moreover, the correlation between MV and HRV was low (R <= 0.25). These findings were consistent among several subgroups, including patients under the age of 65 and those with no history of diabetes or hyperlipidemia. In conclusion, our results suggest that increased variation in the entire heart beat morphology is associated with a considerably elevated risk of death and may provide information complementary to the analysis of heart rate. (C) 2009 Elsevier Inc. (Am J Cardiol 2009;103:307-311) C1 [Syed, Zeeshan; Sung, Phil; Stultz, Collin M.; Guttag, John V.] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Syed, Zeeshan; Stultz, Collin M.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA USA. [Scirica, Benjamin M.; Mohanavelu, Satishkumar; Cannon, Christopher P.; Stone, Peter H.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Michelson, Eric L.] AstraZeneca LP, Wilmington, DE USA. RP Guttag, JV (reprint author), MIT, Dept Elect Engn & Comp Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM gutttg@mit.edu FU Integration of Medicine and Innovative Technology; Harvard-MIT Division of Health Sciences and Technology, and Industrial Technology Research Institute (Taiwan); Astra Zeneca FX This work was supported, in part, by Center for Integration of Medicine and Innovative Technology, Harvard-MIT Division of Health Sciences and Technology, and Industrial Technology Research Institute (Taiwan). The DISPERSE2 trial was supported by Astra Zeneca. NR 11 TC 11 Z9 11 U1 1 U2 3 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 FEB 1 PY 2009 VL 103 IS 3 BP 307 EP 311 DI 10.1016/j.amjcard.2008.09.099 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 406DR UT WOS:000263275700003 PM 19166680 ER PT J AU Chia, S Nagurney, JT Brown, DFM Raffel, OC Bamberg, F Senatore, F Wackers, FJT Jang, IK AF Chia, Stanley Nagurney, John T. Brown, David F. M. Raffel, O. Christopher Bamberg, Fabian Senatore, Fred Wackers, Frans J. Th. Jang, Ik-Kyung TI Association of Leukocyte and Neutrophil Counts With Infarct Size, Left Ventricular Function and Outcomes After Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ANGIOGRAPHIC OUTCOMES; ATHEROSCLEROSIS; PERFUSION; DISEASE; QUANTIFICATION; INFLAMMATION; ANGIOPLASTY; METHODOLOGY; VALIDATION; MECHANISMS AB Elevated leukocyte count during ST-segment elevation myocardial infarction is associated with adverse clinical outcomes. Whether increased leukocyte count after primary percutaneous coronary intervention (PCI) directly reflects larger infarct size and left ventricular impairment is not known. The aim of this study was to assess the relation between leukocyte and neutrophil counts with infarct size and the left ventricular ejection fraction (LVEF) after primary PCI. Three hundred sixty-three patients from the Evaluation of MCC-135 for Left Ventricular Salvage in Acute Myocardial Infarction (EVOLVE) study, a randomized, double-blind, placebo-controlled trial assessing the efficacy of intracellular calcium modulator as an adjunct to primary PCI in patients with first ST-segment elevation myocardial infarctions, were evaluated. Total and differential leukocyte counts were measured before and serially after PCI. Infarct size and the LVEF were assessed using single-photon emission computed tomography after 5 and 30 days, and patients were followed up to 180 days. Total leukocyte and neutrophil counts obtained 24 hours after PCI were significantly correlated with infarct size (r = 0.34 and 0.37, respectively, p <0.001) and inversely correlated with the LVEF (r = -0.20 and -0.22, respectively, p <0.001). Patients with elevated leukocyte and neutrophil counts had larger infarct sizes (12.5% vs 5% and 13.5% vs 5%, respectively, p <0.001). The highest neutrophil quartile was associated with increased 180-day composite cardiac events (19% vs 20% vs 23% vs 45%, log-rank p <0.001). Elevated leukocyte and neutrophil counts independently predicted adverse cardiac events (hazard ratios 2.5 and 2.2, respectively, p = 0.001). In conclusion, elevated leukocyte and neutrophil counts after primary PCI in patients with ST-segment elevation myocardial infarctions are directly related to myocardial infarct size and the LVEF and are independent predictors of cardiovascular outcomes. (C) 2009 Elsevier Inc. (Am J Cardiol 2009;103:333-337) C1 [Chia, Stanley; Raffel, O. Christopher; Jang, Ik-Kyung] Massachusetts Gen Hosp, Ctr Heart, Boston, MA 02114 USA. [Nagurney, John T.; Brown, David F. M.] Massachusetts Gen Hosp, Dept Emergency, Boston, MA 02114 USA. [Bamberg, Fabian] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Senatore, Fred] Mitsubishi Pharma Amer, Warren, NJ USA. [Wackers, Frans J. Th.] Yale Univ, Sch Med, Cardiovasc Nucl Imaging & Stress Labs, New Haven, CT USA. RP Jang, IK (reprint author), Massachusetts Gen Hosp, Ctr Heart, Boston, MA 02114 USA. EM ijang@partners.org NR 21 TC 54 Z9 59 U1 0 U2 0 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 FEB 1 PY 2009 VL 103 IS 3 BP 333 EP 337 DI 10.1016/j.amjcard.2008.09.085 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 406DR UT WOS:000263275700008 PM 19166685 ER PT J AU Delahanty, LM Nathan, DM Lachin, JM Hu, FB Cleary, PA Ziegler, GK Wylie-Rosett, J Wexler, DJ AF Delahanty, Linda M. Nathan, David M. Lachin, John M. Hu, Frank B. Cleary, Patricia A. Ziegler, Georgia K. Wylie-Rosett, Judith Wexler, Deborah J. TI Association of diet with glycated hemoglobin during intensive treatment of type 1 diabetes in the Diabetes Control and Complications Trial SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID HIGH-CARBOHYDRATE DIET; GLYCEMIC CONTROL; GLUCOSE-TOLERANCE; FAT DIET; MELLITUS; WEIGHT; ADULTS AB Background: Persons with type 1 diabetes have received widely varying dietary advice based on putative effects on glycemic control. Objective: The objective was to determine whether diet composition was associated with subsequent glycated hemoglobin (Hb A(1c)) concentrations during intensive therapy for type 1 diabetes. Design: We examined associations between quantiles of dietary intake and Hb A(1c) adjusted for age and sex in 532 intensively treated participants in the Diabetes Control and Complications Trial (DCCT) who had complete dietary data through 5 y of follow-up. Multivariate macronutrient density linear regression models tested the association of Hb A(1c) at year 5 with macronutrient composition and were adjusted for age, sex, exercise, triglyceride concentration, body mass index (BMI), baseline Hb A(1c), and concurrent insulin dose. Results: Higher insulin dose, lower carbohydrate intake, and higher saturated, monounsaturated, and total fat intakes were associated with higher Hb A(1c) concentrations at year 5. In age- and sex-adjusted multivariate macronutrient models, substitution of fat for carbohydrate was associated with higher Hb A(1c) concentrations (P = 0.01); this relation remained significant after adjustment for exercise level, serum triglycerides, and BMI (P = 0.02) but was no longer significant (P = 0.1) after adjustment for baseline Hb A(1c) and concurrent insulin dose. Conclusion: Among intensively treated patients with type 1 diabetes, diets higher in fat and saturated fat and lower in carbohydrate are associated with worse glycemic control, independent of exercise and BMI. Am J Clin Nutr 2009; 89: 518-24. C1 [Delahanty, Linda M.; Nathan, David M.; Wexler, Deborah J.] Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. [Delahanty, Linda M.; Nathan, David M.; Wexler, Deborah J.] Harvard Univ, Sch Med, Boston, MA USA. [Lachin, John M.; Cleary, Patricia A.] George Washington Univ, Ctr Biostat, Rockville, MD USA. [Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Ziegler, Georgia K.] Mayo Clin, Rochester, MN USA. [Wylie-Rosett, Judith] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. RP Wexler, DJ (reprint author), Massachusetts Hosp, Ctr Diabet, Bulfinch 408, Boston, MA 02114 USA. EM dwexler@partners.org OI Lachin, John/0000-0001-9838-2841 FU NIH [K23 DK 080 228] FX Supported by an NIH Career Development Award K23 DK 080 228 (DJW). NR 35 TC 50 Z9 52 U1 1 U2 3 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD FEB 1 PY 2009 VL 89 IS 2 BP 518 EP 524 DI 10.3945/ajcn.2008.26498 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 396RL UT WOS:000262608700008 PM 19106241 ER PT J AU Heyman, MB Garnett, EA Shaikh, N Huen, K Jose, FA Harmatz, P Winter, HS Baldassano, RN Cohen, SA Gold, BD Kirschner, BS Ferry, GD Stege, E Holland, N AF Heyman, Melvin B. Garnett, Elizabeth A. Shaikh, Nishat Huen, Karen Jose, Folashade A. Harmatz, Paul Winter, Harland S. Baldassano, Robert N. Cohen, Stanley A. Gold, Benjamin D. Kirschner, Barbara S. Ferry, George D. Stege, Erin Holland, Nina TI Folate concentrations in pediatric patients with newly diagnosed inflammatory bowel disease SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID CROHNS-DISEASE; FOLIC-ACID; COLORECTAL-CANCER; CHILDREN; DEFICIENCY; QUESTIONNAIRE; FORTIFICATION; HOMOCYSTEINE; DAMAGE AB Background: Folate is postulated to protect against cell injury and long-term risk of cancer. Folate deficiency has been shown to be associated with inflammatory bowel disease (IBD). However, folate concentrations are poorly delineated in children with IBD. Objective: The objective was to compare folate concentrations between children with newly diagnosed IBD and healthy controls. Design: Red blood cell folate (RBCF) and whole-blood folate (WBF) concentrations were measured in 78 children (mean age: 12.8 +/- 2.7 y): 22 patients with newly diagnosed untreated Crohn disease, 11 patients with ulcerative colitis, 4 patients with indeterminate colitis, and 41 controls. Vitamin supplementation and dietary intakes determined by food-frequency questionnaire were recorded for 20 IBD patients and 28 controls. Results: RBCF concentrations were 19.4% lower in controls (587.0 +/- 148.6 ng/mL) than in patients (728.7 +/- 185.8 ng/mL; P = 0.0004), and WBF concentrations were 11.1% lower in controls (218.2 +/- 49.7 ng/mL) than in patients (245.3 +/- 59.1 ng/mL; P = 0.031). Total folate intake was 18.8% higher in controls (444.7 +/- 266.7 mu g/d) than in IBD patients (361.1 +/- 230.6 mu g/d), but this difference was not statistically significant (P = 0.264). Folate intakes were below the Recommended Dietary Allowance (200-400 mu g/d), adjusted for age and sex, in 35.4% of study subjects. Conclusions: In contrast with previous evidence of folate deficiency in adult IBD patients, our data indicate higher folate concentrations in children with newly diagnosed untreated IBD than in controls. This finding was unexpected, especially in light of the higher dietary folate intakes and hematocrit values in children without IBD. The influence of IBD therapy on folate metabolism and the long-term clinical implications of high RBCF and WBF concentrations at the time of IBD diagnosis should be explored further. Am J Clin Nutr 2009; 89: 545-50. C1 [Heyman, Melvin B.; Garnett, Elizabeth A.; Jose, Folashade A.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. [Shaikh, Nishat; Huen, Karen; Holland, Nina] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. [Harmatz, Paul; Stege, Erin] Childrens Hosp & Res Ctr, Oakland, CA USA. Childrens Ctr Digest Hlth Care, Atlanta, GA USA. [Cohen, Stanley A.; Gold, Benjamin D.] Emory Univ, Sch Med, Atlanta, GA USA. [Winter, Harland S.] MassGen Hosp Children, Boston, MA USA. [Baldassano, Robert N.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Kirschner, Barbara S.] Univ Chicago, Comer Childrens Hosp, Chicago, IL 60637 USA. [Ferry, George D.] Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA. RP Heyman, MB (reprint author), Univ Calif San Francisco, Dept Pediat, 500 Parnassus Ave,MU 4 E,Box 0136, San Francisco, CA 94143 USA. EM mheyman@peds.ucsf.edu FU NIH [R03 DK063187, M01 RR01271, UL1 RR024131, K24 DK060617, T32 DK007762-31S1] FX Supported in part by NIH grants R03 DK063187 (to MBH, NH, and PH), M01 RR01271, and UL1 RR024131 (Pediatric Clinical Research Centers at UCSF and Children's Hospital Oakland); K24 DK060617 (to MBH); T32 DK007762-31S1 (to FAJ); the family of Joel Barnett (to BSK); and the family of John Fullerton (to MBH). NR 23 TC 7 Z9 8 U1 2 U2 3 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD FEB 1 PY 2009 VL 89 IS 2 BP 545 EP 550 DI 10.3945/ajcn.2008.26576 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 396RL UT WOS:000262608700012 PM 19116333 ER PT J AU Bagramian, RA Garcia-Godoy, F Volpe, AR AF Bagramian, Robert A. Garcia-Godoy, Franklin Volpe, Anthony R. TI The global increase in dental caries. A pending public health crisis SO AMERICAN JOURNAL OF DENTISTRY LA English DT Editorial Material ID EARLY-CHILDHOOD CARIES; BRAZILIAN CHILDREN; ORAL-HEALTH; PHILIPPINES; PREVALENCE; EXPERIENCE; POVERTY; CHINA AB A current review of the available epidemiological data from many countries clearly indicates that there is a marked increase in the prevalence of dental caries. This global increase in dental caries prevalence affects children as well as adults, primary as well as permanent teeth, and coronal as well as root surfaces. This increase in dental caries signals a pending public health crisis. Although there are differences of opinion regarding the cause of this global dental caries increase, the remedy is well known: a return to the public health strategies that were so successful in the past, a renewed campaign for water fluoridation, topical fluoride application, the use of fluoride rinses, a return to school oral health educational programs, an emphasis on proper tooth brushing with a fluoride dentifrice, as well as flossing, a proper diet and regular dental office visits. If these remedies are not initiated, there could be a serious negative impact upon the future oral health (and systemic health) of the global community, as well as a strain on the dental profession along with a major increase in the cost of dental services. (Am J Dent 2009,22:3-8). C1 [Bagramian, Robert A.] Univ Michigan, Sch Dent, Ann Arbor, MI 48109 USA. [Bagramian, Robert A.] American Univ, Coll Hlth Sci, Yerevan, Armenia. [Garcia-Godoy, Franklin] Nova SE Univ, Biosci Res Ctr, Coll Dent Med, Ft Lauderdale, FL 33314 USA. [Garcia-Godoy, Franklin] Forsyth Inst, Boston, MA USA. [Volpe, Anthony R.] Colgate Palmol Co, Sci Affairs, Piscataway, NJ USA. RP Bagramian, RA (reprint author), Univ Michigan, Sch Dent, Ann Arbor, MI 48109 USA. EM robtbagr@umich.edu NR 35 TC 190 Z9 199 U1 8 U2 47 PU MOSHER & LINDER, INC PI WESTON PA 318 INDIAN TRACE SUITE 500, WESTON, FL 33326 USA SN 0894-8275 J9 AM J DENT JI Am. J. Dent. PD FEB PY 2009 VL 22 IS 1 BP 3 EP 8 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 414FS UT WOS:000263849900001 PM 19281105 ER PT J AU Dabanoglu, A Wood, C Garcia-Godoy, F Kunzelmann, KH AF Dabanoglu, Alp Wood, Claudia Garcia-Godoy, Franklin Kunzelmann, Karl-Heinz TI Whitening effect and morphological evaluation of hydroxyapatite materials SO AMERICAN JOURNAL OF DENTISTRY LA English DT Article ID SCANNING ELECTRON-MICROSCOPY; FIELD-EMISSION SEM; COMPOSITE RESIN; IN-VITRO; BOVINE ENAMEL; HUMAN DENTIN; TOOTHBRUSH; ADHESION; EFFICACY; AGENTS AB To measure the efficacy of the whitening effect of non-oxidizing and non-acidic nano- and micro-hydroxyapatite materials on the enamel surface and to evaluate the surface changes after treatment. Methods: Three hydroxyapatite suspensions and two hydroxyapatite mixtures in dissolvable polymer films were applied to a total of 30 extracted caries-free human premolars. After the last material application, a hydrodynamic shear force was generated and applied for 2 minutes to all teeth to simulate mechanical loading of the surface. The tooth color was measured with a dental spectrophotometer. The mean changes of the L*a*b* values between different measurements in each group were expressed as Delta E and were analyzed with ANOVA and the Tukey's post-hoc test. Results: The groups of the nano-hydroxyapatite, the hydroxyapatite-nanocrystals and the tricalcium-phosphate exhibited significant Delta E values between baseline and after hydrodynamic shear force application (P<0.05). In conclusion, the materials used in the Study are very promising alternatives to oxidizing bleaching agents. (Am J Dent 2009;22:23-29). C1 [Dabanoglu, Alp; Kunzelmann, Karl-Heinz] Univ Munich, Dept Operat Dent & Periodontol, D-80336 Munich, Germany. [Wood, Claudia] BASF AG, Mkt Cosmet Ingredients, D-6700 Ludwigshafen, Germany. [Garcia-Godoy, Franklin] Nova SE Univ, Biosci Res Ctr, Coll Dent Med, Ft Lauderdale, FL 33314 USA. [Garcia-Godoy, Franklin] Forsyth Inst, Boston, MA USA. RP Kunzelmann, KH (reprint author), Univ Munich, Fac Dent, Dept Operat Dent, Goethe Str 70, D-80336 Munich, Germany. EM karl-heinz@kunzelmann.de FU Center of Nano-Science and Department of Physics of Ludwig Maximilians University, Munich, Germany FX The research was supported by the Center of Nano-Science and Department of Physics of Ludwig Maximilians University, Munich, Germany. We would like to thank especially Dipl. Ing. Stefan Schoffberger for his technical support during the SEM evaluations. NR 35 TC 5 Z9 5 U1 1 U2 5 PU MOSHER & LINDER, INC PI WESTON PA 318 INDIAN TRACE SUITE 500, WESTON, FL 33326 USA SN 0894-8275 J9 AM J DENT JI Am. J. Dent. PD FEB PY 2009 VL 22 IS 1 BP 23 EP 29 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 414FS UT WOS:000263849900005 PM 19281109 ER PT J AU Taschner, M Frankenberger, R Garcia-Godoy, F Rosenbusch, S Petschelt, A Kramer, N AF Taschner, Michael Frankenberger, Roland Garcia-Godoy, Franklin Rosenbusch, Silke Petschelt, Anselm Kramer, Norbert TI IPS Empress inlays luted with a self-adhesive resin cement after 1 year SO AMERICAN JOURNAL OF DENTISTRY LA English DT Article ID MICROTENSILE BOND STRENGTH; CERAMIC INLAYS; MARGINAL ADAPTATION; IN-VITRO; LUTING AGENTS; TECHNIQUE-SENSITIVITY; CLINICAL-EVALUATION; SEATING PRESSURE; RINSE ADHESIVES; DENTIN AB Purpose: To prospectively compare the clinical performance of two different resin composites for luting IPS Empress inlays and onlays. Methods: 83 IPS Empress restorations were placed in 30 subjects. All restorations were inserted under rubber dam. 43 inlays/onlays were luted with a self-adhesive resin cement [RelyX Unicem (RX)]. A multi-step adhesive (Syntac) was used with Variolink II low viscosity (SV) and served as control (n=40). The restorations were evaluated after 2 weeks: Baseline = 1st recall (R1), after 6 months (R2) and after 1 year (R3) by two calibrated examiners using the modified USPHS criteria, Results: From RI to R3, one failure was noticed in the SV group (R2) due to marginal enamel chipping. After 1 year of clinical service, SV revealed significantly better results regarding color match and integrity inlay (Mann-Whitney U-test, P<0.05). No statistically significant differences were observed between SV and RX for the remaining criteria (Mann-Whitney U-test, P>0.05). (Am J Dent 2009;22:55-59). C1 [Taschner, Michael; Frankenberger, Roland; Rosenbusch, Silke; Petschelt, Anselm] Univ Erlangen Nurnberg, Dent Clin Operat Dent & Periodontol 1, Univ Med Ctr Erlangen, D-91054 Erlangen, Germany. [Garcia-Godoy, Franklin] Nova SE Univ, Biosci Res Ctr, Coll Dent Med, Ft Lauderdale, FL 33314 USA. [Garcia-Godoy, Franklin] Forsyth Inst, Boston, MA USA. [Kramer, Norbert] Tech Univ Dresden, Dept Pediat Dent, Univ Med Ctr Carl Gustav Carus, Dresden, Germany. RP Frankenberger, R (reprint author), Univ Erlangen Nurnberg, Dent Clin Operat Dent & Periodontol 1, Univ Med Ctr Erlangen, Glueckstr 11, D-91054 Erlangen, Germany. EM frankbg@dent.uni-erlangen.de FU 3M Espe, Seefeld, Germany FX Supported by 3M Espe, Seefeld, Germany. NR 47 TC 15 Z9 15 U1 0 U2 1 PU MOSHER & LINDER, INC PI WESTON PA 318 INDIAN TRACE SUITE 500, WESTON, FL 33326 USA SN 0894-8275 J9 AM J DENT JI Am. J. Dent. PD FEB PY 2009 VL 22 IS 1 BP 55 EP 59 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 414FS UT WOS:000263849900010 PM 19281114 ER PT J AU Radeos, MS Cydulka, RK Rowe, BH Barr, RG Clark, S Camargo, CA AF Radeos, Michael S. Cydulka, Rita K. Rowe, Brian H. Barr, R. Graham Clark, Sunday Camargo, Carlos A., Jr. TI Validation of self-reported chronic obstructive pulmonary disease among patients in the ED SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID PROPORTIONAL VENN-DIAGRAM; LUNG-DISEASE; UNITED-STATES; DIAGNOSIS; COPD C1 [Radeos, Michael S.; Clark, Sunday; Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med,EMNet Coordinating Ctr, Boston, MA 02114 USA. [Radeos, Michael S.] New York Hosp Queens, Dept Emergency Med, Flushing, NY USA. [Radeos, Michael S.] Cornell Univ, Weill Med Coll, New York, NY 10021 USA. [Rowe, Brian H.] Univ Alberta, Dept Emergency Med, Edmonton, AB, Canada. [Cydulka, Rita K.] Metrohlth Med Ctr, Dept Emergency Med, Cleveland, OH USA. [Barr, R. Graham] Columbia Univ, Dept Med, Med Ctr, Div Gen Med, New York, NY USA. RP Camargo, CA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med,EMNet Coordinating Ctr, Boston, MA 02114 USA. EM ccamargo@partners.org FU National Institutes of Health (Bethesda, Md) [HL-07427, ES-07069, HL-63841]; Government of Canada (Ottawa, Ontario); Boehringer-Ingelheim (Ridgefield, Conn) FX Doctors Radeos and Bars were supported by grant HL-07427; Miss Clark, by grant ES-07069; and Doctor Camargo, by grant HL-63841, all from the National Institutes of Health (Bethesda, Md). Doctor Rowe is supported by the 21st Century Research Chairs Program from the Government of Canada (Ottawa, Ontario). Additional funding was provided by an unrestricted grant from Boehringer-Ingelheim (Ridgefield, Conn). NR 13 TC 11 Z9 11 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD FEB PY 2009 VL 27 IS 2 BP 191 EP 196 DI 10.1016/j.ajem.2008.01.011 PG 6 WC Emergency Medicine SC Emergency Medicine GA 416DN UT WOS:000263985600010 PM 19371527 ER PT J AU Laine, L Goldkind, L Curtis, SP Connors, LG Zhang, YQ Cannon, CP AF Laine, Loren Goldkind, Lawrence Curtis, Sean P. Connors, Laurine G. Zhang Yanqiong Cannon, Christoper P. TI How Common Is Diclofenac-Associated Liver Injury? Analysis of 17,289 Arthritis Patients in a Long-Term Prospective Clinical Trial SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; MULTINATIONAL ETORICOXIB; RHEUMATOID-ARTHRITIS; ADVERSE REACTIONS; HEPATOTOXICITY; OSTEOARTHRITIS; EXPERIENCE; PROGRAM AB OBJECTIVES: Few data are available from prospective trials to define the hepatotoxicity of diclofenac, the most widely prescribed non-steroidal anti-inflammatory drug (NSAID) in the world. We determined the rate of laboratory and clinical adverse hepatic effects in a large double-blind trial of diclofenac. METHODS: Patients >= 50 years with rheumatoid arthritis or osteoarthritis were randomly assigned to diclofenac (150 mg daily) or etoricoxib (60 or 90 mg daily). Patients with hepatic disease or who reported >= 14 alcoholic drinks weekly were excluded. Patients had visits (with liver tests) every 4 months and were contacted by phone between visits and every 6 months after discontinuation until the end of the study. Causality assessment was performed for liver-related hospitalizations, Hy's cases (serious adverse events with AST or ALT >3x upper limit of normal (ULN) and bilirubin >2xULN), and liver failure/transplant/death. RESULTS: A total of 17,289 patients received diclofenac for a mean of 18 months. Liver end points with diclofenac were ALT/AST>3xULN: 527(3.1%); ALT/AST>10xULN: 86(0.5%); liver-related hospitalizations: 4(0.023%); Hy's cases: 2(0.012%); liver failure/death/transplant: 0. Aminotransferase elevations occurred primarily within the first 4-6 months of therapy, whereas liver-related hospitalizations occurred between 9 days and 21 months. CONCLUSIONS: Diclofenac is commonly associated with aminotransferase elevations, generally in the first 4-6 months of therapy. Clinical liver events requiring hospitalization are relatively rare (23/100,000 patients), but may develop early or late in therapy. The markedly increased rate of aminotransferase elevation with diclofenac may not be paralleled by a proportional marked increase in clinical liver events, although clinical events potentially also may be decreased with regular monitoring in a clinical trial setting. C1 [Laine, Loren] Univ So Calif, Med Ctr, Los Angeles, CA 90033 USA. [Goldkind, Lawrence] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Curtis, Sean P.; Connors, Laurine G.; Zhang Yanqiong] Merck Res Labs, Rahway, NJ USA. [Cannon, Christoper P.] Harvard Univ, Sch Med, TIMI Study Grp, Boston, MA USA. RP Laine, L (reprint author), Univ So Calif, Med Ctr, Room 12-137 LA Cty,1200 N State St, Los Angeles, CA 90033 USA. EM llaine@usc.edu FU Accumetrics; AstraZeneca; Bristol-Myers Squibb; Glaxo Smith Kline; Merck; Sanofi-Aventis; Schering Plough FX Research support: Christopher Cannon: Accumetrics, AstraZeneca, Bristol-Myers Squibb, Glaxo Smith Kline, Merck, Sanofi-Aventis, Schering Plough. NR 17 TC 57 Z9 57 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD FEB PY 2009 VL 104 IS 2 BP 356 EP 362 DI 10.1038/ajg.2008.149 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 410GU UT WOS:000263566300017 PM 19174782 ER PT J AU Suhrie, EM Hanlon, JT Jaffe, EJ Sevick, MA Ruby, CM Aspinall, SL AF Suhrie, Erin M. Hanlon, Joseph T. Jaffe, Emily J. Sevick, Mary Ann Ruby, Christine M. Aspinall, Sherrie L. TI Impact of a Geriatric Nursing Home Palliative Care Service on Unnecessary Medication Prescribing SO AMERICAN JOURNAL OF GERIATRIC PHARMACOTHERAPY LA English DT Article DE palliative care; unnecessary drug use; Medication Appropriateness Index; geriatrics ID ADVERSE DRUG EVENTS; OLDER-PEOPLE; HOSPICE CARE; APPROPRIATENESS; POLYPHARMACY; MANAGEMENT; QUALITY; LIFE; THERAPY; PAIN AB Background: There is a lack of studies concerning improvement of medication use in palliative care patients in nursing homes. Objective: This study was conducted to evaluate whether a geriatric palliative care team reduced unnecessary medication prescribing for elderly veterans residing in a nursing home. Methods: This was a retrospective, descriptive study of patients who died while residing in a geriatric palliative care unit between August 1, 2005, and July 31, 2007. Prescribed medications were evaluated using the Unnecessary Drug Use Measure, which contains 3 items from the Medication Appropriateness Index concerning lack of indication, lack of effectiveness, and therapeutic duplication. This measure was applied at 2 time points: on transfer/admission to the palliative care unit and at the last 30-day pharmacist medication review before death. Paired t tests and McNemar tests were used to compare medication use at these 2 points. Results: Eighty-nine patients were included in the study. The majority were male (97.8%) and white (78.7%), with a mean (SD) age of 79.7 (7.8) years. The median length of stay on the unit was 39.0 days, and the mean number of chronic medical conditions was 8.4 (4.3). At baseline, the mean number of scheduled medications was 9.7 (4.3). The number Of unnecessary medications per patient decreased from a mean of 1.7 (1.5) at admission to 0.6 (0.8) at closeout (P = 0.003). The decrease was seen in all 3 categories of the Unnecessary Drug Use Measure. Conclusions: The geriatric palliative care team was associated with a reduction in the number of unnecessary medications prescribed for older veterans in this nursing home. Future studies should evaluate the impact of decreasing unnecessary prescribing on clinical outcomes such as adverse drug reactions. (Am J Geriatr Pharmacother. 2009;7:20-25) (C) 2009 Excerpta Medica Inc. C1 [Hanlon, Joseph T.; Sevick, Mary Ann; Aspinall, Sherrie L.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15206 USA. [Suhrie, Erin M.] VA Pittsburgh Healthcare Syst, Dept Pharm, Pittsburgh, PA 15206 USA. [Hanlon, Joseph T.; Ruby, Christine M.; Aspinall, Sherrie L.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15261 USA. [Hanlon, Joseph T.; Jaffe, Emily J.; Sevick, Mary Ann] VA Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA 15206 USA. [Hanlon, Joseph T.; Jaffe, Emily J.; Ruby, Christine M.] Univ Pittsburgh, Sch Med, Dept Med, Div Geriatr & Gerontol, Pittsburgh, PA USA. [Sevick, Mary Ann] Univ Pittsburgh, Sch Med, Dept Med, Div Gen Internal Med, Pittsburgh, PA USA. [Sevick, Mary Ann] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. [Aspinall, Sherrie L.] Hines VA Med Ctr, VA Ctr Medicat Safety, Hines, IL USA. RP Aspinall, SL (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot 151CH, 7180 Highland Dr, Pittsburgh, PA 15206 USA. EM sherrie.aspinall@va.gov FU National Institutes of Health [P30AGO24827, ROIAGO27017]; Veterans Affairs Health Services Research and Development [IIR-06-062] FX This study was supported in part by National Institutes of Health grants P30AGO24827 and ROIAGO27017 and Veterans Affairs Health Services Research and Development grant IIR-06-062 to Dr. Hanlon. The authors thank Yazan Rournard, NIS, MBA, for statistical support. NR 21 TC 18 Z9 19 U1 2 U2 7 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 1543-5946 J9 AM J GERIATR PHARMAC JI Am. J. Geriatr. Pharmacother. PD FEB PY 2009 VL 7 IS 1 BP 20 EP 25 DI 10.1016/j.amjopharm.2009.02.001 PG 6 WC Geriatrics & Gerontology; Pharmacology & Pharmacy SC Geriatrics & Gerontology; Pharmacology & Pharmacy GA 413RK UT WOS:000263810000003 PM 19281937 ER PT J AU Spira, AP Stone, K Beaudreau, SA Ancoli-Israel, S Yaffe, K AF Spira, Adam P. Stone, Katie Beaudreau, Sherry A. Ancoli-Israel, Sonia Yaffe, Kristine TI Anxiety Symptoms and Objectively Measured Sleep Quality in Older Women SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article; Proceedings Paper CT 60th Annual Meeting of the Gerontological-Society-of-America CY NOV 16-20, 2007 CL San Francisco, CA SP Gerontol Soc Amer DE Anxiety; sleep; older adults; depression; actigraphy ID OUTPATIENT ELECTIVE SURGERY; COGNITIVE FUNCTION; ADULTS; POPULATION; PREVALENCE; DISORDERS; LIFE; DISTURBANCES; INFLAMMATION; DEPRESSION AB Objectives: Few studies have examined the association between anxiety symptoms and objectively measured sleep quality in older adults. The authors determined this association in a large cohort of very old community-dwelling women. Design: Cross-sectional. Setting: Participants' homes, sites of the Study of Osteoporotic Fractures. Participants: Three thousand forty women (mean age: 83.6 years) enrolled in a prospective study of aging. Measurements: Participants completed the Goldberg Anxiety Scale (ANX), the 15-item Geriatric Depression Scale (GDS), and >= 3 nights of actigraphy-a method of measuring sleep by recording wrist movement with a device called an actigraph. Elevated anxiety symptoms were defined as ANX >= 6. Elevated depressive symptoms were defined as GDS >= 6. Results: Participants' mean ANX score was 1.4 (standard deviation: 2.2); 9.2% (N = 280) had ANX >= 6. Elevated anxiety symptoms were associated with greater odds of poor sleep efficiency (odds ratio [OR]: 1.73, 95% confidence interval [CI]: 1.34, 2.23) and time awake after sleep onset (OR: 1.64, 95% CI: 1.27, 2.11). Associations remained after adjustment for GDS >= 6, antianxiety medications, and other potential confounders (sleep efficiency OR: 1.50, 95% CI: 1.15, 1.97; time awake after sleep onset OR: 1.33, 95% CI: 1.01, 1.75). Anxiety symptoms were not associated with other sleep parameters. Conclusion: Findings suggest that elevated anxiety symptoms are independently associated with poor objectively measured sleep efficiency and elevated sleep fragmentation in very old women, after accounting for significant depressive symptoms, medical comorbidities, and use of antianxiety medications. (Am J Geriatr Psychiatry 2009; 17:136-143) C1 [Spira, Adam P.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Spira, Adam P.; Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Spira, Adam P.; Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. [Stone, Katie] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Beaudreau, Sherry A.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA. [Beaudreau, Sherry A.] Sierra Pacific Mental Illness Res Educ & Clin Ctr, Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Ancoli-Israel, Sonia] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Ancoli-Israel, Sonia] San Diego Vet Affairs Healthcare Syst, San Diego, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. RP Spira, AP (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, 624 N Broadway,Hampton House,Room 794, Baltimore, MD 21205 USA. EM aspira@jhsph.edu FU NIA NIH HHS [R01 AG027576-24, 2 R01 AG005394-22A1, AG05394, L30 AG030938-01, T32 AG000212-14, 2 R01 AG027574-22A1, AG05407, R01 AG005394, R01 AG005394-24, R01 AG005407-23, R01 AG027574-24, R01 AG027576, R01 AG027576-22, T32 AG000212, R01 AG027574, R01 AG005407, L30 AG030938]; NIAMS NIH HHS [R01 AR035584-21, R01 AR035584, AR35584, R01 AR035582, AR35583, AR35582, R01 AR035583] NR 41 TC 22 Z9 23 U1 1 U2 2 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 FEB PY 2009 VL 17 IS 2 BP 136 EP 143 DI 10.1097/JGP.0b013e3181871345 PG 8 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 548DC UT WOS:000273938800006 PM 19155746 ER PT J AU Gehrman, PR Connor, DJ Martin, JL Shochat, T Corey-Bloom, J Ancoli-Israel, S AF Gehrman, Philip R. Connor, Donald J. Martin, Jennifer L. Shochat, Tamar Corey-Bloom, Jody Ancoli-Israel, Sonia TI Melatonin Fails to Improve Sleep or Agitation in Double-Blind Randomized Placebo-Controlled Trial of Institutionalized Patients With Alzheimer Disease SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE Alzheimer; sleep; agitation; melatonin; dementia ID CIRCADIAN-RHYTHMS; NURSING-HOME; DEMENTIA AB Objectives: Patients with Alzheimer dementia often display both agitated behavior and poor sleep. Given that the disease is often associated with low endogenous levels of melatonin, exogenous melatonin administration may lead to improvements in sleep and agitation. Design: Randomized, placebo-controlled study. Setting: Nursing homes in San Diego, CA, metropolitan area. Participants: Subjects were patients with probable Alzheimer disease. Intervention: Melatonin (8.5 mg immediate release and 1.5 mg sustained release) (N = 24) or placebo (N = 17) administered at 10: 00 P. M. for 10 consecutive nights. The protocol consisted of baseline (3 days), treatment (10 days), and posttreatment (5 days) phases. Measurements: Sleep was measured continuously using actigraphy. Agitation was rated using both the Agitated Behavior Rating Scale and the Cohen-Mansfield Agitation Inventory. Treatment effects were examined both across the 24-hr day and separately by nursing shift. Results: There were no significant effects of melatonin, compared with placebo, on sleep, circadian rhythms, or agitation. Conclusion: This study failed to find a beneficial effect of exogenous melatonin, consistent with a number of other studies. The lack of efficacy may be related to the absence of a true treatment effect or to the superphysiologic dose of melatonin used. (Am J Geriatr Psychiatry 2009; 17:166-169) C1 [Gehrman, Philip R.] Hosp Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Connor, Donald J.] Cleo Roberts Ctr Clin Res, Sun Hlth Res Inst, Sun City, AZ USA. [Martin, Jennifer L.] Geriatr Res Educ & Clin Ctr, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Martin, Jennifer L.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Shochat, Tamar] Univ Haifa, Dept Nursing, IL-31999 Haifa, Israel. [Corey-Bloom, Jody; Ancoli-Israel, Sonia] Vet Affairs San Diego Healthcare Syst, San Diego, CA USA. [Corey-Bloom, Jody] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. [Ancoli-Israel, Sonia] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. RP Ancoli-Israel, S (reprint author), Univ Calif San Diego, Dept Psychiat, 9500 Gilman Dr,Mail Code 0603, La Jolla, CA 92093 USA. EM sancoliisrael@ucsd.edu FU NIA [AG08415, P50 AG05131, K23 AG028452]; Research Service of the Veterans Affairs San Diego Healthcare System FX This study was supported by NIA AG08415 (to SAI), P50 AG05131, NIA K23 AG028452 (to JLM) and the Research Service of the Veterans Affairs San Diego Healthcare System. NR 10 TC 62 Z9 66 U1 4 U2 9 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 FEB PY 2009 VL 17 IS 2 BP 166 EP 169 DI 10.1097/JGP.0b013e318187de18 PG 4 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 548DC UT WOS:000273938800009 PM 19155748 ER PT J AU Ullian, ME Beck, CN Walker, LP Fitzgibbon, WR Morinelli, TA AF Ullian, Michael E. Beck, C. Nicole Walker, Linda P. Fitzgibbon, Wayne R. Morinelli, Thomas A. TI Thiol Antioxidants Regulate Angiotensin II AT1 and Arginine Vasopressin V1 Receptor Functions Differently in Vascular Smooth Muscle Cells SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article ID EPIDERMAL-GROWTH-FACTOR; PROTEIN-KINASE ACTIVATION; EXTRACELLULAR DOMAINS; DISULFIDE BRIDGES; OXIDATIVE STRESS; LIGAND-BINDING; RAT; IDENTIFICATION; RESIDUES; TRANSACTIVATION AB BACKGROUND We compared the effects of the sulfhydryl-containing (thiol) antioxidant dithiothreitol (DTT), which disrupts disulfide bonds, on cell signaling through angiotensin II (Angll) Type 1 receptors (AT1Rs) and arginine vasopressin (AVP)V1 receptors (V1Rs). The AT1R contains two extracellular disulfides bonds but its ligand contains none, whereas the V1R contains no extracellular disufides bonds but its ligand contains 1. METHODS We measured radioligand binding, intracellular calcium responses, and extracellular signal-regulated kinase phosphorylation in cultured rat aortic vascular smooth muscle cells and alterations in urine osmolality in intact rats. RESULTS Preincubation of cells with DTT, a maneuver designed to target receptor disulfides, resulted in concentration-dependent decreases in specific (125)I-Angll binding to AT1Rs and acute angiotensin-stimulated intracellular calcium mobilization but no decreases in specific (125)I-AVP binding to V1Rs or AVP-stimulated intracellular calcium mobilization. In contrast, preincubation of the ligands with DTT followed by acute exposure to the cells, a maneuver designed to target ligand disulfides, blunted calcium mobilization to AVP robustly but to Angll only minimally. In intact rats, the increase in urine osmolality caused by subcutaneous injection with the AVP analogue desmopressin was significantly diminished when the analogue was preincubated with an excess of DTT. CONCLUSION DTT inhibits cell signaling to Angll AT1Rs and AVPV1Rs, at least in part through disruption of disulfide linkages, but the pattern of response depends upon whether disulfides of ligand or receptor are targeted. C1 [Ullian, Michael E.; Beck, C. Nicole; Walker, Linda P.; Fitzgibbon, Wayne R.; Morinelli, Thomas A.] Med Univ S Carolina, Ralph H Johnson Vet Adm Hosp, Dept Med, Div Nephrol, Charleston, SC 29425 USA. RP Ullian, ME (reprint author), Med Univ S Carolina, Ralph H Johnson Vet Adm Hosp, Dept Med, Div Nephrol, Charleston, SC 29425 USA. EM ullianme@musc.edu FU Dialysis Clinic Incorporation, Nashville, TN FX These results were reported in preliminary form at the annual meetings of the American Society of Nephrology in San Diego, CA (November 2006) and in San Francisco, CA (November 2007). These studies were supported by funds from Dialysis Clinic Incorporation, Nashville, TN. NR 29 TC 3 Z9 3 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD FEB PY 2009 VL 22 IS 2 BP 221 EP 227 DI 10.1038/ajh.2008.323 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 395PZ UT WOS:000262537300019 PM 19039312 ER PT J AU Brooks, WW Conrad, CH Robinson, KG Colucci, WS Bing, OHL AF Brooks, Wesley W. Conrad, Chester H. Robinson, Kathleen G. Colucci, Wilson S. Bing, Oscar H. L. TI L-Arginine Fails to Prevent Ventricular Remodeling and Heart Failure in the Spontaneously Hypertensive Rat SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article ID CONVERTING ENZYME-INHIBITION; CHRONIC-RENAL-FAILURE; ORAL L-ARGININE; CARDIAC-HYPERTROPHY; MYOCARDIAL FIBROSIS; ANGIOTENSIN-II; BLOOD-PRESSURE; DOUBLE-BLIND; REGRESSION; SUPPLEMENTATION AB BACKGROUND The effects of long-term oral administration Of L-arginine, a substrate for nitric oxide (NO) production, on left ventricular (LV) remodeling, myocardial function and the prevention of heart failure (HF) was compared to the angiotensin-converting enzyme (ACE) inhibitor captopril in a rat model of hypertensive HF (aged spontaneously hypertensive rat (SHR)). METHODS SHRs and age-matched normotensive Wistar-Kyoto (WKY) rats were assigned to either no treatment, treatment with L-arginine (7.5 g/l in drinking water) or captopril (1 g/l in drinking water) beginning at 14 months of age, a time when SHRs exhibit stable compensated hypertrophy with no hemodynamic impairment; animals were studied at 23 months of age or at the time of HF. RESULTS In untreated SHR, relative to WKY, there was significant LV hypertrophy, myocardial fibrosis, and isolated LV muscle performance and response to isoproterenol (ISO) were depressed; and, 7 of 10 SHRs developed HF. Captopril administration to six SHRs attenuated hypertrophy and prevented impaired inotropic responsiveness to ISO, contractile dysfunction, fibrosis, increased passive stiffness, and HF. In contrast, L-arginine administration to SHR increased LV hypertrophy and myocardial fibrosis while cardiac performance was depressed; and 7 of 9 SHRs developed HF. In WKY, L-arginine treatment but not captopril resulted in increased LV weight and the contractile response to ISO was blunted. Neither L-arginine nor captopril treatment of WKY changed fibrosis and HF did not occur. CONCLUSION These data demonstrate that in contrast to captopril, longterm treatment with L-arginine exacerbates age-related cardiac hypertrophy, fibrosis, and did not prevent contractile dysfunction or the development of HF in aging SHR. C1 [Brooks, Wesley W.; Conrad, Chester H.; Robinson, Kathleen G.; Colucci, Wilson S.; Bing, Oscar H. L.] VA Boston Healthcare Syst, Res Serv, Boston, MA USA. [Brooks, Wesley W.; Conrad, Chester H.; Robinson, Kathleen G.; Colucci, Wilson S.; Bing, Oscar H. L.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. RP Brooks, WW (reprint author), VA Boston Healthcare Syst, Res Serv, Boston, MA USA. EM brooksww@bu.edu FU Department of Veterans Affairs FX This work was supported by medical research funds (Merit Review and REAP grants) from the Department of Veterans Affairs. NR 37 TC 11 Z9 11 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD FEB PY 2009 VL 22 IS 2 BP 228 EP 234 DI 10.1038/ajh.2008.334 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 395PZ UT WOS:000262537300020 PM 19057517 ER PT J AU Risa, KJ McAndrew, JM Muder, RR AF Risa, Kathleen J. McAndrew, Janet M. Muder, Robert R. TI Influenza outbreak management on a locked behavioral health unit SO AMERICAN JOURNAL OF INFECTION CONTROL LA English DT Article ID CARE WORKERS; VACCINATION; DISORDERS; SERVICES AB Background: In January 2006, 8 patients on a locked behavioral health (BH) ward were identified with influenza-like illness (ILI) based on syndrome of fever. malaise, myalgia, cough, and rhinitis. Two patients initially had rapid antigen testing positive for influenza and confirmed by polymerase chain reaction. All patients present on the ward (N = 26) had been ordered influenza immunizations 6 weeks earlier: 46% (12/26) were immunized, 42% (11/26) refused, 12% (3126) had no record of immunization. All direct care staff who worked on the unit during the outbreak had been offered immunizations in the fall: 55% (22/40) were immunized. Methods: When first symptoms were identified, provider notified infection control nurse and hospital epidemiologist, who instituted control measures: patients were confined to unit, unit was closed to admissions, nonimmunized asymptomatic patients were offered immunization, temperatures were recorded every 4 hours, and nonimmunized providers were offered immunizations and prophylaxis. Patients with ILI were either admitted to acute care and placed in Droplet/Contact Precautions until afebrile for 48 hours or managed on the unit with modified isolation. All patients remaining on the unit were instructed in hand hygiene and respiratory etiquette: asymptomatic patients were offered oseltamivir phosphate prophylaxis; and previously nonimmunized patients and staff were again offered the vaccine. Results: Twenty-six patients and 28 staff were on the unit during the outbreak. Eight patients and 8 staff members reported ILI within 5 days. Of the ill patients, 3 had been immunized, 5 had not (2 refused, 3 reason unclear presumed to have refused), and 4 were admitted to acute care and placed in Droplet/Contact Precautions until asymptomatic for 48 hours. Of 22 patients who remained on the unit. 4 were symptomatic: 18 asymptomatic patients took prophylaxis, and I refused 8 (89%) patients who had earlier refused vaccine were immunized. Of the 40 staff members, 55% (22/40) were immunized, and 20% (8/40) were symptomatic (all presumptive, encouraged to remain off duty). Fifty percent (4/8) of symptomatic staff had been immunized. After 7 days, no new cases had been identified, and the unit was reopened to admissions. No ill effects resulted from the prophylaxis. Conclusion: Prompt detection of ILI and institution of control measures effectively contained the outbreaks the relatively high immunization rates among both patients and staff helped curtail spread. Refusal of immunization is a long-standing problem among BH patients and staff. Our study shows importance of immunization in preventing outbreaks in inpatient BH settings. Recommendations included development of more aggressive immunization campaign for patients and staff who historically refuse and continued high priority for provider vigilance in immunization campaign and surveillance for symptoms. (Am J Infect Control 2009;37:76-8.) C1 [Muder, Robert R.] VA Pittsburgh Healthcare Syst, Infect Dis Sect, Pittsburgh, PA 15240 USA. RP Muder, RR (reprint author), VA Pittsburgh Healthcare Syst, Infect Dis Sect, Univ Dr C, Pittsburgh, PA 15240 USA. EM Robert.Muder@va.gov NR 13 TC 1 Z9 1 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-6553 J9 AM J INFECT CONTROL JI Am. J. Infect. Control PD FEB PY 2009 VL 37 IS 1 BP 76 EP 78 DI 10.1016/j.ajic.2008.05.008 PG 3 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 409BI UT WOS:000263480800013 PM 18945518 ER PT J AU De Cosmo, S Minenna, A Zhang, YY Thompson, R Miscio, G Vedovato, M Rauseo, A Saller, A Mastroianno, S Pellegrini, F Trevisan, R Fioretto, P Doria, A Trischitta, V AF De Cosmo, Salvatore Minenna, Antonio Zhang, Yuan-Yuan Thompson, Robert Miscio, Giuseppe Vedovato, Monica Rauseo, Anna Saller, Alois Mastroianno, Sandra Pellegrini, Fabio Trevisan, Roberto Fioretto, Paola Doria, Alessandro Trischitta, Vincenzo TI Association of the Q121 Variant of ENPP1 Gene With Decreased Kidney Function Among Patients With Type 2 Diabetes SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Gene polymorphism; insulin resistance; vascular diabetic complications; PC-1 ID GLOMERULAR-FILTRATION-RATE; MEMBRANE GLYCOPROTEIN PC-1; INSULIN-RESISTANCE; K121Q POLYMORPHISM; PYROPHOSPHATASE/PHOSPHODIESTERASE-1 GENE; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; METABOLIC SYNDROME; ALBUMIN EXCRETION; INCREASED RISK AB Background: Insulin resistance has a role in diabetic kidney complications. The K121Q (lysine to glutamine substitution at amino acid 121, encoded by single-nucleotide polymorphism rs1044498) variant of the ectonucleotide pyrophosphatase/phosphodiesterase gene (ENPP1) has been associated with insulin resistance and related vascular complications in patients with type 2 diabetes (T2D) in many, although not all, studies. This study investigated whether the ENPP1 Q121 variant modulates the risk of decreased glomerular filtration rate (GFR) in patients with T2D. Study Design: Cross-sectional study. Setting & Participants: 2 diabetes units from Italy (in Gargano and Padua) and 1 from the United States (Boston, MA) recruited a total of 1,392 patients with T2D. Predictor: The ENPP1 Q121 variant. Measurements: Estimated GFR from serum creatinine, urinary albumin excretion, blood pressure, hemoglobin A, c, triglycerides, total cholesterol, and high-density lipoprotein cholesterol. Outcomes: Decreased GFRs (ie, estimated GFR <60 mL/min/1.73 m(2)). Results: In the Gargano and Boston populations, according to the dominant model of inheritance, Q121 carriers (ie, individual with either KQ or QQ alleles) had an increased risk of decreased GFR: odds ratios (ORs) of 1.69 (95% confidence interval [CI], 1.1 to 2.6) and 1.50 (95% CI, 1.0 to 2.2), respectively. In the Padua set, the association was in the same direction, but did not reach formal statistical significance (OR, 1.77; 95% Cl, 0.7 to 4.5). When the 3 studies were pooled, Q121 carriers showed an increased risk of decreased GFR (OR, 1.58; 95% Cl, 1.2 to 2.1; P = 0.002). Also, pooled mean differences in absolute GFRs were different across genotype groups, with Q121 carriers showing lower GFRs compared with KK individuals (P = 0.04). Limitations: P values not approaching a genome-wide level of significance. Conclusions: Our data suggest that patients with T2D carrying the ENPP1 Q121 variant are at increased risk of decreased GFR. C1 [De Cosmo, Salvatore; Minenna, Antonio; Rauseo, Anna; Mastroianno, Sandra; Trischitta, Vincenzo] IRCCS Casa Sollievo Sofferenza, Unit Endocrinol, I-71013 San Giovanni Rotondo, FG, Italy. [Zhang, Yuan-Yuan; Thompson, Robert] Joslin Diabet Ctr, Boston, MA 02215 USA. [Miscio, Giuseppe; Pellegrini, Fabio; Trischitta, Vincenzo] IRCCS Casa Sollievo Sofferenza, Res Unit Diabet & Endocrine Dis, I-71013 San Giovanni Rotondo, FG, Italy. [Vedovato, Monica] Univ Padua, Chair Metab Dis, Padua, Italy. [Saller, Alois; Fioretto, Paola] Univ Padua, Dept Med & Surg Sci, Padua, Italy. [Pellegrini, Fabio] Consorzio Mario Negri Sud, Dept Clin Pharmacol & Epidemiol, Santa Maria Imbaro, Italy. [Trevisan, Roberto] Osped Riuniti Bergamo, Diabet Unit, I-24100 Bergamo, Italy. [Trischitta, Vincenzo] Univ Roma La Sapienza, Dept Clin Sci, Rome, Italy. RP De Cosmo, S (reprint author), IRCCS Casa Sollievo Sofferenza, Unit Endocrinol, Cappuccini 1, I-71013 San Giovanni Rotondo, FG, Italy. EM sdecosm@tin.it; vincenzo.trischitta@uniroma1.it RI De Cosmo, Salvatore/J-7420-2016; Trischitta, Vincenzo/K-1487-2016 OI De Cosmo, Salvatore/0000-0001-8787-8286; Trischitta, Vincenzo/0000-0003-1174-127X FU Italian Minister of Health; National Institutes of Health [HL73168, DK36836]; William Randolph Hearst Fellowship FX This work was supported by a research grant from the Italian Minister of Health (RF 2003), National Institutes of Health grants HL73168 and DK36836 (Genetics Core of the Diabetes and Endocrinology Research Center at the Joslin Diabetes Center), and a William Randolph Hearst Fellowship to Dr Zhang. NR 46 TC 14 Z9 14 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD FEB PY 2009 VL 53 IS 2 BP 273 EP 280 DI 10.1053/j.ajkd.2008.07.040 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 404GX UT WOS:000263140600012 PM 18950909 ER PT J AU Nandigam, RNK Viswanathan, A Delgado, P Skehan, ME Smith, EE Rosand, J Greenberg, SM Dickerson, BC AF Nandigam, R. N. K. Viswanathan, A. Delgado, P. Skehan, M. E. Smith, E. E. Rosand, J. Greenberg, S. M. Dickerson, B. C. TI MR Imaging Detection of Cerebral Microbleeds: Effect of Susceptibility-Weighted Imaging, Section Thickness, and Field Strength SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article; Proceedings Paper CT 60th Annual Meeting of the American-Academy-of-Neurology CY APR 12-19, 2008 CL Chicago, IL SP Amer Acad Neurol ID INTRACEREBRAL HEMORRHAGE; AMYLOID ANGIOPATHY; RISK-FACTORS; BRAIN; ECHO; PREVALENCE; ASSOCIATIONS; PROGRESSION; IMAGES; FOCI AB BACKGROUND AND PURPOSE: The emergence of cerebral microbleeds (CMB) as common MR imaging findings raises the question of how MR imaging parameters influence CMB detection, To evaluate the effects of modified gradient recalled-echo (GRE) MR imaging methods, we performed an analysis of sequence, section thickness, and field strength on CMB imaging properties and detection in subjects with cerebral amyloid angiopathy (CAA), a condition associated with microhemorrhage. MATERIALS AND METHODS: Multiple MR images were obtained from subjects with probable CAA, with varying sequences (GRE versus susceptibility-weighted imaging [SWI]), section thicknesses (1.2-1.5 versus 5 mm), and magnetic field strengths (1.5T versus 3T). Individual CMB were manually identified and analyzed for contrast index (lesion intensity normalized to normal-appearing white matter signal intensity) and diameter. CMB counts were compared between 1.5T thick-section GRE and thin-section SWI for 3 subjects who underwent both protocols in the same scanning session. RESULTS: With other parameters constant, use of SWI, thinner sections, and a higher field strength yielded medium-to-large gains in CMB contrast index (Cl, Cohen d 0.71-1.87). SWI was also associated with small increases in CMB diameter (Cohen d <0.3). Conventional thick-section GRE identified only 33% of CMB (103 of 310) seen on thin-section SWI. Lesions prospectively identified on GRE had significantly greater Cl and diameter measured on the GRE image than those not prospectively identified. CONCLUSIONS: The examined alternatives to conventional GRE MR imaging yield substantially improved CMB contrast and sensitivity for detection. Future studies based on these techniques will most likely yield even higher prevalence estimates for CMB. C1 [Greenberg, S. M.] Massachusetts Gen Hosp, Ctr Stroke Res, Hemorrhag Stroke Res Program, Boston, MA 02114 USA. [Dickerson, B. C.] Massachusetts Gen Hosp, Alzheimers Dis Res Ctr, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Dickerson, B. C.] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Greenberg, SM (reprint author), Massachusetts Gen Hosp, Ctr Stroke Res, Hemorrhag Stroke Res Program, 55 Fruit St,CPZ 175,Ste 300, Boston, MA 02114 USA. EM sgreenberg@partners.org RI Smith, Eric/C-5443-2012 OI Smith, Eric/0000-0003-3956-1668 FU NIA NIH HHS [R01 AG029411-02, R01 AG026484, R01 AG029411]; NINDS NIH HHS [K24 NS056207] NR 36 TC 155 Z9 174 U1 0 U2 11 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD FEB PY 2009 VL 30 IS 2 BP 338 EP 343 DI 10.3174/ajnr.A1355 PG 6 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 409FI UT WOS:000263491200022 PM 19001544 ER PT J AU Stefancyk, AL AF Stefancyk, Amanda L. TI High-Use Supplies at the Bedside SO AMERICAN JOURNAL OF NURSING LA English DT Editorial Material C1 Massachusetts Gen Hosp, Gen Med Unit, Boston, MA 02114 USA. RP Stefancyk, AL (reprint author), Massachusetts Gen Hosp, Gen Med Unit, Boston, MA 02114 USA. EM astefancyk@partners.org NR 0 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-936X J9 AM J NURS JI Am. J. Nurs. PD FEB PY 2009 VL 109 IS 2 BP 33 EP 35 PG 3 WC Nursing SC Nursing GA 403KY UT WOS:000263082700014 PM 19299992 ER PT J AU Khurana, SR Bamer, AM Turner, AP Wadhwani, RV Bowen, JD Leipertz, SL Haselkorn, JK AF Khurana, Seema R. Bamer, Alyssa M. Turner, Aaron P. Wadhwani, Rohini V. Bowen, James D. Leipertz, Steve L. Haselkorn, Jodie K. TI The Prevalence of Overweight and Obesity in Veterans with Multiple Sclerosis SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE Multiple Sclerosis; Body Mass Index; Obesity; Overweight; Health Status ID BODY-MASS INDEX; SELF-REPORTED HEIGHT; UNITED-STATES; GENDER-DIFFERENCES; DISEASE; EXERCISE; WEIGHT; ADULTS; RISK; POPULATION AB Objectives: To estimate the prevalence and factors associated with overweight and obesity in veterans with multiple sclerosis (MS) enrolled in the Veterans Health Administration (VA) and to compare the prevalence in this group with gender-specific published rates for the general population of veterans receiving outpatient care at VA medical facilities. Design: Cross-sectional cohort study linking electronic medical record information to mailed survey from 1999 to 2004. A total of 4703 veterans with MS enrolled in VA who returned questionnaires as part of two cross-sectional studies. Main outcome measures included body mass index, demographic information, Veteran RAND 36-item Health Survey, frequency of physical exercise, and other health conditions. Results: Overall, 28% of female and 42.8% of male veterans with MS were overweight. Another 25% of women and 21.2% of male veterans met the criteria for obesity. Compared with a historical cohort of veterans enrolled in the VA, veterans with MS had a slightly higher adjusted prevalence of overweight than did veterans in general (42.3% vs. 39.6%, respectively) but a lower adjusted prevalence of obesity (20.1% vs. 33.1%). In adjusted logistic regression, age, smoking, and lower levels of pain were associated with a lower likelihood of overweight or obesity. Being male, married, employed and having arthritis and diabetes were associated with a greater likelihood of overweight or obesity. Conclusions: Overweight and obesity are a problem for more than 60% of veterans with MS in the VA. Screening for overweight and obesity should be done routinely. Interventions to prevent and manage excessive weight in individuals with MS should be developed and evaluated. C1 [Turner, Aaron P.] VA Puget Sound Hlth Care Syst, Rehabil Care Serv, Seattle, WA 98108 USA. [Khurana, Seema R.] Univ Miami, Dept Rehabil Med, Coral Gables, FL 33124 USA. [Bamer, Alyssa M.; Turner, Aaron P.; Wadhwani, Rohini V.; Haselkorn, Jodie K.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Turner, Aaron P.; Leipertz, Steve L.; Haselkorn, Jodie K.] VA MS Ctr Excellence W, Seattle, WA USA. [Bowen, James D.] Evergreen Hosp, Multiple Sclerosis Ctr, Washington, DC USA. RP Turner, AP (reprint author), VA Puget Sound Hlth Care Syst, Rehabil Care Serv, S-117,1660 S Columbian Way, Seattle, WA 98108 USA. OI Turner, Aaron/0000-0001-6897-8003 FU Department of Veterans Affairs Rehabilitation Research and Development Service Career Development Award [B4927W]; VA Center of Excellence in Substance Abuse Treatment and Education; VA MS Center of Excellence West; VA Office of Quality and Performance; National Institute on Disability and Rehabilitation Research, Department of Education [H13313031129] FX This research was supported by Department of Veterans Affairs Rehabilitation Research and Development Service Career Development Award (B4927W) to Aaron Turner, Phl). Additional support was provided by the VA Center of Excellence in Substance Abuse Treatment and Education, the VA MS Center of Excellence West, and the VA Office of Quality and Performance. Additional support was also provided by a grant from the National Institute on Disability and Rehabilitation Research, Department of Education (Grant #H13313031129). NR 35 TC 32 Z9 32 U1 1 U2 4 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 FEB PY 2009 VL 88 IS 2 BP 83 EP 91 DI 10.1097/PHM.0b013e318194f8b5 PG 9 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 398NX UT WOS:000262739900001 PM 19169174 ER PT J AU Tsuji, T del Monte, F Yoshikawa, Y Abe, T Shimizu, J Nakajima-Takenaka, C Taniguchi, S Hajjar, RJ Takaki, M AF Tsuji, Tsuyoshi del Monte, Federica Yoshikawa, Yoshiro Abe, Takehisa Shimizu, Juichiro Nakajima-Takenaka, Chikako Taniguchi, Shigeki Hajjar, Roger J. Takaki, Miyako TI Rescue of Ca2+ overload-induced left ventriclur dysfunction by targeted ablation of phospholamban SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE in vivo gene transfer; percutaneous; cardiac function; systolic pressure-volume area; myocardial O-2 consumption per beat ID INCREASED OXYGEN COST; CANINE LEFT-VENTRICLE; PRESSURE-VOLUME AREA; NORMAL RAT HEARTS; O-2 USE; SARCOPLASMIC-RETICULUM; STUNNED MYOCARDIUM; MECHANICAL WORK; CONTRACTILITY; ENERGETICS AB Tsuji T, del Monte F, Yoshikawa Y, Abe T, Shimizu J, Nakajima-Takenaka C, Taniguchi S, Hajjar RJ, Takaki M. Rescue of Ca2+ overload-induced left ventriclur dysfunction by targeted ablation of phospholamban. Am J Physiol Heart Circ Physiol 296: H310-H317, 2009; doi:10.1152/ajpheart.00975.2008.-In failing hearts, a deficiency in sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA)2a results in abnormal Ca2+ handling and diminished contraction. In addition, a decrease in the phosphorylation of phospholamban (PLB) has been reported. Gene transfer of antisense PLB (asPLB) can improve contractile function in the failing human myocardium. Gene transfer of SERCA2a improves survival and the energy potential in failing hearts. The aim of present study was to evaluate whether enhancement of SERCA2a function prevents acute Ca2+ overload-induced left ventricular (LV) dysfunction in rat hearts. We ablated PLB using adenoviral gene transfer of asPLB by a new and less invasive gene delivery method, which involved a percutaneous technique. Experiments were performed on 13 excised cross-circulated rat hearts: 5 rats underwent sham operations, 4 rats underwent gene transfer of the reporter gene beta-galactosidase (Ad.beta-gal), and 4 rats underwent gene transfer of asPLB (Ad.asPLB). After clearance of high Ca2+ infused into the coronary, there was LV contractile dysfunction associated with the decreased myocardial O-2 consumption per beat (VO2) intercept (equal to decreased VO2 for Ca2+ handling in excitation-contraction coupling) of the VO2-systolic pressure-volume area (PVA; total mechanical energy per beat) linear relation in the hearts that underwent sham operation and had been infected with Ad.beta-gal. Hearts that had been infected with Ad.asPLB were rescued from LV contractile dysfunction associated with an unchanged VO2 intercept of the VO2-PVA linear relation. We conclude that SERCA2a function enhanced by adenoviral gene transfer of asPLB prevents Ca2+ overload-induced LV contractile dysfunction in terms of mechanical work and especially energetics. C1 [Tsuji, Tsuyoshi; Yoshikawa, Yoshiro; Abe, Takehisa; Shimizu, Juichiro; Nakajima-Takenaka, Chikako; Takaki, Miyako] Nara Med Univ, Dept Physiol 2, Nara 6348521, Japan. [Tsuji, Tsuyoshi; del Monte, Federica; Hajjar, Roger J.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Tsuji, Tsuyoshi; del Monte, Federica; Hajjar, Roger J.] Harvard Univ, Sch Med, Boston, MA USA. [Tsuji, Tsuyoshi; Yoshikawa, Yoshiro; Abe, Takehisa; Taniguchi, Shigeki] Nara Med Univ, Dept Thorac & Cardiovasc Surg, Nara 6348521, Japan. RP Takaki, M (reprint author), Nara Med Univ, Dept Physiol 2, 840 Shijo Cho, Nara 6348521, Japan. EM mtakaki@naramed-u.ac.jp NR 32 TC 19 Z9 19 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 EI 1522-1539 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD FEB PY 2009 VL 296 IS 2 BP H310 EP H317 DI 10.1152/ajpheart.00975.2008 PG 8 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 399DK UT WOS:000262780400009 PM 19074672 ER PT J AU Kurahashi, K Sawa, T Ota, M Kajikawa, O Hong, K Martin, TR Wiener-Kronish, JP AF Kurahashi, Kiyoyasu Sawa, Teiji Ota, Maria Kajikawa, Osamu Hong, Keelung Martin, Thomas R. Wiener-Kronish, Jeanine P. TI Depletion of phagocytes in the reticuloendothelial system causes increased inflammation and mortality in rabbits with Pseudomonas aeruginosa pneumonia SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE counterregulatory response; bacterial clearance; macrophages ID TUMOR-NECROSIS-FACTOR; RETICULO-ENDOTHELIAL SYSTEM; CONTINUOUS MECHANICAL VENTILATION; ALVEOLAR EPITHELIAL INJURY; NOSOCOMIAL PNEUMONIA; FACTOR-ALPHA; HOST-DEFENSE; NITRIC-OXIDE; IN-VITRO; UNANESTHETIZED SHEEP AB Kurahashi K, Sawa T, Ota M, Kajikawa O, Hong K, Martin TR, Wiener-Kronish JP. Depletion of phagocytes in the reticuloendothelial system causes increased inflammation and mortality in rabbits with Pseudomonas aeruginosa pneumonia. Am J Physiol Lung Cell Mol Physiol 296: L198-L209, 2009. First published November 21, 2008; doi:10.1152/ajplung.90472.2008.-Phagocytes of the reticuloendothelial system are important in clearing systemic infection; however, the role of the reticuloendothelial system in the response to localized infection is not well-documented. The major goals of this study were to investigate the roles of phagocytes in the reticuloendothelial system in terms of bacterial clearance and inflammatory modulation in sepsis caused by Pseudomonas pneumonia. Macrophages in liver and spleen were depleted by administering liposome encapsulated dichloromethylene diphosphonate (clodronate) intravenously 36 h before the instillation of Pseudomonas aeruginosa into the lungs of anesthetized rabbits. Blood samples were analyzed for bacteria and cytokine concentrations. Lung injury was assessed by the bidirectional flux of albumin and by wet-to-dry weight ratios. Blood pressure and cardiac outputs decreased more rapidly and bacteremia occurred earlier in the clodronate-treated rabbits compared with the nondepleted rabbits. Plasma TNF-alpha (1.08 +/- 0.54 vs. 0.08 +/- 0.02 ng/ml) and IL-8 (6.8 +/- 1.5 vs. 0.0 +/- 0.0 ng/ml) were higher in the depleted rabbits. The concentration of IL-10 in liver of the macrophage-depleted rabbits was significantly lower than in normal rabbits at 5 h. Treatment of macrophage-depleted rabbits with intravenous IL-10 reduced plasma proinflammatory cytokine concentrations and reduced the decline in blood pressure and cardiac output. These results show that macrophages in the reticuloendothelial system have critical roles in controlling systemic bacteremia and reducing systemic inflammation, thereby limiting the systemic effects of a severe pulmonary bacterial infection. C1 [Kurahashi, Kiyoyasu] Yokohama City Univ, Grad Sch Med, Dept Anesthesiol & Crit Care Med, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan. [Kurahashi, Kiyoyasu; Sawa, Teiji; Ota, Maria] Univ Calif San Francisco, Dept Anesthesia, San Francisco, CA 94143 USA. [Kurahashi, Kiyoyasu; Kajikawa, Osamu; Martin, Thomas R.] Univ Washington, Sch Med, Med Res Serv, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Kurahashi, Kiyoyasu; Kajikawa, Osamu; Martin, Thomas R.] Univ Washington, Sch Med, Dept Med, Div Pulm & Crit Care Med, Seattle, WA 98195 USA. [Hong, Keelung] Univ Calif San Francisco, Dept Biopharmaceut Sci, San Francisco, CA 94143 USA. [Wiener-Kronish, Jeanine P.] Univ Calif San Francisco, Dept Med, Dept Anesthesia & Perioperat Care, San Francisco, CA 94143 USA. [Wiener-Kronish, Jeanine P.] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. RP Kurahashi, K (reprint author), Yokohama City Univ, Grad Sch Med, Dept Anesthesiol & Crit Care Med, Kanazawa Ku, 3-9 Fukuura, Yokohama, Kanagawa 2360004, Japan. EM kiyok@med.yokohama-cu.ac.jp FU National Institutes of Health (NIH) [HL-49810, HL-55980, HL-30542, AI-29103, GM-37696, HL-073996]; Yokohama Foundation for Advancement of Medical Science; Yokohama Academic Foundation FX This study was supported, in part, by the National Institutes of Health (NIH) Grants HL-49810 and HL-55980 (to J.P. Wiener-Kronish), the NIH Grants HL-30542, AI-29103, GM-37696, and HL-073996 (to T. R. Martin), the Yokohama Foundation for Advancement of Medical Science (to K. Kurahashi), and the Yokohama Academic Foundation (to K. Kurahashi). NR 69 TC 9 Z9 9 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD FEB PY 2009 VL 296 IS 2 BP L198 EP L209 DI 10.1152/ajplung.90472.2008 PG 12 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 399CP UT WOS:000262778300007 PM 19028978 ER PT J AU Ricono, JM Wagner, B Gorin, Y Arar, M Kazlauskas, A Choudhury, GG Abboud, HE AF Ricono, Jill M. Wagner, Brent Gorin, Yves Arar, Mazen Kazlauskas, Andrius Choudhury, Goutam Ghosh Abboud, Hanna E. TI PDGF receptor-beta modulates metanephric mesenchyme chemotaxis induced by PDGF AA SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE reactive oxygen species; calcium ID CARDIAC SARCOPLASMIC-RETICULUM; SMOOTH-MUSCLE-CELLS; PROTEASE-ACTIVATED LIGAND; GROWTH-FACTOR RECEPTORS; AKT/PROTEIN KINASE-B; SIGNAL-TRANSDUCTION; MESANGIAL CELLS; ALPHA-RECEPTOR; HYDROGEN-PEROXIDE; OXYGEN RADICALS AB Ricono JM, Wagner B, Gorin Y, Arar M, Kazlauskas A, Choudhury GG, Abboud HE. PDGF receptor-beta modulates metanephric mesenchyme chemotaxis induced by PDGF AA. Am J Physiol Renal Physiol 296: F406-F417, 2009. First published November 19, 2008; doi:10.1152/ajprenal.90368.2008.-PDGF B chain or PDGF receptor (PDGFR)-beta-deficient (-/-) mice lack mesangial cells. To study responses of alpha- and beta-receptor activation to PDGF ligands, metanephric mesenchymal cells (MMCs) were established from embryonic day E11.5 wild-type (+/+) and -/- mouse embryos. PDGF BB stimulated cell migration in +/+ cells, whereas PDGF AA did not. Conversely, PDGF AA was chemotactic for -/- MMCs. The mechanism by which PDGFR-beta inhibited AA-induced migration was investigated. PDGF BB, but not PDGF AA, increased intracellular Ca(2+) and the production of reactive oxygen species (ROS) in +/+ cells. Transfection of -/- MMCs with the wild-type beta-receptor restored cell migration and ROS generation in response to PDGF BB and inhibited AA-induced migration. Inhibition of Ca(2+) signaling facilitated PDGF AA-induced chemotaxis in the wild-type cells. The antioxidant N-acetyl-L-cysteine (NAC) or the NADPH oxidase inhibitor diphenyleneiodonium (DPI) abolished the BB-induced increase in intracellular Ca(2+) concentration, suggesting that ROS act as upstream mediators of Ca(2+) in suppressing PDGF AA-induced migration. These data indicate that ROS and Ca(2+) generated by active PDGFR-beta play an essential role in suppressing PDGF AA-induced migration in +/+ MMCs. During kidney development, PDGFR beta-mediated ROS generation and Ca(2+) influx suppress PDGF AA-induced chemotaxis in metanephric mesenchyme. C1 [Wagner, Brent] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Nephrol, San Antonio, TX 78229 USA. [Ricono, Jill M.] Univ Texas Hlth Sci Ctr San Antonio, Inst Biotechnol, Dept Mol Med, San Antonio, TX 78229 USA. [Arar, Mazen] Univ Texas Hlth Sci Ctr San Antonio, Dept Pediat, San Antonio, TX 78229 USA. [Wagner, Brent; Choudhury, Goutam Ghosh; Abboud, Hanna E.] S Texas Vet Hlth Care Syst, Audie L Murphy Mem Hosp Div, San Antonio, TX USA. [Kazlauskas, Andrius] Harvard Univ, Sch Med, Schepens Eye Inst, Boston, MA USA. RP Wagner, B (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Nephrol, MC 7882,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM wagnerb@uthscsa.edu OI Gorin, Yves/0000-0003-4048-6925 FU National Institute of Diabetes and Digestive and Kidney Diseases [DK-33665, DK-50190, DK-55815]; National American Heart Association; Juvenile Diabetes Research Foundation Regular Research Grant; National Kidney Foundation Young Investigator Award; National Kidney Foundation of South and Central Texas; Department of Veterans Affairs Merit Review grant; Department of Veterans Affairs Research Career Scientist Award; National Institutes of Health Loan Repayment Program; American Heart Association Fellow-to-Faculty Transition Award. FX These studies were supported by National Institute of Diabetes and Digestive and Kidney Diseases Grants DK-33665 (H. E. Abboud), DK-50190, and DK-55815 (G. G. Choudhury). Y. Gorin is supported through a Scientist Development Grant from the National American Heart Association, a Juvenile Diabetes Research Foundation Regular Research Grant, a National Kidney Foundation Young Investigator Award, and a National Kidney Foundation of South and Central Texas, Research Program Award. G. G. Choudbury is supported by a Department of Veterans Affairs Merit Review grant, Regular Research Grant from the Juvenile Diabetes Research Foundation, and by a Department of Veterans Affairs Research Career Scientist Award. B. Wagner is the recipient of the National Institutes of Health Loan Repayment Program, National Kidney Foundation Research Fellowship, National Kidney Foundation Jack C. Kent Third Year Research Fellowship, and an American Heart Association Fellow-to-Faculty Transition Award. NR 64 TC 9 Z9 9 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD FEB PY 2009 VL 296 IS 2 BP F406 EP F417 DI 10.1152/ajprenal.90368.2008 PG 12 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 399EH UT WOS:000262782700022 PM 19019919 ER PT J AU Kyomen, HH Whitfield, TH AF Kyomen, Helen H. Whitfield, Theodore H. TI Psychosis in the Elderly SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID ALZHEIMERS-DISEASE; OLDER-ADULTS; DEMENTIA; SYMPTOMS; DELIRIUM; DRUGS; PHENOMENOLOGY; SCHIZOPHRENIA; DEPRESSION; RISK AB Ms. A, an 85-year-old Caucasian woman, was hospitalized for increased paranoia, visual hallucinations, and agitation. According to her son, Ms. A had had "strange thoughts" for as long as he could remember. For example, for a time, Ms. A would eat only foods that were white. Still, in her adult life, she had actively participated in developing and running a successful family business with her husband and had raised two sons. When her husband died 5 years ago, Ms. A developed a major depressive disorder, single episode, severe with psychotic features. She moved to an assisted living facility and did well there until she was hospitalized 2 years ago with agitation. At that time, she was diagnosed with late-onset Alzheimer's type dementia with delusions, depressed mood, and behavioral disturbance. She returned to the assisted living facility and was stable until a few months before her current hospitalization, which was precipitated by gradually worsening paranoid delusions, visual hallucinations, severe restlessness, and difficulty in being redirected. C1 Massachusetts Gen Hosp, McLean Div, Geriatr Psychiat Program, Dept Psychiat, Belmont, MA USA. Biostat Solut Consulting, Boston, MA USA. RP Kyomen, HH (reprint author), McLean Hosp, 115 Mill St, Belmont, MA 02478 USA. EM helen_kyomen@hms.harvard.edu NR 20 TC 0 Z9 0 U1 0 U2 4 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD FEB PY 2009 VL 166 IS 2 BP 146 EP 150 DI 10.1176/appi.ajp.2008.08020294 PG 5 WC Psychiatry SC Psychiatry GA 402RT UT WOS:000263031500006 PM 19188291 ER PT J AU Goldberg, JF Perlis, RH Bowden, CL Thase, ME Miklowitz, DJ Marangell, LB Calabrese, JR Nierenberg, AA Sachs, GS AF Goldberg, Joseph F. Perlis, Roy H. Bowden, Charles L. Thase, Michael E. Miklowitz, David J. Marangell, Lauren B. Calabrese, Joseph R. Nierenberg, Andrew A. Sachs, Gary S. TI Manic Symptoms During Depressive Episodes in 1,380 Patients With Bipolar Disorder: Findings From the STEP-BD SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 161st Annual Meeting of the American-Psychiatric-Association CY MAY 03-08, 2008 CL Washington, DC SP Amer Psychiat Assoc ID TREATMENT ENHANCEMENT PROGRAM; MIXED DEPRESSION; ANTIDEPRESSANT TREATMENT; AGITATED DEPRESSION; DOUBLE-BLIND; STATES; SCALE; ASSOCIATION; MELANCHOLIA; VALIDATION AB Objective: Little is known about how often bipolar depressive episodes are accompanied by subsyndromal manic symptoms in bipolar I and II disorders. The authors sought to determine the frequency and clinical correlates of manic symptoms during episodes of bipolar depression. Method: From among 4,107 enrollees in the National Institute of Mental Health's Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), 1,380 individuals met criteria for bipolar I or II depressive syndromes at the time of enrollment and were assessed for concomitant manic symptoms. Illness characteristics were compared in patients with pure bipolar depressed episodes and those with mixed depressive presentations. Results: Two-thirds of the subjects with bipolar depressed episodes had concomitant manic symptoms, most often distractibility, flight of ideas or racing thoughts, and psychomotor agitation. Patients with any mixed features were significantly more likely than those with pure bipolar depressed episodes to have early age at illness onset, rapid cycling in the past year, bipolar I subtype, history of suicide attempts, and more days in the preceding year with irritability or mood elevation. Conclusions: Manic symptoms often accompany bipolar depressive episodes but may easily be overlooked when they appear less prominent than depressive features. Subsyndromal manic symptoms during bipolar I or II depression demarcate a more common, severe, and psychopathologically complex clinical state than pure bipolar depression and merit recognition as a distinct nosologic entity. C1 Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. Silver Hill Hosp, Affect Disorders Res Program, New Canaan, CT USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA. Univ Colorado, Dept Psychol, Boulder, CO 80309 USA. Univ Colorado, Dept Psychiat, Boulder, CO 80309 USA. Baylor Coll Med, Dept Psychiat, Houston, TX 77030 USA. Case Western Reserve Univ, Dept Psychiat, Cleveland, OH 44106 USA. RP Goldberg, JF (reprint author), 128 East Ave, Norwalk, CT 06851 USA. EM joseph.goldberg@mssm.edu FU NIMH NIH HHS [K-23 MH-01936, N01 MH-80001] NR 38 TC 138 Z9 140 U1 3 U2 6 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD FEB PY 2009 VL 166 IS 2 BP 173 EP 181 DI 10.1176/appi.ajp.2008.08050746 PG 9 WC Psychiatry SC Psychiatry GA 402RT UT WOS:000263031500010 PM 19122008 ER PT J AU Karlawish, J Rubright, J Casarett, D Cary, M Ten Have, T Sankar, P AF Karlawish, Jason Rubright, Jonathan Casarett, David Cary, Mark Ten Have, Thomas Sankar, Pamela TI Older Adults' Attitudes Toward Enrollment of Non-competent Subjects Participating in Alzheimer's Research SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID INFORMED CONSENT; DISEASE PATIENTS; CLINICAL-TRIAL; PROXY CONSENT; DECISION; CAPACITY; ETHICS; HEALTH; VIEWS; RISK AB Objective: Research that seeks to enroll noncompetent patients with Alzheimer's disease without presenting any potential benefit to participants is the source of substantial ethical controversy. The authors used hypothetical Alzheimer's disease studies that included either a blood draw or a blood draw and lumbar puncture to explore older persons' attitudes on this question. Method: Face-to-face interviews were conducted with 538 persons age 65 and older. Questions explored participants' understanding of research concepts, their views on enrolling persons with Alzheimer's disease in research, and their preferences regarding having a proxy decision maker, granting advance consent, and granting their proxy leeway to override the participant's decision. Additional questions assessed altruism, trust, value for research, and perceptions of Alzheimer's disease. Results: The majority (83%) were willing to grant advance consent to a blood draw study, and nearly half (48%) to a blood draw plus lumbar puncture study. Most (96%) were willing to identify a proxy for research decision making, and most were willing to grant their proxy leeway over their advance consent: 81% for the blood draw study and 70% for the blood draw plus lumbar puncture study. Combining the preferences for advance consent and leeway, the proportion who would permit being enrolled in the blood draw and lumbar puncture studies, respectively, were 92% and 75%. Multivariate models showed that willingness to be enrolled in research was most strongly associated with a favorable attitude toward biomedical research. Conclusions: Older adults generally support enrolling noncompetent persons with Alzheimer's disease into research that does not present a benefit to subjects. Willingness to grant their proxy leeway over advance consent and a favorable attitude about biomedical research substantially explain this willingness. C1 [Karlawish, Jason] Univ Penn, Inst Aging, Philadelphia, PA 19104 USA. Univ Penn, Div Geriatr, Leonard Davis Inst Hlth Econ, Ctr Bioeth,Ctr Clin Epidemiol & Biostat,Alzheimer, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Karlawish, J (reprint author), Univ Penn, Inst Aging, 3615 Chestnut St, Philadelphia, PA 19104 USA. EM jason.karlawish@uphs.upenn.edu FU NIMH [R01 MH-071643] FX Supported by NIMH grant R01 MH-071643, a Greenwall Faculty Scholars Award in Bioethics to Dr. Karlawish, and the Marian S. Ware Alzheimer Program. The authors thank James Beaver, Paige Brookstein, Maysa DeSousa, Lauren Fisher, Kristin Harkins, Margaret Rice, Samantha Schwartz, and Elizabeth Taylor for their assistance in data collection. NR 28 TC 32 Z9 32 U1 0 U2 7 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD FEB PY 2009 VL 166 IS 2 BP 182 EP 188 DI 10.1176/appi.ajp.2008.08050645 PG 7 WC Psychiatry SC Psychiatry GA 402RT UT WOS:000263031500011 PM 18923066 ER PT J AU Andia, I Kaida, A Maier, M Guzman, D Emenyonu, N Pepper, L Bangsberg, DR Hogg, RS AF Andia, Irene Kaida, Angela Maier, Marissa Guzman, David Emenyonu, Nneka Pepper, Larry Bangsberg, David R. Hogg, Robert S. TI Highly Active Antiretroviral Therapy and Increased Use of Contraceptives Among HIV-Positive Women During Expanding Access to Antiretroviral Therapy in Mbarara, Uganda SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID SUB-SAHARAN AFRICA; SEXUAL-BEHAVIOR; HIV-1-INFECTED PATIENTS; RISK BEHAVIOR; CONDOM USE; FERTILITY; IMPACT; INFECTION; KAMPALA; COHORT AB Objectives. We investigated whether the prevalence of contraceptive use among women who are HIV positive varied according to use of highly active antiretroviral therapy (HAART) in Mbarara, Uganda. Methods. We used data from a cross-sectional survey of 484 women who were HIV positive (18-50 years) and were attending Mbarara University's HIV clinic, 45% of whom were receiving HAART. Multivariate logistic regression was used to investigate the association between HAART use and contraceptive use. Data were collected between November 2005 and June 2006. Results. Overall, 45% of the women were sexually active in the previous 3 months. Of these, 85% reported using contraceptive methods, with 84% reporting use of barrier contraceptive methods. Women receiving HAART were more than twice as likely to use contraceptive methods (adjusted odds ratio [AOR]=2.64; 95% confidence interval [CI] = 1.07, 6.49) and more than 3 times as likely to use barrier contraceptive methods (AOR=3.62; 95% CI=11.54, 8.55) than were women not receiving HAART. Conclusions. Our findings support the need for increased attention to better integration of reproductive health and HIV and AIDS services for women who are HIV positive. (Am J Public Health. 2009;99:340-347. doi:10.2105/AJPH.2007.129528) C1 [Andia, Irene] Mbarara Univ Sci & Technol, Dept Internal Med, Mbarara, Uganda. [Kaida, Angela] Univ British Columbia, Fac Med, Dept Hlth Care & Epidemiol, Vancouver, BC V5Z 1M9, Canada. [Maier, Marissa] Oregon Hlth & Sci Univ, Dept Internal Med, Portland, OR 97201 USA. [Guzman, David; Emenyonu, Nneka] Univ Calif San Francisco, Dept Internal Med, San Francisco, CA 94143 USA. [Bangsberg, David R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Hogg, Robert S.] BC Ctr Excellence HIV AIDS, Vancouver, BC, Canada. RP Andia, I (reprint author), Mbarara Univ Sci & Technol, Dept Internal Med, POB 1410, Mbarara, Uganda. EM andiaodanga@yahoo.com RI Hogg, Robert/B-2783-2012; OI Hogg, Robert/0000-0003-3463-5488 FU National Institutes of Health [MH54907]; University of California, San Francisco; Gladstone Institute of Virology & Immunology Center for AIDS Research [P30 AI27763]; National Institute on Alcohol Abuse and Alcoholism [K-24 015287-01]; Canadian Institutes of Health Research; Michael Smith Foundation for Health Research FX We would like to thank the research and clinical staff and clients at the Nibarara Regional Referral Hospital Immune Suppression Syndrome Clinic. NR 28 TC 35 Z9 35 U1 0 U2 6 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 FEB PY 2009 VL 99 IS 2 BP 340 EP 347 DI 10.2105/AJPH.2007.129528 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 399JB UT WOS:000262795100026 PM 19059862 ER PT J AU Choi, JE Lee, SS Sunde, DA Huizar, I Haugk, KL Thannickal, VJ Vittal, R Plymate, SR Schnapp, LM AF Choi, Jung-Eun Lee, Sung-soon Sunde, Donald A. Huizar, Isham Haugk, Kathy L. Thannickal, Victor J. Vittal, Ragini Plymate, Stephen R. Schnapp, Lynn M. TI Insulin-like Growth Factor-I Receptor Blockade Improves Outcome in Mouse Model of Lung Injury SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE insulin-like growth factor; lung injury; lung fibrosis ID RESPIRATORY-DISTRESS-SYNDROME; BRONCHOALVEOLAR LAVAGE FLUID; IGF-I; PULMONARY-FIBROSIS; SIGNALING PATHWAYS; MULTIPLE-MYELOMA; CROSS-TALK; CELLS; EXPRESSION; MICE AB Rationale: The insulin-like growth factor-I (IGF-I) pathway is an important determinant of survival and proliferation in many cells. However, little is known about the role of the IGF-I pathway in lung injury. We previously showed elevated levels of IGF-I in bronchoalveolar lavage fluid from patients with acute respiratory distress syndrome. Furthermore, immunodepletion of IGF from acute respiratory distress syndrome bronchoalveolar lavage increased fibroblast apoptosis. Objectives: We examined the effect of blockade of type 1 IGF tyrosine kinase receptor (IGF-IR) in a murine model of bleomycin-induced lung injury and fibrosis. Methods: Mice were treated with a monoclonal antibody against the IGF-I receptor (A12) or vehicle after intratracheal bleomycin instillation. Measurements and Main Results: Mice treated with All 2 antibody had significantly improved survival after bleomycin injury compared with control mice. Both groups of mice had a similar degree of fibrosis on days 7 and 14, but by Day 28 the A12-treated group had significantly less fibrosis. Delayed treatment with All 2 also resulted in decreased fibrosis. A12-treated mice had significantly decreased apoptotic cells on Day 28 compared with control mice. We confirmed that A12 treatment induced mouse lung fibroblast apoptosis in vitro. In addition, IGF-I increased lung fibroblast migration. The primary pathway activated by IGF-I in lung fibroblasts was the insulin receptor substrate-2/phosphatidylinositol 3-kinase/Akt axis. Conclusions: IGF-I regulated survival and migration of fibrogenic cells in the lung. Blockade of the IGF pathway increased fibroblast apoptosis and subsequent resolution of pulmonary fibrosis. Thus, IGF-IR may be a potential target for treatment of lung injury and fibrosis. C1 [Choi, Jung-Eun; Lee, Sung-soon; Sunde, Donald A.; Huizar, Isham; Schnapp, Lynn M.] Univ Washington, Harborview Med Ctr, Dept Med, Div Pulm & Crit Care Med, Seattle, WA 98104 USA. [Haugk, Kathy L.; Plymate, Stephen R.] Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. [Thannickal, Victor J.; Vittal, Ragini] Univ Michigan, Med Ctr, Dept Med, Div Pulm Med, Ann Arbor, MI 48109 USA. RP Schnapp, LM (reprint author), Box 358052,815 Mercer St, Seattle, WA 98109 USA. EM lschnapp@u.washington.edu NR 36 TC 30 Z9 32 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD FEB 1 PY 2009 VL 179 IS 3 BP 212 EP 219 DI 10.1164/rccm.200802-228OC PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 398ML UT WOS:000262736100006 PM 19011156 ER PT J AU Healey, CM Kumbhani, DJ Healey, NA Crittenden, MD Gibson, SF Khuri, SF AF Healey, Christine M. Kumbhani, Dharam J. Healey, Nancy A. Crittenden, Michael D. Gibson, Stephen F. Khuri, Shukri F. TI Impact of intraoperative myocardial tissue acidosis on postoperative adverse outcomes and cost of care for patients undergoing prolonged aortic clamping during cardiopulmonary bypass SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 31st Annual Surgical Symposium of the Association-of-VA-Surgeons CY MAY 10-12, 2007 CL Little Rock, AR SP Assoc VA Surg DE Aortic cross-clamp; Ischemia; Reperfusion; Outcomes; Cost ID CARDIAC-SURGERY; VETERANS-AFFAIRS; RISK ADJUSTMENT; SURGICAL CARE; COMPLICATIONS; DETERMINANTS; MORTALITY; QUALITY; PH; READMISSION AB BACKGROUND: This study examined the impact of intraoperative myocardial acidosis and adverse postoperative outcomes on the cost of cardiac surgical care. METHODS: Myocardial tissue pH corrected to 37 degrees C (pH(37C)) was measured in 162 patients with cross-clamp (XC) duration of 119 minutes or longer. Perioperative data and outcomes were collected prospectively. The Veterans Affairs cost accounting system was used to determine the cost of care in a subset of 57 patients. RESULTS: Long XC duration was associated with significantly increased acidosis and adverse postoperative outcomes. The cost of care for patients with adverse outcomes was increased by 110% (P < 0001). Patients with acidosis at the end of reperfusion had significantly (P = .0470) increased costs of care. End reperfusion of myocardial tissue pH(37C), of less than 7.0, diabetes mellitus, and body surface area were significant determinants of postoperative adverse outcomes. CONCLUSIONS: Intraoperative myocardial acidosis is a determinant of postoperative adverse outcomes and cost in cardiac Surgery. Reducing XC duration and improving intraoperative myocardial protection should improve outcomes and reduce cost. (C) 2009 Published by Elsevier Inc. C1 [Healey, Christine M.; Kumbhani, Dharam J.; Healey, Nancy A.; Crittenden, Michael D.; Gibson, Stephen F.; Khuri, Shukri F.] VA Boston Healthcare Syst, W Roxbury, MA 02132 USA. [Healey, Christine M.] Albany Med Coll, Albany, NY 12208 USA. [Crittenden, Michael D.; Khuri, Shukri F.] Harvard Univ, Sch Med, Boston, MA USA. [Crittenden, Michael D.; Khuri, Shukri F.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Healey, CM (reprint author), VA Boston Healthcare Syst, Cardiothorac Surg 112,1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM nancy.healy@va.gov NR 40 TC 6 Z9 6 U1 0 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD FEB PY 2009 VL 197 IS 2 BP 203 EP 210 DI 10.1016/j.amjsurg.2008.01.023 PG 8 WC Surgery SC Surgery GA 408SA UT WOS:000263454000014 PM 18722580 ER PT J AU Yantiss, RK Shia, J Klimstra, DS Hahn, HP Odze, RD Misdraji, J AF Yantiss, Rhonda K. Shia, Jinru Klimstra, David S. Hahn, Hejin P. Odze, Robert D. Misdraji, Joseph TI Prognostic Significance of Localized Extra-appendiceal Mucin Deposition in Appendiceal Mucinous Neoplasms SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article; Proceedings Paper CT 97th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 01-07, 2008 CL Denver, CO SP US & Canadian Acad Pathol DE pseudomyxoma peritonei; disseminated peritoneal adenomucinosis; low-grade appendiceal mucinous neoplasm; mucinous adenocarcinoma ID PSEUDOMYXOMA-PERITONEI; CLINICOPATHOLOGICAL ANALYSIS; TUMORS; ORIGIN; CYSTADENOCARCINOMA; CYSTADENOMA; MUCOCELES; FEATURES; OVARY AB Appendiceal mucinous neoplasms confined to the mucosa are benign, whereas those with disseminated peritoneal mucin deposits often follow an indolent, but malignant, course. Not infrequently, appendiceal mucinous neoplasms are associated with localized periappendiceal mucin deposits, but lack diffuse peritoneal involvement. Mucin deposits in these cases may be acellular or contain neoplastic epithelium (cellular mucin). Although some investigators consider both acellular and cellular periappendiceal mucin to pose no, or minimal, risk for recurrent disease, the biologic importance of localized extra-appendiceal mucin has never been evaluated. We identified 65 patients with appendiceal mucinous neoplasms, all of whom had localized periappendiceal mucin deposits without diffuse peritoneal involvement, and assessed them for the presence of extra-appendiceal epithelium and clinical outcome. Forty-nine (75%) appendices were submitted in total for histologic evaluation. Most (77%) cases showed acellular periappendiceal mucin, but 15 (23%) had scant extra-appendiceal epithelium (range: 1 to 12 cell clusters). Upon follow-Lip (mean: 48 mo), 2 (4%) patients with acellular periappendiceal mucin developed diffuse peritoneal disease, but neither of these appendices was submitted in total for histologic evaluation. In contrast, 5 of 15 (33%) patients with cellular periappendiceal mucin developed mucinous ascites, including I who eventually died of disease (P = 0.03). Thus, patients with appendiceal mucinous neoplasms and acellular periappendiceal mucin are unlikely to develop recurrent disease. However, microscopic examination of the entire appendix is necessary, as lesions with extra-appendiceal tumor cells are more likely to progress to disseminated disease and result in death of the patient, even if the mucin is paucicellular and confined to the periappendiceal region. C1 [Yantiss, Rhonda K.] Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY 10065 USA. [Shia, Jinru; Klimstra, David S.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. [Hahn, Hejin P.; Odze, Robert D.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Misdraji, Joseph] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Yantiss, RK (reprint author), Weill Cornell Med Coll, Dept Pathol & Lab Med, 525 E 68th St, New York, NY 10065 USA. EM rhy2001@med.cornell.edu OI Shia, Jinru/0000-0002-4351-2511 NR 17 TC 37 Z9 39 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD FEB PY 2009 VL 33 IS 2 BP 248 EP 255 PG 8 WC Pathology; Surgery SC Pathology; Surgery GA 401DX UT WOS:000262920400011 PM 18852679 ER PT J AU Nielsen, GP Srivastava, A Kattapuram, S Deshpande, V O'Connell, JX Mangham, CD Rosenberg, AE AF Nielsen, G. Petur Srivastava, Amitabh Kattapuram, Susan Deshpande, Vikram O'Connell, John X. Mangham, Chas D. Rosenberg, Andrew E. TI Epithelioid Hemangioma of Bone Revisited A Study of 50 Cases SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE epithelioid hemangioma; hemangioma; vascular tumor; bone ID POTENTIALLY METASTASIZING TUMOR; ANGIOLYMPHOID HYPERPLASIA; HISTIOCYTOID HEMANGIOMA; VASCULAR TUMORS; HEMANGIOENDOTHELIOMA; EOSINOPHILIA; ANGIOSARCOMA; INVOLVEMENT; MIMICKING; DIAGNOSIS AB The clinical and pathologic features of 50 epithelioid hemangiomas of bone are analyzed. There were 29 males and 21 females who ranged in age from 10 to 75 (mean 35) years. The tumors arose in long tubular bones (40%), short tubular bones of the distal lower extremity (18%), flat bones (18%), vertebrae (16%), and small bones of the hands (8%). Nine patients (18%) had involvement of more than 1 bone. Radiographically, the lesions were lucent and well marginated. Microscopically, the neoplasms had a lobular architecture and were composed of epithelioid endothelial cells that formed obvious vascular lumina or grew in solid sheets. No hyalinized or solid appearing extracellular myxoid matrix was present. Thirty-five patients were treated with curettage, 13 patients had a local resection and 2 patients only had a biopsy. One patient had local lymph node involvement. Three patients were treated with surgery and radiation therapy. Follow-up information revealed that 4 patients experienced a local recurrence; and I patient developed limited involvement of a regional lymph node. Epithelioid hemangioma of bone is a benign lesion that may be multifocal and affect separate tissue and is successfully treated with curettage or marginal en bloc excision. C1 [Nielsen, G. Petur; Deshpande, Vikram; Rosenberg, Andrew E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Nielsen, G. Petur; Deshpande, Vikram; Rosenberg, Andrew E.] Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. [Kattapuram, Susan] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Srivastava, Amitabh] Dartmouth Hitchcock Med Ctr, Dept Pathol, Lebanon, NH USA. [O'Connell, John X.] CJ Coady Associates, Dept Pathol, Surry, BC, Canada. [Mangham, Chas D.] Robert Jones & Agnes Hunt Orthopaed Hosp, Dept Pathol, Oswestry SY10 7AG, Shrops, England. [Mangham, Chas D.] Royal Orthopaed Hosp, Dept Pathol, Birmingham B31 2AP, W Midlands, England. RP Nielsen, GP (reprint author), Massachusetts Gen Hosp, Dept Pathol, WRN 2,55 Fruit St, Boston, MA 02114 USA. EM gnielsen@partners.org RI Srivastava, Amitabh/A-9386-2009 NR 36 TC 36 Z9 38 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD FEB PY 2009 VL 33 IS 2 BP 270 EP 277 PG 8 WC Pathology; Surgery SC Pathology; Surgery GA 401DX UT WOS:000262920400014 PM 18852673 ER PT J AU Sparr, JA Bandipalliam, P Redston, MS Syngal, S AF Sparr, Jennifer A. Bandipalliam, Prathap Redston, Mark S. Syngal, Sapna TI Intraductal Papillary Mucinous Neoplasm of the Pancreas With Loss of Mismatch Repair in a Patient With Lynch Syndrome SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE intraductal papillary mucinous neoplasm (IPMN); pancreatic cancer; Lynch syndrome; hereditary nonpolyposis colorectal cancer; MSH2 ID NONPOLYPOSIS COLORECTAL-CANCER; ADDITIONAL PRIMARY CANCERS; MICROSATELLITE INSTABILITY; MEDULLARY CARCINOMA; CLINICAL-FEATURES; ADENOCARCINOMAS; MUTATION; RISK; EXPRESSION; PATTERN AB Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a precancerous lesion with a well-described progression to carcinoma. This case report describes a 61-year-old woman with,I history significant for multiple cancers and a confirmed germline mutation of MSH2, a mismatch repair gene responsible for Lynch syndrome, who was also found to have ail IPMN of the pancreas. Phenotypic manifestations of Lynch syndrome in this patient included multiple adenomas and adenocarcinomas of the colon and also several other Lynch syndrome-associated cancers. The patient's adenocarcinoma of the colon and IPMN of the pancreas showed identical immunohistochemical staining profiles with loss of expression of MSH2 and MSH6 proteins and high levels of microsatellite instability. The immunohistochemical staining and microsatellite instability patterns of the adenocarcinoma of the colon and IPMN gives strong evidence to support the consideration of IPMN as part of the spectrum Of lesions found in Lynch syndrome. C1 [Sparr, Jennifer A.; Bandipalliam, Prathap; Syngal, Sapna] Dana Farber Canc Inst, Div Populat Sci, Dept Med Oncol, Boston, MA 02115 USA. [Redston, Mark S.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Redston, Mark S.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Syngal, Sapna] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. [Syngal, Sapna] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Syngal, S (reprint author), Dana Farber Canc Inst, Div Populat Sci, Dept Med Oncol, 44 Binney St,SM 209, Boston, MA 02115 USA. EM ssyngal@partners.org FU NIH [K24-113433] FX Supported in part by NIH grant K24-113433. NR 24 TC 9 Z9 9 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD FEB PY 2009 VL 33 IS 2 BP 309 EP 312 PG 4 WC Pathology; Surgery SC Pathology; Surgery GA 401DX UT WOS:000262920400019 PM 18987546 ER PT J AU Fishman, JA AF Fishman, J. A. TI Transplantation Microbiology: An Evolving Pillar of Transplant Care SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Editorial Material C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Fishman, JA (reprint author), Massachusetts Gen Hosp, Div Infect Dis, GRJ 504, Boston, MA 02114 USA. EM jfishman@partners.org NR 5 TC 3 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD FEB PY 2009 VL 9 IS 2 BP 249 EP 250 DI 10.1111/j.1600-6143.2008.02437.x PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 399DU UT WOS:000262781400003 PM 18976307 ER PT J AU Reese, PP Yeh, H Thomasson, AM Shults, J Markmann, JF AF Reese, P. P. Yeh, H. Thomasson, A. M. Shults, J. Markmann, J. F. TI Transplant Center Volume and Outcomes After Liver Retransplantation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Center volume; health services research; liver retransplantation ID DONOR RISK INDEX; HOSPITAL VOLUME; UNITED-STATES; MORTALITY; SURVIVAL; SURGERY; RESECTION; QUALITY; IMPACT; FAILURE AB Liver retransplantation surgery has a high rate of allograft failure due to patient comorbidities and technical demands of the procedure. Success of liver retransplantation could depend on surgeon experience and processes of care that relate to center volume. We performed a retrospective cohort study of adult liver retransplantation procedures performed from January 1, 1996 through December 31, 2005 using registry data from the Organ Procurement Transplantation Network. The primary outcome was 1-year allograft failure. Liver transplant centers were categorized as small, intermediate or high volume by dividing overall liver transplants into three tertiles of approximately equal size. Mean annual volume of overall liver transplants was < 50 for low-volume centers, 50-88 for intermediate-volume centers and > 88 for high-volume centers. The primary analysis consisted of 3977 liver retransplantation patients. The unadjusted risk of 1-year allograft failure was 37.8%. In multivariable logistic regression, the risk of 1-year allograft failure was not significantly different between low- (reference), intermediate- (OR 0.86, CI 0.72-1.03, p = 0.11) and high-volume centers (OR 0.88, CI 0.74-1.04, p = 0.14). Results were similar when the analysis was limited to retransplantation performed > 160 days after initial transplantation. Center volume is an imprecise surrogate measure for 1-year outcomes after liver retransplantation. C1 [Reese, P. P.] Univ Penn, Renal Hypertens & Electrolyte Div, Philadelphia, PA 19104 USA. [Yeh, H.; Markmann, J. F.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Thomasson, A. M.; Shults, J.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. RP Reese, PP (reprint author), Univ Penn, Renal Hypertens & Electrolyte Div, Philadelphia, PA 19104 USA. EM peter.reese@uphs.upenn.edu FU Health Resources and Services Administration [234-2005-370011C]; NIH Career Development Award [K23 - DK078688-01] FX This work was supported in part by Health Resources and Services Administration contract 234-2005-370011C. Dr. Reese is supported by NIH Career Development Award, K23 - DK078688-01. NR 28 TC 21 Z9 21 U1 0 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD FEB PY 2009 VL 9 IS 2 BP 309 EP 317 DI 10.1111/j.1600-6143.2008.02488.x PG 9 WC Surgery; Transplantation SC Surgery; Transplantation GA 399DU UT WOS:000262781400011 PM 19120081 ER PT J AU Craig-Mylius, KA Lee, M Jones, KL Glickstein, LJ AF Craig-Mylius, Kathleen A. Lee, Marshall Jones, Kathryn L. Glickstein, Lisa J. TI Arthritogenicity of Borrelia burgdorferi and Borrelia garinii: Comparison of Infection in Mice SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID OUTER SURFACE PROTEIN; LYME-DISEASE MODEL; SENSU-LATO; CLINICAL MANIFESTATIONS; INDUCED ARTHRITIS; MURINE MODEL; T-CELLS; OSPC; RESPONSES; SEVERITY AB Arthritogenicity, as determined by joint swelling and synovial histology, was compared between or within two Borrelia genospecies that cause Lyme arthritis in humans. ne spirochete burden in bladder tissue (a site of spirochete persistence) was documented by quantitative polymerase chain reaction, and immune responses were analyzed. In C3H/HeJ mice, three B. burgdorferi isolates and two of the three B. garinii isolates induced severe arthritis and swelling. Previous designation as invasive or noninvasive B. garinii, or RNA spacer type of B. burgdorferi did not determine arthritis severity induced by isolates. Compared with the other five isolates, the B. garinii PBi isolate induced significantly less arthritis, a lower humoral immune response, and persisted at a much lower level in bladder tissue. However, B. garinii PBi isolates induced similar Borrelia antigen-specific inflammatory T cell responses from the local draining lymph node. Thus, diverse B. burgdorferi and B. garinii isolates were highly arthritogenic in immune competent mice. C1 [Lee, Marshall] Drexel Univ, Sch Med, Philadelphia, PA 19129 USA. [Jones, Kathryn L.; Glickstein, Lisa J.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. RP Glickstein, LJ (reprint author), Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, 149 13th St,Room 8301, Charlestown, MA 02129 USA. EM kcraigmy@vt.edu; mkl36@drexel.edu; kljones@partners.org; lglickstein@waldenhealthcare.com FU Harold G. and Leila Y. Mathers Foundation; National Institutes of Health [T32 RA07570] FX Financial support: This study was supported by a research grant from the Harold G. and Leila Y. Mathers Foundation (Lisa J. Glickstein) and a training award (T32 RA07570) from the National Institutes of Health (Kathlenn A. Craig-Mylius). NR 40 TC 4 Z9 4 U1 1 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD FEB PY 2009 VL 80 IS 2 BP 252 EP 258 PG 7 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 406RG UT WOS:000263312000019 PM 19190223 ER PT J AU McEvoy, MD Sabbagh, MJ Taylor, AG Zavadzkas, JA Koval, CN Stroud, RE Ford, RL McLean, JE Reeves, ST Mukherjee, R Spinale, FG AF McEvoy, Matthew D. Sabbagh, Michel J. Taylor, Anna Greta Zavadzkas, Juozas A. Koval, Christine N. Stroud, Robert E. Ford, Rachael L. McLean, Julie E. Reeves, Scott T. Mukherjee, Rupak Spinale, Francis G. TI Aprotinin Modifies Left Ventricular Contractility and Cytokine Release After Ischemia-Reperfusion in a Dose-Dependent Manner in a Murine Model SO ANESTHESIA AND ANALGESIA LA English DT Article ID TUMOR-NECROSIS-FACTOR; CARDIAC-SURGERY; CARDIOPULMONARY BYPASS; MYOCARDIAL-INFARCTION; INJURY; HEART; RISK; METAANALYSIS; INHIBITION; NEUTROPHIL AB BACKGROUND: Periods of ischemia-reperfusion (I/R) during cardiac surgery are associated with transient left ventricular (LV) dysfunction and an inflammatory response. In this study, we examined the potential dose-dependent effects of aprotinin (APRO) on LV contractility and cytokine release in the setting of I/R. METHODS: An index of LV contractility, LV maximal elastance (E(max)), was measured at baseline, 30 min of ischemia, and 60 min of reperfusion by microtransducer volumetry. Mice were randomized as follows: (a) APRO 20,000 kallikrein-inhibiting units (KIU)/kg (n = 11); (b) APRO 4 x 10(4) KIU/kg (n = 10); (c) APRO 8 x 10(4) KIU/kg (n = 10); and (d) vehicle (saline; n = 10). APRO doses were calculated to reflect half, full, and twice the clinical Hammersmith closing schedule. After I/R, plasma was collected for cytokine measurements. RESULTS: After I/R, E(max) decreased from the baseline value by more than 40% in the vehicle group as well as in the APRO 4 x 10(4) KIU/kg and APRO 8 x 10(4) KIU/kg groups (P < 0.05). However, E(max) returned to near baseline values in the APRO 2 x 10(4) KIU/kg group. Tumor necrosis factor (TNF) increased 10-fold after I/R, but it was reduced with higher APRO doses. CONCLUSIONS: This study demonstrated that a low dose of APRO provided protective effects on LV contractility, whereas higher doses suppressed TNF release. These unique findings suggest that there are distinct and independent mechanisms of action of APRO in the context of I/R. C1 [Spinale, Francis G.] Med Univ S Carolina, Div Cardiothorac Surg, Dept Cardiothorac Surg, Charleston, SC 29403 USA. [McEvoy, Matthew D.; Sabbagh, Michel J.; Taylor, Anna Greta; Reeves, Scott T.] Med Univ S Carolina, Dept Anesthesiol & Perioperat Med, Charleston, SC 29403 USA. [Spinale, Francis G.] Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA. RP Spinale, FG (reprint author), Med Univ S Carolina, Div Cardiothorac Surg, Dept Cardiothorac Surg, 114 Doughty St,Rm 625, Charleston, SC 29403 USA. EM wilburnm@musc.edu FU National Heart, Lung, and Blood Institute [PO1-HL-48788, RO1-HL-59165]; Research Service of the Department of Veterans Affairs; Bayer Pharmaceuticals; Foundation for Anesthesia Education and Research FX Supported by National Heart, Lung, and Blood Institute Grants PO1-HL-48788, RO1-HL-59165, Research Service of the Department of Veterans Affairs, Research Fellowships from Bayer Pharmaceuticals, and the Foundation for Anesthesia Education and Research. NR 27 TC 6 Z9 8 U1 0 U2 1 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 FEB PY 2009 VL 108 IS 2 BP 399 EP 406 DI 10.1213/ane.0b013e31818cdb13 PG 8 WC Anesthesiology SC Anesthesiology GA 396KG UT WOS:000262590000003 PM 19151263 ER PT J AU Bateman, BT Schumacher, HC Wang, S Shaefi, S Berman, MF AF Bateman, Brian T. Schumacher, H. Christian Wang, Shuang Shaefi, Shahzad Berman, Mitchell F. TI Perioperative Acute Ischemic Stroke in Noncardiac and Nonvascular Surgery Incidence, Risk Factors, and Outcomes SO ANESTHESIOLOGY LA English DT Article ID ARTERY-BYPASS SURGERY; HEART-DISEASE; ANESTHESIA AB Background: Perioperative acute ischemic stroke (AIS) is a recognized complication of noncardiac, nonvascular surgery, but few data are available regarding incidence and effect on outcome. This study examines the epidemiology of perioperative AIS in three common surgeries: hemicolectomy, total hip replacement, and lobectomy/segmental lung resection. Methods: Discharges for patients aged 18 yr or older who underwent any of the surgical procedures listed above were extracted from the Nationwide Inpatient Sample, an administrative database that contain 20% of all discharges from non-Federal hospitals each year, for years 2000 to 2004. Using appropriate International Classification of Diseases, 9th revision, Clinical Modification codes, patients with perioperative AIS were identified, as were comorbid conditions that may he risk factor, for perioperative Multivariate logistic regression was performed to identify independent predictors of perioperative AIS and to ascertain the effect of AIS on outcome. Results: A total of 0.7% of 131,067 hemicolectomy patients, 0.2% of 201,235 total hip replacement patients, and 0.6% of 39,339 lobectomy/segmental lung resection patients developed perioperative XIS. For patients older than 65 yr, AIS rose to 1.0% for hemicolectomy, 0.3% for hip replacement, and 0.8% for pulmonary resection. Multivariate logistic regression analysis revealed renal discase (odds ratio, 3.0), atrial fibrillation (odds ratio, 2.0), history of stroke (odds ratio, 1.6), and cardiac valvular disease (odds ratio, 1.5) to be the most significant risk factors for perioperative AIS. Conclusions: Perioperative AIS is an important source of morbidity and mortality associated with noncardiac, nonvascular surgery, particularly in elderly patients and patients with atrial fibrillation, valvular disease, renal disease, or previous stroke. C1 [Bateman, Brian T.; Schumacher, H. Christian; Wang, Shuang; Shaefi, Shahzad; Berman, Mitchell F.] Columbia Univ Coll Phys & Surg, Dept Anesthesiol, New York, NY 10032 USA. RP Bateman, BT (reprint author), Harvard Univ, Sch Med, Dept Anesthesia & Crit Care, Massachusetts Gen Hosp, 55 Fruit Street, Boston, MA 02114 USA. EM BBateman@partners.org NR 26 TC 90 Z9 97 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD FEB PY 2009 VL 110 IS 2 BP 231 EP 238 PG 8 WC Anesthesiology SC Anesthesiology GA 400ZI UT WOS:000262907500009 PM 19194149 ER PT J AU Sonnen, JA Larson, EB Gray, SL Wilson, A Kohama, SG Crane, PK Breitner, JCS Montine, TJ AF Sonnen, Joshua A. Larson, Eric B. Gray, Shelly L. Wilson, Angela Kohama, Steven G. Crane, Paul K. Breitner, John C. S. Montine, Thomas J. TI Free Radical Damage to Cerebral Cortex in Alzheimer's Disease, Microvascular Brain Injury, and Smoking SO ANNALS OF NEUROLOGY LA English DT Article ID ALPHA-TOCOPHEROL; VITAMIN-E; DEMENTIA; F-2-ISOPROSTANES; SUPPRESSION; SUPPLEMENTS; INCREASE; TRIAL; RISK AB Evidence supports a pathogenic role for free radical injury to brain in Alzheimer's disease; however, clinical trial results are only mildly encouraging. Examining brains from The Adult Changes in Thought study offers a unique perspective. Selectively increased free radical damage to cerebral cortex was associated with Alzheimer's disease, microvascular brain injury, and current smoking, but not with antioxidant supplement usage. Our results support suppression of free radical injury to brain as a therapeutic target for Alzheimer's disease and microvascular brain injury; however, future clinical trials should consider other antioxidants or doses than those identified in our study. C1 [Sonnen, Joshua A.; Wilson, Angela; Montine, Thomas J.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Gray, Shelly L.] Univ Washington, Dept Pharm, Seattle, WA 98195 USA. [Kohama, Steven G.] Oregon Natl Primate Res Ctr, Beaverton, OR USA. [Crane, Paul K.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Breitner, John C. S.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Breitner, John C. S.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Sonnen, JA (reprint author), 11838 22nd Ave SW, Seattle, WA 98146 USA. EM jsonnen@u.washington.edu RI Crane, Paul/C-8623-2014; Sonnen, 37382016/H-3738-2016; OI Sonnen, 37382016/0000-0001-9267-8705; Crane, Paul/0000-0003-4278-7465 FU NIH [AG23801, AG05136, AG006781, AG 000258]; Nancy and Buster Alvord Endowment FX This work was Supported by NIH AG23801, (T.J.M.) NIH AG05136, NIH AG006781, (E.B.L.) NIH AG 000258, and the Nancy and Buster Alvord Endowment (T.J.M.). NR 15 TC 32 Z9 32 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD FEB PY 2009 VL 65 IS 2 BP 226 EP 229 DI 10.1002/ana.21508 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 415KM UT WOS:000263932700017 PM 19259965 ER PT J AU Cappuzzo, F Janne, PA Skokan, M Finocchiaro, G Rossi, E Ligorio, C Zucali, PA Terracciano, L Toschi, L Roncalli, M Destro, A Incarbone, M Alloisio, M Santoro, A Varella-Garcia, M AF Cappuzzo, F. Janne, P. A. Skokan, M. Finocchiaro, G. Rossi, E. Ligorio, C. Zucali, P. A. Terracciano, L. Toschi, L. Roncalli, M. Destro, A. Incarbone, M. Alloisio, M. Santoro, A. Varella-Garcia, M. TI MET increased gene copy number and primary resistance to gefitinib therapy in non-small-cell lung cancer patients SO ANNALS OF ONCOLOGY LA English DT Article DE EGFR; gefitinib; MET; non-small cell lung cancer; tyrosine kinase inhibitor ID GROWTH-FACTOR RECEPTOR; TYROSINE KINASE INHIBITORS; IN-SITU HYBRIDIZATION; C-MET; EGFR MUTATIONS; ACQUIRED-RESISTANCE; 1ST-LINE GEFITINIB; T790M MUTATIONS; TUMOR-CELLS; AMPLIFICATION AB Background: MET amplification has been detected in similar to 20% of non-small-cell lung cancer patients (NSCLC) with epidermal growth factor receptor (EGFR) mutations progressing after an initial response to tyrosine kinase inhibitor (TKI) therapy. Patients and methods: We analyzed MET gene copy number using FISH in two related NSCLC cell lines, one sensitive (HCC827) and one resistant (HCC827 GR6) to gefitinib therapy and in two different NSCLC patient populations: 24 never smokers or EGFR FISH-positive patients treated with gefitinib (ONCOBELL cohort) and 182 surgically resected NSCLC not exposed to anti-EGFR agents. Results: HCC827 GR6-resistant cell line displayed MET amplification, with a mean MET copy number > 12, while sensitive HCC827 cell line had a mean MET copy number of 4. In the ONCOBELL cohort, no patient had gene amplification and MET gene copy number was not associated with outcome to gefitinib therapy. Among the surgically resected patients, MET was amplified in 12 cases (7.3%) and only four (2.4%) had a higher MET copy number than the resistant HCC827 GR6 cell line. Conclusions: MET gene amplification is a rare event in patients with advanced NSCLC. The development of anti-MET therapeutic strategies should be focused on patients with acquired EGFR-TKI resistance. C1 [Cappuzzo, F.; Finocchiaro, G.; Ligorio, C.; Zucali, P. A.; Destro, A.; Incarbone, M.; Alloisio, M.; Santoro, A.] Ist Clin Humanitas IRCCS, Dept Hematol Oncol, I-20089 Rozzano, Italy. [Janne, P. A.; Toschi, L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Skokan, M.; Varella-Garcia, M.] Univ Colorado, Ctr Canc, Dept Med Med Oncol, Aurora, CO USA. [Rossi, E.] CINECA Interuniv Consortium, Bologna, Italy. [Terracciano, L.] Univ Basel Hosp, Div Mol Pathol, CH-4031 Basel, Switzerland. [Roncalli, M.] Univ Milan, Dept Pathol, Rozzano, Italy. RP Cappuzzo, F (reprint author), Ist Clin Humanitas IRCCS, Dept Hematol Oncol, Via Manzoni 56, I-20089 Rozzano, Italy. EM federico.cappuzzo@humanitas.it OI Cappuzzo, Federico/0000-0002-6295-6767; Roncalli, Massimo/0000-0002-7901-8910 FU Italian Association for Cancer Research; US National Institute of Health [1R01CA114465-01] FX Italian Association for Cancer Research to FC; US National Institute of Health 1R01CA114465-01 to PAJ. NR 35 TC 141 Z9 146 U1 2 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 FEB PY 2009 VL 20 IS 2 BP 298 EP 304 DI 10.1093/annonc/mdn635 PG 7 WC Oncology SC Oncology GA 408AK UT WOS:000263405200016 PM 18836087 ER PT J AU Pires, VL Mankarious, LA AF Pires, Valerie L. Mankarious, Leila A. TI Inflammatory Cytokine Response to Injury in the Aging Rabbit Subglottis SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE epidermal growth factor; fibroblast growth factor 2; inflammatory cytokine; platelet-derived growth factor; rabbit; subglottic mucosal wound healing; subglottic stenosis; tracheal mucosal wound healing; transforming growth factor beta 1; vascular endothelial growth factor; wound healing model ID GROWTH-FACTORS; MANAGEMENT; ANGIOGENESIS; STENOSIS; MUCOSA C1 [Pires, Valerie L.; Mankarious, Leila A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol, Boston, MA 02114 USA. RP Pires, VL (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD FEB PY 2009 VL 118 IS 2 BP 139 EP 147 PG 9 WC Otorhinolaryngology SC Otorhinolaryngology GA 412PA UT WOS:000263735500010 PM 19326765 ER PT J AU Austen, WG Parrett, BM Taghinia, A Wolfort, SF Upton, J AF Austen, William G. Parrett, Brian M. Taghinia, Amir Wolfort, Sean F. Upton, Joseph TI The Subcutaneous Cervicofacial Flap Revisited SO ANNALS OF PLASTIC SURGERY LA English DT Article DE subcutaneous; cervicofacial flap; reconstruction; periorbital ID LARGE CHEEK DEFECTS; ROTATION FLAPS; RECONSTRUCTION; ADVANCEMENT; REPAIRS; NECK AB The cervicofacial flap has been the reconstruction of choice for midface soft tissue defects for over 30 years. Deep plane dissection has been advocated to decrease complication rates and improve results. However, the subcutaneous approach is still widely used. Over a 20-year period, we reviewed all patients who underwent subcutaneous cervicofacial flaps for cheek defects to analyze complications and results. Thirty-two patients (mean age, 7 1 years) underwent 32 subcutaneous cervicofacial flaps for cheek reconstruction after Mobs micrographic excision of skin cancer. The mean defect size was 7.2 x 5.8 cm. Mean follow-up was 32 months. Only 3 of 32 patients (9%) had minor flap tip or edge necrosis, all managed without further surgery. One patient (3%) had minor long-term ectropion with upward gaze and 31 of 32 patients were happy with their results. The subcutaneous rotation-advancement cervicofacial flap remains an excellent choice for check reconstruction with comparable tip necrosis rates and likely lower ectropion rates when compared with the deep plane technique. C1 [Austen, William G.; Parrett, Brian M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, Boston, MA USA. [Parrett, Brian M.; Taghinia, Amir; Wolfort, Sean F.; Upton, Joseph] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Plast Surg, Boston, MA 02215 USA. RP Upton, J (reprint author), 830 Boylston St,Suite 212, Chestnut Hill, MA 02467 USA. EM jupton3@gmail.com NR 16 TC 25 Z9 25 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-7043 J9 ANN PLAS SURG JI Ann. Plast. Surg. PD FEB PY 2009 VL 62 IS 2 BP 149 EP 153 DI 10.1097/SAP.0b013e31819354f5 PG 5 WC Surgery SC Surgery GA 397RV UT WOS:000262680700011 PM 19158524 ER PT J AU Maduekwe, UN Connors, S Rothrock, C Reinschild, B Ryeom, S Yoon, SS AF Maduekwe, U. N. Connors, S. Rothrock, C. Reinschild, B. Ryeom, S. Yoon, S. S. TI Analysis of 14 circulating angiogenic factors in colorectal cancer patients using a multiplex array reveals profiles associated with nodal or distant metastasis SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract C1 [Maduekwe, U. N.; Rothrock, C.; Reinschild, B.; Yoon, S. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Connors, S.; Ryeom, S.] Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2009 VL 16 SU 1 BP 15 EP 16 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA V16GF UT WOS:000207857400048 ER PT J AU Maduekwe, UM DeLaney, TF Chen, Y Kobayashi, WK Rosenberg, AE Nielsen, GP Sahani, DV Choy, E Harmon, DC Yoon, SS AF Maduekwe, U. M. DeLaney, T. F. Chen, Y. Kobayashi, W. K. Rosenberg, A. E. Nielsen, G. P. Sahani, D. V. Choy, E. Harmon, D. C. Yoon, S. S. TI Proton Beam, Intensity Modulated, and/or Intra-Operative Radiation Therapy Combined with Aggressive Anterior Surgical Resection for Retroperitoneal and Pelvic Sarcomas SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract C1 [Maduekwe, U. M.; DeLaney, T. F.; Chen, Y.; Kobayashi, W. K.; Rosenberg, A. E.; Nielsen, G. P.; Sahani, D. V.; Choy, E.; Harmon, D. C.; Yoon, S. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 FEB PY 2009 VL 16 SU 1 BP 25 EP 26 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA V16GF UT WOS:000207857400080 ER PT J AU Raut, CP Morgan, JA George, S Wagner, AJ Butrynski, JE Wang, Q Manola, J Fletcher, CD Demetri, GD Bertagnolli, MM AF Raut, C. P. Morgan, J. A. George, S. Wagner, A. J. Butrynski, J. E. Wang, Q. Manola, J. Fletcher, C. D. Demetri, G. D. Bertagnolli, M. M. TI Survival Rates in Patients (Pts) with Metastatic Gastrointestinal Stromal Tumor (GIST) Treated with Sunitinib Malate (SU) and Cytoreductive Surgery (CS) SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract C1 [Raut, C. P.; Morgan, J. A.; George, S.; Wagner, A. J.; Butrynski, J. E.; Wang, Q.; Manola, J.; Fletcher, C. D.; Demetri, G. D.; Bertagnolli, M. M.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2009 VL 16 SU 1 BP 27 EP 27 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA V16GF UT WOS:000207857400085 ER PT J AU Baldwin, SW Heinze, EM Chan, G Hansen, J Clements, J Nishimura, R Reeves, M Weisbart, R AF Baldwin, S. W. Heinze, E. M. Chan, G. Hansen, J. Clements, J. Nishimura, R. Reeves, M. Weisbart, R. TI Antibody-Mediated FoxP3 Protein Therapy Induces Apoptosis in Cancer Cells In Vitro and Inhibits Metastasis In Vivo SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract C1 [Baldwin, S. W.; Reeves, M.] Loma Linda VAMC, Loma Linda, CA 91342 USA. [Heinze, E. M.; Chan, G.; Hansen, J.; Clements, J.; Weisbart, R.] Vet Affairs Greater Los Angeles Hlth Care Syst, Sepulveda, CA USA. [Nishimura, R.] Olive View Univ Calif Los Angeles Med Ctr, Sylmar, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 FEB PY 2009 VL 16 SU 1 BP 37 EP 38 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA V16GF UT WOS:000207857400116 ER PT J AU Saidi, RF Ahad, AW Nalbantoglu, I Jacobs, M AF Saidi, R. F. Ahad, A. W. Nalbantoglu, I. Jacobs, M. TI The Expression of Interferon Receptor Alpha/Beta in Human Pancreatic Cancer in Nude Mice is Essential for Tumor Response to Interferon Alpha Treatment SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract C1 [Ahad, A. W.; Jacobs, M.] Providence Hosp, Southfield, MI 48037 USA. [Nalbantoglu, I.] St John Hosp & Med Ctr, Detroit, MI USA. [Saidi, R. F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2009 VL 16 SU 1 BP 40 EP 40 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA V16GF UT WOS:000207857400124 ER PT J AU Bafford, A Gadd, M Lipsitz, S Golshan, M AF Bafford, A. Gadd, M. Lipsitz, S. Golshan, M. TI Diminishing morbidity with the increased use of sentinel node biopsy in breast carcinoma SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract C1 [Bafford, A.; Lipsitz, S.; Golshan, M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Gadd, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 1 U1 0 U2 0 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 FEB PY 2009 VL 16 SU 1 BP 44 EP 45 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA V16GF UT WOS:000207857400140 ER PT J AU Wheeler, AJ Smith, BL Sellergren, AB Nolan, ME Chen, LL Kopans, DB Moore, R Lesnikoski, B Tanabe, KK Michaelson, JS AF Wheeler, A. J. Smith, B. L. Sellergren, A. B. Nolan, M. E. Chen, L. L. Kopans, D. B. Moore, R. Lesnikoski, B. Tanabe, K. K. Michaelson, J. S. TI The Impact of Breast Cancer Screening Practices on Survival over Three Decades: A Proposal for Improving Survival SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract C1 [Wheeler, A. J.; Smith, B. L.; Sellergren, A. B.; Nolan, M. E.; Chen, L. L.; Kopans, D. B.; Moore, R.; Tanabe, K. K.; Michaelson, J. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lesnikoski, B.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2009 VL 16 SU 1 BP 49 EP 49 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA V16GF UT WOS:000207857400154 ER PT J AU Samphao, S Wheeler, AJ Rafferty, E Specht, MC Hughes, KS Gadd, MA Michaelson, JS Smith, BL AF Samphao, S. Wheeler, A. J. Rafferty, E. Specht, M. C. Hughes, K. S. Gadd, M. A. Michaelson, J. S. Smith, B. L. TI Have Genetic Testing, Digital Mammography and MRI Screening Resulted in Earlier Detection of Breast Cancer in Women Under Age 40? SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract C1 [Samphao, S.; Wheeler, A. J.; Specht, M. C.; Hughes, K. S.; Gadd, M. A.; Michaelson, J. S.; Smith, B. L.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp,Div Surg Oncol, Boston, MA 02115 USA. [Rafferty, E.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 FEB PY 2009 VL 16 SU 1 BP 56 EP 57 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA V16GF UT WOS:000207857400181 ER PT J AU Specht, M Hanson, S Niemierko, A Wheeler, AJ Taghian, AG Smith, BL AF Specht, M. Hanson, S. Niemierko, A. Wheeler, A. J. Taghian, A. G. Smith, B. L. TI A nomogram for predicting the likelihood of successful re-excision after lumpectomy for breast cancer in patients with close or positive margins SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract C1 [Specht, M.; Hanson, S.; Niemierko, A.; Wheeler, A. J.; Taghian, A. G.; Smith, B. L.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2009 VL 16 SU 1 BP 60 EP 60 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA V16GF UT WOS:000207857400194 ER PT J AU Konstantinidis, I Deshpande, V Androutsopoulos, V Lauwers, G Castillo, CD Thayer, S Warshaw, A Ferrone, C AF Konstantinidis, I. Deshpande, V. Androutsopoulos, V. Lauwers, G. Fernandez-Del Castillo, C. Thayer, S. Warshaw, A. Ferrone, C. TI Intrapancreatic Cholangiocarcinomas and Pancreatic Head Ductal Adenocarcinoma. Anatomic Neighbors With Different Outcomes SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract C1 [Konstantinidis, I.; Deshpande, V.; Androutsopoulos, V.; Lauwers, G.; Fernandez-Del Castillo, C.; Thayer, S.; Warshaw, A.; Ferrone, C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2009 VL 16 SU 1 BP 83 EP 83 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA V16GF UT WOS:000207857400274 ER PT J AU Meyers, MO Hollis, DR Mayer, RJ Goldberg, RM Benson, AB Cummings, B Gunderson, LL Martenson, JA Macdonald, JS O'Connell, M Tepper, JE AF Meyers, M. O. Hollis, D. R. Mayer, R. J. Goldberg, R. M. Benson, A. B., III Cummings, B. Gunderson, L. L. Martenson, J. A. Macdonald, J. S. O'Connell, M. Tepper, J. E. TI Ratio of Metastatic to Examined Lymph Nodes is Predictive of Local Recurrence in Rectal Cancer: Analysis of Data From Intergroup Trial 0114 SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract C1 [Meyers, M. O.; Goldberg, R. M.; Tepper, J. E.] Univ N Carolina, Chapel Hill, NC USA. [Mayer, R. J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hollis, D. R.] CALGB Stat Ctr, Durham, NC USA. [Benson, A. B., III] Northwestern Univ, Sch Med, Chicago, IL USA. [Gunderson, L. L.] Mayo Clin, Scottsdale, AZ USA. [Martenson, J. A.] Mayo Clin, Rochester, MN USA. [O'Connell, M.] NSABP Operat Off, Pittsburgh, PA USA. [Cummings, B.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Macdonald, J. S.] St Vincent Hosp, New York, NY USA. RI Goldberg , Richard/M-1311-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2009 VL 16 SU 1 BP 90 EP 90 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA V16GF UT WOS:000207857400298 ER PT J AU Honings, J Gaissert, HA Verhagen, AFTM van Dijck, JAAM van der Heijden, HFM van Die, L Bussink, J Kaanders, JHAM Marres, HAM AF Honings, Jimmie Gaissert, Henning A. Verhagen, Ad F. T. M. van Dijck, Jos A. A. M. van der Heijden, Henricus F. M. van Die, Lya Bussink, Johan Kaanders, Johannes H. A. M. Marres, Henri A. M. TI Undertreatment of Tracheal Carcinoma: Multidisciplinary Audit of Epidemiologic Data SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID TUMORS; CANCER; NATIONWIDE; NEOPLASMS; SURVIVAL; FINLAND; CARINA AB National epidemiologic data were examined to determine the eligibility for curative therapy in tracheal carcinoma. An expert audit of primary tracheal carcinomas registered from 2000 to 2005 with the Netherlands Cancer Registry (NCR) included blinded patient data and radiographic review to assess diagnosis and resectability. Actual treatment was compared with the opinions of a multidisciplinary panel (Radboud panel) and a second reviewer. Of 101 NCR-registered primary tracheal carcinomas, the Radboud panel diagnosis was metastatic disease or local extension of adjacent tumors in 34. Seventeen cases were excluded for missing data. In 50 cases confirmed by panel and a second reviewer, actual treatment consisted of surgery in 12 (24%), radiotherapy in 29 (58%), endobronchial treatment in 6 (12%), and observation in 3 (6%). Both panel and second reviewer identified 16 additional surgical candidates, a total of 28 (56%) of 50. Treatment recommendations of panel and second reviewer disagreed in four cases (8%). One-third of NCR-registered primary tracheal carcinomas were misclassified nontracheal primary tumors involving the trachea. A majority of cases meeting audit criteria for diagnosis and surgical resection was treated with other modalities. Interreviewer disagreement was small. The audit of a national cancer registry suggests that incorrect diagnosis and undertreatment are common in rare airway tumors. C1 [Honings, Jimmie; Marres, Henri A. M.] Radboud Univ Nijmegen, Med Ctr, Dept Otorhinolaryngol & Head & Neck Surg, NL-6500 HB Nijmegen, Netherlands. [Honings, Jimmie; van Dijck, Jos A. A. M.] Comprehens Canc Ctr E, Nijmegen, Netherlands. [Gaissert, Henning A.] Harvard Univ, Sch Med, Boston, MA USA. [Gaissert, Henning A.] Massachusetts Gen Hosp, Div Gen Thorac Surg, Boston, MA 02114 USA. [Verhagen, Ad F. T. M.] Radboud Univ Nijmegen, Med Ctr, Dept Cardiothorac Surg, NL-6500 HB Nijmegen, Netherlands. [van Dijck, Jos A. A. M.] Radboud Univ Nijmegen, Med Ctr, Dept Epidemiol & Biostat, NL-6500 HB Nijmegen, Netherlands. [van der Heijden, Henricus F. M.] Radboud Univ Nijmegen, Med Ctr, Dept Pulm Dis, NL-6500 HB Nijmegen, Netherlands. [van Die, Lya] Radboud Univ Nijmegen, Med Ctr, Dept Radiol, NL-6500 HB Nijmegen, Netherlands. [Bussink, Johan; Kaanders, Johannes H. A. M.] Radboud Univ Nijmegen, Med Ctr, Dept Radiat Oncol, NL-6500 HB Nijmegen, Netherlands. RP Honings, J (reprint author), Radboud Univ Nijmegen, Med Ctr, Dept Otorhinolaryngol & Head & Neck Surg, POB 9101, NL-6500 HB Nijmegen, Netherlands. EM j.honings@kno.umcn.nl RI van der Heijden, H.F.M. (Erik)/D-3774-2009; Kaanders, Hans/A-7432-2014; Marres, H.A.M./H-8071-2014; Bussink, Jan/N-3584-2014; Verhagen, A.F.T.M./L-4709-2015; Honings, Jimmie/B-3639-2016 OI van der Heijden, H.F.M. (Erik)/0000-0003-3596-518X; Honings, Jimmie/0000-0001-5077-3472 NR 18 TC 8 Z9 9 U1 0 U2 2 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 FEB PY 2009 VL 16 IS 2 BP 246 EP 253 DI 10.1245/s10434-008-0241-3 PG 8 WC Oncology; Surgery SC Oncology; Surgery GA 401TM UT WOS:000262965300004 PM 19037701 ER PT J AU Puli, S Bechtold, M Reddy, J Choudhary, A Antillon, M Brugge, W AF Puli, Srinivas R. Bechtold, Matthew L. Reddy, Jyotsna B. K. Choudhary, Abhishek Antillon, Mainor R. Brugge, William R. TI How Good is Endoscopic Ultrasound in Differentiating Various T Stages of Rectal Cancer? Meta-Analysis and Systematic Review SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID COMPUTED-TOMOGRAPHY; TRANSRECTAL ULTRASOUND; ENDORECTAL ULTRASONOGRAPHY; COLORECTAL-CANCER; ENDOLUMINAL ULTRASONOGRAPHY; INTRARECTAL ULTRASOUND; DIAGNOSTIC-ACCURACY; LOCAL EXCISION; FOLLOW-UP; CARCINOMA AB Published data on accuracy of endoscopic ultrasound (EUS) in differentiating T stages of rectal cancers is varied. Study selection criteria were to select only EUS studies confirmed with results of surgical pathology. Articles were searched in Medline and Pubmed. Pooling was conducted by both fixed and random effects models. Initial search identified 3,630 reference articles, of which 42 studies (N = 5,039) met the inclusion criteria and were included in this analysis. The pooled sensitivity and specificity of EUS to determine T1 stage was 87.8% [95% confidence interval (CI) 85.3-90.0%] and 98.3% (95% CI 97.8-98.7%), respectively. For T2 stage, EUS had a pooled sensitivity and specificity of 80.5% (95% CI 77.9-82.9%) and 95.6% (95% CI 94.9-96.3%), respectively. To stage T3 stage, EUS had a pooled sensitivity and specificity of 96.4% (95% CI 95.4-97.2%) and 90.6% (95% CI 89.5-91.7%), respectively. In determining the T4 stage, EUS had a pooled sensitivity of 95.4% (95% CI 92.4-97.5%) and specificity of 98.3% (95% CI 97.8-98.7%). The p value for chi-squared heterogeneity for all the pooled accuracy estimates was > 0.10. We conclude that, as a result of the demonstrated sensitivity and specificity, EUS should be the investigation of choice to T stage rectal cancers. The sensitivity of EUS is higher for advanced disease than for early disease. EUS should be strongly considered for T staging of rectal cancers. C1 [Puli, Srinivas R.; Bechtold, Matthew L.; Reddy, Jyotsna B. K.; Choudhary, Abhishek; Antillon, Mainor R.] Univ Missouri, Div Gastroenterol & Hepatol, Columbia, MO 65211 USA. [Puli, Srinivas R.] Div Gastroenterol, Columbia, MO 65212 USA. [Brugge, William R.] Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. RP Puli, S (reprint author), Univ Missouri, Div Gastroenterol & Hepatol, Columbia, MO 65211 USA. EM srinivaspuli@yahoo.com NR 84 TC 82 Z9 96 U1 1 U2 7 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 FEB PY 2009 VL 16 IS 2 BP 254 EP 265 DI 10.1245/s10434-008-0231-5 PG 12 WC Oncology; Surgery SC Oncology; Surgery GA 401TM UT WOS:000262965300005 PM 19018597 ER PT J AU Akins, CW Blackstone, EH Miller, C Kouchoukos, NT Turina, MI AF Akins, Cary W. Blackstone, Eugene H. Miller, Craig Kouchoukos, Nicholas T. Turina, Marko I. TI Guidelines for Reporting Mortality and Morbidity After Cardiac Valve Interventions-Need for a Reappraisal? (Response) SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material ID PROSTHETIC PARAVALVULAR LEAKS; SURGICAL-CORRECTION C1 [Akins, Cary W.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Cleveland Clin Fdn, Inst Heart & Vasc, Dept Thorac & Cardiovasc Surg, Cleveland, OH 44195 USA. Stanford Univ, Sch Med, Dept Cardiovasc & Thorac Surg, Stanford, CA 94305 USA. Thorac & Vasc Surg Inc, St Louis, MO USA. Univ Zurich Hosp, Dept Surg, CH-8091 Zurich, Switzerland. RP Akins, CW (reprint author), Massachusetts Gen Hosp, Dept Surg, White 503,55 Fruit St, Boston, MA 02114 USA. EM cakins@partners.org NR 5 TC 3 Z9 3 U1 0 U2 0 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 FEB PY 2009 VL 87 IS 2 BP 359 EP 360 DI 10.1016/j.athoracsur.2008.10.094 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 396SY UT WOS:000262612600002 ER PT J AU Dai, TH Tegos, GP Burkatovskaya, M Castano, AP Hamblin, MR AF Dai, Tianhong Tegos, George P. Burkatovskaya, Marina Castano, Ana P. Hamblin, Michael R. TI Chitosan Acetate Bandage as a Topical Antimicrobial Dressing for Infected Burns SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID PSEUDOMONAS-AERUGINOSA; IN-VIVO; PHOTODYNAMIC THERAPY; SURFACE INFECTION; PROTEUS-MIRABILIS; WOUND INFECTIONS; VIRULENCE FACTOR; MOUSE MODEL; MICE; BACTERIA AB An engineered chitosan acetate bandage preparation (HemCon) is used as a hemostatic dressing, and its chemical structure suggests that it should also be antimicrobial. We previously showed that when a chitosan acetate bandage was applied to full-thickness excisional wounds in mice that had been infected with pathogenic bioluminescent bacteria (Pseudomonas aeruginosa, Proteus mirabilis, and Staphylococcus aureus), it was able to rapidly kill the bacteria and save the mice from developing fatal infections. Wound healing was also stimulated. In the present study, we asked whether a chitosan acetate bandage could act as a topical antimicrobial dressing when it was applied to third-degree burns in mice contaminated with two of these bacterial species (P. aeruginosa and P. mirabilis). Preliminary experiments established the length of burn time and the number of bacteria needed to produce fatal infections in untreated mice and established that the chitosan acetate bandage could adhere to the infected burn for up to 21 days. In the case of P. aeruginosa infections, the survival rate of mice treated with the chitosan acetate bandage was 73.3% (whereas the survival rate of mice treated with a nanocrystalline silver dressing was 27.3% [P = 0.0055] and that of untreated mice was 13.3% [P < 0.0002]). For P. mirabilis infections, the comparable survival rates were 66.7%, 62.5%, and 23.1% respectively. Quantitative bioluminescent signals showed that the chitosan acetate bandage effectively controlled the growth of bacteria in the burn and prevented the development of systemic sepsis, as shown by blood culture. These data suggest that chitosan acetate bandage is efficacious in preventing fatal burn infections. C1 [Dai, Tianhong; Tegos, George P.; Burkatovskaya, Marina; Castano, Ana P.; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Dai, Tianhong; Tegos, George P.; Castano, Ana P.; 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, 40 Blossom St, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu RI Tegos, George/C-8830-2011; OI Hamblin, Michael/0000-0001-6431-4605 FU HemCon Medical Technologies, Inc.; U. S. National Institutes of Health [R01 AI050875] FX This work was supported in part by HemCon Medical Technologies, Inc., and the U. S. National Institutes of Health (grant R01 AI050875 to M. R. H.). NR 44 TC 55 Z9 58 U1 2 U2 24 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 FEB PY 2009 VL 53 IS 2 BP 393 EP 400 DI 10.1128/AAC.00760-08 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 397EY UT WOS:000262646500005 PM 19015341 ER PT J AU Bin Kim, H Park, CH Kim, CJ Kim, EC Jacoby, GA Hooper, DC AF Bin Kim, Hong Park, Chi Hye Kim, Chung Jong Kim, Eui-Chong Jacoby, George A. Hooper, David C. TI Prevalence of Plasmid-Mediated Quinolone Resistance Determinants over a 9-Year Period SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ESCHERICHIA-COLI; KLEBSIELLA-PNEUMONIAE; UNITED-STATES; FLUOROQUINOLONE RESISTANCE; ENTEROBACTER-CLOACAE; MODIFYING ENZYME; QNR PREVALENCE; MECHANISMS; EMERGENCE; GENE AB Recently, several plasmid-mediated quinolone resistance (PMQR) genes conferring low levels of quinolone resistance have been discovered. To evaluate the temporal change in the prevalence of PMQR genes over a decade in a tertiary hospital in the Republic of Korea, we selected every fifth isolate of Escherichia coli and Klebsiella pneumoniae and every third isolate of Enterobacter cloacae between 1998 and 2001 and between 2005 and 2006 from a collection of blood isolates. Six PMQR genes [qnrA, qnrB, qnrC, qnrS, aac(6')-Ib-cr, and qepA] were screened by multiplex PCR and then confirmed by direct sequencing, and the aac(6')-Ib-positive PCR products were digested with BtsCI to identify the aac(6')-Ib-cr variant. Of 461 isolates, 37 (8%) had one of the six PMQR genes; 13 (5%) of 261 E. coli strains, 13 (10%) of 135 K. pneumoniae strains, and 11 (17%) of 65 E. cloacae strains. qnrB was the most common PMQR gene and was found as early as 1998, whereas qnrS, aac(6')-Ib-cr, and qepA emerged after 2000. None of the isolates carried qnrA or qnrC. Ciprofloxacin resistance increased over time (P < 0.001), and the overall prevalence of PMQR genes tended to increase (P = 0.20). PMQR-positive isolates had significantly higher ciprofloxacin resistance and multidrug resistance rates (P = 0.005 and P < 0.001, respectively). The increasing frequency of ciprofloxacin resistance in Enterobacteriaceae was associated with an increasing prevalence of PMQR genes, and this change involved an increase in the diversity of the PMQR genes and also an increase in the prevalence of the mutations in gyrA, parC, or both in PMQR-positive strains but not PMQR-negative strains. C1 [Bin Kim, Hong; Park, Chi Hye; Hooper, David C.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Bin Kim, Hong] Seoul Natl Univ, Bundang Hosp, Dept Internal Med, Songnam, South Korea. [Bin Kim, Hong; Kim, Chung Jong] Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 151, South Korea. [Kim, Eui-Chong] Seoul Natl Univ, Coll Med, Dept Lab Med, Seoul, South Korea. [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 RI Kim, Hong Bin/J-5452-2012; Kim, Eu Chong/J-5424-2012 OI Kim, Hong Bin/0000-0001-6262-372X; FU National Institutes of Health, U. S. Public Health Service [R01AI057576, R01AI043312] FX This work was supported in part by grants R01AI057576 ( to D. C. H.) and R01AI043312 ( to G. A. J.) from the National Institutes of Health, U. S. Public Health Service. NR 33 TC 123 Z9 127 U1 4 U2 17 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 FEB PY 2009 VL 53 IS 2 BP 639 EP 645 DI 10.1128/AAC.01051-08 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 397EY UT WOS:000262646500037 PM 19064896 ER PT J AU Wang, MH Jacoby, GA Mills, DM Hooper, DC AF Wang, Minghua Jacoby, George A. Mills, Debra M. Hooper, David C. TI SOS Regulation of qnrB Expression SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID MEDIATED QUINOLONE RESISTANCE; ESCHERICHIA-COLI; GENE-EXPRESSION; TRANSFERABLE PLASMID; FLUOROQUINOLONES; DETERMINANTS; MUTAGENESIS; MUTATIONS; INDUCTION; BACTERIA AB In the sequence upstream from qnrB (but not qnrA or qnrS) is a LexA binding site. qnrB was shown to be under SOS control by demonstrating that quinolone susceptibility decreased with increasing temperature in a strain with a recA441(Ts) allele, whereas qnrB expression increased in response to ciprofloxacin or mitomycin C in strains with an intact lexA gene. C1 [Wang, Minghua; Hooper, David C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wang, Minghua] Fudan Univ, Inst Antibiot, Huashan Hosp, Shanghai 200433, Peoples R China. [Jacoby, George A.; Mills, Debra M.] Lahey Clin Fdn, Burlington, MA USA. RP Jacoby, GA (reprint author), 41 Mall Rd, Burlington, MA 01805 USA. EM george.a.jacoby@lahey.org FU National Basic Research Program of China from the Ministry of Science and Technology [2005CB0523101]; National Institutes of Health, U. S. Public Health Service [AI43312, AI57576] FX M. W. was supported by the China Scholarship Council and grant no. 2005CB0523101 from the National Basic Research Program of China from the Ministry of Science and Technology. The work was also supported by grants AI43312 (G.A.J.) and AI57576 (D. C. H.) from the National Institutes of Health, U. S. Public Health Service. NR 24 TC 31 Z9 31 U1 0 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 FEB PY 2009 VL 53 IS 2 BP 821 EP 823 DI 10.1128/AAC.00132-08 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 397EY UT WOS:000262646500069 PM 19029320 ER PT J AU Primack, BA Swanier, B Georgiopoulos, AM Land, SR Fine, MJ AF Primack, Brian A. Swanier, Brandi Georgiopoulos, Anna M. Land, Stephanie R. Fine, Michael J. TI Association Between Media Use in Adolescence and Depression in Young Adulthood A Longitudinal Study SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID SECONDARY-SCHOOL CHILDREN; MAJOR DEPRESSION; BODY-IMAGE; TELEVISION IMAGES; COLLEGE-WOMEN; SEXUAL REGRET; POPULAR-MUSIC; INTERNET USE; RISK-FACTORS; EXPOSURE AB Context: Although certain media exposures have been linked to the presence of psychiatric conditions, few studies have investigated the association between media exposure and depression. Objective: To assess the longitudinal association between media exposure in adolescence and depression in young adulthood in a nationally representative sample. Design: Longitudinal cohort study. Setting and Participants: We used the National Longitudinal Survey of Adolescent Health (Add Health) to investigate the relationship between electronic media exposure in 4142 adolescents who were not depressed at baseline and subsequent development of depression after 7 years of follow-up. Main Outcome Measure: Depression at follow-up assessed using the 9-item Center for Epidemiologic Studies Depression Scale. Results: Of the 4142 participants (47.5% female and 67.0% white) who were not depressed at baseline and who underwent follow-up assessment, 308 (7.4%) reported symptoms consistent with depression at follow-up. Controlling for all covariates including baseline Center for Epidemiologic Studies-Depression Scale score, those reporting more television use had significantly greater odds of developing depression (odds ratio [95% confidence interval], 1.08 [1.01-1.16]) for each additional hour of daily television use. In addition, those reporting more total media exposure had significantly greater odds of developing depression (1.05 [1.0004-1.10]) for each additional hour of daily use. We did not find a consistent relationship between development of depressive symptoms and exposure to videocassettes, computer games, or radio. Compared with young men, young women were less likely to develop depression given the same total media exposure (odds ratio for interaction term, 0.93 [0.88-0.99]). Conclusion: Television exposure and total media exposure in adolescence are associated with increased odds of depressive symptoms in young adulthood, especially in young men. C1 [Primack, Brian A.; Swanier, Brandi; Fine, Michael J.] Univ Pittsburgh, Sch Med, Ctr Res Hlth Care, Pittsburgh, PA 15213 USA. [Primack, Brian A.; Fine, Michael J.] Univ Pittsburgh, Sch Med, Div Gen Internal Med, Dept Med, Pittsburgh, PA 15213 USA. [Primack, Brian A.] Univ Pittsburgh, Sch Med, Div Adolescent Med, Dept Pediat, Pittsburgh, PA 15213 USA. [Land, Stephanie R.