FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Pope, C Davis, BH AF Pope, Charlene Davis, Boyd H. TI Finding a balance: The Carolinas Conversation Collection SO CORPUS LINGUISTICS AND LINGUISTIC THEORY LA English DT Article DE sociolinguistics; health; chronic disease; Alzheimer's disease; ONZE Miner; ethnic groups; social determinants of health ID VISTA-CLINICAL-TRIAL; ALZHEIMERS-DISEASE; CULTURAL COMPETENCE; VERBAL REPETITION; INFORMATION; HEALTH; GALANTAMINE; PEOPLE; COMMUNICATION; DEMENTIA AB The Carolinas Conversations Collection is a password-protected digital collection of transcribed audio and video recordings of conversations about health, supported by the National Libraries of Medicine. It has two cohorts: 125 unimpaired multiethnic older speakers with any of 12 chronic conditions and a longitudinal set of 400 conversations with 125 persons having dementia. Information about health literacy, health status, and cognitive function requires high standards for privacy and confidentiality, and restricted data use agreements. Since contents are housed in an adaptation of the well-established ONZE Miner, users can search and perform online analysis of sound, word or syntax with increasing specificity. C1 [Pope, Charlene] Med Univ S Carolina, Coll Nursing, Charleston, SC 29425 USA. [Pope, Charlene] Ralph H Johnson Vet Affairs VA Med Ctr, Charleston, SC USA. [Davis, Boyd H.] Univ N Carolina Charlotte, Charlotte, NC USA. RP Pope, C (reprint author), Med Univ S Carolina, Coll Nursing, Charleston, SC 29425 USA. EM popec@musc.edu; boydhdavis@yahoo.com OI Davis, Boyd/0000-0003-4773-7715 NR 64 TC 3 Z9 3 U1 0 U2 3 PU MOUTON DE GRUYTER PI BERLIN PA GENTHINER STRASSE 13, 10785 BERLIN, GERMANY SN 1613-7027 J9 CORPUS LINGUIST LING JI Corpus Linguist. Linguist. Theo. PD MAY PY 2011 VL 7 IS 1 SI SI BP 143 EP 161 DI 10.1515/CLLT.2011.007 PG 19 WC Linguistics; Language & Linguistics SC Linguistics GA 776MK UT WOS:000291539000007 ER PT J AU Bell, PD Fitzgibbon, W Sas, K Stenbitt, AE Amria, M Houston, A Reichert, R Gilley, S Siegal, GP Bissler, J Bilgen, M Chou, PCT Guay-Woodford, L Yoder, B Haycraft, CJ Siroky, B AF Bell, P. Darwin Fitzgibbon, Wayne Sas, Kelli Stenbitt, Antine E. Amria, May Houston, Amber Reichert, Ryan Gilley, Sandra Siegal, Gene P. Bissler, John Bilgen, Mehmet Chou, Peter Cheng-te Guay-Woodford, Lisa Yoder, Brad Haycraft, Courtney J. Siroky, Brian TI Loss of Primary Cilia Upregulates Renal Hypertrophic Signaling and Promotes Cystogenesis SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID POLYCYSTIC KIDNEY-DISEASE; REVERSIBLE COMPENSATORY HYPERTROPHY; PLANAR CELL POLARITY; CYST FORMATION; TUBULOGLOMERULAR FEEDBACK; UNILATERAL NEPHRECTOMY; RAT KIDNEYS; SLOW-ONSET; ADULT MICE; PKD1 AB Primary cilia dysfunction alters renal tubular cell proliferation and differentiation and associates with accelerated cyst formation in polycystic kidney disease. However, the mechanism leading from primary ciliary dysfunction to renal cyst formation is unknown. We hypothesize that primary cilia prevent renal cyst formation by suppressing pathologic tubular cell hypertrophy and proliferation. Unilateral nephrectomy initiates tubular cell hypertrophy and proliferation in the contralateral kidney and provides a tool to examine primary cilia regulation of renal hypertrophy. Conditional knockout of the primary cilia ift88 gene leads to delayed, adult-onset renal cystic disease, which provides a window of opportunity to conduct unilateral nephrectomy and examine downstream kinetics of renal hypertrophy and cyst formation. In wild-type animals, unilateral nephrectomy activated the mTOR pathway and produced appropriate structural and functional hypertrophy without renal cyst formation. However, in ift88 conditional knockout animals, unilateral nephrectomy triggered increased renal hypertrophy and accelerated renal cyst formation, leading to renal dysfunction. mTOR signaling also increased compared with wild-type animals, suggesting a mechanistic cascade starting with primary ciliary dysfunction, leading to excessive mTOR signaling and renal hypertrophic signaling and culminating in cyst formation. These data suggest that events initiating hypertrophic signaling, such as structural or functional loss of renal mass, may accelerate progression of adult polycystic kidney disease toward end-stage renal disease. C1 [Bell, P. Darwin; Fitzgibbon, Wayne; Sas, Kelli; Stenbitt, Antine E.; Amria, May; Houston, Amber; Reichert, Ryan; Gilley, Sandra; Haycraft, Courtney J.] Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. [Bell, P. Darwin] Ralph H Johnson Vet Adm Med Ctr, Charleston, SC USA. [Siegal, Gene P.; Yoder, Brad] Univ Alabama, Dept Cell Biol, Birmingham, AL 35294 USA. [Siegal, Gene P.] Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. [Guay-Woodford, Lisa] Univ Alabama, Dept Genet, Birmingham, AL USA. [Bissler, John; Siroky, Brian] Cincinnati Childrens Hosp, Med Ctr, Dept Pediat, Cincinnati, OH USA. [Bilgen, Mehmet; Chou, Peter Cheng-te] Univ Malaya, Fac Med, Med Ctr, Dept Biomed Imaging, Kuala Lumpur, Malaysia. RP Bell, PD (reprint author), Med Univ S Carolina, Dept Med, Div Nephrol, 173 Ashley Ave,210 CRI, Charleston, SC 29425 USA. EM Bellpd@musc.edu FU VA Merit Grants [P30DK074038, DK32032, P30 AR 46031, P30 DK 079337, DK35534, DK065655, DK061458]; Dialysis Clinic, Inc. FX This project was supported by VA Merit Grants (P.D.B.), P30DK074038 (L.G.W.), DK32032 (P.D.B.), P30 AR 46031 (Siegal Core PI), and P30 DK 079337 (Siegal Core PI), DK35534 (L.G.W.), DK065655 (B.Y.) and DK061458 (J.B.) in addition to funds from Dialysis Clinic, Inc. NR 40 TC 28 Z9 28 U1 0 U2 1 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 MAY PY 2011 VL 22 IS 5 BP 839 EP 848 DI 10.1681/ASN.2010050526 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 776FI UT WOS:000291519500011 PM 21493775 ER PT J AU Raina, D Kosugi, M Ahmad, R Panchamoorthy, G Rajabi, H Alam, M Shimamura, T Shapiro, GI Supko, J Kharbanda, S Kufe, D AF Raina, Deepak Kosugi, Michio Ahmad, Rehan Panchamoorthy, Govind Rajabi, Hasan Alam, Maroof Shimamura, Takeshi Shapiro, Geoffrey I. Supko, Jeffrey Kharbanda, Surender Kufe, Donald TI Dependence on the MUC1-C Oncoprotein in Non-Small Cell Lung Cancer Cells SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID BETA-CATENIN; PHOSPHOINOSITIDE 3-KINASE; ACQUIRED-RESISTANCE; KINASE INHIBITOR; REGULATORY LOOP; C-SRC; GROWTH; RECEPTOR; MUTATIONS; PATHWAYS AB Non-small cell lung cancer (NSCLC) cells are often associated with constitutive activation of the phosphoinositide 3-kinase (PI3K) -> Akt -> mTOR pathway. The mucin 1 (MUC1) heterodimeric glycoprotein is aberrantly overexpressed in NSCLC cells and induces gene signatures that are associated with poor survival of NSCLC patients. The present results show that the MUC1 C-terminal subunit (MUC1-C) cytoplasmic domain associates with PI3K p85 in NSCLC cells. We show that inhibition of MUC1-C with cell-penetrating peptides blocks this interaction with PI3K p85 and suppresses constitutive phosphorylation of Akt and its downstream effector, mTOR. In concert with these results, treatment of NSCLC cells with the MUC1-C peptide inhibitor GO-203 was associated with downregulation of PI3K -> Akt signaling and inhibition of growth. GO-203 treatment was also associated with increases in reactive oxygen species (ROS) and induction of necrosis by a ROS-dependent mechanism. Moreover, GO-203 treatment of H1975 (EGFR L858R/T790M) and A549 (K-Ras G12S) xenografts growing in nude mice resulted in tumor regressions. These findings indicate that NSCLC cells are dependent on MUC1-C both for activation of the PI3K -> Akt pathway and for survival. Mol Cancer Ther; 10(5); 806-16. (C) 2011 AACR. C1 [Kosugi, Michio; Ahmad, Rehan; Rajabi, Hasan; Alam, Maroof; Shimamura, Takeshi; Shapiro, Geoffrey I.; Kufe, Donald] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Supko, Jeffrey] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Raina, Deepak; Panchamoorthy, Govind; Kharbanda, Surender] Genus Oncol Boston, Boston, MA USA. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St,Dana 830, Boston, MA 02115 USA. EM Donald_Kufe@dfci.harvard.edu FU Lung Cancer Research Foundation; National Cancer Institute [CA97098, CA42802]; Genus Oncology FX This study was supported by Lung Cancer Research Foundation and National Cancer Institute grants CA97098 and CA42802. J. Supko received research support from Genus Oncology. NR 49 TC 77 Z9 82 U1 0 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD MAY PY 2011 VL 10 IS 5 BP 806 EP 816 DI 10.1158/1535-7163.MCT-10-1050 PG 11 WC Oncology SC Oncology GA 774ZY UT WOS:000291427000010 PM 21421804 ER PT J AU Scaltriti, M Serra, V Normant, E Guzman, M Rodriguez, O Lim, AR Slocum, KL West, KA Rodriguez, V Prudkin, L Jimenez, J Aura, C Baselga, J AF Scaltriti, Maurizio Serra, Violeta Normant, Emmanuel Guzman, Marta Rodriguez, Olga Lim, Alice R. Slocum, Kelly L. West, Kip A. Rodriguez, Varenka Prudkin, Ludmila Jimenez, Jose Aura, Claudia Baselga, Jose TI Antitumor Activity of the Hsp90 Inhibitor IPI-504 in HER2-Positive Trastuzumab-Resistant Breast Cancer SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID FACTOR-I RECEPTOR; SHOCK-PROTEIN 90; METASTATIC BREAST; MONOCLONAL-ANTIBODY; PHASE-II; 1ST-LINE TREATMENT; SINGLE-AGENT; CELLS; GROWTH; EFFICACY AB Hsp90 facilitates the maturation and stability of numerous oncoproteins, including HER2. The aim of this study was to assess the antitumor activity of the Hsp90 inhibitor IPI-504 in trastuzumab-resistant, HER2-overexpressing breast cancer cells. Therapy with trastuzumab, IPI-504, and the combination of trastuzumab and IPI-504 was evaluated in trastuzumab-sensitive and trastuzumab-resistant cells. Inhibition of protein targets, cell proliferation, and tumor growth was assessed in vitro and in xenograft models. IPI-504 inhibited proliferation of both trastuzumab-sensitive and trastuzumab-resistant cells. Administration of IPI-504 markedly reduced total levels of HER2 and Akt, as well as phosphorylated Akt and mitogen-activated protein kinase (MAPK), to an equal extent in trastuzumab-sensitive and trastuzumab-resistant cells. IPI-504, used as single agent or in combination with trastuzumab, also inhibited in vivo the growth of both trastuzumab-sensitive and -resistant tumor xenografts. As a mechanism for the observed antitumor activity, IPI-504 resulted in a marked decrease in the levels of HER2, Akt, p-Akt, and p-MAPK in trastuzumab-resistant xenografts as early as 12 hours after a single dose of IPI-504. IPI-504-mediated Hsp90 inhibition may represent a novel therapeutic approach in trastuzumab refractory HER2-positive breast cancer. Mol Cancer Ther; 10(5); 817-24. (C) 2011 AACR. C1 [Scaltriti, Maurizio; Baselga, Jose] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. [Scaltriti, Maurizio; Serra, Violeta; Guzman, Marta; Rodriguez, Olga; Baselga, Jose] VHIO, Dept Med Oncol, Barcelona, Spain. [Prudkin, Ludmila; Jimenez, Jose; Aura, Claudia] VHIO, Dept Mol Pathol, Barcelona, Spain. [Baselga, Jose] Univ Autonoma Barcelona, Fac Med, E-08193 Barcelona, Spain. [Normant, Emmanuel; Lim, Alice R.; Slocum, Kelly L.; West, Kip A.; Rodriguez, Varenka] Infin Pharmaceut, Cambridge, MA USA. RP Baselga, J (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Hematol & Oncol, 10 N Grove St,LH-108, Boston, MA 02114 USA. EM jbaselga@partners.org FU Breast Cancer Research Foundation; European Research Council [AdG09 250244] FX The work was supported by the Breast Cancer Research Foundation and the European Research Council (AdG09 250244). NR 40 TC 26 Z9 26 U1 4 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD MAY PY 2011 VL 10 IS 5 BP 817 EP 824 DI 10.1158/1535-7163.MCT-10-0966 PG 8 WC Oncology SC Oncology GA 774ZY UT WOS:000291427000011 PM 21383049 ER PT J AU Iwamoto, FM Lamborn, KR Kuhn, JG Wen, PY Yung, WKA Gilbert, MR Chang, SM Lieberman, FS Prados, MD Fine, HA AF Iwamoto, Fabio M. Lamborn, Kathleen R. Kuhn, John G. Wen, Patrick Y. Yung, W. K. Alfred Gilbert, Mark R. Chang, Susan M. Lieberman, Frank S. Prados, Michael D. Fine, Howard A. TI A phase I/II trial of the histone deacetylase inhibitor romidepsin for adults with recurrent malignant glioma: North American Brain Tumor Consortium Study 03-03 SO NEURO-ONCOLOGY LA English DT Article DE glioblastoma; glioma; histone deacetylase inhibitor; romidepsin ID DEPSIPEPTIDE FR901228; PROGNOSTIC-FACTORS; FK228; PHARMACOKINETICS; GLIOBLASTOMA; CELLS; CYTOCHROME-P450; IDENTIFICATION; PROGRESSION; EXPRESSION AB Romidepsin, a potent histone deacetylase inhibitor, has shown activity in preclinical glioma models. The primary objectives of this trial were to determine the pharmacokinetics of romidepsin in patients with recurrent glioma on enzyme-inducing antiepileptic drugs (EIAEDs) and to evaluate the antitumor efficacy of romidepsin in patients with recurrent glioblastoma who were not receiving EIAEDs. Two dose cohorts were studied in the phase I component of the trial (13.3 and 17.7 mg/m(2)/d). Patients in the phase II component were treated with intravenous romidepsin at a dosage of 13.3 mg/m(2)/day on days 1, 8, and 15 of each 28-day cycle. Eight patients were treated on the phase I component. A similar romidepsin pharmacokinetic profile was demonstrated between patients receiving EIAEDs to those not receving EIAEDs. Thirty-five patients with glioblastoma were accrued to the phase II component. There was no objective radiographic response. The median progression-free survival (PFS) was 8 weeks and only 1 patient had a PFS time >= 6 months (PFS6 = 3%). To date, 34 patients (97%) have died, with a median survival duration of 34 weeks. Despite in vitro studies showing that romidepsin is primarily metabolized by CYP3A4, no decrease in exposure to romidepsin was seen in patients receiving potent CYP3A4 inducers. Romidepsin, at its standard dose and schedule, was ineffective for patients with recurrent glioblastomas. C1 [Iwamoto, Fabio M.; Fine, Howard A.] NCI, Neurooncol Branch, Natl Inst Neurol Disorder & Stroke, NIH, Bethesda, MD 20892 USA. [Lamborn, Kathleen R.; Chang, Susan M.; Prados, Michael D.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. [Kuhn, John G.] Univ Texas Hlth Sci Ctr San Antonio, Houston, TX USA. [Yung, W. K. Alfred; Gilbert, Mark R.] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. [Wen, Patrick Y.] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. [Lieberman, Frank S.] Univ Pittsburgh, Med Ctr, Dept Neurol, Pittsburgh, PA USA. RP Fine, HA (reprint author), NCI, Neurooncol Branch, Natl Inst Neurol Disorder & Stroke, NIH, 9030 Old Georgetown Rd,Bloch Bldg 82,Room 225, Bethesda, MD 20892 USA. EM hfine@mail.nih.gov RI Gilbert, Mark/J-7494-2016 OI Gilbert, Mark/0000-0003-2556-9722 FU National Institutes of Health ("The North American Brain Tumor Consortium") [CA 062399] FX National Institutes of Health (CA 062399; "The North American Brain Tumor Consortium"). NR 29 TC 41 Z9 43 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD MAY PY 2011 VL 13 IS 5 BP 509 EP 516 DI 10.1093/neuonc/nor017 PG 8 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 775HS UT WOS:000291450200005 PM 21377994 ER PT J AU Jack, CR Albert, MS Knopman, DS McKhann, GM Sperling, RA Carrillo, MC Thies, B Phelps, CH AF Jack, Clifford R., Jr. Albert, Marilyn S. Knopman, David S. McKhann, Guy M. Sperling, Reisa A. Carrillo, Maria C. Thies, Bill Phelps, Creighton H. TI Introduction to the recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease SO ALZHEIMERS & DEMENTIA LA English DT Article DE Alzheimer's disease; Diagnostic criteria; Biomarkers; Imaging; Cerebrospinal fluid ID MILD COGNITIVE IMPAIRMENT; NEUROFIBRILLARY TANGLES; PROGRESSIVE APHASIA; AMYLOID DEPOSITION; CLINICAL DEMENTIA; SYNAPSE LOSS; LEWY BODIES; CONSORTIUM; NEUROPATHOLOGY; DEGENERATION AB Background: Criteria for the clinical diagnosis of Alzheimer's disease (AD) were established in 1984. A broad consensus now exists that these criteria should be revised to incorporate state-of-the-art scientific knowledge. Methods: The National Institute on Aging (NIA) and the Alzheimer's Association sponsored a series of advisory round table meetings in 2009 whose purpose was to establish a process for revising diagnostic and research criteria for AD. The recommendation from these advisory meetings was that three separate work groups should be formed with each assigned the task of formulating diagnostic criteria for one phase of the disease: the dementia phase; the symptomatic, pre-dementia phase; and the asymptomatic, preclinical phase of AD. Results: Two notable differences from the AD criteria published in 1984 are incorporation of biomarkers of the underlying disease state and formalization of different stages of disease in the diagnostic criteria. There was a broad consensus within all three workgroups that much additional work is needed to validate the application of biomarkers for diagnostic purposes. In the revised NIA-Alzheimer's Association criteria, a semantic and conceptual distinction is made between AD pathophysiological processes and clinically observable syndromes that result, whereas this distinction was blurred in the 1984 criteria. Conclusions: The new criteria for AD are presented in three documents. The core clinical criteria of the recommendations regarding AD dementia and MCI due to AD are intended to guide diagnosis in the clinical setting. However, the recommendations of the preclinical AD workgroup are intended purely for research purposes. (C) 2011 The Alzheimer's Association. All rights reserved. C1 [Jack, Clifford R., Jr.; Knopman, David S.] Mayo Clin, Dept Radiol, Rochester, MN 55905 USA. [Albert, Marilyn S.; McKhann, Guy M.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Sperling, Reisa A.] Harvard Univ, Brigham & Womens Hosp, Massachusetts Gen Hosp, Ctr Alzheimer Res & Treatment,Med Sch, Boston, MA 02115 USA. [Carrillo, Maria C.; Thies, Bill] Alzheimers Assoc, Chicago, IL USA. [Phelps, Creighton H.] NIA, Div Neurosci, Baltimore, MD 21224 USA. RP Jack, CR (reprint author), Mayo Clin, Dept Radiol, Rochester, MN 55905 USA. EM jack.clifford@mayo.edu RI Jack, Clifford/F-2508-2010 OI Jack, Clifford/0000-0001-7916-622X FU Baxter; Pfizer Inc; GE Healthcare; Elan Pharmaceuticals; Forest Pharmaceuticals; Baxter Healthcare FX Clifford Jack serves as a consultant for Eli Lilly, Eisai, and Elan; is an investigator in clinical trials sponsored by Baxter and Pfizer Inc; and owns stock in Johnson and Johnson. Marilyn Albert serves as a consultant to Genentech and Eli Lilly and receives grants to her institution from GE Healthcare. David Knopman serves on a Data Safety Monitoring Board for Lilly Pharmaceuticals; is an investigator for clinical trials sponsored by Elan Pharmaceuticals, Forest Pharmaceuticals, and Baxter Healthcare; and is deputy editor of Neurology and receives compensation for editorial activities. Guy McKhann serves on a Data Safety Monitoring Board for Merck. Reisa Sperling has served as a site investigator and/or consultant to several companies developing imaging biomarkers and pharmacological treatments for early AD, including Avid, Bayer, Bristol-Myers-Squibb, Elan, Eisai, Janssen, Pfizer, and Wyeth. Maria Carrillo is an employee of the Alzheimer's Association and reports no conflicts. Bill Thies is an employee of the Alzheimer's Association and reports no conflicts. Creighton Phelps is an employee of the U.S. Government and reports no conflicts. NR 50 TC 458 Z9 477 U1 7 U2 82 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD MAY PY 2011 VL 7 IS 3 BP 257 EP 262 DI 10.1016/j.jalz.2011.03.004 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 772NC UT WOS:000291239600002 PM 21514247 ER PT J AU McKhann, GM Knopman, DS Chertkow, H Hyman, BT Jack, CR Kawas, CH Klunk, WE Koroshetz, WJ Manly, JJ Mayeux, R Mohs, RC Morris, JC Rossor, MN Scheltens, P Carrillo, MC Thies, B Weintraub, S Phelps, CH AF McKhann, Guy M. Knopman, David S. Chertkow, Howard Hyman, Bradley T. Jack, Clifford R., Jr. Kawas, Claudia H. Klunk, William E. Koroshetz, Walter J. Manly, Jennifer J. Mayeux, Richard Mohs, Richard C. Morris, John C. Rossor, Martin N. Scheltens, Philip Carrillo, Maria C. Thies, Bill Weintraub, Sandra Phelps, Creighton H. TI The diagnosis of dementia due to Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease SO ALZHEIMERS & DEMENTIA LA English DT Article DE Alzheimer's disease; Dementia; Diagnosis; Magnetic resonance brain imaging; Positron emission tomography; Cerebrospinal fluid ID FRONTOTEMPORAL DEMENTIA; WORK GROUP; CRITERIA; BIOMARKERS; CONSENSUS; ATROPHY AB The National Institute on Aging and the Alzheimer's Association charged a workgroup with the task of revising the 1984 criteria for Alzheimer's disease (AD) dementia. The workgroup sought to ensure that the revised criteria would be flexible enough to be used by both general healthcare providers without access to neuropsychological testing, advanced imaging, and cerebrospinal fluid measures, and specialized investigators involved in research or in clinical trial studies who would have these tools available. We present criteria for all-cause dementia and for AD dementia. We retained the general framework of probable AD dementia from the 1984 criteria. On the basis of the past 27 years of experience, we made several changes in the clinical criteria for the diagnosis. We also retained the term possible AD dementia, but redefined it in a manner more focused than before. Biomarker evidence was also integrated into the diagnostic formulations for probable and possible AD dementia for use in research settings. The core clinical criteria for AD dementia will continue to be the cornerstone of the diagnosis in clinical practice, but biomarker evidence is expected to enhance the pathophysiological specificity of the diagnosis of AD dementia. Much work lies ahead for validating the biomarker diagnosis of AD dementia. (C) 2011 The Alzheimer's Association. All rights reserved. C1 [McKhann, Guy M.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [McKhann, Guy M.] Johns Hopkins Univ, Zanvyl Krieger Mind Brain Inst, Baltimore, MD 21205 USA. [Knopman, David S.] Mayo Clin, Dept Neurol, Rochester, MN USA. [Chertkow, Howard] McGill Univ, Dept Neurol, Sch Med, Montreal, PQ H3A 2T5, Canada. [Chertkow, Howard] Lady Davis Inst, Bloomfield Ctr Res Aging, Montreal, PQ, Canada. [Hyman, Bradley T.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Jack, Clifford R., Jr.] Mayo Clin, Dept Radiol, Rochester, MN USA. [Kawas, Claudia H.] Univ Calif Irvine, Dept Neurol, Irvine, CA 92717 USA. [Kawas, Claudia H.] Univ Calif Irvine, Dept Neurobiol & Behav, Irvine, CA USA. [Kawas, Claudia H.] Univ Calif Irvine, Alzheimer Dis Res Ctr, Irvine, CA USA. [Klunk, William E.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Koroshetz, Walter J.] NINDS, Bethesda, MD 20892 USA. [Manly, Jennifer J.; Mayeux, Richard] Columbia Univ, Med Ctr, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY USA. [Manly, Jennifer J.; Mayeux, Richard] Columbia Univ, Gertrude H Sergievsky Ctr, Med Ctr, New York, NY 10027 USA. [Manly, Jennifer J.; Mayeux, Richard] Columbia Univ, Dept Neurol, Med Ctr, New York, NY USA. [Mohs, Richard C.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Morris, John C.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [Rossor, Martin N.] UCL, Dementia Res Ctr, Dept Neurodegenerat, UCL Inst Neurol, London, England. [Scheltens, Philip] Vrije Univ Amsterdam, Dept Neurol, Med Ctr, Amsterdam, Netherlands. [Scheltens, Philip] Vrije Univ Amsterdam, Alzheimer Ctr, Med Ctr, Amsterdam, Netherlands. [Carrillo, Maria C.; Thies, Bill] Alzheimers Assoc, Chicago, IL USA. [Weintraub, Sandra] NW Feinberg Sch Med, Dept Psychiat, Chicago, IL USA. [Weintraub, Sandra] NW Feinberg Sch Med, Dept Neurol, Chicago, IL USA. [Phelps, Creighton H.] NIA, Alzheimers Dis Ctr Program, Bethesda, MD 20892 USA. RP McKhann, GM (reprint author), Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. RI Jack, Clifford/F-2508-2010; Morris, John/A-1686-2012; OI Jack, Clifford/0000-0001-7916-622X; Klunk, William/0000-0001-5512-0251 FU Elan Pharmaceuticals; Forest Pharmaceuticals; Baxter Healthcare; Pfizer Canada; NIH; Alzheimer's Association; Fidelity Biosciences; Baxter; Pfizer Inc.; Avid Radiopharmaceuticals; Eli Lilly and Co. FX Guy McKhann serves on a Data Safety Monitoring Board for Merck. David Knopman serves on a Data Safety Monitoring Board for Lilly Pharmaceuticals and is an investigator for clinical trials sponsored by Elan Pharmaceuticals, Forest Pharmaceuticals, and Baxter Healthcare; he is deputy editor of Neurology and receives compensation for editorial activities. Howard Chertkow serves as a consultant to Pfizer Canada, Lundbeck Canada, Janssen Ortho, Novartis Canada, and Bristol Myers Squibb; he receives a research grant from Pfizer Canada. Bradley Hyman serves as a consultant to EMD Serrano, Janssen, Takeda, BMS, Neurophage, Pfizer, Quanterix, foldrx, Elan, and Link, and receives funding from the NIH, the Alzheimer's Association, and Fidelity Biosciences. Clifford Jack serves as a consultant for Eli Lilly, Eisai, and Elan; he is an investigator in clinical trials sponsored by Baxter and Pfizer Inc., and owns stock in Johnson and Johnson. Claudia Kawas serves on a Data Safety Monitoring Board for Lilly Pharmaceuticals, Elan Pharmaceuticals, and Lundbeck; she is an investigator in a trial sponsored by Avid Radiopharmaceuticals. William Klunk serves as a consultant to GE Healthcare and receives research grants from the same; he also receives royalties from GE Healthcare for PiB PET technology and owns stock or options in Neuroptix, a company seeking to commercialize detection of amyloid in the eye. Walter Koroshetz are employees of the U.S. Government and report no conflicts. Jennifer Manly reports no conflicts of interests. Richard Mayeux serves on scientific advisory board of Psycho-Genics. Richard Mohs is a full-time employee of Eli Lilly and Company and holds stock in Lilly. Avid Radiopharmaceuticals is a wholly owned subsidiary of Eli Lilly and Co. John Morris serves as a consultant to Astra Zeneca, Bristol-Myers Squibb, Eisai, Janssen, Genetic, Eli Lilly, Merck, Novartis, Otsuka, Pfizer, and Schering Plough. University College London receives payment for Martin Rossor serving on the Safety Monitoring Committees for Janssen and Servier trials in AD. Philip Scheltens serves as a consultant to Pfizer Pharmaceuticals, Genetech, Danone Research, Lundbeck Pharmaceuticals, GE Healthcare, Roche, and Novartis; he also serves on a speakers bureau for Lundbeck Pharmaceuticals. Maria Carrillo and Bill Thies are employees of the Alzheimer's Association and reports no conflicts. Sandra Weintraub reports no conflicts of interest and Creighton Phelps. NR 24 TC 2377 Z9 2459 U1 85 U2 564 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD MAY PY 2011 VL 7 IS 3 BP 263 EP 269 DI 10.1016/j.jalz.2011.03.005 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 772NC UT WOS:000291239600003 PM 21514250 ER PT J AU Sperling, RA Aisen, PS Beckett, LA Bennett, DA Craft, S Fagan, AM Iwatsubo, T Jack, CR Kaye, J Montine, TJ Park, DC Reiman, EM Rowe, CC Siemers, E Stern, Y Yaffe, K Carrillo, MC Thies, B Morrison-Bogorad, M Wagster, MV Phelps, CH AF Sperling, Reisa A. Aisen, Paul S. Beckett, Laurel A. Bennett, David A. Craft, Suzanne Fagan, Anne M. Iwatsubo, Takeshi Jack, Clifford R., Jr. Kaye, Jeffrey Montine, Thomas J. Park, Denise C. Reiman, Eric M. Rowe, Christopher C. Siemers, Eric Stern, Yaakov Yaffe, Kristine Carrillo, Maria C. Thies, Bill Morrison-Bogorad, Marcelle Wagster, Molly V. Phelps, Creighton H. TI Toward defining the preclinical stages of Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease SO ALZHEIMERS & DEMENTIA LA English DT Article DE Preclinical Alzheimer's disease; Biomarker; Amyloid; Neurodegeneration; Prevention ID MILD COGNITIVE IMPAIRMENT; AMYLOID DEPOSITION; OLDER-ADULTS; A-BETA; NONDEMENTED INDIVIDUALS; COMMUNITY POPULATION; BIOMARKER SIGNATURE; CSF BIOMARKERS; GENETIC RISK; DECLINE AB The pathophysiological process of Alzheimer's disease (AD) is thought to begin many years before the diagnosis of AD dementia. This long "preclinical" phase of AD would provide a critical opportunity for therapeutic intervention; however, we need to further elucidate the link between the pathological cascade of AD and the emergence of clinical symptoms. The National Institute on Aging and the Alzheimer's Association convened an international workgroup to review the biomarker, epidemiological, and neuropsychological evidence, and to develop recommendations to determine the factors which best predict the risk of progression from "normal" cognition to mild cognitive impairment and AD dementia. We propose a conceptual framework and operational research criteria, based on the prevailing scientific evidence to date, to test and refine these models with longitudinal clinical research studies. These recommendations are solely intended for research purposes and do not have any clinical implications at this time. It is hoped that these recommendations will provide a common rubric to advance the study of preclinical AD, and ultimately, aid the field in moving toward earlier intervention at a stage of AD when some disease-modifying therapies may be most efficacious. (C) 2011 The Alzheimer's Association. All rights reserved. C1 [Sperling, Reisa A.] Harvard Univ, Brigham & Womens Hosp, Massachusetts Gen Hosp, Ctr Alzheimer Res & Treatment,Dept Neurol,Med Sch, Boston, MA 02115 USA. [Aisen, Paul S.] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. [Beckett, Laurel A.] Univ Calif Davis, Div Biostat, Sch Med, Davis, CA 95616 USA. [Bennett, David A.] Rush Univ, Rush Alzheimers Dis Ctr, Med Ctr, Chicago, IL 60612 USA. [Craft, Suzanne] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Ctr Geriatr Res Educ & Clin, Seattle, WA 98195 USA. [Fagan, Anne M.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [Iwatsubo, Takeshi] Univ Tokyo, Grad Sch Sci, Dept Neuropathol, Tokyo 113, Japan. [Jack, Clifford R., Jr.] Mayo Clin Minnesota, Dept Radiol, Rochester, MN USA. [Kaye, Jeffrey] Oregon Hlth & Sci Univ, Dept Neurol, Layton Aging & Alzheimers Dis Ctr, Oregon Ctr Aging & Technol, Portland, OR 97201 USA. [Kaye, Jeffrey] Oregon Hlth & Sci Univ, Dept Biomed Engn, Layton Aging & Alzheimers Dis Ctr, Oregon Ctr Aging & Technol, Portland, OR 97201 USA. [Kaye, Jeffrey] Portland VA Med Ctr, Portland, OR USA. [Montine, Thomas J.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Park, Denise C.] Univ Texas Dallas, Ctr Vital Longev, Dallas, TX 75230 USA. [Siemers, Eric] Banner Alzheimers Inst, Phoenix, AZ USA. [Rowe, Christopher C.] Univ Melbourne, Melbourne, Vic, Australia. [Siemers, Eric] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Stern, Yaakov] Columbia Univ, Coll Phys & Surg, Cognit Neurosci Div, Taub Inst, New York, NY USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco VA Med Ctr, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco VA Med Ctr, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. [Carrillo, Maria C.; Thies, Bill] Alzheimers Assoc, Chicago, IL USA. [Morrison-Bogorad, Marcelle; Wagster, Molly V.; Phelps, Creighton H.] NIA, Div Neurosci, Bethesda, MD 20892 USA. RP Sperling, RA (reprint author), Harvard Univ, Brigham & Womens Hosp, Massachusetts Gen Hosp, Ctr Alzheimer Res & Treatment,Dept Neurol,Med Sch, Boston, MA 02115 USA. EM reisa@rics.bwh.harvard.edu RI Jack, Clifford/F-2508-2010; OI Jack, Clifford/0000-0001-7916-622X; Beckett, Laurel/0000-0002-2418-9843; Kaye, Jeffrey/0000-0002-9971-3478 FU Pfizer Inc.; Baxter International Inc.; Baxter; Avid Pharmaceuticals; Bayer; Janssen; Eli Lilly; Elan FX Reisa Sperling has served as a site investigator and/or consultant to several companies developing imaging biomarkers and pharmacological treatments for early AD, including Avid, Bayer, Bristol-Myers-Squibb, Elan, Eisai, Janssen, Pfizer, and Wyeth. Paul Aisen serves on a scientific advisory board for NeuroPhage; serves as a consultant to Elan Corporation, Wyeth, Eisai Inc., Bristol-Myers Squibb, Eli Lilly and Company, NeuroPhage, Merck & Co., Roche, Amgen, Abbott, Pfizer Inc., Novartis, Bayer, Astellas, Dainippon, Biomarin, Solvay, Otsuka, Daiichi, AstraZeneca, Janssen, and Medivation Inc.; receives research support from Pfizer Inc. and Baxter International Inc.; and has received stock options from Medivation Inc. and NeuroPhage. Clifford Jack serves as a consultant for Eli Lilly, Eisai, and Elan; is an investigator in clinical trials sponsored by Baxter and Pfizer Inc.; and owns stock in Johnson and Johnson. Denise Park has received research support from Avid Pharmaceuticals. Eric Siemers is an employee of Eli Lilly and Company, which acquired Avid Pharmaceuticals. Yaakov Stern has consulted to Bayer Pharmaceuticals and has received research support from Bayer, Janssen, Eli Lilly, and Elan. Maria Carrillo is an employee of the Alzheimer's Association and reports no conflicts. Bill Thies is an employee of the Alzheimer's Association and reports no conflicts. Creighton Phelps is an employee of the U.S. Government and reports no conflicts. NR 71 TC 1680 Z9 1721 U1 45 U2 278 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD MAY PY 2011 VL 7 IS 3 BP 280 EP 292 DI 10.1016/j.jalz.2011.03.003 PG 13 WC Clinical Neurology SC Neurosciences & Neurology GA 772NC UT WOS:000291239600005 PM 21514248 ER PT J AU Marshall, GA Rentz, DM Frey, MT Locascio, JJ Johnson, KA Sperling, RA AF Marshall, Gad A. Rentz, Dorene M. Frey, Meghan T. Locascio, Joseph J. Johnson, Keith A. Sperling, Reisa A. CA Alzheimer's Dis Neuroimaging TI Executive function and instrumental activities of daily living in mild cognitive impairment and Alzheimer's disease SO ALZHEIMERS & DEMENTIA LA English DT Article DE Alzheimer's disease; Executive function; Instrumental activities of daily living; Memory; Mild cognitive impairment ID OLDER-ADULTS; CLINICAL DEMENTIA; DYSFUNCTION; ASSOCIATION; DIAGNOSIS; COMMUNITY; AD AB Background: Impairment in instrumental activities of daily living (IADL) leads to early loss in productivity and adds significant burden to caregivers. Executive dysfunction is thought to be an important contributor to functional impairment. The objective of this study was to investigate the relationship between executive function and IADL in a large cohort of well-characterized normal older controls, mild cognitive impairment (MCI), and patients with mild Alzheimer's disease, separately as well as across the entire sample, while accounting for demographic, cognitive, and behavioral factors. Methods: Subjects with baseline clinical datasets (n = 793) from the Alzheimer's Disease Neuroimaging Initiative study (228 normal older controls, 387 MCI, 178 Alzheimer's disease) were included in the analysis. A multiple regression model was used to assess the relationship between executive function and IADL. Results: A multiple regression model, including diagnosis, global cognitive impairment, memory performance, and other covariates demonstrated a significant relationship between executive dysfunction and IADL impairment across all subjects (R(2) = .60, P < .0001 for model; Digit Symbol, partial beta = -.044, P = .005; Trailmaking Test B-A, quadratic relation, P = .01). Similarly, an analysis using MCI subjects only yielded a significant relationship (R(2) = .16, P < .0001 for model; Digit Symbol, partial beta = -.08, P = .001). Conclusions: These results suggest that executive dysfunction is a key contributor to impairment in IADL. This relationship was evident even after accounting for degree of memory deficit across the continuum of cognitive impairment and dementia. (C) 2011 The Alzheimer's Association. All rights reserved. C1 [Marshall, Gad A.; Rentz, Dorene M.; Frey, Meghan T.; Johnson, Keith A.; Sperling, Reisa A.] Harvard Univ, Brigham & Womens Hosp, Ctr Alzheimer Res & Treatment, Sch Med, Boston, MA 02115 USA. [Marshall, Gad A.; Rentz, Dorene M.; Frey, Meghan T.; Johnson, Keith A.; Sperling, Reisa A.] Harvard Univ, Brigham & Womens Hosp, Dept Neurol, Sch Med, Boston, MA 02115 USA. [Marshall, Gad A.; Rentz, Dorene M.; Locascio, Joseph J.; Johnson, Keith A.; Sperling, Reisa A.] Harvard Univ, Dept Neurol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. [Johnson, Keith A.] Harvard Univ, Dept Radiol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Marshall, GA (reprint author), Harvard Univ, Brigham & Womens Hosp, Ctr Alzheimer Res & Treatment, Sch Med, Boston, MA 02115 USA. EM gamarshall@partners.org RI Scharre, Douglas/E-4030-2011 FU Rosalinde; Arthur Gilbert Foundation; Massachusetts Alzheimer's Disease Research Center [P50 AG005134-24]; ADNI; National Institutes of Health (NIH); [R01 AG027435]; [1K23AG033634-01A1] FX This study was supported by R01 AG027435, 1K23AG033634-01A1, the Rosalinde and Arthur Gilbert Foundation/AFAR New Investigator Awards in Alzheimer's Disease, the Massachusetts Alzheimer's Disease Research Center (P50 AG005134-24), and ADNI. The Foundation for the National Institutes of Health (www.fnih.org) coordinates the private sector participation of the $60 million ADNI public-private partnership that was begun by the National Institute on Aging (NIA) and supported by the National Institutes of Health (NIH). To date, more than $27 million has been provided to the Foundation for NIH by Abbott, AstraZeneca AB, Bayer Schering Pharma AG, Bristol-Myers Squibb, Eisai Global Clinical Development, Elan Corporation, Genentech, GE Healthcare, GlaxoSmithKline, Innogenetics, Johnson & Johnson, Eli Lilly and Co., Merck & Co., Inc., Novartis AG, Pfizer Inc., F. Hoffmann-La Roche, Schering-Plough, Synarc Inc., and Wyeth, as well as non-profit partners the Alzheimer's Association and the Institute for the Study of Aging. NR 42 TC 84 Z9 86 U1 3 U2 22 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD MAY PY 2011 VL 7 IS 3 BP 300 EP 308 DI 10.1016/j.jalz.2010.04.005 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 772NC UT WOS:000291239600007 PM 21575871 ER PT J AU Almandoz, JED Su, HS Schaefer, PW Goldstein, JN Pomerantz, SR Lev, MH Gonzalez, RG Romero, JM AF Almandoz, J. E. Delgado Su, H. S. Schaefer, P. W. Goldstein, J. N. Pomerantz, S. R. Lev, M. H. Gonzalez, R. G. Romero, J. M. TI Frequency of Adequate Contrast Opacification of the Major Intracranial Venous Structures with CT Angiography in the Setting of Intracerebral Hemorrhage: Comparison of 16- and 64-Section CT Angiography Techniques SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID SPOT SIGN; HEMATOMA EXPANSION; HIGHEST RISK; EXTRAVASATION; THROMBOSIS; ETIOLOGY; SCORE AB BACKGROUND AND PURPOSE: DVST is an important cause of ICH because its treatment may require anticoagulation or mechanical thrombectomy. We aimed to determine the frequency of adequate contrast opacification of the major intracranial venous structures in CTAs performed for ICH evaluation, which is an essential factor in excluding DVST as the ICH etiology. MATERIALS AND METHODS: Two readers retrospectively reviewed CTAs performed in 170 consecutive patients with ICH who presented to our emergency department during a 1-year period to determine by consensus whether qualitatively, contrast opacification in each of the major intracranial venous structures was adequate to exclude DVST. "Adequate contrast opacification" was defined as homogeneous opacification of the venous structure examined. "Inadequate contrast opacification" was defined as either inhomogeneous opacification or nonopacification of the venous structure examined. Delayed scans, if obtained, were reviewed by the same readers blinded to the first-pass CTAs to determine the adequacy of contrast opacification in the venous structures according to the same criteria. In patients who did not have an arterial ICH etiology, the same readers determined if thrombosis of an inadequately opacified intracranial venous structure could have potentially explained the ICH by correlating the presumed venous drainage path of the ICH with the presence of inadequate contrast opacification within the venous structure draining the venous territory of the ICH. CTAs were performed in 16- or 64-section CT scanners with bolus-tracking, scanning from Cl to the vertex. Patients with a final diagnosis of DVST were excluded. We used the Pearson chi(2) test to determine the significance of the differences in the frequency of adequate contrast opacification within each of the major intracranial venous structures in scans obtained using either a 16- or 64-section MDCTA technique. RESULTS: Fifty-eight patients were evaluated with a 16-section MDCTA technique (34.1%) and 112 with a 64-section technique (65.9%). Adequate contrast opacification within all major noncavernous intracranial venous structures was significantly less frequent in first-pass CTAs performed with a 64-section technique (33%) than in those performed with a 16-section technique (60%, P value <.0001). Delayed scans were obtained in 50 patients, all of which demonstrated adequate contrast opacification in the major noncavernous intracranial venous structures. In 142 patients with supratentorial or cerebellar ICH without an underlying arterial etiology, we found that thrombosis of an inadequately opacified major intracranial venous structure could have potentially explained the ICH in 38 patients (26.8%), most examined with a 64-section technique (86.8%). CONCLUSIONS: Inadequate contrast pacification of the major intracranial venous structures is common in first-pass CTAs performed for ICH evaluation, particularly if performed with a 64-section technique. Acquiring delayed scans appears necessary to confidently exclude DVST when there is strong clinical or radiologic suspicion. C1 [Almandoz, J. E. Delgado] Washington Univ, Div Neuroradiol, Mallinckrodt Inst Radiol, St Louis, MO 63110 USA. [Almandoz, J. E. Delgado; Su, H. S.; Schaefer, P. W.; Pomerantz, S. R.; Lev, M. H.; Gonzalez, R. G.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp,Div Neuroradiol, Boston, MA 02115 USA. [Goldstein, J. N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Almandoz, JED (reprint author), Washington Univ, Div Neuroradiol, Mallinckrodt Inst Radiol, Campus Box 8131,510 S Kingshighway Blvd, St Louis, MO 63110 USA. EM delgadoj@mir.wustl.edu RI Goldstein, Joshua/H-8953-2016 FU National Institute of Neurological Disorders and Stroke [K23NS059774] FX This work was supported, in part, by the National Institute of Neurological Disorders and Stroke grant K23NS059774. NR 15 TC 3 Z9 3 U1 0 U2 3 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 MAY PY 2011 VL 32 IS 5 BP 839 EP 845 DI 10.3174/ajnr.A2388 PG 7 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 770VW UT WOS:000291117600010 ER PT J AU Mui, K Yoo, AJ Verduzco, L Copen, WA Hirsch, JA Gonzalez, RG Schaefer, PW AF Mui, K. Yoo, A. J. Verduzco, L. Copen, W. A. Hirsch, J. A. Gonzalez, R. G. Schaefer, P. W. TI Cerebral Blood Flow Thresholds for Tissue Infarction in Patients with Acute Ischemic Stroke Treated with Intra-Arterial Revascularization Therapy Depend on Timing of Reperfusion SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID APPARENT DIFFUSION-COEFFICIENT; PERFUSION MAGNETIC-RESONANCE; HYPERACUTE STROKE; WEIGHTED MRI; ARTERY OCCLUSION; WHITE-MATTER; PENUMBRA; THROMBOLYSIS; PREDICTION; CT AB BACKGROUND AND PURPOSE: MR perfusion CBF values can distinguish hypoperfused penumbral tissue likely to infarct from that which is likely to recover. Our aim was to determine if CBF thresholds for tissue infarction depend on the timing of recanalization in patients with acute stroke treated with IAT. MATERIALS AND METHODS: Twenty-six patients with acute proximal anterior circulation strokes underwent DWI and PWI before IAT. rCBF was obtained in the following areas: 1) C with abnormal DWI, reduced CBF, follow-up infarction; 2) PI with normal DWI, reduced CBF, follow-up infarction and 3) PNI with normal DWI, reduced CBF, normal follow-up. rCBF in tissue reperfused at <6 hours (early recanalizers), in tissue reperfused at >6 hours (late RC), and in NRC was compared. RESULTS: For C, mean rCBF was 0.13 (SEM, 0.002), 0.29 (0.007), and 0.21 (0.004) for early recanalizers, late recanalizers, and nonrecanalizers, respectively (P < .001, for all comparisons). For PI, mean rCBF was 0.34 (0.006), 0.38 (0.008), and 0.39 (0.005) for early recanalizers, late recanalizers, and nonrecanalizers, respectively (P < .001 for early-versus-late recanalizers and versus nonrecanalizers; P > .05 for late recanalizers versus nonrecanalizers). For PNI, the mean rCBF was 0.38 (0.002), 0.48 (0.003), and 0.48 (0.004) for early recanalizers, late recanalizers, and nonrecanalizers, respectively (P < .001 for early-versus-late recanalizers and nonrecanalizers; P>.05 for late recanalizers versus nonrecanalizers). ROC analyzis demonstrated optimal rCBF thresholds for tissue infarction of 0.27 (sensitivity, 80%; specificity, 87%), 0.44 (sensitivity, 77%; specificity, 75%), and 0.41 (sensitivity, 78%; specificity, 77%) for early recanalizers, late recanalizers, and nonrecanalizers, respectively. CONCLUSIONS: CBF thresholds for tissue infarction in patients with acute stroke are lower in tissue that is reperfused at earlier time points. This information may be important in selecting patients who might benefit from reperfusion therapy. C1 [Schaefer, P. W.] Harvard Univ, Dept Radiol, Div Neuroradiol, Massachusetts Gen Hosp,Med Sch, Boston, MA 02114 USA. RP Schaefer, PW (reprint author), Harvard Univ, Dept Radiol, Div Neuroradiol, Massachusetts Gen Hosp,Med Sch, Gray 273A,55 Fruit St, Boston, MA 02114 USA. EM pschaefer@partners.org NR 33 TC 9 Z9 9 U1 0 U2 5 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 MAY PY 2011 VL 32 IS 5 BP 846 EP 851 DI 10.3174/ajnr.A2415 PG 6 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 770VW UT WOS:000291117600011 PM 21474633 ER PT J AU Schutz, FAB Jardim, DLF Je, YJ Choueiri, TK AF Schutz, Fabio A. B. Jardim, Denis L. F. Je, Youjin Choueiri, Toni K. TI Haematologic toxicities associated with the addition of bevacizumab in cancer patients SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE Bevacizumab; Meta-analysis; Haematologic toxicities; Bone marrow toxicities; Anaemia; Neutropenia; Thrombocytopenia; Febrile neutropenia ID PHASE-III TRIAL; CELL LUNG-CANCER; METASTATIC BREAST-CANCER; ADVANCED PANCREATIC-CANCER; COLORECTAL-CANCER; HEMATOPOIETIC-CELLS; 1ST-LINE TREATMENT; PLUS GEMCITABINE; TUMOR-GROWTH; STEM-CELLS AB Background: Bevacizumab is currently approved for the treatment of several malignancies. Haematologic toxicities are not among the main concerns associated with bevacizumab, but they have been occasionally reported. We performed a meta-analysis to determine the incidence and risk of haematologic toxicities associated with bevacizumab. Methods: Pubmed databases from 1966 to September 2010 were searched for studies reported, as well as American Society of Clinical Oncology meetings. Bevacizumab randomised clinical trials with adequate safety data profile were included. Statistical analyses were conducted to calculate the summary incidence, relative risk (RR) and 95% confidence intervals (CI). Results: 15,263 patients were included. The incidence of bevacizumab-associated all-grade and high-grade haematologic toxicities were, respectively: anaemia: 18.7% and 3.9%; neutropenia: 25.0% and 18.5%; and thrombocytopenia: 13.9% and 3.4%. Febrile neutropenia incidence was 3.8%. Compared to placebo/control arms, bevacizumab was associated with a decreased risk of all-grade (RR = 0.81; 95%CI 0.68-0.96; p =.016) and high-grade (RR = 0.73; 95%CI 0.60-0.89; p = .002) anaemia, and increased risks of all-grade (RR = 1.15; 95%CI 1.01-1.30; p = .033) and high-grade (RR = 1.08; 95%CI 1.02-1.13; p = .005) neutropenia, all-grade thrombocytopenia (RR = 1.22; 95%CI 1.00-1.48; p = .047) and febrile neutropenia (RR = 1.31; 95%CI 1.08-1.58; p = .006). Conclusions: Bevacizumab is associated with a lower risk of anaemia and increased risks of neutropenia, thrombocytopenia and febrile neutropenia. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Choueiri, Toni K.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Kidney Canc Ctr,Dana Farber Canc Inst, Boston, MA 02115 USA. [Schutz, Fabio A. B.; Jardim, Denis L. F.; Choueiri, Toni K.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Je, Youjin] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Jardim, Denis L. F.] Hosp Sirio Libanes, Sao Paulo, Brazil. RP Choueiri, TK (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Kidney Canc Ctr,Dana Farber Canc Inst, 44 Binney St,Dana 1230, Boston, MA 02115 USA. EM Toni_Choueiri@dfci.harvard.edu FU philanthropic Trust Family Research Fund for Kidney Cancer FX This study was funded by the philanthropic Trust Family Research Fund for Kidney Cancer. The funding source did not have any role in this study. The authors had access to all the data and had the final responsibility for the decision to submit the manuscript for publication. NR 55 TC 14 Z9 14 U1 1 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD MAY PY 2011 VL 47 IS 8 BP 1161 EP 1174 DI 10.1016/j.ejca.2011.03.005 PG 14 WC Oncology SC Oncology GA 772KI UT WOS:000291232400006 PM 21470847 ER PT J AU Fuller, BE Rodriguez, VL Linke, A Sikirica, M Dirani, R Hauser, P AF Fuller, Bret E. Rodriguez, Veronica L. Linke, Alex Sikirica, Mirko Dirani, Riad Hauser, Peter TI Prevalence of liver disease in veterans with bipolar disorder or schizophrenia SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE Liver disease; Veterans; Bipolar disorder; Schizophrenia ID SUBSTANCE USE DISORDERS; SEVERE MENTAL-ILLNESS; HEPATITIS-C; UNITED-STATES; PSYCHIATRIC-DISORDERS; CARE; COMORBIDITY; MANAGEMENT; INFECTION; HEALTH AB Objective: To assess the prevalence of three liver diseases [hepatitis C virus (HCV), nonalcoholic fatty liver disease and alcohol-induced cirrhosis] in patients (veterans) with/without schizophrenia/schizoaffective disorder and bipolar disorder. Methods: A retrospective electronic chart review of Veterans Integrated Services Network 20 facilities from January 1, 2001 to December 21, 2006 selected patients to one of two groups: schizophrenia/schizoaffective disorder or bipolar disorder. Patients in both groups were compared with veterans in an equal-sized random sample from the same data set of veterans without psychiatric diagnoses. Logistic regression models evaluated risk for overall liver diseases as well as HCV, nonalcoholic fatty liver disease and alcoholic-induced cirrhosis. Results: Patients with schizophrenia (n=6521) had a higher prevalence of liver disease [22.4% versus 3.2%; odds ratio (OR)=8.73]; HCV (16.5% versus 1.9%; OR=10.21); and alcohol-related cirrhosis (1.6% versus 0.4%; OR=4.09) than matched controls. Patients with bipolar disorder (n=5319) had a higher prevalence of liver disease (21.5% versus 3.5%; OR=7.58); HCV (15.5% versus 2.1%; OR=8.60); and alcohol-related cirrhosis (1.6% versus 0.4%; OR=3.82) than matched controls. Risk factors for liver disease in patients with schizophrenia (versus matched controls) included diabetes (OR=1.29), hypertension (OR=1.27), HIV (OR=3.54), substance use disorder (SUD) (OR=2.28), alcohol use disorder (OR=3.05) and schizophrenia (OR=2.74). Risk factors for development of liver disease for patients with bipolar disorder: diabetes (OR=1.40), HIV (OR=3.66), SUD (OR=2.68), alcohol use disorder (OR=3.22) and bipolar disorder (OR=2.27). Conclusions: This study in veterans shows that the presence of mental illness and its comorbidities represents a significant risk factor for the diagnosis of liver disease, including HCV and alcohol-related cirrhosis. Published by Elsevier Inc. C1 [Fuller, Bret E.; Rodriguez, Veronica L.; Linke, Alex] Portland VA Med Ctr, Portland, OR 97210 USA. [Sikirica, Mirko; Dirani, Riad] Ortho McNeil Janssen Sci Affairs LLC, Titusville, NJ USA. [Fuller, Bret E.] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. [Hauser, Peter] Long Beach Vet Affairs Med Ctr, Vet Integrated Serv Network 22, Network Off, Long Beach, CA USA. RP Fuller, BE (reprint author), Portland VA Med Ctr, 3170 SW US Vet Pk Rd,Mailcode P3MHDC, Portland, OR 97210 USA. EM bret.fuller@va.gov FU Ortho-McNeil Janssen Scientific Affairs FX This study was funded by a grant from Ortho-McNeil Janssen Scientific Affairs. NR 24 TC 12 Z9 12 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 EI 1873-7714 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD MAY-JUN PY 2011 VL 33 IS 3 BP 232 EP 237 DI 10.1016/j.genhosppsych.2011.03.006 PG 6 WC Psychiatry SC Psychiatry GA 773IR UT WOS:000291300700004 PM 21601719 ER PT J AU Roffman, JL AF Roffman, Joshua L. TI SPECIAL ISSUE Biomarkers and Personalized Psychiatry Introduction SO HARVARD REVIEW OF PSYCHIATRY LA English DT Editorial Material C1 Harvard Univ, Dept Psychiat, Massachusetts Gen Hosp, Med School, Cambridge, MA 02138 USA. RP Roffman, JL (reprint author), Harvard Univ, Dept Psychiat, Massachusetts Gen Hosp, Med School, Cambridge, MA 02138 USA. EM jroffman@partners.org NR 6 TC 0 Z9 0 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD MAY-JUN PY 2011 VL 19 IS 3 SI SI BP 99 EP 101 DI 10.3109/10673229.2011.586547 PG 3 WC Psychiatry SC Psychiatry GA 771MJ UT WOS:000291162300001 PM 21631156 ER PT J AU Iosifescu, DV AF Iosifescu, Dan Vlad TI Electroencephalography-Derived Biomarkers of Antidepressant Response SO HARVARD REVIEW OF PSYCHIATRY LA English DT Review DE antidepressant; EEG source localization; electroencephalography; event-related potentials; major depressive disorder; predictor; quantitative electroencephalography; response ID MAJOR DEPRESSIVE DISORDER; EVENT-RELATED POTENTIALS; STAR-ASTERISK-D; ANTERIOR CINGULATE CORTEX; LOUDNESS DEPENDENCE; CLINICAL-RESPONSE; NORADRENERGIC ANTIDEPRESSANTS; PERCEPTUAL ASYMMETRY; INTENSITY DEPENDENCE; ELECTRICAL-ACTIVITY AB Recent meta-analyses point to the relatively low efficacy of commonly used antidepressant medications. Selecting the most effective medications for depressed subjects having failed previous treatments is especially difficult. There is a clear need for objective biomarkers that could assist and optimize such treatment selection. We will review here a growing body of evidence suggesting that several electroencephalography (EEG)-based methods may be useful for predicting antidepressant response and eventually for guiding clinical treatment decisions. While most of these methods are based on resting-state EEGs (e. g., alpha-and theta-band EEG abnormalities, the combined Antidepressant Response Index (ATR), cordance, referenced EEG), others include EEG source localization and evoked potentials. The limitations of these technologies and the potential clinical uses will also be outlined. (HARV REV PSYCHIATRY 2011;19:144-154.) C1 [Iosifescu, Dan Vlad] Harvard Univ, Dept Psychiat, Mt Sinai Sch Med, Sch Med, New York, NY 10029 USA. [Iosifescu, Dan Vlad] Harvard Univ, Dept Neurosci, Mt Sinai Sch Med, Sch Med, New York, NY 10029 USA. [Iosifescu, Dan Vlad] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Iosifescu, DV (reprint author), Harvard Univ, Dept Psychiat, Mt Sinai Sch Med, Sch Med, 1 Gustave L Levy Pl,Box 1230, New York, NY 10029 USA. EM dan.iosifescu@mssm.edu NR 65 TC 18 Z9 22 U1 4 U2 9 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD MAY-JUN PY 2011 VL 19 IS 3 SI SI BP 144 EP 154 DI 10.3109/10673229.2011.586549 PG 11 WC Psychiatry SC Psychiatry GA 771MJ UT WOS:000291162300005 PM 21631160 ER PT J AU Borairi, S Dougherty, DD AF Borairi, Sahar Dougherty, Darin D. TI The Use of Neuroimaging to Predict Treatment Response for Neurosurgical Interventions for Treatment-Refractory Major Depression and Obsessive-Compulsive Disorder SO HARVARD REVIEW OF PSYCHIATRY LA English DT Review DE biological markers; major depressive disorder; neuroimaging; neurosurgery; neurotherapy; obsessive-compulsive disorder ID MEDIAL PREFRONTAL CORTEX; DEEP BRAIN-STIMULATION; TREATMENT-RESISTANT DEPRESSION; SUBGENUAL CINGULATE CORTEX; GLUCOSE-METABOLISM; POTENTIAL PREDICTORS; ANTERIOR CINGULOTOMY; UNIPOLAR DEPRESSION; BEHAVIORAL-THERAPY; SLEEP-DEPRIVATION AB Neuroimaging has contributed profoundly to our understanding of the pathophysiology of psychiatric disorders but has had little impact on treatment. An important goal in neuroscience research is identifying biological markers that predict subsequent response to given treatments. This approach may be especially valuable when considering high-risk and high-cost treatments such as psychiatric neurosurgery. Here, we review neuroimaging findings pertaining to treatment-refractory major depression and obsessive-compulsive disorder, and imaging markers that predict response to neurotherapeutic interventions. Thus far, studies conducted with neurotherapeutic interventions have found patterns of predictive brain activity that are similar to those conducted with pharmacological treatments. The predictive neural correlates are concordant with pathophysiological models of major depressive and obsessive-compulsive disorder. These promising findings should motivate additional work establishing the reliability and cost-effectiveness of neuroimaging to predict treatment response across psychiatric diagnoses and interventions. (HARV REV PSYCHIATRY 2011;19:155-161.) C1 [Borairi, Sahar] York Univ, Dept Psychol, Boston, MA USA. [Dougherty, Darin D.] Harvard Univ, Sch Med, Boston, MA USA. [Dougherty, Darin D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Dougherty, DD (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 149 13th St,Room 2612, Charlestown, MA 02129 USA. EM ddougherty@partners.org FU NIMH NIH HHS [P50 MH086400] NR 50 TC 2 Z9 2 U1 2 U2 10 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD MAY-JUN PY 2011 VL 19 IS 3 SI SI BP 155 EP 161 DI 10.3109/10673229.2011.581888 PG 7 WC Psychiatry SC Psychiatry GA 771MJ UT WOS:000291162300006 PM 21631161 ER PT J AU Riess, H AF Riess, Helen TI Biomarkers in the Psychotherapeutic Relationship: The Role of Physiology, Neurobiology, and Biological Correlates of EMPATHY SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article DE biomarkers; empathy; neural correlates of empathy; patient-doctor relationship; psychophysiology; psychotherapy; therapeutic alliance ID COGNITIVE-BEHAVIORAL-THERAPY; HUMAN CINGULATE CORTEX; NEURAL BASIS; INTERPERSONAL PSYCHOTHERAPY; MAGNETIC STIMULATION; EMOTIONAL EXPERIENCE; FACIAL EXPRESSIONS; BLOOD-FLOW; DEPRESSION; ALLIANCE AB Emerging biomarker research could powerfully influence the practice of psychotherapy, a standard treatment that is as strongly rooted in brain plasticity as are psychopharmacologic interventions. Psychotherapy is associated with measurable changes in central and peripheral neurophysiology. These markers could be harnessed to aid informed, personalized recommendations for specific psychosocial treatments, to guide a course of treatment, and to predict treatment outcomes, in lieu of relying on costly, trial-and-error approaches. Psychotherapy and empathy research also demonstrate that the patient-doctor relationship has important neurophysiological correlates that can be salient to treatment outcomes, as illustrated in a case example. These correlates include autonomic nervous system arousal manifested by heart rate, respiration rate, muscle tension, and galvanic skin resistance; electroencephalography; and brain-imaging markers. While additional biomarker research is unfolding, there are specific neurobiologically based clinical and subclinical observations, organized by using the E.M.P.A.T.H.Y. mnemonic, that may guide and enhance psychotherapy. Empathic attunement to patients is equally relevant for psychopharmacologic interventions and psychotherapy, and for all patient-doctor relationships. (HARV REV PSYCHIATRY 2011;19:162-174.) C1 [Riess, Helen] Harvard Univ, Sch Med, Boston, MA USA. [Riess, Helen] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Riess, H (reprint author), Wang ACC, Dept Psychiat, Suite 812,15 Parkman St, Boston, MA 02114 USA. EM HRIESS@PARTNERS.ORG NR 107 TC 7 Z9 7 U1 2 U2 31 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD MAY-JUN PY 2011 VL 19 IS 3 SI SI BP 162 EP 174 DI 10.3109/08941939.2011.581915 PG 13 WC Psychiatry SC Psychiatry GA 771MJ UT WOS:000291162300007 PM 21631162 ER PT J AU Villarreal, G Oh, DJ Kang, MH Rhee, DJ AF Villarreal, Guadalupe, Jr. Oh, Dong-Jin Kang, Min Hyung Rhee, Douglas J. TI Coordinated Regulation of Extracellular Matrix Synthesis by the MicroRNA-29 Family in the Trabecular Meshwork SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID OPEN-ANGLE GLAUCOMA; AQUEOUS-HUMOR; VISUAL IMPAIRMENT; OUTFLOW FACILITY; GENE-EXPRESSION; SMAD PROTEINS; TGF-BETA; INTRAOCULAR-PRESSURE; HUMAN EYES; CELLS AB PURPOSE. The microRNA-29 (miR-29) family has emerged, in various tissues, as a key modulator of extracellular matrix (ECM) homeostasis. In this study, the authors investigate the role of the miR-29 family in the regulation of ECM synthesis in the trabecular meshwork (TM) under basal and TGF-beta 2 stimulatory conditions. METHODS. Human TM cells were incubated with 2.5 ng/mL activated, recombinant human TGF-beta 2 for 24, 48, and 72 hours. A specific pharmacologic inhibitor was used to block SMAD3 function in the context of TGF-beta 2 stimulation. Changes in the expression of the miR-29 family were assessed by real-time PCR. The effect of miR-29 molecules and inhibitors on ECM levels was determined by immunoblot analysis. RESULTS. All three members of the miR-29 family were expressed in cultured TM cells. Although the incubation of TM cells with TGF-beta 2 induced miR-29a and suppressed miR-29b levels, no significant effect was observed on miR-29c expression. Additional studies revealed that SMAD3 modulates miR-29b expression under basal and TGF-beta 2 conditions. Subsequent gain-and loss-of-function experiments demonstrated that the miR-29 family functions as a critical suppressor of various ECM proteins under basal and TGF-beta 2 stimulatory conditions. CONCLUSIONS. The findings derived from this study identify the miR-29 family as a critical regulator of ECM expression in the TM and suggest that its modulation by TGF-beta 2 may be important in controlling ECM synthesis. Together, these data provide further insight into the complex regulatory mechanisms mediating TGF-beta 2 signaling and ECM production in the TM. (Invest Ophthalmol Vis Sci. 2011;52:3391-3397) DOI:10.1167/iovs.10-6165 C1 [Villarreal, Guadalupe, Jr.; Oh, Dong-Jin; Kang, Min Hyung; Rhee, Douglas J.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Rhee, DJ (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM dougrhee@aol.com FU Fight for Sight; National Eye Institute [EY 019654-01, EY 014104] FX Supported by a Fight for Sight Summer Student Fellowship (GV) and by National Eye Institute Grants EY 019654-01 (DJR) and EY 014104 (MEEI Vision-Core Grant). NR 59 TC 45 Z9 46 U1 0 U2 5 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2011 VL 52 IS 6 BP 3391 EP 3397 DI 10.1167/iovs.10-6165 PG 7 WC Ophthalmology SC Ophthalmology GA 770PN UT WOS:000291100800067 PM 21330653 ER PT J AU Iovieno, N Dalton, ED Fava, M Mischoulon, D AF Iovieno, Nadia Dalton, Elizabeth D. Fava, Maurizio Mischoulon, David TI Second-tier natural antidepressants: Review and critique SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Review DE Complementary and Alternative Medicine; Depression; Rhodiola rosea; Chromium; 5-Hydroxytryptophan; Inositol ID ROSEA L. EXTRACT; OBSESSIVE-COMPULSIVE DISORDER; LOW-DOSE REGIMEN; RHODIOLA-ROSEA; DOUBLE-BLIND; ALTERNATIVE MEDICINE; CHROMIUM PICOLINATE; INOSITOL TREATMENT; RESONANCE-SPECTROSCOPY; DEPRESSION RESISTANT AB The use of Complementary and Alternative Medicine (CAM) for physical and mental problems has increased significantly in the US over the past two decades, and depression is one of the leading indications for the use of CAM. This article reviews some of the lesser-known natural products with potential psychiatric applications that are starting to emerge with some scientific and clinical evidence and may constitute a next wave of natural antidepressants: Rhodiola rosea, chromium, 5-Hydroxytryptophan (5-HTP) and inositol. Background information, efficacy data, proposed mechanisms of action, recommended doses, side effects, and precautions are reviewed. We found some encouraging data for the use of these natural products in specific populations of depressed patients. R.rosea is an adaptogen plant that can be especially helpful in treating asthenic or lethargic depression, and may be combined with conventional antidepressants to alleviate some of their common side effects. Chromium has a beneficial effect on eating-related atypical symptoms of depression, and may be a valuable agent in treating atypical depression and seasonal affective disorder. Inositol may be useful in the treatment of bipolar depression when combined with mood stabilizers. Evidence for the clinical efficacy of 5-HTP is also promising but still preliminary. Although more well-designed and larger controlled studies are needed before any substantive conclusions can be drawn, the available evidence is compelling and these natural products deserve further investigation as a possibly significant addition to the antidepressant armamentarium. (C) 2010 Elsevier B.V. All rights reserved. C1 [Iovieno, Nadia; Dalton, Elizabeth D.; Fava, Maurizio; Mischoulon, David] Harvard Univ, Depress Clin & Res Program, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Iovieno, Nadia] Univ Pisa, Dept Psychiat, Pisa, Italy. RP Iovieno, N (reprint author), Harvard Univ, Depress Clin & Res Program, Sch Med, Massachusetts Gen Hosp, 50 Staniford St, Boston, MA 02114 USA. EM niovieno@partners.org FU Abbott Laboratories; Alkermes; Aspect Medical Systems; Astra-Zeneca; Bio Research; BrainCells, Inc.; Bristol-Myers Squibb Company; Cephalon; Clinical Trial Solutions; Eli Lilly Company; Forest Pharmaceuticals Inc.; Ganeden; GlaxoSmithKline; J & J Pharmaceuticals; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; NARSAD; NCCAM; NIDA; NIMH; Novartis; Organon Inc.; PamLab; LLC; Pfizer Inc.; Pharmavite; Roche; Sanofi-Aventis; Shire; Solvay Pharmaceuticals, Inc.; Synthelabo; Wyeth-Ayerst Laboratories; Laxdale (Amarin); Nordic Naturals; SwissMedica FX Dr. M. Fava has served has an advisor/consultant for Abbott Laboratories, Amarin, Aspect Medical Systems, Astra-Zeneca, Auspex Pharmaceuticals, Bayer AG, Best Practice Project Management, Inc, Biovail Pharmaceuticals, Inc., BrainCells, Inc, Bristol-Myers Squibb Company, Cephalon, Clinical Trials Solutions, CNS Response, Compellis, Cypress Pharmaceuticals, Dov Pharmaceuticals, Eli Lilly & Company, EPIX Pharmaceuticals, Fabre-Kramer, Pharmaceuticals, Inc., Forest Pharmaceuticals Inc., GlaxoSmithKline, Grunenthal GmBH Janssen Pharmaceutica, Jazz Pharmaceuticals, J & J Pharmaceuticals, Knoll Pharmaceutical Company, Labopharm, Lorex Pharmaceuticals, Lundbeck, MedAvante Inc. Merck, Methylation Sciences. Neuronetics, Novartis, Nutrition 21, Organon Inc., PamLab, LLC, Pfizer Inc., PharmaStar, Pharmavite, Precision Human Biolaboratory, Roche, Sanofi-Aventis, Sepracor, Schering-Plough, Solvay Pharmaceuticals Inc., Somaxon, Somerset Pharmaceuticals, Synthelabo, Takeda, Tetragenex, Transcept Pharmaceuticals, Vanda Pharmaceuticals Inc., Wyeth-Ayerst Laboratories; has received research support from Abbott Laboratories, Alkermes, Aspect Medical Systems, Astra-Zeneca, Bio Research, BrainCells, Inc., Bristol-Myers Squibb Company, Cephalon, Clinical Trial Solutions, Eli Lilly & Company, Forest Pharmaceuticals Inc., Ganeden, GlaxoSmithKline, J & J Pharmaceuticals, Lichtwer Pharma GmbH, Lorex Pharmaceuticals, NARSAD, NCCAM, NIDA, NIMH, Novartis, Organon Inc., PamLab, LLC, Pfizer Inc., Pharmavite, Roche, Sanofi-Aventis, Shire, Solvay Pharmaceuticals, Inc., Synthelabo, Wyeth-Ayerst Laboratories; has served as a speaker for Advanced Meeting Partners, American Psychiatric Association, Astra-Zeneca, Belvoir, Boehringer-Ingelheim, Bristol-Myers Squibb Company, Cephalon. Eli Lilly & Company, Forest Pharmaceuticals Inc., GlaxoSmithKline, Imedex, Novartis, Organon Inc., Pfizer Inc., PharmaStar, MGH Psychiatry Academy/Primedia, MGH Psychiatry Academy/Reed-Elsevier, UBC, Wyeth-Ayerst Laboratories; has equity Holdings in Compellis; and has patent applications for SPCD and for a combination of azapirones and bupropion in MDD, copyright royalties for the MGH CPFQ SFI, ATRQ DESS, and SAFER.; Dr. D. Mischoulon has served as a consultant for Bristol-Myers Squibb Company and PamLab; has received research support from Laxdale (Amarin), Nordic Naturals, Ganeden, SwissMedica; has received honoraria from MGH Psychiatry Academy/Reed Medical Education; has served as a speaker for Pamlab, Virbac; Nordic Naturals; and has royalties for Back Bay Scientific for PMS Escape (patent application pending). NR 116 TC 18 Z9 18 U1 3 U2 32 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 MAY PY 2011 VL 130 IS 3 BP 343 EP 357 DI 10.1016/j.jad.2010.06.010 PG 15 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 771WT UT WOS:000291192100001 PM 20579741 ER PT J AU Mischoulon, D Eddy, KT Keshaviah, A Dinescu, D Ross, SL Kass, AE Franko, DL Herzog, DB AF Mischoulon, David Eddy, Kamryn T. Keshaviah, Aparna Dinescu, Diana Ross, Stephanie L. Kass, Andrea E. Franko, Debra L. Herzog, David B. TI Depression and eating disorders: Treatment and course SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Major depressive disorder; Eating disorders; Anorexia nervosa; Bulimia nervosa; Antidepressants ID ANOREXIA-NERVOSA; BULIMIA-NERVOSA; SUICIDE ATTEMPTS; FLUOXETINE; PLACEBO; OBSESSIONALITY; PSYCHOTHERAPY; COMORBIDITY; RECOVERY; ANXIETY AB Background: We examined the course of major depressive disorder (MDD) and predictors of MOD recovery and relapse in a longitudinal sample of women with eating disorders (ED). Methods: 246 Boston-area women with DSM-IV anorexia nervosa-restricting (ANR; n = 51), AN-binge/purge (ANBP; n = 85), and bulimia nervosa (BN; n = 110) were recruited between 1987 and 1991 and interviewed using the Eating Disorders Longitudinal Interval Follow-up Evaluation (LIFE-EAT-II) every 6-12 months for up to 12 years. 100 participants had MDD at study intake and 45 developed MOD during the study. Psychological functioning and treatment were assessed. Results: Times to MDD onset (1 week-4.3 years), recovery (8 weeks-8.7 years), and relapse (1 week-5.2 years) varied. 70% recovered from MOD, but 65% subsequently relapsed. ANR patients were significantly less likely to recover from MDD than ANBP patients (p = 0.029). Better psychological functioning and history of MDD were associated with higher chance of MDD recovery. Higher baseline depressive severity and full recovery from ED were associated with greater likelihood of MDD relapse; increased weight loss was somewhat protective. Adequate antidepressant treatment was given to 72% of patients with MDD and generally continued after MDD recovery. Time on antidepressants did not predict MOD recovery (p = 0.27) or relapse (p = 0.26). Limitations: Small ED diagnostic subgroups; lack of non-ED control group. Conclusions: The course of MDD in EDs is protracted; MOD recovery may depend on ED type. Antidepressants did not impact likelihood of MOD recovery, nor protect against relapse, which may impact on treatment strategies for comorbid MOD and EDs. (C) 2010 Elsevier B.V. All rights reserved. C1 [Mischoulon, David] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Eddy, Kamryn T.; Dinescu, Diana; Ross, Stephanie L.; Kass, Andrea E.; Franko, Debra L.; Herzog, David B.] Massachusetts Gen Hosp, Harris Ctr Educ & Advocacy Eating Disorders, Dept Psychiat, Boston, MA 02114 USA. [Eddy, Kamryn T.; Herzog, David B.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Keshaviah, Aparna] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Franko, Debra L.] Northeastern Univ, Dept Counseling & Appl Educ Psychol, Boston, MA 02115 USA. RP Mischoulon, D (reprint author), 1 Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM dmischoulon@partners.org FU National Institute of Mental Health [5R01 MH 38333 05]; Rubenstein Charitable Foundation, Boston MA; Laxdale (Amarin); Nordic Naturals; Ganeden; SwissMedica FX This work was supported by the National Institute of Mental Health grant 5R01 MH 38333 05 (DBH) and the Rubenstein Charitable Foundation, Boston MA. Sponsors had no further role in the study design, collection, analysis and interpretation of data, writing of the report, and the decision to submit the paper for publication.; Dr. Mischoulon has received research support from Laxdale (Amarin), Nordic Naturals, Ganeden, and SwissMedica. He has served as a consultant to Bristol-Meyers-Squibb Company. He has received speaking honoraria from Pamlab, Virbac, and Nordic Naturals. He has received writing honoraria from Pamlab. He has received royalties from Back Bay Scientific for PMS Escape, and royalties from Lippincott Williams & Wilkins, for textbook "Natural Medications for Psychiatric Disorders: Considering the Alternatives" (David Mischoulon and Jerrold F Rosenbaum, Eds.). He has received honoraria from Reed Medical Education (a company working as a logistics collaborator for the MGH Psychiatry Academy). The education programs conducted by the MGH Psychiatry Academy were supported through Independent Medical Education (IME) grants from pharmaceutical companies co-supporting programs along with participant tuition. Commercial entities currently supporting the MGH Psychiatry Academy are listed on the Academy's website www.mghcme.org. NR 38 TC 33 Z9 33 U1 1 U2 13 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 MAY PY 2011 VL 130 IS 3 BP 470 EP 477 DI 10.1016/j.jad.2010.10.043 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 771WT UT WOS:000291192100015 PM 21109307 ER PT J AU La Fountaine, MF Gossett, JD De Meersman, RE Bauman, WA AF La Fountaine, Michael F. Gossett, James D. De Meersman, Ronald E. Bauman, William A. TI Increased QT Interval Variability in 3 Recently Concussed Athletes: An Exploratory Observation SO JOURNAL OF ATHLETIC TRAINING LA English DT Article DE autonomic nervous system; heart; cardiovascular system; return to play ID HEART-RATE-VARIABILITY; AUTONOMIC NERVOUS-SYSTEM; POWER SPECTRAL-ANALYSIS; SUDDEN CARDIAC DEATH; EXERCISE; MODULATION; CASCADE; RISK AB Context: The QT interval variability index (QTVI) is a noninvasive measure of beat-to-beat fluctuations of the QT interval as seen from a single electrocardiographic lead. It represents the relationship between the respective variabilities of the QT and R-R intervals. Recently, the QTVI was demonstrated to be an index of vagal cardiac autonomic modulation in resting conditions. Objective: To determine whether QTVI varied in athletes at 48 hours, 1 week, and 2 weeks after a concussive head injury. Design: Case series. Setting: Testing facility. Patients or Other Participants: Three athletes with recent concussions and 3 uninjured athletes with similar demographic factors. Main Outcome Measure(s): Continuous 3-lead electrocardiograms were obtained in a seated, resting position over 2 successive weeks. Separate, unpaired t tests were performed to determine whether group-visit differences were present in the QTVI at 48 hours, 1 week, or 2 weeks. Results: No demographic differences were present between groups. At 48 hours, the QTVI was greater in the concussion group than in the matched controls. At weeks 1 and 2, the QTVI in the concussion group was lower than at 48 hours and not different from that of the control group. Conclusions: Vagal cardiac autonomic modulation, as quantified by the QTVI, appeared to be negatively affected in concussed athletes within 48 hours of injury, resolved within 1 week, and remained at control group levels 2 weeks later. Serial assessments of QTVI may be of clinical utility in identifying suspected cases of acute concussion and may provide helpful information for determining when an athlete can return to play safely. C1 [La Fountaine, Michael F.; Bauman, William A.] James J Peters VA Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Bronx, NY 10468 USA. [La Fountaine, Michael F.; Bauman, William A.] James J Peters VA Med Ctr, SCI Serv, Bronx, NY 10468 USA. [La Fountaine, Michael F.; Bauman, William A.] Mt Sinai Sch Med, Dept Med, New York, NY USA. [Gossett, James D.] Columbia Univ, Dept Sports Med, New York, NY USA. [De Meersman, Ronald E.] Columbia Univ, Teachers Coll, Dept Biobehav Sci, New York, NY 10027 USA. [Bauman, William A.] Mt Sinai Sch Med, Dept Rehabil Med, New York, NY USA. RP La Fountaine, MF (reprint author), James J Peters VA Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Room 7A-13M,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM michael.lafountaine@va.gov NR 32 TC 5 Z9 5 U1 0 U2 5 PU NATL ATHLETIC TRAINERS ASSOC INC PI DALLAS PA 2952 STEMMONS FREEWAY, DALLAS, TX 75247 USA SN 1062-6050 J9 J ATHL TRAINING JI J. Athl. Train. PD MAY-JUN PY 2011 VL 46 IS 3 BP 230 EP 233 PG 4 WC Sport Sciences SC Sport Sciences GA 770YC UT WOS:000291123400002 PM 21669090 ER PT J AU Smith, EG Craig, TJ Ganoczy, D Walters, HM Valenstein, M AF Smith, Eric G. Craig, Thomas J. Ganoczy, Dara Walters, Heather M. Valenstein, Marcia TI Treatment of Veterans With Depression Who Died by Suicide: Timing and Quality of Care at Last Veterans Health Administration Visit SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID PSYCHOLOGICAL AUTOPSY; MENTAL-HEALTH; UNITED-STATES; ANTIDEPRESSANTS; CONTACT; SWEDEN; PEOPLE; ACCESS; PRESCRIPTION; PREVENTION AB Objective: To examine the recency and quality of the last Veterans Health Administration (VHA) visit for patients with depression who died by suicide. Method: We obtained services and pharmacy data for all 1,843 VHA patients with diagnosed depressive disorders (DSM-IV criteria) who died by suicide from April 1999 through September 2004. We ascertained the location and timing of their final VHA visit. For visits occurring within 30 days of suicide, we examined 3 quality indicators: (1) evidence that mental illness was a focus of the final visit, (2) adequacy of antidepressant dosage, and (3) recent receipt of mental health services. Results: Just over half of the patients (51%) with depression diagnoses had a VHA visit within 30 days of suicide. A minority of these patients (43%) died by suicide within 30 days of a final visit with mental health services, although 64% had received such services within 91 days of their suicide. Among the 57% of patients who died by suicide within 30 days and who were seen in non-mental health settings for their final visit, only 34% had a mental health condition coded at the final visit, and only 41% were receiving adequate dosages of antidepressant (versus 55% for those last seen by mental health services) (P <. 0005). Conclusions: Veterans Health Administration patients with depression who died by suicide within 30 days of their final visit received relatively high rates of mental health services, but most final visits still occurred in non-mental health settings. Increased referrals to mental health services, attention to mental health issues in non-mental health settings, and focus on antidepressant treatment adequacy by all providers might have reduced suicide risks for these patients. J Clin Psychiatry 2011;72(5):622-629 (C) Copyright 2010 Physicians Postgraduate Press, Inc. C1 [Smith, Eric G.] Vet Hlth Adm VHA Hlth Serv Res & Dev Ctr Hlth Qua, Bedford, MA USA. [Smith, Eric G.] Univ Massachusetts, Sch Med, Dept Psychiat, Worcester, MA 01655 USA. [Craig, Thomas J.] US Dept Vet Affairs, Washington, DC USA. [Ganoczy, Dara; Walters, Heather M.; Valenstein, Marcia] Serious Mental Illness Treatment Resource & Evalu, Ann Arbor Ctr Excellence COE, Dept Vet Affairs, Ann Arbor, MI USA. [Valenstein, Marcia] Univ Michigan, Sch Med, Dept Psychiat, Ann Arbor, MI USA. RP Smith, EG (reprint author), Edith Nourse Rogers Mem VA Hosp, Room B-29,Bldg 70,200 Springs Rd, Bedford, MA 01730 USA. EM Eric.Smith5@va.gov FU Forest Research Institute, an affiliate of Forest Laboratories, a manufacturer of antidepressants (among other medications); Department of Veterans Affairs [IIR 04-211]; National Institute of Mental Health [R01 MH078698]; Serious Mental Illness Treatment Resource and Evaluation Center; Ann Arbor; VHA Health Services Research and Development [RCD 98-350] FX Dr Smith receives grant funding from Forest Research Institute, an affiliate of Forest Laboratories, a manufacturer of antidepressants (among other medications), for unrelated investigator-initiated research concerning the safety of antidepressants. Dr Smith declares that he received no funds from this grant during the period of preparation of this article and that the grant did not influence this article in any way. Drs Craig and Valenstein and Mss Ganoczy and Walters have no competing financial interests to disclose.\; Supported by Department of Veterans Affairs grant IIR 04-211, by National Institute of Mental Health grant R01 MH078698, and by the Serious Mental Illness Treatment Resource and Evaluation Center, Ann Arbor, Michigan. Dr Smith receives salary support through VHA Health Services Research and Development Center of Excellence funding to the Center for Health Quality, Outcomes, and Economic Research, Bedford, Massachusetts. Support for database and research provided by VHA Health Services Research and Development grant RCD 98-350 (Dr Valenstein, principal investigator). NR 39 TC 14 Z9 14 U1 0 U2 6 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 MAY PY 2011 VL 72 IS 5 BP 622 EP 629 DI 10.4088/JCP.09m05608b1u PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 772NM UT WOS:000291240600008 PM 20868636 ER PT J AU Gitlin, MJ Mintz, J Sokolski, K Hammen, C Altshuler, LL AF Gitlin, Michael J. Mintz, Jim Sokolski, Kenneth Hammen, Constance Altshuler, Lori L. TI Subsyndromal Depressive Symptoms After Symptomatic Recovery From Mania Are Associated With Delayed Functional Recovery SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID PROSPECTIVE FOLLOW-UP; BIPOLAR-II DISORDER; LONG-TERM COURSE; PSYCHOSOCIAL DISABILITY; NATURAL-HISTORY; RATING-SCALE; IMPAIRMENT; HOSPITALIZATION; REMISSION; IMPACT AB Objective: This study examined whether the presence of subsyndromal depressive symptoms predicted functional recovery after an acute manic episode. Method: Subjects with bipolar I disorder (according to the Structured Clinical Interview for DSM-IV) who, at the time of symptomatic recovery from an acute manic or hypomanic episode, had a concomitant functional recovery (n = 52) were compared on demographic variables and mood symptoms to those who had symptomatically recovered but not functionally recovered (n = 33). Demographic and mood variables were examined in the nonfunctionally recovered group to assess predictors of time to functional recovery. The primary functional outcome measure used was the Life Functioning Questionnaire, a 5-minute, gender-neutral self-report scale to measure role function in 4 domains: workplace, duties at home, leisure time with family, and leisure time with friends. Participants in the study were recruited from July 2000 through February 2005. Results: Depressive symptoms, even at a subsyndromal level, were significantly associated with persisting functional impairment after symptomatic recovery from a manic episode (P<.02). Subsyndromal depressive symptoms also significantly predicted a slower time to functional recovery over the next 9 months (P=.006). Conclusion: The presence of even mild subsyndromal depressive symptoms may interfere with functional recovery in patients with bipolar disorder after symptomatic recovery from a manic or hypomanic episode. J Clin Psychiatry 2011;72(5):692-697 (C) Copyright 2010 Physicians Postgraduate Press, Inc. C1 [Gitlin, Michael J.; Altshuler, Lori L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Mintz, Jim] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX USA. [Sokolski, Kenneth] Vet Affairs VA Long Beach Healthcare Syst, Mental Hlth Care Grp, Long Beach, CA USA. [Sokolski, Kenneth] Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine Sch Med, Irvine, CA 92717 USA. [Hammen, Constance] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [Altshuler, Lori L.] VA Greater Los Angeles Healthcare Syst, W Los Angeles Healthcare Ctr, Los Angeles, CA USA. RP Gitlin, MJ (reprint author), 300 UCLA Med Plaza,Ste 2200, Los Angeles, CA 90095 USA. EM mgitlin@mednet.ucla.edu FU National Institute of Mental Health, Bethesda, Maryland [1R01MH057762]; Abbott Laboratories, Abbott Park, Illinois FX Funding for this study was provided by the National Institute of Mental Health (1R01MH057762) (Dr Altshuler), Bethesda, Maryland. Abbott Laboratories (Dr Altshuler), Abbott Park, Illinois, provided funding to obtain divalproex sodium levels at the UCLA laboratory and provided divalproex sodium for some study subjects. NR 39 TC 18 Z9 18 U1 0 U2 2 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAY PY 2011 VL 72 IS 5 BP 692 EP 697 DI 10.4088/JCP.09m05291gre PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 772NM UT WOS:000291240600016 PM 20673560 ER PT J AU Sachs, GS Dupuy, JM Wittmann, CW AF Sachs, Gary S. Dupuy, Jamie M. Wittmann, Curtis W. TI The Pharmacologic Treatment of Bipolar Disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID PLACEBO-CONTROLLED TRIAL; TREATMENT ENHANCEMENT PROGRAM; LITHIUM MAINTENANCE TREATMENT; RELEASE CARBAMAZEPINE CAPSULES; MANIC-DEPRESSIVE DISORDERS; CONTROLLED 18-MONTH TRIAL; NOS MAJOR DEPRESSION; DOUBLE-BLIND TRIAL; OPEN-LABEL TRIAL; I-DISORDER AB Over the past half century, substantial clinical trial data have accumulated to guide clinical management of bipolar disorder, and 13 medications have gained US Food and Drug Administration approval for the treatment of mania or bipolar depression or the maintenance treatment of bipolar disorder. While the number of studies has grown and many controversies related to pharmacologic treatment of bipolar disorder are not yet resolved, the task of transforming the accumulated evidence into useful guidance for clinical practice becomes more manageable and less error prone by limiting consideration to the highest quality studies. Therefore, this article emphasizes points of relative clarity by highlighting findings supported by double-blind, placebo-controlled clinical trials with samples of at least 100 subjects. A MEDLINE search was conducted and augmented by a manual search of bibliographies, textbooks, and abstracts from recent scientific meetings for randomized controlled trials published in English between 1950 and April 2010 with at least 100 subjects. Keywords used in the search included randomized controlled trial, mania, hypomania, depression, relapse prevention, placebo, antidepressant, switch, and maintenance treatment of bipolar disorder. A paradigm for implementing evidence-based treatment is offered along with consideration of patterns emerging across clinical trials. J Clin Psychiatry 2011;72(5):704-715 (C) Copyright 2011 Physicians Postgraduate Press, Inc. C1 [Sachs, Gary S.] Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Bipolar Clin, Boston, MA 02114 USA. [Sachs, Gary S.; Dupuy, Jamie M.; Wittmann, Curtis W.] Massachusetts Gen Hosp, Res Program, Boston, MA 02114 USA. [Sachs, Gary S.] United BioSource Corp, Lexington, MA USA. RP Sachs, GS (reprint author), Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Bipolar Clin, WACC 815,50 Staniford St, Boston, MA 02114 USA. EM sachsg@aol.com FU National Institute of Mental Health and Repligen FX Dr Sachs is an employee of United BioSource Corporation; has been a consultant for Forest, Merck, Sunovion, and Takeda; has received grant/research support from the National Institute of Mental Health and Repligen; has been on the speakers/advisory boards of AstraZeneca, Pfizer, and Otsuka; and is a stock shareholder in Concordant Rater Systems. Drs Dupuy and Wittmann report no financial or other relationships relevant to the subject of this article. NR 157 TC 12 Z9 12 U1 3 U2 6 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAY PY 2011 VL 72 IS 5 BP 704 EP 715 DI 10.4088/JCP.10m06523 PG 12 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 772NM UT WOS:000291240600018 PM 21658351 ER PT J AU Berlin, HA Koran, LM Jenike, MA Shapira, NA Chaplin, W Pallanti, S Hollander, E AF Berlin, Heather A. Koran, Lorrin M. Jenike, Michael A. Shapira, Nathan A. Chaplin, William Pallanti, Stefano Hollander, Eric TI Double-Blind, Placebo-Controlled Trial of Topiramate Augmentation in Treatment-Resistant Obsessive-Compulsive Disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID COMORBID TOURETTES-SYNDROME; TRANSGENIC MODEL; TRANSPORTER GENE; ASSOCIATION; PAROXETINE; SEROTONIN; RECEPTOR; SCALE; OCD; SLC1A1/EAAC1 AB Background: From 40% to 60% of obsessive-compulsive disorder (OCD) patients fail to tolerate or respond to selective serotonin reuptake inhibitors (SSRIs). Preclinical and neuroimaging studies have shown abnormally high glutamatergic concentrations in OCD patients and an association between decreased caudate glutamatergic concentrations and reduced OCD symptom severity after SSRI treatment. Topiramate inhibits glutamatergic conduction. Method: Thirty-six adult patients with DSM-IV-defined OCD were randomly assigned to topiramate (n = 18) and placebo (n = 18) groups in this 12-week, double-blind, placebo-controlled, parallel-groups trial. Subjects were taking the maximum SSRI dose they could tolerate for at least 12 weeks and their current dose for at least 6 weeks, which was maintained throughout the study. Primary outcome measures were changes in the Yale-Brown Obsessive Compulsive Scale (YBOCS) total score and compulsions and obsessions subscores. Patients were recruited and followed up between April 1, 2003, and April 13, 2006. Results: Using mixed regression models (time [weeks] x treatment), we found a significant treatment effect on the YBOCS compulsions (P=.014) subscale, but not the obsessions (P=.99) subscale or the total score (P=.11). Over the 12-week trial, the topiramate group (mean endpoint dose =177.8 +/- 134.2 mg/d; range, 50-400 mg/d) showed an average linear decrease of 5.38 points on the compulsions subscale compared to 0.6 points in the placebo group. Thirteen topiramate and 14 placebo subjects completed the study. Topiramate was not well tolerated in this trial: 28% (5/18) of the subjects discontinued the drug for adverse effects, and 39% (7/18) had a dose reduction for this reason. Conclusions: The results of this first double-blind, placebo-controlled trial of topiramate augmentation for treatment-resistant OCD suggest that topiramate may be beneficial for compulsions, but not obsessions. Modifications in glutamatergic function may be responsible, at least in part, for the improved response in compulsions seen with topiramate. C1 [Berlin, Heather A.; Pallanti, Stefano] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Koran, Lorrin M.] Stanford Univ, Med Ctr, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Jenike, Michael A.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Jenike, Michael A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Shapira, Nathan A.] Emory Univ, Dept Psychiat & Behav Sci, Sch Med, Atlanta, GA USA. [Chaplin, William] St Johns Univ, Dept Psychol, New York, NY USA. [Hollander, Eric] Albert Einstein Coll Med, Dept Psychiat, Montefiore Med Ctr, Univ Hosp, New York, NY USA. RP Berlin, HA (reprint author), Mt Sinai Sch Med, Dept Psychiat, 1 Gustave L Levy Pl,Box 1230, New York, NY 10029 USA. EM heather.berlin@mssm.edu FU Eli Lilly; Forest; Ortho-McNeil Neurologics; Somaxon; Ortho-McNeil Janssen; Ortho-McNeil Janssen Scientific Affairs, LLC FX Dr Koran chaired the American Psychiatric Association (APA) Workgroup that wrote the Practice Guideline for OCD; has received research grants from Eli Lilly, Forest, Ortho-McNeil Neurologics, and Somaxon; and is on the speakers bureau for Forest. Dr Shapira is named on a patent application (No. 11/830,906) relating to this study. Dr Hollander received research grants from and has been a consultant for Ortho-McNeil Janssen and served on the APA Workgroup that wrote the Practice Guideline for OCD and on the DSM-V Anxiety Disorders workgroup. Drs Berlin, Jenike, Chaplin, and Pallanti report no biomedical financial interests or potential conflicts of interest.; This study was funded by Ortho-McNeil Janssen Scientific Affairs, LLC. NR 56 TC 41 Z9 43 U1 1 U2 11 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAY PY 2011 VL 72 IS 5 BP 716 EP 721 DI 10.4088/JCP.09m05266gre PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 772NM UT WOS:000291240600019 PM 20816027 ER PT J AU Gilbertson, MW Pitman, RK AF Gilbertson, Mark W. Pitman, Roger K. TI Does Combat Trauma Cause a Majority of PTSD Symptoms in Combat Veterans? Reply SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Letter ID POSTTRAUMATIC-STRESS-DISORDER C1 [Gilbertson, Mark W.] Manchester VA Med Ctr, Manchester, NH USA. [Pitman, Roger K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gilbertson, Mark W.; Pitman, Roger K.] Harvard Univ, Sch Med, Boston, MA USA. RP Gilbertson, MW (reprint author), Manchester VA Med Ctr, Manchester, NH USA. EM mark.gilbertson@va.gov NR 2 TC 0 Z9 0 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 MAY PY 2011 VL 72 IS 5 BP 725 EP 725 DI 10.4088/JCP.11lr06851a PG 1 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 772NM UT WOS:000291240600026 ER PT J AU Ding, A Abujudeh, H Novelline, RA AF Ding, Alexander Abujudeh, Hani Novelline, Robert A. TI DIAGNOSING CERVICAL SPINE INSTABILITY: ROLE OF THE POST-COMPUTED TOMOGRAPHY SCAN OUT-OF-COLLAR LATERAL RADIOGRAPH SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE cervical spine CT; spine trauma; out-of-collar radiograph; cervical instability; emergency radiology ID BLUNT TRAUMA PATIENTS; CLEARANCE; INJURY; RULE; CT AB Background: Cervical spine injuries may have devastating neurological consequences, which makes accurate diagnosis of injury a key part of the trauma evaluation. Imaging plays a significant role in making the diagnosis and guiding management. Current American College of Radiology Appropriateness Criteria guidelines recommend computed tomography (CT) of the cervical spine with multi-planar reformats as the highest-rated imaging examination for patients meeting clinical criteria, without subsequent need for further imaging with a negative scan in a neurologically intact and non-obtunded patient. Although CT is fast and accurate for evaluation of bony injury, it may overlook ligamentous injury. Objective and Case Report: We report a case in which ligamentous instability was demonstrated as subluxation with an out-of-collar lateral radiograph after a CT scan showed no subluxation or fracture in a patient without neurological deficits. Our Radiology Department routinely performs an out-of-collar lateral radiograph after a negative CT scan, and this case suggests that there may be an important role for this practice. Conclusion: Magnetic resonance is the optimal study for soft tissue and ligamentous evaluation; however, a simple lateral out-of-collar radiograph after CT clearance, in an otherwise neurologically intact and non-obtunded patient, may be a quick and cost-effective means to assess for instability of the cervical spine. (C) 2011 Elsevier Inc. C1 [Ding, Alexander; Abujudeh, Hani; Novelline, Robert A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Ding, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 55 Fruit St,FND-216, Boston, MA 02114 USA. NR 14 TC 0 Z9 0 U1 0 U2 4 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 MAY PY 2011 VL 40 IS 5 BP 518 EP 521 DI 10.1016/j.jemermed.2010.11.039 PG 4 WC Emergency Medicine SC Emergency Medicine GA 771BN UT WOS:000291132300007 PM 21269791 ER PT J AU Platz, E Liteplo, A Hurwitz, S Hwang, J AF Platz, Elke Liteplo, Andrew Hurwitz, Shelley Hwang, James TI ARE LIVE INSTRUCTORS REPLACEABLE? COMPUTER VS. CLASSROOM LECTURES FOR EFAST TRAINING SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE emergency ultrasound; EFAST; education; e-learning; blended learning ID FOCUSED ASSESSMENT; SONOGRAPHY; ULTRASOUND; EDUCATION AB Background: The EFAST (extended focused assessment with sonography for trauma) is part of the recommended curriculum for Emergency Medicine and Surgery residents. Computer-based lectures may represent a time-efficient alternative to traditional lectures. Objectives: Our hypothesis was that computer lectures in basic ultrasound and the EFAST are not inferior to classroom lectures in test score improvement for residents with or without prior training. Methods: First-year Emergency Medicine and Surgery residents were enrolled and completed a pre-test. Subjects were then randomized into a classroom group, which attended traditional lectures, and a computer group, which listened to narrated lectures on computers. After the didactic training, all subjects completed a post-test. Results: Forty-four subjects completed the study: 64% were General Surgery residents, 66% were male. Overall, mean test score improvements were higher in the classroom than in the computer group (28.0% vs. 18.4%). In 25 residents without prior training, mean improvements in the computer and classroom groups were 25% and 27%, respectively. The 95% confidence limit around the difference was 9%, falling within the a priori non-inferiority range of 10%, and consistent with non inferiority of computer-based lectures. In 19 residents with prior training, mean test score improvements for the computer and classroom groups were 13% and 29%, respectively. The 95% confidence limit of 24% exceeded the noninferiority range, consistent with inferiority of computer-based lectures. Conclusions: Computer-based lectures are not inferior to classroom lectures and may represent a worthwhile substitution in subjects without prior ultrasound education. Our data suggest that didactic ultrasound training through classroom lectures is more effective than computer-based lectures in individuals with prior training. (C) 2011 Elsevier Inc. C1 [Platz, Elke; Hwang, James] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Platz, Elke; Liteplo, Andrew; Hurwitz, Shelley; Hwang, James] Harvard Univ, Sch Med, Boston, MA USA. [Liteplo, Andrew] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Hurwitz, Shelley] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Platz, E (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St,Neville House, Boston, MA 02115 USA. FU Department of Emergency Medicine, Brigham; Women's Hospital, Boston, Massachusetts FX This study was generously supported by two faculty seed grants from the Department of Emergency Medicine, Brigham and Women's Hospital, Boston, Massachusetts. NR 11 TC 12 Z9 12 U1 1 U2 5 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 MAY PY 2011 VL 40 IS 5 BP 534 EP 538 DI 10.1016/j.jemermed.2009.08.030 PG 5 WC Emergency Medicine SC Emergency Medicine GA 771BN UT WOS:000291132300010 PM 19892506 ER PT J AU Hayes, JP LaBar, KS McCarthy, G Selgrade, E Nasser, J Dolcos, F Morey, RA AF Hayes, Jasmeet Pannu LaBar, Kevin S. McCarthy, Gregory Selgrade, Elizabeth Nasser, Jessica Dolcos, Florin Morey, Rajendra A. CA VISN 6 Mid-Atlantic MIRECC Workgrp TI Reduced hippocampal and amygdala activity predicts memory distortions for trauma reminders in combat-related PTSD SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE fMRI; Gist; Contextual memory; Military; Subsequent memory paradigm; Precuneus ID POSTTRAUMATIC-STRESS-DISORDER; CHILDHOOD SEXUAL-ABUSE; CORTICOLIMBIC BLOOD-FLOW; SCRIPT-DRIVEN IMAGERY; MEDIAL TEMPORAL-LOBE; FUZZY-TRACE THEORY; FALSE RECOGNITION; AUTOBIOGRAPHICAL MEMORY; NEURAL SYSTEMS; FMRI AB Neurobiological models of posttraumatic stress disorder (PTSD) suggest that altered activity in the medial temporal lobes (MTL) during encoding of traumatic memories contribute to the development and maintenance of the disorder. However, there is little direct evidence in the PTSD literature to support these models. The goal of the present study was to examine MTL activity during trauma encoding in combat veterans using the subsequent memory paradigm. Fifteen combat veterans diagnosed with PTSD and 14 trauma-exposed control participants viewed trauma-related and neutral pictures while undergoing event-related fMRI. Participants returned one week after scanning for a recognition memory test. Region-of-interest (ROI) and voxel-wise whole brain analyses were conducted to examine the neural correlates of successful memory encoding. Patients with PTSD showed greater false alarm rates for novel lures than the trauma-exposed control group, suggesting reliance on gist-based representations in lieu of encoding contextual details. Imaging analyses revealed reduced activity in the amygdala and hippocampus in PTSD patients during successful encoding of trauma-related stimuli. Reduction in left hippocampal activity was associated with high arousal symptoms on the Clinician-Administered PTSD Scale (CAPS). The behavioral false alarm rate for traumatic stimuli co-varied with activity in the bilateral precuneus. These results support neurobiological theories positing reduced hippocampal activity under conditions of high stress and arousal. Reduction in MTL activity for successfully encoded Stimuli and increased precuneus activity may underlie reduced stimulus-specific encoding and greater gist memory in patients with PTSD, leading to maintenance of the disorder. Published by Elsevier Ltd. C1 [Morey, Rajendra A.] Duke Univ, Med Ctr, Duke UNC Brain Imaging & Anal Ctr, Durham, NC 27710 USA. [Hayes, Jasmeet Pannu] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Hayes, Jasmeet Pannu] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Hayes, Jasmeet Pannu; Morey, Rajendra A.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27710 USA. [Hayes, Jasmeet Pannu; McCarthy, Gregory; Selgrade, Elizabeth; Nasser, Jessica; Morey, Rajendra A.] Durham VA Med Ctr, Mental Illness Res Educ & Clin Ctr, Durham, NC USA. [McCarthy, Gregory] Yale Univ, Dept Psychol, New Haven, CT 06520 USA. [LaBar, Kevin S.] Duke Univ, Ctr Cognit Neurosci, Durham, NC 27710 USA. [Dolcos, Florin] Univ Illinois, Dept Psychol, Urbana, IL 61801 USA. [Dolcos, Florin] Univ Illinois, Beckman Inst, Urbana, IL 61801 USA. RP Morey, RA (reprint author), Duke Univ, Med Ctr, Duke UNC Brain Imaging & Anal Ctr, Box 3918, Durham, NC 27710 USA. EM Rajendra.morey@duke.edu FU Department of Veterans Affairs, Mental Illness Research Education and Clinical Center (MIRECC) [K23 MH073091, K23 MH084013]; U.S. National Institutes of Health [2 P01 NS041328] FX This work was supported by the Department of Veterans Affairs, Mental Illness Research Education and Clinical Center (MIRECC) Grant for Post-Deployment Mental Health, National Institute of Mental Health Grants K23 MH073091 and K23 MH084013, and U.S. National Institutes of Health grant 2 P01 NS041328. These funding sources had no further role in the study design, collection, analysis, interpretation of the data, writing of the report, or the decision to submit the paper for publication. NR 76 TC 47 Z9 50 U1 5 U2 24 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 MAY PY 2011 VL 45 IS 5 BP 660 EP 669 DI 10.1016/j.jpsychires.2010.10.007 PG 10 WC Psychiatry SC Psychiatry GA 771OR UT WOS:000291171100012 PM 21047644 ER PT J AU Martin, LF Olincy, A Ross, RG Du, YPP Singel, D Shatti, S Tregellas, JR AF Martin, Laura Frances Olincy, Ann Ross, Randy G. Du, Yiping P. Singel, Debra Shatti, Shireen Tregellas, Jason R. TI Cerebellar hyperactivity during smooth pursuit eye movements in bipolar disorder SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Magnetic resonance imaging; Uvula; Cerebellum; Hippocampus; Affective symptoms; Depression ID REGIONAL CEREBRAL METABOLISM; COGNITIVE-AFFECTIVE SYNDROME; SCHIZOPHRENIC-PATIENTS; NEUROLEPTIC TREATMENT; UNAFFECTED RELATIVES; UNIPOLAR DEPRESSION; GLUCOSE-METABOLISM; PSYCHOTIC-PATIENTS; MAJOR DEPRESSION; BRAIN ACTIVATION AB Introduction: Smooth pursuit eye movements (SPEM) are abnormal in individuals with schizophrenia and individuals with bipolar disorder. Functional imaging methods have revealed greater hippocampal activity and less frontotemporal, visual, and posterior cerebellar activity in individuals with schizophrenia when performing a SPEM task. The underlying neurobiology of SPEM deficits in bipolar disorder is unknown. Methods: Functional magnetic resonance imaging at 3T was performed on fourteen subjects with bipolar disorder and 14 subjects without psychiatric illness during a block design SPEM task. Clinical measures were assessed on the day of testing and related to imaging measures. Results: Subjects with bipolar disorder had greater hemodynamic response than control subjects in cerebellar vermis. Responses were associated with levels of depressive symptoms on the day of study. Discussion: Increased cerebellar vermis activity during the smooth pursuit eye movement task in individuals with bipolar disorder further implicates cerebellar involvement in bipolar disorder. Increased hemodynamic response within the hippocampus was not seen in these individuals and may be a finding specific to schizophrenia. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Martin, Laura Frances; Olincy, Ann; Ross, Randy G.; Du, Yiping P.; Singel, Debra; Shatti, Shireen; Tregellas, Jason R.] Univ Colorado Denver, Sch Med, Aurora, CO 80045 USA. [Tregellas, Jason R.] Eastern Colorado Hlth Care Syst, Denver Vet Affairs Med Ctr, Res Serv, Denver, CO 80220 USA. RP Martin, LF (reprint author), Univ Colorado Denver, Sch Med, Mail Stop F546,13001 E 17th Pl, Aurora, CO 80045 USA. EM laura.martin@ucdenver.edu RI Tregellas, Jason/J-3637-2015 FU Research Service of the Denver VAMC; NARSAD; [829/RCD- 006-05S] FX This work was supported by the Research Service of the Denver VAMC and Program/Study No: 829/RCD- 006-05S (LFM, JRT) and NARSAD (LFM). Neither the Department of Veterans Affairs nor NARSAD had any further role in study design, data collection, data analysis, manuscript preparation or decision to publish the manuscript. NR 97 TC 4 Z9 4 U1 8 U2 10 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 MAY PY 2011 VL 45 IS 5 BP 670 EP 677 DI 10.1016/j.jpsychires.2010.09.015 PG 8 WC Psychiatry SC Psychiatry GA 771OR UT WOS:000291171100013 PM 20950824 ER PT J AU Garbelotti, K AF Garbelotti, Kelly TI PHANTOM LIMB PAIN RELIEVED WITH PULSED RADIO FREQUENCY ENERGY (PRFE) THERAPY SO JOURNAL OF WOUND OSTOMY AND CONTINENCE NURSING LA English DT Meeting Abstract C1 [Garbelotti, Kelly] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. EM kelly.garbelotti@va.gov NR 5 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1071-5754 J9 J WOUND OSTOMY CONT JI J. Wound Ostomy Cont. Nurs. PD MAY-JUN PY 2011 VL 38 IS 3 SU S MA 5426 BP S83 EP S83 PG 1 WC Nursing SC Nursing GA 772LI UT WOS:000291235000232 ER PT J AU McCarthy, MW Giannino, K AF McCarthy, Maureen W. Giannino, Kerri TI COMPLEX ABDOMINAL WOUNDS SO JOURNAL OF WOUND OSTOMY AND CONTINENCE NURSING LA English DT Meeting Abstract C1 [McCarthy, Maureen W.; Giannino, Kerri] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM mmccarthy29@partners.org; KmGiannino@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1071-5754 J9 J WOUND OSTOMY CONT JI J. Wound Ostomy Cont. Nurs. PD MAY-JUN PY 2011 VL 38 IS 3 SU S MA 5148 BP S26 EP S26 PG 1 WC Nursing SC Nursing GA 772LI UT WOS:000291235000067 ER PT J AU Zulkowski, K Ayello, EA Berlowitz, D Parker, VA Lukas, CV Niederhauser, A AF Zulkowski, Karen Ayello, Elizabeth A. Berlowitz, Dan Parker, Victoria A. Lukas, Carol VanDeusen Niederhauser, Andrea TI PREVENTING PRESSURE ULCERS IN HOSPITALS: DEVELOPMENT OF A QUALITY IMPROVEMENT TOOLKIT SO JOURNAL OF WOUND OSTOMY AND CONTINENCE NURSING LA English DT Meeting Abstract C1 [Zulkowski, Karen] Montana State Univ Bozeman, Red Lodge, MT 59068 USA. [Ayello, Elizabeth A.] Excelsior Coll Sch Nursing, New York, NY USA. [Berlowitz, Dan] Bedford VA, Bedford, MA USA. [Parker, Victoria A.] Boston Univ, Boston, MA 02215 USA. [Lukas, Carol VanDeusen; Niederhauser, Andrea] VA Boston Healthcare Syst, Boston, MA USA. EM KarenZ@montatta.edu; elizabeth@ayello.com; Dan.Berlowitz@va.gov; vparker@bu.edu; Carol.VanDeusenLukas@va.gov; anieder@bu.edu NR 1 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1071-5754 J9 J WOUND OSTOMY CONT JI J. Wound Ostomy Cont. Nurs. PD MAY-JUN PY 2011 VL 38 IS 3 SU S MA 5261 BP S51 EP S51 PG 1 WC Nursing SC Nursing GA 772LI UT WOS:000291235000141 ER PT J AU Lorch, JH Goloubeva, O Posner, MR AF Lorch, Jochen H. Goloubeva, Olga Posner, Marshall R. TI How does TPF improve survival over PF? reply SO LANCET ONCOLOGY LA English DT Letter C1 [Lorch, Jochen H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Goloubeva, Olga] Univ Maryland, Med Sch Teaching Facil, Div Biostat, Marlene & Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA. [Posner, Marshall R.] Mt Sinai Sch Med, Tisch Canc Inst, Div Hematol Med Oncol, New York, NY USA. RP Lorch, JH (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM jochen_lorch@dfci.harvard.edu NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD MAY PY 2011 VL 12 IS 5 BP 421 EP 422 PG 2 WC Oncology SC Oncology GA 771FQ UT WOS:000291143000012 ER PT J AU Belov, VV Bonab, AA Fischman, AJ Heartlein, M Calias, P Papisov, MI AF Belov, Vasily V. Bonab, Ali A. Fischman, Alan J. Heartlein, Michael Calias, Pericles Papisov, Mikhail I. TI Iodine-124 as a Label for Pharmacological PET Imaging SO MOLECULAR PHARMACEUTICS LA English DT Article DE Iodine-124; Positron Emission Tomography; Pharmacology; Pharmacokinetics; Biopharmaceuticals; Macromolecules ID POSITRON-EMISSION-TOMOGRAPHY; PERFORMANCE EVALUATION; SPATIAL-RESOLUTION; SCANNER; SYSTEM; SENSITIVITY; EMITTERS AB With the growing number of biotechnology products and drug delivery systems entering preclinical and clinical studies, pharmacological imaging studies with PET play an increasingly significant role. Such studies often require investigation of slow and complex pharmacokinetics (PK). This suggests labeling of the drug candidate with radionuclides that have long physical half-lives. Among the currently available PET positron emitters, (124)1 has the longest physical half-life (4.2 days). This, combined with the well-investigated behavior of iodine in vivo, makes (124)I very attractive for pharmacological studies. However, the high energy of the positrons emitted by (124)I and the presence of single photons in the (124)I emission can potentially introduce limitations in the quantitative analysis of the images. The objective of this research was to determine whether the use of (124)I as a PET label provides data quality suitable for PK studies. The study was carried out using MicroPET P4 scanner (Siemens/Concorde Microsystems). Spatial resolution, count-rate performance, sensitivity and scatter fraction were measured using a line source and a cylindrical phantom. Model animal studies in rats and cynomolgus monkeys were carried out using human recombinant proteins. The proteins were labeled with (124)I, up to 185 MBq/mg. The transaxial and axial spatial resolutions in the center of the camera were satisfactory and higher for OSEM3D/MAP than FORE-2DFBP (FWHM 2.52 vs 3.31 mm, and 3.10 vs 3.69 mm). Linearity of the true coincidence count-rate was observed up to 44 MBq. Animal studies demonstrated excellent delineation and resolution of even very small organs. At optimal doses, 2-10 MBq per animal for rodents and 4-10 MBq per kg of body weight for larger animals, the quality of numerical data was appropriate for PK analysis in all experimental timeframes from minutes (dynamic studies) to 10 days. Overall, the data suggest that (124)I is an excellent label for quantitative pharmacological PET imaging studies. C1 [Belov, Vasily V.; Bonab, Ali A.; Papisov, Mikhail I.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Belov, Vasily V.; Bonab, Ali A.; Fischman, Alan J.; Papisov, Mikhail I.] Harvard Univ, Sch Med, Boston, MA USA. [Belov, Vasily V.; Bonab, Ali A.; Fischman, Alan J.; Papisov, Mikhail I.] Shriners Burns Hosp Boston, Boston, MA USA. [Heartlein, Michael; Calias, Pericles] Shire Human Genet Therapy, Lexington, MA USA. RP Papisov, MI (reprint author), Massachusetts Gen Hosp, Dept Radiol, Bartlett Hall 500R,55 Fruit St, Boston, MA 02114 USA. EM papisov@helix.mgh.harvard.edu OI Papisov, Mikhail/0000-0003-4716-2122 FU Shire HGT (Cambridge, MA) FX This work was supported in part by Shire HGT (Cambridge, MA), which also provided model proteins. NR 34 TC 19 Z9 19 U1 1 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1543-8384 J9 MOL PHARMACEUT JI Mol. Pharm. PD MAY-JUN PY 2011 VL 8 IS 3 BP 736 EP 747 DI 10.1021/mp100358f PG 12 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 772KW UT WOS:000291233800011 PM 21361362 ER PT J AU Hong, IH Jeong, YW Shin, T Hyun, SH Park, JK Ki, MR Han, SY Park, SI Lee, JH Lee, EM Kim, AY You, SY Hwang, WS Jeong, KS AF Hong, Il-Hwa Jeong, Yeon-Woo Shin, Taeyoung Hyun, Sang-Hwan Park, Jin-Kyu Ki, Mi-Ran Han, Seon-Young Park, Se-Il Lee, Ji-Hyun Lee, Eun-Mi Kim, Ah-Young You, Sang-Young Hwang, Woo-Suk Jeong, Kyu-Shik TI Morphological Abnormalities, Impaired Fetal Development and Decrease in Myostatin Expression Following Somatic Cell Nuclear Transfer in Dogs SO MOLECULAR REPRODUCTION AND DEVELOPMENT LA English DT Article ID BECKWITH-WIEDEMANN-SYNDROME; SKELETAL-MUSCLE; MAMMALIAN DEVELOPMENT; GROWTH-HORMONE; IN-VITRO; CATTLE; DIFFERENTIATION; EMBRYOS; CLONING; MICE AB Several mammals, including dogs, have been successfully cloned using somatic cell nuclear transfer (SCNT), but the efficiency of generating normal, live offspring is relatively low. Although the high failure rate has been attributed to incomplete reprogramming of the somatic nuclei during the cloning process, the exact cause is not fully known. To elucidate the cause of death in cloned offspring, 12 deceased offspring cloned by SCNT were necropsied. The clones were either stillborn just prior to delivery or died with dyspnea shortly after birth. On gross examination, defects in the anterior abdominal wall and increased heart and liver sizes were found. Notably, a significant increase in muscle mass and macroglossia lesions were observed in deceased SCNT-cloned dogs. Interestingly, the expression of myostatin, a negative regulator of muscle growth during embryogenesis, was down-regulated at the mRNA level in tongues and skeletal muscles of SCNT-cloned dogs compared with a normal dog. Results of the present study suggest that decreased expression of myostatin in SCNT-cloned dogs may be involved in morphological abnormalities such as increased muscle mass and macroglossia, which may contribute to impaired fetal development and poor survival rates. C1 [Hong, Il-Hwa; Park, Jin-Kyu; Ki, Mi-Ran; Han, Seon-Young; Park, Se-Il; Lee, Eun-Mi; Kim, Ah-Young; You, Sang-Young; Jeong, Kyu-Shik] Kyungpook Natl Univ, Coll Vet Med, Taegu, South Korea. [Jeong, Yeon-Woo; Shin, Taeyoung; Hwang, Woo-Suk] SooAm Biotech Res Fdn, Seoul, South Korea. [Hyun, Sang-Hwan] Chungbuk Natl Univ, Coll Vet Med, Lab Vet Biotechnol, Cheongju, South Korea. [Lee, Ji-Hyun] Harvard Univ, Sch Med, Dept Genet, Ctr Human Genet Res,Massachusetts Gen Hosp, Boston, MA USA. [Jeong, Kyu-Shik] Kyungpook Natl Univ, Stem Cell Therapeut Res Inst, Taegu, South Korea. RP Jeong, KS (reprint author), Kyungpook Natl Univ, Coll Vet Med, Taegu, South Korea. EM hwangws@sooam.org; jeongks@knu.ac.kr FU H Bion, Republic of Korea FX This research was supported by a grant from H Bion, Republic of Korea. NR 38 TC 9 Z9 9 U1 1 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1040-452X J9 MOL REPROD DEV JI Mol. Reprod. Dev. PD MAY PY 2011 VL 78 IS 5 BP 337 EP 346 DI 10.1002/mrd.21309 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology SC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology GA 772CY UT WOS:000291210200005 PM 21520324 ER PT J AU Finch, TH Chae, SR Shafaee, MN Siegel, KR Ali, MK Tomei, R Panjabi, R Kishore, SP AF Finch, Thomas H. Chae, Sae-Rom Shafaee, Maryam N. Siegel, Karen R. Ali, Mohammed K. Tomei, Rachelle Panjabi, Rajesh Kishore, Sandeep P. TI Role of Students in Global Health Delivery SO MOUNT SINAI JOURNAL OF MEDICINE LA English DT Article ID EXPERIENCE AB What role do students have in global health activities? On one hand, students have much to offer, including innovative ideas, fresh knowledge and perspective, and inspiring energy. At the same time, students lack technical credentials and may drain resources from host communities. Here, we examine the dynamic, contemporary roles of students in global health activities, including health delivery. We focus on 3 themes that guide engagement: (I) fostering an enabling policy environment (eg, toward greater health equity); (2) understanding and working within the local context and governments' needs; and (3) leading bidirectional partnerships. We next study the implications of short-term exposure and long-term engagement programs. We conclude with 4 recommendations on how to better equip students to engage in the next frontier of global health education and future action. Mt Sinai J Med 78:373-381, 2011. (C) 2011 Mount Sinai School of Medicine C1 [Kishore, Sandeep P.] Weill Cornell Rockefeller Sloan Kettering Triinst, New York, NY USA. [Finch, Thomas H.] Weill Cornell Med Coll, New York, NY USA. [Chae, Sae-Rom] Univ Illinois, Coll Med, Chicago, IL USA. [Shafaee, Maryam N.] New York Presbyterian Hosp, Dept Med, New York, NY USA. [Siegel, Karen R.] Emory Univ, Laney Grad Sch, Atlanta, GA 30322 USA. [Siegel, Karen R.] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. [Ali, Mohammed K.] Emory Univ, Dept Global Hlth, Atlanta, GA 30322 USA. [Tomei, Rachelle] Weill Cornell Med Coll, Surg Phys Assistant Program, New York, NY USA. [Panjabi, Rajesh] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Panjabi, Rajesh] Tiyatien Hlth Liberia, Boston, MA USA. RP Kishore, SP (reprint author), Weill Cornell Rockefeller Sloan Kettering Triinst, New York, NY USA. EM sunny.kishore@gmail.com FU NIGMS NIH HHS [T32 GM007739] NR 27 TC 7 Z9 7 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0027-2507 J9 MT SINAI J MED JI Mt. Sinai J. Med. PD MAY-JUN PY 2011 VL 78 IS 3 BP 373 EP 381 DI 10.1002/msj.20254 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 772LW UT WOS:000291236400008 PM 21598264 ER PT J AU Weintraub, D Burn, DJ AF Weintraub, Daniel Burn, David J. TI Parkinson's Disease: The Quintessential Neuropsychiatric Disorder SO MOVEMENT DISORDERS LA English DT Review DE Parkinson's; dementia; neuropsychiatric; depression; psychosis ID DEEP-BRAIN-STIMULATION; IMPULSE CONTROL DISORDERS; SLEEP BEHAVIOR DISORDER; RANDOMIZED CONTROLLED-TRIAL; VOXEL-BASED MORPHOMETRY; SUBTHALAMIC NUCLEUS STIMULATION; EXCESSIVE DAYTIME SLEEPINESS; MILD COGNITIVE IMPAIRMENT; PLACEBO-CONTROLLED TRIAL; DRUG-INDUCED PSYCHOSIS AB Although diagnosed by characteristic motor features, Parkinson's disease may be preceded, and is frequently accompanied by, a wide range of cognitive and neuropsychiatric features. In addition to the most commonly studied disorders of dementia, depression, and psychosis, other relatively common and clinically significant psychiatric complications include impulse control disorders, anxiety symptoms, disorders of sleep and wakefulness, and apathy. These problems may be underrecognized and are frequently under-treated. The emergent focus on nonmotor aspects of Parkinson's disease over the past quarter of a century is highlighted by a nonlinear increase in the number of articles published devoted to this topic. Although the development of newer antidepressants, atypical antipsychotics, and cholinesterase inhibitors in recent years has had a positive benefit on the management of these troublesome and distressing symptoms, responses are frequently suboptimal, and this remains an area of major unmet therapeutic need. (C) 2011 Movement Disorder Society C1 [Weintraub, Daniel] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, Parkinsons Dis Ctr, Philadelphia, PA USA. [Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr PADRECC & MIRE, Philadelphia, PA USA. [Burn, David J.] Newcastle Univ, Inst Ageing & Hlth, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Burn, David J.] Newcastle Univ, Clin Ageing Res Unit, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. RP Weintraub, D (reprint author), Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. EM daniel.weintraub@uphs.upenn.edu FU NIMH NIH HHS [K23 MH067894] NR 186 TC 115 Z9 117 U1 6 U2 19 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 EI 1531-8257 J9 MOVEMENT DISORD JI Mov. Disord. PD MAY PY 2011 VL 26 IS 6 BP 1022 EP 1031 DI 10.1002/mds.23664 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 774AO UT WOS:000291353900011 PM 21626547 ER PT J AU Shoulson, I Young, AB AF Shoulson, Ira Young, Anne B. TI Milestones in Huntington Disease SO MOVEMENT DISORDERS LA English DT Review DE Huntington disease; experimental therapeutics; review ID PREIMPLANTATION GENETIC DIAGNOSIS; HISTONE DEACETYLASE INHIBITORS; CAG REPEAT LENGTH; AGE-OF-ONSET; MUTANT HUNTINGTIN; COENZYME Q(10); PREDICT-HD; PROJECTION NEURONS; FUNCTIONAL-ANATOMY; DEPENDENT MANNER AB There have been extraordinary advances in our knowledge of the underlying gene, the protein it encodes, various models of disease, and potential targets for effective therapies for Huntington disease. Huntington disease research has increased exponentially in the past 25 years, and we now understand many of the molecular mechanisms underlying the disease. Still, more work needs to be done before we have a full understanding of the pathophysiology of the disease. Clinical research on biomarkers and clinical trials on potential neuroprotective agents are underway. Here we review our progress in these areas over the last 25 years and speculate on what the next 25 years may hold. (C) 2011 Movement Disorder Society C1 [Shoulson, Ira] Georgetown Univ, Program Regulatory Sci & Med, Washington, DC USA. [Young, Anne B.] Harvard Univ, Sch Med, Boston, MA USA. [Young, Anne B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Shoulson, I (reprint author), 1351 Mt Hope Ave,Suite 218, Rochester, NY 14620 USA. EM Ira.Shoulson@ctcc.rochester.edu NR 81 TC 36 Z9 37 U1 2 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD MAY PY 2011 VL 26 IS 6 BP 1127 EP 1133 DI 10.1002/mds.23685 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 774AO UT WOS:000291353900020 PM 21626556 ER PT J AU Kim, YW Grossmann, TN Verdine, GL AF Kim, Young-Woo Grossmann, Tom N. Verdine, Gregory L. TI Synthesis of all-hydrocarbon stapled alpha-helical peptides by ring-closing olefin metathesis SO NATURE PROTOCOLS LA English DT Article ID HYDROGEN-BOND SURROGATE; COUPLING REAGENTS; BH3 HELIX; ASYMMETRIC-SYNTHESIS; EFFICIENT SYNTHESIS; HIGHLY EFFICIENT; CONFORMATION; INHIBITOR; ACTIVATION; 6-CL-HOBT AB This protocol provides a detailed procedure for the preparation of stapled alpha-helical peptides, which have proven their potential as useful molecular probes and as next-generation therapeutics. Two crucial features of this protocol are (i) the construction of peptide substrates containing hindered alpha-methyl, alpha-alkenyl amino acids and (ii) the ring-closing olefin metathesis (RCM) of the resulting resin-bound peptide substrates. The stapling systems described in this protocol, namely bridging one or two turns of an alpha-helix, are highly adaptable to most peptide sequences, resulting in favorable RCM kinetics, helix stabilization and promotion of cellular uptake. C1 [Kim, Young-Woo; Grossmann, Tom N.; Verdine, Gregory L.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Kim, Young-Woo; Grossmann, Tom N.; Verdine, Gregory L.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Kim, Young-Woo; Verdine, Gregory L.] Dana Farber Canc Inst, Program Canc Chem Biol, Boston, MA 02115 USA. [Verdine, Gregory L.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. RP Verdine, GL (reprint author), Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. EM gregory_verdine@harvard.edu RI Grossmann, Tom/A-4175-2015 OI Grossmann, Tom/0000-0003-0179-4116 FU Harvard and Dana-Farber Program in Cancer Chemical Biology; Deutsche Akademie der Naturforscher Leopoldina [LPDS 2009-2] FX This research was supported by the Harvard and Dana-Farber Program in Cancer Chemical Biology. T.N.G. is grateful for a fellowship from Deutsche Akademie der Naturforscher Leopoldina (LPDS 2009-2). NR 40 TC 127 Z9 127 U1 6 U2 68 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PD MAY PY 2011 VL 6 IS 6 BP 761 EP 771 DI 10.1038/nprot.2011.324 PG 11 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 772EZ UT WOS:000291218300004 PM 21637196 ER PT J AU Zhao, J Wu, H Khosravi, M Cui, HJ Qian, XX Kelly, JA Kaufman, KM Langefeld, CD Williams, AH Comeau, ME Ziegler, JT Marion, MC Adler, A Glenn, SB Alarcon-Riquelme, ME Pons-Estel, BA Harley, JB Bae, SC Bang, SY Cho, SK Jacob, CO Vyse, TJ Niewold, TB Gaffney, PM Moser, KL Kimberly, RP Edberg, JC Brown, EE Alarcon, GS Petri, MA Ramsey-Goldman, R Vila, LM Reveille, JD James, JA Gilkeson, GS Kamen, DL Freedman, BI Anaya, JM Merrill, JT Criswell, LA Scofield, RH Stevens, AM Guthridge, JM Chang, DM Song, YW Park, JA Lee, EY Boackle, SA Grossman, JM Hahn, BH Goodship, THJ Cantor, RM Yu, CY Shen, N Tsao, BP AF Zhao, Jian Wu, Hui Khosravi, Melanie Cui, Huijuan Qian, Xiaoxia Kelly, Jennifer A. Kaufman, Kenneth M. Langefeld, Carl D. Williams, Adrienne H. Comeau, Mary E. Ziegler, Julie T. Marion, Miranda C. Adler, Adam Glenn, Stuart B. Alarcon-Riquelme, Marta E. Pons-Estel, Bernardo A. Harley, John B. Bae, Sang-Cheol Bang, So-Young Cho, Soo-Kyung Jacob, Chaim O. Vyse, Timothy J. Niewold, Timothy B. Gaffney, Patrick M. Moser, Kathy L. Kimberly, Robert P. Edberg, Jeffrey C. Brown, Elizabeth E. Alarcon, Graciela S. Petri, Michelle A. Ramsey-Goldman, Rosalind Vila, Luis M. Reveille, John D. James, Judith A. Gilkeson, Gary S. Kamen, Diane L. Freedman, Barry I. Anaya, Juan-Manuel Merrill, Joan T. Criswell, Lindsey A. Scofield, R. Hal Stevens, Anne M. Guthridge, Joel M. Chang, Deh-Ming Song, Yeong Wook Park, Ji Ah Lee, Eun Young Boackle, Susan A. Grossman, Jennifer M. Hahn, Bevra H. Goodship, Timothy H. J. Cantor, Rita M. Yu, Chack-Yung Shen, Nan Tsao, Betty P. CA BIOLUPUS Network GENLES Network TI Association of Genetic Variants in Complement Factor H and Factor H-Related Genes with Systemic Lupus Erythematosus Susceptibility SO PLOS GENETICS LA English DT Article ID HEMOLYTIC-UREMIC SYNDROME; DENSE DEPOSIT DISEASE; MACULAR DEGENERATION; MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS; ALLOTYPIC VARIANT; INFLUENCES RISK; CFH; C3; HAPLOTYPE; POLYMORPHISMS AB Systemic lupus erythematosus (SLE), a complex polygenic autoimmune disease, is associated with increased complement activation. Variants of genes encoding complement regulator factor H (CFH) and five CFH-related proteins (CFHR1-CFHR5) within the chromosome 1q32 locus linked to SLE, have been associated with multiple human diseases and may contribute to dysregulated complement activation predisposing to SLE. We assessed 60 SNPs covering the CFH-CFHRs region for association with SLE in 15,864 case-control subjects derived from four ethnic groups. Significant allelic associations with SLE were detected in European Americans (EA) and African Americans (AA), which could be attributed to an intronic CFH SNP (rs6677604, in intron 11, P(meta) = 6.6x10(-8), OR = 1.18) and an intergenic SNP between CFHR1 and CFHR4 (rs16840639, P(meta) = 2.9x10(-7), OR = 1.17) rather than to previously identified disease-associated CFH exonic SNPs, including I62V, Y402H, A474A, and D936E. In addition, allelic association of rs6677604 with SLE was subsequently confirmed in Asians (AS). Haplotype analysis revealed that the underlying causal variant, tagged by rs6677604 and rs16840639, was localized to a similar to 146 kb block extending from intron 9 of CFH to downstream of CFHR1. Within this block, the deletion of CFHR3 and CFHR1 (CFHR3-1 Delta), a likely causal variant measured using multiplex ligation-dependent probe amplification, was tagged by rs6677604 in EA and AS and rs16840639 in AA, respectively. Deduced from genotypic associations of tag SNPs in EA, AA, and AS, homozygous deletion of CFHR3-1D (P(meta) = 3.2x10(-7), OR = 1.47) conferred a higher risk of SLE than heterozygous deletion (P(meta) = 3.5x10(-4), OR = 1.14). These results suggested that the CFHR3-1D deletion within the SLE-associated block, but not the previously described exonic SNPs of CFH, might contribute to the development of SLE in EA, AA, and AS, providing new insights into the role of complement regulators in the pathogenesis of SLE. C1 [Zhao, Jian; Wu, Hui; Khosravi, Melanie; Grossman, Jennifer M.; Hahn, Bevra H.; Tsao, Betty P.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Rheumatol, Los Angeles, CA 90095 USA. [Cui, Huijuan; Qian, Xiaoxia; Shen, Nan] Inst Hlth Sci, Joint Mol Rheumatol Lab, Shanghai, Peoples R China. [Cui, Huijuan; Qian, Xiaoxia; Shen, Nan] Shanghai Jiao Tong Univ, Sch Med, Shanghai Inst Biol Sci, Shanghai Renji Hosp, Shanghai 200030, Peoples R China. [Cui, Huijuan; Qian, Xiaoxia; Shen, Nan] Chinese Acad Sci, Shanghai, Peoples R China. [Kelly, Jennifer A.; Kaufman, Kenneth M.; Adler, Adam; Glenn, Stuart B.; Alarcon-Riquelme, Marta E.; Gaffney, Patrick M.; Moser, Kathy L.; James, Judith A.; Scofield, R. Hal; Guthridge, Joel M.] Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Oklahoma City, OK 73104 USA. [Kaufman, Kenneth M.; Scofield, R. Hal] US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. [Langefeld, Carl D.; Williams, Adrienne H.; Comeau, Mary E.; Ziegler, Julie T.; Marion, Miranda C.] Wake Forest Univ Hlth Sci, Dept Biostat Sci, Wake Forest, NC USA. [Alarcon-Riquelme, Marta E.] Pfizer Univ Granada Junta Andalucia, Ctr Genom & Oncol Res, Granada, Spain. [Harley, John B.] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. [Harley, John B.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA. [Bae, Sang-Cheol; Bang, So-Young; Cho, Soo-Kyung] Hanyang Univ Hosp Rheumat Dis, Dept Rheumatol, Seoul, South Korea. [Jacob, Chaim O.] Univ So Calif, Keck Sch Med, Dept Med, Los Angeles, CA 90033 USA. [Vyse, Timothy J.] Kings Coll London, Div Genet & Mol Med, London WC2R 2LS, England. [Vyse, Timothy J.] Kings Coll London, Div Immunol, London WC2R 2LS, England. [Niewold, Timothy B.] Univ Chicago, Rheumatol Sect, Chicago, IL 60637 USA. [Niewold, Timothy B.] Univ Chicago, Gwen Knapp Ctr Lupus & Immunol Res, Chicago, IL 60637 USA. [Kimberly, Robert P.; Edberg, Jeffrey C.; Brown, Elizabeth E.; Alarcon, Graciela S.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. [Brown, Elizabeth E.] Univ Alabama, Dept Epidemiol, Birmingham, AL 35294 USA. [Petri, Michelle A.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Ramsey-Goldman, Rosalind] Northwestern Univ, Feinberg Sch Med, Div Rheumatol, Chicago, IL 60611 USA. [Vila, Luis M.] Univ Puerto Rico Med Sci Campus, Dept Med, Div Rheumatol, San Juan, PR USA. [Reveille, John D.] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA. [James, Judith A.; Scofield, R. Hal] Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA. [Gilkeson, Gary S.; Kamen, Diane L.] Med Univ S Carolina, Div Rheumatol, Charleston, SC 29425 USA. [Freedman, Barry I.] Wake Forest Univ Hlth Sci, Dept Internal Med, Winston Salem, NC USA. [Anaya, Juan-Manuel] Univ Rosario, Ctr Autoimmune Dis Res, Bogota, Colombia. [Merrill, Joan T.] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. [Criswell, Lindsey A.] Univ Calif San Francisco, Dept Med, Rosalind Russell Med Res Ctr Arthrit, San Francisco, CA USA. [Stevens, Anne M.] Univ Washington, Dept Pediat, Div Rheumatol, Seattle, WA 98195 USA. [Stevens, Anne M.] Seattle Childrens Res Inst, Ctr Immun & Immunotherapies, Seattle, WA USA. [Chang, Deh-Ming] Natl Def Med Ctr, Taipei, Taiwan. [Song, Yeong Wook; Park, Ji Ah; Lee, Eun Young] Seoul Natl Univ, Div Rheumatol, Seoul, South Korea. [Boackle, Susan A.] Univ Colorado Denver, Sch Med, Div Rheumatol, Aurora, CO USA. [Adler, Adam; Goodship, Timothy H. J.] Newcastle Univ, Inst Human Genet, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Cantor, Rita M.] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA 90095 USA. [Yu, Chack-Yung] Ohio State Univ, Dept Pediat, Columbus, OH 43210 USA. RP Zhao, J (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Rheumatol, Los Angeles, CA 90095 USA. EM btsao@mednet.ucla.edu RI Yu, Chack-Yung/E-4360-2011; Song, Yeong Wook/J-2765-2012; Lee, Eun Young/J-5594-2012; Zhao, Jian/E-6292-2012; D'Alfonso, Sandra/K-7295-2014; Anaya, Juan-Manuel/J-1960-2016; OI Alarcon Riquelme, Marta Eugenia/0000-0002-7632-4154; Niewold, Timothy/0000-0003-3532-6660; D'Alfonso, Sandra/0000-0002-3983-9925; Anaya, Juan-Manuel/0000-0002-6444-1249; Universidad del Rosario, Biblioteca/0000-0003-3491-9392; Kimberly, Robert/0000-0002-5330-3086; Silva, Berta/0000-0001-6579-5068 FU US National Institutes of Health [R01AR043814, R01AR043274, R01AI063274, N01AR62277, R37AI024717, R01AR042460, P01AI083194, P20RR020143, P01AR049084, R01AR33062, K08AI083790, LRPAI071651, R01CA141700, RC1AR058621, UL1RR024999, R01AR051545-01A2, P30AR053483, AR43727, UL1RR025005, K24AR002138, P602AR30692, P01AR49084, UL1RR025741, P20RR015577, RC1AR058554, U19AI082714, N01AI50026, R21AI070304, P60AR053308, M01RR00079, UL1RR029882, P60AR049459, R01AR054459]; Arthritis National Research Foundation; Ministry for Health and Welfare, Republic of Korea [A080588]; MKE/KEIT [10035615]; US Department of Veterans Affairs; US Department of Defense [PR094002]; Lupus Research Institute; Alliance for Lupus Research; Arthritis Foundation; Lupus Foundation; Swedish Research Council; Swedish Association Against Rheumatism; King Gustaf Vth 80th Jubilee; Fundacion Instituto de Salud Carlos III [PS0900129]; Consejeria de Salud de Andalucia [PI-0012]; Welcome Trust; Arthritis Research UK; UK Medical Research Council [G0701325]; CTSA [I ULI RR025014-02]; National Center for Research Resources (NCRR); Kirkland Scholar Award; Federico Wilhelm Agricola Foundation; Networking Programmers European Science Foundation; ESF FX ` Support for this work was obtained from the US National Institutes of Health grants: R01AR043814 (BP Tsao), R01AR043274 (KL Moser), R01AI063274 (PM Gaffney), N01AR62277 (JB Harley), R37AI024717 (JB Harley), R01AR042460 (JB Harley), P01AI083194 (JB Harley), P20RR020143 (JB Harley), P01AR049084 (RP Kimberly), R01AR33062 (RP Kimberly, EE Brown), K08AI083790 (TB Niewold), LRPAI071651 (TB Niewold), R01CA141700 (ME Alarcon-Riquelme), RC1AR058621 (ME Alarcon-Riquelme) and UL1RR024999 (TB Niewold), R01AR051545-01A2 (AM Stevens), P30AR053483 (JA James and JM Guthridge), AR43727 (MA Petri), UL1RR025005 (MA Petri), K24AR002138 (R Ramsey-Goldman), P602AR30692 (R Ramsey-Goldman), P01AR49084 (R Ramsey-Goldman), UL1RR025741 (R Ramsey-Goldman), P20RR015577 (JA James), RC1AR058554 (JA James), U19AI082714 (JA James), N01AI50026 (JA James and JM Guthridge), R21AI070304 (SA Boackle), P60AR053308 (LA Criswell), M01RR00079 (LA Criswell), UL1RR029882 (GS Gilkeson and DL Kamen), P60AR049459 (GS Gilkeson and DL Kamen), and R01AR054459 (C-Y Yu). The first author (J Zhao) is an Eng Tan Scholar supported by the Arthritis National Research Foundation. This study was also supported by a grant from the Korea Healthcare Technology R&D Project, Ministry for Health and Welfare, Republic of Korea (A080588; S-C Bae), Korean R&D Program of MKE/KEIT (10035615; YW Song), the Merit Award from the US Department of Veterans Affairs (JB Harley and GS Gilkeson), the US Department of Defense PR094002 (JB Harley), Lupus Research Institute (BP Tsao, AM Stevens, and TB Niewold), The Alliance for Lupus Research (KL Moser, TB Niewold, LA Criswell, and CO Jacob), the Arthritis National Research Foundation Eng Tan Scholar Award (TB Niewold), the Arthritis Foundation (AM Stevens and PM Gaffney), and the Lupus Foundation (AM Stevens). Additional funding awarded from the Swedish Research Council, Swedish Association Against Rheumatism, and the King Gustaf Vth 80th Jubilee. Foundation and the Fundacion Instituto de Salud Carlos III PS0900129 and the Consejeria de Salud de Andalucia PI-0012 (ME Alarcon-Riquelme), the Welcome Trust (TJ Vyse), Arthritis Research UK (TJ Vyse), UK Medical Research Council grant (G0701325; THJ Goodship), CTSA Grant Number I ULI RR025014-02 (AM Stevens) from the National Center for Research Resources (NCRR), Kirkland Scholar Award (LA Criswell and JA James), and Federico Wilhelm Agricola Foundation Research Grant (BA Pons-Estel). The work reported on in this publication has been in part financially supported by the ESF, in the framework of the Research Networking Programmers European Science Foundation - The Identification of Novel Genes and Biomarkers for Systemic Lupus Erythematosus (BIOLUPUS)-RNP-083. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 39 TC 68 Z9 69 U1 3 U2 13 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD MAY PY 2011 VL 7 IS 5 AR e1002079 DI 10.1371/journal.pgen.1002079 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 769LI UT WOS:000291014600024 PM 21637784 ER PT J AU Tsai, AC Rosenlicht, NZ Jureidini, JN Parry, PI Spielmans, GI Healy, D AF Tsai, Alexander C. Rosenlicht, Nicholas Z. Jureidini, Jon N. Parry, Peter I. Spielmans, Glen I. Healy, David TI Aripiprazole in the Maintenance Treatment of Bipolar Disorder: A Critical Review of the Evidence and Its Dissemination into the Scientific Literature SO PLOS MEDICINE LA English DT Review ID RANDOMIZED CONTROLLED-TRIALS; CLINICAL-PRACTICE GUIDELINES; CONTROLLED 18-MONTH TRIAL; CONFLICT-OF-INTEREST; I-DISORDER; DOUBLE-BLIND; LONG-TERM; MOOD STABILIZERS; PHARMACOLOGICAL-TREATMENT; PHARMACEUTICAL-INDUSTRY AB Background: Aripiprazole, a second-generation antipsychotic medication, has been increasingly used in the maintenance treatment of bipolar disorder and received approval from the U.S. Food and Drug Administration for this indication in 2005. Given its widespread use, we sought to critically review the evidence supporting the use of aripiprazole in the maintenance treatment of bipolar disorder and examine how that evidence has been disseminated in the scientific literature. Methods and Findings: We systematically searched multiple databases to identify double-blind, randomized controlled trials of aripiprazole for the maintenance treatment of bipolar disorder while excluding other types of studies, such as open-label, acute, and adjunctive studies. We then used a citation search to identify articles that cited these trials and rated the quality of their citations. Our evidence search protocol identified only two publications, both describing the results of a single trial conducted by Keck et al., which met criteria for inclusion in this review. We describe four issues that limit the interpretation of that trial as supporting the use of aripiprazole for bipolar maintenance: (1) insufficient duration to demonstrate maintenance efficacy; (2) limited generalizability due to its enriched sample; (3) possible conflation of iatrogenic adverse effects of abrupt medication discontinuation with beneficial effects of treatment; and (4) a low overall completion rate. Our citation search protocol yielded 80 publications that cited the Keck et al. trial in discussing the use of aripiprazole for bipolar maintenance. Of these, only 24 (30%) mentioned adverse events reported and four (5%) mentioned study limitations. Conclusions: A single trial by Keck et al. represents the entirety of the literature on the use of aripiprazole for the maintenance treatment of bipolar disorder. Although careful review identifies four critical limitations to the trial's interpretation and overall utility, the trial has been uncritically cited in the subsequent scientific literature. C1 [Tsai, Alexander C.] Harvard Univ, Robert Wood Johnson Hlth & Soc Scholars Program, Cambridge, MA 02138 USA. [Rosenlicht, Nicholas Z.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Rosenlicht, Nicholas Z.] San Francisco VA Med Ctr, San Francisco, CA USA. [Jureidini, Jon N.] Univ Adelaide, Discipline Psychiat, Adelaide, SA, Australia. [Parry, Peter I.] Flinders Univ S Australia, Div Mental Hlth, Child & Adolescent Mental Hlth Serv, Adelaide, SA 5001, Australia. [Spielmans, Glen I.] Metropolitan State Univ, Dept Psychol, St Paul, MN USA. [Healy, David] Cardiff Univ, Dept Psychol Med, Cardiff, S Glam, Wales. RP Tsai, AC (reprint author), Harvard Univ, Robert Wood Johnson Hlth & Soc Scholars Program, Cambridge, MA 02138 USA. EM nicholas.rosenlicht@ucsf.edu RI Parry, Peter/G-7663-2015; OI Parry, Peter/0000-0003-1086-0138; Tsai, Alexander/0000-0001-6397-7917 FU Harvard University; Robert Wood Johnson Foundation Health and Society; Vanguard Healthcare FX The authors received no specific funding for this study. ACT received salary support as a Robert Wood Johnson Health and Society Scholar at Harvard University. No funding bodies had any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.; ACT receives salary support through the Robert Wood Johnson Foundation Health and Society Scholars Program. The Robert Wood Johnson Foundation's stated mission is to improve the health and health care of all Americans. NZR is a member of the National Physicians Alliance, a not-for-profit organisation whose stated primary goal is to restore physicians' primary emphasis on the core values of service, integrity, and advocacy. The National Physicians Alliance rejects funding from commercial health care interests and encourages its members to do the same. NZR, JNJ, and PIP are members of Healthy Skepticism, an international not-for-profit organisation whose stated aim is to improve health by reducing harm from misleading drug promotion; GIS joined Healthy Skepticism after this article was accepted for publication. GIS is a current shareholder (<$10,000) in a mutual fund, Vanguard Healthcare, that invests heavily in pharmaceutical companies. DH reports no links to pharmaceutical companies in the past 5 years. ACT is a former board member of the ethics committee, and former member, of the National Physicians Alliance. ACT and NZR are former members of No Free Lunch, a not-for-profit organisation whose stated mission was to encourage health care providers to practice medicine on the basis of scientific evidence rather than on the basis of pharmaceutical promotion. JNJ was engaged by the law firm of Baum, Hedlund, Aristei & Goldman to provide an independent analysis of the data in Glaxo SmithKline's Study 329 of paroxetine in adolescents. DH has been an expert witness in ten legal cases involving antidepressant medications and one case involving the patent on olanzapine (Zyprexa). NR 117 TC 15 Z9 15 U1 5 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1549-1676 J9 PLOS MED JI PLos Med. PD MAY PY 2011 VL 8 IS 5 AR e1000434 DI 10.1371/journal.pmed.1000434 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 771IW UT WOS:000291151400001 PM 21559324 ER PT J AU Farmer, P Almazor, CP Bahnsen, ET Barry, D Bazile, J Bloom, BR Bose, N Brewer, T Calderwood, SB Clemens, JD Cravioto, A Eustache, E Jerome, G Gupta, N Harris, JB Hiatt, HH Holstein, C Hotez, PJ Ivers, LC Kerry, VB Koenig, SP LaRocque, RC Leandre, F Lambert, W Lyon, E Mekalanos, JJ Mukherjee, JS Oswald, C Pape, JW Prosper, AG Rabinovich, R Raymonville, M Rejouit, JR Ronan, LJ Rosenberg, ML Ryan, ET Sachs, JD Sack, DA Surena, C Suri, AA Ternier, R Waldor, MK Walton, D Weigel, JL AF Farmer, Paul Almazor, Charles Patrick Bahnsen, Emily T. Barry, Donna Bazile, Junior Bloom, Barry R. Bose, Niranjan Brewer, Thomas Calderwood, Stephen B. Clemens, John D. Cravioto, Alejandro Eustache, Eddy Jerome, Gregory Gupta, Neha Harris, Jason B. Hiatt, Howard H. Holstein, Cassia Hotez, Peter J. Ivers, Louise C. Kerry, Vanessa B. Koenig, Serena P. LaRocque, Regina C. Leandre, Fernet Lambert, Wesler Lyon, Evan Mekalanos, John J. Mukherjee, Joia S. Oswald, Cate Pape, Jean-William Prosper, Anany Gretchko Rabinovich, Regina Raymonville, Maxi Rejouit, Jean-Renold Ronan, Laurence J. Rosenberg, Mark L. Ryan, Edward T. Sachs, Jeffrey D. Sack, David A. Surena, Claude Suri, Arjun A. Ternier, Ralph Waldor, Matthew K. Walton, David Weigel, Jonathan L. TI Meeting Cholera's Challenge to Haiti and the World: A Joint Statement on Cholera Prevention and Care SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID ORAL REHYDRATION SOLUTION; PRIMARY-HEALTH-CARE; PROTECTIVE EFFICACY; B-SUBUNIT; EPIDEMIC CHOLERA; WATER-TREATMENT; HERD-IMMUNITY; FIELD TRIAL; VACCINE; DIARRHEA AB This joint statement argues for a comprehensive, integrated cholera response in Haiti. The cholera epidemic in Haiti is particularly devastating because of the vulnerability of Haiti's population after the January 12, 2010, earthquake, the long-standing weakness of its health, water, and sanitation systems, and the observed virulence of the El Tor hybrid strain. From October 19, 2010-when the first cases were confirmed in the National Public Health Laboratory-to April 4, 2011, 274,418 cases of cholera and 4,787 deaths related to cholera had been reported across all ten departments of Haiti [1]. The Haitian Ministere de la Sante Publique et de la Population (MSPP, the Ministry of Health) and the Direction Nationale de l'Eau Potable et de l'Assainissement (DINEPA, the government body charged with water and sanitation) have, with the support of many nongovernmental and international groups, made great strides against cholera. Case-fatality rates have dropped to 2.1% from 7% at the outset of the epidemic (and up to 10% in certain regions); incidence has also declined across Haiti, according to recent reports [1]. But fewer cases in the dry season (November-April) should not lead to complacency: seasonal variation is expected in epidemics of waterborne disease. Some have raised doubts about the sustainability of free water distribution within internally displaced persons (IDP) camps. But we believe that such efforts are an essential service that has contributed to the relatively few cases of cholera in the camps (as compared to other urban and rural areas). Given the likelihood of case resurgence and endemicity of cholera in Haiti, this document argues for a comprehensive, integrated strategy for cholera prevention and care in Haiti. We must reduce suffering and preventable death in the short term, and we must build effective water, sanitation, and health delivery infrastructure to fortify Haiti against cholera and other diseases of poverty in the long term. The document identifies three principal goals. First, we must continue aggressive case finding and scale up treatment efforts, including oral rehydration therapy, intravenous rehydration, antibiotic therapy (for moderate and severe cases), and complementary supplementation with zinc and vitamin A. Second, we must shore up Haiti's water infrastructure by building systems for consistent chlorination and filtration at public water sources and by distributing point-of-use water purification technologies. We must also strengthen sanitation infrastructure by improving and expanding waste management facilities (such as sewage systems and latrines) and waste monitoring. Third, we must link prevention to care by bolstering surveillance, education campaigns (about hand-washing, for example), and water, sanitation, and hygiene (WASH) efforts. Prevention must also include advocacy for scaled-up production of cholera vaccine and the development of a vaccine strategy for Haiti. A vaccination campaign should be implemented if adequate vaccine and resources can be mobilized without undermining efforts to treat acutely ill patients or strengthen water and sanitation infrastructure. This document identifies key challenges and outlines the components of a comprehensive cholera response to aid medical and public health practitioners in Haiti and elsewhere. With leadership from the Haitian government, we must work together to bolster responses to the acute problem of cholera today and strengthen Haiti's health, water, and sanitation infrastructure to prevent similar outbreaks in the future. C1 [Farmer, Paul; Bahnsen, Emily T.; Gupta, Neha; Hiatt, Howard H.; Holstein, Cassia; Ivers, Louise C.; Kerry, Vanessa B.; Koenig, Serena P.; Mukherjee, Joia S.; Suri, Arjun A.; Walton, David; Weigel, Jonathan L.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA 02215 USA. [Farmer, Paul; Barry, Donna; Hiatt, Howard H.; Ivers, Louise C.; Koenig, Serena P.; Mukherjee, Joia S.; Walton, David] Brigham & Womens Hosp, Div Global Hlth Equ, Boston, MA 02115 USA. [Farmer, Paul; Bahnsen, Emily T.; Holstein, Cassia; Ivers, Louise C.; Koenig, Serena P.; Leandre, Fernet; Lyon, Evan; Mukherjee, Joia S.; Walton, David; Weigel, Jonathan L.] Partners Hlth, Boston, MA USA. [Almazor, Charles Patrick; Bazile, Junior; Eustache, Eddy; Jerome, Gregory; Leandre, Fernet; Lambert, Wesler; Oswald, Cate; Prosper, Anany Gretchko; Raymonville, Maxi; Rejouit, Jean-Renold; Ternier, Ralph] Zanmi Lasante Partners Hlth, Cange, Haiti. [Bloom, Barry R.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Bose, Niranjan; Brewer, Thomas; Rabinovich, Regina] Bill & Melinda Gates Fdn, Global Hlth Program, Seattle, WA USA. [Calderwood, Stephen B.; Ryan, Edward T.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Calderwood, Stephen B.; Mekalanos, John J.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. [Calderwood, Stephen B.; Harris, Jason B.; LaRocque, Regina C.; Ryan, Edward T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Clemens, John D.] Int Vaccine Inst, Seoul, South Korea. [Cravioto, Alejandro] Int Ctr Diarrhoeal Dis Res ICDDR B, Dhaka, Bangladesh. [Harris, Jason B.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Hotez, Peter J.] Amer Soc Trop Med & Hyg, Deerfield, IL USA. [Hotez, Peter J.] George Washington Univ, Dept Microbiol Immunol & Trop Med, Washington, DC USA. [Hotez, Peter J.] PLoS Neglected Trop Dis, San Francisco, CA USA. [Hotez, Peter J.] Sabin Vaccine Inst, Washington, DC USA. [Kerry, Vanessa B.; Ronan, Laurence J.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Pape, Jean-William] Weill Cornell Med Coll, Ctr Global Hlth, New York, NY USA. [Pape, Jean-William] GHESKIO Ctr, Port Au Prince, Haiti. [Rosenberg, Mark L.] Task Force Global Hlth, Decatur, GA USA. [Ryan, Edward T.] Massachusetts Gen Hosp, Trop & Geog Med Ctr, Boston, MA 02114 USA. [Sachs, Jeffrey D.] Columbia Univ, Earth Inst, New York, NY USA. [Sack, David A.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA. [Surena, Claude] Haitian Med Assoc, Port Au Prince, Haiti. [Waldor, Matthew K.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab, Boston, MA 02115 USA. [Waldor, Matthew K.] HHMI, Boston, MA USA. RP Farmer, P (reprint author), Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA 02215 USA. EM paul_farmer@hms.harvard.edu OI Hotez, Peter/0000-0001-8770-1042 FU NIAID NIH HHS [R37 AI042347] NR 123 TC 32 Z9 34 U1 10 U2 113 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD MAY PY 2011 VL 5 IS 5 AR e1145 DI 10.1371/journal.pntd.0001145 PG 13 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 770OZ UT WOS:000291099100024 PM 21655350 ER PT J AU Friedman, NDB Shedlack, KJ AF Friedman, Nora D. B. Shedlack, Karen J. TI Assessment and Management of Patients with Intellectual Disabilities by Psychiatric Consultants SO PSYCHOSOMATICS LA English DT Review ID MENTAL-RETARDATION; CHALLENGING BEHAVIOR; DEVELOPMENTAL-DISABILITIES; PSYCHOTROPIC MEDICATION; ADULTS; RISPERIDONE; DISORDERS; SYMPTOMS; PEOPLE; INDIVIDUALS AB Background: Although most individuals with intellectual disability (ID) currently reside in the community and receive their health care in general medical settings, there is no specific literature on psychiatric consultation to those requiring inpatient medical or surgical care. Objective: The authors discuss the specialized features of the consultation-liaison (C-L) evaluation and common requests for psychiatric consultation in the hospitalized ID population. Method: This article reviews the literature on general psychiatric care in this population and presents the experience of practitioners in the ID-Psychiatry field who have followed their patients through episodes of inpatient non-psychiatric care. Results: The C-L clinician must adapt the interview to accommodate a patient's cognitive, sensory, and language capacities; integrate information from collateral sources; and serve as a liaison between multiple parties. Discussion: ID should not be a barrier to the delivery of appropriate health care. This article provides evidence and recommendations on C-L assessment, management, and liaison for hospitalized individuals with ID. (Psychosomatics 2011; 52:210-217) C1 [Friedman, Nora D. B.] Harvard Univ, Massachusetts Gen Hosp, Dept Child & Adolescent Psychiat, Sch Med, Boston, MA 02114 USA. [Shedlack, Karen J.] Harvard Univ, Sch Med, McLean Hosp, Boston, MA 02114 USA. [Shedlack, Karen J.] Harvard Univ, Sch Med, State MA Dept Dev Serv, Boston, MA 02114 USA. [Shedlack, Karen J.] Harvard Univ, Sch Med, Riverside Community Care Inc, Boston, MA 02114 USA. [Shedlack, Karen J.] Harvard Univ, Sch Med, Behav Treatment Serv, Boston, MA 02114 USA. RP Friedman, NDB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Child & Adolescent Psychiat, Sch Med, 55 Fruit St,Yawkey 6A, Boston, MA 02114 USA. EM ndfriedman@partners.org NR 48 TC 2 Z9 3 U1 5 U2 12 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD MAY-JUN PY 2011 VL 52 IS 3 BP 210 EP 217 PG 8 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 771UU UT WOS:000291187000002 PM 21565592 ER PT J AU Marques, L LeBlanc, N Robinaugh, D Weingarden, H Keshaviah, A Wilhelm, S AF Marques, Luana LeBlanc, Nicole Robinaugh, Donald Weingarden, Hilary Keshaviah, Aparna Wilhelm, Sabine TI Correlates of Quality of Life and Functional Disability in Individuals with Body Dysmorphic Disorder SO PSYCHOSOMATICS LA English DT Article ID ANXIETY STRESS SCALES; OBSESSIVE-COMPULSIVE DISORDER; MAJOR DEPRESSIVE DISORDER; LARGE NONCLINICAL SAMPLE; CLINICAL CHARACTERISTICS; PSYCHIATRIC-INPATIENTS; COMMUNITY SAMPLE; NORMATIVE DATA; HEALTH; PREVALENCE AB Objective: Body dysmorphic disorder (BDD) is a chronic mental illness characterized by low quality of life and functional disability across multiple domains. Despite the clinical importance of understanding impairment in BDD, there has been little research examining the factors that contribute to these constructs. The present study was designed to examine sociodemographic and clinical correlates of quality of life and disability (work, social, and family) in a sample of individuals with moderately severe BDD symptoms. Method: Participants completed an internet survey with questions about demographics, BDD phenomenology, treatment, and impairment. Only participants who completed all study measures and received a score >= 16 on the 10-item Yale-Brown Obsessive Compulsive Scale, Modified fur BDD (BDD-YBOCS), indicating the presence of clinical BDD symptoms, were included in the analysis (n = 256). Multivariate regression with backwards variable selection was used to identify significant predictors of quality of life and functional disability, assessed with the Quality of Life Enjoyment and Satisfaction Scale-Short Form (QLESQ-SF) and the Sheehan Disability Scale (SDS), respectively Results: BDD symptom severity was inversely associated with quality of life and directly associated with disability in all domains. After controlling statistically for BDD symptom severity, sociodemographic and clinical factors such as age, gender, ethnicity, marital status, insurance, body parts of concern, depression symptoms, and anxiety symptoms were significantly associated with impairment. Conclusion: Results suggest a multidimensional nature of quality of life and functional disability and underscore the importance of developing holistic treatment strategies to address impairment in BDD. (Psychosomatics 2011; 52:245-254) C1 [Marques, Luana; LeBlanc, Nicole; Robinaugh, Donald; Weingarden, Hilary; Keshaviah, Aparna; Wilhelm, Sabine] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Marques, Luana; LeBlanc, Nicole; Robinaugh, Donald; Weingarden, Hilary; Keshaviah, Aparna; Wilhelm, Sabine] Harvard Univ, Sch Med, Boston, MA USA. [LeBlanc, Nicole; Weingarden, Hilary] Tufts Univ, Medford, MA 02155 USA. RP Marques, L (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 1 Bowdoin Sq, Boston, MA 02114 USA. EM lmarques@partners.org FU Massachusetts General Hospital, Boston, MA FX The authors acknowledge the David Judah Fund-Internal Donor Funding donated for research purposes at the Massachusetts General Hospital, Boston, MA. NR 50 TC 11 Z9 11 U1 0 U2 5 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD MAY-JUN PY 2011 VL 52 IS 3 BP 245 EP 254 PG 10 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 771UU UT WOS:000291187000006 PM 21565596 ER PT J AU Beach, SR Stem, TA AF Beach, Scott R. Stem, Theodore A. TI Malingering Involving Insurance Fraud: When it Pays to be Ill SO PSYCHOSOMATICS LA English DT Article C1 [Beach, Scott R.; Stem, Theodore A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Beach, SR (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 55 Fruit St,Warren 605, Boston, MA 02114 USA. EM sbeach1@partners.org NR 6 TC 1 Z9 1 U1 1 U2 4 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD MAY-JUN PY 2011 VL 52 IS 3 BP 280 EP 282 PG 3 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 771UU UT WOS:000291187000010 PM 21565600 ER PT J AU DeBonis, K Pierre, JM AF DeBonis, Katrina Pierre, Joseph M. TI Psychosis, Ivermectin Toxicity, and "Morgellons Disease" SO PSYCHOSOMATICS LA English DT Letter C1 [DeBonis, Katrina] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. W Los Angeles VA Med Ctr, Dept Psychiat, Los Angeles, CA USA. RP DeBonis, K (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. NR 6 TC 2 Z9 2 U1 0 U2 5 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD MAY-JUN PY 2011 VL 52 IS 3 BP 295 EP 296 PG 2 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 771UU UT WOS:000291187000015 PM 21565604 ER PT J AU Boland, GWL AF Boland, Giles W. L. TI Adrenal Imaging: From Addison to Algorithms SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article DE Adrenal lesion; Hyperfunctioning; Computed tomography; Characterization; Algorithm ID DELAYED ENHANCED CT; F-18-FDG PET/CT; INITIAL-EXPERIENCE; UNENHANCED CT; MASSES; ADENOMAS; LESIONS; BENIGN; PHEOCHROMOCYTOMAS; CANCER AB Despite their small size, pathologic condition of the adrenal glands is often far from insignificant. Imagers should therefore be familiar with the principles and techniques that underpin the ability of imaging to characterize most lesions. Ignorance of these techniques fails to deliver the necessary imaging value to referrers and patients alike. This article, outlines the range of possible abnormalities encountered in the adrenal gland, the imaging modalities and specialized techniques used to detect and characterize them, the principles based on which these techniques are used, and finally a working imaging algorithm that can be readily used in daily practice. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Boland, GWL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, White Bldg 270C,55 Fruit St, Boston, MA 02114 USA. EM gboland@partners.org NR 47 TC 7 Z9 9 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 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD MAY PY 2011 VL 49 IS 3 BP 511 EP + DI 10.1016/j.rcl.2011.02.010 PG 19 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 770XC UT WOS:000291120800010 PM 21569908 ER PT J AU Sanz, F Restrepo, MI Fernandez, E Mortensen, EM Aguar, MC Cervera, A Chiner, E Blanquer, J AF Sanz, Francisco Restrepo, Marcos I. Fernandez, Estrella Mortensen, Eric M. Carmen Aguar, Maria Cervera, Angela Chiner, Eusebi Blanquer, Jose CA Neumonia Adquirida Comunidad TI Hypoxemia Adds to the CURB-65 Pneumonia Severity Score in Hospitalized Patients With Mild Pneumonia SO RESPIRATORY CARE LA English DT Article DE hypoxemia; prognosis; pneumonia; CURB-65; outcomes; oxygenation ID COMMUNITY-ACQUIRED PNEUMONIA; LOW-RISK PATIENTS; PREDICTION RULE; MORTALITY; VALIDATION; DISEASE; ABNORMALITIES; OXYGENATION; GUIDELINES; MANAGEMENT AB BACKGROUND: Hypoxemia may influence the prognosis of patients with mild pneumonia, regardless of the initial CURB-65 score (confusion, blood urea nitrogen > 20 mg/dL, respiratory rate > 30 breaths/min, blood pressure < 90/60 mm Hg, and age >= 65 y). OBJECTIVE: To determine the risk factors associated with hypoxemia and the influence of hypoxemia on clinical outcomes in hospitalized patients with mild pneumonia. METHODS: We performed a multicenter prospective cohort study of 585 consecutive hospitalized patients with mild pneumonia (CURB-65 groups 0 and 1). We stratified the patients according to the presence of hypoxemia, defined as a P(aO2)/F(IO2) < 300 mm Hg on admission. We assessed the risk factors associated with hypoxemia, hypoxemia's influence on the course of pneumonia, and clinical outcomes (mortality, hospital stay, and need for intensive care unit admission), with multivariable regression. RESULTS: Fifty percent of the patients (294 cases) had hypoxemia on admission. The risk factors independently associated with hypoxemia were: bilateral radiological involvement (odds ratio 2.8, 95% CI 1.1-7.5), history of COPD (odds ratio 2.5, 95% CI 1.4-4.3), and hypoalbuminemia (odds ratio 2.0, 95% CI 1.1-3.5). The hypoxemic patients had longer hospital stay, higher intensive care unit admission rate, higher rate of severe sepsis, and higher mortality than the non-hypoxemic patients. CONCLUSIONS: Hypoxemia in patients with mild pneumonia is independently associated with several adverse clinical and radiological variables, and the hypoxemic patients had worse clinical outcomes than the non-hypoxemic patients. Therefore, additional attention should be paid to the presence of hypoxemia, regardless of a low CURB-65 score. C1 [Sanz, Francisco] Univ Valencia, Consorci Hosp Gen, Serv Neumol, Valencia 46014, Spain. [Restrepo, Marcos I.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pulm & Crit Care Med, San Antonio, TX 78229 USA. [Restrepo, Marcos I.] S Texas Vet Hlth Care Syst, Vet Evidence Based Res Disseminat & Implementat C, San Antonio, TX USA. [Fernandez, Estrella; Cervera, Angela] Hosp Univ Doctor Peset Valencia, Serv Neumol, Valencia, Spain. [Mortensen, Eric M.] S Texas Vet Hlth Care Syst, VERDICT, San Antonio, TX USA. [Carmen Aguar, Maria] Hosp Arnau Vilanova, Serv Neumol, Valencia, Spain. [Chiner, Eusebi] Hosp St Joan, Serv Neumol, Alacant, Spain. [Blanquer, Jose] Hosp Clin Univ Valencia, Serv Med Intens, Valencia, Spain. RP Sanz, F (reprint author), Univ Valencia, Consorci Hosp Gen, Serv Neumol, Tres Cruces 2, Valencia 46014, Spain. EM sanz_fraher@gva.es RI Restrepo, Marcos/H-4442-2014; OI Mortensen, Eric/0000-0002-3880-5563 FU Department of Veteran Affairs Veterans Integrated Service Network [17]; National Institutes of Health [KL2 RR025766]; Clinical and Translational Science Award [KL2 RR025766/VISN-17] FX Dr Restrepo was partly supported by a Department of Veteran Affairs Veterans Integrated Service Network 17 new faculty grant, by National Institutes of Health grant KL2 RR025766, and by Clinical and Translational Science Award KL2 RR025766/VISN-17. Dr Restrepo has disclosed relationships with Johnson & Johnson, CR Bard, Pfizer, Covidien, Ortho McNeil-Janssen, Whyeth, Theravan. Dr Mortensen EM has disclosed a relationship with the United States National Institutes of Health. The other authors have disclosed no conflicts of interest. The organizations that supported this research had no role in conducting the study or preparing, reviewing, or approving this paper. NR 31 TC 11 Z9 11 U1 0 U2 1 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESP CARE JI Respir. Care PD MAY PY 2011 VL 56 IS 5 BP 612 EP 618 DI 10.4187/respcare.00853 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 771XO UT WOS:000291194200008 PM 21276314 ER PT J AU MacIntyre, NR Nava, S DiBlasi, RM Restrepo, RD Hess, DR AF MacIntyre, Neil R. Nava, Stefano DiBlasi, Robert M. Restrepo, Ruben D. Hess, Dean R. TI Respiratory Care Year in Review 2010: Part 2. Invasive Mechanical Ventilation, Noninvasive Ventilation, Pediatric Mechanical Ventilation, Aerosol Therapy SO RESPIRATORY CARE LA English DT Review DE aerosol therapy; airway pressure release ventilation; high-frequency oscillatory ventilation; inhaled bronchodilator; inhaled corticosteroid; mechanical ventilation; noninvasive ventilation ID POSITIVE AIRWAY PRESSURE; ACUTE LUNG INJURY; END-EXPIRATORY PRESSURE; FREQUENCY PERCUSSIVE VENTILATION; RANDOMIZED CONTROLLED-TRIAL; EXTREMELY PRETERM INFANTS; DISTRESS-SYNDROME; RELEASE VENTILATION; CYSTIC-FIBROSIS; TIDAL VOLUMES AB The purpose of this paper is to review the recent literature related to invasive mechanical ventilation, NIV, pediatric mechanical ventilation, and aerosol therapy. Topics covered related to invasive mechanical ventilation topics include the role of PEEP in providing lung protection during mechanical ventilation, unconventional modes for severe hypoxemia, and strategies to improve patient-ventilator interactions. Topics covered related to NIV include real-life NIV use, NIV and extubation failure, and NIV and pandemics. For pediatric mechanical ventilation, the topics addressed are NIV, invasive respiratory support, and inhaled nitric oxide. Topics covered related to aerosol therapy include short-acting beta-adrenergic agents, long-acting beta-adrenergic agents, long-acting antimuscarinic agents, inhaled corticosteroid therapy, phosphodiesterase type 4 (PDE4) inhibitors, long-acting beta-adrenergic plus inhaled corticosteroid, long-acting antimuscarinic plus inhaled corticosteroid, nebulized hypertonic saline, inhaled mannitol, and inhaled antibiotic therapy. These topics were chosen and reviewed in a manner that is most likely to have interest to the readers of RESPIRATORY CARE. C1 [Hess, Dean R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Resp Care Serv, Boston, MA 02114 USA. [MacIntyre, Neil R.] Duke Univ, Med Ctr, Div Pulm & Crit Care Med, Durham, NC USA. [Nava, Stefano] St Orsola & Malpighi Hosp, Resp & Crit Care Unit, Bologna, Italy. [DiBlasi, Robert M.] Seattle Childrens Hosp, Resp Care Dept, Seattle, WA USA. [DiBlasi, Robert M.] Seattle Childrens Res Inst, Ctr Dev Therapeut, Seattle, WA USA. [Restrepo, Ruben D.] Univ Texas Hlth Sci Ctr San Antonio, Dept Resp Care, San Antonio, TX 78229 USA. RP Hess, DR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Resp Care Serv, Ellison 401,55 Fruit St, Boston, MA 02114 USA. EM dhess@partners.org RI Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X NR 77 TC 3 Z9 4 U1 1 U2 9 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 EI 1943-3654 J9 RESP CARE JI Respir. Care PD MAY PY 2011 VL 56 IS 5 BP 667 EP 680 DI 10.4187/respcare.01310 PG 14 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 771XO UT WOS:000291194200014 PM 21669105 ER PT J AU Barnes, TA Kacmarek, RM Kageler, WV Morris, MJ Durbin, CG AF Barnes, Thomas A. Kacmarek, Robert M. Kageler, Woody V. Morris, Michael J. Durbin, Charles G., Jr. TI Transitioning the Respiratory Therapy Workforce for 2015 and Beyond SO RESPIRATORY CARE LA English DT Article DE respiratory care; respiratory therapist; manpower; education; training; competency; licensure; credentialing; accreditation; credentials; specialty; protocols ID MECHANICAL VENTILATION; CARDIAC-ARREST; EDUCATION; CARE AB The American Association for Respiratory Care established a task force in late 2007 to identify likely new roles and responsibilities of respiratory therapists (RTs) in the year 2015 and beyond. A series of 3 conferences was held between 2008 and 2010. The first task force conference affirmed that the healthcare system is in the process of dramatic change, driven by the need to improve health while decreasing costs and improving quality. This will be facilitated by application of evidence-based care, prevention and management of disease, and closely integrated interdisciplinary care teams. The second task force conference identified specific competencies needed to assure safe and effective execution of RT roles and responsibilities in the future. The third task force conference was charged with creating plans to change the professional education process so that RTs are able to achieve the needed skills, attitudes, and competencies identified in the previous conferences. Transition plans were developed by participants after review and discussion of the outcomes of the first two conferences and 1,011 survey responses from RT department managers and RT education program directors. This is a report of the recommendations of the third task force conference held July 12-14, 2010, on Marco Island, Florida. The participants, who represented groups concerned with RT education, licensure, and practice, proposed, discussed, and accepted that to be successful in the future a baccalaureate degree must be the minimum entry level for respiratory care practice. Also accepted was the recommendation that the Certified Respiratory Therapist examination be retired, and instead, passing of the Registered Respiratory Therapist examination will be required for beginning clinical practice. A date of 2020 for achieving these changes was proposed, debated, and accepted. Recommendations were approved requesting resources be provided to help RT education programs, existing RT workforce, and state societies work through the issues raised by these changes. C1 [Barnes, Thomas A.] Northeastern Univ, Dept Hlth Sci, Boston, MA 02115 USA. [Kacmarek, Robert M.] Massachusetts Gen Hosp, Dept Anesthesiol, Boston, MA 02114 USA. [Kacmarek, Robert M.] Harvard Univ, Sch Med, Boston, MA USA. [Kageler, Woody V.] Tarrant Cty Coll, Dept Hlth Sci, Ft Worth, TX USA. [Morris, Michael J.] Brooke Army Med Ctr, Dept Internal Med, San Antonio, TX USA. [Durbin, Charles G., Jr.] Univ Virginia, Dept Anesthesiol, Charlottesville, VA USA. RP Barnes, TA (reprint author), Northeastern Univ, Dept Hlth Sci, 316 Robinson Hall,360 Huntington Ave, Boston, MA 02115 USA. EM tbarnes@neu.edu NR 29 TC 14 Z9 15 U1 1 U2 4 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESP CARE JI Respir. Care PD MAY PY 2011 VL 56 IS 5 BP 681 EP 690 DI 10.4187/respcare.01169 PG 10 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 771XO UT WOS:000291194200015 PM 21276324 ER PT J AU Hess, DR AF Hess, Dean R. TI How Much PEEP? Do We Need Another Meta-Analysis? SO RESPIRATORY CARE LA English DT Editorial Material ID RESPIRATORY-DISTRESS-SYNDROME; END-EXPIRATORY PRESSURE; ACUTE LUNG INJURY; RANDOMIZED CONTROLLED-TRIAL; VENTILATION STRATEGY; MECHANICAL VENTILATION; TIDAL VOLUMES; RECRUITMENT; PULMONARY; MORTALITY C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Resp Care Serv, Boston, MA 02114 USA. RP Hess, DR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Resp Care Serv, Ellison 401,55 Fruit St, Boston, MA 02114 USA. EM dhess@partners.org NR 23 TC 6 Z9 6 U1 0 U2 0 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 EI 1943-3654 J9 RESP CARE JI Respir. Care PD MAY PY 2011 VL 56 IS 5 BP 710 EP 713 DI 10.4187/respcare.01315 PG 4 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 771XO UT WOS:000291194200021 PM 21669106 ER PT J AU Bajwa, EK AF Bajwa, Ednan K. TI Acute Lung Injury: Time to Find a Way That Works SO RESPIRATORY CARE LA English DT Editorial Material ID RESPIRATORY-DISTRESS-SYNDROME; VENTILATION C1 Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Bajwa, EK (reprint author), Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. EM ebajwa@partners.org NR 7 TC 0 Z9 0 U1 0 U2 0 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESP CARE JI Respir. Care PD MAY PY 2011 VL 56 IS 5 BP 714 EP 715 DI 10.4187/respcare.01350 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 771XO UT WOS:000291194200022 PM 21669107 ER PT J AU Stone, WS Giuliano, AJ Tsuang, MT Braff, DL Cadenhead, KS Calkins, ME Dobie, DJ Faraone, SV Freedman, R Green, MF Greenwood, TA Gur, RE Gur, RC Light, GA Mintz, J Nuechterlein, KH Olincy, A Radant, AD Roe, AH Schork, NJ Siever, LJ Silverman, JM Swerdlow, NR Thomas, AR Tsuang, DW Turetsky, BI Seidman, LJ AF Stone, William S. Giuliano, Anthony J. Tsuang, Ming T. Braff, David L. Cadenhead, Kristin S. Calkins, Monica E. Dobie, Dorcas J. Faraone, Stephen V. Freedman, Robert Green, Michael F. Greenwood, Tiffany A. Gur, Raquel E. Gur, Ruben C. Light, Gregory A. Mintz, Jim Nuechterlein, Keith H. Olincy, Ann Radant, Allen D. Roe, Andrea H. Schork, Nicholas J. Siever, Larry J. Silverman, Jeremy M. Swerdlow, Neal R. Thomas, Alison R. Tsuang, Debby W. Turetsky, Bruce I. Seidman, Larry J. TI Group and site differences on the California Verbal Learning Test in persons with schizophrenia and their first-degree relatives: Findings from the Consortium on the Genetics of Schizophrenia (COGS) SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Verbal declarative memory; Schizophrenia; Endophenotype ID ANTISACCADE PERFORMANCE; NONPSYCHOTIC RELATIVES; 1ST-EPISODE SCHIZOPHRENIA; BIOLOGICAL RELATIVES; COGNITIVE DEFICITS; MEMORY IMPAIRMENTS; DECLARATIVE MEMORY; WORKING-MEMORY; METAANALYSIS; ENDOPHENOTYPES AB Genetic studies of schizophrenia focus increasingly on putative endophenotypes because their genetic etiology may be simpler than clinical diagnosis. The Consortium on the Genetics of Schizophrenia (COGS), a multisite family study, aims to identify the genetic basis of several endophenotypes including verbal declarative memory (VDM), a neurocognitive function that shows robust impairment in schizophrenia. We present data on one type of measure of VDM, the California Verbal Learning Test, Second Edition (CVLT-II), in schizophrenia probands (n = 305), their full biological siblings (n = 449) and parents (n = 232), and in community comparison subjects (CCS: n = 509) across seven sites. Probands performed more poorly on each of five CVLT-II measures compared to related sibling and parent groups and CCS. Siblings and parents performed significantly worse than CCS on one measure (Discriminability), but with smaller effect sizes and less impairment than observed previously. The results raise questions about the homogeneity of VDM as an endophenotype, about methodological issues related to sampling, and about psychometric issues that impact the utility of the CVLT for detecting VDM deficits in nonpsychotic relatives of persons with schizophrenia. (C) 2011 Elsevier B.V. All rights reserved. C1 [Stone, William S.; Giuliano, Anthony J.; Roe, Andrea H.; Thomas, Alison R.; Seidman, Larry J.] Harvard Univ, Massachusetts Mental Hlth Ctr, Beth Israel Deaconess Med Ctr, Publ Psychiat Div,Med Sch, Boston, MA 02215 USA. [Stone, William S.; Tsuang, Ming T.; Seidman, Larry J.] Harvard Inst Psychiat Epidemiol & Genet, Boston, MA USA. [Tsuang, Ming T.; Braff, David L.; Cadenhead, Kristin S.; Greenwood, Tiffany A.; Light, Gregory A.; Schork, Nicholas J.; Swerdlow, Neal R.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Med Genet Res Program, Syracuse, NY 13210 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat & Behav Sci, Syracuse, NY 13210 USA. [Calkins, Monica E.; Gur, Raquel E.; Gur, Ruben C.; Turetsky, Bruce I.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Dobie, Dorcas J.; Radant, Allen D.; Tsuang, Debby W.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Dobie, Dorcas J.; Radant, Allen D.; Tsuang, Debby W.] Dept Vet Affairs VISN 20 Mental Illness Res Educ, Seattle, WA USA. [Green, Michael F.; Mintz, Jim; Nuechterlein, Keith H.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90095 USA. [Freedman, Robert; Olincy, Ann] Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA. [Siever, Larry J.; Silverman, Jeremy M.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Siever, Larry J.] James J Peters VA & VISN3 Mental Illness Res Educ, Bronx, NY USA. RP Stone, WS (reprint author), Harvard Univ, Sch Med, Dept Psychiat BIDMC, 2nd Floor E,401 Pk Dr, Boston, MA 02215 USA. EM wstone@bidmc.harvard.edu; dbraff@ncsd.edu RI Greenwood, Tiffany/F-6356-2012; Tsuang, Debby/L-7234-2016; OI Greenwood, Tiffany/0000-0002-6080-6503; Tsuang, Debby/0000-0002-4716-1894; Faraone, Stephen/0000-0002-9217-3982 FU NIMH [RO1 -MH065562]; Mount Sinai School of Medicine [RO1-MH065554]; University of California Los Angeles [RO1-MH65707]; University of California San Diego [RO1-MH065571]; University of Colorado [RO1-MH65588]; University of Pennsylvania [RO1-MH65578]; University of Washington [RO1-MH65558] FX This work was supported by the NIMH through grants to Harvard University (RO1 -MH065562), Mount Sinai School of Medicine (RO1-MH065554), University of California Los Angeles (RO1-MH65707), University of California San Diego (RO1-MH065571), University of Colorado (RO1-MH65588), University of Pennsylvania (RO1-MH65578) and the University of Washington (RO1-MH65558). NR 46 TC 17 Z9 17 U1 3 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY PY 2011 VL 128 IS 1-3 BP 102 EP 110 DI 10.1016/j.schres.2011.01.005 PG 9 WC Psychiatry SC Psychiatry GA 771QL UT WOS:000291175700018 PM 21288694 ER PT J AU Goldstein, JM Cherkerzian, S Seidman, LJ Petryshen, TL Fitzmaurice, G Tsuang, MT Buka, SL AF Goldstein, Jill M. Cherkerzian, Sara Seidman, Larry J. Petryshen, Tracey L. Fitzmaurice, Garrett Tsuang, Ming T. Buka, Stephen L. TI Sex-specific rates of transmission of psychosis in the New England high-risk family study SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; Psychosis; Genetic transmission; Sex differences; High risk; X-linked inheritance ID BIPOLAR AFFECTIVE-DISORDER; X-CHROMOSOME MARKERS; HOPA(12BP) POLYMORPHISM; COMMON VARIANTS; GENETIC-LINKAGE; WORKING-MEMORY; GENOME SCAN; SCHIZOPHRENIA; ILLNESS; BRAIN AB Recent molecular genetic studies have demonstrated X-chromosome abnormalities in the transmission of psychosis, a finding that may contribute to understanding sex differences in the disorder. Using our family high risk paradigm, we tested the hypothesis that there are sex-specific patterns of transmission of psychosis and whether there is specificity comparing nonaffective- with affective-type psychoses. We identified 159 parents with psychoses (schizophrenia psychosis spectrum disorders (SPS, n = 59) and affective (AP, n = 100)) and 114 comparable, healthy control parents. 203 high risk (HR) and 147 control offspring were diagnostically assessed (185 females: 165 males). We compared the proportion of male:female offspring with psychoses by affected parent sex and the consistency for SPS compared to AP parents, and tested (using exact logistic regression) whether the male:female ratio for affected offspring differed significantly between affected mothers and affected fathers. Risk of psychosis in offspring was a function of the sex of the parent and offspring. Among ill mothers, 18.8% of their male offspring developed psychosis compared with 9.5% of their daughters. In contrast, among ill fathers, 3.1% of their male offspring developed psychosis compared with 15.2% of their daughters. The male: female ratio for affected offspring differed significantly (p < 0.05) between affected mothers and fathers. Similar patterns held for SPS and AP. Results demonstrated sex-specific transmission of psychosis regardless of psychosis-type and suggest X-linked inheritance. This has important implications for molecular genetic studies of psychoses underscoring the impact of one's gender on gene-brain-behavior phenotypes of SCZ. (C) 2011 Elsevier B.V. All rights reserved. C1 [Goldstein, Jill M.; Cherkerzian, Sara] Brigham & Womens Hosp, Div Womens Hlth, Dept Psychiat, Connors Ctr Womens Hlth & Gender Biol, Boston, MA 02120 USA. [Goldstein, Jill M.; Cherkerzian, Sara] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Goldstein, Jill M.; Cherkerzian, Sara] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Goldstein, Jill M.; Cherkerzian, Sara] Brigham & Womens Hosp, Div Womens Hlth, Dept Med, Connors Ctr Womens Hlth & Gender Biol, Boston, MA 02120 USA. [Goldstein, Jill M.; Seidman, Larry J.] Massachusetts Gen Hosp, Dept Psychiat, Div Psychiat Neurosci, Boston, MA 02114 USA. [Seidman, Larry J.; Tsuang, Ming T.] Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Ctr, Dept Psychiat, Div Publ Psychiat, Boston, MA 02115 USA. [Petryshen, Tracey L.] Massachusetts Gen Hosp, Dept Psychiat, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Petryshen, Tracey L.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Boston, MA USA. [Fitzmaurice, Garrett] Harvard Univ, McLean Hosp, Sch Med, Dept Psychiat, Belmont, MA 02178 USA. [Tsuang, Ming T.] Univ Calif San Diego, Dept Psychiat, Ctr Behav Genom, San Diego, CA 92103 USA. [Tsuang, Ming T.] Harvard Univ, Sch Publ Hlth, Harvard Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. [Buka, Stephen L.] Brown Univ, Dept Community Hlth, Providence, RI 02912 USA. RP Goldstein, JM (reprint author), Brigham & Womens Hosp, Div Womens Hlth, Dept Psychiat, Connors Ctr Womens Hlth & Gender Biol, 1 Brigham Circle,1620 Tremont St,3rd Floor, Boston, MA 02120 USA. EM jill_goldstein@hms.harvard.edu RI Buka, Stephen/H-7335-2014 OI Buka, Stephen/0000-0002-8578-9308 FU NIMH [RO1 MHSO647, RO1 MH56956, RO1 MH63951]; Stanley Medical Research Institute; NARSAD FX This work was primarily funded by NIMH RO1 MHSO647 (1999-2003, Tsuang, P.I.; 2003-2006, Goldstein, P.I.) and NIMH RO1 MH56956 (Goldstein, PI). Additional funding included NIMH RO1 MH63951 (LJS), Stanley Medical Research Institute (SB, LJS), and NARSAD (LJS). NIMH had no further role in the study design, in the collection, analysis and interpretation of data, in the writing of the report, and in the decision to submit the paper for publication. NR 62 TC 16 Z9 16 U1 2 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY PY 2011 VL 128 IS 1-3 BP 150 EP 155 DI 10.1016/j.schres.2011.01.019 PG 6 WC Psychiatry SC Psychiatry GA 771QL UT WOS:000291175700025 PM 21334180 ER PT J AU Hermes, E Nasrallah, H Davis, V Meyer, J McEvoy, J Goff, D Davis, S Stroup, TS Swartz, M Lieberman, J Rosenheck, R AF Hermes, Eric Nasrallah, Henry Davis, Vicki Meyer, Jonathan McEvoy, Joseph Goff, Donald Davis, Sonia Stroup, T. Scott Swartz, Marvin Lieberman, Jeffrey Rosenheck, Robert TI The association between weight change and symptom reduction in the CATIE schizophrenia trial SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Antipsychotic agents; Weight gain; Lipids; Schizophrenia; Treatment outcome; Body mass index ID 2ND-GENERATION ANTIPSYCHOTICS; ATYPICAL ANTIPSYCHOTICS; RANDOMIZED-TRIAL; GAIN; OLANZAPINE; CLOZAPINE; IMPROVEMENT; EFFICACY; DRUGS; PANSS AB Background: Weight gain and changes in metabolic indicators associated with some antipsychotics may be related to symptom improvement and thus an unavoidable correlate of clinical benefit. Methods: Data from the CATIE schizophrenia trial comparing the effectiveness of perphenazine, olanzapine, risperidone, quetiapine and ziprasidone in a randomized, double-blind, trial over 18 months were used to evaluate the relationship between percent change in body mass index (BMI) and change in total serum cholesterol and triglycerides with the Positive and Negative Syndrome Scale (PANSS) score. Analysis of covariance for observations at 3 months and a mixed effects model for all observations up to 18 months adjusted for potentially confounding variables were used to examine these associations. Results: In both models, there was a significant association (p = 0.001) between change in PANSS total score and percent change in BMI, equating to a 0.28 and 0.21 point decrease in PANSS total score (range 30-210) per 1% increase in BMI respectively. Change in BMI accounted for 3% or less of variance for change in PANSS scores. There was no evidence that the association of symptoms and weight gain differed across medications in spite of substantial differences in weight gain and other metabolic measures. Neither total serum cholesterol nor triglyceride levels displayed a significant association with change in PANSS. Conclusion: The magnitude of the relationship between change in BMI and PANSS was too small to be clinically important, indicating that switching medications to one with less metabolic risk is unlikely to result in meaningful loss of clinical benefit. (C) 2011 Elsevier B.V. All rights reserved. C1 [Hermes, Eric; Rosenheck, Robert] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06511 USA. [Nasrallah, Henry] Univ Cincinnati, Dept Psychiat & Behav Sci, Cincinnati, OH 45267 USA. [Davis, Vicki] NeuroCog Trials Inc, Durham, NC 27707 USA. [Meyer, Jonathan] Univ Calif San Diego, Dept Psychiat, VA San Diego Healthcare Syst, San Diego, CA 92161 USA. [McEvoy, Joseph] Duke Univ, Dept Psychiat & Behav Sci, Butner, NC 27509 USA. [McEvoy, Joseph] John Umstead Hosp, Butner, NC 27509 USA. [Goff, Donald] Harvard Univ, Massachusetts Gen Hosp, Dept Psychiat,Med Sch,Lindemann Mental Hlth Ctr, Schizophrenia Program,Freedom Trail Clin, Boston, MA 02114 USA. [Davis, Sonia] Quintiles Inc, Morrisville, NC 27560 USA. [Stroup, T. Scott] New York State Psychiat Inst & Hosp, Program Intervent Effectiveness Res, New York, NY 10032 USA. [Swartz, Marvin] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27710 USA. [Lieberman, Jeffrey] Columbia Univ, Inst Psychiat, Dept Psychiat, New York, NY 10032 USA. [Rosenheck, Robert] VA New England Mental Illness Res Educ & Clin Ctr, West Haven, CT 06516 USA. RP Hermes, E (reprint author), Yale Univ, Sch Med, Dept Psychiat, 300 George St,Ste 901, New Haven, CT 06511 USA. EM Eric.Hermes@yale.edu; NASRALHA@ucmail.uc.edu; Vicki.Davis@NeuroCogTrials.com; jmmeyer@ucsd.edu; jpmcevoy@duke.edu; goff@psych.mgh.harvard.edu; sonia.davis@quintiles.com; stroups@pi.cpmc.columbia.edu; marvin.swartz@duke.edu; JL2616@columbia.edu; Robert.Rosenheck@yale.edu RI Stroup, Thomas/F-9188-2014 OI Stroup, Thomas/0000-0002-3123-0672 FU New England Mental Illness Research and Education Center; Janssen Pharmaceutics Products; Wyeth Pharmaceuticals; AstraZeneca Pharmaceuticals LP; Bristol-Myers Squibb; GlaxoSmithKline; Pfizer Inc; Novartis; Solvay; Forest Pharmaceutical Company; Wyeth; Jannsen; Lilly; Pfizer; Sanofi; Cephalon; Dainippon Sumitomo; Solvay/Wyeth; Organon; Vanda; Eli Lilly FX This analysis was supported by the New England Mental Illness Research and Education Center. The funding source had no role in the design, analysis or interpretation of data or in the preparation of the report or decision to publish.; Dr. Rosenheck has received research support from Janssen Pharmaceutics Products and Wyeth Pharmaceuticals within the last year in addition to AstraZeneca Pharmaceuticals LP, Bristol-Myers Squibb, and Eli Lilly and Co. in the past. He has received consulting fees from Bristol-Myers Squibb, Eli Lilly and Co., Roche Pharmaceuticals and Janssen Pharmaceutica Products. He is a testifying expert in Jones ex rel. the State of Texas v. Janssen Pharmaceutica Products.; Dr. Lieberman reports having received research funding from AstraZeneca Pharmaceuticals LP, Bristol-Myers Squibb, GlaxoSmithKline, Janssen Pharmaceutics Products, and Pfizer Inc.; and consulting and educational fees from AstraZeneca Pharmaceuticals LP, Bristol-Myers Squibb, Eli Lilly and Co., Forest Pharmaceutical Company, GlaxoSmithKline, Janssen Pharmaceutica Products, Novartis, Pfizer Inc., and Solvay.; Dr. McEvoy reports having received research funding from AstraZeneca, Forest Research Institute, Eli Lilly and Co., Janssen Pharmaeutica, and Pfizer Inc.; consulting or advisory board fees from Pfizer Inc. and Bristol-Myers Squibb; and lecture fees from Janssen Pharmaceutics, and Bristol-Myers Squibb.; Dr. Swartz reports having received research funding from Eli Lilly and Co., and consulting and educational fees from AstraZeneca Pharmaceuticals LP, Bristol-Myers Squibb, Eli Lilly and Co., and Pfizer Inc.; Dr. Meyer reports having received research support from Bristol-Myers Squibb and Pfizer, Inc., and has received speaking or advising fees from Bristol-Myers Squibb, Janssen Pharmaceutica, Pfizer, Inc., and Wyeth.; Dr. Nasrallah has received grants/research support from AstraZeneca, GSK, Jannsen, Lilly, Pfizer and Sanofi; has been a consultant, an advisory board member and served on the speakers' bureau for Abbott, AstraZeneca, Janssen, Pfizer and Shire.; Dr. Goff has received grants/research support from Pfizer. Cephalon and Janssen, has received consulting, advisory board or lecture fees from Dainippon Sumitomo, Solvay/Wyeth, Bristol-MyerSquibb, Organon, Vanda and Eli Lilly. NR 26 TC 23 Z9 23 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY PY 2011 VL 128 IS 1-3 BP 166 EP 170 DI 10.1016/j.schres.2011.01.022 PG 5 WC Psychiatry SC Psychiatry GA 771QL UT WOS:000291175700028 PM 21334853 ER PT J AU Alter, G Altfeld, M AF Alter, Galit Altfeld, Marcus TI Mutiny or scrutiny: NK cell modulation of DC function in HIV-1 infection SO TRENDS IN IMMUNOLOGY LA English DT Review ID NATURAL-KILLER-CELLS; MHC CLASS-I; PLASMACYTOID-DENDRITIC-CELLS; IMMUNE-RESPONSES; VIRUS-INFECTION; INNATE IMMUNITY; LYMPH-NODES; IFN-GAMMA; HLA-B; ACTIVATION AB Accumulating data suggest that natural killer (NK) cells are involved not only in the innate antiviral response following infection, but also in shaping the quality of the adaptive immune response by modulating the functional properties of myeloid dendritic cells (DC) during the acute immune response to infection. In this role, NK cells ensure that only fully mature, immunogenic DCs gain access to inductive sites, where they might prime effective antiviral adaptive immune responses. However, increasing evidence now suggests that several aspects of this cross-talk between NK cells and DCs are compromised during HIV infection, potentially contributing to immune dysfunction. C1 [Altfeld, Marcus] MIT, Ragon Inst MGH, Charlestown, MA 02120 USA. Massachusetts Gen Hosp, Charlestown, MA 02120 USA. RP Altfeld, M (reprint author), MIT, Ragon Inst MGH, 149 13th St, Charlestown, MA 02120 USA. EM maltfeld@partners.org FU NIAID NIH HHS [P01 AI074415, R01 AI067031, R01 AI067031-05, P01 AI074415-04] NR 69 TC 17 Z9 18 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4906 J9 TRENDS IMMUNOL JI Trends Immunol. PD MAY PY 2011 VL 32 IS 5 BP 219 EP 224 DI 10.1016/j.it.2011.02.003 PG 6 WC Immunology SC Immunology GA 771CX UT WOS:000291135900006 PM 21411368 ER PT J AU Greulich, H Pollock, PM AF Greulich, Heidi Pollock, Pamela M. TI Targeting mutant fibroblast growth factor receptors in cancer SO TRENDS IN MOLECULAR MEDICINE LA English DT Review ID TYROSINE KINASE INHIBITOR; DYSPLASIA TYPE-I; IMMUNOGLOBULIN-LIKE DOMAIN; UROTHELIAL CELL-CARCINOMA; LETHAL SKELETAL DYSPLASIA; POTENT ANTITUMOR-ACTIVITY; GENOME-WIDE ASSOCIATION; MULTIPLE-MYELOMA; FGFR3 MUTATIONS; ACTIVATING MUTATIONS AB Fibroblast growth factor receptors (FGFRs) play diverse roles in the control of cell proliferation, cell differentiation, angiogenesis and development. Activating the mutations of FGFRs in the germline has long been known to cause a variety of skeletal developmental disorders, but it is only recently that a similar spectrum of somatic FGFR mutations has been associated with human cancers. Many of these somatic mutations are gain-of-function and oncogenic and create dependencies in tumor cell lines harboring such mutations. A combination of knockdown studies and pharmaceutical inhibition in preclinical models has further substantiated genomically altered FGFR as a therapeutic target in cancer, and the oncology community is responding with clinical trials evaluating multikinase inhibitors with anti-FGFR activity and a new generation of specific pan-FGFR inhibitors. C1 [Greulich, Heidi] Dana Farber Canc Inst, Boston, MA 02115 USA. [Greulich, Heidi] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Greulich, Heidi] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Greulich, Heidi] Broad Inst, Cambridge, MA 02142 USA. [Pollock, Pamela M.] Queensland Univ Technol, Inst Hlth & Biomed Innovat, Kelvin Grove, Qld 4059, Australia. RP Greulich, H (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM heidig@broadinstitute.org; pamela.pollock@qut.edu.au FU NCI NIH HHS [P50 CA134254] NR 103 TC 56 Z9 59 U1 1 U2 21 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4914 J9 TRENDS MOL MED JI Trends Mol. Med PD MAY PY 2011 VL 17 IS 5 BP 283 EP 292 DI 10.1016/j.molmed.2011.01.012 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 773GL UT WOS:000291294900007 PM 21367659 ER PT J AU Somarouthu, B Rabinov, J Wong, WC Kalva, SP AF Somarouthu, Bhanusupriya Rabinov, James Wong, Waichi Kalva, Sanjeeva P. TI Stent-Assisted Coil Embolization of an Intraparenchymal Renal Artery Aneurysm in a Patient With Neurofibromatosis SO VASCULAR AND ENDOVASCULAR SURGERY LA English DT Article DE Renal artery aneurysm; neurofibromatosis; stent-assisted coil embolization AB True renal artery aneurysms are rare. They are generally asymptomatic, however, a few may present with hypertension, rupture, or renal dysfunction secondary to distal embolization. Indications for intervention include aneurysm of >= 2.0 cm in diameter, renovascular hypertension, enlarging aneurysm, associated dissection /rupture, and aneurysms in women of child-bearing age/pregnancy. Endovascular therapy through coil embolization or stent graft exclusion is the recommended management. Coil embolization of the first and second order branch aneurysms is often associated with distal parenchymal loss and current stent graft technology prohibits use of these endoprostheses in the branch renal arteries. In this report, we describe successful stent-assisted coil embolization of an intraparenchymal aneurysm while preserving the distal parenchyma in a young woman with Neurofibromatosis type I. C1 [Somarouthu, Bhanusupriya; Rabinov, James; Kalva, Sanjeeva P.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Somarouthu, Bhanusupriya; Rabinov, James; Wong, Waichi; Kalva, Sanjeeva P.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Wong, Waichi] Massachusetts Gen Hosp, Dept Nephrol, Boston, MA 02114 USA. RP Kalva, SP (reprint author), Massachusetts Gen Hosp, Dept Radiol, GRB 297,55 Fruit St, Boston, MA 02114 USA. EM skalva@partners.org NR 7 TC 4 Z9 5 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1538-5744 J9 VASC ENDOVASC SURG JI Vasc. Endovasc. Surg. PD MAY PY 2011 VL 45 IS 4 BP 368 EP 371 DI 10.1177/1538574411403327 PG 4 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 771LX UT WOS:000291160600012 PM 21527466 ER PT J AU Perrin, JM Dewitt, TG AF Perrin, James M. Dewitt, Thomas G. TI Future of Academic General Pediatrics-Areas of Opportunity SO ACADEMIC PEDIATRICS LA English DT Article ID HEALTH-CARE NEEDS; MEDICAL HOME; CHILDREN; CHALLENGES; PHYSICIANS; EDUCATION C1 [Perrin, James M.] Harvard Univ, Sch Med, MGH Ctr Child & Adolescent Hlth Policy, MassGen Hosp Children, Boston, MA USA. [Dewitt, Thomas G.] Univ Cincinnati, Coll Med, Div Gen & Community Pediat, Cincinnati Childrens Hosp, Cincinnati, OH USA. RP Perrin, JM (reprint author), 50 Staniford St,901, Boston, MA 02114 USA. EM jperrin@partners.org NR 34 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1876-2859 J9 ACAD PEDIATR JI Acad. Pediatr. PD MAY-JUN PY 2011 VL 11 IS 3 BP 181 EP 188 PG 8 WC Pediatrics SC Pediatrics GA 768IV UT WOS:000290928500003 PM 21570003 ER PT J AU Co, JPT Sternberg, SB Homer, CJ AF Co, John Patrick T. Sternberg, Scot B. Homer, Charles J. TI Measuring Patient and Family Experiences of Health Care for Children SO ACADEMIC PEDIATRICS LA English DT Article DE patient centeredness; patient experience; quality of care; surveys ID PEDIATRIC AMBULATORY-CARE; QUALITY-OF-CARE; PSYCHOMETRIC PROPERTIES; PHYSICIAN COMMUNICATION; CONSUMER ASSESSMENT; TECHNICAL QUALITY; SYSTEM PROVISION; CORE SURVEY; PLANS; SERVICES AB BACKGROUND: The Institute of Medicine considers patient centeredness a core dimension of quality. Several patient/family surveys exist to assess pediatric health care. The Children's Health Insurance Program Reauthorization Act mandates strengthening quality measurement for children, including for patient/family experience of care. OBJECTIVES: The aim of this study was to determine what instruments exist for measuring patient/family experience of pediatric health care and which should be included in the core measurement set for assessing Medicaid and the Children's Health Insurance Program (CHIP) programs; to identify gaps in measurement; and to provide recommendations for measure development. METHODS: We developed a conceptual framework for measuring patient/family experience of care. We conducted a review of national measure clearinghouses and of the literature to assess validity, reliability, and feasibility of existing measures, and how these measures address the conceptual framework. RESULTS: We found valid and reliable instruments for measuring patient/family experience of care include the Consumer Assessment of Healthcare Providers and Systems (CAHPS (R)) instruments, Promoting Healthy Development Survey (PHDS), Young Adult Health Care Survey (YAHCS), and the National Research Corporation Picker Pediatric Inpatient Survey (NRC Picker). We identified the need for matching patients with providers and groups as a barrier for widespread use of the CAHPS (R) pediatric clinician & group instrument. CONCLUSIONS: We recommended to the National Advisory Council for Healthcare Research and Quality Subcommittee on Children's Healthcare Quality Measures for Medicaid and Child Health Insurance Programs (SNAC) the CAHPS (R) Child Medicaid 4.0 and pediatric Clinician & Group Survey for inclusion in the initial recommended list of core measures for voluntary use by Medicaid and CHIP. The Clinician and Group Survey was not included in the list posted for public comment due to concerns at that time (December 2009) about feasibility. We also recommended that development of a child version of the CAHPS (R) behavioral and mental health survey now used in the adult population and of a pediatric hospital CAHPS (R) measure be considered high priorities for development in the next phase of Children's Health Insurance Program Reauthorization Act measurement activity. This phase should also explore methods to increase response rates and lower costs of obtaining consumer feedback. C1 [Co, John Patrick T.] Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA. [Co, John Patrick T.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Sternberg, Scot B.; Homer, Charles J.] Natl Initiat Childrens Healthcare Qual, Boston, MA USA. [Co, John Patrick T.; Homer, Charles J.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Co, JPT (reprint author), Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, 50 Staniford St,Suite 901, Boston, MA 02114 USA. EM jco@partners.org FU US Department of Health and Human Services Agency for Healthcare Research and Quality [HHSP233200900801P]; Centers for Medicare & Medicaid Services FX Funding for this report was provided through purchase order HHSP233200900801P by the US Department of Health and Human Services Agency for Healthcare Research and Quality, with funds provided by its Centers for Medicare & Medicaid Services. NR 59 TC 12 Z9 12 U1 2 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1876-2859 J9 ACAD PEDIATR JI Acad. Pediatr. PD MAY-JUN PY 2011 VL 11 IS 3 SU S BP S59 EP S67 PG 9 WC Pediatrics SC Pediatrics GA 768IX UT WOS:000290928700007 PM 21570018 ER PT J AU Kuhlthau, KA AF Kuhlthau, Karen A. TI Measures of Availability of Health Care Services for Children SO ACADEMIC PEDIATRICS LA English DT Article DE availability; health care; pediatric; provider density ID NEONATAL INTENSIVE-CARE; UNITED-STATES; MANAGED CARE; ACCESS; NEEDS; ACCESSIBILITY; ENVIRONMENT; PHYSICIAN AB OBJECTIVE: The Children's Health Insurance Program Reauthorization Act (CHIPRA) mandates that measures of availability of child health services be included in the recommended core measurement set. The objective of this work was to review and evaluate measures of availability of child health services for potential inclusion in the initial core set of health care quality measures as mandated by CHIPRA. METHODS: To find measures, I searched the published literature, measurement sets, and recommended articles to identify existing measures of availability. I comment on the use of these measures as well as their reliability and validity (where available). RESULTS: I identified measures of geographic availability (n = 11), timeliness (n = 7), and barriers (n = 4). Geographic measures range from counts of the number of providers in a specific area to measures that account for whether providers are open to caring for patients with public insurance and distance. Measures of timeliness address whether patients can see a provider quickly. Barriers measure the ease with which providers can be seen. CONCLUSIONS: Of potential use to the CHIPRA measurement initiative are objective measures of provider density and some existing parent survey questions about timeliness and ease of use. Other measures include more refined measures of density or distance, perhaps looking at providers who are taking new Medicaid and State Children's Health Insurance Program patients and more detailed questions about the timeliness and ease with which patients can get care. However, more work is needed on the validity and reliability of existing measures; more work is also needed to expand measures of availability beyond existing domains of providers and conditions. C1 Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA. RP Kuhlthau, KA (reprint author), Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, 50 Staniford St,Ste 901, Boston, MA 02114 USA. EM kkuhlthau@partners.org FU US HHS AHRQ [HESP233200900701P]; HHS Centers for Medicare & Medicaid Services FX Funding for this report was provided through Purchase Order HESP233200900701P by the US HHS AHRQ, with funds provided by the HHS Centers for Medicare & Medicaid Services. NR 35 TC 4 Z9 4 U1 2 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1876-2859 J9 ACAD PEDIATR JI Acad. Pediatr. PD MAY-JUN PY 2011 VL 11 IS 3 SU S BP S42 EP S48 PG 7 WC Pediatrics SC Pediatrics GA 768IX UT WOS:000290928700005 PM 21570016 ER PT J AU Sternberg, SB Co, JPT Homer, CJ AF Sternberg, Scot B. Co, John Patrick T. Homer, Charles J. TI Review of Quality Measures of the Most Integrated Health Care Settings for Children and the Need for Improved Measures: Recommendations for Initial Core Measurement Set for CHIPRA SO ACADEMIC PEDIATRICS LA English DT Review DE integrated health care; medical home ID PEDIATRIC PRIMARY-CARE; MEDICAL HOME; EXPERIENCES; IMPLEMENTATION; PATIENT; IMPACT AB OBJECTIVE: To identify, assess, and make recommendations for inclusion of measures that assess the domain of "most integrated health care setting," with a specific focus on measures of the medical home, one particular mechanism for integrating care, to identify gaps in measurement; and to make recommendations for new measure development. METHODS: We developed a conceptual framework for care integration and reviewed literature on measures assessing the presence and quality of the medical home to determine their validity, reliability, and feasibility as a proxy for care integration. RESULTS: We identified 2 broad approaches to assessing the extent to which patients receive care that fulfills the aims of the medical home: I) organizational assessment of practice systems and processes thought associated with achieving these desired aims (viz, the National Committee for Quality Assurance Physician Practice Connections Patient Centered Medical Home measure and the Medical Home Index, and 2) direct assessment by patients/families of their experience of care in targeted dimensions. Based on concerns about the absence of reliability data and the feasibility of applying the-practice audit/self-assessment approach on a population level for the purpose of state reporting, as well as the limited data linking performance on the specific measures with important child outcomes, we did not recommend any of the measures of organizational assessments of practice systems for inclusion in the core set as an indicator of care integration. In contrast, measures of the medical home based on items from the National Survey of Child Health on a population level of or the Consumer Assessment of Healthcare Providers and Systems for practice- and state-level assessment are more feasible, have known reliability and performance characteristics, and more closely reflect the aims of the medical home, including care integration. CONCLUSIONS: Measures of health care integration as captured by the experience of care in a medical home can best be assessed for state-level performance through patient/family experience surveys. Better measures of care integration, care coordination, and integration of mental, developmental, and physical health into a comprehensive care system are high-priority topics for measure development. C1 [Co, John Patrick T.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Co, John Patrick T.] Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA. [Sternberg, Scot B.; Homer, Charles J.] Natl Initiat Childrens Healthcare Qual, Boston, MA USA. RP Sternberg, SB (reprint author), Beth Israel Deaconess Med Ctr, Stoneman Ctr Qual Improvement, 330 Brookline Ave, Boston, MA 02215 USA. EM Scot.Sternberg@gmail.com FU US Department of Health and Human Services (HHS) AHRQ [HHSP233200900799P]; HHS CMS FX Funding for this report was provided through Purchase Order HHSP233200900799P by the US Department of Health and Human Services (HHS) AHRQ with funds provided by the HHS CMS. NR 41 TC 8 Z9 8 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1876-2859 J9 ACAD PEDIATR JI Acad. Pediatr. PD MAY-JUN PY 2011 VL 11 IS 3 SU S BP S49 EP S58 PG 10 WC Pediatrics SC Pediatrics GA 768IX UT WOS:000290928700006 PM 21570017 ER PT J AU Mylonakis, E AF Mylonakis, Eleftherios TI The Need to Redefine Antimicrobial Drug Discovery SO CURRENT PHARMACEUTICAL DESIGN LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA. RP Mylonakis, E (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, 55 Fruit St,Gray Jackson 5,Room GRJ-504, Boston, MA 02114 USA. EM emylonakis@partners.org NR 13 TC 3 Z9 3 U1 0 U2 4 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PD MAY PY 2011 VL 17 IS 13 BP 1223 EP 1224 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 768QU UT WOS:000290952300001 PM 21470109 ER PT J AU Anastassopoulou, CG Fuchs, BB Mylonakis, E AF Anastassopoulou, Cleo G. Fuchs, Beth Burgwyn Mylonakis, Eleftherios TI Caenorhabditis elegans-based Model Systems for Antifungal Drug Discovery SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review DE Invertebrate model hosts; non-mammalian animal models; systemic mycoses; Candida albicans; high-throughput in vivo screening; drug bioaccumulation model; Caenorhabditis elegans ID HOST-PATHOGEN INTERACTIONS; ANIMAL INFECTION MODEL; INTENSIVE-CARE-UNIT; CANDIDA-ALBICANS; CRYPTOCOCCUS-NEOFORMANS; C-ELEGANS; FUNGAL-INFECTIONS; INNATE IMMUNITY; IN-VITRO; ANTILEISHMANIAL ACTIVITY AB The substantial morbidity and mortality associated with invasive fungal infections constitute undisputed tokens of their severity. The continued expansion of susceptible population groups (such as immunocompromised individuals, patients undergoing extensive surgery, and those hospitalized with serious underlying diseases especially in the intensive care unit) and the limitations of current antifungal agents due to toxicity issues or to the development of resistance, mandate the development of novel antifungal drugs. Currently, drug discovery is transitioning from the traditional in vitro large-scale screens of chemical libraries to more complex bioassays, including in vivo studies on whole animals; invertebrates, such as Caenorhabditis elegans, are thus gaining momentum as screening tools. Key pathogenesis features of fungal infections, including filament formation, are expressed in certain invertebrate and mammalian hosts; among the various potential hosts, C. elegans provides an attractive platform both for the study of host-pathogen interactions and the identification of new antifungal agents. Advantages of compound screening in this facile, relatively inexpensive and not as ethically challenged whole-animal context, include the simultaneous assessment of antifungal efficacy and toxicity that could result in the identification of compounds with distinct mechanisms of action, for example by promoting host immune responses or by impeding fungal virulence factors. With the recent advent of using predictive models to screen for compounds with improved chances of bioavailability in the nematode a priori, high-throughput screening of chemical libraries using the C. elegans-C. albicans antifungal discovery assay holds even greater promise for the identification of novel antifungal agents in the near future. C1 [Mylonakis, Eleftherios] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Mylonakis, E (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St,Gray Jackson 5,Room GRJ-504, Boston, MA 02114 USA. EM emylonakis@partners.org FU NIH [P01 AI 083214, R01 AI075286, R21 AI079569]; Astellas Pharma Inc. FX This work was supported by NIH grants P01 AI 083214, R01 AI075286 and R21 AI079569 to E.M.; E.M. has served in an Advisory Board and received research support from Astellas Pharma Inc. C. G. A. and B. B. F. report no potential conflicts of interest. NR 113 TC 17 Z9 18 U1 2 U2 11 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 EI 1873-4286 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PD MAY PY 2011 VL 17 IS 13 BP 1225 EP 1233 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 768QU UT WOS:000290952300002 PM 21470110 ER PT J AU Tegos, GP Haynes, M Strouse, J Khan, MMT Bologa, CG Oprea, TI Sklar, LA AF Tegos, George P. Haynes, Mark Strouse, Jacob Khan, Mohiuddin Md. T. Bologa, Cristian G. Oprea, Tudor I. Sklar, Larry A. TI Microbial Efflux Pump Inhibition: Tactics and Strategies SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review DE Multidrug resistance; efflux pump substrates and inhibitors; natural antimicrobials; high-throughput screening ID RESISTANT STAPHYLOCOCCUS-AUREUS; GRAM-NEGATIVE BACTERIA; PSEUDOMONAS-AERUGINOSA BIOFILMS; KLEBSIELLA-PNEUMONIAE STRAINS; ARGININE-BETA-NAPHTHYLAMIDE; CANDIDA-ALBICANS BIOFILMS; MULTIDRUG TRANSPORTER BMR; MEDIATED DRUG-RESISTANCE; LARGE PERIPLASMIC LOOPS; ESCHERICHIA-COLI AB Traditional antimicrobials are increasingly suffering from the emergence of multidrug resistance among pathogenic microorganisms. To overcome these deficiencies, a range of novel approaches to control microbial infections are under investigation as potential alternative treatments. Multidrug efflux is a key target of these efforts. Efflux mechanisms are broadly recognized as major components of resistance to many classes of chemotherapeutic agents as well as antimicrobials. Efflux occurs due to the activity of membrane transporter proteins widely known as Multidrug Efflux Systems (MES). They are implicated in a variety of physiological roles other than efflux and identifying natural substrates and inhibitors is an active and expanding research discipline. One plausible alternative is the combination of conventional antimicrobial agents/antibiotics with small molecules that block MES known as multidrug efflux pump inhibitors (EPIs). An array of approaches in academic and industrial research settings, varying from high-throughput screening (HTS) ventures to bioassay guided purification and determination, have yielded a number of promising EPIs in a series of pathogenic systems. This synergistic discovery platform has been exploited in translational directions beyond the potentiation of conventional antimicrobial treatments. This venture attempts to highlight different tactical elements of this platform, identifying the need for highly informative and comprehensive EPI-discovery strategies. Advances in assay development genomics, proteomics as well as the accumulation of bioactivity and structural information regarding MES facilitates the basis for a new discovery era. This platform is expanding drastically. A combination of chemogenomics and chemoinformatics approaches will integrate data mining with virtual and physical HTS ventures and populate the chemical-biological interface with a plethora of novel chemotypes. This comprehensive step will expedite the preclinical development of lead EPIs. C1 [Tegos, George P.; Haynes, Mark; Strouse, Jacob; Khan, Mohiuddin Md. T.; Bologa, Cristian G.; Oprea, Tudor I.; Sklar, Larry A.] Univ New Mexico, Ctr Mol Discovery, Albuquerque, NM 87131 USA. [Tegos, George P.; Sklar, Larry A.] Univ New Mexico, Dept Pathol, Albuquerque, NM 87131 USA. [Tegos, George P.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Tegos, George P.] Harvard Univ, Sch Med, Dept Dermatol, Cambridge, MA 02138 USA. [Bologa, Cristian G.; Oprea, Tudor I.] Univ New Mexico, Hlth Sci Ctr, Div Biocomp, Albuquerque, NM 87131 USA. RP Tegos, GP (reprint author), 2325 Camino de Salud, CRF 217A MSC 07-4025, Albuquerque, NM 87131 USA. EM gtegos@salud.unm.edu RI Oprea, Tudor/A-5746-2011; OI Oprea, Tudor/0000-0002-6195-6976; Bologa, Cristian/0000-0003-2232-4244 FU Massachusetts Technology Transfer Center (MTTC) [U54, MH084690, R01GM59903, R01AI050875] FX Funding for part of the research presented in this review was provided for by Massachusetts Technology Transfer Center (MTTC) to George Tegos NIH (U54, MH084690 Molecular Libraries Probe Production Centers Network, to George Tegos and Larry Sklar) and (R01GM59903, K. Lewis) and (R01AI050875, M. R. Hamblin). The authors will like to thank Melissa Brown & Laura Piddock for permission to use the MES scheme in Fig. 1 and to Martyn Symmons for kindly providing the PDB model of the AcrAB-TolC efflux pump. NR 184 TC 30 Z9 30 U1 2 U2 40 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PD MAY PY 2011 VL 17 IS 13 BP 1291 EP 1302 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 768QU UT WOS:000290952300009 PM 21470111 ER PT J AU Sharma, SK Dai, TH Kharkwal, GB Huang, YY Huang, LY De Arce, VJB Tegos, GP Hamblin, MR AF Sharma, Sulbha K. Dai, Tianhong Kharkwal, Gitika B. Huang, Ying-Ying Huang, Liyi De Arce, Vida J. Bil Tegos, George P. Hamblin, Michael R. TI Drug Discovery of Antimicrobial Photosensitizers Using Animal Models SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review DE Antimicrobial photodynamic therapy; cationic tetrapyrroles; phenothiazinium dyes; reactive oxygen species; mouse models of localized infections; bioluminescence imaging; drug discovery ID RESISTANT STAPHYLOCOCCUS-AUREUS; GRAM-POSITIVE BACTERIA; MESOSUBSTITUTED CATIONIC PORPHYRINS; TARGETED PHOTODYNAMIC THERAPY; CANDIDA-ALBICANS; IN-VITRO; ESCHERICHIA-COLI; METHYLENE-BLUE; EFFICIENT PHOTOSENSITIZERS; PHOTOBACTERICIDAL ACTIVITY AB Antimicrobial photodynamic therapy (aPDT) is an emerging alternative to antibiotics motivated by growing problems with multi-drug resistant pathogens. aPDT uses non-toxic dyes or photosensitizers (PS) in combination with harmless visible of the correct wavelength to be absorbed by the PS. The excited state PS can form a long-lived triplet state that can interact with molecular oxygen to produce reactive oxygen species such as singlet oxygen and hydroxyl radical that kill the microbial cells. To obtain effective PS for treatment of infections it is necessary to use cationic PS with positive charges that are able to bind to and penetrate different classes of microbial cells. Other drug design criteria require PS with high absorption coefficients in the red/near infra-red regions of the spectrum where light penetration into tissue is maximum, high photostability to minimize photobleaching, and devising compounds that will selectively bind to microbial cells rather than host mammalian cells. Several molecular classes fulfill many of these requirements including phenothiazinium dyes, cationic tetrapyrroles such as porphyrins, phthalocyanines and bacteriochlorins, cationic fullerenes and cationic derivatives of other known PS. Larger structures such as conjugates between PS and cationic polymers, cationic nanoparticles and cationic liposomes that contain PS are also effective. In order to demonstrate in vivo efficacy it is necessary to use animal models of localized infections in which both PS and light can be effectively delivered into the infected area. This review will cover a range of mouse models we have developed using bioluminescent pathogens and a sensitive low light imaging system to non-invasively monitor the progress of the infection in real time. Effective aPDT has been demonstrated in acute lethal infections and chronic biofilm infections; in infections caused by Gram-positive, Gram-negative bacteria and fungi; in infections in wounds, third degree burns, skin abrasions and soft-tissue abscesses. This range of animal models also represents a powerful aid in antimicrobial drug discovery. C1 [Sharma, Sulbha K.; Dai, Tianhong; Kharkwal, Gitika B.; Huang, Ying-Ying; Huang, Liyi; De Arce, Vida J. Bil; Tegos, George P.; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Dai, Tianhong; Kharkwal, Gitika B.; Huang, Ying-Ying; Huang, Liyi; Tegos, George P.; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Huang, Ying-Ying] Guangxi Med Univ, Aesthet & Plast Ctr, Nanning, Peoples R China. [Huang, Liyi] Guangxi Med Univ, Affiliated Coll & Hosp 1, Dept Infect Dis, Nanning, Peoples R China. [Tegos, George P.] Univ New Mexico, Sch Med, Dept Pathol, Albuquerque, NM 87131 USA. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM Hamblin@helix.mgh.harvard.edu OI Hamblin, Michael/0000-0001-6431-4605 FU NIH [R01A1050875, R01CA/AI838801, R01CA137108]; US Air Force MFEL Program [FA9550-04-1-0079]; Center for Integration of Medicine and Innovative Technology [DAMD17-02-2-0006]; CDMRP Program in TBI [W81XWH-09-1-0514] FX Research in the Hamblin laboratory is supported by NIH grants (R01A1050875 and R01CA/AI838801 to MRH; R01CA137108 to Long Y Chiang), US Air Force MFEL Program (FA9550-04-1-0079), Center for Integration of Medicine and Innovative Technology (DAMD17-02-2-0006), CDMRP Program in TBI (W81XWH-09-1-0514). NR 95 TC 42 Z9 44 U1 2 U2 47 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PD MAY PY 2011 VL 17 IS 13 BP 1303 EP 1319 PG 17 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 768QU UT WOS:000290952300010 PM 21504410 ER PT J AU Wain, RM Wilbourne, PL Harris, KW Pierson, H Teleki, J Burling, TA Lovett, S AF Wain, R. Morgan Wilbourne, Paula L. Harris, Keith W. Pierson, Heather Teleki, Jasmine Burling, Thomas A. Lovett, Steven TI Motivational interview improves treatment entry in homeless veterans SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Motivational interview; Homeless veterans; Treatment retention; Wait-list attrition ID SUBSTANCE-ABUSE TREATMENT; BRIEF INTERVENTIONS; RANDOMIZED-TRIAL; CLINICAL-TRIALS; USE DISORDERS; DRUG; EFFICACY; SERVICES; OUTCOMES; LENGTH AB Motivational Interviewing (MI) has successfully been used to facilitate entry and compliance in drug and alcohol treatment programs. Some questions have been raised as to the effectiveness of MI in severely distressed populations. This study aims to assess the effectiveness of MI in a population of homeless, unemployed, and substance dependent veterans who are being wait-listed for entry into a residential treatment program. Seventy-five veterans placed on a wait-list were randomized to receive a single MI or standard (Std) intake interview. Outcomes assessed were entry, and length of stay (LOS). Secondary outcomes assessed included program completion and rates of graduation. Readiness to change and self-efficacy were assessed before and after the interview. Significantly more participants entered the program in the MI group (95%) than in the Std group (71%). Although those in the MI group remained in the program longer, and had higher program completion and graduation rates, these differences were not statistically significant. No significant between-group or within-group differences were found in readiness or self-efficacy. This study demonstrates that a single, easily administered intervention can increase program entry. Also based on the study findings, further research into the question of whether MI can increase program retention, in a severely distressed population, is warranted. Published by Elsevier Ireland Ltd. C1 [Harris, Keith W.] VHA Off Mental Hlth Serv, Homeless & Residential Rehabil Treatment Program, Fremont, CA 94538 USA. [Wilbourne, Paula L.] VA Palo Alto Hlth Care Syst, Addict Treatment Serv, Menlo Pk, CA 94025 USA. [Pierson, Heather] VA Puget Sound Hlth Care Syst, Tacoma, WA 98493 USA. [Teleki, Jasmine] Behav Med Clin, Stanford, CA 94304 USA. [Lovett, Steven] VA Palo Alto Hlth Care Syst, Psychol Serv 116B, Palo Alto, CA 94304 USA. RP Harris, KW (reprint author), VHA Off Mental Hlth Serv, Homeless & Residential Rehabil Treatment Program, 39199 Liberty St, Fremont, CA 94538 USA. EM Keith.Harris@va.gov NR 39 TC 8 Z9 8 U1 3 U2 12 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD MAY 1 PY 2011 VL 115 IS 1-2 BP 113 EP 119 DI 10.1016/j.drugalcdep.2010.11.006 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 770IE UT WOS:000291079400018 PM 21145181 ER PT J AU Wang, JH Cao, ZX Zhao, LL Li, SQ AF Wang, Jihua Cao, Zanxia Zhao, Liling Li, Shuqiang TI Novel Strategies for Drug Discovery Based on Intrinsically Disordered Proteins (IDPs) SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES LA English DT Review DE intrinsically disordered proteins; sequence characterizations; structural characterizations; interaction networks; drug-discovery ID BOUND ALPHA-SYNUCLEIN; UNSTRUCTURED TRANSACTIVATION DOMAIN; NATIVELY UNFOLDED PROTEINS; EXTENDED-HELIX; FUNCTIONAL ANTHOLOGY; INTERACTION NETWORKS; ALPHA-SYN12 PEPTIDE; PARKINSONS-DISEASE; MOLECULAR-DYNAMICS; ALZHEIMERS-DISEASE AB Intrinsically disordered proteins (IDPs) are proteins that usually do not adopt well-defined native structures when isolated in solution under physiological conditions. Numerous IDPs have close relationships with human diseases such as tumor, Parkinson disease, Alzheimer disease, diabetes, and so on. These disease-associated IDPs commonly play principal roles in the disease-associated protein-protein interaction networks. Most of them in the disease datasets have more interactants and hence the size of the disease-associated IDPs interaction network is simultaneously increased. For example, the tumor suppressor protein p53 is an intrinsically disordered protein and also a hub protein in the p53 interaction network; a-synuclein, an intrinsically disordered protein involved in Parkinson diseases, is also a hub of the protein network. The disease-associated IDPs may provide potential targets for drugs modulating protein-protein interaction networks. Therefore, novel strategies for drug discovery based on IDPs are in the ascendant. It is dependent on the features of IDPs to develop the novel strategies. It is found out that IDPs have unique structural features such as high flexibility and random coil-like conformations which enable them to participate in both the. one to many. and. many to one. interaction. Accordingly, in order to promote novel strategies for drug discovery, it is essential that more and more features of IDPs are revealed by experimental and computing methods. C1 [Wang, Jihua; Cao, Zanxia; Zhao, Liling] Shandong Prov Key Lab Funct Macromol Biophys, Dezhou 253023, Peoples R China. [Wang, Jihua; Cao, Zanxia; Zhao, Liling] Dezhou Univ, Dept Phys, Dezhou 253023, Peoples R China. [Li, Shuqiang] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Wang, JH (reprint author), Shandong Prov Key Lab Funct Macromol Biophys, Dezhou 253023, Peoples R China. EM jhwyh@yahoo.com.cn; qiayilai@mail.ustc.edu.cn; zll2008@mail.ustc.edu.cn; shuqiang_li@dfci.harvard.edu FU Chinese Natural Science Foundation; Shandong Natural Science Foundation [30970561, 31000324, 2009ZRA14027, 2009ZRA14028] FX We thank the financial support from the Chinese Natural Science Foundation and Shandong Natural Science Foundation (grant number 30970561, 31000324, 2009ZRA14027 and 2009ZRA14028). NR 92 TC 14 Z9 15 U1 3 U2 35 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1422-0067 J9 INT J MOL SCI JI Int. J. Mol. Sci. PD MAY PY 2011 VL 12 IS 5 BP 3205 EP 3219 DI 10.3390/ijms12053205 PG 15 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary SC Biochemistry & Molecular Biology; Chemistry GA 768QP UT WOS:000290951800032 PM 21686180 ER PT J AU Jang, IK AF Jang, Ik-Kyung TI Optical Coherence Tomography or Intravascular Ultrasound? SO JACC-CARDIOVASCULAR INTERVENTIONS LA English DT Editorial Material DE intravascular ultrasound; optical coherence tomography (OCT); plaque burden; thin capped fibroatheroma (TCFA) ID ATHEROSCLEROTIC PLAQUE; REFLOW AB Intravascular ultrasound (IVUS) has been an important modality in understanding the in vivo pathophysiology of coronary artery disease and in predicting outcome of percutaneous coronary intervention (PCI). The IVUS features associated with acute coronary syndromes include positive remodeling, large plaque burden, ruptured plaque, and intracoronary thrombus. Plaque burden, lesion site calcium, and positive remodeling have been reported to be associated with no-reflow phenomenon and periprocedural myocardial necrosis after PCI (1,2). C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA. RP Jang, IK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, 55 Fruit St, Boston, MA 02114 USA. EM ijang@partners.org NR 8 TC 5 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 1936-8798 J9 JACC-CARDIOVASC INTE JI JACC-Cardiovasc. Interv. PD MAY PY 2011 VL 4 IS 5 BP 492 EP 494 DI 10.1016/j.jcin.2011.02.004 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 769KR UT WOS:000291012500003 PM 21596320 ER PT J AU Rumsfeld, JS Allen, LA AF Rumsfeld, John S. Allen, Larry A. TI Reducing Readmission Rates Does Coronary Artery Bypass Graft Surgery Provide Clarity? SO JACC-CARDIOVASCULAR INTERVENTIONS LA English DT Editorial Material DE coronary artery bypass graft surgery; outcomes; quality measures; readmission; rehospitalization ID HEART-FAILURE AB Because hospital readmissions are costly and potentially avoidable, reducing hospital readmission rates has been touted as a means to improve quality and reduce costs. Cardiovascular disease is a natural focus for this because of overall costs of treatment and frequency of readmission (e.g., nearly 1 in 4 Medicare patients is readmitted within 30 days after hospitalization for heart failure) (1). Since 2009, hospital-level 30-day risk-standardized readmission rates for acute myocardial infarction and heart failure have been publicly reported for Medicare patients (1). C1 [Rumsfeld, John S.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Rumsfeld, John S.; Allen, Larry A.] Colorado Cardiovasc Outcomes Res Consortium, Denver, CO USA. [Rumsfeld, John S.; Allen, Larry A.] Univ Colorado, Div Cardiol, Aurora, CO USA. RP Rumsfeld, JS (reprint author), VA Eastern Colorado Hlth Care Syst, Cardiol 111B,1055 Clermont St, Denver, CO 80220 USA. EM john.rumsfeld@va.gov NR 8 TC 4 Z9 4 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 MAY PY 2011 VL 4 IS 5 BP 577 EP 578 DI 10.1016/j.jcin.2011.04.002 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 769KR UT WOS:000291012500015 PM 21596332 ER PT J AU Goldfarb, JW Bittner, EA George, E Welch, C Schmidt, U AF Goldfarb, Jeremy W. Bittner, Edward A. George, Edward Welch, Charles Schmidt, Ulrich TI Successful management of a morbidly obese patient for electroconvulsive therapy with elective tracheostomy SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Editorial Material DE Elective tracheostomy; Electroconvulsive therapy; Morbid obesity ID PERCUTANEOUS TRACHEOSTOMY; SLEEP-APNEA; SUCCINYLCHOLINE; ANESTHESIA; POSITION AB Electroconvulsive therapy (ECT) is a treatment for affective catatonia and requires multiple general anesthetics. Morbid obesity is an increasingly prevalent condition that may complicate the standard anesthetic management of a patient undergoing ECT. We report the successful airway management of a morbidly obese ECT patient via elective tracheostomy. (C) 2011 Elsevier Inc. All rights reserved. C1 [Goldfarb, Jeremy W.; Bittner, Edward A.; George, Edward; Schmidt, Ulrich] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Anesthesia, Boston, MA 02114 USA. [Welch, Charles] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. RP Goldfarb, JW (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Anesthesia, Boston, MA 02114 USA. EM jwgoldfarb@partners.org NR 28 TC 2 Z9 2 U1 0 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 MAY PY 2011 VL 23 IS 3 BP 241 EP 243 DI 10.1016/j.jclinane.2010.05.009 PG 3 WC Anesthesiology SC Anesthesiology GA 770IN UT WOS:000291080300015 PM 21507618 ER PT J AU Balboni, MJ Babar, A Dillinger, J Phelps, AC George, E Block, SD Kachnic, L Hunt, J Peteet, J Prigerson, HG VanderWeele, TJ Balboni, TA AF Balboni, Michael J. Babar, Amenah Dillinger, Jennifer Phelps, Andrea C. George, Emily Block, Susan D. Kachnic, Lisa Hunt, Jessica Peteet, John Prigerson, Holly G. VanderWeele, Tyler J. Balboni, Tracy A. TI "It Depends": Viewpoints of Patients, Physicians, and Nurses on Patient-Practitioner Prayer in the Setting of Advanced Cancer SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Prayer; spirituality; religion; spiritual care; end-of-life care; palliative care ID QUALITY-OF-LIFE; SPIRITUAL CARE; RELIGIOUS CHARACTERISTICS; NEAR-DEATH; BELIEFS; ATTITUDES; ASSOCIATIONS; PREFERENCES; MEDICINE; WANT AB Context. Although prayer potentially serves as an important practice in offering religious/spiritual support, its role in the clinical setting remains disputed. Few data exist to guide the role of patient-practitioner prayer in the setting of advanced illness. Objectives. To inform the role of prayer in the setting of life-threatening illness, this study used mixed quantitative-qualitative methods to describe the viewpoints expressed by patients with advanced cancer, oncology nurses, and oncology physicians concerning the appropriateness of clinician prayer. Methods. This is a cross-sectional, multisite, mixed-methods study of advanced cancer patients (n = 70), oncology physicians (n = 206), and oncology nurses (n = 115). Semistructured interviews were used to assess respondents' attitudes toward the appropriate role of prayer in the context of advanced cancer. Theme extraction was performed based on interdisciplinary input using grounded theory. Results. Most advanced cancer patients (71%), nurses (83%), and physicians (65%) reported that patient-initiated patient-practitioner prayer was at least occasionally appropriate. Furthermore, clinician prayer was viewed as at least occasionally appropriate by the majority of patients (64%), nurses (76%), and physicians (59%). Of those patients who could envision themselves asking their physician or nurse for prayer (61%), 86% would find this form of prayer spiritually supportive. Most patients (80%) viewed practitioner-initiated prayer as spiritually supportive. Open-ended responses regarding the appropriateness of patient-practitioner prayer in the advanced cancer setting revealed six themes shaping respondents' viewpoints: necessary conditions for prayer, potential benefits of prayer, critical attitudes toward prayer, positive attitudes toward prayer, potential negative consequences of prayer, and prayer alternatives. Conclusion. Most patients and practitioners view patient-practitioner prayer as at least occasionally appropriate in the advanced cancer setting, and most patients view prayer as spiritually supportive. However, the appropriateness of patient-practitioner prayer is case specific, requiring consideration of multiple factors. J Pain Symptom Manage 2011; 41:836-847. (C) 2011 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved. C1 [Balboni, Michael J.; Phelps, Andrea C.; Block, Susan D.; Hunt, Jessica; Peteet, John; Prigerson, Holly G.; Balboni, Tracy A.] Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, Boston, MA 02120 USA. [Balboni, Michael J.; Phelps, Andrea C.; Block, Susan D.; Peteet, John; Prigerson, Holly G.; Balboni, Tracy A.] Dana Farber Canc Inst, Dept Psychooncol, Boston, MA 02120 USA. [Balboni, Michael J.; Phelps, Andrea C.; Block, Susan D.; Peteet, John; Prigerson, Holly G.; Balboni, Tracy A.] Dana Farber Canc Inst, Dept Palliat Care, Boston, MA 02120 USA. [Dillinger, Jennifer] Dana Farber Canc Inst, Dept Chaplaincy, Boston, MA 02120 USA. [Balboni, Tracy A.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02120 USA. [Balboni, Michael J.] Boston Univ, Sch Theol, Boston, MA 02215 USA. [Babar, Amenah] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [VanderWeele, Tyler J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [VanderWeele, Tyler J.