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15213 USA. [Fine, Michael J.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Georgiopoulos, Anna M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Child & Adolescent Psychiat, Boston, MA USA. RP Primack, BA (reprint author), Univ Pittsburgh, Sch Med, Ctr Res Hlth Care, 230 McKee Pl,Ste 600, Pittsburgh, PA 15213 USA. EM bprimack@pitt.edu FU National Cancer Institute [K07-CA114315]; Robert Wood Johnson Foundation; Maurice Falk Foundation FX This study was supported by Career Development Award K07-CA114315 from the National Cancer Institute, a Physician Faculty Scholar Award from the Robert Wood Johnson Foundation, and a grant from the Maurice Falk Foundation (all to Dr Primack). NR 70 TC 80 Z9 82 U1 6 U2 37 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD FEB PY 2009 VL 66 IS 2 BP 181 EP 188 PG 8 WC Psychiatry SC Psychiatry GA 402CQ UT WOS:000262992200010 PM 19188540 ER PT J AU Schjeide, BMM Hooli, B Parkinson, M Hogan, MF DiVito, J Mullin, K Blacker, D Tanzi, RE Bertram, L AF Schjeide, Brit-Maren M. Hooli, Basavaraj Parkinson, Michele Hogan, Meghan F. DiVito, Jason Mullin, Kristina Blacker, Deborah Tanzi, Rudolph E. Bertram, Lars TI GAB2 as an Alzheimer Disease Susceptibility Gene SO ARCHIVES OF NEUROLOGY LA English DT Article ID GENOME-WIDE ASSOCIATION; FAMILY-BASED ASSOCIATION; APOLIPOPROTEIN-E; ONSET; GRB2; EPSILON-4; VARIANTS; PROTEIN; ALLELE; RISK AB Background: Genomewide association (GWA) studies have recently implicated 4 novel Alzheimer disease (AD) susceptibility loci (GAB2, GOLM1, and 2 uncharacterized loci to date on chromosomes 9p and 15q). To our knowledge, these findings have not been independently replicated. Objective: To assess these GWA findings in 4 large data sets of families affected by AD. Design: Follow-up of genetic association findings in previous studies. Setting: Academic research. Participants: More than 4000 DNA samples from almost 1300 families affected with AD. Main Outcome Measures: Genetic association analysis testing of 4 GWA signals (rs7101429 [GAB2], rs7019241 [GOLM1], rs10519262 [chromosome 15q], and rs9886784 [chromosome 9p]) using family-based methods. Results: In the combined analyses, only rs7101429 in GAB2 yielded significant evidence of association with the same allele as in the original GWA study (P=.002). The results are in agreement with recent meta-analyses of this and other GAB2 polymorphisms suggesting approximately a 30% decrease in risk for AD among carriers of the minor alleles. None of the other 3 tested loci showed consistent evidence for association with AD across the investigated data sets. Conclusions: GAB2 contains genetic variants that may lead to a modest change in the risk for AD. Despite these promising results, more data from independent samples are needed to better evaluate the potential contribution of GAB2 to AD risk in the general population. C1 [Schjeide, Brit-Maren M.; Hooli, Basavaraj; Parkinson, Michele; Hogan, Meghan F.; DiVito, Jason; Mullin, Kristina; Tanzi, Rudolph E.; Bertram, Lars] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Genet & Aging Res Unit,Dept Neurol,MassGen Inst N, Charlestown, MA 02129 USA. [Blacker, Deborah] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Gerontol Res Unit, Charlestown, MA 02129 USA. [Blacker, Deborah] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Bertram, L (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Genet & Aging Res Unit,Dept Neurol,MassGen Inst N, 114 16th St, Charlestown, MA 02129 USA. EM bertram.lars@gmail.com RI Bertram, Lars/K-3889-2015 OI Bertram, Lars/0000-0002-0108-124X FU National Institute on Aging [5R01AG23667]; National Institute of Mental Health [R37MH60009]; Extendicare Foundation; Cure Alzheimer's Fund FX This study was supported by grant 5R01AG23667 from the National Institute on Aging (Dr Bertram), by grant R37MH60009 from the National Institute of Mental Health (Dr Tanzi), and by grants from the Extendicare Foundation and the Cure Alzheimer's Fund (Dr Bertram). The AlzGene database project is funded by the Cure Alzheimer's Fund (principal investigator Dr Bertram). NR 23 TC 22 Z9 23 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD FEB PY 2009 VL 66 IS 2 BP 250 EP 254 DI 10.1001/archneurol.2008.552 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 405DP UT WOS:000263203200015 PM 19204163 ER PT J AU Brucker, AJ Qin, H Antoszyk, AN Beck, RW Bressler, NM Browning, DJ Elman, MJ Glassman, AR Gross, JG Kollman, C Wells, JA Browning, D Browning, D Antoszyk, AN Brooks, DR Cowen, MK Stallings, AH Helms, JV Price, AK Murphy, HL Pierce, RE Ruiz, KA George, RJ McOwen, MD Balasubramaniam, UM Powers, ME McClain, D Clark, LM Braverman, JM Ciardella, AP Ryman, LS Dixon, BF Stillberger, MA Zapata, JD Rhodes, RC Brown, DM Elman, MJ Raden, RZ Sloan, MD Butcher, TM Starr, J Salfer-Firestone, D Coffey, T Singletary, PV Gore, N Cain, T Sotirakos, P Shabi, G Lazarus, HS Bunch, DP Ridge, AD Booth, K Davis, LC Trimble, M Moore, J Fish, GE Wang, RC Arnwine, J Arceneaux, S Sanchez, B Gray, K Cummings, K Aguado, H Jaramillo, D Magee, MA Flowers, AM Cummings, PW Gabriel, RA Bland, KK Lovit, HK Mallet, CN Price, RL Christoff, R Edwards, PA Ober, MD Rock, SM Monk, MK Murphy, J Wilson, DF Croswell, M Rusinek, BA Schillace, LM Troszak, TA Stern, BA Wells, JA Clark, WL Gridine, MD Cahill, CP Hickman, AB Spivey, R Kim, JE Han, DP Wirostko, WJ Alvarez, D Drescher, TS Knapp, RJ Barwick, V Flanders, J Backes, DB Selchert, KJ Beringer, JR Keller, KL Chan, CK Salib, DM Lin, SG Nuthi, ASD Dickerson, ED Keith, TL Sage, KE Andresen, TA Aldana, I Wiskirchen, TB Castillo, SU Warren, S Rollins, K Huff, KM Chesbrough, DJ Bretz, SE Sharuk, GS Schlossman, DK Kopple, A Stockman, ME Cavicchi, RW Casazza, EL Fan, JT Rauser, ME Rollins, KE Corliss, CJ Osuna, SL Kiernan, WH Cloud, JD Milam, W Saldana, G Hampton, GR Spalding, SC Torrisi, PF Rutledge, BK Grinnell, CJ DiSano, FM Kwasniewski, LM Czajak, TC Capone, LA Corey, B Hay, PB Martinez, JA Montesclaros, CA Odean, CE Sabo, RA Garcia, CA McCrary, J Garibay, E Lessieur, EM Villeda, PR Paz, HL Montoya, JP Nguyen, CV Santisbon, E Cerda, SM Lopez, RA Ramirez, A Friedman, SM Blackmer, KA Key, JS Carlton, S Fagan, DA Gregory, V Aaberg, TM Scott, S Markus, D Kronlein, S Lewis, S Shami, M Pusser, P Tarter, CL Squires, L Wentlandt, TF Hartnett, MER Garg, S Barnhart, CJ Cantrell, D Esquejo, RL Shields, KD Lyon, AT Kaminski, LA Ackatz, LE O'Donnell, LM Shankle, J Davidorf, FH Green, AM Perry, JG Chaudhuri, CG Savage, SJ Drouilhet, JH Pelke, S Nobler, D Batlle, IR Batlle, KA Williams, GM Parks, M Varner, RS Googe, J McMillan, TA Anderson, NG Perkins, SL Higdon, CT Hunt, C Whetstone, JK Jacobus, M Moore, M Blais, PA Cooney, MJ Sorenson, JA Maranan, L Scolaro, M Agresta, EI Caldwell, WS DuCoty, CL Varadian, S Salinas, C Banalewicz, E Hamel, M Nagle, AL Chen, M Wong, KL Holland, C Hagin, K Sneath, M Miller, R Beck, RW Glassman, AR Barros, J Dale, BB Constantine, SR Dupre, SS Edwards, AR Hutton, M Johnson, PA Kollman, C Lester, LA Loggins, BL McClellan, SL Murtaugh, P Qin, PSMH Pritchard, R Ramirez, H Scott, E Stockdale, CR Brucker, AJ Browning, D Chew, EY AF Brucker, Alexander J. Qin, Haijing Antoszyk, Andrew N. Beck, Roy W. Bressler, Neil M. Browning, David J. Elman, Michael J. Glassman, Adam R. Gross, Jeffrey G. Kollman, Craig Wells, John A., III Browning, David Browning, David Antoszyk, Andrew N. Brooks, Danielle R. Cowen, Melissa K. Stallings, Alison H. Helms, Jennifer V. Price, Angela K. Murphy, Heather L. Pierce, Rachel E. Ruiz, Karen A. George, Richard J. McOwen, Michael D. Balasubramaniam, Uma M. Powers, Michele E. McClain, Donna Clark, Loraine M. Braverman, Jon M. Ciardella, Antonio P. Ryman, Leif S. Dixon, Brenner F. Stillberger, Melissa A. Zapata, Janelle Dane Rhodes, Rosemary C. Brown, Debbie M. Elman, Michael J. Raden, Robert Z. Sloan, Michelle D. Butcher, Tammy M. Starr, Joann Salfer-Firestone, Dena Coffey, Teresa Singletary, Pamela V. Gore, Nancy Cain, Terri Sotirakos, Peter Shabi, Giorya Lazarus, Howard S. Bunch, Debra Paige Ridge, Angela D. Booth, Kelly Davis, Liana C. Trimble, Margaret Moore, Jay Fish, Gary E. Wang, Robert C. Arnwine, Jean Arceneaux, Sally Sanchez, Brenda Gray, Keith Cummings, Kimberly Aguado, Hank Jaramillo, Diana Magee, Michael A. Flowers, Amy M. Cummings, Peggy W. Gabriel, Regina A. Bland, Kristin K. Lovit, Heidi K. Mallet, Chris N. Price, Randall L. Christoff, Rick Edwards, Paul Andrew Ober, Michael D. Rock, Sheila M. Monk, Mary K. Murphy, Janet Wilson, Dorena F. Croswell, Mark Rusinek, Brian A. Schillace, Lisa M. Troszak, Tracy A. Stern, Bradley A. Wells, John A. Clark, W. Lloyd Gridine, Marcia D. Cahill, Cassie P. Hickman, Amy B. Spivey, Robbin Kim, Judy E. Han, Dennis P. Wirostko, William J. Alvarez, Dawn Drescher, Troy S. Knapp, Rowena J. Barwick, Vicki Flanders, Judy Backes, Dennis B. Selchert, Kathy J. Beringer, Joseph R. Keller, Kristy L. Chan, Clement K. Salib, David M. Lin, Steven G. Nuthi, Asha S. D. Dickerson, Eric D. Keith, Trina L. Sage, Kelly E. Andresen, Teri A. Aldana, Isela Wiskirchen, Tina B. Castillo, Sandra U. Warren, Sara Rollins, Kara Huff, Kenneth M. Chesbrough, Donna J. Bretz, Sabrina E. Sharuk, George S. Schlossman, Deborah K. Kopple, Ann Stockman, Margaret E. Cavicchi, Robert W. Casazza, Ellen L. Fan, Joseph T. Rauser, Michael E. Rollins, Kara E. Corliss, Carrousel J. Osuna, Sarina L. Kiernan, William H. Cloud, Johnathan D. Milam, William Saldana, Gene Hampton, G. Robert Spalding, Samuel C. Torrisi, Paul F. Rutledge, Bryan K. Grinnell, Cindy J. DiSano, Fayth M. Kwasniewski, Lynn M. Czajak, Tanya C. Capone, Lynn A. Corey, Bob Hay, Peter B. Martinez, Jose A. Montesclaros, Chris A. Odean, Carrie E. Sabo, Richard A. Garcia, Charles A. McCrary, John Garibay, Elizabeth Lessieur, Emma M. Villeda, Penelope Reyes Paz, Hugo L. Montoya, Juan P. Nguyen, Cecilia Vi Santisbon, Edgardo Cerda, Sindya M. Lopez, Rafael A. Ramirez, Angela Friedman, Scott M. Blackmer, Kelly A. Key, Jolleen S. Carlton, Steve Fagan, Damanda A. Gregory, Virginia Aaberg, Thomas M. Scott, Sarita Markus, Debra Kronlein, Sandy Lewis, Sandra Shami, Michel Pusser, Phyllis Tarter, Carrie L. Squires, Linda Wentlandt, Thom F. Hartnett, Mary Elizabeth R. Garg, Seema Barnhart, Cassandra J. Cantrell, Debra Esquejo, Rona Lyn Shields, Kelly D. Lyon, Alice T. Kaminski, Lori A. Ackatz, Lori E. O'Donnell, Laima M. Shankle, Jonathan Davidorf, Frederick H. Green, Alicia M. Perry, Jerilyn G. Chaudhuri, Chhanda G. Savage, Scott J. Drouilhet, John H. Pelke, Susan Nobler, Deborah Batlle, Ivan R. Batlle, Karla A. Williams, Gwendolyn M. Parks, Michelle Varner, R. Scott Googe, Joseph McMillan, Tod A. Anderson, Nicholas G. Perkins, Stephen L. Higdon, Christina T. Hunt, Cecile Whetstone, Jerry K. Jacobus, Michael Moore, Misty Blais, Paul A. Cooney, Michael J. Sorenson, John A. Maranan, Leandro Scolaro, Maria Agresta, Eugene I. Caldwell, W. Smith DuCoty, Collin L. Varadian, Sylvia Salinas, Claudia Banalewicz, Erika Hamel, Mark Nagle, Alex L. Chen, Melvin Wong, Keye L. Holland, Christine Hagin, Karen Sneath, Mark Miller, Rosa Beck, Roy W. Glassman, Adam R. Barros, Joy Dale, Brian B. Constantine, Sharon R. Dupre, Simone S. Edwards, Allison R. Hutton, Meagan Johnson, Paula A. Kollman, Craig Lester, Lee Anne Loggins, Brenda L. McClellan, Shannon L. Murtaugh, Patricia Qin, Pamela S. Moke Haijing Pritchard, Rosa Ramirez, Hiram Scott, Eureca Stockdale, Cynthia R. Brucker, Alexander J. Browning, David Chew, Emily Y. CA Diabetic Retinopathy Clinical Res TI Observational Study of the Development of Diabetic Macular Edema Following Panretinal (Scatter) Photocoagulation Given in 1 or 4 Sittings SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; PHOTO-COAGULATION; LASER PHOTOCOAGULATION; TRANSIENT MYOPIA; VISUAL-ACUITY; RETINOPATHY; THICKNESS AB Objective: To compare the effects of single-sitting vs 4-sitting panretinal photocoagulation (PRP) on macular edema in subjects with severe nonproliferative or early proliferative diabetic retinopathy with relatively good visual acuity and no or mild center-involved macular edema. Methods: Subjects were treated with 1 sitting or 4 sittings of PRP in a nonrandomized, prospective, multicentered clinical trial. Main Outcome Measure: Central subfield thickness on optical coherence tomography (OCT). Results: Central subfield thickness was slightly greater in the 1-sitting group (n = 84) than in the 4-sitting group (n = 71) at the 3-day (P = .01) and 4-week visits (P = .003). At the 34-week primary outcome visit, the slight differences had reversed, with the thickness being slightly greater in the 4-sitting group than in the 1-sitting group (P = .06). Visual acuity differences paralleled OCT differences. Conclusions: Our results suggest that clinically meaningful differences are unlikely in OCT thickness or visual acuity following application of PRP in 1 sitting compared with 4 sittings in subjects in this cohort. More definitive results would require a large randomized trial. C1 [Antoszyk, Andrew N.; Browning, David; Brooks, Danielle R.; Cowen, Melissa K.; Stallings, Alison H.; Helms, Jennifer V.; Price, Angela K.; Murphy, Heather L.] Charlotte Eye Ear Nose & Throat Associates PA, Charlotte, NC USA. Denver Hlth Med Ctr, Denver, CO USA. Elman Retina Grp PA, Baltimore, MD USA. John Kenyon Amer Eye Inst, New Albany, IN USA. Texas Retina Associates, Dallas, TX USA. Carolina Retina Ctr, Columbia, SC USA. Henry Ford Hlth Syst, Dept Ophthalmol Eye Care Serv, Detroit, MI USA. Palmetto Retina Ctr, W Columbia, SC USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. So Calif Desert Retina Consultants MC, Palm Springs, SC USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Loma Linda Univ Hlth Care, Dept Ophthalmol, Loma Linda, CA USA. Retina Vitreous Surg Cent New York PC, Syracuse, NY USA. Austin Retina Associates, Austin, TX USA. Charles Garcia & Associates PA, Houston, TX USA. Cent Florida Retina Inst, Lakeland, FL USA. Associated Retinal Consultants, Grand Rapids, MI USA. Texas Retina Associates, Lubbock, TX USA. Univ N Carolina, Dept Ophthalmol, Chapel Hill, NC USA. NW Med Fac Fdn, Chicago, IL USA. Ohio State Univ Eye Physicians & Surg LLC, Dublin, Ireland. Retina Associates Hawaii Inc, Honolulu, HI USA. Mid Amer Retina Consultants PA, Kansas City, MO USA. SE Retina Associates PC, Knoxville, TN USA. Manhattan Eye Ear & Throat Hosp, New York, NY 10021 USA. Retina Consultants, Providence, RI USA. Sarasota Retina Inst, Sarasota, FL USA. RP Brucker, AJ (reprint author), Jaeb Ctr Hlth Res, 15310 Amberly Dr,Ste 350, Tampa, FL 33647 USA. EM drcrnetF1@jaeb.org FU National Eye Institute [EY14231, EY14269, EY14229]; National Institute of Diabetes and Digestive and Kidney Diseases FX This work was supported through cooperative agreements EY14231, EY14269, and EY14229 from the National Eye Institute and the National Institute of Diabetes and Digestive and Kidney Diseases. NR 27 TC 40 Z9 42 U1 0 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0003-9950 EI 1538-3601 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD FEB PY 2009 VL 127 IS 2 BP 132 EP 140 PG 9 WC Ophthalmology SC Ophthalmology GA 405DR UT WOS:000263203400001 ER PT J AU Akbari, M Akbari, S Pasquale, LR AF Akbari, Mona Akbari, Sara Pasquale, Louis R. TI The Association of Primary Open-angle Glaucoma With Mortality A Meta-analysis of Observational Studies SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID CORONARY-HEART-DISEASE; BEAVER DAM EYE; TYPE-2 DIABETES-MELLITUS; BLOOD-PRESSURE INDEXES; ALL-CAUSE MORTALITY; ANGELES LATINO EYE; BLUE MOUNTAINS EYE; INTRAOCULAR-PRESSURE; RISK-FACTORS; BARBADOS EYE AB Objective: To conduct a meta-analysis to estimate the relationship between primary open-angle glaucoma (POAG) and mortality. Methods: A systematic search of the PubMed, Embase, and Web of Science databases yielded 9 cohort studies with relative risk (RR) estimates for all-cause mortality. The studies were critically reviewed by an expert in the field. The data were extracted and analyzed in a pooled analysis by the random-effects model. Meta-regression to assess for heterogeneity by several covariates and subgroup analysis on cardiovascular mortality were performed. Results: A significant risk was not detected in the final pooled analysis (RR, 1.13; 95% confidence interval [CI], 0.97-1.31) for all-cause mortality. A meta-regression across mean follow-up time, age, and sex was not significant. A meta-regression across diabetes status in 3 of the 9 studies did not demonstrate significant results (P = .94). Subgroup analysis on cardiovascular mortality from 4 of the 9 studies was marginally significant (RR, 1.20; 95% CI, 1.00-1.43; P = .05), but insignificant after removal of a study in which POAG was ascertained by self and proxy report (RR, 1.12; 95% CI, 0.87-1.46). Conclusion: This meta-analysis does not demonstrate an association between POAG and all-cause or cardiovascular mortality. C1 [Pasquale, Louis R.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Pasquale, Louis R.] Harvard Univ, Sch Med, Boston, MA USA. [Akbari, Sara] Univ Michigan, Kellogg Eye Ctr, Ann Arbor, MI USA. [Akbari, Mona] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. [Akbari, Mona] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Pasquale, LR (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM Louis_Pasquale@meei.harvard.edu FU National Institutes of Health [EY06594] FX Harry A. Quigley, MD, A. Edward Maumenee Professor, Ophthalmology, Wilmer Institute, Johns Hopkins University School of Medicine; and Michael D. Knudtson, Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health (grant EY06594 from the National Institutes of Health). NR 65 TC 12 Z9 12 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD FEB PY 2009 VL 127 IS 2 BP 204 EP 210 PG 7 WC Ophthalmology SC Ophthalmology GA 405DR UT WOS:000263203400012 PM 19204241 ER PT J AU Rhee, DJ AF Rhee, Douglas J. TI Preventing Glaucoma in a High-Risk Population Impact and Observations of the Ocular Hypertension Treatment Study SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID OPEN-ANGLE GLAUCOMA; CENTRAL CORNEAL THICKNESS; INTRAOCULAR-PRESSURE; AFRICAN-AMERICANS; DIABETES-MELLITUS; EYE; TRIAL; ONSET; PREVALENCE; CAUCASIANS C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Glaucoma Div, Boston, MA 02114 USA. RP Rhee, DJ (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Glaucoma Div, 243 Charles St, Boston, MA 02114 USA. EM dougrhee@aol.com NR 25 TC 1 Z9 1 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD FEB PY 2009 VL 127 IS 2 BP 216 EP 218 PG 3 WC Ophthalmology SC Ophthalmology GA 405DR UT WOS:000263203400015 PM 19204244 ER PT J AU Lohavanichbutr, P Houck, J Fan, WH Yueh, B Mendez, E Futran, N Doody, DR Upton, MP Farwell, DG Schwartz, SM Zhao, LP Chen, C AF Lohavanichbutr, Pawadee Houck, John Fan, Wenhong Yueh, Bevan Mendez, Eduardo Futran, Neal Doody, David R. Upton, Melissa P. Farwell, D. Gregory Schwartz, Stephen M. Zhao, Lue Ping Chen, Chu TI Genomewide Gene Expression Profiles of HPV-Positive and HPV-Negative Oropharyngeal Cancer Potential Implications for Treatment Choices SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID HUMAN-PAPILLOMAVIRUS INFECTION; SQUAMOUS-CELL CARCINOMAS; HUMAN BREAST-CANCER; PROGNOSTIC-FACTOR; NECK-CANCER; HEAD; SENSITIVITY; RISK; STATHMIN; E6 AB Objective: To study the difference in gene expression between human papillomavirus (HPV)-positive and HPV-negative oral cavity and oropharyngeal squamous cell carcinoma (OSCC). Design: We used Affymetrix U133 plus 2.0 arrays to examine gene expression profiles of OSCC and normal oral tissue. The HPV DNA was detected using polymerase chain reaction followed by the Roche LINEAR ARRAY HPV Genotyping Test, and the differentially expressed genes were analyzed to examine their potential biological roles using the Ingenuity Pathway Analysis Software, version 5.0. Setting: Three medical centers affiliated with the University of Washington. Patients: A total of 119 patients with primary OSCC and 35 patients without cancer, all of whom were treated at the setting institutions, provided tissues samples for the study. Results: Human papillomavirus DNA was found in 41 of 119 tumors (34.5%) and 2 of 35 normal tissue samples (5.7%); 39 of the 43 HPV specimens were HPV-16. A higher prevalence of HPV DNA was found in oropharyngeal cancer (23 of 31) than in oral cavity cancer (18 of 88). We found no significant difference in gene expression between HPV-positive and HPV-negative oral cavity cancer but found 446 probe sets (347 known genes) differentially expressed in HPV-positive oropharyngeal cancer than in HPV-negative oropharyngeal cancer. The most prominent functions of these genes are DNA replication, DNA repair, and cell cycling. Some genes differentially expressed between HPV-positive and HPV-negative oropharyngeal cancer (eg, TYMS, STMN1, CCND1, and RBBP4) are involved in chemotherapy or radiation sensitivity. Conclusion: These results suggest that differences in the biology of HPV-positive and HPV-negative oropharyngeal cancer may have implications for the management of patients with these different tumors. C1 [Lohavanichbutr, Pawadee; Houck, John; Mendez, Eduardo; Doody, David R.; Schwartz, Stephen M.; Zhao, Lue Ping; Chen, Chu] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, Seattle, WA 98109 USA. [Fan, Wenhong; Zhao, Lue Ping] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Biostat & Biomath, Seattle, WA 98109 USA. [Yueh, Bevan] Univ Minnesota, Dept Otolaryngol Head & Neck Surg, Minneapolis, MN USA. [Mendez, Eduardo] Vet Affairs Puget Sound Hlth Care Syst, Surg & Perioperat Care Serv, Seattle, WA USA. [Farwell, D. Gregory] Univ Calif Davis, Dept Otolaryngol Head & Neck Surg, Davis, CA 95616 USA. [Mendez, Eduardo; Futran, Neal; Chen, Chu] Univ Washington, Dept Otolaryngol Head & Neck Surg, Seattle, WA 98195 USA. [Upton, Melissa P.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Schwartz, Stephen M.; Chen, Chu] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP Chen, C (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, Mail Stop M5-C800,1100 Fairview Ave N, Seattle, WA 98109 USA. EM cchen@fhcrc.org OI Yueh, Bevan/0000-0003-1380-1053 FU National Cancer Institute [R01CA095419] FX This study was supported by grant R01CA095419 from the National Cancer Institute (Dr Chen). NR 24 TC 58 Z9 59 U1 0 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD FEB PY 2009 VL 135 IS 2 BP 180 EP 188 PG 9 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 407QQ UT WOS:000263379800012 PM 19221247 ER PT J AU Cohen, AN Veena, MS Srivatsan, ES Wang, MB AF Cohen, Alen N. Veena, Mysore S. Srivatsan, Eri S. Wang, Marilene B. TI Suppression of Interleukin 6 and 8 Production in Head and Neck Cancer Cells With Curcumin via Inhibition of I kappa beta Kinase SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID B KINASE; TRANSCRIPTION FACTOR; CYTOKINE EXPRESSION; TUMOR-GROWTH; CARCINOMA; SURVIVAL; ACTIVATION; PROLIFERATION; ANGIOGENESIS; DIFERULOYLMETHANE AB Objectives: To evaluate the effect of curcumin on production of interleukin 6 (IL-6) and 8 (IL-8) in head and neck squamous cell carcinoma (HNSCC) cell lines and to determine the mechanism by which these effects are modulated. Curcumin suppression of HNSCC is believed to be partly due to inhibition of the transcription factor nuclear factor-kappa beta (NF-kappa beta). Interleukin 6 and IL-8 are cytokines induced by NF-kappa beta activation with elevated levels in the serum of patients with HNSCC. Design: We treated HNSCC cell lines CCL23, CAL27, UM-SCC1, and UM-SCC14A with increasing doses of curcumin and measured IL-6 and IL-8 levels using an enzyme-linked immunosorbent assay. Setting: Levels of NF-omicron beta, I kappa beta kinase (IKK), and phosphorylated I kappa beta were analyzed bymeans of Western blot. The IKK activity was measured in UM-SCC14A cells using an IKK-specific I kappa beta alpha substrate after treatment with curcumin. Main Outcome Measures: Reverse transcription polymerase chain reaction was performed to determine the effect of curcumin on the expression of IL-6 and IL-8. Results: Curcumin treatment resulted in dose-dependent inhibition of IL-6 and IL-8 in all cell lines. All cell lines had similar NF-kappa beta levels; however, UM-SCC1 and UM-SCC14A had significantly higher I kappa beta kinase levels and required considerably higher doses of curcumin before inhibition of IL-6 and IL-8 occurred. Curcumin treatment resulted in inhibition of IKK activity and inhibition of IL-6 and IL-8 expression. Conclusions: Curcumin significantly reduces IL-6 and IL-8 levels in HNSCC cell lines. This mechanism appears to be mediated via inhibition of I kappa beta-kinase activity in the NF-kappa beta pathway. Interleukins 6 and 8 have potential use as biomarkers to measure the efficacy of treatment with curcumin. C1 [Wang, Marilene B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Div Head & Neck Surg, Los Angeles, CA 90095 USA. [Veena, Mysore S.; Srivatsan, Eri S.; Wang, Marilene B.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA USA. RP Wang, MB (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Div Head & Neck Surg, Room CHS 62-132,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM mbwang@ucla.edu FU University of California, Los Angeles, Academic Senate; Veterans Affairs Merit; National Cancer Institute [CA116826] FX This study was supported by a grant from the University of California, Los Angeles, Academic Senate (Dr Wang), a Veterans Affairs Merit Grant (Dr Srivatsan), and grant CA116826 from the National Cancer Institute(Dr Wang). NR 34 TC 27 Z9 28 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD FEB PY 2009 VL 135 IS 2 BP 190 EP 197 PG 8 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 407QQ UT WOS:000263379800013 PM 19221248 ER PT J AU Hughes, JH Bentz, JS Fatheree, L Souers, RJ Wilbur, DC AF Hughes, Jonathan H. Bentz, Joel S. Fatheree, Lisa Souers, Rhona J. Wilbur, David C. CA Coll Amer Pathologists TI Changes in Participant Performance in the ''Test-Taking'' Environment Observations From the 2006 College of American Pathologists Gynecologic Cytology Proficiency Testing Program SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID INTERLABORATORY COMPARISON PROGRAM; CERVICOVAGINAL CYTOLOGY; VALIDATION AB Context.-Because the consequences of making an interpretive error on a proficiency test are more severe than those made on an educational challenge, the same slide may exhibit different performance characteristics in the 2 different settings. Objective.-The results of the 2006 College of American Pathologists Gynecologic Cytology Proficiency Testing Program (PAP PT) provide the opportunity to compare the performance characteristics of the field-validated slides in the PAP PT environment with those of the same graded slides in the College of American Pathologists Educational Program (formerly known as the PAP Program). Design.-All participant responses for negative (category B) and positive (categories C and D) validated slides in the 2006 PAP PT were used to determine the error rates of participants. These data were compared with the historical error rates observed on the same validated slides in the graded PAP Program. Results.-The performance characteristics of the slides in the PAP PT environment were statistically different from those in the Educational PAP Program. In proficiency testing both cytotechnologists (P < .001) and pathologists (P = .002) were more likely to interpret validated category B slides as category C or D and less likely to interpret category C slides as category B (P < .001). These differences were more pronounced among cytotechnologists than among pathologists. Conclusions.-In the test-taking environment, both cytotechnologists and pathologists appear to use a defensive strategy that results in ''upgrading'' of category B slides. This trend is more pronounced among cytotechnologists. C1 [Hughes, Jonathan H.] Lab Med Consultants Ltd, Dept Pathol, Las Vegas, NV 89109 USA. [Bentz, Joel S.] Univ Utah, Dept Pathol, Salt Lake City, UT USA. [Souers, Rhona J.] Coll Amer Pathologists, Dept Stat, Northfield, MN USA. [Wilbur, David C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Hughes, JH (reprint author), Lab Med Consultants Ltd, Dept Pathol, 3059 S Maryland Pkwy,Suite 100, Las Vegas, NV 89109 USA. EM hughes@lmclabs.com NR 5 TC 7 Z9 7 U1 0 U2 0 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 FEB PY 2009 VL 133 IS 2 BP 279 EP 282 PG 4 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 404LK UT WOS:000263153200014 PM 19195970 ER PT J AU Saha, S AF Saha, Somnath TI Rectifying Institutional Bias in Medical Research SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Editorial Material ID CANCER CLINICAL-TRIALS; CONSPIRACY BELIEFS; AFRICAN-AMERICANS; RACE; AGE C1 Portland VA Med Ctr, Gen Internal Med Sect, Portland, OR 97239 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 NR 14 TC 2 Z9 2 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD FEB PY 2009 VL 163 IS 2 BP 181 EP 182 PG 2 WC Pediatrics SC Pediatrics GA 402CM UT WOS:000262991800013 PM 19188652 ER PT J AU Waddimba, AC Jain, NB Stolzmann, K Gagnon, DR Burgess, JF Kazis, LE Garshick, E AF Waddimba, Anthony C. Jain, Nitin B. Stolzmann, Kelly Gagnon, David R. Burgess, James F., Jr. Kazis, Lewis E. Garshick, Eric TI Predictors of Cardiopulmonary Hospitalization in Chronic Spinal Cord Injury SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Cardiovascular system; Hospitalization; Proportional hazards models; Rehabilitation; Respiratory system; Spinal cord injuries ID MEDICAL-CARE UTILIZATION; LUNG-FUNCTION; RISK-FACTORS; NUTRITION EXAMINATION; RESPIRATORY SYMPTOMS; REVERSE EPIDEMIOLOGY; NATIONAL-HEALTH; VITAL CAPACITY; UNITED-STATES; MORTALITY AB Objective: To investigate longitudinal risk factors of hospitalization for circulatory and pulmonary diseases among veterans with chronic spinal cord injury (SCI). Circulatory and respiratory system illnesses are leading causes of death in patients with chronic SCI, yet risk factors for related hospitalizations have not been characterized. Design: Prospective cohort study. Setting: Veterans Affairs (VA) Boston Healthcare System, Boston, Massachusetts. Participants/Data Sources: Veterans (N=309) greater than or equal to 1 year post-SCI from the VA Boston Chronic SCI cohort who completed a health questionnaire and underwent spirometry at study entry. Baseline data were linked to 1996 through 2003 hospitalization records from the VA National Patient Care Database. Interventions: Not applicable. Main Outcome Measures: Cardiopulmonary hospital admissions, the predictors of which were assessed by multivariate Cox regression. Results: Of 1478 admissions observed, 143 were a result of cardiopulmonary (77 circulatory and 66 respiratory) illnesses. Independent predictors were greater age (3% increase/y), hypertension, and the lowest body mass index quintile (<22.4kg/m(2)). A greater percentage-predicted forced expiratory volume in 1 second was associated with reduced risk. SCI level and completeness of injury were not statistically significant after adjusting for these risk factors. Conclusions: Cardiopulmonary hospitalization risk in persons with chronic SCI is related to greater age and medical factors that, if recognized, may result in strategies for reducing future hospitalizations. C1 [Garshick, Eric] VA Boston Healthcare Syst, Pulm & Crit Care Med Sect, Med Serv, W Roxbury, MA 02132 USA. [Waddimba, Anthony C.; Jain, Nitin B.; Stolzmann, Kelly; Gagnon, David R.; Burgess, James F., Jr.; Kazis, Lewis E.; Garshick, Eric] VA Boston Healthcare Syst, Res & Dev Serv, W Roxbury, MA 02132 USA. [Gagnon, David R.] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, W Roxbury, MA 02132 USA. [Burgess, James F., Jr.] VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, W Roxbury, MA 02132 USA. [Gagnon, David R.] Boston Univ, Dept Biostat, Boston, MA 02215 USA. [Waddimba, Anthony C.; Burgess, James F., Jr.; Kazis, Lewis E.] Boston Univ, Dept Hlth Policy & Management, Boston, MA 02215 USA. [Waddimba, Anthony C.; Jain, Nitin B.; Stolzmann, Kelly; Garshick, Eric] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Waddimba, Anthony C.; Jain, Nitin B.; Garshick, Eric] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. [Jain, Nitin B.] Spaulding Rehabil Hosp, Boston, MA USA. RP Garshick, E (reprint author), VA Boston Healthcare Syst, Pulm & Crit Care Med Sect, Med Serv, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM Eric.Garshick@va.gov OI Burgess, James/0000-0002-6646-7071; Gagnon, David/0000-0002-6367-3179; Kazis, Lewis/0000-0003-1800-5849 FU National Institutes of Health/National Institute of Child Health and Human Development [R01 HD42141] FX Supported by the National Institutes of Health/National Institute of Child Health and Human Development (grant no. R01 HD42141; Garshick), and the Office of Research and Development, Health Services Research and Development, and Massachusetts Veterans Epidemiology Research Information Center Cooperative Studies Program, Department of Veterans Affairs. NR 34 TC 6 Z9 7 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD FEB PY 2009 VL 90 IS 2 BP 193 EP 200 DI 10.1016/j.apmr.2008.07.026 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 410KX UT WOS:000263577000002 PM 19236973 ER PT J AU Silber, JH Rosenbaum, PR Romano, PS Rosen, AK Wang, YL Teng, Y Halenar, MJ Even-Shoshan, O Volpp, KG AF Silber, Jeffrey H. Rosenbaum, Paul R. Romano, Patrick S. Rosen, Amy K. Wang, Yanli Teng, Yun Halenar, Michael J. Even-Shoshan, Orit Volpp, Kevin G. TI Hospital Teaching Intensity, Patient Race, and Surgical Outcomes SO ARCHIVES OF SURGERY LA English DT Article ID QUALITY-OF-CARE; ACUTE MYOCARDIAL-INFARCTION; CLINICAL COMORBIDITY INDEX; ICD-9-CM ADMINISTRATIVE DATA; DUTY HOUR REFORM; HEALTH-CARE; MEDICARE BENEFICIARIES; NONTEACHING HOSPITALS; ADVERSE EVENTS; BLACK PATIENTS AB Objectives: To determine if the lower mortality often observed in teaching-intensive hospitals is because of lower complication rates or lower death rates after complications (failure to rescue) and whether the benefits at these hospitals accrue equally to white and black patients, since black patients receive a disproportionate share of their care at teaching-intensive hospitals. Design: A retrospective study of patient outcomes and teaching intensity using logistic regression models, with and without adjusting for hospital fixed and random effects. Setting: Three thousand two hundred seventy acute care hospitals in the United States. Patients: Medicare claims on general, orthopedic, and vascular surgery admissions in the United States for 20002005 (N = 4 658 954 unique patients). Main Outcome Measures: Thirty-day mortality, in-hospital complications, and failure to rescue (the probability of death following complications). Results: Combining all surgeries, compared with non-teaching hospitals, patients at very major teaching hospitals demonstrated a 15% lower odds of death (P < .001), no difference in complications, and a 15% lower odds of death after complications (failure to rescue) (P < .001). These relative benefits associated with higher resident-to-bed ratio were not experienced by black patients, for whom the odds of mortality and failure to rescue were similar at teaching and non-teaching hospitals, a pattern that is significantly different from that of white patients (P < .001). Conclusions: Survival after surgery is higher at hospitals with higher teaching intensity. Improved survival is because of lower mortality after complications (better failure to rescue) and generally not because of fewer complications. However, this better survival and failure to rescue at teaching-intensive hospitals is seen for white patients, not for black patients. C1 [Silber, Jeffrey H.; Wang, Yanli; Teng, Yun; Even-Shoshan, Orit] Childrens Hosp Philadelphia, Ctr Outcomes Res, Philadelphia, PA 19104 USA. [Silber, Jeffrey H.] Univ Penn, Dept Pediat, Philadelphia, PA 19104 USA. [Silber, Jeffrey H.] Univ Penn, Dept Anesthesiol, Philadelphia, PA 19104 USA. [Silber, Jeffrey H.] Univ Penn, Dept Crit Care, Philadelphia, PA 19104 USA. [Halenar, Michael J.; Volpp, Kevin G.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Silber, Jeffrey H.] Univ Penn, Sch Med, Dept Hlth Care Syst, Philadelphia, PA 19104 USA. [Rosenbaum, Paul R.] Univ Penn, Wharton Sch, Dept Stat, Philadelphia, PA 19104 USA. [Silber, Jeffrey H.; Even-Shoshan, Orit; Volpp, Kevin G.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Halenar, Michael J.; Volpp, Kevin G.] Vet Adm Hosp, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Romano, Patrick S.] Univ Calif Davis, Sch Med, Div Gen Med, Sacramento, CA 95817 USA. [Romano, Patrick S.] Univ Calif Davis, Sch Med, Ctr Healthcare Policy & Res, Sacramento, CA 95817 USA. [Rosen, Amy K.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Rosen, Amy K.] Vet Adm Hosp, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. RP Silber, JH (reprint author), Childrens Hosp Philadelphia, Ctr Outcomes Res, 3535 Market St,Ste 1029, Philadelphia, PA 19104 USA. EM silberj@wharton.upenn.edu RI Rosenbaum, Paul/H-8687-2012; Romano, Patrick/N-4225-2014 OI Romano, Patrick/0000-0001-6749-3979 FU National Heart, Lung, and Blood Institute [R01 HL082637]; Department of Veterans Affairs [IIR 04-202]; National Science Foundation [SES 0646002] FX This work was funded through National Heart, Lung, and Blood Institute grant R01 HL082637, Department of Veterans Affairs grant IIR 04-202, and National Science Foundation grant SES 0646002. NR 52 TC 72 Z9 72 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD FEB PY 2009 VL 144 IS 2 BP 113 EP 120 PG 8 WC Surgery SC Surgery GA 407QP UT WOS:000263379700004 PM 19221321 ER PT J AU Sugimoto, M Yamaoka, Y AF Sugimoto, Mitsushige Yamaoka, Yoshio TI Virulence factor genotypes of Helicobacter pylori affect cure rates of eradication therapy SO ARCHIVUM IMMUNOLOGIAE ET THERAPIAE EXPERIMENTALIS LA English DT Review DE Helicobacter pylori; eradication therapy; virulence factor; cagA; vacA; tailored regimen ID GASTRIC-ACID-SECRETION; PROTON PUMP INHIBITOR; ANTIBIOTIC-RESISTANCE PATTERNS; RANDOMIZED CONTROLLED-TRIAL; CAG PATHOGENICITY ISLAND; ADULT DYSPEPTIC PATIENTS; OUTER-MEMBRANE PROTEINS; TRIPLE THERAPY; VACUOLATING CYTOTOXIN; NONULCER DYSPEPSIA AB The cure rates of Helicobacter pylori infection by using a combination of a proton pump inhibitor (PPI) and antimicrobial agents are mainly influenced by bacterial susceptibility to antimicrobial agents and the magnitude of acid inhibition during the treatment. Currently used empirical triple therapies do not reliably produce a a parts per thousand yen80% cure rate on an intention-to-treat basis. Therefore, tailored regimens based on relevant microbiological findings and pharmacogenomics are recommended for attaining an acceptable a parts per thousand yen95% cure rate. Recently, virulence factors of H. pylori, such as cagA and vacA, are reported to be major factors determining the cure rates. Individuals infected with strains with cagA-negative and vacA s2 genotypes have significantly increased risk of eradication failure of H. pylori infection. These virulence factors enhance gastric mucosal inflammation and are associated with the development of peptic ulcer and gastric cancer. H. pylori virulence factors induce proinflammatory cytokines, such as interleukin (IL)-1, IL-8, and tumor necrosis factor (TNF)- which influence mucosal inflammation and/or gastric acid secretion. When physicians select an H. pylori eradication regimen with an acceptable cure rate, they might need to consider H. pylori virulence factors, especially cagA and vacA. C1 [Yamaoka, Yoshio] Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. RP Yamaoka, Y (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Dept Med, 2002 Holcombe Blvd,111D Rm 3A-320, Houston, TX 77030 USA. EM yyamaoka@bcm.tmc.edu FU National Institutes of Health (NIH) [R01 DK62813] FX The project described was supported by Grant No. R01 DK62813 from the National Institutes of Health (NIH). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. NR 105 TC 28 Z9 33 U1 1 U2 2 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND SN 0004-069X J9 ARCH IMMUNOL THER EX JI Arch. Immunol. Ther. Exp. PD FEB PY 2009 VL 57 IS 1 BP 45 EP 56 DI 10.1007/s00005-009-0007-z PG 12 WC Immunology SC Immunology GA 409NI UT WOS:000263512000006 PM 19219527 ER PT J AU Seon, JK Gadikota, HR Kozanek, M Oh, LS Gill, TJ Li, G AF Seon, Jong Keun Gadikota, Hemanth R. Kozanek, Michal Oh, Luke S. Gill, Thomas J. Li, Guoan TI The Effect of Anterior Cruciate Ligament Reconstruction on Kinematics of the Knee With Combined Anterior Cruciate Ligament Injury and Subtotal Medial Meniscectomy: An In Vitro Robotic Investigation SO ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY LA English DT Article DE Anterior cruciate ligament; Knee kinematics; Reconstruction; Subtotal medial meniscectomy ID SIMULATED MUSCLE LOADS; DEFICIENT KNEE; POSTERIOR MOTION; MENISCAL TEARS; FOLLOW-UP; ACL; TRANSLATION; ROTATION; SURGERY AB Purpose: The aims of this study were to determine: (1) the kinematic effect Of Subtotal medial meniscectomy on the anterior cruciate ligament (ACL)-deficient knee and (2) the effect of ACL reconstruction on kinematics of the knee with combined ACL deficiency and subtotal medial meniscectomy under anterior tibial and simulated quadriceps loads. Methods: Eight human cadaveric knees were sequentially tested using a robotic testing system under 4 conditions: intact, ACL deficiency, ACL deficiency with Subtotal medial meniscectomy, and single-bundle ACL reconstruction using a bone-patellar tendon-bone graft. Knee kinematics were measured at 0 degrees, 15 degrees, 30 degrees, 60 degrees, and 90 degrees of flexion under an anterior tibial load of 130 N and a quadriceps muscle load of 400 N. Results: Subtotal medial meniscectomy in the ACL-deficient knee significantly increased anterior and lateral tibial translations under the anterior tibial and quadriceps loads (P < .05). These kinematic changes were larger at high flexion (>= 60 degrees) than at low flexion angles. ACL reconstruction in knees with ACL deficiency and subtotal medial meniscectomy significantly reduced the increased anterior tibial translation, but Could not restore anterior translation to the intact level with differences ranging from 2.6 mm at 0 degrees to 5.5 min at 30 degrees of flexion. ACL reconstruction did not significantly affect the medial-lateral translation and internal-external tibial rotation in the presence of subtotal meniscectomy. Conclusions: Subtotal medial meniscectomy in knees with ACL deficiency altered knee kinematics, especially at high flexion angles. ACL reconstruction significantly reduced the increased tibial translation in knees with combined ACL deficiency and Subtotal medial meniscectomy, but could not restore the knee kinematics to the intact knee level. Clinical Relevance: This Study suggests that meniscus is an important secondary stabilizer against anterior and lateral tibial translations and should be preserved in the setting of ACL reconstruction for restoration of optimal knee kinematics and function. C1 [Seon, Jong Keun; Gadikota, Hemanth R.; Kozanek, Michal; Oh, Luke S.; Gill, Thomas J.; Li, Guoan] Massachusetts Gen Hosp, Dept Orthopaed Surg, Bioengn Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Seon, Jong Keun] Chonnam Natl Univ, Hwasun Hosp, Jeonnam, South Korea. RP Li, G (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Bioengn Lab, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM glil@partners.org OI Oh, Luke/0000-0002-6610-8204 FU National Institutes of Health [R01-AR055612] FX Supported by Grant No. R01-AR055612 from the National Institutes of Health. The authors report no conflict of interest. NR 28 TC 22 Z9 22 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-8063 J9 ARTHROSCOPY JI Arthroscopy PD FEB PY 2009 VL 25 IS 2 BP 123 EP 130 DI 10.1016/j.arthro.2008.09.020 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 411HV UT WOS:000263641300003 PM 19171270 ER PT J AU Nareika, A Sundararaj, KP Im, YB Game, BA Lopes-Virella, MF Huang, Y AF Nareika, Alena Sundararaj, Kamala P. Im, Yeong-Bin Game, Bryan A. Lopes-Virella, Maria F. Huang, Yan TI High glucose and interferon gamma synergistically stimulate MMP-1 expression in U937 macrophages by increasing transcription factor STAT1 activity SO ATHEROSCLEROSIS LA English DT Article DE Diabetes mellitus; Glucose; Atherosclerosis; Interferon gamma; Inflammation; Matrix metalloproteinase ID MATRIX METALLOPROTEINASE-1 EXPRESSION; CARDIOVASCULAR-DISEASE; DIABETES-MELLITUS; PLAQUE RUPTURE; HISTIOCYTES; LIPOPOLYSACCHARIDE; ATHEROSCLEROSIS; MECHANISMS AB Recent diabetes control and complications trial and epidemiology of diabetes interventions and complications (DCCT/EDIC) and other clinical studies have reported that glucose control in patients with diabetes leads to a significant reduction of cardiovascular events and atherosclerosis, indicating that hyperglycemia plays an essential role in cardiovascular disease in diabetic patients. Although several mechanisms by which hyperglycemia promotes atherosclerosis have been proposed, it remains unclear how hyperglycemia promotes atherosclerosis by interaction with inflammatory cytokines. To test our hypothesis that hyperglycemia interplays with interferon gamma (IFN gamma), a key factor involved in atherosclerosis, to up-regulate the expression of genes such as matrix metalloproteinases (MMPs) and cytokines that are involved in plaque destabilization, U937 macrophages cultured in medium containing either normal or high glucose were challenged with IFN gamma and the expression of MMPs and cytokines were then quantified by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). Results showed that high glucose and IFN gamma had a synergistic effect on the expression of MMP-1, MMP-9 and IL-1 beta. High glucose also enhanced IFN gamma-induced priming effect on lipopolysaccharide (LPS)-stimulated MMP-1 secretion. Furthermore, high glucose and IFN gamma exert the synergistic effect on MMP-1 expression by enhancing STAT1 phosphorylation and STAT1 transcriptional activity. In summary, this study revealed a novel mechanism potentially involved in diabetes-promoted cardiovascular disease. Published by Elsevier Ireland Ltd. C1 [Game, Bryan A.; Lopes-Virella, Maria F.; Huang, Yan] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29403 USA. [Nareika, Alena; Sundararaj, Kamala P.; Im, Yeong-Bin; Lopes-Virella, Maria F.; Huang, Yan] Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, Charleston, SC 29425 USA. RP Huang, Y (reprint author), Ralph H Johnson Vet Affairs Med Ctr, 114 Doughty St, Charleston, SC 29403 USA. EM huangyan@musc.edu FU Department of Veterans Affairs; NIH [DE 16353] FX This work was supported by a Merit Review Grant from Department of Veterans Affairs and NIH grant DE 16353 (to Y.H.). NR 22 TC 15 Z9 16 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD FEB PY 2009 VL 202 IS 2 BP 363 EP 371 DI 10.1016/j.atherosclerosis.2008.05.043 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 408HY UT WOS:000263427300007 PM 18586252 ER PT J AU Hammad, SM Twal, WO Barth, JL Smith, KJ Saad, AF Virella, G Argraves, WS Lopes-Virella, MF AF Hammad, Samar M. Twal, Waleed O. Barth, Jeremy L. Smith, Kent J. Saad, Antonio F. Virella, Gabriel Argraves, W. Scott Lopes-Virella, Maria F. TI Oxidized LDL immune complexes and oxidized LDL differentially affect the expression of genes involved with inflammation and survival in human U937 monocytic cells SO ATHEROSCLEROSIS LA English DT Article DE DNA microarray; Atherosclerosis; Oxidized LDL; Oxidized LDL immune complexes; Fc gamma receptors ID LOW-DENSITY-LIPOPROTEIN; THP-1 CELLS; INDUCED APOPTOSIS; HUMAN MACROPHAGES; HEME OXYGENASE-1; ANTIBODIES; RECEPTOR; ATHEROSCLEROSIS; ACTIVATION; PROTEIN AB Objective: To compare the global effects of oxidized LDL (oxLDL) and oxLDL-containing immune complexes (oxLDL-IC) on gene expression in human monocytic cells and to identify differentially expressed genes involved with inflammation and survival. Methods and results: U937 cells were treated with oxLDL-IC, oxLDL, Keyhole limpet hemocyanin immune complexes (KLH-IC), or vehicle for 4 h. Transcriptome profiling was performed using DNA microarrays. oxLDL-IC uniquely affected the expression of genes involved with pro-survival (RAD548, RUFY3, SNRPB2, and ZBTB24). oxLDL-IC also regulated many genes in a manner similar to KLH-IC. categorization of these genes revealed that 39% are involved with stress responses, including the unfolded protein response which impacts cell survival, 19% with regulation of transcription, 10% with endocytosis and intracellular transport of protein and lipid, and 16% with inflammatory responses including regulation of I-kappa B /NF-kappa B cascade and cytokine activity. One gene in particular, HSPA6, greatly up-regulated by oxLDL-IC, was found to be required for the process by which oxLDL-IC augments IL1-beta secretion. The study also revealed genes uniquely up-regulated by oxLDL, including genes involved with growth inhibition (OKL38, NEK3, and FTH1), oxidoreductase activity (SPXN1 and HMOX1), and transport of amino acids and fatty acids (SLC7A11 and ADFP). Conclusions: These findings highlight early transcriptional responses elicited by oxLDL-IC that may underlie its cytoprotective and proinflammatory effects. Cross-linking of Fc gamma receptors appears to be the trigger for most of the transcriptional responses to oxLDL-IC. The findings further strengthen the hypothesis that oxLDL and oxLDL-IC elicit disparate inflammatory responses and play distinct roles in the process of atherosclerosis. Published by Elsevier Ireland Ltd. C1 [Hammad, Samar M.; Twal, Waleed O.; Barth, Jeremy L.; Smith, Kent J.; Argraves, W. Scott] Med Univ S Carolina, Dept Cell Biol & Anat, Charleston, SC 29425 USA. [Saad, Antonio F.; Lopes-Virella, Maria F.] Med Univ S Carolina, Div Endocrinol, Dept Med, Charleston, SC 29425 USA. [Virella, Gabriel] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. [Lopes-Virella, Maria F.] Ralph H Johnson Vet Affairs Med Ctr, Dept Vet Affairs, Charleston, SC 29401 USA. RP Hammad, SM (reprint author), Med Univ S Carolina, Dept Cell Biol & Anat, 114 Doughty St,630B POB 250776, Charleston, SC 29425 USA. EM hammadsm@musc.edu FU NIH [HL079274, POI-HL55782, HL061873]; South Carolina COBRE in Lipidomics and Pathobiology [RR17677]; American Heart Association Scientist Development [0435259N]; University Research Committee of the Medical University of South Carolina; Department of Veterans Affairs FX This work was supported by the following NIH grants: HL079274 (SMH), POI-HL55782 (MIN), HL061873 (WSA), and the South Carolina COBRE in Lipidomics and Pathobiology (P20 RR17677 from NCRR). The work was also supported by an American Heart Association Scientist Development Grant (0435259N) and a grant from the University Research Committee of the Medical University of South Carolina to SMH, and funding from the Department of Veterans Affairs to MLV We acknowledge the technical assistance of Alena Nareika and the MUSC Proteogenomics Facility (supported by RR016434, RR16461, and MUSC URRF) and their personnel, including Saurin Jani and Victor Fresco. We thank Charlyne Chassereau for assistance with lipoprotein isolation. NR 54 TC 29 Z9 30 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD FEB PY 2009 VL 202 IS 2 BP 394 EP 404 DI 10.1016/j.atherosclerosis.2008.05.032 PG 11 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 408HY UT WOS:000263427300010 PM 18597759 ER PT J AU Avruch, J Long, XM Lin, YS Ortiz-Vega, S Rapley, J Papageorgiou, A Oshiro, N Kikkawa, U AF Avruch, Joseph Long, Xiaomeng Lin, Yenshou Ortiz-Vega, Sara Rapley, Joseph Papageorgiou, Angela Oshiro, Noriko Kikkawa, Ushio TI Activation of mTORC1 in two steps: Rheb-GTP activation of catalytic function and increased binding of substrates to raptor SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article; Proceedings Paper CT Conference on mTOR Signalling, Nutrients and Disease CY SEP 15-16, 2008 CL Univ Oxford, Med Sci Teaching Ctr, Oxford, ENGLAND HO Univ Oxford, Med Sci Teaching Ctr DE insulin; leucine; mammalian target of rapamycin (mTOR); regulatory associated protein of mTOR (raptor); Rheb; tuberous sclerosis complex (TSC) ID P70 S6 KINASE; AMINO-ACID SUFFICIENCY; MAMMALIAN TARGET; RAPAMYCIN MTOR; CELL-GROWTH; INSULIN; PRAS40; TOR; PHOSPHORYLATION; INHIBITOR AB The signalling function of mTOR complex 1 is activated by Rheb-GTP, which controls the catalytic competence of the mTOR (mammalian target of rapamycin) kinase domain by an incompletely understood mechanism. Rheb can bind directly to the mTOR kinase domain, and association with inactive nucleotide-deficient Rheb mutants traps mTOR in a catalytically inactive state. Nevertheless, Rheb-GTP targets other than mTOR, such as FKBP38 (FK506-binding protein 38) and/or PLD1 (phospholipase D(1)), may also contribute to mTOR activation. Once activated, the mTOR catalytic domain phosphorylates substrates only when they are bound to raptor (regulatory associated protein of mTOR), a separate polypeptide within the complex. The mechanism of insulin/nutrient stimulation of mTOR complex 1 signalling, in addition to Rheb-GTP activation of the mTOR catalytic function, also involves a stable modification of the configuration of mTORC1 (mTOR complex 1) that increases access of substrates to their binding site on the raptor polypeptide. The mechanism underlying this second step in the activation of mTORC1 is unknown. C1 [Avruch, Joseph; Long, Xiaomeng; Lin, Yenshou; Ortiz-Vega, Sara; Rapley, Joseph; Papageorgiou, Angela; Oshiro, Noriko] Massachusetts Gen Hosp, Dept Mol Biol, Med Serv, Diabet Unit,Diabet Res Lab, Boston, MA 02114 USA. [Oshiro, Noriko; Kikkawa, Ushio] Kobe Univ, Biosignal Res Ctr, Nada Ku, Kobe, Hyogo 6578501, Japan. RP Avruch, J (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Med Serv, Diabet Unit,Diabet Res Lab, Simches Res Bldg,6408,185 Cambridge St, Boston, MA 02114 USA. EM avruch@molbio.mgh.harvard.edu FU NCI NIH HHS [CA73818]; NIDDK NIH HHS [DK17776] NR 28 TC 35 Z9 35 U1 0 U2 5 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0300-5127 J9 BIOCHEM SOC T JI Biochem. Soc. Trans. PD FEB PY 2009 VL 37 BP 223 EP 226 DI 10.1042/BST0370223 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 402MI UT WOS:000263017400045 PM 19143636 ER PT J AU Devaraj, NK Keliher, EJ Thurber, GM Nahrendorf, M Weissleder, R AF Devaraj, Neat K. Keliher, Edmund J. Thurber, Greg M. Nahrendorf, Matthias Weissleder, Ralph TI F-18 Labeled Nanoparticles for in Vivo PET-CT Imaging SO BIOCONJUGATE CHEMISTRY LA English DT Article ID SUPERPARAMAGNETIC IRON-OXIDE; MYOCARDIAL INFARCT; CYCLOADDITION; CANCER; PEPTIDES AB We report the synthesis and in vivo characterization of an F-18 modified trimodal nanoparticle (F-18-CLIO). This particle consists of cross-linked dextran held together in core-shell formation by a superparamagnetic iron oxide core and functionalized with the radionuclide F-18 in high yield via "click" chemistry. The particle can be detected with positron emission tomography, fluorescence molecular tomography, and magnetic resonance imaging. The presence of F-18 dramatically lowers the detection threshold of the nanoparticles, while the facile conjugation chemistry provides a simple platform for rapid and efficient nanoparticle labeling. C1 [Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Smiches Res Bldg,185 Cambridge St, Boston, MA 02114 USA. EM rweissieder@mgh.harvard.edu RI Devaraj, Neal/B-4712-2014; OI Thurber, Greg/0000-0001-7570-2080 FU Center of Cancer Nanotechnology Excellence [U54-CA 119349]; Translational Program of Excellence in Nanotechnology [UO1-HL080731]; NIH [T32-CA79443] FX The Center of Cancer Nanotechnology Excellence (U54-CA 119349), the Translational Program of Excellence in Nanotechnology (UO1-HL080731), and NIH training grant T32-CA79443 supported this work. The authors would like to thank Jose-Luiz Figureiredo for helpful discussions, Brett Marinelli for conducting the PET-CT imaging, and Nikolay Sergeyev for preparing the CLIO nanoparticles. NR 25 TC 144 Z9 149 U1 6 U2 53 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD FEB PY 2009 VL 20 IS 2 BP 397 EP 401 DI 10.1021/bc8004649 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 409TP UT WOS:000263529000029 PM 19138113 ER PT J AU Deisboeck, TS Couzin, ID AF Deisboeck, Thomas S. Couzin, Iain D. TI Collective behavior in cancer cell populations SO BIOESSAYS LA English DT Article DE biosystems; cancer; collective behavior ID SELF-ORGANIZATION; MALIGNANT GLIOMAS; COHORT MIGRATION; PHASE-TRANSITION; ANIMAL GROUPS; TUMOR SYSTEM; GROWTH; INVASION; GLUTAMATE; BRAIN AB In recent years the argument has been made that malignant tumors represent complex dynamic and self-organizing biosystems. Furthermore, there is increasing evidence that collective cell migration is common during invasion and metastasis of malignant tumors. Here, we argue that cancer systems may be capable of developing multicellular collective patterns that resemble evolved adaptive behavior known from other biological systems including collective sensing of environmental conditions and collective decision-making. We present a concept as to how these properties could arise in tumors and why the emergence of such swarm-like patterns would confer advantageous properties to the spatio-temporal expansion of tumors, and consequently, why understanding and ultimately targeting such collectivity should be of interest for basic and clinical cancer research alike. C1 [Deisboeck, Thomas S.] Massachusetts Gen Hosp, Harvard MIT HST Athinoula A Martinos Ctr Biomed I, Complex Biosyst Modeling Lab, Boston, MA 02114 USA. [Couzin, Iain D.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA. RP Deisboeck, TS (reprint author), Massachusetts Gen Hosp E, Harvard MIT HST Athinoula A Martinos Ctr Biomed I, Complex Biosyst Modeling Lab, 2301 Bldg 149,13th St, Charlestown, MA 02129 USA. EM deisboec@helix.mgh.harvard.edu OI Couzin, Iain/0000-0001-8556-4558 FU NIH [CA 113004]; Harvard-MIT; Searle Scholar Award; DARPA [HR001-05-1-0057] FX This work has been supported in part by NIH grant CA 113004 and by the Harvard-MIT (HST) Athinoula A. Martincis Center for Biomedical Imaging and the Department of Radiology at Massachusetts General Hospital. T S. D. thanks Dr Zhihui Wang (Massachusetts General Hospital) for help with formatting the manuscript. I. D. C. is indebted to Nicola Grimwood for her contribution and gratefully acknowledges support from a Searle Scholar Award and also a DARPA grant HR001-05-1-0057 to Princeton University NR 71 TC 86 Z9 88 U1 2 U2 24 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0265-9247 J9 BIOESSAYS JI Bioessays PD FEB PY 2009 VL 31 IS 2 BP 190 EP 197 DI 10.1002/bies.200800084 PG 8 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 414KX UT WOS:000263863600009 PM 19204991 ER PT J AU Craske, MG Waters, AM Nazarian, M Mineka, S Zinbarg, RE Griffith, JW Naliboff, B Ornitz, EM AF Craske, Michelle G. Waters, Allison M. Nazarian, Maria Mineka, Susan Zinbarg, Richard E. Griffith, James W. Naliboff, Bruce Ornitz, Edward M. TI Does Neuroticism in Adolescents Moderate Contextual and Explicit Threat Cue Modulation of the Startle Reflex? SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Adolescents; context; explicit threat; risk for anxiety and depression; startle reflexes ID FEAR-POTENTIATED STARTLE; POSTTRAUMATIC-STRESS-DISORDER; ANXIETY DISORDERS; ACOUSTIC STARTLE; PERSONALITY; DEPRESSION; RESPONSES; TEMPERAMENT; PREVALENCE; VETERANS AB Background: This study evaluated the relationship between neuroticism (N), a probable risk factor for emotional disorders, and modulation of startle reflexes (SRs). Methods: One hundred thirty-two adolescents with varying levels of N but without anxiety or depressive disorders were evaluated in contextual cue and explicit threat cue paradigms. Results: Within the explicit threat cue paradigm, N potentiated SRs more in conditions that were intermediately associated with threat of an aversive biceps contraction than conditions that were the furthest from and conditions that were the closest to the same threat. Also, N potentiated SRs across the entire experiment, regardless of experimental conditions, in male and not in female subjects. Conclusions: These results suggest that adolescents with high levels of N show greater sensitivity to contexts intermediately associated with threat. Results are discussed in comparison with other studies of groups at risk for anxiety and depressive disorders. C1 [Craske, Michelle G.; Nazarian, Maria] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. [Naliboff, Bruce; Ornitz, Edward M.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Ornitz, Edward M.] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90095 USA. [Naliboff, Bruce] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Waters, Allison M.] Griffith Univ, Sch Psychol, Mt Gravatt, Qld 4122, Australia. [Mineka, Susan; Zinbarg, Richard E.; Griffith, James W.] Northwestern Univ, Dept Psychol, Evanston, IL USA. [Zinbarg, Richard E.] Northwestern Univ, Family Inst, Evanston, IL USA. RP Craske, MG (reprint author), Univ Calif Los Angeles, Dept Psychol, 405 Hilgard Ave, Los Angeles, CA 90095 USA. EM craske@psych.ucla.edu RI Griffith, James/O-2551-2016; OI Griffith, James/0000-0002-4840-8692; Waters, Allison/0000-0003-2453-793X FU National Institutes of Health [MH065651, MH065652]; Virginia Friedhofer Charitable Trust FX Supplementary material cited in this article is available online. NR 33 TC 15 Z9 15 U1 2 U2 4 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 FEB 1 PY 2009 VL 65 IS 3 BP 220 EP 226 DI 10.1016/j.biopsych.2008.07.020 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 395QK UT WOS:000262538400006 PM 18789433 ER PT J AU Devine, H Schmit-Pokorny, K Tierney, DK McDermott, K AF Devine, H. Schmit-Pokorny, K. Tierney, D. K. McDermott, K. TI PERSPECTIVE OF BONE MARROW TRANSPLANT NURSES IN THE UNITED STATES (US) AND EUROPE (EU) OF UNMET EDUCATIONAL NEEDS SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Tandem Meeting on Biology of Blood and Marrow Transplantation CY FEB 11-15, 2009 CL Tampa, FL SP Amer Soc Blood & Marrow Transplantat C1 [Devine, H.] Ohio State Univ, Med Ctr, James Canc Hosp, Columbus, OH 43210 USA. [Schmit-Pokorny, K.] Univ Nebraska Med Ctr, Omaha, NE USA. [Tierney, D. K.] Stanford Univ, Stanford, CA 94305 USA. [McDermott, K.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 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 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2009 VL 15 IS 2 MA 72 BP 30 EP 30 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 402MC UT WOS:000263016800073 ER PT J AU Rosenblatt, J Vasir, B Wu, Z Zarwan, C Stone, R Bissonnette, A Friedman, T Stevenson, K Neuberg, D Mills, H Glotzbecker, B Levine, JD Joyce, R Boussiotis, V Tzachanis, D Spentzos, D Konstantinopoulos, P Kufe, D Avigan, D AF Rosenblatt, J. Vasir, B. Wu, Z. Zarwan, C. Stone, R. Bissonnette, A. Friedman, T. Stevenson, K. Neuberg, D. Mills, H. Glotzbecker, B. Levine, J. D. Joyce, R. Boussiotis, V Tzachanis, D. Spentzos, D. Konstantinopoulos, P. Kufe, D. Avigan, D. TI ADOPTIVE T CELL THERAPY USING EDUCATED T CELLS GENERATED BY THE SEQUENTIAL STIMULATION WITH DC/TUMOR FUSION CELLS AND ANTI-CD3/CD28 SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Tandem Meeting on Biology of Blood and Marrow Transplantation CY FEB 11-15, 2009 CL Tampa, FL SP Amer Soc Blood & Marrow Transplantat C1 [Rosenblatt, J.; Zarwan, C.; Mills, H.; Glotzbecker, B.; Levine, J. D.; Joyce, R.; Boussiotis, V; Tzachanis, D.; Spentzos, D.; Konstantinopoulos, P.; Avigan, D.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Vasir, B.; Wu, Z.; Stone, R.; Bissonnette, A.; Friedman, T.; Stevenson, K.; Neuberg, D.; Kufe, D.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 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 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2009 VL 15 IS 2 MA 161 BP 60 EP 60 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 402MC UT WOS:000263016800162 ER PT J AU Avigan, D Rosenblatt, J Vasir, B Wu, Z Bissonnette, A Somaiya, P MacNamara, C Uhl, L Avivi, I Katz, T Zarwan, C Joyce, R Levine, JD Lowe, K Dombagoda, D Tzachanis, D Boussiotis, V Giallombardo, N Mortellite, J Conway, K Fitzgerald, D Richardson, P Anderson, K Munshi, N Rowe, J Tsumer, M Bishart, L Kufe, D AF Avigan, D. Rosenblatt, J. Vasir, B. Wu, Z. Bissonnette, A. Somaiya, P. MacNamara, C. Uhl, L. Avivi, I Katz, T. Zarwan, C. Joyce, R. Levine, J. D. Lowe, K. Dombagoda, D. Tzachanis, D. Boussiotis, V Giallombardo, N. Mortellite, J. Conway, K. Fitzgerald, D. Richardson, P. Anderson, K. Munshi, N. Rowe, J. Tsumer, M. Bishart, L. Kufe, D. TI FUSION CELL VACCINATION IN CONJUNCTION WITH STEM CELL TRANSPLANTATION IS WELL TOLERATED, INDUCES ANTI-TUMOR IMMUNITY AND IS ASSOCIATED WITH RESPONSES IN PATIENTS WITH MULTIPLE MYELOMA SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Tandem Meeting on Biology of Blood and Marrow Transplantation CY FEB 11-15, 2009 CL Tampa, FL SP Amer Soc Blood & Marrow Transplantat C1 [Avigan, D.; Rosenblatt, J.; Somaiya, P.; MacNamara, C.; Uhl, L.; Zarwan, C.; Joyce, R.; Levine, J. D.; Lowe, K.; Dombagoda, D.; Tzachanis, D.; Boussiotis, V; Giallombardo, N.; Mortellite, J.; Conway, K.; Fitzgerald, D.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Vasir, B.; Wu, Z.; Bissonnette, A.; Richardson, P.; Anderson, K.; Munshi, N.; Kufe, D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Avivi, I; Katz, T.; Rowe, J.; Tsumer, M.; Bishart, L.] Rambam Med Ctr, Haifa, Israel. NR 0 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 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2009 VL 15 IS 2 MA 174 BP 65 EP 65 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 402MC UT WOS:000263016800175 ER PT J AU Sorror, ML Storer, B Sandmaier, BM Chauncey, T Storb, RF Maloney, DG AF Sorror, M. L. Storer, B. Sandmaier, B. M. Chauncey, T. Storb, R. F. Maloney, D. G. TI TANDEM AUTOLOGOUS AND NONMYELOABLATIVE ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION (HCT) FROM HLA-MATCHED RELATED OR UNRELATED DONORS FOR ADVANCED LYMPHOMA OR CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Tandem Meeting on Biology of Blood and Marrow Transplantation CY FEB 11-15, 2009 CL Tampa, FL SP Amer Soc Blood & Marrow Transplantat C1 [Sorror, M. L.; Storer, B.; Sandmaier, B. M.; Chauncey, T.; Storb, R. F.; Maloney, D. G.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Sorror, M. L.; Storer, B.; Sandmaier, B. M.; Chauncey, T.; Storb, R. F.; Maloney, D. G.] Univ Washington, Seattle, WA 98195 USA. [Chauncey, T.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 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 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2009 VL 15 IS 2 MA 178 BP 66 EP 66 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 402MC UT WOS:000263016800179 ER PT J AU Duncan, CN Buonanno, MR Lehmann, LE AF Duncan, C. N. Buonanno, M. R. Lehmann, L. E. TI RELATIONSHIP BETWEEN DAY 0 CYCLOSPORINE LEVEL AND GRAFT-VERSUS-HOST DISEASE IN PEDIATRIC HSCT SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Tandem Meeting on Biology of Blood and Marrow Transplantation CY FEB 11-15, 2009 CL Tampa, FL SP Amer Soc Blood & Marrow Transplantat C1 [Duncan, C. N.; Buonanno, M. R.; Lehmann, L. E.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 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 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2009 VL 15 IS 2 MA 222 BP 81 EP 82 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 402MC UT WOS:000263016800223 ER PT J AU Cutler, C Aldridge, J Kim, HT Ayanian, S Bradwin, G Revta, C Murga, G Ho, V Alyea, E Koreth, J Armand, P Richardson, PG Soiffer, R Ritz, J Antin, JH AF Cutler, C. Aldridge, J. Kim, H. T. Ayanian, S. Bradwin, G. Revta, C. Murga, G. Ho, V Alyea, E. Koreth, J. Armand, P. Richardson, P. G. Soiffer, R. Ritz, J. Antin, J. H. TI PREDICTION OF VOD USING BIOMARKERS OF ENDOTHELIAL INJURY SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Tandem Meeting on Biology of Blood and Marrow Transplantation CY FEB 11-15, 2009 CL Tampa, FL SP Amer Soc Blood & Marrow Transplantat C1 [Cutler, C.; Aldridge, J.; Kim, H. T.; Revta, C.; Murga, G.; Ho, V; Alyea, E.; Koreth, J.; Armand, P.; Richardson, P. G.; Soiffer, R.; Ritz, J.; Antin, J. H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ayanian, S.; Bradwin, G.] Childrens Hosp, Boston, MA 02115 USA. NR 0 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 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2009 VL 15 IS 2 MA 245 BP 89 EP 89 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 402MC UT WOS:000263016800246 ER PT J AU Sarantopoulos, S Stevenson, KE Kim, HT Cutler, CS Bhuiya, NS Schowalter, M Ho, VT Joseph, SJ Antin, JH Jerome, R AF Sarantopoulos, S. Stevenson, K. E. Kim, H. T. Cutler, C. S. Bhuiya, N. S. Schowalter, M. Ho, V. T. Joseph, S. J. Antin, J. H. Jerome, R. TI HIGH BAFF:B CELL RATIOS AND CIRCULATING ACTIVATED B CELLS IN CHRONIC GVHD SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Tandem Meeting on Biology of Blood and Marrow Transplantation CY FEB 11-15, 2009 CL Tampa, FL SP Amer Soc Blood & Marrow Transplantat C1 [Sarantopoulos, S.; Stevenson, K. E.; Kim, H. T.; Cutler, C. S.; Bhuiya, N. S.; Schowalter, M.; Ho, V. T.; Joseph, S. J.; Antin, J. H.; Jerome, R.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 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 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2009 VL 15 IS 2 MA 322 BP 115 EP 116 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 402MC UT WOS:000263016800323 ER PT J AU Davies, JK Singh, H Yuk, D Champlin, RE Nadler, LM Guinan, EC Cooper, LJN AF Davies, J. K. Singh, H. Yuk, D. Champlin, R. E. Nadler, L. M. Guinan, E. C. Cooper, L. J. N. TI TO AUGMENT A GVL EFFECT AND REDUCE GVHD: ALLOREACTIVITY OF HUMAN CD19-SPECIFIC T CELLS CAN BE REDUCED BY ALLOANERGIZATION WITHOUT REDUCTION OF TUMOR-SPECIFIC KILLING SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Tandem Meeting on Biology of Blood and Marrow Transplantation CY FEB 11-15, 2009 CL Tampa, FL SP Amer Soc Blood & Marrow Transplantat C1 [Davies, J. K.; Yuk, D.; Nadler, L. M.; Guinan, E. C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Singh, H.; Cooper, L. J. N.] Univ Texas MD Anderson Canc Ctr, Childrens Canc Hosp, Houston, TX 77030 USA. NR 0 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 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2009 VL 15 IS 2 MA 337 BP 121 EP 121 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 402MC UT WOS:000263016800338 ER PT J AU Treister, N Stevenson, K Kim, H Culter, C AF Treister, N. Stevenson, K. Kim, H. Culter, C. TI ORAL CHRONIC GRAFT-VERSUS-HOST DISEASE SCORING USING THE NIH CONSENSUS CRITERIA SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Tandem Meeting on Biology of Blood and Marrow Transplantation CY FEB 11-15, 2009 CL Tampa, FL SP Amer Soc Blood & Marrow Transplantat C1 [Treister, N.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Treister, N.; Stevenson, K.; Kim, H.; Culter, C.] Dana Farber Canc Inst, Boston, MA USA. NR 0 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 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2009 VL 15 IS 2 MA 345 BP 123 EP 124 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 402MC UT WOS:000263016800346 ER PT J AU Rosenblatt, J Bissonnette, A Wu, Z Vasir, B Zarwan, C Keefe, W Joyce, R Levine, JD Glotzbecker, B Mills, H Tzachanis, D Boussiotis, V Kufe, D Avigan, D AF Rosenblatt, J. Bissonnette, A. Wu, Z. Vasir, B. Zarwan, C. Keefe, W. Joyce, R. Levine, J. D. Glotzbecker, B. Mills, H. Tzachanis, D. Boussiotis, V Kufe, D. Avigan, D. TI IMMUNOMODULATORY EFFECTS OF VITAMIN D: IMPLICATIONS FOR THE TREATMENT OF GRAFT VERSUS HOST DISEASE SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Tandem Meeting on Biology of Blood and Marrow Transplantation CY FEB 11-15, 2009 CL Tampa, FL SP Amer Soc Blood & Marrow Transplantat C1 [Rosenblatt, J.; Bissonnette, A.; Zarwan, C.; Joyce, R.; Levine, J. D.; Glotzbecker, B.; Mills, H.; Tzachanis, D.; Boussiotis, V; Avigan, D.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Wu, Z.; Vasir, B.; Keefe, W.; Kufe, D.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2009 VL 15 IS 2 MA 368 BP 132 EP 132 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 402MC UT WOS:000263016800369 ER PT J AU Matsuoka, KI Kim, HT McDonough, S Herrera, M Cutler, CS Koreth, F Reynolds, C Antin, FH Soiffer, RF Ritz, F AF Matsuoka, K. -, I Kim, H. T. McDonough, S. Herrera, M. Cutler, C. S. Koreth, J. Reynolds, C. Antin, J. H. Soiffer, R. J. Ritz, J. TI HOMEOSTATIC MECHANISMS AFFECT RECONSTITUTION OF CD4+FOXP3+REGULATORY T CELLS AFTER HEMATOPOIETIC STEM CELL TRANSPLANTATION SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Tandem Meeting on Biology of Blood and Marrow Transplantation CY FEB 11-15, 2009 CL Tampa, FL SP Amer Soc Blood & Marrow Transplantat C1 [Matsuoka, K. -, I; Kim, H. T.; McDonough, S.; Herrera, M.; Cutler, C. S.; Koreth, J.; Reynolds, C.; Antin, J. H.; Soiffer, R. J.; Ritz, J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 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 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2009 VL 15 IS 2 MA 381 BP 136 EP 137 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 402MC UT WOS:000263016800382 ER PT J AU Oliansky, DM Antin, JH Bennett, JM Deeg, HJ Engelhardt, C Heptinstall, KV de Lima, M Gore, SD Potts, RG Silverman, LR Jones, RB McCarthy, PL Hahn, T AF Oliansky, Denise M. Antin, Joseph H. Bennett, John M. Deeg, H. Joachim Engelhardt, Christin Heptinstall, Kathleen V. de Lima, Marcos Gore, Steven D. Potts, Ronald G. Silverman, Lewis R. Jones, Roy B. McCarthy, Philip L., Jr. Hahn, Theresa TI The Role of Cytotoxic Therapy with Hematopoietic Stem Cell Transplantation in the Therapy of Myelodysplastic Syndromes: An Evidence-Based Review SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Review DE Myelodysplastic syndromes; Hematopoietic stem cell transplantation; Evidence-based review; Therapy; Adult ID BONE-MARROW-TRANSPLANTATION; ACUTE MYELOID-LEUKEMIA; CHRONIC MYELOMONOCYTIC LEUKEMIA; COLONY-STIMULATING FACTOR; QUALITY-OF-LIFE; ACUTE MYELOGENOUS LEUKEMIA; TOTAL-BODY IRRADIATION; RECOMBINANT-HUMAN-ERYTHROPOIETIN; ACUTE LYMPHOBLASTIC-LEUKEMIA; PROGNOSTIC SCORING SYSTEM AB Clinical research examining the role of hematopoietic stem cell transplantation (SCT) in the therapy of myelodysplastic syndromes (MDS) in adults is presented and critically evaluated in this systematic evidence-based review. Specific criteria were used for searching the published literature and for grading the quality and strength of the evidence and the strength of the treatment recommendations. Treatment recommendations based on the evidence are presented in Table 3, and were reached unanimously by a panel of MDS experts. The identified priority areas of needed future research in MDS include: (1) the benefit of using alternative donor sources (eg, cord blood; haploidentical family donors) for patients without matched sibling or unrelated donors; (2) the role and appropriate timing of allogeneic SCT in combination with hypomethylating and immunomodulatory treatment regimens; (3) randomized trials comparing the safety and efficacy of various novel agents for treating MDS; and (4) the influence of the various MDS treatment modalities on patient-reported quality-of-life outcomes. C1 [Oliansky, Denise M.; McCarthy, Philip L., Jr.; Hahn, Theresa] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Antin, Joseph H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bennett, John M.] Univ Rochester, James P Wilmot Canc Ctr, Rochester, NY USA. [Deeg, H. Joachim] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Engelhardt, Christin] Aplast Anemia & MDS Int Fdn Inc, Churchton, MD USA. [Heptinstall, Kathleen V.] Myelodysplast Syndromes Fdn Inc, Crosswicks, NJ USA. [de Lima, Marcos] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Gore, Steven D.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Potts, Ronald G.] INTERLINK Hlth Serv, Hillsboro, OR USA. [Silverman, Lewis R.] Mt Sinai Sch Med, New York, NY USA. RP Hahn, T (reprint author), Roswell Pk Canc Inst, Elm & Carlton St, Buffalo, NY 14263 USA. EM Theresa.hahn@roswellpark.org NR 103 TC 44 Z9 46 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2009 VL 15 IS 2 BP 137 EP 172 DI 10.1016/j.bbmt.2008.12.003 PG 36 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 402MA UT WOS:000263016600002 PM 19167676 ER PT J AU Davies, FK De Lima, M Cooper, TFN Spitzer, T Kapoor, N Yuk, D Brennan, LL Thall, P McMannis, F Champlin, R Nadler, LM Guinan, EC AF Davies, J. K. De Lima, M. Cooper, T. J. N. Spitzer, T. Kapoor, N. Yuk, D. Brennan, L. L. Thall, P. McMannis, J. Champlin, R. Nadler, L. M. Guinan, E. C. TI DELAYED INFUSION OF ALLOANERGIZED DONOR PERIPHERAL BLOOD MONONUCLEAR CELLS (PBMC) AUGMENTS PATHOGEN-SPECIFIC IMMUNE RECONSTITUTION AFTER T CELL DEPLETED (TCD) HAPLOIDENTICAL HEMATOPOIETIC STEM CELL TRANSPLANTATION (HSCT) FOR HIGH-RISK ACUTE LEUKEMIA/MDS SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Tandem Meeting on Biology of Blood and Marrow Transplantation CY FEB 11-15, 2009 CL Tampa, FL SP Amer Soc Blood & Marrow Transplantat C1 [Davies, J. K.; Yuk, D.; Brennan, L. L.; Nadler, L. M.; Guinan, E. C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Spitzer, T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kapoor, N.] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Cooper, T. J. N.] Univ Texas Houston, MD Anderson Canc Ctr, Childrens Canc Hosp, Houston, TX 77030 USA. NR 0 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 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2009 VL 15 IS 2 MA 387 BP 139 EP 139 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 402MC UT WOS:000263016800388 ER PT J AU Gainer, L Johnson, B Nickley, J Potter-Bynoe, G Scanlon, P Lehmann, L AF Gainer, L. Johnson, B. Nickley, J. Potter-Bynoe, G. Scanlon, P. Lehmann, L. TI A MULTIDISCIPLINARY INITIATIVE TO REDUCE VANCOMYCIN-RESISTANT ENTEROCOCCUS (VRE) INCIDENCE ON A PEDIATRIC HEMATOPOIETIC STEM CELL TRANSPLANT UNIT SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Tandem Meeting on Biology of Blood and Marrow Transplantation CY FEB 11-15, 2009 CL Tampa, FL SP Amer Soc Blood & Marrow Transplantat C1 [Gainer, L.; Johnson, B.; Nickley, J.; Potter-Bynoe, G.; Scanlon, P.] Childrens Hosp Boston, Boston, MA USA. [Lehmann, L.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 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 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2009 VL 15 IS 2 SU 2 MA 424 BP 150 EP 150 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 402MC UT WOS:000263016800425 ER PT J AU Bodugoz-Senturk, H Macias, CE Kung, JH Muratoglu, OK AF Bodugoz-Senturk, Hatice Macias, Celia E. Kung, Jean H. Muratoglu, Orhun K. TI Poly(vinyl alcohol)-acrylamide hydrogels as load-bearing cartilage substitute SO BIOMATERIALS LA English DT Article DE Hydrogel; Polyvinyl alcohol; Polyacrylamide; Cartilage; Lubricity; Coefficient of friction ID AUTOLOGOUS CHONDROCYTE IMPLANTATION; H ARTIFICIAL MENISCUS; ARTICULAR-CARTILAGE; ALCOHOL) HYDROGELS; POLYVINYL-ALCOHOL; PVA HYDROGELS; IN-VIVO; REPAIR; MICROFRACTURE; KNEE AB Poly(vinyl alcohol) (PVA) has been advanced as a biomaterial for the fabrication of medical devices to be used as synthetic articular cartilage because of its viscoelastic nature, high water content, and biocompatibility. Key material requirements for such devices are high creep resistance to prevent mechanical instability in the joint and high water content to maintain a lubricious surface to minimize wear and damage of the cartilage counterface during articulation. The creep resistance of PVA hydrogels can be increased by high temperature annealing: however this process also collapses the pores, reducing the water content and consequently reducing the lubricity of the hydrogel surface [Bodugoz-Senturk H, Choi J, Oral E, Kung JH, Macias CE, Braithwaite G, et al. The effect of polyethylene glycol on the stability of pores in polyvinyl alcohol hydrogels during annealing. Biomaterials 2008;29(2):141-9.]. We hypothesized that polymerizing acrylamide (AAm) in the pores of the PVA hydrogel Would minimize the loss of lubricity during annealing by preventing the collapse of the pores and loss of water content. Increasing AAm content increased porosity and equilibrium water content and decreased the coefficient of friction, tear strength, crystallinity, and creep resistance in annealed PVA hydrogels. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Bodugoz-Senturk, Hatice; Macias, Celia E.; Kung, Jean H.; Muratoglu, Orhun K.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Bodugoz-Senturk, Hatice; Muratoglu, Orhun K.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Muratoglu, OK (reprint author), Massachusetts Gen Hosp, Harris Orthopaed Biomech & Biomat Lab, 55 Fruit St,GRJ 1206, Boston, MA 02114 USA. EM omuratoglu@partners.org NR 52 TC 68 Z9 77 U1 12 U2 68 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD FEB PY 2009 VL 30 IS 4 BP 589 EP 596 DI 10.1016/j.biomaterials.2008.10.010 PG 8 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 389BR UT WOS:000262065500020 PM 18996584 ER PT J AU Sun, XD Jeng, L Bolliet, C Olsen, BR Spector, M AF Sun, Xiao-Dan Jeng, Lily Bolliet, Catherine Olsen, Bjorn R. Spector, Myron TI Non-viral endostatin plasmid transfection of mesenchymal stem cells via collagen scaffolds SO BIOMATERIALS LA English DT Article DE Endostatin; Collagen; Scaffold; Stem cells ID SMOOTH-MUSCLE ACTIN; ARTICULAR-CARTILAGE; TUMOR-GROWTH; IN-VITRO; OSTEOARTHRITIC CARTILAGE; ANTITUMOR-ACTIVITY; GENE DELIVERY; CROSS-LINKING; ANGIOGENESIS; THERAPY AB Angiogenesis is critical in the early stage of reparative processes and tissue regeneration, but the persistence of a vascular network may interfere with later transformation/maturation in naturally avascular tissues such as articular cartilage. Our supposition is that the timed delivery of an anti-angiogenic factor in cartilage tissue engineering may facilitate the formation of hyaline cartilage by inducing the regression of vascularization. To this end our overall goal is to prepare an off-the-shelf scaffold containing the gene for a potent anti-angiogenic factor. The objective of this study was to investigate the use of a type I/III collagen scaffold for the non-viral transfection of marrow stromal cells (MSCs, also referred to as mesenchymal stem cells) with the plasmid encoding endostatin. Caprine MSCs were transfected by the naked plasmid alone and plasmid incorporated into a cationic lipid complex in three experiments: I) cells were transfected in monolayer; 2) monolayer-transfected cells were grown in a collagen sponge-like scaffold; and 3) non-transfected cells were grown in a collagen scaffold containing the naked plasmid and endostatin lipoplex. Independent variables were the passage number of the cells and the plasmid loading. The amount of endostatin released by the cells into the medium was measured using an ELISA. The results demonstrated the overexpression of endostatin by MSCs growing in the endostatin lipoplex-supplemented collagen scaffolds. Endostatin released by the cell-seeded scaffolds reached a peak of 13 ng/ml for scaffolds incorporating as little as 20 mu g of plasmid, at the 3-day collection period ending 5 clays post-seeding. The accumulated endostatin synthesis over a 2-week period began to achieve what may be a therapeutic level. MSCs transfected with the endostatin gene in monolayer continued to express the gene when grown in the collagen scaffolds. The results demonstrate the promise of the non-viral delivery of the gene for this potent anti-angiogenic protein to MSCs via a collagen scaffold. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Sun, Xiao-Dan; Jeng, Lily; Bolliet, Catherine; Spector, Myron] VA Boston Healthcare Syst, Tissue Engn, Boston, MA 02130 USA. [Sun, Xiao-Dan] Tsinghua Univ, Dept Mat Sci & Engn, Adv Mat Lab, Beijing 100084, Peoples R China. [Jeng, Lily] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Olsen, Bjorn R.] Harvard Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. [Spector, Myron] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. RP Spector, M (reprint author), VA Boston Healthcare Syst, Tissue Engn, Mail Stop 151 Res,150 S Huntington Ave, Boston, MA 02130 USA. EM mspector@rics.bwh.harvard.edu FU U.S. Department of Veterans Affairs; Department of Defense; Harvard-China Scholarship Program; National Science Foundation Graduate Research Fellowship FX This work was supported by the Rehabilitation Research and Development Service of the U.S. Department of Veterans Affairs, the Department of Defense, the Harvard-China Scholarship Program (X.D. Sun), and the National Science Foundation Graduate Research Fellowship (L.J.). The authors are grateful for the assistance of Alix Weaver and Naomi Fukai. NR 46 TC 26 Z9 27 U1 0 U2 9 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 EI 1878-5905 J9 BIOMATERIALS JI Biomaterials PD FEB PY 2009 VL 30 IS 6 BP 1222 EP 1231 DI 10.1016/j.biomaterials.2008.10.020 PG 10 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 398RX UT WOS:000262750300026 PM 19059640 ER PT J AU Kozloff, KM Quinti, L Patntirapong, S Hauschka, PV Tung, CH Weissleder, R Mahmood, U AF Kozloff, Kenneth M. Quinti, Luisa Patntirapong, Somying Hauschka, Peter V. Tung, Ching-Hsuan Weissleder, Ralph Mahmood, Umar TI Non-invasive optical detection of cathepsin K-mediated fluorescence reveals osteoclast activity in vitro and in vivo SO BONE LA English DT Article DE Osteoclast; Cathepsin K; Non-invasive imaging; Molecular imaging; Fluorescence ID BONE-RESORBING OSTEOCLASTS; BASAL PLASMA-MEMBRANE; OVARIECTOMY; MICE; MOUSE; PROTEINASES; TRAFFICKING; DEGRADATION; MACROPHAGES; RESORPTION AB Osteoclasts degrade bone matrix by demineralization followed by degradation of type I collagen through secretion of the cysteine protease. cathepsin K. Current imaging modalities are insufficient for sensitive observation of osteoclast activity, and in vivo live imaging of osteoclast resorption of bone has yet to be demonstrated. Here, we describe a near-infrared fluorescence reporter probe whose activation by cathepsin K is shown in live osteoclast cells and in mouse models of development and osteoclast upregulation. Cathepsin K probe activity was monitored in live osteoclast cultures and correlates with cathepsin K gene expression. In ovariectomized mice, cathepsin K probe upregulation precedes detection of bone loss by micro-computed tomography. These results are the first to demonstrate non-invasive visualization of bone degrading enzymes in models of accelerated bone loss, and may provide a means for early diagnosis of upregulated resorption and rapid feedback on efficacy of treatment protocols prior to significant loss of bone in the patient. (C) 2008 Elsevier Inc. All rights reserved. C1 [Kozloff, Kenneth M.; Quinti, Luisa; Tung, Ching-Hsuan; Weissleder, Ralph; Mahmood, Umar] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. [Patntirapong, Somying; Hauschka, Peter V.] Childrens Hosp, Dept Orthopaed Surg, Boston, MA 02215 USA. RP Mahmood, U (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, 149 13th St,Room 5406, Charlestown, MA 02129 USA. EM mahmood@helix.mgh.harvard.edu OI Tung, Ching-Hsuan/0000-0001-6648-6195 FU NIH [T32-CA079443, R24-CA2872, R01EB001872]; CDMRP-DOD Breast Cancer Research Program [BC044721] FX Research Was Supported in part by NIH grants T32-CA079443, R24-CA2872, R01EB001872, and CDMRP-DOD Breast Cancer Research Program (USAMRAA #BC044721). We thank S. Goldstein and E. Daley for assistance with mu C7, J. Tam for assistance with enzyme assays, R Sharma for assistance with in vitro assays, E. Aikawa and V. Lok for technical assistance with histology, and A. Alford for critical review of the manuscript. Mouse cathepsin K was a generous gift from Dr. Jinq-May Chen at Medivir UK Ltd. NR 42 TC 38 Z9 39 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD FEB PY 2009 VL 44 IS 2 BP 190 EP 198 DI 10.1016/j.bone.2008.10.036 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 403PN UT WOS:000263094600001 PM 19007918 ER PT J AU Xu, GF Mclaren, DG Ries, ML Fitzgerald, ME Bendlin, BB Rowley, HA Sager, MA Atwood, C Asthana, S Johnson, SC AF Xu, Guofan Mclaren, Donald G. Ries, Michele L. Fitzgerald, Michele E. Bendlin, Barbara B. Rowley, Howard A. Sager, Mark A. Atwood, Craig Asthana, Sanjay Johnson, Sterling C. TI The influence of parental history of Alzheimers disease and apolipoprotein E 4 on the BOLD signal during recognition memory SO BRAIN LA English DT Article DE Alzheimers disease; risk factors; BOLD; event-related fMRI; d-prime ID MILD COGNITIVE IMPAIRMENT; GENETIC RISK; BRAIN ACTIVATION; HIPPOCAMPAL ACTIVATION; EPISODIC MEMORY; DEFAULT-MODE; FMRI; DEMENTIA; APOE; AGE AB First-degree family history (FH) of sporadic Alzheimers disease and the apolipoprotein E 4 allele (APOE4) are risk factors for Alzheimers disease that may affect brain function prior to onset of clinical symptoms. In this functional MRI (fMRI) study, we used an episodic recognition task that required discrimination of previously viewed (PV) and novel (NV) faces to examine differences in blood oxygen level dependent (BOLD) signal due to risk factors in 74 middle-aged cognitively normal individuals. The group effects on this recognition task were tested with a 2 2 ANCOVA factorial design (FH/FH and APOE4/APOE4). There were significant APOE4 and FH effects in the left dorsal posterior cingulate cortex and precuneus, where decreased risk resulted in greater activity during recollection. Recognition performance was positively correlated with BOLD signal in the left posterior hippocampus, parahippocampalretrosplenial gyrus and left superior frontal cortex regardless of risk factors. To examine condition-specific group effects, both the PV and NV faces were tested further in separate 2 2 ANCOVAs. Both models revealed an APOE effect, with the APOE4 group showing stronger signal than the APOE4 group in anterior cingulate cortices, while a FH effect was found in the dorsal cuneus and medial frontal cortices with the FH group showing stronger signal than the FH group. Finally, interactions between APOE4 and FH effects were found bilaterally in the fusiform gyrus. These results suggest that risk factors and cognitive performance each influence brain activity during recognition. The findings lend further support to the idea that functional brain changes may begin far in advance of symptomatic Alzheimers disease. C1 [Xu, Guofan; Mclaren, Donald G.; Ries, Michele L.; Fitzgerald, Michele E.; Bendlin, Barbara B.; Atwood, Craig; Asthana, Sanjay; Johnson, Sterling C.] William S Middleton Mem Vet Adm Med Ctr, GRECC, Madison, WI 53705 USA. [Xu, Guofan; Mclaren, Donald G.; Ries, Michele L.; Fitzgerald, Michele E.; Bendlin, Barbara B.; Rowley, Howard A.; Sager, Mark A.; Atwood, Craig; Asthana, Sanjay; Johnson, Sterling C.] Univ Wisconsin, Dept Med, Madison, WI USA. [Xu, Guofan; Rowley, Howard A.] Univ Wisconsin, Dept Radiol, Madison, WI USA. RP Johnson, SC (reprint author), William S Middleton Mem Vet Adm Med Ctr, GRECC, 2500 Overlook Terrace 11G, Madison, WI 53705 USA. EM scj@medicine.wisc.edu RI McLaren, Donald/G-9906-2011 FU Department of Veterans Affairs Merit Review [AG21155, AG20013, AG27161] FX Department of Veterans Affairs Merit Review Grant (to S.C.J.); AG21155, AG20013 and AG27161. NR 54 TC 56 Z9 56 U1 3 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD FEB PY 2009 VL 132 BP 383 EP 391 DI 10.1093/brain/awn254 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 408BI UT WOS:000263407700012 PM 18829694 ER PT J AU Faroqi-Shah, Y Dickey, MW AF Faroqi-Shah, Yasmeen Dickey, Michael Walsh TI On-line processing of tense and temporality in agrammatic aphasia SO BRAIN AND LANGUAGE LA English DT Article DE Morphology; Agrammatism; Verbs; Reaction time; Tense; Adverb; Syntax; Anomaly; Aphasia; Comprehension ID FUNCTIONAL CATEGORIES; BROCAS APHASIA; GRAMMATICAL MORPHOLOGY; VERB INFLECTIONS; QUANTITATIVE-ANALYSIS; GERMAN AGRAMMATISM; GREEK APHASIA; PAST-TENSE; COMPREHENSION; DEFICITS AB Agrammatic aphasic individuals exhibit marked production deficits for tense morphology. This paper presents three experiments examining whether a group of English-speaking agrammatic individuals (n=10) exhibit parallel deficits in their comprehension of tense. Results from two comprehension experiments (on-line grammaticality judgment studies) suggest that these individuals are impaired for tense comprehension, and furthermore that their deficit is more pronounced for morphosemantic rather than morphosyntactic aspects of tense processing. Results from a third experiment (an elicited production study) indicate that these individuals exhibit parallel production and comprehension impairments for tense. Across the three experiments, the consistent pattern was that of a significant difficulty in associating verb forms with a pre-specified temporal context when compared to all other processes. Implications for current models of agrammatic tense and morphological deficits are discussed. (C) Published by Elsevier Inc. C1 [Faroqi-Shah, Yasmeen] Univ Maryland, Dept Hearing & Speech Sci, College Pk, MD 20742 USA. [Dickey, Michael Walsh] Univ Pittsburgh, Dept Commun Sci & Disorders, Pittsburgh, PA USA. [Dickey, Michael Walsh] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Faroqi-Shah, Y (reprint author), Univ Maryland, Dept Hearing & Speech Sci, 0100 Lefrak Hall, College Pk, MD 20742 USA. EM yshah@hesp.umd.edu OI Dickey, Michael Walsh/0000-0002-9068-3313 FU University of Maryland, College Park FX This research was supported by a General Research Board award from the University of Maryland, College Park to Y. Faroqi-Shah. We thank Heather McIntosh for helping with timing of verbs. Monica Sampson and Kristin Grunwald helped with data analysis. Sarah Camponeshi and Isabelle Dunn helped with transcription and coding of narratives. The authors are grateful to the aphasic participants and their families for their participation in this research. NR 72 TC 26 Z9 26 U1 2 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD FEB PY 2009 VL 108 IS 2 BP 97 EP 111 DI 10.1016/j.bandl.2008.10.003 PG 15 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA 406GT UT WOS:000263283700004 PM 19081129 ER PT J AU Makris, N Pandya, DN AF Makris, Nikos Pandya, Deepak N. TI The extreme capsule in humans and rethinking of the language circuitry SO BRAIN STRUCTURE & FUNCTION LA English DT Article DE Diffusion imaging; DT-MRI; Tractography; Language; Extreme capsule ID EFFERENT ASSOCIATION PATHWAYS; SUPERIOR TEMPORAL REGION; AUDITORY-CORTEX; PREFRONTAL CORTEX; WHITE-MATTER; RHESUS-MONKEY; HUMAN BRAIN; IN-VIVO; FRONTAL-CORTEX; DISCONNEXION SYNDROMES AB Experimental and imaging studies in monkeys have outlined various long association fiber pathways within the fronto-temporo-parietal region. In the present study, the trajectory of the extreme capsule (EmC) fibers has been delineated in five human subjects using DT-MRI tractography. The EmC seems to be a long association fiber pathway, which courses between the inferior frontal region and the superior temporal gyrus extending into the inferior parietal lobule. Comparison of EmC fibers with the adjacent association fiber pathway, the middle longitudinal fascicle (MdLF), in the same subjects reveals that EmC is located in a medial and rostral position relative to MdLF flanking in part the medial wall of the insula. The EmC can also be differentiated from other neighboring fiber pathways such as the external capsule, uncinate fascicle, arcuate fascicle, superior longitudinal fascicles II and III, and the inferior longitudinal fascicle. Given the location of EmC within the language zone, specifically Broca's area in the frontal lobe, and Wernicke's area in the temporal lobe and inferior parietal lobule, it is suggested that the extreme capsule could have a role in language function. C1 [Makris, Nikos] Massachusetts Gen Hosp, A Martinos Ctr Biomed Imaging, Ctr Morphometr Anal, Charlestown, MA 02129 USA. [Makris, Nikos; Pandya, Deepak N.] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02215 USA. [Makris, Nikos] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02129 USA. [Makris, Nikos] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02129 USA. RP Makris, N (reprint author), Massachusetts Gen Hosp, A Martinos Ctr Biomed Imaging, Ctr Morphometr Anal, Bldg 149,13th St, Charlestown, MA 02129 USA. EM nikos@cma.mgh.harvard.edu FU NCCIH NIH HHS [P01 AT002048] NR 62 TC 92 Z9 92 U1 0 U2 6 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1863-2653 J9 BRAIN STRUCT FUNCT JI Brain Struct. Funct. PD FEB PY 2009 VL 213 IS 3 BP 343 EP 358 DI 10.1007/s00429-008-0199-8 PG 16 WC Anatomy & Morphology; Neurosciences SC Anatomy & Morphology; Neurosciences & Neurology GA 397GB UT WOS:000262649800005 PM 19104833 ER PT J AU Kimmick, GG Cirrincione, C Duggan, DB Bhalla, K Robert, N Berry, D Norton, L Lemke, S Henderson, IC Hudis, C Winer, E AF Kimmick, G. G. Cirrincione, C. Duggan, D. B. Bhalla, K. Robert, N. Berry, D. Norton, L. Lemke, S. Henderson, I. C. Hudis, C. Winer, E. CA Cance Leukemia Grp B TI Fifteen-year median follow-up results after neoadjuvant doxorubicin, followed by mastectomy, followed by adjuvant cyclophosphamide, methotrexate, and fluorouracil (CMF) followed by radiation for stage III breast cancer: a phase II trial (CALGB 8944) SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast cancer; Chemotherapy; Locally advanced; Long-term follow-up; Neoadjuvant; Stage III ID PATHOLOGICAL COMPLETE RESPONSE; COMBINED-MODALITY APPROACH; ESTROGEN-RECEPTOR STATUS; PROJECT PROTOCOL B-27; LEUKEMIA GROUP-B; PRIMARY CHEMOTHERAPY; PREOPERATIVE CHEMOTHERAPY; PROGNOSTIC-SIGNIFICANCE; TUMOR RESPONSE; COMBINATION CHEMOTHERAPY AB Purpose To describe long-term results of a multimodality strategy for stage III breast cancer utilizing neoadjuvant doxorubicin followed by mastectomy, CMF, and radiotherapy. Patients and methods Women with biopsy-proven, clinical stage III breast cancer and adequate organ function were eligible. Neoadjuvant doxorubicin (30 mg/m(2) days 1-3, every 28 days for 4 cycles) was followed by mastectomy, in stable or responding patients. Sixteen weeks of postoperative CMF followed (continuous oral cyclophosphamide (2 mg/kg/day); methotrexate (0.7 mg/kg IV) and fluorouracil (12 mg/kg IV) weekly, weeks 1-8, and than biweekly, weeks 9-16). Radiation therapy followed adjuvant chemotherapy. Results Clinical response rate was 71% (79/111, 95% CI = 62-79%), with 19% complete clinical response. Pathologic complete response was 5% (95% CI = 2-11%). Median follow-up is 15.6 years. Half of the patients progressed by 2.2 years; half died by 5.4 years (range 6 months-15 years). The hazard of dying was greatest in the first 5 years after diagnosis and declined thereafter. Time to progression and overall survival were predicted by number of pathologically involved lymph nodes (TTP: HR [10 vs. 1 node] 2.40, 95% CI = 1.63-3.53, P < 0.0001; OS: HR 2.50, 95% CI = 1.74-3.58, P < 0.0001). Conclusions After multimodality treatment for locally advanced breast cancer, long-term survival was correlated with the number of pathologically positive lymph nodes, but not to clinical response. The hazard of death was highest during the first 5 years after diagnosis and declined thereafter, indicating a possible intermediate endpoint for future trials of neoadjuvant treatment. C1 [Kimmick, G. G.; Cirrincione, C.] Duke Univ, Med Ctr, CALGB Stat Ctr, Durham, NC 27710 USA. [Duggan, D. B.; Lemke, S.] SUNY Upstate Med Univ, Syracuse, NY USA. [Bhalla, K.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Robert, N.] Inova Fairfax Hosp, Inst Res, Falls Church, VA USA. [Berry, D.] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. [Norton, L.; Hudis, C.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Henderson, I. C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Winer, E.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kimmick, GG (reprint author), Duke Univ, Med Ctr, CALGB Stat Ctr, Trent Dr,Suite 3800,Duke South,POB 3204, Durham, NC 27710 USA. EM gretchen.kimmick@duke.edu OI Norton, Larry/0000-0003-3701-9250 FU Memorial Sloan Kettering Cancer Center, New York, NY-L. Norton; University of California San Francisco, San Francisco, CA-I. C. Henderson; National Cancer Institute [CA77651, CA60138, CA31946, CA33601, CA32291, CA47577, CA35406, CA45374, CA12449, CA35279, CA08025, CA02599, CA45808, CA35421, CA21060, CA47545, CA41287, CA31983, CA37135, CA16450, CA12046, CA11789, CA47555, CA03927, CA26806, CA77440, CA07968]; CALGB Statistical Center, Duke University Medical Center, Durham, NC; Dana-Farber Cancer Institute, Boston, MA; Eastern Maine Medical Center, Bangor, ME; Kaiser Permanente, San Diago, CA; Massachusetts General Hospital, Boston, MA; North Shore - Long Island Jewish Medical Center, Manhasset, NY; Rhode Island Hospital, Providence, RI; Roswell Park Cancer Institute, Buffalo, NY; Southeast Cancer Control Consortium Inc.; Southern Nevada Cancer Research Foundation CCOP, Las Vegas, NV; State University of New York Upstate Medical University, Syracuse, NY; Syracuse Hematology-Oncology Association CCOP, Syracuse, NY; University of Alabama Birmingham, Birmingham, AL; University of Chicago, Chicago, IL; University of Maryland Greenebaum Cancer Center, Baltimore, MD; University of Massachusetts Medical School, Worcester, MA; University of Minnesota, Minneapolis, MN; University of Missouri/Ellis Fischel Cancer Center, Columbia, MO; University of California at San Diego, San Diego, CA; University of Tennessee Memphis, Memphis, TN; Wake Forest University School of Medicine, Winston-Salem, NC; Walter Reed Army Medical Center, Washington, DC; Washington University School of Medicine, St. Louis, MO; Weill Medical College of Cornell University, New York, NY FX Memorial Sloan Kettering Cancer Center, New York, NY-L. Norton, supported by CA77651.; University of California San Francisco, San Francisco, CA-I. C. Henderson, supported by CA60138.; This research for CALGB 8944 was supported, in part, by grants from the National Cancer Institute (CA31946) to the Cancer and Leukemia Group B (Richard L. Schilsky, Chairman), to the CALGB Statistical Center (Stephen George, PhD, CA33601) and to the Eastern Cooperative Oncology Group (Robert L. Comis, Chairman). The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute. The following institutions participated in this study: (1) CALGB Statistical Center, Duke University Medical Center, Durham, NC-Stephen George, Ph.D., supported by CA33601; (2) Dana-Farber Cancer Institute, Boston, MA-Eric P. Winer, M. D., supported by CA32291; (3) Duke University Medical Center, Durham, NC-Jeffrey Crawford, M. D., supported by CA47577; (4) Eastern Maine Medical Center, Bangor, ME, Philip L. Brooks, M. D., supported by CA35406; (5) Kaiser Permanente, San Diago, CA, Joathan A. Polikoff, M. D., supported by CA45374; (6) Massachusetts General Hospital, Boston, MA-Michael L. Grossbard, M. D., supported by CA12449; (7) North Shore - Long Island Jewish Medical Center, Manhasset, NY-Daniel R Budman, M. D., supported by CA35279; (8) Rhode Island Hospital, Providence, RI-William Sikov, M. D., supported by CA08025; (9) Roswell Park Cancer Institute, Buffalo, NY-Ellis Levine, M. D., supported by CA02599; (10) Southeast Cancer Control Consortium Inc. CCOP, Goldsboro, NC-James N. Atkins, M. D., supported by CA45808; (11) Southern Nevada Cancer Research Foundation CCOP, Las Vegas, NV-John Ellerton, M. D., supported by CA35421; (12) State University of New York Upstate Medical University, Syracuse, NY Stephen L. Graziano, M. D., supported by CA21060; (13) Syracuse Hematology-Oncology Association CCOP, Syracuse, NY, Stephen L Graziano, M. D., supported by CA21060; (14) University of Alabama Birmingham, Birmingham, AL-Robert Diasio, M. D., supported by CA47545; (15) University of Chicago, Chicago, IL-Gini Fleming, M. D., supported by CA41287; (16) University of Maryland Greenebaum Cancer Center, Baltimore, MD-Martin Edelman, M. D., supported by CA31983; (17) University of Massachusetts Medical School, Worcester, MA-William V. Walsh, M. D., supported by CA37135; (18) University of Minnesota, Minneapolis, MN-Bruce A Peterson, M. D., supported by CA16450; (19) University of Missouri/Ellis Fischel Cancer Center, Columbia, MO - Michael C Perry, M. D., supported by CA12046; (20) University of California at San Diego, San Diego, CA-Joanne Mortimer, M. D., supported by CA11789; (21) University of Tennessee Memphis, Memphis, TN-Harvey B. Niell, M. D., supported by CA47555; (22) Wake Forest University School of Medicine, Winston-Salem, NC-David D Hurd, M. D., supported by CA03927; (23) Walter Reed Army Medical Center, Washington, DC-Thomas Reid, M. D., supported by CA26806; (24) Washington University School of Medicine, St. Louis, MO-Nancy Bartlett, M. D., supported by CA77440; and (25) Weill Medical College of Cornell University, New York, NY-Scott Wadler, M. D., supported by CA07968. NR 44 TC 6 Z9 8 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 EI 1573-7217 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD FEB PY 2009 VL 113 IS 3 BP 479 EP 490 DI 10.1007/s10549-008-9943-2 PG 12 WC Oncology SC Oncology GA 396JB UT WOS:000262586900007 PM 18306034 ER PT J AU Anderson, KS Wong, J Polyak, K Aronzon, D EnerbAck, C AF Anderson, K. S. Wong, J. Polyak, K. Aronzon, D. EnerbAck, C. TI Detection of psoriasin/S100A7 in the sera of patients with psoriasis SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article DE autoantibodies; biomarker; psoriasis; S100A7 ID MAMMARY EPITHELIAL-CELLS; ACID-BINDING PROTEIN; S100A7 PSORIASIN; BREAST-CANCER; IFN-GAMMA; DIFFERENTIATION; KERATINOCYTES; EXPRESSION; ANTIBODIES; ANTIGENS AB Psoriasis is a disease of dysregulated inflammation and epithelial hyperproliferation in the skin, involving both the innate and adaptive immune system. Psoriatic keratinocytes express high levels of psoriasin (S100A7), a small calcium-binding protein. To determine if patients with active psoriasis have elevated serum levels of psoriasin and psoriasin-specific autoantibodies. Blood was collected from 14 patients with psoriasis vulgaris at the start of narrowband ultraviolet (UV) B therapy and from 11 of these patients every 2 weeks during the course of the UVB treatment. Patient and control sera were tested for psoriasin antigen levels by sandwich enzyme-linked immunosorbent assay, and for psoriasin autoantibody titres using recombinant purified psoriasin and overlapping peptides. We confirmed strong and specific expression of psoriasin in psoriatic epidermis by immunohistochemistry. Systemic psoriasin antigen levels tended to be lower in patients (mean 213 ng mL(-1)) than in controls (mean 331 ng mL(-1), P = 0.308) and decreased with increasing disease severity. Psoriasin-specific autoantibodies were detected in a subset of patients with psoriasis and healthy normal donors (mean 0.347 vs. 0.255 units, P = 0.246). The epitopes recognized by the autoantibodies were mapped to an external loop domain of the molecule but did not show corresponding T-cell immunogenicity. Although psoriasin is overexpressed in psoriatic skin lesions, systemic levels of psoriasin tended to be lower with increasing disease severity, which may be due to the presence of psoriasin-specific autoantibodies. Neither psoriasin nor psoriasin-specific autoantibodies appear to be promising serum biomarkers for clinical psoriasis. C1 [Anderson, K. S.; Wong, J.; Aronzon, D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. [Anderson, K. S.; Polyak, K.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [EnerbAck, C.] Sahlgrens Univ Hosp, Dept Clin Genet, S-41345 Gothenburg, Sweden. [EnerbAck, C.] Sahlgrens Univ Hosp, Dept Dermatol, S-41345 Gothenburg, Sweden. RP Anderson, KS (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. EM kanderson@partners.org FU Swedish Psoriasis Foundation; Welander Foundation FX We thank Imgenex for providing monoclonal antibodies for these studies. This study was supported by a research grant from the Swedish Psoriasis Foundation and the Welander Foundation. NR 31 TC 20 Z9 21 U1 0 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-0963 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD FEB PY 2009 VL 160 IS 2 BP 325 EP 332 DI 10.1111/j.1365-2133.2008.08904.x PG 8 WC Dermatology SC Dermatology GA 395FC UT WOS:000262509000013 PM 19016707 ER PT J AU Abramson, JS Chen, W Juszczynski, P Takahashi, H Neuberg, D Kutok, JL Takeyama, K Shipp, MA AF Abramson, Jeremy S. Chen, Wen Juszczynski, Przemyslaw Takahashi, Hidenobu Neuberg, Donna Kutok, Jeffery L. Takeyama, Kunihiko Shipp, Margaret A. TI The heat shock protein 90 inhibitor IPI-504 induces apoptosis of AKT-dependent diffuse large B-cell lymphomas SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE AKT; client; IPI-504; heat shock protein 90; lymphoma ID HSP90 INHIBITOR; HEAT-SHOCK-PROTEIN-90 INHIBITOR; CYCLE ARREST; MULTIPLE-MYELOMA; ANTITUMOR AGENT; LEUKEMIA-CELLS; PHASE-I; TARGET; 17-ALLYLAMINO-17-DEMETHOXYGELDANAMYCIN; GELDANAMYCIN AB Heat shock protein 90 (HSP90) is a molecular chaperone that stabilizes critical client proteins in multiple cancers. Gene expression profiling was utilized to characterize HSP90 isoform expression in primary human diffuse large B-cell lymphomas (DLBCLs). HSP90 alpha and beta isoforms were differentially expressed in subsets of tumours defined by their transcriptional profiles. Thereafter, we assessed the activity of the HSP90 inhibitor, IPI-504, in an extensive panel of DLBCL cell lines. IPI-504, which interacts with the conserved ATP-binding site in both HSP90 isoforms, inhibited proliferation and induced apoptosis in the majority of DLBCL cell lines at low micromolar concentrations. IPI-504-sensitive cell lines expressed high levels of the HSP90 client protein, pAKT, and exhibited dose-dependent decreases in pAKT levels following IPI-504 treatment and significantly reduced proliferation following AKT RNAi. Furthermore, the combination of low-dose (< 1 mu mol/l) IPI-504 and the AKT/Pi3K pathway inhibitor, LY24009, was synergistic in IPI-504-sensitive DLBCL cell lines. Low-dose IPI-504 was also synergistic with the chemotherapeutic agent, doxorubicin. The HSP90 inhibitor IPI-504 warrants further investigation in DLBCL alone and in combination with identified client protein inhibitors and active chemotherapeutic agents. C1 [Abramson, Jeremy S.; Chen, Wen; Juszczynski, Przemyslaw; Takahashi, Hidenobu; Takeyama, Kunihiko; Shipp, Margaret A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. [Kutok, Jeffery L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Shipp, MA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,Mayer 513, Boston, MA 02115 USA. EM margaret_shipp@dfci.harvard.edu OI Abramson, Jeremy/0000-0001-8467-9257 FU NCI NIH HHS [P01 CA092625] NR 52 TC 19 Z9 20 U1 1 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD FEB PY 2009 VL 144 IS 3 BP 358 EP 366 DI 10.1111/j.1365-2141.2008.07484.x PG 9 WC Hematology SC Hematology GA 395FD UT WOS:000262509100008 PM 19036086 ER PT J AU Yi, K Mujat, M Park, BH Sun, W Miller, JW Seddon, JM Young, LH de Boer, JF Chen, TC AF Yi, K. Mujat, M. Park, B. H. Sun, W. Miller, J. W. Seddon, J. M. Young, L. H. de Boer, J. F. Chen, T. C. TI Spectral domain optical coherence tomography for quantitative evaluation of drusen and associated structural changes in non-neovascular age-related macular degeneration SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID ULTRAHIGH-RESOLUTION; HIGH-SPEED; SEVERITY SCALE; HUMAN RETINA; IMAGES; NERVE AB Background/aims: To demonstrate how spectral domain optical coherence tomography (SDOCT) can better evaluate drusen and associated anatomical changes in eyes with non-neovascular age-related macular degeneration (AMD) compared with time domain optical coherence tomography (TDOCT). Methods: Images were obtained from three eyes of three patients with AMD using an experimental SDOCT system. Both a titanium-sapphire (Ti:sapphire) laser and a superluminescent diode (SLD) were used as a broadband light source to achieve cross-sectional images of the retina. A qualitative and quantitative analysis was performed for structural changes associated with non-neovascular AMD. An automated algorithm was developed to analyse drusen area and volume from SDOCT images. TDOCT was performed using the fast macular scan (StratusOCT, Carl Zeiss Meditec, Dublin, California). Results: SDOCT images can demonstrate structural changes associated with non-neovascular AMD. A new SDOCT algorithm can determine drusen area, drusen volume and proportion of drusen. Conclusions: With new algorithms to determine drusen area and volume and its unprecedented simultaneous ultra-high speed ultra-high resolution imaging, SDOCT can improve the evaluation of structural abnormalities in non-neovascular AMD. C1 [Yi, K.; Chen, T. C.] Massachusetts Eye & Ear Infirm, Glaucoma Serv, Boston, MA 02114 USA. [Yi, K.; Mujat, M.; Park, B. H.; Miller, J. W.; Young, L. H.; de Boer, J. F.; Chen, T. C.] Harvard Univ, Sch Med, Boston, MA USA. [Yi, K.] Hallym Univ, Kangnam Sacred Heart Hosp, Seoul, South Korea. [Mujat, M.; Park, B. H.; Sun, W.; de Boer, J. F.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Mujat, M.] Phys Sci Inc, Andover, MA 01810 USA. [Sun, W.] Boston Univ, Dept Phys, Boston, MA 02215 USA. [Miller, J. W.; Young, L. H.] Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. [Seddon, J. M.] Tufts Univ, Sch Med, New England Med Ctr, Boston, MA 02111 USA. [de Boer, J. F.] Vrije Univ Amsterdam, Dept Phys & Astron, Amsterdam, Netherlands. RP Chen, TC (reprint author), Massachusetts Eye & Ear Infirm, Glaucoma Serv, 243 Charles St, Boston, MA 02114 USA. EM teresa_chen@meei.harvard.edu RI de Boer, Johannes/B-7590-2012 OI de Boer, Johannes/0000-0003-1253-4950 FU National Institutes of Health [R01EY014975, R01-RR19768]; JFB's research FX This paper was partially supported by the National Institutes of Health, Bethesda, Maryland (R01EY014975, R01-RR19768). Nidek sponsors JFB's research. Patents in spectral domain optical coherence tomography: JFB, MM, BHP. NR 23 TC 52 Z9 54 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 FEB PY 2009 VL 93 IS 2 BP 176 EP 181 DI 10.1136/bjo.2008.137356 PG 6 WC Ophthalmology SC Ophthalmology GA 399XZ UT WOS:000262833900010 PM 18697811 ER PT J AU Rhee, DJ Gupta, M Moncavage, MB Moster, ML Moster, MR AF Rhee, D. J. Gupta, M. Moncavage, M. B. Moster, M. L. Moster, M. R. TI Idiopathic elevated episcleral venous pressure and open-angle glaucoma SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID CAVERNOUS SINUS FISTULAS; PLATEAU IRIS SYNDROME; VEINS; CLASSIFICATION; SURGERY; VESSELS AB Background/aims: To report a case series of Idiopathic Elevated Episcleral Venous Pressure (IEEVP). Methods: Retrospective chart review of all cases of IEEVP seen over a 5-year period by three physicians. Results: Six cases (five men and one woman) are added to the known 19 documented cases in the English literature, only three of which were reported in the last 10 years. By history, the onset of conjunctival injection of all patients was in early adulthood or late teens. None had an identifiable lesion by modern imaging techniques. All cases had bilateral but asymmetric involvement. Four of the six required glaucoma surgery by the 5th to 7th decade of life. The three eyes that had glaucoma filtration surgery had good outcomes. Choroidal effusions occurred in the postoperative period of one eye which was not hypotonous. Conclusion: IEEVP is a rare cause of glaucoma which is diagnosed by the clinical criteria of dilated episcleral vessels without an identifiable cause. If glaucoma filtration surgery is required, there are generally good results. However, clinicians must be cautious of choroidal effusions occurring at non-hypotonous intraocular pressures. C1 [Rhee, D. J.; Gupta, M.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Glaucoma Serv, Boston, MA 02114 USA. [Moncavage, M. B.; Moster, M. R.] Thomas Jefferson Univ, Wills Eye Hosp, Glaucoma Serv, Philadelphia, PA 19107 USA. [Moster, M. L.] Albert Einstein Med Ctr, Neuroophthalmol Serv, Philadelphia, PA 19141 USA. RP Rhee, DJ (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Glaucoma Serv, 243 Charles St, Boston, MA 02114 USA. EM dougrhee@aol.com FU National Eye Institute, Bethesda [EY 13997] FX National Eye Institute, Bethesda, MD, EY 13997 (to DJR). NR 25 TC 7 Z9 7 U1 3 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 FEB PY 2009 VL 93 IS 2 BP 231 EP 234 DI 10.1136/bjo.2007.126557 PG 4 WC Ophthalmology SC Ophthalmology GA 399XZ UT WOS:000262833900020 PM 18567649 ER PT J AU Fishman, J O'Dwyer, P Lu, HL Henderson, H Asch, DA Casarett, DJ AF Fishman, Jessica O'Dwyer, Peter Lu, Hien L. Henderson, Hope Asch, David A. Casarett, David J. TI Race, Treatment Preferences, and Hospice Enrollment: Eligibility Criteria May Exclude Patients With the Greatest Needs for Care SO CANCER LA English DT Article DE treatment preferences; conjoint analysis; utilities; interview; Medicare Hospice Benefit; services; palliative care; African American; race; economic; finances ID OF-LIFE CARE; RANDOMIZED CONTROLLED-TRIAL; CONJOINT-ANALYSIS; CANCER-PATIENTS; NURSING-HOMES; PALLIATIVE CARE; HEALTH RESEARCH; MANAGEMENT; END; COMMUNITY AB BACKGROUND: The requirement that patients give up curative treatment makes hospice enrollment unappealing for some patients and may particularly limit use among African-American patients. The current study was conducted to determine whether African-American patients with cancer are more likely than white patients to have preferences for cancer treatment that exclude them from hospice and whether they are less likely to want specific hospice services. METHODS: Two hundred eighty-three patients who were receiving treatment for cancer at 6 oncology clinics within the University of Pennsylvania Cancer Network completed conjoint interviews measuring their perceived need for 5 hospice services and their preferences for continuing cancer treatment. Patients were followed for 6 months or until death. RESULTS: African-American patients had stronger preferences for continuing their cancer treatments on a 7-point scale even after adjusting for age, sex, finances, education, Eastern Cooperative Oncology Group performance status, quality of life, and physical and psychologic symptom burden (adjusted mean score, 4.75 vs 3.96; beta coefficient, 0.82; 95% confidence interval, 0.22-1.41 [P=.007]). African-American patients also had greater perceived needs for hospice services after adjusting for these characteristics (adjusted mean score, 2.31 vs 1.83; beta coefficient, 0.51; 95% confidence interval, 0.11-0.92 [P=.01]). However, this effect disappeared after adjusting for household finances. CONCLUSIONS: Hospice eligibility criteria may exclude African-American patients disproportionately despite greater perceived needs for hospice services in this population. The mechanisms driving this health disparity likely include both cultural differences and economic characteristics, and consideration should be given to redesigning hospice eligibility criteria. Cancer 2009;115:689-97. (C) 2008 American Cancer Society. C1 [Fishman, Jessica; O'Dwyer, Peter; Lu, Hien L.; Asch, David A.; Casarett, David J.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Fishman, Jessica] Univ Penn, Annenberg Sch Commun, Philadelphia, PA 19104 USA. [Fishman, Jessica] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Henderson, Hope; Asch, David A.; Casarett, David J.] Vet Affairs Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Asch, David A.; Casarett, David J.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. RP Casarett, DJ (reprint author), Univ Penn, Sch Med, 3615 Chestnut St, Philadelphia, PA 19104 USA. EM casarett@mail.med.upenn.edu OI Asch, David/0000-0002-7970-286X FU American Cancer Society Mentored Scholar Research [MRSGT-08-013-01-CPPB]; University of Pennsylvania's National Institutes of Health [R01CA109540]; Veterans Administration Advanced Research Career Development Award; Presidential Early Career Award for Scientists and Engineers; Abramson Cancer Center; Center for Clinical Epidemiology and Biostatistics; Center For Health Equity Research and Promotion FX Supported by American Cancer Society Mentored Scholar Research grant MRSGT-08-013-01-CPPB (to J.F.), the University of Pennsylvania's National Institutes of Health-funded Center of Excellence for Cancer Communication Research grant (to J.F.), grant R01CA109540 (to D.J.C.), a Veterans Administration Advanced Research Career Development Award, a Presidential Early Career Award for Scientists and Engineers (to D.J.C.), and by grants from the Abramson Cancer Center (to P.O.), the Center for Clinical Epidemiology and Biostatistics (to J.F.), and the Center For Health Equity Research and Promotion (to D.J.C. and J.F.). NR 68 TC 37 Z9 37 U1 2 U2 7 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD FEB 1 PY 2009 VL 115 IS 3 BP 689 EP 697 DI 10.1002/cncr.24046 PG 9 WC Oncology SC Oncology GA 402GY UT WOS:000263003400028 PM 19107761 ER PT J AU Kuo, YC Yu, CL Liu, CY Wang, SF Pan, PC Wu, MT Ho, CK Lo, YS Li, Y Christiani, DC AF Kuo, Yau-Chang Yu, Chu-Ling Liu, Chen-Yu Wang, Su-Fen Pan, Pi-Chen Wu, Ming-Tsang Ho, Chi-Kung Lo, Yu-Shing Li, Yi Christiani, David C. CA Kaohsiung Leukemia Res Grp TI A population-based, case-control study of green tea consumption and leukemia risk in southwestern Taiwan SO CANCER CAUSES & CONTROL LA English DT Article DE Asia; Catechin; Childhood Leukemia; Epidemiology; Green Tea ID ANTICARCINOGENIC ACTIVITY; ANTIMUTAGENIC ACTIVITY; CANCER RISK; POLYPHENOLS; CARCINOMA; CELLS; DIET; (-)-EPIGALLOCATECHIN-3-GALLATE; CHEMOPREVENTION; COMPONENTS AB This study investigated the association between green tea consumption and leukemia. A total of 252 cases (90.3% response) and 637 controls (53.4% response) were enrolled. Controls were matched for cases on age and gender. Information was collected on participants' living habits, including tea consumption. Green tea was used as a standard to estimate the total amount of individual catechin consumption. We stratified individual consumption of catechins into four levels. Conditional logistic regression models were fit to subjects aged 0-15 and 16-29 years to evaluate separate associations between leukemia and catechin consumption. A significant inverse association between green tea consumption and leukemia risk was found in individuals aged 16-29 years, whereas no significant association was found in the younger age groups. For the older group with higher amounts of tea consumption (> 550 units of catechins), the adjusted odds ratio (OR) compared with the group without tea consumption was 0.47 [95% confidence interval (CI) = 0.23-0.97]. After we adjusted for smoking status and medical irradiation exposure, the overall OR for all participants was 0.49 (95% CI = 0.27-0.91), indicating an inverse relation between large amounts of catechins and leukemia. Drinking sufficient amounts of tea, especially green tea, which contains more catechins than oolong tea and black tea, may reduce the risk of leukemia. C1 [Kuo, Yau-Chang; Yu, Chu-Ling; Liu, Chen-Yu; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Environm & Occupat Med & Epidemiol Program, Dept Environm Hlth, Boston, MA 02115 USA. [Kuo, Yau-Chang] Kaohsiung Vet Gen Hosp, Dept Occupat & Environm Med, Kaohsiung, Taiwan. [Kuo, Yau-Chang] Kaohsiung Vet Gen Hosp, Dept Emergency Med, Kaohsiung, Taiwan. [Wang, Su-Fen] Natl Changhua Univ Educ, Dept Geog, Changhua, Taiwan. [Pan, Pi-Chen] Yuh Ing Jr Coll Hlth Care & Management, Kaohsiung, Taiwan. [Wu, Ming-Tsang; Ho, Chi-Kung] Kaohsiung Med Univ, Sch Publ Hlth, Kaohsiung, Taiwan. [Lo, Yu-Shing] Kaohsiung Med Univ, Dept Pathol & Lab Med, Kaohsiung, Taiwan. [Li, Yi] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Christiani, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Unit,Dept Med, Boston, MA USA. [Kaohsiung Leukemia Res Grp] Kaohsiung Leukemia Res Grp, Kaohsiung, Taiwan. RP Kuo, YC (reprint author), 7F 13 LN 8,RongZong Rd, Kaohsiung 813, Taiwan. EM kuo550221@yahoo.com.tw RI Wu, Ming-Tsang/D-2385-2009; OI LIU, CHEN-YU/0000-0002-4693-5667 FU National Institutes of Health [ES09723, ES00002] FX National Institutes of Health (ES09723, ES00002). NR 34 TC 15 Z9 15 U1 2 U2 9 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD FEB PY 2009 VL 20 IS 1 BP 57 EP 65 DI 10.1007/s10552-008-9217-7 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 395DU UT WOS:000262504100007 PM 18752033 ER PT J AU Dhillon, PK Barry, M Stampfer, MJ Perner, S Fiorentino, M Fornari, A Ma, J Fleet, J Kurth, T Rubin, MA Mucci, LA AF Dhillon, Preet K. Barry, Marc Stampfer, Meir J. Perner, Sven Fiorentino, Michelangelo Fornari, Alessandro Ma, Jing Fleet, Julia Kurth, Tobias Rubin, Mark A. Mucci, Lorelei A. TI Aberrant Cytoplasmic Expression of p63 and Prostate Cancer Mortality SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID TRANSITIONAL-CELL CARCINOMA; UPPER URINARY-TRACT; P53 NUCLEAR EXPORT; COLORECTAL ADENOCARCINOMA; PHYSICIANS HEALTH; NEEDLE-BIOPSY; PROTEIN; MDM2; DEGRADATION; SURVIVAL AB Protein expression of p63 is used to differentiate prostate cancer from benign mimickers. Recent studies suggest that it may also distinguish aggressive prostate cancer with down-regulated expression occurring in men with more advanced disease. We conducted a prospective study among 298 men ages 51 to 84 years who were diagnosed with prostate cancer in the Physicians' Health Study in 1983 to 2004 and whose tissue was available for immunohistochemical staining. We used Cox proportional hazards regression to evaluate the association of p63 protein expression with fatal prostate cancer. We correlated p63 expression with tumor cell proliferation (Ki-67) and apoptosis (TUNEL staining). The predominant location of tumor p63 staining occurred in the cytoplasm, an uncommon departure from the strong nuclear staining usually observed in nonneoplastic basal cells. Increasing expression of cytoplasmic p63 (tertiles) was associated with prostate cancer mortality (n = 19 deaths); the hazard ratios (95% confidence intervals) were 1.0 (reference), 4.0 (0.9-18.9), and 5.9 (1.3-27.5; P(trend) = 0.03). The positive trend remained significant (P = 0.047) after multivariable adjustment for age, year of diagnosis, and Gleason score. Higher tertiles of cytoplasmic p63 were also associated with reduced levels of apoptosis (P(trend) = 0.0408) and increased cellular proliferation (P(trend) = 0.0026). We found aberrant expression of p63 in the cytoplasm to be associated with increased prostate cancer-specific mortality up to 20 years after diagnosis. The mislocalized expression was associated with reduced apoptosis and higher proliferative activity and may suggest an oncogenic role in prostate cancer progression and survival. (Cancer Epidemiol Biomarkers Prev 2009;18(2):595-600) C1 [Dhillon, Preet K.; Stampfer, Meir J.; Ma, Jing; Fleet, Julia; Mucci, Lorelei A.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. [Kurth, Tobias] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. [Barry, Marc; Perner, Sven; Rubin, Mark A.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Dhillon, Preet K.; Stampfer, Meir J.; Kurth, Tobias; Mucci, Lorelei A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Cambridge, MA 02138 USA. [Fiorentino, Michelangelo; Fornari, Alessandro] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Perner, Sven; Rubin, Mark A.] Cornell Univ, Weill Med Coll, Dept Pathol, New York, NY 10021 USA. RP Dhillon, PK (reprint author), Brigham & Womens Hosp, Dept Med, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. EM pdhillon@hsph.harvard.edu RI Kurth, Tobias/A-9243-2012; OI Kurth, Tobias/0000-0001-7169-2620; Rubin, Mark/0000-0002-8321-9950 FU National Cancer Institute grants [CA-34944, CA-40360, CA-097193]; National Heart, Lung, ind Blood Institute [FIL-20490, 1-11-34595]; U.S. Army Prostite Cancer program [W81 XWH-05-1-0562]; NIH [5R01 CA090598]; Cancer Epidemiology Training [T32 CA009001] FX Grant support: National Cancer Institute grants CA-34944, CA-40360, and CA-097193 and National Heart, Lung, ind Blood Institute grants FIL-20490 and 1-11-34595 U.S. Army Prostite Cancer program grant W81 XWH-05-1-0562 (PI: L.A. Mucci) and NIH grant 5R01 CA090598 (PI: M.J. Stampfer); and Cancer Epidemiology Training Grant NO T32 CA009001 (P.K. Dhillon). NR 42 TC 30 Z9 30 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD FEB PY 2009 VL 18 IS 2 BP 595 EP 600 DI 10.1158/1055-9965.EPI-08-0785 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 410AS UT WOS:000263547800030 PM 19155438 ER PT J AU Garber, JE AF Garber, Judy E. TI BRCA1/2-Associated and Sporadic Breast Cancers: Fellow Travelers or Not? SO CANCER PREVENTION RESEARCH LA English DT Editorial Material ID CARCINOMA IN-SITU; PROPHYLACTIC MASTECTOMY; MUTATION CARRIERS; BRCA2 MUTATIONS; FOLLOW-UP; WOMEN; RISK; REPAIR; TRIAL; PREVALENCE C1 Dana Farber Canc Inst, Dept Med Oncol, Div Populat Sci, Boston, MA 02115 USA. RP Garber, JE (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Div Populat Sci, 44 Binney St,Smith 210, Boston, MA 02115 USA. EM judy_garber@dfci.harvard.edu NR 32 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD FEB PY 2009 VL 2 IS 2 BP 100 EP 103 DI 10.1158/1940-6207.CAPR-08-0243 PG 4 WC Oncology SC Oncology GA 420MR UT WOS:000264294400002 PM 19174575 ER PT J AU Medarova, Z Rashkovetsky, L Pantazopoulos, P Moore, A AF Medarova, Zdravka Rashkovetsky, Leonid Pantazopoulos, Pamela Moore, Anna TI Multiparametric Monitoring of Tumor Response to Chemotherapy by Noninvasive Imaging SO CANCER RESEARCH LA English DT Article ID BREAST-CANCER-CELLS; LYMPH-NODE METASTASES; POSITRON-EMISSION-TOMOGRAPHY; IN-VIVO; HER-2/NEU RECEPTOR; CARCINOMA; MRI AB With the emerging concept of individualized cancer therapy, it becomes crucial to develop methods for the noninvasive assessment of treatment outcome. With this in mind, we designed a novel approach for the comprehensive evaluation of response to chemotherapy with the established agent doxorubicin in a preclinical breast cancer model. This approach delivers information not only about change in tumor size but also about target antigen expression. Our strategy relies on a tumor-specific contrast agent (MN-EPPT) targeting the underglycosylated MUC-1 (uMUC-1) tumor antigen, found on more than 90% of breast cancers and predictive of chemotherapeutic response. MN-EPPT consists of superparamagnetic iron oxide nanoparticles (MN) for magnetic resonance imaging, modified with Cy5.5 dye (for near-IR fluorescence optical imaging), and conjugated to peptides (EPPT), specifically recognizing uMUC-1. In vivo, treatment of mice bearing orthotopic human breast carcinomas with doxorubicin led to a reduction in tumor mass and resulted in down-regulation of uMUC-1. The tumor-specific accumulation of MN-EPPT allowed the assessment of change in tumor volume by noninvasive imaging. Furthermore, in mice injected with MN-EPPT, tumor delta-T2 was significantly reduced after treatment with doxorubicin, indicating a lower accumulation of MN-EPPT and reflecting the reduced expression of uMUC-1. With these studies, we have shown the utility of magnetic resonance imaging for the multiparametric characterization of breast tumor response to chemotherapy. This approach has the potential of significantly advancing our ability to better direct the development of molecularly targeted individualized therapy protocols because it permits the monitoring of therapy on a molecular scale. [Cancer Res 2009;69(3):1182-9] C1 [Moore, Anna] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Mol Imaging Lab, Dept Radiol,MGH MIT HMS Athinoula A Martinos Ctr, Charlestown, MA 02129 USA. RP Moore, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Mol Imaging Lab, Dept Radiol,MGH MIT HMS Athinoula A Martinos Ctr, Room 2301,Bldg 149,13th St, Charlestown, MA 02129 USA. EM amoore@helix.mgh.harvard.edu FU NIH [EB001727] FX Grant support: NIH grant EB001727 (A. Moore). NR 31 TC 62 Z9 71 U1 1 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 1 PY 2009 VL 69 IS 3 BP 1182 EP 1189 DI 10.1158/0008-5472.CAN-08-2001 PG 8 WC Oncology SC Oncology GA 402YJ UT WOS:000263048700057 PM 19141648 ER PT J AU Lubitz, SA Yi, BA Ellinor, PT AF Lubitz, Steven A. Yi, B. Alexander Ellinor, Patrick T. TI Genetics of Atrial Fibrillation SO CARDIOLOGY CLINICS LA English DT Article DE Atrial fibrillation; Arrhythmia; Mutation; Gene; Genetics ID OF-FUNCTION MUTATION; FAMILIAL AGGREGATION; KCNQ1 MUTATION; HEART-FAILURE; QT SYNDROME; POLYMORPHISM; ASSOCIATION; RISK; LONE; POPULATION AB Recent studies of AF have identified mutations in a series of ion channels; however, these mutations appear to be relatively rare causes of AF. A genome-wide association study has identified novel variants on chromosome 4 associated with AF, although the mechanism of action for these variants remains unknown. Ultimately, a greater understanding of the genetics of AF should yield insights into novel pathways, therapeutic targets, and diagnostic testing for this common arrhythmia. C1 [Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Yi, B. Alexander; Ellinor, Patrick T.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Lubitz, Steven A.] Mt Sinai Sch Med, Cardiovasc Inst, New York, NY 10029 USA. [Lubitz, Steven A.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02446 USA. [Yi, B. Alexander] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Ellinor, PT (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Cardiovasc Res Ctr, Boston, MA 02114 USA. EM pellinor@partners.org FU Disque Deane Foundation; National Institutes of Health [5T32HL007575] FX This work was supported by a grant from the Disque Deane Foundation to Dr. Ellinor and a National Institutes of Health training grant (5T32HL007575) to Dr. Lubitz. NR 68 TC 13 Z9 15 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0733-8651 EI 1558-2264 J9 CARDIOL CLIN JI Cardiol. Clin. PD FEB PY 2009 VL 27 IS 1 BP 25 EP + DI 10.1016/j.ccl.2008.09.007 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 398GI UT WOS:000262720200005 PM 19111761 ER PT J AU Sakhuja, R Shah, AJ Keebler, M Thakur, RK AF Sakhuja, Rahul Shah, Ashok J. Keebler, Mary Thakur, Ranjan K. TI Atrial Fibrillation in Patients with Implantable Defibrillators SO CARDIOLOGY CLINICS LA English DT Article DE Atrial fibrillation; Defibrillator; ICD; Sudden cardiac death; Review ID CARDIAC RESYNCHRONIZATION THERAPY; LEFT-VENTRICULAR DYSFUNCTION; CONGESTIVE-HEART-FAILURE; QUALITY-OF-LIFE; NONISCHEMIC DILATED CARDIOMYOPATHY; PULMONARY-VEIN ISOLATION; CARDIOVERTER-DEFIBRILLATOR; MADIT-II; BRUGADA-SYNDROME; DUAL-CHAMBER AB Atrial fibrillation (AF) is common in patients who have implantable defibrillators, and presents some unique challenges and opportunities. AF burden can be assessed more accurately, allowing for evaluation of therapy efficacy (drugs or ablation). It remains to be shown whether home monitoring of defibrillators to detect and treat AF more quickly can reduce cardiovascular and stroke end points. One major goal will be to reduce inappropriate shocks from atrial fibrillation. Otherwise, the goals of therapy remain the same-reduction of symptoms (including heart failure exacerbation and inappropriate implantable cardioverter defibrillator therapies) by controlling rate or rhythm and anticoagulation for stroke prophylaxis. C1 [Shah, Ashok J.; Thakur, Ranjan K.] Michigan State Univ, Thorac & Cardiovasc Inst, Lansing, MI 48910 USA. [Sakhuja, Rahul; Keebler, Mary] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Thakur, RK (reprint author), Michigan State Univ, Thorac & Cardiovasc Inst, 405 W Greenlawn,Suite 400, Lansing, MI 48910 USA. EM thakur@msu.edu NR 81 TC 2 Z9 2 U1 2 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 0733-8651 J9 CARDIOL CLIN JI Cardiol. Clin. PD FEB PY 2009 VL 27 IS 1 BP 151 EP + DI 10.1016/j.ccl.2008.09.014 PG 13 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 398GI UT WOS:000262720200015 PM 19111771 ER PT J AU Raitt, MH AF Raitt, Meritt H. TI Are n-3 Polyunsaturated Fatty Acids Antiarrhythmic in the Absence of Ischemia? SO CARDIOVASCULAR DRUGS AND THERAPY LA English DT Editorial Material ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATORS; FISH-OIL SUPPLEMENTATION; SUDDEN CARDIAC DEATH; VENTRICULAR-FIBRILLATION; RISK; TRIAL; OMEGA-3-FATTY-ACIDS; MODULATION; PREVENTION; CHANNELS C1 Portland VA Med Ctr, Portland, OR USA. [Raitt, Meritt H.] P 3 CARD, Portland, OR 97239 USA. RP Raitt, MH (reprint author), Portland VA Med Ctr, Portland, OR USA. EM merritt.raitt@va.gov NR 18 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0920-3206 J9 CARDIOVASC DRUG THER JI Cardiovasc. Drugs Ther. PD FEB PY 2009 VL 23 IS 1 BP 1 EP 3 DI 10.1007/s10557-008-6151-6 PG 3 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 396JJ UT WOS:000262587700001 PM 19005746 ER PT J AU Dally, S Monceau, V Corvazier, E Bredoux, R Raies, A Bobe, R del Monte, F Enouf, J AF Dally, Saoussen Monceau, Virginie Corvazier, Elisabeth Bredoux, Raymonde Raies, Aly Bobe, Regis del Monte, Federica Enouf, Jocelyne TI Compartmentalized expression of three novel sarco/endoplasmic reticulum Ca(2+)ATPase 3 isoforms including the switch to ER stress, SERCA3f, in non-failing and failing human heart SO CELL CALCIUM LA English DT Article DE SERCA3; Isoforms; Non-failing and failing human heart; GRP78; XBP-1; ER stress ID CARDIAC-HYPERTROPHY; TRANSGENIC MICE; MESSENGER-RNA; CA2+ AFFINITY; TRANSCRIPTION; PLATELETS; CELLS; GENE; PUMP; IDENTIFICATION AB The human sarco/endoplasmic reticulum (ER) Ca(2+)ATPase 3 (SERCA3) gene gives rise to SERCA3a-3f isoforms, the latter inducing ER stress in vitro. Here, we first demonstrated the co-expression of SERCA3a, -3d and -3f proteins in the heart. Evidence for endogenous proteins was obtained by using isoform-specific antibodies including a new SERCA3d-specific antibody, and either Western blotting of protein lysates or immunoprecipitation of membrane proteins. An immunolocalization study of both left ventricle tissue and isolated cardiomyocytes showed a distinct compartmentalization of the SERCA3 isoforms, as a uniform distribution of SERCA3a was detected while -3d and -3f isoforms were observed around the nucleus and in close vicinity of plasma membrane, respectively. Second, we studied their expressions in failing hearts including mixed (MCM) (n = 1) and idiopathic dilated (IDCM) cardiomyopathies (n = 4). Compared with controls (n = 5), similar expressions of SERCA3a and -3d mRNAs were observed in all patients. In contrast, SERCA3f mRNA was found to be up-regulated in failing hearts (125 +/- 7%). Remarkably, overexpression of SERCA3f paralleled an increase in ER stress markers including processing of X-box-binding protein-1 (XBP-1) mRNA (176 +/- 24%), and expression of XBP-1 protein and glucose-regulated protein (GRP)78 (232 +/- 21%). These findings revisit the human heart's Ca(2+)ATPase system and indicate that SERCA3f may account for the mechanism of ER stress in vivo in heart failure. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Dally, Saoussen; Monceau, Virginie; Corvazier, Elisabeth; Bredoux, Raymonde; Bobe, Regis; Enouf, Jocelyne] Hop Lariboisiere, INSERM, CRCIL, U689, F-75475 Paris 10, France. [Raies, Aly] Fac Sci Tunis, LMBA, Tunis, Tunisia. [del Monte, Federica] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Charlestown, MA USA. RP Enouf, J (reprint author), Hop Lariboisiere, INSERM, CRCIL, U689, 41 Blvd Chapelle, F-75475 Paris 10, France. EM jocelyne.enouf@inserm.fr RI BOBE, Regis/F-4951-2016 OI BOBE, Regis/0000-0002-8225-9117 FU Institut National de la Sante et de la Recherche Medicale (Inserm); Association Francaise contre les Myopathies (AFM); International Society of Thrombosis and Haemostasis (ISTH); Societe Francaise d'Hematologie (SFH) FX This study was supported by grants from the Institut National de la Sante et de la Recherche Medicale (Inserm), and the Association Francaise contre les Myopathies (AFM) and by fellowships from the International Society of Thrombosis and Haemostasis (ISTH) and Societe Francaise d'Hematologie (SFH). NR 32 TC 34 Z9 36 U1 0 U2 5 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0143-4160 J9 CELL CALCIUM JI Cell Calcium PD FEB PY 2009 VL 45 IS 2 BP 144 EP 154 DI 10.1016/j.ceca.2008.08.002 PG 11 WC Cell Biology SC Cell Biology GA 412SO UT WOS:000263744700005 PM 18947868 ER PT J AU O'Day, DH Poloz, Y Myre, MA AF O'Day, Danton H. Poloz, Yekaterina Myre, Michael A. TI Differentiation inducing factor-1 (DIF-1) induces gene and protein expression of the Dictyrostelium nuclear calmodulin-binding protein nucleomorphin SO CELLULAR SIGNALLING LA English DT Article DE Nucleomorphin; Calmodulin binding protein; Morphogen; Differentiation inducing factor; Cyclic AMP; Gene expression; Protein expression ID STALK CELL-DIFFERENTIATION; DICTYOSTELIUM-DISCOIDEUM; INTRACELLULAR CA2+; H+ CONCENTRATIONS; ACID-PHOSPHATASE; LEUKEMIA-CELLS; MORPHOGEN; NUMBER; GROWTH; INDUCTION AB The nucleomorphin gene numA1 from Dicryostelium codes for a multi-domain, calmodulin binding protein that regulates nuclear number. To gain insight into the regulation of numA, we assessed the effects of the stalk cell differentiation inducing factor-1 (DIF-1), an extracellular signalling molecule, on the expression of numA1 RNA and protein. For comparison, the extracellular signalling molecules cAMP (mediates chemotaxis, prestalk and prespore differentiation) and ammonia (NH(3)/NH(4)(+); antagonizes DIF) were also studied. Starvation, which is a signal for multicellular development, results in a greater than 80% decrease in numA I mRNA expression within 4 h. Treatment with ammonium chloride led to a greater than 90% inhibition of numA1 RNA expression within 2 h. In contrast, the addition of DIF-1 completely blocked the decrease in numA1 gene expression caused by starvation. Treatment of vegetative cells with cAMP led to decreases in numA1 RNA expression that were equivalent to those seen with starvation. Western blotting after various morphogen treatments showed that the maintenance of vegetative levels of numA1 RNA by DIF-1 in starved cells was reflected in significantly increased numA1 protein levels. Treatment with cAMP and/or ammonia led to decreased protein expression and each of these morphogens suppressed the stimulatory effects of DIF-1. Protein expression levels of CBP4a, a calcium-dependent binding partner of numA1, were regulated in the same manner as numA1 suggesting this potential co-regulation may be related to their functional relationship. NumA1 is the first calmodulin binding protein shown to be regulated by developmental morphogens in Dictyostelium being upregulated by DIF-1 and down-regulated by cAMP and ammonia. (c) 2008 Elsevier Inc. All rights reserved. C1 [O'Day, Danton H.] Univ Toronto, Dept Biol, Mississauga, ON L5L 1C6, Canada. [Poloz, Yekaterina] Univ Toronto, Dept Cell & Syst Biol, Toronto, ON M5S 3G5, Canada. [Myre, Michael A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA 02114 USA. RP O'Day, DH (reprint author), Univ Toronto, Dept Biol, Mississauga, ON L5L 1C6, Canada. EM danton.oday@utoronto.ca FU Natural Sciences and Engineering Council of Canada FX This research was supported by a grant from the Natural Sciences and Engineering Council of Canada (D.O'D). NR 38 TC 6 Z9 6 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD FEB PY 2009 VL 21 IS 2 BP 317 EP 323 DI 10.1016/j.cellsig.2008.10.019 PG 7 WC Cell Biology SC Cell Biology GA 396LU UT WOS:000262594000016 PM 19000924 ER PT J AU de Oliveira, JC Martinelli, M Nishioka, SAD Varejao, T Uipe, D Pedrosa, AAA Costa, R Danik, SB AF de Oliveira, Julio Cesar Martinelli, Martino D'Orio Nishioka, Silvana Angelina Varejao, Tania Uipe, David Andrade Pedrosa, Anisio Alexandre Costa, Roberto Danik, Stephan B. TI Efficacy of Antibiotic Prophylaxis Before the Implantation of Pacemakers and Cardioverter-Defibrillators Results of a Large, Prospective, Randomized, Double-Blinded, Placebo-Controlled Trial SO CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY LA English DT Article DE antibiotic prophylaxis; pacemaker; surgical procedures; infection ID INFECTIONS; ENDOCARDITIS; MANAGEMENT; COMPLICATIONS; DIAGNOSIS; DEVICES; LEADS AB Background-Although routinely administered, definitive evidence for the benefits of prophylactic antibiotics before the implantation of permanent pacemakers and implantable cardioverter-defibrillators from a large double-blinded placebo-controlled trial is lacking. The purpose of this study was to determine whether prophylactic antibiotic administration reduces the incidence of infection related to device implantation. Methods and Results-This double blinded study included 1000 consecutive patients who presented for primary device (Pacemaker and implantable cardioverter-defibrillators) implantation or generator replacement randomized in a 1:1 fashion to prophylactic antibiotics or placebo. Intravenous administration of I g of cefazolin (group 1) or placebo (group 2) was done immediately before the procedure. Follow-up was performed 10 days, 1, 3, and 6 months after discharge. The primary end point was any evidence of infection at the surgical incision (pulse generator pocket), or systemic infection related to be procedure. The safety committee interrupted the trial after 649 patients were enrolled due to a significant difference in favor of the antibiotic arm (group 1: 2 of 314 infected patients-0.63%; group 11: 11 of 335 to 3.28%; RR=0.19; P=0.016). The following risk factors were positively correlated with infection by univariate analysis: nonuse of preventive antibiotic (P=0.016); implant procedures (versus generator replacement: P=0.02); presence of postoperative hematoma (P=0.03) and procedure duration (P=0.009). Multivariable analysis identified nonuse of antibiotic (P=0.037) and postoperative hematoma (P=0.023) as independent predictors of infection. Conclusions-Anti biotic prophylaxis significantly reduces infectious complications in patients undergoing implantation of pacemakers or cardioverter-defibrillators. (Circ Arrhythmia Electrophysiol. 