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [George, Emily] Boston Med Ctr, Dept Med Oncol, Boston, MA USA. [Kachnic, Lisa] Boston Med Ctr, Dept Radiat Oncol, Boston, MA USA. [Block, Susan D.; Peteet, John; Prigerson, Holly G.; Balboni, Tracy A.] Harvard Univ, Sch Med, Ctr Palliat Care, Boston, MA USA. RP Balboni, MJ (reprint author), Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, 44 Binney St, Boston, MA 02120 USA. EM michael_balboni@dfci.harvard.edu FU American Society of Clinical Oncology FX This research was supported in part by an American Society of Clinical Oncology Young Investigator Award to Dr. Tracy Balboni. NR 35 TC 15 Z9 15 U1 1 U2 6 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 MAY PY 2011 VL 41 IS 5 BP 836 EP 847 DI 10.1016/j.jpainsymman.2010.07.008 PG 12 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 768NQ UT WOS:000290942200007 PM 21276700 ER PT J AU Goebel, JR Compton, P Zubkoff, L Lanto, A Asch, SM Sherbourne, CD Shugarman, L Lorenz, KA AF Goebel, Joy R. Compton, Peggy Zubkoff, Lisa Lanto, Andy Asch, Steven M. Sherbourne, Cathy D. Shugarman, Lisa Lorenz, Karl A. TI Prescription Sharing, Alcohol Use, and Street Drug Use to Manage Pain Among Veterans SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Prescription sharing; substance use disorders; substance misuse; street drugs; mental health; pain management; symptoms; quality of life; spiritual well-being ID SUBSTANCE USE DISORDERS; CHRONIC NONCANCER PAIN; PHYSICAL-DEPENDENCE; ANALGESIC THERAPY; NONMALIGNANT PAIN; OPIOID MISUSE; PRIMARY-CARE; ABUSE; PSEUDOADDICTION; PREVALENCE AB Context. Efforts to promote awareness and management of chronic pain have been accompanied by a troubling increase in prescription medication abuse. At the same time, some patients may misuse substances in an effort to manage chronic pain. Objectives. This study examines self-reported substance misuse for pain management among veterans and identifies the contributing factors. Methods. We analyzed cross-sectional data from the Help Veterans Experience Less Pain study. Results. Of 343 veterans, 35.3% reported an aberrant pain management behavior (24% reported using alcohol, 11.7% reported using street drugs, and 16.3% reported sharing prescriptions to manage pain). Poorer mental health, younger age, substance use disorders (SUDs), number of nonpain symptoms, and greater pain severity and interference were associated with aberrant pain management behaviors. In multivariate analysis, SUDs (odds ratio [OR]: 3.9, 95% confidence interval [CI]: 2.3-6.7, P < 0.000) and poorer mental health (OR: 2.3, 95% CI: 1.3-4.3, P = 0.006) were associated with using alcohol or street drugs to manage pain; SUDs (OR: 2.4, 95% CI: 1.3-4.4, P - 0.006) and pain interference (OR: 1.1, 95% CI: 1.0-1.2, P = 0.047) were associated with prescription sharing; and SUDs (OR: 3.6, 95% CI: 2.2-6.1, P < 0.000) and number of nonpain symptoms (OR: 6.5, 95% CI: 1.2-35.4, P = 0.031) were associated with any aberrant pain management behavior. Conclusion. Veterans with a history of SUDs, greater pain interference, more nonpain symptoms, and mental health concerns should be carefully managed to deter substance misuse for pain management. J Pain Symptom Manage 2011; 41:848-858. (C) 2011 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved. C1 [Goebel, Joy R.] Calif State Univ Long Beach, Sch Nursing, Long Beach, CA 90840 USA. [Compton, Peggy] Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90024 USA. [Asch, Steven M.; Lorenz, Karl A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Zubkoff, Lisa] Vet Affairs Med Ctr, New England HealthCare Engn Partnership, White River Jct, VT USA. [Lanto, Andy; Asch, Steven M.; Lorenz, Karl A.] Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Asch, Steven M.; Sherbourne, Cathy D.; Shugarman, Lisa; Lorenz, Karl A.] RAND Corp, Santa Monica, CA USA. RP Goebel, JR (reprint author), Calif State Univ Long Beach, Sch Nursing, 1250 Bellflower Blvd, Long Beach, CA 90840 USA. EM jgoebel@csulb.edu FU Department of Veterans Affairs Health Services Research Development [IIR 03-152] FX This study was funded by the Department of Veterans Affairs Health Services Research & Development Merit Award IIR 03-152. K. L. is the recipient of a VA HSR&D Advanced Career Development Award. The authors declare no conflicts of interest. NR 69 TC 16 Z9 16 U1 1 U2 4 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 MAY PY 2011 VL 41 IS 5 BP 848 EP 858 DI 10.1016/j.jpainsymman.2010.07.009 PG 11 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 768NQ UT WOS:000290942200008 PM 21256706 ER PT J AU Conley, DM Singer, SJ Edmondson, L Berry, WR Gawande, AA AF Conley, Dante M. Singer, Sara J. Edmondson, Lizabeth Berry, William R. Gawande, Atul A. TI Effective Surgical Safety Checklist Implementation SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID TECHNOLOGY; MORTALITY AB BACKGROUND: Research suggests that surgical safety checklists can reduce mortality and other postoperative complications. The real world impact of surgical safety checklists on patient outcomes, however, depends on the effectiveness of hospitals' implementation processes. STUDY DESIGN: We studied implementation processes in 5 Washington State hospitals by conducting semistructured interviews with implementation leaders and surgeons from September to December 2009. Interviews were transcribed, analyzed, and compared with findings from previous implementation research to identify factors that distinguish effective implementation. RESULTS: Qualitative analysis suggested that effectiveness hinges on the ability of implementation leaders to persuasively explain why and adaptively show how to use the checklist. Coordinated efforts to explain why the checklist is being implemented and extensive education regarding its use resulted in buy-in among surgical staff and thorough checklist use. When implementation leaders did not explain why or show how the checklist should be used, staff neither understood the rationale behind implementation nor were they adequately prepared to use the checklist, leading to frustration, disinterest, and eventual abandonment despite a hospital-wide mandate. CONCLUSIONS: The impact of surgical safety checklists on patient outcomes is likely to vary with the effectiveness of each hospital's implementation process. Further research is needed to confirm these findings and reveal additional factors supportive of checklist implementation. (J Am Coll Surg 2011;212:873-879. (C) 2011 by the American College of Surgeons) C1 [Conley, Dante M.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Conley, Dante M.] Univ Washington, Seattle, WA 98195 USA. [Singer, Sara J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Edmondson, Lizabeth; Gawande, Atul A.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Conley, DM (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, 677 Huntington Ave,Kresge Bldg,Room 112, Boston, MA 02115 USA. EM cdante@uw.edu OI Gawande, Atul/0000-0002-1824-9176 NR 12 TC 98 Z9 101 U1 2 U2 19 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 MAY PY 2011 VL 212 IS 5 BP 873 EP 879 DI 10.1016/j.jamcollsurg.2011.01.052 PG 7 WC Surgery SC Surgery GA 768RU UT WOS:000290956000017 PM 21398154 ER PT J AU Raval, MV Wang, X Cohen, ME Ingraham, AM Bentrem, DJ Dimick, JB Flynn, T Hall, BL Ko, CY AF Raval, Mehul V. Wang, Xue Cohen, Mark E. Ingraham, Angela M. Bentrem, David J. Dimick, Justin B. Flynn, Timothy Hall, Bruce L. Ko, Clifford Y. TI The Influence of Resident Involvement on Surgical Outcomes SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID QUALITY IMPROVEMENT PROGRAM; RISK ADJUSTMENT; PATIENT SAFETY; NONTEACHING HOSPITALS; TEACHING HOSPITALS; INPATIENT SURGERY; MEDICARE PATIENTS; AMERICAN-COLLEGE; GENERAL-SURGERY; MORTALITY AB BACKGROUND: Although the training of surgical residents is often considered in national policy addressing complications and safety, the influence of resident intraoperative involvement on surgical outcomes has not been well studied. STUDY DESIGN: We identified 607,683 surgical cases from 234 hospitals from the 2006 to 2009 American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP). Outcomes were compared by resident involvement for all general and vascular cases as well as for specific general surgical procedures. RESULTS: After typical ACS NSQIP comorbidity risk adjustment and further adjustment for hospital teaching status and operative time in modeling, resident intraoperative involvement was associated with slightly increased morbidity when assessing overall general or vascular procedures (odds ratio [OR] 1.06; 95% CI 1.04 to 1.09), pancreatectomy or esophagectomy (OR 1.26; 95% CI 1.08 to 1.45), and colorectal resections (OR 1.15; 95% CI 1.09 to 1.22). In contrast, for mortality, resident intraoperative involvement was associated with reductions for overall general and vascular procedures (OR 0.91; 95% CI 0.84 to 0.99), colorectal resections (OR 0.88; 95% CI 0.78 to 0.99), and abdominal aortic aneurysm repair (OR 0.71; 95% CI 0.53 to 0.95). Results were moderated somewhat after hierarchical modeling was performed to account for hospital-level variation, with mortality results no longer reaching significance (overall morbidity OR 1.07; 95% CI 1.03 to 1.10, overall mortality OR 0.97; 95% CI 0.90 to 1.05). Based on risk-adjusted event rates, resident intraoperative involvement is associated with approximately 6.1 additional morbidity events but 1.4 fewer deaths per 1,000 general and vascular surgery procedures. CONCLUSIONS: Resident intraoperative participation is associated with slightly higher morbidity rates but slightly decreased mortality rates across a variety of procedures and is minimized further after taking into account hospital-level variation. These clinically small effects may serve to reassure patients and others that resident involvement in surgical care is safe and possibly protective with regard to mortality. (J Am Coll Surg 2011;212:889-898. (C) 2011 by the American College of Surgeons) C1 [Raval, Mehul V.; Wang, Xue; Cohen, Mark E.; Ingraham, Angela M.; Ko, Clifford Y.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL 60611 USA. [Raval, Mehul V.; Bentrem, David J.] Northwestern Univ, Dept Surg, Feinberg Sch Med, Chicago, IL 60611 USA. [Bentrem, David J.] Jesse Brown VA Med Ctr, Chicago, IL USA. [Ingraham, Angela M.] Univ Cincinnati, Coll Med, Dept Surg, Cincinnati, OH 45267 USA. [Dimick, Justin B.] Univ Michigan, Sch Med, Ann Arbor, MI USA. [Flynn, Timothy] Univ Florida, Gainesville, FL USA. Washington Univ, Dept Surg, John Cochran Vet Affairs Med Ctr, St Louis, MO USA. Barnes Jewish Hosp, Dept Surg, St Louis, MO USA. [Hall, Bruce L.] Washington Univ, Ctr Hlth Policy, St Louis, MO 63130 USA. [Hall, Bruce L.] Washington Univ, Olin Business Sch, St Louis, MO 63130 USA. [Ko, Clifford Y.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Raval, MV (reprint author), Amer Coll Surg, Div Res & Optimal Patient Care, 633 N St Clair St,22nd Floor, Chicago, IL 60611 USA. EM m-raval@md.northwestern.edu OI Raval, Mehul/0000-0002-1527-2661 FU John Gray Research Fellowship; Daniel F and Ada L Rice Foundation; Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service FX Drs Raval and Ingraham participate in the American College of Surgeons Clinical Scholars in Residence Program. Dr Raval is supported by the John Gray Research Fellowship and the Daniel F and Ada L Rice Foundation. Dr Bentrem is supported by a career development award from the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service. Dr Hall assists with the conduct of the ACS NSQIP nationally. NR 46 TC 101 Z9 101 U1 0 U2 7 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 MAY PY 2011 VL 212 IS 5 BP 889 EP 898 DI 10.1016/j.jamcollsurg.2010.12.029 PG 10 WC Surgery SC Surgery GA 768RU UT WOS:000290956000019 PM 21398151 ER PT J AU Filley, CM Brodtmann, A AF Filley, Christopher M. Brodtmann, Amy TI Lacunes and cognitive decline Little things matter SO NEUROLOGY LA English DT Editorial Material ID SMALL VESSEL DISEASE; DEMENTIA; ATROPHY; MRI C1 [Filley, Christopher M.] Univ Colorado, Dept Neurol, Sch Med, Aurora, CO USA. [Filley, Christopher M.] Univ Colorado, Sch Med, Dept Psychiat, Aurora, CO USA. [Filley, Christopher M.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Brodtmann, Amy] Univ Melbourne, Florey Neurosci Inst, Melbourne, Vic, Australia. RP Filley, CM (reprint author), Behav Neurol Sect, 12631 E 17th Ave,POB 6511, Aurora, CO 80045 USA. EM filley@ucdenver.edu NR 15 TC 7 Z9 7 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY PY 2011 VL 76 IS 22 BP 1856 EP 1857 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 769WN UT WOS:000291049100005 PM 21543732 ER PT J AU Walcott, BP Kahle, KT Wain, JC Borges, LF AF Walcott, Brian P. Kahle, Kristopher T. Wain, John C. Borges, Lawrence F. TI Giant thoracic meningocele associated with neurofibromatosis 1 SO NEUROLOGY LA English DT Editorial Material RP Borges, LF (reprint author), Massachusetts Gen Hosp, Neurosurg Stereoscop Dimens Video Lab 3, Neurosurg Spine Serv, White 1205,55 Fruit St, Boston, MA 02114 USA. EM LBorges@partners.org NR 2 TC 0 Z9 0 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 MAY PY 2011 VL 76 IS 22 BP 1943 EP 1943 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 769WN UT WOS:000291049100019 PM 21624995 ER PT J AU Groessl, EJ Weingart, KR Gifford, AL Asch, SM Ho, SB AF Groessl, Erik J. Weingart, Kimberly R. Gifford, Allen L. Asch, Steven M. Ho, Samuel B. TI Development of the Hepatitis C Self-Management Program SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE Patient self-management; Cognitive/behavioral interventions; Hepatitis C ID QUALITY-OF-LIFE; PRIMARY-CARE PATIENTS; VIRUS-INFECTION; ANTIVIRAL THERAPY; WEIGHT-REDUCTION; CHRONIC DISEASE; PLUS RIBAVIRIN; UNITED-STATES; HEALTH-CARE; VETERANS AB Objective: Chronic hepatitis C infection (HCV) is a major health problem that disproportionately affects people with limited resources. Many people with HCV are ineligible or refuse antiviral treatment, but less curative treatment options exist. These options include adhering to follow-up health visits, lifestyle changes, and avoiding hepatotoxins like alcohol. Herein, we describe a recently developed self-management program designed to assist HCV-infected patients with adherence and improve their health-related quality of life (HRQOL). Methods: The development of the Hepatitis C Self-Management Program (HCV-SMP) was informed by scientific literature, qualitative interviews with HCV-infected patients, self-management training, and feedback from HCV clinical experts. Results: The Hepatitis C Self-Management Program (HCV-SMP) is a multi-faceted program that employs cognitive-behavioral principles and is designed to provide HCV-infected people with knowledge and skills for improving their HRQOL. The program consists of six 2-h workshop sessions which are held weekly. The sessions consist of a variety of group activities, including disease-specific information dissemination, action planning, and problem-solving. Conclusion: The intervention teaches skills for adhering to challenging treatment recommendations using a validated theoretical model. A randomized trial will test the efficacy of this novel HCV self-management program for improving HRQOL in a difficult to reach population. Published by Elsevier Ireland Ltd. C1 [Groessl, Erik J.; Weingart, Kimberly R.; Ho, Samuel B.] VA San Diego Healthcare Syst, San Diego, CA 92161 USA. [Groessl, Erik J.; Ho, Samuel B.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Gifford, Allen L.] Edith Nourse Rogers Mem Vet Hosp, Bedford, MA USA. [Gifford, Allen L.] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Asch, Steven M.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Asch, Steven M.] Univ Calif Los Angeles, Geffen Sch Med, Los Angeles, CA 90024 USA. RP Groessl, EJ (reprint author), VA San Diego Healthcare Syst, 3350 La Jolla Village Dr 111 N-1, San Diego, CA 92161 USA. EM egroessl@ucsd.edu FU VA HSRD [IAC 05-067] FX This study is funded by a research grant from the VA HSR&D, Project # IAC 05-067. NR 41 TC 5 Z9 5 U1 1 U2 6 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD MAY PY 2011 VL 83 IS 2 BP 252 EP 255 DI 10.1016/j.pec.2010.06.006 PG 4 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 768JC UT WOS:000290929200020 PM 20638216 ER PT J AU McTigue, KM Bhargava, T Bryce, CL Conroy, M Fischer, GS Hess, R Simkin-Silverman, LR Zickmund, S AF McTigue, Kathleen M. Bhargava, Tina Bryce, Cindy L. Conroy, Molly Fischer, Gary S. Hess, Rachel Simkin-Silverman, Laurey R. Zickmund, Susan TI Patient perspectives on the integration of an intensive online behavioral weight loss intervention into primary care SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE Primary health care; Internet; Obesity; Counseling; Preventive medicine ID LIFE-STYLE INTERVENTION; OBESITY; PHYSICIANS; HEALTH; MANAGEMENT; ADULTS; PREVENTION; ATTITUDES; INTERNET; ADVICE AB Objective: To examine patients' perception of how a referral-based online lifestyle intervention contributed to primary care medicine. Methods: We invited 50 adults to complete a semi-structured interview after a 1-year online behavioral weight loss intervention (average weight change: -4.79 kg). We developed an iterative codebook using content analysis. Two coders independently coded all transcripts (kappa = 0.895). We analyzed responses regarding the integration of the program with primary care. Results: Among the 35 participants who completed the interview, 46% described a positive experience between the program and their routine medical care; 14% noted it was fine/OK; 9% reported no effect, 3% were negative, 11% said that the program was unrelated to their medical care, and 14% that the only connection was the referral. Factors such as physician feedback and support, coordination with routine health care, and improved cardiovascular risk factors were cited in support of a positive experience. Physician feedback was reported by 89%, and 80% stated that the program helped them to follow their physician's advice. Conclusion: Physician referral to online education and counseling may facilitate the integration of evidence-based behavioral counseling with primary care. Practice implications: Internet technology may enable improved access to evidence-based counseling for chronic health problems. (C) 2010 Elsevier Ireland Ltd. All rights reserved. C1 [McTigue, Kathleen M.; Bhargava, Tina; Bryce, Cindy L.; Conroy, Molly; Fischer, Gary S.; Hess, Rachel; Zickmund, Susan] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15213 USA. [McTigue, Kathleen M.; Conroy, Molly; Hess, Rachel; Simkin-Silverman, Laurey R.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15213 USA. [Bhargava, Tina] Univ Pittsburgh, Dept Behav & Community Hlth Sci, Pittsburgh, PA 15213 USA. [Zickmund, Susan] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP McTigue, KM (reprint author), Univ Pittsburgh, Dept Med, 230 McKee Pl,Suite 600, Pittsburgh, PA 15213 USA. EM kmm34@pitt.edu; tdb11@pitt.edu; brycecl@upmc.edu; conroymb@upmc.edu; fischerg@upmc.edu; rah67@pitt.edu; lrs@pitt.edu; Susan.Zickmund@va.gov OI Bryce, Cindy/0000-0001-6356-6675; Simkin-Silverman, Lauren/0000-0003-1572-8726 FU Department of Defense through University of Pittsburgh Diabetes Institute [USAMRAA W81XWH-04-2-0030] FX This project was supported with a grant from the Department of Defense [USAMRAA W81XWH-04-2-0030 Siminerio (PI)]. through the University of Pittsburgh Diabetes Institute. While the University of Pittsburgh has licensed the online program's contents to DPS Health, the authors have assigned the copyright to the University and receive no personal royalties from its commercial use. Support for Dr. Zickmund was provided in part by the Veteran's Administration Health Services Research and Development Merit Review funds. NR 33 TC 7 Z9 7 U1 1 U2 9 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD MAY PY 2011 VL 83 IS 2 BP 261 EP 264 DI 10.1016/j.pec.2010.05.009 PG 4 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 768JC UT WOS:000290929200022 PM 21459256 ER PT J AU Chen, YX Gelfond, J McManus, LM Shireman, PK AF Chen, Yongxin Gelfond, Jonathan McManus, Linda M. Shireman, Paula K. TI Temporal microRNA expression during in vitro myogenic progenitor cell proliferation and differentiation: regulation of proliferation by miR-682 SO PHYSIOLOGICAL GENOMICS LA English DT Article DE muscle regeneration; muscle differentiation; muscle regeneration; satellite cell ID MUSCLE SATELLITE CELLS; SKELETAL-MUSCLE; GENE-EXPRESSION; MICROARRAY DATA; STEM-CELLS; REGENERATION; GROWTH; REPRESSION; APOPTOSIS; MIR-206 AB Chen Y, Gelfond J, McManus LM, Shireman PK. Temporal microRNA expression during in vitro myogenic progenitor cell proliferation and differentiation: regulation of proliferation by miR-682. Physiol Genomics 43: 621-630, 2011. First published September 14, 2010; doi:10.1152/physiolgenomics.00136.2010.MicroRNAs (miRNAs) regulate gene expression by repressing target genes at the posttranscriptional level. Since miRNAs have unique expression profiles in different tissues, they provide pivotal regulation of many biological processes. The present study defined miRNA expression during murine myogenic progenitor cell (MPC) proliferation and differentiation to identify miRNAs involved in muscle regeneration. Muscle-related gene expression analyses revealed that the time course and expression of myosin heavy chain (MHC) and transcription factors (Myf5, MyoD, myogenin, and Pax7) were similar during in vitro MPC proliferation/differentiation and in vivo muscle regeneration. Comprehensive profiling revealed that 139 or 16 miRNAs were significantly changed more than twofold [false discovery rate (FDR) < 0.05] during MPC differentiation or proliferation, respectively; cluster analyses revealed five distinct patterns of miRNA expression during the time course of MPC differentiation. Not unexpectedly, the largest miRNA changes occurred in muscle-specific miRNAs (miR-1, -133a, and -499), which were upregulated > 10-fold during MPC differentiation (FDR < 0.01). However, several previously unreported miRNAs were differentially expressed, including miR-10b, -335-3p, and -682. Interestingly, the temporal patterns of miR-1, -499, and -682 expression during in vitro MPC proliferation/differentiation were remarkably similar to those observed during in vivo muscle regeneration. Moreover, in vitro inhibition of miR-682, the only miRNA upregulated in proliferating compared with quiescent MPC, led to decreased MPC proliferation, further validating our in vitro assay system for the identification of miRNAs involved in muscle regeneration. Thus the differentially expressed miRNAs identified in the present study could represent new regulatory elements in MPC proliferation and differentiation. C1 [Chen, Yongxin; Shireman, Paula K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Surg, San Antonio, TX 78229 USA. [Gelfond, Jonathan] 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. [Shireman, Paula K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [McManus, Linda M.; Shireman, Paula K.] Univ Texas Hlth Sci Ctr San Antonio, Sam & Ann Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Chen, Yongxin; Shireman, Paula K.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Chen, YX (reprint author), 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM cheny4@uthscsa.edu FU Department of Veterans Affairs; National Institutes of Health [R01-HL-074236, T32-HL-07446, KL2-RR-025766] FX These studies were supported, in part, by a Department of Veterans Affairs Merit Review grant and National Institutes of Health Grants R01-HL-074236, T32-HL-07446, and KL2-RR-025766. NR 63 TC 29 Z9 30 U1 1 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 EI 1531-2267 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD MAY PY 2011 VL 43 IS 10 BP 621 EP 630 DI 10.1152/physiolgenomics.00136.2010 PG 10 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 769LK UT WOS:000291014800013 PM 20841498 ER PT J AU Sohn, Y Choi, MK Ahn, YY Lee, J Jeong, J AF Sohn, Yunkyu Choi, Myung-Kyu Ahn, Yong-Yeol Lee, Junho Jeong, Jaeseung TI Topological Cluster Analysis Reveals the Systemic Organization of the Caenorhabditis elegans Connectome SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID GRAPH-THEORETICAL ANALYSIS; COMPLEX BRAIN NETWORKS; SMALL-WORLD NETWORKS; C-ELEGANS; ARCHITECTURE; CIRCUIT; PROTEIN AB The modular organization of networks of individual neurons interwoven through synapses has not been fully explored due to the incredible complexity of the connectivity architecture. Here we use the modularity-based community detection method for directed, weighted networks to examine hierarchically organized modules in the complete wiring diagram (connectome) of Caenorhabditis elegans (C. elegans) and to investigate their topological properties. Incorporating bilateral symmetry of the network as an important cue for proper cluster assignment, we identified anatomical clusters in the C. elegans connectome, including a body-spanning cluster, which correspond to experimentally identified functional circuits. Moreover, the hierarchical organization of the five clusters explains the systemic cooperation (e. g., mechanosensation, chemosensation, and navigation) that occurs among the structurally segregated biological circuits to produce higher-order complex behaviors. C1 [Sohn, Yunkyu; Jeong, Jaeseung] Korea Adv Inst Sci & Technol, Dept Bio & Brain Engn, Taejon 305701, South Korea. [Sohn, Yunkyu] Univ Calif San Diego, Dept Polit Sci, San Diego, CA 92103 USA. [Choi, Myung-Kyu; Lee, Junho] Seoul Natl Univ, Inst Mol Biol & Genet, Sch Biol Sci, Res Ctr Cellul,Dept Biophys & Chem Biol, Seoul, South Korea. [Ahn, Yong-Yeol] Northeastern Univ, Dept Phys, Ctr Complex Network Res, Boston, MA 02115 USA. [Ahn, Yong-Yeol] Harvard Univ, Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. RP Sohn, Y (reprint author), Korea Adv Inst Sci & Technol, Dept Bio & Brain Engn, Taejon 305701, South Korea. EM jsjeong@kaist.ac.kr RI Jeong, Jaeseung /C-1620-2011; OI Ahn, Yong-Yeol/0000-0002-4352-4301 FU CHUNG MoonSoul Research Center for BioInformation and BioElectronics (CMSC) in KAIST; Korea government (MOST) [R01-2007-000-21094-0, M10644000028-06N4400-02810]; Ministry of Science and Technology, the Republic of Korea [M103KV010018-08K2201-01810] FX This work was supported by CHUNG MoonSoul Research Center for BioInformation and BioElectronics (CMSC) in KAIST, the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MOST) (No. R01-2007-000-21094-0 and No. M10644000028-06N4400-02810) (J. Jeong). This work was also supported in part by a grant (M103KV010018-08K2201-01810) from the Brain Research Center of the 21st Century Frontier Research Program funded by the Ministry of Science and Technology, the Republic of Korea (J. Lee). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 46 TC 22 Z9 22 U1 0 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-734X EI 1553-7358 J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD MAY PY 2011 VL 7 IS 5 AR e1001139 DI 10.1371/journal.pcbi.1001139 PG 10 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 769LT UT WOS:000291015800013 PM 21625578 ER PT J AU Ranasinghe, SRF Kramer, HB Wright, C Kessler, BM di Gleria, K Zhang, YH Gillespie, GM Blais, ME Culshaw, A Pichulik, T Simmons, A Rowland-Jones, SL McMichael, AJ Dong, T AF Ranasinghe, Srinika R. F. Kramer, Holger B. Wright, Cynthia Kessler, Benedikt M. di Gleria, Katalin Zhang, Yonghong Gillespie, Geraldine M. Blais, Marie-Eve Culshaw, Abigail Pichulik, Tica Simmons, Alison Rowland-Jones, Sarah L. McMichael, Andrew J. Dong, Tao TI The Antiviral Efficacy of HIV-Specific CD8(+) T-Cells to a Conserved Epitope Is Heavily Dependent on the Infecting HIV-1 Isolate SO PLOS PATHOGENS LA English DT Article ID MHC-CLASS-I; IMMUNODEFICIENCY-VIRUS TYPE-1; CELLULAR IMMUNE-RESPONSES; ANTIGEN PRESENTATION; LYMPHOCYTE ESCAPE; VIRAL LOAD; VACCINE; PROTEASOME; NEF; HLA AB A major challenge to developing a successful HIV vaccine is the vast diversity of viral sequences, yet it is generally assumed that an epitope conserved between different strains will be recognised by responding T-cells. We examined whether an invariant HLA-B8 restricted Nef(90-97) epitope FL8 shared between five high titre viruses and eight recombinant vaccinia viruses expressing Nef from different viral isolates (clades A-H) could activate antiviral activity in FL8-specific cytotoxic T-lymphocytes (CTL). Surprisingly, despite epitope conservation, we found that CTL antiviral efficacy is dependent on the infecting viral isolate. Only 23% of Nef proteins, expressed by HIV-1 isolates or as recombinant vaccinia-Nef, were optimally recognised by CTL. Recognition of the HIV-1 isolates by CTL was independent of clade-grouping but correlated with virus-specific polymorphisms in the epitope flanking region, which altered immunoproteasomal cleavage resulting in enhanced or impaired epitope generation. The finding that the majority of virus isolates failed to present this conserved epitope highlights the importance of viral variance in CTL epitope flanking regions on the efficiency of antigen processing, which has been considerably underestimated previously. This has important implications for future vaccine design strategies since efficient presentation of conserved viral epitopes is necessary to promote enhanced anti-viral immune responses. C1 [Ranasinghe, Srinika R. F.; di Gleria, Katalin; Zhang, Yonghong; Gillespie, Geraldine M.; Blais, Marie-Eve; Culshaw, Abigail; Pichulik, Tica; Simmons, Alison; Rowland-Jones, Sarah L.; McMichael, Andrew J.; Dong, Tao] Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, MRC,Human Immunol Unit, Oxford OX3 9DU, England. [Kramer, Holger B.; Wright, Cynthia; Kessler, Benedikt M.] Univ Oxford, Nuffield Dept Clin Med, Oxford OX3 9DU, England. [Zhang, Yonghong] BeiJing Capital Univ, BeiJing YouAn Hosp, Beijing, Peoples R China. RP Ranasinghe, SRF (reprint author), Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, Boston, MA 02114 USA. EM srinika.ranasinghe@bnc.oxon-org; tao.dong@imm.ox.ac.uk OI Kessler, Benedikt/0000-0002-8160-2446 FU MRC FX SRFR was supported by an MRC-funded PhD studentship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 62 TC 12 Z9 12 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD MAY PY 2011 VL 7 IS 5 AR e1001341 DI 10.1371/journal.ppat.1001341 PG 16 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 769LC UT WOS:000291014000006 PM 21589893 ER PT J AU Scioli, A Ricci, M Nyugen, T Scioli, ER AF Scioli, Anthony Ricci, Michael Than Nyugen Scioli, Erica R. TI Hope: Its Nature and Measurement SO PSYCHOLOGY OF RELIGION AND SPIRITUALITY LA English DT Article DE hope; depression; anxiety; health; measurement ID PSYCHOLOGY; VALIDATION AB Hope is a powerful emotion that has been largely neglected by the social sciences. In this paper, we introduce a theory of hope drawn from multiple disciplines, including psychology, philosophy, theology, and medicine. Our integrative approach features four components: the attachment, mastery, and survival motives, as well as spiritual beliefs. In addition, we describe four different empirical analyses aimed at the development and refinement of a comprehensive set of scales for measuring state and trait hope. C1 [Scioli, Anthony; Ricci, Michael; Than Nyugen] Keene State Coll, Dept Psychol, Keene, NH 03435 USA. [Scioli, Erica R.] VA Boston Healthcare Syst, Boston, MA USA. RP Scioli, A (reprint author), Keene State Coll, Dept Psychol, Keene, NH 03435 USA. EM tscioli@keene.edu NR 69 TC 20 Z9 21 U1 3 U2 19 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1941-1022 J9 PSYCHOL RELIG SPIRIT JI Psychol. Relig. Spiritual. PD MAY PY 2011 VL 3 IS 2 BP 78 EP 97 DI 10.1037/a0020903 PG 20 WC Psychology, Multidisciplinary; Religion SC Psychology; Religion GA 768YP UT WOS:000290976200002 ER PT J AU Da Silva, N Cortez-Retamozo, V Reinecker, HC Wildgruber, M Hill, E Brown, D Swirski, FK Pittet, MJ Breton, S AF Da Silva, Nicolas Cortez-Retamozo, Virna Reinecker, Hans-Christian Wildgruber, Moritz Hill, Eric Brown, Dennis Swirski, Filip K. Pittet, Mikael J. Breton, Sylvie TI A dense network of dendritic cells populates the murine epididymis SO REPRODUCTION LA English DT Article ID IMMUNO-COMPETENT CELLS; REGULATORY T-CELLS; RAT EPIDIDYMIS; LUMINAL ACIDIFICATION; PERIPHERAL TOLERANCE; DEPENDENT MECHANISM; REPRODUCTIVE-TRACT; HIV-1 TRANSMISSION; MOUSE EPIDIDYMIS; LANGERHANS CELLS AB One of the most intriguing aspects of male reproductive physiology is the ability to generate spermatogenic cells - which are 'foreign' to the host - without triggering immune activation. After leaving the testis, spermatozoa enter the epididymis where they mature and are stored. In this study, we report a previously unrecognized dense network of dendritic cells (DCs) located at the base of the epididymal epithelium. This network was detected in transgenic mice expressing CD11c-EYFP and CX3CR1-GFP reporters. Epididymal DCs (eDCs) establish intimate interactions with the epithelium and project long dendrites between epithelial cells toward the lumen. We show that isolated eDCs express numerous leukocyte markers described previously in other organs that are in contact with the external environment, and present and cross-present ovalbumin to T cells in vitro. eDCs are, therefore, strategically positioned to regulate the complex interplay between immune tolerance and activation, a balance that is fundamental to male fertility. Reproduction (2011) 141 653-663 C1 [Da Silva, Nicolas; Hill, Eric; Brown, Dennis; Breton, Sylvie] Massachusetts Gen Hosp, Ctr Syst Biol, Program Membrane Biol, Boston, MA 02114 USA. [Da Silva, Nicolas] Massachusetts Gen Hosp, Ctr Syst Biol, Div Nephrol, Boston, MA 02114 USA. [Reinecker, Hans-Christian] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Reinecker, Hans-Christian] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Da Silva, N (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Program Membrane Biol, Boston, MA 02114 USA. EM dasilva.nicolas@mgh.harvard.edu FU National Institutes of Health [DK085715, DK38452]; MGH Center for the Study of Inflammatory Bowel Disease (CSIBD) [DK43351, CA086355, AI084880, R01HL095612]; Boston Area Diabetes and Endocrinology Research Center [DK57521] FX This study was supported by National Institutes of Health grants DK085715 and DK38452 (S Breton), MGH Center for the Study of Inflammatory Bowel Disease (CSIBD) pilot feasibility grant (DK43351, N Da Silva), CA086355 and AI084880 (M J Pittet), R01HL095612 (F K Swirski). The Microscopy Core facility of the MGH Program in Membrane Biology receives support from the Boston Area Diabetes and Endocrinology Research Center (DK57521) and the CSIBD (DK43351). NR 76 TC 37 Z9 37 U1 1 U2 3 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1470-1626 J9 REPRODUCTION JI Reproduction PD MAY PY 2011 VL 141 IS 5 BP 653 EP 663 DI 10.1530/REP-10-0493 PG 11 WC Developmental Biology; Reproductive Biology SC Developmental Biology; Reproductive Biology GA 768DC UT WOS:000290910700011 PM 21310816 ER PT J AU Spencer, J Amin, J Wang, MH Packham, G Alwi, SSS Tizzard, GJ Coles, SJ Paranal, RM Bradner, JE Heightman, TD AF Spencer, John Amin, Jahangir Wang, Minghua Packham, Graham Alwi, Sharifah S. Syed Tizzard, Graham J. Coles, Simon J. Paranal, Ronald M. Bradner, James E. Heightman, Tom D. TI Synthesis and Biological Evaluation of JAHAs: Ferrocene-Based Histone Deacetylase Inhibitors SO ACS MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Ferrocene; HDAC inhibitor; bioinorganic; anticancer; hydroxamic acid ID HDAC INHIBITORS; CANCER-THERAPY; IN-VITRO; VORINOSTAT; COMPLEXES; ANALOGS; ACID AB N-1-Hydroxy-N-8-ferrocenyloctanediamide, JAHA (7), an organometallic analogue of SAHA containing a ferrocenyl group as a phenyl bioisostere, displays nanomolar inhibition of class I HDACs, excellent selectivity over class ha HDACs, and anticancer action in intact cells (IC50 = 2.4 mu M, MCF7 cell line). Molecular docking studies of 7 in HDAC8 (a,b) suggested that the ferrocenyl moiety in 7 can overlap with the aryl cap of SAHA and should display similar HDAC inhibition, which was borne out in an in vitro assay (IC50 values against HDAC8 (mu M, SD in parentheses): SAHA, 1.41 (0.15); 7, 1.36 (0.16). Thereafter, a small library of related JAHA analogues has been synthesized, and preliminary SAR studies are presented. IC50 values as low as 90 pM toward HDAC6 (class IIb) have been determined, highlighting the excellent potential of JAHAs as bioinorganic probes. C1 [Spencer, John; Amin, Jahangir] Univ Greenwich, Sch Sci Medway, Chatham ME4 4TB, Kent, England. [Packham, Graham; Alwi, Sharifah S. Syed] Univ Southampton, Canc Res UK Ctr, Fac Med, Southampton Gen Hosp, Southampton SO16 6YD, Hants, England. [Tizzard, Graham J.; Coles, Simon J.] Univ Southampton, UK Natl Crystallog Serv, Sch Chem, Southampton SO17 1BJ, Hants, England. [Paranal, Ronald M.; Bradner, James E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wang, Minghua; Heightman, Tom D.] Univ Oxford, Struct Genom Consortium, Oxford OX3 7DQ, England. RP Spencer, J (reprint author), Univ Greenwich, Sch Sci Medway, Chatham ME4 4TB, Kent, England. EM j.spencer@gre.ac.uk RI Coles, Simon/A-1795-2009; spencer, john/C-2156-2008; Tizzard, Graham/D-1227-2010 OI Coles, Simon/0000-0001-8414-9272; spencer, john/0000-0001-5231-8836; FU RSC; Greenwich University; CRUK; Malaysian Government; Canadian Institutes for Hearth Research [1097737]; Canadian Foundation for Innovation, Genome Canada through the Ontario Genomics Institute, GlaxoSmithKline, Karolinska Institutet; Knut and Alice Wallenberg Foundation; Ontario Innovation Trust; Ontario Ministry for Research and Innovation; Merck Co Inc.; Novartis Research Foundation; Swedish Agency for Innovation Systems; Swedish Foundation or Strategic Research; Wellcome Trust FX The RSC (Research Fund) and Greenwich University (GRE and the Alumni fund) are thanked for financial assistance (J.S. and J.A., for equipment) as well as CRUK (G.P.) and the Malaysian Government (S.S.S.A.).; The Structural Genomics Consortium is a registered charity (number 1097737) that receives funds from the Canadian Institutes for Hearth Research, the Canadian Foundation for Innovation, Genome Canada through the Ontario Genomics Institute, GlaxoSmithKline, Karolinska Institutet, the Knut and Alice Wallenberg Foundation, the Ontario Innovation Trust, the Ontario Ministry for Research and Innovation, Merck & Co Inc., the Novartis Research Foundation, the Swedish Agency for Innovation Systems, the Swedish Foundation or Strategic Research, and the Wellcome Trust. NR 27 TC 43 Z9 43 U1 2 U2 20 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1948-5875 J9 ACS MED CHEM LETT JI ACS Med. Chem. Lett. PD MAY PY 2011 VL 2 IS 5 BP 358 EP 362 DI 10.1021/ml100295v PG 5 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 765GE UT WOS:000290691400007 PM 21572592 ER PT J AU Deng, XM Wang, JH Zhang, JM Sim, T Kim, ND Sasaki, T Luther, W George, RE Janne, PA Gray, NS AF Deng, Xianming Wang, Jinhua Zhang, Jianming Sim, Taebo Kim, Nam Doo Sasaki, Takaaki Luther, William, II George, Rani E. Jaenne, Pasi A. Gray, Nathanael S. TI Discovery of 3,5-Diamino-1,2,4-triazole Ureas as Potent Anaplastic Lymphoma Kinase Inhibitors SO ACS MEDICINAL CHEMISTRY LETTERS LA English DT Article DE ALK; 3,5-diamino-1,2,4-triazole urea ID CELL LUNG-CANCER; INFLAMMATORY MYOFIBROBLASTIC TUMOR; EML4-ALK FUSION GENE; EXPERIMENTAL-MODELS; THERAPEUTIC TARGET; ANTITUMOR-ACTIVITY; ALK; NEUROBLASTOMA; IDENTIFICATION; PATHOGENESIS AB A series of novel 3,5-diamino-1,2,4-triazole benzyl ureas was identified as having potent anaplastic lymphoma kinase (ALK) inhibition exemplified by 15a, 20a, and 23a, which exhibited antiproliferative IC50 values of 70, 40, and 20 nM in Tel-ALK transformed Ba/F3 cells, respectively. Moreover, 15a and 23a potently inhibited the growth and survival of NPM-ALK positive anaplastic large cell lymphoma cell (SU-DHL-1) and neuroblastoma cell lines (KELLY, SH-SY5Y) containing the F1174L ALK mutation. These compounds provide novel leads for the development of small-molecule ALK inhibitors for cancer therapy. C1 [Deng, Xianming; Wang, Jinhua; Zhang, Jianming; Sim, Taebo; Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Deng, Xianming; Wang, Jinhua; Zhang, Jianming; Sim, Taebo; Gray, Nathanael S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Kim, Nam Doo] Yonsei Univ, Dept Biotechnol, Seoul 120749, South Korea. [Sasaki, Takaaki; Jaenne, Pasi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Luther, William, II; George, Rani E.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Gray, NS (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, 250 Longwood Ave,SGM 628, Boston, MA 02115 USA. EM Nathanael_Gray@dfci.harvard.edu OI Sasaki, Takaaki/0000-0002-6505-8786 FU NCI [1 R01 CA136851-01A1, 1 R01 CA148688-01A1] FX This work was supported by an NCI Grant 1 R01 CA136851-01A1 (N.S.G. and P.A.J.) and 1 R01 CA148688-01A1 (R.E.G.). NR 27 TC 17 Z9 17 U1 0 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1948-5875 J9 ACS MED CHEM LETT JI ACS Med. Chem. Lett. PD MAY PY 2011 VL 2 IS 5 BP 379 EP 384 DI 10.1021/ml200002a PG 6 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 765GE UT WOS:000290691400011 PM 21572589 ER PT J AU Weisbord, SD Palevsky, PM AF Weisbord, Steven D. Palevsky, Paul M. TI Iodinated Contrast Media and the Role of Renal Replacement Therapy SO ADVANCES IN CHRONIC KIDNEY DISEASE LA English DT Article DE Contrast media; Acute kidney injury; Dialysis; Hemofiltration ID RADIOCONTRAST-INDUCED NEPHROPATHY; RANDOMIZED CONTROLLED-TRIAL; OXYGEN-FREE-RADICALS; DIURESIS DVD TRIAL; PROPHYLACTIC HEMODIALYSIS; IOPROMIDE ELIMINATION; CORONARY-ANGIOGRAPHY; DIALYSIS; PREVENTION; FAILURE AB Iodinated contrast media are among the most commonly used pharmacologic agents in medicine. Although generally highly safe, iodinated contrast media are associated with several adverse effects, most significantly the risk of acute kidney injury, particularly in patients with underlying renal dysfunction. By virtue of their pharmacokinetic characteristics, these contrast agents are efficiently cleared by hemodialysis and to a lesser extent, hemofiltration. This has led to research into the capacity for renal replacement therapies to prevent certain adverse effects of iodinated contrast. This review examines the molecular and pharmacokinetic characteristics of iodinated contrast media and critically analyzes data from past studies on the role of renal replacement therapy to prevent adverse effects of these diagnostic agents. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. C1 [Weisbord, Steven D.] VA Pittsburgh Healthcare Syst, Renal Sect, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Dept Med, Pittsburgh, PA USA. RP Weisbord, SD (reprint author), VA Pittsburgh Healthcare Syst, Renal Sect, Ctr Hlth Equ Res & Promot, Univ Dr Div,7 East,Room 120 111F U, Pittsburgh, PA 15240 USA. EM weisbordsd@upmc.edu OI Palevsky, Paul/0000-0002-7334-5400 FU VA Health Services Research and Development Career Development Transition Award [RCD 03-176] FX Dr. Weisbord is the recipient of a VA Health Services Research and Development Career Development Transition Award (RCD 03-176). NR 49 TC 3 Z9 4 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1548-5595 J9 ADV CHRONIC KIDNEY D JI Adv. Chronic Kidney Dis. PD MAY PY 2011 VL 18 IS 3 BP 199 EP 206 DI 10.1053/j.ackd.2010.11.008 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 765KC UT WOS:000290703500008 PM 21531326 ER PT J AU Franek, KJ Butler, J Johnson, J Simensen, R Friez, MJ Bartel, F Moss, T DuPont, B Berry, K Bauman, M Skinner, C Stevenson, RE Schwartz, CE AF Franek, Karl J. Butler, Julia Johnson, John Simensen, Richard Friez, Michael J. Bartel, Frank Moss, Tonya DuPont, Barbara Berry, Katherine Bauman, Margaret Skinner, Cindy Stevenson, Roger E. Schwartz, Charles E. TI Deletion of the Immunoglobulin Domain of IL1RAPL1 Results in Nonsyndromic X-Linked Intellectual Disability Associated With Behavioral Problems and Mild Dysmorphism SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE IL1RAPL1; non-syndromic XLID; deletion; behavior problems ID IDIOPATHIC MENTAL-RETARDATION; ACCESSORY PROTEIN-LIKE; ADRENAL HYPOPLASIA; GENE; FAMILY; CHROMOSOME; INACTIVATION; MUTATIONS; INVERSION; AUTISM AB X-Linked intellectual disability accounts for a significant fraction of males with cognitive impairment. Many of these males present with a non-syndromic phenotype and presently mutations in 17 X-linked genes are associated with these patients. Mutations in IL1RAPL1 have been found in multiple families with non-syndromic X-linked intellectual disability. All of the published mutations predict loss of function of the protein. We have identified an additional two families with deletions of a portion of the gene that give rise to cognitive impairment, as well as some behavioral problems and mild dysmorphism. Our clinical findings better delineate the phenotypic spectrum associated with IL1RAPL1 mutations. (C) 2011 Wiley-Liss, Inc. C1 [Franek, Karl J.; Butler, Julia; Simensen, Richard; Friez, Michael J.; Bartel, Frank; Moss, Tonya; DuPont, Barbara; Skinner, Cindy; Stevenson, Roger E.; Schwartz, Charles E.] Greenwood Genet Ctr, JC Self Res Inst Human Genet, Ctr Mol Studies, Greenwood, SC 29646 USA. [Johnson, John; Berry, Katherine] Shodair Childrens Hosp, Dept Med Genet, Helena, MT USA. [Bauman, Margaret] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Schwartz, CE (reprint author), Greenwood Genet Ctr, JC Self Res Inst Human Genet, Ctr Mol Studies, 113 Gregor Mendel Circle, Greenwood, SC 29646 USA. EM ceschwartz@ggc.org FU NICHD [R01HD26208]; South Carolina Department of Disabilities and Special Needs (SCDDSN) FX We thank the members of the families for their participation in this study. This work was supported by a NICHD grant (R01HD26208) to C.E.S. and in part by a grant from the South Carolina Department of Disabilities and Special Needs (SCDDSN). This article is dedicated to the memory of Ethan Francis Schwartz 1996-1998. NR 23 TC 21 Z9 22 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD MAY PY 2011 VL 155A IS 5 BP 1109 EP 1114 DI 10.1002/ajmg.a.33833 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 765OB UT WOS:000290716700023 PM 21484992 ER PT J AU Lysack, C Lichtenberg, P Schneider, B AF Lysack, Cathy Lichtenberg, Peter Schneider, Brooke TI Effect of a DVD Intervention on Therapists' Mental Health Practices With Older Adults SO AMERICAN JOURNAL OF OCCUPATIONAL THERAPY LA English DT Article DE clinical competence; depression; education, continuing; educational measurement; mental health services ID LATE-LIFE DEPRESSION; HOME-CARE; OCCUPATIONAL-THERAPY; TREATING DEPRESSION; RECOGNITION; COMPETENCE; SCALE AB PURPOSE. We tested the effectiveness of an educational intervention in DVD format aimed at strengthening the mental health practices of occupational therapists working with older adults. METHOD. The DVD intervention was tested in a pretest-posttest design. Occupational therapists (n = 30) completed a brief knowledge and attitude questionnaire; a chart review (n = 383) of therapists' (n = 20) patients at 3 mo before and 3 mo after DVD training was also conducted. RESULTS. Questionnaire data showed that the percentage of therapists with correct answers increased 20%-30% for 5 of the 11 knowledge items. Chart review data showed therapists spoke more often with their older patients about mood, depression, and cognitive impairment; screened more often for depression and cognitive impairment; and reported findings more often to the treatment team after training. CONCLUSION. Educational interventions can significantly improve therapists' mental health practice with older adults. C1 [Lysack, Cathy; Lichtenberg, Peter] Wayne State Univ, Inst Gerontol, Detroit, MI 48202 USA. [Schneider, Brooke] W Los Angeles Vet Affairs Med Ctr, Psychol Serv, Los Angeles, CA 90073 USA. RP Lysack, C (reprint author), Wayne State Univ, Inst Gerontol, Room 231,Knapp Bldg,87 E Ferry St, Detroit, MI 48202 USA. EM c.lysack@wayne.edu NR 30 TC 5 Z9 5 U1 1 U2 2 PU AMER OCCUPATIONAL THERAPY ASSOC, INC PI BETHESDA PA 4720 MONTGOMERY LANE, BETHESDA, MD 20814-3425 USA SN 0272-9490 J9 AM J OCCUP THER JI Am. J. Occup. Ther. PD MAY-JUN PY 2011 VL 65 IS 3 SI SI BP 297 EP 305 DI 10.5014/ajot.2011.001354 PG 9 WC Rehabilitation SC Rehabilitation GA 765KQ UT WOS:000290704900008 PM 21675335 ER PT J AU Schechter-Perkins, EM Mitchell, PM Murray, KA Rubin-Smith, JE Weir, S Gupta, K AF Schechter-Perkins, Elissa M. Mitchell, Patricia M. Murray, Kate A. Rubin-Smith, Julia E. Weir, Susan Gupta, Kalpana TI Prevalence and Predictors of Nasal and Extranasal Staphylococcal Colonization in Patients Presenting to the Emergency Department SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID AUREUS COLONIZATION; UNITED-STATES; RISK-FACTORS; HOSPITAL ADMISSION; HAND HYGIENE; CARE; INFECTIONS; SKIN; SURVEILLANCE; POPULATIONS AB Study objective: Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most common causes of skin and soft tissue infections in patients presenting to the emergency department (ED). The prevalence of asymptomatic MRSA colonization in ED patients is less well described, particularly in the absence of a skin and soft tissue infection related complaint. The goals of this study are to assess the prevalence of nasal and extranasal staphylococcal colonization in ED patients, evaluate risk factors, and molecularly characterize the strains. Methods: We performed active surveillance for methicillin-susceptible S aureus (MSSA) and MRSA colonization in 400 subjects presenting to an urban ED. Risk factor assessment was performed and culture testing was conducted on anterior nares, oropharynx, palms, groin, perirectal area, wounds, and catheter insertion sites. Multiplex polymerase chain reaction was used to identify the USA300/400 clonal types. Results: The prevalence of colonization with MSSA was 39% (95% confidence interval 34.2% to 44.0%), and prevalence of colonization with MRSA was 5% (95% confidence interval 3.1% to 7.6%). Among MRSA-colonized subjects, an extranasal site tested positive in 80% of subjects, and 45% had exclusive extranasal colonization. USA300 was identified in 55% of MRSA-colonized subjects. The main risk factors for MRSA colonization included HIV infection, diabetes, and participation in contact sports. Conclusion: The overall prevalence of MRSA colonization in this ED population was lower than that reported in other high-risk ambulatory care settings. However, extranasal colonization was present in more than half of MRSA-colonized subjects, and USA300 was the predominant clonal type. [Ann Emerg Med. 2011;57:492-499.] C1 [Gupta, Kalpana] Boston Vet Affairs Hlth Care Syst, Boston, MA USA. [Schechter-Perkins, Elissa M.; Mitchell, Patricia M.; Murray, Kate A.; Rubin-Smith, Julia E.] Boston Univ, Sch Med, Dept Emergency Med, Boston, MA 02118 USA. [Weir, Susan; Gupta, Kalpana] Boston Univ, Sch Med, Dept Internal Med, Boston, MA 02118 USA. RP Gupta, K (reprint author), VA Boston HCS, 1400 VFW Pkwy,111 Med, W Roxbury, MA 02132 USA. EM kalpana.gupta@va.gov FU Boston University Department of Medicine; Boston University Clinical and Translational Science Institute (NIH) [UL1RR025771] FX By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article that might create any potential conflict of interest. The authors have stated that no such relationships exist. See the Manuscript Submission Agreement in this issue for examples of specific conflicts covered by this statement. The study was supported in part by a pilot grant award from the Boston University Department of Medicine and the Boston University Clinical and Translational Science Institute (NIH Award UL1RR025771). NR 41 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 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD MAY PY 2011 VL 57 IS 5 BP 492 EP 499 DI 10.1016/j.annemergmed.2010.11.024 PG 8 WC Emergency Medicine SC Emergency Medicine GA 764CQ UT WOS:000290606400014 PM 21239081 ER PT J AU Smith, H Hutson, HR Geoffley, A Strote, J AF Smith, Hayden Hutson, H. Range Geoffley, Alpert Strote, Jared TI Emergency Physician Watchdogs for Law Enforcement: If We Are the Hammer, Everything Will Look Like a Nail Reply SO ANNALS OF EMERGENCY MEDICINE LA English DT Letter C1 [Smith, Hayden; Geoffley, Alpert] Univ S Carolina, Dept Criminol & Criminal Justice, Columbia, SC 29208 USA. [Hutson, H. Range] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Strote, Jared] Univ Washington, Div Emergency Med, Seattle, WA 98195 USA. RP Smith, H (reprint author), Univ S Carolina, Dept Criminol & Criminal Justice, Columbia, SC 29208 USA. NR 2 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD MAY PY 2011 VL 57 IS 5 BP 543 EP 544 DI 10.1016/j.annemergmed.2010.11.005 PG 2 WC Emergency Medicine SC Emergency Medicine GA 764CQ UT WOS:000290606400028 ER PT J AU Hutson, HR Anglin, D Strote, J AF Hutson, H. Range Anglin, Deirdre Strote, Jared TI Regarding Use of Force Reply SO ANNALS OF EMERGENCY MEDICINE LA English DT Letter ID EMERGENCY PHYSICIANS; POLICE C1 [Hutson, H. Range] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02114 USA. [Anglin, Deirdre] Univ So Calif, Cty USC Med Ctr, Dept Emergency Med, Los Angeles, CA USA. [Strote, Jared] Univ Washington, Univ Washington Med Ctr, Div Emergency Med, Seattle, WA 98195 USA. RP Hutson, HR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02114 USA. NR 3 TC 1 Z9 1 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD MAY PY 2011 VL 57 IS 5 BP 546 EP 546 DI 10.1016/j.annemergmed.2010.12.026 PG 1 WC Emergency Medicine SC Emergency Medicine GA 764CQ UT WOS:000290606400031 ER PT J AU Filipits, M Hills, M Salter, J Dafni, U Gelber, RD Piccart, M Gnant, M Smith, BR Leyland-Jones, B Dowsett, M AF Filipits, M. Hills, M. Salter, J. Dafni, U. Gelber, R. D. Piccart, M. Gnant, M. Smith, B. R. Leyland-Jones, B. Dowsett, M. TI TRANSHERA: ANALYSIS OF PTEN, IGF-1R AND STATHMIN AS PUTATIVE PROGNOSTIC/PREDICTIVE MARKERS IN HER2-POSITIVE EARLY BREAST CANCER (BC) PATIENTS TREATED WITH 1-YEAR OF TRASTUZUMAB SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT Conference on Improving Care and Knowledge through Translational Research (IMPAKT) Breast Cancer CY MAY 05-07, 2011 CL Brussels, BELGIUM C1 [Filipits, M.] Med Univ Vienna, Dept Med 1, Vienna, Austria. [Hills, M.; Salter, J.] Royal Marsden Hosp, London SW3 6JJ, England. [Dafni, U.] Frontier Sci Fdn, Athens, Greece. [Gelber, R. D.] Dana Farber Canc Inst, IBCSG Stat Ctr, Boston, MA 02115 USA. [Piccart, M.] Inst Jules Bordet, Dept Med, B-1000 Brussels, Belgium. [Gnant, M.] Med Univ Vienna, Dept Surg, Vienna, Austria. [Smith, B. R.] VM Inst Res, Montreal, PQ, Canada. [Leyland-Jones, B.] Emory Univ, Atlanta, GA 30322 USA. [Dowsett, M.] Royal Marsden NHS Trust, Breakthrough Res Ctr, London, England. NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 2011 VL 22 SU 2 BP 45 EP 45 PG 1 WC Oncology SC Oncology GA 764EB UT WOS:000290610100077 ER PT J AU Chren, MM Torres, JS Stuart, SE Bertenthal, D Labrador, RJ Boscardin, J AF Chren, Mary-Margaret Torres, Jeanette S. Stuart, Sarah E. Bertenthal, Daniel Labrador, Remedios J. Boscardin, John TI Recurrence After Treatment of Nonmelanoma Skin Cancer A Prospective Cohort Study SO ARCHIVES OF DERMATOLOGY LA English DT Article ID BASAL-CELL CARCINOMA; MOHS MICROGRAPHIC SURGERY; FACE AB Objective: To determine long-term tumor recurrence rates after treatment of primary nonmelanoma skin cancer (NMSC). Data are currently insufficient to permit evidence-based choices among treatments for NMSC. Design: Prospective study of an inception cohort observed for a median of 6.6 years after treatment. Setting: Dermatology clinic at a Veterans Affairs hospital. Care was provided by dermatology resident or attending physicians. Patients: Consecutive sample of all 495 patients with 616 primary NMSCs diagnosed in 1999 and 2000 and treated with electrodessication and curettage (ED&C), excision, or Mohs surgery. Follow-up was available for 608 tumors (99%). Main Outcome Measure: Tumor recurrence, deter-mined by medical record review, with validation by clinical examination. Results: The mean age at diagnosis was 71 years; 97% were men. Overall, 127 tumors were treated with ED&C (20.9%); 309 with excision (50.8%); and 172 with Mohs surgery (28.3%). Over the course of the study, 21 tumors recurred (3.5% [95% confidence interval (CI), 2.2%-5.2%]): 2 after ED&C (1.6% [95% CI, 0.2%-5.6%]), 13 after excision (4.2% [95% CI, 2.2%-7.1%]), and 6 after Mohs surgery (3.5% [95% CI, 1.3%-7.4%]). Conclusions: Recurrence of primary NMSC after treatment occurred in less than 5% of tumors. The recurrence rate after ED&C was lower than expected, and the recurrence rate after Mohs surgery was higher than expected. These findings may be related to the risk for recurrence in the treatment groups. C1 [Chren, Mary-Margaret; Torres, Jeanette S.; Stuart, Sarah E.; Bertenthal, Daniel; Labrador, Remedios J.; Boscardin, John] San Francisco VA Med Ctr, Res Enhancement Award Program, Hlth Serv Res & Dev Serv, Dept Vet Affairs, San Francisco, CA USA. [Chren, Mary-Margaret] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [Boscardin, John] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Boscardin, John] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Chren, MM (reprint author), San Francisco VA Med Ctr 151R, 4150 Clement St, San Francisco, CA 94121 USA. EM chrenm@derm.ucsf.edu FU Investigator-Initiated Research Grant [IIR 04-043-3]; Health Services Research and Development Service of the Department of Veterans Affairs; National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health [K24 AR052667, R01 AR 054983] FX This work was supported by Investigator-Initiated Research Grant IIR 04-043-3 and the San Francisco Research Enhancement Award Program (REAP) of the Health Services Research and Development Service of the Department of Veterans Affairs, and by grants K24 AR052667 and R01 AR 054983 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health. NR 16 TC 35 Z9 38 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD MAY PY 2011 VL 147 IS 5 BP 540 EP 546 PG 7 WC Dermatology SC Dermatology GA 764LX UT WOS:000290632100004 PM 21576572 ER PT J AU Hadlock, TA Malo, JS Cheney, ML Henstrom, DK AF Hadlock, Tessa A. Malo, Juan S. Cheney, Mack L. Henstrom, Douglas K. TI Free Gracilis Transfer for Smile in Children The Massachusetts Eye and Ear Infirmary Experience in Excursion and Quality-of-Life Changes SO ARCHIVES OF FACIAL PLASTIC SURGERY LA English DT Article ID FACIAL-NERVE PARALYSIS; FREE MUSCLE TRANSFER; NECK RECONSTRUCTION; FREE FLAPS; REANIMATION; HEAD; FACE; TRANSPLANTATION; VALIDATION; EXPRESSION AB Background: Free muscle transfer for facial reanimation has become the standard of care in recent decades and is now the cornerstone intervention for dynamic smile reanimation. We sought to quantify smile excursion and quality-of-life (QOL) changes in our pediatric free gracilis recipients following reanimation. Methods: We quantified gracilis muscle excursion in 17 pediatric patients undergoing 19 consecutive pediatric free gracilis transplantation operations, using our validated SMILE program, as an objective measure of functional outcome. These were compared against excursion measured the same way in a cohort of 17 adults with 19 free gracilis operations. In addition, we prospectively evaluated QOL outcomes in these children using the Facial Clinimetric Evaluation (FaCE) instrument. Results: The mean gracilis excursion in our pediatric free gracilis recipients was 8.8 mm +/- 5.0 mm, which matched adult results, but with fewer complete failures of less than 2-mm excursion, with 2 (11%) and 4 (21%), respectively. Quality-of-life measures indicated statistically significant improvements following dynamic smile reanimation (P = .01). Conclusions: Dynamic facial reanimation using free gracilis transfer in children has an acceptable success rate, yields improved commissure excursion, and improves QOL in the pediatric population. It should be considered first-line therapy for children with lack of a meaningful smile secondary to facial paralysis. C1 [Hadlock, Tessa A.; Malo, Juan S.; Cheney, Mack L.; Henstrom, Douglas K.] Massachusetts Eye & Ear Infirm, Facial Nerve Ctr, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. RP Hadlock, TA (reprint author), Massachusetts Eye & Ear Infirm, Facial Nerve Ctr, Dept Otolaryngol Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA. EM tessa_hadlock@meei.harvard.edu NR 23 TC 33 Z9 33 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 1521-2491 J9 ARCH FACIAL PLAST S JI Arch. Facial Plast. Surg. PD MAY-JUN PY 2011 VL 13 IS 3 BP 190 EP 194 PG 5 WC Surgery SC Surgery GA 764MA UT WOS:000290632400009 PM 21576665 ER PT J AU Sachs, DH AF Sachs, David H. TI Transplant Tolerance Bench to Bedside 26th Annual Samuel Jason Mixter Lecture SO ARCHIVES OF SURGERY LA English DT Article ID BONE-MARROW-TRANSPLANTATION; REGULATORY T-CELLS; LARGE-ANIMAL-MODEL; MIXED CHIMERISM; PREPARATIVE REGIMEN; ALLOGRAFT TOLERANCE; INDUCTION; KIDNEY; MAINTENANCE; MECHANISMS AB Ever since the first demonstration that transplant tolerance can be induced in neonatal mice by injection of donor bone marrow cells shortly after birth, 1 the establishment of tolerance for organ transplants has been a major goal in the field of transplantation immunology. Indeed, an understanding of tolerance has both theoretical and practical implications for transplantation: from a theoretical point of view, an understanding of tolerance is basic to the requirement for self-/nonself-discrimination in the immune system; from a practical point of view, the induction of tolerance could relieve patients from the need for long-term immunosuppressant medications, thereby avoiding the adverse effects and complications that are a major limitation to the success of clinical transplant at present. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. RP Sachs, DH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Bldg 149-9019,13th St, Boston, MA 02129 USA. EM david.sachs@tbrc.mgh.harvard.edu FU NIAID NIH HHS [N01AI15416, N01 AI015416] NR 22 TC 2 Z9 2 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD MAY PY 2011 VL 146 IS 5 BP 501 EP 505 PG 5 WC Surgery SC Surgery GA 764MH UT WOS:000290633100001 PM 21576601 ER PT J AU Cosimi, AB AF Cosimi, A. Benedict TI Modern Day Bloodletting Is That Laboratory Test Necessary? INVITED CRITIQUE SO ARCHIVES OF SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Cosimi, AB (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St, Boston, MA 02114 USA. EM cosimi@partners.org NR 2 TC 2 Z9 2 U1 2 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD MAY PY 2011 VL 146 IS 5 BP 527 EP 527 PG 1 WC Surgery SC Surgery GA 764MH UT WOS:000290633100009 PM 21739650 ER PT J AU Fikry, K Velmahos, GC Bramos, A Janjua, S de Moya, M King, DR Alam, HB AF Fikry, Karim Velmahos, George C. Bramos, Athanasios Janjua, Sumbal de Moya, Marc King, David R. Alam, Hasan B. TI Successful Selective Nonoperative Management of Abdominal Gunshot Wounds Despite Low Penetrating Trauma Volumes SO ARCHIVES OF SURGERY LA English DT Article ID CONSERVATIVE MANAGEMENT; ROUTINE LAPAROTOMY; STAB WOUNDS; INJURIES; ABDOMEN; MORBIDITY; OPERATION; BACK AB Objective: To determine whether selective nonoperative management of abdominal gunshot wounds (AGSW) is safe in trauma centers with a low volume of penetrating trauma. Design: Retrospective study. Setting: Academic level 1 trauma center with approximately 10% penetrating trauma. Patients: All patients with anterior and posterior AGSW (January 1, 1999, through December 31, 2009), excluding tangential injuries, transfers, and deaths in the emergency department. Patients with hemodynamic instability or peritonitis received an urgent laparotomy. The remaining patients had selective nonoperative management. A delayed laparotomy was offered for worsening symptoms or worrisome computed tomography findings. Main Outcome Measures: Hospital stay, complications, and mortality. Results: Of 125 AGSW patients, 38 (30%) were initially managed by selective nonoperative management (25 of 99 anterior and 13 of 26 posterior AGSW patients). Seven selective nonoperative management patients received delayed laparotomy as late as 11 hours after admission. At the end, 30 of the 125 patients (24%) were successfully managed without an operation (20 of 99 anterior and 10 of 26 posterior AGSW patients). There were no predictors of delayed laparotomy and no complications or mortality attributed to it. Ten patients (8%) had a nontherapeutic laparotomy, and 3 of them developed complications. Conclusions: Selective nonoperative management of AGSW is feasible and safe in trauma centers with low penetrating trauma volumes. Nearly 1 in 4 AGSW patients does not need a laparotomy, and nontherapeutic laparotomies are associated with complications. The volume of AGSW per se should not be an excuse for routine laparotomies. These data become particularly important because penetrating trauma volumes are decreasing around the country. C1 [Fikry, Karim] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Fikry, K (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Ste 810, Boston, MA 02114 USA. EM kfikry@partners.org NR 29 TC 9 Z9 11 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD MAY PY 2011 VL 146 IS 5 BP 528 EP 532 PG 5 WC Surgery SC Surgery GA 764MH UT WOS:000290633100010 PM 21576606 ER PT J AU Haynes, AB Deshpande, V Ingkakul, T Vagefi, PA Szymonifka, J Thayer, SP Ferrone, CR Wargo, JA Warshaw, AL Fernandez-del Castillo, C AF Haynes, Alex B. Deshpande, Vikram Ingkakul, Thun Vagefi, Parsia A. Szymonifka, Jackie Thayer, Sarah P. Ferrone, Cristina R. Wargo, Jennifer A. Warshaw, Andrew L. Fernandez-del Castillo, Carlos TI Implications of Incidentally Discovered, Nonfunctioning Pancreatic Endocrine Tumors Short-term and Long-term Patient Outcomes SO ARCHIVES OF SURGERY LA English DT Article ID GASTROENTEROPANCREATIC NEUROENDOCRINE TUMORS; ISLET CELL TUMORS; NEOPLASMS; EXPERIENCE; MANAGEMENT; SYSTEM AB Objectives: To describe the characteristics and outcomes after resection of incidentally discovered, nonfunctioning pancreatic endocrine tumors (PETs). Design: Case series. Setting: Academic hospital. Patients: Consecutive patients with an incidentally identified, nonfunctioning PET resected from May 1, 1977, through July 31, 2009. Main Outcome Measures: Operative morbidity and survival after resection. Results: A total of 139 patients with median age of 56 years (range, 21-85 years) underwent resection; tumor size ranged from 0.4 to 17.0 cm, with median size of 3.0 cm. No perioperative deaths were reported. Sixty-one patients (43.9%) experienced a perioperative complication. Twenty-six tumors (18.7%) were classified as benign, 39 (28.1%) as malignant, and 72 (51.8%) as uncertain. We were unable to confidently classify 2 tumors due to lack of information regarding mitotic rate in the pathology report. Complete follow-up was available for 112 patients (80.6%) (median, 34.2 months). Five-year actuarial survival rates were 88.8% for patients with benign disease, 92.5% for patients with tumors of uncertain biology, and 49.8% for those with malignant tumors (P=.01). Late metastasis, tumor recurrence, or disease progression were seen in 1 patient (3.8%) with tumors initially classified as benign, 8 patients (11.1%) with uncertain tumors, and 15 patients (38.5%) with tumors classified as malignant (P<.001). Of the 39 patients with tumors 2 cm or smaller, 3 (7.7%) had late metastases or recurrence. When compared with patients with symptomatic, nonfunctioning PETs, no large difference was observed in tumor size, patient age, disease, or survival. Conclusions: Incidentally detected, nonfunctioning PETs can display aggressive behavior, even when small. Although patients with malignant disease had diminished survival and increased rates of recurrence, benign histologic findings did not eliminate the possibility of progression. Patients with incidentally discovered, nonfunctioning PETs should undergo tumor resection and careful postoperative surveillance, even if surgical pathologic findings suggest benign disease. C1 [Fernandez-del Castillo, Carlos] Massachusetts Gen Hosp, Dept Surg, Wang Ambulatory Care Ctr 460, Boston, MA 02114 USA. [Deshpande, Vikram] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Szymonifka, Jackie] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Vagefi, Parsia A.] Univ Calif San Francisco, Sch Med, Dept Surg, San Francisco, CA 94143 USA. RP Fernandez-del Castillo, C (reprint author), Massachusetts Gen Hosp, Dept Surg, Wang Ambulatory Care Ctr 460, 15 Parkman St, Boston, MA 02114 USA. EM cfernandez@partners.org FU NCI NIH HHS [P01 CA117969, P01 CA117969-04S1, P01 CA117969-05, P01 CA117969-06, P50 CA127003, P50 CA127003-03]; NIDDK NIH HHS [K08 DK071329, K08 DK071329-05] NR 16 TC 69 Z9 71 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD MAY PY 2011 VL 146 IS 5 BP 534 EP 538 PG 5 WC Surgery SC Surgery GA 764MH UT WOS:000290633100012 PM 21576607 ER PT J AU Salinas, HM Dursun, A Klos, CL Shellito, P Sylla, P Berger, D Bordeianou, L AF Salinas, Harry M. Dursun, Abdulmetin Klos, Coen L. Shellito, Paul Sylla, Patricia Berger, David Bordeianou, Liliana TI Determining the Need for Radical Surgery in Patients With T1 Rectal Cancer SO ARCHIVES OF SURGERY LA English DT Article ID LYMPH-NODE METASTASIS; LOCAL EXCISION; PREOPERATIVE RADIOTHERAPY; TRANSANAL EXCISION; ADJUVANT THERAPY; UNITED-STATES; RISK; CARCINOMA; RESECTION; ADENOCARCINOMA AB Hypothesis: In the era of modern preoperative staging of patients with rectal cancer, lymph node metastases can be reliably predicted by the histological features of the tumor and preoperative imaging. Local resection can then be safely offered to the patients who are at low risk of having malignant lymph nodes. Design: We reviewed the records of 109 consecutive patients with preoperative imaging results suggestive of T1N0 or T2N0 disease who underwent total mesorectal excision. All patients underwent preoperative endorectal ultrasonography or magnetic resonance imaging and computed tomography, with or without positron emission tomography. Final pathologic investigation identified T3 disease in 27 patients. History, physical examination results, and radiologic and pathologic data were evaluated for predictors of positive nodes in the remaining 82 patients. Setting: Tertiary care referral center. Patients: Patients with preoperative imaging suggestive of T1N0 or T2N0 rectal cancer. Main Outcome Measures: To evaluate different clinical and pathologic tumor features as predictors of positive lymph nodes in T1 and T2 rectal cancers with negative radiographic nodes. Background: Local resection of T1 and T2 rectal cancer results in lower morbidity compared with radical resection. However, recurrence rates after local resection are higher, likely owing to unresected nodal metastasis. Reports on predictors of lymph node metastasis remain inconsistent in the literature. Although local resection may be appropriate for some rectal cancers, selection criteria remain unclear. Results: Despite indications of negative nodes on radiographic examination, 4 of 35 patients with T1 disease (11%) and 13 of 47 with T2 disease (28%) had positive nodes. On univariate analysis, the only significant predictor was depth of invasion: 24 of 65 patients with negative nodes (37%) vs 13 of 17 patients with positive nodes (76%) had tumors invading the lower third of the submucosa and beyond (P=.02). On logistic regression analysis accounting for depth of invasion (lower third of the submucosa and beyond), size, distance from anal verge, differentiation, and lymphovascular and small-vessel invasion, only depth of invasion remained a significant predictor. Conclusions: In all, 89% of patients with T1 disease (31 of 35) and 72% of those with T2 disease (34 of 47) underwent unnecessary radical resection. Endorectal ultrasonography or magnetic resonance imaging and computed tomography, with or without positron emission tomography, for preoperative staging could not identify these patients reliably. In addition, histologic markers of aggressive disease were not helpful. Thus, local resection for T2 rectal cancer is not justified. Local resection should be offered only to patients with superficial T1 tumors who will adhere to aggressive postoperative surveillance. C1 [Bordeianou, Liliana] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. [Salinas, Harry M.; Dursun, Abdulmetin; Shellito, Paul; Sylla, Patricia; Berger, David; Bordeianou, Liliana] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Klos, Coen L.] Univ Amsterdam, Amsterdam, Netherlands. RP Bordeianou, L (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, 15 Parkman St,ACC 460, Boston, MA 02114 USA. EM lbordeianou@partners.org NR 24 TC 10 Z9 11 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD MAY PY 2011 VL 146 IS 5 BP 540 EP 543 PG 4 WC Surgery SC Surgery GA 764MH UT WOS:000290633100014 PM 21576608 ER PT J AU Velmahos, GC AF Velmahos, George C. TI Surprise, Surprise! More Surgery in Rural Areas Than in Cities INVITED CRITIQUE SO ARCHIVES OF SURGERY LA English DT Editorial Material C1 [Velmahos, George C.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Velmahos, George C.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Velmahos, GC (reprint author), Massachusetts Gen Hosp, Dept Surg, 165 Cambridge St,Ste 810, Boston, MA 02114 USA. EM gvelmahos@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD MAY PY 2011 VL 146 IS 5 BP 584 EP 584 PG 1 WC Surgery SC Surgery GA 764MH UT WOS:000290633100023 PM 21739655 ER PT J AU Kuil, J Buckle, T Yuan, HS van den Berg, NS Oishi, S Fujii, N Josephson, L van Leeuwen, FWB AF Kuil, Joeri Buckle, Tessa Yuan, Hushan van den Berg, Nynke S. Oishi, Shinya Fujii, Nobutaka Josephson, Lee van Leeuwen, Fijs W. B. TI Synthesis and Evaluation of a Bimodal CXCR4 Antagonistic Peptide SO BIOCONJUGATE CHEMISTRY LA English DT Article ID CHEMOKINE RECEPTOR CXCR4; CANCER; T140; FLUORESCENCE; EXPRESSION; DTPA AB The antagonistic Ac-TZ14011 peptide, which binds to the chemokine receptor 4, has been labeled with a multifunctional single attachment point reagent that contains a DTPA chelate and a fluorescent dye with Cy5.5 spectral properties. Flow cytometry and confocal microscopy showed that the bimodal labeled peptide gave a specific receptor binding that is similar to monofunctionalized peptide derivatives, Therefore, the newly developed bimodal peptide derivative can be used in multimodal imaging applications. C1 [Kuil, Joeri; Buckle, Tessa; van den Berg, Nynke S.; van Leeuwen, Fijs W. B.] Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, Div Diagnost Oncol, NL-1066 CX Amsterdam, Netherlands. [Yuan, Hushan; Josephson, Lee] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. [Yuan, Hushan; Josephson, Lee] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Oishi, Shinya; Fujii, Nobutaka] Kyoto Univ, Grad Sch Pharmaceut Sci, Dept Bioorgan Med Chem, Kyoto, Japan. RP van Leeuwen, FWB (reprint author), Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, Div Diagnost Oncol, NL-1066 CX Amsterdam, Netherlands. EM fw.v.leeuwen@nki.nl RI Oishi, Shinya/C-1350-2011; OI Oishi, Shinya/0000-0002-2833-2539; van leeuwen, Fijs/0000-0002-6844-4025; Buckle, Tessa/0000-0003-2980-6895 FU KWF [PGF 2009-4344]; Centre for Translational Molecular Medicine [030-104] FX This research is supported, in part, by a KWF-translational research award (Grant No. PGF 2009-4344; FvL), and within the framework of CTMM, the Centre for Translational Molecular Medicine (http://www.ctmm.nl), project Breast CARE (grant 030-104; JK). NR 32 TC 32 Z9 32 U1 1 U2 24 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 MAY PY 2011 VL 22 IS 5 BP 859 EP 864 DI 10.1021/bc2000947 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 765GF UT WOS:000290691600002 PM 21480671 ER PT J AU Petryshen, TL AF Petryshen, Tracey L. TI Characterizing the Role of Ankyrin 3 in Regulating Bipolar-Related Behaviors SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Petryshen, Tracey L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 10 BP 4S EP 4S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800011 ER PT J AU Milad, MR AF Milad, Mohammed R. TI Sex Differences and Influence of Sex Hormones on Fear Extinction in Rats and Humans SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Milad, Mohammed R.] Massachusetts Gen Hosp, Charlestown, MA USA. [Milad, Mohammed R.] Harvard Univ, Sch Med, Charlestown, MA USA. 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 103 BP 27S EP 28S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800088 ER PT J AU Bymaster, F Skolnick, P Huang, NY Bradshaw, M McKinney, A Manthis, J Fava, M Tran, P AF Bymaster, F. Skolnick, P. Huang, N. Y. Bradshaw, M. McKinney, A. Manthis, J. Fava, M. Tran, P. TI Efficacy and Safety of EB-1010, a Triple Reuptake Inhibitor, in the Treatment of Patients with Major Depressive Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Skolnick, P.] DOV Pharmaceut, Clin, Somerset, NJ USA. [Huang, N. Y.] QRx Pharma, Clin, Bedminster, NJ USA. [Bradshaw, M.] Global Consulting Partners, Clin, Princeton, NJ USA. [Fava, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 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 MAY 1 PY 2011 VL 69 IS 9 SU S MA 136 BP 37S EP 38S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800121 ER PT J AU Howland, RH Wisniewski, S Balasubramani, GK Fava, M Trivedi, M Rush, AJ AF Howland, Robert H. Wisniewski, Stephen Balasubramani, G. K. Fava, Maurizo Trivedi, Madukar Rush, A. John TI Thyroid Disease, Major Depression, and Treatment Outcome in the COMED Trial SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Howland, Robert H.] Univ Pittsburgh, Western Psychiat Inst & Clin, Med Ctr, Pittsburgh, PA 15213 USA. [Wisniewski, Stephen; Balasubramani, G. K.] Univ Pittsburgh, Epidemiol Data Ctr, Pittsburgh, PA 15213 USA. [Fava, Maurizo] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Trivedi, Madukar] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Rush, A. John] Singapore Duke NUS, Grad Sch Med, Singapore, Singapore. RI Howland, Robert/K-6937-2015 OI Howland, Robert/0000-0002-6533-6010 NR 0 TC 0 Z9 0 U1 0 U2 5 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 MAY 1 PY 2011 VL 69 IS 9 SU S MA 138 BP 38S EP 38S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800123 ER PT J AU Ripoll, LH Zaki, J Perez-Rodriguez, M New, AS AF Ripoll, Luis H. Zaki, Jamil Perez-Rodriguez, Mercedes New, Antonia S. TI Empathic Accuracy and Social Cognition in Personality Disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Ripoll, Luis H.; New, Antonia S.] James J Peters VA Med Ctr, MIRECC, Bronx, NY USA. [Zaki, Jamil] Harvard Univ, Dept Psychol, Boston, MA 02115 USA. [Perez-Rodriguez, Mercedes] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. NR 0 TC 0 Z9 0 U1 2 U2 8 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 MAY 1 PY 2011 VL 69 IS 9 SU S MA 177 BP 50S EP 50S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800162 ER PT J AU Bevilacqua, L Hadjulis, M Enoch, MA New, AS Hodgkinson, CA Yuan, QP Shen, PH Siever, LJ Roy, A Goldman, D AF Bevilacqua, Laura Hadjulis, Michael Enoch, Mary-Anne New, Antonia S. Hodgkinson, Colin A. Yuan, Qiaoping Shen, Pei-Hong Siever, Larry J. Roy, Alec Goldman, David TI An HTR2B Low-expression Haplotype Predicts Risk of Cocaine Dependence and Aggression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Bevilacqua, Laura; Enoch, Mary-Anne; Hodgkinson, Colin A.; Yuan, Qiaoping; Shen, Pei-Hong; Goldman, David] NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. [Hadjulis, Michael; New, Antonia S.; Siever, Larry J.] Mt Sinai Sch Med, New York, NY USA. [Hadjulis, Michael; New, Antonia S.; Siever, Larry J.] James J Peters VA Med Ctr, New York, NY USA. [Roy, Alec] New Jersey VA Hlth Care Syst, Dept Vet Affairs, E Orange, NJ USA. 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 211 BP 60S EP 61S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800196 ER PT J AU Tsareva, A Lebron-Milad, K Pitman, RK Milad, MR AF Tsareva, Alina Lebron-Milad, Kelimer Pitman, Roger K. Milad, Mohammed R. TI Influence of Selective Serotonin Reuptake Inhibitors on Fear Extinction SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 3 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 MAY 1 PY 2011 VL 69 IS 9 SU S MA 312 BP 93S EP 93S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800297 ER PT J AU Milad, MR AF Milad, Mohammed R. TI Fear Extinction in Post-Traumatic Stress, Obsessive-Compulsive Disorder and Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Milad, Mohammed R.] Massachusetts Gen Hosp, Charlestown, MA USA. [Milad, Mohammed R.] Harvard Univ, Sch Med, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 7 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 MAY 1 PY 2011 VL 69 IS 9 SU S MA 383 BP 113S EP 113S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800360 ER PT J AU Spencer, KM AF Spencer, Kevin M. TI Oscillatory Brain Dynamics in Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Spencer, Kevin M.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 405 BP 120S EP 120S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800382 ER PT J AU Maussion, G Ernst, C Yang, JN Turecki, G AF Maussion, Gilles Ernst, Carl Yang, Jennie Turecki, Gustavo TI Differential DNA Methylation in Frontal Cortex of Suicide Completers SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Maussion, Gilles; Ernst, Carl; Yang, Jennie; Turecki, Gustavo] Douglas Hosp, Mental Hlth Univ Inst, Dept Psychiat, Montreal, PQ, Canada. [Ernst, Carl] Massachusetts Gen Hosp, Ctr Human Genet Res, Dept Neurol, Boston, MA 02114 USA. 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 446 BP 133S EP 133S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800423 ER PT J AU Rabany, L Levkovitz, Y Harel, EV Zangen, A AF Rabany, Liron Levkovitz, Yechiel Harel, Eiran Vadim Zangen, Abraham TI Deep Transcranial Magnetic Stimulation (deep-TMS) Add-on for Treatment of Negative Symptoms and Cognitive Deficits of Schizophrenia: A Feasibility Study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Rabany, Liron; Levkovitz, Yechiel; Harel, Eiran Vadim] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. [Rabany, Liron; Levkovitz, Yechiel; Harel, Eiran Vadim] Shalvata Mental Hlth Care Ctr, Emot Cognit Res Ctr, Hod Hasharon, Israel. [Rabany, Liron] Tel Aviv Univ, Gordon Fac Social Sci, IL-69978 Tel Aviv, Israel. [Levkovitz, Yechiel] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Zangen, Abraham] Weitzman Inst Sci, Dept Neurobiol, Rehovot, Israel. 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 456 BP 136S EP 136S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800433 ER PT J AU Alexander, PR Garrett, CT Fisher, M Vinogradov, S AF Alexander, Phillip R. Garrett, Coleman T. Fisher, Melissa Vinogradov, Sophia TI Insight into Cognition Predicts Response to Cognitive Training in Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Alexander, Phillip R.; Garrett, Coleman T.; Fisher, Melissa; Vinogradov, Sophia] San Francisco VA Med Ctr, Mental Hlth Serv, San Francisco, CA USA. [Alexander, Phillip R.; Garrett, Coleman T.; Fisher, Melissa; Vinogradov, Sophia] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 485 BP 145S EP 145S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800462 ER PT J AU Tyrka, AR Price, LH Marsit, C Walters, C Wilkinson, CW Carpenter, LL AF Tyrka, Audrey R. Price, Lawrence H. Marsit, Carmen Walters, Chris Wilkinson, Charles W. Carpenter, Linda L. TI Epigenetic Modulation of Leukocyte Glucocorticoid Receptor in Healthy Adults: Effects of Childhood Parenting Experiences SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Tyrka, Audrey R.; Price, Lawrence H.; Marsit, Carmen; Carpenter, Linda L.] Brown Med Sch, Providence, RI USA. [Walters, Chris] Butler Hosp, Mood Disorders Res Program, Providence, RI 02906 USA. [Wilkinson, Charles W.] Univ Washington, Dept Psychiat & Behav Sci, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 517 BP 154S EP 155S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800493 ER PT J AU Yao, JK Condray, R Dougherty, GG Keshavan, MS Montrose, DM Matson, WR McEvoy, J Kaddurah-Daouk, R Reddy, RD AF Yao, Jeffrey K. Condray, Ruth Dougherty, George G. Keshavan, Matcheri S. Montrose, Debra M. Matson, Wayne R. McEvoy, Joseph Kaddurah-Daouk, Rima Reddy, Ravinder D. TI Associations between Purine Metabolites and Clinical Symptoms in Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Yao, Jeffrey K.; Condray, Ruth; Dougherty, George G.; Reddy, Ravinder D.] VA Pittsburgh Healthcare Syst, Med Res Serv, Pittsburgh, PA USA. [Yao, Jeffrey K.; Condray, Ruth; Dougherty, George G.; Keshavan, Matcheri S.; Montrose, Debra M.; Reddy, Ravinder D.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Yao, Jeffrey K.] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA. [Keshavan, Matcheri S.] Beth Israel Deaconess Med Ctr 4, Dept Psychiat, Boston, MA USA. [Keshavan, Matcheri S.] Harvard Univ, Boston, MA 02115 USA. [Matson, Wayne R.] Bedford VA Med Ctr, Med Res Serv, Bedford, MA USA. [McEvoy, Joseph; Kaddurah-Daouk, Rima] Duke Univ, Med Ctr, Dept Psychiat, Durham, NC 27710 USA. 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 530 BP 158S EP 158S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800506 ER PT J AU Yao, JK Condray, R Reddy, RD Montrose, DM Keshavan, MS AF Yao, Jeffrey K. Condray, Ruth Reddy, Ravinder D. Montrose, Debra M. Keshavan, Matcheri S. TI Defective Purine Catabolism in High Risk Relatives of Patients with Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Yao, Jeffrey K.; Condray, Ruth; Reddy, Ravinder D.] VA Pittsburgh Healthcare Syst, Med Res Serv, Pittsburgh, PA USA. [Yao, Jeffrey K.; Condray, Ruth; Reddy, Ravinder D.; Montrose, Debra M.; Keshavan, Matcheri S.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Yao, Jeffrey K.] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA. [Keshavan, Matcheri S.] Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02215 USA. [Keshavan, Matcheri S.] Harvard Univ, 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 529 BP 158S EP 158S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800505 ER PT J AU Pousada-Casal, A Thermenos, HW Juelich, RJ Goldstein, JM Gabrieli, SW Makris, N Tsuang, MT Buka, SL Seidman, LJ AF Pousada-Casal, Andrea Thermenos, Heidi W. Juelich, Richard J. Goldstein, Jill M. Gabrieli, Susan W. Makris, Nikos Tsuang, Ming T. Buka, Stephen L. Seidman, Larry J. TI An fMRI Study of Verbal Encoding in Persons with Bipolar Disorder or at Genetic Risk for Bipolar Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Pousada-Casal, Andrea; Thermenos, Heidi W.; Goldstein, Jill M.; Seidman, Larry J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Thermenos, Heidi W.; Juelich, Richard J.; Makris, Nikos; Seidman, Larry J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02215 USA. [Goldstein, Jill M.] Harvard Univ, Sch Med, Div Womens Hlth,Brigham & Womens Hosp, Connors Ctr Womens Hlth & Gender Biol, Boston, MA 02215 USA. [Gabrieli, Susan W.] MIT, Harvard Mit Div Hlth Sci & Technol, Boston, MA USA. [Makris, Nikos] Massachusetts Gen Hosp, Ctr Morphometr Anal, Boston, MA 02114 USA. [Tsuang, Ming T.] Univ Calif San Diego, Ctr Behav Genom, La Jolla, CA 92093 USA. [Buka, Stephen L.] Brown Univ, Providence, RI 02912 USA. RI Buka, Stephen/H-7335-2014 OI Buka, Stephen/0000-0002-8578-9308 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 571 BP 172S EP 172S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800547 ER PT J AU Thermenos, H Whitfield-Gabrieli, S Makris, N Brown, AB Giuliano, AJ Lee, EH Faraone, SV Tsuang, MT Seidman, LJ AF Thermenos, H. Whitfield-Gabrieli, S. Makris, N. Brown, A. B. Giuliano, A. J. Lee, E. H. Faraone, S. V. Tsuang, M. T. Seidman, L. J. TI Default Network Activity Differentiates Adolescent and Young Adult Relatives of Persons With Bipolar Disorder and Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Thermenos, H.; Giuliano, A. J.; Lee, E. H.; Seidman, L. J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Massachusetts Mental Hlth Ctr,Div Publ Psychiat, Boston, MA 02215 USA. [Thermenos, H.; Makris, N.; Seidman, L. J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Whitfield-Gabrieli, S.; Brown, A. B.] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. [Whitfield-Gabrieli, S.; Brown, A. B.] MIT, Poitras Ctr Affect Disorders Res, Cambridge, MA 02139 USA. [Makris, N.] Massachusetts Gen Hosp, Ctr Morphometr Anal, Boston, MA 02114 USA. [Brown, A. B.] Harvard Univ, Sch Med, MIT, Massachusetts Gen Hosp,Martinos Ctr Biomed Imagin, Charlestown, MA USA. [Faraone, S. V.] SUNY Upstate Med Univ, Syracuse, NY USA. [Tsuang, M. T.] Univ Calif San Diego, Ctr Behav Genom, La Jolla, CA 92093 USA. 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 587 BP 177S EP 177S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800563 ER PT J AU Houston, JP Kohler, J Ostbye, KM Heinloth, AN Perlis, R AF Houston, John P. Kohler, Jared Ostbye, Katherine M. Heinloth, Alexandra N. Perlis, Roy TI Association of Additional Common Variants in COMT with Duloxetine Efficacy in Patients with Major Depressive Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Houston, John P.] Lilly USA LLC, Neurosci, Indianapolis, IN USA. [Kohler, Jared; Ostbye, Katherine M.] BioStat Solut Inc, Genom, Mt Airy, MD USA. [Heinloth, Alexandra N.] I3 Statprobe, Sci Commun, Ann Arbor, MI USA. [Perlis, Roy] Massachusetts Gen Hosp, Dept Psychiat, 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 610 BP 184S EP 184S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800586 ER PT J AU Bartzokis, G Lu, PH Raven, EP Amar, CP DeTore, NR Altshuler, LL Mintz, J Ventura, J Casaus, LR Luo, JS Subotnik, KL Nuechterlein, KH AF Bartzokis, George Lu, Po H. Raven, Erika P. Amar, Chetan P. DeTore, Nicole R. Altshuler, Lori L. Mintz, Jim Ventura, Joseph Casaus, Laurie R. Luo, John S. Subotnik, Kenneth L. Nuechterlein, Keith H. TI Abnormal Trajectory of Intracortical Myelination in Schizophrenia Implicates White Matter in Treatment Response and Outcomes SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Bartzokis, George; Lu, Po H.; Raven, Erika P.; Amar, Chetan P.; DeTore, Nicole R.; Altshuler, Lori L.; Ventura, Joseph; Casaus, Laurie R.; Luo, John S.; Subotnik, Kenneth L.; Nuechterlein, Keith H.] Univ Calif Los Angeles, Los Angeles, CA USA. [Lu, Po H.] Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. [Mintz, Jim] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. RI Bartzokis, George/K-2409-2013; Mintz, Jim/N-7385-2014 OI Mintz, Jim/0000-0002-8299-5851 NR 0 TC 3 Z9 3 U1 0 U2 2 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 MAY 1 PY 2011 VL 69 IS 9 SU S MA 611 BP 185S EP 185S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800587 ER PT J AU Levenson, JM Gibson, HE Richardson, KA Ghorashi, S Whitford, TJ Mears, RP Spencer, KM Gerber, D Levin, ME AF Levenson, Jonathan M. Gibson, Helen E. Richardson, Kristen A. Ghorashi, Shahab Whitford, Thomas J. Mears, Ryan P. Spencer, Kevin M. Gerber, David Levin, Margaret E. TI Gamma Oscillation Correlates of Cognition Shared Between Mouse and Man SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Levenson, Jonathan M.; Gibson, Helen E.; Richardson, Kristen A.; Gerber, David; Levin, Margaret E.] Galenea Corp, Target Validat, Cambridge, MA USA. [Ghorashi, Shahab; Whitford, Thomas J.; Mears, Ryan P.; Spencer, Kevin M.] VA Boston Healthcare, Neural Dynam Lab, Boston, MA USA. [Ghorashi, Shahab; Whitford, Thomas J.; Mears, Ryan P.; Spencer, Kevin M.] Harvard Univ, Sch Med, Boston, MA 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 631 BP 191S EP 191S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800607 ER PT J AU Simon, N AF Simon, Naomi TI Theory and Evidence for Telomere Shortening in Depression Modeled as a Chronic Stress-related Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Simon, Naomi] Harvard Univ, Massachusetts Gen Hosp, 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 644 BP 195S EP 195S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800620 ER PT J AU Holtzheimer, PE Dougherty, DD Schlaepfer, T Mayberg, H AF Holtzheimer, Paul E. Dougherty, Darin D. Schlaepfer, Thomas Mayberg, Helen TI Acute Effects of Deep Brain Stimulation for Treatment-Resistant Depression: Using Variability Across Targets to Inform on the Neurobiology of Mood Regulation SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Holtzheimer, Paul E.; Mayberg, Helen] Emory Univ, Atlanta, GA 30322 USA. [Dougherty, Darin D.] Massachusetts Gen Hosp, Charlestown, MA USA. [Schlaepfer, Thomas] Univ Bonn, D-5300 Bonn, Germany. RI Holtzheimer, Paul/B-6212-2015 OI Holtzheimer, Paul/0000-0002-3552-3296 NR 0 TC 1 Z9 1 U1 0 U2 1 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 MAY 1 PY 2011 VL 69 IS 9 SU S MA 668 BP 202S EP 203S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800644 ER PT J AU Siever, LJ AF Siever, Larry J. TI 5-HT2b Alleles, Frontal Activation, and Aggressive Behavior SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Siever, Larry J.] James J Peters VAMC, Mt Sinai Sch Med, New York, NY 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 667 BP 202S EP 202S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800643 ER PT J AU Xie, PX Kranzler, HR Krauthammer, M Oslin, D Anton, RF Zhao, HY Farrer, LA Gelernter, J AF Xie, Pingxing Kranzler, Henry R. Krauthammer, Michael Oslin, David Anton, Raymond F. Zhao, Hongyu Farrer, Lindsay A. Gelernter, Joel TI Protective Effect of Rare Nonsynonymous Variants In the Alpha-4 Subunit of Nicotinic Acetylcholine Receptor Gene (chrna4) for Nicotine Dependence SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Xie, Pingxing] Yale Univ, Dept Genet, West Haven, CT USA. [Xie, Pingxing; Gelernter, Joel] VA CT Healthcare Ctr, West Haven, CT USA. [Kranzler, Henry R.; Oslin, David] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Kranzler, Henry R.; Oslin, David] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Krauthammer, Michael] Yale Univ, Dept Pathol, New Haven, CT USA. [Anton, Raymond F.] Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. [Zhao, Hongyu] Yale Univ, Dept Genet, New Haven, CT USA. [Farrer, Lindsay A.] Boston Univ, Dept Med, Boston, MA 02215 USA. [Farrer, Lindsay A.] Boston Univ, Dept Neurol, Boston, MA 02215 USA. [Farrer, Lindsay A.] Boston Univ, Dept Genet & Genom, Boston, MA 02215 USA. [Farrer, Lindsay A.] Boston Univ, Dept Epidemiol & Biostat, Boston, MA 02215 USA. [Gelernter, Joel] Yale Univ, Dept Genet & Psychiat, West Haven, CT 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 671 BP 203S EP 204S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800647 ER PT J AU Siever, LJ AF Siever, Larry J. TI Schizophrenia Susceptibility Genes and Intermediate Phenotypes in Schizotypal Personality Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Siever, Larry J.] James J Peters VAMC, Mt Sinai Sch Med, New York, NY 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 694 BP 209S EP 209S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800663 ER PT J AU Raskind, MA Redila, VA Olson, VG AF Raskind, Murray A. Redila, Van A. Olson, Valerie G. TI Prazosin Blocks Development of Ethanol, Morphine and Cocaine Conditioned Place Preference in Mice SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Raskind, Murray A.; Olson, Valerie G.] VA Puget Sound Hlth Care Syst, Mental Hlth Serv, Seattle, WA USA. [Redila, Van A.] Univ Washington, Dept Psychol, Seattle, WA 98195 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 745 BP 223S EP 223S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800706 ER PT J AU Frid, SA Pavlidis, P Dracheya, S Byne, W AF Frid, Simon A. Pavlidis, Paul Dracheya, Stella Byne, William TI Differential Gene Expression in Schizophrenia and Bipolar Disorder in the Corpus Collosum SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Frid, Simon A.; Dracheya, Stella; Byne, William] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Pavlidis, Paul] Univ British Columbia, Dept Psychiat, Vancouver, BC, Canada. [Dracheya, Stella; Byne, William] Bronx Vet Affairs Med Ctr, Dept Psychiat, New York, NY USA. RI Pavlidis, Paul/H-8406-2013 OI Pavlidis, Paul/0000-0002-0426-5028 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 756 BP 226S EP 226S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800717 ER PT J AU Ghorashi, S Spencer, KM AF Ghorashi, Shahab Spencer, Kevin M. TI Oscillatory Correlates of Face Gestalt Processing in Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Ghorashi, Shahab; Spencer, Kevin M.] VA Boston Healthcare Syst, Boston, MA USA. [Ghorashi, Shahab; Spencer, Kevin M.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 773 BP 231S EP 231S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800734 ER PT J AU Kuperberg, GR Eddy, M AF Kuperberg, Gina R. Eddy, Marianna TI Seeing The Wood for the Trees: Feedforward Visual Deficits Do Not Fully Explain Semantic Deficits in Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Kuperberg, Gina R.] Massachusetts Gen Hosp, Charlestown, MA USA. [Kuperberg, Gina R.] Tufts Univ, Charlestown, MA USA. [Eddy, Marianna] MIT, Cambridge, MA 02139 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 781 BP 233S EP 234S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800742 ER PT J AU Mears, RP Spencer, KM AF Mears, Ryan P. Spencer, Kevin M. TI Auditory Cortex Neuroplasticity in Schizophrenia: An ERP Assessment of Stimulus-Specific Plasticity SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Mears, Ryan P.; Spencer, Kevin M.] VA Boston Healthcare System, Boston, MA USA. [Mears, Ryan P.; Spencer, Kevin M.] Harvard Univ, Dept Psychiat, Sch Med, Brockton, MA 02401 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 783 BP 234S EP 234S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800744 ER PT J AU Radant, AD Braff, D Calkins, M Cadenhead, K Dobie, D Freedman, R Green, M Greenwood, T Gur, R Gur, R Horan, W Light, G Meichle, S Millard, S Olincy, A Nuechterlein, K Seidman, L Siever, L Silverman, J Stone, W Sprock, J Swerdlow, N Tsuang, M Turetsky, B Tsuang, D AF Radant, Allen D. Braff, David Calkins, Monica Cadenhead, Kristin Dobie, Dorcas Freedman, Robert Green, Michael Greenwood, Tiffany Gur, Raquel Gur, Ruben Horan, William Light, Gregory Meichle, Sean Millard, Steve Olincy, Ann Nuechterlein, Keith Seidman, Larry Siever, Larry Silverman, Jeremy Stone, William Sprock, Joyce Swerdlow, Neal Tsuang, Ming Turetsky, Bruce Tsuang, Debby TI Influence of Duration of Schizophrenia on Antisaccade Performance SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Radant, Allen D.; Dobie, Dorcas; Meichle, Sean; Millard, Steve; Tsuang, Debby] Puget Sound Hlth Care Syst, Vet Adm, Educ & Clin Ctr, Mental Illness Res,Seattle Div, Seattle, WA USA. [Radant, Allen D.; Meichle, Sean; Millard, Steve; Tsuang, Debby] Univ Washington, Seattle, WA 98195 USA. [Braff, David; Cadenhead, Kristin; Greenwood, Tiffany; Sprock, Joyce; Swerdlow, Neal; Tsuang, Ming] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Calkins, Monica; Gur, Raquel; Gur, Ruben; Turetsky, Bruce] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Freedman, Robert; Olincy, Ann] Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA. [Green, Michael; Horan, William; Nuechterlein, Keith] Univ Calif Los Angeles, Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA USA. [Green, Michael; Horan, William; Nuechterlein, Keith] Greater Angeles Hlth Care Syst, Vet Adm, Los Angeles Div, Los Angeles, CA USA. [Seidman, Larry; Stone, William] Harvard Univ, Sch Med, Dept Psychiat, MA Mental Hlth Ctr Publ Psychiat Div,Beth Israel, Boston, MA 02115 USA. [Siever, Larry; Silverman, Jeremy] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Siever, Larry; Silverman, Jeremy] James J Peters VA Med Ctr, Mental Illness Res Educ & Clin Ctr, New York, NY 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 791 BP 237S EP 237S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800752 ER PT J AU Wiste, A McGrath, LM Lee, PH Smoller, JW AF Wiste, Anna McGrath, Lauren M. Lee, Phil H. Smoller, Jordan W. TI Genome-Wide Association Study of Smoking Behavior Among Schizophrenics: Preliminary Results SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Wiste, Anna; Smoller, Jordan W.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Wiste, Anna; McGrath, Lauren M.; Lee, Phil H.; Smoller, Jordan W.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, Boston, MA 02114 USA. [Wiste, Anna; McGrath, Lauren M.; Lee, Phil H.; Smoller, Jordan W.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Boston, MA USA. 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 834 BP 250S EP 251S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800795 ER PT J AU Goldstein, KE Alloy, LB Drabick, DAG New, AS Siever, LJ Hazlett, EA AF Goldstein, Kim E. Alloy, Lauren B. Drabick, Deborah A. G. New, Antonia S. Siever, Larry J. Hazlett, Erin A. TI Cingulum Integrity in Schizotypal Personality Disorder and Borderline Personality Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Goldstein, Kim E.; Alloy, Lauren B.; Drabick, Deborah A. G.] Temple Univ, Philadelphia, PA 19122 USA. [New, Antonia S.; Siever, Larry J.; Hazlett, Erin A.] Mt Sinai Sch Med, New York, NY USA. [New, Antonia S.; Siever, Larry J.; Hazlett, Erin A.] James J Peters VAMC, Mental Illness Res & Clin Ctr MIRECC, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 1 U2 3 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 MAY 1 PY 2011 VL 69 IS 9 SU S MA 851 BP 256S EP 256S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800812 ER PT J AU Hazlett, EA Goodman, M Carpenter, D Avedon, J Goldstein, KE New, AS Siever, LJ AF Hazlett, Erin A. Goodman, Marianne Carpenter, David Avedon, Jennifer Goldstein, Kim E. New, Antonia S. Siever, Larry J. TI Exaggerated Amygdala and Startle Response Predicts Positive Dialectical Behavior Therapy Outcome in Borderline Patients SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Hazlett, Erin A.; Goodman, Marianne; Carpenter, David; Avedon, Jennifer; Goldstein, Kim E.; New, Antonia S.; Siever, Larry J.] Mt Sinai Sch Med, New York, NY USA. [Hazlett, Erin A.; Goodman, Marianne; New, Antonia S.; Siever, Larry J.] James J Peters VAMC, Mental Illness Res Educ & Clin Ctr, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 2 U2 7 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 MAY 1 PY 2011 VL 69 IS 9 SU S MA 852 BP 256S EP 256S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800813 ER PT J AU Levitt, J Pelavin, PE Alvarado, JL McCarley, RW Shenton, ME AF Levitt, James Pelavin, Paula E. Alvarado, Jorge L. McCarley, Robert W. Shenton, Martha E. TI Regionally Selective Differential Effects of Atypical Neuroleptic Medication on Dorsal but not Ventral Striatum in Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Levitt, James; McCarley, Robert W.; Shenton, Martha E.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Brockton, MA 02401 USA. [Levitt, James; Pelavin, Paula E.; Alvarado, Jorge L.; Shenton, Martha E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Psychiat Neuroimaging Lab, Brockton, MA 02401 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 870 BP 262S EP 263S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800831 ER PT J AU Seidman, LJ Thermenos, HW Juelich, R Valera, E Brown, AB Huang, S Salwen, KK Makris, N Whitfield-Gabrieli, S Biederman, J Faraone, SV Tsuang, MT AF Seidman, Larry J. Thermenos, Heidi W. Juelich, Richard Valera, Eve Brown, Ariel B. Huang, Samantha Salwen, Kathryn K. Makris, Nikos Whitfield-Gabrieli, Susan Biederman, Joseph Faraone, Stephen V. Tsuang, Ming T. TI Distinct Pattern of Brain Functioning Underlies Working Memory in ADHD and Individuals at Familial Risk for Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Seidman, Larry J.; Thermenos, Heidi W.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med,Dept Psychiat, Massachusetts Mental Hlth Ctr,Div Publ Psychiat, Boston, MA 02215 USA. [Seidman, Larry J.; Thermenos, Heidi W.; Brown, Ariel B.] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Seidman, Larry J.; Thermenos, Heidi W.; Juelich, Richard; Valera, Eve; Brown, Ariel B.; Huang, Samantha; Salwen, Kathryn K.; Makris, Nikos; Biederman, Joseph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. [Brown, Ariel B.; Makris, Nikos; Whitfield-Gabrieli, Susan] Harvard Mit Div Hlth Sci & Technol, Massachusetts Inst Technol, Dept Brain & Cognit Sci, Boston, MA USA. [Makris, Nikos] Massachusetts Gen Hosp, Dept Neurol, Ctr Morphometr Anal, Boston, MA 02114 USA. [Makris, Nikos] Massachusetts Gen Hosp, Dept Radiol, Ctr Morphometr Anal, Boston, MA 02114 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. [Tsuang, Ming T.] Univ Calif San Diego, Dept Psychiat, Ctr Behav Genom, La Jolla, CA 92093 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 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 MAY 1 PY 2011 VL 69 IS 9 SU S MA 880 BP 266S EP 267S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800841 ER PT J AU Seidman, LJ Goldstein, JM Cherkerzian, S Agnew-Blais, J Tsuang, MT Buka, S AF Seidman, Larry J. Goldstein, Jill M. Cherkerzian, Sara Agnew-Blais, Jessica Tsuang, Ming T. Buka, Stephen TI Was Kraepelin Right? A 30 Year Follow-Up of Neurocognitive Deterioration in Schizophrenia vs Bipolar Psychosis SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Seidman, Larry J.; Goldstein, Jill M.; Tsuang, Ming T.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Psychiat, Boston, MA 02215 USA. [Seidman, Larry J.; Goldstein, Jill M.; Tsuang, Ming T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. [Goldstein, Jill M.; Cherkerzian, Sara] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Agnew-Blais, Jessica] Harvard Univ, Sch Publ Hlth, Dept Psychiat, Boston, MA 02115 USA. [Tsuang, Ming T.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Buka, Stephen] Brown Univ, Dept Psychiat, Providence, RI 02912 USA. RI Buka, Stephen/H-7335-2014; Agnew-Blais, Jessica/L-9236-2015 OI Buka, Stephen/0000-0002-8578-9308; Agnew-Blais, Jessica/0000-0002-0755-6867 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 879 BP 266S EP 266S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800840 ER PT J AU Fryer, SL Watson, TD Jorgensen, KW Yetter, EJ Krystal, JH Mathalon, DH AF Fryer, Susanna L. Watson, Todd D. Jorgensen, Kasper W. Yetter, Elizabeth J. Krystal, John H. Mathalon, Daniel H. TI Cue Reactivity across Stages of Alcohol Dependence: FMRI Reveals Evidence of Altered Attentional Functioning SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Fryer, Susanna L.; Jorgensen, Kasper W.; Yetter, Elizabeth J.; Mathalon, Daniel H.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Fryer, Susanna L.; Jorgensen, Kasper W.; Yetter, Elizabeth J.; Mathalon, Daniel H.] San Francisco VA Med Ctr, Mental Hlth Serv, San Francisco, CA USA. [Watson, Todd D.] Lewis & Clark Coll, Portland, OR 97219 USA. [Krystal, John H.; Mathalon, Daniel H.] Yale Univ, New Haven, CT 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 897 BP 272S EP 272S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800858 ER PT J AU Rabany, L Weiser, M Levkovitz, Y AF Rabany, Liron Weiser, Mark Levkovitz, Yechiel TI Assessment of Depression in Negative Symptoms of Schizophrenia: Revising the Structure of the Calgary Depression Scale for Schizophrenia (CDSS) SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Rabany, Liron; Levkovitz, Yechiel] Shalvata Mental Hlth Ctr, Emot Cognit Res Ctr, Hod Hasharon, Israel. [Rabany, Liron] Tel Aviv Univ, Gordon Fac Social Sci, IL-69978 Tel Aviv, Israel. [Rabany, Liron; Weiser, Mark; Levkovitz, Yechiel] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. [Weiser, Mark] Chaim Sheba Med Ctr, Dept Psychiat, IL-52621 Tel Hashomer, Israel. [Levkovitz, Yechiel] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 915 BP 278S EP 278S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800876 ER PT J AU Dutra, SJ Stoeckel, LE Carlini, SV Pizzagalli, DA Evins, AE AF Dutra, Sunny J. Stoeckel, Luke E. Carlini, Sara V. Pizzagalli, Diego A. Evins, A. Eden TI Varenicline as a Smoking Cessation Aid in Schizophrenia Patients: Effects on Smoking Behavior and Reward Sensitivity SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Dutra, Sunny J.] Yale Univ, New Haven, CT USA. [Stoeckel, Luke E.; Carlini, Sara V.; Evins, A. Eden] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pizzagalli, Diego A.] McLean Hosp, Belmont, MA 02178 USA. [Pizzagalli, Diego A.; Evins, A. Eden] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 1 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 MAY 1 PY 2011 VL 69 IS 9 SU S MA 921 BP 280S EP 280S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800882 ER PT J AU Bashyal, R Malchau, H Nimkin, K Holmes, LB AF Bashyal, R. Malchau, H. Nimkin, K. Holmes, L. B. TI Malformed Pelvis, Hip Dysplasia, and Genital Anomalies: An Association SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Bashyal, R.; Malchau, H.; Nimkin, K.; Holmes, L. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2011 VL 91 IS 5 SI SI BP 342 EP 342 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 762QQ UT WOS:000290494900068 ER PT J AU Thomas, EG Westgate, MN Holmes, LB AF Thomas, E. G. Westgate, M-N Holmes, L. B. TI The Effect of Elective Terminations for Fetal Anomalies on Spectrum of Birth Defects in Liveborn Infants SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Thomas, E. G.; Westgate, M-N; Holmes, L. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Thomas, E. G.; Westgate, M-N; Holmes, L. B.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2011 VL 91 IS 5 SI SI BP 354 EP 354 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 762QQ UT WOS:000290494900088 ER PT J AU Han, TH Martyn, JAJ AF Han, T. -H. Martyn, J. A. J. TI Neuromuscular pharmacodynamics of mivacurium in adults with major burns SO BRITISH JOURNAL OF ANAESTHESIA LA English DT Article DE neuromuscular relaxants, mivacurium; pharmacodynamics; trauma, burns ID DUCHENNE MUSCULAR-DYSTROPHY; ACETYLCHOLINE-RECEPTORS; THERMAL-INJURY; ATRACURIUM; PHARMACOKINETICS; ADOLESCENTS; CHILDREN; CHLORIDE; THERAPY; PATIENT AB Background. Mivacurium is metabolized by plasma pseudocholinesterase (PChE) enzyme, which is decreased in burns. We tested whether the decreased metabolism of mivacurium due to decreased PChE activity can overcome the pharmacodynamic resistance to non-depolarizing relaxants previously seen in major burns. Methods. Thirty adults with 35 (13)% [mean (SD)] burn were studied at 5-91 post-burn days and 31 non-burns matched controls. Mivacurium 0.2 mg kg(-1) was administered as a single bolus. Neuromuscular block was monitored with single-twitch response using TOF-Watch (TM). Onset time (drug administration to maximal twitch suppression) and spontaneous recovery were measured. Results. Onset time was significantly prolonged in burns when compared with non-burns (115 vs 90 s; P < 0.001). The PChE levels were lower in burns [1432 (916) vs 2866 (731) IU litre 21; P < 0.001] and the neuromuscular recovery to 50% of baseline twitch height was prolonged in burns (41 vs 26 min; P < 0.001). There was a significant correlation between PChE and time to 50% recovery for the whole group together (r= -20.6; P < 0.001). The dibucaine numbers were not different. Conclusions. The prolonged onset time suggests resistance to neuromuscular effects, whereas the prolonged recovery suggests increased sensitivity. This divergent response can be explained by qualitative and quantitative changes in acetylcholine receptor expression causing resistance and decreased PChE activity causing sensitivity. Despite using a relatively large dose of mivacurium (0.2 mg kg(-1)) in the presence of decreased PChE levels, this did not overcome the resistance resulting from up-regulated receptors. C1 [Han, T. -H.] Univ Iowa Hosp & Clin, Roy J & Lucille A Carver Coll Med, Dept Anesthesia JCP 6505 3, Iowa City, IA 52242 USA. [Martyn, J. A. J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesiol Crit Care & Pain Med, Boston, MA 02114 USA. [Martyn, J. A. J.] Shriners Hosp Children, Boston, MA 02114 USA. RP Han, TH (reprint author), Univ Iowa Hosp & Clin, Roy J & Lucille A Carver Coll Med, Dept Anesthesia JCP 6505 3, 200 Hawkins Dr, Iowa City, IA 52242 USA. EM anthony-han@uiowa.edu FU Korean Health Industry Development Institute, Seoul, Korea [A06-0093-B41104-06N1-00040B]; National Institute of Health, Bethesda, MD, USA [GM 05882]; Shriners Hospital Research Philanthropy FX T.-H. H. was supported in part by grants from the Korean Health Industry Development Institute, Seoul, Korea A06-0093-B41104-06N1-00040B). J.A.J.M. was supported in part by a grant from the National Institute of Health, Bethesda, MD, USA (GM 05882), and grants from Shriners Hospital Research Philanthropy. NR 25 TC 1 Z9 1 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0007-0912 J9 BRIT J ANAESTH JI Br. J. Anaesth. PD MAY PY 2011 VL 106 IS 5 BP 675 EP 679 DI 10.1093/bja/aer023 PG 5 WC Anesthesiology SC Anesthesiology GA 763MP UT WOS:000290562800008 PM 21354998 ER PT J AU Salemi, VMC Rochitte, CE Shiozaki, AA Andrade, JM Parga, JR de Avila, LF Benvenuti, LA Cestari, IN Picard, MH Kim, RJ Mady, C AF Salemi, Vera M. C. Rochitte, Carlos E. Shiozaki, Afonso A. Andrade, Joalbo M. Parga, Jose R. de Avila, Luiz F. Benvenuti, Luiz A. Cestari, Ismar N. Picard, Michael H. Kim, Raymond J. Mady, Charles TI Late Gadolinium Enhancement Magnetic Resonance Imaging in the Diagnosis and Prognosis of Endomyocardial Fibrosis Patients SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Article DE myocardial cardiomyopathy disease; endomyocardial fibrosis; restrictive cardiomyopathy; heart failure; magnetic resonance imaging; gadolinium; prognosis ID DELAYED-ENHANCEMENT; IN-VIVO; DISEASE; CARDIOMYOPATHIES; VISUALIZATION; THROMBI; MARKER AB Background-Endocardial fibrous tissue (FT) deposition is a hallmark of endomyocardial fibrosis (EMF). Echocardiography is a first-line and the standard technique for the diagnosis of this disease. Although late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) allows FT characterization, its role in the diagnosis and prognosis of EMF has not been investigated. Methods and Results-Thirty-six patients (29 women; age, 54 +/- 12 years) with EMF diagnosis after clinical evaluation and comprehensive 2-dimensional Doppler echocardiography underwent cine-CMR for assessing ventricular volumes, ejection fraction and mass, and LGE-CMR for FT characterization and quantification. Indexed FT volume (FT/body surface area) was calculated after planimetry of the 8 to 12 slices obtained in the short-axis view at end-diastole (mL/m(2)). Surgical resection of FT was performed in 16 patients. In all patients, areas of LGE were confined to the endocardium, frequently as a continuous streak from the inflow tract extending to the apex, where it was usually most prominent. There was a relation between increased FT/body surface area and worse New York Heart Association functional class and with increased probability of surgery (P<0.05). The histopathologic examination of resected FT showed typical features of EMF with extensive endocardial fibrous thickening, proliferation of small vessels, and scarce inflammatory infiltrate. In multivariate analysis, the patients with FT/body surface area >19 mL/m(2) had an increased mortality rate, with a relative risk of 10.8. Conclusions-Our study provides evidence that LGE-CMR is useful in the diagnosis and prognosis of EMF through quantification of the typical pattern of FT deposition. (Circ Cardiovasc Imaging. 2011;4:304-311.) C1 [Salemi, Vera M. C.; Mady, Charles] Univ Sao Paulo, Heart Inst InCor, Fac Med, Cardiomyopathy Unit, Sao Paulo, Brazil. [Rochitte, Carlos E.; Shiozaki, Afonso A.; Andrade, Joalbo M.; Parga, Jose R.; de Avila, Luiz F.] Univ Sao Paulo, Heart Inst InCor, Fac Med, Magnet Resonance Sect, Sao Paulo, Brazil. [Benvenuti, Luiz A.] Univ Sao Paulo, Heart Inst InCor, Fac Med, Pathol Lab, Sao Paulo, Brazil. [Cestari, Ismar N.] Univ Sao Paulo, Heart Inst InCor, Fac Med, Biomed Technol Ctr, Sao Paulo, Brazil. [Picard, Michael H.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Picard, Michael H.] Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. [Picard, Michael H.] Harvard Univ, Sch Med, Boston, MA USA. [Kim, Raymond J.] Duke Univ, Med Ctr, Duke Cardiovasc Magnet Resonance Ctr, Dept Med, Durham, NC USA. [Kim, Raymond J.] Duke Univ, Med Ctr, Dept Radiol, Durham, NC USA. RP Salemi, VMC (reprint author), Av Jandira 185 Apt 41B Indianopolis, BR-04080000 Sao Paulo, Brazil. EM verasalemi@uol.com.br RI Cestari, Ismar /B-7286-2012; Kim, Raymond/B-1426-2008; Benvenuti, Luiz/C-6614-2014; Mady, Charles/C-8870-2012; Salemi, Vera/C-9104-2013; OI Mady, Charles/0000-0002-8838-199X; Salemi, Vera/0000-0002-7152-1810; Picard, Michael/0000-0002-9264-3243 NR 26 TC 23 Z9 24 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-9651 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD MAY PY 2011 VL 4 IS 3 BP 304 EP U163 DI 10.1161/CIRCIMAGING.110.950675 PG 9 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 765NU UT WOS:000290715800016 PM 21415124 ER PT J AU Truong, QA Murphy, SA McCabe, CH Armani, A Cannon, CP AF Truong, Quynh A. Murphy, Sabina A. McCabe, Carolyn H. Armani, Annemarie Cannon, Christopher P. CA TIMI Study Grp TI Benefit of Intensive Statin Therapy in Women Results From PROVE IT-TIMI 22 SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE hydroxymethylglutaryl-CoA reductase inhibitors; sex; acute coronary syndrome; prognosis; secondary prevention ID ACUTE CORONARY SYNDROMES; C-REACTIVE PROTEIN; CARDIOVASCULAR EVENTS; HEART-DISEASE; PRIMARY-PREVENTION; MYOCARDIAL-INFARCTION; CHOLESTEROL LEVELS; CONTROLLED TRIAL; PRAVASTATIN; ATORVASTATIN AB Background-Despite the known benefit of intensive statin therapy for reducing future cardiovascular events, its effectiveness in women has been questioned by some. Methods and Results-In the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) trial, 911 (21.9%) women and 3251 (78.1%) men were randomized to intensive statin (atorvastatin 80 mg) versus standard therapy (pravastatin 40 mg) therapy for a median duration of 2.1 years. The primary end point was death, myocardial infarction, unstable angina; revascularization (occurring after 30 days); or stroke. Safety end points included elevations in liver function tests, creatine kinase, and myalgias/myositis. Women had a reduction in low-density lipoprotein (LDL) of 42.8% from baseline at 30 days (to a median of 60 mg/dL) in the intensive therapy arm, with 88.8% reaching the LDL goal of <100 mg/dL and 65.0% of <70 mg/dL, compared with a 16.8% reduction in LDL (to a median of 88 mg/dL) in the standard therapy arm. Women receiving intensive statin therapy had a significant 25% relative reduction over standard dose (hazard ratio, 0.75; 95% CI, 0.57 to 0.99; P=0.04) for the primary composite end point compared with a 14% reduction for men (hazard ratio, 0.86; 95% CI, 0.75 to 0.99; P=0.04; P-interaction, 0.38). No differences were observed between sexes for safety (all P-interaction >= 0.11). Conclusions-This trial provides evidence that both women and men derived benefit from intensive statin therapy after acute coronary syndrome, and thus, sex should not be a factor in determining who should be treated with intensive statin therapy. C1 [Murphy, Sabina A.; McCabe, Carolyn H.; Armani, Annemarie; Cannon, Christopher P.] Harvard Univ, Sch Med, Brigham & Womens Hosp, TIMI Study Grp,Cardiovasc Div, Boston, MA 02115 USA. [Truong, Quynh A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02115 USA. RP Cannon, CP (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, TIMI Study Grp,Cardiovasc Div, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM cpcannon@partners.org FU Bristol Myers Squibb, Princeton, NJ; Sankyo, Parsippany, NJ; National Institutes of Health [L30HL093896, K23HL098370]; AstraZeneca; Bristol-Myers Squibb/Sanofi Partnership; GlaxoSmithKline; Merck; Accumetrics; Intekrin Therapeutics; Takeda FX The trial was funded by Bristol Myers Squibb, Princeton, NJ, and Sankyo, Parsippany, NJ.; Dr Truong received research grant support from National Institutes of Health grants L30HL093896 and K23HL098370. Ms McCabe received research grant support from AstraZeneca, Bristol-Myers Squibb/Sanofi Partnership, GlaxoSmithKline, and Merck. Dr Cannon received research grant support from Accumetrics, AstraZeneca, GlaxoSmithKline, Merck, Intekrin Therapeutics, and Takeda; has served on advisory boards for Bristol-Myers Squibb/Sanofi-Aventis and Novartis (but funds donated to charity); and reports having equity ownership in Automedics Medical Systems. NR 34 TC 30 Z9 32 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-7705 EI 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD MAY PY 2011 VL 4 IS 3 BP 328 EP 336 DI 10.1161/CIRCOUTCOMES.110.957720 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 765NX UT WOS:000290716100014 PM 21487089 ER PT J AU Attumi, TA Graham, DY AF Attumi, Taraq A. Graham, David Y. TI Follow-up Testing After Treatment of Helicobacter Pylori Infections: Cautions, Caveats, and Recommendations SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Editorial Material ID STOOL ANTIGEN TEST; UREA BREATH TESTS; DIAGNOSIS; GASTRITIS; ANTRUM; CORPUS C1 [Attumi, Taraq A.; Graham, David Y.] Baylor Coll Med, Dept Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Attumi, TA (reprint author), Baylor Coll Med, Dept Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. FU NCI NIH HHS [CA116845]; NIDDK NIH HHS [DK56338, DK067366] NR 13 TC 10 Z9 10 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 MAY PY 2011 VL 9 IS 5 BP 373 EP 375 DI 10.1016/j.cgh.2010.12.025 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 764TV UT WOS:000290657200010 PM 21195791 ER PT J AU LiVolsi, VA Abrosimov, AA Bogdanova, T Fadda, G Hunt, JL Ito, M Rosai, J Thomas, GA Williams, ED AF LiVolsi, V. A. Abrosimov, A. A. Bogdanova, T. Fadda, G. Hunt, J. L. Ito, M. Rosai, J. Thomas, G. A. Williams, E. D. TI The Chernobyl Thyroid Cancer Experience: Pathology SO CLINICAL ONCOLOGY LA English DT Article DE Iodine; papillary cancer; radiation; subtypes; thyroid cancer ID BIOLOGIC BEHAVIOR; CARCINOMA; PAPILLARY; ACCIDENT; CHILDREN; GLAND; CHILDHOOD; PROGNOSIS; EXPOSURE; DISEASES AB The Chernobyl accident was followed by a large increase in the incidence of thyroid carcinoma in the areas exposed to high levels of fallout. The Chernobyl Tumor Bank was set up in 1998 to make tumours available for study internationally, and a pathology panel reviewed all the tumours and established an agreed diagnosis. The thyroid tumours that were discovered after the Chernobyl nuclear accident were virtually all (95%) of the papillary carcinoma type. Rare examples of other tumour types were identified. Within the papillary group, several subtypes were noted, including classical or usual type, follicular variant, solid variant and mixed patterns Diffuse sclerosis variant, cribriform/morular type and Warthin-like variant were rare. No tall cell or columnar cell variants were identified. The tumours examined by the Pathology Panel of the Chernobyl Tumor Bank constitute a large representative sample (estimated at about 50%) of the tumours that developed in this population. This overview describes the method adopted by the panel and the different diagnostic categories adopted; illustrates the pathology of these neoplasms; compares the pathological characteristics of the early lesions with those identified after long latency periods and the institution of screening programmes and outlines the possible associated causes for the various morphological patterns seen. (C) 2011 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved. C1 [LiVolsi, V. A.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Abrosimov, A. A.] Fed State Inst, Med Radiol Res Ctr, Obninsk, Kaluga Region, Russia. [Bogdanova, T.] Ukraine Acad Med Sci, Inst Endocrinol & Metab, Kiev, Ukraine. [Fadda, G.] Univ Cattolica Sacro Cuore, Div Anat Pathol, I-00168 Rome, Italy. [Hunt, J. L.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Ito, M.] Natl Nagasaki Med Ctr, Res Lab, Omura, Japan. [Rosai, J.] Ctr Diagnost Italiano CDI, Ctr Consulenze Anat Patol Oncol, Milan, Italy. [Thomas, G. A.] Hammersmith Hosp, Div Surg & Canc, London, England. [Williams, E. D.] Strangeways Res Lab, Thyroid Carcinogenesis Res Unit, Cambridge CB1 4RN, England. RP LiVolsi, VA (reprint author), Univ Penn, Dept Pathol & Lab Med, 3400 Spruce St, Philadelphia, PA 19104 USA. EM linus@mail.med.upenn.edu RI Abrosimov, A/H-3382-2015 OI Abrosimov, A/0000-0001-8284-9996 NR 31 TC 20 Z9 21 U1 1 U2 9 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0936-6555 J9 CLIN ONCOL-UK JI Clin. Oncol. PD MAY PY 2011 VL 23 IS 4 SI SI BP 261 EP 267 DI 10.1016/j.clon.2011.01.160 PG 7 WC Oncology SC Oncology GA 767GE UT WOS:000290842500005 PM 21333507 ER PT J AU Li, A Zhou, C Moore, J Zhang, P Tsai, TH Lee, HC Romano, DM Mckee, ML Schoenfeld, DA Serra, MJ Raygor, K Cantiello, HF Fujimoto, JG Tanzi, RE AF Li, A. Zhou, C. Moore, J. Zhang, P. Tsai, T. -H. Lee, H. -C. Romano, D. M. McKee, M. L. Schoenfeld, D. A. Serra, M. J. Raygor, K. Cantiello, H. F. Fujimoto, J. G. Tanzi, R. E. TI Changes in the Expression of the Alzheimer's Disease-Associated Presenilin Gene in Drosophila Heart Leads to Cardiac Dysfunction SO CURRENT ALZHEIMER RESEARCH LA English DT Article DE Alzheimer's disease; calcium channel; cardiomyopathy; Drosophila; heart; presenilin ID OPTICAL COHERENCE TOMOGRAPHY; IDIOPATHIC DILATED CARDIOMYOPATHY; AMYLOID PRECURSOR PROTEIN; BETA-CATENIN; GAMMA-SECRETASE; INTRAMEMBRANE PROTEOLYSIS; APOLIPOPROTEIN-E; IN-VIVO; MUTATIONS; MELANOGASTER AB Mutations in the presenilin genes cause the majority of early-onset familial Alzheimer's disease. Recently, presenilin mutations have been identified in patients with dilated cardiomyopathy (DCM), a common cause of heart failure and the most prevalent diagnosis in cardiac transplantation patients. However, the molecular mechanisms, by which presenilin mutations lead to either AD or DCM, are not yet understood. We have employed transgenic Drosophila models and optical coherence tomography imaging technology to analyze cardiac function in live adult Drosophila. Silencing of Drosophila ortholog of presenilins (dPsn) led to significantly reduced heart rate and remarkably age-dependent increase in end-diastolic vertical dimensions. In contrast, overexpression of dPsn increased heart rate. Either overexpression or silencing of dPsn resulted in irregular heartbeat rhythms accompanied by cardiomyofibril defects and mitochondrial impairment. The calcium channel receptor activities in cardiac cells were quantitatively determined via real-time RT-PCR. Silencing of dPsn elevated dIP(3)R expression, and reduced dSERCA expression; overexprerssion of dPsn led to reduced dRyR expression. Moreover, overexpression of dPsn in wing disc resulted in loss of wing phenotype and reduced expression of wingless. Our data provide novel evidence that changes in presenilin level leads to cardiac dysfunction, owing to aberrant calcium channel receptor activities and disrupted Wnt signaling transduction, indicating a pathogenic role for presenilin mutations in DCM pathogenesis. C1 [Li, A.; Moore, J.; Romano, D. M.; Raygor, K.; Tanzi, R. E.] Massachusetts Gen Hosp, Dept Neurol, Genet & Aging Res Unit, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. [Li, A.; Moore, J.; Zhang, P.; Romano, D. M.; McKee, M. L.; Serra, M. J.; Raygor, K.; Cantiello, H. F.; Tanzi, R. E.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Zhou, C.; Tsai, T. -H.; Lee, H. -C.; Fujimoto, J. G.] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Zhang, P.; Serra, M. J.; Cantiello, H. F.] Massachusetts Gen Hosp, Dept Med, Charlestown, MA 02129 USA. [McKee, M. L.] Massachusetts Gen Hosp, Program Membrane Biol, Charlestown, MA 02129 USA. [Schoenfeld, D. A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Cambridge, MA 02138 USA. RP Tanzi, RE (reprint author), Massachusetts Gen Hosp, Dept Neurol, Genet & Aging Res Unit, MassGen Inst Neurodegenerat Dis, 114,16th St, Charlestown, MA 02129 USA. EM jgfuji@mit.edu; tanzi@helix.mgh.harvard.edu RI Zhou, Chao/A-1327-2007; OI Tsai, Tsung-Han/0000-0002-2306-2269 FU Cure Alzheimer's Fund; National Institute of Health [R01AG014713, R01MH60009, R01CA75289, R01HL095717]; Air Force Office of Scientific Research [FA9550-07-1-0014]; Neuroscience Education and Research Foundation; Boston Area Diabetes and Endocrinology Research Center [DK 57521]; Center for the Study of Inflammatory Bowel Disease [DK 43351] FX We wish to thank Mark E. Fortini for kindly providing Drosophila stocks and helpful suggestion, and Brett E. Bouma, Michael A. Choma, Gary Tearney, and Steven N. Fry for their helpful advice and technical assistance. This work was supported by the Cure Alzheimer's Fund [to R.E.T], National Institute of Health [R01AG014713 and R01MH60009 to R.E.T; R01CA75289 and R01HL095717 to J.G.F], Air Force Office of Scientific Research [FA9550-07-1-0014 to J.G.F], and the Neuroscience Education and Research Foundation [to A.L.]. The Microscopy Core Facility at the MGH Program in Membrane Biology receives support from the Boston Area Diabetes and Endocrinology Research Center [DK 57521] and the Center for the Study of Inflammatory Bowel Disease [DK 43351]. NR 52 TC 12 Z9 12 U1 3 U2 9 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 MAY PY 2011 VL 8 IS 3 BP 313 EP 322 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 768BA UT WOS:000290905100012 PM 21524270 ER PT J AU Rosenbaum, JF AF Rosenbaum, Jerrold F. TI Recollections from the ADAA President SO DEPRESSION AND ANXIETY LA English DT Editorial Material C1 [Rosenbaum, Jerrold F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Rosenbaum, JF (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Bulfinch 351, Boston, MA 02114 USA. EM JRosenbaum@partners.org NR 1 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PD MAY PY 2011 VL 28 IS 5 BP 355 EP 357 DI 10.1002/da.20813 PG 3 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 761RN UT WOS:000290416200001 PM 21449007 ER PT J AU Davis, BH Pope, C Mason, PR Magwood, G Jenkins, CM AF Davis, Boyd H. Pope, Charlene Mason, Peyton R. Magwood, Gayenell Jenkins, Carolyn M. TI "It's a Wild Thing, Waiting to Get Me": Stance Analysis of African Americans With Diabetes SO DIABETES EDUCATOR LA English DT Article ID SELF-MANAGEMENT; EDUCATION; CULTURE; HEALTH; CARE; COMMUNICATION AB Purpose This mixed methods study uses a unique approach from social science and linguistics methodologies, a combination of positioning theory and stance analysis, to examine how 20 African Americans with type 2 diabetes make sense of the practices that led to recurrent emergency department visits to identify needs for more effective intervention. Methods In a purposive sample of postemergency department visit interviews with a same-race interviewer, people responded to open-ended questions reflecting on the decision to seek emergency department care. As applied to diabetes education, positioning theory explains that people use their language to position themselves toward their disease, their medications, and the changes in their lives. Transcriptions were coded using discourse analysis to categorize themes. As a form of triangulation, stance analysis measured language patterns using factor analysis to see when and how speakers revealed affect, attitude, and agentive choices for action. Conclusion Final analysis revealed that one third of the sample exhibited high scores for positive agency or capacity for decision-making and self-management, while the rest expressed less control and more negative emotions and fears that may preclude self-management. This approach suggests a means to tailor diabetes education considering alternative approaches focused on communication for those facing barriers. C1 [Pope, Charlene; Magwood, Gayenell; Jenkins, Carolyn M.] Med Univ S Carolina, Coll Nursing, Charleston, SC 29425 USA. [Davis, Boyd H.] Univ N Carolina, Dept English Appl Linguist, Charlotte, NC 28223 USA. [Pope, Charlene] Charleston REAP, Ralph H Johnson Dept, Vet Affairs Med Ctr, Charleston, SC 29425 USA. [Mason, Peyton R.] Next Generat Mkt Insights, Charlotte, NC USA. RP Pope, C (reprint author), Med Univ S Carolina, Coll Nursing, 99 Jonathan Lucas St, Charleston, SC 29425 USA. EM popec@musc.edu OI Davis, Boyd/0000-0003-4773-7715 FU Medical University of South Carolina Center for Health Disparities Research; [NIH/NINR 1 R15 NR009486-01A1] FX This study was supported by Grant #NIH/NINR 1 R15 NR009486-01A1, 2006, entitled "Emergency Department Use-African American with Diabetes," (Dr Carolyn Jenkins, principal investigator), and an intramural grant from the Medical University of South Carolina Center for Health Disparities Research, 2008 (Dr Charlene Pope, principal investigator). Dr Pope's contribution is the result of work supported with resources and the use of facilities at the Charleston, SC, Ralph H. Johnson VAMC, and the HSR&D REAP Center for Disease Prevention and Health Interventions for Diverse Populations (REA 08-261). Disclaimer: The views expressed in this article are those of the authors and do not necessarily represent the views of the US Department of Veterans Affairs. NR 38 TC 2 Z9 2 U1 0 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0145-7217 J9 DIABETES EDUCATOR JI Diabetes Educ. PD MAY-JUN PY 2011 VL 37 IS 3 BP 409 EP 418 DI 10.1177/0145721711404439 PG 10 WC Endocrinology & Metabolism; Public, Environmental & Occupational Health SC Endocrinology & Metabolism; Public, Environmental & Occupational Health GA 764US UT WOS:000290660500007 PM 21515541 ER PT J AU Wander, PL Boyko, EJ Leonetti, DL McNeely, MJ Kahn, SE Fujimoto, WY AF Wander, P. L. Boyko, E. J. Leonetti, D. L. McNeely, M. J. Kahn, S. E. Fujimoto, W. Y. TI Greater hand-grip strength predicts a lower risk of developing type 2 diabetes over 10 years in leaner Japanese Americans SO DIABETES RESEARCH AND CLINICAL PRACTICE LA English DT Article DE Epidemiology; Muscle; Hand strength; Japanese-American ID BODY-COMPOSITION; MUSCLE STRENGTH; LIFETIME RISK; GRIP STRENGTH; MELLITUS; CLASSIFICATION; DIAGNOSIS; ADULTS; HEALTH AB Aims: Much is known about body composition and type 2 diabetes risk but less about body function such as strength. We assessed whether hand-grip strength predicted incident diabetes. Methods: We followed 394 nondiabetic Japanese-American subjects (mean age 51.9) for the development of diabetes. We fit a logistic regression model to examine the association between hand-grip strength at baseline and type 2 diabetes risk over 10 years, adjusted for age, sex, and family history. Results: A statistically significant (p = 0.008) and negative (coefficient -0.208) association was observed between hand-grip strength and diabetes risk that diminished at higher BMI levels. Adjusted ORs for a 10-pound hand-grip strength increase with BMI set at the 25th, 50th or 75th percentiles were 0.68, 0.79, and 0.98, respectively. Conclusions: Among leaner individuals, greater hand-grip strength was associated with lower risk of type 2 diabetes, suggesting it may be a useful marker of risk in this population. (C) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Wander, P. L.; Boyko, E. J.; McNeely, M. J.; Kahn, S. E.; Fujimoto, W. Y.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Boyko, E. J.; Kahn, S. E.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Leonetti, D. L.] Univ Washington, Dept Anthropol, Seattle, WA 98195 USA. RP Wander, PL (reprint author), Univ Washington, Dept Med, 1959 NE Pacific St,Box 356421, Seattle, WA 98195 USA. EM lwander@u.washington.edu OI Wander, Pandora/0000-0003-3671-1464; Kahn, Steven/0000-0001-7307-9002 FU National Institutes of Health [DK-31170, HL-49293, DK-02654]; Diabetes and Endocrinology Research Center [DK-17047]; Clinical Nutrition Research Unit [DK-35816]; General Clinical Research Center at the University of Washington [RR-00037]; VA Puget Sound Health Care System; King County Japanese-American Community FX This work was supported by National Institutes of Health Grants DK-31170, HL-49293, and DK-02654; by facilities and services provided by the Diabetes and Endocrinology Research Center (DK-17047), Clinical Nutrition Research Unit (DK-35816), and the General Clinical Research Center (RR-00037) at the University of Washington. VA Puget Sound Health Care System provides support for Drs. Boyko and Kahn's involvement in this research. We are grateful to the King County Japanese-American Community for support and cooperation. NR 15 TC 9 Z9 9 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-8227 J9 DIABETES RES CLIN PR JI Diabetes Res. Clin. Pract. PD MAY PY 2011 VL 92 IS 2 BP 261 EP 264 DI 10.1016/j.diabres.2011.01.007 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 764ER UT WOS:000290612200020 PM 21281974 ER PT J AU Badr, CE Niers, JM Morse, D Koelen, JA Vandertop, P Noske, D Wurdinger, T Zalloua, PA Tannous, BA AF Badr, C. E. Niers, J. M. Morse, D. Koelen, J. A. Vandertop, P. Noske, D. Wurdinger, T. Zalloua, P. A. Tannous, B. A. TI Suicidal gene therapy in an NF-kappa B-controlled tumor environment as monitored by a secreted blood reporter SO GENE THERAPY LA English DT Article DE suicidal gene therapy; cytosine deaminase; uracil phosphoribosyltransferase; nuclear factor-kappa B; Gaussia luciferase; blood reporter ID CYTOSINE DEAMINASE GENE; ENZYME-PRODRUG THERAPY; CELL LUNG-CANCER; IN-VIVO; URACIL PHOSPHORIBOSYLTRANSFERASE; COLORECTAL-CANCER; OVARIAN-CANCER; EXPRESSION; 5-FLUOROCYTOSINE; ACTIVATION AB The nuclear factor-kappa B (NF-kappa B) is known to be activated in many cancer types including lung, ovarian, astrocytomas, melanoma, prostate as well as glioblastoma, and has been shown to correlate with disease progression. We have cloned a novel NF-kappa B-based reporter system (five tandem repeats of NF-kappa B responsive genomic element (NF; 14 bp each)) to drive the expression cassette for both a fusion between the yeast cytosine deaminase and uracil phosphoribosyltransferase (CU) as a therapeutic gene and the secreted Gaussia luciferase (Gluc) as a blood reporter, separated by an internal ribosomal entry site (NE-CU-IGIuc). We showed that malignant tumor cells have high expression of Gluc, which correlates to high activation of NF-kappa B. When NF-kappa B was further activated by tumor necrosis factor-a in these cells, we observed up to 10-fold increase in Gluc levels and therefore transgene expression in human glioma cells served to greatly enhance the sensitization of these cells to the prodrug, 5-fluorocytosine both in cultured cells and in vivo subcutaneous tumor xenograft model. This inducible system provides a tool to enhance the expression of imaging and therapeutic genes for cancer therapy. Gene Therapy (2011) 18, 445-451; doi:10.1038/gt.2010.156; published online 9 December 2010 C1 [Badr, C. E.; Niers, J. M.; Morse, D.; Koelen, J. A.; Tannous, B. A.] Massachusetts Gen Hosp, Ctr Neurosci, Dept Neurol, Boston, MA 02129 USA. [Badr, C. E.; Niers, J. M.; Morse, D.; Koelen, J. A.; Tannous, B. A.] Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. [Badr, C. E.; Niers, J. M.; Vandertop, P.; Noske, D.; Wurdinger, T.] Canc Ctr Amsterdam, VU Med Ctr, Dept Neurosurg, Neurooncol Res Grp, Amsterdam, Netherlands. [Koelen, J. A.] Univ Utrecht, Grad Sch Life Sci, Utrecht, Netherlands. [Zalloua, P. A.] Lebanese Amer Univ, Sch Med, Chouran Beirut, Lebanon. [Tannous, B. A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA USA. RP Tannous, BA (reprint author), Massachusetts Gen Hosp, Ctr Neurosci, Bldg 149,13th St, Charlestown, MA 02129 USA. EM btannous@hms.harvard.edu FU National Cancer Institute [P50 CA86355]; National Institute of Neurological Disorders [P30 NS045776]; Frem Foundation FX This work was supported by grants from the National Cancer Institute (P50 CA86355), the National Institute of Neurological Disorders (P30 NS045776) as well as the Frem Foundation. We would like to thank: Mr Neemat Frem (Indevco Group Sal, Lebanon) for providing guidance throughout the multiple design phases of the project; Miss Lee-Ann Tjon-Kon-Fat and Lisa Pike for technical assistance; Dr Miguel Sena-Esteves for help with designing the lentivirus vector; and Dr Xandra Breakefield for advice and critical reading of this manuscript. NR 52 TC 11 Z9 11 U1 0 U2 2 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 MAY PY 2011 VL 18 IS 5 BP 445 EP 451 DI 10.1038/gt.2010.156 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 765XK UT WOS:000290742500004 PM 21150937 ER PT J AU Bell-McGuinn, KM Matthews, CM Ho, SN Barve, M Gilbert, L Penson, RT Lengyel, E Palaparthy, R Gilder, K Vassos, A McAuliffe, W Weymer, S Barton, J Schilder, RJ AF Bell-McGuinn, Katherine M. Matthews, Carolyn M. Ho, Steffan N. Barve, Minal Gilbert, Lucy Penson, Richard T. Lengyel, Ernst Palaparthy, Rameshraja Gilder, Kye Vassos, Artemios McAuliffe, William Weymer, Sara Barton, Jeremy Schilder, Russell J. TI A phase II, single-arm study of the anti-alpha 5 beta 1 integrin antibody volociximab as monotherapy in patients with platinum-resistant advanced epithelial ovarian or primary peritoneal cancer SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Volociximab; Ovarian cancer; Platinum resistant; alpha 5 beta 1 integrin ID CIRCULATING TUMOR-CELLS; ALPHA(5)BETA(1) INTEGRIN; LIPOSOMAL DOXORUBICIN; ONCOLOGY-GROUP; BEVACIZUMAB; THERAPY; ANGIOGENESIS; CHEMOTHERAPY; CISPLATIN; FIBRONECTIN AB Objective. This phase II, multicenter, single-arm, two-stage study in platinum-resistant, advanced epithelial ovarian or primary peritoneal cancer evaluated the efficacy, safety, and tolerability of weekly single-agent volociximab. Pharmacokinetic/pharmacodynamic (PK/PD) studies were also performed. Methods. Sixteen patients were enrolled in Stage 1. Volociximab was administered at 15 mg/kg IV qwk until progression of disease or drug intolerability. Tumor response was assessed every 8 weeks. Serum samples for PK or whole blood for the evaluation of circulating tumor cells, endothelial cells, and endothelial progenitor cells were obtained on Days 1, 8, 15, 29, and 50. Ascites from one patient was collected for volociximab concentration analysis. Archived tumor tissue was analyzed by immunohistochemistry (IHC) for alpha 5 integrin expression. Results. Safety data are available on all 16 patients; 14 were evaluable for efficacy. One patient had stable disease at 8 weeks. The remaining 13 progressed on treatment. Twelve patients (75%) experienced study-related adverse events (AEs); the most common (>= 20%) were headache and fatigue. Three patients experienced possible study-related serious AEs (SAEs): reversible posterior leukoencephalopathy syndrome, pulmonary embolism, and hyponatremia. Peak serum concentrations of volociximab increased 2-3 fold from Day 1 to Day 50. Clinically relevant trough levels were achieved (> 150 mu g/mL). IHC analysis of archived tumor sections showed low-to-moderate expression of alpha 5 integrin on all ovarian cancer tissue evaluated. Conclusion. Despite insufficient clinical activity in this refractory patient population to continue the study, weekly volociximab was well tolerated, and the gained understanding of the mechanism of action of volociximab will inform future development efforts. (C) 2011 Elsevier Inc. All rights reserved. C1 [Bell-McGuinn, Katherine M.] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. [Matthews, Carolyn M.] Mary Crowley Med Res Ctr, Dallas, TX USA. [Ho, Steffan N.; Palaparthy, Rameshraja; Gilder, Kye; Vassos, Artemios; McAuliffe, William; Weymer, Sara; Barton, Jeremy] Biogen Idec Inc, San Diego, CA USA. [Barve, Minal] Texas Oncol Presbyterian, Dallas, TX USA. [Gilbert, Lucy] McGill Univ Hosp, Montreal, PQ, Canada. [Penson, Richard T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lengyel, Ernst] Univ Chicago, Chicago, IL 60637 USA. [Schilder, Russell J.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. RP Bell-McGuinn, KM (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10065 USA. EM bell-mck@mskcc.org RI Lengyel, Ernst/D-9220-2014 OI Lengyel, Ernst/0000-0001-8624-1507 FU PDL Biopharma Inc.; PDL FX Richard T. Penson: Research funds from PDL Biopharma Inc.; Ernst lengyel: Received funding from PDL for experiments with the antibody. (Cancer Res. 2008 Apr 1;68(7):2329-39.) NR 34 TC 48 Z9 49 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 MAY 1 PY 2011 VL 121 IS 2 BP 273 EP 279 DI 10.1016/j.ygyno.2010.12.362 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 760AD UT WOS:000290292100007 PM 21276608 ER PT J AU Farley, J Sill, MW Birrer, M Walker, J Schilder, RJ Thigpen, JT Coleman, RL Miller, BE Rose, PG Lankes, HA AF Farley, John Sill, Michael W. Birrer, Michael Walker, Joan Schilder, Russell J. Thigpen, J. Tate Coleman, Robert L. Miller, Brigitte E. Rose, Peter G. Lankes, Heather A. TI Phase II study of cisplatin plus cetuximab in advanced, recurrent, and previously treated cancers of the cervix and evaluation of epidermal growth factor receptor immunohistochemical expression: A Gynecologic Oncology Group study SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Cisplatin; Cetuximab; Cervical cancer ID SQUAMOUS-CELL CARCINOMA; MONOCLONAL-ANTIBODY C225; K-RAS ACTIVATION; UTERINE CERVIX; EXPLORATORY CELIOTOMY; ANTITUMOR-ACTIVITY; COLORECTAL-CANCER; CLINICAL-TRIALS; 2-STAGE DESIGNS; LUNG-CANCER AB Background. The purpose of this study was to evaluate the safety and efficacy of cetuximab (C225), an antibody that inhibits epidermal growth factor receptor (EGFR) activity, with cisplatin and to explore associations between EGFR protein expression with patient demographics or clinical outcome. Methods. Women with advanced, persistent, or recurrent carcinoma of the cervix were eligible. The women received cisplatin at 30 mg/m(2) on days 1 and 8 with a loading dose of cetuximab at 400 mg/m(2) followed by 250 mg/m(2) on days 1, 8, and 15 in a 21 day cycle. Adverse events were assessed with CTCAE v 3.0. Primary measure of efficacy was tumor response by RECIST. The study was stratified by prior chemotherapy (CT). EGFR protein expression in pre-treatment tumor was analyzed by immunohistochemistry. Results. Between September 2004 and March 2008, 76 patients were enrolled. Of these, 69 were eligible and evaluable: 44 (64%) received prior chemotherapy. There were 4 responses in each group, prior chemotherapy and no chemotherapy, 9% and 16%, respectively. Grade 4 toxicities included anemia (1), allergy (1), metabolic (1), and vascular (1). The most common grade 3 toxicities were metabolic (15), dermatologic (8), fatigue (6), and gastrointestinal (6). EGFR protein was expressed in 47/48 (98%) of tumors analyzed with a median cellular expression of 81%. Exploratory analyses revealed a trend between the percentage of cells expressing EGFR protein and PFS (hazard ratio = 1.76, 95% confidence interval = 0.96-3.21). Conclusions. The combination of cetuximab with cisplatin was adequately tolerated but did not indicate additional benefit beyond cisplatin therapy. Published by Elsevier Inc. C1 [Farley, John] Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA. [Sill, Michael W.; Lankes, Heather A.] Roswell Pk Canc Inst, Gynecol Oncol Grp, Stat & Data Ctr, Buffalo, NY 14263 USA. [Sill, Michael W.] SUNY Buffalo, Dept Biostat, Buffalo, NY 14260 USA. [Birrer, Michael] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Walker, Joan] Univ Oklahoma, Hlth Sci Ctr, Dept Obstet Gynecol, Oklahoma City, OK 73190 USA. [Schilder, Russell J.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Thigpen, J. Tate] Univ Mississippi, Med Ctr, Dept Med Oncol, Jackson, MS 39216 USA. [Coleman, Robert L.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77230 USA. [Miller, Brigitte E.] Wake Forest Univ, Dept Obstet Gynecol, Winston Salem, NC 27157 USA. [Rose, Peter G.] Cleveland Clin Fdn, Dept Obstet Gynecol, Cleveland, OH 44195 USA. [Rose, Peter G.] Case Western Reserve Univ, Cleveland, OH 44195 USA. RP Farley, J (reprint author), Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, 4301 Jones Bridge Rd, Bethesda, MD 20832 USA. EM john.farley@us.army.mil FU National Cancer Institute [CA 27469, CA 37517] FX This study was supported by National Cancer Institute grants to the Gynecologic Oncology Group Administrative Office (CA 27469) and the Gynecologic Oncology Group Statistical Office (CA 37517). This trial was registered at www.clinicaltrials.gov, NCT 10101192. The following Gynecologic Oncology Group member institutions participated in the primary treatment studies: University of Mississippi Medical Center, Indiana University School of Medicine, Wake Forest University School of Medicine, The Cleveland Clinic Foundation, MD Anderson Cancer Center, Fox Chase Cancer Center, University of Oklahoma, University of Texas - Galveston and Gynecologic Oncology Network. NR 46 TC 35 Z9 39 U1 1 U2 3 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 MAY 1 PY 2011 VL 121 IS 2 BP 303 EP 308 DI 10.1016/j.ygyno.2011.01.030 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 760AD UT WOS:000290292100012 PM 21329967 ER PT J AU Farley, J Smith, LM Darcy, KM Brady, MF Bell, J McGuire, W Birrer, MJ AF Farley, John Smith, Leia M. Darcy, Kathleen M. Brady, Mark F. Bell, Jeffrey McGuire, William Birrer, Michael J. TI Nuclear P27 expression in benign, borderline (LMP) and invasive tumors of the ovary and its association with prognosis: A gynecologic oncology group study SO GYNECOLOGIC ONCOLOGY LA English DT Article DE p27; Ovary; Carcinogenesis; Prognostic; Immunohistochemistry ID DEPENDENT KINASE INHIBITOR; CELL-CYCLE REGULATORS; BREAST-CANCER CELLS; P27(KIP1) EXPRESSION; GROWTH ARREST; SUBCELLULAR-LOCALIZATION; SURVIVAL; D1; MALIGNANCY; MUTATIONS AB Objective. Nuclear p27 expression was examined in non-invasive and invasive ovarian tumors from a cross-sectional study, and clinical relevance of p27 was evaluated in the primary tumors from women participating in two randomized phase III treatment trials. Methods. An immunohistochemistry assay was used to detect p27 in formalin-fixed paraffin-embedded ovarian tumors from 3 distinct sources. Results. Among the initial 91 ovarian tumors tested, low p27 expression (< 50% positive cells) was observed in 5.4% of non-invasive tumors versus 42.6% of invasive tumors (p < 0.001). In 145 ovarian cancers with high-risk early stage disease, 16.5% exhibited low p27 expression, and categorized p27 was not associated with age, race, or performance status. Low expression of p27 was common in poorly differentiated tumors (35.7%) compared to moderately (15.0%) and well (9.5%) differentiated tumors (p = 0.024) and rare in clear cell carcinomas (2.4%) compared to other histologies (p = 0.014). In the 139 cancers with advanced disease, 60% displayed low p27 expression, and categorized p27 expression was not associated with age, race, performance status, tumor grade, histologic subtype, measurable disease status or survival. Exploratory analyses revealed an association of cyclin E to p27 ratio > 1.0 with an increased risk of death (hazard ratio = 1.53; p = 0.017). Conclusions. Low p27 expression could be associated with malignant transformation of the ovarian epithelium and FIGO stage. A cyclin E to p27 ratio > 1.0 may be associated with shorter survival in these patients. Further study is required to confirm the trend for increased recurrences with low p27 expression in early stage disease. (C) 2010 Published by Elsevier Inc. C1 [Birrer, Michael J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Farley, John] Walter Reed Army Med Ctr, Dept Obstet Gynecol, Div Gynecol Oncol, Washington, DC 20307 USA. [Smith, Leia M.] Seattle Genet Inc, Seattle, WA 98021 USA. [Darcy, Kathleen M.; Brady, Mark F.] Roswell Pk Canc Inst, Gynecol Oncol Grp, Stat & Data Ctr, Buffalo, NY 14263 USA. [Bell, Jeffrey] Riverside Methodist Hosp, Columbus, OH 43214 USA. [McGuire, William] Franklin Sq Hosp, Baltimore, MD 21237 USA. [Birrer, Michael J.] Harvard Canc Ctr, Boston, MA 02114 USA. [Birrer, Michael J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Birrer, MJ (reprint author), Massachusetts Gen Hosp, Yawkey 9,55 Fruit St, Boston, MA 02114 USA. EM mbirrer@partners.org FU National Cancer Institute; GOG Tissue Bank [CA 27469]; GOG Statistical and Data Center [CA 37517]; National Cancer Institute of the National Institute of Health FX This study was supported by National Cancer Institute grants to the Gynecologic Oncology Group (GOG) Administrative Office and the GOG Tissue Bank (CA 27469), the GOG Statistical and Data Center (CA 37517), and the Intramural Research Program of the National Cancer Institute of the National Institute of Health. The following GOG member institutions participated in this study: University of Alabama at Birmingham, Oregon Health Sciences University, Abington Memorial Hospital, University of Rochester Medical Center, Walter Reed Army Medical Center, Wayne State University, University of Southern California at Los Angeles, Colorado Gynecologic Oncology Group, PC, University of California at Los Angeles, University of Washington, Milton S. Hershey Medical Center, Georgetown University Hospital, Wake Forest University School of Medicine, University of California Medical Center at Irvine, Stanford University Medical Center, University of Kentucky, The Cleveland Clinic Foundation, Johns Hopkins Oncology Center, East:ern Pennsylvania GYN/ONC Center, PC, Washington University School of Medicine, Cooper Hospital/University Medical Center, Columbus Cancer Council, University of Massachusetts Medical Center, University of Oklahoma, and Tacoma General Hospital. NR 39 TC 6 Z9 6 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 MAY 1 PY 2011 VL 121 IS 2 BP 395 EP 401 DI 10.1016/j.ygyno.2010.11.023 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 760AD UT WOS:000290292100029 PM 21310472 ER PT J AU Olden, K Freudenberg, N Dowd, J Shields, AE AF Olden, Kenneth Freudenberg, Nicholas Dowd, Jennifer Shields, Alexandra E. TI ANALYSIS & COMMENTARY Discovering How Environmental Exposures Alter Genes Could Lead To New Treatments For Chronic Illnesses SO HEALTH AFFAIRS LA English DT Article ID HUMAN-DISEASE; PHENOTYPIC PLASTICITY; DIABETES-MELLITUS; MONOZYGOTIC TWINS; HUMAN GENOME; EPIGENETICS; PATHOGENESIS; ASSOCIATION; METABOLISM; EPIGENOME AB Emerging research demonstrates that diet, pollution, and other environmental triggers can alter both the function and expression of human genes and lead to a heightened disease risk. These environment-gene interactions can cause so-called epigenetic changes in gene expression-patterns of which genes are switched "on" or "off"-that may account for the rising mortality from chronic diseases in industrialized nations. In this paper, we call for a new transdisciplinary approach to public health that would examine how environmental exposures, both physical and social, influence gene expression and a person's susceptibility to chronic disease. This initiative could lead to new ways to prevent and treat such illnesses. C1 [Olden, Kenneth; Freudenberg, Nicholas; Dowd, Jennifer] CUNY Hunter Coll, Sch Publ Hlth, New York, NY 10021 USA. [Shields, Alexandra E.] Harvard Massachusetts Gen Hosp, Ctr Gen Vulnerable Populat & Hlth Dispar, Boston, MA USA. [Shields, Alexandra E.] Harvard Univ, Sch Med, Boston, MA USA. RP Olden, K (reprint author), CUNY Hunter Coll, Sch Publ Hlth, New York, NY 10021 USA. EM kolden@hunter.cuny.edu RI Dowd, Jennifer/C-1127-2012 OI Dowd, Jennifer/0000-0003-2006-5656 FU National Institutes of Health [P30CA06516-43] FX This work was supported by a Nodal Award grant from the Dana-Farber/Harvard Cancer Center as part of the center's grant from the National Institutes of Health (P30CA06516-43). NR 46 TC 14 Z9 14 U1 0 U2 2 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD MAY PY 2011 VL 30 IS 5 BP 833 EP 841 DI 10.1377/hlthaff.2011.0078 PG 9 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 761WD UT WOS:000290430800005 PM 21555469 ER PT J AU Kharfan-Dabaja, MA Cutler, CS AF Kharfan-Dabaja, Mohamed A. Cutler, Corey S. TI Rituximab for prevention and treatment of graft-versus-host disease SO INTERNATIONAL JOURNAL OF HEMATOLOGY LA English DT Article DE Rituximab; Allogeneic hematopoietic cell transplantation; Acute graft-versus-host disease; Chronic graft-versus-host disease ID MONOCLONAL-ANTIBODY TREATMENT; STEM-CELL TRANSPLANTATION; REFRACTORY CHRONIC GVHD; T-CELLS; HEMATOPOIETIC TRANSPLANTATION; ADOPTIVE IMMUNOTHERAPY; B-CELLS; LYMPHOMA; SURVIVAL; EXPRESSION AB Growing understanding of the important role of B lymphocytes in alloreactivity has paved the way for evaluating anti-B cell therapy with rituximab in patients undergoing allogeneic hematopoietic cell transplantation. Data suggesting a beneficial reduction in incidence and severity of acute graft-versus-host disease (GVHD) are limited to non-randomized studies from single institutions using higher than conventional doses of rituximab. Additionally, rituximab is used as an effective treatment of corticosteroid-refractory chronic GVHD with good responses, particularly in cases of dermatologic and mucosal involvement. Post-transplant administration of rituximab appears to reduce the rate of chronic GVHD in preliminary studies. C1 [Cutler, Corey S.] Harvard Univ, Sch Med, Div Hematol Malignancies, Dept Med Oncol,Dana Farber Canc Inst, Boston, MA 02215 USA. [Kharfan-Dabaja, Mohamed A.] Amer Univ Beirut, Dept Internal Med, Div Hematol Oncol & Bone Marrow Transplantat, Beirut, Lebanon. RP Cutler, CS (reprint author), Harvard Univ, Sch Med, Div Hematol Malignancies, Dept Med Oncol,Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM corey_cutler@dfci.harvard.edu NR 35 TC 19 Z9 20 U1 0 U2 1 PU SPRINGER TOKYO PI TOKYO PA 1-11-11 KUDAN-KITA, CHIYODA-KU, TOKYO, 102-0073, JAPAN SN 0925-5710 J9 INT J HEMATOL JI Int. J. Hematol. PD MAY PY 2011 VL 93 IS 5 BP 578 EP 585 DI 10.1007/s12185-011-0855-2 PG 8 WC Hematology SC Hematology GA 765TZ UT WOS:000290732800003 PM 21547615 ER PT J AU Davies, JK AF Davies, Jeffrey K. TI Costimulatory blockade with monoclonal antibodies to induce alloanergy in donor lymphocytes SO INTERNATIONAL JOURNAL OF HEMATOLOGY LA English DT Article DE Allogeneic hematopoietic transplantation; Graft-versus-Host Disease; Costimulatory blockade; Anergy; Donor lymphocyte infusion ID STEM-CELL TRANSPLANTATION; VERSUS-HOST-DISEASE; ALLOREACTIVE T-CELLS; BONE-MARROW-TRANSPLANTATION; ADOPTIVE IMMUNOTHERAPY; IMMUNE RECONSTITUTION; SELECTIVE DEPLETION; REGULATORY CELL; LEUKEMIA; ANERGY AB Alloreactive donor T cells are central to the pathogenesis of Graft-versus-Host Disease (GvHD). Non-specific T cell depletion of donor grafts reduces GvHD, but increases infection and disease relapse. Several strategies are, therefore, in development to selectively remove alloreactive donor T cells prior to transplant while retaining beneficial donor T cells. An alternative approach is ex vivo alloanergization of donor T cells via allostimulation and blockade of costimulatory signals with fusion proteins or monoclonal antibodies. This strategy, which selectively inactivates alloreactive donor T cells, has been tested with some success in previous clinical trials of HLA-mismatched bone marrow transplantation. To build on the findings of these early trials, the strategy is now being tested in a multi-center clinical study of alloanergized donor lymphocyte infusion after HLA-mismatched stem cell transplantation. Recent advances in the understanding of alloanergization include the recognition of the central role played by CD4(+) regulatory T cells and new applications include the combination of alloanergization with T cell redirection to maximize anti-tumor activity. This mini-review will give an overview of the immunological basis for alloanergization, the previous and current clinical applications, and how new pre-clinical data have helped to create exciting new avenues of translational research in this area. C1 [Davies, Jeffrey K.