2009;2:29-34.) C1 [de Oliveira, Julio Cesar; Martinelli, Martino; D'Orio Nishioka, Silvana Angelina; Varejao, Tania; Uipe, David; Andrade Pedrosa, Anisio Alexandre; Costa, Roberto; Danik, Stephan B.] Univ Sao Paulo, Sch Med, Heart Inst InCor, Sao Paulo, Brazil. RP Danik, SB (reprint author), Massachusetts Gen Hosp, 55 Fruit St,GRB 109, Boston, MA 02114 USA. EM sdanik@partners.org RI Martinelli, Martino/D-9785-2012; Costa, Roberto/F-2682-2012 OI Martinelli, Martino/0000-0003-4440-8078; Costa, Roberto/0000-0001-6104-9113 NR 18 TC 101 Z9 102 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3149 J9 CIRC-ARRHYTHMIA ELEC JI Circ.-Arrhythmia Electrophysiol. PD FEB PY 2009 VL 2 IS 1 BP 29 EP 34 DI 10.1161/CIRCEP.108.795906 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 446NC UT WOS:000266127300006 PM 19808441 ER PT J AU Magnani, JW Williamson, MA Ellinor, PT Monahan, KM Benjamin, EJ AF Magnani, Jared W. Williamson, Mary Ann Ellinor, Patrick T. Monahan, Kevin M. Benjamin, Emelia J. TI P Wave Indices Current Status and Future Directions in Epidemiology, Clinical, and Research Applications SO CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY LA English DT Article DE P-wave indices; epidemiology; PR interval; electrocardiography; atrial fibrillation ID PAROXYSMAL ATRIAL-FIBRILLATION; RADIOFREQUENCY CATHETER ABLATION; GENERAL-HOSPITAL POPULATION; SIGNAL-AVERAGED ECG; YOUNG HEALTHY-MEN; INTERATRIAL BLOCK; SINUS RHYTHM; HYPERTENSIVE PATIENTS; CARDIAC-SURGERY; OBESE SUBJECTS C1 [Magnani, Jared W.; Monahan, Kevin M.; Benjamin, Emelia J.] Boston Univ, Sch Med, Cardiol Sect, Framingham, MA 01702 USA. [Williamson, Mary Ann] Boston Univ, Sch Med, Div Med, Framingham, MA 01702 USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Div Prevent Med, Framingham, MA 01702 USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Framingham, MA 01702 USA. [Benjamin, Emelia J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Benjamin, Emelia J.] Natl Heart Lung & Blood Inst Framingham Study, Framingham, MA USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Benjamin, EJ (reprint author), Boston Univ, Sch Med & Publ Hlth, Framingham Heart Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA. EM emelia@bu.edu OI Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [R01 HL092577-01A1, HL076784, L30 HL097675, L30 HL097675-01, N01 HC025195, N01-HC-25195, N01HC25195, R01 HL076784, R01 HL076784-01, R01 HL076784-02, R01 HL076784-03, R01 HL076784-04, R01 HL076784-05, R01 HL092577, R01 HL104156]; NIA NIH HHS [AG028321, R01 AG028321, R01 AG028321-01, R01 AG028321-02, R01 AG028321-03]; NINDS NIH HHS [6R01-NS 17950, R01 NS017950, R01 NS017950-23, R01 NS017950-24, R01 NS017950-25, R01 NS017950-26, R01 NS017950-27, R01 NS017950-28] NR 68 TC 47 Z9 48 U1 3 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3149 J9 CIRC-ARRHYTHMIA ELEC JI Circ.-Arrhythmia Electrophysiol. PD FEB PY 2009 VL 2 IS 1 BP 72 EP 79 DI 10.1161/CIRCEP.108.806828 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 446NC UT WOS:000266127300012 PM 19808445 ER PT J AU Singh, M Peterson, ED Roe, MT Ou, FS Spertus, JA Rumsfeld, JS Anderson, HV Klein, LW Ho, KKL Holmes, DR AF Singh, Mandeep Peterson, Eric D. Roe, Matthew T. Ou, Fang-Shu Spertus, John A. Rumsfeld, John S. Anderson, H. Vernon Klein, Lloyd W. Ho, Kalon K. L. Holmes, David R. TI Trends in the Association Between Age and In-Hospital Mortality After Percutaneous Coronary Intervention National Cardiovascular Data Registry Experience SO CIRCULATION-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE age; percutaneous coronary interventions; mortality; temporal trends ID ACUTE MYOCARDIAL-INFARCTION; HEALTH-CARE PROFESSIONALS; SCIENTIFIC STATEMENT; GERIATRIC-CARDIOLOGY; CLINICAL CARDIOLOGY; AMERICAN-COLLEGE; HEART-DISEASE; RISK SCORE; ANGIOPLASTY; COLLABORATION AB Background-Temporal trends and contemporary data characterizing the impact of patient age on in-hospital outcomes of percutaneous coronary interventions are lacking. We sought to determine the importance of age by assessing the in-hospital mortality of stratified age groups in the National Cardiovascular Data Registry. Methods and Results-In-hospital mortality after percutaneous coronary intervention on 1 410 069 patients was age stratified into 4 groups-group 1 (age <40, n=25 679), group 2 (40 to 59, n=496 204), group 3 (60 to 79, n=732 574), and group 4 (>= 80, n=155 612)-admitted from January 1, 2001, to December 31, 2006. Overall in-hospital mortality was 1.22%; in-hospital mortality was 0.60%, 0.59%, 1.26%, and 3.16% in groups 1 to 4, respectively, P<0.0001. Overall temporal improvement per calendar year in the adjusted in-hospital mortality after percutaneous coronary intervention was noted in most groups; however, this finding was significant only in the 2 older age groups, group 3 (odds ratio, 0.94; 95% CI, 0.92 to 0.96) and group 4 (odds ratio, 0.95; 95% CI, 0.92 to 0.97). The absolute mortality reduction was greatest in the most elderly group, those over the age of 80 years. Conclusions-In-hospital mortality after percutaneous coronary intervention has fallen for all age groups over the past 6 years. However, the largest absolute reduction was seen among patients 80 years of age or older. (Circ Cardiovasc Intervent. 2009;2:20-26.) C1 [Singh, Mandeep; Holmes, David R.] Mayo Clin, Div Cardiovasc Dis, Rochester, MN 55905 USA. [Peterson, Eric D.; Roe, Matthew T.; Ou, Fang-Shu] Duke Clin Res Inst, Durham, NC USA. [Spertus, John A.] UMKC, Mid Amer Heart Inst, Kansas City, MO USA. [Rumsfeld, John S.] Denver VA Med Ctr, Denver, CO USA. [Anderson, H. Vernon] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA. [Klein, Lloyd W.] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Ho, Kalon K. L.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Singh, M (reprint author), Mayo Clin, Div Cardiovasc Dis, 200 1st St SW, Rochester, MN 55905 USA. EM singh.mandeep@mayo.edu NR 27 TC 36 Z9 36 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7640 J9 CIRC-CARDIOVASC INTE JI Circ.-Cardiovasc. Interv. PD FEB PY 2009 VL 2 IS 1 BP 20 EP 26 DI 10.1161/CIRCINTERVENTIONS.108.826172 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 575EC UT WOS:000276048500005 PM 20031689 ER PT J AU Tannous, B Lee-Lewandrowski, E Sharples, C Brugge, W Bigatello, L Thompson, T Benzer, T Lewandrowski, K AF Tannous, Bakhos Lee-Lewandrowski, Elizabeth Sharples, Cyrrene Brugge, William Bigatello, Luca Thompson, Taylor Benzer, Theodore Lewandrowski, Kent TI Comparison of conventional guaiac to four immunochemical methods for fecal occult blood testing: Implications for clinical practice in hospital and outpatient settings SO CLINICA CHIMICA ACTA LA English DT Article DE Fecal occult blood testing; Gastrointestinal bleeding; Anemia ID COLORECTAL-CANCER AB Background: Fecal occult blood testing (FOBT) is one method to screen for colorectal cancer and to assess for gastrointestinal bleeding in hospitalized patients. Differences in the analytical sensitivity among various methods may have significant clinical repercussions. Methods: We evaluated the analytical performance of 5 different FOBT methods (standard guaiac-based method and four immunochemical methods) using patient samples and spiked stool specimens. Results: The analytical sensitivity measured using spiked stool samples varied from <8 to 1500 ug hemoglobin/gram of stool. In some cases the results differed significantly from the manufacturers reported analytical sensitivity. Analysis of 71 stool samples measured by all 5 methods showed a discrepant result in 31 cases (43.7%). The rate of positive samples varied by method from 8.5% to 42.2%. Conclusions: These results demonstrate significant differences in the analytical performance among FOBT methods. Careful method validation and selection of a method with appropriate sensitivity is essential when choosing an FOBT method for colorectal cancer screening or for the assessment of gastrointestinal bleeding in the emergency department and hospital inpatients. (C) 2008 Elsevier B.V. All rights reserved. C1 [Tannous, Bakhos; Lee-Lewandrowski, Elizabeth; Sharples, Cyrrene; Lewandrowski, Kent] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Tannous, Bakhos; Lee-Lewandrowski, Elizabeth; Sharples, Cyrrene; Brugge, William; Bigatello, Luca; Thompson, Taylor; Benzer, Theodore; Lewandrowski, Kent] Harvard Univ, Sch Med, Boston, MA USA. [Brugge, William] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Bigatello, Luca] Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. [Benzer, Theodore] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Lewandrowski, K (reprint author), Massachusetts Gen Hosp, Dept Pathol, Gray 5, Boston, MA 02114 USA. EM klewandrowski@partners.org NR 8 TC 14 Z9 14 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD FEB PY 2009 VL 400 IS 1-2 BP 120 EP 122 DI 10.1016/j.cca.2008.10.023 PG 3 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 401CZ UT WOS:000262917300025 PM 19000907 ER PT J AU Handrakis, JP DeMeersman, RE Rosado-Rivera, D LaFountaine, MF Spungen, AM Bauman, WA Wecht, JM AF Handrakis, John P. DeMeersman, Ronald E. Rosado-Rivera, Dwindally LaFountaine, Michael F. Spungen, Ann M. Bauman, William A. Wecht, Jill M. TI Effect of hypotensive challenge on systemic hemodynamics and cerebral blood flow in persons with tetraplegia SO CLINICAL AUTONOMIC RESEARCH LA English DT Article DE spinal cord injury; autonomic nervous system disorder; orthostatic hypotension; angiotensin-converting enzyme inhibitor; tilt-table test ID SPINAL-CORD-INJURY; POWER SPECTRAL-ANALYSIS; HEAD-UP TILT; ORTHOSTATIC HYPOTENSION; TRANSCRANIAL DOPPLER; PRESSURE VARIABILITY; HUMANS; AUTOREGULATION; INDIVIDUALS; OXYGENATION AB Individuals with tetraplegia have impaired central control of sympathetic vascular modulation and blood pressure (BP); how this impairment affects cerebral blood flow (CBF) is unclear. To determine if persons with tetraplegia maintain CBF similarly to able-bodied controls after a hypotensive challenge. Seven individuals with chronic tetraplegia and seven age-matched, non-SCI control subjects underwent a hypotensive challenge consisting of angiotensin-converting enzyme (ACE) inhibition (1.25 mg enalaprilat) and 45A degrees head-up tilt (HUT). Heart rate (HR), low frequency systolic BP variability (LFsbp), brachial mean arterial pressure (MAP) and middle cerebral artery CBF were measured before and after the challenge. Group differences for the baseline (BL) to post-challenge response were determined by repeated measures ANOVA. HR did not differ between the groups in response to the hypotensive challenge. LFsbp response was significantly reduced in the tetra compared to the control group (-38 +/- A 51 vs. 72 +/- A 93%, respectively). MAP did not differ between the groups at BL but was significantly lower in the tetra compared to the control group post-challenge (55 +/- A 13 vs. 71 +/- A 9 mmHg, respectively); the percent change in MAP was significantly greater in the tetra than in the control group (-29 +/- A 14.1 vs. -13 +/- A 9%, respectively). However, CBF did not differ between the groups at baseline or post-challenge; the percent change in CBF post-challenge was not different between the tetra and control groups (-29 +/- A 13.2 vs. -23 +/- A 10.3%, respectively). Despite impaired sympathetic vasomotor and BP control, CBF in persons with tetraplegia was comparable to that of control subjects during a hypotensive challenge. C1 [Handrakis, John P.; DeMeersman, Ronald E.; LaFountaine, Michael F.; Spungen, Ann M.; Bauman, William A.; Wecht, Jill M.] James J Peters VA Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Bronx, NY 10468 USA. [Handrakis, John P.] Sch Hlth Profess Behav & Life Sci, NYIT, Old Westbury, NY USA. [DeMeersman, Ronald E.] Columbia Univ, Teachers Coll, New York, NY 10027 USA. [Spungen, Ann M.; Bauman, William A.; Wecht, Jill M.] Mt Sinai Sch Med, Dept Med & Rehabil Med, New York, NY USA. RP Handrakis, JP (reprint author), James J Peters VA Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Rm 1E-02,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM john.handrakis@va.gov FU Veteran Affairs Rehabilitation Research and Development Service; Center of Excellence for the Medical Consequences of SCI [B4162C]; Vidda Foundation FX Veteran Affairs Rehabilitation Research and Development Service, Center of Excellence for the Medical Consequences of SCI (B4162C), James J. Peters VAMC, the Vidda Foundation. NR 28 TC 11 Z9 11 U1 2 U2 3 PU DR DIETRICH STEINKOPFF VERLAG PI HEIDELBERG PA TIERGARTENSTRASSE 17, 69121 HEIDELBERG, GERMANY SN 0959-9851 J9 CLIN AUTON RES JI Clin. Auton. Res. PD FEB PY 2009 VL 19 IS 1 BP 39 EP 45 DI 10.1007/s10286-008-0496-6 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 409NA UT WOS:000263511200007 PM 18850311 ER PT J AU Campos, SM Guastalla, JP Subar, M Abreu, P Winer, EP Cameron, DA AF Campos, Susana M. Guastalla, Jean Paul Subar, Milayna Abreu, Paula Winer, Eric P. Cameron, David A. TI A Comparative Study of Exemestane Versus Anastrozole in Patients with Postmenopausal Breast Cancer with Visceral Metastases SO CLINICAL BREAST CANCER LA English DT Article DE Aromatase inhibitor; Hormone receptor-positive disease; National Cancer Institute Common Toxicity Criteria ID MEGESTROL-ACETATE; THERAPY; WOMEN; TAMOXIFEN; SUPERIOR; FAILURE; TRIALS AB Purpose: Patients developing visceral breast cancer metastases generally receive chemotherapy rather than endocrine therapy. Recent aromatase inhibitor studies have reported activity in such patients; therefore, this study formally evaluated anastrozole and exemestane in postmenopausal patients in this setting. Patients and Methods: Postmenopausal women with advanced breast cancer and >= 1 visceral (liver or lung) lesion were randomized to anastrozole (1 mg/day orally) or exemestane (25 mg/day orally) for >= 8 weeks. The primary endpoint was objective response In visceral lesions based on modified Response Evaluation Criteria in Solid Tumors. Secondary endpoints included clinical benefit (objective response plus stable disease >= 180 days), overall survival, and adverse events. Results: A total of 130 patients were enrolled, and 128 patients (64 anastrozole, 64 exemestane) were included in the intent-to-treat analysis. Accrual delays caused study closure before the target enrollment (N = 200) was reached, limiting the statistical power of the study. Objective response in visceral sites was approximately 15% in both groups. Clinical benefit in visceral sites was 32% of the patients treated with anastrozole and 38% of the patients treated with exemestane. Median survival was 33.3 months and 30.5 months in the anastrozole and exemestane groups, respectively. Toxicities were similar to those previously reported; however, treatment-related adverse events were more frequent with anastrozole (41%) than with exemestane (31%). Both treatments were generally well tolerated in patients with postmenopausal breast cancer with visceral metastases. Conclusion: Efficacy was similar in both treatment groups for all endpoints. Aromatase inhibitors can be considered as a treatment option in postmenopausal patients with hormone receptor-positive visceral breast cancer metastases. C1 [Campos, Susana M.; Winer, Eric P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Guastalla, Jean Paul] Ctr Leon Berard, F-69373 Lyon, France. [Subar, Milayna; Abreu, Paula] Pfizer Inc, New York, NY USA. [Cameron, David A.] Western Gen Hosp, Edinburgh EH4 2XU, Midlothian, Scotland. RP Campos, SM (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM susana_campos@dfci.harvard.edu NR 15 TC 18 Z9 19 U1 0 U2 0 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 FEB PY 2009 VL 9 IS 1 BP 39 EP 44 DI 10.3816/CBC.2009.n.007 PG 6 WC Oncology SC Oncology GA 420IC UT WOS:000264281500006 PM 19299239 ER PT J AU D'Angelo, S Deutscher, M Dickler, M Weinstock, DM AF D'Angelo, Sandra Deutscher, Meredith Dickler, Maura Weinstock, David M. TI Hepatitis C Virus Infection Does Not Preclude Standard Breast Cancer-Directed Therapy SO CLINICAL BREAST CANCER LA English DT Article DE Alanine aminotransferase; Cirrhosis; Cyclophosphamide AB In the United States, over 3 million people are infected with hepatitis C virus (HCV), and over 200,000 women develop breast cancer annually. Yet, no published studies have investigated the tolerability of breast cancer-directed therapy among women with HCV infection. We reviewed records at Memorial Sloan-Kettering Cancer Center and identified 35 patients with chronic HCV infection who were treated for breast cancer between the years 1991 and 2005. One (2.9%) of 35 also had chronic hepatitis B virus infection. There were no complications related to HCV infection during or after surgery or radiation therapy. A total of 29 (82.9%) of the 35 patients received chemotherapy for breast cancer. Of the 29, only 4 required chemotherapy delays or adjustments in dosing because of HCV infection. In conclusion, breast cancer therapy was well tolerated among women with HCV infection. Considering the paucity of complications, routine screening for HCV infection is not warranted among women with breast cancer and no defined risk factors for HCV infection. C1 [Weinstock, David M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [D'Angelo, Sandra] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. [Deutscher, Meredith] Beth Israel Deaconess Med Ctr, Div Infect Dis, New York, NY 10003 USA. [Dickler, Maura] Mem Sloan Kettering Canc Ctr, Breast Canc Med Serv, New York, NY 10021 USA. RP Weinstock, DM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,DA 510B, Boston, MA 02115 USA. EM dweinstock@partners.org NR 6 TC 2 Z9 2 U1 0 U2 0 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 FEB PY 2009 VL 9 IS 1 BP 51 EP 52 DI 10.3816/CBC.2009.n.009 PG 2 WC Oncology SC Oncology GA 420IC UT WOS:000264281500008 PM 19299241 ER PT J AU Akhtar, S Meeran, SM Katiyar, N Katiyar, SK AF Akhtar, Suhail Meeran, Syed M. Katiyar, Nandan Katiyar, Santosh K. TI Grape Seed Proanthocyanidins Inhibit the Growth of Human Non-Small Cell Lung Cancer Xenografts by Targeting Insulin-Like Growth Factor Binding Protein-3, Tumor Cell Proliferation, and Angiogenic Factors SO CLINICAL CANCER RESEARCH LA English DT Article ID BREAST-CARCINOMA CELLS; SKH-1 HAIRLESS MICE; IN-VIVO; THERAPY; MECHANISMS; ACTIVATION; APOPTOSIS; RECEPTOR; ANTIBODY; MITOGEN AB Purpose: Lung cancer is a leading cause of cancer-related deaths worldwide. Here, we assessed the chemotherapeutic effect of grape seed proanthocyanidins (GSPs) on human non-small Cell lung cancer (NSCLC) cells in vitro and in vivo using a tumor xenograft model. Experimental Design: The effects of GSPs on human NSCLC cell lines in terms of cellular proliferation were determined. The chemotherapeutic effects of a GSP-supplemented AIN76A control diet fed to nude mice bearing tumor xenografts (A549 and H1299) were evaluated in terms of biomarkers of cell proliferation and angiogenesis and on insulin-like growth factor binding protein-3 using immunohistochemical detection, ELISA, and Western blotting. Results: In vitro treatment of NSCLC cells with GSPs resulted in inhibition of cellular proliferation. Administration of GSPs (0.1%, 0.2%, and 0.5%, w/w) as a supplement of an AIN76A control diet resulted in a dose-dependent inhibition of the growth of NSCLC (A549 and H1299) tumor xenografts in athymic nude mice (25-76%; P < 0.05-0.001). The growth-inhibitory effect of GSPs on the NSCLC xenograft tumors was associated with the enhancement of the levels of insulin-like growth factor binding protein-3 in the tumor microenvironment and plasma and antiproliferative, antiangiogenic, and proapoptotic effects. Conclusions: This preclinical Study reveals for the first time that dietary GSPs have the ability to inhibit the growth of human NSCLC tumor xenografts grown in vivo in athymic nude mice. More studies are needed to develop GSPs as a pharmacologically safe agent for the prevention of lung cancer in humans. C1 [Akhtar, Suhail; Meeran, Syed M.; Katiyar, Nandan; Katiyar, Santosh K.] Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Univ Alabama, Clin Nutr Res Ctr, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Univ Alabama, Ctr Comprehens Canc, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Birmingham VA Med Ctr, Birmingham, AL USA. RP Katiyar, SK (reprint author), Univ Alabama, Dept Dermatol, 1670 Univ Blvd,Volker Hall 557, Birmingham, AL 35294 USA. EM skatiyar@uab.edu NR 35 TC 43 Z9 45 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 FEB 1 PY 2009 VL 15 IS 3 BP 821 EP 831 DI 10.1158/1078-0432.CCR-08-1901 PG 11 WC Oncology SC Oncology GA 405HK UT WOS:000263213600011 PM 19188152 ER PT J AU Okabe, T Okamoto, I Tsukioka, S Uchida, J Hatashita, E Yamada, Y Yoshida, T Nishio, K Fukuoka, M Janne, PA Nakagawa, K AF Okabe, Takafumi Okamoto, Isamu Tsukioka, Sayaka Uchida, Junji Hatashita, Erina Yamada, Yuki Yoshida, Takeshi Nishio, Kazuto Fukuoka, Masahiro Jaenne, Pasi A. Nakagawa, Kazuhiko TI Addition of S-1 to the Epidermal Growth Factor Receptor Inhibitor Gefitinib Overcomes Gefitinib Resistance in Non-small cell Lung Cancer Cell Lines with MET Amplification SO CLINICAL CANCER RESEARCH LA English DT Article ID PREVIOUSLY TREATED PATIENTS; TYROSINE KINASE INHIBITOR; PHASE-II TRIAL; THYMIDYLATE SYNTHASE; ACQUIRED-RESISTANCE; GENE-MUTATIONS; DIHYDROPYRIMIDINE DEHYDROGENASE; ANTITUMOR-ACTIVITY; DOWN-REGULATION; ERLOTINIB AB Purpose: Most non-small cell lung cancer (NSCLC) tumors with activating mutations in the epidermal growth factor receptor (EGFR) are initially responsive to EGFR tyrosine kinase inhibitors (EGFR-TKI) such as gefitinib and erlotinib, but they almost invariably develop resistance to these drugs. A secondary mutation in EGFR (T790M) and amplification of the MET protooncogene have been identified as mechanisms of such acquired resistance to EGFR-TKIs. We have now investigated whether addition of the oral fluoropyrimidine derivative S-1 to gefitinib might overcome gefitinib resistance in NSCLC cell lines. Experimental Design: The effects of gefitinib on EGFR signaling and on the expression both of thymidylate synthase and of the transcription factor E2F-1 in gefitinib-resistant NSCLC cells were examined by immunoblot analysis. The effects of S-1 (or 5-fluorouracil) and gefitinib on the growth of NSCLC cells were examined in vitro as well as in nude mice. Results: Gefitinib induced down-regulation of thymidylate synthase and E2F-1 in gefitinib-resistant NSCLC cells with MET amplification but not in those harboring the T790M mutation of EGFR. The combination of 5-flucrouracil and gefitinib synergistically inhibited the proliferation of cells with MET amplification, bur. not that of those with the T790M mutation of EGFR, in vitro. Similarly, the combination of S-1 and gefitinib synergistically inhibited the growth only of NSCLC xenografts with MET amplification. Conclusions: Our results suggest that the addition of S-1 to EGFR-TKIs is a promising strategy to overcome EGFR-TKI resistance in NSCLC with MET amplification. C1 [Okabe, Takafumi; Okamoto, Isamu; Hatashita, Erina; Yamada, Yuki; Yoshida, Takeshi; Nakagawa, Kazuhiko] Kinki Univ, Sch Med, Dept Med Oncol, Osaka 5898511, Japan. [Nishio, Kazuto] Kinki Univ, Sch Med, Dept Genome Biol, Osaka 5898511, Japan. [Fukuoka, Masahiro] Kinki Univ, Sch Med, Sakai Hosp, Dept Internal Med,Minami Ku, Osaka 5898511, Japan. [Okabe, Takafumi; Jaenne, Pasi A.] Brigham & Womens Hosp, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. [Okabe, Takafumi; Jaenne, Pasi A.] Brigham & Womens Hosp, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Jaenne, Pasi A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Tsukioka, Sayaka; Uchida, Junji] Taisho Pharmaceut Co Ltd, Tokushima Res Ctr, Tokushima, Japan. RP Okamoto, I (reprint author), Kinki Univ, Sch Med, Dept Med Oncol, 377-2 Ohno Higashi, Osaka 5898511, Japan. EM chi-okamoto@dotd.med.kindai.ac.jp NR 53 TC 39 Z9 40 U1 1 U2 4 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 FEB 1 PY 2009 VL 15 IS 3 BP 907 EP 913 DI 10.1158/1078-0432.CCR-08-2251 PG 7 WC Oncology SC Oncology GA 405HK UT WOS:000263213600020 PM 19188161 ER PT J AU Feldman, AS Banyard, J Wu, CL McDougal, WS Zetter, BR AF Feldman, Adam S. Banyard, Jacqueline Wu, Chin-Lee McDougal, W. Scott Zetter, Bruce R. TI Cystatin B As a Tissue and Urinary Biomarker of Bladder Cancer Recurrence and Disease Progression SO CLINICAL CANCER RESEARCH LA English DT Article ID CYSTEINE PROTEINASE-INHIBITORS; STEFIN-B; ENDOGENOUS INHIBITORS; PROGNOSTIC VALUE; CELL CARCINOMA; CATHEPSINS B; EXPRESSION; MARKER; IDENTIFICATION; MALIGNANCY AB Purpose: Using proteomic techniques, we sought to identify novel protein biomarkers in tissue and urine from patients with transitional cell carcinoma (TCC). Experimental Design: Urinary and tissue proteomes were analyzed and differentially expressed proteins were identified by mass spectrometry. One of the proteins, cystatin B, was further analyzed in TCC tissue by immunohistochemistry and in urine by serniquantitative Western blot analysis. Results: Cystatin B tissue staining intensity significantly increased concordantly with TCC grade (P = 0.0008). Elevated urinary cystatin B levels correlated with increasing tumor grade (P = 0.062) and stage (P = 0.0047). Patients with elevated levels of cystatin B had a shorter mean +/- SE time to disease recurrence (12 +/- 1.82 months) compared with patients who had low levels (28.8 +/- 2.26 months; P = 0.0047). Similarly, patients with elevated cystatin B levels had a shorter time to grade/stage progression compared with patients with low urinary cystatin B (P = 0.0007). By multivariate Cox regression analysis, an elevated cystatin B level was the most significant variable predicting disease recurrence (hazard ratio, 3.8; 95% confidence interval, 1.5-9.5; P = 0.0049) and grade/stage progression (hazard ratio, 10.4; 95% confidence interval, 1.6-201.5; P = 0.0104). Conclusions: Cystatin B is elevated in tissue and urine of bladder cancer patients. Cystatin B urine levels are positively correlated with tumor grade, stage, and shorter time to disease recurrence and progression. Consequently, cystatin B may be useful as a novel predictive biomarker in TCC of the bladder. C1 [Banyard, Jacqueline; Zetter, Bruce R.] Harvard Univ, Childrens Hosp, Sch Med, Dept Surg,Vasc Biol Program, Boston, MA 02115 USA. [Feldman, Adam S.; Wu, Chin-Lee; McDougal, W. Scott] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Wu, Chin-Lee] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Zetter, BR (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Dept Surg,Vasc Biol Program, Boston, MA 02115 USA. EM bruce.zetter@childrens.harvard.edu FU NIH [CA37393] FX NIH grant CA37393. NR 34 TC 31 Z9 35 U1 0 U2 3 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 FEB 1 PY 2009 VL 15 IS 3 BP 1024 EP 1031 DI 10.1158/1078-0432.CCR-08-1143 PG 8 WC Oncology SC Oncology GA 405HK UT WOS:000263213600034 PM 19188175 ER PT J AU Jilaveanu, L Zito, C Lee, SJ Nathanson, KL Camp, RL Rimm, DL Flaherty, KT Kluger, HM AF Jilaveanu, Lucia Zito, Christopher Lee, Sandra J. Nathanson, Katherine L. Camp, Robert L. Rimm, David L. Flaherty, Keith T. Kluger, Harriet M. TI Expression of Sorafenib Targets in Melanoma Patients Treated with Carboplatin, Paclitaxel and Sorafenib SO CLINICAL CANCER RESEARCH LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; REFRACTORY SOLID TUMORS; ANTITUMOR-ACTIVITY; RAF/MEK/ERK PATHWAY; MALIGNANT-MELANOMA; BRAF MUTATIONS; RAF KINASE; PHASE-II; INHIBITOR; ACTIVATION AB Background: Sorafenib, a multitarget kinase inhibitor, inhibits members of the mitogen-activated protein kinase (MAPK) pathway and receptor tyrosine kinases, including vascular endothelial growth factor receptor 2 (VEGF-R2). Sorafenib, carboplatin, and paclitaxel (SCP) has antitumor activity in melanoma patients, but no association was found between response and activating B-Raf(V600E) mutations. We assessed the expression of sorafenib targets in SCIP-treated patient specimens and evaluated the association with response and progression-free survival. Experimental Design: Using automated quantitative analysis, we quantified the expression of VEGF-R1, VEGF-R2, VEGF-R3, fibroblast growth factor receptor 1, platelet-derived growth factor receptor 0, c-Kit, B-Raf, C-Raf, meiosis-specific serine/threonine protein kinase 1, and extracellular regulated kinase 1/2 (ERK1/2) in pretreatment specimens from 46 patients. Furthermore, we assessed ERK1/2 expression in 429 archival melanomas. Results: VEGF-R2 expression was significantly higher in patients with a complete or partial response (P = 0.0435), whereas ERK1/2 was higher in patients who did not respond (P = 0.0417). High ERK1/2 was an independent predictor of poor survival. High ERK1/2 was associated with decreased survival in the archival melanoma cohort, suggesting that high ERK1/2-expressing tumors are biologically more aggressive. All of the six patients with both high VEGF-R2 and low ERK1/2 responded to SCR Conclusions: High VEGF-R2 expression is associated with response to SCP in melanoma, whereas high ERK1/2 is associated with resistance. Collection of specimens from SCP-treated melanoma patients in a cooperative group phase III trial comparing this regimen with the chemotherapy alone is ongoing, and confirmation of these findings is necessary. These markers might be useful for predicting response to sorafenib when given with other chemotherapies and in other diseases, resulting in the possible elimination of unnecessary treatment of patients unlikely to respond. C1 [Kluger, Harriet M.] Yale Univ, Sch Med, Yale Canc Ctr, Sect Med Oncol, New Haven, CT 06510 USA. [Camp, Robert L.; Rimm, David L.] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA. [Lee, Sandra J.] Harvard Univ, Dana Farber Canc Ctr, Boston, MA 02115 USA. [Nathanson, Katherine L.; Flaherty, Keith T.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. RP Kluger, HM (reprint author), Yale Univ, Sch Med, Yale Canc Ctr, Sect Med Oncol, 310 Cedar St, New Haven, CT 06510 USA. EM Harriet.Kluger@yale.edu OI Nathanson, Katherine/0000-0002-6740-0901 FU National Cancer Institute [MeI5011]; Anna Fuller Fund; NIH [CA115756-01] FX Anna Fuller Fund (L. Jilaveanu) and NIH grant CA115756-01 (H. Kluger). NR 50 TC 24 Z9 25 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 FEB 1 PY 2009 VL 15 IS 3 BP 1076 EP 1085 DI 10.1158/1078-0432.CCR-08-2280 PG 10 WC Oncology SC Oncology GA 405HK UT WOS:000263213600042 PM 19188183 ER PT J AU Scirica, BM Cannon, CP Sabatine, MS Jarolim, P Sloane, S Rifai, N Braunwald, E Morrow, DA AF Scirica, Benjamin M. Cannon, Christopher P. Sabatine, Marc S. Jarolim, Petr Sloane, Sarah Rifai, Nader Braunwald, Eugene Morrow, David A. CA PROVE IT-TIMI 22 Investigators TI Concentrations of C-Reactive Protein and B-Type Natriuretic Peptide 30 Days after Acute Coronary Syndromes Independently Predict Hospitalization for Heart Failure and Cardiovascular Death SO CLINICAL CHEMISTRY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; HIGH-DOSE ATORVASTATIN; PROGNOSTIC VALUE; ARTERY-DISEASE; STABLE SURVIVORS; CONTROLLED-TRIAL; STATIN THERAPY; RISK; MORTALITY; MARKERS AB BACKGROUND: Heart failure (HF) is an important cause of morbidity in patients with acute coronary syndromes (ACS). C-reactive protein (CRP) has been implicated in experimental models as exacerbating myocardial injury, but data regarding the clinical relationship of high-sensitivity CRP (hsCRP) and B-type natriuretic peptide (BNP) concentrations with the risk of HF after ACS are few. METHODS: PROVE IT-TIMI 22 randomized 4162 patients who had been stabilized after ACS to either intensive or moderate statin therapy. hsCRP and BNP were measured 30 days after randomization. Hospitalizations for HF and cardiovascular death occurring Ater day 30 were assessed for a mean follow-up of 24 months. RESULTS: Patients who developed HF had higher concentrations of hsCRP (3.7 mg/L vs 1.9 mg/L, P < 0.001) and BNP (59 ng/L vs 22 ng/L, P < 0.0001). HF increased in a stepwise manner with hsCRP quartile [adjusted hazard ratio (HR(adj)) for Q4 vs Q1, 2.5; P = 0.01] and BNP quartile (HR(adj)) for Q4 vs Q1, 5.8; P < 0.001), with similar results obtained for HF and cardiovascular death. In a multivariable analysis, higher concentrations of hsCRP and BNP were both independently associated with HF [HR(adj), 1.9 for hsCRP >2.0 mg/L (P = 0.01) and 4.2 for BNP >80 ng/L (P < 0.001)]. Patients with increases in both markers were at the greatest risk of HF, compared with patients without an increased marker concentration (HR(adj), 8.3; P = 0.01). The benefit of intensive statin therapy in reducing HF was consistent among all patients, regardless of hsCRP or BNP concentration. CONCLUSIONS: Both hsCRP and BNP measured 30 days after ACS are independently associated with the risk of HF and cardiovascular death, with the greatest risk occurring when both markers are increased. (C) 2008 American Association for Clinical Chemistry C1 [Scirica, Benjamin M.; Cannon, Christopher P.; Sabatine, Marc S.; Sloane, Sarah; Braunwald, Eugene; Morrow, David A.] Harvard Univ, Sch Med, Brigham & Womens Hosp, TIMI Study Grp,Cardiovasc Div, Boston, MA 02115 USA. [Jarolim, Petr] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Rifai, Nader] Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. RP Scirica, BM (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, TIMI Study Grp,Cardiovasc Div, 75 Francis St, Boston, MA 02115 USA. EM bscirica@partners.org FU B.M. Scirica; AstraZeneca; Novartis; Merck/Schering-Plough; CV Therapeutics; Roche Diagnostics; Siemens Medical Solutions; Ortho Clinical Diagnostics; Beckman Coulter; Bristol-Myers Squibb; C.P. Cannon, Merck Co.,; GlaxoSmithKline; M.S. Sabatine; Roche Diagnostics and Ortho Clinical Diagnostics; P. Jarolim, Siemens Medical Diagnostics; E. Braunwald, Beckman Coulter; Siemens Medical Solutions, FX B.M. Scirica, AstraZeneca, Novartis, Merck/Schering-Plough, CV Therapeutics, Roche Diagnostics, Siemens Medical Solutions, Ortho Clinical Diagnostics, Beckman Coulter, and Bristol-Myers Squibb; C.P. Cannon, Merck & Co., Merck/Schering-Plough, and GlaxoSmithKline; M.S. Sabatine, Roche Diagnostics and Ortho Clinical Diagnostics; P. Jarolim, Siemens Medical Diagnostics; E. Braunwald, Beckman Coulter, Siemens Medical Solutions, Roche Diagnostics, Ortho Clinical Diagnostics, Merck & Co., and Schering-Plough; D.A. Morrow, Beckman Coulter, Siemens Medical Solutions, Roche Diagnostics, AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Merck & Co., Pfizer, and Schering-Plough. NR 32 TC 27 Z9 30 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 FEB PY 2009 VL 55 IS 2 BP 265 EP 273 DI 10.1373/clinchem.2008.117192 PG 9 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 401ED UT WOS:000262921300010 PM 19074516 ER PT J AU Lee, CC You, NCY Song, YQ Hsu, YH Manson, J Nathan, L Tinker, L Liu, SM AF Lee, Cathy C. You, Nai-chieh Yuko Song, Yiqing Hsu, Yi-Hsiang Manson, JoAnn Nathan, Lauren Tinker, Lesley Liu, Simin TI Relation of Genetic Variation in the Gene Coding for C-Reactive Protein with Its Plasma Protein Concentrations: Findings from the Women's Health Initiative Observational Cohort SO CLINICAL CHEMISTRY LA English DT Article ID TYPE-2 DIABETES-MELLITUS; CORONARY-HEART-DISEASE; SINGLE-NUCLEOTIDE POLYMORPHISMS; CRP LEVELS; POPULATION STRATIFICATION; CARDIOVASCULAR-DISEASE; INFLAMMATORY MARKERS; HUMAN GENOME; RISK; ASSOCIATION AB BACKGROUND: Although common genetic variants of the CRP gene (C-reactive protein, pentraxin related) have been associated with plasma concentrations of high-sensitivity CRP (hsCRP) in several cohorts of European Americans, relatively few studies have comprehensively assessed this association in well-characterized multiethnic populations. METHODS: In a case-control study of diabetes nested in the Women's Health initiative Observational Cohort, we comprehensively evaluated the association of genetic variation in CRP with plasma hsCRP concentrations. Thirteen haplotype-tagging single-nucleotide polymorphisms (tSNPs) were identified and subsequently genotyped in 3782 postmenopausal women. RESULTS: The allele frequencies for these tSNPs and the haplotype blocks defined by these tSNPs varied significantly by ethnic group (P < 0.0001). Consistent with prior studies of whites, rs3093068, rs1130864, and rs1417938 were significantly associated with higher hsCRP concentrations (geometric-mean increase per minor-allele change, 1.20-1.25 mg/L), and rs1205 and rs1800947 were significantly associated with lower hsCRP values (decrease of 1.28-1.48 mg/L). The associations with rs3093068 and rs1205 appeared to be stronger in Asians/Pacific Islanders than in whites (geometric-mean increase, 1.65 mg/L vs 1.25 mg/L, respectively). Minor alleles at rs3093075 and rs3093039 were associated with substantially increased hsCRP concentrations, whereas rs1800947 was associated with lower hsCRP values. All haplotype-based association results tended to be consistent with the associations seen with single CRP SNPs. CONCLUSIONS: Our large multiethnic case-control study of postmenopausal women provides evidence that common genetic variants in the CRP gene are substantially associated with plasma hsCRP concentrations in this case-control subcohort. The data also suggest ethnic variations in these associations. (C) 2008 American Association for Clinical Chemistry C1 [You, Nai-chieh Yuko; Liu, Simin] Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90095 USA. [Lee, Cathy C.; Liu, Simin] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Lee, Cathy C.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Song, Yiqing; Manson, JoAnn] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. [Song, Yiqing; Manson, JoAnn] Harvard Univ, Sch Med, Boston, MA USA. [Hsu, Yi-Hsiang] Harvard Univ, Sch Publ Hlth, Mol & Integrat Physiol Sci Program, Dept Environm Hlth, Boston, MA 02115 USA. [Nathan, Lauren] Univ Calif Los Angeles, David Geffen Sch Med, Dept OB GYN, Los Angeles, CA 90095 USA. [Tinker, Lesley] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Liu, Simin] Univ Calif Los Angeles, David Geffen Sch Med, Johnson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. RP Liu, SM (reprint author), Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Box 951772,650 Charles E Young Dr S, Los Angeles, CA 90095 USA. EM siminliu@ucla.edu RI Liu, Simin/I-3689-2014 OI Liu, Simin/0000-0003-2098-3844 FU National Heart, Lung, and Blood Institute; US Department of Health and Human Services; National Institutes of Health [R01DK062290] FX The Women's Health Initiative is funded by the National Heart, Lung, and Blood Institute, and the US Department of Health and Human Services. This study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases R01DK062290 from the National Institutes of Health. NR 35 TC 23 Z9 24 U1 0 U2 1 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 FEB PY 2009 VL 55 IS 2 BP 351 EP 360 DI 10.1373/clinchem.2008.117176 PG 10 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 401ED UT WOS:000262921300019 PM 19095725 ER PT J AU Lu, Y Chen, QY Corey, E Xie, W Fan, J Mizokami, A Zhang, J AF Lu, Yi Chen, Qiuyan Corey, Eva Xie, Wen Fan, Jie Mizokami, Atsushi Zhang, Jian TI Activation of MCP-1/CCR2 axis promotes prostate cancer growth in bone SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Article DE MCP-1; CCR2; Cell invasion; Osteoclast; Prostate cancer ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; CHEMOKINE RECEPTOR EXPRESSION; ENDOTHELIAL-CELLS; TUMOR PROGRESSION; SOLUBLE RECEPTOR; METASTASIS; CARCINOMA; MIGRATION; MECHANISMS; INVASION AB Prostate cancer (PCa) frequently metastasizes to bone resulting in a mixture of osteolytic and osteoblastic lesions. We have previously reported that monocyte chemotactic protein-1 (MCP-1) is chemotactic for PCa cells, and its receptor, CCR2 expression, correlates with pathological stages. However, the role of MCP-1/CCR2 axis on PCa progression in bone remains unclear. We first evaluated the serum levels of MCP-1 in patients with bone metastases or localized PCa by enzyme-linked immunosorbent assay. We found that MCP-1 levels were elevated in patients with bone metastases compared to localized PCa. We further determined the effects of knockdown CCR2 or MCP-1 on PCa cell invasion and the tumor cell-induced osteoclast activity in vitro, respectively. PCa C4-2B and PC3 cells were transfected stably with either CCR2 short hairpin RNA (shRNA) or a scrambled RNA. CCR2 knockdown significantly diminished the MCP-1-induced PCa cell invasion. In addition, the MCP-1 production was knocked down by MCP-1 shRNA in C4-2B and PC3 cells. Conditioned media (CM) was collected and determined for the CM-induced osteoclast formation in vitro. MCP-1 knockdown significantly decreased the PCa CM-induced osteoclast formation. Finally, MCP-1 knockdown PC3 cells were implanted into the tibia of SCID mice for 4 weeks. Tumor volume was determined by histopathology and bone histomorphometry. MCP-1 knockdown diminished PC3 tumor growth in bone. We concluded that activation of MCP-1/CCR2 axis promotes PCa growth in bone. This study suggests that MCP-1 may be a target for PCa progression. C1 [Lu, Yi; Chen, Qiuyan; Fan, Jie; Zhang, Jian] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15240 USA. [Chen, Qiuyan] Sun Yat Sen Univ, Ctr Canc, Dept Nasopharyngeal Carcinoma, Guangzhou 510275, Guangdong, Peoples R China. [Corey, Eva] Univ Washington, Dept Urol, Seattle, WA 98195 USA. [Xie, Wen] Univ Pittsburgh, Ctr Pharmacogenet, Pittsburgh, PA 15261 USA. [Xie, Wen] Univ Pittsburgh, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA. [Fan, Jie] VA Pittsburgh Healthcare Syst, Dept Surg, Pittsburgh, PA 15240 USA. [Mizokami, Atsushi] Kanazawa Univ, Grad Sch Med Sci, Dept Urol, Kanazawa, Ishikawa, Japan. RP Lu, Y (reprint author), Univ Pittsburgh, Dept Med, Pittsburgh, PA 15240 USA. EM luy3@upmc.edu; zhangj2@upmc.edu RI Xie, Wen/M-1768-2016 FU Department of Defense [PC061231]; University of Pittsburgh Cancer Institute CCSG FX The authors thank Dr. G. David Roodman for his helpful discussion, Dr. Zhong Cai for his technical help, and Mrs. Donna Gaspich for her editing. This study was supported by Department of Defense PC061231 and University of Pittsburgh Cancer Institute CCSG (J. Zhang). NR 37 TC 47 Z9 52 U1 1 U2 7 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD FEB PY 2009 VL 26 IS 2 BP 161 EP 169 DI 10.1007/s10585-008-9226-7 PG 9 WC Oncology SC Oncology GA 407JK UT WOS:000263359200009 PM 19002595 ER PT J AU Graham, DY AF Graham, David Y. TI Efficient Identification and Evaluation of Effective Helicobacter pylori Therapies SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID II CLINICAL-TRIALS; SEQUENTIAL THERAPY; TRIPLE THERAPY; IRON-DEFICIENCY; INFECTION; ERADICATION; METAANALYSIS; REGIMEN; EFFICACY; DESIGNS AB Annually hundreds if not thousands of patients fail empiric H pylori eradication therapy. Failure occurs in part because routine post treatment testing, which provides an early warning of increasing antibiotic resistance, is not universally done and physicians are generally unaware that cure rates with legacy triple therapy (a proton-pump inhibitor, amoxicillin, and clarithromycin) in most places has fallen below 80%. We propose first, institution of routine post eradication testing and second, abandonment of the "better than another therapy" approach to separating acceptable from unacceptable therapies. Instead, we propose using results-based outcomes (ie, >95% cure rates). H pylori should be evaluated as other infectious diseases (ie, few would compare a new antibiotic for pneumonia with the previous best choice whose effectiveness was now impaired because of resistance). Randomized comparisons should be restricted to studies designed to improve (eg, simplify or reduce costs) high cure rate therapies while maintaining efficacy. We also discuss potential ethical issues such as those including known or suspected low cure rate therapies. Legacy therapies cannot be identified as "approved" or "recommended" even if both statements were true. Instead patients and ethics boards must receive "full disclosures" both before and during studies that include all that might affect a patient's decision to enter or to continue. Finally, we provides advice regarding trial design using "best shot" pilot studies to efficiently identify tentative effective regimens which are then confirmed in randomized trials all the while minimizing patient risks and drug exposure. C1 [Graham, David Y.] Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Houston, TX 77030 USA. [Graham, David Y.] Baylor Coll Med, Houston, TX 77030 USA. RP Graham, DY (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Dept Med, RM 3A-320 1111D,2002 Holcombe Blvd, Houston, TX 77030 USA. EM dgraham@bcm.tmc.edu FU NIDDK NIH HHS [P30 DK056338, P30 DK056338-07, DK56338] NR 26 TC 56 Z9 57 U1 0 U2 5 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 FEB PY 2009 VL 7 IS 2 BP 145 EP 148 DI 10.1016/j.cgh.2008.10.024 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 410QE UT WOS:000263592100007 PM 19026766 ER PT J AU Spiegel, BMR Ho, W Esrailian, E Targan, S Higgins, PDR Siegel, CA Dubinsky, M Melmed, GY AF Spiegel, Brennan M. R. Ho, Wayne Esrailian, Eric Targan, Stephan Higgins, Peter D. R. Siegel, Corey A. Dubinsky, Marla Melmed, Gil Y. TI Controversies in Ulcerative Colitis: A Survey Comparing Decision Making of Experts Versus Community Gastroenterologists SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; QUALITY-OF-LIFE; COLORECTAL-CANCER; CROHNS-DISEASE; SURVEILLANCE; GUIDELINES; CYCLOSPORINE; MANAGEMENT; VIGNETTES; PROVIDERS AB Background & Aims: Despite the development of consensus guidelines in ulcerative colitis (UC), there remain several areas of uncertainty in the everyday management of this incompletely understood disease. We performed a national vignette survey to measure variations in decision-making in areas of controversy. Methods: We constructed a survey with 3 vignettes to measure decision-making in 4 areas of controversy in UC: (1) dysplasia management, (2) mesalamine dosing, (3) diagnostic testing for underlying Crohn's disease, and (4) treatment of steroid-refractory inpatient UC. We compared responses between a group of community gastroenterologists and UC experts. Results: We received 192 responses (36% response). Compared with community gastroenterologists, UC experts were more likely to endorse colectomy for both unifocal and multifocal low-grade dysplasia, use narrow band imaging and chromoendoscopy for surveillance colonoscopy, use high-dose mesalamine for inducing remission, use long-term mesalamine for cancer chemoprevention, order computed tomography enterography to evaluate for Crohn's disease, and to have a lower threshold to call for surgery consultation in steroid-refractory UC. There was little agreement regarding the optimal frequency of surveillance colonoscopy, even among experts. Most respondents favored using infliximab over cyclosporine in steroid-refractory UC. Conclusions: Community gastroenterologists and UC experts vary dramatically in their approach to many areas of uncertainty in UC. The only area of consensus between groups is the use of infliximab over cyclosporine in steroid-refractory UC, itself a controversial decision. These data suggest that current practice patterns are highly disparate and focus attention on specific areas of disconnect that should be further investigated. C1 [Spiegel, Brennan M. R.; Ho, Wayne] Vet Adm Greater Angeles Healthcare Syst, Los Angeles, CA USA. [Spiegel, Brennan M. R.; Esrailian, Eric] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Spiegel, Brennan M. R.] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. [Spiegel, Brennan M. R.] CURE Digest Dis Res Ctr, Los Angeles, CA USA. [Targan, Stephan; Dubinsky, Marla; Melmed, Gil Y.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Higgins, Peter D. R.] Univ Michigan, Sch Med, Ann Arbor, MI USA. [Siegel, Corey A.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [Spiegel, Brennan M. R.; Esrailian, Eric] Univ Calif Los Angeles, VA Ctr Outcomes Res & Educ, Los Angeles, CA USA. RP Spiegel, BMR (reprint author), 11301 Wilshire Blvd,Bldg 115,Room 215, Los Angeles, CA 90073 USA. EM bspiegel@mednet.ulca.edu RI Higgins, Peter/A-3511-2009 OI Higgins, Peter/0000-0003-1602-4341 FU Veteran's Affairs Health Services Research and Development (HSR&D) Career Development Transition Award [RCD 03-179-2]; Crohn's and Colitis Foundation Career Development Award; NIH [IK23DK078678-01A1, 2P30 DK 041301-17]; Procter Gamble FX The authors disclose the following: Dr Spiegel is supported by a Veteran's Affairs Health Services Research and Development (HSR&D) Career Development Transition Award (RCD 03-179-2) and the CURE Digestive Disease Research Center (NIH 2P30 DK 041301-17). Dr Corey Siegel is supported by a Crohn's and Colitis Foundation Career Development Award and NIH IK23DK078678-01A1. This study was supported by an investigator-initiated research grant by Procter & Gamble. NR 31 TC 24 Z9 25 U1 0 U2 1 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 FEB PY 2009 VL 7 IS 2 BP 168 EP 174 DI 10.1016/j.cgh.2008.08.029 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 410QE UT WOS:000263592100011 PM 18952199 ER PT J AU Fontana, RJ Bonkovsky, HL Naishadham, D Dienstag, JL Sterling, RK Lok, ASF Su, GL AF Fontana, Robert J. Bonkovsky, Herbert L. Naishadham, Deepa Dienstag, Jules L. Sterling, Richard K. Lok, Anna S. F. Su, Grace L. CA Halt-C Trial Grp TI Serum Fibrosis Marker Levels Decrease After Successful Antiviral Treatment in Chronic Hepatitis C Patients With Advanced Fibrosis SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID LIVER FIBROSIS; INTERFERON-ALPHA; PEGINTERFERON ALPHA-2A; THERAPY; RIBAVIRIN; VIRUS; TRIAL; INFECTION AB Background & Aims: Serum fibrosis marker levels during the lead-in treatment phase of patients enrolled in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) trial were determined. Methods: Week 0, 24, 48, and 72 serum samples were analyzed for YKL-40, tissue inhibitor of matrix metalloproteinase-1, amino-terminal peptide of type III procollagen (PIIINP), and hyaluronic acid (HA) levels. All 456 chronic hepatitis C (CHC) patients received peginterferon alfa 2a and ribavirin for 24 to 48 weeks. Results: Mean age was 49.2 years, 71% were male, and 39% had cirrhosis. Lower pretreatment serum YKL-40, tissue inhibitor of matrix metalloproteinase-1, PIIINP, and HA levels were associated significantly with week-20 virologic response (P < .0001). In multivariate analysis, non-l CHC genotype, non-black race, prior interferon monotherapy, and lower baseline serum aspartate aminotransferase/alanine aminotransferase levels and log(10)YKL-40 levels were associated independently with week-20 virologic response. Statistically significant declines in all marker levels were observed at week 72 compared with baseline in the 81 patients with a sustained virologic response, but not in the 72 patients with breakthrough or relapse. At weeks 24 and 48, significant increases were observed in serum PIIINP and HA levels compared with baseline in virologic responders and nonresponders (P < .0001). Conclusions: Pretreatment YKL-40 levels are an independent predictor of initial virologic response to peginterferon and ribavirin treatment. Levels of all 4 serum fibrosis markers decreased significantly in the SVR patients, consistent with reduced hepatic fibrogenesis. Measuring serum fibrosis marker levels before and after antiviral therapy may provide important prognostic information in CHC patients. C1 [Fontana, Robert J.; Lok, Anna S. F.; Su, Grace L.] Univ Michigan, Med Ctr, Dept Internal Med, Ann Arbor, MI 48109 USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Dept Med, Farmington, CT USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Dept Mol & Struct Biol, Farmington, CT USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Liver Biliary Pancreat Ctr, Farmington, CT USA. [Naishadham, Deepa] New England Res Inst, Watertown, MA 02172 USA. [Dienstag, Jules L.] Massachusetts Gen Hosp, Med Serv, Gastrointestinal Unit, Boston, MA USA. [Dienstag, Jules L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Sterling, Richard K.] Virginia Commonwealth Univ, Med Ctr, Hepatol Sect, Richmond, VA USA. [Su, Grace L.] Ann Arbor Vet Adm Hlth Syst, Gastroenterol Sect, Ann Arbor, MI USA. RP Fontana, RJ (reprint author), Univ Michigan, Med Ctr, Dept Internal Med, 3912 Taubman Ctr, Ann Arbor, MI 48109 USA. EM rfontana@med.umich.edu RI Lok, Anna /B-8292-2009; OI Yang, Shuman/0000-0002-9638-0890 FU National Institute of Diabetes & Digestive & Kidney Diseases; National Institute of Allergy and Infectious Diseases; National Cancer Institute; National Center for Minority Health and Health Disparities; National Center for Research Resources; National Institutes of Health; Hoffmann-La Roche, Inc. FX The authors disclose the following: This study was supported by the National Institute of Diabetes & Digestive & Kidney Diseases (contract numbers are listed later). Additional support was provided by the National Institute of Allergy and Infectious Diseases, the National Cancer Institute, the National Center for Minority Health and Health Disparities, and by General Clinical Research Center grants from the National Center for Research Resources, National Institutes of Health (grant numbers are listed later). Additional funding to conduct this study was supplied by Hoffmann-La Roche, Inc., through a Cooperative Research and Development Agreement with the National Institutes of Health. The financial relationships of the authors with Hoffmann-La Roche, Inc., are as follows: R. J. Fontana Is on the speaker's bureau; H. L. Bonkovsky receives research support; R. K. Sterling is a consultant, receives research support, and is on the speaker's bureau; and A. S. Lok is a consultant. NR 21 TC 27 Z9 28 U1 0 U2 0 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 FEB PY 2009 VL 7 IS 2 BP 219 EP 226 DI 10.1016/j.cgh.2008.10.034 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 410QE UT WOS:000263592100018 PM 19068241 ER PT J AU Neofytos, D Horn, D Anaissie, E Steinbach, W Olyaei, A Fishman, J Pfaller, M Chang, C Webster, K Marr, K AF Neofytos, D. Horn, D. Anaissie, E. Steinbach, W. Olyaei, A. Fishman, J. Pfaller, M. Chang, C. Webster, K. Marr, K. TI Epidemiology and Outcome of Invasive Fungal Infection in Adult Hematopoietic Stem Cell Transplant Recipients: Analysis of Multicenter Prospective Antifungal Therapy (PATH) Alliance Registry SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID FLUCONAZOLE PROPHYLAXIS; MARROW-TRANSPLANTATION; PROGNOSTIC-FACTORS; ASPERGILLOSIS; DEATH; CANCER AB Background. With use of data from the Prospective Antifungal Therapy ( PATH) Alliance registry, we performed this multicenter, prospective, observational study to assess the epidemiologic characters and outcomes of invasive fungal infection (IFI) in hematopoietic stem cell transplant (HSCT) recipients. Methods. Sixteen medical centers from North America reported data on adult HSCT recipients with proven or probable IFI during the period July 2004 through September 2007. The distribution of IFIs and rates of survival at 6 and 12 weeks after diagnosis were studied. We used logistic regression models to determine risk factors associated with 6-week mortality for allogeneic HSCT recipients with invasive aspergillosis (IA). Results. Two hundred thirty-four adult HSCT recipients with a total of 250 IFIs were included in this study. IA (59.2%) was the most frequent IFI, followed by invasive candidiasis (24.8%), zygomycosis (7.2%), and IFI due to other molds (6.8%). Voriconazole was the most frequently administered agent (68.4%); amphotericin B deoxycholate was administered to a few patients (2.1%). Ninety-three (46.7%) of 199 HSCT recipients with known outcome had died by week 12. The 6-week survival rate was significantly greater for patients with IA than for those with invasive candidiasis and for those with IFI due to the Zygomycetes or other molds (P<.001). The 6-week mortality rate for HSCT recipients with IA was 21.5%. At 6 weeks, there was a trend toward a worse outcome among allogeneic HSCT recipients with IA who received myeloablative conditioning (P = .07); absence of mechanical ventilation or/and hemodialysis (P = .01) were associated with improved survival. Conclusions. IA remains the most commonly identified IFI among HSCT recipients, but rates of survival in persons with IA appear to have improved, compared with previously reported data. Invasive candidiasis and IFI due to molds other than Aspergillus species remain a significant problem in HSCT recipients. C1 [Neofytos, D.; Marr, K.] Johns Hopkins Univ, Sch Med, Div Infect Dis, Baltimore, MD 21205 USA. [Neofytos, D.; Horn, D.] Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA. [Anaissie, E.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Steinbach, W.] Duke Univ, Med Ctr, Durham, NC USA. [Olyaei, A.] Oregon Hlth & Sci Univ, Portland, OR USA. [Fishman, J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. [Pfaller, M.] Univ Iowa Hlth Care, Iowa City, IA USA. [Marr, K.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Chang, C.] Info Spectrum, Markham, ON, Canada. [Webster, K.] Axiom Real Time Metr, Oakville, ON, Canada. [Webster, K.] EBM Consulting, Mississauga, ON, Canada. RP Neofytos, D (reprint author), Johns Hopkins Univ, Sch Med, Div Infect Dis, 1830 E Monument St,Rm 421, Baltimore, MD 21205 USA. EM dneofyt1@jhmi.edu FU Astellas; Astellas and Pfizer FX D.N. has received grant support (for educational research) from Astellas. D. H. has received research funding from Astellas and Pfizer, has served as a consultant or advisor to Astellas and Pfizer, has been on the speakers' bureau for Pfizer and Astellas, and has received speaking honoraria from Roche. E. A. has been a consultant to and on the speakers' bureau for Astellas, Pfizer, Gilead, Merck, and Schering-Plough. W. S. has served as consultant to Pfizer, Astellas, and Schering- Plough and on the speakers' bureau for Astellas, Merck, Pfizer. A.O. has been on the speakers' bureau and served as consultant to Pfizer and Astellas. J.F. has been a consultant to Merck, Hoffman LaRoche, Astellas, and Primera; has received grant support ( for educational research) from Astellas; and has been on the speakers' bureau for Astellas and Roche. M. P. has been a consultant to and on the speakers' bureau for Pfizer, Astellas, Merck, and Schering- Plough. C. C. has served as a statistical consultant to Pharmacia, Pfizer, and Eli Lilly; as a marketing analytics consultant to Roche; and as a statistical consultant via third parties to Astellas, Topigen, and AstraZeneca. K. W. has had contract work with Astellas. K. M. has been a consultant and/or part of advisory boards for Astellas, Enzon, Merck, Pfizer, and Schering Plough and has received grant support from Astellas, Enzon, Merck, and Pfizer. NR 18 TC 329 Z9 348 U1 0 U2 13 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD FEB 1 PY 2009 VL 48 IS 3 BP 265 EP 273 DI 10.1086/595846 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 392GM UT WOS:000262291200001 PM 19115967 ER PT J AU Robbins, GK Spritzler, JG Chan, ES Asmuth, DM Gandhi, RT Rodriguez, BA Skowron, G Skolnik, PR Shafer, RW Pollard, RB AF Robbins, Gregory K. Spritzler, John G. Chan, Ellen S. Asmuth, David M. Gandhi, Rajesh T. Rodriguez, Benigno A. Skowron, Gail Skolnik, Paul R. Shafer, Robert W. Pollard, Richard B. CA AIDS Clinicals Trials Grp 384 T TI Incomplete Reconstitution of T Cell Subsets on Combination Antiretroviral Therapy in the AIDS Clinical Trials Group Protocol 384 SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID SEQUENTIAL 3-DRUG REGIMENS; HIV-INFECTED PERSONS; HIV-1-INFECTED PATIENTS; VIROLOGICAL SUPPRESSION; IMMUNOLOGICAL RECOVERY; COLLABORATIVE ANALYSIS; DISEASE PROGRESSION; VIRAL SUPPRESSION; INITIAL THERAPY; COUNT AB Background. Initiation of combination antiretroviral therapy (ART) results in higher total CD4 cell counts, a surrogate for immune reconstitution. Whether the baseline CD4 cell count affects reconstitution of immune cell subsets has not been well characterized. Methods. Using data from 978 patients (621 with comprehensive immunological assessments) from the AIDS [Acquired Immunodeficiency Syndrome] Clinical Trials Group protocol 384, a randomized trial of initial ART, we compared reconstitution of CD4(+), CD4(+) naive and memory, CD4(+) activation, CD8(+), CD8(+) activation, B, and natural killer cells among patients in different baseline CD4(+) strata. Reference ranges for T cell populations in control patients negative for human immunodeficiency virus (HIV) infection were calculated using data from AIDS Clinical Trials Group protocol A5113. Results. Patients in the lower baseline CD4(+) strata did not achieve total CD4(+) cell counts similar to those of patients in the higher strata during 144 weeks of ART, although CD4(+) cell count increases were similar. Ratios of CD4(+) naive-memory cell counts and CD4(+): CD8(+) cell counts remained significantly reduced in patients with lower baseline CD4(+) cell counts (<= 350 cells/mm(3)). These immune imbalances were most notable for those initiating ART with a baseline CD4(+) cell count <= 200 cells/mm(3), even after adjustment for baseline plasma HIV RNA levels. Conclusions. After nearly 3 years of ART, T cell subsets in patients with baseline CD4(+) cell counts >350 cells/mm(3) achieved or approached the reference range those of control individuals without HIV infection. In contrast, patients who began ART with <= 350 CD4(+) cells/mm(3) generally did not regain normal CD4(+) naive-memory cell ratios. These results support current guidelines to start ART at a threshold of 350 cells/mm(3) and suggest that there may be immunological benefits associated with initiating therapy at even higher CD4(+) cell counts. C1 [Robbins, Gregory K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. [Spritzler, John G.; Chan, Ellen S.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Skolnik, Paul R.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Asmuth, David M.; Pollard, Richard B.] Univ Calif Davis, Med Ctr, Sacramento, CA 95817 USA. [Shafer, Robert W.] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. [Rodriguez, Benigno A.] Case Western Reserve Univ, Sch Med, Cleveland, OH USA. [Skowron, Gail] Roger Williams Med Ctr, Providence, RI USA. RP Robbins, GK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Infect Dis Unit, Cox 506B,55 Fruit St, Boston, MA 02114 USA. EM grobbins@partners.org RI Robbins, Gregory/F-7988-2011; Rodriguez, Benigno/C-3365-2009 OI Rodriguez, Benigno/0000-0001-9736-7957 FU NIAID NIH HHS [K01 AI062435-03, AI066992, AI25879, AI27659, AI27666, AI38855, AI38858, IP30AI060354, K01 AI062435, K01 AI062435-01A1, K01 AI062435-02, K01 AI062435-04, K01AI062435, P30 AI060354, R01 AI066992, U01 AI025879, U01 AI027659, U01 AI027666, U01 AI038855, U01 AI038858] NR 43 TC 121 Z9 124 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD FEB 1 PY 2009 VL 48 IS 3 BP 350 EP 361 DI 10.1086/595888 PG 12 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 392GM UT WOS:000262291200013 PM 19123865 ER PT J AU Rubin, K AF Rubin, Krista TI Management of Metastatic Melanoma: Nursing Challenges Today and Tomorrow SO CLINICAL JOURNAL OF ONCOLOGY NURSING LA English DT Article ID LYMPHOCYTE-ASSOCIATED ANTIGEN-4; POSITRON-EMISSION-TOMOGRAPHY; AMERICAN JOINT COMMITTEE; CANCER-IMMUNOTHERAPY; ANTIBODY; BIOCHEMOTHERAPY; DACARBAZINE; INTERFERON; THERAPY; INTERLEUKIN-2 AB Advanced and metastatic melanoma is a devastating and deadly disease. No standard of care has been established to date. As the understanding of the natural history of this disease advances, agents directed at interrupting single and multiple steps in the proliferation, growth, and metastatic processes involved in melanoma are being developed and evaluated. Several agents (particularly anticytotoxic T lymphocyte-associated antigen 4 antibodies) are in development. The role of the oncology nurse in the care of patients with melanoma includes understanding and communicating to patients the disease process and goals for care, knowing the various agents and their associated efficacy and toxicities, and learning how to guide patients through the decision-making process. C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Rubin, K (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. EM kmrubin@partners.org FU Pfizer, Inc. FX Krista Rubin, RN, MS, NP, is a nurse practitioner at Massachusetts General Hospital Cancer Center in Boston. Rubin is a member of the speakers bureau for Schering-Plough Corporation. Editorial assistance was provided by CE Alliance. Rubin received honoraria from CE Alliance through an educational grant from Pfizer, Inc., for her work on this article. (Submitted April 2008. Accepted for publication August 19, 2008.) NR 48 TC 2 Z9 2 U1 0 U2 1 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 FEB PY 2009 VL 13 IS 1 BP 81 EP 89 DI 10.1188/09.CJON.81-89 PG 9 WC Oncology; Nursing SC Oncology; Nursing GA 407DT UT WOS:000263344500013 PM 19193552 ER PT J AU Delmonico, FL AF Delmonico, Francis L. TI The Hazards of Transplant Tourism SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material C1 [Delmonico, Francis L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplant Ctr, Boston, MA USA. RP Delmonico, FL (reprint author), New England Organ Bank Inc, 1 Gateway Ctr, Newton, MA 02458 USA. EM francis_delmonico@neob.org NR 0 TC 10 Z9 10 U1 0 U2 0 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 FEB PY 2009 VL 4 IS 2 BP 249 EP 250 DI 10.2215/CJN.05801108 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 407NY UT WOS:000263372800001 PM 19218470 ER PT J AU Fried, LF Duckworth, W Zhang, JH O'Connor, T Brophy, M Emanuele, N Huang, GD McCullough, PA Palevsky, PM Seliger, S Warren, SR Peduzzi, P AF Fried, Linda F. Duckworth, William Zhang, Jane Hongyuan O'Connor, Theresa Brophy, Mar Emanuele, Nicholas Huang, Grant D. McCullough, Peter A. Palevsky, Paul M. Seliger, Stephen Warren, Stuart R. Peduzzi, Peter CA VA NEPHRON-D Investigators TI Design of Combination Angiotensin Receptor Blocker and Angiotensin-Converting Enzyme Inhibitor for Treatment of Diabetic Nephropathy (VA NEPHRON-D) SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID DOUBLE-BLIND CROSSOVER; CONTROLLED-TRIAL; ACE-INHIBITION; HEART-FAILURE; DUAL BLOCKADE; RANDOMIZED-TRIAL; RENAL OUTCOMES; KIDNEY-DISEASE; SYSTEM; LOSARTAN AB Both angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) can slow the progression of diabetic nephropathy. Even with ACEI or ARB treatment, the proportion of patients who progress to end-stage renal disease (ESRD) remains high. Interventions that achieve more complete blockade of the renin-angiotensin system, such as combination ACEI and ARB, might be beneficial. This approach may decrease progression of nondiabetic kidney disease. In diabetic nephropathy, combination therapy decreases proteinuria, but its effect in slowing progression is unknown. In addition, the potential for hyperkalemia may limit the utility of combined therapy in this population. VA NEPHRON-D is a randomized, double-blind, multicenter clinical trial to assess the effect of combination losartan and lisinopril, compared with losartan alone, on the progression of kidney disease in 1850 patients with diabetes and overt proteinuria. The primary endpoints are time to (1) reduction in estimated GFR (eGFR) of > 50% (if baseline < 60 ml/min/1.73 m(2)); (2) reduction in eGFR of 30 ml/min/1.73 m(2) (if baseline >= 60 ml/min/1.73 m(2)); (3) progression to ESRD (need for dialysis, renal transplant, or eGFR < 15 ml/min/1.73 m(2)); or (4) death. The secondary endpoint is time to change in eGFR or ESRD. Tertiary endpoints are cardiovascular events, slope of change in eGFR, and change in albuminuria at I yr. Specific safety endpoints are serious hyperkalemia (potassium > 6 mEq/L, requiring admission, emergency room visit, or dialysis), all-cause mortality, and other serious adverse events. This paper discusses the design and key methodological issues that arose during the planning of the study. C1 [Fried, Linda F.; Palevsky, Paul M.] Univ Pittsburgh, Sch Med, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. [Fried, Linda F.; Palevsky, Paul M.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15240 USA. [Duckworth, William] Univ Arizona, Dept Med, Phoenix, AZ USA. [Duckworth, William] Arizona State Univ, Sch Life Sci, Carl T Hayden VA Med Ctr, Phoenix, AZ USA. [Zhang, Jane Hongyuan; O'Connor, Theresa; Peduzzi, Peter] West Haven VA Cooperat Studies Program, Coordinating Ctr, West Haven, CT USA. [Brophy, Mar] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Brophy, Mar] Boston Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02118 USA. [Emanuele, Nicholas] Loyola Univ, Med Ctr, Hines VA, Hines, IL USA. [Emanuele, Nicholas] Loyola Univ, Med Ctr, Dept Med, Hines, IL USA. [Huang, Grant D.] VA Off Res & Dev, Cooperat Studies Program Headquarters, Washington, DC USA. [McCullough, Peter A.] William Beaumont Hosp, Dept Med, Royal Oak, MI 48072 USA. [Seliger, Stephen] Univ Maryland, Sch Med, VA Maryland Med Ctr, Baltimore, MD 21201 USA. [Seliger, Stephen] Univ Maryland, Dept Med, Sch Med, Baltimore, MD 21201 USA. [Warren, Stuart R.] Univ New Mexico, Coll Pharm, Albuquerque, NM 87131 USA. [Warren, Stuart R.] VA Cooperat Studies Program Res Pharm, Albuquerque, NM USA. RP Fried, LF (reprint author), Univ Pittsburgh, Sch Med, VA Pittsburgh Healthcare Syst, Univ Dr Div,Mailstop 111F-U, Pittsburgh, PA 15240 USA. EM Linda.Fried@va.gov OI Palevsky, Paul/0000-0002-7334-5400 NR 32 TC 75 Z9 80 U1 1 U2 7 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 FEB PY 2009 VL 4 IS 2 BP 361 EP 368 DI 10.2215/CJN.03350708 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 407NY UT WOS:000263372800017 PM 19118120 ER PT J AU Amin, SB Li, C Minvielle, S Moreau, P Magrangeas, F Anderson, KC Avetloiseau, H Munshi, NC AF Amin, S. B. Li, C. Minvielle, S. Moreau, P. Magrangeas, F. Anderson, K. C. Avetloiseau, H. Munshi, N. C. TI Alternate Splicing Is Frequently Observed in Myeloma and Has Impact on Clinical Outcome SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Amin, S. B.; Li, C.; Anderson, K. C.; Munshi, N. C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Minvielle, S.; Moreau, P.; Magrangeas, F.; Avetloiseau, H.] Hop Nantes, Nantes, France. RI Magrangeas, Florence/L-3080-2015; Minvielle, Stephane/K-8251-2015; richard, chrystelle/K-8595-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S93 EP S93 PG 1 WC Oncology SC Oncology GA 473LB UT WOS:000268206500212 ER PT J AU Azab, AK Roccaro, AM Runnels, J Sacco, A Burwick, N Azab, F Pitsillides, C Ngo, HT Jia, X Melhem, MR Thompson, B Lin, CP Anderson, KC Ghobrial, IM AF Azab, A. K. Roccaro, A. M. Runnels, J. Sacco, A. Burwick, N. Azab, F. Pitsillides, C. Ngo, H. T. Jia, X. Melhem, M. R. Thompson, B. Lin, C. P. Anderson, K. C. Ghobrial, I. M. TI Rho-A and Rac-1 GTPases in Multiple Myeloma SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Azab, A. K.; Roccaro, A. M.; Runnels, J.; Sacco, A.; Burwick, N.; Azab, F.; Ngo, H. T.; Jia, X.; Melhem, M. R.; Anderson, K. C.; Ghobrial, I. M.] Dana Farber Canc Inst, Boston, MA USA. [Pitsillides, C.; Thompson, B.; Lin, C. P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S159 EP S159 PG 1 WC Oncology SC Oncology GA 473LB UT WOS:000268206500366 ER PT J AU Azab, F Roccaro, AM Azab, AK Ngo, HT Jia, X Melhem, MR Runnels, J Sacco, A Quang, P Ghobrial, IM AF Azab, F. Roccaro, A. M. Azab, A. K. Ngo, H. T. Jia, X. Melhem, M. R. Runnels, J. Sacco, A. Quang, P. Ghobrial, I. M. TI The Role of RTK's in Waldenstrom Macroglobulinemia SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Azab, F.; Roccaro, A. M.; Azab, A. K.; Ngo, H. T.; Jia, X.; Melhem, M. R.; Runnels, J.; Sacco, A.; Quang, P.; Ghobrial, I. M.] Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S158 EP S159 PG 2 WC Oncology SC Oncology GA 473LB UT WOS:000268206500365 ER PT J AU Blotta, S Podar, K Franco, B Tai, YT Roccaro, AM Gorgun, G Venuta, S Raje, N Richardson, P Hideshima, T Mitsiades, CS Anderson, KC AF Blotta, S. Podar, K. Franco, B. Tai, Y-T Roccaro, A. M. Gorgun, G. Venuta, S. Raje, N. Richardson, P. Hideshima, T. Mitsiades, C. S. Anderson, K. C. TI Ciliary Proteins and Hedgehog Pathway in Multiple Myeloma SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Blotta, S.; Podar, K.; Tai, Y-T; Roccaro, A. M.; Gorgun, G.; Raje, N.; Richardson, P.; Hideshima, T.; Mitsiades, C. S.; Anderson, K. C.] Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Blotta, S.; Venuta, S.] Magna Graecia Univ Catanzaro, Catanzaro, Italy. [Podar, K.; Tai, Y-T; Roccaro, A. M.; Gorgun, G.; Richardson, P.; Hideshima, T.; Mitsiades, C. S.; Anderson, K. C.] Dana Farber Canc Inst, LeBow Inst, Boston, MA 02115 USA. [Franco, B.] TIGEM, Naples, Italy. [Raje, N.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S120 EP S120 PG 1 WC Oncology SC Oncology GA 473LB UT WOS:000268206500272 ER PT J AU Breitkreutz, I Raab, M Zhang, J Christensen, O Blotta, S Hideshima, T Chauhan, D Wilhelm, S Anderson, KC Podar, K AF Breitkreutz, I. Raab, M. Zhang, J. Christensen, O. Blotta, S. Hideshima, T. Chauhan, D. Wilhelm, S. Anderson, K. C. Podar, K. TI BAY 73-4506, A Novel Orally Available Multikinase Inhibitor in MM SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Breitkreutz, I.; Raab, M.; Zhang, J.; Blotta, S.; Hideshima, T.; Chauhan, D.; Anderson, K. C.; Podar, K.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr, Boston, MA 02115 USA. NR 0 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 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S125 EP S125 PG 1 WC Oncology SC Oncology GA 473LB UT WOS:000268206500283 ER PT J AU Burwick, N Roccaro, AM Moreau, AS Jia, X Leleu, X Runnels, J Ngo, HT Melhem, MR Azab, F Azab, AK Lin, CP Anderson, KC Ghobrial, IM AF Burwick, N. Roccaro, A. M. Moreau, A. S. Jia, X. Leleu, X. Runnels, J. Ngo, H. T. Melhem, M. R. Azab, F. Azab, A. K. Lin, C. P. Anderson, K. C. Ghobrial, I. M. TI CXCR7 Regulates SDF-1 Induced, Adhesion, Homing, and Signaling in Multiple Myeloma SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Burwick, N.; Roccaro, A. M.; Jia, X.; Runnels, J.; Ngo, H. T.; Melhem, M. R.; Azab, F.; Azab, A. K.; Anderson, K. C.; Ghobrial, I. M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Moreau, A. S.] CHRU, Immunol Lab, Serv Malad Sang, Lille, France. [Lin, C. P.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S149 EP S149 PG 1 WC Oncology SC Oncology GA 473LB UT WOS:000268206500342 ER PT J AU Cirstea, D Hideshima, T Rodig, S Pozzi, S Vallet, S Ikeda, H Santo, L Vaghela, N Patel, K Motyckova, G Okawa, Y Perrone, G Gorgun, G Calabrese, E Currie, T Trieu, V Desai, N Sportelli, P Munshi, NC Anderson, KC Raje, N AF Cirstea, D. Hideshima, T. Rodig, S. Pozzi, S. Vallet, S. Ikeda, H. Santo, L. Vaghela, N. Patel, K. Motyckova, G. Okawa, Y. Perrone, G. Gorgun, G. Calabrese, E. Currie, T. Trieu, V. Desai, N. Sportelli, P. Munshi, N. C. Anderson, K. C. Raje, N. TI Unraveling the Synergism of Nab-Rapamycin and Perifosine Combination in Multiple Myeloma SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Cirstea, D.; Hideshima, T.; Ikeda, H.; Santo, L.; Motyckova, G.; Okawa, Y.; Perrone, G.; Gorgun, G.; Calabrese, E.; Munshi, N. C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Dis Ctr, Cambridge, MA 02138 USA. [Rodig, S.; Currie, T.] Harvard Univ, Sch Med, Dept Pathol, Brigham & Womens Hosp, Cambridge, MA 02138 USA. [Pozzi, S.; Vallet, S.; Vaghela, N.; Patel, K.; Raje, N.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Cambridge, MA 02138 USA. [Trieu, V.; Desai, N.] Abraxis Biosci LLC, Los Angeles, CA USA. [Sportelli, P.] Keryx Biopharmaceut Inc, New York, NY USA. RI Pozzi, Samantha/A-7617-2012 OI Pozzi, Samantha/0000-0001-7917-1774 NR 0 TC 0 Z9 0 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S138 EP S139 PG 2 WC Oncology SC Oncology GA 473LB UT WOS:000268206500316 ER PT J AU Cirstea, D Hideshima, T Vallet, S Pozzi, S Vaghela, N Ikeda, H Patel, K Motyckova, G Perrone, G Gorgun, G Calabrese, E Loferer, H Munshi, NC Anderson, KC Raje, N Santo, L Okawa, Y AF Cirstea, D. Hideshima, T. Vallet, S. Pozzi, S. Vaghela, N. Ikeda, H. Patel, K. Motyckova, G. Perrone, G. Gorgun, G. Calabrese, E. Loferer, H. Munshi, N. C. Anderson, K. C. Raje, N. Santo, L. Okawa, Y. TI A Novel Small-Molecule Inhibitor RGB 286638 Induces Apoptosis and Necrosis in Multiple Myeloma SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Cirstea, D.; Hideshima, T.; Vallet, S.; Pozzi, S.; Vaghela, N.; Ikeda, H.; Motyckova, G.; Perrone, G.; Gorgun, G.; Calabrese, E.; Munshi, N. C.; Anderson, K. C.; Raje, N.; Santo, L.; Okawa, Y.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Dis Ctr, Cambridge, MA 02138 USA. [Patel, K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Cambridge, MA 02138 USA. [Loferer, H.] GPC Biotech AG, Munich, Germany. RI Pozzi, Samantha/A-7617-2012 OI Pozzi, Samantha/0000-0001-7917-1774 NR 0 TC 0 Z9 0 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S139 EP S140 PG 2 WC Oncology SC Oncology GA 473LB UT WOS:000268206500318 ER PT J AU Delforge, M Kropff, M Spicka, I Petrucci, M Richardson, PG Schlag, R Khuageva, N Dimopoulos, MA Shpilberg, O Samoilova, O Mateos, MV Liu, K Deraedt, W van de Velde, H San Miguel, J AF Delforge, M. Kropff, M. Spicka, I. Petrucci, M. Richardson, P. G. Schlag, R. Khuageva, N. Dimopoulos, M. A. Shpilberg, O. Samoilova, O. Mateos, M. V. Liu, K. Deraedt, W. van de Velde, H. San Miguel, J. TI VMP Results in Fewer Bone Events and Greater ALP Increases Versus MP in the VISTA Study in Front-Line MM SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Delforge, M.; Kropff, M.] Univ Munster, D-4400 Munster, Germany. [Spicka, I.] Univ Hosp, Prague, Czech Republic. [Petrucci, M.] Univ Roma La Sapienza, Rome, Italy. [Richardson, P. G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Schlag, R.] Praxisklin Dr Schlag, Wurzburg, Germany. [Khuageva, N.] SP Botkin Moscow City Clin Hosp, Moscow, Russia. [Dimopoulos, M. A.] Univ Athens, Sch Med, GR-11527 Athens, Greece. [Shpilberg, O.] Rabin Med Ctr, Petah Tiqwa, Israel. [Samoilova, O.] Nizhnii Novgorod Reg Clin Hosp, Nizhnii Novgorod, Russia. [Mateos, M. V.; San Miguel, J.] Hosp Univ Salamanca, CIC, IBMCC, USAL CSIC, Salamanca, Spain. [Liu, K.] Johnson & Johnson Pharmaceut Res & Dev LLC, Raritan, NJ USA. [Deraedt, W.; van de Velde, H.] Johnson & Johnson Pharmaceut Res & Dev, Beerse, Belgium. NR 0 TC 1 Z9 1 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S43 EP S43 PG 1 WC Oncology SC Oncology GA 473LB UT WOS:000268206500093 ER PT J AU Dhawan, R Meunier, J Regnault, A Robinson, D Rosa, K Cakana, A de Velde, HV Richardson, PG Miguel, JS AF Dhawan, R. Meunier, J. Regnault, A. Robinson, D., Jr. Rosa, K. Cakana, A. de Velde, H. V. Richardson, P. G. Miguel, J. San TI Impact of Complete Response on Quality of Life in Newly Diagnosed Multiple Myeloma Patients SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Dhawan, R.; Meunier, J.; Regnault, A.; Rosa, K.] Mapi Values, Lyon, France. [Robinson, D., Jr.] Johnson & Johnson Pharmaceut Serv, Raritan, NJ USA. [Cakana, A.; de Velde, H. V.] Johnson & Johnson Pharmaceut R&D, Beerse, Belgium. [Richardson, P. G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Miguel, J. San] Hosp Univ Salamanca, Salamanca, Spain. NR 0 TC 4 Z9 4 U1 0 U2 1 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S58 EP S58 PG 1 WC Oncology SC Oncology GA 473LB UT WOS:000268206500128 ER PT J AU Dimopoulos, MA Richardson, PG Schlag, R Khuageva, NK Shpilberg, O Kastritis, E Kropff, M Petruci, M Delforge, M Alexeeva, J Schots, R Masszi, T Mateos, MV Deraedt, V Liu, K Cakana, A van de Velde, H San Miguel, J AF Dimopoulos, M. A. Richardson, P. G. Schlag, R. Khuageva, N. K. Shpilberg, O. Kastritis, E. Kropff, M. Petruci, M. Delforge, M. Alexeeva, J. Schots, R. Masszi, T. Mateos, M. V. Deraedt, V. Liu, K. Cakana, A. van de Velde, H. San Miguel, J. TI VMP in Renally Impaired Newly Diagnosed MM Patients: Cohort Analysis of the VISTA Study SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Dimopoulos, M. A.; Richardson, P. G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Schlag, R.] Praxisklin Dr Schlag, Wurzburg, Germany. [Khuageva, N. K.] SP Botkin Moscow City Clin Hosp, Moscow, Russia. [Shpilberg, O.] Rabin Med Ctr, Petah Tiqwa, Israel. [Kastritis, E.] Univ Athens, Sch Med, Alexandra Hosp, GR-11527 Athens, Greece. [Kropff, M.] Univ Munster, D-4400 Munster, Germany. [Petruci, M.] Univ Roma La Sapienza, Rome, Italy. [Masszi, T.] St Istvan & St Laszlo Hosp Budapest, Budapest, Hungary. [Mateos, M. V.; San Miguel, J.] Hosp Univ Salamanca CIC, USAL CSIC, IBMCC, Salamanca, Spain. [Deraedt, V.; van de Velde, H.] Johnson & Johnson Pharmaceut Res & Dev, Beerse, Belgium. [Liu, K.] Johnson & Johnson Pharmaceut Res & Dev LLC, Raritan, NJ USA. [van de Velde, H.] Johnson & Johnson Pharmaceut Res & Dev, High Wycombe, Bucks, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S29 EP S29 PG 1 WC Oncology SC Oncology GA 473LB UT WOS:000268206500062 ER PT J AU Fulciniti, M Tassone, P Hideshima, T Nanjappa, P Prabhala, R Podar, K Amin, S Adamia, S Anderson, KC Munshi, NC Lopez, R AF Fulciniti, M. Tassone, P. Hideshima, T. Nanjappa, P. Prabhala, R. Podar, K. Amin, S. Adamia, S. Anderson, K. C. Munshi, N. C. Lopez, R. TI Targeting the Sp1 Transcription Factor in Multiple Myeloma SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Fulciniti, M.; Tassone, P.] Magna Graecia Univ Catanzaro, Catanzaro, Italy. [Hideshima, T.; Nanjappa, P.; Prabhala, R.; Podar, K.; Amin, S.; Adamia, S.; Anderson, K. C.; Munshi, N. C.] Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S152 EP S152 PG 1 WC Oncology SC Oncology GA 473LB UT WOS:000268206500350 ER PT J AU Fulciniti, M Vallet, S Ettenberg, S Shen, X Raje, N Tassone, P Hideshima, T Nanjappa, P Prabhala, R Anderson, KC Stover, D Munshi, NC AF Fulciniti, M. Vallet, S. Ettenberg, S. Shen, X. Raje, N. Tassone, P. Hideshima, T. Nanjappa, P. Prabhala, R. Anderson, K. C. Stover, D. Munshi, N. C. TI Anti-DKK1 mAb (BHQ880) as a Potential Therapeutic Agent for Multiple Myeloma SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Fulciniti, M.; Vallet, S.; Raje, N.; Hideshima, T.; Nanjappa, P.; Prabhala, R.; Anderson, K. C.; Munshi, N. C.] Dana Farber Canc Inst, Boston, MA USA. [Shen, X.] Beth Israel Deaconess Med Ctr, Boston, MA USA. [Tassone, P.] Magna Graecia Univ Catanzaro, Catanzaro, Italy. NR 0 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 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S151 EP S151 PG 1 WC Oncology SC Oncology GA 473LB UT WOS:000268206500347 ER PT J AU Ghobrial, IM Roccaro, AM Matous, J Padmanabhan, W Badros, A Schlossman, R Chuma, S Leduc, R Nelson, M O'Connor, K Sam, A Harris, B Soumerai, J Warren, D Birner, A Munshi, NC Treon, SP Anderson, KC Richardson, PG AF Ghobrial, I. M. Roccaro, A. M. Matous, J. Padmanabhan, W. Badros, A. Schlossman, R. Chuma, S. Leduc, R. Nelson, M. O'Connor, K. Sam, A. Harris, B. Soumerai, J. Warren, D. Birner, A. Munshi, N. C. Treon, S. P. Anderson, K. C. Richardson, P. G. TI Phase II Trial of Bortezomib and Rituximab in Relapsed/Refractory Waldenstrom Macroglobulinemia SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Ghobrial, I. M.; Roccaro, A. M.; Schlossman, R.; Chuma, S.; Leduc, R.; Nelson, M.; O'Connor, K.; Sam, A.; Harris, B.; Soumerai, J.; Warren, D.; Munshi, N. C.; Treon, S. P.; Anderson, K. C.; Richardson, P. G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Matous, J.] Rocky Mt Canc Ctr, Denver, CO USA. [Padmanabhan, W.] Roswell Pk Canc Ctr, Buffalo, NY USA. [Badros, A.] Univ Maryland, Washington, DC USA. [Birner, A.] Millennium Pharmaceut Inc, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 SU 1 BP S83 EP S84 PG 2 WC Oncology SC Oncology GA 473LB UT WOS:000268206500188 ER PT J AU Ghobrial, IM Roccaro, AM Sportelli, P Treon, SP Weller, E Leleu, X Rubin, N Hong, F Leduc, R Chuma, S Nelson, M C'Connor, K Sam, A Harris, B Warren, D Anderson, KC Richardson, PG AF Ghobrial, I. M. Roccaro, A. M. Sportelli, P. Treon, S. P. Weller, E. Leleu, X. Rubin, N. Hong, F. Leduc, R. Chuma, S. Nelson, M. C'Connor, K. Sam, A. Harris, B. Warren, D. Anderson, K. C. Richardson, P. G. TI Perifosine: Final Results of a Phase II Trial in Relapsed/Refractory Waldenstrom Macroglobulinemia SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Ghobrial, I. M.; Treon, S. P.; Weller, E.; Leleu, X.; Hong, F.; Leduc, R.; Chuma, S.; Nelson, M.; C'Connor, K.; Sam, A.; Harris, B.; Warren, D.; Anderson, K. C.; Richardson, P. G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Rubin, N.] Community Hosp Monterey Peninsula, Monterey, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 SU 1 BP S83 EP S83 PG 1 WC Oncology SC Oncology GA 473LB UT WOS:000268206500187 ER PT J AU Ghobrial, IM Roccaro, AM Chuma, S Sam, AP Leduc, R Nelson, M O'Connor, K Harris, B Soumerai, J Warren, D Jacobsen, E DeAngelo, D Berg, W Anderson, KC Richardson, PG Witzig, TE Treon, SP AF Ghobrial, I. M. Roccaro, A. M. Chuma, S. Sam, A. P. Leduc, R. Nelson, M. O'Connor, K. Harris, B. Soumerai, J. Warren, D. Jacobsen, E. DeAngelo, D. Berg, W. Anderson, K. C. Richardson, P. G. Witzig, T. E. Treon, S. P. TI RAD001: Phase II Trial in Relapsed/Refractory Waldenstrom Macroglobulinemia, the DFCI Experience SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Ghobrial, I. M.; Roccaro, A. M.; Chuma, S.; Sam, A. P.; Leduc, R.; Nelson, M.; O'Connor, K.; Harris, B.; Soumerai, J.; Warren, D.; Jacobsen, E.; DeAngelo, D.; Anderson, K. C.; Richardson, P. G.; Witzig, T. E.; Treon, S. P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Berg, W.] Novartis Pharmaceut, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S82 EP S83 PG 2 WC Oncology SC Oncology GA 473LB UT WOS:000268206500186 ER PT J AU Ghobrial, IM Roccaro, A Azab, AK Runnels, J Leleu, X AF Ghobrial, Irene M. Roccaro, Aldo Azab, Abdel Kareem Runnels, Judith Leleu, Xavier TI Trafficking of Multiple Myeloma Cells: What Regulates Homing, Adhesion, and Mobilization of Multiple Myeloma to and from the Bone Marrow Niches SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract ID MEDIATED DRUG-RESISTANCE; HEMATOPOIETIC STEM; SDF-1; MIGRATION; INTEGRINS; SURVIVAL; THERAPY; LINES C1 [Ghobrial, Irene M.; Roccaro, Aldo; Azab, Abdel Kareem; Runnels, Judith; Leleu, Xavier] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 15 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 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S26 EP S27 PG 2 WC Oncology SC Oncology GA 472EE UT WOS:000268111400020 ER PT J AU Harousseau, JL Niesvizky, R Palumbo, A Richardson, PG Schlag, R Dimopoulos, MA Shpilberg, O Kropff, M Delforge, M Schots, R Cavo, M Golenkov, A Komarnicki, M Mateos, MV Cakana, A Liu, K Deraedt, W Boral, A van de Velde, H San Miguel, J AF Harousseau, J. L. Niesvizky, R. Palumbo, A. Richardson, P. G. Schlag, R. Dimopoulos, M. A. Shpilberg, O. Kropff, M. Delforge, M. Schots, R. Cavo, M. Golenkov, A. Komarnicki, M. Mateos, M. V. Cakana, A. Liu, K. Deraedt, W. Boral, A. van de Velde, H. San Miguel, J. TI A Prolonged Therapy Improves Quality of Response, and CR Associated with Superior Outcomes, with VMP SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Harousseau, J. L.; Niesvizky, R.] Cornell Univ, Weill Med Coll, New York, NY 10021 USA. [Palumbo, A.] Univ Turin, I-10124 Turin, Italy. [Richardson, P. G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Schlag, R.] Praxisklin Dr Schlag, Wurzburg, Germany. [Dimopoulos, M. A.] Univ Athens, Sch Med, GR-11527 Athens, Greece. [Shpilberg, O.] Rabin Med Ctr, Petah Tiqwa, Israel. [Kropff, M.] Univ Munster, D-4400 Munster, Germany. [Cavo, M.] Univ Bologna, Inst Hematol & Med Oncol Seragnoli, Bologna, Italy. [Komarnicki, M.] Univ Med Sci, Dept Hematol, Poznan, Poland. [Mateos, M. V.; San Miguel, J.] Hosp Univ Salamanca, CIC, IBMCC, USAL CSIC, Salamanca, Spain. [Cakana, A.] Johnson & Johnson Pharmaceut Res & Dev, High Wycombe, Bucks, England. [Liu, K.] Johnson & Johnson Pharmaceut Res & Dev LLC, Raritan, NJ USA. [Deraedt, W.; van de Velde, H.] Johnson & Johnson Pharmaceut Res & Dev, Beerse, Belgium. [Boral, A.] Millennium Takeda Oncol Co, Cambridge, MA USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S40 EP S40 PG 1 WC Oncology SC Oncology GA 473LB UT WOS:000268206500087 ER PT J AU Hideshima, T Ikeda, H Mitsiades, CC Chauhan, D Bradner, JE Munshi, NC Richardson, PG Anderson, KC AF Hideshima, Teru Ikeda, Hiroshi Mitsiades, Constantine C. Chauhan, Darminder Bradner, James E. Munshi, Nikhil C. Richardson, Paul G. Anderson, Kenneth C. TI Modulation of Signaling Cascades by Inhibitors of Histone Deacetylase and Akt SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract ID MULTIPLE-MYELOMA CELLS; CYTOTOXICITY C1 [Hideshima, Teru; Ikeda, Hiroshi; Mitsiades, Constantine C.; Chauhan, Darminder; Bradner, James E.; Munshi, Nikhil C.; Richardson, Paul G.; Anderson, Kenneth C.] Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr, Boston, MA 02115 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S12 EP S13 PG 2 WC Oncology SC Oncology GA 472EE UT WOS:000268111400009 ER PT J AU Husu, EN Roccaro, AM Anderson, KC Ghobrial, IM Leleu, X Sacco, A Melhem, MR Azab, AK Jia, X Ngo, HT Azab, F Runnels, J Quang, P AF Husu, E. N. Roccaro, A. M. Anderson, K. C. Ghobrial, I. M. Leleu, X. Sacco, A. Melhem, M. R. Azab, A. K. Jia, X. Ngo, H. T. Azab, F. Runnels, J. Quang, P. TI Dual PI3K and mTOR Inhibition in Waldenstrom Macroglobulinemia SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Husu, E. N.; Roccaro, A. M.; Anderson, K. C.; Ghobrial, I. M.; Leleu, X.; Sacco, A.; Melhem, M. R.; Azab, A. K.; Jia, X.; Ngo, H. T.; Azab, F.; Runnels, J.; Quang, P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S144 EP S145 PG 2 WC Oncology SC Oncology GA 473LB UT WOS:000268206500332 ER PT J AU Ikeda, H Hideshima, T Fulciniti, M Perrone, G Okawa, Y Yasui, H Vallet, S Santo, L Cristina, D Gorgun, G Calabrese, E Raje, NS Richardson, PG Munshi, NC Lannutti, B Puri, K Giese, N Anderson, KC AF Ikeda, H. Hideshima, T. Fulciniti, M. Perrone, G. Okawa, Y. Yasui, H. Vallet, S. Santo, L. Cristina, D. Gorgun, G. Calabrese, E. Raje, N. S. Richardson, P. G. Munshi, N. C. Lannutti, B. Puri, K. Giese, N. Anderson, K. C. TI CAL-101: A Selective Inhibitor of PI3K p110 delta for the Treatment of Multiple Myeloma SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Ikeda, H.; Hideshima, T.; Fulciniti, M.; Perrone, G.; Okawa, Y.; Yasui, H.; Vallet, S.; Santo, L.; Cristina, D.; Gorgun, G.; Calabrese, E.; Raje, N. S.; Richardson, P. G.; Munshi, N. C.; Anderson, K. C.] Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S98 EP S99 PG 2 WC Oncology SC Oncology GA 473LB UT WOS:000268206500222 ER PT J AU Jakubowiak, AJ Bensinger, W Zimmerman, T Chanan-Khan, A Singhal, A Siegel, D Anderson, KC AF Jakubowiak, A. J. Bensinger, W. Zimmerman, T. Chanan-Khan, A. Singhal, A. Siegel, D. Anderson, K. C. TI Phase I Study of Elotuzumab (HuLuc63) in Combination with Bortezomib in Relapsed Multiple Myeloma SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Jakubowiak, A. J.; Bensinger, W.] Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [Zimmerman, T.] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Chanan-Khan, A.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Singhal, A.] PDL BioPharma Inc, Redwood City, CA USA. [Siegel, D.] Hackensack Univ, Med Ctr, Hackensack, NJ USA. [Anderson, K. C.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 SU 1 BP S45 EP S45 PG 1 WC Oncology SC Oncology GA 473LB UT WOS:000268206500098 ER PT J AU Jakubowiak, AJ Hofmeister, C Campagnaro, E Kendall, T Zimmerman, T Schlossman, R Reece, D Lonial, S Hari, M Hector-Word, Z Griffith, K Tendler, C Esseltine, DL Bock, T Kaminski, M Dollard, A Kelley, S Anderson, KC Richardson, PG AF Jakubowiak, A. J. Hofmeister, C. Campagnaro, E. Kendall, T. Zimmerman, T. Schlossman, R. Reece, D. Lonial, S. Hari, M. Hector-Word, Z. Griffith, K. Tendler, C. Esseltine, D. L. Bock, T. Kaminski, M. Dollard, A. Kelley, S. Anderson, K. C. Richardson, P. G. TI Phase I/II Trial of Lenalidomide, Bortezomib, Doxil, and Dexamethasone in Front-Line Multiple Myeloma SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Jakubowiak, A. J.; Hofmeister, C.] Ohio State Univ, Columbus, OH 43210 USA. [Campagnaro, E.; Kendall, T.; Hari, M.; Hector-Word, Z.; Griffith, K.; Kaminski, M.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Zimmerman, T.] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Schlossman, R.; Anderson, K. C.; Richardson, P. G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Reece, D.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Lonial, S.] Winship Canc Inst, Atlanta, GA USA. [Tendler, C.] Centocor Ortho Biotech LLC, Bridgewater, NJ USA. [Esseltine, D. L.] Millennium Pharmaceut Takeda Oncol Co, Cambridge, MA USA. [Bock, T.] Celgene Inc, Summit, NJ USA. [Dollard, A.; Kelley, S.] Multiple Myeloma Res Consortium, Norwalk, CT USA. NR 0 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 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 SU 1 BP S45 EP S46 PG 2 WC Oncology SC Oncology GA 473LB UT WOS:000268206500099 ER PT J AU Jakubowiak, AJ Hideshima, T Sportelli, P Gardner, L Giusti, K Richardson, PG Zimmerman, T Alsina, M Kaufman, J Brozo, C Kendall, T McAllister, A Harvey, C Anderson, KC AF Jakubowiak, A. J. Hideshima, T. Sportelli, P. Gardner, L. Giusti, K. Richardson, P. G. Zimmerman, T. Alsina, M. Kaufman, J. Brozo, C. Kendall, T. McAllister, A. Harvey, C. Anderson, K. C. TI Phase I Trial of Perifosine, Lenalidomide, and Dexamethasone in Relapsed or Refractory Myeloma SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Jakubowiak, A. J.; Hideshima, T.; Richardson, P. G.; Anderson, K. C.] Dana Farber Canc Inst, Boston, MA USA. [Zimmerman, T.] Univ Chicago, Ctr Canc, Chicago, IL 60637 USA. [Alsina, M.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Brozo, C.; Kendall, T.; McAllister, A.; Harvey, C.] Univ Michigan, Ctr Canc, Ann Arbor, MI 48109 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S56 EP S57 PG 2 WC Oncology SC Oncology GA 473LB UT WOS:000268206500125 ER PT J AU Jia, X Roccaro, AM Azab, AK Ngo, HT Sacco, A Melhem, MR Azab, F Runnels, J Burwick, N Quang, P Husu, EN Leleu, X Anderson, KC Bradner, J Ghobrial, IM AF Jia, X. Roccaro, A. M. Azab, A. K. Ngo, H. T. Sacco, A. Melhem, M. R. Azab, F. Runnels, J. Burwick, N. Quang, P. Husu, E. N. Leleu, X. Anderson, K. C. Bradner, J. Ghobrial, I. M. TI Regulation of Histone Deacetylase in Waldenstrom Macroglobulinemia SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Jia, X.; Roccaro, A. M.; Azab, A. K.; Ngo, H. T.; Sacco, A.; Melhem, M. R.; Azab, F.; Runnels, J.; Burwick, N.; Quang, P.; Husu, E. N.; Leleu, X.; Anderson, K. C.; Bradner, J.; Ghobrial, I. M.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S143 EP S144 PG 2 WC Oncology SC Oncology GA 473LB UT WOS:000268206500329 ER PT J AU Kropff, M Richardson, PG Schlag, R Khuageva, N Dimopoulos, MA Shpilberg, O Schots, R Petrucci, M Neuwirth, R Boral, A Cakana, A Liu, K Deraedt, W Van de Velde, H Miguel, JS AF Kropff, M. Richardson, P. G. Schlag, R. Khuageva, N. Dimopoulos, M. A. Shpilberg, O. Schots, R. Petrucci, M. Neuwirth, R. Boral, A. Cakana, A. Liu, K. Deraedt, W. Van de Velde, H. Miguel, J. San TI Similar Benefit in Patients Aged >= 75 Years Versus < 75 Years with VMP in First-Line MM and Bortezomib in Relapsed MM SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Kropff, M.; Richardson, P. G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Schlag, R.] Praxisklin Dr Schlag, Wurzburg, Germany. [Khuageva, N.] SP Botkin Moscow City Clin Hosp, Moscow, Russia. [Dimopoulos, M. A.] Univ Athens, Sch Med, GR-10679 Athens, Greece. [Shpilberg, O.] Rabin Med Ctr, Petah Tiqwa, Israel. [Petrucci, M.] Univ Roma La Sapienza, Rome, Italy. [Neuwirth, R.] Takeda Oncol Co, Millennium, Cambridge, MA USA. [Cakana, A.] Johnson & Johnson Pharmaceut Res & Dev, High Wycombe, Bucks, England. [Liu, K.] Johnson & Johnson Pharmaceut Res & Dev LLC, Raritan, NJ USA. [Deraedt, W.; Van de Velde, H.] Johnson & Johnson Pharmaceut Res & Dev, Beerse, Belgium. [Miguel, J. San] Hosp Univ Salamanca, CSIC, USAL, IBMCC,CIC, Salamanca, Spain. NR 0 TC 1 Z9 1 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S12 EP S12 PG 1 WC Oncology SC Oncology GA 473LB UT WOS:000268206500024 ER PT J AU Kumar, S Flinn, I Noga, S Hari, R Rifkin, R Callander, N Bhandari, M Wolf, J Gasparetto, C Krishnan, A Grosman, D Glass, J Sahovic, EA Shi, J Webb, I Richardson, PG Rajkumar, SV AF Kumar, S. Flinn, Ian Noga, S. Hari, R. Rifkin, R. Callander, N. Bhandari, M. Wolf, J. Gasparetto, C. Krishnan, A. Grosman, D. Glass, J. Sahovic, E. A. Shi, J. Webb, I. Richardson, P. G. Rajkumar, S. V. TI Bortezomib, Dexamethasone, Cyclophosphamide, Lenalidomide (VDCR) Has High Efficacy in First-Line MM SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Kumar, S.; Flinn, Ian] Sarah Cannon Res Inst, Nashville, TN USA. [Noga, S.] Sinai Hosp, Baltimore, MD 21215 USA. [Hari, R.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Rifkin, R.] Rocky Mt Canc Ctr, Denver, CO USA. [Callander, N.] Univ Wisconsin, Ctr Comprehens Canc, Madison, WI USA. [Bhandari, M.] Christ Hosp Res, Cincinnati, OH USA. [Wolf, J.] Univ Calif San Francisco, Med Ctr, San Francisco, CA 94143 USA. [Gasparetto, C.] Duke Univ, Durham, NC USA. [Krishnan, A.] City Hope Natl Med Ctr, Duarte, CA USA. [Grosman, D.] Mem Canc Inst, Hollywood, FL USA. [Glass, J.] LSUHSC, Shreveport, LA USA. [Sahovic, E. A.] Western Penn Hosp, Pittsburgh, PA 15224 USA. [Webb, I.] Millennium Takeda Oncol Co, Cambridge, MA USA. [Richardson, P. G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Rajkumar, S. V.] Mayo Clin, Div Hematol, Rochester, MN USA. RI Kumar, Shaji/A-9853-2008 OI Kumar, Shaji/0000-0001-5392-9284 NR 0 TC 1 Z9 1 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S43 EP S44 PG 2 WC Oncology SC Oncology GA 473LB UT WOS:000268206500094 ER PT J AU Leleu, X Roccaro, AM Ngo, HT Azab, AK Azab, F Hong, F Jia, X Sacco, A Moreau, AS Runnels, J Melhem, MR Weller, E Anderson, KC Ghobrial, IM AF Leleu, X. Roccaro, A. M. Ngo, H. T. Azab, A. K. Azab, F. Hong, F. Jia, X. Sacco, A. Moreau, A. S. Runnels, J. Melhem, M. R. Weller, E. Anderson, K. C. Ghobrial, I. M. TI Gene Transcriptional Activity Analysis of the 6q Region in Waldenstrom Macroglobulinemia SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Leleu, X.; Roccaro, A. M.; Ngo, H. T.; Azab, A. K.; Azab, F.; Hong, F.; Jia, X.; Sacco, A.; Moreau, A. S.; Runnels, J.; Melhem, M. R.; Weller, E.; Anderson, K. C.; Ghobrial, I. M.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S145 EP S145 PG 1 WC Oncology SC Oncology GA 473LB UT WOS:000268206500333 ER PT J AU Lonial, S Giralt, S Durie, B Barlogie, B Stadtmauer, E Anderson, KC Rajkumar, SV AF Lonial, Sagar Giralt, Sergio Durie, Brian Barlogie, Bart Stadtmauer, Edward Anderson, Kenneth C. Rajkumar, S. Vincent TI US Cooperative Group Trials SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Lonial, Sagar] Emory Univ, Atlanta, GA 30322 USA. [Giralt, Sergio] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Durie, Brian] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Barlogie, Bart] Univ Arkansas, Fayetteville, AR 72701 USA. [Stadtmauer, Edward] Univ Penn, Philadelphia, PA 19104 USA. [Anderson, Kenneth C.] Dana Farber Canc Ctr, Boston, MA USA. [Rajkumar, S. Vincent] Mayo Clin, Rochester, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S34 EP S35 PG 2 WC Oncology SC Oncology GA 472EE UT WOS:000268111400025 ER PT J AU Mateos, MV Richardson, PG Schlag, R Khuageva, N Dimopoulos, MA Shpilberg, O Kropff, M Spicka, I Palumbo, A Schots, R Liu, K Cakana, A van de Velde, H San Miguel, J AF Mateos, M. V. Richardson, P. G. Schlag, R. Khuageva, N. Dimopoulos, M. A. Shpilberg, O. Kropff, M. Spicka, I. Palumbo, A. Schots, R. Liu, K. Cakana, A. van de Velde, H. San Miguel, J. TI Peripheral Neuropathy with VMP Resolves in the Majority of Patients and Shows a Rate Plateau SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Mateos, M. V.; Richardson, P. G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Schlag, R.] Praxisklin Dr Schlag, Wurzburg, Germany. [Khuageva, N.] SP Botkin Moscow City Clin Hosp, Moscow, Russia. [Dimopoulos, M. A.] Univ Athens, Sch Med, GR-11527 Athens, Greece. [Shpilberg, O.] Rabin Med Ctr, Petah Tiqwa, Israel. [Kropff, M.] Univ Munster, D-4400 Munster, Germany. [Spicka, I.] Univ Hosp, Prague, Czech Republic. [Palumbo, A.] Univ Turin, I-10124 Turin, Italy. [Liu, K.] Johnson & Johnson Pharmaceut Res & Dev LLC, Raritan, NJ USA. [Cakana, A.] Johnson & Johnson Pharmaceut Res & Dev, High Wycombe, Bucks, England. [van de Velde, H.] Johnson & Johnson Pharmaceut Res & Dev, Beerse, Belgium. [San Miguel, J.] Hosp Univ Salamanca CIC, IBMCC, USAL CSIC, Salamanca, Spain. NR 0 TC 7 Z9 7 U1 0 U2 1 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S30 EP S30 PG 1 WC Oncology SC Oncology GA 473LB UT WOS:000268206500064 ER PT J AU Melhem, MR Roccaro, AM Ghobrial, IM Quang, P Husu, EN Burwick, N Farag, M Azab, AK Ngo, HT Sacco, A Jia, X Azab, F Runnels, J Hideshima, T Anderson, KC Leleu, X AF Melhem, M. R. Roccaro, A. M. Ghobrial, I. M. Quang, P. Husu, E. N. Burwick, N. Farag, M. Azab, A. K. Ngo, H. T. Sacco, A. Jia, X. Azab, F. Runnels, J. Hideshima, T. Anderson, K. C. Leleu, X. TI The Effect of Insulin-Like Growth Factor-1 in Waldenstrom Macroglobulinemia SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Melhem, M. R.; Roccaro, A. M.; Ghobrial, I. M.; Quang, P.; Husu, E. N.; Burwick, N.; Farag, M.; Azab, A. K.; Ngo, H. T.; Sacco, A.; Jia, X.; Azab, F.; Runnels, J.; Hideshima, T.; Anderson, K. C.; Leleu, X.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S146 EP S147 PG 2 WC Oncology SC Oncology GA 473LB UT WOS:000268206500336 ER PT J AU Melhem, MR Roccaro, AM Azab, AK Ngo, HT Sacco, A Jia, X Azab, F Runnels, J Burwick, N Quang, P Husu, EN Leleu, X Anderson, KC Ghobrial, IM AF Melhem, M. R. Roccaro, A. M. Azab, A. K. Ngo, H. T. Sacco, A. Jia, X. Azab, F. Runnels, J. Burwick, N. Quang, P. Husu, E. N. Leleu, X. Anderson, K. C. Ghobrial, I. M. TI PKC412, Small-Molecule Tyrosine Kinase Inhibitor, Regulates Survival in Waldenstrom Macroglobulinemia SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Melhem, M. R.; Roccaro, A. M.; Azab, A. K.; Ngo, H. T.; Sacco, A.; Jia, X.; Azab, F.; Runnels, J.; Burwick, N.; Quang, P.; Husu, E. N.; Leleu, X.; Anderson, K. C.; Ghobrial, I. M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S144 EP S144 PG 1 WC Oncology SC Oncology GA 473LB UT WOS:000268206500330 ER PT J AU Mitsiades, C Richardson, PG Grant, S Pei, XY Berenson, JR Richon, V Garcia-Vargas, J Rizvi, S Anderson, KC AF Mitsiades, C. Richardson, P. G. Grant, S. Pei, X-Y Berenson, J. R. Richon, V. Garcia-Vargas, J. Rizvi, S. Anderson, K. C. TI Vorinostat in Combination with Other Anti-MM Agents SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Mitsiades, C.; Richardson, P. G.; Anderson, K. C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Grant, S.; Pei, X-Y] Massey Canc Ctr VCU, Richmond, VA USA. [Berenson, J. R.] Inst Myeloma & Bone Canc Res, W Hollywood, CA USA. [Richon, V.; Garcia-Vargas, J.; Rizvi, S.] Merck & Co Inc, Upper Gwynedd, PA USA. NR 0 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 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 SU 1 BP S117 EP S118 PG 2 WC Oncology SC Oncology GA 473LB UT WOS:000268206500266 ER PT J AU Mitsiades, C Richardson, PG Grant, S Pei, XY Berenson, JR Richon, V Garcia-Vargas, J Rizvi, S Anderson, KC AF Mitsiades, C. Richardson, P. G. Grant, S. Pei, X-Y Berenson, J. R. Richon, V. Garcia-Vargas, J. Rizvi, S. Anderson, K. C. TI Serum DKK1 Levels in Multiple Myeloma SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Mitsiades, C.; Richardson, P. G.; Anderson, K. C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Grant, S.; Pei, X-Y] Massey Canc Ctr VCU, Richmond, VA USA. [Berenson, J. R.] Inst Myeloma & Bone Canc Res, W Hollywood, CA USA. [Richon, V.; Garcia-Vargas, J.; Rizvi, S.] Merck & Co Inc, Upper Gwynedd, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 SU 1 BP S117 EP S117 PG 1 WC Oncology SC Oncology GA 473LB UT WOS:000268206500265 ER PT J AU Mitsiades, CS McMillin, DW Delmore, J Negri, J Klippel, S Ooi, M Munshi, NC Richardson, PG Anderson, KC AF Mitsiades, Constantine S. McMillin, Douglas W. Delmore, Jake Negri, Joseph Klippel, Steffen Ooi, Melissa Munshi, Nikhil C. Richardson, Paul G. Anderson, Kenneth C. TI Molecular Pathways Induced by Tumor-Microenvironment Interactions in Myeloma and the Regulatory Role of Heat-Shock Proteins SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Mitsiades, Constantine S.; McMillin, Douglas W.; Delmore, Jake; Negri, Joseph; Klippel, Steffen; Ooi, Melissa; Munshi, Nikhil C.; Richardson, Paul G.; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myelorna Ct, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S13 EP S14 PG 2 WC Oncology SC Oncology GA 472EE UT WOS:000268111400010 ER PT J AU Moran, D Bilotti, E Rome, S Richards, T Faiman, BM Colson, K Westphal, J Tariman, J Spong, JE Miller, K Miceli, T McCullagh, E Mangan, PA Love, G Lilleby, K Jenkins, BS Doss, D Daily, K Bertolotti, P AF Moran, D. Bilotti, E. Rome, S. Richards, T. Faiman, B. M. Colson, K. Westphal, J. Tariman, J. Spong, J. E. Miller, K. Miceli, T. McCullagh, E. Mangan, P. A. Love, G. Lilleby, K. Jenkins, B. S. Doss, D. Daily, K. Bertolotti, P. TI Long-Term Care Guidelines for Myeloma Patients SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Moran, D.; Bilotti, E.] Hackensack Univ Med Ctr, Hackensack, NJ USA. [Rome, S.; Bertolotti, P.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Richards, T.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Faiman, B. M.] Taussig Canc Inst, Cleveland Clin, Cleveland, OH USA. [Colson, K.; Doss, D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Westphal, J.] Meeker Cty Mem Hosp, Litchfield, MN USA. [Tariman, J.] Univ Washington, Seattle, WA 98195 USA. [Spong, J. E.] Mayo Clin Arizona, Scottsdale, AZ USA. [Miller, K.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Miceli, T.] Mayo Clin, Rochester, MN USA. [McCullagh, E.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Mangan, P. A.] Univ Penn, Sch Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Love, G.] Univ Cincinnati Hem Onc Care, Cincinnati, OH USA. [Lilleby, K.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Jenkins, B. S.] Univ Arkansas, Sch Med, Myeloma Inst, Little Rock, AR 72204 USA. [Daily, K.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. NR 0 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 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S6 EP S7 PG 2 WC Oncology SC Oncology GA 473LB UT WOS:000268206500012 ER PT J AU Ngo, HT Ahmann, G Leleu, X Jia, X Hatjiharissi, E Leontovich, AA Chng, W Farag, M Timm, M Melhem, M George, D Runnels, J Roccaro, AM Azab, AK Azab, F Sacco, A Burwick, N Melhem, MM Greipp, P Fonseca, R Gertz, MA Anderson, KC Witzig, TE Ghobrial, IM AF Ngo, H. T. Ahmann, G. Leleu, X. Jia, X. Hatjiharissi, E. Leontovich, A. A. Chng, W. Farag, M. Timm, M. Melhem, M. George, D. Runnels, J. Roccaro, A. M. Azab, A. K. Azab, F. Sacco, A. Burwick, N. Melhem, M. M. Greipp, P. Fonseca, R. Gertz, M. A. Anderson, K. C. Witzig, T. E. Ghobrial, I. M. TI Proteomic Analysis of Multiple Myeloma Identifies Upregulation of the Novel Protein CRIK SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Ahmann, G.; Chng, W.] Mayo Clin, Div Hematol, Rochester, MN 55905 USA. [Ngo, H. T.; Leleu, X.; Jia, X.; Hatjiharissi, E.; Farag, M.; Runnels, J.; Roccaro, A. M.; Azab, A. K.; Azab, F.; Sacco, A.; Burwick, N.; Melhem, M. M.; Anderson, K. C.; Ghobrial, I. M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Leontovich, A. A.; Timm, M.; Greipp, P.; Gertz, M. A.; Witzig, T. E.] Mayo Clin, Div Hematol, Rochester, MN USA. [Melhem, M.; George, D.] Pittsburgh Healthcare Syst, Dept Pathol, Pittsburgh, PA USA. [Fonseca, R.] Mayo Clin, Div Hematol, Scottsdale, AZ USA. NR 0 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 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S146 EP S146 PG 1 WC Oncology SC Oncology GA 473LB UT WOS:000268206500335 ER PT J AU Ngo, HT Roccaro, AM Farag, M Jia, X Burwick, N Melhem, MR Leleu, X Runnels, J Azab, AK Azab, F Sacco, A Quang, P Tai, YT Anderson, KC Ghobrial, IM AF Ngo, H. T. Roccaro, A. M. Farag, M. Jia, X. Burwick, N. Melhem, M. R. Leleu, X. Runnels, J. Azab, A. K. Azab, F. Sacco, A. Quang, P. Tai, Y. T. Anderson, K. C. Ghobrial, I. M. TI The Tyrosine Kinase Src Regulates Adhesion and Survival in Waldenstrom Macroglobulinemia SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Ngo, H. T.; Roccaro, A. M.; Farag, M.; Jia, X.; Burwick, N.; Melhem, M. R.; Leleu, X.; Runnels, J.; Azab, A. K.; Azab, F.; Sacco, A.; Quang, P.; Tai, Y. T.; Anderson, K. C.; Ghobrial, I. M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S144 EP S144 PG 1 WC Oncology SC Oncology GA 473LB UT WOS:000268206500331 ER PT J AU Podar, K Zimmerhacki, A Zhang, J Tonon, G Barila, D Vallet, S Sattler, M Tai, YT Hideshima, T Chauhan, D Anderson, KC AF Podar, K. Zimmerhacki, A. Zhang, J. Tonon, G. Barila, D. Vallet, S. Sattler, M. Tai, Y. T. Hideshima, T. Chauhan, D. Anderson, K. C. TI Mcl-1 Fragment Mcl-1128-350 Induces Inhibition of Multiple Myeloma Cell Proliferation and Apoptosis SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Podar, K.; Zimmerhacki, A.; Zhang, J.; Tonon, G.; Tai, Y. T.; Hideshima, T.; Chauhan, D.; Anderson, K. C.] Dana Farber Canc Inst, HMS, Boston, MA USA. [Barila, D.] Univ Tor Vergata, Rome, Italy. [Vallet, S.] Massachusetts Gen Hosp, Ctr Multiple Myeloma, Boston, MA 02114 USA. RI Barila, Daniela/K-8506-2016 OI Barila, Daniela/0000-0002-6192-1562 NR 0 TC 0 Z9 0 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S137 EP S137 PG 1 WC Oncology SC Oncology GA 473LB UT WOS:000268206500312 ER PT J AU Pozzi, S Yan, H Vallet, S Fulciniti, M Vaghela, N Cirstea, D Santo, L Patel, K Mukherjee, S Hideshima, T Schirtzinger, L Kuhstoss, S Anderson, KC Scadden, D Raje, N AF Pozzi, S. Yan, H. Vallet, S. Fulciniti, M. Vaghela, N. Cirstea, D. Santo, L. Patel, K. Mukherjee, S. Hideshima, T. Schirtzinger, L. Kuhstoss, S. Anderson, K. C. Scadden, D. Raje, N. TI A New Anti-Dkk-1 Antibody Targeting Myeloma Bone Disease SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Pozzi, S.; Yan, H.; Vallet, S.; Vaghela, N.; Patel, K.; Mukherjee, S.; Scadden, D.; Raje, N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Vallet, S.; Fulciniti, M.; Vaghela, N.; Cirstea, D.; Santo, L.; Hideshima, T.; Anderson, K. C.; Raje, N.] Dana Farber Canc Inst, Boston, MA USA. [Schirtzinger, L.; Kuhstoss, S.] Eli Lilly & Co, Indianapolis, IN USA. RI Pozzi, Samantha/A-7617-2012 OI Pozzi, Samantha/0000-0001-7917-1774 NR 0 TC 0 Z9 0 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S111 EP S111 PG 1 WC Oncology SC Oncology GA 473LB UT WOS:000268206500253 ER PT J AU Prabhala, RH Pelluru, D Fulciniti, M Nanjappa, P Prabhala, NS Mitsiaties, C Lefkimmiatis, K Tai, YT Efebera, YA Daley, JF Anderson, KC Munshi, NC AF Prabhala, R. H. Pelluru, D. Fulciniti, M. Nanjappa, P. Prabhala, N. S. Mitsiaties, C. Lefkimmiatis, K. Tai, Y. T. Efebera, Y. A. Daley, J. F. Anderson, K. C. Munshi, N. C. TI IL-17 Promotes Tumor cell Growth and Survival, and Inhibits Immune Function in Myeloma SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Prabhala, R. H.; Pelluru, D.; Fulciniti, M.; Nanjappa, P.; Prabhala, N. S.; Mitsiaties, C.; Lefkimmiatis, K.; Tai, Y. T.; Efebera, Y. A.; Daley, J. F.; Anderson, K. C.; Munshi, N. C.] Dana Farber Canc Inst, VABHS, Boston, MA USA. RI Efebera, Yvonne/E-3012-2011 NR 0 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 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S159 EP S159 PG 1 WC Oncology SC Oncology GA 473LB UT WOS:000268206500367 ER PT J AU Raab, MS Breitkreutz, I Rebacz, B Hayden, PJ Larsen, TO Clausen, MH Fruehauf, JH Goldschmidt, H Anderson, KC Kraemer, A AF Raab, M. S. Breitkreutz, I. Rebacz, B. Hayden, P. J. Larsen, T. O. Clausen, M. H. Fruehauf, J. H. Goldschmidt, H. Anderson, K. C. Kraemer, A. TI Centrosomal Clustering: A Novel Therapeutic Target for Multiple Myeloma SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Raab, M. S.; Breitkreutz, I.; Hayden, P. J.; Anderson, K. C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Rebacz, B.; Kraemer, A.] German Canc Res Ctr, CCU Mol Hematol Oncol, D-6900 Heidelberg, Germany. [Larsen, T. O.; Clausen, M. H.] Tech Univ Denmark, Bioctr, Copenhagen, Denmark. [Fruehauf, J. H.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Goldschmidt, H.] Univ Heidelberg, Dept Med, Natl Ctr Tumor Dis, D-6900 Heidelberg, Germany. RI Clausen, Mads/A-9656-2015 OI Clausen, Mads/0000-0001-9649-1729 NR 0 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 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S153 EP S153 PG 1 WC Oncology SC Oncology GA 473LB UT WOS:000268206500351 ER PT J AU Rajpal, R Dowling, P Meiller, J Murphy, W Murphy, P O'Driscol, L O'Connor, R Anderson, KC Clynes, M O'Gorman, P AF Rajpal, R. Dowling, P. Meiller, J. Murphy, W. Murphy, P. O'Driscol, L. O'Connor, R. Anderson, K. C. Clynes, M. O'Gorman, P. TI Panel of Potential Proteomic Biomarkers for Predicting Response to Thalidomide in Multiple Myeloma SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Rajpal, R.; Dowling, P.; Meiller, J.; O'Driscol, L.; O'Connor, R.] Dublin City Univ, Natl Inst Cellular Biotechnol, Dublin 9, Ireland. [Murphy, W.] Irish Blood Transfus Serv, Dublin, Ireland. [Murphy, P.] Beaumont Hosp, Dublin 9, Ireland. [Anderson, K. C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [O'Gorman, P.] Mater Misericordiae Univ Hosp, Dublin 7, Ireland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S119 EP S120 PG 2 WC Oncology SC Oncology GA 473LB UT WOS:000268206500271 ER PT J AU Richardson, PG Lonial, S Jakubowiak, A Jagannath, S Raje, N Avigan, D Ghobrial, IM Schlossman, R Mazumder, A Munshi, NC Vesole, D Joyce, R Doss, D Warren, D Lunde, L Lukas, R Kaster, S Shea, K Delaney, C Lauria, M Mitsiades, C Hideshima, T Knight, R Esseltine, DL Anderson, KC AF Richardson, P. G. Lonial, S. Jakubowiak, A. Jagannath, S. Raje, N. Avigan, D. Ghobrial, I. M. Schlossman, R. Mazumder, A. Munshi, N. C. Vesole, D. Joyce, R. Doss, D. Warren, D. Lunde, L. Lukas, R. Kaster, S. Shea, K. Delaney, C. Lauria, M. Mitsiades, C. Hideshima, T. Knight, R. Esseltine, D. L. Anderson, K. C. TI Lenalidomide, Bortezomib, and Dexamethasone Has Notable Activity in High-Risk First-Line Myeloma SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Richardson, P. G.; Lonial, S.] Winship Canc Inst, Atlanta, GA 48109 USA. [Jakubowiak, A.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI USA. [Jagannath, S.; Mazumder, A.] St Vincents Comprehens Canc Ctr, New York, NY 02114 USA. [Raje, N.; Kaster, S.; Shea, K.] Massachusetts Gen Hosp, Boston, MA 02215 USA. [Avigan, D.; Joyce, R.; Delaney, C.; Lauria, M.] Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Ghobrial, I. M.; Schlossman, R.; Munshi, N. C.; Doss, D.; Warren, D.; Lunde, L.; Lukas, R.; Mitsiades, C.; Hideshima, T.; Anderson, K. C.] Dana Farber Canc Inst, Boston, MA 60153 USA. [Vesole, D.] Loyola Univ, Med Ctr, Div Hematol Oncol, Maywood, IL USA. [Knight, R.] Celgene Inc, Summit, NJ USA. [Esseltine, D. L.] Millennium Takeda Oncol Co, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S38 EP S38 PG 1 WC Oncology SC Oncology GA 473LB UT WOS:000268206500082 ER PT J AU Richardson, PG Rosovsky, R Hong, F Tocco, D Connell, B Mitsiades, C Schlossman, R Ghobrial, IM Munshi, NC Lockridge, L Warren, D Bradwin, G Doyle, M Soiffer, R Anderson, KC Weller, E Richardson, PG AF Richardson, P. G. Rosovsky, R. Hong, F. Tocco, D. Connell, B. Mitsiades, C. Schlossman, R. Ghobrial, I. M. Munshi, N. C. Lockridge, L. Warren, D. Bradwin, G. Doyle, M. Soiffer, R. Anderson, K. C. Weller, E. Richardson, P. G. TI Endothelial Stress Markers in Multiple Myeloma Patients SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Richardson, P. G.; Rosovsky, R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hong, F.; Tocco, D.; Connell, B.; Mitsiades, C.; Schlossman, R.; Ghobrial, I. M.; Munshi, N. C.; Lockridge, L.; Warren, D.; Soiffer, R.; Anderson, K. C.; Weller, E.; Richardson, P. G.] Dana Farber Canc Inst, Boston, MA USA. [Bradwin, G.] Childrens Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S55 EP S55 PG 1 WC Oncology SC Oncology GA 473LB UT WOS:000268206500121 ER PT J AU Richardson, PG Wolf, J Jakubowiak, A Zonder, J Lonial, S Irwin, D Densmore, J Krishnan, A Raje, N Bar, M Schlossman, R Ghobrial, IM Munshi, NC Martin, T Laubach, J Colson, K Dean, S Tocco, D Steinfield, E Kendall, T O'Riley, K Francis, D Hideshima, T Sportelli, P Gardner, L Anderson, KC AF Richardson, P. G. Wolf, J. Jakubowiak, A. Zonder, J. Lonial, S. Irwin, D. Densmore, J. Krishnan, A. Raje, N. Bar, M. Schlossman, R. Ghobrial, I. M. Munshi, N. C. Martin, T. Laubach, J. Colson, K. Dean, S. Tocco, D. Steinfield, E. Kendall, T. O'Riley, K. Francis, D. Hideshima, T. Sportelli, P. Gardner, L. Anderson, K. C. TI Phase I/II Trial of Perifosine plus Bortezomib in Rel/Ref MM Patients Previously Treated with Bortezomib SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Richardson, P. G.; Wolf, J.; Martin, T.; Steinfield, E.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Jakubowiak, A.; Kendall, T.] Univ Michigan, Ctr Canc, Ann Arbor, MI 48109 USA. [Zonder, J.; O'Riley, K.] Karmanos Canc Ctr, Detroit, MI 48201 USA. [Lonial, S.; Francis, D.] Emory Winship Canc Inst, Atlanta, GA USA. [Irwin, D.] Alta Bates Canc Ctr, Berkeley, CA USA. [Densmore, J.] Univ Virginia, Ctr Canc, Charlottesville, VA 22903 USA. [Krishnan, A.] City Hope Natl Med Ctr, Duarte, CA USA. [Raje, N.] Mass Gen Hosp, Ctr Canc, Boston, MA USA. [Bar, M.] Hematol Oncol Stamford, Stamford, CT USA. [Schlossman, R.; Ghobrial, I. M.; Munshi, N. C.; Laubach, J.; Colson, K.; Dean, S.; Tocco, D.; Hideshima, T.; Anderson, K. C.] Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S57 EP S57 PG 1 WC Oncology SC Oncology GA 473LB UT WOS:000268206500126 ER PT J AU Richardson, PG Hideshima, T Jagannath, S Jakubowiak, A Lonial, S Raje, N Alsina, M Ghobrial, IM Schlossman, R Mazumder, A Munshi, NC Vesole, D Colson McKenney Lunde Kennedy Kosakowski Mitsiades, C Knight Esseltine Anderson, KC AF Richardson, P. G. Hideshima, T. Jagannath, S. Jakubowiak, A. Lonial, S. Raje, N. Alsina, M. Ghobrial, I. M. Schlossman, R. Mazumder, A. Munshi, N. C. Vesole, D. Colson McKenney Lunde Kennedy Kosakowski Mitsiades, C. Knight Esseltine Anderson, K. C. TI Lenalidomide, Bortezomib, and Dexamethasone Is Active in High-Risk Relapsed/Refractory Myeloma SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Richardson, P. G.; Hideshima, T.; Ghobrial, I. M.; Schlossman, R.; Colson; McKenney; Lunde; Mitsiades, C.; Anderson, K. C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Jagannath, S.; Mazumder, A.; Munshi, N. C.; Kennedy] St Vincents Comprehens Canc Ctr, New York, NY USA. [Jakubowiak, A.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Lonial, S.] Winship Canc Inst, Atlanta, GA USA. [Raje, N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Alsina, M.; Kosakowski] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Vesole, D.] Loyola Univ, Med Ctr, Div Hematol Oncol, Maywood, IL 60153 USA. [Knight] Celgene Inc, Summit, NJ USA. [Esseltine] Millennium Takeda Oncol Co, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S38 EP S38 PG 1 WC Oncology SC Oncology GA 473LB UT WOS:000268206500083 ER PT J AU Richardson, PG Schlag, R Khuageva, N Dimopoulos, MA Shpilberg, O Kropff, M Delforge, M Petrucci, M Rossiev, V Hou, J Robak, T Mateos, MV Anderson, KC Cakana, A Liu, A Deraedt, W van de Velde, H San Miguel, J AF Richardson, P. G. Schlag, R. Khuageva, N. Dimopoulos, M. A. Shpilberg, O. Kropff, M. Delforge, M. Petrucci, M. Rossiev, V. Hou, J. Robak, T. Mateos, M. V. Anderson, K. C. Cakana, A. Liu, A. Deraedt, W. van de Velde, H. San Miguel, J. TI Bortezomib and Melphalan as Part of VMP Are Associated with Similar Hematologic Toxicity to MP Alone SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Richardson, P. G.; Schlag, R.] Praxisklin Dr Schlag, Wurzburg, Germany. [Khuageva, N.] SP Botkin Moscow City Clin Hosp, Moscow, Russia. [Dimopoulos, M. A.] Univ Athens, Sch Med, GR-10679 Athens, Greece. [Shpilberg, O.] Rabin Med Ctr, Petah Tiqwa, Israel. [Kropff, M.] Univ Munster, D-4400 Munster, Germany. [Petrucci, M.] Univ Roma La Sapienza, Rome, Italy. [Rossiev, V.] Samara Reg Clin Hosp, Samara, Russia. [Hou, J.] Shanghai Changzheng Hosp, Shanghai, Peoples R China. [Robak, T.] Med Univ Lodz, Lodz, Poland. [Mateos, M. V.; San Miguel, J.] Hosp Univ Salamanca, CIC, IBMCC, USAL CSIC, Salamanca, Spain. [Anderson, K. C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Cakana, A.] Johnson & Johnson Pharmaceut Res & Dev, High Wycombe, Bucks, England. [Liu, A.] Johnson & Johnson Pharmaceut Res & Dev LLC, Raritan, NJ USA. [Deraedt, W.; van de Velde, H.] Johnson & Johnson Pharmaceut Res & Dev, Beerse, Belgium. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S36 EP S37 PG 2 WC Oncology SC Oncology GA 473LB UT WOS:000268206500079 ER PT J AU Richardson, PG Liu, K Deraedt, W van de Velde, H Schlag, R Khuageva, N Dimopoulos, MA Shpilberg, O Kropff, M Delforge, M Petrucci, M Rossiev, V Hou, J Robak, T Mateos, MV Anderson, KC Cakana, A San Miguel, J AF Richardson, P. G. Liu, K. Deraedt, W. van de Velde, H. Schlag, R. Khuageva, N. Dimopoulos, M. A. Shpilberg, O. Kropff, M. Delforge, M. Petrucci, M. Rossiev, V. Hou, J. Robak, T. Mateos, M. V. Anderson, K. C. Cakana, A. San Miguel, J. TI Erythropoiesis-Stimulating Agents: No Impact on Long-Term Outcome in MM Patients in the VISTA Trial SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Richardson, P. G.; Liu, K.] Johnson & Johnson Pharmaceut Res & Dev LLC, Raritan, NJ USA. [Deraedt, W.; van de Velde, H.] Johnson & Johnson Pharmaceut Res & Dev, Beerse, Belgium. [Schlag, R.] Praxisklin Dr Schlag, Wurzburg, Germany. [Khuageva, N.] SP Botkin Moscow City Clin Hosp, Moscow, Russia. [Dimopoulos, M. A.] Univ Athens, Sch Med, GR-10679 Athens, Greece. [Shpilberg, O.] Rabin Med Ctr, Petah Tiqwa, Israel. [Kropff, M.] Univ Munster, D-4400 Munster, Germany. [Petrucci, M.] Univ Roma La Sapienza, Rome, Italy. [Rossiev, V.] Samara Reg Clin Hosp, Samara 443095, Russia. [Hou, J.] Shanghai Changzheng Hosp, Shanghai 200003, Peoples R China. [Robak, T.] Med Univ Lodz, PL-93510 Lodz, Poland. [Mateos, M. V.; San Miguel, J.] Hosp Univ Salamanca, CIC, IBMCC, USAL CSIC, Salamanca, Spain. [Anderson, K. C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Cakana, A.] Johnson & Johnson Pharmaceut Res & Dev, High Wycombe, Bucks, England. NR 0 TC 1 Z9 1 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S35 EP S36 PG 2 WC Oncology SC Oncology GA 473LB UT WOS:000268206500077 ER PT J AU Richardson, P Laubach, J Schlossman, R Ghobrial, I Mitsiades, C Hideshima, T Chauhan, D Raje, N Munshi, NC Anderson, KC AF Richardson, Paul Laubach, Jacob Schlossman, Robert Ghobrial, Irene Mitsiades, Constantine Hideshima, Teru Chauhan, Dharminder Raje, Noopur Munshi, Nikhil C. Anderson, Kenneth C. TI Novel Combination Therapies for the Treatment of Relapsed/Refractory Multiple Myeloma: Current Phase I/II Combinations SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract ID PLUS BORTEZOMIB; LENALIDOMIDE; CHEMOTHERAPY; TRIAL C1 [Richardson, Paul; Laubach, Jacob; Schlossman, Robert; Ghobrial, Irene; Mitsiades, Constantine; Hideshima, Teru; Chauhan, Dharminder; Raje, Noopur; Munshi, Nikhil C.; Anderson, Kenneth C.] Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Raje, Noopur] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. NR 16 TC 0 Z9 0 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 SU 2 BP S40 EP S42 PG 3 WC Oncology SC Oncology GA 472EE UT WOS:000268111400030 ER PT J AU Roccaro, AM Melhem, MR Leleu, X Quang, P Sacco, A Azab, AK Thompson, B Runnels, J Azab, F Jia, X Ngo, HT Rollins, BJ Fonseca, R Lin, CP Anderson, KC Witzig, T Ghobrial, IM AF Roccaro, A. M. Melhem, M. R. Leleu, X. Quang, P. Sacco, A. Azab, A. K. Thompson, B. Runnels, J. Azab, F. Jia, X. Ngo, H. T. Rollins, B. J. Fonseca, R. Lin, C. P. Anderson, K. C. Witzig, T. Ghobrial, I. M. TI MicroRNA Regulate Growth and Angiogenesis in Multiple Myeloma SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Roccaro, A. M.; Melhem, M. R.; Leleu, X.; Quang, P.; Sacco, A.; Azab, A. K.; Runnels, J.; Azab, F.; Jia, X.; Ngo, H. T.; Rollins, B. J.; Fonseca, R.; Anderson, K. C.; Ghobrial, I. M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Witzig, T.] Mayo Clin, Scottsdale, AZ USA. NR 0 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 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S153 EP S154 PG 2 WC Oncology SC Oncology GA 473LB UT WOS:000268206500353 ER PT J AU Roccaro, AM Jia, X Ngo, HT Melhem, MR Sacco, A Chen, C Leleu, X Runnels, J Azab, F Azab, AK Quang, P Varticovski, L Novina, CD Rollins, BJ Anderson, KC Ghobrial, IM AF Roccaro, A. M. Jia, X. Ngo, H. T. Melhem, M. R. Sacco, A. Chen, C. Leleu, X. Runnels, J. Azab, F. Azab, A. K. Quang, P. Varticovski, L. Novina, C. D. Rollins, B. J. Anderson, K. C. Ghobrial, I. M. TI MicroRNA Expression in the Biology, Prognosis, and Therapy of Waldenstrom Macroglobulinemia SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Roccaro, A. M.; Jia, X.; Ngo, H. T.; Melhem, M. R.; Sacco, A.; Chen, C.; Leleu, X.; Runnels, J.; Azab, F.; Azab, A. K.; Quang, P.; Novina, C. D.; Rollins, B. J.; Anderson, K. C.; Ghobrial, I. M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Varticovski, L.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S126 EP S126 PG 1 WC Oncology SC Oncology GA 473LB UT WOS:000268206500285 ER PT J AU Roccaro, AM Leduc, R Nelson, M Sam, A Chuma, S Colson, K O'Connor, K Ghobrial, IM Munshi, NC Schlossman, R Harris, B Warren, D Dollard, AM Laubach, J Vij, R Campagnaro, E Birner, A Dixon-Lipscomb, V Anderson, KC Richardson, PG AF Roccaro, A. M. Leduc, R. Nelson, M. Sam, A. Chuma, S. Colson, K. O'Connor, K. Ghobrial, I. M. Munshi, N. C. Schlossman, R. Harris, B. Warren, D. Dollard, A. M. Laubach, J. Vij, R. Campagnaro, E. Birner, A. Dixon-Lipscomb, V. Anderson, K. C. Richardson, P. G. TI Phase I Trial of CCI-779 and Weekly Bortezomib in Relapsed and/or Refractory Multiple Myeloma SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Roccaro, A. M.; Leduc, R.; Nelson, M.; Sam, A.; Chuma, S.; Colson, K.; O'Connor, K.; Ghobrial, I. M.; Munshi, N. C.; Schlossman, R.; Harris, B.; Warren, D.; Laubach, J.; Anderson, K. C.; Richardson, P. G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Dollard, A. M.] Multiple Myeloma Res Consortium, Norwalk, CT USA. [Vij, R.; Campagnaro, E.] Univ Michigan, Ann Arbor, MI 48109 USA. [Birner, A.] Millennium Pharmaceut Inc, Cambridge, MA USA. [Dixon-Lipscomb, V.] Wyeth Pharmaceut, Collegeville, PA 19426 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S86 EP S86 PG 1 WC Oncology SC Oncology GA 473LB UT WOS:000268206500194 ER PT J AU Roodman, GD Hiruma, Y Kurihara, N AF Roodman, G. David Hiruma, Yuko Kurihara, Noriyoshi TI p62: A Potential Target for Blocking Microenvironmental Support of Myeloma SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract ID MULTIPLE-MYELOMA; BONE MICROENVIRONMENT; OSTEOCLASTOGENESIS; DISEASE; PATHOPHYSIOLOGY; INCREASES; MUTATION; ALPHA C1 [Roodman, G. David; Hiruma, Yuko; Kurihara, Noriyoshi] Univ Pittsburgh, Pittsburgh, PA USA. [Roodman, G. David] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 10 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 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S25 EP S26 PG 2 WC Oncology SC Oncology GA 472EE UT WOS:000268111400019 ER PT J AU Runnels, J Carlson, AL Thompson, B Piitsillides, C Joel, J Wu, J Azab, AK Azab, F Leleu, X Jia, X Burwick, N Roccaro, AM Ngo, HT Melhem, MR Sacco, A Rodig, SJ Kung, A Anderson, KC Lin, CP Ghobrial, IM AF Runnels, J. Carlson, A. L. Thompson, B. Piitsillides, C. Joel, J. Wu, J. Azab, A. Kareem Azab, F. Leleu, X. Jia, X. Burwick, N. Roccaro, A. M. Ngo, H. T. Melhem, M. R. Sacco, A. Rodig, S. J. Kung, A. Anderson, K. C. Lin, C. P. Ghobrial, I. M. TI In Vivo Imaging Model of Multiple Myeloma and its Cellular Interaction with the Bone Marrow Milieu SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Runnels, J.; Azab, A. Kareem; Azab, F.; Leleu, X.; Jia, X.; Burwick, N.; Roccaro, A. M.; Ngo, H. T.; Melhem, M. R.; Sacco, A.; Rodig, S. J.; Kung, A.; Anderson, K. C.; Ghobrial, I. M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Carlson, A. L.; Thompson, B.; Piitsillides, C.; Joel, J.; Wu, J.; Lin, C. P.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S145 EP S146 PG 2 WC Oncology SC Oncology GA 473LB UT WOS:000268206500334 ER PT J AU San Miguel, J Dimopoulos, MA Schlag, R Khuageva, N Shpilberg, O Kropff, M Spicka, I Petrucci, M Palumbo, A Samoilova, O Dmoszynska, A Abdulkadyrov, K Schots, R Jiang, B Mateos, MV Anderson, KC Esseltine, DL Liu, K Cakana, A van de Velde, H Richardson, PG AF San Miguel, J. Dimopoulos, M. A. Schlag, R. Khuageva, N. Shpilberg, O. Kropff, M. Spicka, I. Petrucci, M. Palumbo, A. Samoilova, O. Dmoszynska, A. Abdulkadyrov, K. Schots, R. Jiang, B. Mateos, M. V. Anderson, K. C. Esseltine, D. L. Liu, K. Cakana, A. van de Velde, H. Richardson, P. G. TI Superior Survival with VMP Versus MP After Longer Follow-up and Response to Subsequent Therapy in VISTA SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [San Miguel, J.; Dimopoulos, M. A.] Univ Athens, Sch Med, GR-10679 Athens, Greece. [Schlag, R.] Praxisklin Dr Schlag, Wurzburg, Germany. [Khuageva, N.] SP Botkin Moscow City Clin Hosp, Moscow, Russia. [Shpilberg, O.] Rabin Med Ctr, Petah Tiqwa, Israel. [Kropff, M.] Univ Munster, D-4400 Munster, Germany. [Spicka, I.] Univ Hosp, Prague, Czech Republic. [Petrucci, M.] Univ Roma La Sapienza, Rome, Italy. [Palumbo, A.] Univ Turin, I-10124 Turin, Italy. [Samoilova, O.] Nizhnii Novgorod Reg Clin Hosp, Nizhnii Novgorod, Russia. [Dmoszynska, A.] Med Univ Lublin, Lublin, Poland. [Abdulkadyrov, K.] St Petersburg Clin Res Inst Hematol & Transfusiol, St Petersburg, Russia. [Jiang, B.] Peking Univ, Peoples Hosp, Beijing, Peoples R China. [Mateos, M. V.] Hosp Univ Salamanca, CIC, IBMCC, USAL CSIC, Salamanca, Spain. [Anderson, K. C.; Richardson, P. G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Esseltine, D. L.] Millennium Takeda Oncol Co, Cambridge, MA USA. [Liu, K.] Johnson & Johnson Pharmaceut Res & Dev LLC, Raritan, NJ USA. [Cakana, A.] Johnson & Johnson Pharmaceut Res & Dev, High Wycombe, Bucks, England. [van de Velde, H.] Johnson & Johnson Pharmaceut Res & Dev, Beerse, Belgium. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S39 EP S40 PG 2 WC Oncology SC Oncology GA 473LB UT WOS:000268206500086 ER PT J AU Santo, L Vallet, S Hideshima, T Cirstea, T Pozzi, S Vaghela, N Ikeda, H Okawa, Y Gorgun, G Munshi, NC Squires, MS Iadetto, M Boccadoro, M Anderson, KC Raje, N AF Santo, L. Vallet, S. Hideshima, T. Cirstea, T. Pozzi, S. Vaghela, N. Ikeda, H. Okawa, Y. Gorgun, G. Munshi, N. C. Squires, M. S. Iadetto, M. Boccadoro, M. Anderson, K. C. Raje, N. TI AT7519, a Multi-Cyclin Dependent Kinase Inhibitor, Induces Apoptosis in Multiple Myeloma via GSK3 beta SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Santo, L.; Vallet, S.; Hideshima, T.; Cirstea, T.; Pozzi, S.; Vaghela, N.; Ikeda, H.; Okawa, Y.; Gorgun, G.; Munshi, N. C.; Anderson, K. C.; Raje, N.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Santo, L.; Vallet, S.; Hideshima, T.; Cirstea, T.; Pozzi, S.; Vaghela, N.; Ikeda, H.; Okawa, Y.; Gorgun, G.; Munshi, N. C.; Anderson, K. C.; Raje, N.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Squires, M. S.] Astex Therapeut Ltd, Cambridge, England. [Iadetto, M.; Boccadoro, M.] Univ Turin, I-10124 Turin, Italy. RI Pozzi, Samantha/A-7617-2012 OI Pozzi, Samantha/0000-0001-7917-1774 NR 0 TC 0 Z9 0 U1 1 U2 3 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S137 EP S138 PG 2 WC Oncology SC Oncology GA 473LB UT WOS:000268206500314 ER PT J AU Sezer, O Siegel, D San Miguel, J Mateos, MV Prosser, I Guenther, A Blade, J Cavo, M Jalaluddin, M Hazell, K Bourquelot, PM Anderson, KC AF Sezer, O. Siegel, D. San Miguel, J. Mateos, M. V. Prosser, I. Guenther, A. Blade, J. Cavo, M. Jalaluddin, M. Hazell, K. Bourquelot, P. M. Anderson, K. C. TI Panobinostat and Bortezomib Phase I Trial in Multiple Myeloma SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Sezer, O.; Siegel, D.] Hackensack Univ, Med Ctr, Hackensack, NJ USA. [San Miguel, J.; Mateos, M. V.] Hosp Univ Salamanca, Salamanca, Spain. [Prosser, I.] Canberra Hosp, Canberra, ACT, Australia. [Guenther, A.] Univ Kiel, D-24098 Kiel, Germany. [Blade, J.] IDIBAPS, Hosp Clin, Barcelona, Spain. [Cavo, M.] Univ Bologna, I-40126 Bologna, Italy. [Jalaluddin, M.; Hazell, K.; Bourquelot, P. M.] Novartis Pharmaceut, E Hanover, NJ USA. [Anderson, K. C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Cambridge, MA 02138 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S54 EP S54 PG 1 WC Oncology SC Oncology GA 473LB UT WOS:000268206500119 ER PT J AU Siegel, DS Weber, DM Mitsiades, C Rizvi, S Howe, J Reiser, D Anderson, KC Richardson, PG AF Siegel, D. S. Weber, D. M. Mitsiades, C. Rizvi, S. Howe, J. Reiser, D. Anderson, K. C. Richardson, P. G. TI Vorinostat/Lenalidomide/Dexamethasone: A Phase I Study SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Siegel, D. S.; Weber, D. M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Mitsiades, C.; Anderson, K. C.; Richardson, P. G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Rizvi, S.; Howe, J.; Reiser, D.] Merck & Co Inc, Upper Gwynedd, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 SU 1 BP S41 EP S42 PG 2 WC Oncology SC Oncology GA 473LB UT WOS:000268206500090 ER PT J AU Sophia, A AvetLoiseau, H Amin, SB Tai, YT Treon, SP Moreau, P Minvielle, S Li, C Anderson, KC Munshi, NC AF Sophia, A. AvetLoiseau, H. Amin, S. B. Tai, Y. T. Treon, S. P. Moreau, P. Minvielle, S. Li, C. Anderson, K. C. Munshi, N. C. TI MicroRNA Profile Identifies Distinct Clinically Relevant Subgroups in Multiple Myeloma SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Sophia, A.; Amin, S. B.; Tai, Y. T.; Treon, S. P.; Li, C.; Anderson, K. C.; Munshi, N. C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [AvetLoiseau, H.; Moreau, P.; Minvielle, S.] Hop Nantes, Nantes, France. RI Minvielle, Stephane/K-8251-2015; richard, chrystelle/K-8595-2015 NR 0 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 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S93 EP S94 PG 2 WC Oncology SC Oncology GA 473LB UT WOS:000268206500213 ER PT J AU Tai, YT Soydan, E Fulciniti, M Song, W Kim, K Hong, F Li, XF Burger, P Rumizen, M Nahar, S Podar, K Chauhan, D Hideshima, T Munshi, NC Tonon, G Carrasco, R Anderson, KC AF Tai, Y. T. Soydan, E. Fulciniti, M. Song, W. Kim, K. Hong, F. Li, X-F Burger, P. Rumizen, M. Nahar, S. Podar, K. Chauhan, D. Hideshima, T. Munshi, N. C. Tonon, G. Carrasco, R. Anderson, K. C. TI CS1 Promotes Multiple Myeloma Cell Adhesion, Clonogenic Growth, and Tumorigenicity via c-Maf Mediation SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Tai, Y. T.; Soydan, E.; Fulciniti, M.; Song, W.; Kim, K.; Hong, F.; Li, X-F; Burger, P.; Rumizen, M.; Nahar, S.; Podar, K.; Chauhan, D.; Hideshima, T.; Munshi, N. C.; Tonon, G.; Carrasco, R.; Anderson, K. C.] Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S96 EP S97 PG 2 WC Oncology SC Oncology GA 473LB UT WOS:000268206500218 ER PT J AU Tai, YT Fulciniti, M Tassone, P Neri, P Mitsiades, CC Hideshima, T Chauhan, D Richardson, PG Anderson, KC Munshi, NC AF Tai, Yu-Tzu Fulciniti, Mariateresa Tassone, Pierfrancesco Neri, Paolo Mitsiades, Constantine C. Hideshima, Teru Chauhan, Darminder Richardson, Paul G. Anderson, Kenneth C. Munshi, Nikhil C. TI Monoclonal Antibody-Based Therapies in Human Multiple Myeloma SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract ID CELL-ACTIVATING FACTOR; PHASE-I; CLINICAL-IMPLICATIONS; ANTI-CD40 ANTIBODY; CYTOTOXICITY; ADHESION; SGN-40; MAB C1 [Tai, Yu-Tzu; Fulciniti, Mariateresa; Tassone, Pierfrancesco; Neri, Paolo; Mitsiades, Constantine C.; Hideshima, Teru; Chauhan, Darminder; Richardson, Paul G.; Anderson, Kenneth C.; Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston VA Healthcare Syst, Boston, MA 02115 USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S22 EP S23 PG 2 WC Oncology SC Oncology GA 472EE UT WOS:000268111400017 ER PT J AU Vallet, S Mukherjee, S Vaghela, N Pozzi, S Santo, L Cirstea, D Fulciniti, M Rahemtullah, A Attar, E Xie, W Patel, C Schoonmaker, JA Weller, E Hideshima, T Munshi, NC Seehra, JS Scadden, DT Anderson, KC Raje, N AF Vallet, S. Mukherjee, S. Vaghela, N. Pozzi, S. Santo, L. Cirstea, D. Fulciniti, M. Rahemtullah, A. Attar, E. Xie, W. Patel, C. Schoonmaker, J. A. Weller, E. Hideshima, T. Munshi, N. C. Seehra, J. S. Scadden, D. T. Anderson, K. C. Raje, N. TI Targeting Myeloma Bone Disease via Activin A Inhibition SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Vallet, S.; Mukherjee, S.; Vaghela, N.; Pozzi, S.; Rahemtullah, A.; Attar, E.; Patel, C.; Schoonmaker, J. A.; Scadden, D. T.; Raje, N.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. [Santo, L.; Cirstea, D.; Xie, W.; Weller, E.; Hideshima, T.; Anderson, K. C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Fulciniti, M.; Munshi, N. C.] Harvard Univ, Sch Med, VA Boston Hlth Care Syst, Boston, MA USA. [Seehra, J. S.] Acceleron Pharma Inc, Cambridge, MA USA. RI Pozzi, Samantha/A-7617-2012 OI Pozzi, Samantha/0000-0001-7917-1774 NR 0 TC 1 Z9 1 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S126 EP S127 PG 2 WC Oncology SC Oncology GA 473LB UT WOS:000268206500287 ER PT J AU Vallet, S Raje, N AF Vallet, Sonia Raje, Noopur TI Novel Bone-Targeting Agents in Multiple Myeloma SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract ID INHIBITS OSTEOCLASTOGENESIS; IN-VIVO; SURVIVAL C1 Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S45 EP S46 PG 2 WC Oncology SC Oncology GA 472EE UT WOS:000268111400034 ER PT J AU Weber, DM Badros, A Jagannath, S Siegel, D Richon, V Rizvi, S Garcia-Vargas, J Reiser, D Anderson, KC AF Weber, D. M. Badros, A. Jagannath, S. Siegel, D. Richon, V. Rizvi, S. Garcia-Vargas, J. Reiser, D. Anderson, K. C. TI Vorinostat and Bortezomib in Relapsed/Refractory MM SO CLINICAL LYMPHOMA & MYELOMA LA English DT Meeting Abstract C1 [Weber, D. M.; Badros, A.] Univ Maryland, Baltimore, MA USA. [Jagannath, S.] St Vincents Comprehens Canc Ctr, New York, NY USA. [Siegel, D.] Hackensack Univ, Med Ctr, Hackensack, NJ USA. [Richon, V.; Rizvi, S.; Garcia-Vargas, J.; Reiser, D.] Merck & Co Inc, Upper Gwynedd, PA USA. [Anderson, K. C.