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Davies, JK (reprint author), Queen Mary Univ London, Ctr Haematooncol, Barts Canc Inst, John Vane Sci Ctr, London EC1M 6BQ, England. EM j.k.davies@qmul.ac.uk FU Leukemia and Lymphoma Society; American Society for Blood and Marrow Transplantation FX The author thanks Eva Guinan, Lee Nadler and Laurence Cooper. The author was funded by a Leukemia and Lymphoma Society Career Development Award and a New Investigator award from the American Society for Blood and Marrow Transplantation. NR 37 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER TOKYO PI TOKYO PA 1-11-11 KUDAN-KITA, CHIYODA-KU, TOKYO, 102-0073, JAPAN SN 0925-5710 J9 INT J HEMATOL JI Int. J. Hematol. PD MAY PY 2011 VL 93 IS 5 BP 594 EP 601 DI 10.1007/s12185-011-0819-6 PG 8 WC Hematology SC Hematology GA 765TZ UT WOS:000290732800005 PM 21475951 ER PT J AU Quesnel, AM Lee, GS Nuss, RKC Volk, MS Jones, DT Rahbar, R AF Quesnel, Alicia M. Lee, Gi Soo Nuss, Roger K. C. Volk, Mark S. Jones, Dwight T. Rahbar, Reza TI Minimally invasive endoscopic management of subglottic stenosis in children: Success and failure SO INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY LA English DT Article DE Subglottic stenosis; Endoscopic; Minimally invasive; Airway; Laryngotracheal reconstruction ID PEDIATRIC LARYNGOTRACHEAL RECONSTRUCTION; DIOXIDE LASER-SURGERY; TRACHEAL STENOSIS; MITOMYCIN-C; SINGLE; COMPLICATIONS; LARYNGEAL; OUTCOMES; STAGE AB Objective: To assess the efficacy and safety of endoscopic management of subglottic stenosis both as a primary and as an adjunctive treatment in the pediatric population. Methods: Retrospective review of pediatric patients with subglottic stenosis undergoing endoscopic airway procedures at a tertiary care pediatric medical center. Outcomes were assessed by systematic review to determine the success and failure of the endoscopic approach. Results: Forty patients (22 male, 18 female) underwent endoscopic interventions for a diagnosis of subglottic airway stenosis between 2003 and 2000. Age ranged from 22 days old to 20 years old. Recorded degree of subglottic stenosis ranged from 10% to 99%. Fifty-three percent (21/40) had a history of prematurity, and 40% (16/40) had secondary airway diagnoses. Twenty-four patients underwent an endoscopic intervention initially (including laser or dilation, with or without topical mitomycin treatment), including four patients who underwent tracheostomy prior to the first endoscopic intervention. Sixteen underwent laryngotracheoplasty initially, including ten patients who underwent tracheostomy prior to the laryngotracheoplasty. Endoscopic treatment resulted in resolution of symptoms, and/or decannulation, and no further need for an open procedure in 58% of patients. Of the 24 patients undergoing endoscopic interventions initially, 14 patients underwent two or more endoscopic interventions, and 10 patients subsequently required tracheostomy or laryngotracheoplasty. When endoscopic procedures were used as an adjunct to laryngotracheoplasty, 60% (12/20) had resolution of symptoms, underwent decannulation, and did not require tracheostomy or revision laryngotracheoplasty. Conclusions: The endoscopic approach can be successful in the management of properly selected patients with subglottic stenosis, either as the initial treatment modality or as an adjunctive treatment in cases of re-stenosis after open airway surgery. The likelihood of success with a minimally invasive procedure as the primary treatment decreases with worsening initial grade of subglottic stenosis. (C) 2011 Published by Elsevier Ireland Ltd. C1 [Quesnel, Alicia M.; Lee, Gi Soo; Nuss, Roger K. C.; Volk, Mark S.; Jones, Dwight T.; Rahbar, Reza] Childrens Hosp Boston, Dept Otolaryngol & Commun Enhancement, Boston, MA 02115 USA. [Quesnel, Alicia M.; Lee, Gi Soo; Nuss, Roger K. C.; Volk, Mark S.; Jones, Dwight T.; Rahbar, Reza] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Quesnel, Alicia M.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Rahbar, R (reprint author), Childrens Hosp Boston, Dept Otolaryngol & Commun Enhancement, 300 Longwood Ave, Boston, MA 02115 USA. EM reza.rahbar@childrens.harvard.edu OI Volk, Mark/0000-0001-5708-5808 NR 23 TC 10 Z9 10 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-5876 J9 INT J PEDIATR OTORHI JI Int. J. Pediatr. Otorhinolaryngol. PD MAY PY 2011 VL 75 IS 5 BP 652 EP 656 DI 10.1016/j.ijporl.2011.02.002 PG 5 WC Otorhinolaryngology; Pediatrics SC Otorhinolaryngology; Pediatrics GA 767UF UT WOS:000290882900009 PM 21377219 ER PT J AU Schlett, CL Banerji, D Siegel, E Bamberg, F Lehman, SJ Ferencik, M Brady, TJ Nagurney, JT Hoffmann, U Truong, QA AF Schlett, Christopher L. Banerji, Dahlia Siegel, Emily Bamberg, Fabian Lehman, Sam J. Ferencik, Maros Brady, Thomas J. Nagurney, John T. Hoffmann, Udo Truong, Quynh A. TI Prognostic Value of CT Angiography for Major Adverse Cardiac Events in Patients With Acute Chest Pain From the Emergency Department 2-Year Outcomes of the ROMICAT Trial SO JACC-CARDIOVASCULAR IMAGING LA English DT Article DE computed tomography angiography; coronary artery disease; emergency department; long-term outcome; major adverse cardiac events ID CORONARY-ARTERY-DISEASE; COMPUTED TOMOGRAPHIC ANGIOGRAPHY; ALL-CAUSE MORTALITY; TIMI RISK SCORE; DIAGNOSTIC PERFORMANCE; METAANALYSIS; PREDICTION; POPULATION; DECISION AB OBJECTIVES The aim of this study was to determine the 2-year prognostic value of cardiac computed tomography (CT) for predicting major adverse cardiac events (MACE) in patients presenting to the emergency department (ED) with acute chest pain. BACKGROUND CT has high potential for early triage of acute chest pain patients. However, there is a paucity of data regarding the prognostic value of CT in this ED cohort. METHODS We followed 368 patients from the ROMICAT (Rule Out Myocardial Infarction Using Computer Assisted Tomography) trial (age 53 +/- 12 years; 61% male) who presented to the ED with acute chest pain, negative initial troponin, and a nonischemic electrocardiogram for 2 years. Contrast-enhanced 64-slice CT was obtained during index hospitalization, and caregivers and patients remained blinded to the results. CT was assessed for the presence of plaque, stenosis (> 50% luminal narrowing), and left ventricular regional wall motion abnormalities (RWMA). The primary endpoint was MACE, defined as composite cardiac death, nonfatal myocardial infarction, or coronary revascularization. RESULTS Follow-up was completed in 333 patients (90.5%) with a median follow-up period of 23 months. At the end of the follow-up period, 25 patients (6.8%) experienced 35 MACE (no cardiac deaths, 12 myocardial infarctions, and 23 revascularizations). Cumulative probability of 2-year MACE increased across CT strata for coronary artery disease (CAD) (no CAD 0%; nonobstructive CAD 4.6%; obstructive CAD 30.3%; log-rank p < 0.0001) and across combined CT strata for CAD and RWMA (no stenosis or RWMA 0.9%; 1 feature-either RWMA [15.0%] or stenosis [10.1%], both stenosis and RWMA 62.4%; log-rank p < 0.0001). The c statistic for predicting MACE was 0.61 for clinical Thrombolysis In Myocardial Infarction risk score and improved to 0.84 by adding CT CAD data and improved further to 0.91 by adding RWMA (both p < 0.0001). CONCLUSIONS CT coronary and functional features predict MACE and have incremental prognostic value beyond clinical risk score in ED patients with acute chest pain. The absence of CAD on CT provides a 2-year MACE-free warranty period, whereas coronary stenosis with RWMA is associated with the highest risk of MACE. (J Am Coll Cardiol Img 2011;4:481-91) (C) 2011 by the American College of Cardiology Foundation C1 [Schlett, Christopher L.; Banerji, Dahlia; Siegel, Emily; Lehman, Sam J.; Ferencik, Maros; Brady, Thomas J.; Hoffmann, Udo; Truong, Quynh A.] Harvard Univ, Cardiac MR PET CT Program, Dept Radiol, Massachusetts Gen Hosp,Med Sch, Boston, MA 02114 USA. [Bamberg, Fabian] Univ Munich, Klinikum Grosshadern, Dept Clin Radiol, D-8000 Munich, Germany. [Ferencik, Maros; Truong, Quynh A.] Harvard Univ, Div Cardiol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Nagurney, John T.] Harvard Univ, Dept Emergency Med, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Truong, QA (reprint author), Harvard Univ, Cardiac MR PET CT Program, Dept Radiol, Massachusetts Gen Hosp,Med Sch, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM qtruong@partners.org FU National Institutes of Health (NIH) [R01 HL080053, K23HL098370, L30HL093896]; Siemens Medical Solutions; GE Healthcare FX This work was supported by the National Institutes of Health (NIH) R01 HL080053 and in part supported by Siemens Medical Solutions and GE Healthcare. Dr. Truong was supported by NIH grants K23HL098370 and L30HL093896. All other authors have reported that they have no relationships to disclose. NR 39 TC 69 Z9 72 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD MAY PY 2011 VL 4 IS 5 BP 481 EP 491 DI 10.1016/j.jcmg.2010.12.008 PG 11 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 765MT UT WOS:000290712100006 PM 21565735 ER PT J AU Gewirtz, H AF Gewirtz, Henry TI PET Measurement of Absolute Myocardial Blood Flow and LV Function in Dilated Cardiomyopathy SO JACC-CARDIOVASCULAR IMAGING LA English DT Editorial Material C1 Harvard Univ, Cardiac Unit, Massachusetts Gen Hosp, Dept Med,Cardiol Div,Med Sch, Boston, MA 02114 USA. RP Gewirtz, H (reprint author), Harvard Univ, Cardiac Unit, Massachusetts Gen Hosp, Dept Med,Cardiol Div,Med Sch, Yawkey 5E,55 Fruit St, Boston, MA 02114 USA. EM hgewirtz@partners.org NR 2 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 1936-878X J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD MAY PY 2011 VL 4 IS 5 BP 557 EP 560 DI 10.1016/j.jcmg.2010.06.020 PG 4 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 765MT UT WOS:000290712100016 PM 21565745 ER PT J AU Suvak, MK Litz, BT Sloan, DM Zanarini, MC Barrett, LF Hofmann, SG AF Suvak, Michael K. Litz, Brett T. Sloan, Denise M. Zanarini, Mary C. Barrett, Lisa Feldman Hofmann, Stefan G. TI Emotional Granularity and Borderline Personality Disorder SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article DE borderline personality disorder; emotional processing; emotional granularity; affective dysregulation ID CONFIRMATORY FACTOR-ANALYSIS; AFFECT INTENSITY MEASURE; NEGATIVE AFFECT; INDIVIDUAL-DIFFERENCES; INTERPERSONAL PROBLEMS; MEASUREMENT MODEL; COMMUNITY SAMPLE; MOOD AWARENESS; VALENCE FOCUS; YOUNG-ADULTS AB This study examined the affective dysregulation component of borderline personality disorder (BPD) from an emotional granularity perspective, which refers to the specificity in which one represents emotions. Forty-six female participants meeting criteria for BPD and 51 female control participants without BPD and Axis I pathology completed tasks that assessed the degree to which participants incorporated information about valence (pleasant-unpleasant) and arousal (calm-activated) in their semantic/conceptual representations of emotions and in using labels to represent emotional reactions. As hypothesized, participants with BPD emphasized valence more and arousal less than control participants did when using emotion terms to label their emotional reactions. Implications and future research directions are discussed. C1 [Suvak, Michael K.] VA Boston Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, Womens Hlth Sci Div, Boston, MA 02130 USA. [Litz, Brett T.] Boston Univ, Dept Psychol, Sch Med, Boston, MA 02215 USA. [Litz, Brett T.; Sloan, Denise M.] Boston Univ, Dept Psychiat, Sch Med, Boston, MA 02215 USA. [Zanarini, Mary C.] McLean Hosp, Belmont, MA 02178 USA. [Zanarini, Mary C.] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Barrett, Lisa Feldman] Northeastern Univ, Dept Psychol, Boston, MA USA. [Barrett, Lisa Feldman] Harvard Univ, Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. RP Suvak, MK (reprint author), VA Boston Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, Womens Hlth Sci Div, 116B3,150 S Huntington Ave, Boston, MA 02130 USA. EM Michael.Suvak@VA.GOV RI Hofmann, Stefan/B-8769-2014; OI Hofmann, Stefan/0000-0002-3548-9681; Sloan, Denise/0000-0002-0962-478X FU NIH HHS [DP1OD003312, DP1 OD003312]; NIMH NIH HHS [F31 MH078426, F31 MH078426-02, F31MH078426] NR 60 TC 25 Z9 25 U1 6 U2 10 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD MAY PY 2011 VL 120 IS 2 BP 414 EP 426 DI 10.1037/a0021808 PG 13 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA 763YP UT WOS:000290595900013 PM 21171723 ER PT J AU Hosseini, A Gill, TJ Van de Velde, SK Li, GA AF Hosseini, Ali Gill, Thomas J. Van de Velde, Samuel K. Li, Guoan TI Estimation of In Vivo ACL Force Changes in Response to Increased Weightbearing SO JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME LA English DT Article DE anterior cruciate ligament (ACL); in vivo ACL force changes; knee ID ANTERIOR CRUCIATE-LIGAMENT; GEOMETRIC IMAGE DISTORTION; SITU FORCES; KNEE FLEXION; ANTEROMEDIAL BAND; STRAIN BEHAVIOR; TIBIAL LOADS; KINEMATICS; JOINT; ELONGATION AB Accurate knowledge of in vivo anterior cruciate ligament (ACL) forces is instrumental for understanding normal ACL function and improving surgical ACL reconstruction techniques. The objective of this study was to estimate the change in ACL forces under in vivo loading conditions using a noninvasive technique. A combination of magnetic resonance and dual fluoroscopic imaging system was used to determine ACL in vivo elongation during controlled weightbearing at discrete flexion angles, and a robotic testing system was utilized to determine the ACL force-elongation data in vitro. The in vivo ACL elongation data were mapped to the in vitro ACL force-elongation curve to estimate the change in in vivo ACL forces in response to full body weightbearing using a weighted mean statistical method. The data demonstrated that by assuming that there was no tension in the ACL under zero weightbearing, the changes in in vivo ACL force caused by full body weightbearing were 131.4 +/- 16.8 N at 15 deg, 106.7 +/- 11.2 N at 30 deg, and 34.6 +/- 4.5 N at 45 deg of flexion. However, when the assumed tension in the ACL under zero weightbearing was over 20 N, the change in the estimated ACL force in response to the full body weightbearing approached an asymptotic value. With an assumed ACL tension of 40 N under zero weightbearing, the full body weight caused an ACL force increase in 202.7 +/- 27.6 N at 15 deg, 184.9 +/- 22.5 N at 30 deg, and 98.6 +/- 11.7 N at 45 deg of flexion. The in vivo ACL forces were dependent on the flexion angle with higher force changes at low flexion angles. Under full body weightbearing, the ACL may experience less than 250 N. These data may provide a valuable insight into the biomechanical behavior of the ACL under in vivo loading conditions. [DOI: 10.1115/1.4003780] C1 [Hosseini, Ali; Gill, Thomas J.; Van de Velde, Samuel K.; Li, Guoan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Bioengn Lab, Boston, MA 02114 USA. [Hosseini, Ali] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. RP Li, GA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Bioengn Lab, Boston, MA 02114 USA. EM hosseini@alum.mit.edu; tgill@partners.org; svandevelde@partners.org; gli1@partners.org FU National Institutes of Health [R21 AR051078, R01 AR055612]; Department of Orthopaedic Surgery at the Massachusetts General Hospital FX The authors would like to gratefully acknowledge the financial support of the National Institutes of Health (Grant Nos. R21 AR051078 and R01 AR055612) and the Department of Orthopaedic Surgery at the Massachusetts General Hospital. The technical assistance of Michal Kozanek is greatly appreciated. NR 44 TC 10 Z9 11 U1 0 U2 4 PU ASME-AMER SOC MECHANICAL ENG PI NEW YORK PA THREE PARK AVE, NEW YORK, NY 10016-5990 USA SN 0148-0731 J9 J BIOMECH ENG-T ASME JI J. Biomech. Eng.-Trans. ASME PD MAY PY 2011 VL 133 IS 5 AR 051004 DI 10.1115/1.4003780 PG 9 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 765EQ UT WOS:000290686600004 PM 21599095 ER PT J AU Jackson, LT Aubin, PM Cowley, MS Sangeorzan, BJ Ledoux, WR AF Jackson, Lyle T. Aubin, Patrick M. Cowley, Matthew S. Sangeorzan, Bruce J. Ledoux, William R. TI A Robotic Cadaveric Flatfoot Analysis of Stance Phase SO JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME LA English DT Article DE pes planus; flatfoot; foot structure; cadaver; stance phase; robot ID DEFORMITY; JOINTS AB The symptomatic flatfoot deformity (pes planus with peri-talar subluxation) can be a debilitating condition. Cadaveric flatfoot models have been employed to study the etiology of the deformity, as well as invasive and noninvasive surgical treatment strategies, by evaluating bone positions. Prior cadaveric flatfoot simulators, however, have not leveraged industrial robotic technologies, which provide several advantages as compared with the previously developed custom fabricated devices. Utilizing a robotic device allows the researcher to experimentally evaluate the flatfoot model at many static instants in the gait cycle, compared with most studies, which model only one to a maximum of three instances. Furthermore, the cadaveric tibia can be statically positioned with more degrees of freedom and with a greater accuracy, and then a custom device typically allows. We created a six degree of freedom robotic cadaveric simulator and used it with a flatfoot model to quantify static bone positions at ten discrete instants over the stance phase of gait. In vivo tibial gait kinematics and ground reaction forces were averaged from ten flatfoot subjects. A fresh frozen cadaveric lower limb was dissected and mounted in the robotic gait simulator (RGS). Biomechanically realistic extrinsic tendon forces, tibial kinematics, and vertical ground reaction forces were applied to the limb. In vitro bone angular position of the tibia, calcaneus, talus, navicular, medial cuneiform, and first metatarsal were recorded between 0% and 90% of stance phase at discrete 10% increments using a retroreflective six-camera motion analysis system. The foot was conditioned flat through ligament attenuation and axial cyclic loading. Post-flat testing was repeated to study the pes planus deformity. Comparison was then made between the pre-flat and post-flat conditions. The RGS was able to recreate ten gait positions of the in vivo pes planus subjects in static increments. The in vitro vertical ground reaction force was within +/- 1 standard deviation (SD) of the in vivo data. The in vitro sagittal, coronal, and transverse plane tibial kinematics were almost entirely within +/- 1 SD of the in vivo data. The model showed changes consistent with the flexible flatfoot pathology including the collapse of the medial arch and abduction of the forefoot, despite unexpected hindfoot inversion. Unlike previous static flatfoot models that use simplified tibial degrees of freedom to characterize only the midpoint of the stance phase or at most three gait positions, our simulator represented the stance phase of gait with ten discrete positions and with six tibial degrees of freedom. This system has the potential to replicate foot function to permit both noninvasive and surgical treatment evaluations throughout the stance phase of gait, perhaps eliciting unknown advantages or disadvantages of these treatments at other points in the gait cycle. [DOI: 10.1115/1.4003869] C1 [Jackson, Lyle T.; Aubin, Patrick M.; Cowley, Matthew S.; Sangeorzan, Bruce J.; Ledoux, William R.] VA Puget Sound Hlth Care Syst, Dept Vet Affairs, RR&D Ctr Excellence Limb Loss Prevent & Prosthet, Seattle, WA USA. [Ledoux, William R.] Univ Washington, Dept Mech Engn, Seattle, WA 98195 USA. [Jackson, Lyle T.] Univ Washington, Sch Med, Seattle, WA USA. [Aubin, Patrick M.] Univ Washington, Dept Elect Engn, Seattle, WA 98195 USA. RP Ledoux, WR (reprint author), VA Puget Sound Hlth Care Syst, Dept Vet Affairs, RR&D Ctr Excellence Limb Loss Prevent & Prosthet, Seattle, WA USA. EM wrledoux@u.washington.edu RI Ledoux, William/K-6815-2015 OI Ledoux, William/0000-0003-4982-7714 FU VA Rehabilitation Research and Development Service [A2661C, A4843C]; University of Washington FX The authors thank the VA Rehabilitation Research and Development Service Grant Nos. A2661C and A4843C and the University of Washington Medical Student Research Training Program. NR 14 TC 5 Z9 5 U1 2 U2 8 PU ASME-AMER SOC MECHANICAL ENG PI NEW YORK PA THREE PARK AVE, NEW YORK, NY 10016-5990 USA SN 0148-0731 J9 J BIOMECH ENG-T ASME JI J. Biomech. Eng.-Trans. ASME PD MAY PY 2011 VL 133 IS 5 AR 051005 DI 10.1115/1.4003869 PG 6 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 765EQ UT WOS:000290686600005 PM 21599096 ER PT J AU Jessup, M Albert, NM Lanfear, DE Lindenfeld, J Massie, BM Walsh, MN Zucker, MJ AF Jessup, Mariell Albert, Nancy M. Lanfear, David E. Lindenfeld, Joann Massie, Barry M. Walsh, Mary Norine Zucker, Mark J. CA Aha Heart Failure Transplantation Heart Failure Soc Amer TI ACCF/AHA/HFSA 2011 Survey Results: Current Staffing Profile of Heart Failure Programs, Including Programs That Perform Heart Transplant and Mechanical Circulatory Support Device Implantation SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE ACCF/AHA/HFSA Survey Report; heart failure; heart transplant; mechanical circulatory support device; staffing profile ID TASK-FORCE; MANAGEMENT; CARDIOLOGY; GUIDELINES; STATEMENT; OUTCOMES; SOCIETY AB Objectives: There have been no published recommendations about staffing needs for a heart failure (HF),clinic or an office setting focused on heart transplant. The goal of this survey was to understand the current staffing environment of HF, transplant, and mechanical circulatory support device (MCSD) programs in the United States and abroad. This report identifies current staffing patterns but does not endorse a particular staffing model. Methods: An online survey, jointly sponsored by the American College of Cardiology Foundation (ACCF), American Heart Association (AHA), and the Heart Failure Society of America (HFSA), was sent to the members of all 3 organizations who had identified themselves as interested in HF, heart transplant, or both, between March 12, 2009, and May 12, 2009. Results: The overall response rate to the 1,823 e-mail surveys was 23%. There were 257 unique practices in the United States (81% of total sites) and 58 international sites (19%); approximately 30% of centers were in a cardiovascular group practice and 30% in a medical school hospital setting. The large majority of practices delivered HF care in both an inpatient and outpatient environment, and slightly more centers were implanting MCSDs (47%) than performing cardiac transplantation (39%). Most practices (43%) were small, with <4 staff members, or small- to medium-sized (34%), with 4 to 10 staff members, with only 23% being medium (11-20 staff) or large programs (> 20 staff). On average, a U.S. HF practice cared for 1,641 outpatients annually. An average HF program with transplant performed 10 transplants. Although larger programs were able to perform more transplants and see more outpatient HF visits, their clinician staffing volume tended to double for approximately every 500 to 700 additional HF visits annually. The average staffing utilization was 2.65 physician full-time equivalents (FTEs), 2.21 nonphysician practitioner (nurse practitioner or physician assistant) FTEs, and 2.61 nurse coordinator FTEs annually. Conclusions: The HF patient population is growing in number in the United States and internationally, and the clinicians who provide the highly skilled and time-consuming care to this population are under intense scrutiny as a result of focused quality improvement initiatives and reduced financial resources. Staffing guidelines should be developed to ensure that an adequate number of qualified professionals are hired for a given practice volume. These survey results are an initial step in developing such standards. (J Cardiac Fail 2011;17:349-358) C1 [Jessup, Mariell] Univ Penn, Philadelphia, PA 19104 USA. [Albert, Nancy M.] Cleveland Clin, Cleveland, OH USA. [Lindenfeld, Joann] Univ Colorado, Boulder, CO 80309 USA. [Massie, Barry M.] UCSF, San Francisco VAMC, San Francisco, CA USA. [Zucker, Mark J.] Newark Beth Israel Med Ctr, Newark, NJ USA. RP Jessup, M (reprint author), Univ Penn, Philadelphia, PA 19104 USA. NR 15 TC 3 Z9 4 U1 0 U2 1 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 MAY PY 2011 VL 17 IS 5 BP 349 EP 358 DI 10.1016/j.cardfail.2011.04.001 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 766JE UT WOS:000290777600001 PM 21549290 ER PT J AU Blanchfield, BB Gazelle, GS Khaliif, M Arocha, IS Hacker, K AF Blanchfield, Bonnie B. Gazelle, G. Scott Khaliif, Mursal Arocha, Izabel S. Hacker, Karen TI A Framework to Identify the Costs of Providing Language Interpretation Services SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Article DE Interpreters; language services; cost effectiveness; costs ID HEALTH-CARE; BARRIERS; IMPACT; QUALITY AB The availability of language services for patients with limited English proficiency has become a standard of care in the United States. Finding the resources to pay for language programs is challenging for providers, payers, and policymakers. There is no federal payment policy and states are developing policies using different methodologies for determining costs and reimbursement rates. This paper establishes a conceptual framework that identifies program costs, can be used across health care entities, and can be understood by administrators, researchers, and policymakers to guide research and analysis and establish a common ground for informed strategic discussion of payment and reimbursement policy. Using case study methods, a framework was established to identify costs and included determining the perspective of the cost analysis as well as distinguishing between the financial accounting costs (direct, indirect, and overheard costs) and the economic opportunity and subsequent utilization costs. C1 [Blanchfield, Bonnie B.; Gazelle, G. Scott] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Khaliif, Mursal; Arocha, Izabel S.; Hacker, Karen] Cambridge Hlth Alliance, Cambridge, MA USA. RP Blanchfield, BB (reprint author), Massachusetts Gen Hosp, Inst Technol Assessment, 101 Merrimac St,Suite 10th Floor, Boston, MA 02114 USA. EM gsmbbb@gmail.com NR 15 TC 2 Z9 2 U1 0 U2 1 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 MAY PY 2011 VL 22 IS 2 BP 523 EP 531 PG 9 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 762GB UT WOS:000290461800013 PM 21551931 ER PT J AU Meo, N Hwang, U Morrison, RS AF Meo, Nicholas Hwang, Ula Morrison, R. Sean TI Resident Perceptions of Palliative Care Training in the Emergency Department SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID END-OF-LIFE; EDUCATION AB Objectives: To characterize the level of formal training and perceived educational needs in palliative care of emergency medicine (EM) residents. Methods: This descriptive study used a 16-question survey administered at weekly resident didactic sessions in 2008 to EM residency programs in New York City. Survey items asked residents to: (1) respond to Likert-scaled statements about the role of palliative care in the emergency department (ED); (2) quantify their level of formal training and personal comfort in symptom management, discussion of bad news and prognosis, legal issues, and withdrawing/withholding therapy; and (3) express their interest in future palliative care training. Results: Of 228 total residents, 159 (70%) completed the survey. Of those surveyed, 50% completed some palliative care training before residency; 71.1% agreed or strongly agreed that palliative care was an important competence for an EM physician. However, only 24.3% reported having a "clear idea of the role of palliative care in EM." The highest self-reported level of formal training was in the area of advanced directives or legal issues at the end of life; the lowest levels were in areas of patient management at the end of life. The highest level of self-reported comfort was in giving bad news and the lowest was in withholding/withdrawing therapy. A slight majority of residents (54%) showed positive interest in receiving future training in palliative care. Conclusions: New York City EM residents reported palliative care as an important competency for emergency medicine physicians, yet also reported low levels of formal training in palliative care. The majority of residents surveyed favored additional training. C1 [Meo, Nicholas; Hwang, Ula] Mt Sinai Sch Med, Dept Emergency Med, New York, NY 10029 USA. [Meo, Nicholas; Hwang, Ula; Morrison, R. Sean] Mt Sinai Sch Med, Brookdale Dept Geriatr & Palliat Care, New York, NY 10029 USA. [Hwang, Ula; Morrison, R. Sean] James J Peters Vet Affairs Med Ctr, REAP, Bronx, NY USA. [Hwang, Ula; Morrison, R. Sean] James J Peters Vet Affairs Med Ctr, GRECC, Bronx, NY USA. RP Hwang, U (reprint author), Mt Sinai Sch Med, Dept Emergency Med, Gustave L Levy Pl,Box 1620, New York, NY 10029 USA. EM ula.hwang@mountsinai.org FU American Federation on Aging Research (AFAR); National Institute on Aging (NIA) [K23 AG031218, K24 AG022345] FX Nicholas Meo was supported by a Medical Student Training on Aging Research summer program award from the American Federation on Aging Research (AFAR). Ula Hwang is supported by a National Institute on Aging (NIA) K23 career development award (K23 AG031218). R. Sean Morrison is supported by a NIA K24 mid-career mentoring award (K24 AG022345). NR 19 TC 25 Z9 25 U1 0 U2 5 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 MAY PY 2011 VL 14 IS 5 BP 548 EP 555 DI 10.1089/jpm.2010.0343 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 766CE UT WOS:000290756700007 PM 21291326 ER PT J AU Zerzan, J Lee, CA Haverhals, LM Nowels, CT AF Zerzan, Judy Lee, Courtney A. Haverhals, Leah M. Nowels, Carolyn T. TI Exploring Physician Decisions about End-of-Life Opiate Prescribing: A Qualitative Study SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID HEALTH-CARE PROVIDERS; PAIN MANAGEMENT; KNOWLEDGE; ATTITUDES; COMMUNICATION; BARRIERS; STATE AB Background: Opiates are commonly used for symptoms at the end of life (EOL). Little is known about the decision-making process physicians go through when deciding to prescribe opiates for their EOL patients. The study's objective was to explore physician factors affecting EOL opiate prescribing. Methods: Qualitative study of 38 physicians in the Denver area in the specialties of outpatient and inpatient medicine, geriatrics, oncology, and palliative care. Semi-structured qualitative interviews by trained interviewers asked physicians about their knowledge, attitudes, and experiences in prescribing opiates, reasons for prescribing opiates, barriers to prescribing opiates, changes in prescribing habits, and perceived patient factors that influence prescribing. Interviews were analyzed using ATLAS.ti qualitative analysis software and independently coded by two reviewers. Results: We found a spectrum of beliefs ranging from the viewpoint that opiates are underused at EOL to overused. We found five key themes: practices in when and how to use opiates, barriers to prescribing, personal experiences drive prescribing, social meaning of opiates, and differences in the role of physician. Physicians interviewed described experiences, both personal and professional, that influenced their opiate-prescribing habits. All respondents expressed positive experiences with prescribing opiates in being able to ease patients' suffering at EOL and to improve their functionality and quality of life. Conclusions: Differences in prescribing habits, attitudes, and experiences of physicians influence opiate prescribing, which may lead to over- and underprescribing. Knowledge, barriers, and fears about EOL opiate prescribing need to be addressed to ensure EOL patients are receiving appropriate symptom relief. C1 [Zerzan, Judy; Nowels, Carolyn T.] Univ Colorado Denver, Div Gen Internal Med, Aurora, CO 80045 USA. [Lee, Courtney A.] Univ Colorado Denver, Dept Hlth & Behav Sci, Aurora, CO 80045 USA. [Haverhals, Leah M.] Eastern Colorado Hlth Care Syst, US Dept Vet Affairs, Denver, CO USA. RP Zerzan, J (reprint author), Univ Colorado Denver, Div Gen Internal Med, 12631 E 17th Ave,Mail Stop B180, Aurora, CO 80045 USA. EM Judy.Zerzan@ucdenver.edu FU University of Colorado Denver FX The results of this study were presented at the 32nd SGIM Annual Meeting in May 2009. This study was funded from the University of Colorado Denver General Internal Medicine Small Grants Program. NR 14 TC 3 Z9 3 U1 2 U2 3 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 MAY PY 2011 VL 14 IS 5 BP 567 EP 572 DI 10.1089/jpm.2010.0505 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 766CE UT WOS:000290756700011 PM 21413855 ER PT J AU Malin, JL O'Neill, SM Asch, SM Dy, SM Walling, AM Tisnado, D Antonio, AL Lorenz, KA AF Malin, Jennifer L. O'Neill, Sean M. Asch, Steven M. Dy, Sydney M. Walling, Anne M. Tisnado, Diana Antonio, Anna Liza Lorenz, Karl A. TI Quality of Supportive Care for Patients with Advanced Cancer in a VA Medical Center SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID EVIDENCE-BASED RECOMMENDATIONS; SYMPTOM PREVALENCE; TELEHEALTH; MANAGEMENT; LIFE AB Purpose: Using the Assessing Symptoms Side Effects and Indicators of Supportive Treatment (ASSIST) quality indicators (QIs), we conducted a comprehensive evaluation of the quality of care provided in our institution to patients diagnosed with advanced cancer in 2006. Methods: Patients diagnosed with a Stage IV solid tumor were identified from the hospital's cancer registry. Using data abstracted from medical records, care was assessed using 41 explicit QIs. Mean percent adherence to QIs was calculated overall, as well as across five clinical domains: (1) Pain, (2) Depression and Psychosocial Distress, (3) Dyspnea, (4) Treatment Toxicity, (5) Other Symptoms, and (6) Information and Care Planning. Results: The study cohort (n = 118) was almost all male (2% female) and mean age was 65.9 years (standard deviation [SD] 9.9 years). The most common cancers were lung and head and neck cancer (23% each); 17% had prostate cancer; 13% had colorectal cancer; and the rest (24%) had breast, esophageal, stomach, genitourinary, liver/biliary, or pancreas cancer. Patients received 51% (95% confidence interval [CI] 48%-54%) of recommended care. Adherence to recommended care within domains ranged from 38% (95% CI 35%-42%) for Other Symptoms to 79% (95% CI 73%-86%) for Information and Care Planning. Conclusions: This study suggests that the quality of supportive care for patients with advanced cancer can be greatly improved. Future efforts should use the ASSIST indicators to evaluate the quality of supportive care in larger and more diverse cohorts of advanced cancer patients. C1 [Malin, Jennifer L.] Univ Calif Los Angeles, Div Hematol Oncol 111H, VA Greater Los Angeles Healthcare Syst, David Geffen Sch Med,RAND Hlth, Los Angeles, CA 90073 USA. [O'Neill, Sean M.] Northwestern Univ, Feinberg Sch Med, Pardee RAND Grad Sch, Chicago, IL 60611 USA. [Dy, Sydney M.] Johns Hopkins Univ, Dept Hlth Policy & Management, Baltimore, MD 21218 USA. [Dy, Sydney M.] Johns Hopkins Univ, Dept Oncol, Baltimore, MD USA. [Dy, Sydney M.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA. [Walling, Anne M.; Tisnado, Diana] Univ Calif Los Angeles, VA Greater Los Angeles, Div Gen Internal Med & Hlth Serv Res, Sch Publ Hlth, Los Angeles, CA 90073 USA. RP Malin, JL (reprint author), Univ Calif Los Angeles, Div Hematol Oncol 111H, VA Greater Los Angeles Healthcare Syst, David Geffen Sch Med,RAND Hlth, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jennifer.malin@va.gov OI O'Neill, Sean/0000-0001-7759-8942 FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service [SHP 08-196] FX The research reported here was supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service SHP 08-196. The authors are solely responsible for its content and the views do not necessarily represent the views of the Department of Veterans Affairs. NR 17 TC 9 Z9 9 U1 0 U2 7 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 MAY PY 2011 VL 14 IS 5 BP 573 EP 577 DI 10.1089/jpm.2010.0464 PG 5 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 766CE UT WOS:000290756700012 PM 21413885 ER PT J AU Jackson, V Arnold, RM AF Jackson, Vicki Arnold, Robert M. TI The Joys and Complications of Working on a Team SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Editorial Material C1 [Jackson, Vicki] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Jackson, V (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM VJackson@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD MAY PY 2011 VL 14 IS 5 BP 649 EP 649 DI 10.1089/jpm.2011.9697 PG 1 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 766CE UT WOS:000290756700022 PM 21592032 ER PT J AU Sylvia, LG Nierenberg, AA Stange, JP Peckham, AD Deckersbach, T AF Sylvia, Louisa G. Nierenberg, Andrew A. Stange, Jonathan P. Peckham, Andrew D. Deckersbach, Thilo TI Development of an Integrated Psychosocial Treatment to Address the Medical Burden Associated with Bipolar Disorder SO JOURNAL OF PSYCHIATRIC PRACTICE LA English DT Article DE bipolar disorder; psychosocial treatment; diet; exercise; cognitive-behavioral therapy ID NEUROPSYCHIATRIC INTERVIEW MINI; RANDOMIZED CONTROLLED-TRIAL; PHYSICAL-ACTIVITY; I-DISORDER; BEHAVIORAL-THERAPY; RELAPSE PREVENTION; COGNITIVE THERAPY; MAJOR DEPRESSION; MENTAL-DISORDERS; BLOOD-PRESSURE AB We developed an integrated psychosocial treatment for bipolar disorder to decrease the disproportionate medical burden associated with this illness. Three treatment modules, Nutrition/weight loss, Exercise, and Wellness Treatment (NEW Tx) were administered in twelve 60-minute group sessions over 14 weeks. After the first group (N = 4) had completed the treatment, it was revised, and then a second group (N = 6) completed the revised treatment. Participants completed all of the study assessments and attended 82% of the sessions. Both groups added over 100 minutes of weekly exercise to their baseline duration. Participants in the second group showed improvements in their quality of life, depressive symptoms, and weight. It appears that NEW Tx may be a feasible intervention with promising pilot data for reducing the medical burden in bipolar disorder, but future research is needed to further evaluate the efficacy of NEW Tx. (Journal of Psychiatric Practice 2011; 17: 224-232) C1 [Sylvia, Louisa G.; Nierenberg, Andrew A.; Peckham, Andrew D.; Deckersbach, Thilo] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Sylvia, Louisa G.; Nierenberg, Andrew A.; Deckersbach, Thilo] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Stange, Jonathan P.] Temple Univ, Dept Psychol, Philadelphia, PA 19122 USA. RP Sylvia, LG (reprint author), Bipolar Clin & Res Program, 50 Staniford St,Suite 580, Boston, MA 02114 USA. EM lsylvia2@partners.org FU NIMH NIH HHS [K23 MH091182] NR 55 TC 19 Z9 19 U1 3 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1527-4160 J9 J PSYCHIATR PRACT JI J. Psychiatr. Pract. PD MAY PY 2011 VL 17 IS 3 BP 224 EP 232 DI 10.1097/01.pra.0000398419.82362.32 PG 9 WC Psychiatry SC Psychiatry GA 765QX UT WOS:000290724800012 PM 21587004 ER PT J AU Htoon, J Nadig, A Hughes, T Yavuz, S Direskenel, H Saruhan-Direskeneli, G Sawalha, AH AF Htoon, Jasmine Nadig, Ajay Hughes, Travis Yavuz, Sule Direskenel, Haner Saruhan-Direskeneli, Guher Sawalha, Amr H. TI IL18 Polymorphism Is Associated with Behcet's Disease But Not Lupus in Patients from Turkey SO JOURNAL OF RHEUMATOLOGY LA English DT Letter ID PROMOTER POLYMORPHISMS; INTERLEUKIN-18 LEVELS; SERUM INTERLEUKIN-18; GENE POLYMORPHISMS; ERYTHEMATOSUS; IL-18; CRITERIA C1 [Htoon, Jasmine; Nadig, Ajay; Hughes, Travis; Sawalha, Amr H.] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. [Yavuz, Sule; Direskenel, Haner] Marmara Univ, Dept Rheumatol, Sch Med, Istanbul, Turkey. [Saruhan-Direskeneli, Guher] Istanbul Univ, Istanbul Sch Med, Dept Physiol, Istanbul, Turkey. [Sawalha, Amr H.] Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA. [Sawalha, Amr H.] US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. RP Sawalha, AH (reprint author), 825 NE 13th St,MS 24, Oklahoma City, OK 73104 USA. EM amr-sawalha@omrf.ouhsc.edu FU NCRR NIH HHS [P20RR020143, P20 RR020143]; NIAID NIH HHS [R03 AI076729, R03AI076729, R03 AI076729-01, R03 AI076729-02]; NIAMS NIH HHS [P30 AR053483, P30AR053483] NR 14 TC 12 Z9 12 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD MAY PY 2011 VL 38 IS 5 BP 962 EP 963 DI 10.3899/jrheum.101202 PG 2 WC Rheumatology SC Rheumatology GA 766KJ UT WOS:000290780700028 PM 21532063 ER PT J AU Sisto, R Moleti, A Botti, T Bertaccini, D Shera, CA AF Sisto, Renata Moleti, Arturo Botti, Teresa Bertaccini, Daniele Shera, Christopher A. TI Distortion products and backward-traveling waves in nonlinear active models of the cochlea SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID OTOACOUSTIC EMISSIONS; REVERSE PROPAGATION; BASILAR-MEMBRANE; FINE-STRUCTURE; AMPLIFICATION; REFLECTION; SOUND; EAR AB This study explores the phenomenology of distortion products in nonlinear cochlear models, predicting their amplitude and phase along the basilar membrane. The existence of a backward-traveling wave at the distortion-product frequency, which has been recently questioned by experiments measuring the phase of basilar-membrane vibration, is discussed. The effect of different modeling choices is analyzed, including feed-forward asymmetry, micromechanical roughness, and breaking of scaling symmetry. The experimentally observed negative slope of basilar-membrane phase is predicted by numerical simulations of nonlinear cochlear models under a wide range of parameters and modeling choices. In active models, positive phase slopes are predicted by the quasi-linear analytical computations and by the fully nonlinear numerical simulations only if the distortion-product sources are localized apical to the observation point and if the stapes reflectivity is unrealistically small. The results of this study predict a negative phase slope whenever the source is distributed over a reasonably wide cochlear region and/or a reasonably high stapes reflectivity is assumed. Therefore, the above-mentioned experiments do not contradict "classical" models of cochlear mechanics and of distortion-product generation. (C) 2011 Acoustical Society of America. [DOI:10.1121/1.3569700] C1 [Moleti, Arturo] Univ Roma Tor Vergata, Dipartimento Fis, I-00133 Rome, Italy. [Sisto, Renata] INAIL, Dipartimento Igiene Lavoro, I-00040 Monte Porzio Catone, Italy. [Botti, Teresa] Univ Insubria, Dipartimento Fis & Matemat, I-22100 Como, Italy. [Bertaccini, Daniele] Univ Roma Tor Vergata, Dipartimento Matemat, I-00133 Rome, Italy. [Shera, Christopher A.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. [Shera, Christopher A.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Moleti, A (reprint author), Univ Roma Tor Vergata, Dipartimento Fis, Via Ric Sci 1, I-00133 Rome, Italy. EM moleti@roma2.infn.it RI Moleti, Arturo/P-6812-2016; OI Moleti, Arturo/0000-0002-2465-8849; BERTACCINI, Daniele/0000-0002-3662-278X; Renata, Sisto/0000-0002-5086-7003 FU PRIN [20083KLJEZ] FX The contribution of D. Bertaccini has been partially supported by PRIN Grant 20083KLJEZ. NR 33 TC 12 Z9 12 U1 1 U2 4 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD MAY PY 2011 VL 129 IS 5 BP 3141 EP 3152 DI 10.1121/1.3569700 PG 12 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 762CR UT WOS:000290450400048 PM 21568417 ER PT J AU Pugh, MJ Tabares, J Finley, E Bollinger, M Tortorice, K VanCott, AC AF Pugh, Mary Jo Tabares, Jeffrey Finley, Erin Bollinger, Mary Tortorice, Kathy VanCott, Anne C. TI CHANGES IN ANTIEPILEPTIC DRUG CHOICE FOR OLDER VETERANS WITH NEW-ONSET EPILEPSY: 2002 TO 2006 SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Letter C1 [Pugh, Mary Jo; Tabares, Jeffrey; Finley, Erin; Bollinger, Mary] VERDICT REAP, S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Pugh, Mary Jo] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA. [Tortorice, Kathy] Hines Vet Affairs, Pharm Benefits Management Strateg Hlth Grp, Hines, IL USA. [VanCott, Anne C.] Univ Pittsburgh, Dept Neurol, Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA 15260 USA. RP Pugh, MJ (reprint author), VERDICT REAP, S Texas Vet Hlth Care Syst, San Antonio, TX USA. OI Pugh, Mary Jo/0000-0003-4196-7763; Finley, Erin/0000-0003-4497-7721 FU NINR NIH HHS [R01-NR010828] NR 6 TC 4 Z9 4 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAY PY 2011 VL 59 IS 5 BP 955 EP 956 PG 3 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 763RZ UT WOS:000290578700038 PM 21568976 ER PT J AU Freedman, RA Garber, JE AF Freedman, Rachel A. Garber, Judy E. TI Family Cancer History: Healthy Skepticism Required SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID BREAST-CANCER; POPULATION; VALIDATION; ACCURACY C1 [Freedman, Rachel A.; Garber, Judy E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Garber, JE (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,SM210, Boston, MA 02115 USA. EM jegarber@partners.org NR 16 TC 2 Z9 2 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAY PY 2011 VL 103 IS 10 BP 776 EP U84 DI 10.1093/jnci/djr142 PG 2 WC Oncology SC Oncology GA 766VA UT WOS:000290813400001 PM 21562244 ER PT J AU Smith, BD Pan, IW Shih, YCT Smith, GL Harris, JR Punglia, R Pierce, LJ Jagsi, R Hayman, JA Giordano, SH Buchholz, TA AF Smith, Benjamin D. Pan, I-Wen Shih, Ya-Chen T. Smith, Grace L. Harris, Jay R. Punglia, Rinaa Pierce, Lori J. Jagsi, Reshma Hayman, James A. Giordano, Sharon H. Buchholz, Thomas A. TI Adoption of Intensity-Modulated Radiation Therapy for Breast Cancer in the United States SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID IN-FIELD TECHNIQUE; CLINICAL COMORBIDITY INDEX; ACTIVE BREATHING CONTROL; CONFORMAL RADIOTHERAPY; RANDOMIZED-TRIALS; CLAIMS DATA; IRRADIATION; MEDICARE; IMRT; COST AB Background Although intensity modulation of the radiation beam has been shown to lower toxic effects for patients receiving whole-breast irradiation, relatively simple techniques may suffice. It is thus controversial whether such treatment justifies billing for intensity-modulated radiation therapy (IMRT). Methods We used the claims data to determine billing for IMRT from Surveillance, Epidemiology, and End Results-Medicare records from 2001 to 2005 for 26 163 women aged 66 years or older with nonmetastatic breast cancer treated with surgery and radiotherapy. The impact of individual covariates (demographic, health services, tumor, and treatment factors) on cost of treatment was assessed using the Wilcoxon two-sample test. Two-sided multivariable logistic regression was used to identify predictors for IMRT use. Cost of radiation was calculated in 2005 dollars. All statistical tests were two-sided. Results The number of patients with IMRT billing claims increased from 0.9% (49 of 5196) of patients diagnosed in 2001 to 11.2% (564 of 5020) in 2005. In multivariable analysis, IMRT billing was more likely for patients with left-sided tumors (odds ratio [OR] = 1.30, 95% confidence interval [CI] = 1.16 to 1.45), for those residing in a health service area with high radiation oncologist density (OR = 2.32, 95% CI = 1.47 to 3.68), for those treated at freestanding radiation centers (OR = 1.36, 95% CI = 1.20 to 1.53), or for those residing in regions where the Medicare intermediary allowed breast IMRT (OR = 10.87, 95% CI = 9.26 to 12.76, all P <.001). The mean cost of radiation was $7179 without IMRT and $15 230 with IMRT. IMRT adoption contributed to an increase in the mean cost of breast radiation from $6334 in 2001 to $8473 in 2005. Conclusions IMRT billing increased 10-fold from 2001 through 2005, contributing to a 33% increase in the cost of breast radiation. These findings suggest that reimbursement policy and practice setting strongly influenced adoption of IMRT billing for breast cancer. C1 [Smith, Benjamin D.; Smith, Grace L.; Buchholz, Thomas A.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. [Pan, I-Wen; Shih, Ya-Chen T.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. [Giordano, Sharon H.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX 77030 USA. [Harris, Jay R.; Punglia, Rinaa] Dept Radiat Oncol, Brigham, Cumbria, England. [Harris, Jay R.; Punglia, Rinaa] Womens Hosp Med Ctr, Boston, MA USA. [Harris, Jay R.; Punglia, Rinaa] Dana Farber Canc Inst, Boston, MA 02115 USA. [Pierce, Lori J.; Jagsi, Reshma; Hayman, James A.] Univ Michigan, Dept Radiat Oncol, Ann Arbor, MI 48109 USA. RP Smith, BD (reprint author), Univ Texas Houston, MD Anderson Canc Ctr, Dept Radiat Oncol, 1515 Holcombe Blvd,Unit 1202, Houston, TX 77030 USA. EM bsmith3@mdanderson.org OI Jagsi, Reshma/0000-0001-6562-1228; Smith, Benjamin/0000-0001-7866-1093; Pan, Iwen/0000-0002-2781-2629 FU Department of Radiation Oncology at the University of Texas M. D. Anderson Cancer Center; American Cancer Society [MRSG-09-145-01]; Cancer Prevention and Research Institute of Texas [RP101207]; Agency for Healthcare Research and Quality [R01 HS018535] FX This work was supported in part by a research grant from Varian Medical Equipment to the Department of Radiation Oncology at the University of Texas M. D. Anderson Cancer Center. T. A. B. was the principal investigator for a portion of this grant. This work was also supported in part by a Mentored Research Scholar Grant from the American Cancer Society (MRSG-09-145-01 to R.J.), the Cancer Prevention and Research Institute of Texas (RP101207 to B. D. S.), and the Agency for Healthcare Research and Quality (R01 HS018535 to Y.T.S.). NR 42 TC 61 Z9 63 U1 0 U2 15 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAY PY 2011 VL 103 IS 10 BP 798 EP 809 DI 10.1093/jnci/djr100 PG 12 WC Oncology SC Oncology GA 766VA UT WOS:000290813400008 PM 21525437 ER PT J AU Kuklina, EV Bateman, BT AF Kuklina, Elena V. Bateman, Brian T. TI Pregnancy Complications and Prevention of Cardiovascular Disease in Women: Stay Tuned SO JOURNAL OF WOMENS HEALTH LA English DT Editorial Material ID GENDER-SPECIFIC ASPECTS; C-REACTIVE PROTEIN; RISK-FACTORS; PREECLAMPSIA C1 [Kuklina, Elena V.] Ctr Dis Control & Prevent, Div Heart Dis & Stroke Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30341 USA. [Bateman, Brian T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. RP Kuklina, EV (reprint author), Ctr Dis Control & Prevent, Div Heart Dis & Stroke Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, 4770 Buford Highway NE,MS K-37, Atlanta, GA 30341 USA. EM ekuklina@cdc.gov NR 22 TC 1 Z9 1 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD MAY PY 2011 VL 20 IS 5 BP 657 EP 659 DI 10.1089/jwh.2011.2827 PG 3 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 766MF UT WOS:000290785800003 PM 21599426 ER PT J AU Meltzer, EO Hamilos, DL AF Meltzer, Eli O. Hamilos, Daniel L. TI Rhinosinusitis Diagnosis and Management for the Clinician: A Synopsis of Recent Consensus Guidelines SO MAYO CLINIC PROCEEDINGS LA English DT Review ID PLACEBO-CONTROLLED TRIAL; FUROATE NASAL SPRAY; ACUTE MAXILLARY SINUSITIS; RANDOMIZED CONTROLLED-TRIAL; CILIARY-BEAT FREQUENCY; ACUTE BACTERIAL RHINOSINUSITIS; APPROPRIATE ANTIBIOTIC USE; DOUBLE-BLIND; FLUTICASONE PROPIONATE; MUCOCILIARY CLEARANCE AB Rhinosinusitis (RS) affects approximately 1 in 7 adults In the United States, and its effect on quality of life, productivity, and finances Is substantial. During the past 10 years, several expert panels from authoritative bodies have published evidence-based guidelines for the diagnosis and management of RS and its subtypes, Including acute viral RS, acute bacterial RS, chronic RS (CRS) without nasal polyposis, CRS with nasal polyposis, and allergic fungal RS. This review examines and compares the recommendations of the Rhinosinusitis initiative, the Joint Task Force on Practice Parameters, the Clinical Practice Guideline: Adult Sinusitis, the European Position Paper on Rhinosinusitis and Nasal Polyps 2007, and the British Society for Allergy and Clinical immunology. Points of consensus and divergent opinions expressed In these guidelines regarding classification, diagnosis, and management of adults with acute RS (ARS) and CRS and their various subtypes are highlighted for the practicing clinician. Key points of agreement regarding therapy in the guidelines for ARS include the efficacy of symptomatic treatment, such as intranasal corticosteroids, and the importance of reducing the unnecessary use of antibiotics in ARS; however, guidelines do not agree precisely regarding when antibiotics should be considered as a reasonable treatment strategy. Although the guidelines diverge markedly on the management of CRS, the diagnostic utility of nasal airway examination is acknowledged by all. Important and relevant data from MEDLINE-Indexed articles published since the most recent guidelines were issued are also considered, and needs for future research are discussed. C1 [Meltzer, Eli O.] Allergy & Asthma Med Grp & Res Ctr, San Diego, CA 92123 USA. [Hamilos, Daniel L.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. RP Meltzer, EO (reprint author), Allergy & Asthma Med Grp & Res Ctr, 9610 Granite Ridge Dr,Ste B, San Diego, CA 92123 USA. EM eomeltzer@aol.com FU Alcon; Alexza Pharmaceuticals; Amgen; Antigen Labs; Apotex; Astellas; AstraZeneca; Boehringer Ingelheim; Forest; GlaxoSmithKline; Johnson Johnson; MAP; MEDA; Medimmune; Merck; Novartis; Proctor Gamble; Schering-Plough; Sepracor; Teva; UCB; Schering Corp, now Merck Co. FX Dr Meltzer has received grant/research support from Alcon, Alexza Pharmaceuticals, Amgen, Antigen Labs, Apotex, Astellas, AstraZeneca, Boehringer Ingelheim, Forest, GlaxoSmithKline, Johnson & Johnson, MAP, MEDA, Medimmune, Merck, Novartis, Proctor & Gamble, Schering-Plough, Sepracor, Teva, and UCB. He has served as a consultant/speaker for Alcon, Alexza Pharmaceuticals, Amgen, AstraZeneca, Boehringer Ingelheim, Capnia, Dainippon Sumitomo, Dey, GlaxoSmithKline, ISTA, Johnson & Johnson, Kalypsys, MAR Meda, Merck, Sandoz, sanofi-aventis, Schering-Plough, Sepracor, SRxA, Stallergenes, Teva, VentiRx, Wockhardt, and Wyeth. Dr. Hamilos has received book royalties from UpToDate and lnforma. Editorial assistance for the submitted manuscript was funded by Schering Corp, now Merck & Co. NR 161 TC 83 Z9 90 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD MAY PY 2011 VL 86 IS 5 BP 427 EP 443 DI 10.4065/mcp.2010.0392 PG 17 WC Medicine, General & Internal SC General & Internal Medicine GA 763IF UT WOS:000290549300009 PM 21490181 ER PT J AU Tsiamas, P Seco, J Han, Z Bhagwat, M Maddox, J Kappas, C Theodorou, K Makrigiorgos, M Marcus, K Zygmanski, P AF Tsiamas, P. Seco, J. Han, Z. Bhagwat, M. Maddox, J. Kappas, C. Theodorou, K. Makrigiorgos, M. Marcus, K. Zygmanski, P. TI A modification of flattening filter free linac for IMRT SO MEDICAL PHYSICS LA English DT Article DE Monte Carlo; flattening filter free; electron beam modification; peripheral dose; IMRT ID MODULATED RADIATION-THERAPY; FREE CLINICAL ACCELERATOR; MULTILEAF COLLIMATOR TRANSMISSION; MEDICAL LINEAR-ACCELERATOR; DOSE CALCULATION ALGORITHM; UNFLATTENED PHOTON BEAMS; MONTE-CARLO-SIMULATION; STOPPING-POWER RATIOS; STEREOTACTIC RADIOTHERAPY; SPATIAL DEPENDENCE AB Purpose: This study investigates the benefits of a modified flattening filter free (FFF) linac over the standard (STD) linac equipped with the flattening filter. Energy and angular spread of the electron beam of the FFF linac were modified. Modification of FFF beam parameters is explored to maximize the monitor unit efficiency and to minimize the head scatter in IMRT delivery for large target volumes or targets lying away from the central axis. Methods: The EGSnrc code is used to model FFF and STD linacs and study basic beam properties for both linac types in various beam configurations. Increasing energy of FFF linac results in similar beam attenuation properties and maximized dose rate compared to STD linac. Matching beam attenuation properties allows a more direct exploration of beam flatness of FFF linac in regard to IMRT delivery, especially away from the central axis where the effective dose rate is considerably smaller than the one at the central axis. Flatness of open beam dose profile of FFF linac is improved by increasing the angular spread of the electron beam. The resulting dose rate within the treatment field and outside of the field (peripheral dose) are characterized and compared to the unmodified FFF and STD linacs. Results: In order to match beam penetration properties, the energy of FFF is adjusted from 6.5 to 8.0 MeV for small to medium field sizes and from 6.5 to 8.5 MeV for larger ones. Dose rate of FFF vs STD linac increased by a factor of 1.9 (6.5 MeV) and 3.4-4.1 (8.0-8.5 MeV). Adjusting the mean angular spread of the electron beam from 0 degrees to 5 degrees-10 degrees resulted in complete flattening of photon beam for field sizes between 10 x 10 cm(2) and 15 x 15 cm(2) and partial flattening for field sizes from 15 x 15 cm(2) to 30 x 30 cm(2). Values of angular spread >= 14 degrees are not recommended as they exceed the opening of the primary collimator, affecting the area at the edges of the field. FFF fields of sizes smaller than 6 x 6 cm(2) are already flat and beam flattening is not necessary. Overall, the angular spread of 5 degrees-10 degrees is sufficient and can satisfactorily flatten open beam dose profiles even for larger field sizes. Increasing the electron beam angular spread amounts to a slight decrease of dose rate of FFF linac. However, for angular spread, 5 degrees-10 degrees dose rate factor of FFF vs STD is still about 1.6-2.6, depending on the field size (and the adjusted energy). Similarly, in case of peripheral dose, a moderate increase in dose can be observed for angular spread of 5 degrees-10 degrees and for field sizes 10 x 10 cm(2) to 30 x 30 cm(2). Lastly, beam flatness of not modified FFF linac can be conveniently described by an analytical function representing a ratio of STD vs FFF doses: 1 + b vertical bar r vertical bar(n). Conclusions: A modified FFF beamline with increased energy and electron beam angular spread results in satisfactory flattened beam and high dose rate within the field. Peripheral dose remaining at similar (or smaller) level than that of STD linac for the same delivered dose within the treatment field. (C) 2011 American Association of Physicists in Medicine. [DOI: 10.1118/1.3571419] C1 [Tsiamas, P.; Han, Z.; Bhagwat, M.; Maddox, J.; Makrigiorgos, M.; Marcus, K.; Zygmanski, P.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Tsiamas, P.; Han, Z.; Bhagwat, M.; Maddox, J.; Makrigiorgos, M.; Marcus, K.; Zygmanski, P.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Tsiamas, P.; Kappas, C.; Theodorou, K.] Univ Thessaly, Sch Med, Dept Med Phys, Larisa 4100, Greece. [Seco, J.] Massachusetts Gen Hosp, Boston, MA 02138 USA. [Seco, J.] Harvard Med, Boston, MA 02138 USA. RP Marcus, K (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM kmarcus@lroc.harvard.edu; pzygmanski@lroc.harvard.edu NR 45 TC 12 Z9 12 U1 0 U2 3 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 MAY PY 2011 VL 38 IS 5 BP 2342 EP 2352 DI 10.1118/1.3571419 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 764JL UT WOS:000290625700007 PM 21776768 ER PT J AU Kalamarides, M Stemmer-Rachamimov, AO Niwa-Kawakita, M Chareyre, F Taranchon, E Han, ZY Martinelli, C Lusis, EA Hegedus, B Gutmann, DH Giovannini, M AF Kalamarides, M. Stemmer-Rachamimov, A. O. Niwa-Kawakita, M. Chareyre, F. Taranchon, E. Han, Z-Y Martinelli, C. Lusis, E. A. Hegedus, B. Gutmann, D. H. Giovannini, M. TI Identification of a progenitor cell of origin capable of generating diverse meningioma histological subtypes SO ONCOGENE LA English DT Article DE neurofibromatosis type 2; arachnoid; brain tumours ID PROSTAGLANDIN-D SYNTHASE; BETA-TRACE; NATURAL-HISTORY; INCIDENTAL MENINGIOMAS; CHOROID-PLEXUS; SKULL BASE; ADULT-RAT; IN-VIVO; NF2; MICE AB Meningiomas are among the most common primary central nervous system tumours in adults. Studies focused on the molecular basis for meningioma development are hampered by a lack of information with regard to the cell of origin for these brain tumours. Herein, we identify a prostaglandin D synthase-positive meningeal precursor as the cell of origin for murine meningioma, and show that neurofibromatosis type 2 (Nf2) inactivation in prostaglandin D2 synthase (PGDS) (+) primordial meningeal cells, before the formation of the three meningeal layers, accounts for the heterogeneity of meningioma histological subtypes. Using a unique PGDSCre strain, we define a critical embryonic and early postnatal developmental window in which biallelic Nf2 inactivation in PGDS (+) progenitor cells results in meningioma formation. Moreover, we identify differentially expressed markers that characterize the two major histological meningioma subtypes both in human and mouse tumours. Collectively, these findings establish the cell of origin for these common brain tumours as well as a susceptible developmental period in which signature genetic mutations culminate in meningioma formation. Oncogene (2011) 30, 2333-2344; doi: 10.1038/onc.2010.609; published online 17 January 2011 C1 [Giovannini, M.] House Ear Res Inst, Ctr Neural Tumor Res, Los Angeles, CA 90057 USA. [Kalamarides, M.; Niwa-Kawakita, M.; Chareyre, F.; Taranchon, E.; Han, Z-Y; Martinelli, C.; Giovannini, M.] INSERM, U674, Paris, France. [Kalamarides, M.; Niwa-Kawakita, M.; Chareyre, F.; Taranchon, E.; Han, Z-Y; Martinelli, C.; Giovannini, M.] Univ Paris 07, Inst Univ Hematol, Paris, France. [Kalamarides, M.] Hop Beaujon, AP HP, Serv Neurochirurg, Clichy, France. [Stemmer-Rachamimov, A. O.] Massachusetts Gen Hosp, Mol Neurooncol & Pathol Dept, Boston, MA 02114 USA. [Stemmer-Rachamimov, A. O.] Harvard Univ, Sch Med, Boston, MA USA. [Lusis, E. A.] Washington Univ, Sch Med, Dept Neurosurg, St Louis, MO USA. [Hegedus, B.; Gutmann, D. H.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. RP Giovannini, M (reprint author), House Ear Res Inst, Ctr Neural Tumor Res, 2100W 3rd St, Los Angeles, CA 90057 USA. EM mgiovannini@hei.org RI Hegedus, Balazs/B-6076-2008 OI Hegedus, Balazs/0000-0002-4341-4153 FU US Army Medical Research and Materiel Command [DAMD17-02-1-0645]; James S McDonnell Foundation; Association Neurofibromatoses et Recklinghausen; Vincent Buono Research Fund; Inserm FX We thank A Berns for p16Ink4a and p53flox mutant mice; S Dufour and JP Thiery for HtPACre mice; Y Urade for the PGDS genomic fragment; M Pla and staff of the Institut Universitaire d'Hematologie (IUH), Universite Paris 7, for mouse housing; N Karboul for technical assistance; and M Catala and W Van Furth for helpful discussions. This work was supported by Grants from the US Army Medical Research and Materiel Command (DAMD17-02-1-0645 to MG), James S McDonnell Foundation (to DHG and MG), Association Neurofibromatoses et Recklinghausen, the Vincent Buono Research Fund (to DHG and MG) and Inserm. NR 44 TC 32 Z9 33 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAY PY 2011 VL 30 IS 20 BP 2333 EP 2344 DI 10.1038/onc.2010.609 PG 12 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 766NF UT WOS:000290789200005 PM 21242963 ER PT J AU Tavernier, SS Beck, SL Clayton, MF Pett, MA Berry, DL AF Tavernier, Susan S. Beck, Susan L. Clayton, Margaret F. Pett, Marjorie A. Berry, Donna L. TI Validity of the Patient Generated Index as a Quality-of-Life Measure in Radiation Oncology SO ONCOLOGY NURSING FORUM LA English DT Article ID DISTRESS THERMOMETER; CANCER-PATIENTS; CLINICAL-TRIALS; CENTERED ASSESSMENT; RESPONSE SHIFT; QUESTIONNAIRE; INSTRUMENTS; VALIDATION; DISORDERS AB Purpose/Objectives: To evaluate psychometric properties of an instrument designed to measure individualized health-related quality of life (HRQOL). Design: Repeated measures of self-reported quality of life. Setting: An outpatient radiation therapy department in the western part of the United States. Sample: 86 adults with cancer receiving their first course of radiation therapy. Methods: The Patient Generated Index (PGI), the National Comprehensive Cancer Network's Distress Thermometer (DT), and the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire-Core30 (QLQ-C30). Main Research Variables: Convergent validity, responsiveness, sensitivity, and response shift. Findings: PGI scores were inversely correlated with scores on the DT (r = -0.49, -0.55, -0.44; p < 0.001), as well as the role (r = 0.31, 0.4, 0.38; p < 0.01), emotional (r = 0.33, 0.41, 0.33; p < 0.01), social functioning (r = 0.27, 0.49, 0.42; p < 0.05), pain (r = -0.29, -0.39, -0.39; p < 0.01), and fatigue (r = -0.35, -0.25, -0.47; p < 0.05) QLQ-C30 subscales at all measurement times. The PGI was responsive to those reporting high or low DT scores (t = 4.42, 3.32, 2.9; p < 0.05). A small-to-moderate effect size was detected in those who had an increase (effect size = 0.51) or decrease (effect size = 0.38) in HRQOL over time. Participants reconceptualized HRQOL over time. Conclusions: Data supported the PGI as a valid measure of individualized HRQOL. Implications for Nursing: The PGI potentially provides a more patient-centered measure of HRQOL in patients with cancer. Additional testing is needed in larger, more diverse groups. C1 [Tavernier, Susan S.] St Alphonsus Reg Med Ctr, Boise, ID 83706 USA. [Beck, Susan L.; Clayton, Margaret F.; Pett, Marjorie A.] Univ Utah, Coll Nursing, Salt Lake City, UT 84112 USA. [Berry, Donna L.] Dana Farber Canc Inst, Phyllis F Cantor Ctr Res Nursing & Patient Care S, Boston, MA 02115 USA. RP Tavernier, SS (reprint author), St Alphonsus Reg Med Ctr, Boise, ID 83706 USA. EM susatave@sarmc.org FU National Cancer Institute [R25 CA093831]; Sigma Theta Tau Mu Gamma Chapter; University of Utah FX Susan S. Tavernier, PhD, RN, APRN-CNS, AOCN (R), is an oncology clinical nurse specialist at Saint Alphonsus Regional Medical Center in Boise, ID when this article was written; Susan L. Beck, PhD, APRN, AOCN (R), FAAN, is a professor, Margaret F. Clayton, PhD, RN, FNP-CS, is an assistant professor, and Marjorie A. Pett, MStat, DSW, is a research professor, all in the College of Nursing at the University of Utah in Salt Lake City; and Donna L. Berry, PhD, RN, AOCN (R), FAAN, is the director of the Phyllis F. Cantor Center for Research in Nursing and Patient Care Services at the Dana-Farber Cancer Institute in Boston, MA. This article presents findings from the lead author's dissertation and was funded in part by a National Cancer Institute training grant (R25 CA093831 [K. Mooney, principal investigator]), Sigma Theta Tau Mu Gamma Chapter, and the University of Utah George S. and Dolores Dore Eccles Scholarship Fund. Tavernier can be reached at susatave@sarmc.org, with copy to the editor at ONFEditor@ons.org. (Submitted April 2010. Accepted for publication April 26, 2010). NR 46 TC 4 Z9 4 U1 1 U2 1 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAY PY 2011 VL 38 IS 3 BP 319 EP 329 DI 10.1188/11.ONF.319-329 PG 11 WC Oncology; Nursing SC Oncology; Nursing GA 761TL UT WOS:000290423800013 PM 21531682 ER PT J AU Sheldon, LK Hilaire, D Berry, DL AF Sheldon, Lisa Kennedy Hilaire, Dany Berry, Donna L. TI Provider Verbal Responses to Patient Distress Cues During Ambulatory Oncology Visits SO ONCOLOGY NURSING FORUM LA English DT Article ID COMMUNICATION-SKILLS; CANCER-PATIENTS; NURSES; ANXIETY AB Purpose/Objectives: To explore healthcare provider cue-responding behaviors to patient cues of distress and socioemotional concerns during ambulatory, on-treatment oncology visits. Design: Descriptive secondary analysis of a data set of audio recordings of oncology visits and reports of symptoms and quality of life recorded with an electronic self-report assessment-cancer (ESRA-C) tool. Setting: Comprehensive cancer center, ambulatory care. Sample: 31 randomly selected cases from an existing data set (with one used as a training tool) of 590 audio recordings of patient-provider communication. Methods: Patients were placed in Group 1 (n = 20) and Group 2 (n = 10) to explore differences in patient-provider communication and decrease coder bias. Both groups completed the ESRA-C questionnaire prior to the visit. Providers in Group 2 received a printed ESRA-C summary report for use during the visit. Audio files of the visit were coded using the Medical Interview Aural Rating System (MIARS). Main Research Variables: Patient cues of distress and provider cue-responding behaviors. Findings: Patient cues of distress and socioemotional concerns ranged from 0-13 cues per visit, with a mean of 4.6 cues per visit. Providers acknowledged 57% of patient cues, but only acknowledged and explored 22% of all patient cues. Providers in Group 2 acknowledged patient concerns more often but explored the concerns less frequently. The number of patient cues distanced from by providers was lower in Group 2 and the overall provider score for responsiveness to patient cues of distress was higher, indicating more responsiveness than from Group 1. Conclusions: The use of a summary report of patient concerns may have enhanced provider responsiveness, in general. Distancing behaviors by providers in response to patient verbal cues may indicate a lack of knowledge, time limitations, or a lack of confidence. Implications for Nursing: To effectively support patients with cancer through active therapy, a greater level of acknowledgment, exploration, and responsive action by providers is indicated. These findings have implications for provider education, with regard to appropriate responses, and for researchers to test methods that best prompt and support effective provider behaviors, ultimately improving patient outcomes. C1 [Sheldon, Lisa Kennedy; Hilaire, Dany] Univ Massachusetts, Boston, MA 02125 USA. [Sheldon, Lisa Kennedy] St Joseph Hosp, Nashua, NH USA. [Sheldon, Lisa Kennedy] Dana Farber Harvard Canc Ctr, Boston, MA USA. [Berry, Donna L.] Dana Farber Canc Inst, Cantor Ctr Res Nursing & Patient Care Serv, Boston, MA USA. [Berry, Donna L.] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. RP Sheldon, LK (reprint author), Univ Massachusetts, Boston, MA 02125 USA. EM lisa.kennedysheldon@umb.edu OI Sheldon, Lisa Kennedy/0000-0002-5958-8529 NR 30 TC 11 Z9 11 U1 1 U2 3 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAY PY 2011 VL 38 IS 3 BP 369 EP 375 DI 10.1188/11.ONF.369-375 PG 7 WC Oncology; Nursing SC Oncology; Nursing GA 761TL UT WOS:000290423800019 ER PT J AU Dighe, MK Wieseler, KM Bhargava, P Kanal, KM Vaidya, S Stewart, BK AF Dighe, Manjiri K. Wieseler, Karen M. Bhargava, Puneet Kanal, Kalpana M. Vaidya, Sandeep Stewart, Brent K. TI Re: More Cautions on Imaging of Pregnant Patients Response SO RADIOGRAPHICS LA English DT Letter C1 [Dighe, Manjiri K.; Wieseler, Karen M.; Bhargava, Puneet; Kanal, Kalpana M.; Vaidya, Sandeep; Stewart, Brent K.] Univ Washington, Med Ctr, Dept Radiol, Seattle, WA 98195 USA. [Bhargava, Puneet] Vet Affairs Puget Sound Healthcare Syst, Dept Radiol, Seattle, WA USA. [Vaidya, Sandeep] Univ Washington, Harborview Med Ctr, Dept Radiol, Seattle, WA 98104 USA. RP Dighe, MK (reprint author), Univ Washington, Med Ctr, Dept Radiol, Box 357115,1959 NE Pacific St, Seattle, WA 98195 USA. EM dighe@u.washington.edu RI Bhargava, Puneet /F-1330-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD MAY-JUN PY 2011 VL 31 IS 3 BP 891 EP 892 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 763WN UT WOS:000290590500023 ER PT J AU Quillard, T Croce, K Jaffer, FA Weissleder, R Libby, P AF Quillard, Thibaut Croce, Kevin Jaffer, Farouc A. Weissleder, Ralph Libby, Peter TI Molecular imaging of macrophage protease activity in cardiovascular inflammation in vivo SO THROMBOSIS AND HAEMOSTASIS LA English DT Article DE Proteases; imaging; macrophage ID MATRIX-METALLOPROTEINASE ACTIVITY; ABDOMINAL AORTIC-ANEURYSMS; CARDIAC ALLOGRAFT-REJECTION; MAGNETIC-RESONANCE; ATHEROSCLEROTIC PLAQUES; MYOCARDIAL-INFARCTION; VASCULAR INFLAMMATION; SCAVENGER RECEPTOR; TREATMENT RESPONSE; ENZYME-ACTIVITY AB Macrophages contribute pivotally to cardiovascular diseases (CVD), notably to atherosclerosis. Imaging of macrophages in vivo could furnish new tools to advance evaluation of disease and therapies. Proteolytic enzymes serve as key effectors of many macrophage contributions to CVD. Therefore, intravital imaging of protease activity could aid evaluation of the progress and outcome of atherosclerosis, aortic aneurysm formation, or rejection of cardiac allografts.Among the large families of proteases, matrix metalloproteinases (MMPs) and cysteinyl cathepsins have garnered the most interest because of their participation in extracellular matrix remodelling. These considerations have spurred the development of dedicated imaging agents for protease activity detection. Activatable fluorescent probes, radiolabelled inhibitors, and nanoparticles are currently under exploration for this purpose. While some agents and technologies may soon see clinical use, others will require further refinement. Imaging of macrophages and protease activity should provide an important adjunct to understanding pathophysiology in vivo, evaluating the effects of interventions, and ultimately aiding clinical care. C1 [Quillard, Thibaut; Croce, Kevin; Libby, Peter] Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp,Div Cardiovasc Med, Boston, MA 02115 USA. [Jaffer, Farouc A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr,Cardiol Div, Boston, MA 02115 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02115 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02115 USA. RP Libby, P (reprint author), Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp,Div Cardiovasc Med, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM plibby@rics.bwh.harvard.edu RI Quillard, Thibaut/K-8150-2015; OI Quillard, Thibaut/0000-0002-8096-2597; Jaffer, Farouc/0000-0001-7980-384X FU National Institutes of Health [R01 -HL080472]; Translational Program of Excellence in Nanotechnology (TPEN) [U01 HL080731]; American Heart Association FX We thank our colleagues affiliated with the Donald W. Reynolds Clinical Cardiovascular Research Center at Harvard Medical School, who contributed to our efforts to develop molecular imaging of atherosclerosis and cardiovascular diseases. We also acknowledge the National Institutes of Health (R01 -HL080472), the Translational Program of Excellence in Nanotechnology (TPEN) (U01 HL080731), and the American Heart Association for their support. NR 93 TC 26 Z9 27 U1 3 U2 15 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD MAY PY 2011 VL 105 IS 5 SI SI BP 828 EP 836 DI 10.1160/TH10-09-0589 PG 9 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 767TE UT WOS:000290878400014 PM 21225096 ER PT J AU Porter, MP Kerrigan, MC Donato, BMK Ramsey, SD AF Porter, Michael P. Kerrigan, Matthew C. Donato, Bonnie M. K. Ramsey, Scott D. TI Patterns of use of systemic chemotherapy for Medicare beneficiaries with urothelial bladder cancer SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE Bladder neoplasms; Drug therapy; Delivery of health care; SEER program; Medicare ID NEOADJUVANT CHEMOTHERAPY; ELDERLY-PATIENTS; CARCINOMA; METHOTREXATE; METAANALYSIS; CARBOPLATIN; PACLITAXEL; MANAGEMENT; TRIAL AB Objectives: Examine the association between clinical, demographic, and socioeconomic factors and the receipt of systemic chemotherapy for bladder cancer. Examine factors influencing the use of combination chemotherapy plus cystectomy and use of specific chemotherapy drugs over time for bladder cancer. Materials and methods: Data from the SEER-Medicare database were analyzed for patients diagnosed with urothelial carcinoma of the bladder between 1992 and 2002. Cox proportional hazards regression analyses were used to assess differences in use of systemic chemotherapy based on demographic and clinical factors, site of care, and year of diagnosis. We assessed the proportion of patients who received chemotherapy in the adjuvant and neoadjuvant settings as well as use of chemotherapy in the monotherapy setting. We estimated the proportion of claims made for several commonly used chemotherapy agents in the outpatient setting by year. Results: During follow-up, 13%, 28%, 37%, and 57% of patients with stages 1 through 4, respectively, received systemic chemotherapy for bladder cancer. Chemotherapy use in the neoadjunvant or adjuvant settings within 6 months of diagnosis was not commonly found. Neoadjuvant chemotherapy was delivered to 1.4% Of stage 2 patients and 11% of stage 4 patients. In 2003, the most frequent claims for intravenous chemotherapy were for gemcitabine, carboplatin, and placlitaxel. Conclusions: Chemotherapy was not generally used as recommended for persons with invasive bladder cancer in this patient population. Studies to clarify potential underutilization and variation in patterns of;administration are warranted. (C) 2011 Elsevier Inc. All rights reserved. C1 [Ramsey, Scott D.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Porter, Michael P.] Univ Washington, Dept Urol, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Kerrigan, Matthew C.] GlaxoSmithKline Inc, Philadelphia, PA 19102 USA. [Donato, Bonnie M. K.] Bristol Myers Squibb Co, Wallingford, CT 06492 USA. RP Ramsey, SD (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. EM sramsey@fhcrc.org FU Bristol-Myers Squibb FX This study was funded by Bristol-Myers Squibb. The study has been approved by the Fred Hutchinson Cancer Research Center Institutional Review Board and by the SEER Medicare Institutional Review Board. NR 22 TC 57 Z9 58 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD MAY-JUN PY 2011 VL 29 IS 3 BP 252 EP 258 DI 10.1016/j.urolonc.2009.03.021 PG 7 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 766JW UT WOS:000290779400005 PM 19450992 ER PT J AU Nguyen, PL Lin, DI Lei, JY Fiorentino, M Mueller, E Weinstein, MH Pagano, M Loda, M AF Nguyen, Paul L. Lin, Douglas I. Lei, Junyi Fiorentino, Michelangelo Mueller, Elke Weinstein, Michael H. Pagano, Michele Loda, Massimo TI The impact of Skp2 overexpression on recurrence-free survival following radical prostatectomy SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE Skp2; Biomarker; Prostate cancer; Recurrence ID KINASE INHIBITOR P27(KIP1); LIGASE SUBUNIT SKP2; HUMAN BREAST-CANCER; UBIQUITIN LIGASE; PROTEIN EXPRESSION; P27; DEGRADATION; RADIOTHERAPY; ANTIGEN; CELLS AB Background: In several human cancers, overexpression of Skp2 (S-phase kinase associated protein 2), which targets p27 for degradation, portends a poorer prognosis. We examined whether Skp2 overexpression is associated with recurrence following radical prostatectomy (RP) for prostate cancer. Methods: Immunohistochemical staining for Skp2, p27, and MIB-1 was performed on 109 men with node-negative prostate cancer surgically managed from 1985-1996. Associations between the stains were tested and Cox regression was used to determine the association between Skp2 expression and time to biochemical recurrence following RP. Results: The 12 tumors (11%) with Skp2 overexpression all had correspondingly low p27 expression (P = 0.006), and a similar inverse Skp2/p27 relationship was seen in vitro in LNCap cells. Skp2 overexpression in tissue was associated with higher Gleason score (P = 0.002), more advanced pathological stage (P = 0.01), and higher MIB-1 index (P = 0.03), but a more favorable PSA profile (P = 0.04). Five men received a TURP. Among 104 who received RP, median follow-up was 67 months (range: 0.2-218). After adjusting for PSA, pathologic stage, and Gleason score, Skp2 overexpression remained significantly associated with a shorter time to biochemical recurrence (adjusted hazard ratio 4.8 (95% C.I. 1.6-14, P = 0.004)). The median time to recurrence with high vs. low Skp2 was 4 vs. 54 months. Conclusions: Skp2 overexpression was seen in a significant minority of surgically-managed men and was independently associated with a higher risk of recurrence, raising the possibility that Skp2 could be useful as a prognostic biomarker and as a potential molecular target for novel systemic agents in prostate cancer. (C) 2011 Elsevier Inc. All rights reserved. C1 [Nguyen, Paul L.; Lin, Douglas I.; Lei, Junyi; Fiorentino, Michelangelo; Mueller, Elke; Weinstein, Michael H.; Pagano, Michele; Loda, Massimo] Brigham & Womens Hosp, Harvard Radiat Oncol Program, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Nguyen, PL (reprint author), Brigham & Womens Hosp, Harvard Radiat Oncol Program, Dana Farber Canc Inst, Boston, MA 02115 USA. EM pnguyen@LROC.harvard.edu OI pagano, michele/0000-0003-3210-2442 FU NCI NIH HHS [R01 CA076584] NR 18 TC 9 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD MAY-JUN PY 2011 VL 29 IS 3 BP 302 EP 308 DI 10.1016/j.urolonc.2009.03.022 PG 7 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 766JW UT WOS:000290779400014 PM 19450994 ER PT J AU Caposio, P Orloff, SL Streblow, DN AF Caposio, Patrizia Orloff, Susan L. Streblow, Daniel N. TI The role of cytomegalovirus in angiogenesis SO VIRUS RESEARCH LA English DT Article DE Angiogenesis; Cytomegalovirus; Endothelial cell ID SMOOTH-MUSCLE-CELLS; TRANSPLANT VASCULAR SCLEROSIS; APOE KNOCKOUT MICE; ENDOTHELIAL-CELLS; CHRONIC REJECTION; EXTRACELLULAR-MATRIX; ADHESION MOLECULES; ALTERED EXPRESSION; CORONARY-ARTERIES; HEART-TRANSPLANTS AB Human cytomegalovirus (HCMV) infection has been associated with the acceleration of vascular disease including atherosclerosis and transplant associated vasculopathy in solid organ transplants. HCMV promotes vascular disease at many of the different stages of the disease development. These include the initial injury phase, enhancing the response to injury and inflammation, as well as by increasing SMC hyperplasia and foamy macrophage cell formation. Angiogenesis is a critical process involved in the development of vascular diseases. Recently, HCMV has been shown to induce angiogenesis and this process is thought to contribute to HCMV-accelerated vascular disease and may also be important for HCMV-enhanced tumor formation. This review will highlight the role of HCMV in promoting angiogenesis. (C) 2010 Elsevier B.V. All rights reserved. C1 [Caposio, Patrizia; Orloff, Susan L.; Streblow, Daniel N.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97239 USA. [Caposio, Patrizia; Orloff, Susan L.; Streblow, Daniel N.] Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Portland, OR 97239 USA. [Orloff, Susan L.] Oregon Hlth & Sci Univ, Dept Surg, Portland, OR 97239 USA. [Orloff, Susan L.] Portland VA Med Ctr, Portland, OR 97239 USA. RP Streblow, DN (reprint author), Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, 505 SW 185th, Beaverton, OR 97006 USA. EM streblow@ohsu.edu FU National Institutes of Health [HL 083194, HL 085451, HL 088603] FX This work was supported by research grants from the National Institutes of Health to D.N. Streblow (HL 083194), S.L. Orloff (HL 085451) and J.A. Nelson (HL 088603). NR 89 TC 33 Z9 33 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1702 J9 VIRUS RES JI Virus Res. PD MAY PY 2011 VL 157 IS 2 SI SI BP 204 EP 211 DI 10.1016/j.virusres.2010.09.011 PG 8 WC Virology SC Virology GA 767WM UT WOS:000290889500010 PM 20869406 ER PT J AU Hwang, U McCarthy, ML Aronsky, D Asplin, B Crane, PW Craven, CK Epstein, SK Fee, C Handel, DA Pines, JM Rathlev, NK Schafermeyer, RW Zwemer, FL Bernstein, SL AF Hwang, Ula McCarthy, Melissa L. Aronsky, Dominik Asplin, Brent Crane, Peter W. Craven, Catherine K. Epstein, Stephen K. Fee, Christopher Handel, Daniel A. Pines, Jesse M. Rathlev, Niels K. Schafermeyer, Robert W. Zwemer, Frank L., Jr. Bernstein, Steven L. TI Measures of Crowding in the Emergency Department: A Systematic Review SO ACADEMIC EMERGENCY MEDICINE LA English DT Review ID LENGTH-OF-STAY; PATIENT FLOW; REAL-TIME; OVERCROWDING SCALE; SAFETY NET; MODELS; SIMULATION; MORTALITY; VARIABLES; CAPACITY AB Objectives: Despite consensus regarding the conceptual foundation of crowding, and increasing research on factors and outcomes associated with crowding, there is no criterion standard measure of crowding. The objective was to conduct a systematic review of crowding measures and compare them in conceptual foundation and validity. Methods: This was a systematic, comprehensive review of four medical and health care citation databases to identify studies related to crowding in the emergency department (ED). Publications that "describe the theory, development, implementation, evaluation, or any other aspect of a 'crowding measurement/definition' instrument (qualitative or quantitative)" were included. A "measurement/definition" instrument is anything that assigns a value to the phenomenon of crowding in the ED. Data collected from papers meeting inclusion criteria were: study design, objective, crowding measure, and evidence of validity. All measures were categorized into five measure types (clinician opinion, input factors, throughput factors, output factors, and multidimensional scales). All measures were then indexed to six validation criteria (clinician opinion, ambulance diversion, left without being seen (LWBS), times to care, forecasting or predictions of future crowding, and other). Results: There were 2,660 papers identified by databases; 46 of these papers met inclusion criteria, were original research studies, and were abstracted by reviewers. A total of 71 unique crowding measures were identified. The least commonly used type of crowding measure was clinician opinion, and the most commonly used were numerical counts (number or percentage) of patients and process times associated with patient care. Many measures had moderate to good correlation with validation criteria. Conclusions: Time intervals and patient counts are emerging as the most promising tools for measuring flow and nonflow (i.e., crowding), respectively. Standardized definitions of time intervals (flow) and numerical counts (nonflow) will assist with validation of these metrics across multiple sites and clarify which options emerge as the metrics of choice in this "crowded" field of measures. ACADEMIC EMERGENCY MEDICINE 2011; 18:527-538 (C) 2011 by the Society for Academic Emergency Medicine C1 [Hwang, Ula] Mt Sinai Sch Med, Dept Emergency Med, New York, NY USA. [Hwang, Ula] James J Peters Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. [McCarthy, Melissa L.] Johns Hopkins Univ, Sch Med, Dept Emergency Med, Baltimore, MD USA. [Craven, Catherine K.] Johns Hopkins Univ, Sch Med, William H Welch Med Lib, Baltimore, MD USA. [Aronsky, Dominik] Vanderbilt Univ, Med Ctr, Dept Biomed Informat & Emergency Med, Nashville, TN USA. [Asplin, Brent] Mayo Clin, Dept Emergency Med, Rochester, MN USA. [Crane, Peter W.] Univ Rochester, Dept Emergency Med, Rochester, NY USA. [Epstein, Stephen K.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Emergency Med, Boston, MA 02215 USA. [Fee, Christopher] Univ Calif San Francisco, Dept Emergency Med, San Francisco, CA 94143 USA. [Handel, Daniel A.] Oregon Hlth & Sci Univ, Dept Emergency Med, Portland, OR 97201 USA. [Pines, Jesse M.] George Washington Univ, Med Ctr, Dept Emergency Med, Washington, DC 20037 USA. [Pines, Jesse M.] George Washington Univ, Med Ctr, Dept Hlth Policy, Washington, DC 20037 USA. [Rathlev, Niels K.] Baystate Med Ctr, Dept Emergency Med, Springfield, MA USA. [Schafermeyer, Robert W.] Carolinas Med Ctr, Dept Emergency Med, Charlotte, NC 28203 USA. [Zwemer, Frank L., Jr.] Virginia Commonwealth Univ, Dept Emergency Med, McGuire VA Med Ctr, Richmond, VA USA. [Bernstein, Steven L.] Yale Univ, Sch Med, Dept Emergency Med, New Haven, CT USA. RP Hwang, U (reprint author), Mt Sinai Sch Med, Dept Emergency Med, New York, NY USA. EM ula.hwang@mountsinai.org NR 77 TC 60 Z9 66 U1 9 U2 60 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD MAY PY 2011 VL 18 IS 5 BP 526 EP 537 DI 10.1111/j.1553-2712.2011.01054.x PG 12 WC Emergency Medicine SC Emergency Medicine GA 763SJ UT WOS:000290579700011 PM 21569171 ER PT J AU Ginde, AA Camargo, CA Shapiro, NI AF Ginde, Adit A. Camargo, Carlos A., Jr. Shapiro, Nathan I. TI Vitamin D Insufficiency and Sepsis Severity in Emergency Department Patients With Suspected Infection SO ACADEMIC EMERGENCY MEDICINE LA English DT Article ID SYSTEM; CARE AB Objectives: Vitamin D is increasingly recognized as an important mediator of immune function and may have a preventive role in the pathogenesis of sepsis. We sought to evaluate the association between vitamin D status and sepsis severity and hypothesized that vitamin D insufficiency would be associated with increased sepsis severity. Methods: This was a pilot study of emergency department (ED) patients age >= 18 years evaluated for suspected infection at an urban, teaching hospital. The authors measured illness severity using the following assessments at baseline and 24 hours: 1) severe sepsis, defined as suspected infection plus two or more elements of systemic inflammatory response syndrome criteria and acute dysfunction of one or more organ systems; 2) Acute Physiology Age Chronic Health Evaluation (APACHE) II scores; and 3) Sepsis-related Organ Failure Assessment (SOFA) scores. Vitamin D insufficiency was defined as baseline serum 25-hydroxyvitamin D (25OHD) levels <75 nmol/L. Results: Eighty-one patients were enrolled, with a median age of 62 years (interquartile range [IQR] = 48-76 years), 47% were female, and 77% were white. At baseline, 64 (79%) had 25OHD levels of <75 nmol/L, and 43 (53%) had severe sepsis. At 24 hours, 48 (59%) had severe sepsis. Patients with baseline 25OHD levels of <75 nmol/L, compared to patients with 25OHD levels of >= 75 nmol/L, were more likely to have severe sepsis (61% vs. 24%; p = 0.006) and SOFA scores >= 2 (44% vs. 18%; p = 0.049). Additionally, at 24 hours, those with 25OHD levels of <75 nmol/L were more likely to have severe sepsis (67% vs. 29%; p = 0.005), dysfunction of two or more organ systems (50% vs. 18%; p = 0.02), APACHE II score of >= 25 (19% vs. 0%; p = 0.06), and SOFA scores of >= 2 (63% vs. 29%; p = 0.02). Additionally, all four patients who died during the index hospitalization had 25OHD levels of <75 nmol/L. Conclusions: Vitamin D insufficiency was associated with higher sepsis severity in ED patients hospitalized for suspected infection. Larger observational studies, mechanistic studies, and ultimately randomized controlled trials are needed to determine causation and to evaluate if vitamin D supplementation can reduce the risk of sepsis as a preventive or therapeutic strategy. ACADEMIC EMERGENCY MEDICINE 2011; 18:551-554 (C) 2011 by the Society for Academic Emergency Medicine C1 [Ginde, Adit A.] Univ Colorado, Sch Med, Dept Emergency Med, Aurora, CO USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Shapiro, Nathan I.] Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Emergency Med, Sch Med, Boston, MA 02215 USA. RP Ginde, AA (reprint author), Univ Colorado, Sch Med, Dept Emergency Med, Aurora, CO USA. EM adit.ginde@ucdenver.edu RI Shapiro, Nathan/F-1718-2016; Siry, Bonnie/D-7189-2017 NR 12 TC 42 Z9 46 U1 1 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD MAY PY 2011 VL 18 IS 5 BP 550 EP 553 DI 10.1111/j.1553-2712.2011.01047.x PG 4 WC Emergency Medicine SC Emergency Medicine GA 763SJ UT WOS:000290579700015 PM 21518095 ER PT J AU Gibson, CM Mega, JL Burton, P Goto, S Verheugt, F Bode, C Plotnikov, A Sun, X Cook-Bruns, N Braunwald, E AF Gibson, C. Michael Mega, Jessica L. Burton, Paul Goto, Shinya Verheugt, Freek Bode, Christoph Plotnikov, Alexei Sun, Xiang Cook-Bruns, Nancy Braunwald, Eugene TI Rationale and design of the Anti-Xa Therapy to Lower cardiovascular events in Addition to standard therapy in Subjects with Acute Coronary Syndrome-Thrombolysis in Myocardial Infarction 51 (ATLAS-ACS 2 TIMI 51) trial: A randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of rivaroxaban in subjects with acute coronary syndrome SO AMERICAN HEART JOURNAL LA English DT Article ID TOTAL KNEE ARTHROPLASTY; ST-SEGMENT ELEVATION; HIP-ARTHROPLASTY; ASPIRIN; ENOXAPARIN; THROMBOPROPHYLAXIS; CLOPIDOGREL; PHARMACODYNAMICS; PHARMACOKINETICS; METAANALYSIS AB Background Although therapy with aspirin or aspirin plus a thienopyridine reduces the incidence of long-term adverse cardiovascular events among patients with acute coronary syndrome (ACS), there remains a significant residual risk of cardiovascular death, recurrent myocardial infarction (MI), and stroke. In a phase 2 trial (ClinicalTrials.gov NCT00402597) in which the addition of the factor Xa inhibitor rivaroxaban was compared with placebo, among ACS patients receiving either aspirin alone or dual-antiplatelet therapy with aspirin and a thienopyridine, the end point of death, MI, or stroke compared with placebo was reduced (87/2331 [3.9%] vs 62/1160 [5.5%]; hazard ratio 0.69, [95% CI 0.50-0.96], P = .027). Two candidate doses of rivaroxaban were selected for further evaluation in a pivotal phase 3. Design The second ATLAS-ACS 2 TIMI 51 Trial is an international, randomized, double-blind, event-driven (n = 983) phase 3 trial involving more than 15,570 patients hospitalized with ACS (ClinicalTrials.gov NCT00809965). All patients are treated with a background of standard therapy including low-dose aspirin, and patients are stratified by the administration of a thienopyridine (clopidogrel or ticlopidine; stratum 2) or not (stratum 1). Within each stratum, patients are randomly assigned in a 1: 1: 1 ratio to receive rivaroxaban 2.5 mg twice daily, or rivaroxaban 5 mg twice daily, or placebo twice daily. The primary efficacy end point is the composite of cardiovascular death, MI, or stroke. The primary safety end point is thrombolysis in MI major bleeding not associated with coronary artery bypass graft surgery. Summary The ATLAS-ACS 2 TIMI 51 is testing the hypothesis that anticoagulation with the oral factor Xa inhibitor rivaroxaban reduces cardiovascular death, MI, and stroke among patients with ACS treated with guideline-based therapies for ACS. (Am Heart J 2011;161:815-821.e6.) C1 [Gibson, C. Michael; Mega, Jessica L.; Braunwald, Eugene] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [Burton, Paul; Plotnikov, Alexei; Sun, Xiang] Johnson & Johnson Pharmaceut Res & Dev, Raritan, NJ USA. [Goto, Shinya] Tokai Univ, Sch Med, Dept Med, Kanagawa 2591100, Japan. [Verheugt, Freek] Onze Lieve Vrouw Hosp, Dept Cardiol, Amsterdam, Netherlands. [Bode, Christoph] Univ Freiburg, Freiburg, Germany. [Cook-Bruns, Nancy] Bayer Schering Pharma, Berlin, Germany. RP Gibson, CM (reprint author), 185 Pilgrim Rd,Deaconess 319, Boston, MA 02215 USA. EM mgibson@perfuse.org RI Verheugt, F.W.A./H-8105-2014 FU Johnson and Johnson; Bayer Inc. FX All authors received research grant support from the sponsors of the trial (Johnson and Johnson and Bayer Inc.). Dr. Gibson reports receiving consulting monies from Johnson and Johnson and Bayer Inc. Dr. Mega reports receiving honoraria from Bayer Inc. Drs. Burton, Plotnikov and Sun are employees of Johnson and Johnson. Dr. Bruns is an employee of Bayer Inc. NR 16 TC 41 Z9 43 U1 1 U2 10 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD MAY PY 2011 VL 161 IS 5 BP 815 EP + DI 10.1016/j.ahj.2011.01.026 PG 13 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 763LV UT WOS:000290559300009 PM 21570509 ER PT J AU Kontos, MC Diercks, DB Ho, PM Wang, TY Chen, AY Roe, MT AF Kontos, Michael C. Diercks, Debra B. Ho, P. Michael Wang, Tracy Y. Chen, Anita Y. Roe, Matthew T. TI Treatment and outcomes in patients with myocardial infarction treated with acute beta-blocker therapy: Results from the American College of Cardiology's NCDR (R) SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE CORONARY SYNDROMES; INTERNATIONAL TRIAL; HEART-DISEASE; ELEVATION; THROMBOLYSIS; PREDICTORS; METOPROLOL; MORTALITY AB Background Although beta-blockers (BBs) reduce long-term mortality in patients after myocardial infarction (MI), data regarding acute usage are conflicting. Methods We examined acute (<= 24 hours) BB use in 34,661 patients with ST-elevation MI (STEMI) and non-ST-segment MI (NSTEMI) included in the NCDR (R) ACTION Registry (R)-GWTG (TM) (291 US hospitals) between January 2007 and June 2008. Patients with contraindications or did not receive BBs or with missing data were excluded. We analyzed the use and impact of BB stratified by variables associated with increased risk for shock specified in the recent guidelines: age > 70 years, symptoms > 12 hours (STEMI patients), systolic blood pressure < 120 mm Hg, and heart rate > 110 beat/min on presentation. Results Among patients without contraindications, at least 1 high-risk variable was found in 45% of STEMI and 63% of NSTEMI patients. In-hospital complications including cardiogenic shock, mortality, and the composite outcome of shock or mortality were significantly increased with more shock risk factors in both STEMI and NSTEMI patients. Very early use in the emergency department was associated with a significantly increased risk of shock for both STEMI and NSTEMI patients compared to patients treated later but within 24 hours. Conclusions Risk factors for shock are common in STEMI and NSTEMI patients treated with early BBs. Increasing numbers of risk factors were associated with increased risk for shock or death in patients treated with BBs. These results are consistent with current recommendations for avoiding early BB treatment for patients with acute MI. (Am Heart J 2011;161:864-70.) C1 [Kontos, Michael C.] Virginia Commonwealth Univ, Dept Internal Med, Div Cardiol, Pauley Heart Ctr, Richmond, VA USA. [Diercks, Debra B.] Univ Calif Davis, Sacramento, CA 95817 USA. [Ho, P. Michael] Denver VA Med Ctr, Denver, CO USA. [Wang, Tracy Y.; Chen, Anita Y.; Roe, Matthew T.] Duke Clin Res Inst, Durham, NC USA. RP Kontos, MC (reprint author), Rm 285,Gateway Bldg,2nd Floor,POB 980051,1200 E M, Richmond, VA 23298 USA. EM mkontos@mcvh-vcu.edu NR 24 TC 23 Z9 23 U1 0 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD MAY PY 2011 VL 161 IS 5 BP 864 EP 870 DI 10.1016/j.ahj.2011.01.006 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 763LV UT WOS:000290559300015 PM 21570515 ER PT J AU Sawaya, H Sebag, IA Plana, JC Januzzi, JL Ky, B Cohen, V Gosavi, S Carver, JR Wiegers, SE Martin, RP Picard, MH Gerszten, RE Halpern, EF Passeri, J Kuter, I Scherrer-Crosbie, M AF Sawaya, Heloisa Sebag, Igal A. Plana, Juan Carlos Januzzi, James L. Ky, Bonnie Cohen, Victor Gosavi, Sucheta Carver, Joseph R. Wiegers, Susan E. Martin, Randolph P. Picard, Michael H. Gerszten, Robert E. Halpern, Elkan F. Passeri, Jonathan Kuter, Irene Scherrer-Crosbie, Marielle TI Early Detection and Prediction of Cardiotoxicity in Chemotherapy-Treated Patients SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID HIGH-DOSE CHEMOTHERAPY; BREAST-CANCER PATIENTS; ADJUVANT THERAPY; CARDIAC TOXICITY; TRASTUZUMAB; ANTHRACYCLINE; DYSFUNCTION; DOXORUBICIN; PACLITAXEL AB As breast cancer survival increases, cardiotoxicity associated with chemotherapeutic regimens such as anthracyclines and trastuzumab becomes a more significant issue. Assessment of the left ventricular (LV) ejection fraction fails to detect subtle alterations in LV function. The objective of this study was to evaluate whether more sensitive echocardiographic measurements and biomarkers could predict future cardiac dysfunction in chemotherapy-treated patients. Forty-three patients diagnosed with breast cancer who received anthracyclines and trastuzumab therapy underwent echocardiography and blood sampling at 3 time points (baseline and 3 and 6 months during the course of chemotherapy). The LV ejection fraction; peak systolic myocardial longitudinal, radial, and circumferential strain; echocardiographic markers of diastolic function; N-terminal pro B-type natriuretic peptide; and high-sensitivity cardiac troponin I were measured. Nine patients (21%) developed cardiotoxicity (1 at 3 months and 8 at 6 months) as defined by the Cardiac Review and Evaluation Committee reviewing trastuzumab. A decrease in longitudinal strain from baseline to 3 months and detectable high-sensitivity cardiac troponin I at 3 months were independent predictors of the development of cardiotoxicity at 6 months. The LV ejection fraction, parameters of diastolic function, and N-terminal pro B-type natriuretic peptide did not predict cardiotoxicity. In conclusion, cardiac troponin plasma concentrations and longitudinal strain predict the development of cardiotoxicity in patients treated with anthracyclines and trastuzumab. The 2 parameters may be useful to detect chemotherapy-treated patients who may benefit from alternative therapies, potentially decreasing the incidence of cardio toxicity and its associated morbidity and mortality. (C) 2011 Elsevier Inc. All rights reserved. (Am J Cardiol 2011;107:1375-1380) C1 [Sawaya, Heloisa; Januzzi, James L.; Gosavi, Sucheta; Picard, Michael H.; Gerszten, Robert E.; Passeri, Jonathan; Scherrer-Crosbie, Marielle] Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. [Sawaya, Heloisa; Januzzi, James L.; Gosavi, Sucheta; Picard, Michael H.; Gerszten, Robert E.; Passeri, Jonathan; Scherrer-Crosbie, Marielle] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Kuter, Irene] Massachusetts Gen Hosp, Gillette Ctr Breast Canc, Boston, MA 02114 USA. [Halpern, Elkan F.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Sebag, Igal A.] Sir Mortimer B Davis Jewish Hosp, Echocardiog Lab, Montreal, PQ, Canada. [Cohen, Victor] Sir Mortimer B Davis Jewish Hosp, Dept Med, Div Cardiol, Montreal, PQ, Canada. [Cohen, Victor] Sir Mortimer B Davis Jewish Hosp, Abramson Canc Ctr, Montreal, PQ, Canada. McGill Univ, Montreal, PQ, Canada. [Plana, Juan Carlos] Univ Texas MD Anderson Canc Ctr, Div Cardiol, Houston, TX 77030 USA. [Ky, Bonnie; Carver, Joseph R.; Wiegers, Susan E.] Hosp Univ Penn, Div Cardiol, Philadelphia, PA 19104 USA. [Martin, Randolph P.] Piedmont Heart Inst, Atlanta, GA USA. RP Scherrer-Crosbie, M (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. EM marielle@crosbie.com OI Picard, Michael/0000-0002-9264-3243 FU Susan G. Komen for the Cure Foundation, Dallas, Texas; Claflin Distinguished Scholar Award; Clinical Innovation Award, Boston, Massachusetts; Kynett Focus Junior Faculty Investigator Award, Philadelphia, Pennsylvania; Roche Diagnostics GmbH, Mannheim, Germany; Siemens Medical Systems, Erlangen, Germany; Critical Diagnostics, San Diego, California FX Dr. Seherrer-Crosbie was supported by an investigator-initiated grant from the Susan G. Komen for the Cure Foundation, Dallas, Texas, a Claflin Distinguished Scholar Award, and a Clinical Innovation Award, Boston, Massachusetts. Dr. Ky was supported by the Kynett Focus Junior Faculty Investigator Award, Philadelphia, Pennsylvania.; Dr. Januzzi has received grant support from Roche Diagnostics GmbH, Mannheim, Germany, Siemens Medical Systems, Erlangen, Germany, and Critical Diagnostics, San Diego, California. Dr. Plana is on the speaker's bureau of GE Healthcare, Milwaukee, Wisconsin. NR 16 TC 182 Z9 190 U1 2 U2 19 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 MAY 1 PY 2011 VL 107 IS 9 BP 1375 EP 1380 DI 10.1016/j.amjcard.2011.01.006 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 764CI UT WOS:000290605600020 PM 21371685 ER PT J AU Chen, JC Goetz, MB Feld, JE Taylor, A Anaya, H Burgess, J Flores, RD Gidwani, RA Knapp, H Ocampo, EH Asch, SM AF Chen, Jennifer C. Goetz, Matthew Bidwell Feld, Jamie E. Taylor, Anne Anaya, Henry Burgess, Jane Flores, Richard de Mesa Gidwani, Risha A. Knapp, Herschel Ocampo, Elizabeth H. Asch, Steven M. TI A provider participatory implementation model for HIV testing in an ED SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID FOR-DISEASE-CONTROL; EMERGENCY-DEPARTMENT; MISSED OPPORTUNITIES; PREVALENCE AREA; CARE SETTINGS; INFECTION; HEALTH; RECOMMENDATIONS; DIAGNOSIS; WOMEN AB Background: The Centers for Disease Control and Prevention recommends routine HIV screening for adults. Objectives: Community-based participatory research incorporates subjects in the design and conduct of research. We included nurses and physicians in the implementation of HIV rapid test use in the emergency department (ED). We explored the process, facilitators, and barriers. Methods: We identified clinical champions and trained staff. Physicians obtained consent and ordered HIV testing; nurses performed rapid testing. Testing rates were tracked by electronic medical record. We conducted regular meetings between staff and researchers. Semistructured qualitative interviews with providers were conducted at 3 months. Results: By week 15, we administered 121 tests. After the eligibility protocol evolved to incorporate ED nursing concerns regarding staffing limitations from a random sampling model to one focused on testing during nonpeak hours, the weekly number of tests increased. Eighteen percent of providers favored nontargeted HIV screening, 27% favored the current model of testing at nonpeak hours, 32% supported diagnostic testing, and 18% favored no testing or "other." Barriers include written consent, electronic documentation, time constraints, and belief that screening is not a core ED duty. Facilitators include ease of test administration, belief that ED patients are at higher risk, and flexibility to tailor screening efforts according to patient volume. Conclusions: The ED-based HIV testing is feasible within a Veterans Hospital Administration setting. Involvement of nursing in a community-based participatory research implementation model may facilitate staff acceptance of nontargeted HIV screening and be a mechanism to initiate administration of clinical preventive services to ED patients with limited primary care contact. Published by Elsevier Inc. C1 [Chen, Jennifer C.] VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA 90073 USA. [Chen, Jennifer C.; Goetz, Matthew Bidwell; Asch, Steven M.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. [Gidwani, Risha A.] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. RP Chen, JC (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA 90073 USA. OI Chen, Jennifer/0000-0002-4801-5397; Goetz, Matthew/0000-0003-4542-992X NR 24 TC 14 Z9 14 U1 2 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 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD MAY PY 2011 VL 29 IS 4 BP 418 EP 426 DI 10.1016/j.ajem.2009.11.016 PG 9 WC Emergency Medicine SC Emergency Medicine GA 763QK UT WOS:000290574600010 PM 20825814 ER PT J AU Rosenthal, RA Fish, B Hill, RP Huffman, KD Lazarova, Z Mahmood, J Medhora, M Molthen, R Moulder, JE Sonis, ST Tofilon, PJ Doctrow, SR AF Rosenthal, Rosalind A. Fish, Brian Hill, Richard P. Huffman, Karl D. Lazarova, Zelmira Mahmood, Javed Medhora, Meetha Molthen, Robert Moulder, John E. Sonis, Stephen T. Tofilon, Philip J. Doctrow, Susan R. TI Salen Mn Complexes Mitigate Radiation Injury in Normal Tissues SO ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY LA English DT Article DE Salen manganese complex; radiation injury; radiation mitigation; catalytic antioxidant ID SUPEROXIDE DISMUTASE/CATALASE MIMETICS; CHRONIC OXIDATIVE STRESS; INDUCED ORAL MUCOSITIS; IONIZING-RADIATION; CATALYTIC SCAVENGERS; CATALASE MIMETICS; GENE-EXPRESSION; REDOX CONTROL; NITRIC-OXIDE; MICE AB Salen Mn complexes, including EUK-134, EUK-189 and a newer cyclized analog EUK-207, are synthetic SOD/catalase mimetics that have beneficial effects in many models of oxidative stress. As oxidative stress is implicated in some forms of delayed radiation injury, we are investigating whether these compounds can mitigate injury to normal tissues caused by ionizing radiation. This review describes some of this research, focusing on several tissues of therapeutic interest, namely kidney, lung, skin, and oral mucosa. These studies have demonstrated suppression of delayed radiation injury in animals treated with EUK-189 and/or EUK-207. While an antioxidant mechanism of action is postulated, it is likely that the mechanisms of radiation mitigation by these compounds in vivo are complex and may differ in the various target tissues. Indicators of oxidative stress are increased in lung and skin radiation injury models, and suppressed by salen Mn complexes. The role of oxidative stress in the renal injury model is unclear, though EUK-207 does mitigate. In certain experimental models, salen Mn complexes have shown "mito-protective" properties, that is, attenuating mitochondrial injury. Consistent with this, EUK-134 suppresses effects of ionizing radiation on mitochondrial function in rat astrocyte cultures. In summary, salen Mn complexes could be useful to mitigate delayed radiation injury to normal tissues following radiation therapy, accidental exposure, or radiological terrorism. Optimization of their mode of delivery and other key pharmaceutical properties, and increasing understanding of their mechanism(s) of action as radiation mitigators, are key issues for future study. C1 [Rosenthal, Rosalind A.; Huffman, Karl D.; Doctrow, Susan R.] Boston Univ, Sch Med, Dept Med, Ctr Pulm, Boston, MA 02118 USA. [Sonis, Stephen T.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Sonis, Stephen T.] Brigham & Womens Hosp, Div Oral Med, Boston, MA 02115 USA. [Sonis, Stephen T.] Brigham & Womens Hosp, Div Dent, Boston, MA 02115 USA. [Sonis, Stephen T.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Fish, Brian; Medhora, Meetha; Moulder, John E.] Med Coll Wisconsin, Dept Radiat Oncol, Milwaukee, WI 53226 USA. [Lazarova, Zelmira] Med Coll Wisconsin, Dept Dermatol, Milwaukee, WI 53226 USA. [Molthen, Robert] Med Coll Wisconsin, Dept Pulm Med, Milwaukee, WI 53226 USA. [Hill, Richard P.; Mahmood, Javed] Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada. [Tofilon, Philip J.] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Doctrow, SR (reprint author), Boston Univ, Sch Med, Dept Med, Ctr Pulm, Boston, MA 02118 USA. EM sdoctrow@bu.edu RI Moulder, John/E-6799-2012 FU [AI067734]; [AI81294]; [CA72156] FX Development of the salen Mn complexes, including EUK-207, was funded in part by GM57770 (SRD). Renal, cutaneous, and pulmonary studies and further compound development were supported by AI067734 (JEM), including a pilot grant (RAR) to study EUK-400 compounds. Some pulmonary studies were also supported by AI81294 (MM). The mucositis study was performed by Biomodels, LLC. (Wellesley, MA) under the direction of STS. The mitochondrial injury studies were supported by CA72156 (PJT). NR 106 TC 31 Z9 32 U1 1 U2 10 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1871-5206 J9 ANTI-CANCER AGENT ME JI Anti-Cancer Agents Med. Chem. PD MAY PY 2011 VL 11 IS 4 BP 359 EP 372 PG 14 WC Oncology; Chemistry, Medicinal SC Oncology; Pharmacology & Pharmacy GA 764FL UT WOS:000290614400005 PM 21453241 ER PT J AU Atri, A O'Brien, JL Sreenivasan, A Rastegar, S Salisbury, S DeLuca, AN O'Keefe, KM LaViolette, PS Rentz, DM Locascio, JJ Sperling, RA AF Atri, Alireza O'Brien, Jacqueline L. Sreenivasan, Aishwarya Rastegar, Sarah Salisbury, Sibyl DeLuca, Amy N. O'Keefe, Kelly M. LaViolette, Peter S. Rentz, Dorene M. Locascio, Joseph J. Sperling, Reisa A. TI Test-Retest Reliability of Memory Task Functional Magnetic Resonance Imaging in Alzheimer Disease Clinical Trials SO ARCHIVES OF NEUROLOGY LA English DT Article ID MILD COGNITIVE IMPAIRMENT; RANDOMIZED CONTROLLED-TRIAL; CHOLINERGIC ENHANCEMENT; HIPPOCAMPAL ACTIVATION; PHARMACOLOGICAL FMRI; MRI; AD; DONEPEZIL; DEMENTIA; MODERATE AB Objective: To examine the feasibility and test-retest reliability of encoding-task functional magnetic resonance imaging (fMRI) in mild Alzheimer disease (AD). Design: Randomized, double-blind, placebocontrolled study. Setting: Memory clinical trials unit. Participants: We studied 12 patients with mild AD (mean [SEM] Mini-Mental State Examination score, 24.0 [0.7]; mean Clinical Dementia Rating score, 1.0) who had been taking donepezil hydrochloride for more than 6 months from the placebo arm of a larger 24-week study (n = 24, 4 scans on weeks 0, 6, 12, and 24, respectively). Interventions: Placebo and 3 face-name, paired-associate encoding, block-design blood oxygenation level-dependent fMRI scans in 12 weeks. Main Outcome Measures: We performed whole-brain t maps (P < .001, 5 contiguous voxels) and hippocampal regions-of-interest analyses of extent (percentage of active voxels) and magnitude (percentage of signal change) for novel-greater-than-repeated face-name contrasts. We also calculated intraclass correlation coefficients and power estimates for hippocampal regions of interest. Results: Task tolerability and data yield were high (95 of 96 scans yielded favorable-quality data). Whole brain maps were stable. Right and left hippocampal regions-of-interest intraclass correlation coefficients were 0.59 to 0.87 and 0.67 to 0.74, respectively. To detect 25.0% to 50.0% changes in week-0 to week-12 hippocampal activity using left-right extent or right magnitude with 80.0% power (2-sided alpha = .05) requires 14 to 51 patients. Using left magnitude requires 125 patients because of relatively small signal to variance ratios. Conclusions: Encoding-task fMRI was successfully implemented in a single-site, 24-week, AD randomized controlled trial. Week 0 to 12 whole-brain t maps were stable, and test-retest reliability of hippocampal fMRI measures ranged from moderate to substantial. Right hippocampal magnitude may be the most promising of these candidate measures in a leveraged context. These initial estimates of test-retest reliability and power justify evaluation of encoding-task fMRI as a potential biomarker for signal of effect in exploratory and proof-of-concept trials in mild AD. Validation of these results with larger sample sizes and assessment in multisite studies is warranted. C1 [Atri, Alireza] Massachusetts Gen Hosp, Memory Disorders Unit, Boston, MA 02114 USA. [Sreenivasan, Aishwarya; Rastegar, Sarah; LaViolette, Peter S.; Locascio, Joseph J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [O'Brien, Jacqueline L.; Salisbury, Sibyl; DeLuca, Amy N.; O'Keefe, Kelly M.; Rentz, Dorene M.; Sperling, Reisa A.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Atri, Alireza; Rentz, Dorene M.; Locascio, Joseph J.; Sperling, Reisa A.] Martinos Ctr Biomed Imaging, Boston, MA USA. [Atri, Alireza; Rentz, Dorene M.; Locascio, Joseph J.; Sperling, Reisa A.] Harvard Univ, Sch Med, Boston, MA USA. [Atri, Alireza] Bedford Med Ctr, Vet Hlth Adm, Geriatr Res Educ & Clin Ctr, Bedford, MA USA. RP Atri, A (reprint author), Massachusetts Gen Hosp, Memory Disorders Unit, 15 Parkman St,Wang Ambulatory Care Ctr 715, Boston, MA 02114 USA. EM atri@nmr.mgh.harvard.edu OI Atri, Alireza/0000-0003-4405-6973 FU National Institute on Aging [1K23 AG027171, RO1 AG027435]; Harvard-Massachusetts Institute of Technology Health Sciences and Technology Pfizer-Merck; National Institutes of Health; Forest Pharmaceuticals Inc; Harvard Center for Neurodegeneration and Repair; Clinical, Neuroimaging, and Statistics Cores of the Massachusetts Alzheimer's Disease Research Center (National Institute on Aging ) [5 P50AG05134]; Geriatric Research Education and Clinical Center at the Edith Nourse Rogers Memorial Veterans Administration Bedford Medical Center FX The study was supported by National Institute on Aging grants 1K23 AG027171 (Dr Atri) and RO1 AG027435 (Dr Sperling); the Harvard-Massachusetts Institute of Technology Health Sciences and Technology Pfizer-Merck Clinical Investigator Training Program (Dr Atri); the National Institutes of Health loan repayment program (Dr Atri); Investigator-Initiated Research Grants from Forest Pharmaceuticals Inc and the Harvard Center for Neurodegeneration and Repair; the Clinical, Neuroimaging, and Statistics Cores of the Massachusetts Alzheimer's Disease Research Center (National Institute on Aging grant 5 P50AG05134 to Dr Growdon and Bradley T. Hyman, MD, PhD); and the Geriatric Research Education and Clinical Center at the Edith Nourse Rogers Memorial Veterans Administration Bedford Medical Center. Less than 30% of this research was supported by an Investigator-Initiated Research Grant from Forest Pharmaceuticals Inc. NR 46 TC 16 Z9 17 U1 1 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD MAY PY 2011 VL 68 IS 5 BP 599 EP 606 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 761YB UT WOS:000290438000008 PM 21555634 ER PT J AU Berson, EL Rosner, B Sandberg, MA Weigel-DiFranco, C Willett, WC AF Berson, Eliot L. Rosner, Bernard Sandberg, Michael A. Weigel-DiFranco, Carol Willett, Walter C. TI Letter From the DSMC Regarding a Clinical Trial of Lutein in Patients With Retinitis Pigmentosa reply SO ARCHIVES OF OPHTHALMOLOGY LA English DT Letter ID RECEIVING VITAMIN-A; RANDOMIZED-TRIAL; ASPIRIN C1 [Berson, Eliot L.; Rosner, Bernard; Sandberg, Michael A.; Weigel-DiFranco, Carol] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab, Boston, MA USA. [Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. RP Berson, EL (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Berman Gund Lab Study Retinal Degenerat, 243 Charles St, Boston, MA 02114 USA. EM linda_berard@meei.harvard.edu NR 6 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD MAY PY 2011 VL 129 IS 5 BP 675 EP 676 PG 6 WC Ophthalmology SC Ophthalmology GA 761XU UT WOS:000290437100030 ER PT J AU Bartels, CM Kind, AJH Everett, C Mell, M McBride, P Smith, M AF Bartels, Christie M. Kind, Amy J. H. Everett, Christine Mell, Matthew McBride, Patrick Smith, Maureen TI Low Frequency of Primary Lipid Screening Among Medicare Patients With Rheumatoid Arthritis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID GLUCOCORTICOID-INDUCED OSTEOPOROSIS; POSITIVE PREDICTIVE-VALUE; PRIMARY-CARE PHYSICIANS; QUALITY-OF-CARE; MYOCARDIAL-INFARCTION; CARDIOVASCULAR RISK; ADMINISTRATIVE DATA; ORTHOPEDIC-SURGERY; ISCHEMIC-STROKE; CLAIMS AB Objective. Although studies have demonstrated suboptimal preventive care in RA patients, performance of primary lipid screening (i.e., testing before cardiovascular disease [CVD], CVD risk equivalents, or hyperlipidemia is evident) has not been systematically examined. The purpose of this study was to examine associations between primary lipid screening and visits to primary care providers (PCPs) and rheumatologists among a national sample of older RA patients. Methods. This retrospective cohort study examined a 5% Medicare sample that included 3,298 RA patients without baseline CVD, diabetes mellitus, or hyperlipidemia, who were considered eligible for primary lipid screening during the years 2004-2006. The outcome was probability of lipid screening by the relative frequency of primary care and rheumatology visits, or seeing a PCP at least once each year. Results. Primary lipid screening was performed in only 45% of RA patients. Overall, 65% of patients received both primary and rheumatology care, and 50% saw a rheumatologist as often as a PCP. Any primary care predicted more lipid screening than lone rheumatology care (26% [95% confidence interval (95% CI) 21-32]). As long as a PCP was involved, performance of lipid screening was similar regardless of the balance between primary and rheumatology visits (44-48% [95% CI 41-51]). Not seeing a PCP at least annually decreased screening by 22% (adjusted risk ratio 0.78 [95% CI 0.71-0.84]). Conclusion. Primary lipid screening was performed in fewer than half of eligible RA patients, highlighting a key target for CVD risk reduction efforts. Annual visits to a PCP improved lipid screening, although performance remained poor (51%). Half of RA patients saw their rheumatologist as often or more often than they saw a PCP, illustrating the need to study optimal partnerships between PCPs and rheumatologists for screening patients for CVD risks. C1 [Bartels, Christie M.] Univ Wisconsin, Sch Med & Publ Hlth, Clin Sci Ctr H6, Madison, WI 53792 USA. [Kind, Amy J. H.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Mell, Matthew] Stanford Univ, Palo Alto, CA 94304 USA. RP Bartels, CM (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Clin Sci Ctr H6, Box 3244,600 Highland Ave, Madison, WI 53792 USA. EM cb4@medicine.wisc.edu FU University of Wisconsin Institute for Clinical and Translational Research from National Center for Research Resources, NIH [1UL1-RR-025011]; University of Wisconsin Institute for Clinical and Translational Research (NIH) [5KL2-RR-025012-02] FX Supported by the Health Innovation Program and the Community-Academic Partnerships core of the University of Wisconsin Institute for Clinical and Translational Research (grant 1UL1-RR-025011 from the Clinical and Translational Science Award program of the National Center for Research Resources, NIH) and by the University of Wisconsin Institute for Clinical and Translational Research (NIH training grant 5KL2-RR-025012-02). NR 49 TC 20 Z9 22 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD MAY PY 2011 VL 63 IS 5 BP 1221 EP 1230 DI 10.1002/art.30239 PG 10 WC Rheumatology SC Rheumatology GA 764DY UT WOS:000290609800009 PM 21305507 ER PT J AU Castelino, FV Seiders, J Bain, G Brooks, SF King, CD Swaney, JS Lorrain, DS Chun, J Luster, AD Tager, AM AF Castelino, Flavia V. Seiders, Jon Bain, Gretchen Brooks, Sarah F. King, Christopher D. Swaney, James S. Lorrain, Daniel S. Chun, Jerold Luster, Andrew D. Tager, Andrew M. TI Amelioration of Dermal Fibrosis by Genetic Deletion or Pharmacologic Antagonism of Lysophosphatidic Acid Receptor 1 in a Mouse Model of Scleroderma SO ARTHRITIS AND RHEUMATISM LA English DT Article ID TGF-BETA ACTIVATION; GROWTH-FACTOR; INCREASED EXPRESSION; SYSTEMIC-SCLEROSIS; PULMONARY-FIBROSIS; TISSUE-REPAIR; FIBROBLASTS; SKIN; MYOFIBROBLAST; DISEASE AB Objective. Scleroderma (systemic sclerosis [SSc]), is characterized by progressive multiorgan fibrosis. We recently implicated lysophosphatidic acid (LPA) in the pathogenesis of pulmonary fibrosis. The purpose of the present study was to investigate the roles of LPA and two of its receptors, LPA(1) and LPA(2), in dermal fibrosis in a mouse model of SSc. Methods. Wild type (WT), and LPA(1)-knockout (KO) and LPA(2)-KO mice were injected subcutaneously with bleomycin or phosphate buffered saline (PBS) once daily for 28 days. Dermal thickness, collagen content, and numbers of cells positive for alpha-smooth muscle actin (alpha-SMA) or phospho-Smad2 were determined in bleomycin-injected and PBS-injected skin. In separate experiments, a novel selective LPA(1) antagonist AM095 or vehicle alone was administered by oral gavage to C57BL/6 mice that were challenged with 28 daily injections of bleomycin or PBS. AM095 or vehicle treatments were initiated concurrently with, or 7 or 14 days after, the initiation of bleomycin and PBS injections and continued to the end of the experiments. Dermal thickness and collagen content were determined in injected skin. Results. The LPA(1)-KO mice were markedly resistant to bleomycin-induced increases in dermal thickness and collagen content, whereas the LPA(2)-KO mice were as susceptible as the WT mice. Bleomycin-induced increases in dermal alpha-SMA+ and phospho-Smad2+ cells were abrogated in LPA(1)-KO mice. Pharmacologic antagonism of LPA(1) with AM095 significantly attenuated bleomycin-induced dermal fibrosis when administered according to either a preventive regimen or two therapeutic regimens. Conclusion. These results suggest that LPA/LPA(1) pathway inhibition has the potential to be an effective new therapeutic strategy for SSc, and that LPA(1) is an attractive pharmacologic target in dermal fibrosis. C1 [Castelino, Flavia V.; Brooks, Sarah F.; Luster, Andrew D.; Tager, Andrew M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Castelino, Flavia V.; Brooks, Sarah F.; Luster, Andrew D.; Tager, Andrew M.] Harvard Univ, Sch Med, Boston, MA USA. [Seiders, Jon; Bain, Gretchen; King, Christopher D.; Swaney, James S.; Lorrain, Daniel S.] Amira Pharmaceut, San Diego, CA USA. [Chun, Jerold] Scripps Res Inst, La Jolla, CA 92037 USA. RP Tager, AM (reprint author), Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, 149 13th St,Room 8301, Charlestown, MA 02129 USA. EM amtager@partners.org FU American College of Rheumatology Research and Education Foundation; NIH [R01-DA-019674, R01-NS-048478, R01-DC-009505, T32-AR-007258-32, R01-HL-095732]; Scleroderma Research Foundation; Amira Pharmaceuticals FX Supported by an American College of Rheumatology Research and Education Foundation Physician Scientist Development Award to Dr. Castelino, by NIH grants R01-DA-019674, R01-NS-048478, and R01-DC-009505 to Dr. Chun, T32-AR-007258-32 to Dr. Luster, and R01-HL-095732 to Dr. Tager, and by a Scleroderma Research Foundation grant to Dr. Tager.; Drs. Seiders, Bain, King, Swaney, Lorrain, and Chun own stock or stock options in Amira Pharmaceuticals. Drs. Chun and Tager have received consulting fees and/or honoraria from Amira Pharmaceuticals (less than $ 10,000 each) and serve as members of the company's Scientific Advisory Board. Drs. Luster and Tager have filed a patent cooperation treaty application on lysophosphatidic acid receptor targeting in lung disease. NR 43 TC 74 Z9 75 U1 0 U2 11 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD MAY PY 2011 VL 63 IS 5 BP 1405 EP 1415 DI 10.1002/art.30262 PG 11 WC Rheumatology SC Rheumatology GA 764DY UT WOS:000290609800030 PM 21305523 ER PT J AU Morita, Y Chu, CQ AF Morita, Yoshiaki Chu, Cong-Qiu TI Is transforming growth factor beta always necessary for generation of pathogenic Th17 cells in autoimmune disease? Comment on the article by Morita et al Reply SO ARTHRITIS AND RHEUMATISM LA English DT Letter ID TGF-BETA; T-CELLS; INTERLEUKIN-23 PROMOTES; DIFFERENTIATION; DISTINCT; LINEAGE; INFLAMMATION C1 [Morita, Yoshiaki] Astellas Pharma, Tsukuba, Ibaraki, Japan. [Chu, Cong-Qiu] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Chu, Cong-Qiu] Portland VA Med Ctr, Portland, OR USA. RP Morita, Y (reprint author), Astellas Pharma, Tsukuba, Ibaraki, Japan. NR 9 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD MAY PY 2011 VL 63 IS 5 BP 1467 EP 1468 DI 10.1002/art.30304 PG 2 WC Rheumatology SC Rheumatology GA 764DY UT WOS:000290609800040 ER PT J AU Hausmann, LRM Hanusa, BH Kresevic, DM Zickmund, S Ling, BS Gordon, HS Kwoh, CK Mor, MK Hannon, MJ Cohen, PZ Grant, R Ibrahim, SA AF Hausmann, Leslie R. M. Hanusa, Barbara H. Kresevic, Denise M. Zickmund, Susan Ling, Bruce S. Gordon, Howard S. Kwoh, C. Kent Mor, Maria K. Hannon, Michael J. Cohen, Peter Z. Grant, Richard Ibrahim, Said A. TI Orthopedic Communication About Osteoarthritis Treatment: Does Patient Race Matter? SO ARTHRITIS CARE & RESEARCH LA English DT Article ID INTERACTION ANALYSIS SYSTEM; INFORMED DECISION-MAKING; TOTAL KNEE REPLACEMENT; PRIMARY-CARE VISITS; JOINT REPLACEMENT; PHYSICIAN COMMUNICATION; ETHNIC-DIFFERENCES; AFRICAN-AMERICANS; RACIAL DISPARITIES; UNITED-STATES AB Objective. To understand racial disparities in the use of total joint replacement, we examined whether there were racial differences in patient-provider communication about treatment of chronic knee and hip osteoarthritis in a sample of African American and white patients referred to Veterans Affairs orthopedic clinics. Methods. Audio recorded visits between patients and orthopedic surgeons were coded using the Roter Interaction Analysis System and the Informed Decision-Making model. Racial differences in communication outcomes were assessed using linear regression models adjusted for study design, patient characteristics, and clustering by provider. Results. The sample (n = 402) included 296 white and 106 African American patients. Most patients were men (95%) and ages 50-64 years (68%). Almost half (41%) reported an income <$20,000. African American patients were younger and reported lower incomes than white patients. Visits with African American patients contained less discussion of biomedical topics (beta = -9.14; 95% confidence interval [95% CI] -16.73, -1.54) and more rapport-building statements (beta = 7.84; 95% CI 1.85, 13.82) than visits with white patients. However, no racial differences were observed with regard to length of visit, overall amount of dialogue, discussion of psychosocial issues, patient activation/engagement statements, physician verbal dominance, display of positive affect by patients or providers, or discussion related to informed decision making. Conclusion. In this sample, communication between orthopedic surgeons and patients regarding the management of chronic knee and hip osteoarthritis did not, for the most part, vary by patient race. These findings diminish the potential role of communication in Veterans Affairs orthopedic settings as an explanation for well-documented racial disparities in the use of total joint replacement. C1 [Hausmann, Leslie R. M.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA 15206 USA. [Hausmann, Leslie R. M.; Hanusa, Barbara H.; Zickmund, Susan; Ling, Bruce S.; Kwoh, C. Kent; Mor, Maria K.; Hannon, Michael J.] Univ Pittsburgh, Pittsburgh, PA USA. [Kresevic, Denise M.; Grant, Richard] Univ Hosp Case Med Ctr, Louis Stokes Cleveland VA Med Ctr, Cleveland, OH USA. [Gordon, Howard S.] Univ Illinois, Coll Med, Chicago, IL USA. [Gordon, Howard S.] Jesse Brown VA Med Ctr, Chicago, IL USA. [Cohen, Peter Z.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Ibrahim, Said A.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Ibrahim, Said A.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Hausmann, LRM (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, 7180 Highland Dr 151C-H, Pittsburgh, PA 15206 USA. EM leslie.hausmann@gmail.com RI Gordon, Howard/E-4420-2010 OI Gordon, Howard/0000-0002-6712-5954 FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development Service [IIR 04-137]; VA Health Services Research and Development Career Development [RCD 06-287, ER 0280-1]; National Institute of Arthritis and Musculoskeletal and Skin Diseases [1K24AR055259-01]; Harold Amos Robert Wood Johnson Scholar FX Supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development Service (study IIR 04-137). Dr. Hausmann's work was supported by the VA Health Services Research and Development Career Development Program (awards RCD 06-287 and ER 0280-1). Dr. Ibrahim's work was supported in part by a K24 Award (grant 1K24AR055259-01) from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and is recipient of a VA Health Services Research Career Development Award and the Harold Amos Robert Wood Johnson Scholar Award. NR 43 TC 7 Z9 7 U1 3 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 2151-464X J9 ARTHRIT CARE RES JI Arthritis Care Res. PD MAY PY 2011 VL 63 IS 5 BP 635 EP 642 DI 10.1002/acr.20429 PG 8 WC Rheumatology SC Rheumatology GA 761ZK UT WOS:000290441800001 PM 21225676 ER PT J AU Cutler, C Stevenson, K Kim, HT Brown, J McDonough, S Herrera, M Reynolds, C Liney, D Kao, G Ho, V Armand, P Koreth, J Alyea, E Dey, BR Attar, E Spitzer, T Boussiotis, VA Ritz, J Soiffer, R Antin, JH Ballen, K AF Cutler, C. Stevenson, K. Kim, H. T. Brown, J. McDonough, S. Herrera, M. Reynolds, C. Liney, D. Kao, G. Ho, V. Armand, P. Koreth, J. Alyea, E. Dey, B. R. Attar, E. Spitzer, T. Boussiotis, V. A. Ritz, J. Soiffer, R. Antin, J. H. Ballen, K. TI Double umbilical cord blood transplantation with reduced intensity conditioning and sirolimus-based GVHD prophylaxis SO BONE MARROW TRANSPLANTATION LA English DT Article DE umbilical cord blood; graft-vs-host disease; sirolimus ID STEM-CELL TRANSPLANTATION; VERSUS-HOST-DISEASE; EPSTEIN-BARR-VIRUS; POSTTRANSPLANT LYMPHOPROLIFERATIVE DISEASE; BONE-MARROW; THYMIC FUNCTION; IMMUNE RECONSTITUTION; LYMPHOID MALIGNANCIES; UNRELATED DONORS; RISK-FACTORS AB The main limitations to umbilical cord blood (UCB) transplantation (UCBT) in adults are delayed engraftment, poor immunological reconstitution and high rates of non-relapse mortality (NRM). Double UCBT (DUCBT) has been used to circumvent the issue of low cell dose, but acute GVHD remains a significant problem. We describe our experience in 32 subjects, who underwent DUCBT after reduced-intensity conditioning with fludarabine/melphalan/antithymocyte globulin and who received sirolimus and tacrolimus to prevent acute GVHD. Engraftment of neutrophils occurred in all patients at a median of 21 days, and platelet engraftment occurred at a median of 42 days. Three subjects had grade II-IV acute GVHD (9.4%) and chronic GVHD occurred in four subjects (cumulative incidence 12.5%). No deaths were caused by GVHD and NRM at 100 days was 12.5%. At 2 years, NRM, PFS and OS were 34.4, 31.2 and 53.1%, respectively. As expected, immunologic reconstitution was slow, but PFS and OS were associated with reconstitution of CD4(+) and CD8(+) lymphocyte subsets, suggesting that recovery of adaptive immunity is required for the prevention of infection and relapse after transplantation. In summary, sirolimus and tacrolimus provide excellent GVHD prophylaxis in DUCBT, and this regimen is associated with low NRM after DUCBT. Bone Marrow Transplantation (2011) 46, 659-667; doi:10.1038/bmt.2010.192; published online 9 August 2010 C1 [Cutler, C.; McDonough, S.; Herrera, M.; Reynolds, C.; Liney, D.; Kao, G.; Ho, V.; Armand, P.; Koreth, J.; Alyea, E.; Ritz, J.; Soiffer, R.; Antin, J. H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Stevenson, K.; Kim, H. T.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Brown, J.; Boussiotis, V. A.] Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol Oncol & Canc Biol, Boston, MA 02215 USA. [Dey, B. R.; Attar, E.; Spitzer, T.; Ballen, K.] Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02114 USA. RP Cutler, C (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,D1B13, Boston, MA 02115 USA. EM corey_cutler@dfci.harvard.edu OI Ritz, Jerome/0000-0001-5526-4669 FU NCI [P01 CA142106, R01 CA123855]; Jock and Bunny Adams Research and Education Fund; Eileen Pasquarello Research Fund; Astellas, Inc; Genzyme, Inc.; Stem Cell Cyclists of the Pan Mass Challenge FX Supported by NCI P01 CA142106, NCI R01 CA123855, the Jock and Bunny Adams Research and Education Fund, and the Ted and Eileen Pasquarello Research Fund. Funded in part by unrestricted research grants from Astellas, Inc and Genzyme, Inc. CC is supported by the Stem Cell Cyclists of the Pan Mass Challenge. NR 32 TC 55 Z9 58 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAY PY 2011 VL 46 IS 5 BP 659 EP 667 DI 10.1038/bmt.2010.192 PG 9 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 762JM UT WOS:000290472500005 PM 20697368 ER PT J AU Brown, JR AF Brown, Jennifer R. TI Insulin Receptor Activation in Deletion 11q Chronic Lymphocytic Leukemia SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID B-CELL RECEPTOR; SURVIVAL; INHIBITOR; CAL-101; SIGNALS AB The chromosomal abnormalities characteristic of chronic lymphocytic leukemia (CLL) are well studied, but the mechanisms underlying their contribution to pathogenesis are only partially elucidated. Integrated genomic profiling, focused on deletion 11q, has identified elevated expression of the insulin receptor in a subgroup of CLLs and associated it with worse outcomes. Clin Cancer Res; 17(9); 2605-7. (C) 2011 AACR. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Brown, JR (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM Jennifer_Brown@dfci.harvard.edu NR 12 TC 3 Z9 3 U1 0 U2 1 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 MAY 1 PY 2011 VL 17 IS 9 BP 2605 EP 2607 DI 10.1158/1078-0432.CCR-11-0295 PG 3 WC Oncology SC Oncology GA 757NH UT WOS:000290093600001 PM 21427241 ER PT J AU Pettersson, F Yau, C Dobocan, MC Culjkovic-Kraljacic, B Retrouvay, H Puckett, R Flores, LM Krop, IE Rousseau, C Cocolakis, E Borden, KLB Benz, CC Miller, WH AF Pettersson, Filippa Yau, Christina Dobocan, Monica C. Culjkovic-Kraljacic, Biljana Retrouvay, Helene Puckett, Rachel Flores, Ludmila M. Krop, Ian E. Rousseau, Caroline Cocolakis, Eftihia Borden, Katherine L. B. Benz, Christopher C. Miller, Wilson H., Jr. TI Ribavirin Treatment Effects on Breast Cancers Overexpressing eIF4E, Biomarker with Prognostic Specificity for Luminal B-Type Breast Cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID INITIATION-FACTOR 4E; MAMMARY EPITHELIAL-CELLS; TRANSLATION FACTOR EIF4E; CAP-BINDING PROTEIN; MESSENGER-RNA CAP; GENE-EXPRESSION; ONCOGENIC TRANSFORMATION; SIGNALING PATHWAY; MTOR INHIBITION; TUMOR-GROWTH AB Purpose: We have evaluated the eukaryotic translation initiation factor 4E (eIF4E) as a potential biomarker and therapeutic target in breast cancer. eIF4E facilitates nuclear export and translation of specific, growth-stimulatory mRNAs and is frequently overexpressed in cancer. Experimental Design: Breast cancer cells were treated with ribavirin, an inhibitor of eIF4E, and effects on cell proliferation and on known mRNA targets of eIF4E were determined. eIF4E expression was assessed, at the mRNA and protein level, in breast cancer cell lines and in skin biopsies from patients with metastatic disease. Additionally, pooled microarray data from 621 adjuvant untreated, node-negative breast cancers were analyzed for eIF4E expression levels and correlation with distant metastasis-free survival (DMFS), overall and within each intrinsic breast cancer subtype. Results: At clinically relevant concentrations, ribavirin reduced cell proliferation and suppressed clonogenic potential, correlating with reduced mRNA export and protein expression of important eIF4E targets. This effect was suppressed by knockdown of eIF4E. Although eIF4E expression is elevated in all breast cancer cell lines, variability in ribavirin responsiveness was observed, indicating that other factors contribute to an eIF4E-dependent phenotype. Assessment of the prognostic value of high eIF4E mRNA in patient tumors found that significant discrimination between good and poor outcome groups was observed only in luminal B cases, suggesting that a specific molecular profile may predict response to eIF4E-targeted therapy. Conclusions: Inhibition of eIF4E is a potential breast cancer therapeutic strategy that may be especially promising against specific molecular subtypes and in metastatic as well as primary tumors. Clin Cancer Res; 17(9); 2874-84. (C) 2011 AACR. C1 [Pettersson, Filippa; Dobocan, Monica C.; Retrouvay, Helene; Rousseau, Caroline; Cocolakis, Eftihia; Miller, Wilson H., Jr.] McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ H3T 1E2, Canada. [Pettersson, Filippa; Dobocan, Monica C.; Retrouvay, Helene; Rousseau, Caroline; Cocolakis, Eftihia; Miller, Wilson H., Jr.] McGill Univ, Jewish Gen Hosp, Segal Canc Ctr, Montreal, PQ H3T 1E2, Canada. [Culjkovic-Kraljacic, Biljana; Borden, Katherine L. B.] Univ Montreal, Inst Res Immunol & Canc, Montreal, PQ, Canada. [Culjkovic-Kraljacic, Biljana; Borden, Katherine L. B.] Univ Montreal, Dept Pathol & Cell Biol, Montreal, PQ, Canada. [Yau, Christina; Puckett, Rachel; Benz, Christopher C.] Buck Inst Age Res, Novato, CA USA. [Flores, Ludmila M.; Krop, Ian E.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Miller, WH (reprint author), McGill Univ, Jewish Gen Hosp, Lady Davis Inst, 3755 Cote Ste Catherine Rd, Montreal, PQ H3T 1E2, Canada. EM wmiller@jgh.mcgill.ca FU BCRF-AACR; Canadian Institute for Health Research [CIHR MOP-12863, MOP-43979]; National Cancer Institute of Canada (NCIC ) [19202]; [NIH-P50-CA58207]; [RL1-AG032113]; [U24-CA14358]; [NIH-98571] FX This research was supported in part by a BCRF-AACR Grant for Translational Breast Cancer Research (W. H. Miller). Other financial support was received from the Canadian Institute for Health Research (CIHR MOP-12863, W. H. Miller and F. Pettersson; MOP-43979, W. H. Miller), National Cancer Institute of Canada (NCIC #19202, W. H. Miller), NIH-P50-CA58207, RL1-AG032113, and U24-CA14358 (C. C. Benz and C. Yau), and NIH-98571 (K. L. B. Borden). W. H. Miller is a Chercheur National of Fonds de la Recherche en Sante du Quebec (FRSQ) and K. L. B. Borden holds a Canada Research Chair. NR 48 TC 42 Z9 46 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 MAY 1 PY 2011 VL 17 IS 9 BP 2874 EP 2884 DI 10.1158/1078-0432.CCR-10-2334 PG 11 WC Oncology SC Oncology GA 757NH UT WOS:000290093600028 PM 21415224 ER PT J AU Amrein, PC Attar, EC Takvorian, T Hochberg, EP Ballen, KK Leahy, KM Fisher, DC LaCasce, AS Jacobsen, ED Armand, P Hasserjian, RP Werner, L Neuberg, D Brown, JR AF Amrein, Philip C. Attar, Eyal C. Takvorian, Tak Hochberg, Ephraim P. Ballen, Karen K. Leahy, Kathleen M. Fisher, David C. LaCasce, Ann S. Jacobsen, Eric D. Armand, Philippe Hasserjian, Robert P. Werner, Lillian Neuberg, Donna Brown, Jennifer R. TI Phase II Study of Dasatinib in Relapsed or Refractory Chronic Lymphocytic Leukemia SO CLINICAL CANCER RESEARCH LA English DT Article ID GNAS1 T393C POLYMORPHISM; CHRONIC MYELOID-LEUKEMIA; B-CELL RECEPTOR; KINASE INHIBITOR; TYROSINE KINASE; IN-VITRO; APOPTOSIS; FLUDARABINE; RESISTANCE; ACTIVATION AB Purpose: Chronic lymphocytic leukemia (CLL) cells treated with dasatinib in vitro undergo apoptosis via inhibition of Lyn kinase. Thus, in this study we tested the activity of dasatinib in patients with relapsed CLL. Experimental Design: Patients were eligible for this phase II trial if they had documented CLL/SLL and had failed at least 1 prior therapy with a fludarabine-containing regimen and if they required therapy according to NCI-WG criteria. The starting dose of dasatinib was 140 mg daily. Results: Fifteen patients were enrolled, with a median age of 59 and a median of 3 prior regimens. All patients had received fludarabine, and 5 were fludarabine-refractory. Eleven of the 15 (73%) had high risk del(11q) or del(17p) cytogenetics. The primary toxicity was myelosuppression, with grade 3 or 4 neutropenia and thrombocytopenia in 10 and 6 patients, respectively. Partial responses by NCI-WG criteria were achieved in 3 of the 15 patients (20%; 90% CI: 6-44). Among the remaining 12 patients, 5 had nodal responses by physical exam, and 1 patient had a nodal and lymphocyte response but with severe myelosuppression. Pharmacodynamic studies indicated apoptosis in peripheral blood CLL cells within 3 to 6 hours after dasatinib administration, associated with downregulation of Syk (spleen tyrosine kinase) mRNA. Conclusions: Dasatinib as a single agent has activity in relapsed and refractory CLL. Clin Cancer Res; 17(9); 2977-86. (C) 2011 AACR. C1 [Amrein, Philip C.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Werner, Lillian; Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. [Hasserjian, Robert P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Amrein, Philip C.; Attar, Eyal C.; Takvorian, Tak; Hochberg, Ephraim P.; Ballen, Karen K.; Fisher, David C.; LaCasce, Ann S.; Jacobsen, Eric D.; Armand, Philippe; Brown, Jennifer R.] Harvard Univ, Sch Med, Boston, MA USA. RP Amrein, PC (reprint author), Massachusetts Gen Hosp, Ctr Canc, Yawkey 7-942, Boston, MA 02114 USA. EM pamrein@partners.org FU Bristol Myers Squibb [205309]; Celgene; Genzyme; NIH [K23 CA115682] FX This study is an investigator-initiated study supported by per patient funding from Bristol Myers Squibb, which also supplied dasatinib. P. C. Amrein received $1,500 for attending a Bristol-Myers Squibb Advisory Board Meeting regarding Hematologic Malignancies in 2007. J. R. Brown served as a consultant for Calistoga, Celgene, and Genentech and received research funding from Celgene and Genzyme. The other authors have no conflict-of-interest to report.; This work was supported in part by grant 205309 from Bristol-Myers Squibb (to help support the management of data and the processing of blood and bone marrow samples). J. R. Brown was supported in part by NIH K23 CA115682. NR 32 TC 77 Z9 77 U1 0 U2 10 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 MAY 1 PY 2011 VL 17 IS 9 BP 2977 EP 2986 DI 10.1158/1078-0432.CCR-10-2879 PG 10 WC Oncology SC Oncology GA 757NH UT WOS:000290093600038 PM 21402714 ER PT J AU Leleu, X Xie, WL Bagshaw, M Banwait, R Leduc, R Roper, N Weller, E Ghobrial, IM AF Leleu, Xavier Xie, Wanling Bagshaw, Meghan Banwait, Ranjit Leduc, Renee Roper, Nitin Weller, Edie Ghobrial, Irene M. TI The Role of Serum Immunoglobulin Free Light Chain in Response and Progression in Waldenstrom Macroglobulinemia SO CLINICAL CANCER RESEARCH LA English DT Article ID MULTIPLE-MYELOMA; IMMUNOFIXATION ELECTROPHORESIS; INTERNATIONAL WORKSHOP; RECOMMENDATIONS; DIAGNOSIS; CRITERIA; ASSAYS AB Introduction: The serum free light chain (sFLC) has been widely used in the assessment of response in patients with multiple myeloma and other plasma cell dyscrasias. However, its use in Waldenstrom macroglobulinemia (WM) has not been previously assessed. We sought to examine the role of sFLC in response and progression of patients with WM. Methods: This study was conducted in a cohort of 48 patients with a diagnosis of WM, untreated (n = 20) or relapsed/refractory (n = 28), prospectively treated on a bortezomib and rituximab trial. Results: Involved FLC (iFLC) response occurred in 79% patients versus 60% by M-spike protocol criteria. The median time to response was shorter with iFLC than per protocol (2.1 and 3.7 months; P = 0.05). Progression defined using iFLC also correlated well to progression in the protocol (kappa = 0.63). However, the median time to progression (TTP) was more rapid by iFLC than per protocol (13.7 and 18.9 months). We also confirmed that a flare in iFLC in post-rituximab therapy did not correlate with lack of response or shorter TTP. Conclusion: Involved sFLC may be a useful marker of tumor measurement, showing earlier response and progression compared with IgM or M-spike measurements. Clin Cancer Res; 17(9); 3013-8. (C) 2011 AACR. C1 [Leleu, Xavier; Bagshaw, Meghan; Banwait, Ranjit; Leduc, Renee; Roper, Nitin; Ghobrial, Irene M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Xie, Wanling; Weller, Edie] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Leleu, Xavier] CHRU, Hop Huriez, Serv Malad Sang, Lille, France. RP Ghobrial, IM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,Mayer 1B127, Boston, MA 02115 USA. EM irene_ghobrial@dfci.harvard.edu NR 15 TC 18 Z9 21 U1 1 U2 3 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 MAY 1 PY 2011 VL 17 IS 9 BP 3013 EP 3018 DI 10.1158/1078-0432.CCR-10-2954 PG 6 WC Oncology SC Oncology GA 757NH UT WOS:000290093600042 PM 21415221 ER PT J AU Haining, WN AF Haining, W. N. TI INTEGRATIVE GENOMIC ANALYSIS OF T CELL IMMUNITY IN HUMANS SO CLINICAL CHEMISTRY AND LABORATORY MEDICINE LA English DT Meeting Abstract C1 [Haining, W. N.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Haining, W. N.] Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. [Haining, W. N.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 1434-6621 J9 CLIN CHEM LAB MED JI Clin. Chem. Lab. Med. PD MAY PY 2011 VL 49 SU 1 BP S10 EP S10 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 755XR UT WOS:000289974200005 ER PT J AU Januzzi, JL AF Januzzi, James L., Jr. TI NT-PROBNP GUIDED HEART FAILURE THERAPY SO CLINICAL CHEMISTRY AND LABORATORY MEDICINE LA English DT Meeting Abstract C1 [Januzzi, James L., Jr.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Januzzi, James L., Jr.] Massachusetts Gen Hosp, Cardiac Intens Care Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 1434-6621 J9 CLIN CHEM LAB MED JI Clin. Chem. Lab. Med. PD MAY PY 2011 VL 49 SU 1 BP S174 EP S174 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 755XR UT WOS:000289974200197 ER PT J AU Melanson, SEF Stevenson, K Kim, H Antin, JH Ho, VT Ritz, J Soiffer, RJ Court, MH Kuo, FC Longtine, JA Jarolim, P AF Melanson, S. E. F. Stevenson, K. Kim, H. Antin, J. H. Ho, V. T. Ritz, J. Soiffer, R. J. Court, M. H. Kuo, F. C. Longtine, J. A. Jarolim, P. TI REDUCED OVERALL SURVIVAL OF CYP2C19*2/*2 HOMOZYGOTES AFTER MYELOABLATIVE HEMATOPOIETIC STEM CELL TRANSPLANTATION SO CLINICAL CHEMISTRY AND LABORATORY MEDICINE LA English DT Meeting Abstract C1 [Melanson, S. E. F.; Kuo, F. C.; Longtine, J. A.; Jarolim, P.] Harvard Univ, Sch Med, Dept Pathol, Brigham & Womens Hosp, Boston, MA 02115 USA. [Stevenson, K.; Kim, H.; Antin, J. H.; Ho, V. T.; Ritz, J.; Soiffer, R. J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. [Court, M. H.] Tufts Univ, Sch Med, Dept Pharmacol & Expt Therapeut, Boston, MA 02111 USA. EM pjarolim@partners.org NR 0 TC 0 Z9 0 U1 0 U2 1 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 1434-6621 J9 CLIN CHEM LAB MED JI Clin. Chem. Lab. Med. PD MAY PY 2011 VL 49 SU 1 BP S667 EP S667 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 755XR UT WOS:000289974201332 ER PT J AU Pratchett, LC Yehuda, R AF Pratchett, Laura C. Yehuda, Rachel TI Foundations of posttraumatic stress disorder: Does early life trauma lead to adult posttraumatic stress disorder? SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Article ID CHILD SEXUAL-ABUSE; CORTICOTROPIN-RELEASING-FACTOR; NATIONAL COMORBIDITY SURVEY; URINARY CORTISOL EXCRETION; INTIMATE PARTNER VIOLENCE; FOLLOW-UP; HOLOCAUST SURVIVORS; MALTREATED CHILDREN; NEGLECTED CHILDREN; PHYSICAL ABUSE AB The effects of childhood abuse are diverse, and although pathology is not the only outcome, psychiatric illness, including posttraumatic stress disorder (PTSD), can develop. However, adult PTSD is less common among those who experienced single-event traumas as children than it is among those who experienced childhood abuse. In addition, PTSD is more common among adults than children who experienced childhood abuse. Such evidence raises doubt about the direct, causal link between childhood trauma and adult PTSD. The experience of childhood trauma, and in particular abuse, has been identified as a risk factor for subsequent development of PTSD following exposure to adult trauma, and a substantial literature identifies revictimization as a factor that plays a pivotal role in this trajectory. The literature on the developmental effects of childhood abuse and pathways to revictimization, when considered in tandem with the biological effects of early stress in animal models, may provide some explanations for this. Specifically, it seems possible that permanent sensitization of the hypothalamic-pituitary-adrenal axis and behavioral outcomes are a consequence of childhood abuse, and these combine with the impact of retraumatization to sustain, perpetuate, and amplify symptomatology of those exposed to maltreatment in childhood. C1 [Pratchett, Laura C.; Yehuda, Rachel] James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA. [Yehuda, Rachel] Mt Sinai Sch Med, New York, NY 10029 USA. RP Pratchett, LC (reprint author), James J Peters Vet Affairs Med Ctr, 526 OOMH,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM laura.pratchett@va.gov FU NIMH NIH HHS [MH088101] NR 206 TC 20 Z9 21 U1 17 U2 37 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0954-5794 J9 DEV PSYCHOPATHOL JI Dev. Psychopathol. PD MAY PY 2011 VL 23 IS 2 BP 477 EP 491 DI 10.1017/S0954579411000186 PG 15 WC Psychology, Developmental SC Psychology GA 757OP UT WOS:000290097900009 PM 23786690 ER PT J AU Pasquale, LR Kang, JH AF Pasquale, L. R. Kang, J. H. TI Female reproductive factors and primary open-angle glaucoma in the Nurses' Health Study SO EYE LA English DT Article DE female reproductive factors; age at menarche; parity; oral contraceptives; primary open angle glaucoma ID HORMONE REPLACEMENT THERAPY; DOSE ORAL-CONTRACEPTIVES; INTRAOCULAR-PRESSURE; POSTMENOPAUSAL WOMEN; BREAST-CANCER; PROSPECTIVE COHORT; SEX-HORMONES; RISK-FACTORS; EYE DISEASE; ESTROGEN AB Purpose The purpose of this study was to explore the relation between age at menarche, parity, and oral contraceptive (OC) use, and primary open-angle glaucoma (POAG). Methods We followed 79 440 women in the Nurses' Health Study prospectively from 1980 to 2006 and identified 813 cases of incident POAG. Eligible participants were >= 40 years old, free of POAG at baseline, had information on reproductive history, and reported receiving eye examinations during follow-up. Relevant exposure data and POAG risk factors were updated using biennial questionnaires. We used proportional hazards models to calculate multivariable rate ratios (MVRRs) of POAG and 95% confidence intervals (CI). Results In multivariable analysis, there were no significant linear trends between age at menarche (P for trend=0.65) or reproductive duration defined as time between age at menarche and menopause (P for trend=0.30) and POAG. Although ever using OCs was not associated with POAG risk (MVRR=1.14; 95% CI, 0.98, 1.34), >= 5 years of OC use was associated with a modest 25% increased risk of POAG (MVRR=1.25; 95% CI, 1.02, 1.53; P for linear trend=0.04). Furthermore, among past OC users, a shorter time since stopping OC use was also associated with an increased risk of POAG (P for linear trend=0.02). Parity was not associated with POAG risk. Conclusion The >= 5 years of OC use was associated with a modestly increased risk of POAG. These data add further support for a role of circulating estrogen in the pathogenesis of POAG. Eye (2011) 25, 633-641; doi:10.1038/eye.2011.34; published online 18 February 2011 C1 [Pasquale, L. R.