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD FEB PY 2009 VL 9 BP S42 EP S42 PG 1 WC Oncology SC Oncology GA 473LB UT WOS:000268206500091 ER PT J AU Beales, JL Edes, T AF Beales, Julie Leftwich Edes, Thomas TI Veteran's Affairs Home Based Primary Care SO CLINICS IN GERIATRIC MEDICINE LA English DT Article DE Home care; Chronic disease; Non-institutional long-term care; Interdisciplinary team; Home based primary care AB In response to the anticipated growth of the veteran population with chronic disabling diseases, the Department of Veterans Affairs (VA) established Home Based Primary Care (HBPC). This article focuses on that program, a home care program that specifically targets individuals with complex chronic disabling disease, with the goal of maximizing the independence of the patient and reducing preventable emergency room visits and hospitalizations. HBPC programs provide comprehensive longitudinal primary care by an interdisciplinary team in the homes of veterans with complex chronic disease, who are not effectively managed by routine clinic-based care. HBPC is very different from and complementary to standard skilled home care services, in population, processes and outcomes. HBPC targets persons with advanced chronic disease, rather than remediable conditions. HBPC provides comprehensive care of multiple co-morbidities, rather than problem-focused care. HBPC is delivered by an interdisciplinary team, rather than one or two independent providers. Currently operating in three-fourths of VA facilities, HBPC expansion continues to be driven by clinical success and the highest satisfaction of all VA services. VA HBPC is a model to emulate for the care of persons with complex, chronic disabling conditions, improving quality without added cost, and maximizing their independence through comprehensive longitudinal interdisciplinary care delivered in their homes. C1 [Beales, Julie Leftwich] VAMC, Richmond, VA 23249 USA. [Edes, Thomas] US Dept Vet Affairs, Home & Community Based Care, Washington, DC 20420 USA. RP Beales, JL (reprint author), VAMC, 1201 Broad Rock Blvd, Richmond, VA 23249 USA. EM julie.beales@va.gov NR 9 TC 47 Z9 48 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 0749-0690 J9 CLIN GERIATR MED JI Clin. Geriatr. Med. PD FEB PY 2009 VL 25 IS 1 BP 149 EP + DI 10.1016/j.cger.2008.11.002 PG 8 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 421ZM UT WOS:000264396800012 PM 19217499 ER PT J AU Gow, DW Segawa, JA AF Gow, David W., Jr. Segawa, Jennifer A. TI Articulatory mediation of speech perception: A causal analysis of multi-modal imaging data SO COGNITION LA English DT Review DE Speech perception; Coarticulation; Assimilation; Motor theory; MEG; EEG; Granger causality; Cognitive neuroscience ID SPOKEN WORD RECOGNITION; EVENT-RELATED FMRI; ADAPTIVE PATTERN-CLASSIFICATION; GRANGER CAUSALITY; CORTICAL SURFACE; FUNCTIONAL NEUROANATOMY; ELECTRICAL-STIMULATION; LEXICAL AMBIGUITY; TRADING RELATIONS; CEREBRAL-CORTEX AB The inherent confound between the organization of articulation and the acoustic-phonetic structure of the speech signal makes it exceptionally difficult to evaluate the competing claims of motor and acoustic-phonetic accounts of how listeners recognize coarticulated speech. Here we use Granger causation analyzes of high spatiotemporal resolution neural activation data derived from the integration of magnetic resonance imaging, magneto-encephalography and electroencephalography, to examine the role of lexical and articulatory mediation in listeners' ability to use phonetic context to compensate for place assimilation. Listeners heard two-word phrases such as pen pad and then saw two pictures, from which they had to select the one that depicted the phrase. Assimilation, lexical competitor environment and the phonological validity of assimilation context were all manipulated. Behavioral data showed an effect of context on the interpretation of assimilated segments. Analysis of 40 Hz gamma phase locking patterns identified a large distributed neural network including 16 distinct regions of interest (ROIs) spanning portions of both hemispheres in the first 200 ms of post-assimilation context. Granger analyzes of individual conditions showed differing patterns of causal interaction between ROIs during this interval, with hypothesized lexical and articulatory structures and pathways driving phonetic activation in the posterior superior temporal gyrus in assimilation conditions, but not in phonetically unambiguous conditions. These results lend strong support for the motor theory of speech perception, and clarify the role of lexical mediation in the phonetic processing of assimilated speech. (c) 2008 Elsevier B.V. All rights reserved. C1 [Gow, David W., Jr.] Massachusetts Gen Hosp, Cognit Behav Neurol Grp, Neuropsychol Lab, Boston, MA 02114 USA. [Gow, David W., Jr.; Segawa, Jennifer A.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, MGH MIT HMS, Boston, MA 02114 USA. [Gow, David W., Jr.] Salem State Coll, Dept Psychol, Salem, MA 01970 USA. RP Gow, DW (reprint author), Massachusetts Gen Hosp, Cognit Behav Neurol Grp, Neuropsychol Lab, 175 Cambridge St,Suite S340, Boston, MA 02114 USA. EM gow@helix.mgh.harvard.edu RI Preston, Jonathan/E-9310-2010 OI Preston, Jonathan/0000-0001-9971-6321 FU NIDCD NIH HHS [R01 DC003108] NR 108 TC 20 Z9 20 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0010-0277 J9 COGNITION JI Cognition PD FEB PY 2009 VL 110 IS 2 BP 222 EP 236 DI 10.1016/j.cognition.2008.11.011 PG 15 WC Psychology, Experimental SC Psychology GA 411EN UT WOS:000263631100008 PM 19110238 ER PT J AU Chosak, A Marques, L Fama, J Renaud, S Wilhelm, S AF Chosak, Anne Marques, Luana Fama, Jeanne Renaud, Stefanie Wilhelm, Sabine TI Cognitive Therapy for Obsessive-Compulsive Disorder: a Case Example SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Article ID BELIEFS AB Cognitive therapy for OCD is an empirically validated alternative to the more widely used and validated behavioral therapy for OCD. The cognitive approach is based on the premise that belief systems contribute importantly to the development and maintenance of all types of OCD. By identifying and challenging maladaptive thoughts, beliefs, and core beliefs, patients can improve significantly and maintain their grains over time. This approach is demonstrated in detail with the case of Caroline, a 51-year-old woman with contamination obsessions. RP Wilhelm, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Obsess Compuls Disorder Clin,Dept Psychiat, 185 Cambridge St, Boston, MA 02114 USA. EM wilhelm@psych.mgh.harvard.edu NR 16 TC 5 Z9 5 U1 2 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1077-7229 J9 COGN BEHAV PRACT JI Cogn. Behav. Pract. PD FEB PY 2009 VL 16 IS 1 BP 7 EP 17 DI 10.1016/j.cbpra.2008.01.005 PG 11 WC Psychology, Clinical SC Psychology GA 405VE UT WOS:000263251500003 ER PT J AU Maserejian, NN Tavares, MA Hayes, C Soncini, JA Trachtenberg, FL AF Maserejian, Nancy Nairi Tavares, Mary A. Hayes, Catherine Soncini, Jennifer A. Trachtenberg, Felicia L. TI Prospective study of 5-year caries increment among children receiving comprehensive dental care in the New England children's amalgam trial SO COMMUNITY DENTISTRY AND ORAL EPIDEMIOLOGY LA English DT Article DE child; dental caries; epidemiology; high risk; incidence; pediatric dentistry; prospective studies ID RISK-ASSESSMENT MODEL; PERMANENT DENTITION; SEALANT PROGRAM; PRIMARY TEETH; FOLLOW-UP; EXPERIENCE; DISPARITIES; PREDICTION; AGE; ADOLESCENTS AB To measure the 5-year caries increment among high-risk children during their participation in the New England Children's Amalgam Trial (NECAT), and to evaluate sociodemographic factors that may account for any observed disparities. NECAT recruited 534 children aged 6-10 with at least two decayed posterior occlusal surfaces from urban Boston and rural Maine. After restoration of baseline caries and application of sealants to sound surfaces, NECAT continued to provide free comprehensive semiannual dental care to participants. The net caries increment of children who completed the 5-year follow-up (n = 429) was calculated and predictors of caries increment were investigated using multivariate negative binomial models. The majority of children (89%) experienced new caries by the end of the 5-year follow-up. Almost half (45%) had at least one newly decayed surface by the first annual visit. At year 5, the mean number of new decayed teeth was 4.5 +/- 3.6 (range 0-25) and surfaces was 6.9 +/- 6.5 (range 0-48). Time trends showed a noticeably higher increment rate among older children and young teenagers. Multivariate models showed that age (P < 0.001), number of baseline carious surfaces (P < 0.001), and toothbrushing frequency (< 1/day versus >= 2/day, P = 0.04) were associated with caries increment. Only 48 children (11%) did not develop new caries. Despite the receipt of comprehensive semiannual dental care, the vast majority of these high-risk children continued to develop new caries within 5 years. While disparities were observed by age, extent of prior decay, and toothbrushing frequency, no other sociodemographic factors were associated with caries increment, suggesting that the dental care provided during the trial reduced sociodemographic disparities in prior caries experience that were observed at baseline. C1 [Maserejian, Nancy Nairi; Trachtenberg, Felicia L.] New England Res Inst, Watertown, MA 02472 USA. [Tavares, Mary A.; Soncini, Jennifer A.] Forsyth Inst, Boston, MA USA. [Hayes, Catherine] Tufts Univ, Sch Dent Med, Dept Publ Hlth & Community Serv, Boston, MA 02111 USA. [Soncini, Jennifer A.] Boston Univ, Goldman Sch Grad Dent, Dept Pediat Dent, Boston, MA 02215 USA. RP Maserejian, NN (reprint author), New England Res Inst, 9 Galen St, Watertown, MA 02472 USA. EM nmaserejian@neriscience.com FU New England Research Institutes [U01 DE11886]; National Institute of Dental and Craniofacial Research; National Center for Research Resources [M01-RR01032]; Forsyth Institute Clinical Research Facility FX Funded by a cooperative agreement (U01 DE11886) between the New England Research Institutes and the National Institute of Dental and Craniofacial Research, and also in part by the National Center for Research Resources grant M01-RR01032, which supports the Forsyth Institute Clinical Research Facility. NR 41 TC 10 Z9 10 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0301-5661 EI 1600-0528 J9 COMMUNITY DENT ORAL JI Community Dentist. Oral Epidemiol. PD FEB PY 2009 VL 37 IS 1 BP 9 EP 18 DI 10.1111/j.1600-0528.2008.00437.x PG 10 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA 395FI UT WOS:000262509600002 PM 18782333 ER PT J AU Warren, HS AF Warren, H. Shaw TI Peroxisome proliferator-activated receptor-gamma agonists, control of bacterial outgrowth, and inflammation SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE peroxisome proliferator-activated receptor-gamma; inflammation; bacteria; mouse model; pneumonia ID PNEUMOCOCCAL PNEUMONIA; CIGLITAZONE C1 Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. RP Warren, HS (reprint author), Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. FU NIAID NIH HHS [AI059010]; NIGMS NIH HHS [GM 59694] NR 10 TC 1 Z9 1 U1 0 U2 0 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 FEB PY 2009 VL 37 IS 2 BP 773 EP 774 DI 10.1097/CCM.0b013e318194c4f9 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 402LI UT WOS:000263014800068 PM 19325383 ER PT J AU Wei, HF Xie, ZC AF Wei, Huafeng Xie, Zhongcong TI Anesthesia, Calcium Homeostasis and Alzheimer's Disease SO CURRENT ALZHEIMER RESEARCH LA English DT Article DE Anesthesia; inhalational anesthetics; calcium; Alzheimer's disease; Huntington's disease; neurodegeneration; apoptosis; preconditioning ID POSTOPERATIVE COGNITIVE DYSFUNCTION; ENDOPLASMIC-RETICULUM STRESS; ISOFLURANE INDUCES APOPTOSIS; MEDIUM SPINY NEURONS; DEVELOPING RAT-BRAIN; INTRACELLULAR CALCIUM; VOLATILE ANESTHETICS; GENERAL-ANESTHESIA; IN-VITRO; HIPPOCAMPAL-NEURONS AB While anesthetics are indispensable clinical tools generally safe and effective, in some situations there is grown concern about selective neurotoxicity of these agents; the clinical significance is unclear as of yet. The mechanisms for inhalational anesthetics mediated cell damage are still not clear, although a role for calcium dysregulation has been suggested. For example, the inhaled anesthetic isoflurane decreases endoplasmic reticulum (ER) calcium concentration and increases that in the cytosol and mitochondria. Inhibition of ER calcium release, via either IP(3) or ryanodine receptors, significantly inhibited isoflurane neurotoxicity. Neurons made vulnerable to calcium dysregulation by overexpression of mutated presenilin-1 (PS1) or huntingtin (Q-111) proteins showed enhanced apoptosis upon isoflurane exposure. Sevoflurane and desflurane were less potent than isoflurane in altering intracellular calcium, and produced less apoptosis. Short exposures to inhalational anesthetics may provide neuroprotection by preconditioning via a sublethal stress, while prolonged exposures to inhalational anesthetics may induce cell damage by apoptosis through direct cytotoxic effects. C1 [Wei, Huafeng] Univ Penn, Sch Med, Dept Anesthesiol & Crit Care, Philadelphia, PA 19104 USA. [Xie, Zhongcong] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Genet & Aging Res Unit,Dept Anesthesia & Crit Car, Charlestown, MA 02129 USA. RP Wei, HF (reprint author), Univ Penn, Sch Med, Dept Anesthesiol & Crit Care, 305 John Morgan Bldg,3620 Hamilton Walk, Philadelphia, PA 19104 USA. EM weih@uphs.upenn.edu FU NIA NIH HHS [R21 AG029856-01A2, R21 AG029856]; NIGMS NIH HHS [K08 GM073224, R01 GM088801, R01 GM088801-01A1]; NINDS NIH HHS [K08 NS048140-04, K08 NS048140] NR 72 TC 53 Z9 57 U1 0 U2 15 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1567-2050 J9 CURR ALZHEIMER RES JI Curr. Alzheimer Res. PD FEB PY 2009 VL 6 IS 1 BP 30 EP 35 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 406HT UT WOS:000263286300004 PM 19199872 ER PT J AU Platt, M Metson, R Stankovic, K AF Platt, Michael Metson, Ralph Stankovic, Konstantina TI Gene-expression signatures of nasal polyps associated with chronic rhinosinusitis and aspirin-sensitive asthma SO CURRENT OPINION IN ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Review DE aspirin-sensitive asthma; chronic rhinosinusitis; expression signatures; gene-expression profiling; microarray; nasal polyps ID RECEPTOR TYROSINE KINASE; CHRONIC SINUSITIS; C-MET; STAPHYLOCOCCUS-AUREUS; BINDING-PROTEIN; CANCER; GROWTH; UTEROGLOBIN; MICROARRAY; PERIOSTIN AB Purpose of review The purpose of this review is to highlight recent advances in gene-expression profiling of nasal polyps in patients with chronic rhinosinusitis and aspirin-sensitive asthma. Recent findings Gene-expression profiling has allowed simultaneous interrogation of thousands of genes, including the entire genome, to better understand distinct biological and clinical phenotypes associated with nasal polyps. The genes with altered expression in nasal polyps are involved in many cellular processes, including growth and development, immune functions, and signal transduction. The wide-ranging and typically nonoverlapping results reported in the published studies reflect methodological and demographic differences. The identified genes present possible novel therapeutic targets for nasal polyps associated with chronic rhinosinusitis and aspirin-sensitive asthma. Summary Gene-expression profiling is a powerful technology that allows definition of expression signatures to characterize patient subgroups, predict response to treatment, and offer novel therapies. Although the ability to interpret the meaning of the individual gene in these signatures remains a challenge, integrated analysis of a large number of these signatures with other genome-scale data sets and more traditional targeted approaches has a potential to revolutionarize understanding and treatment of chronic rhinosinusitis and aspirin-sensitive asthma. C1 [Stankovic, Konstantina] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Platt, Michael] Boston Univ, Dept Otolaryngol Head & Neck Surg, Boston, MA 02215 USA. [Stankovic, Konstantina] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Metson, Ralph; Stankovic, Konstantina] Harvard Univ, Sch Med, Dept Otol & Laryngol, Cambridge, MA 02138 USA. RP Stankovic, K (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM konstantina_stankovic@meei.harvard.edu NR 53 TC 8 Z9 8 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1528-4050 J9 CURR OPIN ALLERGY CL JI Curr. Opin. Allergy Clin. Immunol. PD FEB PY 2009 VL 9 IS 1 BP 23 EP 28 DI 10.1097/ACI.0b013e32831d8170 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA 400SH UT WOS:000262888400005 PM 19532090 ER PT J AU Bouma, BE Yun, SH Vakoc, BJ Suter, MJ Tearney, GJ AF Bouma, Brett E. Yun, Seok-Hyun Vakoc, Benjamin J. Suter, Melissa J. Tearney, Guillermo J. TI Fourier-domain optical coherence tomography: recent advances toward clinical utility SO CURRENT OPINION IN BIOTECHNOLOGY LA English DT Review ID SWEPT SEMICONDUCTOR-LASER; 1.3 MU-M; IN-VIVO; SPECTRAL-DOMAIN; HIGH-RESOLUTION; POLARIZATION MODULATION; BIREFRINGENCE CHARACTERIZATION; MOLECULAR CONTRAST; DOPPLER TOMOGRAPHY; BIOLOGICAL TISSUE AB With the advent of Fourier-domain techniques, optical coherence tomography (OCT) has advanced from high-resolution 'point' imaging over small fields-of-view to comprehensive microscopic imaging over three-dimensional volumes that are comparable to the dimensions of luminal internal organs. This advance has required the development of new lasers, improved spectrometers, minimally invasive catheters and endoscopes, and novel optical and signal processing strategies. In recent cardiovascular, ophthalmic, and gastrointestinal clinical studies, the capabilities of Fourier-domain OCT have enabled a new paradigm for diagnostic screening of large tissue areas, which addresses the shortcomings of existing technologies and focal biopsy. C1 [Bouma, Brett E.; Yun, Seok-Hyun; Vakoc, Benjamin J.; Suter, Melissa J.; Tearney, Guillermo J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med,MGH, Harvard Mit Div Hlth Sci & Technol,Wellman Ctr Ph, Boston, MA 02114 USA. RP Bouma, BE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,MGH, Harvard Mit Div Hlth Sci & Technol,Wellman Ctr Ph, BAR 701,40 Blossom St, Boston, MA 02114 USA. EM bouma@helix.mgh.harvard.edu; syun@hms.harvard.edu; bvakoc@partners.org; msuter@partners.org; tearney@helix.mgh.harvard.edu FU National Institutes of Health [R01CA103869, R01HL076398, R33-CA125560, R33CA110130, K25-CA127465] FX The authors gratefully acknowledge the following collaborators who have helped to shape the perspectives and technical analysis presented in this review: M Shishkov, JF de Boer, WY Oh, A Desjardins, BH Park, and RC Chan. BE Bouma and GJ Tearney are supported by the National Institutes of Health, Grants R01CA103869, R01HL076398, and R33-CA125560. SH Yun is supported by the National Institutes of Health, Grant R33CA110130. BJ Vakoc is supported by National Institutes of Health, Grant K25-CA127465. NR 81 TC 50 Z9 51 U1 3 U2 15 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0958-1669 J9 CURR OPIN BIOTECH JI Curr. Opin. Biotechnol. PD FEB PY 2009 VL 20 IS 1 BP 111 EP 118 DI 10.1016/j.copbio.2009.02.007 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 452JB UT WOS:000266535200015 PM 19264475 ER PT J AU Levitsky, LL Misra, M Boepple, PA Hoppin, AG AF Levitsky, Lynne L. Misra, Madhusmita Boepple, Paul A. Hoppin, Alison G. TI Adolescent obesity and bariatric surgery SO CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY LA English DT Article DE adolescent obesity; bariatric surgery; endocrine effects; outcomes; weight loss ID GASTRIC-BYPASS-SURGERY; VERTICAL BANDED GASTROPLASTY; TYPE-2 DIABETES-MELLITUS; NONALCOHOLIC FATTY LIVER; BODY-MASS INDEX; AMBULATORY BLOOD-PRESSURE; GLUCAGON-LIKE PEPTIDE-1; INTIMA-MEDIA THICKNESS; QUALITY-OF-LIFE; MORBID-OBESITY AB Purpose of review Examines the effects of bariatric surgery on adolescent obesity. Recent findings The risks and outcomes of bariatric surgery in adolescence are presently being defined and may be somewhat different from those in adults. Adolescents may have a greater risk of weight regain, and greater risk of noncompliance to treatment after surgery. However, long-term outcomes are not yet available, and the underlying metabolic benefits appear to be substantial and similar to those of adults. Summary Morbid obesity in adolescents has severe acute and chronic complications. Bariatric surgery in adolescents seems as well tolerated as in adults when performed in centers with appropriate experience and adequate surgical volume. The pathophysiologic implications of bariatric surgery are profound. A better understanding of the mechanisms leading to postsurgical improvement in insulin resistance and weight loss could lead to the development of other therapies to achieve the same effects with lesser morbidities. C1 [Levitsky, Lynne L.; Misra, Madhusmita; Boepple, Paul A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA. [Boepple, Paul A.; Hoppin, Alison G.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Weight Ctr, Boston, MA 02114 USA. [Hoppin, Alison G.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat GI Unit, Boston, MA 02114 USA. RP Levitsky, LL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Endocrine Unit, 175 Cambridge St,5th Floor, Boston, MA 02114 USA. EM LLevitsky@partners.org NR 119 TC 6 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1752-296X J9 CURR OPIN ENDOCRINOL JI Curr. Opin. Endocrinol. Diabetes Obes. PD FEB PY 2009 VL 16 IS 1 BP 37 EP 44 DI 10.1097/MED.0b013e32832101ff PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 691BK UT WOS:000285055100007 PM 19104236 ER PT J AU Downward, J Hahn, WC AF Downward, Julian Hahn, William C. TI Genetic and cellular mechanisms of oncogenesis SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Editorial Material C1 [Downward, Julian] Canc Res UK London Res Inst, London WC2A 3PX, England. [Hahn, William C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Downward, J (reprint author), Canc Res UK London Res Inst, 44 Lincolns Inn Fields, London WC2A 3PX, England. EM julian.downward@cancer.org.uk; william_hahn@dfci.harvard.edu NR 0 TC 1 Z9 1 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD FEB PY 2009 VL 19 IS 1 BP 1 EP 3 PG 3 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 422LX UT WOS:000264430600001 PM 19208465 ER PT J AU Mlarotta, LLC Polyak, K AF Mlarotta, Lauren L. Campbell Polyak, Kornelia TI Cancer stem cells: a model in the making SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Review ID BREAST-TUMOR HETEROGENEITY; LEUKEMIA-INITIATING CELLS; SOLID TUMORS; PANCREATIC-CANCER; PROGENITOR CELLS; IDENTIFICATION; GROWTH; CHEMOTHERAPY; POPULATIONS; MARKERS AB Cancer stem cells and their potential roles in tumor heterogeneity are currently subjects of intense investigation. Studies suggest that these cells may develop from any normal cell and have begun to elucidate their molecular profiles. The percentage of a tumor composed of cancer stem cells varies greatly, and researchers believe that multiple types of these cells may exist in a single neoplasm. Cancer stem cells may be formed by epithelial-mesenchymal transition and seem to be less prevalent in metastases than in corresponding primary tumors. These cells appear to have therapeutic sensitivities different from those of cancer cells with more differentiated features. Looking into the many questions that remain about the cancer stem cells model might lead to more effective cancer prevention, diagnosis, and treatment. C1 [Mlarotta, Lauren L. Campbell; Polyak, Kornelia] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Program Biol & Biomed Sci, Boston, MA 02115 USA. [Polyak, Kornelia] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Polyak, K (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Program Biol & Biomed Sci, 44 Binney St,D740C, Boston, MA 02115 USA. EM kornelia_polyak@dfci.harvard.edu FU Novartis Pharmaceuticals, Inc.; National Cancer Institute [CA89393, CA94074]; Department of Defense [W81XWH-04-1-0452] FX This work was supported by Novartis Pharmaceuticals, Inc. and National Cancer Institute (CA89393 and CA94074) and Department of Defense (W81XWH-04-1-0452) grants awarded to RP. NR 53 TC 8 Z9 9 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD FEB PY 2009 VL 19 IS 1 BP 44 EP 50 DI 10.1016/j.gde.2008.12.003 PG 7 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 422LX UT WOS:000264430600008 PM 19167210 ER PT J AU Chandhok, NS Pellman, D AF Chandhok, Namrata S. Pellman, David TI A little CIN may cost a lot: revisiting aneuploidy and cancer SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Review ID MEROTELIC KINETOCHORE ORIENTATION; CHROMOSOME INSTABILITY; GENOME INSTABILITY; MITOTIC CHECKPOINT; SACCHAROMYCES-CEREVISIAE; INITIATE TUMORIGENESIS; ASYMMETRIC DIVISION; GENETIC INSTABILITY; COLORECTAL CANCERS; SPINDLE CHECKPOINT AB Despite over 100 years of study, the role of aneuploidy in cancer remains poorly understood. This review highlights the advances in understanding the causes and consequences of aneuploidy. Recent work has illuminated ways in which aneuploidy could have either tumor-promoting or tumor-suppressing effects, similar to what is known for other forms of genetic instability such as telomere attrition [Maser RS, DePinho RA: Connecting chromosomes, crisis, and cancer. Science 2002, 297:565-569]. We explore the possibility that aneuploidy could be just another type of 'mutation', with potential beneficial and deleterious effects, depending on the chromosomes involved and the specific selective pressures the cells experience. We also discuss the potential therapeutic implications of changes in physiology associated with aneuploidy. C1 [Chandhok, Namrata S.; Pellman, David] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Pellman, David] Childrens Hosp, Dept Pediat Hematol Oncol, Boston, MA 02115 USA. [Pellman, David] Howard Hughes Med Inst, Boston, MA 02115 USA. RP Chandhok, NS (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St,Rm M663, Boston, MA 02115 USA. EM Namrata_Chandhok@dfci.harvard.edu; David_Pellman@dfci.harvard.edu FU National Institutes of Health [GM083299] FX We apologize to the authors whose work was not discussed or cited owing to space constraints. We are grateful to Susana Godinho, Neil Ganem, Shawnna Buttery and Anna Sehnecki for critical reading of the manuscript. Our work is supported by National Institutes of Health grant GM083299 to David Pellman. David Pellman is an Investigator of the Howard Hughes Medical Institute. NR 65 TC 38 Z9 38 U1 1 U2 4 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD FEB PY 2009 VL 19 IS 1 BP 74 EP 81 DI 10.1016/j.gde.2008.12.004 PG 8 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 422LX UT WOS:000264430600012 PM 19195877 ER PT J AU Vrooman, LM Silverman, LB AF Vrooman, Lynda M. Silverman, Lewis B. TI Childhood acute lymphoblastic leukemia: update on prognostic factors SO CURRENT OPINION IN PEDIATRICS LA English DT Review DE childhood acute lymphoblastic leukemia; gene expression profiling; minimal residual disease; pharmacogenomics; prognostic factors ID MINIMAL RESIDUAL DISEASE; CHILDRENS ONCOLOGY GROUP; THYMIDYLATE SYNTHASE GENE; EARLY TREATMENT RESPONSE; CANCER-GROUP CCG; PHILADELPHIA-CHROMOSOME; CLINICAL-SIGNIFICANCE; INDUCTION FAILURE; INTRACHROMOSOMAL AMPLIFICATION; CYTOGENETIC ABNORMALITIES AB Purpose of review With current treatment regimens, event-free survival rates for childhood acute lymphoblastic leukemia (ALL) approach or exceed 80%. This success was achieved in, part, through the implementation of risk-stratified therapy. However, for the 15-20% of children with newly diagnosed ALL who will ultimately relapse traditional risk, assessment remains inadequate. This review highlights recent advances in our understanding of prognostic factors that may be used to refine risk group classification. Recent findings An increasingly sophisticated understanding of genetic abnormalities in leukemia cells (including chromosomal abnormalities and patterns of gene expression), response to treatment, and host pharmacogenomics offers the potential to enhance or supplant currently applied prognostic criteria for use in treatment planning for childhood ALL. Summary Identification of biologically distinctive subsets of ALL through cytogenetic, molecular, and gene expression studies, as well as investigations of minimal residual disease and host pharmacogenomics, offer promising avenues of research. Integration of molecular tools into clinical practice will ultimately allow for more precise risk stratification and individualized treatment planning. C1 [Vrooman, Lynda M.; Silverman, Lewis B.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Vrooman, LM (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM lynda-vrooman@dfci.harvard.edu FU NCI NIH HHS [T32 CA009172] NR 84 TC 48 Z9 52 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8703 J9 CURR OPIN PEDIATR JI CURR. OPIN. PEDIATR. PD FEB PY 2009 VL 21 IS 1 BP 1 EP 8 DI 10.1097/MOP.0b013e32831f1f24 PG 8 WC Pediatrics SC Pediatrics GA 423QN UT WOS:000264510900001 PM 19242236 ER PT J AU Dong, ZM Aplin, AC Nicosia, RF AF Dong, Zhao Ming (David) Aplin, Alfred C. Nicosia, Roberto F. TI Regulation of Angiogenesis by Macrophages, Dendritic Cells, and Circulating Myelomonocytic Cells SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review DE Macrophages; dendritic cells; myeloid cells; neovascularization; arteriogenesis ID ENDOTHELIAL GROWTH-FACTOR; TUMOR-ASSOCIATED MACROPHAGES; ADENOSINE A(2A) RECEPTORS; COLONY-STIMULATING FACTOR; HEMATOPOIETIC STEM-CELLS; HUMAN PERIPHERAL-BLOOD; NECROSIS-FACTOR-ALPHA; ADIPOSE-TISSUE; MYELOID CELLS; BREAST-CANCER AB Angiogenesis during reactive and pathologic processes is characteristically associated with inflammation. Macrophages and dendritic cells present in the inflammatory infiltrate contribute to the angiogenic process by multiple mechanisms. Macrophages produce a broad array of angiogenic growth factors and cytokines, generate conduits for blood flow through proteolytic mechanisms, and promote the remodeling of arterioles into arteries. They can also inhibit angiogenesis and cause reabsorption of neovessels by inducing endothelial cell death. Dendritic cells can stimulate or inhibit angiogenesis depending on their activation status and subset specificity. Dendritic cells stimulate angiogenesis by secreting angiogenic factors and cytokines, promoting the proangiogenic activity of T lymphocytes, and trans-differentiating into endothelial cells. Inflammatory infiltrates associated with angiogenesis also contain Tie2+, VEGFR2+, and GR1+ myelomonocytic cells which actively regulate the angiogenic process through paracrine mechanisms. In this paper we review our current knowledge of this field and discuss how recent advances have provided the rationale for novel therapeutic approaches against cancer. C1 [Nicosia, Roberto F.] VA Puget Sound Hlth Care Syst, Div Pathol & Lab Med, Lab S 113, Pathol & Lab Med Serv, Seattle, WA 98108 USA. [Aplin, Alfred C.; Nicosia, Roberto F.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. RP Nicosia, RF (reprint author), VA Puget Sound Hlth Care Syst, Div Pathol & Lab Med, Lab S 113, Pathol & Lab Med Serv, 1660 S Columbian Way, Seattle, WA 98108 USA. EM roberto.nicosia@va.gov NR 171 TC 32 Z9 32 U1 0 U2 2 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PD FEB PY 2009 VL 15 IS 4 BP 365 EP 379 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 415VF UT WOS:000263963500004 ER PT J AU Thomas, MK Tsang, SW Yeung, ML Leung, PS Yao, KM AF Thomas, Melissa K. Tsang, Siu Wai Yeung, Man-Lung Leung, Po Sing Yao, Kwok-Ming TI The Roles of the PDZ-containing Proteins Bridge-1 and PDZD2 in the Regulation of Insulin Production and Pancreatic Beta-Cell Mass SO CURRENT PROTEIN & PEPTIDE SCIENCE LA English DT Review DE PDZ; Bridge-1; PDZD2; insulin; pancreas ID COACTIVATOR BRIDGE-1; TRANSCRIPTIONAL ACTIVATION; NEURONAL INTERLEUKIN-16; DOMAIN COACTIVATOR; TUMOR-SUPPRESSOR; PROSTATE-CANCER; PROLIFERATION; APOPTOSIS; PROTEOME; CLASSIFICATION AB PDZ domains are versatile protein interaction modules with the ability to dimerize and to recognize internal and carboxy-terminal peptide motifs. Their function in mediating the formation of multi-molecular signaling complexes is best understood at neuronal and epithelial membranes. In a screen for interactors that regulate transcription factor function in pancreatic beta cells, we isolated two PDZ-containing proteins Bridge-1 (PSMD9) and PDZD2, which contain one and six PDZ domains, respectively. Here, we review their functions in the regulation of pancreatic beta cells as a nuclear coactivator or extracellular signaling molecule. Bridge-1 interacts with both E12 and PDX-1 to stimulate insulin promoter activity. Recent gain-of-function analysis in both cell and transgenic models has revealed its functions to regulate both insulin gene expression and pancreatic beta-cell survival. Little is known about the intracellular function of PDZD2 that is predominantly localized to the endoplasmic reticulum of INS-1E cells. Interestingly, PDZD2 is proteolytically processed by caspase-3 to generate a carboxy-terminal secreted protein (sPDZD2) containing two PDZ domains. Expressed in fetal pancreatic progenitor and INS-1E cells, sPDZD2 when added as recombinant protein exerts concentration-dependent mitogenic effects on beta-like cells. We propose that the PDZ domain proteins Bridge-1 and PDZD2 likely transduce signals that regulate insulin production, proliferation, and survival of pancreatic beta cells. C1 [Tsang, Siu Wai; Yeung, Man-Lung; Yao, Kwok-Ming] Univ Hong Kong, Dept Biochem, LKS Fac Med, Hong Kong, Hong Kong, Peoples R China. Massachusetts Gen Hosp, Mol Endocrinol Lab, Boston, MA 02114 USA. [Thomas, Melissa K.] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. [Thomas, Melissa K.] Harvard Univ, Sch Med, Boston, MA USA. [Leung, Po Sing] Chinese Univ Hong Kong, Dept Physiol, Fac Med, Shatin, Hong Kong, Peoples R China. [Leung, Po Sing] Chinese Univ Hong Kong, Li Ka Shing Inst Hlth Sci, Shatin, Hong Kong, Peoples R China. RP Yao, KM (reprint author), Univ Hong Kong, Dept Biochem, LKS Fac Med, 3-F Lab Block,Lks Fac Med Bldg,21 Sassoon Rd, Hong Kong, Hong Kong, Peoples R China. EM mthomas1@partners.org; kmyao@hkusua.hku.hk RI Yao, Kwok Ming/C-4457-2009; Leung, Po Sing/P-5758-2014 NR 50 TC 4 Z9 4 U1 0 U2 6 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-2037 J9 CURR PROTEIN PEPT SC JI Curr. Protein Pept. Sci. PD FEB PY 2009 VL 10 IS 1 BP 30 EP 36 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 415WZ UT WOS:000263968500005 PM 19275670 ER PT J AU Nierenberg, AA AF Nierenberg, Andrew A. TI LESSONS FROM STEP-BD FOR THE TREATMENT OF BIPOLAR DEPRESSION SO DEPRESSION AND ANXIETY LA English DT Editorial Material ID TREATMENT ENHANCEMENT PROGRAM; LITHIUM MAINTENANCE TREATMENT; CONTROLLED 18-MONTH TRIAL; DOUBLE-BLIND; I DEPRESSION; DISORDER; LAMOTRIGINE; OLANZAPINE; EFFICACY C1 [Nierenberg, Andrew A.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Nierenberg, Andrew A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Nierenberg, AA (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. EM anierenberg@partners.org NR 23 TC 8 Z9 10 U1 2 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1091-4269 EI 1520-6394 J9 DEPRESS ANXIETY JI Depress. Anxiety PD FEB PY 2009 VL 26 IS 2 BP 106 EP 109 DI 10.1002/da.20547 PG 4 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 406PN UT WOS:000263307500001 PM 19177467 ER PT J AU McFarland, BR Klein, DN AF McFarland, Brian R. Klein, Daniel N. TI EMOTIONAL REACTIVITY IN DEPRESSION: DIMINISHED RESPONSIVENESS TO ANTICIPATED REWARD BUT NOT TO ANTICIPATED PUNISHMENT OR TO NONREWARD OR AVOIDANCE SO DEPRESSION AND ANXIETY LA English DT Article DE depression; reward; punishment; appetitive; approach; withdrawal; behavioral activation; behavioral inhibition ID BEHAVIORAL ACTIVATION; MAJOR DEPRESSION; AFFECTIVE-DISORDERS; TRIPARTITE MODEL; ANXIETY; SYSTEMS; PSYCHOPATHOLOGY; INHIBITION; DIMENSIONS; THERAPY AB Objectives: This study compared depressed and nondepressed participants' emotional reactivity to anticipated reward, anticipated punishment, failure to obtain a reward, and successful avoidance of punishment. Experimental design: This study compared residualized change scores on target emotions for currently depressed (n = 19), previously depressed (n = 19), and never-depressed (n = 43) participants during four experimental conditions: anticipated reward (cash), anticipated punishment (cold pressor), nonreward (failure to earn cash), and avoidance (successful avoidance of a cold pressor). Principal observations: Currently depressed participants' reactivity in response to anticipated reward was significantly diminished compared with never depressed participants', and marginally diminished compared with previously depressed participants'. Currently depressed, previously depressed, and never-depressed participants did not differ significantly in their emotional reactivity to anticipated punishment or to nonreward or avoidance. Conclusions: These results suggest that depressed individuals' diminished emotional reactivity may be mainly it state effect and may be limited to anticipated reward. Depression and Anxiety 26:117-122, 2009. (C) 2008 Wiley-Liss, Inc. C1 [McFarland, Brian R.; Klein, Daniel N.] SUNY Stony Brook, Dept Psychol, Stony Brook, NY 11794 USA. RP McFarland, BR (reprint author), Birmingham VAMC, 700 S 19th St, Birmingham, AL 35233 USA. EM brian.macfarland@va.gov NR 37 TC 36 Z9 36 U1 2 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1091-4269 EI 1520-6394 J9 DEPRESS ANXIETY JI Depress. Anxiety PD FEB PY 2009 VL 26 IS 2 BP 117 EP 122 DI 10.1002/da.20513 PG 6 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 406PN UT WOS:000263307500003 PM 18972567 ER PT J AU Risebro, CA Searles, RG Melville, AAD Ehler, E Jina, N Shah, S Pallas, J Hubank, M Dillard, M Harvey, NL Schwartz, RJ Chien, KR Oliver, G Riley, PR AF Risebro, Catherine A. Searles, Richelle G. Melville, Athalie A. D. Ehler, Elisabeth Jina, Nipurna Shah, Sonia Pallas, Jacky Hubank, Mike Dillard, Miriam Harvey, Natasha L. Schwartz, Robert J. Chien, Kenneth R. Oliver, Guillermo Riley, Paul R. TI Prox1 maintains muscle structure and growth in the developing heart SO DEVELOPMENT LA English DT Article DE Prox1; Mouse; Heart development; Myocardium; Sarcomere; Hypertrophy; Myopathy; N-RAP (Nrap); Zyxin ID CARDIAC-HYPERTROPHY; DILATED CARDIOMYOPATHY; LYMPHATIC ENDOTHELIUM; TARGETED DISRUPTION; GENE-EXPRESSION; MOUSE HEART; N-RAP; PROSPERO; CARDIOMYOCYTES; TRANSCRIPTION AB Impaired cardiac muscle growth and aberrant myocyte arrangement underlie congenital heart disease and cardiomyopathy. We show that cardiac-specific inactivation of the murine homeobox transcription factor Prox1 results in the disruption of expression and localisation of sarcomeric proteins, gross myofibril disarray and growth-retarded hearts. Furthermore, we demonstrate that Prox1 is required for direct transcriptional regulation of the genes encoding the structural proteins alpha-actinin, N-RAP and zyxin, which collectively function to maintain an actin-alpha-actinin interaction as the fundamental association of the sarcomere. Aspects of abnormal heart development and the manifestation of a subset of muscular-based disease have previously been attributed to mutations in key structural proteins. Our study reveals an essential requirement for direct transcriptional regulation of sarcomere integrity, in the context of enabling foetal cardiomyocyte hypertrophy, maintenance of contractile function and progression towards inherited or acquired myopathic disease. C1 [Risebro, Catherine A.; Searles, Richelle G.; Melville, Athalie A. D.; Riley, Paul R.] UCL Inst Child Hlth, Mol Med Unit, London WC1N 1EH, England. [Ehler, Elisabeth] Kings Coll London, Randall Ctr Cell & Mol Biophys, London SE1 1UL, England. [Ehler, Elisabeth] Kings Coll London, Div Cardiovasc, London SE1 1UL, England. [Jina, Nipurna; Hubank, Mike] UCL Inst Child Hlth, Mol Haematol & Canc Biol Unit, London WC1N 1EH, England. [Shah, Sonia; Pallas, Jacky] UCL, Dept Comp Sci, Bloomsbury Ctr Bioinformat, London WC1E 6BT, England. [Dillard, Miriam; Oliver, Guillermo] St Jude Childrens Hosp, Dept Genet & Tumor Cell Biol, Memphis, TN 38105 USA. [Harvey, Natasha L.] Hanson Inst, Div Haematol, Adelaide, SA 5000, Australia. [Schwartz, Robert J.] Texas A&M Univ, Hlth Sci Ctr, Inst Biosci & Technol, Houston, TX 77030 USA. [Chien, Kenneth R.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Chien, Kenneth R.] Harvard Univ, Sch Med, Dept Cell Biol, Cambridge, MA 02138 USA. [Chien, Kenneth R.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Riley, PR (reprint author), UCL Inst Child Hlth, Mol Med Unit, London WC1N 1EH, England. EM p.riley@ich.ucl.ac.uk RI Pallas, Jacqueline/C-2994-2008; Hubank, Michael/C-1837-2008; Shah, Sonia/N-7547-2013; OI Hubank, Michael/0000-0002-2901-0742; Shah, Sonia/0000-0001-5860-4526; Pallas, Jacqueline/0000-0002-2207-3185; Ehler, Elisabeth/0000-0001-5646-5964 FU British Heart Foundation,; Medical Research Council [R01-HL073402]; National Institutes of Health; American Lebanese Syrian Associated Charities (ALSAC) FX We thank K. Venner for technical assistance with electron microscopy, A. Cook for advice on E18.5 heart analysis, C. Shang for advice on the ChIP protocol, D. Kelberman for advice on the EMSA protocol, and D. Furst ( titin and alpha-actinin) and T. Obinata (MyBP-C) for antibodies. This work was funded by the British Heart Foundation, the Medical Research Council, and by R01-HL073402 ( G. O.) from the National Institutes of Health and by the American Lebanese Syrian Associated Charities (ALSAC). Deposited in PMC for release after 12 months. NR 48 TC 47 Z9 48 U1 0 U2 3 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD FEB 1 PY 2009 VL 136 IS 3 BP 495 EP 505 DI 10.1242/dev.030007 PG 11 WC Developmental Biology SC Developmental Biology GA 393XJ UT WOS:000262409500015 PM 19091769 ER PT J AU Jimenez-Chillaron, JC Isganaitis, E Charalambous, M Gesta, S Pentinat-Pelegrin, T Faucette, RR Otis, JP Chow, A Diaz, R Ferguson-Smith, A Patti, ME AF Jimenez-Chillaron, Josep C. Isganaitis, Elvira Charalambous, Marika Gesta, Stephane Pentinat-Pelegrin, Thais Faucette, Ryan R. Otis, Jessica P. Chow, Alice Diaz, Ruben Ferguson-Smith, Anne Patti, Mary-Elizabeth TI Intergenerational Transmission of Glucose Intolerance and Obesity by In Utero Undernutrition in Mice SO DIABETES LA English DT Article ID FOR-GESTATIONAL-AGE; INTRAUTERINE GROWTH-RETARDATION; LOW-BIRTH-WEIGHT; METABOLIC-SYNDROME; INSULIN-SECRETION; DIABETES-MELLITUS; DNA METHYLATION; TRANSGENERATIONAL INHERITANCE; DEVELOPMENTAL ORIGINS; SOUTH-INDIA AB OBJECTIVE-Low birth weight (LBW) is associated with increased risk of obesity, diabetes, and cardiovascular disease during adult life. Moreover, this programmed disease risk can progress to subsequent generations. We previously described a mouse model of LBW, produced by maternal caloric undernutrition (UN) during late gestation. LBW offspring (F(1)-UN generation) develop progressive obesity and impaired glucose tolerance (IGT) with aging. We aimed to determine whether such metabolic phenotypes can be transmitted to subsequent generations in an experimental model, even in the absence of altered nutrition during the second pregnancy. RESEARCH DESIGN AND METHODS-We intercrossed female and male F(1) adult control (C) and UN mice and characterized metabolic phenotypes in F(2) offspring. RESULTS-We demonstrate that 1) reduced birth weight progresses to F(2) offspring through the paternal line (C female-C male = 1.64 g; C female-UN male = 1.57 g, P < 0.05; UN female-C male = 1.64 g; UN female-UN male = 1.60 g, P < 0.05), 2) obesity progresses through the maternal line (percent body fat: C female-C male = 22.4%; C female-UN male = 22.9%; UN female-C male = 25.9%, P < 0.05; UN female-UN male = 27.5%, P < 0.05), and 3) IGT progresses through both parental lineages (glucose tolerance test area under curve C female-C male = 100; C female-UN male - 122, P < 0. 05; UN female-C male = 131, P < 0.05; UN female-UN male = 151, P < 0.05). Mechanistically, IGT in both F(1) and F(2) generations is linked to impaired beta-cell function, explained, in part, by dysregulation of Sur1 expression. CONCLUSIONS-Maternal undernutrition during pregnancy (F(0)) programs reduced birth weight, IGT, and obesity in both first- and second-generation offspring. Sex-specific transmission of phenotypes implicates complex mechanisms including alterations in the maternal metabolic environment (transmaternal inheritance of obesity), gene expression mediated by developmental and epigenetic pathways (transpaternal inheritance of LBW), or both (IGT). Diabetes 58:460-468, 2009 C1 [Jimenez-Chillaron, Josep C.; Isganaitis, Elvira; Gesta, Stephane; Faucette, Ryan R.; Otis, Jessica P.; Chow, Alice; Patti, Mary-Elizabeth] Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. [Charalambous, Marika; Ferguson-Smith, Anne] Univ Cambridge, Cambridge, England. [Pentinat-Pelegrin, Thais; Diaz, Ruben] Univ Barcelona, Hosp St Joan Den, Barcelona, Spain. [Diaz, Ruben] Harvard Univ, Sch Med, Div Endocrinol, Childrens Hosp Boston, Boston, MA 02115 USA. RP Patti, ME (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. EM mary.elizabeth.patti@joslin.harvard.edu RI Ferguson-Smith, Anne/G-7534-2011; OI Charalambous, Marika/0000-0002-1684-5783 FU American Diabetes Association; Graetz Farnily Fund; Marie Curie International Reintegration [MIRG-CT-2007-046542]; Diabetes Endocrinology Research Center [P30-DK36836] FX No potential conflicts of interest. relevant to this article were reported. NR 50 TC 128 Z9 133 U1 2 U2 21 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD FEB PY 2009 VL 58 IS 2 BP 460 EP 468 DI 10.2337/db08-0490 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 401GI UT WOS:000262927500023 PM 19017762 ER PT J AU Utzschneider, KM Prigeon, RL Faulenbach, MV Tong, J Carr, DB Boyko, EJ Leonetti, DL McNeely, MJ Fujimoto, WY Kahn, SE AF Utzschneider, Kristina M. Prigeon, Ronald L. Faulenbach, Mirjam V. Tong, Jenny Carr, Darcy B. Boyko, Edward J. Leonetti, Donna L. McNeely, Marguerite J. Fujimoto, Wilfred Y. Kahn, Steven E. TI Oral Disposition Index Predicts the Development of Future Diabetes Above and Beyond Fasting and 2-h Glucose Levels SO DIABETES CARE LA English DT Article ID BETA-CELL FUNCTION; HEPATIC INSULIN EXTRACTION; HIGH-RISK; 1ST-DEGREE RELATIVES; PREVENTION PROGRAM; TOLERANCE TEST; SENSITIVITY; RESISTANCE; SECRETION; MELLITUS AB OBJECTIVE - We sought to determine whether an oral disposition index (DI(O)) predicts the development of diabetes over a 10-year period. First, we assessed the validity of the DI(O) by demonstrating that a hyperbolic relationship exists between oral indexes of insulin sensitivity and beta-cell function. RESEARCH DESIGN AND METHODS - A total of 613 Japanese-American subjects (322 men and 291 women) underwent a 75-g Oral glucose tolerance test (OGTT) at baseline, 5 years, and 1.0 years. Insulin sensitivity was estimated as 1/fasting insulin or homeostasis model assessment of insulin sensitivity (HOMA-S). Insulin response Was estimated as the change in insulin divided by change in glucose from 0 to 30 min (Delta l(0-30)/Delta G(0-30)). RESULTS - Delta l(0-30)/Delta G(0-30) demonstrated a curvilinear relationship with 1/fasting insulin and HOMA-S With a left and downward shift as glucose tolerance deteriorated. The confidence limits for the slope of the log(e)-transformed estimates included -1 for Delta l(0-30)/Delta G(0-30) versus 1/fasting insulin for all glucose tolerance groups, consistent with a hyperbolic relationship. When HOMA-S was used as the insulin Sensitivity measure, the confidence limits for the slope included - I only for Subjects With normal glucose tolerance (NCT) or impaired fasting glucose (IFG/impaired glucose tolerance (IGT) but not diabetes. On the basis of this hyperbolic relationship, the product of Delta l(0-30)/Delta G(0-30) and 1/fasting insulin was calculated (DI(O)) and decreased fron NGT to IFG/IGT to diabetes (P < 0.001). Among nondiabetic subjects at baseline, baseline DI(O) predicted cumulative diabetes at 10 years (P<0.001) independent of age, sex, BMI, family history of diabetes, and baseline fasting and 2-h glucose concentrations. CONCLUSIONS- The DI(O) provides a measure of beta-cell function adjusted for insulin sensitivity and is predictive of development of diabetes over 10 years. C1 [Utzschneider, Kristina M.; Faulenbach, Mirjam V.; Tong, Jenny; Kahn, Steven E.] Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA USA. [Utzschneider, Kristina M.; Faulenbach, Mirjam V.; Tong, Jenny; McNeely, Marguerite J.; Fujimoto, Wilfred Y.; Kahn, Steven E.] Univ Washington, Dept Med, Seattle, WA USA. [Prigeon, Ronald L.] Baltimore Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Baltimore, MD USA. [Prigeon, Ronald L.] Univ Maryland, Sch Med, Div Gerontol, Baltimore, MD 21201 USA. [Carr, Darcy B.] Univ Washington, Dept Obstet & Gynecol, Div Maternal Fetal Med, Seattle, WA 98195 USA. [Boyko, Edward J.] Vet Affairs Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA USA. [Leonetti, Donna L.] Univ Washington, Dept Anthropol, Seattle, WA 98195 USA. RP Utzschneider, KM (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA USA. EM kutzschn@u.washington.edu OI Kahn, Steven/0000-0001-7307-9002 FU Department of Veteran Affairs; Veteran Affairs Geriatrics Research, Education, and Clinical Center; National Institutes of Health [DK-02654, DK-31170, HL-49293, RR-00037, DK-35816, P30 DK-17047] FX This work was supported by the Department of Veteran Affairs and the Veteran Affairs Geriatrics Research, Education, and Clinical Center, National Institutes of Health grants DK-02654, DK-31170, HL-49293, RR-00037, DK-35816, and P30 DK-17047. NR 25 TC 184 Z9 189 U1 0 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD FEB PY 2009 VL 32 IS 2 BP 335 EP 341 DI 10.2337/dc08-1478 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 402MV UT WOS:000263018700024 PM 18957530 ER PT J AU Lopez, X Bouche, C Tatro, E Goldfine, AB AF Lopez, X. Bouche, C. Tatro, E. Goldfine, A. B. TI Family history of diabetes impacts on interactions between minimal model estimates of insulin sensitivity and glucose effectiveness SO DIABETES OBESITY & METABOLISM LA English DT Article DE family history; glucose effectiveness; impaired glucose tolerance; insulin sensitivity; minimal model; type 2 diabetes ID SKELETAL-MUSCLE; GLUTAMINE-FRUCTOSE-6-PHOSPHATE AMIDOTRANSFERASE; PYRUVATE-DEHYDROGENASE; 2-COMPARTMENT MODEL; GLYCOGEN-SYNTHESIS; TISSUE SITES; BETA-CELL; IN-VIVO; RESISTANCE; NIDDM AB Insulin resistance and glucose effectiveness (S(G)) are major determinants of glucose tolerance and independently predict the development of type 2 diabetes in individuals with a family history of disease. We examined the inter-relationship between insulin sensitivity (S(I)) and S(G) in offspring of two parents with type 2 diabetes and in individuals with no family history of diabetes. Fifty non-diabetic individuals, including 26 offspring of two type 2 diabetic parents (family history, FH+) and 24 with no family history of diabetes (FH-) similar in gender, age, ethnicity and body mass index (BMI) were studied. Each subject underwent a 100-g oral glucose tolerance test (OGTT) and insulin modified frequently sampled intravenous glucose tolerance, analysed using the Bergman's minimal model (MINMOD). Thirteen subjects of the FH+ group and nine of the FH- group had impaired glucose tolerance (IGT). S(I) and S(G) were independent variables in the FH+ group, while they correlated highly with each other in the FH- group (r = 0.69, p = 0.0002). The relationship between S(I) and S(G) persisted when analysing the IGT and normal glucose tolerance subgroups separately, demonstrating that these associations were not because of differences in glycaemia. Consistently, S(G) strongly correlated with additional measures of insulin resistance only in the FH- group, including fasting insulin (r = 0.56, p = 0.004), homeostasis model assessment of insulin resistance (r = 0.57 p = 0.003) and BMI (r = 0.66, p = 0.0004). These results demonstrate that familial factors impart important physiological differences in the inter-relationship between insulin-dependent and insulin-independent glucose disposal, which may be important in modulating risk for development of disease. C1 [Lopez, X.; Bouche, C.; Tatro, E.; Goldfine, A. B.] Joslin Diabet Ctr, Dept Clin Res, Boston, MA 02215 USA. [Lopez, X.; Goldfine, A. B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Lopez, X.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Goldfine, AB (reprint author), Joslin Diabet Ctr, Dept Clin Res, 1 Joslin Pl, Boston, MA 02215 USA. EM allison.goldfine@joslin.harvard.edu FU National Institutes of Health [K23-DK02795, R01DK070648]; American Diabetes Association [06-CD-07]; Eleanor and Miles Shore 50th Anniversary Fellowship Award; Joslin Diabetes and Endocrinology Research Center (DERC) National Institutes of Health [P30 DK36836]; Beth Israel Deaconess General Clinical Research Center [M01 RR001032] FX This work was supported by National Institutes of Health K23-DK02795 (A. B. G.) and R01DK070648 (A. B. G., X. L.), American Diabetes Association 06-CD-07 (A. B. G.), The Eleanor and Miles Shore 50th Anniversary Fellowship Award (C. B.), Joslin Diabetes and Endocrinology Research Center (DERC) National Institutes of Health (P30 DK36836) Specialized Assay Core at the Joslin Diabetes Center and Beth Israel Deaconess General Clinical Research Center M01 RR001032. NR 46 TC 5 Z9 5 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1462-8902 J9 DIABETES OBES METAB JI Diabetes Obes. Metab. PD FEB PY 2009 VL 11 IS 2 BP 123 EP 130 DI 10.1111/j.1463-1326.2008.00913.x PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 389PA UT WOS:000262105800007 PM 18518893 ER PT J AU Hanauer, DA Wentzell, K Laffel, N Laffel, LM AF Hanauer, David A. Wentzell, Katherine Laffel, Nikki Laffel, Lori M. TI Computerized Automated Reminder Diabetes System (CARDS): E-Mail and SMS Cell Phone Text Messaging Reminders to Support Diabetes Management SO DIABETES TECHNOLOGY & THERAPEUTICS LA English DT Article ID GLYCEMIC CONTROL; METABOLIC-CONTROL; MELLITUS; YOUTH; YOUNG; CHILDREN; ADOLESCENTS; PREDICTORS; MORTALITY; ADULTHOOD AB Background: Cell phone text messaging, via the Short Messaging Service (SMS), offers the promise of a highly portable, well-accepted, and inexpensive modality for engaging youth and young adults in the management of their diabetes. This pilot and feasibility study compared two-way SMS cell phone messaging with e-mail reminders that were directed at encouraging blood glucose (BG) monitoring. Methods: Forty insulin-treated adolescents and young adults with diabetes were randomized to receive electronic reminders to check their BG levels via cell phone text messaging or e-mail reminders for a 3-month pilot study. Electronic messages were automatically generated, and participant replies with BG results were processed by the locally developed Computerized Automated Reminder Diabetes System (CARDS). Participants set their schedule for reminders on the secure CARDS website where they could also enter and review BG data. Results: Of the 40 participants, 22 were randomized to receive cell phone text message reminders and 18 to receive e-mail reminders; 18 in the cell phone group and 11 in the e-mail group used the system. Compared to the e-mail group, users in the cell phone group received more reminders (180.4 vs. 106.6 per user) and responded with BG results significantly more often (30.0 vs. 6.9 per user, P = 0.04). During the first month cell phone users submitted twice as many BGs as e-mail users (27.2 vs. 13.8 per user); by month 3, usage waned. Conclusions: Cell phone text messaging to promote BG monitoring is a viable and acceptable option in adolescents and young adults with diabetes. However, maintaining interest levels for prolonged intervals remains a challenge. C1 [Laffel, Lori M.] Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, Sect Genet & Epidemiol, Boston, MA 02215 USA. [Hanauer, David A.] Univ Michigan, Sch Med, Dept Pediat, Ann Arbor, MI USA. RP Laffel, LM (reprint author), Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, Sect Genet & Epidemiol, 1 Joslin Pl, Boston, MA 02215 USA. EM lori.laffel@joslin.harvard.edu FU Katherine Adler Astrove Fund; Maria Griffin Drury Pediatric Research Fund FX D.A.H. provided the technical capabilities for the design and implementation of CARDS. We would also like to thank Robert A. Greenes, Andrew Seger, Steven Labkoff, and the Joslin Information Technology staff. Financial support was provided by the Katherine Adler Astrove Fund and the Maria Griffin Drury Pediatric Research Fund. NR 47 TC 126 Z9 127 U1 1 U2 7 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1520-9156 J9 DIABETES TECHNOL THE JI Diabetes Technol. Ther. PD FEB PY 2009 VL 11 IS 2 BP 99 EP 106 DI 10.1089/dia.2008.0022 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 399PG UT WOS:000262811200007 PM 19848576 ER PT J AU Dodge, R Loomans, C Sharma, A Bonner-Weir, S AF Dodge, Rikke Loomans, Cindy Sharma, Arun Bonner-Weir, Susan TI Developmental pathways during in vitro progression of human islet neogenesis SO DIFFERENTIATION LA English DT Article DE Islet; Neogenesis; Differentiation; Ductal cells; Pancreas ID BETA-CELL MASS; TERMINAL DIFFERENTIATION; TRANSGENIC MICE; ENDOCRINE PANCREAS; EPITHELIAL-CELLS; PROGENITOR CELLS; DEVELOPING MOUSE; GENE-EXPRESSION; PRECURSOR CELLS; RAT AB Islet neogenesis, or the differentiation of islet cells from precursor cells, is seen in vitro and in vivo both embryonically and after birth. However, little is known about the differentiation pathways during embryonic development for human pancreas. Our previously reported in vitro generation of islets from human pancreatic tissue provides a unique system to identify potential markers of neogenesis and to determine the molecular mechanisms underlying this process. To this end, we analyzed the gene expression profiles of three different stages during in vitro islet generation: the Initially Adherent, Expanded, and Differentiated stages. Samples from four human pancreases were hybridized to Affymetrix U95A GeneChips, and data analyzed using GeneSpring 7.0/9.0 software. Using scatter plots we selected genes with a 2-fold or greater differential expression. Of the 12,000 genes/ESTs present on these arrays, 295 genes including 38 acinar-enriched genes were selectively lost during the progression from the Initially Adherent stage to the Expanded stage; 468 genes were increased in this progression to Expanded tissue; and 529 genes had a two-fold greater expression in the Differentiated stage than in the Expanded tissue. Besides the expected increases in insulin, glucagon, and duct markers (mucin 6, aquaporin 1 and 5), the beta cell auto-antigen IA-2/phogrin was increased 5-fold in Differentiated. In addition, developmentally important pathways, including notch/jagged, Wnt/frizzled, TGF beta superfamily (follistatin, BMPs, and SMADs), and retinoic acid (COUP-TFI, CRABP1,2, and RAIG1) were differentially regulated during the expansion/differentiation. Two putative markers for islet precursor cells, UCHL1/PGP9.5 and DMBT1, were enhanced during the progression to differentiated cells, but only the latter could be a marker of islet precursor cells. We suggest that appropriate manipulation of these differentiation-associated pathways will enhance the efficiency of differentiation of insulin-producing beta-cells in this in vitro model. (C) 2008 International Society of Differentiation. Published by Elsevier Ltd. All rights reserved. C1 [Dodge, Rikke; Loomans, Cindy; Sharma, Arun; Bonner-Weir, Susan] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. RP Bonner-Weir, S (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, 1 Joslin Pl, Boston, MA 02215 USA. EM susan.bonner-weir@joslin.harvard.edu OI Bonner-Weir, Susan/0000-0003-4682-0656 FU NIDDK NIH HHS [R01 DK044523, DK44523, U19DK61251, R01 DK044523-12, P30 DK036836, P30 DK036836-219020, U19 DK061251, U19 DK061251-020001, DK36836] NR 53 TC 9 Z9 12 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0301-4681 J9 DIFFERENTIATION JI Differentiation PD FEB PY 2009 VL 77 IS 2 BP 135 EP 147 DI 10.1016/j.diff.2008.09.015 PG 13 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 555RH UT WOS:000274531100004 PM 19281773 ER PT J AU Goldstein, JN Greer, DM AF Goldstein, Joshua N. Greer, David M. TI Rapid Focused Neurological Assessment in the Emergency Department and ICU SO EMERGENCY MEDICINE CLINICS OF NORTH AMERICA LA English DT Article DE Neurologic examination; Physical examination; Emergency medicine; Critical care ID EARLY STROKE TREATMENT; RT-PA STROKE; ISCHEMIC-STROKE; RULE; PSEUDOSEIZURES; ASSOCIATION; EPILEPSY; CRITERIA; QUALITY; PATIENT AB In the emergency and critical care setting, a comprehensive and thorough neurologic examination can be impractical. The clinical context should therefore focus the examination on those features relevant to acute diagnosis and management. This article discusses how to direct the history and examination in patients who have focal complaints, possible strokes affecting the anterior or posterior circulations, neck or back pain, neuromuscular complaints, global symptoms, or nonanatomic complaints. C1 [Goldstein, Joshua N.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Greer, David M.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Goldstein, JN (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Zero Emerson Pl,Suite 3B, Boston, MA 02114 USA. EM jgoldstein@partners.org RI Goldstein, Joshua/H-8953-2016 NR 26 TC 4 Z9 4 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 0733-8627 J9 EMERG MED CLIN N AM JI Emerg. Med. Clin. N. Am. PD FEB PY 2009 VL 27 IS 1 BP 1 EP + DI 10.1016/j.emc.2008.07.002 PG 17 WC Emergency Medicine SC Emergency Medicine GA 420MC UT WOS:000264292900003 PM 19218015 ER PT J AU Wheless, JW Carmant, L Bebin, M Conry, JA Chiron, C Elterman, RD Frost, M Paolicchi, JM Shields, WD Thiele, EA Zupanc, ML Collins, SD AF Wheless, James W. Carmant, Lionel Bebin, Martina Conry, Joan A. Chiron, Catherine Elterman, Roy D. Frost, Michael Paolicchi, Juliann M. Shields, W. Donald Thiele, Elizabeth A. Zupanc, Mary L. Collins, Stephen D. TI Magnetic resonance imaging abnormalities associated with vigabatrin in patients with epilepsy SO EPILEPSIA LA English DT Article DE Vigabatrin; Magnetic resonance imaging abnormalities; Infantile spasms; Infants; Seizures; Epilepsy ID INDUCED INTRAMYELINIC EDEMA; SEMIALDEHYDE DEHYDROGENASE-DEFICIENCY; GABA-TRANSAMINASE INHIBITOR; COMPLEX PARTIAL SEIZURES; INFANTILE SPASMS; RANDOMIZED TRIAL; INDUCED LESIONS; BASAL GANGLIA; WEST-SYNDROME; DOUBLE-BLIND AB Vigabatrin used to treat infantile spasms (IS) has been associated with transient magnetic resonance imaging (MRI) abnormalities. We carried out a retrospective review to better characterize the frequency of those abnormalities in IS and in children and adults treated with vigabatrin for refractory complex partial seizures (CPS). Medical records and 332 cranial MRIs from 205 infants (aged <= 24 months) with IS treated at 10 sites in the United States and Canada were collected. Similarly, 2,074 images from 668 children (aged 2-16 years) and adults (aged > 16 years) with CPS were re-reviewed. Prespecified MRI abnormalities were defined as any hyperintensity on T(2)-weighted or fluid-attenuated inversion-recovery (FLAIR) sequences with or without diffusion restriction not readily explained by a radiographically well-characterized pathology. MRIs were read by two neuroradiologists blinded to treatment group. The incidence and prevalence of MRI abnormalities associated with vigabatrin were estimated. Among infants with IS, the prevalence of prespecified MRI abnormalities was significantly higher among vigabatrin-treated versus vigabatrin-naive subjects (22% vs. 4%; p < 0.001). Of nine subjects in the prevalence population with at least one subsequent determinate MRI, resolution of MRI abnormalities occurred in six (66.7%)-vigabatrin was discontinued in four. Among adults and children treated with vigabatrin for CPS, there was no statistically significant difference in the incidence or prevalence of prespecified MRI abnormalities between vigabatrin-exposed and vigabatrin-naive subjects. Vigabatrin is associated with transient, asymptomatic MRI abnormalities in infants treated for IS. The majority of these MRI abnormalities resolved, even in subjects who remained on vigabatrin therapy. C1 [Wheless, James W.] Univ Tennessee, Lebonheur Childrens Med Ctr, Hlth Sci Ctr, Memphis, TN 38105 USA. [Wheless, James W.] Univ Tennessee, LeBonheur Neurosci Inst, Memphis, TN 38105 USA. [Carmant, Lionel] St Justines Mother Child Univ Hosp, Montreal, PQ, Canada. [Bebin, Martina] Univ Alabama, Dept Neurol, Birmingham, AL 35294 USA. [Conry, Joan A.] Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA. [Chiron, Catherine] Hop Necker Enfants Malad, Dept Pediat Neurol, Paris, France. [Elterman, Roy D.] Dallas Pediat Neurol Associates, Dallas, TX USA. [Frost, Michael] Minnesota Epilepsy Grp, St Paul, MN USA. [Paolicchi, Juliann M.] Monroe Carell Jr Childrens Hosp Vanderbilt, Nashville, TN USA. [Shields, W. Donald] Univ Calif Los Angeles, Mattel Childrens Hosp, Dept Pediat Neurol, Los Angeles, CA USA. [Thiele, Elizabeth A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Zupanc, Mary L.] Childrens Hosp Wisconsin, Milwaukee, WI 53201 USA. [Collins, Stephen D.] Ovat Pharmaceut Inc, Deerfield, IL USA. RP Wheless, JW (reprint author), Univ Tennessee, Lebonheur Childrens Med Ctr, Hlth Sci Ctr, 777 Washington Ave,P335, Memphis, TN 38105 USA. EM jwheless@utmem.edu RI Chiron, Catherine/E-8506-2016 FU Ovation Pharmaceuticals FX Disclosures of conflicts of interest: JW, CC, JC, RE, and ET have served as paid consultants to Ovation Pharmaceuticals. JW, RE, DS, and ET have received grants from Ovation Pharmaceuticals for other research or activities not reported in this article. The remaining authors have no conflicts of interest. NR 36 TC 51 Z9 52 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD FEB PY 2009 VL 50 IS 2 BP 195 EP 205 DI 10.1111/j.1528-1167.2008.01896.x PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA 399DY UT WOS:000262781800004 PM 19054414 ER PT J AU Muzykewicz, DA Costello, DJ Halpern, EF Thiele, EA AF Muzykewicz, David A. Costello, Daniel J. Halpern, Elkan F. Thiele, Elizabeth A. TI Infantile spasms in tuberous sclerosis complex: Prognostic utility of EEG SO EPILEPSIA LA English DT Article DE Tuberous sclerosis complex; Infantile spasms; Electroencephalography; Cognitive impairment; Epilepsy ID LONG-TERM PROGNOSIS; WEST-SYNDROME; EPILEPSY; TSC1; HYPSARRHYTHMIA; CHILDREN; IDENTIFICATION; VIGABATRIN; DIAGNOSIS; GENE AB To assess cognitive and epilepsy outcomes in tuberous sclerosis complex (TSC) patients with a history of infantile spasms (IS), in relation to spasm history, electroencephalography (EEG) characteristics, genetic mutation, and treatment history. The authors conducted a retrospective review of 45 children and adults with TSC and a history of IS. EEG reports from the time of spasms were evaluated for all patients, and EEG tracings were accessible and evaluated for 20 patients. Clinical outcome was unfavorable for the majority of patients. However, 33% had experienced at least one year of seizure freedom at follow-up, and 24% of those tested had IQs above 70. Hypsarrhythmia severity scores varied widely, with some EEGs severely hypsarrhythmic and others essentially normal. Lower IQ was significantly associated with higher hypsarrhythmia severity scores on EEG report, the presence of background disorganization on EEG report, the absence of normal sleep patterns on EEG, and a lower degree of treatment success on vigabatrin. A relationship between poor cognitive outcome and poor epilepsy outcome was confirmed. The correlation between poor epilepsy outcome and a greater degree of background disorganization on EEG approached significance, as did the association between subsequent intractable epilepsy and an older age at IS cessation. A greater than expected ratio of TSC2 to TSC1 patients was observed across this IS population. Early detection and successful treatment portend a more favorable outcome in TSC patients with IS. Although EEG findings in these patients vary, specific characteristics may serve as clinically useful prognostic markers. C1 [Muzykewicz, David A.; Costello, Daniel J.; Thiele, Elizabeth A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Halpern, Elkan F.] MGH Inst Technol Assessment, Boston, MA USA. RP Thiele, EA (reprint author), Carol & James Herscot Ctr Tuberous Sclerosis Comp, 175 Cambridge St,Suite 340, Boston, MA 02114 USA. EM ethiele@partners.org FU Carol and James Herscot Center for Tuberous Sclerosis Complex FX This study was supported by the Carol and James Herscot Center for Tuberous Sclerosis Complex. We confirm that we have read the Journal's positions on issues involved in ethical publication and affirm that this report is consistent with those guidelines. NR 30 TC 27 Z9 27 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0013-9580 EI 1528-1167 J9 EPILEPSIA JI Epilepsia PD FEB PY 2009 VL 50 IS 2 BP 290 EP 296 DI 10.1111/j.1528-1167.2008.01788.x PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 399DY UT WOS:000262781800014 PM 18801034 ER PT J AU Kossoff, EH Zupec-Kania, BA Amark, PE Ballaban-Gil, KR Bergqvist, AGC Blackford, R Buchhalter, JR Caraballo, RH Cross, JH Dahlin, MG Donner, EJ Klepper, J Jehle, RS Kim, HD Liu, YMC Nation, J Nordli, DR Pfeifer, HH Rho, JM Stafstrom, CE Thiele, EA Turner, Z Wirrell, EC Wheless, JW Veggiotti, P Vining, EPG AF Kossoff, Eric H. Zupec-Kania, Beth A. Amark, Per E. Ballaban-Gil, Karen R. Bergqvist, A. G. Christina Blackford, Robyn Buchhalter, Jeffrey R. Caraballo, Roberto H. Cross, J. Helen Dahlin, Maria G. Donner, Elizabeth J. Klepper, Joerg Jehle, Rana S. Kim, Heung Dong Liu, Y. M. Christiana Nation, Judy Nordli, Douglas R., Jr. Pfeifer, Heidi H. Rho, Jong M. Stafstrom, Carl E. Thiele, Elizabeth A. Turner, Zahava Wirrell, Elaine C. Wheless, James W. Veggiotti, Pierangelo Vining, Eileen P. G. CA Charlie Fdn Practice Comm Child Neurol Soc TI Optimal clinical management of children receiving the ketogenic diet: Recommendations of the International Ketogenic Diet Study Group SO EPILEPSIA LA English DT Article; Proceedings Paper CT International Symposium on Dietary Therapies for Epilepsy and other Neurological Disorders CY APR, 2008 CL Phoenix, AZ DE Children; Consensus; Diet; Epilepsy; Ketogenic ID MODIFIED ATKINS DIET; MYOCLONIC-ASTATIC EPILEPSY; INTRACTABLE EPILEPSY; PEDIATRIC EPILEPSY; CHILDHOOD EPILEPSY; RISK-FACTORS; ANTIEPILEPTIC DRUGS; TUBEROUS-SCLEROSIS; INFANTILE SPASMS; DRAVET SYNDROME AB The ketogenic diet (KD) is an established, effective nonpharmacologic treatment for intractable childhood epilepsy. The KD is provided differently throughout the world, with occasionally significant variations in its administration. There exists a need for more standardized protocols and management recommendations for clinical and research use. In December 2006, The Charlie Foundation commissioned a panel comprised of 26 pediatric epileptologists and dietitians from nine countries with particular expertise using the KD. This group was created in order to create a consensus statement regarding the clinical management of the KD. Subsequently endorsed by the Practice Committee of the Child Neurology Society, this resultant manuscript addresses issues such as patient selection, pre-KD counseling and evaluation, specific dietary therapy selection, implementation, supplementation, follow-up management, adverse event monitoring, and eventual KD discontinuation. This paper highlights recommendations based on best evidence, including areas of agreement and controversy, unanswered questions, and future research. C1 [Kossoff, Eric H.; Turner, Zahava; Vining, Eileen P. G.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. [Zupec-Kania, Beth A.] Childrens Hosp Wisconsin, Milwaukee, WI 53201 USA. [Amark, Per E.; Dahlin, Maria G.] Karolinska Hosp, S-10401 Stockholm, Sweden. [Ballaban-Gil, Karen R.; Jehle, Rana S.] Montefiore Med Ctr, Bronx, NY 10467 USA. [Bergqvist, A. G. Christina] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Blackford, Robyn; Nordli, Douglas R., Jr.] Childrens Mem Hosp, Chicago, IL 60614 USA. [Buchhalter, Jeffrey R.] Phoenix Childrens Hosp, Phoenix, AZ USA. [Caraballo, Roberto H.] Hosp Pediat Prof Dr Juan P Garrahan, Buenos Aires, DF, Argentina. [Cross, J. Helen] Great Ormond St Hosp Sick Children, London WC1N 3JH, England. [Cross, J. Helen] Inst Child Hlth, London, England. [Donner, Elizabeth J.; Liu, Y. M. Christiana] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Klepper, Joerg] Childrens Hosp, Aschaffenburg, Germany. [Kim, Heung Dong] Severance Childrens Hosp, Seoul, South Korea. [Nation, Judy] Royal Childrens Hosp, Melbourne, Vic, Australia. [Pfeifer, Heidi H.; Thiele, Elizabeth A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rho, Jong M.] Barrow Neurol Inst, Phoenix, AZ 85013 USA. [Stafstrom, Carl E.] Univ Wisconsin, Madison, WI USA. [Wirrell, Elaine C.] Mayo Clin, Rochester, MN USA. [Wheless, James W.] St Jude Childrens Res Hosp, Lebonheur Childrens Med Ctr, Memphis, TN 38101 USA. [Veggiotti, Pierangelo] Univ Pavia, I-27100 Pavia, Italy. RP Kossoff, EH (reprint author), Johns Hopkins Univ Hosp, Suite 2158,200 N Wolfe St, Baltimore, MD 21287 USA. EM ekossoff@jhmi.edu NR 84 TC 184 Z9 203 U1 5 U2 21 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD FEB PY 2009 VL 50 IS 2 BP 304 EP 317 DI 10.1111/j.1528-1167.2008.01765.x PG 14 WC Clinical Neurology SC Neurosciences & Neurology GA 399DY UT WOS:000262781800016 PM 18823325 ER PT J AU Singh, SM d'Avila, A Reddy, VY AF Singh, Sheldon M. d'Avila, Andre Reddy, Vivek Y. TI Congestive heart failure after atrial fibrillation ablation SO EUROPACE LA English DT Article C1 [d'Avila, Andre; Reddy, Vivek Y.] Univ Miami Hosp, Cardiac Arrhythmia Serv, Miami, FL 33126 USA. [Singh, Sheldon M.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP Reddy, VY (reprint author), Univ Miami Hosp, Cardiac Arrhythmia Serv, 1400 NW 12th Ave,Suite 4062, Miami, FL 33126 USA. EM vreddy@med.miami.edu RI d'Avila, Andre/A-7693-2009; d'Avila, Andre Luiz/F-8009-2010 OI d'Avila, Andre Luiz/0000-0001-8769-1411 FU Royal College of Physicians and Surgeons of Canada, Ottawa, Ontario, Canada FX M. S. is a recipient of a Detweiler Traveling Fellowship from the Royal College of Physicians and Surgeons of Canada, Ottawa, Ontario, Canada. NR 0 TC 7 Z9 7 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1099-5129 J9 EUROPACE JI Europace PD FEB PY 2009 VL 11 IS 2 BP 272 EP 272 DI 10.1093/europace/eun313 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 398FW UT WOS:000262719000034 PM 19010797 ER PT J AU Sanna, K Rachel, PW Hanna, E Tuula, H Leena, J Marja-Leena, M Katja, J Irma, M AF Sanna, Kuusikko Rachel, Pollock-Wurman Hanna, Ebeling Tuula, Hurtig Leena, Joskitt Marja-Leena, Mattila Katja, Jussila Irma, Moilanen TI Psychometric evaluation of social phobia and anxiety inventory for children (SPAI-C) and social anxiety scale for children-revised (SASC-R) SO EUROPEAN CHILD & ADOLESCENT PSYCHIATRY LA English DT Article DE social anxiety; social phobia; SPAI-C; SASC-R ID SCHOOL-AGE-CHILDREN; CONSTRUCT-VALIDITY; NORMATIVE DATA; ADOLESCENTS; DISORDERS; MORBIDITY; SAMPLE; METAANALYSIS; COMORBIDITY; RELIABILITY AB The study evaluated the psychometric properties of Finnish versions of the Social Phobia and Anxiety Inventory for Children (SPAI-C) and the Social Anxiety Scale for Children-Revised (SASC-R). 352 students (M=12.2 years) participated in the study and completed the SPAI-C and SASC-R. In addition, 68 participants (M=12.2 years) and their parents were interviewed with the Schedule for Affective Disorders and Schizophrenia for School Aged Children (K-SADS-PL). The SPAI-C was more sensitive for identifying youth meeting criteria for social phobia (SP), whereas the SASC-R demonstrated greater specificity. The youth in this sample had lower mean total scores on the self-report questionnaires than did those in the original validitation studies of the SPAI-C and SASC-R conducted in America. These findings question whether cross-cultural differences in the expression of SP influence the clinical cut-off scores used in translated versions of social anxiety questionnaires. C1 [Sanna, Kuusikko; Hanna, Ebeling; Tuula, Hurtig; Leena, Joskitt; Marja-Leena, Mattila; Katja, Jussila; Irma, Moilanen] Child Psychiat Clin Univ, Dept Child Psychiat, Oys 90029, Finland. [Sanna, Kuusikko; Hanna, Ebeling; Tuula, Hurtig; Leena, Joskitt; Marja-Leena, Mattila; Katja, Jussila; Irma, Moilanen] Univ Hosp Oulu, Oys 90029, Finland. [Rachel, Pollock-Wurman] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Sanna, K (reprint author), Child Psychiat Clin Univ, Dept Child Psychiat, POB 26, Oys 90029, Finland. EM kuusisan@paju.oulu.fi FU The Alma and K. A. Snellman Foundation, Oulu, Finland; Child Psychiatric Research Foundation, Finland; Emil Aaltonen Foundation, Finland FX The research was supported by The Alma and K. A. Snellman Foundation, Oulu, Finland; Child Psychiatric Research Foundation, Finland; and Emil Aaltonen Foundation, Finland. We want to thank the participants of the study and Ms. Katja Larinen for her assistance in data collection. NR 38 TC 8 Z9 8 U1 3 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1018-8827 EI 1435-165X J9 EUR CHILD ADOLES PSY JI Eur. Child Adolesc. Psych. PD FEB PY 2009 VL 18 IS 2 BP 116 EP 124 DI 10.1007/s00787-008-0712-x PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 427YD UT WOS:000264814100006 PM 18807111 ER PT J AU Blankstein, R Durst, R Picard, MH Cury, RC AF Blankstein, Ron Durst, Ronen Picard, Michael H. Cury, Ricardo C. TI Progression of mitral annulus calcification to caseous necrosis of the mitral valve: complementary role of multi-modality imaging SO EUROPEAN HEART JOURNAL LA English DT Article C1 [Blankstein, Ron; Cury, Ricardo C.] Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Blankstein, Ron; Durst, Ronen; Picard, Michael H.] Massachusetts Gen Hosp, Div Cardiol Med, Boston, MA 02114 USA. RP Blankstein, R (reprint author), Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM rblankstein@partners.org OI Picard, Michael/0000-0002-9264-3243 NR 0 TC 4 Z9 4 U1 0 U2 1 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 FEB PY 2009 VL 30 IS 3 BP 304 EP 304 DI 10.1093/eurheartj/ehn411 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 404OS UT WOS:000263163500007 PM 18784062 ER PT J AU Metra, M Dei Cas, L Massie, BM AF Metra, Marco Dei Cas, Livio Massie, Barry M. TI Treatment of heart failure in the elderly: never say it's too late SO EUROPEAN HEART JOURNAL LA English DT Editorial Material ID EJECTION FRACTION; MORTALITY; TRIAL; MANAGEMENT; MORBIDITY; DIGOXIN C1 [Metra, Marco; Dei Cas, Livio] Univ Brescia, Dept Expt & Appl Med, Sect Cardiovasc Dis, I-25100 Brescia, Italy. [Massie, Barry M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Massie, Barry M.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Metra, M (reprint author), Univ Brescia, Dept Expt & Appl Med, Sect Cardiovasc Dis, I-25100 Brescia, Italy. EM metramarco@libero.it OI Metra, Marco/0000-0001-6691-8568 NR 15 TC 10 Z9 10 U1 0 U2 0 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 FEB PY 2009 VL 30 IS 4 BP 391 EP 393 DI 10.1093/eurheartj/ehp024 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 410UN UT WOS:000263603900003 PM 19181708 ER PT J AU Sammalisto, S Hiekkalinna, T Schwander, K Kardia, S Weder, AB Rodriguez, BL Doria, A Kelly, JA Bruner, GR Harley, JB Redline, S Larkin, EK Patel, SR Ewan, AJH Weber, JL Perola, M Peltonen, L AF Sammalisto, Sampo Hiekkalinna, Tero Schwander, Karen Kardia, Sharon Weder, Alan B. Rodriguez, Beatriz L. Doria, Alessandro Kelly, Jennifer A. Bruner, Gail R. Harley, John B. Redline, Susan Larkin, Emma K. Patel, Sanjay R. Ewan, Amy J. H. Weber, James L. Perola, Markus Peltonen, Leena TI Genome-wide linkage screen for stature and body mass index in 3.032 families: evidence for sex- and population-specific genetic effects SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE body height; body mass index; linkage mapping; quantitative trait loci ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; OBSTRUCTIVE SLEEP-APNEA; QUANTITATIVE TRAITS; COMMON VARIANT; ADULT HEIGHT; OBESITY; SCAN; ASSOCIATION; CHILDHOOD; DISEASES AB Stature (adult body height) and body mass index (BMI) have a strong genetic component explaining observed variation in human populations; however, identifying those genetic components has been extremely challenging. It seems obvious that sample size is a critical determinant for successful identification of quantitative trait loci (QTL) that underlie the genetic architecture of these polygenic traits. The inherent shared environment and known genetic relationships in family studies provide clear advantages for gene mapping over studies utilizing unrelated individuals. To these ends, we combined the genotype and phenotype data from four previously performed family-based genome-wide screens resulting in a sample of 9.371 individuals from 3.032 African-American and European-American families and performed variance-components linkage analyses for stature and BMI. To our knowledge, this study represents the single largest family-based genome-wide linkage scan published for stature and BMI to date. This large study sample allowed us to pursue population- and sex-specific analyses as well. For stature, we found evidence for linkage in previously reported loci on 11q23, 12q12, 15q25 and 18q23, as well as 15q26 and 19q13, which have not been linked to stature previously. For BMI, we found evidence for two loci: one on 7q35 and another on 11q22, both of which have been previously linked to BMI in multiple populations. Our results show both the benefit of (1) combining data to maximize the sample size and (2) minimizing heterogeneity by analyzing subgroups where within-group variation can be reduced and suggest that the latter may be a more successful approach in genetic mapping. C1 [Peltonen, Leena] Univ Helsinki, Natl Publ Hlth Inst, Dept Med Genet, Fac Med, FIN-00251 Helsinki, Finland. [Sammalisto, Sampo; Hiekkalinna, Tero; Perola, Markus; Peltonen, Leena] Natl Publ Hlth Inst, Dept Mol Med, Helsinki, Finland. [Schwander, Karen] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA. [Kardia, Sharon] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Weder, Alan B.] Univ Michigan, Sch Publ Hlth, Dept Internal Med, Ann Arbor, MI 48109 USA. [Rodriguez, Beatriz L.] Pacific Hlth Res Inst, Honolulu, HI USA. [Doria, Alessandro] Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. [Kelly, Jennifer A.; Bruner, Gail R.; Harley, John B.] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. [Redline, Susan; Larkin, Emma K.] Case Western Reserve Univ, Sch Med, Ctr Clin Invest, Cleveland, OH USA. [Patel, Sanjay R.] Case Western Reserve Univ, Sch Med, Div Pulm Med, Cleveland, OH USA. [Ewan, Amy J. H.; Weber, James L.] Marshfield Clin Res Fdn, Marshfield, WI USA. [Peltonen, Leena] MIT, Broad Inst, Boston, MA USA. RP Peltonen, L (reprint author), Univ Helsinki, Natl Publ Hlth Inst, Dept Med Genet, Fac Med, Haartmaninkatu 8, FIN-00251 Helsinki, Finland. EM leena.peltonen@ktl.fi OI Patel, Sanjay/0000-0002-9142-5172 FU European Commission [QLG2-CT-2002-01254]; Center of Excellence in Disease Genetics of the Finnish Academy, Biocentrum Helsinki; NIH [DK55523, AR062277, AR042460, AI024717]; National Heart, Lung, and Blood Institute (NHLBI) FX This study was supported by the European Commission under the program 'Quality of Life and Management of the Living Resources' of 5th Framework Program no. QLG2-CT-2002-01254 (SS, TH, MP and LP) and by the Center of Excellence in Disease Genetics of the Finnish Academy, Biocentrum Helsinki (LP). Joslin Diabetes study (AD) is supported by NIH Grant DK55523. FBPP is supported by the National Heart, Lung, and Blood Institute (NHLBI). This manuscript has been reviewed by FBPP investigators for scientific content and consistency of data interpretation with previous FBPP publications, and significant comments have been incorporated before submission for publication. The SLE study (JAK, GRB and JBH) is supported by NIH Grants AR062277, AR042460 and AI024717. We thank the study participants of the Cleveland Family Study for generously donating their time. The Cleveland Family Study authors are indebted also to our staff members: Joan Aylor, Kathryn Clark, Heather Rogers, Rawan Nawabit and Jennifer Frame for their dedication to this research. We declare no competing interests. All genotypes analyzed in the study were produced by the NHLBI Mammalian Genotyping Service, Marshfield, WI, USA. NR 48 TC 7 Z9 7 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD FEB PY 2009 VL 17 IS 2 BP 258 EP 266 DI 10.1038/ejhg.2008.152 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 395CJ UT WOS:000262499600019 PM 18781184 ER PT J AU Tian, J Gu, YW Su, DS Wu, YC Wang, XR AF Tian, Jie Gu, Yiwen Su, Diansan Wu, Yichao Wang, Xiangrui TI Effects of intrathecal lidocaine on hyperalgesia and allodynia following chronic constriction injury in rats SO EUROPEAN JOURNAL OF PAIN LA English DT Article DE Intrathecal lidocaine; Neuropathic pain; Thermal hyperalgesia; Tactile allodynia; Chronic constriction injury ID SPINAL SUBARACHNOID SPACE; DORSAL-HORN NEURONS; NEUROPATHIC PAIN; TACTILE ALLODYNIA; INTRAVENOUS LIDOCAINE; CORD; CATHETERIZATION; ANESTHESIA; RESPONSES; RELIEF AB The present study investigated the effects of different doses of intrathecal lidocaine on established thermal hyperalgesia and tactile allodynia in the chronic constriction injury model of neuropathic pain, defined the effective drug dose range, the duration of pain-relief effects, and the influence of this treatment on the body and tissues. Mate Sprague-Dawley rats were divided into five groups and received intrathecal saline or lidocaine (2, 6.5, 15, and 35 mg/kg) 7 days after loose sciatic ligation. Respiratory depression and hemodynamic instability were found to become more severe as doses of lidocaine increased during intrathecal therapy. Two animals in the group receiving 35 mg/kg lidocaine developed pulmonary oedema and died. Behavioral tests indicated that 6.5, 15, and 35 mg/kg intrathecal lidocaine showed different degrees of reversal of thermal hyperalgesia, and lasted for 2-8 days, while 2 mg/kg lidocaine did not. The inhibition of tactile allodynia was only observed in rats receiving 15 and 35 mg/kg lidocaine, and the anti-allodynic effects were identical in these two groups. Histopathologic examinations on the spinal cords revealed mild changes in rats receiving 2-15 mg/kg lidocaine. However, lesions were severe after administration of 35 mg/kg lidocaine. These findings indicate that intrathecal lidocame has prolonged therapeutic effects on established neuropathic pain. The balance between sympathetic and parasympathetic nervous activities could be well preserved in most cases, except for 35 mg/kg. Considering the ratio between useful effects and side effects, doses of 15 mg/kg are suitable for intrathecal injection for relief of neuropathic pain. (C) 2008 European Federation of Chapters of the International Association for the Study of Pain. Published by Elsevier Ltd. All rights reserved. C1 [Tian, Jie; Gu, Yiwen; Su, Diansan; Wang, Xiangrui] Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Dept Anesthesiol, Shanghai 200030, Peoples R China. [Wu, Yichao] Harvard Med Sch, CBR Inst Biomed Res, Boston, MA USA. RP Wang, XR (reprint author), Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Dept Anesthesiol, Shanghai 200030, Peoples R China. EM xiangruiwang@gmail.com FU Program Foundation from Medical School of Shanghai Jiaotong University [BXJ0720] FX The work was supported by Doctoral Innovation Program Foundation from Medical School of Shanghai Jiaotong University (BXJ0720), Shanghai, China. NR 23 TC 18 Z9 20 U1 1 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1090-3801 J9 EUR J PAIN JI Eur. J. Pain PD FEB PY 2009 VL 13 IS 2 BP 130 EP 137 DI 10.1016/j.ejpain.2008.03.013 PG 8 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 407IA UT WOS:000263355600004 PM 18486505 ER PT J AU Tsai, TT Trimarchi, S Nienaber, CA AF Tsai, T. T. Trimarchi, S. Nienaber, C. A. TI Acute Aortic Dissection: Perspectives from the International Registry of Acute Aortic Dissection (IRAD) SO EUROPEAN JOURNAL OF VASCULAR AND ENDOVASCULAR SURGERY LA English DT Article DE aorta; aortic dissection; mortality; follow-up studies ID TRUE-LUMEN COLLAPSE; INTRAMURAL HEMATOMA; COMPUTED-TOMOGRAPHY; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; VASCULAR COMPLICATIONS; PULSATILE FLOW; FALSE LUMEN; PART II; COCAINE; MANAGEMENT AB Acute aortic dissection is a rare but deadly disease first described over 200 years ago by the physician to the late King George II on necropsy. Over the ensuing 2 centuries, the understanding of the pathophysiology, presentation, diagnosis, treatment and follow-up has matured. In an effort to understand the contemporary treatment of this disease, the International Registry of Acute Aortic Dissection (IRAD) has enrolled over 2000 patients over the past 12 years. In this article we summarize the key lessons learned from this multi-national registry of patients presenting with acute aortic dissection. Published by Elsevier Ltd on behalf of European Society for Vascular Surgery. C1 [Tsai, T. T.] Univ Colorado, Div Cardiovasc Med, Dept Internal Med, Denver, CO 80202 USA. [Tsai, T. T.] Denver Vet Affairs Med Ctr, Hlth Serv Res & Dev Ctr, Denver, CO 80220 USA. [Trimarchi, S.] Policlin S Donato IRCCS, Cardiovasc Ctr E Malan, San Donato Milanese, Italy. [Nienaber, C. A.] Univ Rostock, Rostock, Germany. RP Tsai, TT (reprint author), Univ Colorado, Div Cardiovasc Med, Dept Internal Med, Denver, CO 80202 USA. EM thomas.tsai@ucdenver.edu RI Trimarchi, Santi/J-7361-2016 OI Trimarchi, Santi/0000-0001-5996-3264 NR 58 TC 134 Z9 164 U1 3 U2 8 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1078-5884 J9 EUR J VASC ENDOVASC JI Eur. J. Vasc. Endovasc. Surg. PD FEB PY 2009 VL 37 IS 2 BP 149 EP 159 DI 10.1016/j.ejvs.2008.11.032 PG 11 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 407HX UT WOS:000263355300005 PM 19097813 ER PT J AU Ba-Ssalamah, A Uffmann, M Saini, S Bastati, N Herold, C Schima, W AF Ba-Ssalamah, Ahmed Uffmann, Martin Saini, Sanjai Bastati, Nina Herold, Christian Schima, Wolfgang TI Clinical value of MRI liver-specific contrast agents: a tailored examination for a confident non-invasive diagnosis of focal liver lesions SO EUROPEAN RADIOLOGY LA English DT Article DE Liver lesions; MR contrast agents; Characterization ID GD-EOB-DTPA; SUPERPARAMAGNETIC IRON-OXIDE; DIMEGLUMINE-ENHANCED MRI; FAST SPIN-ECHO; HEPATOCELLULAR-CARCINOMA; PATHOLOGICAL CORRELATION; GADOBENATE DIMEGLUMINE; NODULAR HYPERPLASIA; HEPATIC-LESIONS; IMAGING FEATURES AB Screening of the liver for hepatic lesion detection and characterization is usually performed with either ultrasound or CT. However, both techniques are suboptimal for liver lesion characterization and magnetic resonance (MR) imaging has emerged as the preferred radiological investigation. In addition to unenhanced MR imaging techniques, contrast-enhanced MR imaging can demonstrate tissue-specific physiological information, thereby facilitating liver lesion characterization. Currently, the classes of contrast agents available for MR imaging of the liver include non-tissue-specific extracellular gadolinium chelates and tissue-specific hepatobiliary or reticuloendothelial agents. In this review, we describe the MR features of the more common focal hepatic lesions, as well as appropriate imaging protocols. A special emphasis is placed on the clinical use of non-specific and liver-specific contrast agents for differentiation of focal liver lesions. This may aid in the accurate diagnostic workup of patients in order to avoid invasive procedures, such as biopsy, for lesion characterization. A diagnostic strategy that considers the clinical situation is also presented. C1 [Ba-Ssalamah, Ahmed; Uffmann, Martin; Bastati, Nina; Herold, Christian; Schima, Wolfgang] Med Univ Vienna, Dept Radiol, A-1090 Vienna, Austria. [Saini, Sanjai] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Saini, Sanjai] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Ba-Ssalamah, A (reprint author), Med Univ Vienna, Dept Radiol, Waehringer Guertel 18-20, A-1090 Vienna, Austria. EM ahmed.ba-ssalamah@meduniwien.ac.at NR 66 TC 84 Z9 92 U1 0 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0938-7994 J9 EUR RADIOL JI Eur. Radiol. PD FEB PY 2009 VL 19 IS 2 BP 342 EP 357 DI 10.1007/s00330-008-1172-x PG 16 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 396GA UT WOS:000262579000010 PM 18810454 ER PT J AU Kremke, B Bergwitz, C Ahrens, W Schutt, S Schumacher, M Wagner, V Holterhus, PM Juppner, H Hiort, O AF Kremke, B. Bergwitz, C. Ahrens, W. Schuett, S. Schumacher, M. Wagner, V. Holterhus, P. -M. Jueppner, H. Hiort, O. TI Hypophosphatemic Rickets with Hypercalciuria due to Mutation in SLC34A3/NaPi-IIc can be Masked by Vitamin D Deficiency and can be Associated with Renal Calcifications SO EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY & DIABETES LA English DT Article DE nephrocalcinosis; HHRH; Na-PiIIc ID PHOSPHATE COTRANSPORTER; PARATHYROID-HORMONE; GENE; OSTEOMALACIA; SLC34A3 AB Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is caused by mutations in SLC34A3, the gene encoding the renal sodium-phosphate co-transporter NaPi-IIc. Despite increased urinary calcium excretion, HHRH is typically not associated with kidney stones prior to treatment. However, here we describe two sisters, who displayed nephrolithiasis or nephrocalcinosis upon presentation. The index patient, II-4, presented with short stature, bone pain, and knee X-rays suggestive of mild rickets at age 8.5 years. Laboratory evaluation showed hypophosphatemia, elevated 1,25(OH)2 vitamin D levels, and hypercalciuria, later also developing vitamin D deficiency. Her sister, II-6, had a low normal serum phosphorous level, biochemically vitamin D deficiency and no evidence for osteomalacia, but had undergone left nephro-ureterectomy at age 17 because of ureteral stricture secondary to renal calculi. Nucleotide sequence analysis of DNA from II-4 and II-6 revealed a homozygous missense mutation c.586G > A (p.G196R) in SLC34A3/ NaPi-IIc. Ultrasonographic examinations prior to treatment showed grade I nephrocalcinosis for 114, while II-6 had grade I-II nephrocalcinosis in her remaining kidney. Four siblings and the mother were heterozygous carriers of the mutation, but showed no biochemical abnormalities. With oral phosphate supplements, hypophosphatemia and hypercalciuria improved in both homozygous individuals. Renal calcifications that are presumably due to increased urinary calcium excretion can be the presenting finding in homozygous carriers of G196R in SLC34A3/NaPi-IIc, and some or all laboratory features of HHRH may be masked by vitamin D deficiency. C1 [Kremke, B.; Ahrens, W.; Schuett, S.; Schumacher, M.; Wagner, V.; Hiort, O.] Med Univ Lubeck, Dept Pediat & Adolescent Med, Div Pediat Endocrinol & Diabetol, D-23538 Lubeck, Germany. [Bergwitz, C.; Jueppner, H.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Bergwitz, C.; Jueppner, H.] Harvard Univ, Sch Med, Boston, MA USA. [Holterhus, P. -M.] Univ Kiel, Dept Pediat, Div Pediat Endocrinol & Diabetol, D-2300 Kiel, Germany. RP Hiort, O (reprint author), Med Univ Lubeck, Dept Pediat & Adolescent Med, Div Pediat Endocrinol & Diabet, Ratzeburger Allee 160, D-23538 Lubeck, Germany. EM hiort@paedia.ukl.mu-luebeck.de FU Else-Krohner-Fresenius Foundation; National Kidney Foundation FX This work was funded in part by the Else-Krohner-Fresenius Foundation (to OH) and the National Kidney Foundation (to CB). The authors are grateful for the technical assistance of Claudia Havel for molecular analysis of the PHEX gene. NR 25 TC 19 Z9 19 U1 0 U2 6 PU JOHANN AMBROSIUS BARTH VERLAG MEDIZINVERLAGE HEIDELBERG GMBH PI STUTTGART PA RUEDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0947-7349 J9 EXP CLIN ENDOCR DIAB JI Exp. Clin. Endocrinol. Diabet. PD FEB PY 2009 VL 117 IS 2 BP 49 EP 56 DI 10.1055/s-2008-1076716 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 413YW UT WOS:000263832100001 PM 18523928 ER PT J AU Jacobs, JV Nutt, JG Carlson-Kuhta, P Stephens, M Horak, FB AF Jacobs, Jesse V. Nutt, John G. Carlson-Kuhta, Patricia Stephens, Marilee Horak, Fay B. TI Knee trembling during freezing of gait represents multiple anticipatory postural adjustments SO EXPERIMENTAL NEUROLOGY LA English DT Article DE Freezing of gait; FoG; Parkinson's disease; Balance; Anticipatory postural adjustment; Gait initiation ID PARKINSONS-DISEASE; STEP INITIATION; MUSCLE TONE; MOVEMENT; LEVODOPA; COORDINATION; ONSET; CAT AB Freezing of gait (FoG) is an episodic, brief inability to step that delays gait initiation or interrupts ongoing gait. FoG is often associated with an alternating shaking of the knees, clinically referred to as knee trembling or trembling in place. The pathophysiology of FoG and of the concomitant trembling knees is unknown; impaired postural adjustment in preparation for stepping is one hypothesis. We examined anticipatory postural adjustments (APAs) prior to protective steps induced by a forward loss of balance in 10 Parkinson's disease (PD) subjects with marked FoG and in 10 control subjects. The amplitude and timing of the APAs were determined from changes in the vertical ground-reaction forces recorded by a force plate under each foot and were confirmed by electromyographic recordings of bilateral medial gastrocnemius, tibialis anterior and tensor fascia latae muscles. Protective steps were accomplished with a single APA followed by a step for control subjects, whereas PD subjects frequently exhibited multiple, alternating APAs coexistent with the knee trembling commonly observed during FoG as well as delayed, inadequate or no stepping. These Multiple APAs were not delayed in onset and were of similar or larger amplitude than the single APAs exhibited by the control subjects. These observations suggest that multiple APAs produce the knee trembling commonly associated with FoG and that FoG associated with a forward loss of balance is caused by an inability to couple a normal APA to the stepping motor pattern. Published by Elsevier Inc. C1 [Jacobs, Jesse V.; Nutt, John G.; Carlson-Kuhta, Patricia; Stephens, Marilee; Horak, Fay B.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Nutt, John G.; Horak, Fay B.] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97239 USA. [Nutt, John G.] Portland VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Portland, OR USA. RP Nutt, JG (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, OP-32,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM nuttj@ohsu.edu FU National Institutes of Health [AG06457] FX We thank the subjects who participated in the protocol. We are grateful for the help with data analysis from Edward King, Michael Amos, and Christine Ryciewcz, and for the technical assistance from Dr. Charles Russell and Edward King. This study was funded by the National Institutes of Health, grant AG06457. NR 35 TC 93 Z9 95 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD FEB PY 2009 VL 215 IS 2 BP 334 EP 341 DI 10.1016/j.expneurol.2008.10.019 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 400TG UT WOS:000262890900016 PM 19061889 ER PT J AU Martella, G Platania, P Vita, D Sciamanna, G Cuomo, D Tassone, A Tscherter, A Kitada, T Bonsi, P Shen, J Pisani, A AF Martella, G. Platania, P. Vita, D. Sciamanna, G. Cuomo, D. Tassone, A. Tscherter, A. Kitada, T. Bonsi, P. Shen, J. Pisani, A. TI Enhanced sensitivity to group II mGlu receptor activation at corticostriatal synapses in mice lacking the familial parkinsonism-linked genes PINK1 or Parkin SO EXPERIMENTAL NEUROLOGY LA English DT Article DE Striatum; Metabotropic glutamate receptor; Monogenic parkinsonism; Electrophysiology ID METABOTROPIC GLUTAMATE RECEPTORS; STRIATAL CHOLINERGIC INTERNEURONS; BASAL GANGLIA; SUBTHALAMIC NUCLEUS; DISTINCT ROLES; DISEASE; MUTATIONS; NEURONS; RAT; AGONIST AB An altered glutamatergic input at corticostriatal synapses has been shown in experimental models of Parkinson's disease (PD). In the present work, we analyzed the membrane and synaptic responses of striatal neurons to metabotropic glutamate (mGlu) receptor activation in two different mouse models of inherited PD, linked to mutations in PINK1 or Parkin genes. Both in PINK1 and Parkin knockout ((-/-)) mice, activation of group I mGlu receptors by 3,5-DHPG caused a membrane depolarization coupled to an increase in firing frequency in striatal cholinergic interneurons that was comparable to the response observed in the respective wild-type (WT) interneurons. The sensitivity to group II and III mGlu receptors was tested on cortically-evoked excitatory postsynaptic potentials (EPSPs) recorded from medium spiny neurons (MSNs). Both LY379268 and L-AP4, agonists for group II and III, respectively, had no effect on intrinsic membrane properties, but dose-dependently reduced the amplitude of corticostriatal EPSPs. However, both in PINK1(-/-) and Parkin(-/-) mice, LY379268, but not L-AP4, exhibited a greater potency as compared to WT in depressing EPSP amplitude. Accordingly, the dose-response curve for the response to LY379268 in both knockout mice was shifted leftward. Moreover, consistent with a presynaptic site of action, both LY379268 and L-AP4 increased the paired-pulse ratio either in PINK1(-/-) and Parkin(-/-) or in WT mice. Acute pretreatment with L-dopa did not rescue the enhanced sensitivity to LY379268. Together, these results suggest that the selective increase in sensitivity of striatal group II mGlu receptors represents an adaptive change in mice in which an altered dopamine metabolism has been documented. (c) 2008 Elsevier Inc. All rights reserved. C1 [Martella, G.; Platania, P.; Cuomo, D.; Tscherter, A.; Pisani, A.] Univ Roma Tor Vergata, Dept Neurosci, I-00133 Rome, Italy. [Vita, D.; Sciamanna, G.; Tassone, A.; Bonsi, P.; Pisani, A.] IRCCS, Fdn Santa Lucia, Rome, Italy. [Kitada, T.; Shen, J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Pisani, A (reprint author), Univ Roma Tor Vergata, Dept Neurosci, Via Montpellier 1, I-00133 Rome, Italy. EM pisani@uniroma2.it RI Sciamanna, Giuseppe/B-6553-2013; Tassone, Annalisa/J-9950-2016; Bonsi, Paola/K-4688-2012; OI Sciamanna, Giuseppe/0000-0002-0070-1638; Tassone, Annalisa/0000-0001-9643-2446; Bonsi, Paola/0000-0001-5940-9028; Tscherter, Anne/0000-0002-6972-482X FU Ministero Salute [RF06.55]; Italian Space Agency, DCMC grant; MIUR [PRIN 2006] FX This work was supported by grants from Ministero Salute (Prog. Ricerca Finalizzata, RF06.55); from the Italian Space Agency, DCMC grant and MIUR (PRIN 2006). NR 55 TC 19 Z9 19 U1 1 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD FEB PY 2009 VL 215 IS 2 BP 388 EP 396 DI 10.1016/j.expneurol.2008.11.001 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 400TG UT WOS:000262890900022 PM 19071114 ER PT J AU Adelmant, G Marto, JA AF Adelmant, Guillaume Marto, Jarrod A. TI Protein complexes: the forest and the trees SO EXPERT REVIEW OF PROTEOMICS LA English DT Editorial Material ID QUANTITATIVE MASS-SPECTROMETRY; SACCHAROMYCES-CEREVISIAE; AFFINITY PURIFICATION; SYSTEMS BIOLOGY; PROTEOMICS; IDENTIFICATION C1 [Marto, Jarrod A.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Adelmant, Guillaume] Harvard Univ, Sch Med, Dept Canc Biol, Boston, MA 02115 USA. [Adelmant, Guillaume] Harvard Univ, Sch Med, Blois Prote Ctr, Dana Farber Canc Inst,Dept Biol Chem & Mol Pharma, Boston, MA 02115 USA. RP Marto, JA (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St,Smith 1158A, Boston, MA 02115 USA. EM jarrod_marto@dfci.harvard.edu FU NHGRI NIH HHS [P50 HG004233] NR 24 TC 5 Z9 5 U1 0 U2 0 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1478-9450 J9 EXPERT REV PROTEOMIC JI Expert Rev. Proteomics PD FEB PY 2009 VL 6 IS 1 BP 5 EP 10 DI 10.1586/14789450.6.1.5 PG 6 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 412YZ UT WOS:000263761400002 PM 19210120 ER PT J AU Platt, MP Metson, R AF Platt, Michael P. Metson, Ralph TI Endoscopic Management of Exophthalmos SO FACIAL PLASTIC SURGERY LA English DT Article DE Orbital decompression; Graves' disease; Graves' ophthalmopathy; proptosis; diplopia ID BALANCED ORBITAL DECOMPRESSION; GRAVES OPHTHALMOPATHY; RADIOTHERAPY; DIPLOPIA; DISEASE; STRUT AB Endoscopic orbital decompression is a valuable technique for treatment of patients with proptosis, exposure keratopathy, or optic neuropathy from Graves' orbitopathy. Compared with traditional open approaches, the endoscopic technique provides enhanced visualization and avoids the morbidity of incisions within the facial skin, oral cavity, or conjunctiva. This article describes the authors' techniques for performing endoscopic orbital decompression. C1 [Platt, Michael P.; Metson, Ralph] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Metson, Ralph] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Metson, R (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Zero Emerson Pl, Boston, MA 02114 USA. EM Ralph_metson@meei.harvard.edu NR 20 TC 0 Z9 0 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0736-6825 J9 FACIAL PLAST SURG JI Facial Plast. Surg. PD FEB PY 2009 VL 25 IS 1 BP 38 EP 42 DI 10.1055/s-0028-1112230 PG 5 WC Surgery SC Surgery GA 449GB UT WOS:000266317700007 PM 19206027 ER PT J AU Resnick, CM Kaban, LB Troulis, MJ AF Resnick, Cory M. Kaban, Leonard B. Troulis, Maria J. TI Minimally Invasive Orthognathic Surgery SO FACIAL PLASTIC SURGERY LA English DT Article DE Orthognathic surgery; minimally invasive; endoscopy; distraction osteogenesis; technique ID MANDIBULAR DISTRACTION OSTEOGENESIS; ENDOSCOPICALLY ASSISTED REPAIR; VERTICAL RAMUS OSTEOTOMY; SAGITTAL SPLIT OSTEOTOMY; FORT-I OSTEOTOMY; TERM-FOLLOW-UP; NEUROSENSORY DISTURBANCE; GRADUAL DISTRACTION; FRACTURES; RECONSTRUCTION AB Minimally invasive surgery is defined as the discipline in which operative procedures are performed in novel ways to diminish the sequelae of standard surgical dissections. The goals of minimally invasive surgery are to reduce tissue trauma and to minimize bleeding, edema, and injury, thereby improving the rate and quality of healing. In orthognathic surgery, there are two minimally invasive techniques that can be used separately or in combination: (1) endoscopic exposure and (2) distraction osteogenesis. This article describes the historical developments of the fields of orthognathic surgery and minimally Invasive surgery, as well as the integration of the two disciplines. Indications, techniques, and the most current outcome data for specific minimally invasive orthognathic surgical procedures are presented. C1 [Resnick, Cory M.; Kaban, Leonard B.; Troulis, Maria J.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP Resnick, CM (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, 55 Fruit St,Warren Bldg,Suite 1201, Boston, MA 02114 USA. EM cresnick@partners.org OI Resnick, Cory/0000-0002-6391-9618 NR 79 TC 5 Z9 5 U1 0 U2 2 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0736-6825 J9 FACIAL PLAST SURG JI Facial Plast. Surg. PD FEB PY 2009 VL 25 IS 1 BP 49 EP 62 DI 10.1055/s-0028-1112232 PG 14 WC Surgery SC Surgery GA 449GB UT WOS:000266317700009 PM 19206029 ER PT J AU Sun, DX Martinez, CO Ochoa, O Ruiz-Willhite, L Bonilla, JR Centonze, VE Waite, LL Michalek, JE McManus, LM Shireman, PK AF Sun, Dongxu Martinez, Carlo O. Ochoa, Oscar Ruiz-Willhite, Lourdes Bonilla, Jose R. Centonze, Victoria E. Waite, Lindsay L. Michalek, Joel E. McManus, Linda M. Shireman, Paula K. TI Bone marrow-derived cell regulation of skeletal muscle regeneration SO FASEB JOURNAL LA English DT Article DE CC chemokine receptor 2; CCR2; chimera; inflammation; monocyte/macrophage; myogenic progenitor cell ID HEMATOPOIETIC STEM-CELLS; MONOCYTE CHEMOATTRACTANT PROTEIN-1; CC-CHEMOKINE RECEPTOR-2; SATELLITE CELLS; IN-VIVO; PROGENITOR CELLS; CCR2-/-MICE; ALTERED INFLAMMATION; TUMOR ANGIOGENESIS; ENDOTHELIAL-CELLS AB Limb regeneration requires the coordination of multiple stem cell populations to recapitulate the process of tissue formation. Therefore, bone marrow (BM) -derived cell regulation of skeletal muscle regeneration was examined in mice lacking the CC chemokine receptor 2 (CCR2). Myofiber size, numbers of myogenic progenitor cells (MPCs), and recruitment of BM-derived cells and macrophages were assessed after cardiotoxin-induced injury of chimeric mice produced by transplanting BM from wild-type (WT) or CCR2(-/-) mice into irradiated WT or CCR2(-/-) host mice. Regardless of the host genotype, muscle regeneration and recruitment of BM-derived cells and macrophages were similar in mice replenished with WT BM, whereas BM-derived cells and macrophage accumulation were decreased and muscle regeneration was impaired in all animals receiving CCR2(-/-) BM. Furthermore, numbers of MPCs (CD34(+)/Sca-1(-)/CD45(-) cells) were significantly increased in mice receiving CCR2(-/-) BM despite the decreased size of regenerated myofibers. Thus, the expression of CCR2 on BM-derived cells regulated macrophage recruitment into injured muscle, numbers of MPC, and the extent of regenerated myofiber size, all of which were independent of CCR2 expression on host-derived cells. Future studies in regenerative medicine must include consideration of the role of BM-derived cells, possibly macrophages, in CCR2-dependent events that regulate effective skeletal muscle regeneration. - Sun, D., Martinez, C. O., Ochoa, O., Ruiz-Willhite, L., Bonilla, J. R., Centonze, V. E., Waite, L. L., Michalek, J. E., McManus, L. M., Shireman, P. K. Bone marrow-derived cell regulation of skeletal muscle regeneration. FASEB J. 23, 382-395 (2009) C1 [Sun, Dongxu; Martinez, Carlo O.; Ochoa, Oscar; Ruiz-Willhite, Lourdes; Bonilla, Jose R.; Shireman, Paula K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Surg, San Antonio, TX 78229 USA. [Centonze, Victoria E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cell & Struct Biol, San Antonio, TX 78229 USA. [Waite, Lindsay L.; Michalek, Joel E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA. [McManus, Linda M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [McManus, Linda M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Periodont, San Antonio, TX 78229 USA. [McManus, Linda M.; Shireman, Paula K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Shireman, Paula K.] Univ Texas Hlth Sci Ctr San Antonio, Sam & Ann Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Shireman, Paula K.] Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 USA. RP Shireman, PK (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Surg, 7703 Floyd Curl Dr,MC 7741, San Antonio, TX 78229 USA. EM shireman@uthscsa.edu FU UTHSCSA; San Antonio Cancer Institute [CA54174]; Nathan Shock Center [AG013319]; Veterans Administration Merit Review; San Antonio Area Foundation [Sun-UTHSCSA-060104]; National Institutes of Health, National Heart, Lung, and Blood Institute [R01HL074236, F32HL090196]; [AG19316] FX We acknowledge the expert technical assistance of Michael D. Wetzel and Jimmy Wewer in these studies. A portion of the statistical analyses was expertly performed by Lee Ann Zarzabal. The flow cytometry portion of this work was performed at the Institutional Flow Cytometry Core of the University of Texas Health Science Center, San Antonio (UTHSCSA). Images were generated in the UTHSCSA Core Optical Imaging Facility, which is supported by UTHSCSA, CA54174 (San Antonio Cancer Institute), AG013319 (Nathan Shock Center), and AG19316. These studies were supported, in part, by a Veterans Administration Merit Review grant, the San Antonio Area Foundation (Sun-UTHSCSA-060104), and the National Institutes of Health (R01HL074236 and F32HL090196) from the National Heart, Lung, and Blood Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors have no relationships that pose a conflict of interest for these studies. NR 71 TC 53 Z9 53 U1 1 U2 7 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 FEB PY 2009 VL 23 IS 2 BP 382 EP 395 DI 10.1096/fj.07-095901 PG 14 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 400TZ UT WOS:000262892900010 PM 18827026 ER PT J AU Sun, W Hu, W Xu, RJ Jin, JF Szulc, ZM Zhang, GF Galadari, SH Obeid, LM Mao, CG AF Sun, Wei Hu, Wei Xu, Ruijuan Jin, Junfei Szulc, Zdzislaw M. Zhang, Guofeng Galadari, Sehamuddin H. Obeid, Lina M. Mao, Cungui TI Alkaline ceramidase 2 regulates beta 1 integrin maturation and cell adhesion SO FASEB JOURNAL LA English DT Article DE retinoic acid; protein kinase C; Golgi; sphingolipid ID INTEGRIN RECEPTORS; ALPHA-5-BETA-1 INTEGRIN; MOLECULAR-CLONING; CARCINOMA-CELLS; SPHINGOID BASES; DOWN-REGULATION; RETINOIC ACID; GLYCOSYLATION; APOPTOSIS; EXPRESSION AB The polypeptide core of the integrin beta 1 subunit (beta 1) is glycosylated sequentially in the endoplasmic reticulum and the Golgi complex to form beta 1 precursor and mature beta 1, respectively. The beta 1 precursor to mature beta 1 conversion, termed beta 1 maturation, regulates the cell surface levels and function of beta 1-containing integrins, beta 1 integrins. Here we demonstrate that the human alkaline ceramidase 2 (ACER2), a Golgi enzyme, regulates beta 1 maturation by controlling the generation of sphingosine. ACER2 overexpression inhibited beta 1 maturation, thus leading to a decrease in the levels of mature beta-1 in T-REx HeLa cells, whereas RNA interference-mediated knockdown of ACER2 enhanced beta 1 maturation in MCF-7 cells. ACER2 overexpression decreased the cell surface levels of beta 1 integrins, thus inhibiting cell adhesion to fibronectin or collagen, whereas ACER2 knockdown has the opposite effects. Treatment with all-trans retinoic acid (ATRA) increased both the expression of ACER2 and the generation of sphingosine in HeLa cells and inhibited beta 1 maturation. ACER2 knockdown attenuated the inhibitory effects of ATRA on both beta 1 maturation and cell adhesion. In contrast, treatment with phorbol myristate acetate (PMA), a protein kinase C activator, decreased the expression of ACER2 and sphingosine in T-REx HeLa cells, thus enhancing beta 1 maturation. ACER2 overexpression inhibited the stimulatory effects of PMA on both beta 1 maturation and cell adhesion. These results suggest that the ACER2/sphingosine pathway plays an important role in regulating beta 1 maturation and cell adhesion mediated by beta 1 integrins. Sun, W., Hu, W., Xu, R., Jin, J., Szulc, Z. M., Zhang, G., Galadari, S. H., Obeid, L. M, Mao, C. Alkaline ceramidase 2 regulates beta 1 integrin maturation and cell adhesion. FASEB J. 23, 656-666 (2009) C1 [Sun, Wei; Xu, Ruijuan; Obeid, Lina M.; Mao, Cungui] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Hu, Wei; Jin, Junfei; Szulc, Zdzislaw M.; Obeid, Lina M.; Mao, Cungui] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Zhang, Guofeng] NIH, Div Bioengn & Phys Sci, Bethesda, MD 20892 USA. [Galadari, Sehamuddin H.] United Arab Emirates Univ, Fac Med & Hlth Sci, Dept Biochem, Al Ain, U Arab Emirates. [Obeid, Lina M.] Ralph H Johnson Vet Adm Hosp, Charleston, SC USA. RP Mao, CG (reprint author), Div Gen Internal Med, 114 Doughty St,Rm 605 STB,POB 250779, Charleston, SC 29425 USA. EM maoc@musc.edu OI obeid, lina/0000-0002-0734-0847 FU National Institutes of Health [R01CA104834]; Veterans Affairs Merit award FX This work is supported by the National Institutes of Health grant R01CA104834 (to C.M.) and a Veterans Affairs Merit award (to L.M.O.). NR 40 TC 21 Z9 24 U1 0 U2 1 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 FEB PY 2009 VL 23 IS 2 BP 656 EP 666 DI 10.1096/fj.08-115634 PG 11 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 400TZ UT WOS:000262892900036 PM 18945876 ER PT J AU Baddley, JW AF Baddley, John W. TI Pinpointing prognostic indicators of fungal infections in transplant patients SO FUTURE MICROBIOLOGY LA English DT Review DE Aspergillus; Candida; mortality; prognostic factors; transplant ID SOLID-ORGAN TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTS; INVASIVE ASPERGILLOSIS; RISK-FACTORS; IMMUNOCOMPROMISED PATIENTS; FLUCONAZOLE PROPHYLAXIS; ATTRIBUTABLE MORTALITY; CONTROLLED TRIAL; RECIPIENTS AB A number of advances have been made in the prevention and treatment of invasive fungal Infections (IFIs) in transplant recipients. However, despite best clinical efforts, patient outcomes are often disappointing. The study of prognostic indicators of IFI for transplant patients may aid in the development of improved prevention measures, or determine more aggressive treatment pathways. Owing to the rarity of IFI, appropriately powered studies are often difficult to achieve; moreover, a lack of standardized outcome definitions make study comparisons difficult. Herein, prognostic indicators for mortality in transplant patients with IFI are reviewed, with a focus on invasive aspergillosis and invasive candidiasis C1 [Baddley, John W.] Univ Alabama, Birmingham, AL 35294 USA. [Baddley, John W.] Birmingham VA Med Ctr, Birmingham, AL USA. RP Baddley, JW (reprint author), Univ Alabama, Birmingham, AL 35294 USA. EM jbaddley@uab.ed NR 40 TC 1 Z9 1 U1 1 U2 1 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1746-0913 J9 FUTURE MICROBIOL JI Future Microbiol. PD FEB PY 2009 VL 4 IS 1 BP 77 EP 84 DI 10.2217/17460913.4.1.77 PG 8 WC Microbiology SC Microbiology GA 412VO UT WOS:000263752500011 PM 19207101 ER PT J AU Quinlan, MP Settleman, J AF Quinlan, Margaret P. Settleman, Jeffrey TI Isoform-specific ras functions in development and cancer SO FUTURE ONCOLOGY LA English DT Review DE cancer; development; GTPases; Ras; stem cells ID EMBRYONAL CARCINOMA-CELLS; FACIO-CUTANEOUS SYNDROME; K-RAS; PLASMA-MEMBRANE; H-RAS; N-RAS; GERMLINE MUTATIONS; COSTELLO-SYNDROME; NOONAN-SYNDROME; STEM-CELLS AB The three closely related mammalian ras genes, Was, Nras and Kras, have each been implicated in human tumorigenesis by virtue of mutational activation. However, while these genes encode proteins with very similar biochemical properties, activating ras alleles corresponding to the various isoforms have been linked to particular malignancies. Accumulating evidence suggests that these proteins exert distinct activities in a tissue-specific context, apparently reflecting developmental lineage-specific roles for the various ras isoforms, Some of these distinct functions appear to reflect differences in their C-termini, which determine distinct subcellular localization, thereby suggesting a role for compartmentalized signaling, In this review, we discuss the biological functions of the ras isoforms in the context of tissue-specific function as it relates to ras function in development and human cancer. C1 [Quinlan, Margaret P.; Settleman, Jeffrey] Harvard Univ, Ctr Canc, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 02129 USA. RP Settleman, J (reprint author), Harvard Univ, Ctr Canc, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 02129 USA. EM settleman@helix.mgh.harvard.edu NR 81 TC 42 Z9 42 U1 0 U2 6 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1479-6694 J9 FUTURE ONCOL JI Future Oncol. PD FEB PY 2009 VL 5 IS 1 BP 105 EP 116 DI 10.2217/14796694.5.1.105 PG 12 WC Oncology SC Oncology GA 419PN UT WOS:000264231800017 PM 19243303 ER PT J AU Yachimski, P Puricelli, WR Nishioka, NS AF Yachimski, Patrick Puricelli, William R. Nishioka, Norman S. TI Patient predictors of histopathologic response after photodynamic therapy of Barrett's esophagus with high-grade dysplasia or intramucosal carcinoma SO GASTROINTESTINAL ENDOSCOPY LA English DT Article; Proceedings Paper CT Digestive Disease Week Meeting/109th Annual Meeting of the American-Gastroenterological-Association CY MAY 17-22, 2008 CL San Diego, CA SP Amer Gastroenterol Assoc ID ARGON PLASMA COAGULATION; LONG-TERM SURVIVAL; FOLLOW-UP; SURGICAL-TREATMENT; ACID SUPPRESSION; UNITED-STATES; ESOPHAGECTOMY; ADENOCARCINOMA; ABLATION; CANCER AB Background: Photodynamic therapy (PDT) has been used extensively for endoscopic ablation of Barrett's esophagus with high-grade dysplasia (HGD) or intramucosal carcinoma. Objective: To identify patient variables that influence the likelihood of response to PDT. Design: A retrospective cohort Study. Setting: Tertiary-referral center. Patients: A total of 116 patients with Barrett's esophagus and with HGD, intramucosal carcinoma, or T1 cancer. Interventions: PDT with porfimer sodium. Main Outcome Measurements: (1) Ablation of HGD and/or intramucosal carcinoma and (2) eradication of all Barrett's epithelium. Results: Of the patients, 51% underwent treatment for HGD and 49% of patients had intramucosal carcinoma or T1 cancer. At 12-month follow-up, ablation of HGD and/or cancer was observed in 70% of patients, and ablation of all Barrett's epithelium was observed in 39%. In multivariate analysis, the pretreatment length of Barrett's esophagus was inversely correlated With Successful ablation of all Barrett's epithelium. Patients with Barrett's esophagus length more than 3 cm were less likely to experience complete ablation compared with patients with Barrett's esophagus length 3 cm or less (odds ratio [OR] 0.15 [95% CI, 0.04-0.50]). Patients with intramucosal carcinoma were not significantly less likely to experience elimination of HGD and/or cancer (OR 0.77 [95% CI, 0.30-2.00]) or ablation of all Barrett's epithelium (OR 0.82 [95% CI, 0.32-2.07]) compared with patients with HGD alone. Limitations: Retrospective study, limited sample size without a control group for comparison. Conclusions: PDT of Barrett's esophagus with HGD, intramucosal carcinoma, or T1 cancer can result in ablation of dysplasia and/or eradication of all Barrett's epithelium. Factors associated with the likelihood of response include length of Barrett's esophagus. The presence of intramucosal carcinoma or T1 cancer was not associated with higher likelihood of treatment failure. (Gastrointest Endosc 2009;69:205-12.) C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Yachimski, P (reprint author), Massachusetts Gen Hosp, Blake Gastrointestinal Unit 4, 55 Fruit St, Boston, MA 02114 USA. EM pyachimski@partners.org NR 36 TC 13 Z9 13 U1 0 U2 0 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 FEB PY 2009 VL 69 IS 2 BP 205 EP 212 DI 10.1016/j.gie.2008.05.032 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 402JF UT WOS:000263009300003 PM 18950764 ER PT J AU Artifon, ELA Kumar, A Eloubeidi, MA Chu, A Halwan, B Sakai, P Bhutani, MS AF Artifon, Everson L. A. Kumar, Atul Eloubeidi, Mohamad A. Chu, Adrienne Halwan, Bhawna Sakai, Paulo Bhutani, Manoop S. TI Prospective randomized trial of EUS versus ERCP-guided common bile duct stone removal: an interim report (with video) SO GASTROINTESTINAL ENDOSCOPY LA English DT Article; Proceedings Paper CT Digestive Disease Week Meeting/108th Annual Meeting of the American-Gastroenterological-Association CY MAY 19-24, 2007 CL Washington, DC SP Amer Gastroenterol Assoc, Amer Assoc Study Liver Dis, Amer Soc Gastrointestinal Endoscopy, Soc Surg Alimentary Tract ID MAGNETIC-RESONANCE CHOLANGIOPANCREATOGRAPHY; ENDOSCOPIC ULTRASOUND; MANAGEMENT AB Background: EUS is being increasingly utilized for the diagnosis of choledocholithiasis and microlithiasis, especially in patients with biliary colic. Simultaneously, there is also a rising interest in the use of EUS for therapeutic interventions. Objectives: Our goal was to assess the effectiveness of EUS-directed common bile duct (CBD) stone removal to compare its safety and effectiveness with ERCP-directed intervention. Design: interim results of a prospective, randomized, single-center blinded clinical trial. Setting: A single tertiary care referral center. Patients: Fifty-two patients with uncomplicated CBD stones were prospectively randomized to CBD cannulation and stone removal under EUS or ERCP guidance. Main Outcome Measurements and Interventions: Primary outcome measure was the rate of successful cannulation of the CBD. Secondary Outcome measures included Successful removal of stones and overall complication rates. Results: CBD cannulation followed by stone extraction was successful in 23 of 26 patients (88.5%) in the EUS group (1) versus 25 of 26 patients (96.2%) in the ERCP group (11) (95% CI, -27.65%, 9.88%). Overall, there were 3 complications in the EUS group and 4 complications in the ERCP group. Limitation: The current study is an interim report from a single center report and performed by a single operator. Conclusions: Our preliminary analysis indicates that Outcomes following EUS-guided CBD stone retrieval are equivalent to those following ERCP EUS-related adverse events are similar to those following ERCP. ERCP and EUS-guided stone retrieval appears to be equally effective for therapeutic interventions of the bile duct. Additional studies are required to validate these preliminary results and to determine predictors of success of EUS-guided stone removal. (Gastrointest Endosc 2009;69:238-43.) C1 [Kumar, Atul] SUNY Stony Brook, US Dept Vet Affairs, Stony Brook, NY 11794 USA. [Artifon, Everson L. A.; Sakai, Paulo] Univ Sao Paulo, Sch Med, Sao Paulo, Brazil. [Halwan, Bhawna] Suny Downstate Univ, Med Ctr, Brooklyn, NY USA. [Eloubeidi, Mohamad A.] Univ Alabama, Birmingham, AL USA. [Bhutani, Manoop S.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Kumar, A (reprint author), SUNY Stony Brook, US Dept Vet Affairs, Stony Brook, NY 11794 USA. EM atul.kumar2@va.gov NR 9 TC 15 Z9 16 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 FEB PY 2009 VL 69 IS 2 BP 238 EP 243 DI 10.1016/j.gie.2008.05.020 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 402JF UT WOS:000263009300008 PM 19185687 ER PT J AU Brugge, WR AF Brugge, William R. TI EUS-guided tumor ablation with heat, cold, microwave, or radiofrequency: will there be a winner? SO GASTROINTESTINAL ENDOSCOPY LA English DT Article; Proceedings Paper CT 16th International Symposium on Endoscopic Ultrasonography CY SEP 12-13, 2008 CL San Francisco, CA ID PORTAL-VEIN CATHETERIZATION; ENDOSCOPIC ULTRASOUND; PANCREATIC TISSUE; PORCINE PANCREAS; INTERSTITIAL BRACHYTHERAPY; PHOTODYNAMIC THERAPY; ETHANOL INJECTION; ALCOHOL ABLATION; MODEL; DRAINAGE C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Brugge, WR (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 32 TC 4 Z9 4 U1 1 U2 3 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 FEB PY 2009 VL 69 IS 2 BP S212 EP S216 DI 10.1016/j.gie.2008.12.031 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 402JG UT WOS:000263009400050 PM 19179160 ER PT J AU Brugge, WR AF Brugge, William R. TI The use of EUS to diagnose cystic neoplasms of the pancreas SO GASTROINTESTINAL ENDOSCOPY LA English DT Article; Proceedings Paper CT 16th International Symposium on Endoscopic Ultrasonography CY SEP 12-13, 2008 CL San Francisco, CA ID PAPILLARY MUCINOUS NEOPLASMS; FINE-NEEDLE-ASPIRATION; ALCOHOL-RETENTION SCLEROTHERAPY; PERCUTANEOUS ETHANOL INJECTION; PROPOSED MANAGEMENT ALGORITHM; COST-BENEFIT-ANALYSIS; SIMPLE RENAL CYSTS; ENDOSCOPIC ULTRASOUND; PREOPERATIVE EVALUATION; MOLECULAR-GENETICS C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Brugge, WR (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 53 TC 20 Z9 20 U1 0 U2 2 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 FEB PY 2009 VL 69 IS 2 BP S203 EP S209 DI 10.1016/j.gie.2008.12.029 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 402JG UT WOS:000263009400048 PM 19179158 ER PT J AU Ho, KY Brugge, WR AF Ho, Khek-Yu Brugge, Wifliam R. TI EUS 2008 Working Group document: evaluation of EUS-guided pancreatic-cyst ablation SO GASTROINTESTINAL ENDOSCOPY LA English DT Article; Proceedings Paper CT 16th International Symposium on Endoscopic Ultrasonography CY SEP 12-13, 2008 CL San Francisco, CA ID PERCUTANEOUS ETHANOL INJECTION; PAPILLARY MUCINOUS NEOPLASMS; SIMPLE RENAL CYSTS; CHEMICAL ABLATION; THYROID-NODULES; HEPATIC CYSTS; ENDOSCOPIC ULTRASOUND; SCLEROTHERAPY; SCLEROSIS; GALLBLADDER AB Pancreatic cysts encompass a wide spectrum of morphologic and histopathologic types.(1) Broadly, they are classified into 2 main types, mucinous and nonmucinous, which differ in natural history and clinical characteristics. The nonmucinous lesions include serous cystaclenomas and cystic endocrine tumors. Mucinous\ Cystic lesions may be benign, borderline, or malignant in nature and include benign mucinolis cystic neoplasms and intraductal papillary mucinous neoplasms (IPMN). Mucinous cysts are unique in their predisposition toward malignant transformation. The traditional therapy of cystic neoplasms, particularly mucinous lesions, has been Surgical resection. There is now evidence to Support clinical monitoring of low-risk mucinous lesions, such as side-branch IPMN lesions or in those patients who are poor surgical candidates. Although small, incidental simple pancreatic cysts 2 cm or smaller may enlarge over a prolonged time. Morbidity or mortality because of these small simple cysts is extremely unlikely, and observation appears to be a safe management option.(2) Sahani et al(3) reporated on 86 patients with cystic lesions sions less that' 3 c1l, in diameter that were resected after EUS-guided FNA. The majority (n = 75) of small pancreatic cysts were benign. Thirty-six cysts were unilocular, and virtually all of these (n = 35) were benign. The presence of septa was associated with borderline or "in situ" malignancy in 20% of cases (10 of 50). Low-risk IPMNs in the elderly are probably best managed with periodic imaging. A report of a recent task force also recommended periodic imaging for cysts less than 3 cm in diameter 5 A general schema for management of pancreatic-cyst neoplasm is shown in Table 1. As an alternative to surgical resection or monitoring, EUS-guided ethanol ablation of pancreatic-cystic lesions may have a role in carefully selected patients. This section of the EUS 2008 Working Group Proceedings will evaluate the current role of EUS-guided ethanol ablation in the management of pancreatic cyst neoplasms and provide recommendations for future research in this area. C1 [Brugge, Wifliam R.] Massachusetts Gen Hosp, GI Endoscopy Unit, Boston, MA 02114 USA. [Ho, Khek-Yu] Natl Univ Singapore Hosp, Dept Med, Singapore, Singapore. RP Brugge, WR (reprint author), Massachusetts Gen Hosp, GI Endoscopy Unit, 55 Fruit St,Blake 452C, Boston, MA 02114 USA. NR 39 TC 5 Z9 5 U1 0 U2 2 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 FEB PY 2009 VL 69 IS 2 BP S22 EP S27 DI 10.1016/j.gie.2008.10.059 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 402JG UT WOS:000263009400005 PM 19179162 ER PT J AU Broekman, MLD Tierney, LA Benn, C Chawla, P Cha, JH Sena-Esteves, M AF Broekman, M. L. D. Tierney, L. A. Benn, C. Chawla, P. Cha, J. H. Sena-Esteves, M. TI Mechanisms of distribution of mouse beta-galactosidase in the adult GM1-gangliosidosis brain SO GENE THERAPY LA English DT Article DE GM1-gangliosidosis; AAV; beta-galactosidase; axonal transport mRNA; lysosomal storage disease ID MUCOPOLYSACCHARIDOSIS-VII MICE; LYSOSOMAL STORAGE; BETA-GLUCURONIDASE; GENE-THERAPY; GENERALIZED GANGLIOSIDOSIS; MEDIATED CORRECTION; AAV VECTORS; LONG-TERM; BRAIN; DISEASE AB GM1-gangliosidosis is a lysosomal storage disease (LSD) caused by an autosomal recessive deficiency of lysosomal acid beta-galactosidase (beta gal). This leads to accumulation of GM1-ganglioside and its asialo derivative GA1 in the central nervous system (CNS), and progressive neurodegeneration. Therapeutic AAV-mediated gene delivery to the brain for LSDs has proven very successful in several animal models. GM1-gangliosidosis is also a prime candidate for AAV-mediated gene therapy in the CNS. As global neuropathology characterizes the most severe forms of this disease, therapeutic interventions need to achieve distribution of bgal throughout the entire CNS. Therefore, careful consideration of routes of administration and target structures from where metabolically active enzyme can be produced, released and distributed throughout the CNS, is necessary. The goal of this study was to investigate the pattern and mechanism of distribution of bgal in the adult GM1-gangliosidosis mouse brain upon hippocampal injection of an AAV vector-encoding bgal. We found evidence that three different mechanisms contribute to its distribution in the brain: (1) diffusion; (2) axonal transport within neurons from the site of production; (3) CSF flow in the perivascular space of Virchow-Robin. In addition, we found evidence of axonal transport of vector-encoded mRNA. C1 [Broekman, M. L. D.; Tierney, L. A.; Sena-Esteves, M.] Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Charlestown, MA 02129 USA. [Benn, C.; Chawla, P.; Cha, J. H.] Massachusetts Gen Hosp, Dept Neurol, MassGen Inst Neurodegenerat Dis, Charlestown, MA USA. [Broekman, M. L. D.] Univ Med Ctr Utrecht, Dept Neurosurg, Utrecht, Netherlands. [Broekman, M. L. D.] Univ Med Ctr Utrecht, Rudolf Magnus Inst Neurosci, Utrecht, Netherlands. RP Sena-Esteves, M (reprint author), Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Gen Hosp Bldg 149,13th St,Room 6309, Charlestown, MA 02129 USA. EM msesteves@partners.org FU NIH [R21NS053993, P30NS045776] FX This work was supported by NIH Grant R21NS053993. We thank Deidre McCarthy for her help with laser capture microdissection, and the Massachusetts General Hospital Neuroscience Center Microscopy and Image Analysis Core (NIH Grant P30NS045776) for use of the laser capture microdissection system and Nikon Supercoolscan 9000 slide scanner. NR 31 TC 15 Z9 15 U1 1 U2 1 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 FEB PY 2009 VL 16 IS 2 BP 303 EP 308 DI 10.1038/gt.2008.149 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 414VH UT WOS:000263892800015 PM 18818671 ER PT J AU Freeman, JL Ceol, C Feng, H Langenau, DM Belair, C Stern, HM Song, A Paw, BH Look, AT Zhou, Y Zon, LI Lee, C AF Freeman, Jennifer L. Ceol, Craig Feng, Hui Langenau, David M. Belair, Cassandra Stern, Howard M. Song, Anhua Paw, Barry H. Look, A. Thomas Zhou, Yi Zon, Leonard I. Lee, Charles TI Construction and Application of a Zebrafish Array Comparative Genomic Hybridization Platform SO GENES CHROMOSOMES & CANCER LA English DT Article ID COPY NUMBER VARIATION; REGULATED TRANSGENIC ZEBRAFISH; MICROARRAY ANALYSIS; MALIGNANT-MELANOMA; HOMEOBOX GENES; MOUSE STRAINS; EXPRESSION; CANCER; TUMORS; PROGRESSION AB The zebrafish is emerging as a prominent model system for studying the genetics of human development and disease. Genetic alterations that underlie each mutant model can exist in the form of single base changes, balanced chromosomal rearrangements, or genetic imbalances. To detect genetic imbalances in an unbiased genome-wide fashion, array comparative genomic hybridization (CGH) can be used. We have developed a 5-Mb resolution array CGH platform specifically for the zebrafish. This platform contains 286 bacterial artificial chromosome (BAC) clones, enriched for orthologous sequences of human oncogenes and tumor suppressor genes. Each BAC clone has been end-sequenced and cytogenetically assigned to a specific location within the zebrafish genome, allowing for ease of integration of array CGH data with the current version of the genome assembly. This platform has been applied to three zebrafish cancer models. Significant genomic imbalances were detected in each model, identifying different regions that may potentially play a role in tumorigenesis. Hence, this platform should be a useful resource for genetic dissection of additional zebrafish developmental and disease models as well as a benchmark for future array CGH platform development. (c) 2008 Wiley-Liss, Inc. C1 [Freeman, Jennifer L.; Stern, Howard M.; Lee, Charles] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Freeman, Jennifer L.; Ceol, Craig; Feng, Hui; Langenau, David M.; Belair, Cassandra; Song, Anhua; Paw, Barry H.; Look, A. Thomas; Zhou, Yi; Zon, Leonard I.; Lee, Charles] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Ceol, Craig; Langenau, David M.; Belair, Cassandra; Song, Anhua; Zhou, Yi; Zon, Leonard I.] Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. [Ceol, Craig; Langenau, David M.; Belair, Cassandra; Song, Anhua; Zhou, Yi; Zon, Leonard I.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Feng, Hui; Look, A. Thomas] Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. [Paw, Barry H.] Brigham & Womens Hosp, Dept Hematol, Boston, MA 02115 USA. RP Lee, C (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM clec@rics.bwh.harvard.cdu OI Feng, Hui/0000-0003-1318-821X FU National Institutes of Health [R01-CA111560]; Kirsclistein National Research Service Award FX .Supported by: National Institutes of Health, Grant number: R01-CA111560; Ruth L, Kirsclistein National Research Service Award. NR 50 TC 12 Z9 12 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD FEB PY 2009 VL 48 IS 2 BP 155 EP 170 DI 10.1002/gcc.20623 PG 16 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 391CJ UT WOS:000262210300005 PM 18973135 ER PT J AU Gusev, A Lowe, JK Stoffel, M Daly, MJ Altshuler, D Breslow, JL Friedman, JM Pe'er, I AF Gusev, Alexander Lowe, Jennifer K. Stoffel, Markus Daly, Mark J. Altshuler, David Breslow, Jan L. Friedman, Jeffrey M. Pe'er, Itsik TI Whole population, genome-wide mapping of hidden relatedness SO GENOME RESEARCH LA English DT Article ID COPY-NUMBER VARIATION; IDENTITY-BY-DESCENT; LINKAGE ANALYSIS; HAPLOTYPE MAP; ASSOCIATION; PREDICTION; TRAIT; TOOL; POLYMORPHISM; PEDIGREES AB We present GERMLINE, a robust algorithm for identifying segmental sharing indicative of recent common ancestry between pairs of individuals. Unlike methods with comparable objectives, GERMLINE scales linearly with the number of samples, enabling analysis of whole-genome data in large cohorts. Our approach is based on a dictionary of haplotypes that is used to efficiently discover short exact matches between individuals. We then expand these matches using dynamic programming to identify long, nearly identical segmental sharing that is indicative of relatedness. We use GERMLINE to comprehensively survey hidden relatedness both in the HapMap as well as in a densely typed island population of 3000 individuals. We verify that GERMLINE is in concordance with other methods when they can process the data, and also facilitates analysis of larger scale studies. We bolster these results by demonstrating novel applications of precise analysis of hidden relatedness for (1) identification and resolution of phasing errors and (2) exposing polymorphic deletions that are otherwise challenging to detect. This finding is supported by concordance of detected deletions with other evidence from independent databases and statistical analyses of fluorescence intensity not used by GERMLINE. C1 [Gusev, Alexander; Pe'er, Itsik] Columbia Univ, Dept Comp Sci, New York, NY 10027 USA. [Lowe, Jennifer K.; Breslow, Jan L.; Friedman, Jeffrey M.] Rockefeller Univ, New York, NY 10065 USA. [Lowe, Jennifer K.; Daly, Mark J.; Altshuler, David] Harvard Univ, Broad Inst, Cambridge, MA 02142 USA. [Lowe, Jennifer K.; Daly, Mark J.; Altshuler, David] MIT, Cambridge, MA 02142 USA. [Lowe, Jennifer K.; Altshuler, David] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Stoffel, Markus] ETH, CH-8093 Zurich, Switzerland. [Daly, Mark J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Daly, Mark J.; Altshuler, David] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Friedman, Jeffrey M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Friedman, Jeffrey M.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. [Pe'er, Itsik] Ctr Computat Biol & Bioinformat, New York, NY 10032 USA. RP Gusev, A (reprint author), Columbia Univ, Dept Comp Sci, New York, NY 10027 USA. EM gusev@cs.columbia.edu; itsik@cs.columbia.edu RI Altshuler, David/A-4476-2009; Breslow, Jan/B-7544-2008 OI Altshuler, David/0000-0002-7250-4107; FU NIH [5 U54 CA121852]; NSF [NOA CCF-0829882]; NIH/NIDDK [5R01 DK60089]; Massachusetts Biomedical Research Corporation Tosteson Postdoctoral Fellowship; Starr Foundation; Howard Hughes Medical Institute FX We thank the anonymous reviewers of this manuscript for their support and insightful comments. A. G. was supported by NIH grant 5 U54 CA121852 and the NSF Graduate Research Fellowship; I. P. was supported by NIH grant 5 U54 CA121852 and NSF grant NOA CCF-0829882; J. K. L. was supported in part by an NIH/NIDDK grant (5R01 DK60089) and by a Massachusetts Biomedical Research Corporation Tosteson Postdoctoral Fellowship. This work was further supported by grants from the Starr Foundation and Howard Hughes Medical Institute. NR 36 TC 167 Z9 167 U1 1 U2 13 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD FEB PY 2009 VL 19 IS 2 BP 318 EP 326 DI 10.1101/gr.081398.108 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 404ED UT WOS:000263132600015 PM 18971310 ER PT J AU Di Gesu, V Lo Bosco, G Pinello, L Yuan, GC Corona, DFV AF Di Gesu, Vito Lo Bosco, Giosue Pinello, Luca Yuan, Guo-Cheng Corona, Davide F. V. TI A multi-layer method to study genome-scale positions of nucleosomes SO GENOMICS LA English DT Article DE Nucleosome positioning; Hidden Markov Model; Classification; Multi-layer method ID PROTEIN-DNA INTERACTIONS; CHIP-CHIP; SACCHAROMYCES-CEREVISIAE; YEAST; WIDE; TRANSCRIPTION; RESOLUTION; OCCUPANCY; PROMOTERS; CODE AB The basic unit of eukaryotic chromatin is the nucleosome, consisting of about 150 by of DNA wrapped around a protein core made of histone proteins. Nucleosomes position is modulated in vivo to regulate fundamental nuclear processes. To measure nucleosome positions on a genomic scale both theoretical and experimental approaches have been recently reported. We have developed a new method, Multi-Layer Model (MLM), for the analysis of nucleosome position data obtained with microarray-based approach. The MLM is a feature extraction method in which the input data is processed by a classifier to distinguish between several kinds of patterns. We applied our method to simulated-synthetic and experimental nucleosome position data and found that besides a high nucleosome recognition and a strong agreement with standard statistical methods, the MLM can identify distinct classes of nucleosomes, making it an important tool for the genome wide analysis of nucleosome position and function. In conclusion, the MLM allows a better representation of nucleosome position data and a significant reduction in computational time. (C) 2008 Elsevier Inc. All rights reserved. C1 [Di Gesu, Vito; Lo Bosco, Giosue; Pinello, Luca] Univ Palermo, Dipartimento Matemat & Applicaz, I-90123 Palermo, Italy. [Yuan, Guo-Cheng] Harvard Univ, Sch Publ Hlth, Dept Biostat, Cambridge, MA 02138 USA. [Yuan, Guo-Cheng] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Corona, Davide F. V.] Univ Palermo, Ist Telethon Dulbecco, I-90133 Palermo, Italy. [Corona, Davide F. V.] Univ Palermo, Dipartimento Sci Biochim, I-90133 Palermo, Italy. RP Lo Bosco, G (reprint author), Univ Palermo, Dipartimento Matemat & Applicaz, Via Archirafi 34, I-90123 Palermo, Italy. EM lobosco@math.unipa.it RI Corona, Davide/H-8467-2012; Lo Bosco, Giosue/C-7644-2011 OI Lo Bosco, Giosue/0000-0002-1602-0693 FU Italian Ministry of University and Research (MIUR); Piano Operativo Nazionale "Ricerca Scientifica, Sviluppo Tecnologico, Alta Formazione"; Fondazione Telethon, Giovanni Armenise Harvard Foundation; MIUR; HFSP; Dana-Farber Cancer Institute; Claudia Adams Barr Program FX This work makes use of results produced by the P12S2 Project managed by the Consorzio COMETA, a project co-funded by the Italian Ministry of University and Research (MIUR) within the Piano Operativo Nazionale "Ricerca Scientifica, Sviluppo Tecnologico, Alta Formazione" (PON 2000-2006). More information is available at httll://www.pi2s2.it and http://www.consorzio-cometa.it. D.FV.C. was supported by Fondazione Telethon, Giovanni Armenise Harvard Foundation, MIUR, HFSP and Compagnia San Paolo. GX's research was funded by Dana-Farber Cancer Institute and the Claudia Adams Barr Program. NR 30 TC 10 Z9 10 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD FEB PY 2009 VL 93 IS 2 BP 140 EP 145 DI 10.1016/j.ygeno.2008.09.012 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 405LZ UT WOS:000263227600005 PM 18951969 ER PT J AU Shub, D Darvishi, R Kunik, ME AF Shub, Denis Darvishi, Roham Kunik, Mark E. TI Non-pharmacologic treatment of insomnia in persons with dementia SO GERIATRICS LA English DT Article DE aging; circadian rhythm; dementia; insomnia; light therapy; sleep hygiene ID ALZHEIMERS-DISEASE; CONTROLLED-TRIAL; OLDER-ADULTS; SLEEP; DISTURBANCES; MANAGEMENT; EXERCISE; PROJECT AB The prevalence of insomnia increases with age and affects up to 35% of community-dwelling adults with dementia. Sleep disturbances and associated cognitive and behavioral symptoms in this patient population can be a significant contributor to morbidity, mortality, and caregiver burden. Despite the frequency with which sleep disorders are encountered in primary care, few evidence-based guidelines are available to guide physician treatment plans. Sedative-hypnotic medications are commonly prescribed but are associated with significant adverse effects and have limited efficacy data. Non-pharmacologic treatments can be safe and effective adjuncts or alternatives to medications but are often underused in clinical practice. This article reviews practical applications of modalities such as light therapy, exercise, and sleep-hygiene modification in treating insomnia In persons with dementia. C1 [Shub, Denis; Kunik, Mark E.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Darvishi, Roham] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Darvishi, Roham] Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. [Kunik, Mark E.] Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. RP Shub, D (reprint author), Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. NR 16 TC 20 Z9 20 U1 4 U2 11 PU ADVANSTAR COMMUNICATIONS INC PI WOODLAND HILLS PA 6200 CANOGA AVE, 2ND FLR, WOODLAND HILLS, CA 91367 USA SN 0016-867X J9 GERIATRICS JI Geriatrics PD FEB PY 2009 VL 64 IS 2 BP 22 EP 26 PG 5 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 409UN UT WOS:000263531400004 PM 19256583 ER PT J AU Nevadunsky, NS Barbieri, JS Kwong, J Merritt, MA Welch, WR Berkowitz, RS Mok, SC AF Nevadunsky, Nicole S. Barbieri, John S. Kwong, Joseph Merritt, Melissa A. Welch, William R. Berkowitz, Ross S. Mok, Samuel C. TI RUNX3 protein is overexpressed in human epithelial ovarian cancer SO GYNECOLOGIC ONCOLOGY LA English DT Article; Proceedings Paper CT 38th Annual Meeting of the Society-of-Gynecologic Oncologists CY MAR 03-07, 2007 CL San Diego, CA SP Soc Gynecol Oncologists DE Ovarian cancer; Oncogene; RUNX3 ID PROMOTER HYPERMETHYLATION; GENE-EXPRESSION; GASTRIC-CANCER; MISLOCALIZATION; INACTIVATION AB Objective. RUNX family genes, including RUNX3, are developmental regulators that are important in human cancers. The purpose of this study was to evaluate expression and oncogenic potential of RUNX3 in ovarian carcinoma. Methods. Immunohistochemical staining was performed on 60 malignant, 14 borderline, and 5 normal ovarian specimens. Correlation between RUNX3 expression with tumor histology was performed. RUNX3 expression was evaluated by quantitative real-time polymerase chain reaction (QRT-PCR) in microdissected normal and malignant epithelial ovarian tissues. Cell proliferation and viability studies were performed on cells expressing RUNX3 by lentiviral infection and cells with silenced RUNX3 expression by siRNA. Results. RUNX3 expression by immunohistochemistry was higher in serous ovarian carcinomas versus normal ovarian epithelium (P<0.001). Immunofluorescent staining confirmed upregulation of cytoplasmic RUNX3 in ovarian cancer cell lines and tissues. QRT-PCR showed higher RUNX3 mRNA expression in microdissected borderline and malignant ovarian tumor tissues compared with the normal ovarian surface epithelial cells (HOSE) (P=0.006 and P=0.023). Forced RUNX3 expression by lentiviral gene delivery in ovarian cancer cells, SKOV3, that initially showed undetectable RUNX3 expression, resulted in increased cell viability (P=0.043). Silencing RUNX3 expression by siRNA transfection into ovarian cancer cells, OVCAR429, initially expressing high levels of endogenous RUNX3 resulted in a decrease in proliferation (P=0.021). Conclusion. These results suggest that RUNX3 has a role in cell proliferation and viability in ovarian cancer. (C) 2008 Elsevier Inc. All rights reserved. C1 [Nevadunsky, Nicole S.; Barbieri, John S.; Kwong, Joseph; Merritt, Melissa A.; Berkowitz, Ross S.; Mok, Samuel C.] Harvard Univ, Brigham & Womens Hosp, Sch Med,Lab Gynecol Oncol, Dept Obstet & Gynecol,Div Gynecol Oncol, Boston, MA 02115 USA. [Welch, William R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Berkowitz, Ross S.; Mok, Samuel C.] Dana Farber Harvard Canc Ctr, Gillette Ctr Womens Canc, Boston, MA USA. RP Berkowitz, RS (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med,Lab Gynecol Oncol, Dept Obstet & Gynecol,Div Gynecol Oncol, Boston, MA 02115 USA. EM RBERKOWITZ@partners.org RI Kwong, Joseph/H-2368-2013 FU NCI NIH HHS [P50CA165009, R33CA103595] NR 13 TC 27 Z9 28 U1 0 U2 5 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 FEB PY 2009 VL 112 IS 2 BP 325 EP 330 DI 10.1016/j.ygyno.2008.09.006 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 404JS UT WOS:000263148400008 PM 18937968 ER PT J AU Growdon, WB Wolfberg, AJ Goldstein, DP Feltmate, CM Chinchilla, ME Lieberman, ES Berkowitz, RS AF Growdon, Whitfield B. Wolfberg, Adam J. Goldstein, Donald P. Feltmate, Colleen M. Chinchilla, Manuel E. Lieberman, Ellice S. Berkowitz, Ross S. TI Evaluating methotrexate treatment in patients with low-risk postmolar gestational trophoblastic neoplasia SO GYNECOLOGIC ONCOLOGY LA English DT Article; Proceedings Paper CT 14th World Congress on Gestational Trophoblastic Diseases CY NOV 11-14, 2007 CL Fukuoka, JAPAN DE Low risk gestational trophoblastic disease; Single agent methotrexate; Persistent GTN ID SINGLE-AGENT METHOTREXATE; REPEAT UTERINE EVACUATION; PARTIAL HYDATIDIFORM MOLE; POSTEVACUATION HCG LEVELS; FOLINIC ACID; PRIMARY THERAPY; DISEASE; TUMORS; PREGNANCY; WOMEN AB Objective. To identify clinical factors associated with requiring more than a single course of Methotrexate (MTX) to achieve remission among women with low-risk postmolar gestational trophoblastic neoplasia (GTN). Methods. We studied 150 women with persistent GTN after diagnosis of complete (n=110) or partial mole (n=40) to identify possible predictors of requiring additional treatment after a single treatment of methotrexate (MTX). All women had low-risk disease using FIGO and WHO scoring systems. Results. Seventy women (47%) required additional courses of chemotherapy, of whom 45 (64%) received chemotherapy other than MTX. Multivariate analysis revealed that complete mole histology, presence of metastasis, single day MTX infusion and any increase in serum beta human chorionic gonadotropin (beta-hCG) level 1 week after MTX therapy were independent predictors of requiring additional MTX or alternative chemotherapy. Dilatation and curettage (D+C) within I week after the diagnosis of persistence did not affect future chemotherapy requirements (p>0.64). Following complete mole, beta-hCG levels>2000 mIU/mL at 1 week post MTX were associated with a 89% risk of additional cycles chemotherapy including MTX and a 65% risk of alternative chemotherapy. Conclusions. Metastatic disease, MTX infusion protocol and complete mole histology were independently associated with the need for additional chemotherapy after an initial course of MTX for women with low risk CTN. D+C at persistence did not alter the chemotherapy requirement. Elevated beta-hCG level at I week after the initial course of MTX was also an independent factor predicting the need for additional courses of MTX or alternative chemotherapy. (C) 2008 Elsevier Inc. All rights reserved. C1 [Goldstein, Donald P.; Feltmate, Colleen M.; Chinchilla, Manuel E.; Lieberman, Ellice S.; Berkowitz, Ross S.] Brigham & Womens Hosp, Dept OBGYN, Div Gynecol Oncol, Boston, MA 02115 USA. [Growdon, Whitfield B.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Boston, MA 02114 USA. [Wolfberg, Adam J.] Tufts Univ New England Med Ctr, Dept Obstet & Gynecol, Div Maternal Fetal Med, Boston, MA USA. [Goldstein, Donald P.; Feltmate, Colleen M.; Berkowitz, Ross S.] Donald P Goldstein MD Tumor Registry, New England Trophoblast Dis Ctr, Boston, MA USA. [Growdon, Whitfield B.; Goldstein, Donald P.; Feltmate, Colleen M.; Berkowitz, Ross S.] Dana Farber Canc Inst, Harvard Canc Ctr, Boston, MA 02115 USA. [Growdon, Whitfield B.; Goldstein, Donald P.; Feltmate, Colleen M.; Chinchilla, Manuel E.; Lieberman, Ellice S.; Berkowitz, Ross S.] Harvard Univ, Sch Med, Boston, MA USA. RP Berkowitz, RS (reprint author), Brigham & Womens Hosp, Dept OBGYN, Div Gynecol Oncol, ASBI,75 Francis St, Boston, MA 02115 USA. EM rberkowitz@partners.org NR 29 TC 25 Z9 27 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 FEB PY 2009 VL 112 IS 2 BP 353 EP 357 DI 10.1016/j.ygyno.2008.11.003 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 404JS UT WOS:000263148400013 PM 19059633 ER PT J AU Matulonis, UA Krag, KJ Krasner, CN Atkinson, T Horowitz, NS Lee, H Penson, RT AF Matulonis, Ursula A. Krag, Karen J. Krasner, Carolyn N. Atkinson, Tina Horowitz, Neil S. Lee, Hang Penson, Richard T. TI Phase II prospective study of paclitaxel and carboplatin in older patients with newly diagnosed Mullerian tumors SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Ovarian cancer; Elderly; Older patients; Chemotherapy ID GYNECOLOGIC-ONCOLOGY-GROUP; OVARIAN-CANCER PATIENTS; CELL LUNG-CANCER; QUALITY-OF-LIFE; ELDERLY-PATIENTS; COMORBIDITY INDEX; PROGNOSTIC FACTOR; CLINICAL-TRIALS; STAGE-III; AGE AB Objectives: The primary objective was to determine the completion rate of 6 cycles of paclitaxel and carboplatin chemotherapy with no dose reductions in patients >= 70 years of age. Methods: Phase II study of intravenous (IV) carboplatin Area Under the Curve (AUC) of 5 and paclitaxel 175 mg/m(2) given to patients 70 years of age, had any stage Mullerian cancer, and an ECOG performance status (PS) of 0-2. Results: Twelve patients were enrolled (median age of 82 years, range 75 to 86 years). Six of 12 completed 6 cycles of chemotherapy with no dose reductions. Three patients died on study precipitating study closure; one with refractory cancer following cycle 1, one of aspiration pneumonia after cycle 1, and one with sudden death on day 5 of cycle 6. Patients undergoing upfront debulking surgery tolerated chemotherapy better compared to patients receiving neoadjuvant chemotherapy. Grade 3 or higher hematologic toxicities included 2 patients with febile neutropenia (17%). >= Grade 3 non-hematologic toxicities included fatigue (8%), nausea (8%), constipation (8%), obstipation (8%), vomiting (8%), and hypoxia (8%). Conclusions: In this prospective trial of standard carboplatin and paclitaxel chemotherapy in a heterogeneous population of elderly patients, chemotherapy was well tolerated by patients who underwent upfront debulking surgery, had a PS of 0-1, and had few comorbidities. Patients not undergoing upfront debulking surgery because of either advanced cancer or poor surgical risk had excess morbidity/mortality. Prospective studies to identify risk factors for toxicity prediction are needed. (C) 2008 Elsevier Inc. All rights reserved. C1 [Matulonis, Ursula A.; Atkinson, Tina] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Krag, Karen J.] N Shore Canc Ctr, Salem, MA USA. [Krasner, Carolyn N.; Penson, Richard T.] Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. [Horowitz, Neil S.] Brigham & Womens Hosp, Div Gynecol Oncol, Boston, MA 02115 USA. [Lee, Hang] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Matulonis, UA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM ursula_matulonis@dfci.harvard.edu NR 29 TC 13 Z9 13 U1 1 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 FEB PY 2009 VL 112 IS 2 BP 394 EP 399 DI 10.1016/j.ygyno.2008.10.015 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 404JS UT WOS:000263148400020 PM 19058838 ER PT J AU Baron, E Munro, EG Ahmed, J Goodman, A Del Cannen, MG AF Baron, E. Munro, E. G. Ahmed, J. Goodman, A. Del Cannen, M. G. TI Comorbidity and prognosis in serous and papillary serous ovarian cancer SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Baron, E.; Munro, E. G.; Ahmed, J.; Goodman, A.; Del Cannen, M. G.] Massachusetts Gen Hosp, Dept Gynecol Oncol, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD FEB PY 2009 VL 112 IS 2 MA 229 BP S116 EP S117 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 419OY UT WOS:000264230200228 ER PT J AU Growdon, WB Duska, L AF Growdon, W. B. Duska, L. TI Complete surgical staging in isolated stage I papillary serous cancer of the uterus obviates the need for adjuvant therapy SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Growdon, W. B.; Duska, L.] Massachusetts Gen Hosp, Div Gynecol Oncol, Dept Obstet & Gynecol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 FEB PY 2009 VL 112 IS 2 MA 140 BP S70 EP S71 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 419OY UT WOS:000264230200140 ER PT J AU Growdon, WB Curley, M Friel, A Ferguson, J Mandley, E Foster, R MacDougal, J Rueda, B AF Growdon, W. B. Curley, M. Friel, A. Ferguson, J. Mandley, E. Foster, R. MacDougal, J. Rueda, B. TI Hedgehog pathway inhibitor cyclopamine suppresses GLI1 expression and inhibits serous ovarian cancer xenograft growth SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Growdon, W. B.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Boston, MA 02114 USA. [Ferguson, J.; Mandley, E.; MacDougal, J.] Infin Pharmaceut Inc, Boston, MA USA. [Foster, R.] Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD FEB PY 2009 VL 112 IS 2 MA 18 BP S10 EP S10 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 419OY UT WOS:000264230200019 ER PT J AU Moore, RG Jabre-Raughley, M Brown, AK Robison, KM Miller, CM Allard, JW Nilsson, O Kurman, RJ Bast, RC Skates, SJ AF Moore, R. G. Jabre-Raughley, M. Brown, A. K. Robison, K. M. Miller, C. M. Allard, J. W. Nilsson, O. Kurman, R. J. Bast, R. C. Skates, S. J. TI Comparison of a novel multiple marker assay versus the risk of malignancy index for the prediction of epithelial ovarian cancer in patients with a pelvic mass SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Moore, R. G.; Jabre-Raughley, M.; Robison, K. M.] Brown Univ, Women & Infants Hosp, Dept Obstet & Gynecol, Providence, RI USA. [Brown, A. K.] Hartford Hosp, Dept Obstet & Gynecol, Hartford, CT 06115 USA. [Miller, C. M.; Allard, J. W.; Nilsson, O.] Fujirebio Diagnost Inc, Malvern, PA USA. [Kurman, R. J.] Johns Hopkins Med Sch, Dept Pathol, Baltimore, MD USA. [Bast, R. C.] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA. [Skates, S. J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA USA. RI Bast, Robert/E-6585-2011 OI Bast, Robert/0000-0003-4621-8462 NR 0 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD FEB PY 2009 VL 112 IS 2 MA 45 BP S25 EP S26 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 419OY UT WOS:000264230200046 ER PT J AU Rauh-Hain, JA Alarcon, IA Ko, E Del Carmen, MG Olawaiye, AB AF Rauh-Hain, J. A. Alarcon, I. A. Ko, E. Del Carmen, M. G. Olawaiye, A. B. TI Does bowel obstruction at the time of primary presentation affect prognosis in ovarian cancer? SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Rauh-Hain, J. A.; Ko, E.; Del Carmen, M. G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Alarcon, I. A.] St Elizabeths Med Ctr, Boston, MA USA. [Olawaiye, A. B.] Univ Pittsburgh, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD FEB PY 2009 VL 112 IS 2 MA 245 BP S125 EP S125 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 419OY UT WOS:000264230200244 ER PT J AU Rauh-Hain, JA Olawaiye, AB Munro, EG Ko, E Alarcon, IA Del Carmen, MG Duska, L AF Rauh-Hain, J. A. Olawaiye, A. B. Munro, E. G. Ko, E. Alarcon, I. A. Del Carmen, M. G. Duska, L. TI A model for predicting outcome in patients with bowel obstruction secondary to ovarian carcinoma using CT SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Rauh-Hain, J. A.; Munro, E. G.; Ko, E.; Del Carmen, M. G.] Massachusetts Gen Hosp, Dept Gynecol Oncol, Boston, MA 02114 USA. [Olawaiye, A. B.] Univ Pittsburgh, Dept Gynecol Oncol, Pittsburgh, PA USA. [Alarcon, I. A.] St Elizabeths Med Ctr, Dept Med, Boston, MA USA. [Duska, L.] Univ Virginia, Dept Gynecol Oncol, Charlottesville, VA USA. NR 0 TC 0 Z9 0 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD FEB PY 2009 VL 112 IS 2 MA 198 BP S99 EP S100 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 419OY UT WOS:000264230200197 ER PT J AU Schorge, JO Drake, RD Xiao, G Wingo, SN Xie, Y AF Schorge, J. O. Drake, R. D. Xiao, G. Wingo, S. N. Xie, Y. TI Gene expression profiling to predict early relapse in ovarian cancer SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Schorge, J. O.] Massachusetts Gen Hosp, Dept Gynecol Oncol, Boston, MA 02114 USA. [Drake, R. D.] Cleveland Clin, Dept Gynecol Oncol, Cleveland, OH 44106 USA. [Xiao, G.; Xie, Y.] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA. [Wingo, S. N.] Univ Texas SW Med Ctr Dallas, Dept Gynecol Oncol, Dallas, TX 75390 USA. NR 0 TC 1 Z9 1 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 FEB PY 2009 VL 112 IS 2 MA 210 BP S105 EP S106 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 419OY UT WOS:000264230200209 ER PT J AU Tung, CS Mok, SC Tsang-Lee, YT Zu, Z Wolf, JK Birrer, MJ Gershenson, DM Wong, K AF Tung, C. S. Mok, S. C. Tsang-Lee, Y. T. Zu, Z. Wolf, J. K. Birrer, M. J. Gershenson, D. M. Wong, K. TI Validation of PAX2 expression in low-grade and low-malignant potential serous ovarian carcinoma SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Tung, C. S.; Mok, S. C.; Tsang-Lee, Y. T.; Zu, Z.; Wolf, J. K.; Gershenson, D. M.; Wong, K.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA. [Birrer, M. J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Internal Med, Boston, MA USA. NR 0 TC 0 Z9 0 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD FEB PY 2009 VL 112 IS 2 MA 54 BP S30 EP S30 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 419OY UT WOS:000264230200055 ER PT J AU Vranceanu, AM Cooper, C Ring, D AF Vranceanu, Ana-Maria Cooper, Cynthia Ring, David TI Integrating Patient Values into Evidence-Based Practice: Effective Communication for Shared Decision-Making SO HAND CLINICS LA English DT Article DE Patient centered; Evidence based; Shared decision-making ID EVIDENCE-BASED ORTHOPEDICS; LOCAL INJECTION TREATMENT; CHRONIC PAIN; GENERAL-PRACTICE; TENNIS ELBOW; ARM PAIN; DISABILITY; PHYSICIAN; MODEL; CARE AB Increasing data suggest that the traditional clinician-centered or disease-focused, biomedical approach to illness is less effective than a biopsychosocial, evidence-based, patient-centered approach to illness, particularly for chronic pain conditions. This article distinguishes patient-centered care from more traditional and outdated biomedical decisionmaking models; illustrates the complexity of illness behavior with a patient example; delves into the communication issues raised by this complexity, thereby demonstrating how best evidence can sometimes run counter to biases and intuition; provides a summary of evidence that patient-centered care positively affects outcomes; and explores how the shared decision-making approach along with cultivation of good communication skills can facilitate evidence-based practice. C1 [Vranceanu, Ana-Maria; Ring, David] Massachusetts Gen Hosp, Dept Orthoped Surg, Orthoped Hand & Upper Extrem Serv, Boston, MA 02114 USA. [Cooper, Cynthia] Scottsdale Healthcare, Scottsdale, AZ 85260 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Dept Orthoped Surg, Orthoped Hand & Upper Extrem Serv, Yawkey 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 64 TC 24 Z9 24 U1 4 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 0749-0712 J9 HAND CLIN JI Hand Clin. PD FEB PY 2009 VL 25 IS 1 BP 83 EP + DI 10.1016/j.hcl.2008.09.003 PG 15 WC Orthopedics SC Orthopedics GA 422GQ UT WOS:000264415900010 PM 19232919 ER PT J AU Liu, CF Rubenstein, LV Kirchner, JE Fortney, JC Perkins, MW Ober, SK Pyne, JM Chaney, EF AF Liu, Chuan-Fen Rubenstein, Lisa V. Kirchner, JoAnn E. Fortney, John C. Perkins, Mark W. Ober, Scott K. Pyne, Jeffrey M. Chaney, Edmund F. TI Organizational Cost of Quality Improvement for Depression Care SO HEALTH SERVICES RESEARCH LA English DT Article DE Quality improvement; depression; primary care ID RANDOMIZED CONTROLLED-TRIAL; CHRONIC ILLNESS CARE; TRANSLATING EVIDENCE; COLLABORATIVE CARE; HEALTH-CARE; MANAGEMENT; IMPLEMENTATION; IMPACT; INTERVENTIONS; INNOVATIONS AB We documented organizational costs for depression care quality improvement (QI) to develop an evidence-based, Veterans Health Administration (VA) adapted depression care model for primary care practices that performed well for patients, was sustained over time, and could be spread nationally in VA. Project records and surveys from three multistate VA administrative regions and seven of their primary care practices. Descriptive analysis. We documented project time commitments and expenses for 86 clinical QI and 42 technical expert support team participants for 4 years from initial contact through care model design, Plan-Do-Study-Act cycles, and achievement of stable workloads in which models functioned as routine care. We assessed time, salary costs, and costs for conference calls, meetings, e-mails, and other activities. Over an average of 27 months, all clinics began referring patients to care managers. Clinical participants spent 1,086 hours at a cost of $84,438. Technical experts spent 2,147 hours costing $197,787. Eighty-five percent of costs derived from initial regional engagement activities and care model design. Organizational costs of the QI process for depression care in a large health care system were significant, and should be accounted for when planning for implementation of evidence-based depression care. C1 [Liu, Chuan-Fen; Kirchner, JoAnn E.; Fortney, John C.; Pyne, Jeffrey M.] VA Puget Sound Healthcare Syst, NW Ctr Outcomes Res Older Adults, Seattle, WA 98101 USA. [Rubenstein, Lisa V.] VA Greater Los Angeles Healthcare Syst, Ctr Excellence Study Healthcare Provider Behav, Sepulveda, CA USA. [Rubenstein, Lisa V.] RAND Hlth Program, Santa Monica, CA USA. [Rubenstein, Lisa V.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Kirchner, JoAnn E.; Fortney, John C.; Pyne, Jeffrey M.] S Cent Mental Hlth Illness Res & Educ & Clin Ctr, N Little Rock, AR USA. [Kirchner, JoAnn E.; Fortney, John C.; Pyne, Jeffrey M.] Cent Arkansas Vet Healthcare Syst, Ctr Mental Healthcare & Outcomes Res, N Little Rock, AR USA. [Kirchner, JoAnn E.; Fortney, John C.; Pyne, Jeffrey M.] Univ Arkansas Med Sci, Div Hlth Serv Res, Dept Psychiat & Behav Sci, Little Rock, AR 72205 USA. [Ober, Scott K.] Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA. [Ober, Scott K.] Cleveland VA Med Ctr, Cleveland, OH USA. [Chaney, Edmund F.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Liu, Chuan-Fen] Univ Washington, Sch Publ Hlth & Community Med, Dept Hlth Serv, Seattle, WA 98195 USA. RP Liu, CF (reprint author), VA Puget Sound Healthcare Syst, NW Ctr Outcomes Res Older Adults, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM chuan-fen.liu@va.gov FU Health Services Research and Development, Department of Veterans Affairs [MNT-02-209, MNT-01-027]; TIDES/WAVES/COVES FX Joint Acknowledgement/Disclosure Statement: Funding provided by Health Services Research and Development, Department of Veterans Affairs (grant numbers MNT-02-209 and MNT-01-027).; We would like to acknowledge the support and assistance from TIDES/WAVES/COVES project research staff in submitting detailed project records and contributing their comments to this paper. In addition, we would like to acknowledge the participation and support from our three VISN partners (VISNs 10, 16, and 23).; There are no contractual rights to review the manuscript before submission, but there is a requirement that Health Services Research and Development, Department of Veterans Affairs, be given a copy of the accepted manuscript before publication. The views expressed herein are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs and other affiliated Institutions. NR 42 TC 25 Z9 26 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0017-9124 EI 1475-6773 J9 HEALTH SERV RES JI Health Serv. Res. PD FEB PY 2009 VL 44 IS 1 BP 225 EP 244 DI 10.1111/j.1475-6773.2008.00911.x PG 20 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 394TM UT WOS:000262470800014 PM 19146566 ER PT J AU Pappo, AS Janeway, KA AF Pappo, Alberto S. Janeway, Katherine A. TI Pediatric Gastrointestinal Stromal Tumors SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Pediatric; Gastrointestinal stromal tumors; IGF-1; Imatinib; Sunitinib; Carney triad ID OF-THE-LITERATURE; CARNEY TRIAD; SUCCINATE-DEHYDROGENASE; PULMONARY CHONDROMA; GERMLINE MUTATIONS; IMATINIB MESYLATE; 12-YEAR-OLD GIRL; KIT ACTIVATION; YOUNG-ADULTS; FOLLOW-UP AB Gastrointestinal stromal tumors (GISTs) rarely occur in pediatric patients, but increased recognition of adult GIST has led to better awareness of the existence of this entity in the pediatric population. GIST occurring in pediatric patients has a unique biology and clinical behavior and warrants discussion as an independent entity. The generally accepted definition of pediatric GIST is a tumor that is diagnosed at the age of 18 years or younger. This review highlights the clinical features, molecular biology, and clinical management of this rare pediatric entity. C1 [Pappo, Alberto S.] Texas Childrens Canc Ctr, Dept Pediat, Houston, TX 77030 USA. [Janeway, Katherine A.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02125 USA. [Janeway, Katherine A.] Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Pappo, AS (reprint author), Texas Childrens Canc Ctr, Dept Pediat, 6621 Fannin St,CC1510-00, Houston, TX 77030 USA. EM aspappo@txccc.org NR 62 TC 35 Z9 37 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 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD FEB PY 2009 VL 23 IS 1 BP 15 EP + DI 10.1016/j.hoc.2008.11.005 PG 21 WC Oncology; Hematology SC Oncology; Hematology GA 423JC UT WOS:000264491600003 PM 19248968 ER PT J AU Quek, R George, S AF Quek, Richard George, Suzanne TI Gastrointestinal Stromal Tumor: A Clinical Overview SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Gastrointestinal stromal tumors; GIST; Review; Imatinib; Sunitinib; Tyrosine kinase inhibitor ID AUTONOMIC NERVE TUMORS; SMOOTH-MUSCLE TUMORS; IMATINIB MESYLATE; TYROSINE KINASE; C-KIT; DOSE IMATINIB; MUTATIONS; TRIAL; IDENTIFICATION; MASTOCYTOSIS AB Gastrointestinal stromal tumor (GIST) is a disease that was poorly understood historically. In the last decade, it has undergone a major transformation, sparked by the landmark discovery of the central role of activating KIT mutations in its pathogenesis and recognition of KIT protein expression (CD 117) as a reliable diagnostic marker of disease. The introduction and subsequent US Food and Drug administration approval of imatinib mesylate in the treatment of metastatic or unresectable GIST in February 1, 2002 has thrust this hitherto little known disease into the center stage of oncology, and GIST has served as a model for rationally designed drug trials in the field of cancer therapeutics since. C1 [Quek, Richard; George, Suzanne] Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. [Quek, Richard] Natl Canc Ctr Singapore, Dept Med Oncol, Singapore 169610, Singapore. [George, Suzanne] Harvard Univ, Sch Med, Boston, MA USA. RP George, S (reprint author), Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, 44 Binney St, Boston, MA 02115 USA. EM sgeorge2@partners.org NR 55 TC 16 Z9 18 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 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD FEB PY 2009 VL 23 IS 1 BP 69 EP + DI 10.1016/j.hoc.2008.11.006 PG 11 WC Oncology; Hematology SC Oncology; Hematology GA 423JC UT WOS:000264491600006 PM 19248971 ER PT J AU Simpson, CL Lemmens, R Miskiewicz, K Broom, WJ Hansen, VK van Vught, PWJ Landers, JE Sapp, P Van Den Bosch, L Knight, J Neale, BM Turner, MR Veldink, JH Ophoff, RA Tripathi, VB Beleza, A Shah, MN Proitsi, P Van Hoecke, A Carmeliet, P Horvitz, HR Leigh, PN Shaw, CE van den Berg, LH Sham, PC Powell, JF Verstreken, P Brown, RH Robberecht, W Al-Chalabi, A AF Simpson, Claire L. Lemmens, Robin Miskiewicz, Katarzyna Broom, Wendy J. Hansen, Valerie K. van Vught, Paul W. J. Landers, John E. Sapp, Peter Van Den Bosch, Ludo Knight, Joanne Neale, Benjamin M. Turner, Martin R. Veldink, Jan H. Ophoff, Roel A. Tripathi, Vineeta B. Beleza, Ana Shah, Meera N. Proitsi, Petroula Van Hoecke, Annelies Carmeliet, Peter Horvitz, H. Robert Leigh, P. Nigel Shaw, Christopher E. van den Berg, Leonard H. Sham, Pak C. Powell, John F. Verstreken, Patrik Brown, Robert H., Jr. Robberecht, Wim Al-Chalabi, Ammar TI Variants of the elongator protein 3 (ELP3) gene are associated with motor neuron degeneration SO HUMAN MOLECULAR GENETICS LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; WIDE ASSOCIATION; POOLED DNA; MUTATIONS; GENOME; SUSCEPTIBILITY; ELONGATOR; MITOCHONDRIA; POLYMORPHISM; DISEASE AB Amyotrophic lateral sclerosis (ALS) is a spontaneous, relentlessly progressive motor neuron disease, usually resulting in death from respiratory failure within 3 years. Variation in the genes SOD1 and TARDBP accounts for a small percentage of cases, and other genes have shown association in both candidate gene and genome-wide studies, but the genetic causes remain largely unknown. We have performed two independent parallel studies, both implicating the RNA polymerase II component, ELP3, in axonal biology and neuronal degeneration. In the first, an association study of 1884 microsatellite markers, allelic variants of ELP3 were associated with ALS in three human populations comprising 1483 people (P = 1.96 x 10(-9)). In the second, an independent mutagenesis screen in Drosophila for genes important in neuronal communication and survival identified two different loss of function mutations, both in ELP3 (R475K and R456K). Furthermore, knock down of ELP3 protein levels using antisense morpholinos in zebrafish embryos resulted in dose-dependent motor axonal abnormalities [Pearson correlation: -0.49, P = 1.83 x 10(-12) (start codon morpholino) and -0.46, P = 4.05 x 10(-9) (splice-site morpholino), and in humans, risk-associated ELP3 genotypes correlated with reduced brain ELP3 expression (P = 0.01). These findings add to the growing body of evidence implicating the RNA processing pathway in neurodegeneration and suggest a critical role for ELP3 in neuron biology and of ELP3 variants in ALS. C1 [Knight, Joanne; Neale, Benjamin M.] Kings Coll London, Inst Psychiat, MRC, Social Genet & Dev Psychiat Ctr, London SE5 8AF, England. [Proitsi, Petroula; Powell, John F.] Kings Coll London, Inst Psychiat, MRC, Ctr Neurodegenerat Res,Dept Neurosci, London SE5 8AF, England. [Simpson, Claire L.; Hansen, Valerie K.; Turner, Martin R.; Tripathi, Vineeta B.; Beleza, Ana; Shah, Meera N.; Leigh, P. Nigel; Shaw, Christopher E.; Al-Chalabi, Ammar] Kings Coll London, Inst Psychiat, Dept Neurol, London SE5 8AF, England. [Lemmens, Robin; Van Den Bosch, Ludo; Van Hoecke, Annelies; Robberecht, Wim] Univ Leuven, Sect Expt Neurol, Neurobiol Lab, B-3000 Louvain, Belgium. [Lemmens, Robin; Van Den Bosch, Ludo; Van Hoecke, Annelies; Robberecht, Wim] Katholieke Univ Leuven Hosp, Serv Neurol, B-3000 Louvain, Belgium. [Van Den Bosch, Ludo; Van Hoecke, Annelies; Carmeliet, Peter; Robberecht, Wim] Flanders Inst Biotechnol VIB, Vesalius Res Ctr, B-3000 Louvain, Belgium. [Miskiewicz, Katarzyna; Verstreken, Patrik] Katholieke Univ Leuven, Lab Neuronal Commun, Ctr Human Genet, B-3000 Louvain, Belgium. [Miskiewicz, Katarzyna; Verstreken, Patrik] VIB, Dept Mol & Dev Genet, B-3000 Louvain, Belgium. [Broom, Wendy J.; Landers, John E.; Sapp, Peter; Brown, Robert H., Jr.] Massachusetts Gen Hosp East, Cecil B Day Lab Neuromuscular Res, Charlestown, MA USA. [van Vught, Paul W. J.; Veldink, Jan H.] Univ Med Ctr, Dept Neurol, Utrecht, Netherlands. [Ophoff, Roel A.] Univ Med Ctr, Rudolf Magnus Inst Neurosci, Dept Med Genet, Utrecht, Netherlands. [Sapp, Peter; Horvitz, H. Robert] MIT, Howard Hughes Med Inst, Dept Biol, Cambridge, MA USA. [Ophoff, Roel A.] Univ Calif Los Angeles, Inst Neuropsychiat, Los Angeles, CA 90024 USA. [Sham, Pak C.] Univ Hong Kong, Dept Psychiat, Hong Kong, Hong Kong, Peoples R China. [Sham, Pak C.] Univ Hong Kong, Genome Ctr, Hong Kong, Hong Kong, Peoples R China. RP Al-Chalabi, A (reprint author), Kings Coll London, Inst Psychiat P 043, MRC, Ctr Neurodegenerat Res, London SE5 8AF, England. EM ammar@iop.kcl.ac.uk RI Al-Chalabi, Ammar/E-5361-2010; Turner, Martin/F-7240-2011; Powell, John/G-4412-2011; Van Den Bosch, Ludo/B-7258-2012; Knight, Jo/F-4946-2011; OI Al-Chalabi, Ammar/0000-0002-4924-7712; Turner, Martin/0000-0003-0267-3180; Knight, Joanne/0000-0002-7148-1660; Powell, John/0000-0001-6124-439X; Verstreken, Patrik/0000-0002-5073-5393 FU Medical Research Council (UK); Motor Neurone Disease Association; University of Leuven; Belgian government; Howard Hughes Medical Institute; The National Institutes of Neurological Disease and Stroke; National Institute on Aging; Al-Athel ALS Research Foundation; ALS Therapy Alliance; ALS Research Foundation; Medical Research Council (MRC) Clinician Scientist Fellow; GKT PhD Studentship; Marie Curie Excellence Grant; Medical Research Council FX This work was supported by the Medical Research Council (UK) to A.A.-C.; ALS Association to A.A.-C. and R. H. B.; Motor Neurone Disease Association to A.A.-C.; University of Leuven to W. R.; the Belgian government (Interuniversity Attraction Poles Programme 6/43-Belgian State-Belgian Science Policy) to W.R.; VIB to W.R. and P.V.; the Robert Packard Center for ALS Research to W.R.; the Howard Hughes Medical Institute to H.R.H.; The National Institutes of Neurological Disease and Stroke to R.H.B.; the National Institute on Aging to R.H.B.; the Al-Athel ALS Research Foundation to R.H.B.; the ALS Therapy Alliance to R.H.B., the Angel Fund to R.H.B.; Project ALS to R.H.B.; and the Pierre L. de Bourgknecht ALS Research Foundation to R. H. B. For much of this work, A.A.-C. was a Medical Research Council (MRC) Clinician Scientist Fellow and C.L.S. was funded by GKT PhD Studentship. P. S. and H.R.H. were supported by the Howard Hughes Medical Institute. W.R. was supported through the Evon Behring Chair for Neuromuscular and Neurodegenerative Disorders. P.V. was supported through a Marie Curie Excellence Grant. Funding to pay the Open Access Charge was provided by the Medical Research Council. NR 41 TC 114 Z9 120 U1 1 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 FEB 1 PY 2009 VL 18 IS 3 BP 472 EP 481 DI 10.1093/hmg/ddn375 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 395JB UT WOS:000262519300008 PM 18996918 ER PT J AU Ferland, RJ Batiz, LF Neal, J Lian, G Bundock, E Lu, J Hsiao, YC Diamond, R Mei, D Banham, AH Brown, PJ Vanderburg, CR Joseph, J Hecht, JL Folkerth, R Guerrini, R Walsh, CA Rodriguez, EM Sheen, VL AF Ferland, Russell J. Batiz, Luis Federico Neal, Jason Lian, Gewei Bundock, Elizabeth Lu, Jie Hsiao, Yi-Chun Diamond, Rachel Mei, Davide Banham, Alison H. Brown, Philip J. Vanderburg, Charles R. Joseph, Jeffrey Hecht, Jonathan L. Folkerth, Rebecca Guerrini, Renzo Walsh, Christopher A. Rodriguez, Esteban M. Sheen, Volney L. TI Disruption of neural progenitors along the ventricular and subventricular zones in periventricular heterotopia SO HUMAN MOLECULAR GENETICS LA English DT Article ID ACTIN-BINDING PROTEIN; CONGENITAL MUSCULAR-DYSTROPHIES; CEREBRAL CORTICAL DEVELOPMENT; NEURONAL MIGRATION DISORDER; DOUBLECORTIN-LIKE-KINASE; DOUBLE CORTEX SYNDROME; FILAMIN-A; NODULAR HETEROTOPIA; CYTOPLASMIC DYNEIN; EPENDYMAL DENUDATION AB Periventricular heterotopia (PH) is a disorder characterized by neuronal nodules, ectopically positioned along the lateral ventricles of the cerebral cortex. Mutations in either of two human genes, Filamin A (FLNA) or ADP-ribosylation factor guanine exchange factor 2 (ARFGEF2), cause PH (Fox et al. in 'Mutations in filamin 1 prevent migration of cerebral cortical neurons in human periventricular heterotopia'. Neuron, 21, 1315-1325, 1998; Sheen et al. in 'Mutations in ARFGEF2 implicate vesicle trafficking in neural progenitor proliferation and migration in the human cerebral cortex'. Nat. Genet., 36, 69-76, 2004). Recent studies have shown that mutations in mitogen-activated protein kinase kinase kinase-4 (Mekk4), an indirect interactor with FlnA, also lead to periventricular nodule formation in mice (Sarkisian et al. in 'MEKK4 signaling regulates filamin expression and neuronal migration'. Neuron, 52, 789-801, 2006). Here we show that neurons in post-mortem human PH brains migrated appropriately into the cortex, that periventricular nodules were primarily composed of later-born neurons, and that the neuroependyma was disrupted in all PH cases. As studied in the mouse, loss of FlnA or Big2 function in neural precursors impaired neuronal migration from the germinal zone, disrupted cell adhesion and compromised neuroepithelial integrity. Finally, the hydrocephalus with hop gait (hyh) mouse, which harbors a mutation in Napa [encoding N-ethylmaleimide-sensitive factor attachment protein alpha (alpha-SNAP)], also develops a progressive denudation of the neuroepithelium, leading to periventicular nodule formation. Previous studies have shown that Arfgef2 and Napa direct vesicle trafficking and fusion, whereas FlnA associates dynamically with the Golgi membranes during budding and trafficking of transport vesicles. Our current findings suggest that PH formation arises from a final common pathway involving disruption of vesicle trafficking, leading to impaired cell adhesion and loss of neuroependymal integrity. C1 [Neal, Jason; Lian, Gewei; Walsh, Christopher A.; Sheen, Volney L.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Joseph, Jeffrey; Hecht, Jonathan L.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Neuropathol, Boston, MA 02115 USA. [Ferland, Russell J.; Hsiao, Yi-Chun] Rensselaer Polytech Inst, Dept Biol, Ctr Biotechnol & Interdisciplinary Studies, Troy, NY 12180 USA. [Ferland, Russell J.] Wadsworth Ctr, Albany, NY 12201 USA. [Batiz, Luis Federico; Rodriguez, Esteban M.] Univ Austral Chile, Inst Anat Histol & Patol, Valdivia, Chile. [Bundock, Elizabeth; Folkerth, Rebecca] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neuropathol, Boston, MA 02115 USA. [Diamond, Rachel; Vanderburg, Charles R.] Massachusetts Gen Hosp, Harvard Ctr Neurodegenerat & Repair, Ctr Mol Pathol, Adv Tissue Resource Ctr, Boston, MA 02114 USA. [Mei, Davide; Guerrini, Renzo] Univ Pisa, Dept Child Neurol & Psychiat, I-56018 Pisa, Italy. [Mei, Davide; Guerrini, Renzo] IRCCS Fdn Stella Maris, I-56018 Pisa, Italy. [Banham, Alison H.; Brown, Philip J.] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Clin Lab Sci, Oxford OX3 9DU, Oxon, England. [Walsh, Christopher A.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. [Walsh, Christopher A.] Harvard Univ, Sch Med, Div Genet, Childrens Hosp, Boston, MA 02115 USA. RP Sheen, VL (reprint author), Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. EM vsheen@bidmc.harvard.edu RI Banham, Alison/B-2966-2009; Ferland, Russell/E-3500-2010; OI Banham, Alison/0000-0002-3197-273X; Ferland, Russell/0000-0002-8044-2479; Batiz, Luis Federico/0000-0002-3043-8797; Mei, Davide/0000-0001-6790-6251; Lu, Jie/0000-0001-6843-9720 FU NIMH [1K01MH71801]; Alzheimer's Association; Harvard Center for Neurodegeneration [1R21HD054347]; Fondecyt, Chile [1070241]; ID-UACh [DID-2005-12]; CONICYT,Chike; Doris Duke Clinical Scientist Development Award Recipient; Howard Hughes Medical Institute; Leukaemia Research Fund FX This work was supported by grants to R.J.F. from the NIMH (1K01MH71801) and a Young Investigator Award from Cure Autism Now; to V. L. S. from Julian and Carol Cohen, Alzheimer's Association, Harvard Center for Neurodegeneration, and 1R21HD054347; to E. M. R. from Fondecyt, Chile (Fondecyt 1070241) and to L. F. B. from DID-UACh (DID-2005-12) and CONICYT, Chile. V. L. S. is a Beckman Young Investigator and Doris Duke Clinical Scientist Development Award Recipient. C. A. W. is an Investigator of the Howard Hughes Medical Institute. A. H. B. and P. J. B. are supported by the Leukaemia Research Fund. We are very grateful to Genaro Alvial and Ricardo Silva (Univerisdad Austral de Chile) for their technical assistance. NR 86 TC 78 Z9 83 U1 1 U2 13 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD FEB 1 PY 2009 VL 18 IS 3 BP 497 EP 516 DI 10.1093/hmg/ddn377 PG 20 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 395JB UT WOS:000262519300010 PM 18996916 ER PT J AU Simon, RA di Sant'Agnese, PA Huang, LS Xu, HD Yao, JL Yang, Q Liang, SR Liu, JS Yu, R Cheng, L Oh, WK Palapattu, GS Wei, JJ Huang, JT AF Simon, Rochelle A. di Sant'Agnese, P. Anthony Huang, Li-Shan Xu, Haodong Yao, Jorge L. Yang, Qi Liang, Sharon Liu, Jinsong Yu, Rena Cheng, Liang Oh, William K. Palapattu, Ganesh S. Wei, Jianjun Huang, Jiaoti TI CD44 expression is a feature of prostatic small cell Carcinoma and Distinguishes it from its Mimickers SO HUMAN PATHOLOGY LA English DT Article DE Prostate; Adenocarcinoma; Small cell carcinoma; CD44; Immunohistochemistry ID V6 SPLICED VARIANT; CANCER CELLS; LUNG-CANCER; STEM-CELLS; PROSPECTIVE IDENTIFICATION; DIFFERENTIAL EXPRESSION; ISOFORM EXPRESSION; NEUROENDOCRINE; TUMORS; PROGRESSION AB Small cell neuroendocrine carcinoma of the prostate is a rare variant of prostatic cancer that shares morphologic similarity with prostatic adenocarcinoma of Gleason 5 pattern. It has also been considered morphologically and immunohistochemically indistinguishable from small cell neuroendocrine carcinomas of other origins. CD44 is a cell-surface molecule proposed to identify cancer stem/progenitor cells in prostate cancer. We performed immunohistochemical study for CD44 expression in I I cases of prostatic small cell neuroendocrine carcinoma and compared its patterns of expression with 73 cases of prostatic adenocarcinoma and 47 cases of small cell neuroendocrine carcinomas of other organs. Strong and diffuse membrane staining for CD44 was observed in 100% of the prostatic small cell neuroendocrine carcinomas. In conventional adenocarcinomas of the prostate, positive staining was only seen in rare, scattered tumor cells; and CD44 staining was negative in most of the small cell neuroendocrine carcinomas of nonprostate origin. The difference in CD44 expression between small cell neuroendocrine carcinomas of the prostate and those of other organs are statistically significant (P < .001). Our study demonstrates the utility of immunohistochemical staining for CD44 in distinguishing prostatic small cell neuroendocrine carcinoma from its mimickers including prostatic adenocarcinoma of Gleason 5 pattern and small cell neuroendocrine carcinomas of other organs. CD44 is the first marker that shows a high degree of tissue/organ specificity for small cell neuroendocrine carcinomas. Because CD44 is a putative marker of prostate cancer stein cells, the strong and diffuse expression of CD44 and the lack of expression of prostate luminal differentiation markers androgen receptor and prostatic specific antigen in prostatic small cell neuroendocrine carcinomas Suggest that the tumor Cells may retain cancer stem cell features. (C) 2009 Elsevier Inc. Ail rights reserved. C1 [Simon, Rochelle A.; di Sant'Agnese, P. Anthony; Xu, Haodong; Yao, Jorge L.; Yang, Qi; Huang, Jiaoti] Univ Rochester, Med Ctr, Dept Pathol, Rochester, NY 14642 USA. [Huang, Li-Shan] Univ Rochester, Med Ctr, Dept Biostat, Rochester, NY 14642 USA. [Liang, Sharon] SUNY Stony Brook, Dept Pathol, Stony Brook, NY 11794 USA. [Liu, Jinsong] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Yu, Rena] NYU, Med Ctr, Dept Pathol, New York, NY 10016 USA. [Cheng, Liang] Indiana Univ, Sch Med, Dept Pathol, Indianapolis, IN 46202 USA. [Oh, William K.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Palapattu, Ganesh S.; Huang, Jiaoti] Univ Rochester, Med Ctr, Dept Urol, Rochester, NY 14642 USA. [Wei, Jianjun] Northwestern Univ, Sch Med, Dept Pathol, Chicago, IL 60611 USA. RP Huang, JT (reprint author), Univ Rochester, Med Ctr, Dept Pathol, Box 626, Rochester, NY 14642 USA. EM jiaoti-huang@urmc.rochester.edu RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 FU Department of Defense Prostate Cancer Research Program [PC061456]; American Cancer Society [RSG-07-092-01-TBE] FX J. Huang is supported by the Department of Defense Prostate Cancer Research Program (PC061456) and American Cancer Society (RSG-07-092-01-TBE). NR 47 TC 36 Z9 41 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD FEB PY 2009 VL 40 IS 2 BP 252 EP 258 DI 10.1016/j.humpath.2008.07.014 PG 7 WC Pathology SC Pathology GA 400NT UT WOS:000262875800014 PM 18835619 ER PT J AU Rosendorff, C AF Rosendorff, Clive TI The Chicken and the Egg Sympathetic Nervous System Activity and Left Ventricular Diastolic Dysfunction SO HYPERTENSION LA English DT Editorial Material ID MYOCARDIAL-INFARCTION; RATS C1 [Rosendorff, Clive] James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA. [Rosendorff, Clive] Mt Sinai Sch Med, Dept Med, New York, NY USA. RP Rosendorff, C (reprint author), James J Peters Vet Affairs Med Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM clive.rosendorff@va.gov NR 8 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD FEB PY 2009 VL 53 IS 2 BP 108 EP 109 DI 10.1161/HYPERTENSIONAHA.108.126177 PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 396XM UT WOS:000262625400002 PM 19124677 ER PT J AU Du, YH Chen, AF AF Du, Yan-Hua Chen, Alex F. TI A New Role for Caveolin-1 Regulation of Guanosine Triphosphate Cyclohydrolase I and Tetrahydrobiopterin in Endothelial Cells SO HYPERTENSION LA English DT Editorial Material ID SIGNAL-TRANSDUCTION; VASCULAR-DISEASE; ACTIVATION C1 [Du, Yan-Hua; Chen, Alex F.] Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA 15240 USA. [Chen, Alex F.] Vet Affairs Pittsburgh Healthcare Syst, Vasc Surg Res, Pittsburgh, PA USA. RP Chen, AF (reprint author), Univ Pittsburgh, Sch Med, Dept Surg, 2W109 151L-U,VAPHS,Univ Dr, Pittsburgh, PA 15240 USA. EM chena5@upmc.edu FU NIGMS NIH HHS [R01 GM077352-02, R01 GM077352-03, R01 GM077352, R01 GM077352-01] NR 10 TC 3 Z9 4 U1 0 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 FEB PY 2009 VL 53 IS 2 BP 115 EP 117 DI 10.1161/HYPERTENSIONAHA.108.123356 PG 3 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 396XM UT WOS:000262625400005 PM 19104002 ER PT J AU Palmas, W Pickering, TG Teresi, J Schwartz, JE Moran, A Weinstock, RS Shea, S AF Palmas, Walter Pickering, Thomas G. Teresi, Jeanne Schwartz, Joseph E. Moran, Andrew Weinstock, Ruth S. Shea, Steven TI Ambulatory Blood Pressure Monitoring and All-Cause Mortality in Elderly People With Diabetes Mellitus SO HYPERTENSION LA English DT Article DE mortality; ambulatory blood pressure; diabetes mellitus; arterial stiffness ID ARTERIAL STIFFNESS INDEX; PULSE PRESSURE; HEART-RATE; PROGNOSTIC VALUE; CARDIOVASCULAR MORTALITY; GENERAL-POPULATION; SYSTOLIC HYPERTENSION; INDEPENDENT PREDICTOR; ALBUMIN EXCRETION; OLDER PATIENTS AB In a multiethnic cohort of older people with diabetes (n = 1178), we assessed whether ambulatory blood pressure (BP) monitoring improves prediction of all-cause mortality and cardiovascular mortality when added to baseline covariates, including office BP and heart rate (HR). Secondary analyses assessed whether albuminuria may mediate the association of pulse pressure with mortality. The ambulatory arterial stiffness index was calculated as "1-slope" from the within-person regression of diastolic-on-systolic ambulatory BP readings. Mean follow-up was 6.6 +/- 0.4 years. There were 287 deaths; death certificates were available for 215 deaths (75%), and 110 of them were deemed of cardiovascular cause. Cox models were built incrementally. First, models using clinical and laboratory variables selected albuminuria and office HRs as independent predictors of all-cause and cardiovascular mortality. When ambulatory monitoring data were added, sleep: wake HR ratio and ambulatory arterial stiffness index added significantly to the prediction of all-cause mortality, but only sleep: wake HR ratio added to the prediction of cardiovascular mortality. Office HR and albuminuria retained significance as predictors of both types of mortality. Secondary analyses without adjustment for albuminuria confirmed the predictive value of office HR and sleep/wake HR, whereas 24-hour pulse pressure and sleep systolic BP were also independently predictive of all-cause and cardiovascular mortality, respectively. In conclusion, office HR and albuminuria were strong predictors of mortality. Ambulatory monitoring improved the prediction of risk through its assessment of sleep HR dipping and of ambulatory arterial stiffness index, a measure of the dynamic relationship between systolic and diastolic BPs. Albuminuria may mediate the association between BP and mortality. (Hypertension. 2009; 53: 120-127.) C1 [Palmas, Walter] Columbia Univ, Dept Med, Div Gen Med, New York, NY 10032 USA. [Shea, Steven] Columbia Univ, Dept Biomed Informat, New York, NY 10032 USA. [Pickering, Thomas G.] Columbia Univ, Behav Cardiovasc Hlth & Hypertens Program, New York, NY 10032 USA. [Shea, Steven] Columbia Univ, Joseph Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA. [Teresi, Jeanne] Hebrew Home Aged, Div Res, Bronx, NY USA. [Teresi, Jeanne] Columbia Univ, Stroud Ctr, New York, NY 10032 USA. [Teresi, Jeanne] Fac Med, New York, NY USA. [Schwartz, Joseph E.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Schwartz, Joseph E.] SUNY Stony Brook, Dept Psychiat & Behav Sci, Stony Brook, NY 11794 USA. [Weinstock, Ruth S.] SUNY Upstate Med Univ, Joslin Diabet Ctr, Syracuse, NY USA. [Weinstock, Ruth S.] SUNY Upstate Med Univ, Div Endocrinol Diabet & Metab, Syracuse, NY USA. [Weinstock, Ruth S.] Vet Affairs Med Ctr, Dept Vet Affairs, Syracuse, NY USA. RP Palmas, W (reprint author), Columbia Univ, Dept Med, Div Gen Med, 622 W 168th ST,PH 9 E, New York, NY 10032 USA. EM wp56@columbia.edu FU Centers for Medicare and Medicaid Services [95-C-90998] FX This research was supported by Cooperative Agreement 95-C-90998 from the Centers for Medicare and Medicaid Services. NR 44 TC 45 Z9 48 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD FEB PY 2009 VL 53 IS 2 BP 120 EP U46 DI 10.1161/HYPERTENSIONAHA.108.118398 PG 15 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 396XM UT WOS:000262625400007 PM 19124681 ER PT J AU Phipps, JA Clermont, AC Sinha, S Chilcote, TJ Bursell, SE Feener, EP AF Phipps, Joanna A. Clermont, Allen C. Sinha, Sukanto Chilcote, Tamie J. Bursell, Sven-Erik Feener, Edward P. TI Plasma Kallikrein Mediates Angiotensin II Type 1 Receptor-Stimulated Retinal Vascular Permeability SO HYPERTENSION LA English DT Article DE kallikrein; retina; angiotensin II; diabetes; AT(1) receptor; hypertension ID BLOOD-PRESSURE CONTROL; ROSTRAL VENTROLATERAL MEDULLA; CONVERTING ENZYME-INHIBITION; ENDOTHELIAL GROWTH-FACTOR; DIABETIC MACULAR EDEMA; HEREDITARY ANGIOEDEMA; B-2 RECEPTORS; KININ SYSTEM; NITRIC-OXIDE; RISK-FACTORS AB Hypertension is a leading risk factor for the development and progression of diabetic retinopathy and contributes to a variety of other retinal diseases in the absence of diabetes mellitus. Inhibition of the renin-angiotensin system has been shown to provide beneficial effects against diabetic retinopathy, both in the absence and presence of hypertension, suggesting that angiotensin II (Ang II) and the Ang II type 1 receptor may contribute to retinal vascular dysfunction. We investigated the effects of the Ang II type 1 receptor antagonist candesartan on retinal vascular permeability (RVP) in normotensive rats with streptozotocin-induced diabetes mellitus and in rats with Ang II-induced hypertension. We showed that candesartan treatment decreased diabetes mellitus- and Ang II-stimulated RVP by 58% (P < 0.05) and 79% (P < 0.05), respectively, compared with untreated controls, suggesting that activation of the Ang II type 1 receptor contributes to blood-retinal barrier dysfunction. We found that plasma kallikrein levels are increased in the retina of rats with Ang II-stimulated hypertension and that intravitreal injection of either plasma kallikrein or bradykinin is sufficient to increase RVP. We showed that a novel small molecule inhibitor of plasma kallikrein, 1-benzyl-1H-pyrazole-4-carboxylic acid 4-carbamimidoyl-benzylamide, delivered systemically via a subcutaneous pump, decreased Ang II-stimulated RVP by 70% (P < 0.05) and ameliorates Ang II-induced hypertension, measured from the carotid artery by telemetry, but did not reduce Ang II-induced retinal leukostasis. These findings demonstrate that activation of the Ang II type 1 receptor increases RVP and suggest that systemic plasma kallikrein inhibition may provide a new therapeutic approach for ameliorating blood-retinal barrier dysfunction induced by hypertension. (Hypertension. 2009; 53: 175-181.) C1 [Phipps, Joanna A.; Clermont, Allen C.; Feener, Edward P.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Med,Res Div, Boston, MA 02215 USA. [Sinha, Sukanto; Chilcote, Tamie J.] ActiveSite Pharmaceut Inc, San Francisco, CA USA. [Bursell, Sven-Erik] Univ Hawaii, Telehealth Res Inst, Honolulu, HI 96822 USA. RP Feener, EP (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Med,Res Div, 1 Joslin Pl, Boston, MA 02215 USA. EM Edward.Feener@joslin.harvard.edu FU National Health and Medical Research Council Australia; National Institutes of Health [DK 60165, EY019029]; Juvenile Diabetes Research Foundation [DK 36836, R43HL090132]; Massachusetts Lions Eye Research Fund FX This work was supported in part by the National Health and Medical Research Council Australia C.J. Martin Research Fellowship ( to J.A.P.); the National Institutes of Health grants DK 60165 and EY019029 and Juvenile Diabetes Research Foundation ( to E. P. F.), grant DK 36836 ( to Joslin's Diabetes and Endocrinology Research Center), grant R43HL090132 ( to T.J.C.), and the Massachusetts Lions Eye Research Fund ( to S.-E.B.). NR 42 TC 36 Z9 38 U1 0 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 FEB PY 2009 VL 53 IS 2 BP 175 EP U127 DI 10.1161/HYPERTENSIONAHA.108.117663 PG 12 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 396XM UT WOS:000262625400014 PM 19124682 ER PT J AU Armoundas, AA AF Armoundas, Antonis A. TI Mechanism of Abnormal Sarcoplasmic Reticulum Calcium Release in Canine Left-Ventricular Myocytes Results in Cellular Alternans SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE Cellular alternans; model; myocyte; ryanodine receptor (RyR); sarcoplasmic reticulum (SR) ID T-WAVE ALTERNANS; RYANODINE RECEPTOR ADAPTATION; CA2+-INDUCED CA2+ RELEASE; INTRACELLULAR CALCIUM; ELECTRICAL ALTERNANS; CARDIAC ALTERNANS; FAILING HEARTS; DYNAMICS; TACHYCARDIA; MUSCLE AB Electrocardiographic alternans are known to predispose to increased susceptibility to life threatening arrhythmias and sudden cardiac death. While deficiencies in Ca(2+) transport processes have been implicated in the genesis of cellular alternans, the underlying mechanisms have been elusive, and are the goal of this study. A novel reverse engineering approach that applies a simultaneous action potential (AP) and [Ca(2+)](i) clamp of experimentally obtained data, to a previously described left-ventricular canine myocyte model, is employed to isolate the molecular and cellular mechanisms underlying cardiac alternans. The model-derived sarcoplasmic reticulum (SR) Ca(2+) in control beats (102.1 +/- 12.9 nM, n = 639), although larger, is not statistically significantly different as compared to beats corresponding to small [Ca(2+)](i), (99.3 +/- 35.4 nM, n = 310, p = NS), but is significantly smaller as compared to beats corresponding to large [Ca(2+)](i) (122.6 +/- 31.0 nM, n = 311, p < 0.000001) during alternans. The model indicates that the increased SR Ca(2+) in these beats triggers multiple ryanodine receptor (RyR) channel openings and delayed Ca(2+) release that subsequently triggers an inward depolarizing current, a subthreshold early after depolarization, and AP prolongation. In conclusion, the results presented in this study support the idea that aberrant RyR openings on alternate beats are responsible for the [Ca(2+)](i) alternans-type oscillations, which, in turn, give rise to AP alternans. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Armoundas, AA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. EM aarmoundas@partners.org FU Scientist Development [0365304U]; American Heart Association Awards [0635127 N] FX The work was supported in part by the Beginning Grant-in-Aid (#0365304U) and in part by the Scientist Development Grant (#0635127 N) American Heart Association Awards. NR 44 TC 6 Z9 6 U1 1 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD FEB PY 2009 VL 56 IS 2 BP 220 EP 228 DI 10.1109/TBME.2008.2003283 PG 9 WC Engineering, Biomedical SC Engineering GA 435VZ UT WOS:000265372700004 PM 19272939 ER PT J AU Malik, WQ AF Malik, Wasim Q. TI MIMO Capacity Convergence in Frequency-Selective Channels SO IEEE TRANSACTIONS ON COMMUNICATIONS LA English DT Article DE Capacity; fading; multiple-input multiple-ouput (MIMO); ultrawideband (UWB) AB The dependence of multi-antenna capacity on hand-width is characterized empirically for narrowband, wideband and ultrawideband indoor channels using spatial and polar arrays. It is shown that both the mean and the outage MIMO capacity increase with bandwidth, whilst the capacity coefficient of variation asymptotically vanishes. C1 [Malik, Wasim Q.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Malik, Wasim Q.] Harvard Univ, Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA 02115 USA. RP Malik, WQ (reprint author), MIT, Dept Brain & Cognit Sci, E25-618, Cambridge, MA 02139 USA. EM wqm@mit.edu RI Malik, Wasim/C-9982-2011 NR 15 TC 5 Z9 6 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0090-6778 J9 IEEE T COMMUN JI IEEE Trans. Commun. PD FEB PY 2009 VL 57 IS 2 BP 353 EP 356 DI 10.1109/TCOMM.2009.02.070105 PG 4 WC Engineering, Electrical & Electronic; Telecommunications SC Engineering; Telecommunications GA 406LY UT WOS:000263298200012 ER PT J AU He, LL Greenshields, IR AF He, Lili Greenshields, Ian R. TI A Nonlocal Maximum Likelihood Estimation Method for Rician Noise Reduction in MR Images SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE Denoising; magnetic resonance (MR) images; nonlocal maximum likelihood estimation (NLML); nonlocal (NL) means; Rician distribution ID ALGORITHM; DIFFUSION; RATIO AB Postacquisition denoising of magnetic resonance (MR) images is of importance for clinical diagnosis and computerized analysis, such as tissue classification and segmentation. It has been shown that the noise in MR magnitude images follows a Rician distribution, which is signal-dependent when signal-to-noise ratio (SNR) is low. It is particularly difficult to remove the random fluctuations and bias introduced by Rician noise. The objective of this paper is to estimate the noise free signal from MR magnitude images. We model images as random fields and assume that pixels which have similar neighborhoods come from the same distribution. We propose a nonlocal maximum likelihood (NLML) estimation method for Rician noise reduction. Our method yields an optimal estimation result that is more accurate in recovering the true signal from Rician noise than NL means algorithm in the sense of SNR, contrast, and method error. We demonstrate that NLML performs better than the conventional local maximum likelihood (LML) estimation method in preserving and defining sharp tissue boundaries in terms of a well-defined sharpness metric while also having superior performance in method error. C1 [He, Lili] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [He, Lili] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Greenshields, Ian R.] Univ Connecticut, Dept Comp Sci & Engn, Storrs, CT 06269 USA. RP He, LL (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. EM lhe2@partners.org; ian@engr.uconn.edu NR 35 TC 60 Z9 63 U1 1 U2 7 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD FEB PY 2009 VL 28 IS 2 BP 165 EP 172 DI 10.1109/TMI.2008.927338 PG 8 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 405LG UT WOS:000263225700001 PM 19188105 ER PT J AU Hernandez, MD Mansouri, MD Aslam, S Zeluff, B Darouiche, RO AF Hernandez, Maria D. Mansouri, Mohammad D. Aslam, Saima Zeluff, Barry Darouiche, Rabih O. TI Efficacy of Combination of N-acetylcysteine, Gentamicin, and Amphotericin B for Prevention of Microbial Colonization of Ventricular Assist Devices SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID STAPHYLOCOCCUS-AUREUS INFECTION; CENTRAL VENOUS CATHETERS; BACTERIA; BIOFILM AB We assessed the in vitro antimicrobial activity and the in vivo efficacy of dipping ventricular assist devices in a combination of N-acetylcysteine, gentamicin, and amphotericin B (NAC/G/A). Ventricular assist devices dipped in NAC/G/A exhibited broad-spectrum antimicrobial activity in vitro and were less likely than undipped devices to become colonized with Staphylococcus aureus in a rabbit model. C1 [Mansouri, Mohammad D.; Darouiche, Rabih O.] Baylor Coll Med, Ctr Prostheses Infect, Houston, TX 77030 USA. [Mansouri, Mohammad D.; Aslam, Saima; Darouiche, Rabih O.] Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. [Aslam, Saima; Zeluff, Barry] St Lukes Episcopal Hosp, Houston, TX 77030 USA. [Hernandez, Maria D.; Aslam, Saima; Darouiche, Rabih O.] Baylor Coll Med, Infect Dis Sect, Houston, TX 77030 USA. RP Darouiche, RO (reprint author), Baylor Coll Med, Ctr Prostheses Infect, 1333 Moursund Ave,Suite A221, Houston, TX 77030 USA. EM rdarouiche@aol.com NR 10 TC 13 Z9 13 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD FEB PY 2009 VL 30 IS 2 BP 190 EP 192 DI 10.1086/593205 PG 3 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 394YV UT WOS:000262490000013 PM 19090771 ER PT J AU Sonnenberg, A AF Sonnenberg, Amnon TI Date of Birth in the Occurrence of Inflammatory Bowel Disease SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE birth date; cyclic pattern; environmental risk factors; epidemiology of inflammatory bowel disease; hospital statistics; seasonality of births; time trends ID CROHNS-DISEASE; ULCERATIVE-COLITIS; RECORD LINKAGE; TIME TRENDS; CHILDHOOD; MORTALITY; RISK AB Background: It has been Speculated that prenatal or perinatal exposure to infections affects the risk for developing inflammatory bowel disease (11313). The aims of the study were to investigate the seasonal and monthly variations of birth dates among patients with Crohn's disease (CD) and ulcerative colitis (UC). Methods: The Hospital Episode Statistics (HES) comprises data of all patients admitted to hospitals in England. The data between April 1997 and March 2006 served to analyze birth dates of subjects with CD and UD, using the entirety of patients in the HES as controls. Results: Monthly birth dates were aggregated for the same months across Consecutive birth years from January 1920 to December 1989 to determine whether a seasonal birth pattern existed among patients with CD and UC, No different seasonal birth patterns were observed between IBD patients and controls. A second analysis of individual months of birth, year after year, found that rates of births among 11313 patients fluctuated from month to month. These fluctuations were different for CD and UC, with an overall weak correlation of r = 0.078, P = 0.018. There was a slight trend for stronger correlations to occur during more recent decades of birth, with r = 0.237 (P = 0.009) and r = 0.168 (P = 0.067) for the last 2 decades 1970-1979 and 1980-1989, respectively. Conclusions: The patterns of birth dates among IBD patients do not support the contention that seasonally or monthly varying environmental factors during early childhood shape the Subsequent risk of developing IBD. C1 [Sonnenberg, Amnon] Portland VA Med Ctr, Portland, OR 97239 USA. [Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Portland, OR 97201 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 NR 20 TC 10 Z9 12 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD FEB PY 2009 VL 15 IS 2 BP 206 EP 211 DI 10.1002/ibd.20730 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 402TU UT WOS:000263036800008 PM 18831526 ER PT J AU Guillemette, MD Cui, B Roy, E Gauvin, R Giasson, CJ Esch, MB Carrier, P Deschambeault, A Dumoulin, M Toner, M Germain, L Veres, T Auger, FA AF Guillemette, Maxime D. Cui, Bo Roy, Emmanuel Gauvin, Robert Giasson, Claude J. Esch, Mandy B. Carrier, Patrick Deschambeault, Alexandre Dumoulin, Michel Toner, Mehmet Germain, Lucie Veres, Teodor Auger, Francois A. TI Surface topography induces 3D self-orientation of cells and extracellular matrix resulting in improved tissue function SO INTEGRATIVE BIOLOGY LA English DT Article ID SMOOTH-MUSCLE-CELLS; CONTACT GUIDANCE; WOUND REEPITHELIALIZATION; HUMAN CORNEA; IN-VITRO; FIBROBLASTS; ALIGNMENT; SKIN; TRANSPARENCY; ORGANIZATION AB The organization of cells and extracellular matrix (ECM) in native tissues plays a crucial role in their functionality. However, in tissue engineering, cells and ECM are randomly distributed within a scaffold. Thus, the production of engineered-tissue with complex 3D organization remains a challenge. In the present study, we used contact guidance to control the interactions between the material topography, the cells and the ECM for three different tissues, namely vascular media, corneal stroma and dermal tissue. Using a specific surface topography on an elastomeric material, we observed the orientation of a first cell layer along the patterns in the material. Orientation of the first cell layer translates into a physical cue that induces the second cell layer to follow a physiologically consistent orientation mimicking the structure of the native tissue. Furthermore, secreted ECM followed cell orientation in every layer, resulting in an oriented self-assembled tissue sheet. These self-assembled tissue sheets were then used to create 3 different structured engineered-tissue: cornea, vascular media and dermis. We showed that functionality of such structured engineered-tissue was increased when compared to the same qnon-structured tissue. Dermal tissues were used as a negative control in response to surface topography since native dermal fibroblasts are not preferentially oriented in vivo. Non-structured surfaces were also used to produce randomly oriented tissue sheets to evaluate the impact of tissue orientation on functional output. This novel approach for the production of more complex 3D tissues would be useful for clinical purposes and for in vitro physiological tissue model to better understand long standing questions in biology. C1 [Guillemette, Maxime D.; Gauvin, Robert; Carrier, Patrick; Deschambeault, Alexandre; Germain, Lucie; Auger, Francois A.] CHA Quebec, LOEX, Ctr Rech FRSQ, Quebec City, PQ, Canada. [Guillemette, Maxime D.; Gauvin, Robert; Germain, Lucie; Veres, Teodor; Auger, Francois A.] Univ Laval, Fac Med, Dept Surg, Quebec City, PQ G1K 7P4, Canada. [Guillemette, Maxime D.; Cui, Bo; Roy, Emmanuel; Dumoulin, Michel; Veres, Teodor] Natl Res Council Canada, Inst Ind Mat, Boucherville, PQ, Canada. [Giasson, Claude J.] Univ Montreal, Sch Optometry, Res Unit Ophthalmol, Montreal, PQ, Canada. [Esch, Mandy B.] Cornell Univ, Dept Biomed Engn, Ithaca, NY USA. [Toner, Mehmet] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med & Surg Serv, Boston, MA USA. [Toner, Mehmet] Shriners Hosp Children, Boston, MA USA. RP Guillemette, MD (reprint author), CHA Quebec, LOEX, Ctr Rech FRSQ, Quebec City, PQ, Canada. EM francois.auger@chg.ulaval.ca FU National Research Council of Canada [NRC-66473]; Canadian Institutes of Health Research [MOP-53170] FX The authors would like to thank D. Larouche for help in figure preparation and C. Roberge for useful comments during the preparation of the manuscript. The authors would also like to thank Richard Janvier for the preparation of specimen for electron microscopy. We also thank the Reseau de Recherche en Sante de la Vision from the FRSQ. This work was supported by a joint collaborative program between The National Research Council of Canada grant no NRC-66473 and the Canadian Institutes of Health Research grant no MOP-53170. NR 34 TC 44 Z9 44 U1 0 U2 12 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1757-9694 J9 INTEGR BIOL JI Integr. Biol. PD FEB PY 2009 VL 1 IS 2 BP 196 EP 204 DI 10.1039/b820208g PG 9 WC Cell Biology SC Cell Biology GA 459OU UT WOS:000267113600006 PM 20023803 ER PT J AU Calfee, C Eisner, M Parsons, P Thompson, B Conner, E Matthay, M Ware, L AF Calfee, Carolyn S. Eisner, Mark D. Parsons, Polly E. Thompson, B. Taylor Conner, Edward R., Jr. Matthay, Michael A. Ware, Lorraine B. CA NHLBI Acute Resp Distress Syndrome TI Soluble intercellular adhesion molecule-1 and clinical outcomes in patients with acute lung injury SO INTENSIVE CARE MEDICINE LA English DT Article DE Acute respiratory distress syndrome; Acute lung injury; Intracellular adhesion molecule-1; Pulmonary edema ID RESPIRATORY-DISTRESS-SYNDROME; VON-WILLEBRAND-FACTOR; ALVEOLAR EPITHELIAL-CELLS; TIDAL VOLUME VENTILATION; ICAM-1 EXPRESSION; PULMONARY-EDEMA; ENDOTHELIAL-CELLS; CONTROLLED-TRIAL; FACTOR ANTIGEN; SICAM-1 LEVELS AB To determine if levels of soluble intercellular adhesion molecule-1 (sICAM-1), a marker of alveolar epithelial and endothelial injury, differ in patients with hydrostatic pulmonary edema and acute lung injury (ALI) and are associated with clinical outcomes in patients with ALI. Measurement of sICAM-1 levels in (1) plasma and edema fluid from 67 patients with either hydrostatic pulmonary edema or ALI enrolled in an observational, prospective single center study, and (2) in plasma from 778 patients with ALI enrolled in a large multi-center randomized controlled trial of ventilator strategy. In the single-center study, levels of sICAM-1 were significantly higher in both edema fluid and plasma (median 938 and 545 ng/ml, respectively) from ALI patients compared to hydrostatic edema patients (median 384 and 177 ng/ml, P < 0.03 for both comparisons). In the multi-center study, higher plasma sICAM-1 levels were associated with poor clinical outcomes in both unadjusted and multivariable models. Subjects with ALI whose plasma sICAM-1 levels increased over the first 3 days of the study had a higher risk of death, after adjusting for other important predictors of outcome (odds ratio 1.48; 95% CI 1.03-2.12, P = 0.03). Both plasma and edema fluid levels of sICAM-1 are higher in patients with ALI than in patients with hydrostatic pulmonary edema. Higher plasma sICAM-1 levels and increasing sICAM-1 levels over time are associated with poor clinical outcomes in ALI. Measurement of sICAM-1 levels may be useful for identifying patients at highest risk of poor outcomes from ALI. C1 [Calfee, Carolyn S.; Eisner, Mark D.; Conner, Edward R., Jr.] Univ Calif San Francisco, Dept Med, Div Pulm & Crit Care Med, San Francisco, CA 94143 USA. [Eisner, Mark D.] Univ Calif San Francisco, Dept Med, Div Occupat Environm Med, San Francisco, CA 94143 USA. [Parsons, Polly E.] Univ Vermont, Dept Med, Div Pulm & Crit Care Med, Burlington, VT USA. [Thompson, B. Taylor] Massachusetts Gen Hosp, Dept Med, Pulm Crit Care Unit, Boston, MA 02114 USA. RP Calfee, C (reprint author), Univ Calif San Francisco, Dept Med, Div Pulm & Crit Care Med, 505 Parnassus Ave, San Francisco, CA 94143 USA. EM carolyn.calfee@ucsf.edu FU NCRR NIH HHS [KL2 RR024130, KL2RR024130]; NHLBI NIH HHS [N0-1 HR 46057, HL 04201, HL 081332, HL 51856, K23 HL004201, N0-1 HR 46054, N0-1 HR 46055, N0-1 HR 46056, N0-1 HR 46058, N0-1 HR 46060, N0-1 HR 46061, N0-1 HR 46062, N0-1 HR 46063, N0-1 HR 46064, N01HR46054, P50 HL074005, P50 HL74005, R01 HL051856, R37 HL051856, R37 HL051856-14, U01 HL081332] NR 46 TC 53 Z9 56 U1 0 U2 2 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 FEB PY 2009 VL 35 IS 2 BP 248 EP 257 DI 10.1007/s00134-008-1235-0 PG 10 WC Critical Care Medicine SC General & Internal Medicine GA 404NT UT WOS:000263160600009 PM 18670758 ER PT J AU Chiu, YH Hart, JE Smith, TJ Hammond, SK Garshick, E Laden, F AF Chiu, Yueh-Hsiu Hart, Jaime E. Smith, Thomas J. Hammond, S. Katharine Garshick, Eric Laden, Francine TI Nicotine Contamination in Particulate Matter Sampling SO INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH LA English DT Article DE Nicotine; particulate matter; sampling filter; contamination; secondhand smoke exposure; cigarette smoke ID ENVIRONMENTAL TOBACCO-SMOKE; SUSPENDED PARTICLE EXPOSURES; DIESEL EXHAUST; TRUCKING INDUSTRY; WORKERS; NONSMOKERS; CARBON; PM2.5 AB We have addressed potential contamination of PM(2.5) filter samples by nicotine from cigarette smoke. We collected two nicotine samples - one nicotine sampling filter was placed in-line after the collection of PM(2.5) and the other stood alone. The overall correlation between the two nicotine filter levels was 0.99. The nicotine collected on the "stand-alone" filter was slightly greater than that on the "in-line" filter (mean difference = 1.10 mu g/m(3)), but the difference was statistically significant only when PM(2.5) was low (<= 50 mu g/m(3)). It is therefore important to account for personal and secondhand smoke exposure while assessing occupational and environmental PM. C1 [Chiu, Yueh-Hsiu; Hart, Jaime E.; Smith, Thomas J.; Laden, Francine] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Exposure Epidemiol & Risk Program, Boston, MA 02215 USA. [Hart, Jaime E.; Garshick, Eric; Laden, Francine] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Hart, Jaime E.; Garshick, Eric; Laden, Francine] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Hammond, S. Katharine] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. [Garshick, Eric] VA Boston Healthcare Syst, Pulm & Crit Care Med Sect, Boston, MA 02130 USA. [Hart, Jaime E.; Laden, Francine] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Chiu, YH (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Exposure Epidemiol & Risk Program, Boston, MA 02215 USA. EM yhchiu@hsph.harvard.edu; jaime.hart@channing.harvard.edu; tsmith@hohp.harvard.edu; hammondk@berkeley.edu; Eric.Garshick@va.gov; francine.laden@channing.harvard.edu RI Smith, Thomas/A-9640-2010 FU NCI NIH HHS [R01 CA090792, R01 CA90792] NR 13 TC 2 Z9 2 U1 0 U2 3 PU MOLECULAR DIVERSITY PRESERVATION INTERNATIONAL-MDPI PI BASEL PA KANDERERSTRASSE 25, CH-4057 BASEL, SWITZERLAND SN 1660-4601 J9 INT J ENV RES PUB HE JI Int. J. Environ. Res. Public Health PD FEB PY 2009 VL 6 IS 2 BP 601 EP 607 DI 10.3390/ijerph6020601 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 451BI UT WOS:000266445300013 PM 19440403 ER PT J AU Scranton, RE Farwell, WR Gaziano, JM AF Scranton, Richard E. Farwell, Wildon R. Gaziano, John M. TI Lack of Cholesterol Awareness among Physicians Who Smoke SO INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH LA English DT Article DE Disease prevention; cholesterol; lifestyle behavior; tobacco smoking ID CIGARETTE-SMOKING; RANDOMIZED-TRIAL; NUTRIENT INTAKE; RISK-FACTORS; PREVENTION; CAROTENE; DIETARY; DISEASE; DESIGN; MEN AB Cigarette use is a known risk factor for the development of coronary artery disease (CAD) as it adversely affects HDL cholesterol levels and promotes thrombogenesis. Smoking may also be associated with behavioral characteristics that potentiate the risk of CAD. A lack of cholesterol knowledge would indicate an aversion to a prevention-oriented lifestyle. Thus, our goal was to determine the association between tobacco use and knowledge of self-reported cholesterol among male physicians. Using the 1982 and follow-up questionnaires from the physician health study, we report the changes in the frequencies of awareness of self-reported total cholesterol and cardiovascular risk factors among the 22,067 participants. We classified physicians as being aware of their cholesterol if they reported a cholesterol level and unaware if the question was left unanswered. In 1997, 207 physicians were excluded, as the recorded cholesterol was not interpretable, leaving 21,860 for our follow up analyses. Using unadjusted logistic models, we determined the odds ratios (OR) and 95% confidence intervals (CI) of not reporting a cholesterol level in either 1982 or 1997 for each specified risk factor. We then evaluated whether the lack of cholesterol awareness at both time points was associated with the use of tobacco throughout the study. After 14-years of follow up, cholesterol awareness increased from 35.9 to 58.6 percent. During this period, the frequency of hypertension and hyperlipidemia treatment increased (13.5 to 40.5% and 0.57% to 19.6% respectively), as did the diagnosis of diabetes (2.40 to 7.79%). Behavioral characteristics such as a sedentary lifestyle and obesity also increased (27.8 to 42% and 43.5 to 53.5%, respectively), however the proportion of current smokers deceased from 11.1 to 4.05%. The percentages of individuals being unaware of their cholesterol decreased in all risk factor groups. However, individuals were likely to be unaware of their cholesterol at both time points if they were current smokers (1982 OR 1.44, CI 1.4-1.7; 1997 OR 1.71, CI 1.48-1.97), past smokers (1982 OR 1.12, CI 1.05-1.18; 1997 OR 1.13, CI 1.06-1.20), overweight (BMI 25 kg/m(2)) or sedentary. In addition, physicians who never quit smoking were likely to be unaware of their cholesterol throughout the study (OR 1.42, CI 1.21-1.67). Cholesterol awareness in general and among those with CAD risk factors improved after 14-years of follow-up. However, the likelihood of being unaware was greater among smokers at both time points. Therefore, smokers do not appear to take advantage of other preventive strategies that would minimize their risk of developing CAD. C1 [Scranton, Richard E.; Farwell, Wildon R.; Gaziano, John M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Aging, Tiverton, RI 02878 USA. [Scranton, Richard E.; Farwell, Wildon R.; Gaziano, John M.] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. [Gaziano, John M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Prevent Med, Boston, MA USA. RP Scranton, RE (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Aging, 1334 Main Rd, Tiverton, RI 02878 USA. EM richardscrantonmd@rcn.com; wildon.farwell@va.gov; jmgaziano@partners.org FU National Institutes of Health [CA 97193, CA 34944, CA 40360, HL 26490, HL 34595] FX We are indebted to the participants of the Physicians' Health Study for their outstanding commitment and cooperation, and to the entire Physicians' Health Study staff for their expert and unfailing assistance. The study was supported by grants CA 97193, CA 34944, CA 40360, HL 26490, and HL 34595 from the National Institutes of Health. This material is also the result of work supported with resources and the use of facilities at the VA Boston Healthcare System, Boston, MA, USA. NR 14 TC 1 Z9 1 U1 1 U2 2 PU MOLECULAR DIVERSITY PRESERVATION INTERNATIONAL-MDPI PI BASEL PA KANDERERSTRASSE 25, CH-4057 BASEL, SWITZERLAND SN 1660-4601 J9 INT J ENV RES PUB HE JI Int. J. Environ. Res. Public Health PD FEB PY 2009 VL 6 IS 2 BP 635 EP 642 DI 10.3390/ijerph6020635 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 451BI UT WOS:000266445300016 PM 19440406 ER PT J AU Orezzoli, JP Wain, JC Fuller, AF AF Orezzoli, Jorge P. Wain, John C. Fuller, Arlan F., Jr. TI Surgical Management of the Subdiaphragmatic Mass A Sequential Combined Approach With Laparoscopy Followed by Posterior Thoracotomy SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Article DE Ovarian carcinoma; Thoracotomy; Diaphragm resection; Liver metastasis ID THICKNESS DIAPHRAGMATIC RESECTION; RECURRENT OVARIAN-CANCER; EPITHELIAL OVARIAN; CYTOREDUCTIVE SURGERY; FALLOPIAN-TUBE; CARCINOMA; SURVIVAL; DISEASE AB Recurrent ovarian cancer in the upper abdomen involving the liver parenchyma and diaphragmatic muscle traditionally requires a major abdominal surgical procedure; this involves pubis to xyphoid incision and complete mobilization of the liver. We present a strategy for evaluating 4 cases with apparently isolated recurrence to the diaphragm and liver approached by a sequential 2-phase procedure, involving diagnostic laparoscopy and Subsequent posterior lateral thoracotomy. Preliminary diagnostic laparoscopy was performed to distinguish candidates for either definitive laparoscopic treatment or posterior thoracotomy. Two patients with disease confined to the diaphragm were successfully treated by laparoscopy alone, whereas full-thickness diaphragmatic resection and liver metastasis excision with cavitational ultrasonic surgical aspirator was performed in the other 2 patients. Argon beam coagulation was used to control local hemostasis and to fulgurate any possible residual turner at the margin of resection. This is a multidisciplinary approach that is technically feasible and safe, requiring a short hospital stay. C1 [Orezzoli, Jorge P.] Massachusetts Gen Hosp, Div Gynecol Oncol, Vincent Mem Dept Obstet & Gynecol, Boston, MA 02114 USA. [Orezzoli, Jorge P.] Harvard Univ, Sch Med, Boston, MA USA. [Wain, John C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Thorac Surg,Canc Ctr, Boston, MA USA. [Fuller, Arlan F., Jr.] Winchester Hosp, Canc Care Ctr, Winchester, MA USA. RP Fuller, AF (reprint author), Winchester Hosp, Canc Care Ctr, 88 Montvale Ave,1, Stoneham, MA 02180 USA. EM afuller@winhosp.org NR 18 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1048-891X J9 INT J GYNECOL CANCER JI Int. J. Gynecol. Cancer PD FEB PY 2009 VL 19 IS 2 BP 294 EP 299 DI 10.1111/IGC.0b013e31819c13f5 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 457ZD UT WOS:000266976400023 PM 19396012 ER PT J AU Schlett, CL Massaro, JM Lehman, SJ Bamberg, F O'Donnell, CJ Fox, CS Hoffmann, U AF Schlett, C. L. Massaro, J. M. Lehman, S. J. Bamberg, F. O'Donnell, C. J. Fox, C. S. Hoffmann, U. TI Novel measurements of periaortic adipose tissue in comparison to anthropometric measures of obesity, and abdominal adipose tissue SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE adipose tissue; intra-abdominal fat; tomography; spiral computed; Framingham Heart Study; metabolic risk factors ID CORONARY-ARTERY-DISEASE; COMPUTED-TOMOGRAPHY; RISK-FACTORS; CARDIOVASCULAR-DISEASE; PERIADVENTITIAL FAT; PERICARDIAL FAT; EPICARDIAL FAT; HEART-FAILURE; MEN; ATHEROSCLEROSIS AB Background: Perivascular adipose tissue may be associated with the amount of local atherosclerosis. We developed a novel and reproducible method to standardize volumetric quantification of periaortic adipose tissue by computed tomography (CT) and determined the association with anthropometric measures of obesity, and abdominal adipose tissue. Methods: Measurements of adipose tissue were performed in a random subset of participants from the Framingham Heart Study (n = 100) who underwent multidetector CT of the thorax (ECG triggering, 2.5mm slice thickness) and the abdomen (helical CT acquisition, 2.5mm slice thickness). Abdominal periaortic adipose tissue (AAT) was defined by a 5mm cylindrical region of interest around the aortic wall; thoracic periaortic adipose tissue (TAT) was defined by anatomic landmarks. TAT and AAT were defined as any voxel between -195 and -45 HU and volumes were measured using dedicated semiautomatic software. Measurement reproducibility and association with anthropometric measures of obesity, and abdominal adipose tissue were determined. Results: The intra-and inter-observer reproducibility for both AAT and TAT was excellent (ICC: 0.97 and 0.97; 0.99 and 0.98, respectively). Similarly, the relative intra-and inter-observer difference was small for both AAT (-1.85 +/- 1.28% and 7.85 +/- 6.08%; respectively) and TAT (3.56 +/- 0.83% and -4.56 +/- 0.85%, respectively). Both AAT and TAT were highly correlated with visceral abdominal fat (r = 0.65 and 0.77, P<0.0001 for both) and moderately correlated with subcutaneous abdominal fat (r = 0.39 and 0.42, P<0.0001 and P = 0.009), waist circumference (r = 0.49 and 0.57, P<0.0001 for both) and body mass index (r = 0.47 and 0.58, P<0.0001 for both). Conclusion: Standardized semiautomatic CT-based volumetric quantification of periaortic adipose tissue is feasible and highly reproducible. Further investigation is warranted regarding associations of periaortic adipose tissue with other body fat deposits, cardiovascular risk factors and clinical outcomes. C1 [Schlett, C. L.; Lehman, S. J.; Bamberg, F.; Hoffmann, U.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Massaro, J. M.] Boston Univ, Dept Math, Boston, MA 02215 USA. [O'Donnell, C. J.; Fox, C. S.] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA. [O'Donnell, C. J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Cardiol Div, Boston, MA 02114 USA. [Fox, C. S.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Endocrinol Diabet & Metab,Dept Med, Boston, MA 02114 USA. RP Hoffmann, U (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM uhoffmann@partners.org OI Massaro, Joseph/0000-0002-2682-4812 FU National Heart, Lung and Blood Institute [N01-HC-25195]; German Federal Ministry of Education and Research; Foundation of German Business, Berlin FX The Framingham Heart Study is supported by the National Heart, Lung and Blood Institute (N01-HC-25195). CL Schlett is supported in part by grants from the German Federal Ministry of Education and Research and the Foundation of German Business, Berlin. NR 31 TC 44 Z9 46 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD FEB PY 2009 VL 33 IS 2 BP 226 EP 232 DI 10.1038/ijo.2008.267 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 407JU UT WOS:000263360200006 PM 19139753 ER PT J AU Weamer, EA Emanuel, JE Varon, D Miyahara, S Wilkosz, PA Lopez, OL DeKosky, ST Sweet, RA AF Weamer, Elise A. Emanuel, James E. Varon, Daniel Miyahara, Sachiko Wilkosz, Patricia A. Lopez, Oscar L. DeKosky, Steven T. Sweet, Robert A. TI The relationship of excess cognitive impairment in MCI and early Alzheimer's disease to the subsequent emergence of psychosis SO INTERNATIONAL PSYCHOGERIATRICS LA English DT Article DE Alzheimer's disease; MCI (mild cognitive impairment); psychosis; cognitive neuropsychology in dementia; assessment of cognitive disorders/dementia ID INCREASED FAMILIAL RISK; LAST 2 DECADES; RATING-SCALE; MOUSE MODELS; SYMPTOMS; DELUSIONS; DIAGNOSIS; DEMENTIA; SCHIZOPHRENIA; HALLUCINATIONS AB Background: Psychotic symptoms in Alzheimer disease (AD + P) identify a heritable phenotype associated with greater cognitive impairment. Knowing when the cognitive course of AD + P subjects diverges from that of subjects without psychosis would enhance understanding of how genetic variation results in AD + P and its associated cognitive burden. This study seeks to determine whether the degree of cognitive impairment and cognitive decline in early AD predicts subsequent AD + P onset. Methods: 361 subjects with possible or probable AD or mild cognitive impairment (MCI) without psychosis were evaluated every 6 months until psychosis onset. Results: Severity of cognitive dysfunction was a strong predictor of AD + P up to two years prior to psychosis onset. Cognition did not decline more rapidly prior to onset of AD + P. Conclusions: Individuals who will develop AD + P already demonstrate excess cognitive impairment during the mild stages of disease. Genetic variation and brain pathophysiology may lead to a cognitive risk phenotype which is present prior to dementia onset. C1 [Weamer, Elise A.; Emanuel, James E.; Varon, Daniel; Wilkosz, Patricia A.; Lopez, Oscar L.; DeKosky, Steven T.; Sweet, Robert A.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Weamer, Elise A.; Lopez, Oscar L.; Sweet, Robert A.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA USA. [Miyahara, Sachiko] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA USA. [Sweet, Robert A.] VA Pittsburgh Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr 4, Pittsburgh, PA USA. RP Sweet, RA (reprint author), Biomed Sci Tower,Rm W-1645,3811 OHara St, Pittsburgh, PA 15213 USA. EM sweetra@upmc.edu FU National Institute of Aging [AG05133, AG027224] FX This study was supported in part by USPHS grant AG05133 and AG027224 from the National Institute of Aging. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Aging or the National Institutes of Health. NR 46 TC 22 Z9 22 U1 1 U2 4 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1041-6102 J9 INT PSYCHOGERIATR JI Int. Psychogeriatr. PD FEB PY 2009 VL 21 IS 1 BP 78 EP 85 DI 10.1017/S1041610208007734 PG 8 WC Psychology, Clinical; Geriatrics & Gerontology; Gerontology; Psychiatry; Psychology SC Psychology; Geriatrics & Gerontology; Psychiatry GA 408NI UT WOS:000263441300010 PM 18814807 ER PT J AU Kim, MS Casserly, IP Garcia, JA Klein, AJ Salcedo, EE Carroll, JD AF Kim, Michael S. Casserly, Ivan P. Garcia, Joel A. Klein, Andrew J. Salcedo, Ernesto E. Carroll, John D. TI Percutaneous Transcatheter Closure of Prosthetic Mitral Paravalvular Leaks Are We There Yet? SO JACC-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE paravalvular leak; perivalvular leak; mitral valve; prosthetic valve; 3-dimensional echocardiography; percutaneous transcatheter closure; rapid prototyping ID AMPLATZER DUCT OCCLUDER; VALVE-REPLACEMENT; HEART-DISEASE; REGURGITATION; HEMOLYSIS; ECHOCARDIOGRAPHY; COMPLICATION; MANAGEMENT; OCCLUSION AB A potential complication of mitral valve replacement surgery is the development of a paravalvular leak (PVL). Percutaneous transcatheter closures of PVLs using a wide array of devices have been reported in the literature, although the procedural success rate of this approach remains variable. One major challenge of transcatheter mitral PVL closure lies in the ability to adequately visualize the area of interest to facilitate defect crossing and equipment selection. Furthermore, the current spectrum of devices available for off-label use in the closure of these unique defects remains limited. This review examines the current state of transcatheter. prosthetic mitral PVL closure, describes our institution's experience using advanced imaging modalities for procedural guidance, and illustrates some of the limitations associated with using existing devices in transcatheter PVL closure. (J Am Coll Cardiol Intv 2009;2: 81-90) (C) 2009 by the American College of Cardiology Foundation C1 [Kim, Michael S.; Casserly, Ivan P.; Garcia, Joel A.; Klein, Andrew J.; Salcedo, Ernesto E.; Carroll, John D.] Univ Colorado Denver, Aurora, CO 80045 USA. [Casserly, Ivan P.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Garcia, Joel A.] Denver Hlth Med Ctr, Denver, CO USA. RP Carroll, JD (reprint author), Univ Colorado Denver, Anschutz Med Campus,Leprino Off Bldg,Room 524,124, Aurora, CO 80045 USA. EM John.Carroll@ucdenver.edu NR 27 TC 66 Z9 70 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-8798 J9 JACC-CARDIOVASC INTE JI JACC-Cardiovasc. Interv. PD FEB PY 2009 VL 2 IS 2 BP 81 EP 90 DI 10.1016/j.jcin.2008.10.012 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 613HP UT WOS:000278970300001 PM 19463407 ER PT J AU Dixon, SR Henriques, JPS Mauri, L Sjauw, K Civitello, A Kar, B Loyalka, P Resnic, FS Teirstein, P Makkar, R Palacios, IF Collins, M Moses, J Benali, K O'Neill, WW AF Dixon, Simon R. Henriques, Jose P. S. Mauri, Laura Sjauw, Krischan Civitello, Andrew Kar, Biswajit Loyalka, Pranav Resnic, Frederic S. Teirstein, Paul Makkar, Raj Palacios, Igor F. Collins, Michael Moses, Jeffrey Benali, Karim O'Neill, William W. TI A Prospective Feasibility Trial Investigating the Use of the Impel la 2.5 System in Patients Undergoing High-Risk Percutaneous Coronary Intervention (The PROTECT I Trial) Initial US Experience SO JACC-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE percutaneous coronary intervention; high risk; circulatory support ID LEFT-VENTRICULAR SUPPORT; ASSIST DEVICE AB Objectives We sought to evaluate the safety and feasibility of the Impel la 2.5 system (Abiomed Inc., Danvers, Massachusetts) in patients undergoing high-risk percutaneous coronary intervention (PCI). Background The Impella 2.5 is a miniaturized percutaneous cardiac assist device, which provides up to 2.5 l/min forward flow from the left ventricle into the systemic circulation. Methods In a prospective, multicenter study, 20 patients underwent high-risk PCI with minimally invasive circulatory support employing the Impella 2.5 system. All patients had poor left ventricular function (ejection fraction <= 35%) and underwent PCI on an unprotected left main coronary artery or last patent coronary conduit. Patients with recent ST-segment elevation myocardial infarction or cardiogenic shock were excluded. The primary safety end point was the incidence of major adverse cardiac events at 30 days. The primary efficacy end point was freedom from hemodynamic compromise during PCI (defined as a decrease in mean arterial pressure below 60 mm Hg for >10 min). Results The Impella 2.5 device was implanted successfully in all patients. The mean duration of circulatory support was 1.7 +/- 0.6 h (range: 0.4 to 2.5 h). Mean pump flow during PCI was 2.2 +/- 0.3 l/min. At 30 days, the incidence of major adverse cardiac events was 20% (2 patients had a periprocedural myocardial infarction; 2 patients died at days 12 and 14). There was no evidence of aortic valve injury, cardiac perforation, or limb ischemia. Two patients (10%) developed mild, transient hemolysis without clinical sequelae. None of the patients developed hemodynamic compromise during PCI. Conclusions The Impella 2.5 system is safe, easy to implant, and provides excellent hemodynamic support during high-risk PCI. (The PROTECT I Trial; NCT00534859) (J Am Coll Cardiol Intv 2009;2:91-6) (C) 2009 by the American College of Cardiology Foundation C1 [O'Neill, William W.] Univ Miami, Leonard M Miller Sch Med, Miami, FL 33101 USA. [Dixon, Simon R.] William Beaumont Hosp, Royal Oak, MI 48072 USA. [Henriques, Jose P. S.; Sjauw, Krischan] Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands. [Mauri, Laura; Resnic, Frederic S.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Civitello, Andrew; Kar, Biswajit; Loyalka, Pranav] Texas Heart Inst, Houston, TX 77025 USA. [Teirstein, Paul] Scripps Clin, La Jolla, CA USA. [Makkar, Raj] Cedars Sinai, Los Angeles, CA USA. [Palacios, Igor F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Collins, Michael; Moses, Jeffrey] Columbia Presbyterian, New York, NY USA. [Benali, Karim] Abiomed Inc, Danvers, MA USA. RP O'Neill, WW (reprint author), Univ Miami, Leonard M Miller Sch Med, POB 016099,R-699, Miami, FL 33101 USA. EM woneill@med.miami.edu OI Civitello, Andrew/0000-0003-0731-1891 FU Abiomed Inc., Danvers, Massachusetts FX From *William Beaumont Hospital, Royal Oak, Michigan; I-Academic Medical Center, Amsterdam, the Netherlands; double dagger Brigham and Women's Hospital, Boston, Massachusetts; Texas Heart Institute, Houston, Texas; parallel to Scripps Clinic, La Jolla, California; Cedars Sinai, Los Angeles, California; #Massachusetts General Hospital, Boston, Massachusetts; **Columbia Presbyterian, New York, New York; dagger dagger Abiomed Inc., Danvers, Massachusetts; and the double dagger double dagger University of Miami, Miami, Florida. Supported by a grant from Abiomed Inc., Danvers, Massachusetts. Dr. Benali is a paid employee of Abiomed Inc. Presented in part at Transcatheter Cardiovascular Therapeutics 2007, Washington, DC. NR 7 TC 70 Z9 75 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-8798 J9 JACC-CARDIOVASC INTE JI JACC-Cardiovasc. Interv. PD FEB PY 2009 VL 2 IS 2 BP 91 EP 96 DI 10.1016/j.jcin.2008.11.005 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 613HP UT WOS:000278970300002 PM 19463408 ER PT J AU Morasco, BJ Rifai, MA Loftis, JM Indest, DW Moles, JK Hauser, P AF Morasco, Benjamin J. Rifai, Muhamad Aly Loftis, Jennifer M. Indest, David W. Moles, James Kelly Hauser, Peter TI A randomized trial of paroxetine to prevent interferon-alpha-induced depression in patients with hepatitis C (vol 103, pg 83, 2007) SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Correction C1 [Morasco, Benjamin J.; Rifai, Muhamad Aly; Loftis, Jennifer M.; Indest, David W.; Hauser, Peter] Portland VA Med Ctr, Behav Hlth & Clin Neurosci Div, Portland, OR USA. [Rifai, Muhamad Aly; Moles, James Kelly] Salem VA Med Ctr, Salem, VA USA. [Morasco, Benjamin J.; Rifai, Muhamad Aly; Loftis, Jennifer M.; Indest, David W.; Hauser, Peter] Portland VA Med Ctr, NW Hepatitis C Resource Ctr, Portland, OR USA. [Rifai, Muhamad Aly; Moles, James Kelly] Univ Virginia, Sch Med, Roanoke Salem, VA USA. [Morasco, Benjamin J.; Rifai, Muhamad Aly; Loftis, Jennifer M.; Indest, David W.; Hauser, Peter] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Loftis, Jennifer M.; Hauser, Peter] Portland VA Med Ctr, JENS Lab, Portland, OR USA. [Hauser, Peter] Oregon Hlth & Sci Univ, Dept Internal Med, Portland, OR 97201 USA. RP Hauser, P (reprint author), Portland VA Med Ctr, Behav Hlth & Clin Neurosci Div, 3710 SW US Vet Hosp Rd, Portland, OR USA. EM peter.hauser@med.va.gov 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 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD FEB PY 2009 VL 113 IS 1-2 BP 201 EP 201 DI 10.1016/j.jad.2008.10.001 PG 1 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 402IN UT WOS:000263007500024 ER PT J AU Hedrick, SC Guihan, M Chapko, MK Sullivan, J Zhou, XH Manheim, LM Forsberg, CW Mambourg, FJ AF Hedrick, Susan C. Guihan, Marylou Chapko, Michael K. Sullivan, Jean Zhou, Xiao-Hua Manheim, Larry M. Forsberg, Christopher W. Mambourg, Floss J. TI Assisted Living Pilot Program Health Outcomes SO JOURNAL OF AGING AND HEALTH LA English DT Article DE assisted living; residential care facilities; long-term care; outcomes; longitudinal design ID RESIDENTIAL CARE; FACILITIES AB Objectives: Assisted living programs demonstrate variation in structure and services. The Department of Veterans Affairs funded this care for the first time in the Assisted Living Pilot Program (ALPP). This article presents resident health outcomes and the relationship between facility characteristics and outcomes. Method: This article presents results on 393 ALPP residents followed for 12 months after admission to 95 facilities. Results: A total of 19.8% residents died, and the average activities of daily living impairment did not change significantly. Half of the residents remained in an ALPP facility, with the average resident spending 315 days in the community during the 12-month follow-up period. This article found a limited number of characteristics of structure and staffing to be significantly associated with outcomes. Discussion: If differences among facility characteristics are not clearly related to differences in outcomes, then choices among type of setting can be based on the match of needs to available services, location, or preferences. C1 [Hedrick, Susan C.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA 98101 USA. [Hedrick, Susan C.; Chapko, Michael K.; Zhou, Xiao-Hua] Univ Washington, Seattle, WA 98195 USA. [Guihan, Marylou; Manheim, Larry M.] Northwestern Univ, Evanston, IL 60208 USA. [Mambourg, Floss J.] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97201 USA. RP Hedrick, SC (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM susan.hedrick@va.gov NR 19 TC 4 Z9 4 U1 2 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0898-2643 J9 J AGING HEALTH JI J. Aging Health PD FEB PY 2009 VL 21 IS 1 BP 190 EP 207 DI 10.1177/0898264308328929 PG 18 WC Gerontology; Health Policy & Services SC Geriatrics & Gerontology; Health Care Sciences & Services GA 399QL UT WOS:000262814300009 PM 19074647 ER PT J AU Chapko, MK Manheim, LM Guihan, M Sullivan, JH Zhou, XHA Wang, L Mambourg, FJ Hedrick, SC AF Chapko, Michael K. Manheim, Larry M. Guihan, Marylou Sullivan, Jean H. Zhou, Xiao-Hua Andrew Wang, Li Mambourg, Floss J. Hedrick, Susan C. TI Assisted Living Pilot Program Utilization and Cost Findings SO JOURNAL OF AGING AND HEALTH LA English DT Article DE assisted living; residential care facilities; long-term care; cost ID HEALTH-CARE; FACILITIES; HOMES AB Objective: The Department of Veterans Affairs funded assisted living, adult family home, and adult residential care for the first time in the Assisted Living Pilot Program (ALPP) This article compares the use and cost for individuals that entered ALPP and a comparison group. Method: This was a nonrandomized study. The comparison group consisted of VA patients who were eligible but did not enter an ALPP facility. The ALPP (n = 393) and comparison (n = 259) groups were followed for 12 months to assess ALPP facility, case management, and health care costs. Results: ALPP facility and ALPP case management costs were respectively $5,560 and $2,830 per individual. Total health care costs, including ALPP costs, were $11,533 higher for the ALPP group compared to the comparison group after adjusting for baseline differences. Discussion: Although ALPP successfully helped individuals transition to longer term care in these facilities, it was more costly than the comparison group. C1 [Chapko, Michael K.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA 98101 USA. [Chapko, Michael K.; Zhou, Xiao-Hua Andrew; Hedrick, Susan C.] Univ Washington, Seattle, WA 98195 USA. [Manheim, Larry M.; Guihan, Marylou] Edward Hines Jr VA Hosp, Hines, IL 60141 USA. [Manheim, Larry M.; Guihan, Marylou] Northwestern Univ, Evanston, IL 60208 USA. [Mambourg, Floss J.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Chapko, MK (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM chapko@u.washington.edu NR 30 TC 1 Z9 1 U1 1 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0898-2643 J9 J AGING HEALTH JI J. Aging Health PD FEB PY 2009 VL 21 IS 1 BP 208 EP 225 DI 10.1177/0898264308328930 PG 18 WC Gerontology; Health Policy & Services SC Geriatrics & Gerontology; Health Care Sciences & Services GA 399QL UT WOS:000262814300010 PM 19144975 ER PT J AU Tsai, CL Sullivan, AF Gordon, JA Kaushal, R Magid, DJ Blumenthal, D Camargo, CA AF Tsai, Chu-Lin Sullivan, Ashley F. Gordon, James A. Kaushal, Rainu Magid, David J. Blumenthal, David Camargo, Carlos A., Jr. TI Quality of care for acute asthma in 63 US emergency departments SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Acute asthma; emergency department; guidelines; quality of care ID UNITED-STATES; HEALTH-CARE; ADULTS; OUTCOMES; GUIDELINES; ADMISSION; ADHERENCE AB Background: Little is known about the quality of acute asthma care in the emergency department (ED). Objectives: We sought to determine the concordance of ED management of acute asthma with National Institutes of Health asthma guidelines, to identify ED characteristics predictive of higher guideline concordance, and to assess whether guideline concordance was associated with hospital admission. Methods: We conducted a retrospective chart review study of acute asthma as part of the National Emergency Department Safety Study. Using a principal diagnosis of asthma, we identified ED visits for acute asthma in 63 urban EDs in 23 US states between 2003 and 2006. Concordance with guideline recommendations was evaluated by using item-by-item quality measures and composite concordance scores both at the patient and ED level. These scores ranged from 0 to 100, with 100 indicating perfect concordance. Results: The cohort consisted of 4,053 subjects; their median age was 34 years, and 64% were women. The overall patient guideline concordance score was 67 (interquartile range, 63-83), and the ED concordance score was 71 (SD, 7). Multivariable analysis showed southern EDs were associated with lower ED concordance scores (beta-coefficient, -8.2; 95% CI, -13.8 to -2.7) compared with northeastern EDs. After adjustment for the severity on ED presentation, patients who received all recommended treatments had a 46% reduction in the risk of hospital admission compared with others. Conclusions: Concordance with treatment recommendations in the National Institutes of Health asthma guidelines was moderate. Significant variations in ED quality of asthma care were found, and geographic differences existed. Greater concordance with guideline-recommended treatments might reduce hospitalizations. (J Allergy Clin Immunol 2009;123:354-61.) C1 [Tsai, Chu-Lin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Emergency Med Network Coordinating Ctr,Dept Emerg, Boston, MA 02114 USA. [Blumenthal, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. [Kaushal, Rainu] Cornell Univ, Weill Med Coll, New York, NY 10021 USA. [Kaushal, Rainu] New York Presbyterian Hosp, New York, NY USA. [Magid, David J.] Univ Colorado, Hlth Sci Ctr, Kaiser Permanente Colorado, Inst Hlth Res, Aurora, CO USA. [Magid, David J.] Univ Colorado, Hlth Sci Ctr, Dept Emergency Med, Aurora, CO USA. [Magid, David J.] Univ Colorado, Hlth Sci Ctr, Dept Prevent Med & Biometr, Aurora, CO USA. RP Tsai, CL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Emergency Med Network Coordinating Ctr,Dept Emerg, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM cltsai@post.harvard.edu OI TSAI, CHU-LIN/0000-0003-4639-1513 FU AHRQ HHS [R01 HS013099]; NHLBI NIH HHS [R01 HL084401] NR 37 TC 41 Z9 41 U1 0 U2 1 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 FEB PY 2009 VL 123 IS 2 BP 354 EP 361 DI 10.1016/j.jaci.2008.10.051 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 409GU UT WOS:000263495000010 PM 19070357 ER PT J AU Baker, JW Sheffer, A Christensen, J Hurewitz, D Lazar, R Kalfus, I Banerji, A AF Baker, J. W. Sheffer, A. Christensen, J. Hurewitz, D. Lazar, R. Kalfus, I. Banerji, A. TI Cinryze (TM) Replacement Therapy in Hereditary Angioedema and Pregnancy SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 13-17, 2009 CL Washington, DC SP Amer Acad Allergy, Asthma & Immunol C1 [Baker, J. W.] Allergy Asthma & Dermatol Res Ctr, Lake Oswego, OR USA. [Sheffer, A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Christensen, J.] Nevada Access Res & Educ Soc, Las Vegas, NV USA. [Hurewitz, D.] Allergy Clin Tulsa, Tulsa, OK USA. [Lazar, R.] Grand Traverse Allergy, Traverse City, MA USA. [Kalfus, I.] Lev Pharmaceut, New York, NY USA. [Banerji, A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 2 Z9 2 U1 0 U2 1 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 FEB PY 2009 VL 123 IS 2 MA 400 BP S106 EP S106 DI 10.1016/j.jaci.2008.12.385 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 410RR UT WOS:000263596300413 ER PT J AU Banerji, A Perkins, A Corel, B Caceres, A Rudders, S Clark, S Camargo, CA AF Banerji, A. Perkins, A. Corel, B. Caceres, A. Rudders, S. Clark, S. Camargo, C. A. TI Repeat Epinephrine Treatments For Food-related Allergic Reactions That Present To The Emergency Department SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 13-17, 2009 CL Washington, DC SP Amer Acad Allergy, Asthma & Immunol C1 [Banerji, A.; Perkins, A.; Corel, B.; Caceres, A.; Camargo, C. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rudders, S.] Childrens Hosp, Boston, MA 02115 USA. [Clark, S.] Univ Pittsburgh, Pittsburgh, PA 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 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2009 VL 123 IS 2 MA 708 BP S185 EP S185 DI 10.1016/j.jaci.2008.12.700 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 410RR UT WOS:000263596301181 ER PT J AU Borzutzky, A Crompton, B Neuwirth, AK Giliani, S Neufeld, EJ Notarangelo, LD AF Borzutzky, A. Crompton, B. Neuwirth, A. K. Giliani, S. Neufeld, E. J. Notarangelo, L. D. TI Reversible Severe Combined Immunodeficiency Phenotype Secondary to a Mutation of the Proton-Coupled Folate Transporter SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 13-17, 2009 CL Washington, DC SP Amer Acad Allergy, Asthma & Immunol C1 [Borzutzky, A.; Crompton, B.; Neuwirth, A. K.; Giliani, S.; Neufeld, E. J.; Notarangelo, L. D.] Childrens Hosp, Boston, MA 02115 USA. [Crompton, B.; Neufeld, E. J.] Dana Farber Canc Inst, Boston, MA 02115 USA. RI Neufeld, Ellis/F-9331-2011; Notarangelo, Luigi/F-9718-2016 OI Notarangelo, Luigi/0000-0002-8335-0262 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 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2009 VL 123 IS 2 MA 246 BP S67 EP S67 DI 10.1016/j.jaci.2008.12.227 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 410RR UT WOS:000263596300259 ER PT J AU Camargo, CA Clark, S Pearson, JF Kaplan, MS Lieberman, P Wood, RA AF Camargo, C. A., Jr. Clark, S. Pearson, J. F. Kaplan, M. S. Lieberman, P. Wood, R. A. TI Latitude, UVB Exposure, And EpiPen Prescriptions In 38 Urban Areas SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 13-17, 2009 CL Washington, DC SP Amer Acad Allergy, Asthma & Immunol C1 [Camargo, C. A., Jr.; Pearson, J. F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Clark, S.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Kaplan, M. S.] Kaiser Permanente, Los Angeles, CA USA. [Lieberman, P.] Univ Tennessee, Memphis, TN USA. [Wood, R. A.] Johns Hopkins Med Ctr, Baltimore, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 1 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 FEB PY 2009 VL 123 IS 2 MA 412 BP S109 EP S109 DI 10.1016/j.jaci.2008.12.397 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 410RR UT WOS:000263596300425 ER PT J AU Chyung, YH Luster, AD AF Chyung, Y. H. Luster, A. D. TI Silencing STATE-Regulated Genes Through A Chimeric Transcription Factor SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 13-17, 2009 CL Washington, DC SP Amer Acad Allergy, Asthma & Immunol C1 [Chyung, Y. H.; Luster, A. D.] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 FEB PY 2009 VL 123 IS 2 MA 523 BP S137 EP S137 DI 10.1016/j.jaci.2008.12.510 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 410RR UT WOS:000263596300536 ER PT J AU Long, AA Means, T Luster, AD AF Long, A. A. Means, T. Luster, A. D. TI Omalizumab Therapy Influences the Phenotype of Peripheral Blood Dendritic Cells in Asthma SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 13-17, 2009 CL Washington, DC SP Amer Acad Allergy, Asthma & Immunol C1 [Long, A. A.; Means, T.; Luster, A. D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Long, A. A.] Harvard Univ, Sch Med, Boston, MA 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 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2009 VL 123 IS 2 MA 744 BP S194 EP S194 DI 10.1016/j.jaci.2008.12.737 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 410RR UT WOS:000263596301217 ER PT J AU Murali, MR AF Murali, M. R. TI Beta 2 Transferrin (B2T) as a Biomarker of Cerebrospinal Fluid (CSF) Rhinorrhoea SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 13-17, 2009 CL Washington, DC SP Amer Acad Allergy, Asthma & Immunol C1 [Murali, M. R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 FEB PY 2009 VL 123 IS 2 MA 646 BP S169 EP S169 DI 10.1016/j.jaci.2008.12.637 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 410RR UT WOS:000263596301119 ER PT J AU Patel, NC Chinen, J Rosenblatt, HM Hanson, IC Krance, RA Paul, ME Abramson, SL Noroski, LM Davis, CM Brown, BS Ritz, J Shearer, WT AF Patel, N. C. Chinen, J. Rosenblatt, H. M. Hanson, I. C. Krance, R. A. Paul, M. E. Abramson, S. L. Noroski, L. M. Davis, C. M. Brown, B. S. Ritz, J. Shearer, W. T. TI Outcomes of 48 Severe Combined Immunodeficiency Patients Treated with Hematopoietic Stem Cell Transplantation at a Single Center Between 1981 and 2007 SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 13-17, 2009 CL Washington, DC SP Amer Acad Allergy, Asthma & Immunol C1 [Patel, N. C.; Chinen, J.; Hanson, I. C.; Krance, R. A.; Paul, M. E.; Abramson, S. L.; Noroski, L. M.; Davis, C. M.; Brown, B. S.; Shearer, W. T.] Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA. [Rosenblatt, H. M.] Dell Childrens Med Ctr Cent Texas, Austin, TX USA. [Ritz, J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Ritz, J.] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Boston, MA 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 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2009 VL 123 IS 2 MA 1029 BP S265 EP S265 DI 10.1016/j.jaci.2008.12.1027 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 410RR UT WOS:000263596301501 ER PT J AU Springston, EE Gupta, RS Kim, JS Smith, B Pongracic, JA Wang, X Holl, JL AF Springston, E. E. Gupta, R. S. Kim, J. S. Smith, B. Pongracic, J. A. Wang, X. Holl, J. L. TI Food Allergy Knowledge, Attitudes, and Beliefs in the United States SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 13-17, 2009 CL Washington, DC SP Amer Acad Allergy, Asthma & Immunol C1 [Springston, E. E.; Gupta, R. S.; Kim, J. S.; Pongracic, J. A.; Wang, X.; Holl, J. L.] Childrens Mem Hosp, Chicago, IL 60614 USA. [Gupta, R. S.; Smith, B.; Holl, J. L.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Smith, B.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 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 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2009 VL 123 IS 2 MA 688 BP S180 EP S180 DI 10.1016/j.jaci.2008.12.679 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 410RR UT WOS:000263596301161 ER PT J AU Wilson, DA Castaldo, AJ Vernon, MK Rentz, AM Blaustein, MB AF Wilson, D. A. Castaldo, A. J. Vernon, M. K. Rentz, A. M. Blaustein, M. B. TI Effect of Hereditary Angioedema: Health-Related Quality of Life, Depression, Productivity, and Social Consequences SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 13-17, 2009 CL Washington, DC SP Amer Acad Allergy, Asthma & Immunol C1 [Wilson, D. A.] Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. [Castaldo, A. J.] US Hereditary Angioedema Assoc, New Bedford, MA USA. [Vernon, M. K.; Rentz, A. M.] United BioSource Corp, Ctr Hlth Outcomes Res, Bethesda, MD USA. [Blaustein, M. B.] Dyax Corp, Cambridge, MA USA. NR 0 TC 2 Z9 2 U1 0 U2 2 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 FEB PY 2009 VL 123 IS 2 MA 543 BP S142 EP S142 DI 10.1016/j.jaci.2008.12.531 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 410RR UT WOS:000263596301016 ER PT J AU Yong, PL Werner, RM AF Yong, P. L. Werner, R. M. TI The Impact of Geographic Variation on Racial Disparities in Asthma: Controller Medication Use among Medicaid Asthmatics in Four Large States SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 13-17, 2009 CL Washington, DC SP Amer Acad Allergy, Asthma & Immunol C1 [Yong, P. L.; Werner, R. M.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Yong, P. L.; Werner, R. M.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. NR 0 TC 1 Z9 1 U1 0 U2 1 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 FEB PY 2009 VL 123 IS 2 MA 581 BP S152 EP S152 DI 10.1016/j.jaci.2008.12.569 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 410RR UT WOS:000263596301054 ER PT J AU Bredella, MA Utz, AL Torriani, M Thomas, B Schoenfeld, DA Miller, KK AF Bredella, Miriam A. Utz, Andrea L. Torriani, Martin Thomas, Bijoy Schoenfeld, David A. Miller, Karen K. TI Anthropometry, CT, and DXA as predictors of GH deficiency in premenopausal women: ROC curve analysis SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE obesity; body composition; growth hormone deficiency; waist circumference; computed tomography; dual-energy X-ray absorptiometry; receiver operator characteristic curve analysis ID GROWTH-HORMONE TREATMENT; VISCERAL ADIPOSE-TISSUE; X-RAY ABSORPTIOMETRY; WAIST CIRCUMFERENCE; BODY-COMPOSITION; ABDOMINAL ADIPOSITY; COMPUTED-TOMOGRAPHY; METABOLIC SYNDROME; HEALTHY-ADULTS; OBESE WOMEN AB Bredella MA, Utz AL, Torriani M, Thomas B, Schoenfeld DA, Miller KK. Anthropometry, CT, and DXA as predictors of GH deficiency in premenopausal women: ROC curve analysis. J Appl Physiol 106: 418-422, 2009. First published December 18, 2008; doi: 10.1152/japplphysiol.90998.2008.-Visceral adiposity is a strong determinant of growth hormone (GH) secretion, and states of GH deficiency are associated with increased visceral adiposity and decreased lean body mass. The purpose of our study was to determine the sensitivity and specificity of different methods of assessing body composition [anthropometry, dual-energy X-ray absorptiometry (DXA), and computed tomography (CT)] to predict GH deficiency in premenopausal women and threshold values for each technique to predict GH deficiency, using receiver operator characteristic (ROC) curve analysis. We studied a group of 45 healthy lean, overweight, and obese premenopausal women who underwent anthropometric measurements (body mass index, waist and hip circumferences, skin fold thickness), DXA, CT, and a GH-releasing hormone-arginine stimulation test. ROC curve analysis was used to determine cutoff values for each method to identify GH deficiency. Visceral adiposity measured by CT showed the highest sensitivity and specificity for identifying subjects with GH deficiency with a cutoff of >9,962 mm(2) [area under the curve (AUC), 0.95; sensitivity, 100%; specificity, 77.8%; P = 0.0001]. Largest waist circumference showed high sensitivity and specificity with a cutoff of >101.7 cm (AUC, 0.89; sensitivity, 88.9%; specificity, 75%; P = 0.0001). When the ROC curves of visceral fat measured by CT and largest waist circumference were compared, the difference between the two methods was not statistically significant ( P = 0.36). Our study showed that the largest waist circumference predicts the presence of GH deficiency in healthy premenopausal women with high sensitivity and specificity and nearly as well as CT measurement of visceral adiposity. It can be used to identify women in whom GH deficiency is likely and therefore in whom formal GH stimulation testing might be indicated. C1 [Bredella, Miriam A.; Torriani, Martin; Thomas, Bijoy] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Utz, Andrea L.; Miller, Karen K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Schoenfeld, David A.] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. RP Bredella, MA (reprint author), Massachusetts Gen Hosp, Dept Radiol, Yawkey 6E,55 Fruit St, Boston, MA 02114 USA. EM mbredella@partners.org FU National Institutes of Health [HL-077674, M01 RR-01066, K23 RR-23090] FX This work was supported in part by National Institutes of Health Grants HL-077674, M01 RR-01066, and K23 RR-23090. NR 35 TC 8 Z9 10 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 EI 1522-1601 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD FEB PY 2009 VL 106 IS 2 BP 418 EP 422 DI 10.1152/japplphysiol.90998.2008 PG 5 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 403ZL UT WOS:000263120400012 PM 19095751 ER PT J AU Yang, JN Bjorklund, O Lindstrom-Tornqvist, K Lindgren, E Eriksson, TM Kahlstrom, J Chen, JF Schwarzschild, MA Tobler, I Fredholm, BB AF Yang, Jiang-Ning Bjorklund, Olga Lindstrom-Tornqvist, Karin Lindgren, Eva Eriksson, Therese M. Kahlstrom, Johan Chen, Jiang-Fan Schwarzschild, Michael A. Tobler, Irene Fredholm, Bertil B. TI Mice heterozygous for both A(1) and A(2A) adenosine receptor genes show similarities to mice given long-term caffeine SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE knockout; locomotor activity; tolerance; receptor binding; lipolysis ID BLOOD-PRESSURE; RAT-BRAIN; TOLERANCE; EXPRESSION; TEMPERATURE; ANTAGONISM; BLOCKADE; EXERCISE; BEHAVIOR; LACKING AB Yang JN, Bjorklund O, Lindstrom-Tornqvist K, Lindgren E, Eriksson TM, Kahlstrom J, Chen JF, Schwarzschild MA, Tobler I, Fredholm BB. Mice heterozygous for both A(1) and A(2A) adenosine receptor genes show similarities to mice given long-term caffeine. J Appl Physiol 106: 631-639, 2009. First published November 26, 2008; doi: 10.1152/japplphysiol.90971.2008.-Caffeine is believed to exert its stimulant effects by blocking A(2A) and A(1) adenosine receptors (A(2A)R and A(1)R). Although a genetic knockout of A(2A)R eliminates effects of caffeine, the phenotype of the knockout animal does not resemble that of caffeine treatment. In this study we explored the possibility that a mere reduction of the number of A(1)Rs and A(2A)Rs, achieved by deleting one of the two copies of the A(1)R and A(2A)R genes, would mimic some aspects of long-term caffeine ingestion. The A(1)R and A(2)AR double heterozygous (A(1)R-A(2A)R dHz) mice indeed had approximately one-half the number of A(1)R and A(2A)R, and there were little compensatory changes in A(2B) or A(3) adenosine receptor (A(2B)R or A(3)R) expression. The ability of a stable adenosine analog to activate receptors was shifted to the right by caffeine and in A(1)R-A(2A)R dHz tissue. Caffeine (0.3 g/l in drinking water for 7-10 days) and A(1)R-A(2A)R dHz genotype increased locomotor activity (LA) and decreased heart rate without significantly influencing body temperature. The acute stimulatory effect of a single injection of caffeine was reduced in A(1)R-A(2A)R dHz mice and in mice treated long term with oral caffeine. Thus at least some aspects of long-term caffeine use can be mimicked by genetic manipulation of the A(1)R and A(2A)R. C1 [Yang, Jiang-Ning] Karolinska Inst, Sect Mol Neuropharmacol, Dept Physiol & Pharmacol, S-17177 Stockholm, Sweden. [Yang, Jiang-Ning] Karolinska Inst, Dept Surg Sci, S-17177 Stockholm, Sweden. [Chen, Jiang-Fan] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Schwarzschild, Michael A.] Massachusetts Gen Hosp, Mass Gen Inst Neurodegenerat Dis, Boston, MA 02114 USA. [Tobler, Irene] Univ Zurich, Inst Pharmacol & Toxicol, Zurich, Switzerland. RP Yang, JN (reprint author), Karolinska Inst, Sect Mol Neuropharmacol, Dept Physiol & Pharmacol, S-17177 Stockholm, Sweden. EM jiangning.yang@ki.se FU Swedish Science Council [2553]; National Institute of Neurological Disorders and Stroke [R01 NS048995]; Swedish Heart and Lung Foundation; Karolinska Institutet; European Commission; National Institutes of Health [ES10804]; US Department of Defence [W81XWH-04-1-0881] FX This study was supported by Swedish Science Council Grant 2553, National Institute of Neurological Disorders and Stroke Grant R01 NS048995, the Swedish Heart and Lung Foundation, Karolinska Institutet, and the European Commission (STREP "Enough sleep"), National Institutes of Health Grant ES10804, US Department of Defence Grant W81XWH-04-1-0881. NR 37 TC 25 Z9 25 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD FEB PY 2009 VL 106 IS 2 BP 631 EP 639 DI 10.1152/japplphysiol.90971.2008 PG 9 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 403ZL UT WOS:000263120400037 PM 19036889 ER PT J AU Zarin, JS Zurakowski, D Burke, DW AF Zarin, Jeffrey S. Zurakowski, David Burke, Dennis W. TI Claw Plate Fixation of the Greater Trochanter in Revision Total Hip Arthroplasty SO JOURNAL OF ARTHROPLASTY LA English DT Article DE trochanteric plate; revision hip arthroplasty; nonunion; extended trochanteric osteotomy ID LOW FRICTION ARTHROPLASTY; CABLE-GRIP SYSTEM; RE-ATTACHMENT; WIRE FIXATION; UNION RATE; REATTACHMENT; REPLACEMENT; OSTEOTOMY; COMPLICATIONS AB The purpose of this retrospective Study was to evaluate a new trochanteric claw plate for trochanteric fixation. From 1998 to 2004, 31 procedures were performed by one Surgeon. Mean follow-up was 2.2 years. Indications for the procedure included 16 nonunion, 7 trochanteric osteotomy, 5 periprosthetic fractures, and 3 intraoperative fractures. Median Harris hip scores improved from 47 to 92 points (P < .0001). No patient had an abductor lurch postoperatively (P < .0001). No patient had moderate or severe pain postoperatively (P <.0001). Median active abduction increased front 0 degrees to 25 degrees (P < .0001). Osseous union Occurred in 28 of 31 hips. Plate-related complications occurred in 6 of 31 hips. No significant difference was identified for outcomes based on indication. in conclusion, the claw plate in this study can sufficiently treat the complex situation of trochanteric nonunion, fracture, or osteotomy. C1 [Zarin, Jeffrey S.] Boston Univ, Dept Orthoped, DOB, Boston, MA 02118 USA. [Zurakowski, David] Boston Childrens Hosp, Dept Orthoped Surg, Boston, MA USA. [Burke, Dennis W.] Massachusetts Gen Hosp, Dept Orthoped, Boston, MA 02114 USA. RP Zarin, JS (reprint author), Boston Univ, Dept Orthoped, DOB, Suite 808,720 Harrison Ave, Boston, MA 02118 USA. NR 25 TC 6 Z9 7 U1 3 U2 3 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD FEB PY 2009 VL 24 IS 2 BP 272 EP 280 DI 10.1016/j.arth.2007.09.016 PG 9 WC Orthopedics SC Orthopedics GA 404IB UT WOS:000263143900016 PM 18534490 ER PT J AU Sah, AP Scott, RD Springer, BD Bono, JV Deshmukh, RV Thornhill, TS AF Sah, Alexander P. Scott, Richard D. Springer, Bryan D. Bono, James V. Deshmukh, Rahul V. Thornhill, Thomas S. TI Custom-Made Angled inserts for Tibial Coronal Malalignment in Total Knee Arthroplasty SO JOURNAL OF ARTHROPLASTY LA English DT Article DE insert exchange; angled; malalignment; knee arthroplasty; custom; coronal ID POLYETHYLENE WEAR; ALIGNMENT GUIDES; REPLACEMENT; COMPONENT; INTRAMEDULLARY; EXTRAMEDULLARY; REVISION; FAILURE; SURVIVORSHIP; PROSTHESIS AB Component malalignment continues to be common after knee arthroplasty, with treatment often requiring prosthesis revision. From 1993 to 2005, 9 angled inserts were placed to correct coronal plane deformities due to tibial component malposition. Insert exchange occurred at an average of 67 months (range, 5-149 months) from the index procedure. Two patients died before 2-year follow-up, for an overall average of 60 months (range, 12-157 months) follow-up. Limb alignment improved and Knee Society knee and function scores increased from 68 and 71, respectively, to 92 and 91, postoperatively. All patients reported excellent satisfaction with no revisions at average 5-year follow-up. It is important to be aware that specifically designed angled inserts are available and may provide a conservative method to correct mild to moderate tibial malalignment in rare cases. C1 [Sah, Alexander P.; Thornhill, Thomas S.] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. [Scott, Richard D.; Bono, James V.] Nevv England Baptist Hosp, Dept Orthoped Surg, Boston, MA USA. [Springer, Bryan D.] Charlotte Hip & Knee Ctr, Charlotte, NC USA. [Deshmukh, Rahul V.] St Vincents Hlth Syst, Jacksonville, FL USA. RP Sah, AP (reprint author), Massachusetts Gen Hosp, Dept Orthoped, 55 Fruit St,GRB 624, Boston, MA 02114 USA. NR 49 TC 1 Z9 1 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD FEB PY 2009 VL 24 IS 2 BP 288 EP 296 DI 10.1016/j.arth.2007.08.014 PG 9 WC Orthopedics SC Orthopedics GA 404IB UT WOS:000263143900018 PM 18534507 ER PT J AU Wagner, JK Heindl, JE Gray, AN Jain, S Goldberg, MB AF Wagner, Jennifer K. Heindl, Jason E. Gray, Andrew N. Jain, Sumita Goldberg, Marcia B. TI Contribution of the Periplasmic Chaperone Skp to Efficient Presentation of the Autotransporter IcsA on the Surface of Shigella flexneri SO JOURNAL OF BACTERIOLOGY LA English DT Article ID DISULFIDE BOND FORMATION; OUTER-MEMBRANE PROTEIN; ACTIN-BASED MOTILITY; ESCHERICHIA-COLI; BACTERIAL AUTOTRANSPORTER; INTERCELLULAR SPREAD; POLAR LOCALIZATION; SECRETION; CLEAVAGE; IDENTIFICATION AB IcsA is an outer membrane protein in the autotransporter family that is required for Shigella flexneri pathogenesis. Following its secretion through the Sec translocon, IcsA is incorporated into the outer membrane in a process that depends on YaeT, a component of an outer membrane beta-barrel insertion machinery. We investigated the role of the periplasmic chaperone Skp in IcsA maturation. Skp is required for the presentation of the mature amino terminus (alpha-domain) of IcsA on the bacterial surface and contributes to cell-to-cell spread of S. flexneri in cell culture. A mutation in skp does not prevent the insertion of the beta-barrel into the outer membrane, suggesting that the primary role of Skp is the folding of the IcsA alpha-domain. In addition, the requirement for skp can be partially bypassed by disrupting icsP, an ortholog of Escherichia coli ompT, which encodes the protease that processes IcsA between the mature amino terminus and the beta-barrel outer membrane anchor. These findings are consistent with a model in which Skp plays a critical role in the chaperoning of the alpha-domain of IcsA during transit through the periplasm. C1 [Goldberg, Marcia B.] Massachusetts Gen Hosp, Div Infect Dis, Dept Med, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Goldberg, MB (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Dept Med, 65 Landsdowne St, Cambridge, MA 02139 USA. EM mgoldberg1@partners.org OI Herman, Jennifer/0000-0003-4100-8167 FU National BioResource Project ( Japan); NIH [AI035817, AI061073, T32 AI07061]; Mustard Seed Foundation; AHA [0325770T] FX We thank T. Silhavy for providing Skp antibody, D. Kahne for providing OmpA antibody, J. Beckwith for providing DsbA antibody, and the National BioResource Project ( Japan): E. coli for providing the E. coli skp mutant. We also thank members of the Goldberg laboratory for critical reading of the manuscript.; This work was supported by NIH grants AI035817 ( to M. B. G.) and AI061073 ( to M. B. G.), NIH postdoctoral fellowship T32 AI07061 ( to J. K. W.), a predoctoral Harvey Fellowship from the Mustard Seed Foundation ( to J. E. H.), and AHA award 0325770T ( to S. J.). NR 39 TC 44 Z9 45 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD FEB 1 PY 2009 VL 191 IS 3 BP 815 EP 821 DI 10.1128/JB.00989-08 PG 7 WC Microbiology SC Microbiology GA 396RQ UT WOS:000262609200017 PM 19047350 ER PT J AU de Velde, SKV Gill, TJ Li, G AF de Velde, Samuel K. Van Gill, Thomas J. Li, Guoan TI Evaluation of Kinematics of Anterior Cruciate Ligament-Deficient Knees with Use of Advanced Imaging Techniques, Three-Dimensional Modeling Techniques, and Robotics SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-Orthopaedic-Surgeons/Orthopaedic-Research-Society CY MAY 15-17, 2008 CL Providence, RI SP Amer Acad Orhopaed Surg, Orthopaed Res Soc ID IN-SITU FORCES; ACUTE TRAUMATIC HEMARTHROSIS; CARTILAGE CONTACT; TIBIOFEMORAL KINEMATICS; VIVO KINEMATICS; JOINT; FLEXION; ACL; OSTEOARTHRITIS; WEIGHTBEARING AB Measuring knee biomechanics in six degrees of freedom with acceptable accuracy has been proven to be technically challenging. At our bioengineering laboratory, we have employed both an in vitro robotic testing system and an in vivo combined dual fluoroscopic and magnetic resonance imaging technique to analyze the impact of anterior cruciate ligament rupture on the knee joint. When measuring the tibiofemoral kinematics of nine cadavers with the robotic testing system, we found that anterior cruciate ligament deficiency not only altered anterior translation and axial rotation of the tibia, but it also increased the medial translation of the tibia as well. The in vivo dual fluoroscopic imaging analysis of tibiofemoral kinematics in ten anterior cruciate ligament-deficient patients revealed analogous findings: an increased medial translation of the tibia of approximately 1 mm between 15 degrees and 9 degrees of flexion was found in anterior cruciate ligament-deficient knees, in addition to an increased anterior translation (approximately 3 mm) and internal rotation (approximately 2) of the tibia at low flexion angles. In a subsequent study of tibiofemoral cartilage contact, we found that the cartilage contact points shifted posteriorly-as was expected on the basis of the increased anterior tibial translation-as well as laterally on the surface of the tibial plateau. The data demonstrate how rupture of the anterior cruciate ligament initiates a cascade of events that eventually results in abnormal tibiofemoral cartilage contact in both the anteroposterior and mediolateral directions. If the restoration of normal knee homeostasis is the ultimate goal of ligament reconstruction, the normal function of the anterior cruciate ligament should be restored as closely as possible in all degrees of freedom. C1 [de Velde, Samuel K. Van; Gill, Thomas J.; Li, Guoan] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Bioengn Lab, Boston, MA 02114 USA. RP de Velde, SKV (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Bioengn Lab, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM gli1@partners.org NR 42 TC 0 Z9 0 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD FEB PY 2009 VL 91A BP 108 EP 114 DI 10.2106/JBJS.H.01382 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 405RX UT WOS:000263243000025 ER PT J AU Guitton, TG Doornberg, JN Raaymakers, ELFB Ring, D Kloen, P AF Guitton, Thierry G. Doornberg, Job N. Raaymakers, Ernst L. F. B. Ring, David Kloen, Peter TI Fractures of the Capitellum and Trochlea SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID HUMERUS; ELBOW; DISLOCATION; HEAD AB Background: Recent work has established that apparently isolated fractures of the capitellum are often more complex and involve the lateral epicondyle, trochlea, and posterior aspect of the distal part of the humerus. We assessed the experience with operative stabilization of fractures of the capitellum and trochlea at one level-I trauma center over a twenty-eight-year period. Methods: Thirty classifiable partial articular fractures involving the capitellum and trochlea were included in the study. Twenty-seven patients were followed for a minimum of twelve months, and fourteen patients returned for long-term follow-up at a median of seventeen years. The early and long-term results were evaluated according to the Broberg and Morrey Functional Rating Index. The long-term results were also evaluated according to the Mayo Elbow Performance Index (MEPI), the American Shoulder and Elbow Surgeons (ASES) score, and the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire. Results: Eighteen patients (67%) had one or more subsequent surgical procedures, and eight of these patients had the procedure to address surgical complications. Five of the eight patients with complications and ten additional patients underwent routine removal of implants; these fifteen patients included twelve of the fourteen patients in the long-term cohort. In addition to the fracture of the distal part of the humerus, four patients had a dislocation of the elbow; three, a fracture of the olecranon or the proximal part of the ulna; and two, a fracture of the radial head. The median arc of flexion improved from 1061 at the time of early follow-up to 1190 at the time of long-term follow-up (p < 0.05). In the group of fourteen patients with long-term follow-up, the median Broberg and Morrey score was 93 points at the time of early follow-up and 95 points at the time of late follow-up. The functional results were worse for patients with a Type-3 fracture, as classified with the system of Dubberley et al., than they were for those with a Type-1 fracture. The fourteen patients with long-term follow-up had a median MEN of 98 points, a median ASES score of 88 points, and a median DASH score of 8 points; nine of the fourteen patients had radiographic signs of arthrosis. Conclusions: The vast majority of what appear to be capitellar fractures are actually complex fractures of the articular surface involving both the capitellum and the trochlea. More complex fractures have worse functional results; however, the functional results of operative treatment seem to be durable over time. C1 [Guitton, Thierry G.; Doornberg, Job N.; Raaymakers, Ernst L. F. B.; Ring, David; Kloen, Peter] Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands. RP Guitton, TG (reprint author), Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org; p.Kloen@amc.uva.nl OI Guitton, Thierry/0000-0002-2599-1985 NR 26 TC 18 Z9 26 U1 0 U2 7 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD FEB PY 2009 VL 91A IS 2 BP 390 EP 397 DI 10.2106/JBJS.G.01660 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 403LA UT WOS:000263082900016 PM 19181983 ER PT J AU Elhassan, B Ozbaydar, M Diller, D Higgins, LD Warner, JJP AF Elhassan, Bassem Ozbaydar, Mehmet Diller, David Higgins, Lawrence D. Warner, Jon J. P. TI Soft-Tissue Resurfacing of the Glenoid in the Treatment of Glenohumeral Arthritis in Active Patients Less Than Fifty Years Old SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID TOTAL SHOULDER ARTHROPLASTY; ARTHROSCOPIC DEBRIDEMENT; OSTEOARTHRITIS; HEMIARTHROPLASTY; JOINT; MULTICENTER; MANAGEMENT; SURGERY; LESIONS AB Background: Soft-tissue resurfacing of the glenoid, with arthroplasty of the humeral head, has been proposed as a viable treatment option for younger patients with symptomatic osteoarthritis of the shoulder. The purpose of this study was to evaluate our results with soft-tissue resurfacing of the glenoid in patients with glenohumeral arthritis who were less than fifty years of age, as we were concerned that this type of procedure was leading to poor outcomes. Methods: Between 2000 and 2006, thirteen patients with an average age of thirty-four years underwent soft-tissue resurfacing of the glenoid and humeral head arthroplasty. Achilles tendon allograft was used in eleven patients; fascia lata autograft, in one; and anterior shoulder joint capsule, in one. Three patients had resurfacing of the humeral head with a stemless resurfacing implant, and ten patients had a hemiarthroplasty. The patients were followed for a minimum of two years or until failure, and the duration of follow-up averaged forty-eight months. The results were graded with a visual analog pain scale, the subjective shoulder value, and the Constant and Murley score. Radiographic review was performed in order to determine the degree of joint space loss and glenoid erosion. Results: Ten of the thirteen patients required a revision total shoulder arthroplasty at a mean of fourteen months (range, six to thirty-four months) postoperatively. The principal reasons for revision were persistent pain and a decreased range of motion. Radiographic evaluation at the time of the revision surgery demonstrated loss of joint space and glenoid erosion in all cases. At the revision surgery, the allograft was found to be absent, and thick scar tissue, which may have been a graft remnant, was found at the perimeter of the glenoid. Of the three patients who did not have a revision arthroplasty, one had good function, pain relief, and an improved range of motion; however, the postoperative course of the other two was complicated by infection. One of them had a salvage with early irrigation and debridement as well as intravenous antibiotics, whereas the other underwent resection arthroplasty because of persistent infection. Conclusions: Soft-tissue resurfacing of the glenoid with an Achilles tendon allograft combined with humeral head arthroplasty is nota reliable method of treatment of glenohumeral arthritis in an active patient younger than fifty years of age, as the clinical outcome is poor. Moreover, we found no evidence that the graft acts as a durable bearing surface. C1 [Elhassan, Bassem] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg,Div Shoulder Surg, Boston, MA 02114 USA. RP Elhassan, B (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg,Div Shoulder Surg, 55 Fruit St, Boston, MA 02114 USA. EM mozbaydar@partners.org; ddiller@partners.org; ldhiggins@partners.org; jwarner@partners.org RI Ozbaydar, Mehmet/D-7391-2016 NR 32 TC 43 Z9 43 U1 0 U2 1 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD FEB PY 2009 VL 91A IS 2 BP 419 EP 424 DI 10.2106/JBJS.H.00318 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 403LA UT WOS:000263082900019 PM 19181986 ER PT J AU Goebel, JR Doering, LV Evangelista, LS Nyamathi, AM Maliski, SL Asch, SM Sherbourne, CD Shugarman, LR Lanto, AB Cohen, A Lorenz, KA AF Goebel, Joy R. Doering, Lynn V. Evangelista, Lorraine S. Nyamathi, Adeline M. Maliski, Sally L. Asch, Steven M. Sherbourne, Cathy D. Shugarman, Lisa R. Lanto, Andy B. Cohen, Angela Lorenz, Karl A. TI A Comparative Study of Pain in Heart Failure and Non-Heart Failure Veterans SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE Palliative care; non-malignant pain; chronic pain; symptoms ID QUALITY-OF-LIFE; PALLIATIVE CARE; CARDIAC-FAILURE; HEALTH; COMMUNITY; SYMPTOMS; DEPRESSION; MANAGEMENT; DISEASE; ASSOCIATION AB Background: Progress has been made in addressing pain in specific diseases such as cancer, but less attention has focused on understanding pain in nonmalignant states, including heart failure (HF). Methods and Results: From March 2006 to June 2007, 672 veterans were surveyed and scores for the Brief Pain Inventory, pain distress, clinically significant pain levels (moderate to severe pain), and pain locations were compared using univariate and multivariate models. Fifteen percent of the final sample had HF (95/634). In our study, the HF patients were older (P < .000), reported lower levels of general health (P = .018), had more co-morbidities (P < .000), were more likely to have a history of cancer (P = .035), and suffered more chest pain and fewer headaches (P = .026, P = .03, respectively) than their non-HF cohorts. When controlling for age, co-morbidity and cancer disorders, HF and non-HF patients did not differ in pain severity, interference, distress or locations. Of the patients Currently experiencing pain, 67.3% of HF patients and 68.4% of non-HF patients rated their pain as moderate or severe (pain >= 4 on a 0 to 10 scale). Conclusions: Although HF has not been identified as a painful condition, this study suggests the burden of pain is significant for both HF and non-HF ambulatory care patients. (J Cardiac Fail 2009:15:24-30) C1 [Goebel, Joy R.] Calif State Univ Long Beach, Dept Nursing, Long Beach, CA 90840 USA. [Doering, Lynn V.; Evangelista, Lorraine S.; Nyamathi, Adeline M.; Maliski, Sally L.] Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90024 USA. [Asch, Steven M.; Sherbourne, Cathy D.; Shugarman, Lisa R.; Lorenz, Karl A.] RAND Corp, Santa Monica, CA USA. [Asch, Steven M.; Lorenz, Karl A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Asch, Steven M.; Lanto, Andy B.; Cohen, Angela; Lorenz, Karl A.] Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Goebel, JR (reprint author), Calif State Univ Long Beach, Dept Nursing, 1250 Bellflower Blvd, Long Beach, CA 90840 USA. OI Cohen, Angela B./0000-0002-0620-1909 FU Veterans Administration Health Services Research and Development [IIR03-150]; VA HSR&D Career Development Award FX Supported by a grant (IIR03-150) from the Veterans Administration Health Services Research and Development. Dr. Karl Lorenz was supported by a VA HSR&D Career Development Award. NR 64 TC 10 Z9 10 U1 2 U2 3 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 FEB PY 2009 VL 15 IS 1 BP 24 EP 30 DI 10.1016/j.cardfail.2008.09.002 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 408NJ UT WOS:000263441400004 PM 19181290 ER PT J AU Shiotani, B Zou, L AF Shiotani, Bunsyo Zou, Lee TI ATR signaling at a glance SO JOURNAL OF CELL SCIENCE LA English DT Article ID DNA-DAMAGE CHECKPOINT; DOUBLE-STRAND BREAKS; CELL-CYCLE; END RESECTION; HOMOLOGOUS RECOMBINATION; ACTIVATION; REPLICATION; CLASPIN; CHK1; PHOSPHORYLATION C1 [Shiotani, Bunsyo; Zou, Lee] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Zou, Lee] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Zou, L (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. EM zou.lee@mgh.harvard.edu FU NIH FX We apologize to those researchers whose work could not be cited due to space constraints. L. Z. is supported by a grant from the NIH. Deposited in PMC for release after 12 months. NR 66 TC 24 Z9 25 U1 1 U2 5 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD FEB 1 PY 2009 VL 122 IS 3 BP 301 EP 304 DI 10.1242/jcs.035105 PG 4 WC Cell Biology SC Cell Biology GA 396HE UT WOS:000262582000001 PM 19158338 ER PT J AU Lopez-Larson, M Michael, ES Terry, JE Breeze, JL Hodge, SM Tang, L Kennedy, DN Moore, CM Makris, N Caviness, VS Frazier, JA AF Lopez-Larson, Melissa Michael, Emily S. Terry, Janine E. Breeze, Janis L. Hodge, Steven M. Tang, Lena Kennedy, David N. Moore, Constance M. Makris, Nikos Caviness, Verne S. Frazier, Jean A. TI Subcortical Differences among Youths with Attention-Deficit/Hyperactivity Disorder Compared to Those with Bipolar Disorder With and Without Attention-Deficit/Hyperactivity Disorder SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID DEFICIT-HYPERACTIVITY DISORDER; VOXEL-BASED MORPHOMETRY; GRAY-MATTER VOLUME; BASAL GANGLIA; YOUNG-ADULTS; HUMAN BRAIN; ADOLESCENTS; AMYGDALA; CHILDREN; MRI AB Introduction: A significant number of children with bipolar disorder (BP) have co-morbid attention-deficit/hyperactivity disorder (ADHD). It is unknown if these children have neuroimaging findings unique to their co-morbid presentation, or if their brain findings are similar to children diagnosed with BP alone. Method: Fifty three children with Diagnostic and Statistical Manual of Mental Disorders, 4(th) edition (DSM-IV) BP (23 with ADHD, 30 without), 29 healthy controls (HC), and 23 children with ADHD, similar in sex and age, had magnetic resonance imaging (MRI) scans on a 1.5T GE scanner. Volumetric assessments were performed for basal ganglia and limbic subcortical structures. Results: Youths with ADHD had smaller caudate and putamen volumes compared to both BP groups and they had moderately smaller total amygdala volumes compared to the other three groups. Youths with BP+ADHD had moderately larger nucleus accumbens volumes than HC, and females in both BP groups had smaller hippocampal volumes compared to ADHD and HC. No differences were found between the BP and BP+ADHD groups. Conclusion: These data suggest that morphometric subcortical volumes in youths with BP+ADHD are more similar to those in youths with BP. They do not share subcortical neuroanatomic correlates with the ADHD group. These findings suggest that BP+ADHD is a subtype of pediatric BP rather than severe ADHD. C1 [Lopez-Larson, Melissa; Terry, Janine E.] Univ Utah, Inst Brain, Salt Lake City, UT 84108 USA. [Lopez-Larson, Melissa] Univ Utah, Sch Med, Dept Psychiat, Salt Lake City, UT 84108 USA. [Michael, Emily S.; Breeze, Janis L.] Cambridge Hlth Alliance, Child & Adolescent Neuropsychiat Res Program, Cambridge, MA USA. [Breeze, Janis L.; Moore, Constance M.; Makris, Nikos; Caviness, Verne S.] Harvard Univ, Sch Med, Boston, MA USA. [Hodge, Steven M.; Tang, Lena; Kennedy, David N.; Makris, Nikos; Caviness, Verne S.] Massachusetts Gen Hosp, Ctr Morphometr Anal, Charlestown, MA USA. [Hodge, Steven M.; Kennedy, David N.] UMASS Med Sch, Div Neuroinformat, Dept Psychiat, Worcester, MA USA. [Moore, Constance M.] McLean Hosp, Brain Imaging Ctr, Belmont, MA 02178 USA. [Kennedy, David N.; Makris, Nikos; Caviness, Verne S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Frazier, Jean A.] UMASS Mem Med Ctr, Div Child & Adolescent Psychiat, Worcester, MA USA. [Frazier, Jean A.] UMASS Med Sch, Child & Adolescent Neurodev Initiat, Worcester, MA USA. RP Lopez-Larson, M (reprint author), Univ Utah, Inst Brain, 383 Colorow Dr, Salt Lake City, UT 84108 USA. EM Melissa.Lopez-Larson@hsc.utah.edu RI Kennedy, David/H-3627-2012 FU National Institutes of Health [K08 MH01573, U24 RR021382, K01 MH01798]; American Psychiatric Association's Program for Minority Research Training in Psychiatry [5T32 MH19126]; Harvard Medical School's Dupont-Warren Fellowship FX This work was supported by several research grants from the National Institutes of Health: K08 MH01573 to J.A.F., U24 RR021382 to D.N.K., and K01 MH01798 to C. M. M.; and training awards through the American Psychiatric Association's Program for Minority Research Training in Psychiatry (5T32 MH19126) and Harvard Medical School's Dupont-Warren Fellowship to M. L. L. NR 48 TC 29 Z9 30 U1 3 U2 4 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD FEB PY 2009 VL 19 IS 1 BP 31 EP 39 DI 10.1089/cap.2008.041 PG 9 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 415DC UT WOS:000263913500005 PM 19232021 ER PT J AU Redden, L DelBello, M Wagner, KD Wilens, TE Malhotra, S Wozniak, P Vigna, NV Greco, N Kovacs, X Abi-Saab, W Saltarelli, M AF Redden, Laura DelBello, Melissa Wagner, Karen Dineen Wilens, Timothy E. Malhotra, Shishuka Wozniak, Patricia Vigna, Namita V. Greco, Nicholas Kovacs, Xenia Abi-Saab, Walid Saltarelli, Mario CA Depakote ER Pediat Mania Grp TI Long-Term Safety of Divalproex Sodium Extended-Release in Children and Adolescents with Bipolar I Disorder SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID PLASMA AMMONIA; RATING-SCALE; ACUTE MANIA; PLACEBO; RELIABILITY; VALPROATE; VALIDITY; IMPACT; LITHIUM; TRIAL AB Objective: The objective of this open-label study was to assess the safety of divalproex sodium extended-release in the treatment of children and adolescents with acute mania associated with bipolar I disorder. Methods: This was a 6-month, Phase 3, open-label study in healthy subjects aged 9-17 years with a current Diagnostic and Statistical Manual of Mental Disorders, 4(th) edition, Text Revision (DSM-IV-TR) diagnosis of bipolar I disorder manic or mixed episode. Divalproex sodium extended-release (DVPX-ER) was initiated at 15 mg/kg per day on day 1 (not to exceed 750 mg/day) with increases allowed to a maximum of 35 mg/kg per day. Study visits were conducted on day 1 and at months 1, 2, 3, and 6. Assessments included standard safety evaluations and appropriate rating scales for clinical effect. Results: A total of 226 subjects were enrolled; 109 subjects completed the study. The most common adverse events were weight gain (16%), nausea (9%), and increased appetite (8%). Nonsymptomatic elevations of mean ammonia levels in plasma were observed. The mean Young Mania Rating Scale (YMRS) decreased 12.4 from baseline to final visit; small improvements were seen in behavior and caregiver stress ratings. Conclusions: DVPX-ER was generally well tolerated in children and adolescents with acute mania, with a side-effect profile similar to that observed in adults. C1 [Redden, Laura; Vigna, Namita V.; Greco, Nicholas; Kovacs, Xenia; Abi-Saab, Walid; Saltarelli, Mario] Abbott, Abbott Pk, IL 60064 USA. [DelBello, Melissa] Univ Cincinnati, Med Ctr, Cincinnati, OH 45267 USA. [Wagner, Karen Dineen] Univ Texas Galveston, Med Branch, Galveston, TX 77550 USA. [Wilens, Timothy E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wozniak, Patricia] Abbott, Bannockburn, IL USA. RP Redden, L (reprint author), Abbott, 100 Abbott Pk Rd, Abbott Pk, IL 60064 USA. EM Laura.Redden@abbott.com FU Muriel Cunningham FX Financial support for the study and manuscript was provided by Abbott. Abbott personnel performed statistical analyses on the data, and the paper was written by the authors in collaboration with an Abbott-funded medical writer, Muriel Cunningham. NR 36 TC 14 Z9 14 U1 1 U2 5 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD FEB PY 2009 VL 19 IS 1 BP 83 EP 89 DI 10.1089/cap.2008.0106 PG 7 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 415DC UT WOS:000263913500010 PM 19232026 ER PT J AU Rosman, NP Douglass, LM Sharif, UM Paolini, J AF Rosman, N. Paul Douglass, Laurie M. Sharif, Uzma M. Paolini, Jan TI The Neurology of Benign Paroxysmal Torticollis of Infancy: Report of 10 New Cases and Review of the Literature SO JOURNAL OF CHILD NEUROLOGY LA English DT Review DE torticollis; paroxysmal; migraine; motor development ID CLINICAL-FEATURES; MIGRAINE; CHILDHOOD; PROGNOSIS AB Benign paroxysmal torticollis is an under-recognized cause of torticollis of early infancy. The attacks usually last for less than 1 week, recur from every few days to every few months, improve by age 2 years, and end by age 3. There very frequently is a family history of migraine. We did a detailed analysis of 10 cases of benign paroxysmal torticollis, seen over 5 years, and compared our findings with those in the 103 cases in the literature. Detailed neurodevelopmental assessments, available only in our cases, showed accompanying gross motor delays in 5/10 children, with additional fine motor delays in 3/5. As the benign paroxysmal torticollis improved, so did the gross motor delays in 3/5, and the fine motor delays in 1/3. In all of our cases, at least 2 other family members had migraine. Benign paroxysmal torticollis is likely an age-sensitive, migraine-related disorder, commonly accompained by delayed motor development. C1 [Rosman, N. Paul; Douglass, Laurie M.] Boston Med Ctr, Dept Pediat, Div Pediat Neurol, Boston, MA 02118 USA. [Rosman, N. Paul; Douglass, Laurie M.] Boston Med Ctr, Dept Neurol, Div Pediat Neurol, Boston, MA 02118 USA. [Rosman, N. Paul; Douglass, Laurie M.; Sharif, Uzma M.; Paolini, Jan] Tufts Med Ctr, Boston, MA USA. [Sharif, Uzma M.] Childrens Hosp Wisconsin, Milwaukee, WI 53201 USA. [Paolini, Jan] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Rosman, NP (reprint author), Boston Med Ctr, Dept Pediat, Div Pediat Neurol, Pl Dowling 3 S, Boston, MA 02118 USA. EM npaul.rosman@bmc.org NR 31 TC 31 Z9 31 U1 0 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0883-0738 J9 J CHILD NEUROL JI J. Child Neurol. PD FEB PY 2009 VL 24 IS 2 BP 155 EP 160 DI 10.1177/0883073808322338 PG 6 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 399RY UT WOS:000262818200003 PM 19182151 ER PT J AU Lowenthal, MS Sadow, PM Raut, C Metzler, EC AF Lowenthal, Marissa S. Sadow, Peter M. Raut, Chandrajit Metzler, Elise C. TI Intraoperative diagnosis of a functional paraganglioma presenting as a gastrointestinal stromal cell tumor (GIST) SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Article DE Anesthesia; Gastrointestinal stromal tumor; Paraganglioma; Takotsubo cardiomyopathy ID TAKOTSUBO CARDIOMYOPATHY; PHEOCHROMOCYTOMA; CT AB The case of a young woman with a history of resolved Takotsubo cardiomyopathy, anxiety and abdominal mass is presented. Pathologic examination confirmed paraganglioma. Despite catecholamine secretion and preoperative beta-blockers, cardiomyopathy did not recur. (c) 2009 published by Elsevier Inc. C1 [Lowenthal, Marissa S.; Metzler, Elise C.] Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. [Lowenthal, Marissa S.; Raut, Chandrajit; Metzler, Elise C.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Raut, Chandrajit] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Sadow, Peter M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Sadow, Peter M.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Metzler, EC (reprint author), Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, 75 Francis St, Boston, MA 02115 USA. EM emetzler@partners.org NR 14 TC 3 Z9 3 U1 1 U2 1 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 FEB PY 2009 VL 21 IS 1 BP 57 EP 60 DI 10.1016/j.jclinane.2008.06.026 PG 4 WC Anesthesiology SC Anesthesiology GA 413NY UT WOS:000263801000012 PM 19232943 ER PT J AU Bateman, BT Alston, TA AF Bateman, Brian T. Alston, Theodore A. TI Commonly used eponyms in anesthesia SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Article DE Anesthesiology; Biography, etymology, history ID DIFFICULT TRACHEAL INTUBATION; SELLICK MANEUVER; CRICOID PRESSURE; CLINICAL SIGN; TRENDELENBURG; CATHETER AB Names with eponym status in present-day anesthesia include Apgar, Bier, Bovie. Esmarch, Fick. Foley, Ganz, Hofmann. Huber, Joule, Luer, Macintosh. Magill, Mallampati, Miller, Ovassapian Pascal, Ringer, Seldinger, Sellick, Swan, Trendelenburg, Tuohy, Valsalva, and Yankauer. A discussion of the people behind the eponyms, which may make these commonly used terms more interesting, and provides a sense of the history of the specialty of anesthesia, is presented. (c) 2009 Elsevier Inc. All rights reserved. C1 [Alston, Theodore A.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02115 USA. RP Alston, TA (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. EM talston@partners.org NR 41 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 0952-8180 EI 1873-4529 J9 J CLIN ANESTH JI J. Clin. Anesth. PD FEB PY 2009 VL 21 IS 1 BP 67 EP 71 DI 10.1016/j.jclinane.2008.05.027 PG 5 WC Anesthesiology SC Anesthesiology GA 413NY UT WOS:000263801000015 PM 19232946 ER PT J AU Khan, AA Bilezikian, JP Potts, JT AF Khan, Aliya A. Bilezikian, John P. Potts, John T., Jr. CA Third Int Workshop Asymptomatic TI The Diagnosis and Management of Asymptomatic Primary Hyperparathyroidism Revisited SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material C1 [Khan, Aliya A.] McMaster Univ, Dept Med, Hamilton, ON L8S 4L8, Canada. [Bilezikian, John P.] Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY 10032 USA. [Bilezikian, John P.] Columbia Univ, Coll Phys & Surg, Dept Pharmacol, New York, NY 10032 USA. [Potts, John T., Jr.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Khan, AA (reprint author), McMaster Univ, 331 Sheddon Ave,209, Oakville, ON L6J 5T4, Canada. EM aliya@mcmaster.ca FU NIDDK NIH HHS [R01 DK032333] NR 4 TC 43 Z9 49 U1 0 U2 0 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 FEB PY 2009 VL 94 IS 2 BP 333 EP 334 DI 10.1210/jc.2008-1757 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 403HC UT WOS:000263072700001 PM 19193907 ER PT J AU Bilezikian, JP Khan, AA Potts, JT AF Bilezikian, John P. Khan, Aliya A. Potts, John T., Jr. CA Third Int Workshop Management TI Guidelines for the Management of Asymptomatic Primary Hyperparathyroidism: Summary Statement from the Third International Workshop SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material AB Objective: Asymptomatic primary hyperparathyroidism (PHPT) is a common clinical problem. The purpose of this report is to guide the use of diagnostics and management for this condition in clinical practice. Participants: Interested professional societies selected representatives for the consensus committee and provided funding for a one-day meeting. A subgroup of this committee set the program and developed key questions for review. Consensus was established at a closed meeting that followed and at subsequent discussions. Evidence: Each question was addressed by a relevant literature search (on PubMed), and the data were presented for discussion at the group meeting. Consensus Process: Consensus was achieved by a group meeting. Statements were prepared and reviewed by all authors who represented the Planning Committee and the participating professional societies. (J Clin Endocrinol Metab 94: 335-339, 2009) C1 [Bilezikian, John P.] Columbia Univ, Dept Med, Div Endocrinol, Coll Phys & Surg, New York, NY 10032 USA. [Khan, Aliya A.] McMaster Univ, Hamilton, ON L8S 4L8, Canada. [Potts, John T., Jr.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Bilezikian, JP (reprint author), Columbia Univ, Dept Med, Div Endocrinol, Coll Phys & Surg, 630 W 168th St,MB 92, New York, NY 10032 USA. EM jpb2@columbia.edu FU NIDDK NIH HHS [R01 DK032333] NR 4 TC 394 Z9 411 U1 2 U2 10 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 FEB PY 2009 VL 94 IS 2 BP 335 EP 339 DI 10.1210/jc.2008-1763 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 403HC UT WOS:000263072700002 PM 19193908 ER PT J AU Moore, AF Jablonski, KA Mason, CC McAteer, JB Arakaki, RF Goldstein, BJ Kahn, SE Kitabchi, AE Hanson, RL Knowler, WC Florez, JC AF Moore, Allan F. Jablonski, Kathleen A. Mason, Clinton C. McAteer, Jarred B. Arakaki, Richard F. Goldstein, Barry J. Kahn, Steven E. Kitabchi, Abbas E. Hanson, Robert L. Knowler, William C. Florez, Jose C. CA Diabet Prevention Program Res Grp TI The Association of ENPP1 K121Q with Diabetes Incidence Is Abolished by Lifestyle Modification in the Diabetes Prevention Program SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID MEMBRANE GLYCOPROTEIN PC-1; INSULIN-RESISTANCE; GENETIC SUSCEPTIBILITY; NO EVIDENCE; POLYMORPHISM; GLUCOSE; OBESITY; VARIANTS; RECEPTOR; RISK AB Context: Insulin resistance is an important feature of type 2 diabetes. Ectoenzyme nucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) inhibits insulin signaling, and a recent meta-analysis reported a nominal association between the Q allele in the K121Q(rs1044498) single nucleotide polymorphism in its gene ENPP1 and type 2 diabetes. Objective and Intervention: We examined the impact of this polymorphism on diabetes incidence as well as insulin secretion and sensitivity at baseline and after treatment with a lifestyle intervention or metformin vs. placebo in the Diabetes Prevention Program (DPP). Design, Setting, Participants, and Outcome: We genotyped ENPP1 K121Q in 3548 DPP participants and performed Cox regression analyses using genotype, intervention, and interactions as predictors of diabetes incidence. Results: Fasting glucose and glycated hemoglobin were higher in QQ homozygotes at baseline (P < 0.001 for both). There was a significant interaction between genotype at rs1044498 and intervention under the dominant model (P = 0.03). In analyses stratified by treatment arm, a positive association with diabetes incidence was found in Q allele carriers compared to KK homozygotes [hazard ratio (HR), 1.38; 95% confidence interval (CI), 1.08-1.76; P = 0.009] in the placebo arm (n = 996). Lifestyle modification eliminated this increased risk. These findings persisted after adjustment for body mass index and race/ethnicity. Association of ENPP1 K121Q genotype with diabetes incidence under the additive and recessive genetic models showed consistent trends [HR, 1.10(95% CI, 0.99-1.23), P = 0.08; and HR, 1.16 (95% CI, 0.92-1.45), P = 0.20, respectively] but did not reach statistical significance. Conclusions: ENPP1 K121Q is associated with increased diabetes incidence; the DPP lifestyle intervention eliminates this increased risk. (J Clin Endocrinol Metab 94: 449-455, 2009) C1 [Moore, Allan F.; McAteer, Jarred B.; Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Moore, Allan F.; McAteer, Jarred B.; Florez, Jose C.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Moore, Allan F.; McAteer, Jarred B.; Florez, Jose C.] Harvard & Massachusetts Inst Technol, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Moore, Allan F.; Florez, Jose C.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Jablonski, Kathleen A.] George Washington Univ, Ctr Biostat, Rockville, MD 20852 USA. [Mason, Clinton C.; Hanson, Robert L.; Knowler, William C.] NIDDKD, Phoenix, AZ 85014 USA. [Arakaki, Richard F.] Univ Hawaii, Dept Med Diabet & Endocrinol, Honolulu, HI 96813 USA. [Goldstein, Barry J.] Thomas Jefferson Univ, Jefferson Med Coll, Div Endocrinol Diabet & Metab Dis, Philadelphia, PA 19107 USA. [Kahn, Steven E.] Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Kitabchi, Abbas E.] Univ Tennessee, Hlth Sci Ctr, Div Endocrinol Diabet & Metab, Memphis, TN 38163 USA. RP Florez, JC (reprint author), George Washington Univ, Diabet Prevent Program, Coordinating Ctr, 6110 Execut Blvd,Suite 750, Rockville, MD 20852 USA. EM dppmail@biostat.bsc.gwu.edu RI Hanson, Robert/O-3238-2015; OI Hanson, Robert/0000-0002-4252-7068; Kahn, Steven/0000-0001-7307-9002 FU National Institutes of Health [R01 DK072041, K23 DK65978-05]; Indian Health Service; Office of Research on Minority Health; National Institute of Child Health and Human Development; National Institute on Aging, the Centers for Disease Control and Prevention; Office of Research on Women's Health; American Diabetes Association FX The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health provided funding to the clinical centers and the Coordinating Center for the design and conduct of the study and for collection, management, analysis, and interpretation of the data. The Southwestern American Indian Centers were supported directly by the NIDDK and the Indian Health Service. The General Clinical Research Center Program, National Center for Research Resources, supported data collection at many of the clinical centers. Funding for data collection and participant support was also provided by the Office of Research on Minority Health, the National Institute of Child Health and Human Development, the National Institute on Aging, the Centers for Disease Control and Prevention, Office of Research on Women's Health, and the American Diabetes Association. Bristol-Myers Squibb and Parke-Davis provided medication. This research was also supported, in part, by the intramural research program of the NIDDK. LifeScan Inc., Health-O-Meter, Hoechst Marion Roussel, Inc., Merck-Medco Managed Care, Inc., Merck and Co., Nike Sports Marketing, Slim Fast Foods Co., and Quaker Oats Co. donated materials, equipment, or medicines for concomitant conditions. McKesson BioServices Corp., Matthews Media Group, Inc., and the Henry M. Jackson Foundation provided support services under subcontract with the Coordinating Center. The opinions expressed are those of the investigators and do not necessarily reflect the views of the Indian Health Service or other funding agencies. A complete list of centers, investigators, and staff can be found in the Appendix(published as supplemental data on The Endocrine Society's Journals Online web site at http://jcem.endojournals.org). NR 36 TC 29 Z9 30 U1 0 U2 0 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 FEB PY 2009 VL 94 IS 2 BP 449 EP 455 DI 10.1210/jc.2008-1583 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 403HC UT WOS:000263072700019 PM 19017751 ER PT J AU Wesseling-Perry, K Pereira, RC Wang, HJ Elashoff, RM Sahney, S Gales, B Juppner, H Salusky, IB AF Wesseling-Perry, Katherine Pereira, Renata C. Wang, Hejing Elashoff, Robert M. Sahney, Shobha Gales, Barbara Jueppner, Harald Salusky, Isidro B. TI Relationship between Plasma Fibroblast Growth Factor-23 Concentration and Bone Mineralization in Children with Renal Failure on Peritoneal Dialysis SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID TUMOR-INDUCED OSTEOMALACIA; VITAMIN-D METABOLISM; CALCITRIOL THERAPY; SECONDARY HYPERPARATHYROIDISM; SERUM CONCENTRATIONS; PEDIATRIC-PATIENTS; PREDICTIVE-VALUE; KIDNEY-DISEASE; HYP MICE; FGF23 AB Context: Fibroblast growth factor (FGF)-23 is produced in bone, and circulating levels are markedly elevated in patients with end-stage kidney disease, but the relationship between plasma levels of FGF-23 and bone histology in dialysis patients with secondary hyperparathyroidism is unknown. Objective: The aim of the study was to evaluate the correlation between plasma levels of FGF-23 and bone histology in pediatric patients with end- stage kidney disease who display biochemical evidence of secondary hyperparathyroidism. Design: We performed a cross-sectional analysis of the relationship between plasma FGF-23 levels and bone histomorphometry. Setting: The study was conducted in a referral center. Study Participants: Participants consisted of forty-nine pediatric patients who were treated with maintenance peritoneal dialysis and who had serum PTH levels (1st generation Nichols assay) greater than 400 pg/ml. Intervention: There were no interventions. Main Outcome Measure: Plasma FGF-23 levels and bone histomorphometry were measured. Results: No correlation existed between values of PTH and FGF-23. Bone formation rates correlated with PTH (r=0.44; P < 0.01), but not with FGF-23. Higher FGF-23 concentrations were associated with decreased osteoid thickness (r=-0.49; P < 0.01) and shorter osteoid maturation time (r=-0.48; P < 0.01). Conclusions: High levels of FGF-23 are associated with improved indices of skeletal mineralization in dialyzed pediatric patients with high turnover renal osteodystrophy. Together with other biomarkers, FGF-23 measurements may indicate skeletal mineralization status in this patient population. (J Clin Endocrinol Metab 94: 511-517, 2009) C1 [Wesseling-Perry, Katherine] Univ Calif Los Angeles, David Geffen Sch Med, Div Pediat Nephrol, Dept Pediat, Los Angeles, CA 90095 USA. [Wesseling-Perry, Katherine; Pereira, Renata C.; Gales, Barbara; Salusky, Isidro B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biomath, Los Angeles, CA 90095 USA. [Sahney, Shobha] Loma Linda Univ, Dept Pediat, Loma Linda, CA 92354 USA. [Jueppner, Harald] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02115 USA. [Jueppner, Harald] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Wesseling-Perry, K (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Pediat Nephrol, Dept Pediat, A2-383 MDCC,10833 LeConte Blvd, Los Angeles, CA 90095 USA. EM kwesseling@mednet.ucla.edu FU U. S. Public Health Service [DK-35423, DK-67563, MO1-RR00865]; Casey Lee Ball Foundation FX This work was supported by grants and fellowships supporting the writing of the paper: U. S. Public Health Service Grants DK-35423, DK-67563, and MO1-RR00865, as well as funds from the Casey Lee Ball Foundation. K. W.-P. is a recipient of a National Kidney Foundation Award. NR 40 TC 97 Z9 103 U1 1 U2 4 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 FEB PY 2009 VL 94 IS 2 BP 511 EP 517 DI 10.1210/jc.2008-0326 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 403HC UT WOS:000263072700028 PM 19050056 ER PT J AU Voruganti, VS Nath, SD Cole, SA Thameem, F Jowett, JB Bauer, R MacCluer, JW Blangero, J Comuzzie, AG Abboud, HE Arar, NH AF Voruganti, V. Saroja Nath, Subrata D. Cole, Shelley A. Thameem, Farook Jowett, Jeremy B. Bauer, Richard MacCluer, Jean W. Blangero, John Comuzzie, Anthony G. Abboud, Hanna E. Arar, Nedal H. TI Genetics of Variation in Serum Uric Acid and Cardiovascular Risk Factors in Mexican Americans SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID QUANTITATIVE-TRAIT LOCUS; METABOLIC SYNDROME; BLOOD-PRESSURE; LINKAGE ANALYSIS; ATHEROSCLEROSIS RISK; CHEMOKINE RECEPTOR; RENAL-DISEASE; FAMILY; HEART; HYPERURICEMIA AB Background: Elevated serum uric acid is associated with several cardiovascular disease (CVD) risk factors such as hypertension, inflammation, endothelial dysfunction, insulin resistance, dyslipidemia, and obesity. However, the role of uric acid as an independent risk factor for CVD is not yet clear. Objective: The aim of the study was to localize quantitative trait loci regulating variation in serum uric acid and also establish the relationship between serum uric acid and other CVD risk factors in Mexican Americans (n = 848; men = 310, women = 538) participating in the San Antonio Family Heart Study. Methods: Quantitative genetic analysis was conducted using variance components decomposition method, implemented in the software program SOLAR. Results: Mean +/- SD of serum uric acid was 5.35 +/- 1.38 mg/dl. Univariate genetic analysis showed serum uric acid and other CVD risk markers to be significantly heritable (P < 0.005). Bivariate analysis showed significant correlation of serum uric acid with body mass index, waist circumference, waist/hip ratio, total body fat, plasma insulin, serum triglycerides, high-density lipoprotein cholesterol, C-reactive protein, and granulocyte macrophage-colony stimulating factor (P < 0.05). A genome-wide scan for detecting quantitative trait loci regulating serum uric acid variation showed a significant logarithm of odds (LOD) score of 4.72 (empirical LOD score = 4.62; P < 0.00001) on chromosome 3p26. One LOD support interval contains 25 genes, of which an interesting candidate gene is chemokine receptor 2. Summary: There is a significant genetic component in the variation in serum uric acid and evidence of pleiotropy between serum uric acid and other cardiovascular risk factors. (J Clin Endocrinol Metab 94: 632-638, 2009) C1 [Voruganti, V. Saroja; Cole, Shelley A.; MacCluer, Jean W.; Blangero, John; Comuzzie, Anthony G.] SW Fdn Biomed Res, Dept Genet, San Antonio, TX 78227 USA. [Nath, Subrata D.; Thameem, Farook; Bauer, Richard; Abboud, Hanna E.; Arar, Nedal H.] Univ Texas Hlth Sci Ctr San Antonio, George OBrien Kidney Res Ctr, Div Nephrol, San Antonio, TX 78229 USA. [Nath, Subrata D.; Thameem, Farook; Bauer, Richard; Abboud, Hanna E.; Arar, Nedal H.] Univ Texas Hlth Sci Ctr San Antonio, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Jowett, Jeremy B.] Int Diabet Inst, Caulfield, Vic 3162, Australia. RP Voruganti, VS (reprint author), SW Fdn Biomed Res, Dept Genet, POB 760549, San Antonio, TX 78245 USA. EM svorugan@sfbrgenetics.org RI Jowett, Jeremy/A-3809-2009 FU San Antonio Family Heart Study; Fredric C. Bartter General Clinical Research Center; University of Texas Health Science Center at San Antonio, San Antonio, Texas [M01-RR01346] FX We thank all participants of the San Antonio Family Heart Study for their cooperation and generous participation. We also acknowledge the Fredric C. Bartter General Clinical Research Center, University of Texas Health Science Center at San Antonio, San Antonio, Texas (supported by M01-RR01346), for providing clinical support for this project. NR 48 TC 21 Z9 23 U1 0 U2 0 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 FEB PY 2009 VL 94 IS 2 BP 632 EP 638 DI 10.1210/jc.2008-0682 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 403HC UT WOS:000263072700046 PM 19001525 ER PT J AU Vardeh, D Wang, DR Costigan, M Lazarus, M Saper, CB Woolf, CJ FitzGerald, GA Samad, TA AF Vardeh, Daniel Wang, Dairong Costigan, Michael Lazarus, Michael Saper, Clifford B. Woolf, Clifford J. FitzGerald, Garret A. Samad, Tarek A. TI COX2 in CNS neural cells mediates mechanical inflammatory pain hypersensitivity in mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID PROSTAGLANDIN E-2 RELEASE; CENTRAL-NERVOUS-SYSTEM; BLOOD-BRAIN-BARRIER; PROSTANOID RECEPTORS; FORMALIN INJECTION; CYCLOOXYGENASE-2 INHIBITOR; SECONDARY HYPERALGESIA; SELECTIVE INHIBITORS; TISSUE-INJURY; EP2 SUBTYPE AB A cardinal feature of peripheral inflammation is pain. The most common way of managing inflammatory pain is to use nonsteroidal antiinflammatory agents (NSAIDs) that reduce prostanoid production, for example, selective inhibitors of COX2. Prostaglandins produced after induction of COX2 in immune cells in inflamed tissue contribute both to the inflammation itself and to pain hypersensitivity, acting on peripheral terminals of nociceptors. COX2 is also induced after peripheral inflammation in neurons in the CNS, where it aids in developing a central component of inflammatory pain hypersensitivity by increasing neuronal excitation and reducing inhibition. We engineered mice with conditional deletion of Cox2 in neurons and glial cells to determine the relative contribution of peripheral and central COX2 to inflammatory pain hypersensitivity. In these mice, basal nociceptive pain was unchanged, as was the extent of peripheral inflammation, inflammatory thermal pain hypersensitivity, and fever induced by lipopolysaccharide. By contrast, peripheral inflammation-induced COX2 expression in the spinal cord was reduced, and mechanical hypersensitivity after both peripheral soft tissue and periarticular inflammation was abolished. Mechanical pain is a major symptom of most inflammatory conditions, such as postoperative pain and arthritis, and induction of COX2 in neural cells in the CNS seems to contribute to this. C1 [Vardeh, Daniel; Costigan, Michael; Woolf, Clifford J.; Samad, Tarek A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care,Neural Plastic Res Gr, Boston, MA USA. [Wang, Dairong; FitzGerald, Garret A.] Univ Penn, Inst Translat Med & Therapeut, Philadelphia, PA USA. [Wang, Dairong; FitzGerald, Garret A.] Univ Penn, Dept Pharmacol, Philadelphia, PA USA. [Lazarus, Michael; Saper, Clifford B.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Lazarus, Michael; Saper, Clifford B.] Harvard Univ, Sch Med, Program Neurosci, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. RP Woolf, CJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 149 13th St, Charlestown, MA 02129 USA. EM cwoolf@partners.org; garret@spirit.gcrc.upenn.edu RI FitzGerald, Garret/A-4222-2010; Lazarus, Michael/G-3130-2010; OI Lazarus, Michael/0000-0003-3863-4474; Lazarus, Michael/0000-0003-4700-7894 FU NHLBI NIH HHS [HL62250, P01 HL062250]; NINDS NIH HHS [NS039518, R01 NS033987, R01 NS039518, R37 NS039518] NR 71 TC 63 Z9 67 U1 0 U2 7 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 FEB PY 2009 VL 119 IS 2 BP 287 EP 294 DI 10.1172/JCI37098 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 403LP UT WOS:000263084400009 PM 19127021 ER PT J AU Lim, G Wang, SX Zhang, Y Tian, YH Mao, JR AF Lim, Grewo Wang, Shuxing Zhang, Yi Tian, Yinghong Mao, Jianren TI Spinal leptin contributes to the pathogenesis of neuropathic pain in rodents SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID GENE-EXPRESSION; PERIPHERAL MONONEUROPATHY; PITUITARY-GLAND; ADIPOSE-TISSUE; SERUM LEPTIN; FOOD-INTAKE; RAT-BRAIN; RECEPTOR; NEURONS; SYSTEM AB Pain after nerve injury, a phenomenon referred to as neuropathic pain, is a debilitating clinical condition, but the underlying mechanisms remain unclear. As leptin, an adipocytokine produced mainly by nonneuronal tissue, has been implicated in the regulation of neuronal functions, we examined the role of leptin in neuropathic pain using a rat model of the condition chronic constriction sciatic nerve injury (CCI). We report that leptin critically contributed to pain behaviors following CCI. Specifically, spinal administration of a leptin antagonist prevented and reversed neuropathic pain behaviors in rats. Further examination revealed that levels of both leptin and the long form of the leptin receptor (Ob-Rb) were substantially increased within the ipsilateral spinal cord dorsal horn after peripheral nerve injury. Mechanistic studies showed that leptin upregulated the expression of both the spinal NMDA receptor and IL-1 beta through the JAK/STAT pathway. Furthermore, these CCI-induced behavioral and cellular responses were diminished in leptin-deficient mice and mimicked by spinal administration of exogenous leptin in naive rats. Our findings reveal a critical role for spinal leptin in the pathogenesis of neuropathic pain and suggest what we believe to be a novel form of nonneuronal and neuronal interactions in the mechanisms of pathological pain. C1 [Mao, Jianren] Harvard Univ, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Sch Med,MGH Ctr Translat Pain Res,WACC 324, Boston, MA 02115 USA. RP Mao, JR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Sch Med,MGH Ctr Translat Pain Res,WACC 324, Boston, MA 02115 USA. EM jmao@partners.org FU NIH RO1 [DE018214, DE018538, NS45681] FX This study was supported by NIH RO1 grants DE018214, DE018538, and NS45681. (to J. Mao). We would like to thank Kaiyuan Fu of Beijing University for his assistance in immunohistochemistry. NR 50 TC 41 Z9 43 U1 0 U2 3 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 FEB PY 2009 VL 119 IS 2 BP 295 EP 304 DI 10.1172/JCI36785 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 403LP UT WOS:000263084400010 PM 19139561 ER PT J AU Collins, ED Moore, CP Clay, KF Kearing, SA O'Connor, AM Llewellyn-Thomas, HA Barth, RJ Sepucha, KR AF Collins, E. Dale Moore, Caroline P. Clay, Kate F. Kearing, Stephen A. O'Connor, Annette M. Llewellyn-Thomas, Hilary A. Barth, Richard J. Sepucha, Karen R. TI Can Women With Early-Stage Breast Cancer Make an Informed Decision for Mastectomy? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 29th Annual Meeting of the Society-for-Medical-Decision-Making CY OCT 20-24, 2007 CL Pittsburgh, PA SP Soc Med Decis Making ID 20-YEAR FOLLOW-UP; CONSERVING SURGERY; RADICAL-MASTECTOMY; RANDOMIZED-TRIAL; OLDER WOMEN; THERAPY; CONSERVATION; CARCINOMA; KNOWLEDGE; CHOICE AB Purpose The purpose of this study was to measure the degree to which informed women chose mastectomy, and to reveal their reasons for this choice. Patients and Methods This was a prospective cohort study of patients radiographically and pathologically eligible for either mastectomy or breast-conserving surgery (BCS; n = 125). Participants completed questionnaires at three time points: baseline, after viewing a decision aid, and after a surgical consultation. Questionnaires assessed clinical history, preference for participation in decision making, information comprehension, values, decisional conflict, and preferred treatment. Results Of 125 participants, 44 (35%) chose mastectomy. Most understood that BCS and mastectomy offer an equivalent survival benefit (98%) and that BCS has a slightly higher local recurrence risk (63%); most accurately identified the magnitude of ipsilateral local recurrence risk (91%). Values assigned to three treatment attributes/outcomes ("remove breast for peace of mind," "avoid radiation," and "keep breast") clearly discriminated between patients choosing mastectomy or BCS. High decisional conflict scores improved after both the decision aid and surgical consultation. Conclusion Although conventional wisdom may view BCS as the preferred treatment, a notable proportion of well informed women choose mastectomy. Whereas prior studies have linked objective factors to treatment choice, this study reveals subjective preferences that underlie decision making. The systematic use of a decision aid before the surgical consultation may help women make informed, values-based decisions, while clearly reducing decisional conflict. C1 [Collins, E. Dale] Dartmouth Hitchcock Med Ctr, Norris Cotton Canc Ctr, Comprehens Breast Program, Ctr Shared Decis Making, Lebanon, NH 03756 USA. Dartmouth Med Sch, Dartmouth Inst Hlth Policy & Clin Practice, Hanover, NH USA. Massachusetts Gen Hosp, Hlth Decis Res Unit, Boston, MA 02114 USA. Univ Ottawa, Fac Hlth Sci, Sch Nursing, Ottawa, ON, Canada. RP Collins, ED (reprint author), Dartmouth Hitchcock Med Ctr, Norris Cotton Canc Ctr, Comprehens Breast Program, Ctr Shared Decis Making, 1 Med Ctr Dr, Lebanon, NH 03756 USA. EM e.dale.collins@hitchcock.org NR 29 TC 112 Z9 115 U1 1 U2 11 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 FEB 1 PY 2009 VL 27 IS 4 BP 519 EP 525 DI 10.1200/JCO.2008.16.6215 PG 7 WC Oncology SC Oncology GA 400UK UT WOS:000262894400009 PM 19114703 ER PT J AU Fidias, PM Dakhil, SR Lyss, AP Loesch, DM Waterhouse, DM Bromund, JL Chen, RQ Hristova-Kazmierski, M Treat, J Obasaju, CK Marciniak, M Gill, J Schiller, JH AF Fidias, Panos M. Dakhil, Shaker R. Lyss, Alan P. Loesch, David M. Waterhouse, David M. Bromund, Jane L. Chen, Ruqin Hristova-Kazmierski, Maria Treat, Joseph Obasaju, Coleman K. Marciniak, Martin Gill, John Schiller, Joan H. TI Phase III Study of Immediate Compared With Delayed Docetaxel After Front-Line Therapy With Gemcitabine Plus Carboplatin in Advanced Non-Small-Cell Lung Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-05, 2007 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) ID PLATINUM-BASED CHEMOTHERAPY; RANDOMIZED-TRIAL; SUPPORTIVE CARE; SEQUENTIAL CHEMOTHERAPY; 1ST-LINE CHEMOTHERAPY; PACLITAXEL; DURATION; MULTICENTER; SCHEDULES; CISPLATIN AB Purpose Gemcitabine plus carboplatin (GC) is active as front-line treatment for advanced non-small-cell lung cancer (NSCLC). For patients without progression, timing of second-line chemotherapy for optimum clinical benefit remains uncertain. This phase III, randomized trial assessed the efficacy and safety of docetaxel administered either immediately after GC or at disease progression. Patients and Methods The chemotherapy-nave patients enrolled had either stage IIIB NSCLC with pleural effusion or stage IV NSCLC. Gemcitabine (1,000 mg/m(2)) was administered on days 1 and 8 followed by carboplatin (area under the curve = 5) on day 1. After four 21-day cycles, patients who did not have progression were randomly assigned either to an immediate docetaxel group (docetaxel 75 mg/m2 on day 1 every 21 days, with maximum of six cycles) or to a delayed docetaxel group. The primary end point was overall survival (OS) measured from random assignment. Additional analyses included tumor response, toxicity, progression-free survival (PFS), and quality of life (QOL). Results Enrollment totaled 566 patients; 398 patients completed GC; 309 patients were randomly assigned equally to the two docetaxel treatment groups. Toxicity profiles were generally comparable for the docetaxel groups. Median PFS for immediate docetaxel (5.7 months) was significantly greater (P = .0001) than for delayed docetaxel (2.7 months). Median OS for immediate docetaxel (12.3 months) was greater than for delayed docetaxel (9.7 months), but the difference was not statistically significant (P = .0853). QOL results were not statistically different (P =. 76) between docetaxel groups. Conclusion We observed a statistically significant improvement in PFS and a nonstatistically significant increase in OS when docetaxel was administered immediately after front-line GC, without increasing toxicity or decreasing QOL. C1 [Fidias, Panos M.] Massachusetts Gen Hosp, Ctr Thorac Canc, Boston, MA 02114 USA. Penrose Canc Ctr Kansas, Wichita, KS USA. Missouri Baptist Canc Ctr, St Louis, MO USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. Oncol Hematol Care Inc, Cincinnati, OH USA. Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. RP Fidias, PM (reprint author), Massachusetts Gen Hosp, Ctr Thorac Canc, 55 Fruit St, Boston, MA 02114 USA. EM pfidias2@partners.org NR 36 TC 226 Z9 240 U1 1 U2 8 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 FEB 1 PY 2009 VL 27 IS 4 BP 591 EP 598 DI 10.1200/JCO.2008.17.1405 PG 8 WC Oncology SC Oncology GA 400UK UT WOS:000262894400019 PM 19075278 ER PT J AU Haffajee, AD Socransky, SS AF Haffajee, Anne D. Socransky, Sigmund Sidney TI Relation of body mass index, periodontitis and Tannerella forsythia SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE BMI; periodontal; subgingival plaque; Tannerella forsythia ID DNA-DNA HYBRIDIZATION; SUBGINGIVAL MICROBIOTA; METABOLIC SYNDROME; JAPANESE WOMEN; UNITED-STATES; RISK-FACTORS; OBESITY; DISEASE; ADULTS; POPULATION AB Haffajee AD, Socransky SS. Relation of body mass index, periodontitis and Tannerella forsythia. J Clin Periodontol 2009; 36: -. doi: 10.1111/j.1600-051X.2008.01356.x. To determine if there were differences in periodontal status and the composition of the subgingival microbiota in individuals who exhibited different body mass indices (BMI). One hundred and twenty-one periodontally healthy/gingivitis and 574 chronic periodontitis subjects had height and weight determined and were measured for probing pocket depth, clinical attachment level, bleeding on probing, gingival redness and presence of visible plaque. Subgingival plaque samples taken from each tooth were individually analysed for their content of 40 bacterial species using checkerboard DNA-DNA hybridization. Crude odds ratios (ORs) [95% confidence interval (CI)] of overweight and obese individuals exhibiting periodontitis were 3.1 (1.9-4.8) and 5.3 (2.8-9.5), respectively, when compared with subjects with normal BMI. Logistic regression analysis indicated an OR (95% CI) of 2.3 (1.2-4.5) for an obese subject to exhibit periodontitis after adjusting for age, gender and smoking status. Individuals < 46.8 years (median age) were responsible for this association. Only Tannerella forsythia differed significantly in proportions among BMI groups and was significantly higher in obese periodontally healthy/gingivitis individuals. The data suggest that an overgrowth of T. forsythia occurs in the subgingival biofilms of periodontally healthy, overweight and obese individuals that might put them at risk for initiation and progression of periodontitis. C1 [Haffajee, Anne D.; Socransky, Sigmund Sidney] Forsyth Inst, Dept Periodontol, Boston, MA 02115 USA. RP Haffajee, AD (reprint author), Forsyth Inst, Dept Periodontol, 140 Fenway, Boston, MA 02115 USA. EM ahaffajee@forsyth.org FU National Institute of Dental and Craniofacial Research [DE-12108, DE12861, DE14242, DE14368, DE17400] FX This work was supported in part by research grants DE-12108, DE12861, DE14242, DE14368, DE17400 from the National Institute of Dental and Craniofacial Research. We would also like to acknowledge the clinical contributions of Dr. R. Teles, Dr. F. Teles, Dr. E. Arguello, Ms. D. Guerrero, Ms. M. Letteri, Ms. L. Murray, Ms. C. Roberts, Ms. M. Thompson, Ms. G. Torresyap, Ms. N. Viega, and the laboratory contributions of Ms. L. Martin, Ms. M. Patel, Ms. C. Smith, Ms. X. Song and Ms. T. Yaskell. Finally, we would like to thank the subjects who provided clinical measurements and microbiological samples. NR 41 TC 35 Z9 37 U1 1 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0303-6979 J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD FEB PY 2009 VL 36 IS 2 BP 89 EP 99 DI 10.1111/j.1600-051X.2008.01356.x PG 11 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 397MG UT WOS:000262666200001 PM 19207883 ER PT J AU Goldberg, JF Brooks, JO Kurita, K Hoblyn, JC Ghaemi, N Perlis, RH Miklowitz, DJ Ketter, TA Sachs, GS Thase, ME AF Goldberg, Joseph F. Brooks, John O. Kurita, Keiko Hoblyn, Jennifer C. Ghaemi, Nassir Perlis, Roy H. Miklowitz, David J. Ketter, Terence A. Sachs, Gary S. Thase, Michael E. TI Depressive Illness Burden Associated With Complex Polypharmacy in Patients With Bipolar Disorder: Findings From the STEP-BD SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID PSYCHOTROPIC-DRUG PRESCRIPTION; SUBSTANCE USE DISORDERS; DOUBLE-BLIND; I-DISORDER; MOOD STABILIZER; PSYCHIATRIC-HOSPITALIZATION; RISK-FACTORS; ACUTE MANIA; LITHIUM; COMBINATION AB Background: Many patients with bipolar disorder receive multi-drug treatment regimens, but the distinguishing profiles of patients who receive complex pharmacologies have not been established. Method: Prescribing patterns of lithium, anti-convulsants, antidepressants, and antipsychotics were examined for 4035 subjects with bipolar disorder (DSM-IV) immediately prior to entering the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), Subjects were recruited for participation across 22 centers in the United States between November 1999 and July 2005. The quality receiver operating characteristic (ROC) method was used to develop composite profiles of patients receiving complex regimens (p < .01 for all iterations). Results: Use of 3 or more medications occurred in 40% of subjects, while 18% received 4 or more agents. Quality ROC analyses revealed that subjects had a 64% risk for receiving a complex regimen (>= 4 medications) if they had (I) ever taken an atypical antipsychotic, (2) >= 6 lifetime depressive episodes, (3) attempted suicide, and (4) an annual income >= $75,000. Complex polypharmacy was least often associated with lithium, divalproex, or carbamaze-pine and most often associated with atypical antipsychotics or antidepressants. Contrary to expectations, a history of psychosis, age at onset, bipolar I versus 11 subtype, history of rapid cycling, prior hospitalizations, Current illness state, and history of alcohol or substance use disorders did not significantly alter the risk profiles for receiving complex regimens. Conclusion: Complex polypharmacy involving at least 4 medications occurs in approximately I in 5 individuals with bipolar disorder. Use of traditional mood stabilizers is associated with fewer cotherapies. Complex regimens are especially common in patients with substantial depressive illness burden and suicidality, for whom simpler drug regimens may fail to produce acceptable levels of response. C1 [Goldberg, Joseph F.] Silver Hill Hosp, Affect Disorders Res Program, New Canaan, CT USA. [Brooks, John O.; Kurita, Keiko; Hoblyn, Jennifer C.] Palo Alto Vet Affairs Hlth Care Syst, Palo Alto, CA USA. [Brooks, John O.; Kurita, Keiko; Hoblyn, Jennifer C.; Ketter, Terence A.] Stanford Univ, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA. [Ghaemi, Nassir] Tufts Univ New England Med Ctr, Dept Psychiat, Boston, MA USA. [Perlis, Roy H.; Sachs, Gary S.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Perlis, Roy H.; Sachs, Gary S.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Miklowitz, David J.] Univ Colorado, Dept Psychol, Boulder, CO 80309 USA. [Miklowitz, David J.] Univ Colorado, Dept Psychiat, Boulder, CO 80309 USA. [Thase, Michael E.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Thase, Michael E.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA. [Goldberg, Joseph F.] Mt Sinai Hosp, Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. RP Goldberg, JF (reprint author), 128 East Ave, Norwalk, CT 06851 USA. EM Joseph.goldberg@mssm.edu RI Ghaemi, Nassir/J-4934-2013 FU Abbott; AstraZeneca; Bristol-Myers Squibb; Cephalon; Eli Lilly; GlaxoSmithKline; Pfizer; Repligen; Wyeth; Sepracor FX Dr. Goldberg has received honoraria from Abbott and Eli Lilly and has participated in speakers/advisory boards for AstraZeneca, GlaxoSmithKline, Eli Lilly, and Pfizer. Dr. Brooks has participated in speakers/advisory boards for AstraZeneca, Bristol-Myers Squibb, Eli Lilly, and Pfizer. Dr. Hoblyn has participated in speakers/advisory boards for Bristol-Myers Squibb and Eli Lilly. Dr. Ghaemi has received grant/research support from Pfizer and has participated in speakers/advisory boards for AstraZeneca and Pfizer. Dr. Perlis is a consultant for Bristol-Myers Squibb. Eli Lilly, GlaxoSmithKline, and Pfizer. Dr. Miklowitz has received book royalties from Guilford Press and John Wiley and Sons. Dr. Ketter has received grant/research support from Abbott, AstraZeneca, Bristol-Myers Squibb, Cephalon, Eli Lilly, GlaxoSmithKline, Pfizer, Repligen, and Wyeth; is a consultant to Abbott, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen, Jazz, Novartis, Organon, Solvay, Vanda, Wyeth, and XenoPort; and has received lecture honoraria from Abbott, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Otsuka, and Pfizer, Dr. Ketter's spouse is an employee of Johnson & Johnson. Dr. Sachs is a consultant to or a member of advisory boards for AstraZeneca, Bristol-Myers Squibb, Cephalon, Concordant Rater Systems, Eli Lilly, GlaxoSmithKline, Janssen, Memory, Novartis, Organon, Otsuka, Pfizer, Repligen, Sanofi-Aventis, Schering-Plough, Sepracor, and Wyeth; is a member of speakers bureaus for Abbott, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen, Memory, Novartis, Pfizer. Sanofi-Aventis, and Wyeth; and Dr. Sachs' spouse is a stock shareholder of Concordant Rater Systems. Dr. Thase is a consultant to AstraZeneca, Bristol-Myers Squibb, Cephalon, Cyberonics, Eli Lilly, Forest, GlaxoSmithKline, Janssen, MedAvante, Neuronetics, Novartis, Organon, Sepracor, Shire, Supernus, and Wyeth; has received grant/research support from Eli Lilly and Sepracor; has participated in speakers bureaus for AstraZeneca, Bristol-Myers Squibb, Cyberonics, Eli Lilly, GlaxoSmithKline, Sanofi-Aventis, Schering Plough (formerly Organon), and Wyeth; has delivered expert testimony for Jones Day (Wyeth Litigation), Phillips Lytle (GlaxoSmithKline Litigation), and Pepper Hamilton LLP (Eli Lilly Litigation); has equity holdings in MedAvante; and has received royalties/patents from American Psychiatric Publishing, Guilford Publications, Herald House, and W.W. Norton & Company. Dr. Thase's spouse is Senior Medical Director of Advogent (formerly Cardinal Health). Ms. Kurita reports no additional financial or other relationships relevant to the subject of this article. NR 39 TC 82 Z9 86 U1 2 U2 7 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 FEB PY 2009 VL 70 IS 2 BP 155 EP 162 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 411DD UT WOS:000263627300001 PM 19210946 ER PT J AU Sayers, SL Farrow, VA Ross, J Oslin, DW AF Sayers, Steven L. Farrow, Victoria A. Ross, Jennifer Oslin, David W. TI Family Problems Among Recently Returned Military Veterans Referred for a Mental Health Evaluation SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID CONFIRMATORY FACTOR-ANALYSIS; MEMORY-CONCENTRATION TEST; US ARMY SOLDIERS; PRIMARY-CARE; DOMESTIC VIOLENCE; SYMPTOM STRUCTURE; DSM-IV; DEPRESSION; RELIABILITY; DEPLOYMENT AB Context: Existing evidence suggests, that military veterans with mental health disorders have poorer Family functioning, although little research has focused on this topic. Objective: To test whether psychiatric symptoms are associated with family reintegration problems in recently returned military veterans. Design: Cross-sectional survey of a clinical population. Respondents who were referred to behavioral health evaluation from April 2006 through August 2007 were considered for the survey. Setting: Philadelphia Veterans Affairs Medical Center, Pa. Participants: 199 military veterans who served in Iraq or Afghanistan after 2001 and were referred for behavioral health evaluation from primary care (mean age = 32.7 years, SD = 9.1). Main Outcome Measures: Measures included the Mini-International Neuropsychiatric Interview for psychiatric diagnoses, the 9-item Patient Health Questionnaire for depression diagnosis and severity, and screening measures of alcohol abuse and illicit substance use. A measure of military family readjustment problems and a screening measure of domestic abuse were developed for this study. Results: Three fourths of the married/cohabiting veterans reported some type of family problem in the past week, such as feeling like a guest in their household (40.7%), reporting their children acting afraid or not being warm toward them (25.0%), or being unsure about their family role (37.2%). Among veterans with current or recently separated partners, 53.7% reported conflicts involving "shouting, pushing, or shoving," and 27.6% reported that this partner was "afraid " of them." Depression and posttraumatic stress disorder symptoms were both associated with higher rates of family reintegration problems. Conclusions: Mental health problems may complicate veterans' readjustment and reintegration into family life. The findings suggest an opportunity to improve the treatment of psychiatric disorders by addressing family problems. C1 [Sayers, Steven L.; Farrow, Victoria A.; Ross, Jennifer; Oslin, David W.] Philadelphia VA Med Ctr, VISN 4, MIRECC 116, Philadelphia, PA 19104 USA. [Sayers, Steven L.; Ross, Jennifer; Oslin, David W.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. RP Sayers, SL (reprint author), Philadelphia VA Med Ctr, VISN 4, MIRECC 116, 3900 Woodland Ave, Philadelphia, PA 19104 USA. EM Steven.sayers@va.gov NR 38 TC 156 Z9 159 U1 10 U2 24 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 FEB PY 2009 VL 70 IS 2 BP 163 EP 170 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 411DD UT WOS:000263627300002 PM 19210950 ER PT J AU Husain, MM Rush, J Wisniewski, SR McClintock, SM Fava, M Nierenberg, AA Davis, L Balasubramani, GK Young, E Albala, AA Trivedi, MH AF Husain, Mustafa M. Rush, John Wisniewski, Stephen R. McClintock, Shawn M. Fava, Maurizio Nierenberg, Andrew A. Davis, Lori Balasubramani, G. K. Young, Elizabeth Albala, A. Ari Trivedi, Madhukar H. TI Family History of Depression and Therapeutic Outcome: Findings From STAR*D SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID SEQUENCED TREATMENT ALTERNATIVES; DIAGNOSTIC SCREENING QUESTIONNAIRE; POSTTRAUMATIC-STRESS-DISORDER; INTERACTIVE VOICE RESPONSE; CHRONIC MAJOR DEPRESSION; ILLNESS RATING-SCALE; REPORT QIDS-SR; RELIEVE DEPRESSION; QUICK INVENTORY; PSYCHOMETRIC EVALUATION AB Objective: It is unclear whether a positive family history of depression affects the clinical presentation or effectiveness of treatment for major depressive disorder (MDD). We aimed to determine whether depressed patients with it positive family history of depression differed from those without in terms of baseline sociodemographic and clinical characteristics, including concurrent comorbid conditions and treatment Outcome with citalopram in it large, Multicenter effectiveness trial. Method: Clinical outcome and sociodemographic information were collected on 2876 participants with DSM-IV MDD enrolled from July 2001 through April 2004 in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Participants with and without it family history of depression, its determined by self-report at initial assessment, were compared. Results: Over half (55.6%) (1585/2853) of the evaluable sample reported a positive family history of depression. A positive family history of depression was associated with in earlier age at onset of MDD, it longer length of illness, and more comorbid generalized anxiety disorder and prior suicide attempts. These participants had it slightly faster onset of remission, and slightly greater side effect burden, but they did not differ overall in response or remission rates. Conclusion.: A family history of depression was associated with several clinical characteristics, although its usefulness is a predictor of treatment outcome is questionable. The slightly faster remission with an SSRI despite the slightly greater side effect burden indicates the effectiveness of using an SSRI in treating depressed patients both with and without it family history of depression. Trial Registration: clinicaltrials.gov Identifier: NCT00021528 C1 [Husain, Mustafa M.; Rush, John; McClintock, Shawn M.; Trivedi, Madhukar H.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Rush, John] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA. [Rush, John] Duke NUS Grad Med Sch, Dept Clin Sci, Singapore, Singapore. [Wisniewski, Stephen R.; Balasubramani, G. K.] Univ Pittsburgh, Epidemiol Data Ctr, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA. [McClintock, Shawn M.] Columbia Univ, Dept Psychiat, Brain Stimulat & Therapeut Modulat Div, New York State Psychiat Inst, New York, NY USA. [Fava, Maurizio; Nierenberg, Andrew A.] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Davis, Lori] Tuscaloosa Vet Affairs Med Ctr, Dept Res, Tuscaloosa, AL USA. [Young, Elizabeth] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Young, Elizabeth] Univ Michigan, Med Ctr, Mental Hlth Res Inst, Ann Arbor, MI 48109 USA. [Albala, A. Ari] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. RP Husain, MM (reprint author), Univ Texas SW Med Ctr Dallas, Dept Psychiat, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM mustafa.husain@utsouthwestern.edu OI Wisniewski, Stephen/0000-0002-3877-9860; Rush, Augustus/0000-0003-2004-2382; Goundappa K, Balasubramani/0000-0001-7221-1825 FU NIMH NIH HHS [N01 MH90003] NR 67 TC 15 Z9 16 U1 0 U2 1 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 FEB PY 2009 VL 70 IS 2 BP 185 EP 195 PG 11 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 411DD UT WOS:000263627300005 PM 19192454 ER PT J AU Wilens, TE Martelon, M Kruesi, MJP Parcell, T Westerberg, D Schillinger, M Gignac, M Biederman, J AF Wilens, Timothy E. Martelon, MaryKate Kruesi, Markus J. P. Parcell, Tiffany Westerberg, Diana Schillinger, Mary Gignac, Martin Biederman, Joseph TI Does Conduct Disorder Mediate the Development of Substance Use Disorders in Adolescents With Bipolar Disorder? A Case-Control Family Study SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID ATTENTION-DEFICIT HYPERACTIVITY; SPECTRUM DISORDERS; FOLLOW-UP; CIGARETTE-SMOKING; DRUG-USE; CHILDREN; CHILDHOOD; MANIA; RISK; ONSET AB Background: Recent work has highlighted important relationships among conduct disorder (CD), substance use disorders (SUD), and bipolar disorder in youth. However, because bipolar disorder and CD are frequently comorbid in the young, the impact of CD in mediating SUD in bipolar disorder youth remains unclear. Method: 105 adolescents with DSM-IV bipolar disorder (mean +/- SD age = 13.6 +/- 2.50 years) and 98 controls (mean SD age = 13.7 +/- 2.10 years) were comprehensively assessed with a structured psychiatric diagnostic interview for psychopathology and SUD. The study was conducted from January 2000 through December 2004. Results: Among bipolar disorder youth, those with CD were more likely to report cigarette smoking and/or SUD than youth without CD. However, CD preceding SUD or cigarette smoking did not significantly increase the subsequent risk of SUD or cigarette smoking. Adolescents with bipolar disorder and CD were significantly more likely to manifest a combined alcohol plus drug use disorder compared to subjects with bipolar disorder without CD chi(2) = 11.99, p < .001). Conclusions: While bipolar disorder is a risk factor for SUD and cigarette smoking in a sample of adolescents, comorbidity with preexisting CD does not increase the risk for SUD. Further follow-up of this sample through the full risk of SUD into adulthood is necessary to confirm these findings. C1 [Wilens, Timothy E.; Martelon, MaryKate; Parcell, Tiffany; Westerberg, Diana; Schillinger, Mary; Biederman, Joseph] Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. [Wilens, Timothy E.; Martelon, MaryKate; Parcell, Tiffany; Westerberg, Diana; Schillinger, Mary; Biederman, Joseph] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA USA. [Kruesi, Markus J. P.] Med Univ S Carolina, Div Child Psychiat, Charleston, SC 29425 USA. [Gignac, Martin] Univ Montreal, Inst Philippe Pinel, Quebec City, PQ, Canada. RP Wilens, TE (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, 55 Parkman St,YAW 6A, Boston, MA 02114 USA. EM twilens@partners.org FU NIDA NIH HHS [R01 DA012945-05, K24 DA016264, K24 DA016264-05, K24 DA016264-06A1, R01 DA012945, R01 DA012945-09, R01 DA12945] NR 52 TC 12 Z9 12 U1 5 U2 7 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 FEB PY 2009 VL 70 IS 2 BP 259 EP 265 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 411DD UT WOS:000263627300015 PM 19210945 ER PT J AU Freeman, MP AF Freeman, Marlene P. TI Breastfeeding and Antidepressants: Clinical Dilemmas and Expert Perspectives SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID NURSING INFANTS; FLUOXETINE; DEPRESSION; MILK; NORFLUOXETINE; DISORDERS; EXCRETION; MOOD C1 Massachusetts Gen Hosp, Perinatal & Reprod Psychiat Program, Boston, MA 02114 USA. RP Freeman, MP (reprint author), Massachusetts Gen Hosp, Perinatal & Reprod Psychiat Program, Boston, MA 02114 USA. NR 14 TC 4 Z9 4 U1 2 U2 3 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 FEB PY 2009 VL 70 IS 2 BP 291 EP 292 PG 2 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 411DD UT WOS:000263627300019 PM 19265645 ER PT J AU van Noord, C Straus, SMJM Sturkenboom, MCJM Hofman, A Aarnoudse, AJLHJ Bagnardi, V Kors, JA Newton-Cheh, C Witteman, JCM Stricker, BHC AF van Noord, Charlotte Straus, Sabine M. J. M. Sturkenboom, Miriam C. J. M. Hofman, Albert Aarnoudse, Albert-Jan L. H. J. Bagnardi, Vincenzo Kors, Jan A. Newton-Cheh, Christopher Witteman, Jacqueline C. M. Stricker, Bruno H. C. TI Psychotropic Drugs Associated With Corrected QT Interval Prolongation SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE QTc interval; psychotropic drugs; electrocardiography; arrhythmia ID TORSADE-DE-POINTES; LEFT-VENTRICULAR HYPERTROPHY; NON-ANTIARRHYTHMIC DRUGS; MYOCARDIAL-INFARCTION; HEART-FAILURE; ROTTERDAM; RISK; POPULATION; ELECTROCARDIOGRAMS; REPOLARIZATION AB Aims: To study whether listed putative corrected QT (QTc)-prolonging psychotropic drugs indeed prolong the QTc interval under everyday circumstances and to evaluate whether this is a class effect or an individual drue effect. we conducted a prospective population-based cohort study. Methods: This study was conducted as part of the Rotterdam Study and included 3377 men and 4845 women (>= 55 years) who had triennial electrocardiograms (ECGs). The primary end point,; of the study were the length of the QTc interval at each ECG. the difference in QTc interval between consecutive ECGs within one person, and the risk of ail abnormally prolonged QTc interval. Drug use at the index date was obtained from automated dispensing records. The associations were examined by means of a repeated measurement analysis, adjusted for age. sex, diabetes mellitus. hypertension, myocardial infarction, heart failure. and use of class I QTc-prolonging drugs. Results: Of the 8222 participants. 813 participants (9.9%) developed QTc prolongation during follow-up and 492 participants (74.4% women) used psychotropic drugs at the time of an ECG. Starting tricyclic antidepressants increased the QTc interval significantly with 6.9 milliseconds (95% confidence interval [CI], 3.1-10.7 milliseconds) between consecutive ECGs in comparison With Consecutive ECGs of participants not using tricyclic antidepressants. in particular starting amitriptyline (8.5 milliseconds: 95% CI. 2.8-14.2 milliseconds), maprotiline (13.9 milliseconds: 9 % CI, 3.6-24.3 milliseconds), and nortriptyline (35.3 milliseconds: 95% CI. 8.0-62.6 milliseconds). Starting lithium also increased the QTc interval significantly (18.6 milliseconds; 95% Cl 4.8-32.4 milliseconds). Conclusions: In this population-based prospective cohort Stud),, we confirmed the importance of antidepressants and antipsychotics as potential contributors to QTc prolongation. Especially, starting tricyclic antidepressant drugs (as a class) is associated with a significant intraindividual increase in the QTc interval in comparison to the change in nonusers. The tricyclic antidepressants seem to prolong the QTc interval as a class effect. C1 [van Noord, Charlotte; Straus, Sabine M. J. M.; Sturkenboom, Miriam C. J. M.; Hofman, Albert; Aarnoudse, Albert-Jan L. H. J.; Witteman, Jacqueline C. M.; Stricker, Bruno H. C.] Erasmus MC, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands. [van Noord, Charlotte; Straus, Sabine M. J. M.] Dutch Med Evaluat Board, The Hague, Netherlands. [Aarnoudse, Albert-Jan L. H. J.; Stricker, Bruno H. C.] Inspectorate Hlth Care, The Hague, Netherlands. [Bagnardi, Vincenzo] Univ Milano Bicocca, Dept Stat, Milan, Italy. [Bagnardi, Vincenzo] European Inst Oncol, Div Epidemiol & Biostat, Milan, Italy. [Newton-Cheh, Christopher] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Newton-Cheh, Christopher] Broad Inst Harvard, Program Med & Populat Genet, Cambridge, England. [Newton-Cheh, Christopher] MIT, Cambridge, MA 02139 USA. [Newton-Cheh, Christopher] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA. [Stricker, Bruno H. C.] Erasmus MC, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands. RP Stricker, BHC (reprint author), Erasmus MC, Dept Epidemiol, Dr Molewaterpl 50,POB 2040, NL-3000 CA Rotterdam, Netherlands. EM b.stricker@erasmusmc.nl NR 39 TC 49 Z9 49 U1 1 U2 5 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 FEB PY 2009 VL 29 IS 1 BP 9 EP 15 DI 10.1097/JCP.0b013e318191c6a8 PG 7 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 395YA UT WOS:000262558200003 PM 19142100 ER PT J AU Adler, LA Spencer, T Brown, TE Holdnack, J Saylor, K Schuh, K Trzepacz, PT Williams, DW Kelsey, D AF Adler, Lenard A. Spencer, Thomas Brown, Thomas E. Holdnack, James Saylor, Keith Schuh, Kory Trzepacz, Paula T. Williams, David W. Kelsey, Douglas TI Once-Daily Atomoxetine for Adult Attention-Deficit/Hyperactivity Disorder A 6-Month, Double-Blind Trial SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE atomxetine; ADHD; adult; once-daily; duration of effect ID LIFE SCALE AAQOL; ADHD; METHYLPHENIDATE; DISEASE AB This randomized. double-blind. placebo-controlled, 6-month trial examined the efficacy and safety of once-daily morning-dosed atomoxetine in adult patients with attention -deficit/hyperactivity disorder (ADHD) and the efficacy of atomoxetine in ameliorating symptoms through the evening hours. Patients received once-daily atomoxetine (n = 250) or placebo In = 251) in the morning for approximately 6 months. The efficacy measures included the Adult ADHD Investigator Symptom Rating Scale (AISRS), Conners' Adult ADHD Rating Scale-Investigator Rated: Screening Version, Clinical Global Impressions-ADHD-Severity of Illness, and Adult ADHD Quality of Life Scale. Overall, 94 patients randomized to atomoxetine and 112 patients randomized to placebo completed the study. On the AISRS total score, Conners' Adult ADHD Rating Scale-Investigator Rated: Screening Version evening index total score, Clinical Global Impressions-ADGD-Severity of Illness score, and Adult ADHD Quality of Life Scale total score, atomoxetine was statistically superior to placebo at the 10-week and 6-month time points. From the visitwise analysis, the mean (SD) AISRS total scores for atomoxetine decreased from 38.2 (7.5) at baseline to 21.4 (12.3) at the 6-month end point compared with 38.6 (7.0) to 25.8 (13.2) for placebo (P = 0.035). Nausea, dry mouth. fatigue, decreased appetite, urinary hesitation, and erectile dysfunction were the treatment-emergent adverse events reported significantly more often with atomoxetine. Discontinuations due to adverse event were 17.2% and 5.6% for atomoxetine and placebo, respectively (P < 0.00 1). Once-daily morning-dosed atomoxetine is efficacious for treating ADHD in adults when measured 10 weeks and 6 months after initiating treatment. Atomoxetine demonstrated significant efficacy that continued into the evening. Adverse events were similar to previous trials. C1 [Adler, Lenard A.] NYU, Sch Med, New York, NY 10016 USA. [Adler, Lenard A.] New York VA Harbor Healthcare Syst, New York, NY USA. [Spencer, Thomas] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Brown, Thomas E.] Yale Univ, Sch Med, Hamden, CT USA. [Holdnack, James] Harcourt Assessment Inc, Bear, DE USA. [Saylor, Keith] NeuroScience Inc, Herndon, VA USA. [Schuh, Kory; Williams, David W.; Kelsey, Douglas] Lilly Res Labs, Indianapolis, IN USA. [Trzepacz, Paula T.] Univ Mississippi, Sch Med, Jackson, MS 39216 USA. [Trzepacz, Paula T.] Indiana Univ, Sch Med, Indianapolis, IN USA. [Trzepacz, Paula T.] Tufts Univ, Sch Med, Boston, MA 02111 USA. RP Adler, LA (reprint author), NYU, Sch Med, HCC 7D,530 1st Ave, New York, NY 10016 USA. EM lenard.adler@med.nyu.edu OI Adler, Len/0000-0002-9812-8234 FU Eli Lilly and Company FX This research was funded by Eli Lilly and Company. NR 27 TC 90 Z9 91 U1 1 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 FEB PY 2009 VL 29 IS 1 BP 44 EP 50 DI 10.1097/JCP.0b013e318192e4a0 PG 7 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 395YA UT WOS:000262558200010 PM 19142107 ER PT J AU Matthews, JD Siefert, C Dording, C Denninger, JW Park, L van Nieuwenhuizen, AO Sklarsky, K Hilliker, S Homberger, C Rooney, K Fava, M AF Matthews, John D. Siefert, Caleb Dording, Christina Denninger, John W. Park, Lawrence van Nieuwenhuizen, Adrienne O. Sklarsky, Katherine Hilliker, Sarah Homberger, Caitlin Rooney, Kathryn Fava, Maurizio TI An Open Study of Aripiprazole and Escitalopram for Psychotic Major Depressive Disorder SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE major depression with psychotic features; lexapro; abilify ID SEROTONIN-REUPTAKE INHIBITORS; 5-HT1A RECEPTOR ACTIVATION; MEDIAL PREFRONTAL CORTEX; DOPAMINE RELEASE; ANTIPSYCHOTIC-DRUGS; NUCLEUS-ACCUMBENS; MOOD DISORDERS; CLINICAL PREDICTORS; RATING-SCALE; QUETIAPINE AB Objective: This 7-week trial assessed the efficacy and tolerability of aripiprazole combined with escitalopram in the acute treatment of major depressive disorder, with psychotic features (MD-Psy). Methods: Sixteen male and female patients with a Diagnostic Statistical Manual of Mental Disorders. Fourth Edition, diagnosis of MD-Psy were recruited for this study from September 13, 2004 to August 9. 2006. Escitalopram and aripiprazole were flexibly dosed for 7 weeks. with maximum dosages of 20 and 30 mg/d, respectively. The 17-item Hamilton Rating Scale for Depression (HAM-D-17) and Structured Clinical Interview for L)DSM-IV psychosis module were used to measure depression and psychosis responses. The Barnes Akathisia Scale and the Simpson Angus Scale were used to assess for akathisia and extrapyramidal symptoms. Results: Thirteen of the 16,objects completed the study The MD-Psy response rate (50% or greater drop in HAM-D-17 and no psychosis) (intent-to-treat, last observation carried forward) was 62.5%, and the MD-Psy remission rate (HAM-D-17, <8, and no psychosis) (intent-to-treat. last observation carried forward) was 50.0%. Ten of the 16 subjects developed akathisia however. 9 of the 10 subjects had resolution or partial resolution of akathisia with dose adjustment or treatment with propranolol. Conclusions: The combination of escitalopram and aripiprazole seems to be an effective and safe treatment for MD-Psy. C1 [Matthews, John D.; Siefert, Caleb; Park, Lawrence; van Nieuwenhuizen, Adrienne O.; Sklarsky, Katherine; Hilliker, Sarah; Homberger, Caitlin; Rooney, Kathryn] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inpatient Psychiat Serv, Boston, MA 02114 USA. [Dording, Christina; Denninger, John W.; Fava, Maurizio] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, Boston, MA 02114 USA. RP Matthews, JD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inpatient Psychiat Serv, 55 Fruit St,Warren 12, Boston, MA 02114 USA. EM JMatthews@partners.org FU Bristol-Myers Squibb; Massachusetts General Hospital FX This study was funded by Bristol-Myers Squibb and Departmental Funds from Massachusetts General Hospital. NR 34 TC 7 Z9 7 U1 0 U2 1 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 FEB PY 2009 VL 29 IS 1 BP 73 EP 76 DI 10.1097/JCP.0b013e318193dfb4 PG 4 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 395YA UT WOS:000262558200016 PM 19142112 ER PT J AU Bartlett, BL Tyring, SK Fife, K Gnann, JW Hadala, JT Kianifard, F Berberd, E AF Bartlett, Brenda L. Tyring, Stephen K. Fife, Kenneth Gnann, John W., Jr. Hadala, Joseph T. Kianifard, Farid Berberd, Erhan TI Famciclovir treatment options for patients with frequent outbreaks of recurrent genital herpes: The RELIEF trial (vol 43, pg 190, 2008) SO JOURNAL OF CLINICAL VIROLOGY LA English DT Correction C1 [Bartlett, Brenda L.; Tyring, Stephen K.] Univ Texas Houston, Hlth Sci Ctr, Houston, TX 77030 USA. [Fife, Kenneth] Indiana Univ, Sch Med, Indianapolis, IN USA. [Gnann, John W., Jr.] Univ Alabama, Birmingham, AL USA. [Gnann, John W., Jr.] Birmingham VA Med Ctr, Birmingham, AL USA. [Hadala, Joseph T.; Kianifard, Farid; Berberd, Erhan] Novartis Pharmaceut, E Hanover, NJ 07936 USA. RP Tyring, SK (reprint author), Univ Texas Houston, Hlth Sci Ctr, 6655 Travis, Houston, TX 77030 USA. EM bbartlett@ccstexas.com; styring@ccstexas.com; kfife@iupui.edu; jgnann@uab.edu; joseph.hadala@novartis.com; farid.kianifard@novartis.com; erhan.berber@novartis.com 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 1386-6532 J9 J CLIN VIROL JI J. Clin. Virol. PD FEB PY 2009 VL 44 IS 2 BP 183 EP 183 DI 10.1016/j.jcv.2008.11.012 PG 1 WC Virology SC Virology GA 416DU UT WOS:000263986400024 ER PT J AU Lauer, AM Dooling, RJ Leek, MR AF Lauer, Amanda M. Dooling, Robert J. Leek, Marjorie R. TI Psychophysical evidence of damaged active processing mechanisms in Belgian Waterslager Canaries SO JOURNAL OF COMPARATIVE PHYSIOLOGY A-NEUROETHOLOGY SENSORY NEURAL AND BEHAVIORAL PHYSIOLOGY LA English DT Article DE Psychophysical tuning curve; Harmonic complex; Active processing; Masking; Bird hearing ID PARAKEET MELOPSITTACUS-UNDULATUS; HEARING-IMPAIRED LISTENERS; AUDITORY HAIR-CELLS; TUNING CURVES; SERINUS-CANARIUS; FREQUENCY-SELECTIVITY; HARMONIC COMPLEXES; BASILAR-MEMBRANE; MASKING; THRESHOLDS AB Belgian Waterslager canaries (BWC), bred for a distinct low-pitched song, have an inherited high-frequency hearing loss associated with hair cell abnormalities. Hair cells near the abneural edge of the papilla, which receive primarily efferent innervation in normal birds, are among the most severely affected. These cells are thought to support nonlinear active processing in the avian ear, though the mechanisms are poorly understood. Here we present psychophysical evidence that suggests degraded active processing in BWC compared to normal-hearing non-BWC. Critical ratios, psychophysical masking patterns and phase effects on masking by harmonic complexes were measured in BWC and non-BWC using operant conditioning procedures. Critical ratios were much larger in BWC than in non-BWC at high frequencies. Psychophysical tuning curves derived from the masking patterns for BWC were broadened at high frequencies. BWC also showed severely reduced phase effects on masking by harmonic complexes compared to non-BWC. As has been hypothesized previously for hearing-impaired humans, these results are consistent with a loss of active processing mechanisms in BWC. C1 [Lauer, Amanda M.; Dooling, Robert J.] Univ Maryland, Dept Psychol, College Pk, MD 20742 USA. [Leek, Marjorie R.] Portland VA Med Ctr, Natl Ctr Rehabil Auditory Res, Portland, OR 97207 USA. RP Lauer, AM (reprint author), Johns Hopkins Univ, Dept Otolaryngol, 720 Rutland Ave,521 Traylor Res Bldg, Baltimore, MD 21205 USA. EM alauer2@jhmi.edu OI Lauer, Amanda/0000-0003-4184-7374 FU NIH [DC01372, DC-005450, DC-00626, DC-04664]; National Institutes of Health; Animal Welfare Act of the USA FX This work was supported by NIH Grants DC01372 to RJD, DC-005450 to AML, DC-00626 to MRL, and DC-04664 ( Core Center grant) to the University of Maryland. These experiments comply with the "Principles of care,'' publication No. 86-23, revised 1985 of the National Institutes of Health and with the Animal Welfare Act of the USA. NR 60 TC 6 Z9 6 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-7594 J9 J COMP PHYSIOL A JI J. Comp. Physiol. A -Neuroethol. Sens. Neural Behav. Physiol. PD FEB PY 2009 VL 195 IS 2 BP 193 EP 202 DI 10.1007/s00359-008-0398-z PG 10 WC Behavioral Sciences; Neurosciences; Physiology; Zoology SC Behavioral Sciences; Neurosciences & Neurology; Physiology; Zoology GA 402AS UT WOS:000262987200008 PM 19082827 ER PT J AU Yuan, GC AF Yuan, Guo-Cheng TI Targeted Recruitment of Histone Modifications in Humans Predicted by Genomic Sequences SO JOURNAL OF COMPUTATIONAL BIOLOGY LA English DT Article DE DNA sequence; histone modification; human ID EMBRYONIC STEM-CELLS; HUMAN CENTROMERIC CHROMATIN; RNA-POLYMERASE-II; HIGH-RESOLUTION; DEVELOPMENTAL REGULATORS; TRANSPOSABLE ELEMENTS; NUCLEOSOME OCCUPANCY; SILENT CHROMATIN; WIDE PREDICTION; YEAST GENOME AB Histone modifications are important epigenetic regulators and play a critical role in development. The targeting mechanism for histone modifications is complex and still incompletely understood. Here we applied a computational approach to predict genome-scale histone modification targets in humans by the genomic DNA sequences using a set of recent ChIP-seq data. We found that a number of histone modification marks could be predicted with high accuracy. On the other hand, the impact of DNA sequences for each mark is intrinsically different dependent upon the target-and tissue-specificity. Diverse patterns are associated with different repetitive elements. Unexpectedly, we found that non-overlapping, functionally opposite histone modification marks could share similar sequence features. We propose that these marks may target a common set of loci but are mutually exclusive and that the competition may be important for developmental control. Taken together, we show that our computational approach has provided new insights into the targeting mechanism of histone modifications. C1 [Yuan, Guo-Cheng] Harvard Univ, Sch Publ Hlth, Dept Biostat, Cambridge, MA 02466 USA. [Yuan, Guo-Cheng] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Cambridge, MA USA. RP Yuan, GC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, Cambridge, MA 02466 USA. EM gcyuan@jimmy.harvard.edu FU Claudia Adams Barr FX We are grateful to Yujiang Shi and Rui Fang for helpful discussions. We also thank Dustin Schones for information about their ChIP-seq data. This research was supported by the Claudia Adams Barr program. NR 55 TC 14 Z9 15 U1 0 U2 5 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1066-5277 J9 J COMPUT BIOL JI J. Comput. Biol. PD FEB PY 2009 VL 16 IS 2 BP 341 EP 355 DI 10.1089/cmb.2008.18TT PG 15 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 403BS UT WOS:000263057400018 PM 19193151 ER PT J AU Song, D Wang, Z Marmarelis, VZ Berger, TW AF Song, Dong Wang, Zhuo Marmarelis, Vasilis Z. Berger, Theodore W. TI Parametric and non-parametric modeling of short-term synaptic plasticity. Part II: Experimental study SO JOURNAL OF COMPUTATIONAL NEUROSCIENCE LA English DT Article DE Nonlinear modeling; Facilitation. Depression; Poisson stimulus; Volterra kernels ID PAIRED-PULSE DEPRESSION; GLUTAMATE-RECEPTOR DESENSITIZATION; NONLINEAR-SYSTEMS ANALYSIS; PATH-DENTATE PROJECTION; PURKINJE-CELL SYNAPSES; NEUROMUSCULAR-JUNCTION; PRESYNAPTIC TERMINALS; RELEASE PROBABILITY; FACILITATION; RAT AB This paper presents a synergistic parametric and non-parametric modeling study of short-term plasticity (STP) in the Schaffer collateral to hippocampal CA1 pyramidal neuron (SC) synapse. Parametric models in the form of sets of differential and algebraic equations have been proposed on the basis of the current understanding of biological mechanisms active within the system. Non-parametric Poisson-Volterra models are obtained herein from broadband experimental input-output data. The non-parametric model is shown to provide better prediction of the experimental output than a parametric model with a single set of facilitation/depression (FD) process. The parametric model is then validated in terms of its input-output transformational properties using the non-parametric model since the latter constitutes a canonical and more complete representation of the synaptic nonlinear dynamics. Furthermore, discrepancies between the experimentally-derived non-parametric model and the equivalent non-parametric model of the parametric model suggest the presence of multiple FD processes in the SC synapses. Inclusion of an additional set of FD process in the parametric model makes it replicate better the characteristics of the experimentally-derived non-parametric model. This improved parametric model in turn provides the requisite biological interpretability that the non-parametric model lacks. C1 [Song, Dong; Marmarelis, Vasilis Z.; Berger, Theodore W.] Univ So Calif, Dept Biomed Engn, Los Angeles, CA 90089 USA. [Berger, Theodore W.] Univ So Calif, Program Neurosci, Los Angeles, CA 90089 USA. [Song, Dong; Marmarelis, Vasilis Z.; Berger, Theodore W.] Univ So Calif, Ctr Neural Engn, Los Angeles, CA 90089 USA. [Wang, Zhuo] VA Greater Angeles Healthcare Syst, Ctr Neurovisceral Sci & Womens Hlth, Los Angeles, CA USA. RP Song, D (reprint author), Univ So Calif, Dept Biomed Engn, 403 Hedco Neurosci Bldg, Los Angeles, CA 90089 USA. EM dsong@usc.edu RI Song, Dong/A-8314-2010 FU NSF ERC; DARPA; ONR, NSF; NIH/NIBIB FX This research was supported by the NSF ERC (BMES), DARPA ( HAND),ONR, NSF ( BITS), and NIH/NIBIB (BMSR). We thank the two anonymous reviewers for their insightful comments on this manuscript. NR 39 TC 15 Z9 15 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5313 J9 J COMPUT NEUROSCI JI J. Comput. Neurosci. PD FEB PY 2009 VL 26 IS 1 BP 21 EP 37 DI 10.1007/s10827-008-0098-2 PG 17 WC Mathematical & Computational Biology; Neurosciences SC Mathematical & Computational Biology; Neurosciences & Neurology GA 407QI UT WOS:000263379000002 PM 18504530 ER PT J AU Rosenblatt, A Stamford, TCM Niederman, R AF Rosenblatt, A. Stamford, T. C. M. Niederman, R. TI Silver diamine Fluoride: A Caries "Silver- Fluoride Bullet" SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE systematic review; caries; prevention; fluoride; silver ID 1ST PERMANENT MOLARS; DENTAL PLAQUE INVIVO; ESCHERICHIA-COLI; ANTIMICROBIAL ACTIVITY; PRESCHOOL-CHILDREN; PRIMARY TEETH; COPPER; IONS; ACIDOGENICITY; PURIFICATION AB The antimicrobial use of silver compounds pivots on the 100-year-old application of silver nitrate, silver foil, and silver sutures for the prevention and treatment of ocular, surgical, and dental infections. Ag(+) kills pathogenic organisms at concentrations of < 50ppm, and current/potential anti-infective applications include: acute burn coverings, catheter linings, water purification systems, hospital gowns, and caries prevention. To distill the current best evidence relative to caries, this systematic review asked: Will silver diamine fluoride (SDF) more effectively prevent caries than fluoride varnish? A five-database search, reference review, and hand search identified 99 human clinical trials in three languages published between 1966 and 2006. Dual review for controlled clinical trials with the patient as the unit of observation, and excluding cross-sectional, animal, in vitro studies, and opinions, identified 2 studies meeting the inclusion criteria. The trials indicated that SDF's lowest prevented fractions for caries arrest and caries prevention were 96.1% and 70.3%, respectively. In contrast, fluoride varnish's highest prevented fractions for caries arrest and caries prevention were 21.3% and 55.7%, respectively. Similarly, SDF's highest numbers needed to treat for caries arrest and caries prevention were 0.8 (95% CI = 0.5-1.0) and 0.9 (95% CI = 0.4-1.1), respectively. For fluoride varnish, the lowest numbers needed to treat for caries arrest and prevention were 3.7 (95% CI = 3.4-3.9) and 1.1 (95% CI = 0.7-1.4), respectively. Adverse events were monitored, with no significant differences between control and experimental groups. These promising results suggest that SDF is more effective than fluoride varnish, and may be a valuable caries-preventive intervention. As well, the availability of a safe, effective, efficient, and equitable caries-preventive agent appears to meet the criteria of both the WHO Millennium Goals and the US Institute of Medicine's criteria for 21st century medical care. C1 [Rosenblatt, A.; Niederman, R.] Forsyth Inst, Boston, MA 02115 USA. [Rosenblatt, A.] Childrens Hosp Med Ctr, Boston, MA USA. [Rosenblatt, A.; Stamford, T. C. M.] Univ Pernambuco, Sch Dent, Recife, PE, Brazil. [Niederman, R.] Boston Univ, Goldman Sch Dent Med, Boston, MA 02215 USA. RP Rosenblatt, A (reprint author), Forsyth Inst, 140 Fenway, Boston, MA 02115 USA. EM arosenblatt@forsyth.org FU Fulbright Program; The Forsyth Institute FX We thank the Fulbright Program and The Forsyth Institute for providing support for Dr. Rosenblatt to initiate and complete this work. We also thank Drs. Patrick McDonald and Henry Margolis for reviewing and commenting on the text and particularly the chemistry. Finally, we thank Dr. Dana Graves and the reviewers who provided counseling on the literature, the delivery, and the illustration of the information presented here. NR 82 TC 72 Z9 76 U1 1 U2 23 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD FEB PY 2009 VL 88 IS 2 BP 116 EP 125 DI 10.1177/0022034508329406 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 415CX UT WOS:000263913000003 PM 19278981 ER PT J AU Egan, DJ Bisanzo, MC Hutson, HR AF Egan, Daniel J. Bisanzo, Mark C. Hutson, H. Range TI EMERGENCY DEPARTMENT EVALUATION AND MANAGEMENT OF PERIPARTUM CARDIOMYOPATHY SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE cardiomyopathy; peripartum; heart failure; pregnancy; postpartum ID ACUTE MYOCARDIAL-INFARCTION; LEFT-VENTRICULAR FUNCTION; CARDIAC TROPONIN-I; GESTATIONAL HYPERTENSION; HEART-FAILURE; NORMAL LABOR; PREGNANCY; PUERPERIUM; SURVIVAL; PAIN AB Peripartum cardiomyopathy (PPCM) affects 1000-1300 women In the United States each year. We present three cases of PPCM seen in our Emergency Department (ED) that cover the entire spectrum of disease from mild heart failure to sudden cardiac death. Without previous heart disease, these women develop cardiomyopathy with impairment of left ventricullar function in the last month of pregnancy, or during the first 5 months postpartum. The etiology of PPCM Is not clear, although various mechanisms have been proposed, including infection, auto-immune response, prolonged tocolysis during labor, and maladaptive responses to the hemodynamic changes of pregnancy. The initial presentation of these patients is frequently to the ED. The differential diagnosis and key characteristics of PPCM are discussed. ED management should focus on three elements: reduction in pre-load, reduction in afterload, and increase In inotropy. Key differences between the antepartum and postpartum states are highlighted. (c) 2009 Elsevier Inc. C1 [Egan, Daniel J.; Bisanzo, Mark C.] Massachusetts Gen Hosp, Brigham & Womens Hosp, Boston, MA 02114 USA. [Hutson, H. Range] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Egan, DJ (reprint author), St Vincents Hosp Manhattan, Dept Emergency Med, 170 W 12th St, New York, NY 10011 USA. NR 37 TC 7 Z9 7 U1 1 U2 2 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 FEB PY 2009 VL 36 IS 2 BP 141 EP 147 DI 10.1016/j.jemermed.2007.04.006 PG 7 WC Emergency Medicine SC Emergency Medicine GA 411CK UT WOS:000263625400006 PM 17976813 ER PT J AU Lefebvre, CW Hoekstra, JW Bonaca, M Giugliano, R AF Lefebvre, Cedric W. Hoekstra, James W. Bonaca, Marc Giugliano, Robert TI GLYCOPROTEIN IIb-IIIa INHIBITORS IN THE EMERGENCY DEPARTMENT FOR PATIENTS WITH NON-ST-ELEVATION ACUTE CORONARY SYNDROMES: PRINCIPLES AND PRACTICES SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE non-ST-elevation acute coronary syndrome; GP IIb-IIIa inhibitors; emergency department; percutaneous coronary intervention; risk stratification ID ACUTE MYOCARDIAL-INFARCTION; RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; IIB/IIIA RECEPTOR; SEGMENT ELEVATION; UNSTABLE ANGINA; UNFRACTIONATED HEPARIN; CLINICAL-OUTCOMES; INTERVENTION; TIROFIBAN AB Non-ST-elevation acute coronary syndrome is associated with significant morbidity and mortality. Although the benefit of platelet inhibition by glycoprotein (GP) IIb-IIIa inhibitors in patients undergoing percutaneous coronary intervention (PCI) is well established, emergency physicians and cardiologists have different perspectives regarding their optimum administration, especially upstream before PCI. In this article, two emergency physicians and two cardiologists analyze data and discuss relevant issues, including the ischemic benefits vs. the risk of bleeding associated with GP IIb-IIIa inhibitors in appropriate patients, for example, those with an elevated troponin level or who undergo revascularization. The emergency physicians support early identification of high-risk non-ST-ellevation acute coronary syndrome patients and early administration of GP IIb-IIIa inhibitors, which are linked to improved patient outcomes. The cardiologists emphasize risk stratification to identify patients in whom the expected reduction in ischemic complications outweighs the risk of increased bleeding with these agents. GP IIb-IIIa inhibitors should be considered in patients with unstable angina and non-ST-segment elevation myocardial infarction (UA/NSTEMI) in whom PCI is planned, especially those with high-risk features or elevated serum troponin levels. It is reasonable to start this treatment upstream of intervention, pending further studies investigating the optimal timing of initiation of therapy in appropriate patients. (c) 2009 Elsevier Inc. C1 [Lefebvre, Cedric W.; Hoekstra, James W.] Wake Forest Univ Hlth Sci, Dept Emergency Med, Winston Salem, NC 27157 USA. [Bonaca, Marc] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Giugliano, Robert] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. RP Lefebvre, CW (reprint author), Wake Forest Univ Hlth Sci, Dept Emergency Med, Med Ctr Blvd,Watlington Hall,4th Floor, Winston Salem, NC 27157 USA. NR 34 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 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD FEB PY 2009 VL 36 IS 2 BP 162 EP 170 DI 10.1016/j.jemermed.2007.10.020 PG 9 WC Emergency Medicine SC Emergency Medicine GA 411CK UT WOS:000263625400009 PM 18353601 ER PT J AU Baugh, CW Brown, DFM Nadel, ES AF Baugh, Christopher W. Brown, David F. M. Nadel, Eric S. TI HORNER'S SYNDROME, HOARSENESS, AND UNSTEADY GAIT SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID LATERAL MEDULLARY INFARCTION; WALLENBERGS-SYNDROME; STROKE C1 [Brown, David F. M.; Nadel, Eric S.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Baugh, Christopher W.; Brown, David F. M.; Nadel, Eric S.] Harvard Univ, Sch Med, Div Emergency Med, Boston, MA USA. [Nadel, Eric S.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. RP Brown, DFM (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Founders 114,Fruit St, Boston, MA 02114 USA. NR 14 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 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD FEB PY 2009 VL 36 IS 2 BP 176 EP 180 PG 5 WC Emergency Medicine SC Emergency Medicine GA 411CK UT WOS:000263625400011 PM 19168307 ER PT J AU Jha, AK Bates, DW Jenter, C Orav, EJ Zheng, J Cleary, P Simon, SR AF Jha, Ashish K. Bates, David W. Jenter, Chelsea Orav, E. John Zheng, Jie Cleary, Paul Simon, Steven R. TI Electronic health records: Use, barriers and satisfaction among physicians who care for black and Hispanic patients SO JOURNAL OF EVALUATION IN CLINICAL PRACTICE LA English DT Article DE electronic health records; physician satisfaction; racial disparities ID INFORMATION-TECHNOLOGY; QUALITY AB Electronic health records (EHRs) are a promising tool to improve the quality of health care, although it remains unclear who will benefit from this new technology. Given that a small group of providers care for most racial/ethnic minorities, we sought to determine whether minority-serving providers adopt EHR systems at comparable rates to other providers. We used survey data from stratified random sample of all medical practices in Massachusetts in 2005. We determined rates of EHR adoption, perceived barriers to adoption, and satisfaction with EHR systems. Physicians who reported patient panels of more than 40% black or Hispanic had comparable levels of EHR adoption than other physicians (27.9% and 21.8%, respectively, P = 0.46). Physicians from minority-serving practices identified financial and other barriers to implementing EHR systems at similar rates, although these physicians were less likely to be concerned with privacy and security concerns of EHRs (47.1% vs. 64.4%, P = 0.01). Finally, physicians from high-minority practices had similar perceptions about the positive impact of EHRs on quality (73.7% vs. 76.6%, P = 0.43) and costs (46.9% vs. 51.5%, P = 0.17) of care. In a state with a diverse minority population, we found no evidence that minority-serving providers had lower EHR adoption rates, faced different barriers to adoption or were less satisfied with EHRs. Given the importance of ensuring that minority-serving providers have equal access to EHR systems, we failed to find evidence of a new digital divide. C1 [Jha, Ashish K.; Bates, David W.; Zheng, Jie] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Jha, Ashish K.; Bates, David W.; Jenter, Chelsea; Orav, E. John] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. [Jha, Ashish K.] VA Boston Healthcare Syst, Boston, MA USA. [Jha, Ashish K.; Bates, David W.; Orav, E. John; Cleary, Paul] Harvard Univ, Sch Med, Boston, MA USA. [Simon, Steven R.] Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. RP Jha, AK (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, 677 Huntington Ave, Boston, MA 02115 USA. EM ajha@hsph.harvard.edu FU Program for Health Systems Improvement of the Harvard University Interfaculty Initiative; Agency for Healthcare Research and Quality [1 UC1 HS015397]; Massachusetts Health Collaborative [1 UC1 HS015397] FX The project was supported by a grant from the Program for Health Systems Improvement of the Harvard University Interfaculty Initiative. The survey was supported by grant number 1 UC1 HS015397 from the Agency for Healthcare Research and Quality and by the Massachusetts Health Collaborative. NR 13 TC 23 Z9 23 U1 2 U2 10 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1356-1294 J9 J EVAL CLIN PRACT JI J. Eval. Clin. Pract. PD FEB PY 2009 VL 15 IS 1 BP 158 EP 163 DI 10.1111/j.1365-2753.2008.00975.x PG 6 WC Health Care Sciences & Services; Medical Informatics; Medicine, General & Internal SC Health Care Sciences & Services; Medical Informatics; General & Internal Medicine GA 407AY UT WOS:000263337200023 PM 18759752 ER PT J AU Sheesley, RJ Schauer, JJ Garshick, E Laden, F Smith, TJ Blicharz, AP Deminter, JT AF Sheesley, Rebecca J. Schauer, James J. Garshick, Eric Laden, Francine Smith, Thomas J. Blicharz, Andrew P. Deminter, Jeffrey T. TI Tracking personal exposure to particulate diesel exhaust in a diesel freight terminal using organic tracer analysis SO JOURNAL OF EXPOSURE SCIENCE AND ENVIRONMENTAL EPIDEMIOLOGY LA English DT Article DE epidemiology; particulate matter; personal exposure; polycyclic aromatic hydrocarbons ID THERMAL-OPTICAL METHOD; AIR-POLLUTION SOURCES; RAILROAD WORKERS; ELEMENTAL CARBON; LUNG-CANCER; URBAN ATMOSPHERE; SOURCE APPORTIONMENT; ULTRAFINE PARTICLES; TRUCKING INDUSTRY; ACE-ASIA AB Personal exposure to particle-phase molecular markers was measured at a trucking terminal in St Louis, MO, as part of a larger epidemiologic project aimed at assessing carbonaceous fine particulate matter (PM) exposure in this occupational setting. The integration of parallel personal exposure, ambient worksite area and ambient urban background (St Louis Supersite) measurements provided a unique opportunity to track the work-related exposure to carbonaceous. ne PM in a freight terminal. The data were used to test the proposed personal exposure model in this occupational setting: Personal exposure = urban background + work site background + personal activity To accurately assess the impact of PM emission sources, particularly motor vehicle exhaust, and organic elemental carbon (OCEC) analysis and nonpolar organic molecular marker analysis by thermal desorption-gas chromatography/mass spectrometry (TD-GCMS) were conducted on all of the PM samples. EC has been used as a tracer for diesel exhaust in urban areas, however, the emission profile for diesel exhaust is dependent upon the operating conditions of the vehicle and can vary considerably within a fleet. Hopanes, steranes, polycyclic aromatic hydrocarbons and alkanes were measured by TD-GCMS. Hopanes are source-specific organic molecular markers for lubricating oil present in motor vehicle exhaust. The concentrations of OC, EC and the organic tracers were averaged to obtain average profiles to assess differences in the personal, worksite area and urban background samples, and were also correlated individually by sample time to evaluate the exposure model presented above. Finally, a chemical mass balance model was used to apportion the motor vehicle and cigarette-smoke components of the measured OC and EC for the average personal exposure, worksite area and urban background samples. C1 [Sheesley, Rebecca J.; Schauer, James J.] Univ Wisconsin, Environm Chem & Technol Program, Madison, WI 53706 USA. [Schauer, James J.; Deminter, Jeffrey T.] Univ Wisconsin, Wisconsin State Lab Hyg, Madison, WI 53706 USA. [Garshick, Eric] VA Boston Healthcare Syst, Med Serv, Pulm & Crit Care Med Sect, Boston, MA USA. [Garshick, Eric; Laden, Francine] Harvard Univ, Sch Med, Channing Lab, Brigham & Womens Hosp,Dept Med, Boston, MA 02115 USA. [Laden, Francine; Smith, Thomas J.; Blicharz, Andrew P.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Exposure Epidemiol & Risk Program, Boston, MA 02115 USA. RP Schauer, JJ (reprint author), Univ Wisconsin, Environm Chem & Technol Program, 660 N Pk St, Madison, WI 53706 USA. EM jjschauer@wisc.edu RI Smith, Thomas/A-9640-2010; Sheesley, Rebecca/I-6655-2015; OI Sheesley, Rebecca/0000-0002-8187-0571 FU NIH/NCI [R01 CA90792, HEI 4705-RFA03-1/04-1] FX This sampling and organic and elemental analysis were funded by NIH/NCI R01 CA90792 and the organic speciation analysis was funded by HEI 4705-RFA03-1/04-1. We acknowledge the work by Mark Meirtiz at the Wisconsin State Laboratory of Hygiene in assisting in the development of the TD-GCMS method used in this study. We thank Jay Turner for assistance in coordinating sample collection at the St Louis Supersite. We also thank the International Brotherhood of Teamsters Safety and Health Dept. (LaMont Byrd) and the participating companies. NR 47 TC 10 Z9 10 U1 3 U2 20 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1559-0631 J9 J EXPO SCI ENV EPID JI J. Expo. Sci. Environ. Epidemiol. PD FEB PY 2009 VL 19 IS 2 BP 172 EP 186 DI 10.1038/jes.2008.11 PG 15 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 395CT UT WOS:000262500600003 PM 18322451 ER PT J AU Finan, KR Renton, D Vick, CC Hawn, MT AF Finan, Kelly R. Renton, David Vick, Catherine C. Hawn, Mary T. TI Prevention of Post-operative Leak Following Laparoscopic Heller Myotomy SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article CT Annual Meeting of the Society-of-American-Gastrointestinal-and-Endoscopic-Surgeons CY APR 16-22, 2007 CL Las Vegas, NV SP Soc Amer Gastrointestinal & Endoscop Surg DE Esophageal achalasia; Laparoscopic surgery; Post-operative complication; Intra-operative procedures; Heller myotomy ID PREVIOUS ENDOSCOPIC TREATMENT; BOTULINUM TOXIN INJECTION; LONG-TERM EFFICACY; ESOPHAGEAL ACHALASIA; TOUPET FUNDOPLICATION; FORCEFUL DILATATION; DOR FUNDOPLICATION; ESOPHAGOMYOTOMY; DILATION; OUTCOMES AB Laparoscopic Heller myotomy is the preferred treatment for achalasia. Post-operative leaks cause significant morbidity and impair functional outcome. This study assesses the efficacy of intra-operative leak testing on post-operative leak rate. A retrospective analysis of 106 consecutive patients undergoing laparoscopic Heller myotomy by a single surgeon between November 2001 and August 2006 was undertaken. Intra-operative leak testing was performed in all patients. Variables associated with intra-operative mucosotomy were assessed by univariate analysis and logistic regression modeling. Intra-operative mucosotomy occurred in 25% of patients. All mucosotomies were repaired primarily and tested with methylene-blue-stained saline. Dor fundoplication was performed in 74% of the patients. There were no post-operative leaks and patients were started on diet day of surgery. Mean LOS was 1.4(+/- 0.7) days. Logistic regression modeling demonstrated that prior myotomy was associated with a statistically significant increase in the rate of mucosotomy (p = 0.033), while previous botox injection (p = 0.193), pneumatic dilation (p = 0.599) or concomitant hiatal hernia (p = 0.874) were not significantly associated with mucosotomy. Laparoscopic Heller myotomy for the treatment of achalasia is a safe procedure. Intra-operative leak testing minimizes the risk of post-operative leaks and expedites post-operative management. Prior endoscopic treatment does not impair operative results. C1 [Finan, Kelly R.; Renton, David; Vick, Catherine C.; Hawn, Mary T.] Univ Alabama, Dept Surg, Sect Gastrointestinal Surg, Birmingham, AL 35294 USA. [Vick, Catherine C.; Hawn, Mary T.] Birmingham Vet Affairs Med Ctr, Deep S Ctr Effectiveness Res, Birmingham, AL USA. RP Hawn, MT (reprint author), Univ Alabama, Dept Surg, Sect Gastrointestinal Surg, KB 417 1530 3rd Ave S, Birmingham, AL 35294 USA. EM mhawn@uab.edu NR 42 TC 6 Z9 7 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD FEB PY 2009 VL 13 IS 2 BP 200 EP 205 DI 10.1007/s11605-008-0687-4 PG 6 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 402AU UT WOS:000262987400004 PM 18781365 ER PT J AU Quinn, VP Hollis, JF Smith, KS Rigotti, NA Solberg, LI Hu, WM Stevens, VJ AF Quinn, Virginia P. Hollis, Jack F. Smith, K. Sabina Rigotti, Nancy A. Solberg, Leif I. Hu, Weiming Stevens, Victor J. TI Effectiveness of the 5-As Tobacco Cessation Treatments in Nine HMOs SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE smoking; HMOs; 5-As tobacco cessation treatment ID SMOKING-CESSATION; PATIENT SATISFACTION; PHYSICIANS; CARE; UPDATE AB Smoking remains the leading cause of preventable mortality in the US. The national clinical guideline recommends an intervention for tobacco use known as the 5-As (Ask, Advise, Assess, Assist, and Arrange). Little is known about the model's effectiveness outside the research setting. To assess the effectiveness of tobacco treatments in HMOs. Smokers identified from primary care visits in nine nonprofit health plans. Smokers were surveyed at baseline and at 12-month follow-up to assess smoking status and tobacco treatments offered by clinicians and used by smokers. Analyses include the 80% of respondents who reported having had a visit in the previous year with their clinician when they were smoking (n = 2,325). Smokers were more often offered Advice (77%) than the more effective Assist treatments-classes/counseling (41%) and pharmacotherapy (33%). One third of smokers reported using pharmacotherapy, but only 16% used classes or counseling. At follow-up, 8.9% were abstinent for > 30 days. Smokers who reported being offered pharmacotherapy were more likely to quit than those who did not (adjusted OR = 1.73, CI = 1.22-2.45). Compared with smokers who didn't use classes/counseling or pharmacotherapy, those who did use these services were more likely to quit (adjusted OR = 1.82, CI = 1.16-2.86 and OR = 2.23, CI = 1.56-3.20, respectively). Smokers were more likely to report quitting if they were offered cessation medications or if they used either medications or counseling. Results are similar to findings from clinical trials and highlight the need for clinicians and health plans to provide more than just advice to quit. C1 [Quinn, Virginia P.] Kaiser Permanente So Calif, Res & Evaluat Dept, Pasadena, CA 91188 USA. [Hollis, Jack F.; Smith, K. Sabina; Hu, Weiming; Stevens, Victor J.] Kaiser Permanente NW, Ctr Hlth Res, Portland, OR USA. [Rigotti, Nancy A.] Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. [Rigotti, Nancy A.] Harvard Univ, Sch Med, Boston, MA USA. [Solberg, Leif I.] HealthPartners Res Fdn, Minneapolis, MN USA. RP Quinn, VP (reprint author), Kaiser Permanente So Calif, Res & Evaluat Dept, 100 So Los Robles Ave,2nd Fl, Pasadena, CA 91188 USA. EM virginia.p.quinn@kp.org FU National Cancer Institute [U19 CA79689] FX This study was conducted within the Cancer Research Network (CRN), a consortium of non-profit HMOs funded by the National Cancer Institute to increase the effectiveness of preventive, curative, and supportive cancer-related interventions. We are grateful for the work and dedication of the investigators and research staff from the health plans participating in the HMOs Investigating Tobacco (HIT) study: Group Health Cooperative of Puget Sound, Seattle, WA; Harvard Pilgrim Health Care, Boston, MA; Health Alliance Plan of Michigan, Detroit, MI; HealthPartners, Minneapolis, MN; Kaiser Permanente Colorado, Denver, CO; Kaiser Permanente Hawaii, Honolulu, HI; Kaiser Permanente Northern California, Oakland, CA; Kaiser Permanente Northwest, Portland, OR; Kaiser Permanente Southern California, Pasadena, CA. Special thanks are given to the staff at the Survey Center at Health Partners. This study was funded by grant U19 CA79689 from the National Cancer Institute. NR 37 TC 32 Z9 32 U1 2 U2 4 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 FEB PY 2009 VL 24 IS 2 BP 149 EP 154 DI 10.1007/s11606-008-0865-9 PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 397GO UT WOS:000262651100001 PM 19083066 ER PT J AU Percac-Lima, S Grant, RW Green, AR Ashburner, JM Gamba, G Oo, S Richter, JM Atlas, SJ AF Percac-Lima, Sanja Grant, Richard W. Green, Alexander R. Ashburner, Jeffrey M. Gamba, Gloria Oo, Sarah Richter, James M. Atlas, Steven J. TI A Culturally Tailored Navigator Program for Colorectal Cancer Screening in a Community Health Center: A Randomized, Controlled Trial SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE colon cancer; screening; colonoscopy; patient navigation; randomized control trial ID URBAN MINORITY POPULATION; NON-HISPANIC WHITES; NEW-YORK-CITY; LOW-INCOME; AFRICAN-AMERICANS; ASIAN-AMERICANS; LIFE EXPECTANCY; UNITED-STATES; FOLLOW-UP; CARE AB Minority racial/ethnic groups have low colorectal cancer (CRC) screening rates. To evaluate a culturally tailored intervention to increase CRC screening, primarily using colonoscopy, among low income and non-English speaking patients. Randomized controlled trial conducted from January to October of 2007. Single, urban community health center serving a low-income, ethnically diverse population. A total of 1,223 patients 52-79 years of age overdue for CRC screening, randomized to intervention (n = 409) vs. usual care control (n = 814) groups. Intervention patients received an introductory letter with educational material followed by phone or in-person contact by a language-concordant "navigator." Navigators (n = 5) were community health workers trained to identify and address patient-reported barriers to CRC screening. Individually tailored interventions included patient education, procedure scheduling, translation and explanation of bowel preparation, and help with transportation and insurance coverage. Rates of colorectal cancer screening were assessed for intervention and usual care control patients. Over a 9-month period, intervention patients were more likely to undergo CRC screening than control patients (27% vs. 12% for any CRC screening, p < 0.001; 21% vs. 10% for colonoscopy completion, p < 0.001). The higher screening rate resulted in the identification of 10.5 polyps per 100 patients in the intervention group vs. 6.8 in the control group (p = 0.04). Patients were from one health center. Some patients may have obtained CRC screening outside our system. A culturally tailored, language-concordant navigator program designed to identify and overcome barriers to colorectal cancer screening can significantly improve colonoscopy rates for low income, ethnically and linguistically diverse patients. ClinicalTrials.gov registration number: NCT00476970. C1 [Percac-Lima, Sanja; Gamba, Gloria; Oo, Sarah] Massachusetts Gen Hosp, Chelsea HealthCare Ctr, Chelsea, MA 02150 USA. [Percac-Lima, Sanja; Grant, Richard W.; Green, Alexander R.; Ashburner, Jeffrey M.; Richter, James M.; Atlas, Steven J.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Percac-Lima, Sanja; Green, Alexander R.; Atlas, Steven J.] Massachusetts Gen Hosp, Dispar Solut Ctr, Boston, MA 02114 USA. [Richter, James M.] Massachusetts Gen Hosp, Gastroenterol Unit, Boston, MA 02114 USA. [Percac-Lima, Sanja; Grant, Richard W.; Green, Alexander R.; Richter, James M.; Atlas, Steven J.] Harvard Univ, Sch Med, Boston, MA USA. RP Percac-Lima, S (reprint author), Massachusetts Gen Hosp, Chelsea HealthCare Ctr, 151 Everett Ave, Chelsea, MA 02150 USA. EM spercaclima@partners.org OI Grant, Richard/0000-0002-6164-8025 FU Clinical Innovation Award; Massachusetts General Primary Care Practice- Based Research Network [NCI 1CA121908] FX The authors thank the staff from Clinical Research Program and Community Benefits Program at Massachusetts General Hospital. The paper was presented at the Annual Meeting of the Society of General Medicine in Pittsburg, PA, on April 10, 2008. The study was funded by: Clinical Innovation Award through the Massachusetts General Hospital, Community Benefits Program at Massachusetts General Hospital, Jane's Trust, Massachusetts Cancer Prevention Community Research Network, and a grant for the Massachusetts General Primary Care Practice- Based Research Network (NCI 1CA121908). NR 58 TC 133 Z9 133 U1 1 U2 13 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 FEB PY 2009 VL 24 IS 2 BP 211 EP 217 DI 10.1007/s11606-008-0864-x PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 397GO UT WOS:000262651100009 PM 19067085 ER PT J AU Starrels, JL Barg, FK Metlay, JP AF Starrels, Joanna L. Barg, Frances K. Metlay, Joshua P. TI Patterns and Determinants of Inappropriate Antibiotic Use in Injection Drug Users SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE antibiotics; adherence; injection drug use; self-medication ID RESISTANT STAPHYLOCOCCUS-AUREUS; METHICILLIN-RESISTANT; ANTIRETROVIRAL THERAPY; SAN-FRANCISCO; COMMUNITY; INFECTIONS; ADHERENCE; ABSCESSES; METAANALYSIS; PREVALENCE AB Inappropriate antibiotic use contributes to the emergence and spread of drug resistant infections. Though injection drug users are at increased risk for drug resistant infections, few studies have examined antibiotic use in this population. To understand patterns and determinants of antibiotic use among injection drug users. Five focus groups were conducted with 28 current injection drug users recruited from a syringe exchange program in Philadelphia and analyzed using the constant comparative method to identify emergent themes. Twenty-six participants also completed a written survey instrument. Injection drug users reported frequent antibiotic exposure, with 12 of 26 participants reporting use of antibiotic medications at least once in the previous 30 days. Participants reported several patterns of antibiotic use that were potentially harmful, including delays in seeking medical care, failing to fill prescriptions, obtaining antibiotics from non-provider sources, and poor adherence to prescribed regimens. The major determinants of inappropriate antibiotic use were delayed recognition of severity of illness, reluctance to wait to be seen, previous mistreatment by providers, lack of insurance, prioritizing purchasing drugs of abuse over antibiotics, forgetting to take antibiotics because of distractions that accompany drug use, concerns about interactions between antibiotics and other substances, and an irregular diet. Additionally, injection drug users commonly misunderstood the concept of antibiotic resistance and equated it with tolerance. Injection drug users reported potentially dangerous antibiotic use behaviors and described determinants of these behaviors. Outreach and educational interventions to improve antibiotic use should target high-risk populations, such as injection drug users, and consider their distinct antibiotic use behaviors and determinants. C1 [Starrels, Joanna L.; Metlay, Joshua P.] Univ Penn, Sch Med, Robert Wood Johnson Clin Scholars Program, Philadelphia, PA 19104 USA. [Starrels, Joanna L.; Metlay, Joshua P.] Vet Affairs Med Ctr, Philadelphia, PA USA. [Starrels, Joanna L.; Metlay, Joshua P.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Metlay, Joshua P.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Barg, Frances K.] Univ Penn, Dept Anthropol, Philadelphia, PA 19104 USA. [Barg, Frances K.] Univ Penn, Sch Med, Dept Family Med & Community Hlth, Philadelphia, PA 19104 USA. [Starrels, Joanna L.] Albert Einstein Coll Med, Div Gen Internal Med, Bronx, NY 10467 USA. [Starrels, Joanna L.] Montefiore Med Ctr, Bronx, NY 10467 USA. RP Starrels, JL (reprint author), Albert Einstein Coll Med, Div Gen Internal Med, 111 E 210th St, Bronx, NY 10467 USA. EM jostarre@montefiore.org FU NIDA NIH HHS [K23 DA027719] NR 44 TC 1 Z9 2 U1 0 U2 4 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 FEB PY 2009 VL 24 IS 2 BP 263 EP 269 DI 10.1007/s11606-008-0859-7 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 397GO UT WOS:000262651100018 PM 19082860 ER PT J AU Jawa, A Zucchini, M Lauri, G Jupiter, J AF Jawa, Andrew Zucchini, Maura Lauri, Guilio Jupiter, Jesse TI Modified Step-Cut Osteotomy for Metacarpal and Phalangeal Rotational Deformity SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Metacarpal; osteotomy; rotational; step-cut ID MALUNION; FINGERS AB Purpose Rotational deformity of metacarpal and phalangeal fractures can jeopardize normal hand function and cause aesthetic problems for patients. We have found the Z-cut metacarpal osteotomy, initially described by Manktelow, to prove predictable and provide precise restoration of rotation and function. Therefore, we reviewed our experience with this technique. Methods The senior authors identified 12 patients treated with rotational step-cut osteotomies for digital rotatory deformities. The cases were reviewed retrospectively. Seven had metacarpal and five had phalangeal malunions. Results All 12 patients had correction of their deformities, obtained union of the osteotomy, and maintained or improved their motion. There were no perioperative complications. Conclusions Metacarpal step-cut osteotomies are a technically simple and effective method for correction of digital rotational deformities resulting from fracture malunions. Unlike other types of osteotomies, this technique affords precise intraoperative control at the osteotomy site, a large surface area for bony healing, and rigid fixation with early digital motion. (J Hand Surg 2009;34A:335-340. (C) 2009 Published by Elsevier Inc. on behalf of the American Society for Surgery of the Hand.) C1 [Jawa, Andrew] Massachusetts Gen Hosp, Yawkey Ctr, Dept Orthopaed Surg, Boston, MA 02114 USA. SODC Chirurg Mano & Microchirurg, Florence, Italy. RP Jawa, A (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Dept Orthopaed Surg, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM ajawa@partners.org NR 14 TC 10 Z9 11 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 FEB PY 2009 VL 34A IS 2 BP 335 EP 340 DI 10.1016/j.jhsa.2008.11.018 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 404EQ UT WOS:000263134000022 PM 19181235 ER PT J AU De Jesus, M AF De Jesus, Maria TI The Importance of Social Context in Understanding and Promoting Low-Income Immigrant Women's Health SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Article DE Cape Verdean health promoters; immigrant women; health promotion; social context ID COMMUNITY-HEALTH; MODEL; INTERVENTION; STRATEGIES; PROGRAM; WORKERS AB Understanding the social context and realities of Cape Verdean women in the U.S. as well as other immigrant and ethnic/racial groups is important to promote their overall health and well-being more effectively. The aim of this study was to gain a contextual understanding from the perspectives of health promoters who work with marginalized women. In-depth, semi-structured interviews were conducted with nine Cape Verdean women health promoters about their perspectives and experiences of health promotion practice with immigrant women in their community. Using a Glaserian grounded theory approach to analysis, six salient themes describing women's social context emerged: community and domestic violence, loss and isolation, economic injustice, immigration-related issues and abuse, unequal gender-based power relations, and cultural taboos. These findings challenge health researchers and practitioners to understand health problems and health promotion not only at an individual level, but at multiple levels of influence including interpersonal, family, neighborhood, and structural levels. C1 [De Jesus, Maria] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [De Jesus, Maria] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. RP De Jesus, M (reprint author), 44 Binney St,LW703, Boston, MA 02115 USA. EM Maria_Dejesus@dfci.harvard.edu NR 26 TC 7 Z9 7 U1 0 U2 5 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 1049-2089 J9 J HEALTH CARE POOR U JI J. Health Care Poor Underserved PD FEB PY 2009 VL 20 IS 1 BP 90 EP 97 PG 8 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 409BA UT WOS:000263480000011 PM 19202249 ER PT J AU Aoyayna, A Ng, CY Millington, TM Boskovic, S Ito, S Wain, JC Houser, SI Madsen, JC Sachs, DH Kawai, T Allan, JS AF Aoyayna, A. Ng, C. Y. Millington, T. M. Boskovic, S. Ito, S. Wain, J. C. Houser, S. I. Madsen, J. C. Sachs, D. H. Kawai, T. Allan, J. S. TI Cellular Immunity Is Enhanced in a Non-Human Primate Lung Transplantation Model, as Compared to an Analogous Kidney Transplantation Model SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 29th Annual Meeting and Scientific Session of the International-Society-for-Heart-and-Lung-Transplantation CY APR 22-25, 2009 CL Paris, FRANCE SP Int Soc Heart & Lung Transplantat C1 Massachusetts Gen Hosp, Div Thorac & Cardiac Surg, Transplant Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplanat Biol Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 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 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2009 VL 28 IS 2 SU S MA 449 BP S221 EP S222 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 409XT UT WOS:000263539800445 ER PT J AU Baker, JN Ennis, SC Camuso, JM Ennis, CA Lam, KM Moore, SA MacGillivray, TE AF Baker, J. N. Ennis, S. C. Camuso, J. M. Ennis, C. A. Lam, K. M. Moore, S. A. MacGillivray, T. E. TI Tackling Pseudomonas Infection in Our HeartMate II Patients SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 29th Annual Meeting and Scientific Session of the International-Society-for-Heart-and-Lung-Transplantation CY APR 22-25, 2009 CL Paris, FRANCE SP Int Soc Heart & Lung Transplantat C1 [Baker, J. N.; Ennis, S. C.; Camuso, J. M.; Ennis, C. A.; Lam, K. M.; Moore, S. A.; MacGillivray, T. E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2009 VL 28 IS 2 MA 631 BP S285 EP S285 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 409XT UT WOS:000263539800627 ER PT J AU Baker, JN Ennis, SC Gonczarek, KM Kleinkauf, L Ennis, CA Lam, KM Moore, SA MacGillivray, TE AF Baker, J. N. Ennis, S. C. Gonczarek, K. M. Kleinkauf, L. Ennis, C. A. Lam, K. M. Moore, S. A. MacGillivray, T. E. TI Trend or Treason: No Increase in Thromboembolic Events in LVAD Patients with Atrial Fibrillation Off Coumadin SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 29th Annual Meeting and Scientific Session of the International-Society-for-Heart-and-Lung-Transplantation CY APR 22-25, 2009 CL Paris, FRANCE SP Int Soc Heart & Lung Transplantat C1 [Baker, J. N.; Ennis, S. C.; Gonczarek, K. M.; Kleinkauf, L.; Ennis, C. A.; Lam, K. M.; Moore, S. A.; MacGillivray, T. E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2009 VL 28 IS 2 MA 16 BP S70 EP S70 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 409XT UT WOS:000263539800017 ER PT J AU Drazner, MH Brown, RN Kaiser, PA Cabuay, B Lewis, NP Semigran, MJ Torre-Amione, G Naftel, DC Kirklin, JK AF Drazner, M. H. Brown, R. N. Kaiser, P. A. Cabuay, B. Lewis, N. P. Semigran, M. J. Torre-Amione, G. Naftel, D. C. Kirklin, J. K. TI The Relationship of Right and Left Ventricular Filling Pressures in Patients Undergoing Cardiac Transplantation: A 17-Year Multi-institutional Analysis SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 29th Annual Meeting and Scientific Session of the International-Society-for-Heart-and-Lung-Transplantation CY APR 22-25, 2009 CL Paris, FRANCE SP Int Soc Heart & Lung Transplantat C1 [Drazner, M. H.; Kaiser, P. A.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Brown, R. N.; Naftel, D. C.; Kirklin, J. K.] Univ Alabama, Birmingham, AL USA. [Semigran, M. J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Torre-Amione, G.] Methodist Hosp, Houston, TX 77030 USA. [Lewis, N. P.] Virginia Commonwealth Univ, Richmond, VA USA. [Cabuay, B.] Univ Iowa, Iowa City, IA USA. NR 0 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 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2009 VL 28 IS 2 MA 87 BP S96 EP S96 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 409XT UT WOS:000263539800087 ER PT J AU Millington, TM Boenisch, O Boskovic, S Najaflan, N Sayegh, MH Madsen, JC AF Millington, T. M. Boenisch, O. Boskovic, S. Najaflan, N. Sayegh, M. H. Madsen, J. C. TI Expansion of CD4+CD25+FoxP3+Regulatory T Lymphocytes with Low-Dose Anti-Thymocyte Globulin Leads to Prolonged Survival of Cardiac Allografts but Not Tolerance SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 29th Annual Meeting and Scientific Session of the International-Society-for-Heart-and-Lung-Transplantation CY APR 22-25, 2009 CL Paris, FRANCE SP Int Soc Heart & Lung Transplantat C1 [Millington, T. M.; Boskovic, S.; Madsen, J. C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Boenisch, O.; Najaflan, N.; Sayegh, M. H.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 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 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2009 VL 28 IS 2 MA 29 BP S75 EP S75 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 409XT UT WOS:000263539800030 ER PT J AU Millington, TM Tena, A Boskovic, S Kawai, T Wain, J Allan, J Sachs, DH Madsen, JC AF Millington, T. M. Tena, A. Boskovic, S. Kawai, T. Wain, J. Allan, J. Sachs, D. H. Madsen, J. C. TI Regeneration of Naive T-Lymphocytes from Heart-Thymus Grafts Occurs at a Low Level and Is Associated with Prolonged Survival but Not Tolerance SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 29th Annual Meeting and Scientific Session of the International-Society-for-Heart-and-Lung-Transplantation CY APR 22-25, 2009 CL Paris, FRANCE SP Int Soc Heart & Lung Transplantat C1 [Millington, T. M.; Tena, A.; Boskovic, S.; Kawai, T.; Wain, J.; Allan, J.; Sachs, D. H.; Madsen, J. C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2009 VL 28 IS 2 MA 32 BP S76 EP S76 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 409XT UT WOS:000263539800032 ER PT J AU Moazami, N Ewald, GA Pagant, FD John, R MacGillivray, TE Chen, L Dembitsky, WP Farrar, DJ Frazier, OH AF Moazami, N. Ewald, G. A. Pagant, F. D. John, R. MacGillivray, T. E. Chen, L. Dembitsky, W. P. Farrar, D. J. Frazier, O. H. TI Clinical Durability and Low Incidence of Pump Replacement of a Continuous-Flow Left Ventricular Assist Device SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 29th Annual Meeting and Scientific Session of the International-Society-for-Heart-and-Lung-Transplantation CY APR 22-25, 2009 CL Paris, FRANCE SP Int Soc Heart & Lung Transplantat C1 [Moazami, N.; Ewald, G. A.] Washington Univ, Sch Med, St Louis, MO USA. [Pagant, F. D.] Univ Michigan, Ann Arbor, MI 48109 USA. [John, R.] Univ Minnesota, Minneapolis, MN USA. [MacGillivray, T. E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chen, L.] Univ Rochester, Rochester, NY USA. [Dembitsky, W. P.] Sharp Mem Hosp & Rehabil Ctr, San Diego, CA USA. [Farrar, D. J.] Thoratec Corp, Pleasanton, CA USA. [Frazier, O. H.] Texas Heart Inst, Houston, TX 77025 USA. NR 0 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 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2009 VL 28 IS 2 MA 407 BP S207 EP S207 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 409XT UT WOS:000263539800404 ER PT J AU Parks, KA Gonczarek, K Onuma, O Moukarbel, GV Rosengard, BR Semigran, MJ Carlson, WD AF Parks, K. A. Gonczarek, K. Onuma, O. Moukarbel, G. V. Rosengard, B. R. Semigran, M. J. Carlson, W. D. TI Short Term Outcomes Using CD3 Guided Low Dose Anti Thymocyte Globulin To Avoid Early Calcineurin inhibition after Cardiac Transplantation SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 29th Annual Meeting and Scientific Session of the International-Society-for-Heart-and-Lung-Transplantation CY APR 22-25, 2009 CL Paris, FRANCE SP Int Soc Heart & Lung Transplantat C1 [Parks, K. A.; Gonczarek, K.; Onuma, O.; Moukarbel, G. V.; Rosengard, B. R.; Semigran, M. J.; Carlson, W. D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2009 VL 28 IS 2 MA 75 BP S91 EP S91 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 409XT UT WOS:000263539800075 ER PT J AU Singh, TP Semigran, M Gauvreau, K Costantino, F DeNofrio, D Evans, S Givertz, M AF Singh, T. P. Semigran, M. Gauvreau, K. Costantino, F. DeNofrio, D. Evans, S. Givertz, M. TI Relationship of Race and Socioeconomic Position with Rejection Incidence in Heart Transplant Recipients SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 29th Annual Meeting and Scientific Session of the International-Society-for-Heart-and-Lung-Transplantation CY APR 22-25, 2009 CL Paris, FRANCE SP Int Soc Heart & Lung Transplantat C1 [Singh, T. P.; Gauvreau, K.; Costantino, F.; Evans, S.] Childrens Hosp, Boston, MA 02115 USA. [Semigran, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Givertz, M.] Brigham & Womens Hosp, Boston, MA 02115 USA. New England Organ Bank Inc, Watertown, MA USA. [DeNofrio, D.] Tufts Med Ctr, Boston, MA USA. NR 0 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 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2009 VL 28 IS 2 MA 561 BP S261 EP S261 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 409XT UT WOS:000263539800557 ER PT J AU Veillette, GR Meltzer, AJ Kim, KM Millington, Y Aoyama, A Cochrane, M Houser, S Sachs, DH Allan, JS Madsen, JC Rosengard, BR AF Veillette, G. R. Meltzer, A. J. Kim, K. M. Millington, Y. Aoyama, A. Cochrane, M. Houser, S. Sachs, D. H. Allan, J. S. Madsen, J. C. Rosengard, B. R. TI Donor Brain Death Causes Acute Allograft Rejection in an Established Model of Cardiac Tolerance SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 29th Annual Meeting and Scientific Session of the International-Society-for-Heart-and-Lung-Transplantation CY APR 22-25, 2009 CL Paris, FRANCE SP Int Soc Heart & Lung Transplantat C1 [Veillette, G. R.; Meltzer, A. J.; Kim, K. M.; Millington, Y.; Aoyama, A.; Cochrane, M.; Houser, S.; Sachs, D. H.; Allan, J. S.; Madsen, J. C.; Rosengard, B. R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2009 VL 28 IS 2 MA 356 BP S189 EP S189 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 409XT UT WOS:000263539800354 ER PT J AU Weynand, B Collins, AR Smith, RN AF Weynand, B. Collins, A. R. Smith, R. N. TI Combined Positive C4d and C3d Immunofluorescence in Human Heart Transplants: How Frequent Is the Coexpression Seen? SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 29th Annual Meeting and Scientific Session of the International-Society-for-Heart-and-Lung-Transplantation CY APR 22-25, 2009 CL Paris, FRANCE SP Int Soc Heart & Lung Transplantat C1 [Weynand, B.] Clin Univ St Luc, B-1200 Brussels, Belgium. [Collins, A. R.; Smith, R. N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2009 VL 28 IS 2 MA 35 BP S77 EP S77 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 409XT UT WOS:000263539800035 ER PT J AU Tai, AW Chung, RT AF Tai, Andrew W. Chung, Raymond T. TI Treatment failure in hepatitis C: Mechanisms of non-response SO JOURNAL OF HEPATOLOGY LA English DT Review DE Hepatitis C; Interferon; Treatment; Race; Immune system ID SUSTAINED VIROLOGICAL RESPONSE; CAUCASIAN AMERICAN PATIENTS; VIRUS-RNA REPLICATION; ANTIVIRAL THERAPY; PLUS RIBAVIRIN; CORE PROTEIN; IN-VITRO; ANTIINTERFERON ANTIBODIES; PEGINTERFERON ALPHA-2B; CYTOKINE SIGNALING-3 AB Hepatitis C virus (HCV) has evolved remarkable mechanisms that favor viral persistence by interfering with host innate and adaptive immune responses. These same mechanisms are likely to contribute to resistance to exogenously administered interferon used for HCV treatment. We review the host innate and adaptive immune responses in the context of HCV infection as well as the strategies by which these responses are subverted by the virus. In addition, the contribution of host factors, such as race and insulin resistance, to interferon non-responsiveness is discussed. Our progress in understanding the molecular underpinnings of interferon treatment failure in HCV infection has resulted in several promising and novel treatment strategies for HCV treatment non-responders. (C) 2008 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. C1 [Chung, Raymond T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, WRN 1007,55 Fruit St, Boston, MA 02114 USA. EM rtchung@partners.org OI Tai, Andrew/0000-0002-6877-450X FU National Institutes of Health [AI080122, AI069939, DK078772]; Massachusetts Biomedical Research Corporation FX This publication was made possible by Grant Numbers AI080122 (to A.W.T.), AI069939, and DK078772 (to R.T.C.) from the National Institutes of Health as well as by a Tosteson Postdoctoral Fellowship from the Massachusetts Biomedical Research Corporation (to A.W.T.). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. This invited review is based on Dr. Raymond Chung's talk at the 2008 EASL-AASLD-APASL-ALEH-IASL Conference oil Hepatitis B & C Virus Resistance to Antiviral Thcrapics. NR 55 TC 36 Z9 39 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD FEB PY 2009 VL 50 IS 2 BP 412 EP 420 DI 10.1016/j.jhep.2008.11.010 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 406QC UT WOS:000263309000024 PM 19070928 ER PT J AU Piccini, JP Hernandez, AF Dibernardo, LR Rogers, JG Dhallwal, G AF Piccini, Jonathan P. Hernandez, Adrian F. Dibernardo, Louis R. Rogers, Joseph G. Dhallwal, Gurpreet TI A Change of Heart SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID RIGHT-VENTRICULAR DYSPLASIA; DYSPLASIA/CARDIOMYOPATHY C1 [Piccini, Jonathan P.; Hernandez, Adrian F.; Rogers, Joseph G.] Duke Univ, Duke Clin Res Inst, Div Cardiovasc Med, Med Ctr, Durham, NC 27710 USA. [Dibernardo, Louis R.] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. [Dhallwal, Gurpreet] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Dhallwal, Gurpreet] San Francisco VA Med Ctr, San Francisco, CA USA. RP Piccini, JP (reprint author), Duke Univ, Duke Clin Res Inst, Div Cardiol, Med Ctr, DUMC 3115, Durham, NC 27710 USA. EM jonathan.piccini@duke.edu RI Hernandez, Adrian F./A-7818-2016 OI Hernandez, Adrian F./0000-0003-3387-9616 NR 11 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1553-5592 J9 J HOSP MED JI J. Hosp. Med. PD FEB PY 2009 VL 4 IS 2 BP 131 EP 136 DI 10.1002/jhm.426 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 413QK UT WOS:000263807400008 PM 19219930 ER PT J AU Chauhan, SK El Annan, J Ecoiffier, T Goyal, S Zhang, Q Saban, DR Dana, R AF Chauhan, Sunil K. El Annan, Jaafar Ecoiffier, Tatiana Goyal, Sunali Zhang, Qiang Saban, Daniel R. Dana, Reza TI Autoimmunity in Dry Eye Is Due to Resistance of Th17 to Treg Suppression SO JOURNAL OF IMMUNOLOGY LA English DT Article ID REGULATORY T-CELLS; KERATOCONJUNCTIVITIS SICCA; IMMUNOLOGICAL-TOLERANCE; TEAR FLUID; DISEASE; INFLAMMATION; ARTHRITIS; SJOGRENS; ENCEPHALOMYELITIS; INTERLEUKIN-1 AB Dry eye disease (DED), an inflammatory autoimmune disorder affecting the ocular surface, degrades visual performance and the quality of life of >10 million people in the United States alone. The primary limitation in the effective treatment of DED is an incomplete understanding of its specific cellular and molecular pathogenic elements. Using a validated mouse model of DIED, herein we functionally characterize the different T cell subsets, including regulatory T cells (Tregs) and pathogenic effector T cells, and determine their contribution to the pathogenesis of DED. Our data demonstrate the presence of dysfunctional Tregs and the resistance of pathogenic T cells, particularly Th17 cells, to Treg suppression in DIED. In addition, we clearly show that in vivo blockade of IL-17 significantly reduces the severity and progression of disease, which is paralleled by a reduction in the expansion of Th17 cells and restoration of Treg function. Our findings elucidate involvement of a previously unknown pathogenic T cell subset (Th17) in DED that is associated specifically with Treg dysfunction and disease pathogenesis and suggest a new target for dry eye therapy. The Journal of Immunology, 2009, 182: 1247-1252. C1 [Chauhan, Sunil K.; El Annan, Jaafar; Ecoiffier, Tatiana; Goyal, Sunali; Zhang, Qiang; Saban, Daniel R.; Dana, Reza] Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. [Dana, Reza] Harvard Univ, Massachusetts Eye & Ear Infirm, 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 [NEI R01-12963] FX This work was supported in part by National Institutes of Health Grant NEI R01-12963. NR 31 TC 109 Z9 117 U1 1 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 2009 VL 182 IS 3 BP 1247 EP 1252 PG 6 WC Immunology SC Immunology GA 400BD UT WOS:000262842100006 PM 19155469 ER PT J AU Tabrizi, SJ Niiro, H Masui, M Yoshimoto, G Iino, T Kikushige, Y Wakasaki, T Baba, E Shimoda, S Miyamoto, T Hara, T Akashi, K AF Tabrizi, Siamak Jabbarzadeh Niiro, Hiroaki Masui, Mariko Yoshimoto, Goichi Iino, Tadafumi Kikushige, Yoshikane Wakasaki, Takahiro Baba, Eishi Shimoda, Shinji Miyamoto, Toshihiro Hara, Toshiro Akashi, Koichi TI T Cell Leukemia/Lymphoma 1 and Galectin-1 Regulate Survival/Cell Death Pathways in Human Naive and IgM(+) Memory B Cells through Altering Balances in Bcl-2 Family Proteins SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; MEMBER BIM; PROAPOPTOTIC PROTEIN; INDUCED APOPTOSIS; UP-REGULATION; MCL-1; EXPRESSION; TCL1; PHOSPHORYLATION; MITOCHONDRIA AB BCR signaling plays a critical role in purging the self-reactive repertoire, or in rendering it anergic to establish self-tolerance in the periphery. Differences in self-reactivity between human naive and IgM(+) memory B cells may reflect distinct mechanisms by which BCR signaling dictates their survival and death. Here we demonstrate that BCR stimulation protected naive B cells from apoptosis with induction of prosurvival Bcl-2 family proteins, Bcl-x(L) and Mcl-1, whereas it rather accelerated apoptosis of IgM(+) memory B cells by inducing proapoptotic BH3-only protein Bim. We found that BCR-mediated PI3K activation induced the expression of Mcl-1, whereas it inhibited Bim expression in B cells. Phosphorylation of Akt, a downstream molecule of PI3K, was more sustained in naive than IgM(+) memory B cells. Abundant expression of T cell leukemia/lymphoma 1 (Tell), an Akt coactivator, was found in naive B cells, and enforced expression of Tell induced a high level of Mcl-1 expression, resulting in prolonged B cell survival. In contrast, Galectin-1 (Gal-1) was abundantly expressed in IgM(+) memory B cells, and inhibited Akt phosphorylation, leading to Bim up-regulation. Enforced expression of Gal-1 induced accelerated apoptosis in B cells. These results suggest that a unique set of molecules, Tell and Gal-1, defines distinct BCR signaling cascades, dictating survival and death of human naive and IgM(+) memory B cells. The Journal of Immunology, 2009, 182: 1490-1499. C1 [Niiro, Hiroaki] Kyushu Univ, Grad Sch Med Sci, Dept Med & Biosyst Sci, Higashi Ku, Fukuoka 8128582, Japan. [Tabrizi, Siamak Jabbarzadeh; Hara, Toshiro] Kyushu Univ, Grad Sch Med Sci, Dept Pediat, Fukuoka 8128582, Japan. [Masui, Mariko; Miyamoto, Toshihiro] Kyushu Univ Hosp, Ctr Cellular & Mol Med, Fukuoka 812, Japan. [Iino, Tadafumi; Akashi, Koichi] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Wakasaki, Takahiro] Kyushu Univ, Grad Sch Med Sci, Dept Otorhinolaryngol, Fukuoka 8128582, Japan. RP Niiro, H (reprint author), Kyushu Univ, Grad Sch Med Sci, Dept Med & Biosyst Sci, Higashi Ku, 3-1-1 Maidashi, Fukuoka 8128582, Japan. EM hniiro@med.kyushu-u.ac.jp FU Ministry of Education, Culture, Sports, Science, and Technology in Japan FX This work was supported in part by a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science, and Technology in Japan (to S.J.T., H.N., T.H., and K.A.). NR 39 TC 28 Z9 28 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 2009 VL 182 IS 3 BP 1490 EP 1499 PG 10 WC Immunology SC Immunology GA 400BD UT WOS:000262842100033 PM 19155496 ER PT J AU Maier, LM Anderson, DE Severson, CA Baecher-Allan, C Healy, B Liu, DV Wittrup, KD De Jager, PL Hafler, DA AF Maier, Lisa M. Anderson, David E. Severson, Christopher A. Baecher-Allan, Clare Healy, Brian Liu, David V. Wittrup, K. Dane De Jager, Philip L. Hafler, David A. TI Soluble IL-2RA Levels in Multiple Sclerosis Subjects and the Effect of Soluble IL-2RA on Immune Responses SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTERLEUKIN-2 RECEPTOR LEVELS; REGULATORY T-CELLS; CEREBROSPINAL-FLUID; DISEASE; EXPRESSION; TOLERANCE; MONOCYTES; BINDING; SYSTEM; REGION AB Multiple sclerosis (MS) is an organ-specific autoimmune disorder that is in part genetically determined. The gene encoding the a-chain of the IL-2 receptor, IL2RA, harbors alleles associated with risk to MS and other autoimmune diseases. In addition, IL2RA genetic variants correlate with the levels of a soluble form of the IL-2 receptor in subjects with type 1 diabetes and multiple sclerosis. Here, we show that the IL2RA genotypes differentially affects soluble IL-2RA (sIL-2RA) levels in MS cases vs healthy controls; the two variants associated with MS (rs12722489 and rs2104286) account for 15 and 18% of the total variance in log(10)-transformed sIL-2RA concentration in control subjects but less so in subjects with MS (2 and 5%), suggesting that perturbations associated with disease or treatment may influence sIL-2RA levels in subjects with MS. Whereas analyses demonstrate that sIL-2RA serum concentrations are a remarkably stable phenotype in both healthy controls and untreated MS subjects, a difference is observed between benign and malignant MS. These data indicate that, in addition to specific allelic variants at IL2RA, immunological perturbations associated with aggressive forms of the disease can influence sIL-2RA levels in serum of MS subjects. We also demonstrate, functionally, that sIL-2RA can inhibit IL-2 signaling, yet enhance T cell proliferation and expansion. In summary, we propose that before disease onset, strong genetic factors associated with disease risk dictate sIL-2RA levels that may be further modulated with onset of chronic systemic inflammation associated with MS. The Journal of Immunology, 2009, 182: 1541-1547. C1 [Maier, Lisa M.; Anderson, David E.; Severson, Christopher A.; Baecher-Allan, Clare; Healy, Brian; De Jager, Philip L.; Hafler, David A.] Brigham & Womens Hosp, Ctr Neurol Dis, Div Mol Immunol, Dept Neurol, Boston, MA 02115 USA. [Maier, Lisa M.; Anderson, David E.; Severson, Christopher A.; Baecher-Allan, Clare; Healy, Brian; De Jager, Philip L.; Hafler, David A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Maier, Lisa M.; De Jager, Philip L.; Hafler, David A.] MIT, Broad Inst, Cambridge, MA 02139 USA. [Maier, Lisa M.; De Jager, Philip L.; Hafler, David A.] Harvard Univ, Cambridge, MA 02139 USA. [Healy, Brian] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02115 USA. [Liu, David V.; Wittrup, K. Dane] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Wittrup, K. Dane] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [De Jager, Philip L.] Partners Ctr Personalized Med, Boston, MA 02115 USA. RP Maier, LM (reprint author), Brigham & Womens Hosp, Ctr Neurol Dis, Div Mol Immunol, Dept Neurol, New Res Bldg,77 Louis Pasteur Ave, Boston, MA 02115 USA. EM lmaier@rics.bwh.harvard.edu FU National Multiple Sclerosis Society; National Institutes of Health-National Institute of Allergy and Infectious Diseases [P01 AI39671]; National Institutes of Health [RO1 NS049477]; JDRF Postdoctoral Fellowship; American Cancer Society; National Institute of Neurological Disorders and Stroke [NS2427] FX This work was funded by the National Multiple Sclerosis Society, the National Institutes of Health-National Institute of Allergy and Infectious Diseases (P01 AI39671) and the National Institutes of Health (RO1 NS049477). Further support was provided by a JDRF Postdoctoral Fellowship (to L.M.M.), a grant by the American Cancer Society (to D.E.A.), a Harry Weaver Neuroscience Scholar award by the National Multiple Sclerosis Society (to P.L.D.), and Jacob Javits Merit Award NS2427 (to D.A.H.) from the National Institute of Neurological Disorders and Stroke. NR 35 TC 69 Z9 70 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 2009 VL 182 IS 3 BP 1541 EP 1547 PG 7 WC Immunology SC Immunology GA 400BD UT WOS:000262842100039 PM 19155502 ER PT J AU Cho, DC Puzanov, I Regan, MM Schwarzberg, T Seery, V Lee, MY Liu, V Bhatt, R Koon, H Mier, JW Sosman, JA Atkins, MB McDermott, DF AF Cho, Daniel C. Puzanov, Igor Regan, Meredith M. Schwarzberg, Talya Seery, Virginia Lee, Mee-Young Liu, Vivian Bhatt, Rupal Koon, Henry Mier, James W. Sosman, Jeffrey A. Atkins, Michael B. McDermott, David F. TI Retrospective Analysis of the Safety and Efficacy of Interleukin-2 After Prior VEGF-targeted Therapy in Patients With Advanced Renal Cell Carcinoma SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE interleukin-2; renal cancer; VEGF; tyrosine kinase inhibitors ID DOSE RECOMBINANT INTERLEUKIN-2; TYROSINE KINASE INHIBITOR; PHASE-III TRIAL; SUPPRESSOR-CELLS; SUNITINIB; CANCER; BEVACIZUMAB; CARDIOTOXICITY; INTERFERON; SORAFENIB AB Agents targeting vascular endothelial growth factor (VEGF) signaling have been advocated as frontline therapy for advanced renal cancer. The role of interleukin 2 (IL-2) therapy after resistance to VEGF-targeted therapy remains Unexplored. We conducted a retrospective analysis of the tolerability and efficacy of IL-2 therapy in patients who had previously received VEGF-targeted therapy. Twenty-three consecutive patients who received salvage IL-2 therapy were analyzed. Fifteen patients had received prior tyrosine kinase inhibitors (TKIs) (sorafenib or sunitinib), whereas 8 patients had received bevacizumab alone. Six of 23 patients did not receive week 2 of cycle 1 of treatment. All 6 of these patients had received prior TKIs. The incidence of severe cardiac toxicities, including 1 sudden cardiac death, in patients receiving prior TKI was 40% (95% confidence interval, 16.3-67.7%), significantly higher than what is expected from historical experience. Only 1 or 23 patients proceeded to receive a second cycle of IL-2. No patients achieved a partial or complete response to therapy. This retrospective analysis highlights inexpected and severe cardiac toxicities in patients receiving IL-2 after VEGF-targeted TKI therapy. The assumption that IL-2 therapy can be safely administered after TKI therapy may not be valid. Further examination of the safety of this sequential approach is necessary and more cautious patient selection seems warranted. C1 [Cho, Daniel C.; Schwarzberg, Talya; Seery, Virginia; Lee, Mee-Young; Liu, Vivian; Bhatt, Rupal; Mier, James W.; Atkins, Michael B.; McDermott, David F.] Beth Israel Deaconess Med Ctr, Div Hematol & Oncol, Boston, MA 02215 USA. [Regan, Meredith M.] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. [Sosman, Jeffrey A.] Vanderbilt Ingram Canc Ctr, Div Hematol & Oncol, Nashville, TN USA. [Koon, Henry] Case Comprehens Canc Ctr, Div Hematol & Oncol, Cleveland, OH USA. RP Cho, DC (reprint author), Beth Israel Deaconess Med Ctr, Div Hematol & Oncol, 330 Brookline Ave,MASCO 4, Boston, MA 02215 USA. EM dchol@bidmc.harvard.edu RI Puzanov, Igor/A-7179-2009 FU Novartis and Bayer, FX Daniel C. Cho served on the Advisory Board for Novartis and Genentech Pharmaceuticals and speakers' bureau for Pfizer. Igor Puzanov served on speakers' bureaus for Novartis and Pfizer. Michael B. Atkins served on the Advisory Board for Novartis. Bayer, Onyx, Genentech, and Wyeth. Michael B. Atkins served on speakers' bureaus for Novartis and Wyeth and was provided research support from Novartis and Bayer, David F. McDermott served on the Advisory Board and speakers' bureau for Novartis. All other authors declare there are no financial conflicts of interest in regard to this research. NR 28 TC 33 Z9 33 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD FEB-MAR PY 2009 VL 32 IS 2 BP 181 EP 185 PG 5 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 411NC UT WOS:000263655300010 PM 19238017 ER PT J AU La Bash, HAJ Vogt, DS King, LA King, DW AF La Bash, Heidi A. J. Vogt, Dawne S. King, Lynda A. King, Daniel W. TI Deployment Stressors of the Iraq War Insights From the Mainstream Media SO JOURNAL OF INTERPERSONAL VIOLENCE LA English DT Review DE stressors; media; war; deployment; Iraq; review ID MENTAL-HEALTH PROBLEMS; MALE VIETNAM VETERANS; GULF-WAR; MILITARY SERVICE; NATIONAL SAMPLE; FEMALE SOLDIERS; ZONE STRESSORS; RISK-FACTORS; US ARMY; DISORDER AB A comprehensive understanding of the stressors of the Iraq War is needed to ensure appropriate postdeployment assessments and to inform empirical inquiries. Yet we are unaware of any published studies that address the range of stressors experienced by this cohort. Thus, in the present study, we report the results of an interpretive literature review of mainstream media reports published from the beginning of the Iraq War in March 2003 to March 2005. This literature revealed a combination of stressors associated with traditional combat, insurgency warfare, and peacekeeping operations. The increasing deployment of National Guard/Reservist personnel, older soldiers, and women highlights additional stressors associated with sexual harassment and assault, preparedness and training, and life and family disruptions. This is a cause for concern as war-zone stressors have been implicated in postdeployment health outcomes, including intimate partner violence and child maltreatment, immediate physical and mental health, and long-term adjustment. C1 [La Bash, Heidi A. J.] Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MD USA. [Vogt, Dawne S.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Vogt, Dawne S.] Boston Univ, Sch Med, Boston, MA 02215 USA. [King, Lynda A.; King, Daniel W.] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. RP La Bash, HAJ (reprint author), Univ Nevada, Dept Psychol, MS 296, Reno, NV 89557 USA. EM hlabash@unr.edu NR 161 TC 28 Z9 28 U1 1 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0886-2605 J9 J INTERPERS VIOLENCE JI J. Interpers. Violence PD FEB PY 2009 VL 24 IS 2 BP 231 EP 258 DI 10.1177/0886260508317177 PG 28 WC Criminology & Penology; Family Studies; Psychology, Applied SC Criminology & Penology; Family Studies; Psychology GA 389HM UT WOS:000262083500001 PM 18467690 ER PT J AU Goldstein, NB Johannes, WU Gadeliya, AV Green, MR Fujita, M Norris, DA Shellman, YG AF Goldstein, Nathaniel B. Johannes, Widya U. Gadeliya, Agnessa V. Green, Matthew R. Fujita, Mayumi Norris, David A. Shellman, Yiqun G. TI Active N-Ras and B-Raf Inhibit Anoikis by Downregulating Bim Expression in Melanocytic Cells SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID EPIDERMAL-GROWTH-FACTOR; EPITHELIAL-CELLS; BH3-ONLY PROTEIN; APOPTOSIS; MELANOMA; SUPPRESSION; PATHWAY; CANCER; DEGRADATION; ACTIVATION AB B-Raf and N-Ras proteins are often activated in melanoma, yet their roles in producing inherent survival signals are not fully understood. In this study, we investigated how N-RAS(Q61K) and B-RAF(V600E) contribute to melanoma's resistance to apoptosis induced by detachment from the extracellular matrix (anoikis). We found that expression of constitutively active N-RAS(Q61K) and B-RAF(V600E) downregulated the proapoptotic Bim protein in an immortalized melanocyte cell line. Bim is one of the main proapoptotic mediators of anoikis. Western blot analysis showed that detachment increased Bim expression in melanocytes, and Annexin V staining indicated that detachment induced cell death significantly in melanocytes. Blocking Bim expression by using RNAi vectors or by expressing N-RAS(Q61K) significantly inhibited anoikis in melanocytes. In summary, this report indicates that N-RAS(Q61K) and B-RAF(V600E) contribute to melanoma's resistance to apoptosis in part by downregulating Bim expression, suggesting that Bim is a possible treatment target for overriding melanoma's inherent defenses against cell death. C1 [Goldstein, Nathaniel B.; Johannes, Widya U.; Gadeliya, Agnessa V.; Green, Matthew R.; Fujita, Mayumi; Norris, David A.; Shellman, Yiqun G.] Univ Colorado Denver, Sch Med, Dept Dermatol, Aurora, CO 80010 USA. [Norris, David A.] US Dept Vet Affairs, Med Ctr, Dermatol Sect, Denver, CO USA. RP Shellman, YG (reprint author), Univ Colorado Denver, Sch Med, Dept Dermatol, Mail Stop 8127,POB 6511, Aurora, CO 80010 USA. EM Yiqun.Shellman@uchsc.edu FU Dermatology Foundation Career Award; NIAMS [R01AR26427-18]; Veterans Administrations merit grant [PN: 0012] FX This work was supported in part by Dermatology Foundation Career Award (YGS), NIAMS grant R01AR26427-18 (DAN), and Veterans Administrations merit grant PN: 0012 (DAN). We thank Anne Brauweiler for her critique of the paper. NR 28 TC 12 Z9 12 U1 0 U2 0 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 FEB PY 2009 VL 129 IS 2 BP 432 EP 437 DI 10.1038/jid.2008.227 PG 6 WC Dermatology SC Dermatology GA 397IH UT WOS:000262655600024 PM 18668139 ER PT J AU Marucci, A Miscio, G Padovano, L Boonyasrisawat, W Florez, JC Doria, A Trischitta, V Paola, R AF Marucci, Antonella Miscio, Giuseppe Padovano, Libera Boonyasrisawat, Watip Florez, Jose C. Doria, Alessandro Trischitta, Vincenzo Di Paola, Rosa TI The role of HSP70 on ENPP1 expression and insulin-receptor activation SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Article DE Inhibitors of insulin signaling; Insulin resistance; 3 ' untranslated regions; Tyrosine-kinase receptors ID MEMBRANE GLYCOPROTEIN PC-1; K121Q POLYMORPHISM; MESSENGER-RNA; GLUCOSE-INTOLERANCE; PROTEIN-CONTENT; RESISTANCE; GENE; INHIBITOR; OBESITY; ABNORMALITIES AB Ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) inhibits insulin-receptor (IR) signaling and, when over-expressed, induces insulin resistance in vitro and in vivo. Understanding the regulation of ENPP1 expression may, thus, unravel new molecular mechanisms of insulin resistance. Recent data point to a pivotal role of the ENPP1 3'UTR, in modulating ENPP1 mRNA stability and expression. We sought to identify trans-acting proteins binding the ENPP1-3' UTR and to investigate their role on ENPP1 expression and on IR signaling. By RNA electrophoresis mobility shift analysis and tandem mass spectrometry, we demonstrated the binding of heat shock protein 70 (HSP70) to ENPP1-3'UTR. Through this binding, HSP70 stabilizes ENPP1 mRNA and increases ENPP1 transcript and protein levels. This positive modulation of ENPP1 expression is paralleled by a reduced insulin-induced IR and IRS-1 phosphorylation. Taken together these data suggest that HSP70, by affecting ENPP1 expression, may be a novel mediator of altered insulin signaling. C1 [Marucci, Antonella; Miscio, Giuseppe; Padovano, Libera; Trischitta, Vincenzo; Di Paola, Rosa] Inst Sci, Res Unit Diabet & Endocrine Dis, I-71013 San Giovanni Rotondo, Italy. [Boonyasrisawat, Watip; Doria, Alessandro] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Boonyasrisawat, Watip; Florez, Jose C.; Doria, Alessandro] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Diabet Unit, Boston, MA 02114 USA. [Florez, Jose C.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. [Trischitta, Vincenzo] Sapienza Univ, Dept Clin Sci, Rome, Italy. [Trischitta, Vincenzo] CSS Mendel Inst, Rome, Italy. RP Trischitta, V (reprint author), Inst Sci, Res Unit Diabet & Endocrine Dis, Poliambulatorio Giovanni Paolo II,Viale Padre Pio, I-71013 San Giovanni Rotondo, Italy. EM vincenzo.trischitta@uniroma1.it; r.dipaola@operapadrepio.it RI Trischitta, Vincenzo/K-1487-2016; marucci, antonella/B-8722-2017 OI Trischitta, Vincenzo/0000-0003-1174-127X; marucci, antonella/0000-0001-8131-8317 FU Italian Ministry of Health [RC2004, C2005, RC2006, RC2007, RF05ED01]; Italian Ministry of University and Research [RBNE01N4Z9_009]; Telethon Grants [E1239, GGP02423]; National Institutes of Health [HL73168, DK55523, DK36836]; National Institutes of Health Research Development Career Award [K23 DK65978-04] FX This research was supported by Italian Ministry of Health Grants: RC2004 (G. M) C2005 (R. D. P. and G. M.), RC2006 (G. M.), RC2007 (R. D. P.), RF05ED01 (R. D. P.); Italian Ministry of University and Research Grant: RBNE01N4Z9_009; Telethon Grants: E1239 (V. T.), and GGP02423 (R. D. P.). National Institutes of Health Grants HL73168 and DK55523 (A. D.) and DK36836 (Genetics Core of the Diabetes & Endocrinology Research Center at the Joslin Diabetes Center), and a National Institutes of Health Research Development Career Award K23 DK65978-04 (J.C.F.). NR 26 TC 8 Z9 8 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0946-2716 J9 J MOL MED-JMM JI J. Mol. Med. PD FEB PY 2009 VL 87 IS 2 BP 139 EP 144 DI 10.1007/s00109-008-0429-9 PG 6 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 414DC UT WOS:000263843100004 PM 19083193 ER PT J AU Chang, Z Guo, CL Ahronowitz, I Stemmer-Rachamimov, AO MacCollin, M Nunes, FP AF Chang, ZeNan Guo, Chin-Lin Ahronowitz, Iris Stemmer-Rachamimov, Anat O. MacCollin, Mia Nunes, Fabio P. TI A role for the p53 pathway in the pathology of meningiomas with NF2 loss SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE NF2; Mdm2; p53; Pro72; Meningiomas ID TUMOR-SUPPRESSOR GENE; CODON-72 POLYMORPHIC VARIANTS; SPORADIC MENINGIOMAS; DNA-DAMAGE; MDM2; EXPRESSION; INACTIVATION; CANCER; CELLS; NEUTRALIZES AB The neurofibromatosis 2 locus (NF2) is inactivated through mutation and loss of heterozygosity (LOH) in 40-65% of all sporadic meningiomas, while the role of the p53 tumor suppression pathway in meningioma initiation and progression is still unclear. This study aims to determine if a p53 codon 72 arginine-to-proline polymorphism, found to be correlated with cancer development and cancer patient survival in other tumors, is associated with sporadic meningioma initiation or progression. We investigated Pro72 incidence in a cohort of 92 sporadic meningiomas and analyzed its association with histological grade (WHO classification) and with NF2 LOH (determined using polymorphic microsatellite markers on 22q). The Pro72 allele was not found to be selected for in the cohort. However, in the subgroup of meningiomas with NF2 LOH and carrying Pro72, 50.0% had high grade tumors (WHO grades II and III) compared to only 14.3% of those without NF2 LOH (OR = 6.0, CI = 1.56-23.11, P = 0.012). The significant association occurred only when considering subgroups of meningiomas with or without NF2 LOH, suggesting that not including NF2 status when analyzing study cohorts may explain the variability seen in the literature where all meningiomas were grouped together. Our data suggests a role for the p53 pathway in the progression of meningiomas in which NF2 is inactivated, and highlights the importance of accounting for NF2 LOH in future studies of meningiomas and the p53 pathway. C1 [Ahronowitz, Iris; MacCollin, Mia; Nunes, Fabio P.] MGH, Dept Neurol, Boston, MA 02114 USA. [Ahronowitz, Iris; MacCollin, Mia; Nunes, Fabio P.] Harvard Univ, Sch Med, Simches Res Ctr, Boston, MA 02114 USA. [Chang, ZeNan] CALTECH, Div Biol, Pasadena, CA 91125 USA. [Guo, Chin-Lin] CALTECH, Dept Appl Phys & Opt Bioengn, Pasadena, CA USA. [Stemmer-Rachamimov, Anat O.] Massachusetts Gen Hosp, Ctr Canc, Mol Neurooncol Lab, Charlestown, MA 02129 USA. [Stemmer-Rachamimov, Anat O.] Massachusetts Gen Hosp, Ctr Canc, Pathol Lab, Charlestown, MA 02129 USA. [Stemmer-Rachamimov, Anat O.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Nunes, FP (reprint author), MGH, Dept Neurol, 185 Cambridge St,CPZN 5-820, Boston, MA 02114 USA. EM fnunes@partners.org FU National Institutes of Health [1 R01 NS40527] FX Funded by National Institutes of Health; Grant Number: 1 R01 NS40527 to MM. The authors would also like to thank all the patients who donated tissues for this study and to thank the Center for Excellence in Education for supporting ZC. NR 50 TC 10 Z9 10 U1 0 U2 2 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 FEB PY 2009 VL 91 IS 3 BP 265 EP 270 DI 10.1007/s11060-008-9721-3 PG 6 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 391OB UT WOS:000262241500004 PM 18974932 ER PT J AU Li, XL Lu, L Bush, DJ Zhang, XW Zheng, L Suswam, EA King, PH AF Li, Xuelin Lu, Liang Bush, Donald J. Zhang, Xiaowen Zheng, Lei Suswam, Esther A. King, Peter H. TI Mutant copper-zinc superoxide dismutase associated with amyotrophic lateral sclerosis binds to adenine/uridine-rich stability elements in the vascular endothelial growth factor 3'-untranslated region SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE RNA stability; HuR; RNA-binding proteins; electrophoresis mobility shift assay ID MESSENGER-RNA STABILITY; MALIGNANT GLIOMA-CELLS; CENTRAL-NERVOUS-SYSTEM; ANGIOGENIC FACTOR; PROTEIN HUR; CU,ZN-SUPEROXIDE DISMUTASE; GENE-EXPRESSION; IN-VITRO; ELAV; MUTATIONS AB Vascular endothelial growth factor (VEGF) is a neurotrophic factor essential for maintenance of motor neurons. Loss of this factor produces a phenotype similar to amyotrophic lateral sclerosis (ALS). We recently showed that ALS-producing mutations of Cu/Zn-superoxide dismutase (SOD1) disrupt post-transcriptional regulation of VEGF mRNA, leading to significant loss of expression [Lu et al., J. Neurosci.27 (2007), 7929]. Mutant SOD1 was present in the ribonucleoprotein complex associated with adenine/uridine-rich elements (ARE) of the VEGF 3'-untranslated region (UTR). Here, we show by electrophoretic mobility shift assay that mutant SOD1 bound directly to the VEGF 3'-UTR with a predilection for AREs similar to the RNA stabilizer HuR. SOD1 mutants A4V and G37R showed higher affinity for the ARE than L38V or G93A. Wild-type SOD1 bound very weakly with an apparent K(d) 11- to 72-fold higher than mutant forms. Mutant SOD1 showed an additional lower shift with VEGF ARE that was accentuated in the metal-free state. A similar pattern of binding was observed with AREs of tumor necrosis factor-alpha and interleukin-8, except only a single shift predominated. Using an ELISA-based assay, we demonstrated that mutant SOD1 competes with HuR and neuronal HuC for VEGF 3'-UTR binding. To define potential RNA-binding domains, we truncated G37R, G93A and wild-type SOD1 and found that peptides from the N-terminal portion of the protein that included amino acids 32-49 could recapitulate the binding pattern of full-length protein. Thus, the strong RNA-binding affinity conferred by ALS-associated mutations of SOD1 may contribute to the post-transcriptional dysregulation of VEGF mRNA. C1 [Li, Xuelin; Lu, Liang; Bush, Donald J.; Zhang, Xiaowen; Zheng, Lei; Suswam, Esther A.; King, Peter H.] Univ Alabama, Dept Neurol, Birmingham, AL 35294 USA. [Li, Xuelin; Lu, Liang; Zheng, Lei; King, Peter H.] Birmingham VA Med Ctr, Birmingham, AL USA. [King, Peter H.] Univ Alabama, Dept Genet, Birmingham, AL 35233 USA. [King, Peter H.] Univ Alabama, Dept Physiol & Biophys, Birmingham, AL 35233 USA. RP King, PH (reprint author), Suite 260 Sparks Ctr,1720 7th Ave S, Birmingham, AL 35233 USA. EM pking@uab.edu FU NIH/NINDS [NS058538]; Department of Veterans Affairs FX This study was supported by NIH/NINDS NS058538 (PHK) and a Merit Review Award from Department of Veterans Affairs (PHK). NR 76 TC 19 Z9 19 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD FEB PY 2009 VL 108 IS 4 BP 1032 EP 1044 DI 10.1111/j.1471-4159.2008.05856.x PG 13 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 395IF UT WOS:000262517100017 PM 19196430 ER PT J AU Micsenyi, MC Dobrenis, K Stephney, G Pickel, J Vanier, MT Slaugenhaupt, SA Walkley, SU AF Micsenyi, Matthew C. Dobrenis, Kostantin Stephney, Gloria Pickel, James Vanier, Marie T. Slaugenhaupt, Susan A. Walkley, Steven U. TI Neuropathology of the Mcoln1(-/-) Knockout Mouse Model of Mucolipidosis Type IV SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE Axonal spheroids; Bis(monoacylglycero) phosphate; Gangliosides; Lysosomal disease; Mucolipin 1; P62/Sequestosome 1 ID NEURONAL-CEROID-LIPOFUSCINOSIS; LYSOSOMAL STORAGE DISORDERS; LYSOBISPHOSPHATIDIC ACID; CULTURED FIBROBLASTS; CATION CHANNEL; DISEASE; AUTOPHAGY; ACCUMULATION; P62/SQSTM1; GENE AB The recently developed Mcoln1(-/-) knockout mouse provides a novel model for analyzing mucolipin 1 function and mucolipidosis type IV disease. Here we characterize the neuropathology of Mcoln1(-/-) mouse at the end stage. Evidence of ganglioside accumulation, including increases in GM2, GM3, and GD3 and redistribution of GM1, was found throughout the central nervous system (CNS) independent of significant cholesterol accumulation. Unexpectedly, colocalization studies using immunofluorescence confocal microscopy revealed that GM1 and GM2 were present in separate vesicles within individual neurons. While GM2 was significantly colocalized with LAMP2, consistent with late-endosomal/lysosomal processing, some GIM2-immunoreactivity occurred in LAMP2-negative sites, suggesting involvement of other vesicular systems. P62/Sequestosome 1 (P62/SQSTM1) inclusions were also identified in the CNS of the Mcoln1(-/-) mouse, Suggesting deficiencies in protein degradation. Glial cell activation was increased in brain, and there was evidence of reduced myelination in cerebral and cerebellar white matter tracts. Autofluorescent material accumulated throughout the brains of the knockout mice. Finally, axonal spheroids were prevalent in white matter tracts and Purkinje cell axons. This neuropathological characterization of the Mcoln1(-/-) mouse provides an important step in understanding how mucolipin I loss of function affects the CNS and contributes to mucolipidosis type IV disease. C1 [Micsenyi, Matthew C.; Dobrenis, Kostantin; Walkley, Steven U.] Albert Einstein Coll Med, Dominick P Purpura Dept Neurosci, Rose Kennedy Ctr Res Mental Retardat & Human Dev, Bronx, NY 10461 USA. [Pickel, James] NIMH, NIH, Bethesda, MD 20892 USA. [Vanier, Marie T.] Laennec Med Sch, INSERM, Lyon, France. [Vanier, Marie T.] Lyon Univ, Lyon, France. [Slaugenhaupt, Susan A.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Slaugenhaupt, Susan A.] Harvard Univ, Sch Med, Boston, MA USA. RP Walkley, SU (reprint author), Albert Einstein Coll Med, Dominick P Purpura Dept Neurosci, Rose Kennedy Ctr Res Mental Retardat & Human Dev, 1410 Pelham Pkwy S,Room 618, Bronx, NY 10461 USA. EM walkley@accom.yu.edu FU NICHD NIH HHS [P30 HD001799, R01 HD045561]; NINDS NIH HHS [R01 NS039995, R01 NS39995] NR 48 TC 38 Z9 39 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD FEB PY 2009 VL 68 IS 2 BP 125 EP 135 PG 11 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 402KN UT WOS:000263012700002 PM 19151629 ER PT J AU Hedley-Whyte, ET Goldman, JE Nedergaard, M Friedman, A Han, XN Schmidt, RE Powers, JM AF Hedley-Whyte, E. Tessa Goldman, James E. Nedergaard, Maiken Friedman, Alan Han, Xiaoning Schmidt, Robert E. Powers, James M. TI Hyaline Protoplasmic Astrocytopathy of Neocortex SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE Cytoglobin; Glutamate; Hyalin; Inclusion; Proteomics; Protoplasmic astrocyte; Seizure ID HEREDITARY FERRITINOPATHY; CYTOPLASMIC INCLUSIONS; CYTOGLOBIN; BRAIN; EPILEPSY; PATIENT; EXPRESSION; HYPOXIA; TISSUES; STRESS AB Eosinophilic inclusions in the cytoplasm of protoplasmic astrocytes of the neocortex, usually in the clinical setting of epilepsy and/or psychomotor retardation, were first recognized and illustrated by Alois Alzheimer in 1910. Traditional special stains have failed to elucidate the specific nature of these inclusions. Ultrastructurally, the material was composed predominantly of highly electron-dense, non-membrane-bound, granular material distinct from Rosenthal fibers. Immunohistochemical examination has been informative but also sometimes inconsistent; it has recently been suggested that they may represent a filaminopathy (filamin A). We examined 5 cases with neocortical eosinophilic inclusions (3 autopsies, 2 surgical resections) using a standardized immunohistochemical protocol at a single institution. The specimens were immunostained with 32 antibodies to 30 potentially relevant proteins using several antigen retrieval protocols. We confirmed the presence of filamin A ill these inclusions, but several additional proteins, particularly cytoglobin and glutamate transporter 1, were also identified. By electron microscopy in 2 cases, the granular fine structure of the inclusions was confirmed; mitochondria adjacent to, and perhaps within, the inclusions that contained many pleomorphic vesicular and membranous elements were also noted in I case. The pathophysiologic relevance of these proteins and the clinical significance of the hyaline inclusions are discussed. C1 [Powers, James M.] Univ Rochester, Med Ctr, Dept Pathol, Rochester, NY 14642 USA. [Hedley-Whyte, E. Tessa] Massachusetts Gen Hosp, Dept Pathol, Charles S Kubik Lab Neuropathol, Boston, MA 02114 USA. [Hedley-Whyte, E. Tessa] Harvard Univ, Sch Med, Boston, MA USA. [Goldman, James E.] Columbia Univ, Dept Pathol & Cell Biol, New York, NY USA. [Nedergaard, Maiken; Han, Xiaoning] Univ Rochester, Med Ctr, Ctr Translat Neuromed, Dept Neurosurg,Div Glial Dis & Therapeut, Rochester, NY 14642 USA. [Friedman, Alan] Univ Rochester, Med Ctr, Dept Environm Med, Rochester, NY 14642 USA. [Schmidt, Robert E.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA. [Powers, James M.] Univ Rochester, Med Ctr, Dept Neurol, Rochester, NY 14642 USA. RP Powers, JM (reprint author), Univ Rochester, Med Ctr, Dept Pathol, Box 626,601 Elmwood Ave, Rochester, NY 14642 USA. EM james_powers@urmc.rochester.edu NR 35 TC 20 Z9 20 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD FEB PY 2009 VL 68 IS 2 BP 136 EP 147 PG 12 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 402KN UT WOS:000263012700003 PM 19151628 ER PT J AU Bell, AH Hadj-Bouziane, F Frihauf, JB Tootell, RBH Ungerleider, LG AF Bell, Andrew H. Hadj-Bouziane, Fadila Frihauf, Jennifer B. Tootell, Roger B. H. Ungerleider, Leslie G. TI Object Representations in the Temporal Cortex of Monkeys and Humans as Revealed by Functional Magnetic Resonance Imaging SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID POSTERIOR INFEROTEMPORAL CORTEX; HUMAN EXTRASTRIATE CORTEX; MACAQUE CEREBRAL-CORTEX; SURFACE-BASED ANALYSIS; MIDDLE FUSIFORM GYRUS; FACE PERCEPTION; TOPOGRAPHICAL DISORIENTATION; ACQUIRED PROSOPAGNOSIA; RESPONSE PATTERNS; INDIVIDUAL FACES AB Bell AH, Hadj-Bouziane F, Frihauf JB, Tootell RB, Ungerleider LG. Object representations in the temporal cortex of monkeys and humans as revealed by functional magnetic resonance imaging. J Neurophysiol 101: 688-700, 2009. First published December 3, 2008; doi:10.1152/jn.90657.2008. Increasing evidence suggests that the neural processes associated with identifying everyday stimuli include the classification of those stimuli into a limited number of semantic categories. How the neural representations of these stimuli are organized in the temporal lobe remains under debate. Here we used functional magnetic resonance imaging (fMRI) to identify correlates for three current hypotheses concerning object representations in the inferior temporal (IT) cortex of monkeys and humans: representations based on animacy, semantic categories, or visual features. Subjects were presented with blocked images of faces, body parts (animate stimuli), objects, and places (inanimate stimuli), and multiple overlapping contrasts were used to identify the voxels most selective for each category. Stimulus representations appeared to segregate according to semantic relationships. Discrete regions selective for animate and inanimate stimuli were found in both species. These regions could be further subdivided into regions selective for individual categories. Notably, face-selective regions were contiguous with body-part-selective regions, and object-selective regions were contiguous with placeselective regions. When category-selective regions in monkeys were tested with blocks of single exemplars, individual voxels showed preferences for visually dissimilar exemplars from the same category and voxels with similar preferences tended to cluster together. Our results provide some novel observations with respect to how stimulus representations are organized in IT cortex. In addition, they further support the idea that representations of complex stimuli in IT cortex are organized into multiple hierarchical tiers, encompassing both semantic and physical properties. C1 [Bell, Andrew H.; Hadj-Bouziane, Fadila; Frihauf, Jennifer B.; Tootell, Roger B. H.; Ungerleider, Leslie G.] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. [Tootell, Roger B. H.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Tootell, Roger B. H.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Bell, AH (reprint author), NIMH, Lab Brain & Cognit, NIH, 49 Convent Dr, Bethesda, MD 20892 USA. EM bellah@mail.nih.gov RI Hadj-Bouziane, Fadila/A-1180-2013; OI Bell, Andrew/0000-0001-8420-4622 FU National Institutes of Health [R01MH-67529, R01 EY-017081] FX This work was supported by grants from the National Institutes of Health (R01MH-67529 and R01 EY-017081 to R. B. H. Tootell, the Athinoula A. Martinos Center for Biomedical Imaging, the National Center for Research Resources, and the National Institute of Mental Health Intramural Research Program to A. H. Bell, F. Hadj-Bouziane, J. B. Frihauf, and L. G. Ungerleider. NR 88 TC 90 Z9 91 U1 1 U2 10 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD FEB PY 2009 VL 101 IS 2 BP 688 EP 700 DI 10.1152/jn.90657.2008 PG 13 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 403ZK UT WOS:000263120300018 PM 19052111 ER PT J AU Park, JW Jang, YH Kim, JM Lee, H Park, WK Lim, MB Chu, YK Lo, EH Lee, SR AF Park, Jong-Wan Jang, Young-Ho Kim, Jin-Mo Lee, Hung Park, Weon-Kyun Lim, Man-Bin Chu, Yeun-Kyung Lo, Eng H. Lee, Seong-Ryong TI Green Tea Polyphenol (-)-Epigallocatechin Gallate Reduces Neuronal Cell Damage and Up-Regulation of MMP-9 Activity in Hippocampal CA1 and CA2 Areas Following Transient Global Cerebral Ischemia SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE global cerebral ischemia; hippocampus; matrix metalloproteinase; green tea ID GENE KNOCK-OUT; MATRIX METALLOPROTEINASES; BRAIN-INJURY; LIPID-PEROXIDATION; FOREBRAIN ISCHEMIA; NERVOUS-SYSTEM; DEATH; EXPRESSION; EGCG; MATRIX-METALLOPROTEINASE-9 AB Previous studies have demonstrated that H-epigallocatechin gallate (EGCG), a green tea polyphenol, protects against ischemia and reperfusion-induced injury in many organ systems. Here, we test the hypothesis that part of EGCG's neuroprotective effects may involve a modulation of matrix metalloproteinases (MMPs) after cerebral ischemia. C57BL/6 mice were subjected to 20 min of transient global cerebral ischemia. EGCG (50 mg/kg) or vehicle (saline) was administered i.p. immediately after ischemia. Brains were examined 3 days after ischemia. The effects of EGCG on MMP (gelatinase) activity and neuronal damage in the hippocampus were assessed. Gelatin gel zymography showed induction of active forms of MMP-9 protein after transient global cerebral ischemia. In situ zymography showed that ischemic gelatinase activity occurred primarily in pyramidal neuronal areas after brain ischemia. Mice treated with EGCG showed significantly reduced gelatinase levels. Neuronal damage was evident in CA1 and CA2 pyramidal sectors, corresponding to TUNEL-positive signals. In EGCG-treated mice, delayed neuronal damage was significantly reduced compared with vehicle-treated mice. These results demonstrate that the green tea polyphenol EGCG suppresses MMP-9 activation and reduces the development of delayed neuronal death after transient global cerebral ischemia in mouse brain. (C) 2008 Wiley-Liss, Inc. C1 [Park, Jong-Wan; Lee, Seong-Ryong] Keimyung Univ, Sch Med, Dept Pharmacol, Taegu 700712, South Korea. [Park, Jong-Wan; Jang, Young-Ho; Kim, Jin-Mo] Keimyung Univ, Sch Med, Dept Anesthesiol, Taegu 700712, South Korea. [Lee, Hung; Park, Weon-Kyun; Lim, Man-Bin; Lee, Seong-Ryong] Keimyung Univ, Brain Res Inst, Taegu 700712, South Korea. [Chu, Yeun-Kyung] Yeungnam Univ, Sch Kinesiol, Gyongsan, Gyeongbuk, South Korea. [Lo, Eng H.; Lee, Seong-Ryong] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Neuroprotect Res Lab, Boston, MA USA. [Lo, Eng H.; Lee, Seong-Ryong] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. RP Lee, SR (reprint author), Keimyung Univ, Sch Med, Dept Pharmacol, 194 Dongsan Dong, Taegu 700712, South Korea. EM srlee@kmu.ac.kr NR 41 TC 27 Z9 31 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD FEB 1 PY 2009 VL 87 IS 2 BP 567 EP 575 DI 10.1002/jnr.21847 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 403JQ UT WOS:000263079300027 PM 18752302 ER PT J AU Christine, CW Langston, JW Turner, RS Starr, PA AF Christine, Chadwick W. Langston, J. William Turner, Robert S. Starr, Philip A. TI The neurophysiology and effect of deep brain stimulation in a patient with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism SO JOURNAL OF NEUROSURGERY LA English DT Article; Proceedings Paper CT 9th International Congress of Parkinsons Disease and Movement Disorders CY MAR 05-08, 2005 CL New Orleans, LA DE deep brain stimulation; Parkinson disease; physiology; subthalamic nucleus; toxin ID MPTP-TREATED PRIMATE; SUBTHALAMIC NUCLEUS; NEURONAL-ACTIVITY; DISEASE; MODEL; LEVODOPA; LESIONS AB Parkinsonism caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) exposure was first identified in intravenous drug users. This neurotoxicant has since been used extensively in nonhuman primates to induce an experimental model of Parkinson disease (PD). In this study, the authors examined the intraoperative physiological characteristics and efficacy of subthalamic nucleus deep brain stimulation (DBS) in 1 of only 4 known living patients with MPTP-induced parkinsonism. The physiological recordings were consistent with recordings from MPTP-treated primates and humans with PD, thus providing further validation for the MPTP model in the study of the neurophysiology of the nigrostriatal dopaminergic deficit in PD. Furthermore, DBS produced a significant clinical improvement in this patient similar to the improvement seen after DBS in patients with idiopathic PD. This unique case has important implications for translational research that employs the MPTP-primate model for symptomatic therapy in PD. (DOI: 10.3171/2008.8.JNS08882) C1 [Christine, Chadwick W.; Starr, Philip A.] Univ Calif San Francisco, Sch Med, Dept Neurol, San Francisco, CA 94143 USA. [Christine, Chadwick W.] Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA 94143 USA. [Langston, J. William] Parkinsons Inst, Sunnyvale, CA USA. [Turner, Robert S.] Univ Pittsburgh, Dept Neurobiol, Pittsburgh, PA USA. [Starr, Philip A.] San Francisco VA Med Ctr, Parkinson Dis Res Educ & Clin Ctr, San Francisco, CA USA. RP Christine, CW (reprint author), Univ Calif San Francisco, Sch Med, Dept Neurol, 400 Parnassus Ave,Room A838, San Francisco, CA 94143 USA. EM chad.christine@ucsf.edu FU NINDS NIH HHS [R01 NS044551, R21 NS055197-01A2, R21 NS055197, R01 NS044551-06] NR 15 TC 3 Z9 3 U1 0 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD FEB PY 2009 VL 110 IS 2 BP 234 EP 238 DI 10.3171/2008.8.JNS08882 PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 399GI UT WOS:000262788000005 PM 19099380 ER PT J AU Voorhees, JR Tubbs, RS Nahed, B Cohen-Gadol, AA AF Voorhees, Jennifer R. Tubbs, R. Shane Nahed, Brian Cohen-Gadol, Aaron A. TI William S. Halsted and Harvey W. Cushing: reflections on their complex association SO JOURNAL OF NEUROSURGERY LA English DT Editorial Material DE Harvey W. Cushing; history of neurosurgery; William S. Halsted AB William Stewart Halsted, the father of modern surgery, and Harvey Williams Cushing, the father of neurosurgery, are remembered for their countless innovations and contributions to the discipline of surgery. Between 1896 and 1912, they worked together at Johns Hopkins Hospital making many of their respective achievements possible. In the later years, their complex relationship, somewhat strained during Cushing's residency, grew into a mutual respect and deep appreciation for one another. In this offering, the authors attempt to elucidate the evolution of this complex relationship. (DOI: 10.3171/2008.4.17516) C1 [Cohen-Gadol, Aaron A.] Clarian Neurosci Inst, Indianapolis Neurosurg Grp, Indianapolis, IN 46202 USA. [Cohen-Gadol, Aaron A.] Indiana Univ, Dept Neurosurg, Indianapolis, IN 46204 USA. [Nahed, Brian] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Nahed, Brian] Harvard Univ, Sch Med, Boston, MA USA. [Tubbs, R. Shane] Childrens Hosp, Sect Pediat Neurosurg, Birmingham, AL USA. [Voorhees, Jennifer R.] Yale Univ, Sch Med, New Haven, CT USA. RP Cohen-Gadol, AA (reprint author), Clarian Neurosci Inst, Indianapolis Neurosurg Grp, 1801 N Senate Blvd,Suite 610, Indianapolis, IN 46202 USA. EM acohenmd@gmail.com NR 16 TC 2 Z9 2 U1 1 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD FEB PY 2009 VL 110 IS 2 BP 384 EP 390 DI 10.3171/2008.4.17516 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 399GI UT WOS:000262788000031 PM 18976064 ER PT J AU Shelton, BA O'Hara, E Tubbs, RS Shoja, MM Barker, FG Cohen-Gadol, AA AF Shelton, Beth Ann O'Hara, Edward Tubbs, R. Shane Shoja, Mohammadli M. Barker, Fred G., II Cohen-Gadol, Aaron A. TI Emergency suboccipital decompression for respiratory arrest during supratentorial surgery: the untold story of a surgeon's courage in times of despair SO JOURNAL OF NEUROSURGERY LA English DT Editorial Material DE cerebellar tonsillar herniation; Harvey Cushing; history of neurosurgery; respiratory arrest ID CEREBRAL COMPRESSION; UNCAL HERNIATION; MUTTER-LECTURE; BLOOD-PRESSURE AB The odyssey leading to the discovery of herniation syndromes was prolonged due to a lack of early understanding of the underlying pathophysiology. In 1896, Leonard Hill documented transtentorial pressure gradients as the intervening phenomenon involved in uncal herniation. In 1904, James Collier became the first to describe cerebellar tonsillar herniation as a "false localizing sign" often associated with intracranial tumors. During the infancy of neurological Surgery, management of increased intracranial pressure and an improved understanding of brain herniation syndromes were of the utmost importance in achieving a safe technique. Harvey Cushing provided seminal contributions in understanding the pathophysiology of increased intracranial pressure and resulting cardiopulmonary effects. Cushing believed that tonsillar herniation was a cause of acute cardiorespiratory compromise in patients with intracranial tumors. In this vignette, we describe the untold story of Cushing's heroic attempt to treat respiratory arrest operatively during supratentorial tumor Surgery with an emergency suboccipital craniectomy to relieve the medullary dysfunction that he believed was caused by compression from tonsillar herniation. This case illustrates a Surgeon's determination and courage in fighting for his patient's life in the most desperate of times. (DOI: 10.3171/2008.8.JNS08773) C1 [Cohen-Gadol, Aaron A.] Indiana Univ, Indianapolis Neurosurg Grp, Dept Neurosurg, Indianapolis, IN 46202 USA. [Shelton, Beth Ann; O'Hara, Edward; Shoja, Mohammadli M.; Cohen-Gadol, Aaron A.] Clarian Neurosci Inst, Indianapolis Neurosurg Grp, Indianapolis, IN USA. [Tubbs, R. Shane] Univ Alabama, Sch Med, Sect Pediat Neurosurg, Birmingham, AL USA. [Tubbs, R. Shane] Univ Alabama, Sch Med, Dept Cell Biol, Birmingham, AL USA. [Barker, Fred G., II] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosurg Serv, Boston, MA USA. RP Cohen-Gadol, AA (reprint author), Indiana Univ, Indianapolis Neurosurg Grp, Dept Neurosurg, 1801 N Senate Blvd 610, Indianapolis, IN 46202 USA. EM acohenmd@gmail.com NR 16 TC 1 Z9 3 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD FEB PY 2009 VL 110 IS 2 BP 391 EP 394 DI 10.3171/2008.8.JNS08773 PG 4 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 399GI UT WOS:000262788000032 PM 18976053 ER PT J AU Akutsu, Y Gregory, SA Kardan, A Zervos, GD Thomas, GS Gewirtz, H Yasuda, T AF Akutsu, Yasushi Gregory, Shawn A. Kardan, Arash Zervos, Gerasimos D. Thomas, Gregory S. Gewirtz, Henry Yasuda, Tsunehiro TI Delayed heart rate recovery after adenosine stress testing with supplemental arm exercise predicts mortality SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Article DE Sestamibi; adenosine; Technetium-99m; heart rate recovery; mortality ID EMISSION COMPUTED-TOMOGRAPHY; MYOCARDIAL-PERFUSION SPECT; TREADMILL EXERCISE; PROGNOSTIC VALUE; HUMANS; PROTOCOL; IMPACT; DEATH AB Background. Delayed heart rate (HR) recovery after treadmill exercise testing predicts mortality. Patients with suspected ischemic heart disease who cannot perform adequate treadmill exercise are typically evaluated with pharmacological stress myocardial perfusion imaging (MPI) studies, but little prognostic significance has been attributed to the hemodynamic response to vasodilator stress testing with low-level exercise. We hypothesized that a delay in HR recovery after adenosine stress testing with arm exercise is associated with increased mortality. Methods and Results. Technetium 99m-Sestamibi MPI was performed in 1,455 consecutive patients (70 +/- 12 years, 50.2% men) with adenosine stress and supplemental arm exercise. HRs were recorded at rest, continuously during infusion, and then 5 minutes post-infusion. Delayed HR recovery was defined as a decline of <= 12 bpm from peak HR at 5 minutes after discontinuation of the infusion. Of 1,356 patients during 5 years of follow up, there were 135 deaths (10%). Delayed HR recovery was strongly predictive of all-cause mortality (16.5% vs 5.3% in those with normal HR recovery, P <.001) with an adjusted hazard ratio of 2.5 (95% CI, 1.7-3.6; P <.001). Conclusion. Delayed HR recovery after adenosine stress testing with arm exercise is a readily available and powerful predictor of all-cause mortality. (J Nucl Cardiol 2009; 16: 54-62) C1 [Akutsu, Yasushi; Gregory, Shawn A.; Kardan, Arash; Zervos, Gerasimos D.; Gewirtz, Henry; Yasuda, Tsunehiro] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA. [Akutsu, Yasushi] Showa Univ, Sch Med, Dept Med, Div Cardiol, Tokyo 142, Japan. [Thomas, Gregory S.] Mission Internal Med Grp, Mission Viejo, CA USA. RP Yasuda, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Yawkey 5E 55 Fruit St, Boston, MA 02114 USA. EM tyasuda@partners.org NR 30 TC 2 Z9 2 U1 0 U2 0 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 FEB PY 2009 VL 16 IS 1 BP 54 EP 62 DI 10.1007/s12350-008-9014-4 PG 9 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 419CO UT WOS:000264196900009 PM 19152129 ER PT J AU Liu, E Meigs, JB Pittas, AG McKeown, NM Economos, CD Booth, SL Jacques, PF AF Liu, Enju Meigs, James B. Pittas, Anastassios G. McKeown, Nicola M. Economos, Christina D. Booth, Sarah L. Jacques, Paul F. TI Plasma 25-Hydroxyvitamin D Is Associated with Markers of the Insulin Resistant Phenotype in Nondiabetic Adults SO JOURNAL OF NUTRITION LA English DT Article ID VITAMIN-D STATUS; FOOD FREQUENCY QUESTIONNAIRE; PARATHYROID-HORMONE LEVELS; D RESPONSE ELEMENT; METABOLIC SYNDROME; SERUM 25-HYDROXYVITAMIN-D; 1,25-DIHYDROXYVITAMIN D-3; 3T3-L1 PREADIPOCYTES; GLUCOSE-TOLERANCE; DIABETES-MELLITUS AB We examined the cross-sectional association between plasma 25-hydroxyvitamin D [25(OH)D] and markers of the insulin resistant phenotype. Plasma 25(OH)D concentrations were measured in 808 nondiabetic participants of the Framingham Offspring Study. Outcome measures included fasting and 2-h post 75-g oral glucose tolerance test (OGTT) glucose and insulin; these were used to calculate the homeostatic model assessment-insulin resistance (HOMA-IR) and insulin sensitivity index (ISI(0.120)). We also measured plasma adiponectin, triacylglycerol, and HDL cholesterol concentrations as markers of the insulin-resistant phenotype, After adjusting for age, sex, BMI, waist circumference, and current smoking status, plasma 25(OH)D concentration was inversely associated with fasting plasma glucose and insulin concentrations, and HOMA-IR. Compared with the participants in the lowest tertile category of plasma 25(OH)D, those in the highest tertile category had a 1.6% lower concentration of fasting plasma glucose (P-trend = 0.007), 9.8% lower concentration of fasting plasma insulin (P-trend=0.001), and 12.7% lower HOMA-IR score (P-trend < 0.001). After adjusting for age and sex, plasma 25(OH)D was positively associated with ISI0,120, plasma adiponectin, and HDL cholesterol and inversely associated with plasma triacylglycerol, but these associations were no longer significant after further adjustment for BMI, waist circumference, and current smoking status. 25(OH)D and 2-h post-OGTT glucose were not associated. Among adults without diabetes, vitamin D status was inversely associated with surrogate fasting measures of insulin resistance. These results suggest that vitamin D status may be an important determinant for type 2 diabetes mellitus. J. Nutr. 139: 329-334, 2009. C1 [Liu, Enju; McKeown, Nicola M.; Booth, Sarah L.; Jacques, Paul F.] Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [Liu, Enju; McKeown, Nicola M.; Economos, Christina D.; Booth, Sarah L.; Jacques, Paul F.] Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA. [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Meigs, James B.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Meigs, James B.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Pittas, Anastassios G.] Tufts Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02111 USA. RP Jacques, PF (reprint author), Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA. EM paul.jacques@tufts.edu RI liu, enju/B-2136-2010; liu, enju/F-4062-2010 FU NHLBI NIH HHS [N01 HC025195, N01-HC-25195]; NIA NIH HHS [R01 AG014759, AG14759]; NIDDK NIH HHS [K24 DK080140, R01DK076092, R21 DK078867, R21DK078867] NR 52 TC 143 Z9 150 U1 0 U2 1 PU AMER SOC NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD FEB PY 2009 VL 139 IS 2 BP 329 EP 334 DI 10.3945/jn.108.093831 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 398MC UT WOS:000262735200020 PM 19106328 ER PT J AU Crosier, MD Booth, SL Peter, I Dawson-Hughes, B Price, PA O'Donnell, CJ Hoffmann, U Williamson, MK Ordovas, JM AF Crosier, Michael D. Booth, Sarah L. Peter, Inga Dawson-Hughes, Bess Price, Paul A. O'Donnell, Christopher J. Hoffmann, Udo Williamson, Matthew K. Ordovas, Jose M. TI Matrix Gla Protein Polymorphisms are Associated with Coronary Artery Calcification in Men SO JOURNAL OF NUTRITIONAL SCIENCE AND VITAMINOLOGY LA English DT Article DE matrix gla protein; coronary artery calcification; polymorphism; vitamin K; atherosclerosis ID COMPUTED-TOMOGRAPHY; RISK-FACTORS; ATHEROSCLEROSIS; DISEASE; SERUM; GENE; RAT AB Matrix Gla protein (MGP) is a key regulator of vascular calcification. Genetic variation at the MGP locus could modulate the development of coronary artery calcification (CAC). Our aim was to examine the cross-sectional association between MGP single nucleotide polymorphisms (SNPs) [rs1800802 (T-138C), rs1800801 (G-7A), and rs4236 (Ala102Thr)] and CAC. CAC was measured by multidetector computed tomography (MDCT), in older men and women of European descent. (n=386; 60 to 80 3, of age). Serum MGP was measured by radioimmunoassay. Linear, Tobit and Ordinal regression analyses all revealed that in men, homozygous carriers of the minor allele of rs1800802, rs1800801. or rs4236 (minor allele frequency: 21, 38, and 40%. respectively) were associated with a decreased quantity of CAC. relative to major allele carriers. This association was not found in women. Although genetic variation in MGP was associated with serum MGP concentrations, there were no associations between serum MGP and CAC. The results of this study suggest a role for MGP genetic variants in coronary atherosclerosis among men that is not reflected in serum MGP concentrations. C1 [Crosier, Michael D.; Booth, Sarah L.; Dawson-Hughes, Bess; Ordovas, Jose M.] Tufts Univ, Human Nutr Res Ctr Aging, USDA, Boston, MA 02111 USA. [Peter, Inga] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY 10029 USA. [Price, Paul A.; Williamson, Matthew K.] Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA. [O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [O'Donnell, Christopher J.; Hoffmann, Udo] Massachusetts Gen Hosp, Cardiovasc CT Core Lab, Boston, MA 02114 USA. RP Booth, SL (reprint author), Tufts Univ, Human Nutr Res Ctr Aging, USDA, 711 Washington St, Boston, MA 02111 USA. EM sarah.booth@tufts.edu OI Ordovas, Jose/0000-0002-7581-5680 FU U.S. Department of Agriculture, Agricultural Research Service under Cooperative Agreement [58-1950-7-707]; National Institute of Aging [AG14759, HL69272, NIDDK T32DK62032] FX Based upon work supported by the U.S. Department of Agriculture, Agricultural Research Service under Cooperative Agreement No. 58-1950-7-707, National Institute of Aging (AG14759, HL69272 and NIDDK T32DK62032). Any opinions. findings, conclusions or recommendations expressed in this publication are those of the authors, and do not necessarily reflect the view of the U.S. Department of Agriculture. NR 27 TC 28 Z9 31 U1 0 U2 0 PU CENTER ACADEMIC PUBL JAPAN PI TOKYO PA 2-4-16 YAYOI, BUNKYO-KU, TOKYO, 113-0032, JAPAN SN 0301-4800 J9 J NUTR SCI VITAMINOL JI J. Nutr. Sci. Vitaminol. PD FEB PY 2009 VL 55 IS 1 BP 59 EP 65 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 413BF UT WOS:000263767200008 PM 19352064 ER PT J AU Abukawa, H Zhang, W Young, CS Asrican, R Vacanti, JP Kaban, LB Troulis, MJ Yelick, PC AF Abukawa, Harutsugi Zhang, Weibo Young, Conan S. Asrican, Rose Vacanti, Joseph P. Kaban, Leonard B. Troulis, Maria J. Yelick, Pamela C. TI Reconstructing Mandibular Defects Using Autologous Tissue-Engineered Tooth and Bone Constructs SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID PERIODONTAL-LIGAMENT CELLS; IN-VITRO; TEETH; DIFFERENTIATION; ERUPTION; OSTEOGENESIS; CULTURE; GROWTH; GENES AB Purpose: Current strategies for jaw reconstruction require multiple operations to replace bone and teeth. To improve on these methods, we investigated simultaneous mandibular and tooth reconstruction, using a Yucatan minipig model. Materials and Methods: Tooth and bone constructs were prepared from third molar tooth tissue and iliac-crest bone marrow-derived osteoblasts isolated from, and implanted back into, the same pig as an autologous reconstruction. Implants were harvested after 12 and 20 weeks and evaluated by x-ray, ultrahigh-resolution volume computed tomographic (VCT), histological, and immunohistochemical analyses. Results: Small tooth structures were identified, and consisted of organized dentin, enamel, pulp, and periodontal ligament tissues, surrounded by new bone. No dental tissues formed in implants without tooth-bud cells, and bone regeneration was observed to a limited extent. Immunohistochemical analyses using tooth-specific and bone-specific antibodies confirmed the identity of regenerated tissues. Conclusions: This pilot study supports the feasibility of tissue-engineering approaches for coordinated autologous tooth and mandible reconstruction, and provides a basis for future improvement of this technique for eventual clinical use in humans. (C) 2009 American Association of Oral and Maxillofacial Surgeons C1 [Yelick, Pamela C.] Tufts Univ, Div Craniofacial & Mol Genet, Dept Oral & Maxillofacial Surg, Boston, MA 02111 USA. [Abukawa, Harutsugi; Kaban, Leonard B.; Troulis, Maria J.] Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Asrican, Rose] Harvard Univ, Sch Dent Med, Dept Cytokine Biol, Boston, MA 02115 USA. [Vacanti, Joseph P.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp,Div Pediat Surg, Boston, MA 02115 USA. RP Yelick, PC (reprint author), Tufts Univ, Div Craniofacial & Mol Genet, Dept Oral & Maxillofacial Surg, 136 Harrison Ave,Room M824, Boston, MA 02111 USA. EM pamela.yelick@tufts.edu RI Zhang, Weibo/S-1546-2016 OI Zhang, Weibo/0000-0001-6246-2487 FU NIDCR NIH HHS [R01 DE016132, R21 DE016370] NR 33 TC 33 Z9 41 U1 3 U2 12 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD FEB PY 2009 VL 67 IS 2 BP 335 EP 347 DI 10.1016/j.joms.2008.09.002 PG 13 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 401XD UT WOS:000262975100015 PM 19138608 ER PT J AU Reinold, MM Escamilla, R Wilk, KE AF Reinold, Michael M. Escamilla, Rafael Wilk, Kevin E. TI Current Concepts in the Scientific and Clinical Rationale Behind Exercises for Glenohumeral and Scapulothoracic Musculature SO JOURNAL OF ORTHOPAEDIC & SPORTS PHYSICAL THERAPY LA English DT Article DE electromyography; infraspinatus; serratus anterior; supraspinatus; trapezius ID ROTATOR CUFF MUSCLES; SHOULDER EXTERNAL ROTATION; ELECTROMYOGRAPHIC ANALYSIS; SUBACROMIAL SPACE; REHABILITATION EXERCISES; SCAPULAR KINEMATICS; SERRATUS ANTERIOR; DELTOID MUSCLES; STABILIZING STRUCTURES; SUPRASPINATUS TENDON AB The biomechanical analysis of rehabilitation exercises has led to more scientifically based rehabilitation programs. Several investigators have sought to quantify the biomechanics and electromyographic data of common rehabilitation exercises in an attempt to fully understand their clinical indications and usefulness. Furthermore, the effect of pathology on normal shoulder biomechanics has been documented. It is important to consider the anatomical, biomechanical, and clinical implications when designing exercise programs. The purpose of this paper is to provide the clinician with a thorough overview of the available literature relevant to develop safe, effective, and appropriate exercise programs for injury rehabilitation and prevention of the glenohumeral and scapulothoracic joints. LEVEL OF EVIDENCE: Level 5. J Orthop Sports Phys Thor 2009; 39(2)105-117 doi:10.2519/jospt.2009.2835 C1 [Reinold, Michael M.] Boston Red Sox Baseball Club, Boston, MA 02215 USA. [Reinold, Michael M.] Massachusetts Gen Hosp, Dept Orthoped Surg, Div Sports Med, Boston, MA 02114 USA. [Escamilla, Rafael] Calif State Univ Sacramento, Dept Phys Therapy, Sacramento, CA 95819 USA. [Wilk, Kevin E.] Champ Sports Med, Birmingham, AL USA. [Wilk, Kevin E.] Amer Sports Med Inst, Birmingham, AL USA. RP Reinold, MM (reprint author), Boston Red Sox Baseball Club, Fenway Pk,4 Yawkey Way, Boston, MA 02215 USA. EM mreinold@redsox.com NR 88 TC 71 Z9 72 U1 2 U2 27 PU J O S P T, PI ALEXANDRIA PA 1111 NORTH FAIRFAX ST, STE 100, ALEXANDRIA, VA 22314-1436 USA SN 0190-6011 J9 J ORTHOP SPORT PHYS JI J. Orthop. Sports Phys. Ther. PD FEB PY 2009 VL 39 IS 2 BP 105 EP 117 DI 10.2519/jospt.2009.2835 PG 13 WC Orthopedics; Rehabilitation; Sport Sciences SC Orthopedics; Rehabilitation; Sport Sciences GA 406DW UT WOS:000263276200007 PM 19194023 ER PT J AU Chou, R Fanciullo, GJ Fine, PG Adler, JA Ballantyne, JC Davies, P Donovan, MI Fishbain, DA Foley, KM Fudin, J Gilson, AM Kelter, A Mauskop, A O'Connor, PG Passik, SD Pasternak, GW Portenoy, RK Rich, BA Roberts, RG Todd, KH Miaskowski, C AF Chou, Roger Fanciullo, Gilbert J. Fine, Perry G. Adler, Jeremy A. Ballantyne, Jane C. Davies, Pamela Donovan, Marilee I. Fishbain, David A. Foley, Kathy M. Fudin, Jeffrey Gilson, Aaron M. Kelter, Alexander Mauskop, Alexander O'Connor, Patrick G. Passik, Steven D. Pasternak, Gavril W. Portenoy, Russell K. Rich, Ben A. Roberts, Richard G. Todd, Knox H. Miaskowski, Christine CA Amer Pain Soc Amer Acad Pain Med O TI Clinical Guidelines for the Use of Chronic Opioid Therapy in Chronic Noncancer Pain SO JOURNAL OF PAIN LA English DT Review DE Clinical practice guideline; opioids; opioid analgesics; risk assessment; monitoring; chronic pain ID CHRONIC NONMALIGNANT PAIN; LOW-BACK-PAIN; PRIMARY-CARE PHYSICIANS; CONTROLLED-RELEASE OXYCODONE; LONG-TERM TREATMENT; HIGH-DOSE METHADONE; BREAKTHROUGH PAIN; NEUROPSYCHOLOGICAL PERFORMANCE; TRANSDERMAL FENTANYL; BEHAVIORAL TREATMENT AB Use of chronic opioid therapy for chronic noncancer pain has increased substantially. The American Pain Society and the American Academy of Pain Medicine commissioned a systematic review of the evidence on chronic opioid therapy for chronic noncancer pain and convened a multidisciplinary expert panel to review the evidence and formulate recommendations. Although evidence is limited, the expert panel concluded that chronic opioid therapy can be an effective therapy for carefully selected and monitored patients with chronic noncancer pain. However, opioids are also associated with potentially serious harms, including opioid-related adverse effects and outcomes related to the abuse potential of opioids. The recommendations presented in this document provide guidance on patient selection and risk stratification; informed consent and opioid management plans; initiation and titration of chronic opioid therapy; use of methadone; monitoring of patients on chronic opioid therapy; dose escalations, high-dose opioid therapy, opioid rotation, and indications for discontinuation of therapy; prevention and management of opioid-related adverse effects; driving and work safety; identifying a medical home and when to obtain consultation; management of breakthrough pain; chronic opioid therapy in pregnancy; and opioid-related polices. Perspective: Safe and effective chronic opioid therapy for chronic noncancer pain requires clinical skills and knowledge in both the principles of opioid prescribing and on the assessment and management of risks associated with opioid abuse, addiction, and diversion. Although evidence is limited in many areas related to use of opioids for chronic noncancer pain, this guideline provides recommendations developed by a multidisciplinary expert panel after a systematic review of the evidence. (c) 2009 by the American Pain Society C1 [Chou, Roger] Oregon Hlth & Sci Univ, Dept Med, Dept Med Informat & Clin Epidemiol, Oregon Evidence Based Practice Ctr, Portland, OR 97201 USA. [Fanciullo, Gilbert J.] Dartmouth Hitchcock Med Ctr, Dept Anesthesiol, Pain Management Ctr, Lebanon, NH 03766 USA. [Fine, Perry G.] Univ Utah, Dept Anesthesiol, Pain Res Ctr, Salt Lake City, UT USA. [Adler, Jeremy A.] Pacific Pain Med Consultants, Encinitas, CA USA. [Ballantyne, Jane C.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Div Pain Med, Boston, MA 02114 USA. [Davies, Pamela] Seattle Canc Care Alliance, Seattle, WA USA. [Donovan, Marilee I.] Kaiser Permanente NW, Pain Management Clin, Portland, OR USA. [Fishbain, David A.] Univ Miami, Sch Med Neurol Surg & Anesthesiol, Miami, FL USA. [Foley, Kathy M.] Mem Sloan Kettering Canc Ctr, Dept Neurol, Pain & Palliat Care Serv, New York, NY 10021 USA. [Fudin, Jeffrey] Samuel S Stratton Dept Vet Affairs Med Ctr, Albany, NY USA. [Fudin, Jeffrey] Albany Coll Pharm & Hlth Sci, Albany, NY USA. [Gilson, Aaron M.] Univ Wisconsin, Paul P Carbone Comprehens Canc Ctr, Pain & Policy Studies Grp, Madison, WI 53706 USA. [Kelter, Alexander] Calif Dept Hlth Serv, EPIC Branch, Sacramento, CA USA. [Mauskop, Alexander] New York Headache Ctr, New York, NY USA. [O'Connor, Patrick G.] Yale Univ, Sch Med, Gen Internal Med Sect, New Haven, CT USA. [O'Connor, Patrick G.] Yale New Haven Med Ctr, New Haven, CT 06504 USA. [Passik, Steven D.] Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, New York, NY 10021 USA. [Pasternak, Gavril W.] Mem Sloan Kettering Canc Ctr, Dept Mol Pharmacol & Chem, Lab Mol Neuropharmacol, New York, NY 10021 USA. [Portenoy, Russell K.] Beth Israel Deaconess Med Ctr, Dept Pain Med & Palliat Care, New York, NY 10003 USA. [Rich, Ben A.] Univ Calif Davis, Div Bioeth, Sch Med, Davis, CA USA. [Roberts, Richard G.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Todd, Knox H.] Beth Israel Deaconess Med Ctr, Pain & Emergency Med Inst, New York, NY 10003 USA. [Miaskowski, Christine] Univ Calif San Francisco, Dept Physiol Nursing, San Francisco, CA 94143 USA. RP Chou, R (reprint author), 3181 SW Sam Jackson Pk Rd,Mail Code BICC, Portland, OR 97239 USA. EM chour@ohsu.edu FU NIDA NIH HHS [R01 DA002615, R01 DA006241, R01 DA007242, K05 DA000220] NR 137 TC 889 Z9 905 U1 16 U2 91 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD FEB PY 2009 VL 10 IS 2 BP 113 EP 130 DI 10.1016/j.jpain.2008.10.008 PG 18 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 409IC UT WOS:000263498400001 PM 19187889 ER PT J AU Chou, R Ballantyne, JC Fanciullo, GJ Fine, PG Miaskowski, C AF Chou, Roger Ballantyne, Jane C. Fanciullo, Gilbert J. Fine, Perry G. Miaskowski, Christine TI Research Gaps on Use of Opioids for Chronic Noncancer Pain: Findings From a Review of the Evidence for an American Pain Society and American Academy of Pain Medicine Clinical Practice Guideline SO JOURNAL OF PAIN LA English DT Review DE Analgesics; opioid; pain; evidence-based medicine; risk assessment; drug monitoring; treatment outcomes; harms; research gaps; systematic review ID LOW-BACK-PAIN; RANDOMIZED CONTROLLED-TRIALS; CHRONIC NONMALIGNANT PAIN; OXYMORPHONE EXTENDED-RELEASE; INDUCED BOWEL DYSFUNCTION; PLACEBO-CONTROLLED TRIAL; NAIVE CANCER-PATIENTS; CONTROLLED PHASE-III; LONG-TERM TREATMENT; DOUBLE-BLIND AB Chronic noncancer pain is common and use of opioids is increasing. Previously published guidelines on use of opioids for chronic noncancer pain have been based primarily on expert consensus due to lack of strong evidence. We conducted searches on Ovid MEDLINE and the Cochrane databases through July 2008 to identify studies that addressed one or more of 37 Key Questions that a multidisciplinary expert panel identified as important to be answered to generate evidence-based recommendations on the use of opioids for chronic noncancer pain. A total of 14 systematic reviews, 38 randomized trials not included in a previously published systematic review, and 13 other studies met inclusion criteria. Almost all of the randomized trials of opioids for chronic noncancer pain were short-term efficacy studies. Critical research gaps on use of opioids for chronic noncancer pain include: lack of effectiveness studies on long-term benefits and harms of opioids (including drug abuse, addiction, and diversion); insufficient evidence to draw strong conclusions about optimal approaches to risk stratification, monitoring, or initiation and titration of opioid therapy; and lack of evidence on the utility of informed consent and opioid management plans, the utility of opioid rotation, the benefits and harms specific to methadone or higher doses of opioids, and treatment of patients with chronic noncancer pain at higher risk for drug abuse or misuse. Perspective: Currently, clinical decisions regarding the use of opioids for chronic noncancer pain need to be made based on weak evidence. Research funding priorities need to be set to address these critical research needs if the care of patients with chronic noncancer pain is to improve. (c) 2009 by the American Pain Society C1 [Chou, Roger] Oregon Hlth & Sci Univ, Dept Med, Dept Med Informat & Clin Epidemiol, Oregon Evidence Based Practice Ctr, Portland, OR 97201 USA. [Ballantyne, Jane C.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Div Pain Med, Boston, MA 02114 USA. [Fanciullo, Gilbert J.] Dartmouth Hitchcock Med Ctr, Dept Anesthesiol, Pain Management Ctr, Lebanon, NH 03766 USA. [Fine, Perry G.] Univ Utah, Dept Anesthesiol, Pain Res Ctr, Salt Lake City, UT USA. [Miaskowski, Christine] Univ Calif San Francisco, Sch Nursing, Dept Physiol Nursing, San Francisco, CA 94143 USA. RP Chou, R (reprint author), 3181 SW Sam Jackson Pk Rd,Mail Code BICC, Portland, OR 97239 USA. EM chour@ohsu.edu NR 142 TC 155 Z9 157 U1 2 U2 11 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD FEB PY 2009 VL 10 IS 2 BP 147 EP 159 DI 10.1016/j.jpain.2008.10.007 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 409IC UT WOS:000263498400003 PM 19187891 ER PT J AU Gulur, P Rodi, SW Washington, TA Cravero, JP Fanciullo, GJ McHugo, GJ Baird, JC AF Gulur, Padma Rodi, Scott W. Washington, Tabitha A. Cravero, Joseph P. Fanciullo, Gilbert J. McHugo, Gregory J. Baird, John C. TI Computer Face Scale for Measuring Pediatric Pain and Mood SO JOURNAL OF PAIN LA English DT Article DE Pediatric pain; computer assessment; pain intensity; pediatric mood AB This investigation determined the psychometric properties and acceptability of an animated face scale presented on a hand-held computer as a means to measure pediatric pain and mood. In study 1, 79 hospitalized, pediatric patients indicated their levels of pain by adjusting the expression of an animated cartoon face. The first objective was to determine feasibility, concurrent validity, and acceptability of the method. All patients were tested both with the Computer Face Scale and the poster format of the Wong-Baker Faces Scale. A second objective was to evaluate test-retest reliability of the method. In study 2, 50 hospitalized, pediatric patients were tested on 2 occasions, but in this case the patients used the Computer Face Scale to indicate both their pain (how much they hurt) and their mood (how they felt). Children in study 1 were able to use the Computer Face Scale to express relative amounts of pain/hurt; the method showed concurrent validity with the Wong-Baker Face Scale; and most children expressed a preference for the Computer Face Scale. The method also showed adequate test-retest reliability. In study 2, adequate test-retest reliability was demonstrated for ratings of both pain and mood. Perspective: The Computer Face Scale allows the health provider to obtain reliable and valid measures of pediatric pain and mood The method can be understood and used by children as young as 3 years and is appropriate for use with adults. (c) 2009 by the American Pain Society C1 [Gulur, Padma] Massachusetts Gen Hosp, Dept Anesthesiol, Boston, MA 02114 USA. [Rodi, Scott W.] Dartmouth Hitchcock Med Ctr, Emergency Dept, Lebanon, NH 03766 USA. [Washington, Tabitha A.; Cravero, Joseph P.; Fanciullo, Gilbert J.] Dartmouth Hitchcock Med Ctr, Dept Anesthesiol, Lebanon, NH 03766 USA. [McHugo, Gregory J.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Community & Family Med, Hanover, NH 03756 USA. [McHugo, Gregory J.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Psychiat, Hanover, NH 03756 USA. [Baird, John C.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Med, Hanover, NH 03756 USA. [Baird, John C.] Psychol Applicat, S Pomfret, VT 05067 USA. RP Baird, JC (reprint author), Psychol Applicat, Box 178,2564 Stage Rd, S Pomfret, VT 05067 USA. EM psychapp@wildblue.net FU NICHD NIH HHS [R43 HD052324-01A1, R43 HD052324] NR 20 TC 8 Z9 8 U1 1 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD FEB PY 2009 VL 10 IS 2 BP 173 EP 179 DI 10.1016/j.jpain.2008.08.005 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 409IC UT WOS:000263498400006 PM 19010740 ER PT J AU O'Neill, SM Ettner, SL Lorenz, KA AF O'Neill, Sean M. Ettner, Susan L. Lorenz, Karl A. TI Are Rural Hospices at a Financial Disadvantage? Evidence from California SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article CT Annual Meeting of the American-Academy-of-Hospice-and-Palliative-Medicine CY FEB 08-11, 2006 CL Nashville, TN SP Amer Acad Hospice & Palliat Med DE Hospice; palliative care; rural health care; economics ID ACCESS; CARE AB Concerns have been voiced about financial pressures faced by rural hospices, because of possible implications for hospice access in rural areas. To assess whether financial performance differs between existing urban and rural hospices, we used the 2003 California Office of Statewide Health Planning and Development survey to compare revenues, costs, and profitability (with and without charitable donations). We adjusted for factors related to financial performance, including agency size, years in operation, profit status, whether hospices were freestanding or chain-, home-health or hospital-based, and the proportion of patients by insurance type and referral source, race/ethnicity, and diagnosis. One hundred forty-four (91%) hospices were urban, and 14 (9%) were rural. Mean values per patient for total revenue, total cost, and post-tax profil were $7203, $7440 and -$256, respectively, for urban hospices and $6726, $6274 and $452, respectively, for-rural hospices. Compared with urban hospices, rural hospices were at least as profitable per patient-day (+$33, P = 0.15). They were significantly more profitable (+$47, P = 0.05) when charitable donations were excluded. In summary, we found that in California, rural hospices fared no worse financially than urban hospices. These counterintuitive findings underscore the need to examine urban-rural hospice financial differences using a national sample. J Pain Symptom Manage 2009;37:189-195. (c) 2009 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved. C1 [O'Neill, Sean M.] Pardee RAND Grad Sch, Santa Monica, CA 90407 USA. [Ettner, Susan L.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Lorenz, Karl A.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP O'Neill, SM (reprint author), Pardee RAND Grad Sch, 1776 Main St,POB 2138, Santa Monica, CA 90407 USA. EM soneill@prgs.edu OI O'Neill, Sean/0000-0001-7759-8942 NR 12 TC 2 Z9 2 U1 0 U2 2 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 FEB PY 2009 VL 37 IS 2 BP 189 EP 195 DI 10.1016/j.jpainsymman.2008.01.008 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 412BO UT WOS:000263698400006 PM 18599260 ER PT J AU Sullivan, AM Gadmer, NM Block, SD AF Sullivan, Amy M. Gadmer, Nina M. Block, Susan D. TI The Project on Death in America Faculty Scholars Program: A Report on Scholars' Progress SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID OF-LIFE CARE; PALLIATIVE CARE AB Background: The Project on Death in America's (PDIA) Faculty Scholars' Program (FSP) was created to develop a cadre of faculty and clinician leaders in palliative care. The purpose of this study was to document Scholars' progress since their participation in this program. Methods: Key outcome variables included grants awarded in palliative care, peer-reviewed publications, academic promotions, editorships held, honors, and certifications since their FSP grant award. Methods included a self-administered survey in 2003, and an update in 2007 through collection of Scholars' CVs and a review of literature and websites of national medical palliative care organizations. Results: Of 740 applicants who applied during the granting period 1995-2003, 87 were selected as Faculty Scholars (8 cohorts, 2-3 years each). All Scholars responded to the survey (100% response). Forty percent were female; 82.8% were physicians and 12.6% were nurses. Scholars reported receiving a total of more than $113 million dollars in grants. As of 2007, Scholars had published a total of 2171 papers in peer-reviewed journals. Sixty percent of physicians were certified by the American Board of Hospice and Palliative Medicine. Scholars have been represented in the leadership of all major medical organizations related to end-of-life care and national end-of-life initiatives. Conclusion: Our results suggest the PDIA Faculty Scholars Program has been successful in accomplishing its objective of developing a core group of clinical and academic leaders to advance the field of palliative care. C1 [Sullivan, Amy M.] Virginia Commonwealth Univ, Sch Med, Dept Social & Behav Hlth, Richmond, VA 23298 USA. [Gadmer, Nina M.] Massachusetts Gen Hosp, Dept Nursing, Inst Hlth, Boston, MA 02114 USA. [Block, Susan D.] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. [Block, Susan D.] Harvard Univ, Sch Med, Dept Psychiat, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Sullivan, AM (reprint author), Virginia Commonwealth Univ, Sch Med, Dept Social & Behav Hlth, POB 980149,112 E Clay St, Richmond, VA 23298 USA. EM asullivan@vcu.edu NR 12 TC 7 Z9 7 U1 0 U2 0 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 FEB PY 2009 VL 12 IS 2 BP 155 EP 159 DI 10.1089/jpm.2008.0220 PG 5 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 405YJ UT WOS:000263259800019 PM 19207059 ER PT J AU Chanudet, E Ye, H Ferry, J Bacon, CM Adam, P Muller-Hermelink, HK Radford, J Pileri, SA Ichimura, K Collins, VP Hamoudi, RA Nicholson, AG Wotherspoon, AC Isaacson, PG Du, MQ AF Chanudet, E. Ye, H. Ferry, J. Bacon, C. M. Adam, P. Mueller-Hermelink, H. K. Radford, J. Pileri, S. A. Ichimura, K. Collins, V. P. Hamoudi, R. A. Nicholson, A. G. Wotherspoon, A. C. Isaacson, P. G. Du, M. Q. TI A20 deletion is associated with copy number gain at the TNFA/B/C locus and occurs preferentially in translocation-negative MALT lymphoma of the ocular adnexa and salivary glands SO JOURNAL OF PATHOLOGY LA English DT Article DE A20; TNF; MALT lymphoma; array comparative genomic hybridization ID B-CELL LYMPHOMA; COMPARATIVE GENOMIC HYBRIDIZATION; HELICOBACTER-PYLORI ERADICATION; RHEUMATOID-ARTHRITIS; VARIABLE FREQUENCIES; FOLLICULAR LYMPHOMA; CHLAMYDIA-PSITTACI; DIFFERENT SITES; INHIBITOR A20; ARRAY-CGH AB The genetic basis of MALT lymphoma is largely unknown. Characteristic chromosomal translocations are frequently associated with gastric and pulmonary cases, but are rare at other sites. We compared the genetic profiles of 33 ocular adnexal and 25 pulmonary MALT lymphomas by 1 Mb array-comparative genomic hybridization (CGH) and revealed recurrent 6q23 losses and 6p21.2-6p22.1 gains exclusive to ocular cases. High-resolution chromosome 6 tile-path array-CGH identified NF-kappa B inhibitor A20 as the target of 6q23.3 deletion and TNFA/B/C locus as a putative target of 6p21.2-22.1 gain. Interphase fluorescence in situ hybridization showed that A20 deletion occurred in MALT lymphoma of the ocular adnexa (8/42 = 19%), salivary gland (2/24 = 8%), thyroid (1/9 = 11%) and liver (1/2), but not in the lung (26), stomach (45) and skin (13). Homozygous deletion was observed in three cases. A20 deletion and TNFA/B/C gain were significantly associated (P < 0.001) and exclusively found in cases without characteristic translocation. In ocular cases, A20 deletion was associated with concurrent involvement of different adnexal tissues or extraocular sites at diagnosis (p = 0.007), a higher proportion of relapse (67% versus 37%) and a shorter relapse-free survival (p = 0.033). A20 deletion and gain at TNFA/B/C locus may thus play an important role in the development of translocation-negative MALT lymphoma. Copyright (C) 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. C1 [Chanudet, E.; Ferry, J.; Ichimura, K.; Collins, V. P.; Hamoudi, R. A.; Du, M. Q.] Univ Cambridge, Dept Pathol, Div Mol Histopathol, Cambridge CB2 0QQ, England. [Ye, H.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Adam, P.; Mueller-Hermelink, H. K.] Univ Wurzburg, Inst Pathol, D-97070 Wurzburg, Germany. [Radford, J.] Christie Hosp, Dept Med Oncol, Canc Res UK, Manchester, Lancs, England. [Pileri, S. A.] Univ Bologna, Unita Operat Emolinfopatol, I-40126 Bologna, Italy. [Nicholson, A. G.] Royal Brompton Hosp, Dept Histopathol, London SW3 6LY, England. [Wotherspoon, A. C.] Royal Marsden Hosp, Dept Pathol, London SW3 6JJ, England. [Isaacson, P. G.] UCL, Dept Pathol, London WC1E 6BT, England. RP Du, MQ (reprint author), Univ Cambridge, Dept Pathol, Div Mol Histopathol, Addenbrookes Hosp, Box 231,Level 3,Lab Block,Hills Rd, Cambridge CB2 0QQ, England. EM mqd20@cam.ac.uk RI Radford, John/N-1331-2015; Chanudet, Estelle/N-4064-2015 OI Radford, John/0000-0001-7898-2786; FU Health Foundation; Royal College of Pathologists; Pathological Society of Great Britain and Ireland; Cambridge Fund for the Prevention of Disease (CAMPOD); Openwork Foundation, Swindon FX We thank Dr Paul Duthie, Christie Hospital NHS Foundation Trust, Dr Campidelli, University of Bologna, and Ms Site Goddard, University College London, for their help in retrieving clinical data, as well as Dr Danita Pearson and Miss Alison Goatly for providing BAC clones and probe-labelling protocol for fluorescence in situ hybridization. The Du lab is supported by the Leukaemia and Lymphoma Society, the Elimination of Leukaemia fund, and Leukemia Research Fund. CB is Supported by it Senior Clinician Scientist Fellowship from The Health Foundation, The Royal College of Pathologists and The Pathological Society of Great Britain and Ireland. The fluorescence microscope used in this study Was funded by Cambridge Fund for the Prevention of Disease (CAMPOD), the Pathological Society of Great Britain and Ireland, and Openwork Foundation, Swindon. Array-CGH row data are available in the supporting information to this article. NR 43 TC 66 Z9 67 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0022-3417 J9 J PATHOL JI J. Pathol. PD FEB PY 2009 VL 217 IS 3 BP 420 EP 430 DI 10.1002/path.2466 PG 11 WC Oncology; Pathology SC Oncology; Pathology GA 403IS UT WOS:000263076900010 PM 19006194 ER PT J AU Donahoe, PK AF Donahoe, Patricia K. TI A pediatric surgeon retools in genetics and genomics to study congenital diaphragmatic hernia SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article DE Congenital diaphragmatic hernia; aCGH; SNP; CNV; Lipoprotein receptor related protein 2; Bioinformatics ID LUNG DEVELOPMENT; RETINOIC ACID; VITAMIN-A; DEFECTS; MICE; MOUSE; CDH; INVOLVEMENT; HYPOPLASIA; MUTATIONS AB Prof Donahoe outlines her career-long interest in congenital diaphragmatic hernia and how this has led to tier current investigations into its etiology and possible treatment using gene probes. (C) 2009 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Pediat Surg Res Labs, Boston, MA 02114 USA. RP Donahoe, PK (reprint author), Massachusetts Gen Hosp, Pediat Surg Res Labs, Boston, MA 02114 USA. EM donahoe.patricia@mgh.harvard.edu FU NICHD NIH HHS [R01 HD055150, R01 HD055150-02, R01 HD055150-01, R01 HD055150-03] NR 34 TC 2 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD FEB PY 2009 VL 44 IS 2 BP 307 EP 311 DI 10.1016/j.jpedsurg.2008.10.077 PG 5 WC Pediatrics; Surgery SC Pediatrics; Surgery GA 415MY UT WOS:000263939100001 PM 19231523 ER PT J AU Lievens, S Vandeffoost, N Van der Heyden, J Gesellchen, V Vidal, M Tavernier, J AF Lievens, Sam Vandeffoost, Nele Van der Heyden, Jose Gesellchen, Viola Vidal, Marc Tavernier, Jan TI Array MAPPIT: High-Throughput Interactome Analysis in Mammalian Cells SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE interactome; protein-protein interaction; two-hybrid; MAPPIT; screening ID PROTEIN INTERACTION NETWORK; MOLECULAR-INTERACTIONS; LEPTIN RECEPTOR; COMPLEXES; RESOURCE; BIOLOGY; MOTIFS; YEAST; TRAP; CIS AB Physical interactions between proteins play a key role in probably every cellular process. Efforts to chart the protein interaction networks are ongoing in a number of model organisms using a diversity of approaches. The resulting genome-wide interaction maps will provide a scaffold for further detailed functional analysis. We developed MAPPIT, a mammalian two-hybrid approach that allows identification and analysis of mammalian protein-protein interactions in their native environment. Here, we introduce an efficient MAPPIT assay that permits high-throughput screening of arrayed collections of proteins and complements a previously published cDNA library screening approach. We validated both methods in screens for interaction partners of the Cullin-based E3 ubiquitin ligase subunits SKP1 and Elongin C. In addition to a number of known interactors, novel SKP1 and Elongin C binding proteins were identified. The array assay is an important addition to the MAPPIT suite of technologies that is expected to significantly increase its utility as a toolbox to screen for novel interactors of proteins or small molecules. C1 [Lievens, Sam; Vandeffoost, Nele; Van der Heyden, Jose; Gesellchen, Viola; Tavernier, Jan] VIB, Dept Med Prot Res, B-9000 Ghent, Belgium. [Lievens, Sam; Vandeffoost, Nele; Van der Heyden, Jose; Gesellchen, Viola; Tavernier, Jan] Univ Ghent, Dept Biochem, B-9000 Ghent, Belgium. [Vidal, Marc] Dana Farber Canc Inst, CCSB, Boston, MA 02115 USA. [Vidal, Marc] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Vidal, Marc] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Tavernier, J (reprint author), Baertsoenkaai 3, B-9000 Ghent, Belgium. EM jan.tavernier@ugent.be FU The Fund of Scientific Research-Flanders [G.0031.06]; Ghent University [12051401]; [IUAP-6 P6:28] FX We thank N. Kley for a sample of the IIEK293T-derived MAPPIT prey cDNA library. This research was supported by grants from The Fund of Scientific Research-Flanders (No. G.0031.06), from Ghent University (GOA No. 12051401) and from the IUAP-6 (No. P6:28). NR 34 TC 34 Z9 34 U1 1 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD FEB PY 2009 VL 8 IS 2 BP 877 EP 886 DI 10.1021/pr8005167 PG 10 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 405AC UT WOS:000263193300048 PM 19159283 ER PT J AU Young, EA Kornstein, SG Marcus, SM Harvey, AT Warden, D Wisniewski, SR Balasubramani, GK Fava, M Trivedi, MH Rush, AJ AF Young, Elizabeth A. Kornstein, Susan G. Marcus, Sheila M. Harvey, Anne T. Warden, Diane Wisniewski, Stephen R. Balasubramani, G. K. Fava, Maurizio Trivedi, Madhukar H. Rush, A. John TI Sex differences in response to citalopram: A STAR*D report SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Antidepressants; Gender differences; Estradiol; Women's health; Depression ID SEQUENCED TREATMENT ALTERNATIVES; MAJOR DEPRESSIVE DISORDER; INTERACTIVE VOICE RESPONSE; MEASUREMENT-BASED CARE; REPORT QIDS-SR; GENDER-DIFFERENCES; RELIEVE DEPRESSION; PSYCHOMETRIC EVALUATION; PSYCHIATRIC-DISORDERS; SYMPTOMATOLOGY IDS AB Objective: Controversy exists as to whether women with depression respond better to selective serotonin reuptake inhibitors (SSRIs) than men. The purpose of this report was to determine whether men and women differ in their responses to treatment with the SSRI citalopram using a large sample of real world patients from primary and psychiatric specialty care settings. Method: As part of the sequenced treatment alternatives to relieve depression (STAR D) study, 2876 participants were treated with citalopram for up to 12-14 weeks. Baseline demographic and clinical characteristics and outcomes were gathered and compared between men and women. Results: At baseline, women were Younger, had more severe depressive symptoms and were more likely to have: early onset; previous suicide attempt(s); a family history of depression, alcohol abuse or drug abuse: atypical symptom features; and one or more of several concurrent psychiatric disorders. Despite greater baseline severity and more Axis I comorbidities, women were more likely to reach remission and response with citalopram than men. Conclusions: Women have a better response to the SSRI citalopram than men, which may be due to sex-specific biological differences particularly in serotonergic systems. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Young, Elizabeth A.; Marcus, Sheila M.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Young, Elizabeth A.] Univ Michigan, Mol & Behav Neurosci Inst, Ann Arbor, MI 48109 USA. [Kornstein, Susan G.] Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA USA. [Harvey, Anne T.] Via Christi Res Inc, Wichita, KS USA. [Warden, Diane; Trivedi, Madhukar H.; Rush, A. John] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Wisniewski, Stephen R.; Balasubramani, G. K.] Univ Pittsburgh, GSPH, Epidemiol Data Ctr, Pittsburgh, PA USA. [Fava, Maurizio] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Young, EA (reprint author), Univ Michigan, Dept Psychiat, 4250 Plymouth Rd, Ann Arbor, MI 48109 USA. EM eayoung@umich.edu OI Wisniewski, Stephen/0000-0002-3877-9860; Rush, Augustus/0000-0003-2004-2382 FU NIMH NIH HHS [N01 MH090003, N01MH90003] NR 41 TC 62 Z9 63 U1 0 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD FEB PY 2009 VL 43 IS 5 BP 503 EP 511 DI 10.1016/j.jpsychires.2008.07.002 PG 9 WC Psychiatry SC Psychiatry GA 419MW UT WOS:000264224700002 PM 18752809 ER PT J AU Levine, S Garfein, ES Weiner, H Yaremchuk, MJ Saadeh, PB Gurtner, G Levine, JP Warren, SM AF Levine, Steven Garfein, Evan S. Weiner, Howard Yaremchuk, Michael J. Saadeh, Pierre B. Gurtner, Geoffrey Levine, Jamie P. Warren, Stephen M. TI Intracranial Microvascular Free Flaps SO JOURNAL OF RECONSTRUCTIVE MICROSURGERY LA English DT Article DE Microvascular free flap; intracranial; infection; reconstruction; salvage ID RECONSTRUCTION; HEMISPHERECTOMY; MUSCLE; OSTEOMYELITIS; DEFECTS AB Large acquired intracranial defects can result from trauma or surgery. When reoperation is required because of infection or tumor recurrence, management of the intracranial dead space can be challenging. By providing well-vascularized bulky tissue, intracranial microvascular free flaps offer potential solutions to these life-threatening complications. A multi-institutional retrospective chart and radiographic review was performed of all patients who underwent microvascular free-flap surgery for salvage treatment of postoperative intracranial infections between 1998 and 2006. A total of six patients were identified with large intracranial defects and postoperative intracranial infections. Four patients had parenchymal resections for tumor or seizure and two patients had posttraumatic encephalomalacia. All patients underwent operative debridement and intracranial free-flap reconstruction using the latissimus dorsi muscle (n=2), rectus abdominis muscle (n=2), or omentum (n=2). All patients had titanium (n=4) or Medpor (n=2) cranioplasties. We concluded that surgery or trauma can results In significant intracranial dead,pace. Treatment of postoperative intracranial infection can be challenging. Vascularized free tissue transfer not only fills the void, but also provides a delivery system for Immune cells, antibodies, and systemically administered antibiotics. The early use of this technique when intracranial dead space and infection coexist is beneficial. C1 [Levine, Steven] NYU, Med Ctr, Inst Reconstruct Plast Surg, Sch Med, New York, NY 10016 USA. [Weiner, Howard] NYU, Sch Med, Dept Neurosurg, New York, NY 10016 USA. [Yaremchuk, Michael J.] Massachusetts Gen Hosp, Div Plast Surg, Boston, MA 02114 USA. [Gurtner, Geoffrey] Stanford Univ, Med Ctr, Div Plast Surg, Stanford, CA 94305 USA. RP Levine, S (reprint author), NYU, Med Ctr, Inst Reconstruct Plast Surg, Sch Med, 560 1st Ave,TH-169, New York, NY 10016 USA. EM Stephen.Warren.MD@gmail.com OI Saadeh, Pierre/0000-0001-9818-8598 NR 12 TC 3 Z9 3 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0743-684X J9 J RECONSTR MICROSURG JI J. Reconstr. Microsurg. PD FEB PY 2009 VL 25 IS 2 BP 89 EP 95 DI 10.1055/s-0028-1090609 PG 7 WC Surgery SC Surgery GA 401IC UT WOS:000262933400002 PM 18925548 ER PT J AU Parrett, BM Winograd, JM Lin, SJ Borud, LJ Taghinia, A Lee, BT AF Parrett, Brian M. Winograd, Jonathan M. Lin, Samuel J. Borud, Loren J. Taghinia, Amir Lee, Bernard T. TI The Posterior Tibial Artery Perforator Flap: An Alternative to Free-Flap Closure in the Comorbid Patient SO JOURNAL OF RECONSTRUCTIVE MICROSURGERY LA English DT Article DE Perforator flap; posterior tibial artery perforator flap; lower extremity reconstruction ID MICROSURGICAL TISSUE TRANSFERS; LOWER-EXTREMITY TRAUMA; FASCIOCUTANEOUS FLAPS; NECK RECONSTRUCTION; ACHILLES-TENDON; LOWER-LIMB; HEAD; COMPLICATIONS; MANAGEMENT; FRACTURES AB Wounds of the distal third of the leg with exposed bone traditionally require free flaps for coverage. Although this often provides good results, patients with multiple comorbidities cannot undergo the long operating times and Multiple surgical sites required for these complex procedures. We reviewed the use of posterior tibial (PT) perforator flaps as an alternative to free flaps for distal leg wound coverage in ill patients. Six patients (mean age, 53 years) with multiple comorbidities that precluded free-flap closures were treated with PT perforator flaps to cover complex distal leg wounds. The most common comorbidity was cardiac disease. Five patients bad Gustilo grade IIIB open tibial fractures and one had a chronic Wound. Mean flap size was 8 x 5.5 cm with a mean of one perforator per flap. Mean operating room time was 103 minutes. Four flaps were done without general anesthesia. There were no perioperative cardiopulmonary events. With a mean follow-tip of 15 months, all flaps survived and all patients were ambulatory. There were no cases of malunion, nonunion, infection, wound breakdown, or partial flap loss. The PT perforator flap is a reliable choice for patients with open leg wounds and comorbidities precluding free-flap closure. C1 [Parrett, Brian M.; Lin, Samuel J.; Borud, Loren J.; Taghinia, Amir; Lee, Bernard T.] Beth Israel Deaconess Med Ctr, Div Plast Surg, Boston, MA 02215 USA. [Winograd, Jonathan M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, Boston, MA USA. RP Lee, BT (reprint author), Beth Israel Deaconess Med Ctr, Div Plast 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 NR 20 TC 5 Z9 7 U1 0 U2 1 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0743-684X J9 J RECONSTR MICROSURG JI J. Reconstr. Microsurg. PD FEB PY 2009 VL 25 IS 2 BP 105 EP 109 DI 10.1055/s-0028-1090616 PG 5 WC Surgery SC Surgery GA 401IC UT WOS:000262933400004 PM 18924067 ER PT J AU Bates-Jensen, BM Guihan, M Garber, SL Chin, AS Burns, SP AF Bates-Jensen, Barbara M. Guihan, Marylou Garber, Susan L. Chin, Amy S. Burns, Stephen P. TI Characteristics of Recurrent Pressure Ulcers in Veterans With Spinal Cord Injury SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Article DE Pressure ulcers, recurrent; Spinal cord injuries; Paraplegia; Closure, mucocutaneous flap; Wound healing; Veterans; Bates-Jensen Wound Assessment Tool; Salzburg Pressure Ulcer Risk Score ID SURGICAL-TREATMENT; RISK-FACTORS; SORES; PREVALENCE; PREVENTION; COVERAGE; EXPERIENCE; PEOPLE AB Background/Objective: To describe characteristics of recurrent pressure ulcers (PrUs) in veterans with spinal cord injury (SCI). Design: Descriptive, cohort study. Settings and Participants: Twenty-four veterans with SCI from 6 SCI centers in the Department of Veterans Affairs. Methods: Data from a prospective study evaluating PrUs were analyzed for 24 veterans with 29 recurrent PrUs during 9 months. Additional retrospective medical record data were analyzed for 15 veterans who received inpatient treatment. Results: Participants were male, 50% non-Hispanic white, with paraplegia (63%), complete SCI (83%), a mean age of 56 years, and mean time since SCI of 21 years. Most PrUs recurred (63%, n = 15 patients) in the same location as the most recent ulcer and at the ischial tuberosities (63%). Mean time to recurrence was 16.6 weeks. PrUs were stage III (28%, n = 8) or IV (45%, n = 13) with undermining (48%), necrotic slough (50%), and minimal exudate. One third were (n = 9) larger than 16 cm(2). Mean Bates-Jensen Wound Assessment Tool Score was 33.63. Inpatient medical record data (n = 15) showed 73% with documentation indicating infection treated with antibiotics (53%, n = 8 patients), osteomyelitis (47%, n = 7), and/or cellulitis (13%, n = 2) noted. Plastic surgery consultation was obtained for 67% with surgery as an option for 73% (1 without consultation). Scheduled repositioning was documented for 21%. Conclusions: Most PrUs were severe, located at the same anatomic site, and recurred within 4 months, suggesting that the recurrent ulcers were more likely incomplete healing of the initial PrUs. This sample of veterans with SCI provides early data on recurrent PrU characteristics. C1 [Bates-Jensen, Barbara M.] Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90095 USA. [Bates-Jensen, Barbara M.] VA Greater Angeles Healthcare Syst, Ctr Clin, Los Angeles, CA USA. [Bates-Jensen, Barbara M.] Univ Calif Los Angeles, David Geffen Sch Med, Div Geriatr, Los Angeles, CA 90095 USA. [Guihan, Marylou; Chin, Amy S.] Edward Hines Jr VA Hosp, Ctr Management Complex Chron Care, Hines, IL USA. [Guihan, Marylou] Northwestern Univ, Inst Healthcare Studies, Chicago, IL 60611 USA. [Garber, Susan L.] Baylor Coll Med, Dept Phys Med & Rehabil, Houston, TX 77030 USA. [Burns, Stephen P.] VA Puget Sound Hlth Care Syst, SCI Serv, Seattle, WA USA. [Burns, Stephen P.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. RP Bates-Jensen, BM (reprint author), Univ Calif Los Angeles, Sch Nursing, 5-954 Factor Bldg,700 Tiverton Ave, Los Angeles, CA 90095 USA. EM bbatesjensen@sonnet.ucla.edu NR 36 TC 29 Z9 30 U1 2 U2 2 PU AMER PARAPLEGIA SOC PI JACKSON HWIGHTS PA 75-20 ASTORIA BLVD, JACKSON HWIGHTS, NY 11370-1177 USA SN 1079-0268 J9 J SPINAL CORD MED JI J. Spinal Cord. Med. PD FEB PY 2009 VL 32 IS 1 BP 34 EP 42 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 413ME UT WOS:000263796400005 PM 19264047 ER PT J AU Goss, PE Qj, SL Hu, FQ AF Goss, Paul E. Qj, Shangle Hu, Flaicling TI Comparing the effects of atamestane, toremifene and tamoxifen alone and in combination, on bone, serum lipids and uterus in ovariectomized rats SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article DE Atamestane; Toremifene; Tamoxifen; Bone; Lipids; Uterus ID ADVANCED BREAST-CANCER; INDUCED MAMMARY-TUMORS; AROMATASE INHIBITOR; MECHANICAL-PROPERTIES; FEMALE RATS; PHASE-III; ESTROGEN; MODEL; TRIAL; ESTRADIOL AB Complete estrogen blockade remains under investigation as a means to optimize anti-estrogen therapy in breast cancer thus both the efficacy and end-organ toxicities are of interest with combinations. We hypothesized that a steroidal aromatase inhibitor (At) atamestane (ATA) alone, and in combination with the anti-estrogens tamoxifen (TAM) or toremifene (TOR) would have beneficial effects in ovariectomized (OVX) rats on key end-organ functions including bone and lipid metabolism and on the endometrium. Significant positive effects on bone were noted with ATA, TOR, TAM, ATA+TOR, or ATA+TAM. TOR, TAM, ATA+TOR, or ATA+TAM caused significant decreases in serum cholesterol and low-density lipoprotein cholesterol whereas ATA had no effect. Uterine weight and epithelium lining height were not increased by ATA but were by TOR and TAM. No significant differences were found in the key parameters outlined above between OVX rats given TOR and ATA+TOR, or TAM and ATA+TAM. Our data show that ATA in combination with TOR or TAM is equivalent to TOR or TAM alone in terms of end-organ effects within a range of clinically relevant doses. Further studies of combinations of Als with anti-estrogens on end-organ function are merited. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Goss, Paul E.; Qj, Shangle; Hu, Flaicling] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc,Breast Canc Dis Program,Dana Farber Harv, Boston, MA 02114 USA. RP Goss, PE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc,Breast Canc Dis Program,Dana Farber Harv, 55 Fruit St,Lawrence House,LRH-302, Boston, MA 02114 USA. EM pgoss@partners.org NR 35 TC 7 Z9 7 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD FEB PY 2009 VL 113 IS 3-5 BP 233 EP 240 DI 10.1016/j.jsbmb.2009.01.005 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 425WE UT WOS:000264667700013 PM 19429427 ER PT J AU Sallee, FR McGgough, J Wigal, T Donahue, J Lyne, A Biederman, J AF Sallee, Floyd R. McGgough, James Wigal, Tim Donahue, Jessica Lyne, Andrew Biederman, Joseph CA SPD503 Study Grp TI Guanfacine Extended Release in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder: A Placebo-Controlled Trial SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE alpha(2)-adrenoceptor agonist; attention-deficit/hyperactivity disorder; ADHD; guanfacine; nonstimulant ID DEFICIT HYPERACTIVITY DISORDER; DAILY ATOMOXETINE TREATMENT; DOUBLE-BLIND; WORKING-MEMORY; ALPHA-2A-ADRENOCEPTORS; METHYLPHENIDATE; METAANALYSIS; EFFICACY; MONKEYS; TABLETS AB Objective: This Study compared the efficacy of guanfacine extended release (GXR), a selective alpha(2A)-adrenoceptor agonist, with placebo in children and adolescents with attention-deficit/hyperactivity disorder (ADHD). Method: This double-blind, 9-week, dose-ranging, parallel-design, multicenter trial randomized 6- to 17-year-olds with ADHD to once-daily oral GXR in 1-, 2-, 3-, and 4-mg doses or placebo. Primary outcome was change in total ADHD Rating Scale-IV score from baseline to endpoint. Secondary outcomes included changes in scores of hyperactive/impulsive and inattentive subscales; clinician and parent ratings; duration of clinical effect; and safety measures. Results: Statistically significant reductions in ADHD Rating Scale-IV scores were observed from baseline to endpoint at all doses of GXR, with effect sizes ranging from 0.43 to 0.62. In subjects receiving GXR, mean heart rate and systolic and diastolic blood pressure decreased as the dose of GXR increased and then returned toward baseline during the dose-maintenance and dose-tapering phases of the trial. Most frequent treatment-emergent adverse events (>= 5%) were somnolence, headache, fatigue, sedation, dizziness, irritability, upper abdominal pain, and nausea. Somnolence, sedation, and fatigue adverse events emerged within the first 2 weeks of dosing and generally resolved by study end. Conclusions: Guanfacine extended-release was effective in reducing symptoms of ADHD. Adverse events were mild to moderate, did not interfere with improvements in attention, and rarely led to discontinuation. J. Am. Acad. Child Adolesc. Psychiatry, 2009;48(2):155-165. C1 [Sallee, Floyd R.] Univ Cincinnati, Dept Psychiat, Cincinnati, OH 45267 USA. Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA. [Biederman, Joseph] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. RP Sallee, FR (reprint author), Univ Cincinnati, Dept Psychiat, 231 Albert Sabin Way, Cincinnati, OH 45267 USA. EM floyd.sallee@uc.edu FU Shire Development, Wayne, PA FX This study was supported by Shire Development, Wayne, PA. NR 35 TC 109 Z9 110 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD FEB PY 2009 VL 48 IS 2 BP 155 EP 165 DI 10.1097/CHI.0b013e318191769e PG 11 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 397XO UT WOS:000262695900008 PM 19106767 ER PT J AU Krzyzanowska, MK Regan, MM Powell, M Earle, CC Weeks, JC AF Krzyzanowska, Monika K. Regan, Meredith M. Powell, Mark Earle, Craig C. Weeks, Jane C. TI Impact of Patient Age and Comorbidity on Surgeon Versus Oncologist Preferences for Adjuvant Chemotherapy for Stage III Colon Cancer SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article; Proceedings Paper CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol ID ADVANCED COLORECTAL-CANCER; POPULATION-BASED COHORT; ELDERLY-PATIENTS; POOLED ANALYSIS; BREAST-CANCER; FINAL REPORT; OLDER WOMEN; PHASE-III; THERAPY; FLUOROURACIL AB BACKGROUND: To study surgeons' versus oncologists' preferences for adjuvant chemotherapy for elderly patients with stage III colon cancer, as population studies indicate that such patients are less likely to receive treatment. STUDY DESIGN: A vignette-based survey was mailed to a nationally representative sample of 1,000 general surgeons and 1,000 oncologists in the United States. Patient age, comorbidity level, and preference were varied across eight vignettes. Physician preference for referral (surgeons) or treatment (oncologists) was measured using a 7-point Likert scale. Mixed-effects linear regression was used to evaluate the results. RESULTS: One thousand twenty-nine surveys were returned (response rate of 54%). Among surgeons, increasing age and more severe comorbidity resulted in lower likelihood of referral to oncologist: mean difference in preference scores for vignettes describing a 61-year-old versus an 83-year-old patient (adjusted for comorbidity) was 0.77 (p < 0.0001); mean difference in scores between vignettes describing a patient with none versus severe comorbidity, adjusted for age, was 1.94 (p < 0.0001). Among oncologists, patient age and comorbidity interacted significantly (p < 0.0001) to affect oncologists' preferences: both increasing age and more severe comorbidity resulted in decreased preference for recommending adjuvant chemotherapy, but-oncologists were more heavily influenced by comorbidity at younger patient age. Patient preference against therapy also affected physicians' recommendations (p < 0.0001), but the magnitude of effect was small relative to age and comorbidity. CONCLUSION: Patient age and comorbidity level influence both types of physicians' preferences about adjuvant chemotherapy for colon cancer and might explain some of the patterns of care seen for this disease in population-based studies. (J Am Coll Surg 2009;208:202-209. (C) 2009 by the American College of Surgeons) C1 [Krzyzanowska, Monika K.] Princess Margaret Hosp, Dept Med Oncol & Hematol, Toronto, ON M5G 2M9, Canada. [Krzyzanowska, Monika K.] Univ Toronto, Dept Med, Toronto, ON, Canada. [Regan, Meredith M.; Powell, Mark] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Earle, Craig C.; Weeks, Jane C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Regan, Meredith M.; Earle, Craig C.; Weeks, Jane C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Krzyzanowska, MK (reprint author), Princess Margaret Hosp, Dept Med Oncol & Hematol, 610 Univ Ave,Ste 5-206, Toronto, ON M5G 2M9, Canada. EM monika.krzyzanowska@uhn.on.ca NR 31 TC 27 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 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD FEB PY 2009 VL 208 IS 2 BP 202 EP 209 DI 10.1016/j.jamcollsurg.2008.10.016 PG 8 WC Surgery SC Surgery GA 407TP UT WOS:000263387500005 PM 19228531 ER PT J AU Lerner, LB Stolzmann, KL Gulla, VD AF Lerner, Lori B. Stolzmann, Kelly L. Gulla, Vanessa D. TI Birth Trends and Pregnancy Complications among Women Urologists SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID PLASTIC SURGEONS; MATERNAL AGE; RESIDENCY; POPULATION; PHYSICIANS; DIRECTORS; RISK AB BACKGROUND: As the number of women entering urology grows, so should discussions and awareness about pregnancy. To understand if urology training and practice potentially put women and their pregnancies at risk, we set out to assess the childbearing differences between the average American woman and the female urologist. STUDY DESIGN: A 114-item anonymous survey was sent to all 365 American board certified female urologists in 2007. Data concerning,birth trends, pregnancy, assisted reproduction, and complications were analyzed. Findings were compared with 2004 CDC data. RESULTS: Two mailings yielded a 69% (n = 243) response rate; average age was 43 years; 67.4% had biologic children (average 2.0 children). Women urologists were older by 7 to 8 years for all births. An assisted reproduction technology birth was nearly 10 times more likely. Pregnancy complications were high, with a prevalence greater than that in the lowest income brackets in the United States. The induction rate was above average; the rate of cesarean deliveries was similar, with only 21 elective procedures performed. Ninety-two percent of women urologists would choose to have the same number of children: 66% at the same point in their career; 16%, earlier; 4%, later; 15%, uncertain. CONCLUSIONS: Women urologists have children later in life, a smaller number, a higher induction rate, and a higher incidence of pregnancy complications. These are likely related to the older age at pregnancy, which certainly contributes to the higher number conceived by assisted reproduction technology. Cesarean delivery rates, which were expected to be higher, were similar. To avoid complications, childbearing should not be delayed, and residency programs and practice groups will need to develop programs that support the growing number of women urologists. (J Am Coll Surg 2009;208:293-297. (C) 2009 by the American College of Surgeons) C1 [Lerner, Lori B.] VA Boston Healthcare Syst, Dept Surg, Boston, MA USA. [Stolzmann, Kelly L.] VA Boston Healthcare Syst, Res & Dev Serv, Boston, MA USA. [Gulla, Vanessa D.] Dartmouth Hitchcock Med Ctr, Dept Urol, Lebanon, NH 03766 USA. RP Lerner, LB (reprint author), VA Boston Healthcare Syst, Dept Surg, 12 Water St, Hingham, MA 02043 USA. NR 21 TC 16 Z9 17 U1 0 U2 1 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 FEB PY 2009 VL 208 IS 2 BP 293 EP 297 DI 10.1016/j.jamcollsurg.2008.10.012 PG 5 WC Surgery SC Surgery GA 407TP UT WOS:000263387500016 PM 19228542 ER PT J AU Friedlander, AH Yoshikawa, TT Chang, DS Feliciano, Z Scully, C AF Friedlander, Arthur H. Yoshikawa, Thomas T. Chang, Donald S. Feliciano, Zenaida Scully, Crispian TI Atrial fibrillation Pathogenesis, medical-surgical management and dental implications SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Review DE Cardiovascular diseases; stroke; anticoagulation therapy ID ORAL ANTICOAGULANT-THERAPY; INTERNATIONAL NORMALIZED RATIO; DRUG-INTERACTIONS; ANTITHROMBOTIC THERAPY; VITAMIN-K; CARDIOVERTER-DEFIBRILLATORS; CARDIOVASCULAR HEALTH; ISCHEMIC-STROKE; RHYTHM CONTROL; RISK-FACTORS AB Background. Atrial fibrillation (AF) is a cardiac rhythm disturbance arising from disorganized electrical activity in the atria, and it is accompanied by an irregular and often rapid ventricular response. It is the most common clinically significant dysrhythmia in the general and older population. Types of Studies Reviewed. The authors conducted a MEDLINE search using the key terms "atrial fibrillation," "epidemiology," "pathophysiology," "treatment" and "dentistry." They selected contemporaneous articles published in peer-reviewed journals and gave preference to articles reporting randomized controlled trials. Clinical Implications. The anticoagulant warfarin frequently is prescribed to prevent stroke caused by cardiogenic thromboemboli arising from stagnant blood in poorly contracting atria. Most dental procedures and a limited number of surgical procedures can be performed without altering warfarin dosage if the international normalized ratio value is within the therapeutic range of 2.0 to 3.0. Certain analgesic agents, antibiotic agents, antifungal agents and sedative hypnotics, however, should not be prescribed without consultation with the patient's physician because these medications may alter the patient's risk of hemorrhage and stroke. Conclusions. AF affects nearly 2.5 million Americans, most of who are older than 60 years. Consultation with the patient's physician to discuss the planned dental treatment often is appropriate, especially for people, who frequently have comorbid diseases such as coronary artery disease, congestive heart failure, diabetes and thyrotoxicosis, which are treated with multiple drug regimens. C1 [Friedlander, Arthur H.; Yoshikawa, Thomas T.] VA Greater Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, Los Angeles, CA 90073 USA. [Friedlander, Arthur H.] Univ Calif Los Angeles, Med Ctr, Hosp Dent Serv, Los Angeles, CA 90024 USA. [Friedlander, Arthur H.] Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90024 USA. [Yoshikawa, Thomas T.; Chang, Donald S.; Feliciano, Zenaida] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Chang, Donald S.] UCLA VA, VA Greater Los Angeles, San Fernando Valley Program, Los Angeles, CA USA. [Scully, Crispian] UCL, Eastman Dent Inst, WHO Collaborating Ctr Res Educ & Serv Oral Hlth D, London WC1E 6BT, England. RP Friedlander, AH (reprint author), VA Greater Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM arthur.friedlander@med.va.gov NR 91 TC 2 Z9 2 U1 0 U2 3 PU AMER DENTAL ASSOC PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD FEB PY 2009 VL 140 IS 2 BP 167 EP 177 PG 11 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 406EL UT WOS:000263277700019 PM 19188413 ER PT J AU Arnold, SV Alexander, KP Masoudi, FA Ho, PM Xiao, L Spertus, JA AF Arnold, Suzanne V. Alexander, Karen P. Masoudi, Frederick A. Ho, P. Michael Xiao, Lan Spertus, John A. TI The Effect of Age on Functional and Mortality Outcomes After Acute Myocardial Infarction SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE aging; functional status; quality of life; myocardial infarction ID QUALITY-OF-LIFE; CORONARY-ARTERY-BYPASS; TIMI RISK SCORE; ACTIVITY QUESTIONNAIRE; INTERNATIONAL TRIAL; GLOBAL REGISTRY; HEART-DISEASE; EVENTS GRACE; HEALTH; CAPACITY AB To determine the prevalence of post-myocardial infarction (MI) functional decline and to describe its association with chronological age in survivors of MI. Prospective observational registry. Nineteen U.S. hospitals. Two thousand four hundred eighty-one patients with acute MI. Baseline and 1-year interviews identified subjects with functional decline, defined as a more than 5-point decline in Medical Outcomes Study 12-item Short Form Questionnaire (SF-12) Physical Component score or being "too ill" to provide a follow-up interview at 1 year. The relationship between age and functional decline was evaluated using logistic regression models adjusted for baseline SF-12 score, comorbidities, sociodemographics, and treatment characteristics. One-year mortality and a combined endpoint of death or decline were also compared across age. Of 2,009 patients who survived to 1 year, 582 (29%) experienced a functional decline. In survivors, age was not associated with functional decline in unadjusted (odds ratio (OR)=0.95/decade, 95% confidence interval (CI)=0.88-1.03) or multivariable (OR=0.94, 95% CI=0.85-1.05) models. Although age was strongly associated with 1-year mortality (adjusted hazard ratio=1.42, 95% CI=1.21-1.66), there was no association between age and the combined endpoint of death or functional decline (adjusted OR=1.02, 95% CI=0.92-1.12). More than one in four survivors of MI experiences a significant decline in physical function by 1 year. Although age is strongly associated with mortality, it had no association with functional decline. Because older patients have the same potential for favorable functional outcomes after an MI, age alone should not preclude aggressive treatment after an MI. C1 [Arnold, Suzanne V.; Xiao, Lan; Spertus, John A.] St Lukes Mid Amer Heart Inst, Kansas City, MO 64111 USA. [Alexander, Karen P.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Masoudi, Frederick A.; Ho, P. Michael] Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. [Masoudi, Frederick A.] Denver Hlth Med Ctr, Dept Med, Denver, CO USA. [Ho, P. Michael] Denver Vet Affairs Med Ctr, Denver, CO USA. [Spertus, John A.] Univ Missouri, Dept Med, Div Cardiol, Kansas City, MO 64110 USA. RP Spertus, JA (reprint author), St Lukes Mid Amer Heart Inst, 4401 Wornall Rd, Kansas City, MO 64111 USA. EM spertusj@umkc.edu FU Cardiovascular Therapeutics, Inc.; Cardiovascular Outcomes, Inc., Kansas City FX Sponsor's Role: The sponsors did not play a role in the design or conduct of the study; in the collection, management, analysis, or interpretation of the data; or in the preparation, review, or approval of the manuscript. NR 43 TC 14 Z9 14 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC 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 FEB PY 2009 VL 57 IS 2 BP 209 EP 217 DI 10.1111/j.1532-5415.2008.02106.x PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 399WE UT WOS:000262829200003 PM 19170779 ER PT J AU Little, DM Crooks, VC Petitti, DB Chiu, V Schellenberg, GD Slezak, JM Jacobsen, SJ AF Little, Deborah M. Crooks, Valerie C. Petitti, Diana B. Chiu, Vicki Schellenberg, Gerard D. Slezak, Jeff M. Jacobsen, Steven J. TI Mortality, Dementia, and Apolipoprotein E Genotype in Elderly White Women in the United States SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE dementia; APOE; genotype ID E EPSILON-4 ALLELE; CORONARY-HEART-DISEASE; ALZHEIMERS-DISEASE; APOE GENOTYPE; CEREBROVASCULAR-DISEASE; COGNITIVE IMPAIRMENT; POPULATION-SAMPLE; CACHE COUNTY; E PHENOTYPES; OLDEST-OLD AB To assess the risk of death in relation to apolipoprotein E (APOE) genotype and to evaluate how APOE genotype interacts with dementia and with other major medical conditions to affect survival. A 6-year prospective cohort study of dementia, APOE genotype and survival. Health maintenance organization in southern California. One thousand eight hundred forty-two white women aged 75 and older. Dementia was determined using a multistage assessment procedure, medical record, and death certificate review. With women with the APOE 3/3 genotype as the referent, age-adjusted hazard ratios (HRs) for death according to genotype were 1.25 (95% confidence interval (CI)=1.00-1.56) for APOE 2/4, 3/4, or 4/4 and 0.83 (95% CI=0.62-1.13) for APOE 2/3 or 2/2. Survival was associated with APOE genotype (log rank test P=.02). Women with the APOE 2/4, 3/4, or 4/4 genotype died at an earlier age, and those with APOE 2/2 or 2/3 died later than those with the APOE 3/3 genotype. After adjustment for age, education, and hormone use, HRs for death were significantly higher in women with the APOE 2/4, 3/4, or 4/4 genotype who developed dementia (HR=3.74; 95% CI=2.81-4.99) and the APOE 2/3 genotype (HR=3.23; 95%=CI=1.97-5.28) than in women without dementia and the APOE 3/3 genotype. The HRs for death were greater with other medical conditions, but no interaction with any APOE genotype was found. In this population of elderly women, although having at least one epsilon 4 allele increased the chances of an earlier death, having dementia increased the risk of death regardless of APOE genotype. C1 [Little, Deborah M.] Kaiser Permanente So Calif, Dept Res & Evaluat, Pasadena, CA 91101 USA. [Schellenberg, Gerard D.] Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98195 USA. RP Crooks, VC (reprint author), Kaiser Permanente So Calif, Dept Res & Evaluat, 100 S Robles,2nd Floor, Pasadena, CA 91101 USA. EM valerie.c.crooks@kp.org OI Jacobsen, Steven/0000-0002-8174-8533 FU National Institute on Aging [AG14745] FX Sponsor's Role: The funding organization (NIA) did not have any role in the design or conduct of the study; collection, management, analysis, or interpretation of the data; or preparation, review, or approval of the manuscript. NR 42 TC 16 Z9 16 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC 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 FEB PY 2009 VL 57 IS 2 BP 231 EP 236 DI 10.1111/j.1532-5415.2008.02113.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 399WE UT WOS:000262829200006 PM 19207139 ER PT J AU Pugh, MJV Knoefel, JE Mortensen, EM Amuan, ME Berlowitz, DR Van Cott, AC AF Pugh, Mary Jo V. Knoefel, Janice E. Mortensen, Eric M. Amuan, Megan E. Berlowitz, Dan R. Van Cott, Anne C. TI New-Onset Epilepsy Risk Factors in Older Veterans SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE epilepsy; risk factors; cohort study; race; aged ID UNPROVOKED SEIZURES; ELDERLY PATIENTS; DISORDERS; DISEASE; HYPERTENSION; PREVENTION; DEMENTIA; STROKE AB To identify risk factors for new-onset geriatric epilepsy that may trigger clinicians to consider a differential diagnosis of epilepsy at symptom onset. Retrospective cohort study. National Veterans Affairs (VA) databases. Veterans aged 66 and older in fiscal year 2000 (FY00) who received VA care in FY99 and FY00. Individuals with new-onset epilepsy based on a validated algorithm constituted the epilepsy cohort (n=1,843), and individuals without epilepsy constituted the geriatric cohort (n=1,023,376). Age, sex, and race were derived from VA databases. Clinical conditions associated with new-onset geriatric epilepsy (e.g., cerebrovascular disease, dementia, brain tumor) and stroke risk-factors (e.g., hypertension, diabetes mellitus, cardiovascular disease) were identified using validated International Classification of Diseases, Ninth Revision, Clinical Modification, codes before epilepsy onset (epilepsy cohort) and in FY00 (geriatric cohort). Multivariable logistic regression analysis indicated that patients with cerebrovascular disease (odds ratio (OR)=3.50, 95% confidence interval (CI)=3.13-3.91), cerebrovascular disease and dementia (OR=4.14, 95% CI=3.46-4.96), brain tumor (OR=2.14, 95% CI=1.46-3.13), head injury (OR=2.11, 95% CI=1.41-3.14), and other central nervous system (CNS) conditions (OR=1.57, 95% CI=1.32-1.88) were more likely to experience new-onset epilepsy. Statin prescription (OR=0.64, 95% CI=0.56-0.73), older age (>= 85 vs 66-74, OR=0.66, 95% CI=0.50-0.87), obesity (OR=0.74, 95% CI=0.62-0.87), and hypercholesterolemia (OR=0.87, 95% CI=0.76-0.98) were associated with a lower likelihood of epilepsy. These data suggest greater epilepsy risk for older individuals with CNS insult and an additive effect of cerebrovascular disease and dementia. The statin finding requires further exploration but points to a possible target for prevention of geriatric epilepsy. C1 [Pugh, Mary Jo V.; Mortensen, Eric M.] S Texas Vet Hlth Care Syst, Vet Evidence Based Res Disseminat Implementat Res, Hlth Serv Res & Dev Serv, Dept Vet Affairs, San Antonio, TX USA. [Pugh, Mary Jo V.; Mortensen, Eric M.] Univ Texas Hlth Sci Ctr San Antonio, Div Internal Med, San Antonio, TX 78229 USA. [Knoefel, Janice E.] New Mexico Vet Hlth Care Syst, Albuquerque, NM USA. [Amuan, Megan E.; Berlowitz, Dan R.] Bedford Vet Affairs Hosp, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Berlowitz, Dan R.; Van Cott, Anne C.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Van Cott, Anne C.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Van Cott, Anne C.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. RP Pugh, MJV (reprint author), S Texas Vet Hlth Care Syst VERDICT, Audie L Murphy Div 11C6, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM PughM@uthscsa.edu OI Pugh, Mary Jo/0000-0003-4196-7763; Mortensen, Eric/0000-0002-3880-5563 FU VA Health Services Research and Development Service [IIR 02-274]; GlaxoSmithKline FX Sponsor's Role: The funding source did not have a role in the study design, methods, subject recruitment, data collections, or analysis and preparation of the manuscript. NR 34 TC 34 Z9 34 U1 0 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC 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 FEB PY 2009 VL 57 IS 2 BP 237 EP 242 DI 10.1111/j.1532-5415.2008.02124.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 399WE UT WOS:000262829200007 PM 19207140 ER PT J AU Wright, RM Roumani, YF Boudreau, R Newman, AB Ruby, CM Studenski, SA Shorr, RI Bauer, DC Simonsick, EM Hilmer, SN Hanlon, JT AF Wright, Rollin M. Roumani, Yazan F. Boudreau, Robert Newman, Anne B. Ruby, Christine M. Studenski, Stephanie A. Shorr, Ronald I. Bauer, Douglas C. Simonsick, Eleanor M. Hilmer, Sarah N. Hanlon, Joseph T. CA Hlth Aging & Body Composition Stud TI Effect of Central Nervous System Medication Use on Decline in Cognition in Community-Dwelling Older Adults: Findings from the Health, Aging and Body Composition Study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE cognition; aged; medications ID BENZODIAZEPINE USE; ELDERLY PERSONS; INFLAMMATORY MARKERS; FUNCTIONAL DECLINE; PREDICTIVE MODEL; RISK-FACTORS; DRUG-USE; DELIRIUM; IMPAIRMENT; PERFORMANCE AB To evaluate whether combined use of multiple central nervous system (CNS) medications over time is associated with cognitive change. Longitudinal cohort study. Pittsburgh, Pennsylvania, and Memphis, Tennessee. Two thousand seven hundred thirty-seven healthy adults (aged >= 65) enrolled in the Health, Aging and Body Composition study without baseline cognitive impairment (modified Mini-Mental State Examination (3MS) score >= 80). CNS medication (benzodiazepine- and opioid-receptor agonists, antipsychotics, antidepressants) use, duration, and dose were determined at baseline (Year 1) and Years 3 and 5. Cognitive function was measured using the 3MS at baseline and Years 3 and 5. The outcome variables were incident cognitive impairment (3MS score < 80) and cognitive decline (>= 5-point decline on 3MS). Multivariable interval-censored survival analyses were conducted. By Year 5, 7.7% of subjects had incident cognitive impairment; 25.2% demonstrated cognitive decline. CNS medication use increased from 13.9% at baseline to 15.3% and 17.1% at Years 3 and 5, respectively. It was not associated with incident cognitive impairment (adjusted hazard ratio (adj HR)=1.11, 95% confidence interval (CI)=0.73-1.69) but was associated with cognitive decline (adj HR 1.37, 95% CI=1.11-1.70). Longer duration (adj HR=1.39, CI=1.08-1.79) and higher doses (> 3 standardized daily doses) (adj HR=1.87, 95% CI=1.25-2.79) of CNS medications suggested greater risk of cognitive decline than with nonuse. Combined use of CNS medications, especially at higher doses, appears to be associated with cognitive decline in older adults. Future studies must explore the effect of combined CNS medication use on vulnerable older adults. C1 [Wright, Rollin M.; Roumani, Yazan F.; Newman, Anne B.; Studenski, Stephanie A.; Hanlon, Joseph T.] Univ Pittsburgh, Sch Med, Dept Med, Div Geriatr, Pittsburgh, PA 15213 USA. [Boudreau, Robert; Newman, Anne B.] Univ Pittsburgh, Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA. [Ruby, Christine M.; Hanlon, Joseph T.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15213 USA. [Studenski, Stephanie A.; Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res, Pittsburgh, PA USA. [Studenski, Stephanie A.; Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. [Shorr, Ronald I.] N Florida S Georgia Vet Hlth Syst, Ctr Geriatr Res Educ & Clin, Gainesville, FL USA. [Bauer, Douglas C.] Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94143 USA. [Simonsick, Eleanor M.] Johns Hopkins Univ, Inst Med, Div Geriatr Med & Gerontol, Baltimore, MD USA. [Simonsick, Eleanor M.; Hilmer, Sarah N.] NIA, Intramural Res Program, Baltimore, MD 21224 USA. [Hilmer, Sarah N.] Univ Sydney, Sydney, NSW 2006, Australia. [Hilmer, Sarah N.] Royal N Shore Hosp, Sydney, NSW, Australia. RP Wright, RM (reprint author), Univ Pittsburgh, Dept Med Geriatr, Kaufmann Med Bldg,Suite 500,3471 5th Ave, Pittsburgh, PA 15213 USA. EM rmw27@pitt.edu RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Hilmer, Sarah/0000-0002-5970-1501; Boudreau, Robert/0000-0003-0162-5187 FU National Institutes of Health (NIH), National Institute on Aging; NIH c [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, R01AG027017]; Pittsburgh Claude D. Pepper Older Americans Independence Center [P30AG024827]; John A. Hartford Foundation Center FX Sponsors' Roles: The organizations that funded this study did not influence the interpretation of the data or the development of this manuscript. NR 53 TC 37 Z9 38 U1 2 U2 5 PU WILEY-BLACKWELL PUBLISHING, INC 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 FEB PY 2009 VL 57 IS 2 BP 243 EP 250 DI 10.1111/j.1532-5415.2008.02127.x PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 399WE UT WOS:000262829200008 PM 19207141 ER PT J AU Nazem, S Siderowf, AD Duda, JE Have, TT Colcher, A Horn, SS Moberg, PJ Wilkinson, JR Hurtig, HI Stern, MB Weintraub, D AF Nazem, Sarra Siderowf, Andrew D. Duda, John E. Have, Tom Ten Colcher, Amy Horn, Stacy S. Moberg, Paul J. Wilkinson, Jayne R. Hurtig, Howard I. Stern, Matthew B. Weintraub, Daniel TI Montreal Cognitive Assessment Performance in Patients with Parkinson's Disease with "Normal" Global Cognition According to Mini-Mental State Examination Score SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE cognitive impairment; Parkinson's disease; Mini-Mental State Examination; Montreal Cognitive Assessment; neuropsychology ID COMMUNITY POPULATION; DIAGNOSTIC-CRITERIA; ELDERLY-PEOPLE; SCREENING TOOL; IMPAIRMENT; DEMENTIA; DYSFUNCTION; PROFILE; COHORT AB To examine Montreal Cognitive Assessment (MoCA) performance in patients with Parkinson's disease (PD) with "normal" global cognition according to Mini-Mental State Examination (MMSE) score. A cross-sectional comparison of the MoCA and the MMSE. Two movement disorders centers at the University of Pennsylvania and the Philadelphia Veterans Affairs Medical Center. A convenience sample of 131 patients with idiopathic PD who were screened for cognitive and psychiatric complications. Subjects were administered the MoCA and MMSE, and only subjects defined as having a normal age- and education-adjusted MMSE score were included in the analyses (N=100). As previously recommended in patients without PD, a MoCA score less than 26 was used to indicate the presence of at least mild cognitive impairment (MCI). Mean MMSE and MoCA scores +/- standard deviation were 28.8 +/- 1.1 and 24.9 +/- 3.1, respectively. More than half (52.0%) of subjects with normal MMSE scores had cognitive impairment according to their MoCA score. Impairments were seen in numerous cognitive domains, including memory, visuospatial and executive abilities, attention, and language. Predictors of cognitive impairment on the MoCA using univariate analyses were male sex, older age, lower educational level, and greater disease severity; older age was the only predictor in a multivariate model. Approximately half of patients with PD with a normal MMSE score have cognitive impairment based on the recommended MoCA cutoff score. These results suggest that MCI is common in PD and that the MoCA is a more sensitive instrument than the MMSE for its detection. C1 [Nazem, Sarra; Moberg, Paul J.; Weintraub, Daniel] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Siderowf, Andrew D.; Duda, John E.; Colcher, Amy; Horn, Stacy S.; Moberg, Paul J.; Hurtig, Howard I.; Stern, Matthew B.; Weintraub, Daniel] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Have, Tom Ten] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr, Philadelphia, PA USA. RP Weintraub, D (reprint author), 3615 Chestnut St,Room 330, Philadelphia, PA 19104 USA. EM weintrau@mail.med.upenn.edu FU National Institutes of Mental Health [067894] FX Sponsor's Role: NA. NR 31 TC 139 Z9 156 U1 4 U2 33 PU WILEY-BLACKWELL PUBLISHING, INC 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 FEB PY 2009 VL 57 IS 2 BP 304 EP 308 DI 10.1111/j.1532-5415.2008.02096.x PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 399WE UT WOS:000262829200017 PM 19170786 ER PT J AU Hanlon, JT Aspinall, SL Semla, TP Weisbord, SD Fried, LF Good, CB Fine, MJ Stone, RA Pugh, MJV Rossi, MI Handler, SM AF Hanlon, Joseph T. Aspinall, Sherrie L. Semla, Todd P. Weisbord, Steven D. Fried, Linda F. Good, C. Bernie Fine, Michael J. Stone, Roslyn A. Pugh, Mary Jo V. Rossi, Michelle I. Handler, Steven M. TI Consensus Guidelines for Oral Dosing of Primarily Renally Cleared Medications in Older Adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE aged; chronic kidney disease; suboptimal prescribing ID PHARMACOKINETICS; EFFICACY; CARE; INSUFFICIENCY; TRIAL; ALLOPURINOL; INFORMATION; LORATADINE; FAILURE; DISEASE AB To establish consensus oral dosing guidelines for primarily renally cleared medications prescribed for older adults. Literature search followed by a two-round modified Delphi survey. A nationally representative survey of experts in geriatric clinical pharmacy. Eleven geriatric clinical pharmacists. After a comprehensive literature search and review by an investigative group of six physicians (2 general internal medicine, 2 nephrology, 2 geriatrics), 43 dosing recommendations for 30 medications at various levels of renal function were created. The expert panel rated its agreement with each of these 43 dosing recommendations using a 5-point Likert scale (1=strongly disagree to 5=strongly agree). Recommendation-specific means and 95% confidence intervals were estimated. Consensus was defined as a lower 95% confidence limit of greater than 4.0 for the recommendation-specific mean score. The response rate was 81.8% (9/11) for the first round. All respondents who completed the first round also completed the second round. The expert panel reached consensus on 26 recommendations involving 18 (60%) medications. For 10 medications (chlorpropamide, colchicine, cotrimoxazole, glyburide, meperidine, nitrofurantoin, probenecid, propoxyphene, spironolactone, and triamterene), the consensus recommendation was not to use the medication in older adults below a specified level of renal function (e.g., creatinine clearance < 30 mL/min). For the remaining eight medications (acyclovir, amantadine, ciprofloxacin, gabapentin, memantine, ranitidine, rimantadine, and valacyclovir), specific recommendations for dose reduction or interval extension were made. An expert panel of geriatric clinical pharmacists was able to reach consensus agreement on a number of oral medications that are primarily renally cleared. C1 [Hanlon, Joseph T.] Univ Pittsburgh, Dept Geriatr Med, Div Geriatr Med, Pittsburgh, PA 15213 USA. [Weisbord, Steven D.; Fried, Linda F.] Univ Pittsburgh, Div Renal Electrolyte, Pittsburgh, PA 15213 USA. [Good, C. Bernie; Fine, Michael J.] Univ Pittsburgh, Div Gen Internal Med, Dept Med, Pittsburgh, PA 15213 USA. [Handler, Steven M.] Univ Pittsburgh, Sch Med, Dept Biomed Informat, Pittsburgh, PA 15213 USA. [Hanlon, Joseph T.; Aspinall, Sherrie L.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15213 USA. [Stone, Roslyn A.; Rossi, Michelle I.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15213 USA. [Hanlon, Joseph T.; Rossi, Michelle I.; Handler, Steven M.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. [Hanlon, Joseph T.; Aspinall, Sherrie L.; Weisbord, Steven D.; Fried, Linda F.; Good, C. Bernie; Fine, Michael J.; Stone, Roslyn A.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Aspinall, Sherrie L.; Semla, Todd P.; Good, C. Bernie] Vet Affairs Ctr Medicat Safety, Hines, IL USA. [Pugh, Mary Jo V.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Pugh, Mary Jo V.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. RP Hanlon, JT (reprint author), Univ Pittsburgh, Dept Geriatr Med, Div Geriatr Med, Kaufman Med Bldg,Suite 500,3471 5th Ave, Pittsburgh, PA 15213 USA. EM jth14@pitt.edu OI Handler, Steven/0000-0002-3940-3224; Pugh, Mary Jo/0000-0003-4196-7763 FU National Institutes of Health (NIH) [1 KL2 RR024154-01, 5T32AG021885, P30AG024827, R01AG027017]; Education and Clinical Center Pilot; Pittsburgh Veterans Affairs (VA) Geriatric Research [IIR-06-062] FX Sponsor's Role: None. NR 37 TC 39 Z9 39 U1 1 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC 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 FEB PY 2009 VL 57 IS 2 BP 335 EP 340 DI 10.1111/j.1532-5415.2008.02098.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 399WE UT WOS:000262829200022 PM 19170784 ER PT J AU Bambery, M Porcerelli, JH Ablon, JS AF Bambery, Michael Porcerelli, John H. Ablon, J. Stuart TI PROTOTYPES OF PSYCHODYNAMIC AND CBT PSYCHOTHERAPY WITH ADOLESCENTS: DEVELOPMENT AND APPLICATIONS FOR TRAINING SO JOURNAL OF THE AMERICAN PSYCHOANALYTIC ASSOCIATION LA English DT Meeting Abstract ID ABLON; JONES C1 [Bambery, Michael] Univ Detroit Mercy, Detroit, MI 48221 USA. [Porcerelli, John H.] Wayne State Univ, Sch Med, Detroit, MI 48202 USA. [Ablon, J. Stuart] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ablon, J. Stuart] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. EM mbambery@msn.com NR 13 TC 1 Z9 1 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0003-0651 J9 J AM PSYCHOANAL ASS JI J. Am. Psychoanal. Assoc. PD FEB PY 2009 VL 57 IS 1 BP 175 EP 181 PG 7 WC Psychiatry; Psychology, Psychoanalysis SC Psychiatry; Psychology GA 427DM UT WOS:000264760000009 PM 19270250 ER PT J AU Thibault, H Gomez, L Donal, E Augeul, L Scherrer-Crosbie, M Ovize, M Derumeaux, G AF Thibault, Helene Gomez, Ludovic Donal, Erwan Augeul, Lionel Scherrer-Crosbie, Marielle Ovize, Michel Derumeaux, Genevieve TI Regional Myocardial Function After Myocardial Infarction in Mice: A Follow-Up Study by Strain Rate Imaging SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article DE Echocardiography; Myocardial infarction; Remodeling; Murine model ID MYOCYTE CONTRACTILE FUNCTION; DOPPLER-ECHOCARDIOGRAPHY; NONINFARCTED MYOCARDIUM; TRANSMURALITY; DYSFUNCTION; REPERFUSION; VALIDATION; HEART; MOUSE; ISCHEMIA AB Background: New therapeutic strategies aim to reduce the extent of myocardial infarction (MI) to decrease long-term left ventricular (LV) remodeling. These innovations are often developed on murine models of MI and have led to the need for a sensitive tool allowing follow-up. The aim of this study was to investigate by strain rate (SR) imaging early and long-term alteration in regional LV function occurring after MI in mice. Methods: Echocardiography was serially performed during a 4-month follow-up period in 3 groups of C57BL6 male mice: 7 normal, 5 sham operated, and 27 with left coronary artery ligation (the MI group). In addition to conventional measurements, SR was obtained from short-axis views in the anterior wall and posterior wall (PW). Triphenyltetrazolium chloride staining allowed the localization and measurement of the transmural extent of MI. A transmural MI was defined as an extension > 75% of the wall thickness. Results: In the MI group, LV ejection fractions significantly decreased, while LV dimensions and PW thicknesses increased from baseline to 4 months. On day 3, SR could differentiate transmural from nontransmural (1 +/- 1 vs 10 +/- 1 s(-1); P < .05) and noninfarcted myocardium (25 +/- 1 s(-1)). SR values did not significantly change between day 3 and month 4 and could still differentiate those segments at month 4. Wall thickening was not able to differentiate transmural from nontransmural infarcted segments at day 3 (16 +/- 3% vs 21 +/- 3%; P = NS) or at month 4. Conclusion: In this murine model of MI, SR was able to predict the transmural extent of MI as early as 3 days after MI, then remained stable and still differentiated them at 4 months. (J Am Soc Echocardiogr 2009; 22: 198-205.) C1 [Derumeaux, Genevieve] Univ Lyon 1, Fac Med Lyon Nord, INSERM, U886, F-69373 Lyon 8, France. [Thibault, Helene; Ovize, Michel; Derumeaux, Genevieve] Hosp Civils Lyon, Hop Louis Pradel, Lyon, France. [Donal, Erwan] Hop Pontchaillou, Rennes, France. [Scherrer-Crosbie, Marielle] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Derumeaux, G (reprint author), Univ Lyon 1, Fac Med Lyon Nord, INSERM, U886, Ave Rockefeller, F-69373 Lyon 8, France. EM genevieve.derumeaux@chu-lyon.fr FU Academie Nationale de Medecine, Paris, France FX Dr Thibault was a recipient of a grant from Academie Nationale de Medecine, Paris, France. NR 43 TC 19 Z9 22 U1 0 U2 0 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 FEB PY 2009 VL 22 IS 2 BP 198 EP 205 DI 10.1016/j.echo.2008.11.019 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 401YH UT WOS:000262979500013 PM 19121566 ER PT J AU Isakova, T Gutierrez, OM Chang, YC Shah, A Tamez, H Smith, K Thadhani, R Wolf, M AF Isakova, Tamara Gutierrez, Orlando M. Chang, Yuchiao Shah, Anand Tamez, Hector Smith, Kelsey Thadhani, Ravi Wolf, Myles TI Phosphorus Binders and Survival on Hemodialysis SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CHRONIC KIDNEY-DISEASE; STAGE RENAL-DISEASE; LEFT-VENTRICULAR HYPERTROPHY; PHOSPHATE BINDER; SERUM PHOSPHORUS; DIALYSIS PATIENTS; MAINTENANCE HEMODIALYSIS; CARDIOVASCULAR RISK; PARATHYROID-HORMONE; MINERAL METABOLISM AB Although hyperphosphatemia is a risk factor for mortality, there are limited data on whether therapy with phosphorus binders affects survival. We analyzed a prospective cohort study of 10,044 incident hemodialysis patients using Cox proportional hazards analyses to compare 1-yr all-cause mortality among patients who were or were not treated with phosphorus binders. We performed intention-to-treat analyses to compare patients who began treatment with phosphorus binders during the first 90 d after initiating hemodialysis (n = 3555) with those who remained untreated during that period (n = 5055). We also performed as-treated analyses that modeled phosphorus binder treatment as a time-dependent exposure. We compared survival in a subcohort of treated (n = 3186) and untreated (n = 3186) patients matched by their baseline serum phosphate levels and propensity score of receiving phosphorus binders during the first 90 d. One-year mortality was 191 deaths/1000 patient-years at risk. Treatment with phosphorus binders was independently associated with decreased mortality compared with no treatment in the intention-to-treat, as-treated, and matched analyses. The results were independent of baseline and follow-up serum phosphate levels and persisted in analyses that excluded deaths during the first 90 d of hemodialysis. In summary, treatment with phosphorus binders is independently associated with improved survival among incident hemodialysis patients. Although confirmatory studies are needed in the dialysis setting, future placebo-controlled, randomized trials of phosphorus binders might focus on predialysis patients with chronic kidney disease and normal serum phosphate levels. C1 [Gutierrez, Orlando M.; Smith, Kelsey; Wolf, Myles] Univ Miami, Miller Sch Med, Div Nephrol & Hypertens, Miami, FL 33136 USA. [Isakova, Tamara; Shah, Anand; Tamez, Hector; Thadhani, Ravi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Renal Unit, Boston, MA USA. [Chang, Yuchiao] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. RP Wolf, M (reprint author), Univ Miami, Miller Sch Med, Div Nephrol & Hypertens, 1120 NW 14th St, Miami, FL 33136 USA. EM mwolf2@med.miami.edu FU Abbott Laboratories [R21 DK071674]; National Institutes of Health [K30RR02229207, K23RR017376, R01DK076116]; American Kidney Fund Clinical Scientist in Nephrology; Center for D-receptor Activation Research (CeDAR) FX The overall ArMORR Study was Supported by a seed grant from Abbott Laboratories and grant R21 DK071674 (R.T.) from the National Institutes of Health. This Study was supported by grants from the American Kidney Fund Clinical Scientist in Nephrology Fellowship (T.I., and O.M.G.); the Center for D-receptor Activation Research (CeDAR) at the Massachusetts General Hospital; and grants K30RR02229207, K23RR017376 (M.W.), and R01DK076116 (M.W.) from the National Institutes of Health. NR 40 TC 184 Z9 192 U1 0 U2 5 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD FEB PY 2009 VL 20 IS 2 BP 388 EP 396 DI 10.1681/ASN.2008060609 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 406HE UT WOS:000263284800021 PM 19092121 ER PT J AU Rim, CS Kim, P Yun, SH AF Rim, Cheon-Seog Kim, Philhan Yun, Seok-Hyun TI Design of an Endoscope Objective Lens with a High Numerical Aperture and a Minimally-Invasive Outer Diameter (vol 51, pg 52, 2007) SO JOURNAL OF THE KOREAN PHYSICAL SOCIETY LA English DT Correction C1 [Rim, Cheon-Seog] Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Rim, CS (reprint author), Harvard Univ, Sch Med, 50 Blossom St,BAR822, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU KOREAN PHYSICAL SOC PI SEOUL PA 635-4, YUKSAM-DONG, KANGNAM-KU, SEOUL 135-703, SOUTH KOREA SN 0374-4884 J9 J KOREAN PHYS SOC JI J. Korean Phys. Soc. PD FEB PY 2009 VL 54 IS 2 BP 812 EP 812 PG 1 WC Physics, Multidisciplinary SC Physics GA 407NJ UT WOS:000263371300048 ER PT J AU Burstein, HJ AF Burstein, Harold J. TI Personalized Medicine and Breast Cancer Care 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 02115 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 0 TC 1 Z9 1 U1 0 U2 0 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PINE DR, SUDBURY, MA 01776 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD FEB PY 2009 VL 7 IS 2 BP 109 EP 109 PG 1 WC Oncology SC Oncology GA 499ZA UT WOS:000270264400003 PM 19241643 ER PT J AU Svahn, TH Niland, JC Carlson, RW Hughes, ME Ottesen, RA Theriault, RL Edge, SB Schott, AF Bookman, MA Weeks, JC AF Svahn, Tiffany H. Niland, Joyce C. Carlson, Robert W. Hughes, Melissa E. Ottesen, Rebecca A. Theriault, Richard L. Edge, Stephen B. Schott, Anne F. Bookman, Michael A. Weeks, Jane C. TI Predictors and Temporal Trends of Adjuvant Aromatase Inhibitor Use in Breast Cancer SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article DE Aromatase inhibitors; tamoxifen; breast neoplasms; adjuvant therapy ID ONCOLOGY-TECHNOLOGY-ASSESSMENT; POSTMENOPAUSAL WOMEN; RANDOMIZED-TRIAL; TAMOXIFEN THERAPY; ATAC ARIMIDEX; ANASTROZOLE; COMBINATION; RECURRENCE AB After the first report of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial, adjuvant aromatase inhibitor use increased rapidly among National Comprehensive Cancer Network member institutions. Increased aromatase inhibitor use was associated with older age, vascular disease, overexpression of human epidermal growth factor receptor 2 (HER2), or more advanced stage, and substantial variation was seen among institutions. This article examines adjuvant endocrine therapy in postmenopausal women after the first report of the trial, identifies temporal relationships in aromatase inhibitor use, and examines characteristics associated with choice of endocrine therapy among 4044 postmenopausal patients with hormone receptor-positive nonmetastatic breast cancer presenting from July 1997 to December 2004. Multivariable logistic regression analysis examined temporal associations and characteristics associated with aromatase inhibitor use. Time-trend analysis showed increased aromatase inhibitor and decreased tamoxifen use after release of ATAC results (P<.0001). In multivariable regression analysis, institution (P<.0001), vascular disease (P<.0001), age (P=.0002), stage (P=.0002), and HER2 status (P=.0009) independently predicted aromatase inhibitor use. Institutional rates of use ranged from 15% to 66%. Adjuvant aromatase inhibitor use increased after the first report of ATAC, with this increase associated with older age, vascular disease, overexpression of HER2, or more advanced stage. Substantial variation was seen among institutions. (JNCCN 2009;7:115-121) C1 [Svahn, Tiffany H.; Carlson, Robert W.] Stanford Univ, Div Oncol, Stanford, CA 94305 USA. [Niland, Joyce C.; Ottesen, Rebecca A.] City Hope Natl Med Ctr, Dept Biostat, Duarte, CA 91010 USA. [Hughes, Melissa E.; Weeks, Jane C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Theriault, Richard L.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX 77030 USA. [Edge, Stephen B.] Roswell Pk Canc Inst, Dept Surg, Buffalo, NY 14263 USA. [Schott, Anne F.] Univ Michigan, Div Hematol Oncol, Ann Arbor, MI 48109 USA. [Bookman, Michael A.] Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA. RP Carlson, RW (reprint author), Stanford Univ, Div Oncol, 875 Blake Wilbur Dr, Stanford, CA 94305 USA. EM rcarlson@stanford.edu NR 21 TC 11 Z9 11 U1 2 U2 2 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PINE DR, SUDBURY, MA 01776 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD FEB PY 2009 VL 7 IS 2 BP 115 EP 121 PG 7 WC Oncology SC Oncology GA 499ZA UT WOS:000270264400004 PM 19200415 ER PT J AU Carlson, RW Allred, DC Anderson, BO Burstein, HJ Carter, WB Edge, SB Erban, JK Farrar, WB Goldstein, LJ Gradishar, WJ Hayes, DF Hudis, CA Jahanzeb, M Kiel, K Ljung, BM Marcom, PK Mayer, IA McCormick, B Nabell, LM Pierce, LJ Reed, EC Smith, ML Somlo, G Theriault, RL Topham, NS Ward, JH Winer, EP Wolff, AC AF Carlson, Robert W. Allred, D. Craig Anderson, Benjamin O. Burstein, Harold J. Carter, W. Bradford Edge, Stephen B. Erban, John K. Farrar, William B. Goldstein, Lori J. Gradishar, William J. Hayes, Daniel F. Hudis, Clifford A. Jahanzeb, Mohammad Kiel, Krystyna Ljung, Britt-Marie Marcom, P. Kelly Mayer, Ingrid A. McCormick, Beryl Nabell, Lisle M. Pierce, Lori J. Reed, Elizabeth C. Smith, Mary Lou Somlo, George Theriault, Richard L. Topham, Neal S. Ward, John H. Winer, Eric P. Wolff, Antonio C. TI Breast Cancer SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review ID SURGICAL ADJUVANT BREAST; RANDOMIZED CONTROLLED-TRIAL; PHASE-III TRIAL; PLACEBO-CONTROLLED TRIAL; GROWTH-FACTOR RECEPTOR; OF-CLINICAL-ONCOLOGY; SENTINEL-NODE BIOPSY; FIRST-LINE THERAPY; CARCINOMA IN-SITU; DOXORUBICIN PLUS CYCLOPHOSPHAMIDE C1 [Carlson, Robert W.] Stanford Comprehens Canc Ctr, Stanford, CA USA. [Allred, D. Craig] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Erban, John K.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Farrar, William B.] Ohio State Univ, Arthur G James Canc Hosp, Columbus, OH 43210 USA. [Farrar, William B.] Ohio State Univ, Richard J Solove Res Inst, Columbus, OH 43210 USA. [Gradishar, William J.; Kiel, Krystyna] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Hayes, Daniel F.; Pierce, Lori J.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Jahanzeb, Mohammad] Univ Tennessee, Inst Canc, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Nabell, Lisle M.] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA. [Reed, Elizabeth C.] Univ Nebraska Med Ctr, Eppley Canc Ctr, Nebraska Med Ctr, Omaha, NE USA. [Theriault, Richard L.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Ward, John H.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Wolff, Antonio C.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21218 USA. RP Carlson, RW (reprint author), Stanford Comprehens Canc Ctr, Stanford, CA USA. OI Wolff, Antonio/0000-0003-3734-1063 NR 296 TC 225 Z9 238 U1 2 U2 15 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD FEB PY 2009 VL 7 IS 2 BP 122 EP + PG 38 WC Oncology SC Oncology GA 499ZA UT WOS:000270264400005 PM 19200416 ER PT J AU Dogra, N Betancourt, JR Park, ER Sprague-Martinez, L AF Dogra, Nisha Betancourt, Joseph R. Park, Elyse R. Sprague-Martinez, Linda TI The Relationship Between Drivers and Policy in the Implementation of Cultural Competency Training in Health Care SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION LA English DT Article DE cultural competence; health care organizations AB In recent years, cultural competence has appeared on the agendas of the medical profession as well as other health care providers. Through semistructured interviews with staff at different types of health care institutions, we explored the motivation for and barriers against the implementation of cultural competence training. The findings show that while some progress has been made, there is still work to be done in making cultural competency an integral part of the organizational fabric of health care. National organizations need to consider their leadership role in helping health care organizations translate broad statements of cultural competence into meaningful action. C1 [Dogra, Nisha] Univ Leicester, Greenwood Inst Child Hlth, Leicester LE3 0QU, Leics, England. [Betancourt, Joseph R.] Dispar Solut Ctr, Boston, MA USA. [Betancourt, Joseph R.] Inst Hlth Policy, Boston, MA USA. [Betancourt, Joseph R.; Park, Elyse R.; Sprague-Martinez, Linda] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Betancourt, Joseph R.; Park, Elyse R.] Harvard Univ, Sch Med, Boston, MA USA. RP Dogra, N (reprint author), Univ Leicester, Greenwood Inst Child Hlth, Westcotes House,Westcotes Dr, Leicester LE3 0QU, Leics, England. EM nd13@le.ac.uk FU Commonwealth Fund FX The support of the Commonwealth Fund through the Fellowship is acknowledged as is the support of the University of Leicester. The contents of the paper cannot be attributed to either institution. NR 14 TC 4 Z9 4 U1 0 U2 2 PU NATL MED ASSOC PI WASHINGON PA 1012 10TH ST, N W, WASHINGON, DC 20001 USA SN 0027-9684 J9 J NATL MED ASSOC JI J. Natl. Med. Assoc. PD FEB PY 2009 VL 101 IS 2 BP 127 EP 133 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 425XW UT WOS:000264672300005 PM 19378628 ER PT J AU Katz, RV Green, BL Kressin, NR James, SA Wang, MQ Claudio, C Russell, SL AF Katz, Ralph V. Green, B. Lee Kressin, Nancy R. James, Sherman A. Wang, Min Qi Claudio, Cristina Russell, Stephanie Luise TI Exploring the "Legacy" of the Tuskegee Syphilis Study: A Follow-up Study From the Tuskegee Legacy Project SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION LA English DT Article ID AFRICAN-AMERICANS; BIOMEDICAL-RESEARCH; MEDICAL-RESEARCH; PARTICIPATION; WILLINGNESS; COMMUNITY; TRUST; CARE; RACE AB The purpose of this follow-up 2003 3-City Tuskegee Legacy Project (TLP) Study was to validate or refute our prior findings from the 1999-2000 4 City TLP Study, which found no evidence to support the widely acknowledged "legacy" of the Tuskegee Syphilis Study (TSS), ie, that blacks are reluctant to participate in biomedical studies due to their knowledge of the TSS. The TLP Questionnaire was administered in this random-digit-dial telephone survey to a stratified random sample of 1162 black, white, and Puerto Rican Hispanic adults in 3 different US cities. The findings from this current 3-City TLP Study fail to support the widely acknowledged "legacy" of the TSS, as awareness of the TSS was not statistically associated with the willingness to participate in biomedical studies, These findings, being in complete agreement with our previous findings from our 1999-2000 4-City TLP, validate those prior findings. C1 [Katz, Ralph V.; Russell, Stephanie Luise] NYU, Coll Dent, Dept Epidemiol & Hlth Promot, New York, NY 10003 USA. [Green, B. Lee] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Off Inst Divers, Tampa, FL 33612 USA. [Kressin, Nancy R.] Boston Univ, Sch Med, Healthcare Dispar Res Unit, Gen Internal Med Sect, Boston, MA 02118 USA. [Kressin, Nancy R.] VA Boston Healthcare Syst, Dept Vet Affairs Hlth Serv, Res & Dev Serv, Boston, MA USA. [James, Sherman A.] Duke Univ, Terry Sanford Inst Publ Policy, Durham, NC USA. [James, Sherman A.] Duke Univ, Dept Community & Family Med, Durham, NC USA. [Wang, Min Qi] Univ Maryland, Dept Publ & Community Hlth, Sch Publ Hlth, College Pk, MD 20742 USA. [Claudio, Cristina] Univ Puerto Rico, Dept Community Dent, Sch Dent, San Juan, PR 00936 USA. RP Katz, RV (reprint author), NYU, Coll Dent, Dept Epidemiol & Hlth Promot, 250 Pk Ave S, New York, NY 10003 USA. EM ralph.katz@nyu.edu FU National Institute of Dental and Craniofacial Research/National Institutes of Health [U54 DE 14257]; New York University Oral Cancer Research on Adolescent; Adult Health Promotion Center; Oral Health Disparities Research Center FX This study was supported by National Institute of Dental and Craniofacial Research/National Institutes of Health grant U54 DE 14257, the New York University Oral Cancer Research on Adolescent and Adult Health Promotion Center, an Oral Health Disparities Research Center. NR 36 TC 15 Z9 16 U1 3 U2 6 PU NATL MED ASSOC PI WASHINGON PA 1012 10TH ST, N W, WASHINGON, DC 20001 USA SN 0027-9684 J9 J NATL MED ASSOC JI J. Natl. Med. Assoc. PD FEB PY 2009 VL 101 IS 2 BP 179 EP 183 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 425XW UT WOS:000264672300014 PM 19378637 ER PT J AU Zellos, L Richards, WG Capalbo, L Jaklitsch, MT Chirieac, LR Johnson, BE Bueno, R Sugarbaker, DJ AF Zellos, Lambros Richards, William G. Capalbo, Leah Jaklitsch, Michael T. Chirieac, Lucian R. Johnson, Bruce E. Bueno, Raphael Sugarbaker, David J. TI A phase I study of extrapleural pneumonectomy and intracavitary intraoperative hyperthermic cisplatin with amifostine cytoprotection for malignant pleural mesothelioma SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID CELL LUNG-CANCER; OVARIAN-CANCER; ONCOLOGY-GROUP; CHEMOTHERAPY; TRIAL; RESECTION; PLEURECTOMY/DECORTICATION; GEMCITABINE; RADIATION; SURVIVAL AB Objective: This study was undertaken to determine maximum tolerated dose and toxicity of intraoperative intracavitary hyperthermic cisplatin perfusion with amifostine after extrapleural pneumonectomy for malignant pleural mesothelioma. Methods: Patients with mesothelioma were prospectively enrolled. Those with resectable disease received amifostine and 1-hour hyperthermic cisplatin perfusion of ipsilateral hemithorax and abdomen. Morbidity, recurrence, and survival were recorded. Results: Forty-two patients were enrolled; 29 underwent resection (operative mortality 7%, 2/29). Median age was 57 years. Eighteen were in pathologic stage I or II; 11 were in stage III. Median hospitalization was 15 days. Common complications were atrial fibrillation (66%, 19 patients), deep venous thrombosis (31%, 9 patients), and grade 3+renal toxicity (31%, 9 patients). Feasibility was determined. Renal toxicity was unrelated to cisplatin dose, with no maximum tolerated dose determined. Overall median survival was 17 months (resected 20 months, unresected 10 months). Median survivals were 26 months for patients receiving higher cisplatin doses and 16 months for those receiving lower doses (P = .35). Survival was significantly longer with negative extrapleural nodes (31 vs 14 months, P = .0115) and early stage (all resected 35 months for stage I-II vs 14 months for stage III, P = .0022, epithelial 39 months for stage I-II vs 15 months for stage III, P = .0072). Conclusion: Early stage and negative extrapleural lymph nodes were associated with prolonged survival. Single-dose amifostine did not protect adequately against cisplatin-induced renal toxicity. Additional cytoprotective strategies are needed to allow determination of cisplatin maximum tolerated dose. C1 [Johnson, Bruce E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Johnson, Bruce E.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Zellos, Lambros; Richards, William G.; Capalbo, Leah; Jaklitsch, Michael T.; Chirieac, Lucian R.; Bueno, Raphael; Sugarbaker, David J.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Zellos, Lambros; Richards, William G.; Capalbo, Leah; Jaklitsch, Michael T.; Chirieac, Lucian R.; Bueno, Raphael; Sugarbaker, David J.] Brigham & Womens Hosp, Div Thorac Surg, Boston, MA 02115 USA. RP Zellos, L (reprint author), 75 Francis St, Boston, MA 02115 USA. EM lzellos@partners.org NR 24 TC 25 Z9 25 U1 0 U2 3 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 FEB PY 2009 VL 137 IS 2 BP 453 EP 458 DI 10.1016/j.jtcvs.2008.07.055 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 401DN UT WOS:000262919000029 PM 19185169 ER PT J AU Souza, FF Chen, E AF Souza, Frederico F. Chen, Eleanor TI Mesenchymal Cystic Hamartoma of the Lung MRI and PET/CT Appearance SO JOURNAL OF THORACIC IMAGING LA English DT Article DE MRI; PET/CT; cystic hamartoma; lung; diaphragm AB We report the magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT) findings of it patient who presented with lower thoracic pain, nausea, and vomiting and had a CT scan of the chest in which a well-defined homogeneous mass was identified. Further evaluation with MRI and PET/CT showed a nonenhancing homogeneous paraspinal mass in the left lung base involving the left hemidiaphragm. The mass showed lack of enhancement on MRI and wits photopenic on PET/CT. Video-assisted thoracoscopic surgery and resection of the mass was performed and showed it mesenchymal cystic hamartoma invading the left hemidiaphragm. Such a growing hemartoma with pleural and diaphragmatic invasion is very atypical and to our knowledge, has not been previously reported. C1 [Souza, Frederico F.] Dana Farber Canc Inst, Dept Radiol, Boston, MA 02215 USA. [Chen, Eleanor] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Souza, FF (reprint author), Dana Farber Canc Inst, Dept Radiol, 44 Binney St, Boston, MA 02215 USA. EM ffsouza@partners.org NR 10 TC 3 Z9 5 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0883-5993 J9 J THORAC IMAG JI J. Thorac. Imaging PD FEB PY 2009 VL 24 IS 1 BP 52 EP 55 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 414TB UT WOS:000263887000012 PM 19242306 ER PT J AU Wiggins, KL Smith, NL Glazer, NL Rosendaal, FR Heckbert, SR Psaty, BM Rice, KM Lumley, T AF Wiggins, K. L. Smith, N. L. Glazer, N. L. Rosendaal, F. R. Heckbert, S. R. Psaty, B. M. Rice, K. M. Lumley, T. TI ABO genotype and risk of thrombotic events and hemorrhagic stroke SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Article DE ABO genotype; genetic polymorphism; hemorrhagic stroke; ischemic stroke; myocardial infarction; venous thrombosis ID VON-WILLEBRAND-FACTOR; BLOOD-GROUP GENOTYPE; VENOUS THROMBOEMBOLIC DISEASE; FACTOR-VIII LEVELS; MYOCARDIAL-INFARCTION; HAPLOTYPE RECONSTRUCTION; POSTMENOPAUSAL WOMEN; CEREBRAL-HEMORRHAGE; HEART-DISEASE; PLASMA-LEVELS AB Background: The non-O alleles of the ABO genotype have been associated with an increased risk of thrombosis. Risk associated with the specific A(1), A(2) or B alleles is not well defined. Objectives: To examine the association of the ABO genotype with myocardial infarction (MI), ischemic stroke, hemorrhagic stroke, and venous thrombosis (VT). Patients and methods: We used data from two ongoing population-based case-control studies of MI, stroke, and VT. Cases included hypertensive adults and postmenopausal women with incident non-fatal MI (n = 1063), ischemic stroke (n = 469), and hemorrhagic stroke (n = 91), and postmenopausal women with incident non-fatal VT (n = 504). Controls were frequency matched to cases on age, sex, hypertension status, and year of identification. ABO genotypes were determined using single-nucleotide polymorphisms, and subjects were grouped by diplotype according to the presence of O(1), O(2), A(11), A(2) and B alleles. Logistic regression was used to test the association of diplotypes with risk of each outcome. Results: As compared with the O(1)O(1) group, the A(11) allele was associated with an increased risk of VT [odds ratio (OR) 1.79; 95% confidence interval (CI) 1.41-2.26] and MI (OR 1.23; 95% CI 1.05-1.44). The B allele was associated with an increased risk of VT (OR 1.82; 95% CI 1.29-2.57) and ischemic stroke (OR 1.59; 95% CI 1.17-2.17). The AB diplotype category was associated with a 2.7-fold risk of VT (OR 2.70; 95% CI 1.73-4.21). No other associations reached significance. Conclusions: The VT and MI findings are confirmatory, and the ischemic stroke finding with the B allele is a novel finding and needs replication. C1 [Wiggins, K. L.; Glazer, N. L.; Psaty, B. M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA. [Smith, N. L.; Heckbert, S. R.; Psaty, B. M.] Univ Washington, Dept Epidemiol, Seattle, WA 98101 USA. [Smith, N. L.] Seattle Epidemiol Res & Informat Ctr, VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Rosendaal, F. R.] Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands. [Rosendaal, F. R.] Leiden Univ, Med Ctr, Dept Haematol, Leiden, Netherlands. [Psaty, B. M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Rice, K. M.; Lumley, T.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. RP Wiggins, KL (reprint author), Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, 1730 Minor Ave,Suite 1360, Seattle, WA 98101 USA. EM kwiggins@u.washington.edu RI Rice, Kenneth/A-4150-2013 OI Rice, Kenneth/0000-0001-5779-4495 FU National Heart, Lung, and Blood Institute [HL073410, HL068639, HL043201, HL060739, HL074745, HL068986]; National Institutes of Health [AG00956] FX This study was supported by grants HL073410, HL068639, HL043201, HL060739, HL074745 and HL068986 from the National Heart, Lung, and Blood Institute, AG00956 from the National Institutes of Health, and The Leducq Foundation, Paris, France, for the development of Transatlantic Networks of Excellence in Cardiovascular Research. NR 42 TC 45 Z9 46 U1 2 U2 7 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1538-7933 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD FEB PY 2009 VL 7 IS 2 BP 263 EP 269 DI 10.1111/j.1538-7836.2008.03243.x PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 399ED UT WOS:000262782300004 PM 19036074 ER PT J AU Appelbaum, E Kirtane, AJ Clark, A Pride, YB Gelfand, EV Harrigan, CJ Kissinger, KV Manning, WJ Gibson, CM AF Appelbaum, Evan Kirtane, Ajay J. Clark, Alicia Pride, Yuri B. Gelfand, Eli V. Harrigan, Caitlin J. Kissinger, Kraig V. Manning, Warren J. Gibson, C. Michael TI Association of TIMI Myocardial Perfusion Grade and ST-segment resolution with cardiovascular magnetic resonance measures of microvascular obstruction and infarct size following ST-segment elevation myocardial infarction SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Article DE Microvascular obstruction; ST-segment elevation myocardial infarction; TIMI Myocardial Perfusion Grade; Cardiovascular magnetic resonance; Primary percutaneous coronary intervention ID PERCUTANEOUS CORONARY INTERVENTION; VENTRICULAR-FUNCTION; COMPUTED-TOMOGRAPHY; EPICARDIAL FLOW; FRAME COUNT; THROMBOLYSIS; ANGIOPLASTY; DYSFUNCTION; INSIGHTS; FAILURE AB Background Impairment of coronary microvascular perfusion is common among patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI). Cardiovascular magnetic resonance imaging (CMR) can identify microvascular obstruction (MO) following reperfusion of STEMI. We hypothesized that myocardial perfusion, as assessed by the Thrombolysis in Myocardial Infarction (TIMI) Myocardial Perfusion Grade (TMPG), would be associated with a CMR metric of MO in this population. Methods Twenty-one STEMI patients who underwent successful primary PCI were evaluated. Contrast-enhanced CMR was performed within 7 days of presentation and repeated at three months. TIMI Flow Grade (TFG), corrected TIMI Frame Count (cTFC), TMPG, MO, infarct size, and left ventricular ejection fraction (EF) were assessed. Results The median peak creatine phosphokinase (CPK) was 1,775 IU/l (interquartile range 838-3,321). TFG 3 was present following PCI in 19 (90%) patients. CMR evidence of MO was present in 52% following PCI. Abnormal post-PCI TMPG (0/1/2) was present in 48% of subjects and was associated with MO on CMR (90% MO with TMPG 0/1/2 vs. 18% MO with TMPG 3, P < 0.01). Abnormal post-PCI TMPG was also associated with a greater peak CK (median 3,623 IU/l vs. 838 IU/l, P < 0.001) and greater relative infarct size (17.3% vs. 5.2%, P < 0.01). Conclusion Among STEMI patients undergoing primary PCI, post-PCI TMPG correlates with CMR measures of MO and infarct size. The combined use of both metrics in a comprehensive assessment of microvascular integrity and infarct size following STEMI may aid in the evaluation of future therapeutic strategies. C1 [Appelbaum, Evan; Kirtane, Ajay J.; Harrigan, Caitlin J.; Gibson, C. Michael] PERFUSE Core Labs, TIMI Data Coordinating Ctr, Boston, MA 02115 USA. [Clark, Alicia; Pride, Yuri B.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med, Boston, MA 02215 USA. [Appelbaum, Evan; Kirtane, Ajay J.; Gelfand, Eli V.; Kissinger, Kraig V.; Manning, Warren J.; Gibson, C. Michael] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Cardiovasc Med, Boston, MA 02215 USA. RP Appelbaum, E (reprint author), PERFUSE Core Labs, TIMI Data Coordinating Ctr, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM mgibson@perfuse.org FU American College of Cardiology Foundation/ Merck Adult Cardiology Research; Harvard/Massachusetts Institute of Technology/Pfizer; Merck Clinical Investigator Training Program. FX Funding sources: Supported in part by grants from American College of Cardiology Foundation/ Merck Adult Cardiology Research Fellowship Award and the Harvard/Massachusetts Institute of Technology/Pfizer, Merck Clinical Investigator Training Program. NR 27 TC 17 Z9 18 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5305 J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD FEB PY 2009 VL 27 IS 2 BP 123 EP 129 DI 10.1007/s11239-008-0197-y PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 414PJ UT WOS:000263877400001 PM 18246410 ER PT J AU Shipherd, JC Pineles, SL Gradus, JL Resick, PA AF Shipherd, Jillian C. Pineles, Suzanne L. Gradus, Jaimie L. Resick, Patricia A. TI Sexual Harassment in the Marines, Posttraumatic Stress Symptoms, and Perceived Health: Evidence for Sex Differences SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID EXPERIENCES QUESTIONNAIRE SEQ; PHYSICAL HEALTH; WAR VETERANS; PRIMARY-CARE; DISORDER SYMPTOMS; MENTAL-DISORDERS; COMBAT EXPOSURE; DEPRESSION; MILITARY; TRAUMA AB Sex differences and pretrauma functioning have been understudied in examinations of posttraumatic stress symptoms (PSS) and health. this study examined relationships between sexual harassment and assault in the military (MST), PSS, and perceived physical health when accounting for pre-MST PSS, pre-MST health, and current depression. Relationships were examined separately ire 226 female and 91 male Marines endorsing recent MST (past 6 months). MST predicted increased PSS for women and especially men. For men, higher levels of MST were associated with worse perceived physical health, whereas for women, lower levels of MST were associated with worse perceived health. For men with MST, there was some evidence for the association being partially mediated by PSS, but no mediation teas found in women. C1 Boston Univ, Sch Med, Boston, MA 02118 USA. Natl Ctr PTSD Womens Hlth Sci Div, VA Boston Healthcare Syst, Boston, MA USA. RP Shipherd, JC (reprint author), VA Med Ctr, Natl Ctr PTSD, Womens Hlth Sci Div 116B 3, 150 S Huntington Ave, Boston, MA 02130 USA. EM Jillian.Shipherd@va.gov OI Gradus, Jaimie/0000-0003-1459-5327 NR 45 TC 23 Z9 23 U1 7 U2 13 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD FEB PY 2009 VL 22 IS 1 BP 3 EP 10 DI 10.1002/jts.20386 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 414TQ UT WOS:000263888500002 PM 19177491 ER PT J AU Murphy, RA France, H Sunpath, H Gordon, ML Marconi, VC Kuritzkes, DR McIntosh, K AF Murphy, Richard A. France, Holly Sunpath, Henry Gordon, Michelle L. Marconi, Vincent C. Kuritzkes, Daniel R. McIntosh, Kenneth TI Development of Dual-class Antiretroviral Drug Resistance in a Child Coinfected with HIV and Tuberculosis: A Case Report from KwaZulu-Natal, South Africa SO JOURNAL OF TROPICAL PEDIATRICS LA English DT Article ID INFECTED CHILDREN; RITONAVIR; THERAPY AB The treatment of concurrent HIV and tuberculosis (TB) in children < 3 years of age has not been well-studied and is complicated by potential drug-drug interactions. The recommended antiretroviral therapy (ART) in coinfected children in South Africa consists of full-strength ritonavir, lamivudine and stavudine. We report on a child initiated on this regimen, during concurrent TB treatment, who promptly developed an adverse reaction, virologic failure and dual-class antiretroviral drug resistance, compromising subsequent salvage ART. C1 [Murphy, Richard A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Murphy, Richard A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [France, Holly] McCord Hosp, Sinikithemba Clin, Durban, South Africa. [Sunpath, Henry] McCord Hosp, Dept Med, Durban, South Africa. [Gordon, Michelle L.] Univ KwaZulu Natal, Nelson Mandela Sch Med, Dept Virol, Durban, South Africa. [Marconi, Vincent C.] Wilford Hall USAF Med Ctr, Tri Serv AIDS Clin Consortium, Lackland AFB, San Antonio, TX 78236 USA. [Kuritzkes, Daniel R.] Brigham & Womens Hosp, Sect Retroviral Therapeut, Boston, MA 02115 USA. [Kuritzkes, Daniel R.] Harvard Univ, Sch Med, Boston, MA USA. [McIntosh, Kenneth] Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA. RP Murphy, RA (reprint author), Med Sans Frontieres USA, New York, NY USA. EM richard.murphy@newyork.msf.org RI Marconi, Vincent/N-3210-2014 OI Marconi, Vincent/0000-0001-8409-4689 FU NCRR NIH HHS [K24 RR16482]; NIAID NIH HHS [P30 AI60354] NR 9 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0142-6338 J9 J TROP PEDIATRICS JI J. Trop. Pediatr. PD FEB PY 2009 VL 55 IS 1 BP 60 EP 62 DI 10.1093/tropej/fmn074 PG 3 WC Pediatrics; Tropical Medicine SC Pediatrics; Tropical Medicine GA 425TG UT WOS:000264659400015 PM 18786985 ER PT J AU Richie, JP AF Richie, Jerome P. TI Diagnostic Accuracy of Transitional Cell Carcinoma on Multidetector Computerized Tomography Urography in Patients With Gross Hematuria COMMENT SO JOURNAL OF UROLOGY LA English DT Editorial Material C1 Brigham & Womens Hosp, Div Urol, Boston, MA 02115 USA. RP Richie, JP (reprint author), Brigham & Womens Hosp, Div Urol, 75 Francis St, Boston, MA 02115 USA. NR 0 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 0022-5347 J9 J UROLOGY JI J. Urol. PD FEB PY 2009 VL 181 IS 2 BP 531 EP 531 DI 10.1016/j.juro.2008.10.206 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 394BJ UT WOS:000262419900023 ER PT J AU Jung, HS Kalva, SP Greenfield, AJ Waltman, AC Walker, TG Athanasoulis, CA Wicky, ST AF Jung, Hyun S. Kalva, Sanjeeva Prasad Greenfield, Alan J. Waltman, Arthur C. Walker, Thomas G. Athanasoulis, Christos A. Wicky, Stephan T. TI TIPS: Comparison of Shunt Patency and Clinical Outcomes between Bare Stents and Expanded Polytetrafluoroethylene Stent-Grafts SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID INTRAHEPATIC PORTOSYSTEMIC SHUNT; BUDD-CHIARI-SYNDROME; COVERED STENT; MELD SCORE; SURVIVAL; CREATION; MULTICENTER; WALLSTENTS; STENOSIS; MODEL AB PURPOSE: To compare shunt patency and clinical outcomes in two groups of patients who received a transjugular intrahepatic portosystemic shunt (TIPS): one group with bare stents and one with expanded polytetrafluoroethylene stent-grafts. MATERIALS AND METHODS: TIPS were created with bare stents (n = 41) or stent-grafts (n = 40). Overall TIPS patency rates were compared between these two groups, as were clinical outcomes in patients with variceal bleeding and those with ascites. RESULTS: In the bare stent group, primary shunt patency rates were 63%, 48%, and 24% at 3, 6, and 12 months, respectively. Secondary patency rates were 75% and 62% at 3 and 6 months, respectively. In the stent-graft group, primary patency rates were 94%, 67%, and 38% at 3, 6, and 12 months, respectively. Secondary patency rates were 100% and 92% at 3 and 6 months, respectively. All stent patency rates were higher in the stent-graft group, but only the difference in the 3-month primary patency rate (63% vs 94%) reached significance (P = .03). In patients with variceal bleeding as well as those with ascites, early and overall clinical success rates were higher in the stent-graft group, but only the 3-month and 12-month differences were statistically significant. CONCLUSIONS: TIPS created with stent-grafts had better 3-month primary patency rates and better 3-month and 12-month clinical success rates compared with those created with bare stents. C1 [Kalva, Sanjeeva Prasad] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Kalva, SP (reprint author), Massachusetts Gen Hosp, Dept Radiol, GRB 290,55 Fruit St, Boston, MA 02114 USA. EM skalva@partners.org NR 25 TC 32 Z9 44 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 FEB PY 2009 VL 20 IS 2 BP 180 EP 185 DI 10.1016/j.jvir.2008.11.005 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 403HZ UT WOS:000263075000005 PM 19097918 ER PT J AU Kang, JL Chung, TK Lancaster, RT LaMuraglia, GM Conrad, MF Cambria, RP AF Kang, Jeanwan L. Chung, Thomas K. Lancaster, Robert T. LaMuraglia, Glenn M. Conrad, Mark F. Cambria, Richard P. TI Outcomes after carotid endarterectomy: Is there a high-risk population? A National Surgical Quality Improvement Program report SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID RANDOMIZED-TRIAL; ADVERSE OUTCOMES; ARTERY STENOSIS; SURGERY TRIAL; UNITED-STATES; DEATH RATES; ANGIOPLASTY; STROKE; OCTOGENARIANS; CARE AB Objective: Carotid endarterectomy (CEA) is the standard treatment of carotid stenosis for symptomatic and asymptomatic patients. Carotid angioplasty and stenting (CAS), however, has been proposed as alternative therapy for patients deemed at high-risk for CEA. This study examined 30-day adjudicated outcomes in a contemporary series of CEAs and assessed the validity of criteria used to define a potential high-risk patient population for CEA. Methods: Patients undergoing isolated CEA in private sector hospitals between Jan 1, 2005, and Dec 31, 2006, were identified using the prospectively gathered National Surgical Quality Improvement Program database. The primary study end points were 30-day stroke and death rates. Demographic, preoperative, and intraoperative variables were examined using multivariate models to identify variables associated with the study end points. Variables used to define systemic "high-risk" patients in the Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) study (active cardiac disease, severe chronic obstructive pulmonary disease, and octogenarian status) were examined individually and in composite fashion for association with study endpoints. Results. Of the 3949 CEAs performed, 59% were in men, 30% were "high-risk" (19% age >80), and 43% had a previous neurologic event. The 30-day stroke rate was 1.6%, the death rate was 0.7%, and combined stroke/death rate was 2.2%. Multivariate analysis showed that intraoperative transfusion (odds ratio [OR], 5.95; 95% confidence interval [CI], 1.71-20.66; P=.005), prior majorstroke (OR, 5.34; 95% CI, 2.96-9.64; P<.0001), shorter height (surrogate for small artery size; OF, 1.09; 95% CI, 1.02-1.16; P=.010), and increased anesthesia time (OF, 1.02; 95% CI, 1.00-1.03; P=.008) were predictive of stroke. Critical limb ischemia (OR, 12.72; 95% CI, 3.49-46.40; P<.0001) and poor functional status (OR, 7.05; 95% CI, 2.95-16.82; P<.0001) were independent correlates of death. Systemic high-risk variables, either combined or individually, did not increase risk of stroke or death on multivariate analysis. Conclusion: CEA is associated with favorable 30-day outcomes across a spectrum of patient comorbidity features including octogenarian status. Anatomic and technical features are the important predictors of perioperative stroke, whereas critical limb ischemia and poor functional status are important predictors of death for patients undergoing CEA. These data refute the concept that CAS is preferred for patients deemed high-risk by virtue of systemic comorbidities. (J Vast: Surg 2009;49:331-9.) C1 [Kang, Jeanwan L.; Chung, Thomas K.; LaMuraglia, Glenn M.; Conrad, Mark F.; Cambria, Richard P.] Massachusetts Gen Hosp, Dept Surg, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. [Lancaster, Robert T.] Massachusetts Gen Hosp, Dept Surg, Ernnest Amory Codman Ctr Clin Effectiveness Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Kang, JL (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Vasc & Endovasc Surg, 55 Fruit St,GRB-425, Boston, MA 02114 USA. EM jkang1@partners.org OI Chung, Thomas/0000-0001-6148-1184 NR 44 TC 34 Z9 35 U1 2 U2 2 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 FEB PY 2009 VL 49 IS 2 BP 331 EP 338 DI 10.1016/j.jvs.2008.09.018 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 407ND UT WOS:000263370700013 PM 19216952 ER PT J AU Kwolek, CJ Clagett, GP AF Kwolek, Christopher J. Clagett, G. Patrick TI Changing demographics in patients with vascular disease SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID RACIAL DISPARITIES; HEALTH-CARE; SURGERY AB The United States population with vascular disease has changed dramatically during the past 2 decades, with large increases in the proportion of Hispanic, African American, and other minority patients. Not only has the number of these patients increased, but the types and distribution of vascular disease in minority populations is also different from that encountered in non-Hispanic whites. Although genetic makeup accounts for some of these differences, access to vascular care is also an important determinant, with many minority patients presenting late in the course of the disease process. These factors create significant challenges for the vascular specialists caring for these patients. The vascular surgery workforce is composed of >90% white men and does not currently represent the changes in the population of patients with vascular disease. In addition, women with vascular disease comprise up to 50% of many vascular surgery practices. In many parts of the country, Hispanics and African Americans outnumber non-Hispanic whites with vascular disease. Yet, women and minority physicians are still significantly under-represented in the field of vascular surgery. This year's E. Stanley Crawford Critical Issues Forum at the Society for Vascular Surgery meeting addressed the disconnect between the vascular surgery workforce and the patients whom we serve. This article reviews the projected demographic changes in the population of the United States, which supports the need for training a vascular surgery workforce that is more diverse. This article also reviews the current status of minority and female representation in medical schools, surgical training programs, and vascular surgery programs in the United States. (J Vasc Surg 2009;49:528-31.) C1 [Kwolek, Christopher J.] Massachusetts Gen Hosp, Vasc Ctr, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. [Clagett, G. Patrick] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. RP Kwolek, CJ (reprint author), Massachusetts Gen Hosp, Vasc Ctr, Div Vasc & Endovasc Surg, 15 Parkman St,WAC 442, Boston, MA 02114 USA. EM ckwolek@partners.org NR 13 TC 4 Z9 4 U1 0 U2 1 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 FEB PY 2009 VL 49 IS 2 BP 528 EP 531 DI 10.1016/j.jvs.2008.11.075 PG 4 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 407ND UT WOS:000263370700051 PM 19216973 ER PT J AU Siddappa, NB Song, R Kramer, VG Chenine, AL Velu, V Ong, H Rasmussen, RA Grisson, RD Wood, C Zhang, H Kankasa, C Amara, RR Else, JG Novembre, FJ Montefiori, DC Ruprecht, RM AF Siddappa, Nagadenahalli B. Song, Ruijiang Kramer, Victor G. Chenine, Agnes-Laurence Velu, Vijayakumar Ong, Helena Rasmussen, Robert A. Grisson, Ricky D. Wood, Charles Zhang, Hong Kankasa, Chipeppo Amara, Rama Rao Else, James G. Novembre, Francis J. Montefiori, David C. Ruprecht, Ruth M. TI Neutralization-Sensitive R5-Tropic Simian-Human Immunodeficiency Virus SHIV-2873Nip, Which Carries env Isolated from an Infant with a Recent HIV Clade C Infection SO JOURNAL OF VIROLOGY LA English DT Article ID T-CELL DEPLETION; HUMAN MONOCLONAL-ANTIBODY; PROXIMAL EXTERNAL REGION; PIG-TAILED MACAQUES; TYPE-1 SUBTYPE-C; RHESUS MACAQUES; DISEASE PROGRESSION; IN-VITRO; GASTROINTESTINAL-TRACT; PERSISTENT INFECTION AB Human immunodeficiency virus clade C (HIV-C) accounts for >56% of all HIV infections worldwide. To investigate vaccine safety and efficacy in nonhuman primates, a pathogenic, R5-tropic, neutralization-sensitive simian-human immunodeficiency virus (SHIV) carrying HIV-C env would be desirable. We have constructed SHIV-2873Ni, an R5-tropic SHIV carrying a primary pediatric HIV-C env gene isolated from a 2-month-old Zambian infant, who died within 1 year of birth. SHIV-2873Ni was constructed using SHIV-1157ipd3N4 ( R. J. Song, A. L. Chenine, R. A. Rasmussen, C. R. Ruprecht, S. Mirshahidi, R. D. Grisson, W. Xu, J. B. Whitney, L. M. Goins, H. Ong, P. L. Li, E. Shai-Kobiler, T. Wang, C. M. McCann, H. Zhang, C. Wood, C. Kankasa, W. E. Secor, H. M. McClure, E. Strobert, J. G. Else, and R. M. Ruprecht. J. Virol. 80: 8729-8738, 2006) as the backbone, since the latter contains additional NF-kappa B sites in the long terminal repeats to enhance viral replicative capacity. The parental virus, SHIV-2873Ni, was serially passaged through five rhesus monkeys (RMs); SHIV-2873Nip, the resulting passaged virus, was reisolated from the fourth recipient about 1 year postinoculation. SHIV-2873Nip was replication competent in RM peripheral blood mononuclear cells of all random donors tested and was exclusively R5 tropic, and its env gene clustered with HIV-C by phylogenetic analysis; its high sensitivity to neutralization led to classification as a tier 1 virus. Indian-origin RMs were inoculated by different mucosal routes, resulting in high peak viral RNA loads. Signs of virus-induced disease include depletion of gut CD4(+) T lymphocytes, loss of memory T cells in blood, and thrombocytopenia that resulted in fatal cerebral hemorrhage. SHIV-2873Nip is a highly replication-competent, mucosally transmissible, pathogenic R5-tropic virus that will be useful to study viral pathogenesis and to assess the efficacy of immunogens targeting HIV-C Env. C1 [Siddappa, Nagadenahalli B.; Song, Ruijiang; Kramer, Victor G.; Chenine, Agnes-Laurence; Ong, Helena; Rasmussen, Robert A.; Grisson, Ricky D.; Ruprecht, Ruth M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Siddappa, Nagadenahalli B.; Song, Ruijiang; Chenine, Agnes-Laurence; Rasmussen, Robert A.; Grisson, Ricky D.; Ruprecht, Ruth M.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Wood, Charles; Zhang, Hong] Univ Nebraska, Nebraska Ctr Virol, Lincoln, NE 68588 USA. [Wood, Charles; Zhang, Hong] Univ Nebraska, Sch Biol Sci, Lincoln, NE 68588 USA. [Kankasa, Chipeppo] Univ Teaching Hosp, Lusaka, Zambia. [Velu, Vijayakumar; Amara, Rama Rao; Novembre, Francis J.] Emory Univ, Yerkes Natl Primate Res Ctr, Div Microbiol & Immunol, Atlanta, GA 30322 USA. [Amara, Rama Rao; Novembre, Francis J.] Emory Univ, Yerkes Natl Primate Res Ctr, Dept Microbiol & Immunol, Atlanta, GA 30322 USA. [Else, James G.] Emory Univ, Yerkes Natl Primate Res Ctr, Div Anim Resources, Atlanta, GA 30322 USA. [Montefiori, David C.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. RP Ruprecht, RM (reprint author), Dana Farber Canc Inst, JFB809,44 Binney St, Boston, MA 02115 USA. EM ruth_ruprecht@dfci.harvard.edu OI Byrareddy, Siddappa /0000-0002-7423-1763; Velu, Vijayakumar/0000-0003-4238-1924 FU National Institutes of Health [R01 DE012937, R01 DE016013, R37 AI034266, HD39620, TW01429, RR15635, P01 AI048240, AI30034]; Yerkes National Primate Research Center [RR-000165] FX This work was supported by National Institutes of Health grants R01 DE012937, R01 DE016013, and R37 AI034266 to R. M. R.; HD39620, TW01429, and RR15635 to C. W.; P01 AI048240 to R. M. R., C. W., R. A. R., and R. D. G.; contract AI30034 to D. C. M.; and base grant RR-000165 to the Yerkes National Primate Research Center. NR 66 TC 27 Z9 27 U1 1 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 FEB 1 PY 2009 VL 83 IS 3 BP 1422 EP 1432 DI 10.1128/JVI.02066-08 PG 11 WC Virology SC Virology GA 392TR UT WOS:000262325600025 PM 19019970 ER PT J AU Van Remmen, H Jones, DP AF Van Remmen, Holly Jones, Dean P. TI Current Thoughts on the Role of Mitochondria and Free Radicals in the Biology of Aging SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Editorial Material C1 [Van Remmen, Holly] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78245 USA. [Van Remmen, Holly] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78245 USA. [Van Remmen, Holly] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Jones, Dean P.] Emory Univ, Dept Med, Atlanta, GA 30322 USA. RP Van Remmen, H (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, 15355 Lambda Dr, San Antonio, TX 78245 USA. EM vanremmen@uthscsa.edu NR 6 TC 31 Z9 31 U1 0 U2 5 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD FEB PY 2009 VL 64 IS 2 BP 171 EP 174 DI 10.1093/gerona/gln058 PG 4 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 419AB UT WOS:000264190400006 PM 19181714 ER PT J AU Miller, RL Lucero, OM Riemondy, KA Baumgartner, BK Brown, D Breton, S Nelson, RD AF Miller, R. Lance Lucero, Olivia M. Riemondy, Kent A. Baumgartner, Brett K. Brown, Dennis Breton, Sylvie Nelson, Raoul D. TI The V-ATPase B1-subunit promoter drives expression of Cre recombinase in intercalated cells of the kidney SO KIDNEY INTERNATIONAL LA English DT Article DE collecting kidney tubules; kidney metabolism; knockout mice; promoter regions; transgenic mice; vascular proton-translocating ATPases ID DUCT-SPECIFIC KNOCKOUT; BLOOD-PRESSURE; CAUSES HYPERTENSION; SODIUM RETENTION; PENDRIN; MICE AB The collecting duct of the kidney is composed of two morphologically and physiologically distinct cell types, principal and intercalated cells. To better understand intercalated cell function we generated a transgenic mouse expressing Cre recombinase under the control of a cell type-specific promoter. We used 7 kb of the ATP6V1B1 5' untranslated region (B1 promoter), a gene found in the intercalated cells of the kidney and the male reproductive tract. We first crossed these B1-Cre transgenic mice with the ROSA26-loxP-stop-loxP-yellow fluorescent protein reporter mice to assess the specificity of Cre expression. Immunohistochemistry and confocal fluorescence microscopy showed that Cre is selectively active in all intercalated cells (type A, type B, and non-A/B cells) within the collecting duct and most cells of the connecting segment. About half of the principal cells of the connecting segment also expressed Cre, a pattern also seen in B1-driven enhanced green fluorescent protein transgenic mice. Cre was found to be active in the male reproductive tract and at a low level in limited non-ATP6V1B1 expressing tissues. The B1-Cre transgenic mice are healthy, breed normally, produce regular sized litters, and transmit the transgene in Mendelian fashion. This new cell-specific Cre expressing mouse should prove useful for the study of intercalated cell physiology and development. C1 [Miller, R. Lance; Lucero, Olivia M.; Riemondy, Kent A.; Baumgartner, Brett K.; Nelson, Raoul D.] Sch Med, Div Nephrol, Dept Pediat, Salt Lake City, UT 84132 USA. [Brown, Dennis; Breton, Sylvie] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Membrane Biol, Boston, MA USA. RP Nelson, RD (reprint author), Sch Med, Div Nephrol, Dept Pediat, Sch Med 2A100,30 North 1900 East, Salt Lake City, UT 84132 USA. EM Raoul.Nelson@hsc.utah.edu FU NIH [DK053990, R01 DK-00-015] FX This work was presented in part in abstract form (J Am Soc Nephrol 16: 340A, 2005). Fluorescent confocal micrographs were obtained using the University of Utah Image Core Facility. This work was, in part, funded by grants from the NIH including DK053990 (RDN) and R01 DK-00-015 (SB, DB, and RDN). NR 11 TC 16 Z9 16 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD FEB PY 2009 VL 75 IS 4 BP 435 EP 439 DI 10.1038/ki.2008.569 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 404IU UT WOS:000263145800015 PM 19052537 ER PT J AU Suggs, JF Kwon, YM Durbhakula, SM Hanson, GR Li, GA AF Suggs, Jeremy F. Kwon, Young-Min Durbhakula, Sridhar M. Hanson, George R. Li, Guoan TI In vivo flexion and kinematics of the knee after TKA: comparison of a conventional and a high flexion cruciate-retaining TKA design SO KNEE SURGERY SPORTS TRAUMATOLOGY ARTHROSCOPY LA English DT Article DE Total knee arthroplasty; High flexion; In vivo kinematics; Biomechanics; Knee ID IMPROVED PERFORMANCE; OPTIMIZING FLEXION; MOBILE-BEARING; FOLLOW-UP; ARTHROPLASTY; MOTION; RANGE AB This study investigated the in vivo 6DOF knee kinematics and tibiofemoral contact location after total knee arthroplasty using a conventional and a high flexion cruciate retaining component (15 NexGen CR, 11 NexGen CR-Flex). Each patient performed a single-leg lunge while being imaged by a dual fluoroscopic imaging system. Data were analyzed at hyperextension, 0A degrees to 90A degrees in 15A degrees intervals, and at maximum flexion. The average maximum weight-bearing flexion for all the CR patients was 110.1A degrees A A +/- A 13.4A degrees, and for all the CR-Flex patients was 108.2A degrees A A +/- A 13.2A degrees. No difference was seen in the maximum flexion achieved by the patients, and the kinematics demonstrated by the groups was similar. However, at high flexion, the tibiofemoral articulating surfaces were more conforming in the CR-Flex design than the CR design, suggesting that the use of the high flexion component improved the tibiofemoral contact environment at high flexion in patients who could achieve high flexion. C1 [Suggs, Jeremy F.; Kwon, Young-Min; Durbhakula, Sridhar M.; Hanson, George R.; Li, Guoan] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg,Bioengn Lab, Boston, MA 02114 USA. [Suggs, Jeremy F.] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Suggs, Jeremy F.] Exponent Inc, Philadelphia, PA USA. RP Li, GA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg,Bioengn Lab, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM jsuggs@exponent.com; gli1@partners.org FU Zimmer Inc. FX This study was supported by a research grant from Zimmer Inc. The guidance of Dr. Harry Rubash and Dr. Andrew Freiberg and the technical assistance of Elizabeth Desouza and Angela Moynihan were greatly appreciated. The experiments performed in the course of this study comply with the laws of the United States. NR 25 TC 24 Z9 27 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0942-2056 J9 KNEE SURG SPORT TR A JI Knee Surg. Sports Traumatol. Arthrosc. PD FEB PY 2009 VL 17 IS 2 BP 150 EP 156 DI 10.1007/s00167-008-0637-4 PG 7 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 399FL UT WOS:000262785700007 PM 18839144 ER PT J AU Montalescot, G Wiviott, SD Brounwald, E Murphy, SA Gibson, CM McCabe, CH Antman, EM AF Montalescot, Gilles Wiviott, Stephen D. Brounwald, Eugene Murphy, Sabina A. Gibson, C. Michael McCabe, Carolyn H. Antman, Elliott M. CA TRITON-TIMI 38 Investigators TI Prasugrel compared with clopidogrel in patients undergoing percutaneous coronary intervention for ST-elevation myocardial infarction (TRITON-TIMI 38): double-blind, randomised controlled trial SO LANCET LA English DT Article ID ORAL ANTIPLATELET THERAPY; DRUG-ELUTING STENTS; PLATELET INHIBITION; UNCOATED STENTS; ASPIRIN; ANGIOPLASTY; TICLOPIDINE; ABCIXIMAB; DISEASE; SAFETY AB Background Mechanical reperfusion with stenting for ST-elevation myocardial infarction (STEMI) is supported by dual antiplatelet treatment with aspirin and clopidogrel. Prasugrel, a potent and rapid-acting thienopyridine, is a potential alternative to clopidogrel. We aimed to assess prasugrel versus clopidogrel in patients undergoing percutaneous coronary intervention (PCI) for STEMI. Methods We under-took a double-blind, randomised controlled trial in 707 sites in 30 countries. 3534 participants presenting with STEMI were randomly assigned by interactive voice response system either prasugrel (60 mg loading, 10 mg maintenance [n=1769]) or clopidogrel (300 mg loading, 75 mg maintenance [n=1765]) and were unaware of the allocation. The primary endpoint was cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke. Efficacy analyses were by intention to treat. Follow-up was to 15 months, with secondary analyses at 30 days. This trial is registered with ClinicalTrials.gov, number NCT00097591. Findings At 30 days, 115 (6.5%) individuals assigned prasugrel had met the primary endpoint compared with 166 (9.5%) allocated clopidogrel (hazard ratio 0.68 [95% Cl 0.54-0.87]; p=0.0017). This effect continued to 15 months (174 [10.0%] vs 216 [12.4%]; 0.79 [0.65-0.97]; p=0.0221). The key secondary endpoint of cardiovascular death, myocardial infarction, or urgent target vessel revascularisation was also significantly reduced with prasugrel at 30 days (0.75 [0.59-0.96]; p=0.0205) and 15 months (0.79 [0.65-0.97]; p=0.0250), as was stent thrombosis. Treatments did not differ with respect to thrombolysis in myocardial infarction (TIMI) major bleeding unrelated to coronary-artery bypass graft (CABG) surgery at 30 days (p=0.3359) and 15 months (p=0.6451). TIMI life-threatening bleeding and TIMI major or minor bleeding were also similar with the two treatments, and only TIMI major bleeding after CABG surgery was significantly increased with prasugrel (p=0.0033). Interpretation In patients with STEMI undergoing PCI, prasugrel is more effective than clopidogrel for prevention of ischaemic events, without an apparent excess in bleeding. C1 [Montalescot, Gilles] Univ Paris 06, Pitie Salpetriere Hosp, AP HP, INSERM,Inst Cardiol,U856, F-75013 Paris, France. [Wiviott, Stephen D.; Brounwald, Eugene; Murphy, Sabina A.; Gibson, C. Michael; McCabe, Carolyn H.; Antman, Elliott M.] Brigham & Womens Hosp, Dept Med, Div Cardiol, TIMI Study Grp, Boston, MA 02115 USA. RP Montalescot, G (reprint author), Univ Paris 06, Pitie Salpetriere Hosp, AP HP, INSERM,Inst Cardiol,U856, Bur 236,437 Boul Hop, F-75013 Paris, France. EM gilles.montalescot@psl.aphp.fr FU Daiichi Sankyo; Eli Lilly FX The TRITON-TIMI 38 trial is supported by Daiichi Sankyo and Eli Lilly. NR 32 TC 565 Z9 587 U1 2 U2 22 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD FEB-MAR PY 2009 VL 373 IS 9665 BP 723 EP 731 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 412LD UT WOS:000263725400031 PM 19249633 ER PT J AU Schnabel, RB Sullivan, LM Levy, D Pencina, M Massaro, JM D'Agostino, RB Newton-Cheh, C Yamamoto, JF Magnani, JW Tadros, TM Kannel, WB Wang, TJ Ellinor, PT Wolf, PA Vasan, RS Benjamin, EJ AF Schnabel, Renate B. Sullivan, Lisa M. Levy, Daniel Pencina, Michael Massaro, Joseph M. D'Agostino, Ralph B., Sr. Newton-Cheh, Christopher Yamamoto, Jennifer F. Magnani, Jared W. Tadros, Thomas M. Kannel, William B. Wang, Thomas J. Ellinor, Patrick T. Wolf, Philip A. Vasan, Ramachandran S. Benjamin, Emelia J. TI Development of a risk score for atrial fibrillation (Framingham Heart Study): a community-based cohort study SO LANCET LA English DT Article ID OLDER-ADULTS; PHYSICAL-ACTIVITY; PREVENTION; OBESITY; HEALTH; METAANALYSIS; PREVALENCE; PREDICTION; MORTALITY; SURVIVAL AB Background Atrial fibrillation contributes to substantial increases in morbidity and mortality. We aimed to develop a risk score to predict individuals' absolute risk of developing the condition, and to provide a framework for researchers to assess new risk markers. Methods We assessed 4764 participants in the Framingham Heart Study from 8044 examinations (55% women, 45-95 years of age) undertaken between June, 1968, and September, 1987. Thereafter, participants were monitored for the first event of atrial fibrillation for a maximum of 10 years. Multivariable Cox regression identified clinical risk factors associated with development of atrial fibrillation in 10 years. Secondary analyses incorporated routine echocardiographic measurements (5152 participants, 7156 examinations) to reclassify the risk of atrial fibrillation and to assess whether these measurements improved risk prediction. Findings 457 (10%) of the 4764 participants developed atrial fibrillation. Age, sex, body-mass index, systolic blood pressure, treatment for hypertension, PR interval, clinically significant cardiac murmur, and heart failure were associated with atrial fibrillation and incorporated in a risk score (p<0.05, except body-mass index p=0.08), clinical model C statistic 0.78 (95% Cl 0.76-0.80). Risk of atrial fibrillation in 10 years varied with age: more than 15% risk was recorded in 53 (1%) participants younger than 65 years, compared with 783 (27%) older than 65 years. Additional incorporation of echocardiographic measurements to enhance the risk prediction model only slightly improved the C statistic from 0.78 (95% CI 0.75-0.80) to 0.79 (0.77-0.82), p=0.005. Echocardiographic measurements did not improve risk reclassification (p=0.18). Interpretation From clinical factors readily accessible in primary care, our risk score could help to identify risk of atrial fibrillation for individuals in the community; assess technologies or markers for improvement of risk prediction, and target high-risk individuals for preventive measures. C1 [Benjamin, Emelia J.] Boston Univ, Sch Med, Framingham Heart Study, Framingham, MA 01702 USA. [Sullivan, Lisa M.; Pencina, Michael; Massaro, Joseph M.; Yamamoto, Jennifer F.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Kannel, William B.; Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [D'Agostino, Ralph B., Sr.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Evans Mem Dept Med, Boston, MA 02118 USA. [Levy, Daniel; Massaro, Joseph M.; Tadros, Thomas M.; Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Cardiol Sect, Evans Mem Dept Med, Boston, MA 02118 USA. [Levy, Daniel; Kannel, William B.; Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Prevent Med Sect, Evans Mem Dept Med, Boston, MA 02118 USA. [Wolf, Philip A.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Newton-Cheh, Christopher; Wang, Thomas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Newton-Cheh, Christopher] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA USA. [Schnabel, Renate B.] Johannes Gutenberg Univ Mainz, Dept Med 2, Mainz, Germany. RP Benjamin, EJ (reprint author), Boston Univ, Sch Med, Framingham Heart Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA. EM emelia@bu.edu RI Schnabel, Renate/F-6527-2014; OI Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU US National Institutes of Health (NIH)/National Heart, Lung and Blood Institute [N01-HC-25195]; NIH [HL076784, AG028321, AG029451, HL092577, HL080124, HL077477, HL71039, HL093328, R01 NS 17950, 2K24 HL04334]; Deutsche Forschungsgemeinschaft (German Research Foundation) [SCHN 1149/1-1]; Doris Duke Charitable Foundation Clinical Scientist Development Award [HL080025]; Burroughs Wellcome Fund Career Award for Medical Scientists FX Supported by US National Institutes of Health (NIH)/National Heart, Lung and Blood Institute contract N01-HC-25195 and NIH grants HL076784, AG028321. and AG029451 (E)B) HL092577 (EJB, PTE); HL080124, HL077477, HL71039, and HL093328 (RSV); R01 NS 17950 (PAW). NIH Research Career Award 2K24 HL04334 (RSV); Deutsche Forschungsgemeinschaft (German Research Foundation) Research Fellowship SCHN 1149/1-1 (RBS); HL080025, Doris Duke Charitable Foundation Clinical Scientist Development Award, and Burroughs Wellcome Fund Career Award for Medical Scientists (CN-C). NR 35 TC 395 Z9 408 U1 3 U2 25 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD FEB-MAR PY 2009 VL 373 IS 9665 BP 739 EP 745 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 412LD UT WOS:000263725400033 PM 19249635 ER PT J AU Schunemann, HJ Woodhead, M Anzueto, A Buist, S MacNee, W Rabe, KF Heffner, J AF Schuenemann, Holger J. Woodhead, Mark Anzueto, Antonio Buist, Sonia MacNee, William Rabe, Klaus F. Heffner, John TI A vision statement on guideline development for respiratory disease: the example of COPD SO LANCET LA English DT Editorial Material ID RECOMMENDATIONS; STRENGTH; QUALITY C1 [Schuenemann, Holger J.] McMaster Univ, Dept Clin Epidemiol & Biostat, Med Ctr 2C9, CLARITY Res Grp, Hamilton, ON L8N 3Z5, Canada. [Schuenemann, Holger J.] SUNY Buffalo, Dept Med, Buffalo, NY USA. [Woodhead, Mark] Manchester Royal Infirm, Manchester M13 9WL, Lancs, England. [Woodhead, Mark] Univ Manchester, Manchester, Lancs, England. [Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Buist, Sonia; Heffner, John] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [MacNee, William] Queens Med Res Inst, ELEGI Colt Res Labs, UoE MRC, Ctr Inflammat Res, Edinburgh, Midlothian, Scotland. [Rabe, Klaus F.] Leiden Univ, Med Ctr, Dept Pulmonol, Leiden, Netherlands. RP Schunemann, HJ (reprint author), McMaster Univ, Dept Clin Epidemiol & Biostat, Med Ctr 2C9, CLARITY Res Grp, 1200 Main St W, Hamilton, ON L8N 3Z5, Canada. EM schuneh@mcmaster.ca OI MacNee, William/0000-0002-3692-1448 FU NHLBI NIH HHS [1R13HL 90485-01] NR 11 TC 31 Z9 35 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD FEB-MAR PY 2009 VL 373 IS 9665 BP 774 EP 779 DI 10.1016/S0140-6736(08)61347-1 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 412LD UT WOS:000263725400037 PM 18835641 ER PT J AU Hacke, W Furlan, AJ Al-Rawi, Y Davalos, A Fiebach, JB Gruber, F Kaste, M Lipka, LJ Pedraza, S Ringleb, PA Rowley, HA Schneider, D Schwamm, LH Leal, JS Sooehngen, M Teal, PA Wilhelm-Ogunbiyi, K Wintermark, M Warach, S AF Hacke, Werner Furlan, Anthony J. Al-Rawi, Yasir Davalos, Antoni Fiebach, Jochen B. Gruber, Franz Kaste, Markku Lipka, Leslie J. Pedraza, Salvador Ringleb, Peter A. Rowley, Howard A. Schneider, Dietmar Schwamm, Lee H. Leal, Joaquin Serena Soehngen, Mariola Teal, Phil A. Wilhelm-Ogunbiyi, Karin Wintermark, Max Warach, Steven TI Intravenous desmoteplase in patients with acute ischaemic stroke selected by MRI perfusion-diffusion weighted imaging or perfusion CT (DIAS-2): a prospective, randomised, double-blind, placebo-controlled study SO LANCET NEUROLOGY LA English DT Article ID TISSUE-PLASMINOGEN ACTIVATOR; ACUTE HEMISPHERIC STROKE; CONTROLLED-TRIAL; ALTEPLASE; THROMBOLYSIS; ECASS; ATLANTIS; ONSET AB Background Previous studies have suggested that desmoteplase, a novel plasminogen activator, has clinical benefit when given 3-9 h after the onset of the symptoms of stroke in patients with presumptive tissue at risk that is identified by magnetic resonance perfusion imaging (PI) and diffusion-weighted imaging (DWI). Methods In this randomised, placebo-controlled, double-blind, dose-ranging study, patients with acute ischaemic stroke and tissue at risk seen on either MRI or CT imaging were randomly assigned (11:1) to 90 mu g/kg desmoteplase, 125 mu g/kg desmoteplase, or placebo within 3-9 h after the onset of symptoms of stroke. The primary endpoint was clinical response rates at day 90, defined as a composite of improvement in National Institutes of Health stroke scale (NIHSS) score of 8 points or more or an NIHSS score of 1 point or less, a modified Rankin scale score of 0-2 points, and a Barthel index of 75-100. Secondary endpoints included change in lesion volume between baseline and day 30, rates of symptomatic intracranial haemorrhage, and mortality rates. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, NCT00111852. Findings Between June, 2005, and March, 2007, 193 patients were randomised, and 186 patients received treatment: 57 received 90 mu g/kg desmoteplase; 66 received 125 mu g/kg desmoteplase; and 63 received placebo. 158 patients completed the study. The median baseline NIHSS score was 9 (IQR 6-14) points, and 30% (53 of 179) of the patients had a visible occlusion of a vessel at presentation. The core lesion and the mismatch volumes were small (median volumes were 10.6 cm(3) and 52.5 cm(3), respectively). The clinical response rates at day 90 were 47% (27 of 57) for 90 mu g/kg desmoteplase, 36% (24 of 66) for 125 mu g/kg desmoteplase, and 46% (29 of 63) for placebo. The median changes in lesion volume were: 90 mu g/kg desmoteplase 14.0% (0.5 cm(3)); 125 mu g/kg desmoteplase 10.8% (0.3 cm(3)); placebo -10.0% (-0.9 cm(3)). The rates of symptomatic intracranial haemorrhage were 3.5% (2 of 57) for 90 mu g/kg desmoteplase, 4.5% (3 of 66) for 125 mu g/kg desmoteplase, and 0% for placebo. The overall mortality rate was 11% (5% 13 of 571 for 90 mu g/kg desmoteplase; 21% [14 of 66] for 125 mu g/kg desmoteplase; and 6% [4 of 63] for placebo). Interpretation The DIAS-2 study did not show a benefit of desmoteplase given 3-9 h after the onset of stroke. ne high response rate in the placebo group could be explained by the mild strokes recorded (low base-line NIHSS scores, small core lesions, and small mismatch volumes that were associated with no vessel occlusions), which possibly reduced the potential to detect any effect of desmoteplase. C1 [Hacke, Werner; Ringleb, Peter A.] Univ Heidelberg, Dept Neurol, D-69120 Heidelberg, Germany. [Furlan, Anthony J.] Case Western Reserve Univ, Univ Hosp Case Med Ctr, Neurol Inst, Dept Neurol, Cleveland, OH USA. [Al-Rawi, Yasir] MEGA Pharma Solut FZE, Rak, U Arab Emirates. [Davalos, Antoni] Univ Autonoma Barcelona, Hosp Germans Trias & Pujol, Dept Neurosci, Barcelona, Spain. [Fiebach, Jochen B.] Dept Neurol, Berlin, Germany. [Fiebach, Jochen B.] Berlin Neuroimaging Ctr, Berlin, Germany. [Gruber, Franz] Gen Hosp Linz, Dept Neurol & Psychiat, Neuro ICU, Linz, Austria. [Kaste, Markku] Univ Helsinki, Cent Hosp, Dept Neurol, Helsinki, Finland. [Lipka, Leslie J.] Forest Labs Inc, Jersey City, NJ USA. [Leal, Joaquin Serena] Hosp Univ Dr Josep Trueta Girona, Dept Neurol, Girona, Spain. [Pedraza, Salvador] Hosp Univ Dr Josep Trueta Girona, Dept Radiol, Girona, Spain. [Rowley, Howard A.] Univ Wisconsin, Dept Radiol, Madison, WI 53706 USA. [Schneider, Dietmar] Univ Leipzig, Neurol ICU, Leipzig, Germany. [Schneider, Dietmar] Univ Leipzig, Stroke Unit, Leipzig, Germany. [Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Soehngen, Mariola; Wilhelm-Ogunbiyi, Karin] PAION AG, Aachen, Germany. [Ringleb, Peter A.] Univ British Columbia, Vancouver Gen Hosp, Div Neurol, Vancouver, BC V5Z 1M9, Canada. [Wintermark, Max] Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. [Warach, Steven] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. RP Hacke, W (reprint author), Univ Heidelberg, Dept Neurol, Neuenheimer Feld 400, D-69120 Heidelberg, Germany. EM werner.hacke@med.uni-heidelberg.de OI Ringleb, Peter/0000-0002-5473-8671; Fiebach, Jochen B./0000-0002-7936-6958; Schwamm, Lee/0000-0003-0592-9145; Wintermark, Max/0000-0002-6726-3951; Kaste, Markku/0000-0001-6557-6412 FU PAION Deutschland GmbH; Forest Laboratories FX Funding PAION Deutschland GmbH; Forest Laboratories. NR 18 TC 316 Z9 330 U1 0 U2 23 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1474-4422 J9 LANCET NEUROL JI Lancet Neurol. PD FEB PY 2009 VL 8 IS 2 BP 141 EP 150 DI 10.1016/S1474-4422(08)70267-9 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 398SO UT WOS:000262752000012 PM 19097942 ER PT J AU Greenberg, SM Vernooij, MW Cordonnier, C Viswanathan, A Salman, RAS Warach, S Launer, LJ Van Buchem, MA Breteler, MMB AF Greenberg, Steven M. Vernooij, Meike W. Cordonnier, Charlotte Viswanathan, Anand Salman, Rustorn Al-Shahi Warach, Steven Launer, Lenore J. Van Buchem, Mark A. Breteler, Monique M. B. CA Microbleed Study Grp TI Cerebral microbleeds: a guide to detection and interpretation SO LANCET NEUROLOGY LA English DT Review ID T2-ASTERISK-WEIGHTED MR-IMAGES; GRADIENT-ECHO MRI; INTRACEREBRAL HEMORRHAGE; AMYLOID ANGIOPATHY; ASYMPTOMATIC MICROBLEEDS; INTRACRANIAL HEMORRHAGE; CAVERNOUS MALFORMATIONS; HEMOSIDERIN SPOTS; LOBAR HEMORRHAGE; RISK-FACTORS AB Cerebral microbleeds (CMBs) are increasingly recognised neuroimaging findings in individuals with cerebrovascular disease and dementia, and in normal ageing. There has been substantial progress in the understanding of CMBs in recent years, particularly in the development of newer MRI methods for the detection of CMBs and the application of these techniques to population-based samples of elderly people. In this Review, we focus on these recent developments and their effects on two main questions: how CMBs are detected, and how CMBs should be interpreted. The number of CMBs detected depends on MRI characteristics, such as pulse sequence, sequence parameters, spatial resolution, magnetic field strength, and image post-processing, emphasising the importance of taking into account MRI technique in the interpretation of study results. Recent investigations with sensitive MRI techniques have indicated a high prevalence of CMBs in community-dwelling elderly people. We propose a procedural guide for identification of CMBs and suggest possible future approaches for elucidating the role of these common lesions as markers for, and contributors to, small-vessel brain disease. C1 [Greenberg, Steven M.; Viswanathan, Anand] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. [Vernooij, Meike W.] Univ Med Ctr, Erasmus MC, Dept Radiol, Rotterdam, Netherlands. [Vernooij, Meike W.; Breteler, Monique M. B.] Univ Med Ctr, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Cordonnier, Charlotte] Lille Univ Hosp, Dept Neurol, Stroke Dept, Lille, France. [Salman, Rustorn Al-Shahi] Univ Edinburgh, Western Gen Hosp, Div Clin Neurosci, Edinburgh, Midlothian, Scotland. [Warach, Steven] Natl Inst Neurol Disorders & Stroke, Stroke Branch, Bethesda, MD USA. [Launer, Lenore J.] NIA, Lab Epidemiol Biometry & Demog, Bethesda, MD 20892 USA. [Van Buchem, Mark A.] Leiden Univ, Med Ctr, Dept Radiol, Leiden, Netherlands. RP Greenberg, SM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, 175 Cambridge St,Suite 300, Boston, MA 02114 USA. EM sgreenberg@partners.org RI Breteler, Monique /J-5058-2014; Vernooij, Meike/E-4061-2016; Gurol, Edip/J-2279-2014; OI Gurol, Edip/0000-0002-2169-4457; Al-Shahi Salman, Rustam/0000-0002-2108-9222 FU sundry research funds; Massachusetts General Hospital Hemorrhagic Stroke Research Program FX Other members of the Microbleed Study Group who participated in the Cerebral Microbleeds: Detection and Definition conference and contributed valuable discussions and criticisms for this paper were M A Ikram, M J Bos, M M F Poets (Rotterdam, Netherlands), I van der Grond (Leiden, Netherlands), M E Gurol, and R N K Nandigam (Boston, USA). The conference was held by the Microbleed Study Group on April 12, 2008 in Chicago, USA and was supported by sundry research funds provided by individual donors to the Massachusetts General Hospital Hemorrhagic Stroke Research Program without commercial interests or contributions from industry. NR 71 TC 534 Z9 561 U1 6 U2 68 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1474-4422 J9 LANCET NEUROL JI Lancet Neurol. PD FEB PY 2009 VL 8 IS 2 BP 165 EP 174 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 398SO UT WOS:000262752000015 PM 19161908 ER PT J AU Lin, HW Bhattacharyya, N AF Lin, Harrison W. Bhattacharyya, Neil TI Survival Impact of Nodal Disease in Hard Palate and Maxillary Alveolus Cancer SO LARYNGOSCOPE LA English DT Article DE Survival impact; nodal disease; maxillary alveolus cancer ID SQUAMOUS-CELL CARCINOMA; EPIDERMOID CARCINOMA; GINGIVAL; OUTCOMES; TAIWAN AB Objective: Evaluate the impact of primary site stage and cervical metastasis on the survival of patients with squamous cell carcinoma (SCC) of the hard palate or maxillary alveolus. Study Design: Cross-sectional population analysis of prospectively maintained database. Methods: Cases of hard palate and maxillary alveolus SCC from 1988-2004 were extracted from the Surveillance, Epidemiology, and End Results database. Demographic data and extent of disease were extracted for each case, and T-stage, and N-stage were computed. Survival differences according to T-stage and N-stage were determined with the Kaplan-Meier method and the log-rank test. Results: Four hundred eleven cases of maxillary alveolus and 314 cases of hard palate SCC were identified, for a total of 725 cases (53.9% female, mean age: 70.9 years). The prevalence of cervical metastasis was not significantly different according to primary site (P = .181); advanced N-stage significantly correlated with more advanced T-stage (P < .001). Of the 725 cases, 4.1% of T1 tumors, 14.9% of T2 tumors, 10.3% of T3 tumors, and 24.7% of T4 tumors had cervical nodal metastases. The mean overall survivals were 96.5, 69.1, 67.8, and 49.3 months for T1-T4 tumors, respectively (P < .001). With regard to N-stage, the mean survivals were 73.7, 69.7, 29.8, and 5.5 months for N0-N3 lesions, respectively (P < .001). Nodal metastasis effect on survival remained significant (P < .039) in stratified survival analysis except for T3 lesions (P = .205). Conclusions: Survival in patients with SCC of either the hard palate or maxillary alveolus is significantly influenced by T-stage and a nonnegligible rate of cervical nodal metastases. C1 [Bhattacharyya, Neil] Brigham & Womens Hosp, Div Otolaryngol Head & Neck Surg, Boston, MA 02115 USA. [Lin, Harrison W.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Lin, Harrison W.; Bhattacharyya, Neil] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Bhattacharyya, N (reprint author), Brigham & Womens Hosp, Div Otolaryngol Head & Neck Surg, 45 Francis St, Boston, MA 02115 USA. EM neiloy@massmed.org NR 15 TC 19 Z9 21 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD FEB PY 2009 VL 119 IS 2 BP 312 EP 315 DI 10.1002/lary.20054 PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 402VP UT WOS:000263041500015 PM 19172612 ER PT J AU Burns, JA Hillman, RE Stadelman-Cohen, T Zeitels, SM AF Burns, James A. Hillman, Robert E. Stadelman-Cohen, Tara Zeitels, Steven M. TI Phonomicrosurgical Treatment of Intracordal Vocal-Fold Cysts in Singers SO LARYNGOSCOPE LA English DT Article DE Larynx; vocal fold; vocal cord; cyst; phonomicrosurgery; microlaryngoscopy; microsurgery; singer; voice ID EPIDERMOID CYSTS; MANAGEMENT C1 [Stadelman-Cohen, Tara; Zeitels, Steven M.] Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. [Burns, James A.; Zeitels, Steven M.] Harvard Univ, Ctr Laryngeal Surg & Voice Rehabil, Sch Med, Dept Surg, Boston, MA USA. [Hillman, Robert E.] Harvard Univ, Ctr Laryngeal Surg & Voice Rehabil, Sch Med, Dept Surg & Hlth Sci & Technol, Boston, MA USA. RP Zeitels, SM (reprint author), Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, 1 Bowdoin Sq,11th Floor, Boston, MA 02114 USA. EM zeitels.steven@MGH.Harvard.edu NR 14 TC 5 Z9 5 U1 2 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD FEB PY 2009 VL 119 IS 2 BP 419 EP 422 DI 10.1002/lary.20001 PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 402VP UT WOS:000263041500032 PM 19160407 ER PT J AU Laubach, HJ Astner, S Watanabe, K Clifford, J Rius-Diaz, F Zurakowski, D Manstein, D AF Laubach, Hans-Joachim Astner, Susanne Watanabe, Kanna Clifford, Joan Rius-Diaz, Francisca Zurakowski, David Manstein, Dieter TI Effects of a 1,450 nm Diode Laser on Facial Sebum Excretion SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE photothermolysis; sebum; laser; diode laser; 1,450 nm; Sebumeter (R); sebum excretion rate; skin; sebaceous glands; human; adult; acne; clinical trial ID RANDOMIZED CONTROLLED-TRIAL; INFLAMMATORY ACNE-VULGARIS; PULSED-DYE-LASER; 13-CIS-RETINOIC ACID; COMBINATION; SKIN; THERAPY AB Background and Objective: Laser therapy with a 1,450 nm diode laser is a clinically effective treatment for acne vulgaris, although the mechanism of action is unknown. To investigate this, we conducted a small, prospective, controlled clinical trial to assess this laser's effects on the facial sebum excretion rate (SER). Materials and Methods: Fourteen healthy volunteers without active acne were enrolled in this study and received three laser treatments on test areas of the nose and forehead. Nine subjects completed the treatment regimen and were available for follow-up. SER was measured with Sebumeter (R) prior to the first treatment, and at 1 week and 1 month after the third treatment. Photographs were taken and subjective assessment of skin oiliness and pore size determined by questionnaires at 1 month follow-up. Results: No significant reduction in SER was observed comparing treated with control on all treatment sites (P > 0.05) on the nose. Reduction in the absolute SER was observed for both test and control sites on the forehead, reaching significance on the treatment site (P = 0.04) and marginal significance on the control site (P = 0.08). Conclusion: While our study was designed to detect only large changes in SER, we conclude that three 1,450 nm laser treatment sessions did not cause marked changes in SER compared to the control (i.e., > 44%). Thus, major destruction of sebaceous glands as a result of this treatment is unlikely. However, reduced sebum production was observed on both treatment and control sides at 1 month. Therefore alternative mechanisms should also be considered to explain the clinical efficacy of this treatment for acne vulgaris. Lasers Surg. Med. 41:110-115, 2009. (C) 2009 Wiley-Liss, Inc. C1 [Laubach, Hans-Joachim; Astner, Susanne; Watanabe, Kanna; Rius-Diaz, Francisca; Zurakowski, David; Manstein, Dieter] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. [Clifford, Joan] Candela Corp, Wayland, MA 01778 USA. RP Laubach, HJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, BAR 304,50 Blossom St, Boston, MA 02114 USA. EM hlaubach@partners.org FU Candela Cooperation, Wayland, M.A FX Contract grant sponsor: Candela Cooperation, Wayland, M.A. NR 23 TC 13 Z9 13 U1 1 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD FEB PY 2009 VL 41 IS 2 BP 110 EP 115 DI 10.1002/lsm.20672 PG 6 WC Dermatology; Surgery SC Dermatology; Surgery GA 414WZ UT WOS:000263897200006 PM 19226569 ER PT J AU Chan, HHL AF Chan, Henry H. L. TI Introduction to the Basic Science Section by Dr. Chan SO LASERS IN SURGERY AND MEDICINE LA English DT Editorial Material C1 [Chan, Henry H. L.] Univ Hong Kong, Div Dermatol, Hong Kong, Hong Kong, Peoples R China. [Chan, Henry H. L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. RP Chan, HHL (reprint author), Univ Hong Kong, Div Dermatol, Hong Kong, Hong Kong, Peoples R China. RI Chan, Henry Hin Lee/L-2267-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD FEB PY 2009 VL 41 IS 2 BP 141 EP 141 DI 10.1002/lsm.20752 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 414WZ UT WOS:000263897200011 PM 19226582 ER PT J AU Manstein, D Zurakowski, D Thongsima, S Laubach, H Chan, HH AF Manstein, Dieter Zurakowski, David Thongsima, Siremon Laubach, Hans Chan, Henry H. TI The Effects of Multiple Passes on the Epidermal Thermal Damage Pattern in Nonablative Fractional Resurfacing SO LASERS IN SURGERY AND MEDICINE LA English DT Article ID LASER; SKIN; PHOTOTHERMOLYSIS; COMBINATION; RHYTIDES AB Background and Objective: Nonablative fractional resurfacing is a concept of cutaneous re-modeling whereby laser-induced microscopic treatment zones (MTZs) are surrounded by normal viable tissue. Such thermal damage pattern with a small diameter of individual lesions allows fast re-epithelialization with minimal side effects. The purpose of this in vitro study was to determine the fraction of thermal injury per unit surface area (fill factor) and lesion size in relation to pulse energy and number of passes. Methods: Full thickness abdominal skin samples were exposed ex vivo to the Fraxel SR 750 laser (Reliant Technologies, Mountain View, CA). One set of exposures was performed for pulse energies in the range of 8 to 40 mJ for a single pass at 250 MTZ/cm(2). A second set of exposures was performed at 10 mJ with number of passes from 1 to 30. The thermal damage pattern was assessed by incubation of epidermal sheets with NitroBlueTetrazoliumChloride (NBTC) stain. Size of individual MTZ and fill factor were determined by image analysis (ImageJ, NIH, Bethesda, MD) of digital micrographs. Results: Width of the thermal injury zone was directly related to the pulse energy used. The fill factor did not have a uniform relationship with the number of passes. Due to the stochastic placement of individual MTZs, even for greater number of passes, some residual undamaged tissue was found. Due to formation of thermal damage clusters, defined as overlapping individual MTZs, the size of the resulting clustering lesions which we defined as microscopic treatment cluster (MTC) increased linearly as a function of the number of passes. Conclusion: We have described the fill factor as it relates to the number of passes and have demonstrated that the average size of individual lesions depends on the number of passes. Clustering of MTZs lead to the development of MTC, the average size of which increased with the number of passes. The clinical implications of these findings are contingent on further studies. Lasers Surg. Med. 41:149-153, 2009. (C) 2009 Wiley-Liss, Inc. C1 [Manstein, Dieter; Zurakowski, David; Thongsima, Siremon; Laubach, Hans; Chan, Henry H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Ctr Photomed, Boston, MA 02114 USA. [Chan, Henry H.] Univ Hong Kong, Div Dermatol, Hong Kong, Hong Kong, Peoples R China. RP Manstein, D (reprint author), Harvard Univ, Sch Med, Dept Dermatol, Wellman Ctr Photomed, 50 Blossom St,BHX 630, Boston, MA 02114 USA. EM dmanstein@partners.org RI Chan, Henry Hin Lee/L-2267-2013 NR 17 TC 14 Z9 14 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD FEB PY 2009 VL 41 IS 2 BP 149 EP 153 DI 10.1002/lsm.20711 PG 5 WC Dermatology; Surgery SC Dermatology; Surgery GA 414WZ UT WOS:000263897200013 PM 19226571 ER PT J AU Sakamoto, FH Tannous, Z Doukas, AG Farinelli, WA Smith, NA Zurakowski, D Anderson, RR AF Sakamoto, Fernanda H. Tannous, Zeina Doukas, Apostolos G. Farinelli, William A. Smith, Nicholas A. Zurakowski, David Anderson, R. Rox TI Porphyrin Distribution After Topical Aminolevulinic Acid in a Novel Porcine Model of Sebaceous Skin SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE acne; animal model; apocrine glands; eccrine glands; sebaceous glands; sweat glands; time perception; physiology; photodynamic therapy ID PHOTODYNAMIC THERAPY; ACNE-VULGARIS; 5-AMINOLEVULINIC ACID; HUMAN SEBUM; RABBIT EAR; PROTOPORPHYRIN; PATHOGENESIS; INTEGUMENT; PREVALENCE; INJECTION AB Background and Objective: Aminolevulinic acid photodynamic therapy (ALA-PDT) depends on drug metabolism into porphyrins. Clinically, ALA-PDT has been used with a wide range of protocols for treating both epidermal and dermal targets, despite limited understanding of porphyrin biodistribution over time. We studied porphyrin accumulation after topical application of ALA in vivo, and also describe the porcine ear as a new animal model to study adnexal glands. Study Design/Materials and Methods: The microanatomy of anterior ear skin of swine was measured. Topical 20% ALA in water/ethanol was applied under occlusion. Biopsies taken after 5, 10, 15, and then every 15 minutes for a total of 3 hours were examined by fluorescence microscopy of frozen sections to assess accumulation and distribution of porphyrins. Results: Porphyrin fluorescence of digital photomicrograph images was not visually apparent until 3045 minutes after application, although quantitative pixel analysis showed a statistically significant increase in epidermal fluorescence only 15 minutes after ALA application. From 30 to 120 minutes, epidermis, hair follicles (HF), and sebaceous glands (SG) became progressively more fluorescent. Eccrine gland fluorescence began to be detected after 30 minutes; SG showed fluorescence starting at 45-75 minutes. Fluorescence in all sites reached maximum intensity from 75 to 180 minutes of incubation. There was a trend for HF and SG to express stronger fluorescence compared with epidermis and eccrine glands. Conclusion: Anterior pig ear skin is microanatomically similar to human sebaceous skin. The time-dependent accumulation of porphyrins in pilosebaceous units and eccrine glands in this model suggests other routes of uptake of topical ALA in addition to the trans-epidermal route. Apparently, time interval between ALA application and light exposure could be optimized for different uses of ALA-PDT. Lasers Surg. Med. 41:154-160, 2009. (C) 2009 Wiley-Liss, Inc. C1 [Zurakowski, David] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Surg, Boston, MA 02115 USA. [Sakamoto, Fernanda H.; Tannous, Zeina; Doukas, Apostolos G.; Farinelli, William A.; Smith, Nicholas A.; Anderson, R. Rox] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. [Smith, Nicholas A.] Harvard Univ, Cambridge, MA 02138 USA. [Tannous, Zeina] Harvard Univ, Sch Med, Boston VA Hosp, Jamaica Pl, MA 02130 USA. [Sakamoto, Fernanda H.] Univ Fed Sao Paulo, Dept Dermatol, Escola Paulista Med UNIFESP EPM, BR-04023900 Sao Paulo, Brazil. RP Anderson, RR (reprint author), 55 Fruit St,BHX 630, Boston, MA 02114 USA. EM rranderson@partners.org FU Wellman Center for Photomedicine in Boston, Massachusetts FX This work was performed at the Wellman Center for Photomedicine in Boston, Massachusetts. NR 29 TC 14 Z9 17 U1 2 U2 8 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD FEB PY 2009 VL 41 IS 2 BP 154 EP 160 DI 10.1002/lsm.20734 PG 7 WC Dermatology; Surgery SC Dermatology; Surgery GA 414WZ UT WOS:000263897200014 PM 19226576 ER PT J AU Dispenzieri, A Kyle, R Merlini, G Miguel, JS Ludwig, H Hajek, R Palumbo, A Jagannath, S Blade, J Lonial, S Dimopoulos, M Comenzo, R Einsele, H Barlogie, B Anderson, K Gertz, M Harousseau, JL Attal, M Tosi, P Sonneveld, P Boccadoro, M Morgan, G Richardson, P Sezer, O Mateos, MV Cavo, M Joshua, D Turesson, I Chen, W Shimizu, K Powles, R Rajkumar, SV Durie, BGM AF Dispenzieri, A. Kyle, R. Merlini, G. Miguel, J. S. Ludwig, H. Hajek, R. Palumbo, A. Jagannath, S. Blade, J. Lonial, S. Dimopoulos, M. Comenzo, R. Einsele, H. Barlogie, B. Anderson, K. Gertz, M. Harousseau, J. L. Attal, M. Tosi, P. Sonneveld, P. Boccadoro, M. Morgan, G. Richardson, P. Sezer, O. Mateos, M. V. Cavo, M. Joshua, D. Turesson, I. Chen, W. Shimizu, K. Powles, R. Rajkumar, S. V. Durie, B. G. M. CA Int Myeloma Working Grp TI International Myeloma Working Group guidelines for serum-free light chain analysis in multiple myeloma and related disorders SO LEUKEMIA LA English DT Review DE immunoglobulin-free light chain; prognosis; myeloma; amyloid ID STEM-CELL TRANSPLANTATION; CAPILLARY-ZONE-ELECTROPHORESIS; PRIMARY SYSTEMIC AMYLOIDOSIS; INDEPENDENT RISK-FACTOR; MONOCLONAL GAMMOPATHIES; PROGNOSTIC VALUE; STAGING SYSTEM; IMMUNOGLOBULIN; URINE; ASSAYS AB The serum immunoglobulin-free light chain (FLC) assay measures levels of free kappa and lambda immunoglobulin light chains. There are three major indications for the FLC assay in the evaluation and management of multiple myeloma and related plasma cell disorders (PCD). In the context of screening, the serum FLC assay in combination with serum protein electrophoresis (PEL) and immunofixation yields high sensitivity, and negates the need for 24-h urine studies for diagnoses other than light chain amyloidosis (AL). Second, the baseline FLC measurement is of major prognostic value in virtually every PCD. Third, the FLC assay allows for quantitative monitoring of patients with oligosecretory PCD, including AL, oligosecretory myeloma and nearly two-thirds of patients who had previously been deemed to have non-secretory myeloma. In AL patients, serial FLC measurements outperform PEL and immunofixation. In oligosecretory myeloma patients, although not formally validated, serial FLC measurements reduce the need for frequent bone marrow biopsies. In contrast, there are no data to support using FLC assay in place of 24-h urine PEL for monitoring or for serial measurements in PCD with measurable disease by serum or urine PEL. This paper provides consensus guidelines for the use of this important assay, in the diagnosis and management of clonal PCD. C1 [Dispenzieri, A.] Mayo Clin, Div Hematol, Dept Hematol, Rochester, MN 55905 USA. [Dispenzieri, A.; Kyle, R.; Gertz, M.; Rajkumar, S. V.] Mayo Clin, Dept Lab Med, Rochester, MN 55905 USA. [Dispenzieri, A.; Kyle, R.; Gertz, M.; Rajkumar, S. V.] Mayo Clin, Dept Pathol, Rochester, MN 55905 USA. [Merlini, G.] Univ Hosp San Matteo, Dept Biochem, Pavia, Italy. [Miguel, J. S.; Mateos, M. V.] USAL CSIC, IBMCC, CIC, Hosp Univ Salamanca,Serv Hepatol,Dept Hematol, Madrid, Spain. [Ludwig, H.] Wilhelminenspital Stat Wien, Med Dept & Oncol 1, Vienna, Austria. [Hajek, R.] Fn Brno, Dept Internal Med, Brno, Czech Republic. [Hajek, R.] LF MM Brno, Brno, Czech Republic. [Palumbo, A.; Boccadoro, M.] Univ Turin, Div Ematol, Turin, Italy. [Jagannath, S.] St Vincents Comprehens Canc Ctr, Dept Med Oncol Internal Med, New York, NY USA. [Blade, J.] IDIBAPS, Hosp Clin, Dept Hematol, Barcelona, Spain. [Lonial, S.] Emory Univ, Atlanta, GA USA. [Dimopoulos, M.] Alexandra Hosp, Dept Therapeut, Athens, Greece. [Comenzo, R.] Mem Sloan Kettering Canc Ctr, Dept Clin Labs, New York, NY 10021 USA. [Einsele, H.] Univ Wurzburg, Dept Internal Med, Wurzburg, Germany. [Barlogie, B.] MIRT UAMS, Dept Hematol, Little Rock, AR USA. [Barlogie, B.] MIRT UAMS, Dept Pathol, Little Rock, AR USA. [Anderson, K.] DFCI, Dept Med Oncol Hematol Malignancies, Boston, MA USA. [Harousseau, J. L.] Inst Biol, Dept Hematol, Nantes, France. [Attal, M.] Purpan Hosp, Dept Hematol, Toulouse, France. [Attal, M.] Purpan Hosp, Dept Biostat, Toulouse, France. [Tosi, P.; Cavo, M.] Univ Bologna, Inst Hematol & Med Oncol, Bologna, Italy. [Sonneveld, P.] Dept Hematol, Rotterdam, Netherlands. [Morgan, G.] Leukemia & Myeloma Program, Dept Hematol Oncol, Wimbledon, England. [Sezer, O.] Univ Berlin, Dept Hematol Oncol, Berlin, Germany. [Joshua, D.] Royal Prince Alfred Hosp, Inst Hematol, Sydney, NSW, Australia. [Turesson, I.] Malmo Univ Hosp, Dept Med Hematol, Malmo, Sweden. [Chen, W.] Beijing Chaoyang Hosp, Dept Hematol Oncol, Beijing, Peoples R China. [Shimizu, K.] Nagoya City Higashi Gen Hosp, Dept Internal Med, Nagoya, Aichi, Japan. [Powles, R.] Parkside Canc Ctr, Dept Hematol Oncol, London, England. [Durie, B. G. M.] Aptium Oncol Inc, Cedars Sinai Outpatient Canc Ctr, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA USA. RP Dispenzieri, A (reprint author), Mayo Clin, Div Hematol, Dept Hematol, 200 1st St SW,200 1st, Rochester, MN 55905 USA. EM dispenzieri.angela@mayo.edu RI 2009, Secribsal/A-1266-2012; Waage, Anders/D-7705-2013; Sangue, Inct/I-1919-2013; FACON, THIERRY/M-9736-2014; OI FACON, THIERRY/0000-0001-7705-8460; CAVO, MICHELE/0000-0003-4514-3227; Rajkumar, S. Vincent/0000-0002-5862-1833; Merlini, Giampaolo/0000-0001-7680-3254; Dispenzieri, Angela/0000-0001-8780-9512 NR 43 TC 329 Z9 348 U1 4 U2 36 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD FEB PY 2009 VL 23 IS 2 BP 215 EP 224 DI 10.1038/leu.2008.307 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA 406RJ UT WOS:000263312300001 PM 19020545 ER PT J AU Lang, K Marciniak, MD Faries, D Stokes, M Buesching, D Earle, C Treat, J Morissette, N Thompson, D AF Lang, Kathleen Marciniak, Martin D. Faries, Doug Stokes, Michael Buesching, Don Earle, Craig Treat, Joseph Morissette, Nathalie Thompson, David TI Trends and predictors of first-line chemotherapy use among elderly patients with advanced non-small cell lung cancer in the United States SO LUNG CANCER LA English DT Article DE NSCLC; Treatment; Predictor; Lung cancer; Trend; SEER ID PHASE-III TRIAL; GEMCITABINE PLUS CISPLATIN; RANDOMIZED-TRIAL; REGIMENS; CARE AB Purpose: This study assessed first-line chemotherapy treatment patterns over time and identified predictors of chemotherapy use and treatment selection among elderly patients with newly diagnosed Stage IIIB/IV non-small cell lung cancer (NSCLC) in the United States. Methods: Patients aged 65 years and older newly diagnosed with Stage IIIB/IV NSCLC between 1997 and 2002 were identified and followed through 2003 using the Surveillance, Epidemiology and End Results (SEER)-Medicare database to evaluate temporal trends in chemotherapy treatment. Multivariate logistic regression models were estimated to identify predictors of chemotherapy treatment and factors associated with use of cisplatin/carboplatin (platinum) and either a taxane or gemcitabine versus other treatments. Results: Chemotherapy use increased from approximately 28% of Stage IIIB/IV NSCLC patients diagnosed in 1997 to 36% of patients diagnosed in 2002. Doublet therapy was most commonly used as first-line therapy, received by 74% of chemotherapy-treated patients across all study years. Use of doublet therapy with platinum and either a taxane or gemcitabine also increased over time (with the largest increase for gemcitabine combinations from 0.3% in 1997 to 11.8% in 2002). Males were more likely than females to be treated with chemotherapy (odds ratios [95% CI]: 1.14 [1.06-1.22]), as were patients in the Northeast and South relative to patients in the West (1.24 [1.13-1.36] and 1.33 [1.20-1.47], respectively). Conclusion: Use of first-line chemotherapy treatment among elderly Stage IIIB/IV NSCLC patients is low, but appears to be increasing, with potential regional and gender differences in treatment. These findings are likely to be of interest to clinicians and policymakers. (C) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Marciniak, Martin D.] Eli Lilly & Co, Lilly Corp Ctr, US Outcomes Res, Indianapolis, IN 46285 USA. [Lang, Kathleen; Stokes, Michael; Morissette, Nathalie; Thompson, David] i3 Innovus, Medford, MA USA. [Earle, Craig] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Marciniak, MD (reprint author), Eli Lilly & Co, Lilly Corp Ctr, US Outcomes Res, DC 6831, Indianapolis, IN 46285 USA. EM marciniak_martin@lilly.com FU Eli Lilly and Company FX Funding for this study provided by Eli Lilly and Company. NR 22 TC 33 Z9 34 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER JI Lung Cancer PD FEB PY 2009 VL 63 IS 2 BP 264 EP 270 DI 10.1016/j.lungcan.2008.05.003 PG 7 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 402NP UT WOS:000263020700016 PM 18649969 ER PT J AU Paige, NM Nagami, GT AF Paige, Neil M. Nagami, Glenn T. TI The Top 10 Things Nephrologists Wish Every Primary Care Physician Knew SO MAYO CLINIC PROCEEDINGS LA English DT Review ID CHRONIC KIDNEY-DISEASE; CHRONIC-RENAL-FAILURE; BOWEL PREPARATION; METABOLIC EVALUATION; COMBINATION THERAPY; ALUMINUM ABSORPTION; URINE SAMPLES; PROTEINURIA; HEMOGLOBIN; HYPERPHOSPHATEMIA AB Renal disease is commonly encountered by primary care physicians during their day-to-day visits with patients. Common renal disorders include hypertension, proteinuria, kidney stones, and chronic kidney disease. Despite their prevalence, many physicians may be unfamiliar with the diagnosis and Initial treatment of these common renal disorders. Early recognition and intervention are Important In slowing the progression of chronic kidney disease and preventing Its complications. The evidence-based pearls In this article will help primary care physicians avoid common pitfalls In the recognition and treatment of such disorders and guide their decision to refer their patients to a specialist. C1 [Paige, Neil M.] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Dept Med,Div Gen Internal Med, Los Angeles, CA 90073 USA. [Nagami, Glenn T.] Univ Calif Los Angeles, David Geffen Sch Med, Nephrol Sect, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Paige, NM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Dept Med,Div Gen Internal Med, 11301 Wilshire Blvd 111A, Los Angeles, CA 90073 USA. EM neil.paige@va.gov NR 43 TC 10 Z9 11 U1 0 U2 1 PU MAYO CLINIC PROCEEDINGS PI ROCHESTER PA 660 SIEBENS BLDG MAYO CLINIC, ROCHESTER, MN 55905 USA SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD FEB PY 2009 VL 84 IS 2 BP 180 EP 186 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 402CT UT WOS:000262992500012 PM 19181652 ER PT J AU Pickard, AS Lin, HW Knight, SL Sharifi, R Wu, ZG Hung, SY Witt, WP Chang, CH Bennett, CL AF Pickard, A. Simon Lin, Hsiang-Wen Knight, Sara L. Sharifi, Roohollah Wu, Zhigang Hung, Shih-Ying Witt, Whitney P. Chang, Chih-Hung Bennett, Charles L. TI Proxy Assessment of Health-Related Quality of Life in African American and White Respondents With Prostate Cancer Perspective Matters SO MEDICAL CARE LA English DT Article DE quality of life; proxy; prostate cancer; Veterans ID UROLOGIC RESEARCH ENDEAVOR; RADICAL PROSTATECTOMY; SYMPTOM EXPERIENCES; SIGNIFICANT OTHERS; FUNCTIONAL STATUS; MEDICARE SURVEY; PATIENT HEALTH; MEN; CAREGIVERS; OUTCOMES AB Objectives: An emerging issue in the proxy literature is whether specifying different proxy viewpoints contributes to different health-related quality of life (HRQL) assessments, and if so, how might each perspective be informative in medical decision making. The aims of this study were to determine if informal caregiver assessments of patients with prostate cancer differed when prompted from both the patient perspective (proxy-patient) and their own viewpoint (proxy-proxy), and to identify factors associated with differences in proxy perspectives (ie, the intraproxy gap). Research Design and Methods: Using a cross-sectional design, prostate cancer patients and their informal caregivers were recruited from urology clinics in the Jesse Brown Veterans Affairs Healthcare System in Chicago. Dyads assessed HRQL using the EQ-5D visual analog scale (VAS) and EORTC QLQ-C30. Results: Of 87 dyads, most caregivers were female (83%) and were spouses/partners (58%). Mean difference scores between proxy-patient and proxy-proxy perspectives were statistically significant for QLQ-C30 physical and emotional functioning, and VAS (all P < 0.05), with the proxy-patient perspective closer to patient self-report. Emotional functioning had the largest difference, mean 6.0 (SD 12.8), an effect size = 0.47. Factors weakly correlated with the intraproxy gap included relationship (spouse) and proxy gender for role functioning, and health literacy (limited/functional) for physical functioning (all P < 0.05, 0.20 < r < 0.35). Conclusions: Meaningful differences between proxy-patient and proxy-proxy perspectives on mental health were consistent with a conceptual framework for understanding proxy perspectives. Prompting different proxy viewpoints on patient health could help clinicians identify patients who may benefit from clinical intervention. C1 [Pickard, A. Simon; Lin, Hsiang-Wen; Hung, Shih-Ying] Univ Illinois, Coll Pharm, Ctr Pharmacoecon Res, Dept Pharm Practice & Pharm Adm, Chicago, IL 60612 USA. [Pickard, A. Simon; Hung, Shih-Ying; Bennett, Charles L.] Hines VA Hosp, Midwest Ctr Hlth Serv & Policy Res, Hines, IL USA. [Knight, Sara L.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. [Knight, Sara L.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Knight, Sara L.] Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. [Sharifi, Roohollah; Wu, Zhigang] Univ Illinois, Coll Pharm, Dept Urol, Chicago, IL 60612 USA. [Sharifi, Roohollah; Wu, Zhigang; Bennett, Charles L.] Jesse Brown Vet Affairs Hlth Syst, Chicago, IL USA. Univ Wisconsin, Dept Social & Adm Pharm, Madison, WI USA. [Witt, Whitney P.] Univ Wisconsin, Dept Hlth Sci Res, Sch Publ Hlth, Madison, WI USA. [Chang, Chih-Hung] Northwestern Univ, Buehler Ctr Aging Hlth & Soc, Chicago, IL 60611 USA. [Bennett, Charles L.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. RP Pickard, AS (reprint author), Univ Illinois, Coll Pharm, Ctr Pharmacoecon Res, Dept Pharm Practice & Pharm Adm, 833 S Wood St,Rm 164,MC 886, Chicago, IL 60612 USA. EM pickard1@uic.edu FU National Cancer Institute/ National Institutes of Health [R03 CA 108395] FX Supported by grant R03 CA 108395 from the National Cancer Institute/ National Institutes of Health. NR 51 TC 12 Z9 12 U1 1 U2 6 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 FEB PY 2009 VL 47 IS 2 BP 176 EP 183 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 401BN UT WOS:000262913200007 PM 19169118 ER PT J AU Sepucha, K Mulley, AG AF Sepucha, Karen Mulley, Albert G., Jr. TI A Perspective on the Patient's Role in Treatment Decisions SO MEDICAL CARE RESEARCH AND REVIEW LA English DT Article DE decision making; patient involvement; decision quality; decision aids ID BREAST-CANCER; PATIENTS PREFERENCES; INFORMATION NEEDS; INFORMED-CONSENT; CARE OUTCOMES; OF-LIFE; COMMUNICATION; PHYSICIANS; AIDS; INVOLVEMENT AB There is considerable evidence, across different clinical contexts, that treatment decisions are characterized by poor communication, significant knowledge gaps, and a lack of attention to patients' preferences for different health states. Over the past two decades, patient decision aids have been shown to be an effective means to improve the quality of decisions. More recently, the Internet has increased expectations about the impact of information and decision aids on the involvement of patients in decisions. However, there are several challenges to effective dissemination and implementation of decision support interventions, through the Internet or other media. The authors recommend specific policy and research initiatives to facilitate the local and system-level changes necessary to support patients more effectively in making treatment choices. More attention to measurement and policy-level interventions will be required to increase the use of proven tools and to achieve significant improvements in the quality of treatment decisions. C1 [Sepucha, Karen; Mulley, Albert G., Jr.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Sepucha, K (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 93 TC 19 Z9 19 U1 5 U2 10 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 FEB PY 2009 VL 66 IS 1 BP 53S EP 74S DI 10.1177/1077558708325511 PG 22 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 393RH UT WOS:000262389900004 PM 19001081 ER PT J AU Dhaliwal, G AF Dhaliwal, Gurpreet TI Medical expertise: begin with the end in mind SO MEDICAL EDUCATION LA English DT Editorial Material ID DELIBERATE PRACTICE; EDUCATION C1 Univ Calif San Francisco Med, San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Dhaliwal, G (reprint author), Univ Calif San Francisco Med, San Francisco VA Med Ctr, 4150 Clement St 111, San Francisco, CA 94121 USA. EM gurpreet.dhaliwal@va.gov NR 11 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0308-0110 J9 MED EDUC JI Med. Educ. PD FEB PY 2009 VL 43 IS 2 BP 105 EP 107 DI 10.1111/j.1365-2923.2008.03262.x PG 3 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 397EJ UT WOS:000262644900003 PM 19161478 ER PT J AU Klein, AJ Casserly, IP Messenger, JC Carroll, JD Chen, SYJ AF Klein, Andrew J. Casserly, Ivan P. Messenger, John C. Carroll, John D. Chen, S. -Y. James TI In vivo 3D modeling of the femoropopliteal artery in human subjects based on x-ray angiography: Methodology and validation SO MEDICAL PHYSICS LA English DT Article DE biomechanics; blood vessels; diagnostic radiography; diseases ID SUPERFICIAL FEMORAL-ARTERY; QUANTITATIVE-ANALYSIS; 3-D RECONSTRUCTION; CORONARY-ARTERIES; TREE; STENTS AB Endovascular revascularization of the femoropopliteal (FP) artery has been limited by high rates of restenosis and stent fracture. The unique physical forces that are applied to the FP artery during leg movement have been implicated in these phenomena. The foundation for measuring the effects of physical forces on the FP artery in a clinically relevant environment is based on the ability to develop 3D models of this vessel in different leg positions in vivo in patients with peripheral arterial disease (PAD). By acquiring paired angiographic images of the FP artery, and using angiography-based 3D modeling algorithms previously validated in the coronary arteries, the authors generated 3D models of ten FP arteries in nine patients with PAD with the lower extremity in straight leg (SL) and crossed leg (CL) positions. Due to the length of the FP artery, overlapping paired angiographic images of the entire FP artery were required to image the entire vessel, which necessitated the development of a novel fusion process in order to generate a 3D model of the entire FP artery. The methodology of angiographic acquisition and 3D model generation of the FP artery is described. In a subset of patients, a third angiographic view (i.e., validation view) was acquired in addition to the standard paired views for the purpose of validating the 3D modeling process. The mean root-mean-square (rms) error of the point-to-point distances between the centerline of the main FP artery from the 2D validation view and the centerline from the 3D model placed in the validation view for the SL and CL positions were 0.93 +/- 0.19 mm and 1.12 +/- 0.25 mm, respectively. Similarly, the mean rms error of the same comparison for the main FP artery and sidebranches for the SL and CL positions were 1.09 +/- 0.38 mm and 1.21 +/- 0.25 mm, respectively. A separate validation of the novel fusion process was performed by comparing the 3D model of the FP artery derived from fusion of 3D models of adjacent FP segments with the 2D validation view incorporating the region of fusion. The mean rms error of vessel centerline points of the main FP artery, the main FP artery plus directly connected sidebranches, and the mean rms error of upstream, downstream, and sidebranch directional vectors at bifurcation points in the overlap region were 1.41 +/- 0.79 mm, 2.13 +/- 1.12 mm, 3.16 +/- 3.72 degrees, 3.60 +/- 5.39 degrees, and 8.68 +/- 8.42 degrees in the SL position, respectively, and 1.29 +/- 0.35 mm, 1.61 +/- 0.78 mm, 4.68 +/- 4.08 degrees, 3.41 +/- 2.23 degrees, and 5.52 +/- 4.41 degrees in the CL position, respectively. Inter- and intraobserver variability in the generation of 3D models of individual FP segments and the fusion of overlapping FP segments were assessed. The mean rms errors between the centerlines of nine 3D models of individual FP segments generated by two independent observers, and repeated measurement by the same observer were 2.78 +/- 1.26 mm and 3.50 +/- 1.15 mm, respectively. The mean rms errors between the centerline of four 3D models of fused overlapping FP segments generated by two independent observers, and repeated measurement by the same observer were 4.99 +/- 0.99 mm and 5.98 +/- 1.22 mm, respectively. This study documents the ability to generate 3D models of the entire FP artery in vivo in patients with PAD in both SL and CL positions using routine angiography, and validates the methodologies used. C1 [Klein, Andrew J.; Casserly, Ivan P.; Messenger, John C.; Carroll, John D.; Chen, S. -Y. James] Univ Colorado Denver, Aurora, CO 80045 USA. [Casserly, Ivan P.] Denver VA Med Ctr, Denver, CO 80220 USA. RP Klein, AJ (reprint author), Univ Colorado Denver, Aurora, CO 80045 USA. FU Boston Scientific Corporation FX The authors would like to acknowledge Adam Hansgen for assistance with graphics, the cardiac catheterization laboratory staff at the Denver VA Medical Center for assistance during acquisition of angiographic data (Sarah Doran, Mary Hall, Marsha Hallahan, Lori Harvey, Mary Ann Olson, Tracy Rankin), Philip Li and Yu- Li Liang for their efforts in reconstructing the FP arteries, and Kathy Kioussopoulos for her assistance in preparing the clinical protocol for institutional review board approval. This study was supported and funded by the research grant from Boston Scientific Corporation. NR 20 TC 5 Z9 5 U1 0 U2 2 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 FEB PY 2009 VL 36 IS 2 BP 289 EP 310 DI 10.1118/1.3006195 PG 22 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 400FE UT WOS:000262852600003 PM 19291969 ER PT J AU Ouyang, JS Zhu, XP Trott, CM El Fakhri, G AF Ouyang, Jinsong Zhu, Xuping Trott, Cathryn M. El Fakhri, Georges TI Quantitative simultaneous Tc-99m/I-123 cardiac SPECT using MC-JOSEM SO MEDICAL PHYSICS LA English DT Article DE cardiology; expectation-maximisation algorithm; image reconstruction; iodine compounds; iterative methods; medical image processing; Monte Carlo methods; muscle; organic compounds; phantoms; single photon emission computed tomography; technetium compounds ID ACUTE MYOCARDIAL-INFARCTION; HEART-DISEASE; BRAIN SPECT; SIMULATION; SCATTER; VALIDATION AB Simultaneous rest Tc-99m-Sestamibi/I-123-BMIPP cardiac SPECT imaging has the potential to replace current clinical Tc-99m-Sestamibi rest/stress imaging and therefore has great potential in the case of patients with chest pain presenting to the emergency department. Separation of images of these two radionuclides is difficult, however, because their emission energies are close. The authors previously developed a fast Monte Carlo (MC)-based joint ordered-subset expectation maximization (JOSEM) iterative reconstruction algorithm (MC-JOSEM), which simultaneously compensates for scatter and cross talk as well as detector response within the reconstruction algorithm. In this work, the authors evaluated the performance of MC-JOSEM in a realistic population of Tc-99m/I-123 studies using cardiac phantom data on a Siemens e.cam system using a standard cardiac protocol. The authors also compared the performance of MC-JOSEM for estimation tasks to that of two other methods: standard OSEM using photopeak energy windows without scatter correction (NSC-OSEM) and standard OSEM using a Compton-scatter energy window for scatter correction (SC-OSEM). For each radionuclide the authors separately acquired high-count projections of radioactivity in the myocardium wall, liver, and soft tissue background compartments of a water-filled torso phantom, and they generated synthetic projections of various dual-radionuclide activity distributions. Images of different combinations of myocardium wall/background activity concentration ratios for each radionuclide were reconstructed by NSC-OSEM, SC-OSEM, and MC-JOSEM. For activity estimation in the myocardium wall, MC-JOSEM always produced the best relative bias and relative standard deviation compared with NSC-OSEM and SC-OSEM for all the activity combinations. On average, the relative biases after 100 iterations were 8.1% for Tc-99m and 3.7% for I-123 with MC-JOSEM, 39.4% for Tc-99m and 23.7% for I-123 with NSC-OSEM, and 20.9% for Tc-99m with SC-OSEM. The relative standard deviations after 30 iterations were 0.7% for Tc-99m and 1.0% for I-123 with MC-JOSEM, as compared to 1.1% for Tc-99m and 1.2% for I-123 with NSC-OSEM and 1.3% for Tc-99m with SC-OSEM. Finally, the authors compared the relative standard deviation after 30 iterations with the minimum theoretical variance on activity estimation, the Cramer-Rao lower bound (CRB), and with the biased CRB. The measured precision was larger than the biased bound values by factors of 2-4, suggesting that further improvement could be made to the method. C1 [Ouyang, Jinsong] Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Ouyang, JS (reprint author), Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. EM ouyang.jinsong@mgh.harvard.edu RI Trott, Cathryn/B-5325-2013 OI Trott, Cathryn/0000-0001-6324-1766 FU NIH [RO1-EB005876, RO1-EB001989]; Society of Nuclear Medicine Pilot Research Grant FX This work was supported by NIH Grant Nos. RO1-EB005876 and RO1-EB001989. Part of the image reconstructions for this paper was performed on a cluster supported by a Society of Nuclear Medicine Pilot Research Grant. NR 18 TC 15 Z9 15 U1 0 U2 2 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 FEB PY 2009 VL 36 IS 2 BP 602 EP 611 DI 10.1118/1.3063544 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 400FE UT WOS:000262852600034 PM 19292000 ER PT J AU Zhang, WB Abukawa, H Troulis, MJ Kaban, LB Vacanti, JP Yelick, PC AF Zhang, Weibo Abukawa, Harutsugi Troulis, Maria J. Kaban, Leonard B. Vacanti, Joseph P. Yelick, Pamela C. TI Tissue engineered hybrid tooth-bone constructs SO METHODS LA English DT Article DE Hybrid tooth-bone constructs; Tooth tissue regeneration; Bone regeneration; Stem cells derived from tooth bud ID MESENCHYMAL STEM-CELLS; HUMAN DENTAL-PULP; IN-VITRO; RECONSTRUCTION; TEETH; DEFECTS; COMPLEX; SURGERY; MARROW; SPONGE AB Proper rehabilitation of craniofacial defects is challenging because of the complexity of the anatomy and the component tissue types. The ability to simultaneously coordinate the regeneration of multiple tissues would make reconstruction more efficient and might reduce morbidity and improve outcomes. The craniofacial complex is unique because of the presence of teeth, in addition to skin, bone, cartilage, muscle, vascular, and neural tissues since teeth naturally grow in coordination with the craniofacial skeleton, our group developed an autologous, tooth-bone hybrid model to facilitate repair of mandibular defects in the Yucatan minipig. The hybrid tooth-bone construct was prepared by combining tooth bud cell-seeded scaffolds with autologous iliac crest bone marrow derived stem cell-seeded scaffolds, which were transplanted back into surgically created mandibular defects in the same minipig. The constructs were harvested after 12 and 20 weeks of growth. The resulting bone/tooth constructs were evaluated by X-ray, ultra high-resolution volume computed tomography (VCT), histological, immunohistochemical analyses, and transmission electron microscopy (TEM). The observed formation of small tooth-like structures consisting of organized dentin, enamel, pulp, cementum, periodontal ligament, and surrounded by regenerated alveolar bone, suggests the feasibility for regeneration of teeth and associated alveolar bone, in a single procedure. This model provides an accessible method for future clinical applications in humans. (C) 2008 Elsevier Inc. All rights reserved. C1 [Zhang, Weibo; Yelick, Pamela C.] Tufts Univ, Dept Oral & Maxillofacial Pathol, Div Craniofacial & Mol Genet, Boston, MA 02111 USA. [Abukawa, Harutsugi; Troulis, Maria J.; Kaban, Leonard B.] Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Vacanti, Joseph P.] Harvard Univ, Sch Med, Dept Pediat Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Yelick, PC (reprint author), Tufts Univ, Dept Oral & Maxillofacial Pathol, Div Craniofacial & Mol Genet, 136 Harrison Ave,Room M824, Boston, MA 02111 USA. EM pamela.yelick@tufts.edu RI Liu, Yifei/L-7828-2014; Zhang, Weibo/S-1546-2016 OI Liu, Yifei/0000-0002-1087-9827; Zhang, Weibo/0000-0001-6246-2487 NR 34 TC 35 Z9 36 U1 3 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 J9 METHODS JI Methods PD FEB PY 2009 VL 47 IS 2 BP 122 EP 128 DI 10.1016/j.ymeth.2008.09.004 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 400RO UT WOS:000262886500008 PM 18845257 ER PT J AU Morgan, CA Hazlett, G Southwick, S Rasmusson, A Lieberman, HR AF Morgan, Charles A., III Hazlett, Gary Southwick, Steven Rasmusson, Ann Lieberman, Harris R. TI Effect of Carbohydrate Administration on Recovery From Stress-Induced Deficits in Cognitive Function: A Double-Blind, Placebo-Controlled Study of Soldiers Exposed to Survival School Stress SO MILITARY MEDICINE LA English DT Article ID UNCONTROLLABLE STRESS; NEUROPEPTIDE-Y; PERFORMANCE; EXERCISE; HUMANS; MOOD; CAFFEINE; CORTISOL AB Objective: The goal of this project was to evaluate the effects of energy supplementation, as liquid carbohydrate (CHO), on facilitating recovery of cognitive function in soldiers who have been exposed to sustained psychological and physical stress during Survival School Training. Project Design: A double-blind, placebo-controlled design was used. Healthy, male volunteers attending survival training were recruited for participation in the study. At the conclusion of the mock captivity phase of survival training and before a recovery night of sleep, subjects participated in cognitive testing. After this, subjects were randomly assigned to one of three treatment groups. Subjects received either a 6% CHO (35.1 kJ/kg), 12% CHO (70.2 kJ/kg), or placebo beverage in four isovolemic doses. In the morning of the following day, all subjects participated in a second assessment of cognitive functioning. Results: Compared to subjects who received placebo, those who received supplemental CHO beverages exhibited significantly improved performance on a complex cognitive task (i.e., Stroop Test) involving concentration effectiveness associated with selective attention and response inhibition. No differences were observed on a variety of cognitive tasks of lesser complexity. Discussion: These data suggest nutritional interventions enhance the rapid recovery of complex cognitive functions impaired by exposure to significant or sustained stressful conditions. In addition to enhancing speed of recovery of function between operational intervals, the current data suggest that dietary supplement strategies may hold promise for enhancing field performance and a capacity to assist in sustaining operations by military personnel over time. C1 [Morgan, Charles A., III; Southwick, Steven; Rasmusson, Ann] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06511 USA. [Morgan, Charles A., III; Southwick, Steven; Rasmusson, Ann] VA New England Hlth Care Syst, Clin Neurosci Div, Natl Ctr PTSD, West Haven, CT 06519 USA. [Hazlett, Gary] Woodard Cody Specialty Consulting Inc, Chapel Hill, NC 27514 USA. [Rasmusson, Ann] Boston Univ, Sch Med, VA Natl Ctr PTSD, Womens Hlth Sci Div,VA Boston Hlth Care Syst, Boston, MA 02130 USA. [Lieberman, Harris R.] USA, Mil Nutr Div, Army Res Inst Environm Med, Natick, MA 01760 USA. RP Morgan, CA (reprint author), Yale Univ, Sch Med, Dept Psychiat, 300 George St, New Haven, CT 06511 USA. FU United States Special Operations Command Biomedical Initiatives Steering Committee FX Funding for this research was provided by a grant to Charles A. Morgan III from the United States Special Operations Command Biomedical Initiatives Steering Committee. NR 25 TC 5 Z9 5 U1 1 U2 2 PU ASSOC MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 J9 MIL MED JI Milit. Med. PD FEB PY 2009 VL 174 IS 2 BP 132 EP 138 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 601LO UT WOS:000278061200007 PM 19317193 ER PT J AU Patursky-Polischuk, I Stolovich-Rain, M Hausner-Hanochi, M Kasir, J Cybulski, N Avruch, J Ruegg, MA Hall, MN Meyuhas, O AF Patursky-Polischuk, Ilona Stolovich-Rain, Miri Hausner-Hanochi, Mirit Kasir, Judith Cybulski, Nadine Avruch, Joseph Rueegg, Markus A. Hall, Michael N. Meyuhas, Oded TI The TSC-mTOR Pathway Mediates Translational Activation of TOP mRNAs by Insulin Largely in a Raptor- or Rictor-Independent Manner SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID RIBOSOMAL-PROTEIN; RPS6 PHOSPHORYLATION; LENTIVIRAL VECTOR; HUMAN-DISEASE; CELL-CYCLE; S6 KINASE; RAPAMYCIN; RHEB; EXPRESSION; STIMULATION AB The stimulatory effect of insulin on protein synthesis is due to its ability to activate various translation factors. We now show that insulin can increase protein synthesis capacity also by translational activation of TOP mRNAs encoding various components of the translation machinery. This translational activation involves the tuberous sclerosis complex (TSC), as the knockout of TSC1 or TSC2 rescues TOP mRNAs from translational repression in mitotically arrested cells. Similar results were obtained upon overexpression of Rheb, an immediate TSC1-TSC2 target. The role of mTOR, a downstream effector of Rheb, in translational control of TOP mRNAs has been extensively studied, albeit with conflicting results. Even though rapamycin fully blocks mTOR complex 1 (mTORC1) kinase activity, the response of TOP mRNAs to this drug varies from complete resistance to high sensitivity. Here we show that mTOR knockdown blunts the translation efficiency of TOP mRNAs in insulin-treated cells, thus unequivocally establishing a role for mTOR in this mode of regulation. However, knockout of the raptor or rictor gene has only a slight effect on the translation efficiency of these mRNAs, implying that mTOR exerts its effect on TOP mRNAs through a novel pathway with a minor, if any, contribution of the canonical mTOR complexes mTORC1 and mTORC2. This conclusion is further supported by the observation that raptor knockout renders the translation of TOP mRNAs rapamycin hypersensitive. C1 [Patursky-Polischuk, Ilona; Stolovich-Rain, Miri; Hausner-Hanochi, Mirit; Kasir, Judith; Meyuhas, Oded] Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Biochem, IL-91120 Jerusalem, Israel. [Cybulski, Nadine; Rueegg, Markus A.; Hall, Michael N.] Univ Basel, Biozentrum, CH-4056 Basel, Switzerland. [Avruch, Joseph] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Avruch, Joseph] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Avruch, Joseph] Massachusetts Gen Hosp, Med Serv, Diabet Unit, Boston, MA 02114 USA. RP Meyuhas, O (reprint author), Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Biochem, POB 12272, IL-91120 Jerusalem, Israel. EM meyuhas@cc.huji.ac.il FU United States-Israel Binational Science Foundation [BSF 2005034]; Israel Science Foundation [296/05]; German-Israeli Foundation [819/05f]; Otto Stieber Foundation; Swiss National Science Foundation; Canton of Basel FX We thank Howard Green for the 3T3-L1 cells, Derek LeRoith for the NIH-IR cells, David Kwiatkowski for the TSC2+/+/p53-/-, TSC2-/-/p53-/-, TSC1+/+, and TSC1-/- MEF lines (26), John Blenis for the FLAG-Rheb plasmid, Kum-Liang Guan for the Myc-Rheb(5A) plasmid, Akira Kurisaki for the pcDNA3-6myc-hFKBP12 plasmid, and Michal Gropp for the Sin18 plasmid. NR 61 TC 77 Z9 79 U1 1 U2 5 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 FEB 1 PY 2009 VL 29 IS 3 BP 640 EP 649 DI 10.1128/MCB.00980-08 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 396RP UT WOS:000262609100003 PM 19047368 ER PT J AU Chen, YT Hims, MM Shetty, RS Mull, J Liu, LJ Leyne, M Slaugenhaupt, SA AF Chen, Yei-Tsung Hims, Matthew M. Shetty, Ranjit S. Mull, James Liu, Lijuan Leyne, Maire Slaugenhaupt, Susan A. TI Loss of Mouse Ikbkap, a Subunit of Elongator, Leads to Transcriptional Deficits and Embryonic Lethality That Can Be Rescued by Human IKBKAP SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID B KINASE COMPLEX; FAMILIAL DYSAUTONOMIA; HISTONE ACETYLATION; TIE2 RECEPTOR; CELL-DEATH; GENE; PROTEIN; IKAP; HEMATOPOIESIS; MUTATION AB Familial dysautonomia (FD), a devastating hereditary sensory and autonomic neuropathy, results from an intronic mutation in the IKBKAP gene that disrupts normal mRNA splicing and leads to tissue-specific reduction of IKBKAP protein (IKAP) in the nervous system. To better understand the roles of IKAP in vivo, an Ikbkap knockout mouse model was created. Results from our study show that ablating Ikbkap leads to embryonic lethality, with no homozygous Ikbkap knockout (Ikbkap(-/-)) embryos surviving beyond 12.5 days postcoitum. Morphological analyses of the Ikbkap(-/-) conceptus at different stages revealed abnormalities in both the visceral yolk sac and the embryo, including stunted extraembryonic blood vessel formation, delayed entry into midgastrulation, disoriented dorsal primitive neural alignment, and failure to establish the embryonic vascular system. Further, we demonstrate downregulation of several genes that are important for neurulation and vascular development in the Ikbkap(-/-) embryos and show that this correlates with a defect in transcriptional elongation-coupled histone acetylation. Finally, we show that the embryonic lethality resulting from Ikbkap ablation can be rescued by a human IKBKAP transgene. For the first time, we demonstrate that IKAP is crucial for both vascular and neural development during embryogenesis and that protein function is conserved between mouse and human. C1 [Slaugenhaupt, Susan A.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Slaugenhaupt, SA (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, CPZN-5254,185 Cambridge St, Boston, MA 02114 USA. EM Slaugenhaupt@chgr.mgh.harvard.edu FU Dysautonomia Foundation, Inc.,; National Institute for Neurological Disorders and Stroke FX This work was supported by grants from the Dysautonomia Foundation, Inc., and the National Institute for Neurological Disorders and Stroke. NR 49 TC 41 Z9 42 U1 0 U2 0 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 FEB 1 PY 2009 VL 29 IS 3 BP 736 EP 744 DI 10.1128/MCB.01313-08 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 396RP UT WOS:000262609100011 PM 19015235 ER PT J AU Browning, M Olivova, P van der Veen, K Zhang, XK Cullen, E Rose, M Sims, K Keutzer, J AF Browning, Marsha Olivova, Petra van der Veen, Kristen Zhang, X. Kate Cullen, Emmaline Rose, Michael Sims, Katherine Keutzer, Joan TI Biological variation and sample collection effects on alpha-galactosidase A enzyme measurements in Fabry and non-Fabry populations SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 4th Annual World Symposium of the Lysosomal-Disease-Network CY FEB 13-15, 2009 CL Las Vegas, NV SP Lysosomal Dis Network C1 [van der Veen, Kristen; Sims, Katherine] Massachusetts Gen Hosp, Lysosomal Disorders Unit, Boston, MA 02114 USA. [van der Veen, Kristen; Sims, Katherine] MGH Ctr Human Genet Res, Boston, MA USA. [Sims, Katherine] Harvard Univ, Sch Med, Boston, MA USA. [Olivova, Petra; Zhang, X. Kate; Cullen, Emmaline; Rose, Michael; Keutzer, Joan] Genzyme Corp, Framingham, MA 01701 USA. NR 0 TC 0 Z9 0 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 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 2009 VL 96 IS 2 MA 17 BP S15 EP S16 DI 10.1016/j.ymgme.2008.11.018 PG 2 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 399QG UT WOS:000262813800025 ER PT J AU Cornford, E Hyman, S Cornford, M Suzuki, T Yamagata, T Yamakawa, K Rhee, J Delgado-Escueta, A AF Cornford, Eain Hyman, Shigeyo Cornford, Marcia Suzuki, Toshimitsu Yamagata, Tetsushi Yamakawa, Kazuhiro Rhee, Jennifer Delgado-Escueta, Antonio TI Immunoliposome-based, non-viral gene delivery in a knock-out mouse model of Lafora inclusion body disease SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 4th Annual World Symposium of the Lysosomal-Disease-Network CY FEB 13-15, 2009 CL Las Vegas, NV SP Lysosomal Dis Network C1 [Cornford, Eain; Rhee, Jennifer; Delgado-Escueta, Antonio] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Hyman, Shigeyo; Delgado-Escueta, Antonio] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Cornford, Marcia] Harbor UCLA Med Ctr, Los Angeles, CA USA. [Suzuki, Toshimitsu; Yamagata, Tetsushi; Yamakawa, Kazuhiro] RIKEN Brain Sci Inst, Saitama, Japan. RI Yamakawa, Kazuhiro/N-5050-2015 NR 0 TC 0 Z9 0 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 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 2009 VL 96 IS 2 MA 30 BP S19 EP S19 DI 10.1016/j.ymgme.2008.11.031 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 399QG UT WOS:000262813800038 ER PT J AU Eichler, F Giannikopoulos, O Sathe, S Crawford, K Tifft, C AF Eichler, Florian Giannikopoulos, Ourania Sathe, Swati Crawford, Kim Tifft, Cynthia TI Diagnostic delay in GM2 gangliosidosis SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 5th Annual World Symposium of the Lysosomal-Disease-Network CY FEB 18-20, 2009 CL San Diego, NV SP Lysosomal Dis Network C1 [Eichler, Florian; Giannikopoulos, Ourania; Sathe, Swati; Crawford, Kim; Tifft, Cynthia] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. [Giannikopoulos, Ourania; Sathe, Swati; Crawford, Kim; Tifft, Cynthia] NYU, New York, NY USA. [Giannikopoulos, Ourania; Sathe, Swati; Crawford, Kim; Tifft, Cynthia] Georgetown Univ, Childrens Med Ctr, Washington, DC 20007 USA. NR 0 TC 0 Z9 0 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 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 2009 VL 96 IS 2 MA 48 BP S22 EP S22 DI 10.1016/j.ymgme.2008.11.049 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 399QG UT WOS:000262813800056 ER PT J AU Eichler, F Grodd, W Grant, E Sessa, M Bizzi, A Bley, A Kohlschuetter, A Loes, D Kraegeloh-Mann, I AF Eichler, Florian Grodd, Wolfgang Grant, Ellen Sessa, Maria Bizzi, Alessandra Bley, Annette Kohlschuetter, Alfried Loes, Daniel Kraegeloh-Mann, Ingeborg TI Metachromatic leukodystrophy: A scoring system for brain MR observations SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 5th Annual World Symposium of the Lysosomal-Disease-Network CY FEB 18-20, 2009 CL San Diego, NV SP Lysosomal Dis Network C1 [Eichler, Florian; Grant, Ellen] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. [Grodd, Wolfgang; Kraegeloh-Mann, Ingeborg] Univ Tubingen, D-72074 Tubingen, Germany. [Sessa, Maria; Bizzi, Alessandra] Ist Sci San Raffaele, I-20132 Milan, Italy. [Bley, Annette; Kohlschuetter, Alfried] Univ Med Ctr Hamburg Eppendorf, Hamburg, Germany. NR 0 TC 0 Z9 0 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 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 2009 VL 96 IS 2 MA 47 BP S22 EP S22 DI 10.1016/j.ymgme.2008.11.048 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 399QG UT WOS:000262813800055 ER PT J AU Slaugenhaupt, S Curcio-Morelli, C Charles, F Venugopal, B Cao, Y Browning, M Walkley, S Pickel, J Cotman, S Purpura, DP AF Slaugenhaupt, Susan Curcio-Morelli, Cyntia Charles, Florie Venugopal, Bhuvarahamurthy Cao, Yi Browning, Marsha Walkley, Steven Pickel, James Cotman, Susan Purpura, Dominck P. TI Characterization of neuronal storage in the mucolipidosis type IV murine model SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 4th Annual World Symposium of the Lysosomal-Disease-Network CY FEB 13-15, 2009 CL Las Vegas, NV SP Lysosomal Dis Network C1 [Slaugenhaupt, Susan; Curcio-Morelli, Cyntia; Charles, Florie; Venugopal, Bhuvarahamurthy; Cao, Yi; Browning, Marsha; Cotman, Susan] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Slaugenhaupt, Susan; Curcio-Morelli, Cyntia; Charles, Florie; Venugopal, Bhuvarahamurthy; Cao, Yi; Browning, Marsha; Cotman, Susan] Harvard Univ, Sch Med, Boston, MA USA. [Walkley, Steven; Purpura, Dominck P.] Albert Einstein Coll Med, Rose F Kennedy Ctr, Dept Neurosci, Bronx, NY 10467 USA. [Pickel, James] Natl Inst Hlth, NIMH Transgen Core, Bethesda, MD USA. NR 0 TC 0 Z9 0 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 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 2009 VL 96 IS 2 MA 134 BP S41 EP S42 DI 10.1016/j.ymgme.2008.11.135 PG 2 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 399QG UT WOS:000262813800142 ER PT J AU Saxena, S Gorbis, E O'Neill, J Baker, SK Mandelkern, MA Maidment, KM Chang, S Salamon, N Brody, AL Schwartz, JM London, ED AF Saxena, S. Gorbis, E. O'Neill, J. Baker, S. K. Mandelkern, M. A. Maidment, K. M. Chang, S. Salamon, N. Brody, A. L. Schwartz, J. M. London, E. D. TI Rapid effects of brief intensive cognitive-behavioral therapy on brain glucose metabolism in obsessive-compulsive disorder SO MOLECULAR PSYCHIATRY LA English DT Article DE obsessive-compulsive disorder; cognitive-behavioral therapy; intensive treatment; functional neuroimaging; positron emission tomography; anterior cingulate ID CEREBRAL-BLOOD-FLOW; ANTERIOR CINGULATE CORTEX; POSITRON-EMISSION-TOMOGRAPHY; SEROTONIN REUPTAKE INHIBITORS; MAJOR DEPRESSION; SYMPTOM PROVOCATION; UNMEDICATED PATIENTS; RESPONSE PREVENTION; CONTROLLED TRIAL; FDG-PET AB Brief intensive cognitive-behavioral therapy (CBT) using exposure and response prevention significantly improves obsessive-compulsive disorder (OCD) symptoms in as little as 4 weeks. However, it has been thought that much longer treatment was needed to produce the changes in brain function seen in neuroimaging studies of OCD. We sought to elucidate the brain mediation of response to brief intensive CBT for OCD and determine whether this treatment could induce functional brain changes previously seen after longer trials of pharmacotherapy or standard CBT. [(18)F]-fluorodeoxyglucose positron emission tomography brain scans were obtained on 10 OCD patients before and after 4 weeks of intensive individual CBT. Twelve normal controls were scanned twice, several weeks apart, without treatment. Regional glucose metabolic changes were compared between groups. OCD symptoms, depression, anxiety and overall functioning improved robustly with treatment. Significant changes in normalized regional glucose metabolism were seen after brief intensive CBT (P = 0.04). Compared to controls, OCD patients showed significant bilateral decreases in normalized thalamic metabolism with intensive CBT but had a significant increase in right dorsal anterior cingulate cortex activity that correlated strongly with the degree of improvement in OCD symptoms (P = 0.02). The rapid response of OCD to intensive CBT is mediated by a distinct pattern of changes in regional brain function. Reduction of thalamic activity may be a final common pathway for improvement in OCD, but response to intensive CBT may require activation of dorsal anterior cingulate cortex, a region involved in reappraisal and suppression of negative emotions. C1 [Saxena, S.] Univ Calif San Diego, Sch Med, Dept Psychiat, La Jolla, CA 92093 USA. [Gorbis, E.; O'Neill, J.; Baker, S. K.; Maidment, K. M.; Chang, S.; Brody, A. L.; Schwartz, J. M.; London, E. D.] Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst Neurosci & Human Behav, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Mandelkern, M. A.; Brody, A. L.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Salamon, N.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiol, Los Angeles, CA 90095 USA. RP Saxena, S (reprint author), Univ Calif San Diego, Obsess Compuls Disorders Program, Dept Psychiat, VA San Diego Healthcare Syst, 3350 La Jolla Village Dr, San Diego, CA 92161 USA. EM ssaxena@ucsd.edu FU NIMH [R01 MH069433]; Brain Mapping Medical Research Organization; Brain Mapping Support Foundation; Pierson-Lovelace Foundation; Ahmanson Foundation; Tamkin Foundation; Jennifer Jones-Simon Foundation; Capital Group Companies Charitable Foundation; Northern Piedmont Community Foundation; National Center for Research Resources [RR12169, RR13642, RR08655] FX This work was supported by an NIMH grant (R01 MH069433) to Dr Saxena and by donations to the Westwood Institute for Anxiety Disorders (Dr Gorbis). For generous support, we thank the Brain Mapping Medical Research Organization, Brain Mapping Support Foundation, Pierson- Lovelace Foundation, Ahmanson Foundation, Tamkin Foundation, Jennifer Jones-Simon Foundation, Capital Group Companies Charitable Foundation, Robson Family, William M and Linda R Dietel Philanthropic Fund at the Northern Piedmont Community Foundation, Northstar Fund and the National Center for Research Resources grants RR12169, RR13642 and RR08655. This work was presented in part at the American College of Neuropsychopharmacology 43rd Annual Meeting (San Juan, Puerto Rico, 15 December 2004). NR 70 TC 63 Z9 65 U1 4 U2 24 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD FEB PY 2009 VL 14 IS 2 BP 197 EP 205 DI 10.1038/sj.mp.4002134 PG 9 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 395VD UT WOS:000262550700009 PM 18180761 ER PT J AU Tyler, KL AF Tyler, Kenneth L. TI Prednisolone-but not antiviral drugs-improves outcome in patients with Bell's palsy SO NATURE CLINICAL PRACTICE NEUROLOGY LA English DT Editorial Material DE acyclovir; Bell's palsy; peripheral facial palsy; prednisolone; valacyclovir ID HERPES-SIMPLEX-VIRUS; DOUBLE-BLIND; VALACYCLOVIR; REACTIVATION; MULTICENTER; ACYCLOVIR; TYPE-1; TRIAL AB Randomized, double-blind, placebo-controlled trials have provided compelling evidence that treatment with prednisolone improves outcome in patients with acute idiopathic peripheral facial ( Bell's) palsy. The low rate of adverse effects, the small number needed to treat, and the modest cost of therapy indicate that prednisolone should be used in all patients with facial palsy of <72 h duration who do not have contraindications to steroid therapy. By contrast, the best-designed recent clinical trials have failed to suggest any significant beneficial effect on Bell's palsy of treatment with acyclovir or valacyclovir, either as single agents or in combination with prednisolone. Antiviral therapy should not, therefore, be routinely used in the treatment of Bell's palsy. C1 [Tyler, Kenneth L.] Univ Colorado, Denver Hlth Sci Ctr, Denver, CO 80202 USA. [Tyler, Kenneth L.] Denver Vet Affairs Med Ctr, Neurol Serv, Denver, CO USA. RP Tyler, KL (reprint author), Univ Colorado, Denver Hlth Sci Ctr, Dept Neurol, B-182,RC-2,12700 E 19th Ave, Aurora, CO 80045 USA. EM ken.tyler@uchsc.edu OI Tyler, Kenneth/0000-0003-3294-5888 NR 10 TC 6 Z9 6 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1745-834X J9 NAT CLIN PRACT NEURO JI Nat. Clin. Pract. Neurol. PD FEB PY 2009 VL 5 IS 2 BP 74 EP 75 DI 10.1038/ncpneuro1002 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 403OB UT WOS:000263090800005 PM 19139743 ER PT J AU Morris, REA Guimaraes, AR AF Morris, Richard E. A. Guimaraes, Alexander R. TI A case of an asymptomatic hypoechoic testicular mass in the setting of contralateral orchitis SO NATURE CLINICAL PRACTICE UROLOGY LA English DT Article DE focal; orchitis; pseudolesion; sonography; testis ID ULTRASOUND; TUMORS AB Background A 28-year-old heterosexual man presented to an emergency department with a 2-day history of left testicular pain and swelling that began after he started having unprotected sex with a new partner. He also had a 1-day history of fever and chills. Investigations Physical examination, urinalysis, complete blood count, polymerase chain reaction testing for gonorrhea and chlamydia, serial scrotal ultrasonography with color Doppler imaging, and measurement of serum tumor marker levels. Diagnosis Left orchitis with right testicular mass suspicious for malignancy. Management The patient received antibiotic therapy (ceftriaxone and azithromycin), which resulted in resolution of his presenting symptoms. He was discharged from hospital with plans to undergo follow-up evaluation by the urology service. He opted to delay surgical intervention; repeat ultrasonography at 4 weeks revealed signs consistent with treated left-sided orchitis and revealed near-complete resolution of the right-sided lesion. The patient's right-sided mass probably represented subclinical bacterial orchitis, which responded to antibiotic therapy. C1 [Morris, Richard E. A.] Waldo Cty Gen Hosp, Belfast, ME 04915 USA. [Guimaraes, Alexander R.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Morris, REA (reprint author), Waldo Cty Gen Hosp, 116 Northport Ave,Suite 216, Belfast, ME 04915 USA. EM richard_morris_md98@post.harvard.edu NR 18 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1743-4270 J9 NAT CLIN PRACT UROL JI Nat. Clin. Pract. Urol. PD FEB PY 2009 VL 6 IS 2 BP 108 EP 112 DI 10.1038/ncpuro1291 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 407JY UT WOS:000263360600011 PM 19198624 ER PT J AU Weiner, L Brissette, JL AF Weiner, Lorin Brissette, Janice L. TI Hair lost in translation SO NATURE GENETICS LA English DT Editorial Material ID S-ADENOSYLMETHIONINE DECARBOXYLASE; OPEN READING FRAME; HR GENE; MUTATION; ALOPECIA; MOUSE; SKIN AB A new study identifies mutations in the HR gene as the cause of Marie Unna hereditary hypotrichosis (MUHH). The mutations seem to disrupt an unusual leader sequence-based mechanism of translational repression, making MUHH the first example of a disease linked to this form of repression. C1 [Weiner, Lorin] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Weiner, L (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. EM lorin.weiner@cbrc2.mgh.harvard.edu; janice.brissette@cbrc2.mgh.harvard.edu NR 15 TC 1 Z9 1 U1 0 U2 1 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 FEB PY 2009 VL 41 IS 2 BP 141 EP 142 DI 10.1038/ng0209-141 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 403OG UT WOS:000263091300003 PM 19174834 ER PT J AU Ioannidis, JPA Allison, DB Ball, CA Coulibaly, I Cui, XQ Culhane, AC Falchi, M Furlanello, C Game, L Jurman, G Mangion, J Mehta, T Nitzberg, M Page, GP Petretto, E van Noort, V AF Ioannidis, John P. A. Allison, David B. Ball, Catherine A. Coulibaly, Issa Cui, Xiangqin Culhane, Aedin C. Falchi, Mario Furlanello, Cesare Game, Laurence Jurman, Giuseppe Mangion, Jon Mehta, Tapan Nitzberg, Michael Page, Grier P. Petretto, Enrico van Noort, Vera TI Repeatability of published microarray gene expression analyses SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ANALYSIS; REPRODUCIBILITY; ASSOCIATIONS; ARRAYEXPRESS; INFORMATION; REPOSITORY; SIGNATURE; MIAME; CELLS AB Given the complexity of microarray-based gene expression studies, guidelines encourage transparent design and public data availability. Several journals require public data deposition and several public databases exist. However, not all data are publicly available, and even when available, it is unknown whether the published results are reproducible by independent scientists. Here we evaluated the replication of data analyses in 18 articles on microarray-based gene expression profiling published in Nature Genetics in 2005-2006. One table or figure from each article was independently evaluated by two teams of analysts. We reproduced two analyses in principle and six partially or with some discrepancies; ten could not be reproduced. The main reason for failure to reproduce was data unavailability, and discrepancies were mostly due to incomplete data annotation or specification of data processing and analysis. Repeatability of published microarray studies is apparently limited. More strict publication rules enforcing public data availability and explicit description of data processing and analysis should be considered. C1 [Ioannidis, John P. A.] Univ Ioannina, Sch Med, Clin & Mol Epidemiol Unit, Dept Hyg & Epidemiol, GR-45110 Ioannina, Greece. [Ioannidis, John P. A.] Fdn Res & Technol Hellas, Biomed Res Inst, Ioannina 45110, Greece. [Ioannidis, John P. A.] Tufts Univ, Sch Med, Ctr Genet Epidemiol & Modeling, Tufts Med Ctr, Boston, MA 02111 USA. [Ioannidis, John P. A.] Tufts Univ, Sch Med, Dept Med, Boston, MA 02111 USA. [Allison, David B.; Coulibaly, Issa; Cui, Xiangqin; Mehta, Tapan; Page, Grier P.] Univ Alabama, Dept Biostat, Sect Stat Genet, Birmingham, AL 35294 USA. [Ball, Catherine A.; Nitzberg, Michael] Stanford Univ, Dept Biochem, Sch Med, Stanford, CA 94305 USA. [Culhane, Aedin C.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Culhane, Aedin C.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Falchi, Mario] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Fac Med, London W12 0NN, England. [Falchi, Mario] Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England. [Furlanello, Cesare; Jurman, Giuseppe] Fdn Bruno Kessler, I-38100 Trento, Italy. [Game, Laurence; Mangion, Jon; Petretto, Enrico] Hammersmith Hosp, MRC, Ctr Clin Sci, Microarray Ctr, London W12 0NN, England. [Page, Grier P.] RTI Int, Stat & Epidemiol Unit, Atlanta, GA 30341 USA. [Petretto, Enrico] Univ London Imperial Coll Sci Technol & Med, Fac Med, Dept Epidemiol Publ Hlth & Primary Care, London W2 1PG, England. [van Noort, Vera] European Mol Biol Lab, D-69117 Heidelberg, Germany. RP Ioannidis, JPA (reprint author), Univ Ioannina, Sch Med, Clin & Mol Epidemiol Unit, Dept Hyg & Epidemiol, GR-45110 Ioannina, Greece. EM jioannid@cc.uoi.gr RI van Noort, Vera/E-1053-2011; Ioannidis, John/G-9836-2011; Falchi, Mario/F-5956-2013; OI van Noort, Vera/0000-0002-8436-6602; Furlanello, Cesare/0000-0002-5384-3605; Cui, Xiangqin/0000-0003-0621-9313; Allison, David/0000-0003-3566-9399; Jurman, Giuseppe/0000-0002-2705-5728 FU Medical Research Council [MC_U120097112]; NCI NIH HHS [R01 CA098522] NR 42 TC 201 Z9 206 U1 3 U2 29 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 FEB PY 2009 VL 41 IS 2 BP 149 EP 155 DI 10.1038/ng.295 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 403OG UT WOS:000263091300011 PM 19174838 ER PT J AU Silverberg, MS Cho, JH Rioux, JD McGovern, DPB Wu, J Annese, V Achkar, JP Goyette, P Scott, R Xu, W Barmada, MM Klei, L Daly, MJ Abraham, C Bayless, TM Bossa, F Griffiths, AM Ippoliti, AF Lahaie, RG Latiano, A Pare, P Proctor, DD Regueiro, MD Steinhart, AH Targan, SR Schumm, LP Kistner, EO Lee, AT Gregersen, PK Rotter, JI Brant, SR Taylor, KD Roeder, K Duerr, RH AF Silverberg, Mark S. Cho, Judy H. Rioux, John D. McGovern, Dermot P. B. Wu, Jing Annese, Vito Achkar, Jean-Paul Goyette, Philippe Scott, Regan Xu, Wei Barmada, M. Michael Klei, Lambertus Daly, Mark J. Abraham, Clara Bayless, Theodore M. Bossa, Fabrizio Griffiths, Anne M. Ippoliti, Andrew F. Lahaie, Raymond G. Latiano, Anna Pare, Pierre Proctor, Deborah D. Regueiro, Miguel D. Steinhart, A. Hillary Targan, Stephan R. Schumm, L. Philip Kistner, Emily O. Lee, Annette T. Gregersen, Peter K. Rotter, Jerome I. Brant, Steven R. Taylor, Kent D. Roeder, Kathryn Duerr, Richard H. TI Ulcerative colitis-risk loci on chromosomes 1p36 and 12q15 found by genome-wide association study SO NATURE GENETICS LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; CROHNS-DISEASE; SUSCEPTIBILITY LOCI; SEQUENCE VARIANTS; GENE; EXPRESSION; MULTIPLE; PATHOGENESIS; REPLICATION; CONTRIBUTE AB Ulcerative colitis is a chronic inflammatory disease of the colon that presents as diarrhea and gastrointestinal bleeding. We performed a genome-wide association study using DNA samples from 1,052 individuals with ulcerative colitis and preexisting data from 2,571 controls, all of European ancestry. In an analysis that controlled for gender and population structure, ulcerative colitis loci attaining genome-wide significance and subsequent replication in two independent populations were identified on chromosomes 1p36 (rs6426833, combined P = 5.1 x 10(-13), combined odds ratio OR = 0.73) and 12q15 (rs1558744, combined P = 2.5 x 10(-12), combined OR = 1.35). In addition, combined genome-wide significant evidence for association was found in a region spanning BTNL2 to HLA-DQB1 on chromosome 6p21 (rs2395185, combined P = 1.0 x 10(-16), combined OR = 0.66) and at the IL23R locus on chromosome 1p31 (rs11209026, combined P = 1.3 x 10(-8), combined OR = 0.56; rs10889677, combined P = 1.3 x 10(-8), combined OR = 1.29). C1 [Silverberg, Mark S.; Steinhart, A. Hillary] Univ Toronto, Mt Sinai Hosp, Inflammatory Bowel Dis Grp, Toronto, ON M5G 1X5, Canada. [Cho, Judy H.; Proctor, Deborah D.] Yale Univ, Sect Digest Dis, Dept Med, New Haven, CT 06520 USA. [Cho, Judy H.] Yale Univ, Dept Genet, New Haven, CT 06520 USA. [Rioux, John D.; Goyette, Philippe; Abraham, Clara] Univ Montreal, Montreal, PQ H1T 1C8, Canada. [Rioux, John D.; Goyette, Philippe] Montreal Heart Inst, Res Ctr, Montreal, PQ H1T 1C8, Canada. [McGovern, Dermot P. B.; Ippoliti, Andrew F.; Targan, Stephan R.; Rotter, Jerome I.; Taylor, Kent D.] Cedars Sinai Med Ctr, Ctr Inflammatory Bowel Dis, Los Angeles, CA 90048 USA. [Wu, Jing; Roeder, Kathryn] Carnegie Mellon Univ, Dept Stat, Pittsburgh, PA 15213 USA. [Annese, Vito; Bossa, Fabrizio; Latiano, Anna] IRCCS CSS Hosp, I-71013 San Giovanni Rotondo, FG, Italy. [Achkar, Jean-Paul] Cleveland Clin, Inst Digest Dis, Cleveland, OH 44195 USA. [Scott, Regan; Regueiro, Miguel D.; Duerr, Richard H.] Univ Pittsburgh, Dept Med, Div Gastroenterol Hepatol & Nutr, Sch Med,UPMC PUH, Pittsburgh, PA 15213 USA. [Xu, Wei] Univ Toronto, Princess Margaret Hosp, Dept Publ Hlth Sci, Toronto, ON M5G 2M9, Canada. [Barmada, M. Michael; Duerr, Richard H.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA. [Klei, Lambertus] Univ Pittsburgh, Med Ctr, Dept Psychiat, Pittsburgh, PA 15213 USA. [Daly, Mark J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA 02114 USA. [Bayless, Theodore M.; Brant, Steven R.] Johns Hopkins Univ, Sch Med, Dept Med, Harvey M & Lyn P Meyerhoff Infammatory Bowel Dis, Baltimore, MD 21287 USA. [Griffiths, Anne M.] Hosp Sick Children, Dept Pediat, Toronto, ON M5G 1X8, Canada. [Lahaie, Raymond G.] Univ Montreal, Dept Med, Montreal, PQ H2X 3J4, Canada. [Lahaie, Raymond G.] CHUM, Hop St Luc, Montreal, PQ H2X 3J4, Canada. [Pare, Pierre; Rotter, Jerome I.] Univ Laval, Dept Med, Div Gastroenterol, Quebec City, PQ G1K 7P4, Canada. [Pare, Pierre] CHAUQ Hop St Sacrement, Ste Foy, PQ G1S 4L8, Canada. [Schumm, L. Philip; Kistner, Emily O.] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. [Lee, Annette T.; Gregersen, Peter K.] Feinstein Inst Med Res, Manhasset, NY 11030 USA. [Taylor, Kent D.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Brant, Steven R.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21231 USA. RP Duerr, RH (reprint author), Univ Toronto, Mt Sinai Hosp, Inflammatory Bowel Dis Grp, 600 Univ Ave, Toronto, ON M5G 1X5, Canada. EM duerr@pitt.edu RI Silverberg, Mark/B-4183-2008; Rioux, John/A-9599-2015; Latiano, Anna/R-1965-2016; Bossa, Fabrizio/B-3078-2017 OI Duerr, Richard/0000-0001-6586-3905; Barmada, M Michael/0000-0002-3604-6460; Rioux, John/0000-0001-7560-8326; Latiano, Anna/0000-0003-3719-2061; Bossa, Fabrizio/0000-0002-4518-9949 FU NIDDK IBD Genetics Consortium [DK062431, DK062422, DK062420, DK062432, DK062423, DK062413, DK062429]; Atran Foundation; Board of Governor's Chair in Medical Genetics at Cedars-Sinai Medical Center; Bohmfalk Funds for Medical Research; Burroughs Wellcome Medical Foundation; Crohn's and Colitis Foundation of America; Crohn's and Colitis Foundation of Canada; Feintech Chair in Immunobiology; Gale and Graham Wright Research Chair in Digestive Diseases; Harvey M. and Lyn P. Meyerhoff Inflammatory Bowel Disease Center; US National Institutes of Health [RR00052, DK077905, DK068112, DK072373, RR024139, DK076025, DK064869, MH057881, DK046763, RR00425]; Rainin IBD Genetics Research Fund; W. Buford Lewis family FX Thanks to L. Wu Datta, J. Fultz and J. Stempak for coordinating study subject recruitment, to A. Andriulli and O. Palmieri for providing clinical data and to J. Lian, A. Liew and H. Khalili for technical support. The NIDDK IBD Genetics Consortium is funded by the following grants: DK062431 (S. R. B.), DK062422 (J. H. C.), DK062420 (R. H. D.), DK062432 (J. D. R.), DK062423 (M. S. S.), DK062413 (K. D. T.) and DK062429 (J. H. C.). The authors would also like to acknowledge additional support from the Atran Foundation (S. R. B.), Board of Governor's Chair in Medical Genetics at Cedars-Sinai Medical Center (J. I. R.), Bohmfalk Funds for Medical Research (J. H. C.), Burroughs Wellcome Medical Foundation (J. H. C.), Crohn's and Colitis Foundation of America (C. A., T. M. B., S. R. B., J. H. C., R. H. D., J. D. R.), Crohn's and Colitis Foundation of Canada (M. S. S.), Feintech Chair in Immunobiology (S. R. T.), Gale and Graham Wright Research Chair in Digestive Diseases (M. S. S.), Harvey M. and Lyn P. Meyerhoff Inflammatory Bowel Disease Center (T. M. B., S. R. B.), US National Institutes of Health grants RR00052 (S. R. B.), DK077905 (C. A.), DK068112 (J.-P. A.), DK072373 (J. H. C.), RR024139 H. C.), DK076025 (R. H. D.), DK064869 (J. D. R.), MH057881 (K. R.), DK046763 (J. I. R., S. R. T., K. D. T.) and RR00425 (K. D. T.), the Rainin IBD Genetics Research Fund (J.-P. A.) and the W. Buford Lewis family (S. R. B.). NR 28 TC 230 Z9 239 U1 0 U2 5 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 FEB PY 2009 VL 41 IS 2 BP 216 EP 220 DI 10.1038/ng.275 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 403OG UT WOS:000263091300023 PM 19122664 ER PT J AU Kerdiles, YM Beisner, DR Tinoco, R Dejean, AS Castrillon, DH DePinho, RA Hedrick, SM AF Kerdiles, Yann M. Beisner, Daniel R. Tinoco, Roberto Dejean, Anne S. Castrillon, Diego H. DePinho, Ronald A. Hedrick, Stephen M. TI Foxo1 links homing and survival of naive T cells by regulating L-selectin, CCR7 and interleukin 7 receptor SO NATURE IMMUNOLOGY LA English DT Article ID FORKHEAD TRANSCRIPTION FACTOR; PHOSPHATIDYLINOSITOL 3-KINASE; IN-VIVO; TRANSGENIC MICE; FACTOR FKHR-L1; IMMUNE-SYSTEM; FAMILY-MEMBER; HOMEOSTASIS; EXPRESSION; IL-7 AB Foxo transcription factors have a conserved role in the adaptation of cells and organisms to nutrient and growth factor availability. Here we show that Foxo1 has a crucial, nonredundant role in T cells. In naive T cells, Foxo1 controlled the expression of the adhesion molecule L-selectin, the chemokine receptor CCR7 and the transcription factor Klf2, and its deletion was sufficient to alter lymphocyte trafficking. Furthermore, Foxo1 deficiency resulted in a severe defect in interleukin 7 receptor alpha-chain (IL-7R alpha) expression associated with its ability to bind an Il7r enhancer. Finally, growth factor withdrawal induced a Foxo1-dependent increase in Sell, Klf2 and Il7r expression. These data suggest that Foxo1 regulates the homeostasis and life span of naive T cells by sensing growth factor availability and regulating homing and survival signals. C1 [Kerdiles, Yann M.; Beisner, Daniel R.; Tinoco, Roberto; Dejean, Anne S.; Hedrick, Stephen M.] Univ Calif San Diego, Mol Biol Sect, Div Biol Sci, La Jolla, CA 92093 USA. [Kerdiles, Yann M.; Beisner, Daniel R.; Tinoco, Roberto; Dejean, Anne S.; Hedrick, Stephen M.] Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA. [Castrillon, Diego H.; DePinho, Ronald A.] Harvard Univ, Sch Med, Dana Farber Canc Inst,Dept Adult Oncol, Ctr Appl Canc Sci,Belfer Inst Innovat Canc Sci, Boston, MA 02115 USA. [Castrillon, Diego H.; DePinho, Ronald A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. [Castrillon, Diego H.; DePinho, Ronald A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Genet, Boston, MA 02115 USA. RP Hedrick, SM (reprint author), Univ Calif San Diego, Mol Biol Sect, Div Biol Sci, La Jolla, CA 92093 USA. EM shedrick@ucsd.edu RI Dejean, Anne/K-6739-2014 FU University of California; San Diego Division of Biological Sciences FX We thank W. D'Souza and M. McGargill for discussions and assistance with adoptive transfer experiments; T. Ludwig (Columbia University) for ERCre mice; C. Murre (University of California at San Diego) for PTENf/f-ERCre mice; H. Cheroutre (La Jolla Institute for Allergy and Immunology) for Il7r-/- mice; S. Kaech for identifying the evolutionarily conserved regions of Il7r; and A. Goldrath and P. Marrack for critical reading of the manuscript. Supported by funds made available by the University of California, San Diego Division of Biological Sciences. NR 62 TC 238 Z9 241 U1 2 U2 13 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 FEB PY 2009 VL 10 IS 2 BP 176 EP 184 DI 10.1038/ni.1689 PG 9 WC Immunology SC Immunology GA 404UM UT WOS:000263178500011 PM 19136962 ER PT J AU Ali, OA Huebsch, N Cao, L Dranoff, G Mooney, DJ AF Ali, Omar A. Huebsch, Nathaniel Cao, Lan Dranoff, Glenn Mooney, David J. TI Infection-mimicking materials to program dendritic cells in situ SO NATURE MATERIALS LA English DT Article ID GROWTH-FACTOR DELIVERY; CANCER-IMMUNOTHERAPY; ANTITUMOR IMMUNITY; T-CELLS; MELANOMA; VACCINES; RECEPTOR; MATURATION; SCAFFOLDS; VITILIGO AB Cancer vaccines typically depend on cumbersome and expensive manipulation of cells in the laboratory, and subsequent cell transplantation leads to poor lymph-node homing and limited efficacy. We propose that materials mimicking key aspects of bacterial infection may instead be used to directly control immune-cell trafficking and activation in the body. It is demonstrated that polymers can be designed to first release a cytokine to recruit and house host dendritic cells, and subsequently present cancer antigens and danger signals to activate the resident dendritic cells and markedly enhance their homing to lymph nodes. Specific and protective anti-tumour immunity was generated with these materials, as 90% survival was achieved in animals that otherwise die from cancer within 25 days. These materials show promise as cancer vaccines, and more broadly suggest that polymers may be designed to program and control the trafficking of a variety of cell types in the body. C1 [Ali, Omar A.; Huebsch, Nathaniel; Cao, Lan; Mooney, David J.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Huebsch, Nathaniel] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02138 USA. [Dranoff, Glenn] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Dranoff, Glenn] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. [Dranoff, Glenn] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Dranoff, Glenn] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Mooney, David J.] Wyss Inst Biologically Inspired Engn, Cambridge, MA 02138 USA. RP Ali, OA (reprint author), Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. EM mooneyd@seas.harvard.edu FU NIH [R01 DE013033] FX We are grateful to the Bauer research centres at Harvard University for assistance in NanoDrop measurements of nucleotide content. We thank B. Tilton for technical assistance with flow cytometry. The project has been made possible by NIH financial support (NIH R01 DE013033) and internal financial support at Harvard University to D.J.M NR 34 TC 110 Z9 111 U1 7 U2 68 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1476-1122 J9 NAT MATER JI Nat. Mater. PD FEB PY 2009 VL 8 IS 2 BP 151 EP 158 DI 10.1038/NMAT2357 PG 8 WC Chemistry, Physical; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Materials Science; Physics GA 403NZ UT WOS:000263090600017 PM 19136947 ER EF