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Massachusetts Eye & Ear Infirm,Dept Ophthalmol, Boston, MA 02114 USA. [Pasquale, L. R.; Kang, J. H.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Channing Lab, Boston, MA 02114 USA. RP Pasquale, LR (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Massachusetts Eye & Ear Infirm,Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM Louis_Pasquale@meei.harvard.edu FU National Institutes of Health [CA87969, CA55075, EY09611, HL35464, EY015473]; Research to Prevent Blindness in New York City FX We thank the participants of the Nurses Health Study and Frank Spiezer and Susan Hankinson, the founding and current principal investigators of the Nurses Health Study. Finally, we also thank Rong Chen, Maureen Ireland and Ann Wohlhueter for their contributions to this study. Financial support for this work was provided by grants CA87969, CA55075, EY09611, HL35464, and EY015473 from the National Institutes of Health. A Physician Scientist Award from Research to Prevent Blindness in New York City also supports Dr Pasquale. NR 44 TC 19 Z9 19 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-222X J9 EYE JI Eye PD MAY PY 2011 VL 25 IS 5 BP 633 EP 641 DI 10.1038/eye.2011.34 PG 9 WC Ophthalmology SC Ophthalmology GA 763LE UT WOS:000290557300012 PM 21336255 ER PT J AU Thomas, V Daly, MK Cakiner-Egilmez, T Baker, E AF Thomas, V. Daly, M. K. Cakiner-Egilmez, T. Baker, E. TI Reliability of tonosafe disposable tonometer prisms: clinical implications from the Veterans Affairs Boston Healthcare System Quality Assurance Study SO EYE LA English DT Article DE intraocular pressure; disposable prisms; cross-infection; tonometry ID INTRAOCULAR-PRESSURE MEASUREMENT; EPIDEMIC KERATOCONJUNCTIVITIS; APPLANATION TONOMETRY; GOLDMANN TONOMETERS; DISINFECTION; ACCURACY; OUTBREAK; TIPS AB Purpose Given the Veterans Affairs Boston Healthcare System's recent introduction of single-use Tonosafe disposable tonometer prisms as an alternative to Goldmann applanation tonometers (GATs), this study had two aims: to conduct a large-scale quality assurance trial to assess the reliability of intraocular pressure (IOP) measurements of the Tonosafe disposable tonometer compared with GAT, particularly at extremes of pressure; to evaluate the suitability of Tonosafe disposable tonometer prisms as an acceptable substitute for GATs and for clinic-wide implementation in an academic tertiary referral setting. Methods Ophthalmology resident physicians measured the IOPs of patients in general and specialty eye clinics with the Tonosafe disposable tonometer and GAT. Tonosafe test-retest reliability data were also collected. A retrospective review of patient charts and data analysis were performed to determine the reliability of measurements. Results The IOPs of 652 eyes (326 patients) were measured with both GAT and Tonosafe, with a range of 3-34 mm Hg. Linear regression analysis showed R=0.93, slope=0.91, both of which supported the proposed hypothesis, and the y-intercept=-1.05 was significantly different from the hypothesized value. The Tonosafe test-retest repeatability (40 eyes of 40 patients), r=0.977, was very high, which was further supported by linear regression slope-0.993, y-intercept-0.118, and a Tonosafe repeatability coefficient of 2.06, similar to GAT repeatability. Conclusions The IOP measurements by Tonosafe disposable prisms correlated closely with Goldmann measurements, with similar repeated measurement variability to GAT. This suggests that the Tonosafe is an acceptable substitute for GAT to measure IOP in ophthalmology clinic settings. Eye (2011) 25, 651-656; doi:10.1038/eye.2011.40; published online 1 April 2011 C1 [Thomas, V.; Daly, M. K.; Cakiner-Egilmez, T.; Baker, E.] Vet Affairs Boston Healthcare Syst, Boston, MA USA. [Thomas, V.; Daly, M. K.] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Thomas, V (reprint author), VA Boston Healthcare, Ophthalmol Sect, 150 S Huntington,Off 8C-29, Boston, MA 02130 USA. EM vthomas@bu.edu NR 27 TC 1 Z9 1 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-222X J9 EYE JI Eye PD MAY PY 2011 VL 25 IS 5 BP 651 EP 656 DI 10.1038/eye.2011.40 PG 6 WC Ophthalmology SC Ophthalmology GA 763LE UT WOS:000290557300014 PM 21455241 ER PT J AU Kellogg, DL Zhao, JL Wu, YB Johnson, JM AF Kellogg, Dean L., Jr. Zhao, Joan L. Wu, Yubo Johnson, John M. TI Antagonism of soluble guanylyl cyclase attenuates cutaneous vasodilation during whole body heat stress and local warming in humans SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE nitric oxide; guanosine 3 ',5 '-cyclic monophosphate; microdialysis; skin; thermoregulation ID SKIN BLOOD-FLOW; HUMAN CARDIOVASCULAR ADJUSTMENTS; SYNTHASE CONTROL MECHANISMS; NITRIC-OXIDE CONCENTRATION; ACTIVE VASODILATATION; S-NITROSYLATION; IN-VIVO; REACTIVE HYPEREMIA; VASCULAR-RESPONSES; MUNC18-1 BINDING AB Kellogg DL Jr, Zhao JL, Wu Y, Johnson JM. Antagonism of soluble guanylyl cyclase attenuates cutaneous vasodilation during whole body heat stress and local warming in humans. J Appl Physiol 110: 1406-1413, 2011. First published February 3, 2011; doi: 10.1152/japplphysiol.00702.2010.-We hypothesized that nitric oxide activation of soluble guanylyl cyclase (sGC) participates in cutaneous vasodilation during whole body heat stress and local skin warming. We examined the effects of the sGC inhibitor, 1H-[1,2,4] oxadiazolo[4,3-a] quinoxalin-1-one (ODQ), on reflex skin blood flow responses to whole body heat stress and on nonreflex responses to increased local skin temperature. Blood flow was monitored by laser-Doppler flowmetry, and blood pressure by Finapres to calculate cutaneous vascular conductance (CVC). Intradermal microdialysis was used to treat one site with 1 mM ODQ in 2% DMSO and Ringer, a second site with 2% DMSO in Ringer, and a third site received Ringer. In protocol 1, after a period of normothermia, whole body heat stress was induced. In protocol 2, local heating units warmed local skin temperature from 34 to 41 C to cause local vasodilation. In protocol 1, in normothermia, CVC did not differ among sites [ ODQ, 15 +/- 3% maximum CVC (CVC(max)); DMSO, 14 +/- 3% CVC(max); Ringer, 17 +/- 6% CVC(max); P > 0.05]. During heat stress, ODQ attenuated CVC increases (ODQ, 54 +/- 4% CVC(max); DMSO, 64 +/- 4% CVC(max); Ringer, 63 +/- 4% CVC(max); P < 0.05, ODQ vs. DMSO or Ringer). In protocol 2, at 34 degrees C local temperature, CVC did not differ among sites (ODQ, 17 +/- 2% CVC(max); DMSO, 18 +/- 4% CVC(max); Ringer, 18 +/- 3% CVC(max); P < 0.05). ODQ attenuated CVC increases at 41 degrees C local temperature (ODQ, 54 +/- 5% CVC(max); DMSO, 86 +/- 4% CVC(max); Ringer, 90 +/- 2% CVCmax; P < 0.05 ODQ vs. DMSO or Ringer). sGC participates in neurogenic active vasodilation during heat stress and in the local response to direct skin warming. C1 [Kellogg, Dean L., Jr.; Zhao, Joan L.; Wu, Yubo] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Geriatr Gerontol & Palliat Med, San Antonio, TX 78229 USA. [Kellogg, Dean L., Jr.; Johnson, John M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Kellogg, Dean L., Jr.; Zhao, Joan L.; Wu, Yubo] Univ Texas Hlth Sci Ctr San Antonio, Audie L Murphy Mem Vet Hosp Div, S Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA. RP Kellogg, DL (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Geriatr Gerontol & Palliat Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM kelloggd@uthscsa.edu FU National Heart, Lung, and Blood Institute [HL-065599] FX This work was supported in part by National Heart, Lung, and Blood Institute Grant HL-065599. NR 64 TC 14 Z9 14 U1 0 U2 2 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 MAY PY 2011 VL 110 IS 5 BP 1406 EP 1413 DI 10.1152/japplphysiol.00702.2010 PG 8 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 762JL UT WOS:000290472400036 PM 21292837 ER PT J AU Winkler, T Venegas, JG AF Winkler, Tilo Venegas, Jose G. TI Self-organized patterns of airway narrowing SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Review DE asthma; bronchoconstriction; airway smooth muscle; emergence; complex behavior ID OBSTRUCTIVE PULMONARY-DISEASE; SYNCHROTRON-RADIATION CT; SMOOTH-MUSCLE; VENTILATION; ASTHMA; BRONCHOCONSTRICTION; METHACHOLINE; RESPONSES; HETEROGENEITY; IMPEDANCE AB Winkler T, Venegas JG. Self-organized patterns of airway narrowing. J Appl Physiol 110: 1482-1486, 2011. First published January 20, 2011; doi: 10.1152/japplphysiol.01163.2010.-The behavior of respiratory diseases such as asthma and COPD may involve complicated interactions among multiple factors. Theoretical and experimental data suggest that interdependence among the airways of the bronchial tree leads to the emergence of self-organized patterns of airway narrowing, ventilation defects, and other phenomena when a tipping point is passed. Additionally, evidence from several studies shows that the behavior of an isolated airway is different from an identical airway embedded in the bronchial tree so that experimental results of isolated elements such as airways, airway smooth muscle, or inflammatory pathways may not explain the whole organ behavior. However, there may be factors in the isolated elements that can dramatically change the complex system's behavior. More effective strategies for prevention or recovery from a disease, such as asthma, will depend on our progress in identifying and understanding the essential parts of the self-organized behavior that is involved. C1 [Winkler, Tilo] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Winkler, T (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM twinkler@vqpet.mgh.harvard.edu RI Winkler, Tilo/B-5337-2009 OI Winkler, Tilo/0000-0002-7276-5550 NR 32 TC 9 Z9 9 U1 0 U2 2 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 MAY PY 2011 VL 110 IS 5 BP 1482 EP 1486 DI 10.1152/japplphysiol.01163.2010 PG 5 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 762JL UT WOS:000290472400046 PM 21252219 ER PT J AU Fang, Y Fu, XJ Gu, C Xu, P Wang, Y Yu, WR Sun, Q Sun, XJ Yao, M AF Fang, Yong Fu, Xiu-Jun Gu, Chuan Xu, Peng Wang, Ying Yu, Wei-Rong Sun, Qiang Sun, Xue-Jun Yao, Min TI Hydrogen-Rich Saline Protects Against Acute Lung Injury Induced by Extensive Burn in Rat Model SO JOURNAL OF BURN CARE & RESEARCH LA English DT Article ID SMOKE-INHALATION INJURY; NF-KAPPA-B; OXIDATIVE STRESS; BACTERIAL TRANSLOCATION; ENDOTHELIAL-CELLS; THERMAL-INJURY; SHEEP; PATHOPHYSIOLOGY; INFLAMMATION; DYSFUNCTION AB Hydrogen has been reported to selectively quench detrimental reactive oxygen species, particularly hydroxyl radical, and to prevent myocardial or hepatic ischemia/reperfusion injury in multiple models. The aim of this study is to investigate whether hydrogen protects against severe burn-induced acute lung injury in rats. Rats were divided into four groups: sham plus normal saline, burn injury plus normal saline, burn injury plus hydrogen-rich saline, and burn injury plus edaravone. Animals were given full-thickness burn wounds (30% TBSA) using boiling water, except the sham group that was treated with room temperature water. The rats in hydrogen group received 5 ml/kg of hydrogen-rich saline, sham and burn controls obtained the same amount of saline, and the edaravone group was treated with 9 mg/kg of edaravone in saline. Lactated Ringer's solution was given at 6 hours postburn. The lungs were harvested 12 hours postburn for laboratory investigations. Severe burns with delayed resuscitation rapidly caused lung edema and impaired oxygenation in rats. These dysfunctions were ameliorated by administration of hydrogen-rich saline or edaravone. When compared with the burn injury plus normal saline group, hydrogen-rich saline or edaravone group significantly attenuated the pulmonary oxidative products, such as malondialdehyde, carbonyl, and 8-hydroxy-2'-deoxyguanosine. Furthermore, administration of hydrogen-rich saline or edaravone dramatically reduced the pulmonary levels of pulmonary inflammation mediators and myeloperoxidase. Intraperitoneal administration of hydrogen-rich saline improves pulmonary function by reducing oxidative stress and inflammatory response in severe burn-induced acute lung injury. (J Burn Care Res 2011;32:e82-e91) C1 [Yao, Min] Shanghai Jiao Tong Univ, Dept Burns & Plast Surg, Peoples Hosp 3, Sch Med,Inst Traumat Med, Shanghai 201900, Peoples R China. [Sun, Qiang; Sun, Xue-Jun] Second Mil Med Univ, Dept Diving Med, Shanghai, Peoples R China. [Yao, Min] Harvard Univ, Sch Med, Dept Dermatol, Wellman Ctr Photomed,Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Yao, M (reprint author), Shanghai Jiao Tong Univ, Dept Burns & Plast Surg, Peoples Hosp 3, Sch Med,Inst Traumat Med, 280 Mohe Rd, Shanghai 201900, Peoples R China. RI sun, xuejun/G-5212-2011; sun, xuejun/C-2844-2013; sun, xuejun/A-5561-2010 OI sun, xuejun/0000-0003-2387-5531 FU Foundation of Nature and Science at the School of Medicine, Shanghai Jiao Tong University [2008XZDXK]; National Natural Science Foundation of China [30872682] FX Supported, in part, by a grant from the Foundation of Nature and Science at the School of Medicine, Shanghai Jiao Tong University (2008XZDXK), and the National Natural Science Foundation of China (30872682). NR 40 TC 21 Z9 27 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1559-047X EI 1559-0488 J9 J BURN CARE RES JI J. Burn Care Res. PD MAY-JUN PY 2011 VL 32 IS 3 BP E82 EP E91 DI 10.1097/BCR.0b013e318217f84f PG 10 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA 760EZ UT WOS:000290308500007 PM 21436720 ER PT J AU Zarraga, IGE MacMurdy, KS Raitt, MH AF Zarraga, Ignatius Gerardo E. MacMurdy, Karen S. Raitt, Merritt H. TI Tachycardia With Typical Left Bundle Branch Block Morphology and VA Block: What is the Differential Diagnosis? SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Editorial Material ID REENTRY; MECHANISM C1 [Zarraga, Ignatius Gerardo E.; MacMurdy, Karen S.; Raitt, Merritt H.] Portland VA Med Ctr, Div Cardiol, Portland, OR 97239 USA. RP Zarraga, IGE (reprint author), Portland VA Med Ctr, Div Cardiol, 3710 SW,US Vet Hos Rd, Portland, OR 97239 USA. EM Ignatius.Zarraga@va.gov OI Raitt, Merritt/0000-0001-5638-7732 NR 6 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD MAY PY 2011 VL 22 IS 5 BP 601 EP 604 DI 10.1111/j.1540-8167.2010.01965.x PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 762OT UT WOS:000290490000021 PM 21561505 ER PT J AU Mohr, DC Warren, N Hodgson, MJ Drummond, DJ AF Mohr, David C. Warren, Nicholas Hodgson, Michael J. Drummond, David J. TI Assault Rates and Implementation of a Workplace Violence Prevention Program in the Veterans Health Care Administration SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID EMPLOYERS REPORTS; WORKERS; AGGRESSION; FACILITIES; CALIFORNIA; SETTINGS; INJURIES; BEHAVIOR AB Objective: This study examined the relationship between changes in assault rates over time and the implementation of a workplace violence prevention (WVP) program in 138 Department of Veterans Affairs health care facilities. Methods: Data on WVP implementation were assessed for each facility by a three-person team. We computed three WVP dimension scores: training, workplace practices, and environmental control and security. We obtained 6 years of assault rate data from the national injury system. Using a linear mixed model, we analyzed whether the WVP implementation was associated with lower assault rates controlling for time and organizational characteristics. Results: Training implementation was negatively associated with assault rates. Facilities with smaller bed sizes and without academic affiliates had lower assault rates. Conclusions: Particular attention should be given to these dimensions because they may be associated with lower facility-level assault rates. C1 [Mohr, David C.] Boston Univ, Sch Publ Hlth, Ctr Org Leadership & Management Res, Dept Vet Affairs,VA Boston Healthcare Syst, Boston, MA USA. [Mohr, David C.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Warren, Nicholas] Univ Connecticut, Ctr Hlth, Div Publ Hlth & Populat Sci, Farmington, CT USA. [Hodgson, Michael J.; Drummond, David J.] Dept Vet Affairs, Off Publ Hlth & Environm Hazards, Washington, DC USA. RP Mohr, DC (reprint author), VA Boston Healthcare Syst 152M, 150 S Huntington Ave, Boston, MA 02130 USA. EM david.mohr2@va.gov FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development [IIR 05-221] FX This material is based upon the work supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development for IIR 05-221. The authors are also grateful for the advice and support of Dr Charles Welch. NR 37 TC 8 Z9 8 U1 3 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD MAY PY 2011 VL 53 IS 5 BP 511 EP 516 DI 10.1097/JOM.0b013e31820d101e PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 761WA UT WOS:000290430500008 PM 21555925 ER PT J AU Ahmed, S Gibson, CM Cannon, CP Murphy, SA Sabatine, MS AF Ahmed, Shaheeda Gibson, C. Michael Cannon, Christopher P. Murphy, Sabina A. Sabatine, Marc S. TI Impact of reduced glomerular filtration rate on outcomes in patients with ST-segment elevation myocardial infarction undergoing fibrinolysis: a CLARITY-TIMI 28 analysis SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Article DE Myocardial infarction; Glomerular filtration rate; Fibrinolysis; Platelet ID ACUTE CORONARY SYNDROMES; CHRONIC KIDNEY-DISEASE; CARDIOVASCULAR OUTCOMES; SUBSEQUENT MORTALITY; REPERFUSION THERAPY; DIABETES-MELLITUS; RENAL DYSFUNCTION; PERFUSION GRADE; ARTERY-DISEASE; ASSOCIATION AB Reduced glomerular filtration rate (GFR) is associated with adverse outcomes in patients with cardiovascular disease. We explored the relationship between GFR and angiographic and clinical outcomes in ST-segment elevation myocardial infarction (STEMI) patients receiving pharamacologic reperfusion, with or without clopidogrel. Data were available to estimate GFR in 3,252 STEMI patients undergoing fibrinolysis, randomized to clopidogrel versus placebo in the CLARITY-TIMI 28 trial. Patients with a creatinine > 2.5 mg/dl were excluded from the trial. We compared outcomes between patients with no, mild or moderate reductions in baseline estimated GFR (ml/min/1.73 m(2)) of a parts per thousand yen90, 60-89, and < 60, respectively. Compared to patients with no (n = 841) or mildly reduced GFR (n = 1897), those with moderately reduced GFR (n = 514) were older, more often female, and were more likely to have diabetes and hypertension (P a parts per thousand currency sign 0.001 for all). The risk of the primary endpoint (an occluded infarct-related artery on angiography or death/myocardial infarction by day 8), 30 day cardiovascular events (death, myocardial infarction, or urgent revascularization for recurrent ischemia) and 30 day Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding increased as GFR declined (P for trend 0.003, < 0.0001, and 0.0008 respectively). The adjusted risk of 30 day ischemic complications remained higher in patients with moderately reduced versus normal GFR (OR 1.5, 95% CI 1.0-2.1, P = 0.04). Treatment with clopidogrel tended to yield greater benefit in patients with normal or mildly reduced GFR versus in patients with moderately reduced GFR. In conclusion, STEMI patients with reduced GFR treated with medical reperfusion, including dual antiplatelet therapy, have higher rates of adverse clinical outcome. Further research on optimal STEMI therapy in this high-risk group is warranted. C1 [Ahmed, Shaheeda; Gibson, C. Michael; Cannon, Christopher P.; Murphy, Sabina A.; Sabatine, Marc S.] Brigham & Womens Hosp, Dept Med, Cardiovasc Div, TIMI Study Grp, Boston, MA 02115 USA. [Ahmed, Shaheeda; Gibson, C. Michael; Cannon, Christopher P.; Murphy, Sabina A.; Sabatine, Marc S.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Sabatine, MS (reprint author), Brigham & Womens Hosp, Dept Med, Cardiovasc Div, TIMI Study Grp, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM msabatine@partners.org NR 21 TC 4 Z9 4 U1 2 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 MAY PY 2011 VL 31 IS 4 BP 493 EP 500 DI 10.1007/s11239-011-0566-9 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 762DA UT WOS:000290451300014 PM 21318582 ER PT J AU Moore, FO Goslar, PW Coimbra, R Velmahos, G Brown, CVR Coopwood, TB Lottenberg, L Phelan, HA Bruns, BR Sherck, JP Norwood, SH Barnes, SL Matthews, MR Hoff, WS de Moya, MA Bansal, V Hu, CKC Karmy-Jones, RC Vinces, F Pembaur, K Notrica, DM Haan, JM AF Moore, Forrest O. Goslar, Pamela W. Coimbra, Raul Velmahos, George Brown, Carlos V. R. Coopwood, Thomas B., Jr. Lottenberg, Lawrence Phelan, Herb A. Bruns, Brandon R. Sherck, John P. Norwood, Scott H. Barnes, Stephen L. Matthews, Marc R. Hoff, William S. de Moya, Marc A. Bansal, Vishal Hu, Charles K. C. Karmy-Jones, Riyad C. Vinces, Fausto Pembaur, Karl Notrica, David M. Haan, James M. TI Blunt Traumatic Occult Pneumothorax: Is Observation Safe?-Results of a Prospective, AAST Multicenter Study SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article; Proceedings Paper CT 69th Annual Meeting of the American-Association-for-the-Surgery-of-Trauma CY SEP 22-25, 2010 CL Boston, MA SP Amer Assoc Surg Trauma DE Occult pneumothorax; Tube thoracostomy; Computed tomography ID TUBE THORACOSTOMY; COMPUTED-TOMOGRAPHY; CRITICAL-CARE; CHEST TRAUMA; MANAGEMENT; CT; COMPLICATIONS; PATIENT AB Background: An occult pneumothorax (OPTX) is found incidentally in 2% to 10% of all blunt trauma patients. Indications for intervention remain controversial. We sought to determine which factors predicted failed observation in blunt trauma patients. Methods: A prospective, observational, multicenter study was undertaken to identify patients with OPTX. Successfully observed patients and patients who failed observation were compared. Multivariate logistic regression was used to identify predictors of failure of observation. OPTX size was calculated by measuring the largest air collection along a line perpendicular from the chest wall to the lung or mediastinum. Results: Sixteen trauma centers identified 588 OPTXs in 569 blunt trauma patients. One hundred twenty-one patients (21%) underwent immediate tube thoracostomy and 448 (79%) were observed. Twenty-seven patients (6%) failed observation and required tube thoracostomy for OPTX progression, respiratory distress, or subsequent hemothorax. Fourteen percent (10 of 73) failed observation during positive pressure ventilation. Hospital and intensive care unit lengths of stay, and ventilator days were longer in the failed observation group. OPTX progression and respiratory distress were significant predictors of failed observation. Most patient deaths were from traumatic brain injury. Fifteen percentage of patients in the failed observation group developed complications. No patient who failed observation developed a tension PTX, or experienced adverse events by delaying tube thoracostomy. Conclusion: Most blunt trauma patients with OPTX can be carefully monitored without tube thoracostomy; however, OPTX progression and respiratory distress are independently associated with observation failure. C1 [Moore, Forrest O.; Goslar, Pamela W.] St Josephs Hosp, Phoenix, AZ 85013 USA. [Moore, Forrest O.; Goslar, Pamela W.] Med Ctr, Phoenix, AZ 85013 USA. [Coimbra, Raul; Bansal, Vishal] UCSD, Med Ctr, San Diego, CA USA. [Velmahos, George; de Moya, Marc A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Brown, Carlos V. R.; Coopwood, Thomas B., Jr.] Univ Med Ctr Brackenridge, Austin, TX USA. [Lottenberg, Lawrence] Univ Florida, Hlth Sci Ctr, Gainesville, FL USA. [Phelan, Herb A.] UT Southwestern, Med Ctr, Dallas, TX USA. [Bruns, Brandon R.] Univ Penn, Med Ctr, Philadelphia, PA 19104 USA. [Sherck, John P.] Santa Clara Valley Med Ctr, San Jose, CA 95128 USA. [Norwood, Scott H.] E Texas Med Ctr, Tyler, TX USA. [Barnes, Stephen L.] Univ Missouri, Columbia, MO USA. [Matthews, Marc R.] Maricopa Cty Gen Hosp, Phoenix, AZ USA. [Hoff, William S.] St Lukes Hosp, Bethlehem, PA USA. [Hoff, William S.] Med Ctr, Bethlehem, PA USA. [Hu, Charles K. C.] Scottsdale Osborne Med Ctr, Scottsdale, AZ USA. [Karmy-Jones, Riyad C.] Southwest Washington Med Ctr, Vancouver, WA USA. [Vinces, Fausto; Pembaur, Karl] Lutheran Med Ctr, Brooklyn, NY USA. [Notrica, David M.] Phoenix Childrens Hosp, Phoenix, AZ USA. [Haan, James M.] Via Christi Reg Med Ctr, Wichita, KS USA. RP Moore, FO (reprint author), St Josephs Hosp, 350 W Thomas Rd, Phoenix, AZ 85013 USA. EM moore677@aol.com NR 21 TC 31 Z9 35 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5282 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD MAY PY 2011 VL 70 IS 5 BP 1019 EP 1023 DI 10.1097/TA.0b013e318213f727 PG 5 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 762LQ UT WOS:000290480300009 PM 21610419 ER PT J AU Rodriguez, A Lisboa, T Martin-Loeches, I Diaz, E Trefler, S Restrepo, MI Rello, J AF Rodriguez, Alejandro Lisboa, Thiago Martin-Loeches, Ignacio Diaz, Emili Trefler, Sandra Restrepo, Marcos I. Rello, Jordi TI Mortality and Regional Oxygen Saturation Index in Septic Shock Patients: A Pilot Study SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article DE Near-infrared spectroscopy; Sepsis; Microcirculation; Tissue oxygenation; Hypoxia ID NEAR-INFRARED SPECTROSCOPY; MUSCLE-TISSUE OXYGENATION; SEVERE SEPSIS; TRAUMA PATIENTS; BLOOD-FLOW; PERFUSION; RESUSCITATION; CONSUMPTION; DYSFUNCTION; INSTRUMENT AB Background: Peripheral muscle tissue oxygenation determined noninvasively using near-infrared spectroscopy may help to identify tissue hypoperfusion in septic patients. The aim of this study was to investigate regional oxygen saturation index (rSO(2)) in the brachioradialis (forearm) muscle by comparing measurements in healthy subjects and in intensive care unit (ICU) septic shock patients, and determine whether brachioradialis muscle rSO2 is associated with poor outcome in ICU septic shock patients. Methods: We conducted a prospective observational study in healthy volunteers (n = 50) and ICU septic shock patients (n = 19). Brachioradialis (forearm) rSO2 measurements in healthy volunteers at rest and in ICU septic shock patients were compared. Pulmonary artery catheter monitoring was used in ICU patients. Results: Significant differences in rSO(2) were observed between healthy volunteers and ICU septic shock patients at ICU admission (68.7 +/- 4.9 vs. 55.0 +/- 13.0; p < 0.001). When comparing septic shock survivors and nonsurvivors, significant differences were observed in rSO(2) at baseline (64.5 +/- 8.9 vs. 47.5 +/- 10.7; p < 0.01), 12 hours (67.3 +/- 9.6 vs. 45.0 +/- 14.9; p < 0.01), and 24 hours (65.7 +/- 7.0 vs. 50.1 +/- 10.3; p < 0.01). Lactate concentration was lower in survivors than nonsurvivors at 24 hours (12.0 +/- 7.5 mmol/L vs. 23.2 +/- 12.5 mmol/L; p < 0.04). Cardiac index was greater in nonsurvivors than survivors at baseline (4.6 + 1.9 L/min/m(2) vs. 3.0 + 0.9 L/min/m(2); p < 0.05) and 12 h (3.9 + 0.5 L/min/m(2) vs. 3.1 + 0.3 L/min/m(2); p < 0.05). Conclusions: We observed that septic shock patients with forearm skeletal muscle rSO(2) <= 60% throughout first 24 hours after ICU admission had significantly greater mortality rate than patients with forearm skeletal muscle rSO2 >60% throughout this critical time. C1 [Rodriguez, Alejandro; Lisboa, Thiago; Martin-Loeches, Ignacio; Diaz, Emili; Trefler, Sandra] Univ Rovira & Virgili, Crit Care Dept, Joan XXIII Univ Hosp, IISPV,CIBER Enfermedades Resp, Tarragona 43007, Spain. [Lisboa, Thiago] Clin Univ Hosp, Crit Care Dept, Porto Alegre, RS, Brazil. [Restrepo, Marcos I.] Univ Texas Hlth Sci Ctr San Antonio, VERDICT S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Restrepo, Marcos I.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Pulm & Crit Care Med, San Antonio, TX 78229 USA. [Rello, Jordi] Vall Hebron Univ Hosp, Crit Care Dept, CIBER Enfermedades Resp, Barcelona, Spain. RP Rodriguez, A (reprint author), Univ Rovira & Virgili, Crit Care Dept, Joan XXIII Univ Hosp, IISPV,CIBER Enfermedades Resp, Carrer Dr Mallafre Guasch 4, Tarragona 43007, Spain. EM ahr1161@yahoo.es RI Martin-Loeches, Ignacio/H-4633-2013; Restrepo, Marcos/H-4442-2014; OI Rodriguez Oviedo, Alejandro/0000-0001-8828-5984; Rello, Jordi/0000-0003-0676-6210 FU Instituto de Salud Carlos III [FIS PI10/01538]; CIBER Enfermedades respiratorias; AGAUR [2009/SGR/1226]; Department of Veterans Affairs, Veterans Integrated Service Network; National Health Institute [KL2 RR025766] FX Supported by FIS PI10/01538 Instituto de Salud Carlos III (FEDER), CIBER Enfermedades respiratorias, and AGAUR (2009/SGR/1226).; Dr. Restrepo is supported by a Department of Veterans Affairs, Veterans Integrated Service Network 17 new faculty grant and National Health Institute Grant KL2 RR025766. NR 52 TC 14 Z9 15 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5282 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD MAY PY 2011 VL 70 IS 5 BP 1145 EP 1152 DI 10.1097/TA.0b013e318216f72c PG 8 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 762LQ UT WOS:000290480300035 PM 21610429 ER PT J AU Burns, JA Lopez-Guerra, G Kobler, JB Faquin, W LeClair, M Zeitels, SM AF Burns, James A. Lopez-Guerra, Gerardo Kobler, James B. Faquin, William LeClair, Matthew Zeitels, Steven M. TI Pulsed Potassium-Titanyl-Phosphate Laser Photoangiolytic Treatment of Mucosal Squamous Cell Carcinoma in the Hamster Cheek Pouch SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT Combined Section Meeting on Triological-Society CY JAN 27-30, 2011 CL Scottsdale, AZ SP Triolog Soc DE Photoangiolysis; KTP laser; squamous cell carcinoma; hamster cheek pouch ID CHORIOALLANTOIC MEMBRANE; GLOTTAL DYSPLASIA; DYE-LASER; CARCINOGENESIS; PAPILLOMATOSIS; ANGIOGENESIS; ANESTHESIA; MODEL AB Objectives/Hypothesis: Early glottic cancer has been involuted by treatment with the 532 nm pulsed potassium-titanyl-phosphate (KTP) laser in initial clinical studies. Selective photoangiolysis of the sublesional circulation that allows for relative sparing of surrounding tissue is the presumed mechanism. No prior controlled animal-model study has analyzed the ability of selective coagulation of lesional microvasculature coagulation with the KTP laser to involute malignant lesions. This study tests the efficacy of photoangiolysis with the KTP laser in treating squamous cell carcinoma in an established animal model. Study Design: In vivo. Methods: Malignant lesions were induced unilaterally in the cheek pouches of 21 hamsters by applying 9,10-dimethyl-1,2-benzanthrancene. The contralateral cheek pouch served as a control. Weekly lesion photodocumentation and pulsed KTP laser (30 W, 15 msec pulse width, 2 pulses/sec) treatments were done. The endpoint of each treatment was a uniform white-blanching of the lesion. Hamsters were sacrificed 1 week after the last treatment and cheek pouches were analyzed histologically. Results: Carcinoma was confirmed in 19 hamsters, and lesions that were initially < 2 mm were more effectively treated than lesions that were > 2 mm (P = .0004). Every lesion (10/10) that initially measured < 2 mm resolved completely after laser treatment with minimal scarring noted at the treatment site based on histology. Lesions measuring between 2 and 5 mm resolved 33% of the time (2/6), and none (0/3) of the lesions > 5 mm resolved after completion of the treatment period. Conclusions: Pulsed KTP laser photoangiolysis can effectively involute small malignant lesions, but may be less effective at involuting larger (> 2 mm) lesions. C1 [Burns, James A.; Lopez-Guerra, Gerardo; Kobler, James B.; Zeitels, Steven M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil,Dept Surg, Boston, MA 02114 USA. [Faquin, William] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil,Dept Pathol, Boston, MA 02114 USA. [LeClair, Matthew] Harvard Univ, Cambridge, MA 02138 USA. RP Burns, JA (reprint author), Harvard Univ, Sch Med, Ctr Laryngeal Surg & Voice Rehabil, 1 Bowdoin Sq,11th Floor, Boston, MA 02114 USA. EM burns.james@mgh.harvard.edu OI Lopez-Guerra, Gerardo/0000-0003-0305-4680 NR 22 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD MAY PY 2011 VL 121 IS 5 BP 942 EP 946 DI 10.1002/lary.21811 PG 5 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 761JX UT WOS:000290395200009 PM 21495047 ER PT J AU Lee, LN Bhattacharyya, N AF Lee, Linda N. Bhattacharyya, Neil TI Regional and Specialty Variations in the Treatment of Chronic Rhinosinusitis SO LARYNGOSCOPE LA English DT Article DE Chronic rhinosinusitis; treatment; antibiotics; antihistamines; steroids ID CHRONIC SINUSITIS; MEDICAL THERAPY; UNITED-STATES; OUTCOMES; HEALTH; CARE; DIAGNOSIS; CULTURES; IMPACT AB Objectives/Hypothesis: To identify regional and specialty differences in the medical treatment of chronic rhinosinusitis (CRS). Study Design: Cross-sectional analysis of a national database. Methods: Ambulatory visits for CRS were extracted from the National Ambulatory Medical Care Survey (NAMCS) for years 2005 to 2006. Medication utilization associated with CRS (antibiotics, antihistamines, nasal steroids, and oral steroids) was tabulated for medication class and individual drug. Statistical analyses were conducted to determine variations in medication class and specific drug utilization by U.S. geographic region and physician specialty, specifically primary care physicians (PCP) versus otolaryngologists (ORL). Results: Among an estimated 36.2 +/- 0.3 million visits for CRS (mean age, 36.8 +/- 1.4 years; 60.1 +/- 1.9% female), the ratio of PCP to ORL visits was 10:1. The percent of clinician visits with prescriptions for antibiotics (47.3 +/- 3.0% of overall visits), nasal steroids (10.8 +/- 1.4%) and oral steroids (2.8 +/- 0.7%) did not vary significantly by geographic region (P = .79,.66, and.34, respectively). Antihistamines were prescribed significantly more often in the South (15.3 +/- 3.4% of visits vs. 11.3 +/- 1.8% nationally, P = .04). PCPs were significantly more likely to prescribe antibiotics compared to ORLs (53.3 +/- 2.9% vs. 27.4 +/- 4.2%, respectively, P < .001) and less likely to prescribe both nasal steroids (9.7 +/- 1.5% vs. 17.5 +/- 2.8%, P = .01) and oral steroids (2.3 +/- 0.7% vs. 6.6 +/- 2.0%, P = .01). Significant differences existed for specific drugs prescribed according to specialty. Conclusions: There are significant variations in the outpatient medical treatment of CRS according to geography and specialty. This study highlights the need for evidence-based medical treatment protocols for CRS. C1 [Bhattacharyya, Neil] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Otol & Laryngol,Div Otolaryngol, Boston, MA 02115 USA. [Lee, Linda N.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Bhattacharyya, N (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Otol & Laryngol,Div Otolaryngol, 45 Francis St, Boston, MA 02115 USA. EM neiloy@massmed.org NR 25 TC 18 Z9 18 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD MAY PY 2011 VL 121 IS 5 BP 1092 EP 1097 DI 10.1002/lary.21550 PG 6 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 761JX UT WOS:000290395200037 PM 21520129 ER PT J AU Lewis, RF Priesol, AJ Nicoucar, K Lim, K Merfeld, DM AF Lewis, Richard F. Priesol, Adrian J. Nicoucar, Keyvan Lim, Koeun Merfeld, Daniel M. TI Abnormal Motion Perception in Vestibular Migraine SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT Meeting on the Association-for-Research-in Otolaryngology CY FEB 06-10, 2010 CL Anaheim, CA SP Assoc Res Otolaryngol DE Vestibular; migraine; vertigo; psychophysics; thresholds C1 [Lewis, Richard F.; Priesol, Adrian J.; Nicoucar, Keyvan; Lim, Koeun; Merfeld, Daniel M.] Massachusetts Eye & Ear Infirm, Jenks Vestibular Physiol Lab, Boston, MA 02114 USA. [Lewis, Richard F.; Priesol, Adrian J.; Nicoucar, Keyvan; Lim, Koeun; Merfeld, Daniel M.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Lewis, Richard F.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Nicoucar, Keyvan] Univ Hosp Geneva, Dept Clin Neurosci, Serv Otorhinolaryngol Head & Neck Surg, Geneva, Switzerland. RP Lewis, RF (reprint author), Massachusetts Eye & Ear Infirm, Jenks Vestibular Physiol Lab, 243 Charles St, Boston, MA 02114 USA. EM richard_lewis@meei.harvard.edu FU NIDCD NIH HHS [R01 DC004158, DC04158] NR 3 TC 20 Z9 20 U1 1 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD MAY PY 2011 VL 121 IS 5 BP 1124 EP 1125 DI 10.1002/lary.21723 PG 2 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 761JX UT WOS:000290395200043 PM 21520135 ER PT J AU Baer, MR George, SL Sanford, BL Mrozek, K Kolitz, JE Moore, JO Stone, RM Powell, BL Caligiuri, MA Bloomfield, CD Larson, RA AF Baer, M. R. George, S. L. Sanford, B. L. Mrozek, K. Kolitz, J. E. Moore, J. O. Stone, R. M. Powell, B. L. Caligiuri, M. A. Bloomfield, C. D. Larson, R. A. CA Canc Leukemia Group B TI Escalation of daunorubicin and addition of etoposide in the ADE regimen in acute myeloid leukemia patients aged 60 years and older: Cancer and Leukemia Group B Study 9720 SO LEUKEMIA LA English DT Article DE acute myeloid leukemia; age; daunorubicin; dose escalation; etoposide ID RISK MYELODYSPLASTIC SYNDROME; RESISTANCE MODULATOR PSC-833; ACUTE MYELOGENOUS LEUKEMIA; RANDOMIZED PHASE-III; ELDERLY-PATIENTS; MULTIDRUG-RESISTANCE; COMPLETE REMISSION; DOSE CYTARABINE; INDUCTION CHEMOTHERAPY; EUROPEAN ORGANIZATION AB Untreated de novo (n=421) and secondary (n=189) acute myeloid leukemia (AML) patients >= 60 years received intensified chemotherapy, including daunorubicin 60 mg/m(2) and etoposide 100 mg/m(2) during days 1, 2, 3 with cytarabine 100 mg/m(2) during days 1-7, with a second induction if needed and one consolidation course with these drugs and doses for 2, 2 and 5 days, respectively. In all, 287 (47%) achieved complete remission (CR), 136 (22%) died and 187 (31%) were non-responders. CR rates were 27, 44 and 52% for complex karyotypes, rare aberrations and neither (P<0.001), 52 and 37% for de novo and secondary AML (P=0.003), and 53 and 42% for age 60-69 and >= 70 years (P=0.015). In multivariable analysis, CR predictors included non-complex/non-rare karyo-types (P<0.001), de novo AML (P<0.001), better performance status (PS) (P<0.001) and younger age (P=0.001). Disease-free (DFS) and overall (OS) survival medians were 6.8 (95% CI: 6.2, 7.8) and 7.2 (95% CI: 6.4, 8.6) months. In multivariable analysis, DFS was shorter for complex karyotypes (P<0.001) and increasing white blood count (WBC) (P<0.001) and age (P=0.038), and OS for complex karyotypes (P<0.001), increasing WBC (P=0.001) and age (P<0.001), poorer PS (P<0.001) and secondary AML (P=0.010). Outcomes and prognostic factors were similar to those in previous Cancer and Leukemia Group B studies. Leukemia (2011) 25, 800-807; doi: 10.1038/leu.2011.9; published online 15 February 2011 C1 [Baer, M. R.] Univ Maryland, Dept Med, Baltimore, MD 21201 USA. [Baer, M. R.] Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. [Baer, M. R.] Roswell Pk Canc Inst, Dept Med, Buffalo, NY 14263 USA. [George, S. L.] Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC USA. [George, S. L.; Sanford, B. L.] Duke Univ, Med Ctr, CALGB Stat Ctr, Durham, NC USA. [Mrozek, K.; Caligiuri, M. A.; Bloomfield, C. D.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Kolitz, J. E.] Hofstra N Shore LIJ Sch Med, Monter Canc Ctr, Div Hematol Oncol, Manhasset, NY USA. [Moore, J. O.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Stone, R. M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Powell, B. L.] Wake Forest Univ, Ctr Comprehens Canc, Winston Salem, NC 27109 USA. [Larson, R. A.] Univ Chicago, Dept Med, Chicago, IL 60637 USA. RP Baer, MR (reprint author), Univ Maryland, Dept Med, 22 S Greene St, Baltimore, MD 21201 USA. EM mbaer@umm.edu RI Mrozek, Krzysztof/A-3142-2008; OI Larson, Richard/0000-0001-9168-3203 FU National Cancer Institute [CA31946, CA31983, CA02599, CA33601, CA77658, 101140, CA35279, CA47577, CA32291, CA03927, CA41287]; Coleman Leukemia Research Foundation FX The research for CALGB 9720 was supported, in part, by grants from the National Cancer Institute (CA31946) to the Cancer and Leukemia Group B (Richard L. Schilsky, MD, Chairman) and to the CALGB Statistical Center (Stephen George, PhD, CA33601), and by grants CA31983 and CA02599 (to MRB), CA33601 (to SLG and BLS), CA77658, 101140 and grants from the Coleman Leukemia Research Foundation (to KM, MAC, CDB), CA35279 (to JEK), CA47577 (to JOM), CA32291 (to RMS), CA03927 (to BLP) and CA41287 (to RAL). The authors thank the many patients, treating physicians, nurses and CALGB clinical research associates who participated in this study, and also thank CALGB Protocol Coordinator Michael Kelly for his assistance. NR 40 TC 14 Z9 14 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD MAY PY 2011 VL 25 IS 5 BP 800 EP 807 DI 10.1038/leu.2011.9 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA 762IZ UT WOS:000290471100007 PM 21321569 ER PT J AU Kozora, E Brown, MS Filley, CM Zhang, L Miller, DE West, SG Pelzman, J Arciniegas, DB AF Kozora, E. Brown, M. S. Filley, C. M. Zhang, L. Miller, D. E. West, S. G. Pelzman, J. Arciniegas, D. B. TI Memory impairment associated with neurometabolic abnormalities of the hippocampus in patients with non-neuropsychiatric systemic lupus erythematosus SO LUPUS LA English DT Article DE hippocampal volume; lupus; memory function; neurometabolites ID MAGNETIC-RESONANCE-SPECTROSCOPY; MILD COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; NEUROPSYCHOLOGICAL BATTERY; H-1-MR SPECTROSCOPY; LEARNING-ABILITY; GLIAL-CELLS; ANTI-DNA; BRAIN; ATROPHY AB Objective: Memory impairment is common in patients with systemic lupus erythematosus (SLE). This study examined hippocampal volumes and neurometabolic alterations in relation to memory function in SLE patients without a history of neuropsychiatric syndromes (nonNPSLE). Methods: Subjects included 81 nonNPSLE patients and 34 healthy controls. Volumetric magnetic resonance imaging and magnetic resonance spectroscopy of the right and left hippocampal areas (RH, LH) were performed. Verbal and visual memory tests were administered and a Memory Impairment Index (MII) was derived from standardized tests. Results: Higher memory impairment (MII) was correlated with lower RH glutamate + glutamine/creatine (p = 0.009) and lower RH N-acetylaspartic acid/creatine (p = 0.012) in nonNPSLE patients. A trend for a negative correlation between RH and LH volumes and MII was evident for absolute hippocampal volumes. Lower RH glutamate + glutamine/creatine was also correlated with worse performance in a mean visual memory index (p = 0.017). Conclusions: An association between reduced memory and lower N-acetylaspartic acid/creatine in the RH suggests neuronal damage in nonNPSLE patients with very mild and early disease. Alterations in glutamate + glutamine/creatine further indicate early metabolic changes in nonNPSLE are related to memory impairment, a finding that might suggest that memory impairment relates to presynaptic glutamatergic dysfunction in the hippocampus. Lupus (2011) 20, 598-606. C1 [Kozora, E.; Zhang, L.; Pelzman, J.] Natl Jewish Hlth, Dept Med, Denver, CO 80206 USA. [Kozora, E.; Filley, C. M.; Arciniegas, D. B.] Univ Colorado, Denver Sch Med, Dept Neurol, Denver, CO 80202 USA. [Kozora, E.; Filley, C. M.; Arciniegas, D. B.] Univ Colorado, Denver Sch Med, Dept Psychiat, Denver, CO 80202 USA. [Brown, M. S.; Miller, D. E.] Univ Colorado, Denver Sch Med, Dept Radiol, Denver, CO 80202 USA. [West, S. G.] Univ Colorado, Denver Sch Med, Dept Rheumatol, Denver, CO 80202 USA. [Filley, C. M.] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Kozora, E (reprint author), Natl Jewish Hlth, Dept Med, 1400 Jackson St, Denver, CO 80206 USA. EM kozorae@njhealth.org FU National Institute of Musculoskeletal and Skin Diseases [RO1 AR049152] FX This funding was supported by the National Institute of Musculoskeletal and Skin Diseases (grant number RO1 AR049152). NR 52 TC 16 Z9 18 U1 2 U2 5 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0961-2033 J9 LUPUS JI Lupus PD MAY PY 2011 VL 20 IS 6 BP 598 EP 606 DI 10.1177/0961203310392425 PG 9 WC Rheumatology SC Rheumatology GA 761DX UT WOS:000290376600007 PM 21335397 ER PT J AU Filippova, N Yang, XH Wang, YM Gillespie, GY Langford, C King, PH Wheeler, C Nabors, LB AF Filippova, Natalia Yang, Xiuhua Wang, Yimin Gillespie, G. Yancey Langford, Cathy King, Peter H. Wheeler, Crystal Nabors, L. Burt TI The RNA-Binding Protein HuR Promotes Glioma Growth and Treatment Resistance SO MOLECULAR CANCER RESEARCH LA English DT Article ID INCREASED CYCLOOXYGENASE-2 EXPRESSION; TUMOR-NECROSIS-FACTOR; MESSENGER-RNA; POSTTRANSCRIPTIONAL REGULATION; STABILITY FACTOR; XENOGRAFT MODEL; BREAST-CANCER; RICH ELEMENTS; CARCINOMA; CELLS AB Posttranscriptional regulation is a critical control point for the expression of genes that promote or retard tumor growth. We previously found that the mRNA-binding protein, ELAV 1 (HuR), is upregulated in primary brain tumors and stabilizes growth factor mRNAs such as VEGF and IL-8. To better understand the role of HuR in brain tumor growth, we altered levels of HuR in glioma cells by short hairpin RNA or ectopic expression and measured tumor cell phenotype using in vitro and in vivo models. In HuR-silenced cells, we found a significant decrease in anchorage-independent growth and cell proliferation with a concomitant induction of apoptosis. Using an intracranial tumor model with primary glioblastoma cells, HuR silencing produced a significant decrease in tumor volume. In contrast, overexpression of HuR produced in vitro chemoresistance to standard glioma therapies. Because bcl-2 is abundantly expressed in glioma and associated with tumor growth and survival, we determined the impact of HuR on its regulation as a molecular validation to the cellular and animal studies. Using UV cross-linking and RNA immunoprecipitation, we show that HuR bound to the 3'-untranslated region of all bcl-2 family members. Silencing of HuR led to transcript destabilization and reduced protein expression. Polysome profiling indicated loss of HuR from the translational apparatus. In summary, these findings reveal a HuR-dependent mechanism for cancer cell survival and sensitivity to chemotherapeutic drugs suggesting that HuR should be considered as a new therapeutic target. Mol Cancer Res; 9(5); 648-59. (C) 2011 AACR. C1 [Nabors, L. Burt] Univ Alabama, Dept Neurol, Neurooncol Program, Birmingham, AL 35294 USA. [Gillespie, G. Yancey; Langford, Cathy] Univ Alabama, Dept Surg, Div Neurosurg, Birmingham, AL 35294 USA. [Wang, Yimin] So Res Inst, Div Drug Discovery, Birmingham, AL 35255 USA. [King, Peter H.] Birmingham VA Med Ctr, Birmingham, AL USA. RP Nabors, LB (reprint author), Univ Alabama, Dept Neurol, Neurooncol Program, 510 20th St S,FOT 1020, Birmingham, AL 35294 USA. EM bnabors@uab.edu FU NCI [R01 CA112397]; VA Merit Review; UAB Small Animal Imaging Shared Facility [P30CA013148] FX This study was supported by NCI R01 CA112397 (L. B. Nabors), VA Merit Review (P. H. King), and by UAB Small Animal Imaging Shared Facility (P30CA013148). NR 33 TC 43 Z9 45 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD MAY PY 2011 VL 9 IS 5 BP 648 EP 659 DI 10.1158/1541-7786.MCR-10-0325 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 764EF UT WOS:000290610600012 PM 21498545 ER PT J AU Hawes, MJ Grove, AS Hink, EM AF Hawes, Michael J. Grove, Arthur S., Jr. Hink, Eric M. TI Comparison of Free Tarsoconjunctival Grafts and Hughes Tarsoconjunctival Grafts for Lower Eyelid Reconstruction SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article; Proceedings Paper CT 113th Annual Meeting of the American-Academy-of-Ophthalmology/28th Congress of the Pan-American-Association-of-Ophthalmology CY OCT 24-27, 2009 CL San Francisco, CA SP Amer Acad Ophthalmol, Pan Amer Assoc Ophthalmol ID FLAP; DIVISION; MANAGEMENT; PEDICLE; HEIGHT AB Purpose: To review the use of free autogenous tarsoconjunctival (TC) grafts and Hughes TC flaps in the practice of one of the authors (MJH) and compare complications and outcomes and develop a rationale for the selection of surgical technique. Methods: Retrospective comparative case series of 70 patients who underwent reconstructive surgery for a major full-thickness lower eyelid defect using a free autogenous TC graft or Hughes TC pedicle flap by one of the authors (MJH). Rates of complications, including erythema of the eyelid margin, eyelid position abnormalities, and need for additional surgeries, were reviewed. Results: During a 15-year period, 70 patients with full-thickness lower eyelid defects were treated with autogenous TC grafts and flaps. The average age of the patients receiving a free TC graft was younger than the average age of patients receiving a Hughes TC graft (63 versus 73 years, p < 0.001). Patients with a free TC graft were more likely to have a smaller eyelid defect than the patients receiving a Hughes TC graft (52% versus 72%, p < 0.001). Patients receiving a free TC graft were less likely to require surgery to repair eyelid margin erythema than those in receiving a Hughes TC flap (one patient [2%] versus 5 patients [19%], respectively [odds ratio = 0.10, confidence interval = 0.01 to 0.95]). The average follow up was 22 months. Conclusions: Free TC flaps associated with mycocutaneous advancement flaps are less likely to lead to complications of eyelid margin erythema and subsequent revision surgery than Hughes TC flaps with full-thickness skin grafts. (Ophthal Plast Reconstr Surg 2011;27:219-223) C1 [Grove, Arthur S., Jr.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Hink, Eric M.] Univ Colorado, Dept Ophthalmol, Denver, CO 80202 USA. RP Hawes, MJ (reprint author), 850 E Harvard Ave 345, Denver, CO 80210 USA. EM mjhawes1@mac.com NR 35 TC 11 Z9 12 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD MAY-JUN PY 2011 VL 27 IS 3 BP 219 EP 223 DI 10.1097/IOP.0b013e318217e194 PG 5 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 762XH UT WOS:000290515000035 PM 21562393 ER PT J AU Shalaby, A Atwood, CW Selzer, F Suffoletto, M Gorcsan, J Strollo, P AF Shalaby, Alaa Atwood, Charles W. Selzer, Faith Suffoletto, Matthew Gorcsan, John, III Strollo, Patrick TI Cardiac Resynchronization Therapy and Obstructive Sleep-Related Breathing Disorder in Patients with Congestive Heart Failure SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Article DE congestive heart failure; CRT; pacing ID POSITIVE AIRWAY PRESSURE; CHEYNE-STOKES RESPIRATION; RESYNCHRONISATION THERAPY; VENTRICULAR DYSSYNCHRONY; RATE-VARIABILITY; APNEA; TRIAL; DYSFUNCTION; IMPROVEMENT; PREDICTORS AB Introduction: CRT may have a positive influence on SRBD in patients who qualify for the therapy. Data are inconclusive in patients with obstructive SRBD. Methods: Consenting patients eligible for CRT underwent a baseline polysomnography (PSG) 2 weeks after implantation during which pacing was withheld. Patients with an apnea hypopnea index (AHI) >= 15 but < 50 were enrolled and randomized to atrial overdrive pacing (DDD) versus atrial synchronous pacing (VDD) with biventricular pacing in both arms. Patients underwent two further PSGs 12 weeks apart. Results: Nineteen men with New York Heart Association class III congestive heart failure participated in the study (age 67.2 +/- 7.5, Caucasian 78.9%, ischemic 73.7%). The score on Epworth Sleepiness Score was 7.3 +/- 4.0, Pittsburgh Sleep Quality Index 7.4 +/- 3.1, and Minnesota Living with Heart Failure Questionnaire 36.9 +/- 21.9. There were no differences between the groups. At baseline, patients exhibited poor sleep efficiency (65.3 +/- 16.6%) with nadir oxygen saturation of 83.5 +/- 5.3% and moderate to severe SRBD (AHI 21.5 +/- 15.3) that was mainly obstructive (central apnea index 3.3 +/- 6.7/hour). On both follow-up assessments, there was no improvement in indices of SRBD (sleep efficiency [68.3 +/- 17.9%], nadir oxygen saturation of 82.8 +/- 4.6%, and AHI 24.9 +/- 21.9). Conclusion: In a cohort of elderly male CHF patients receiving CRT, CRT had no impact on obstructive SRBD burden with or without atrial overdrive pacing. (PACE 2011; 34:593-603). C1 [Shalaby, Alaa; Atwood, Charles W.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Shalaby, Alaa; Suffoletto, Matthew; Gorcsan, John, III] Univ Pittsburgh, Med Ctr, Div Cardiol, Pittsburgh, PA USA. [Atwood, Charles W.; Strollo, Patrick] Univ Pittsburgh, Grad Sch Publ Hlth, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA USA. [Selzer, Faith] Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA USA. RP Shalaby, A (reprint author), 111C Univ Dr, Pittsburgh, PA 15240 USA. EM Alaa.Shalaby@va.gov FU Boston Scientific, Inc. Cardiac Rhythm Management Division; Boston Scientific FX This study was supported by Boston Scientific, Inc. Cardiac Rhythm Management Division.; Alaa Shalaby: Research support from Boston Scientific. NR 41 TC 5 Z9 5 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0147-8389 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD MAY PY 2011 VL 34 IS 5 BP 593 EP 603 DI 10.1111/j.1540-8159.2010.03015.x PG 11 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA 762CK UT WOS:000290449700014 PM 21609340 ER PT J AU Naeser, MA Saltmarche, A Krengel, MH Hamblin, MR Knight, JA AF Naeser, Margaret A. Saltmarche, Anita Krengel, Maxine H. Hamblin, Michael R. Knight, Jeffrey A. TI Improved Cognitive Function After Transcranial, Light-Emitting Diode Treatments in Chronic, Traumatic Brain Injury: Two Case Reports SO PHOTOMEDICINE AND LASER SURGERY LA English DT Article ID LEVEL LASER THERAPY; TERM NEUROLOGICAL DEFICITS; ANTERIOR CINGULATE CORTEX; NEAR-INFRARED LIGHT; SUSTAINED ATTENTION; ISCHEMIC-STROKE; WORKING-MEMORY; UNITED-STATES; RAT-BRAIN; IRRADIATION AB Objective: Two chronic, traumatic brain injury (TBI) cases, where cognition improved following treatment with red and near-infrared light-emitting diodes (LEDs), applied transcranially to forehead and scalp areas, are presented. Background: Significant benefits have been reported following application of transcranial, low-level laser therapy (LLLT) to humans with acute stroke and mice with acute TBI. These are the first case reports documenting improved cognitive function in chronic, TBI patients treated with transcranial LED. Methods: Treatments were applied bilaterally and to midline sagittal areas using LED cluster heads [2.1 '' diameter, 61 diodes (9 x 633 nm, 52 x 870 nm); 12-15 mW per diode; total power: 500 mW; 22.2 mW/cm(2); 13.3 J/cm(2) at scalp (estimated 0.4 J/cm(2) to cortex)]. Results: Seven years after closed-head TBI from a motor vehicle accident, Patient 1 began transcranial LED treatments. Pre-LED, her ability for sustained attention (computer work) lasted 20 min. After eight weekly LED treatments, her sustained attention time increased to 3 h. The patient performs nightly home treatments (5 years); if she stops treating for more than 2 weeks, she regresses. Patient 2 had a history of closed-head trauma (sports/military, and recent fall), and magnetic resonance imaging showed frontoparietal atrophy. Pre-LED, she was on medical disability for 5 months. After 4 months of nightly LED treatments at home, medical disability discontinued; she returned to working full-time as an executive consultant with an international technology consulting firm. Neuropsychological testing after 9 months of transcranial LED indicated significant improvement (+1, +2SD) in executive function (inhibition, inhibition accuracy) and memory, as well as reduction in post-traumatic stress disorder. If she stops treating for more than 1 week, she regresses. At the time of this report, both patients are continuing treatment. Conclusions: Transcranial LED may improve cognition, reduce costs in TBI treatment, and be applied at home. Controlled studies are warranted. C1 [Naeser, Margaret A.; Knight, Jeffrey A.] VA Boston Healthcare Syst, Natl Ctr, PTSD Behav Sci Div, Boston, MA 02130 USA. [Naeser, Margaret A.; Krengel, Maxine H.; Knight, Jeffrey A.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Saltmarche, Anita] MedX Hlth Inc, Mississauga, ON, Canada. [Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Hamblin, Michael R.] Harvard Mit Div Hlth Sci & Technol, Boston, MA USA. RP Naeser, MA (reprint author), VA Boston Healthcare Syst, Natl Ctr, PTSD Behav Sci Div, 12-A,150 So Huntington Ave, Boston, MA 02130 USA. EM mnaeser@bu.edu OI Krengel, Maxine/0000-0001-7632-590X; Hamblin, Michael/0000-0001-6431-4605 FU Department of Veterans Affairs; NIH [RO1AI050875]; US Air Force [FA9550-04-1-0079]; Center for Integration of Medicine and Innovative Technology [DAMD17-02-2-0006]; Congressionally Directed Medical Research Program [W81XWH-09-1-0514] FX The authors thank Charles Foltz for the graphics art in Figure 5; Carole Palumbo, Ph.D. for assistance with MRI analysis; Paula Martin, Anna Kharaz, Michael Ho, Ph.D., and Ethan Treglia, M. S., for manuscript assistance; and Michael and Winter Robinson for photography. M. Naeser was supported by Merit Review Funding, Department of Veterans Affairs. M. Hamblin was supported by the NIH (grant RO1AI050875), US Air Force MFEL program (contract FA9550-04-1-0079), Center for Integration of Medicine and Innovative Technology (DAMD17-02-2-0006), and Congressionally Directed Medical Research Program (W81XWH-09-1-0514). NR 56 TC 57 Z9 59 U1 3 U2 13 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1549-5418 J9 PHOTOMED LASER SURG JI Photomed. Laser Surg. PD MAY PY 2011 VL 29 IS 5 BP 351 EP 358 DI 10.1089/pho.2010.2814 PG 8 WC Surgery SC Surgery GA 762JC UT WOS:000290471400009 PM 21182447 ER PT J AU Schlett, CL Hoffmann, U AF Schlett, C. L. Hoffmann, U. TI Identification and quantification of fat compartments with CT and MRI and their importance SO RADIOLOGE LA German DT Article DE Visceral fat; Subcutaneous adipose tissue; Pericardial adipose tissue; Perivascular adipose tissue; Atherosclerosis ID SUBCUTANEOUS ADIPOSE-TISSUE; VISCERAL ABDOMINAL FAT; PERICARDIAL FAT; CORONARY ATHEROSCLEROSIS; COMPUTED-TOMOGRAPHY; RISK-FACTORS; ASSOCIATION; DISEASE; OBESITY; CALCIFICATION AB In addition to being overweight, as defined by the BMI, the distribution, composition and biological activity of adipose tissue are key elements in the cardiovascular risk stratification of patients. Several non-invasive techniques have been developed to quantify local fat depots, whereby computed tomography (CT) and magnetic resonance imaging (MRI) are the most important. In general adipose tissue is subdivided into subcutaneous and visceral compartments and although both are associated with cardiovascular risk factors and disease, visceral fat has on average a stronger association and a clearly higher biological activity independent of traditional risk factors. This maybe explained by the higher endocrine activity and secretion of pro-inflammatory cytokines by visceral fat. Especially pericardial adipose tissue, a local visceral fat depot surrounding the coronary arteries, is associated with the presence, extent and severity of coronary artery disease. However, several other local fat depots have been identified and associations with various diseases have been established. This article gives an overview over the current methods for the identification and quantification of local fat depots and summarizes the hypothesized and known associations. Furthermore, it gives an overview of the potential significance of individual local fat depots for cardiovascular risk stratification. C1 [Schlett, C. L.; Hoffmann, U.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Cardiac MR PET CT Program, Boston, MA 02114 USA. RP Schlett, CL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Cardiac MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM cschlett@partners.org NR 29 TC 2 Z9 2 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-832X EI 1432-2102 J9 RADIOLOGE JI Radiologe PD MAY PY 2011 VL 51 IS 5 BP 372 EP 378 DI 10.1007/s00117-010-2088-4 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 762OX UT WOS:000290490400007 PM 21487800 ER PT J AU Manzano-Fernandez, S Januzzi, JL Garcia, MB Bonaque-Gonzalez, JC Munoz-Esparza, C Albaladejo-Oton, MD Pastor-Perez, FJ Pastor, P Valdes, M Pascual-Figal, DA AF Manzano-Fernandez, Sergio Januzzi, James L. Boronat Garcia, Miguel Bonaque-Gonzalez, Juan C. Munoz-Esparza, Carmen Albaladejo-Oton, Maria D. Pastor-Perez, Francisco J. Pastor, Patricia Valdes, Mariano Pascual-Figal, Domingo A. TI Comparative Prognostic Value of Plasma and Urinary N-Terminal Pro-B-Type Natriuretic Peptide in Patients With Acute Destabilized Heart Failure SO REVISTA ESPANOLA DE CARDIOLOGIA LA English DT Article DE Heart failure; Natriuretic peptide; Prognosis ID DIAGNOSIS; MANAGEMENT; SERUM AB Introduction and objectives: Urinary concentrations of amino-terminal pro-B type natriuretic peptide (NT-proBNP) may be prognostically meaningful; however, direct comparison to plasma concentrations of this marker have not been performed in patients with acutely decompensated heart failure (ADHF). The aims of this study were to compare the prognostic value of plasma versus urinary NT-proBNP concentration for the risk stratification of patients with ADHF. Methods: Consecutive hospitalized patients with ADHF were prospectively studied. Blood and urine samples were simultaneously collected on hospital arrival to determine NT-proBNP concentrations. Clinical follow-up was obtained, and the occurrence of mortality and heart failure hospitalization was registered. Results: The study included 138 patients (median, 74 years [interquartile range, 67-80]; 54% men). During amedian follow-up period of 387 days [interquartile range, 161-559], 65 patients (47%) suffered adverse clinical events. Plasma NT-proBNP concentration was higher among patients who presented adverse events (4561 pg/mL [2191-8631] vs 2906 pg/mL [1643-5823]; P = .03), whereas urinary NT-proBNP was similar in both groups (P = .62). After multivariable Cox regression analyses, plasma NT-proBNP concentration was associated with a higher risk of adverse events, whether considered continuously (per 100 pg/mL; hazard ratio [HR] = 1.004; 95% confidence interval [CI], 1.001-1.007; P = .003) or categorically (>= 3345 pg/mL; HR = 2.35; 95% CI, 1.41-3.93; P =.001). In contrast, urinary NTproBNP concentration was not associated with adverse outcomes. Conclusions: Plasma NT-proBNP concentration is superior to urinary NT-proBNP concentration for the prediction of adverse clinical outcomes among unselected patients with ADHF. (C) 2010 Sociedad Espanola de Cardiologia. Published by Elsevier Espana, S. L. All rights reserved. C1 [Manzano-Fernandez, Sergio; Bonaque-Gonzalez, Juan C.; Munoz-Esparza, Carmen; Pastor-Perez, Francisco J.; Valdes, Mariano; Pascual-Figal, Domingo A.] Hosp Univ Virgen de la Arrixaca, Dept Cardiol, Murcia 30120, Spain. [Januzzi, James L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Boronat Garcia, Miguel; Albaladejo-Oton, Maria D.] Hosp Univ Virgen de la Arrixaca, Dept Bioquim, Murcia 30120, Spain. [Pastor, Patricia] Hosp Univ Virgen de la Arrixaca, Dept Cirugia Gen, Murcia 30120, Spain. RP Manzano-Fernandez, S (reprint author), Hosp Univ Virgen de la Arrixaca, Dept Cardiol, Ctra Madrid Cartagena S-N, Murcia 30120, Spain. EM sergiosmf13@hotmail.com RI Pascual Figal, Domingo /B-3794-2008 OI Pascual Figal, Domingo /0000-0002-4993-9540 FU Roche Diagnostics; Siemens; Critical Diagnostics FX Dr. Januzzi reports receiving grant support from Roche Diagnostics, Siemens, and Critical Diagnostics. Dr. Pascual-Figal reports receiving grant support from Roche Diagnostics. No other potential conflicts of interest exist. NR 17 TC 4 Z9 4 U1 0 U2 2 PU EDICIONES DOYMA S A PI BARCELONA PA TRAV DE GRACIA 17-21, 08021 BARCELONA, SPAIN SN 0300-8932 J9 REV ESP CARDIOL JI Rev. Esp. Cardiol. PD MAY PY 2011 VL 64 IS 5 BP 365 EP 372 DI 10.1016/j.rec.2010.10.018 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 763MJ UT WOS:000290561400004 PM 21397374 ER PT J AU Spiegel, BMR Talley, J Shekelle, P Agarwal, N Snyder, B Bolus, R Kurzbard, N Chan, M Ho, A Kaneshiro, M Cordasco, K Cohen, H AF Spiegel, Brennan M. R. Talley, Jennifer Shekelle, Paul Agarwal, Nikhil Snyder, Bradley Bolus, Roger Kurzbard, Nicole Chan, Michael Ho, Andrew Kaneshiro, Marc Cordasco, Kristina Cohen, Hartley TI Development and Validation of a Novel Patient Educational Booklet to Enhance Colonoscopy Preparation SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID BOWEL PREPARATION; COLORECTAL-CANCER; PREPARATION QUALITY; IMPACT; ENDOSCOPY; VETERANS; SCALE; COST AB OBJECTIVES: The success of colonoscopy depends on high-quality bowel preparation by patients; yet inadequate preparation is common. We developed and tested an educational booklet to improve bowel preparation quality. METHODS: We conducted patient cognitive interviews to identify knowledge and belief barriers to colonoscopy preparation. We used these interviews to create an educational booklet to enhance preparatory behaviors. We then prospectively randomized patients scheduled for outpatient colonoscopy at a VA Medical Center to receive usual instructions vs. the booklet before colonoscopy. Patients in both groups received standard pharmacy instructions for single-dose bowel preparation; the protocol did not specify which purgatives to prescribe. The primary outcome was preparation quality based on blinded ratings using the validated Ottawa score. We performed bivariate analyses to compare mean scores between groups using a t-test, and logistic regression to measure the booklet effect on preparation quality, adjusting for potential confounders. RESULTS: A total of 436 patients were randomized between arms. In an intention-to-treat analysis of the primary outcome, mean Ottawa scores were superior in patients allocated to booklet vs. controls (P = 0.03). An intention-to-treat analysis of the secondary outcome revealed a "good" preparation in 68 vs. 46% of booklet and control patients, respectively (P = 0.054). In a per-protocol analysis limited to patients who actually received the booklet, preparation was good in 76 vs. 46% patients, respectively (P < 0.00001). Regression analysis revealed that booklet receipt increased the odds of good preparation by 3.7 times (95% confi dence interval = 2.3-5.8). CONCLUSIONS: Provision of a novel educational booklet considerably improves preparation quality in patients receiving single-dose purgatives. The effect of the booklet on split-dose purgatives remains untested and will be evaluated in future research. C1 [Spiegel, Brennan M. R.] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, UCLA VA Ctr Outcomes Res & Educ CORE,Dept Med, Los Angeles, CA 90073 USA. [Spiegel, Brennan M. R.; Snyder, Bradley; Bolus, Roger; Kurzbard, Nicole; Chan, Michael; Cohen, Hartley] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Digest Dis, Los Angeles, CA 90073 USA. [Spiegel, Brennan M. R.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90073 USA. CURE Digest Dis Res Ctr, Los Angeles, CA USA. RP Spiegel, BMR (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, UCLA VA Ctr Outcomes Res & Educ CORE,Dept Med, 11301 Wilshire Blvd,Bldg 115,Room 215, Los Angeles, CA 90073 USA. EM bspiegel@mednet.ucla.edu FU Veteran's Affairs Health Services Research and Development (HSRD) [RCD 03-179-2]; Veterans Affairs [IIR 08-310] FX This research was supported by a Veteran's Affairs Health Services Research and Development (HSR&D) Career Development Transition Award (RCD 03-179-2) and by a Veterans Affairs Merit Award (IIR 08-310) to Dr Spiegel. NR 24 TC 54 Z9 57 U1 2 U2 5 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 MAY PY 2011 VL 106 IS 5 BP 875 EP 883 DI 10.1038/ajg.2011.75 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 759MP UT WOS:000290250100010 PM 21483463 ER PT J AU Fontana, RJ Sanyal, AJ Ghany, MG Bonkovsky, HL Morgan, TR Litman, HJ Reid, AE Lee, WM Naishadham, D AF Fontana, Robert J. Sanyal, Arun J. Ghany, Marc G. Bonkovsky, Herbert L. Morgan, Timothy R. Litman, Heather J. Reid, Andrea E. Lee, William M. Naishadham, Deepa CA HALT-C Trial Study Grp TI Development and Progression of Portal Hypertensive Gastropathy in Patients With Chronic Hepatitis C SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID VENOUS-PRESSURE GRADIENT; VIRUS-RELATED CIRRHOSIS; NATURAL-HISTORY; ADVANCED FIBROSIS; LIVER-CIRRHOSIS; THERAPY; PREVALENCE; INFECTION; TRIAL AB OBJECTIVES: The objective of this study was to determine the incidence and risk factors associated with new-onset and worsening portal hypertensive gastropathy (PHG) in patients with chronic hepatitis C (CHC). METHODS: A total of 831 CHC patients with bridging fibrosis or cirrhosis at the time of entry were prospectively monitored for clinical and histological liver disease progression while receiving either low-dose peginterferon alpha 2a or no antiviral therapy in the HALT-C (Hepatitis C Antiviral Long-term Treatment against Cirrhosis) trial. Upper endoscopy with grading of PHG was performed at baseline and at year 4 of the study. The presence and severity of PHG were determined using the NIEC (New Italian Endoscopy Conference) criteria, and worsening PHG was defined as a score increase of >= 1 point. RESULTS: During a median follow-up of 3.85 years, 50 % of 514 subjects without PHG developed new-onset PHG, whereas 26% of 317 patients with baseline PHG had worsening PHG. Independent predictors of new-onset PHG included higher alkaline phosphatase and being diabetic, whereas predictors of worsening PHG were Caucasian race, lower albumin, as well as higher serum aspartate transaminase/alanine transaminase ratio and homeostatic model assessment levels. New-onset and worsening PHG were significantly associated with clinical and histological progression. They were also associated with new-onset and worsening gastroesophageal varices. CONCLUSIONS: New-onset and worsening PHG develop at a rate of 12.9% per year and 6.7% per year, respectively, in non-responder CHC patients with advanced fibrosis. If confirmed in other studies, endoscopic surveillance for PHG may need to be tailored to individual patient risk factors. C1 [Fontana, Robert J.] Univ Michigan, Sch Med, Dept Internal Med, Div Gastroenterol,Taubman Ctr 3912, Ann Arbor, MI 48109 USA. [Sanyal, Arun J.] Virginia Commonwealth Univ, Med Ctr, Dept Internal Med, Div Gastroenterol, Richmond, VA USA. [Ghany, Marc G.] NIDDKD, US Dept HHS, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Dept Med, Farmington, CT USA. [Bonkovsky, Herbert L.] Carolinas Med Ctr, Dept Internal Med, Charlotte, NC 28203 USA. [Morgan, Timothy R.] Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA. [Morgan, Timothy R.] VA Long Beach Healthcare Syst, Gastroenterol Serv, Dept Internal Med, Long Beach, CA USA. [Litman, Heather J.; Naishadham, Deepa] New England Res Inst, Watertown, MA 02172 USA. [Reid, Andrea E.] Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA. [Lee, William M.] Univ Texas SW Med Ctr Dallas, Div Digest & Liver Dis, Dallas, TX 75390 USA. RP Fontana, RJ (reprint author), Univ Michigan, Sch Med, Dept Internal Med, Div Gastroenterol,Taubman Ctr 3912, Ann Arbor, MI 48109 USA. EM rfontana@med.umich.edu FU National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Allergy and Infectious Diseases (NIAID); National Cancer Institute; National Center for Minority Health and Health Disparities; New England Research Institutes, Watertown, MA [N01-DK-9-2328]; National Center for Research Resources, National Institutes of Health; University of Massachusetts Medical Center, Worcester, MA [N01-DK-9-2326]; University of Connecticut Health Center, Farmington, CT [M01RR-06192]; Saint Louis University School of Medicine, St Louis, MO [N01-DK-9-2324]; Massachusetts General Hospital, Boston, MA [N01-DK-9-2319, M01RR-01066, 1 UL1 RR025758-01]; Harvard Clinical and Translational Science Center; University of Colorado Denver, School of Medicine, Aurora, CO [N01-DK-9-2327, M01RR-00051, 1 UL1 RR 025780-01]; University of California-Irvine, Irvine, CA [N01-DK-9-2320, M01RR-00827]; University of Texas Southwestern Medical Center, Dallas, TX [N01-DK-9-2321, M01RR-00633, 1 UL1 RR024982-01]; North and Central Texas Clinical and Translational Science Initiative); University of Michigan Medical Center, Ann Arbor, MI [RR024986]; Michigan Center for Clinical and Health Research; Virginia Commonwealth University Health System, Richmond, VA [N01-DK-9-2322, M01RR-00065]; Liver Diseases Branch; National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD; National Institute of Diabetes and Digestive and Kidney Diseases, Division of Digestive Diseases and Nutrition, Bethesda, MD; University of Washington, Seattle, WA [N01-DK-9-2318]; Armed Forces Institute of Pathology, Washington, DC FX This study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (contract numbers are listed below). Additional support was provided by the National Institute of Allergy and Infectious Diseases (NIAID), the National Cancer Institute, the National Center for Minority Health and Health Disparities, and Minjun Chung Apodaca, BS, ASCP, Rohit Shankar, BC, ASCP, Natalia Antonov, MEd; New England Research Institutes, Watertown, MA (contract N01-DK-9-2328): Kristin K. Snow, MSc, ScD, Anne M. Stoddard, ScD, Linda Massey; Armed Forces Institute of Pathology, Washington, DC: Zachary D. Goodman, MD, PhD, Fanny Monge, Michelle Parks; Data and Safety Monitoring Board Members: (Chair) Gary L. Davis, MD, Guadalupe Garcia-Tsao, MD, Michael Kutner, PhD, Stanley M. Lemon, MD, Robert P. Perrillo, MD. by the General Clinical Research Center and Clinical and Translational Science Center grants from the National Center for Research Resources, National Institutes of Health (grant numbers are listed below). Additional funding to conduct this study was supplied by Hoffmann-La Roche through a Cooperative Research and Development Agreement (CRADA) with the National Institutes of Health. In addition to the authors of this manuscript, the following individuals were instrumental in the planning, conduct, and/or care of patients enrolled in this study at each of the participating institutions as follows: University of Massachusetts Medical Center, Worcester, MA (contract N01-DK-9-2326): Gyongyi Szabo, MD, Barbara F. Banner, MD, Maureen Cormier, RN, Donna Giansiracusa, RN; University of Connecticut Health Center, Farmington, CT (Grant no, M01RR-06192): Gloria Borders, RN, Michelle Kelley, RN, ANP; Saint Louis University School of Medicine, St Louis, MO (contract N01-DK-9-2324): Adrian M. Di Bisceglie, MD, Bruce Bacon, MD, Brent Neuschwander-Tetri, MD, Elizabeth M. Brunt, MD, Debra King, RN; Massachusetts General Hospital, Boston, MA (contract N01-DK-9-2319, Grant no. M01RR-01066; Grant no. 1 UL1 RR025758-01, Harvard Clinical and Translational Science Center): Jules L. Dienstag, MD, Raymond T. Chung, MD, Atul K. Bhan, MD, Wallis A. Molchen, David P. Lundmark; University of Colorado Denver, School of Medicine, Aurora, CO (contract N01-DK-9-2327, Grant no. M01RR-00051, Grant no. 1 UL1 RR 025780-01): Gregory T. Everson, MD, Thomas Trouillot, MD, Marcelo Kugelmas, MD, S. Russell Nash, MD, Jennifer DeSanto, RN, Carol McKinley, RN; University of California-Irvine, Irvine, CA (contract N01-DK-9-2320, Grant no. M01RR-00827): John C. Hoefs, MD, John R. Craig, MD, M. Mazen Jamal, MD, MPH, Muhammad Sheikh, MD, Choon Park, RN; University of Texas Southwestern Medical Center, Dallas, TX (contract N01-DK-9-2321, Grant no. M01RR-00633, Grant no. 1 UL1 RR024982-01, North and Central Texas Clinical and Translational Science Initiative): Thomas E. Rogers, MD, Peter F. Malet, MD, Janel Shelton, Nicole Crowder, LVN, Rivka Elbein, RN, BSN, Nancy Liston, MPH; University of Southern California, Los Angeles, CA (contract N01-DK-9-2325, Grant no. M01RR-00043): Karen L. Lindsay, MD, MMM, Sugantha Govindarajan, MD, Carol B. Jones, RN, Susan L. Milstein, RN; University of Michigan Medical Center, Ann Arbor, MI (contract N01-DK-9-2323, Grant no. M01RR-00042, Grant no. 1 UL1 RR024986, Michigan Center for Clinical and Health Research): Anna S. Lok, MD, Joel K. Greenson, MD, Pamela A. Richtmyer, LPN, CCRC, R. Tess Bonham, BS; Virginia Commonwealth University Health System, Richmond, VA (contract N01-DK-9-2322, Grant no. M01RR-00065): Mitchell L.; Shiffman, MD, RichardK. Sterling, MD, MSc, Melissa J. Contos, MD, A. Scott Mills, MD, Charlotte Hofmann, RN, Paula Smith, RN; Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD: T. Jake Liang, MD, David Kleiner, MD, PhD, Yoon Park, RN, Elenita Rivera, RN, Vanessa Haynes-Williams, RN; National Institute of Diabetes and Digestive and Kidney Diseases, Division of Digestive Diseases and Nutrition, Bethesda, MD: James E. Everhart, MD, Leonard B. Seeff, MD, Patricia R. Robuck, PhD, Jay H. Hoofnagle, MD, Elizabeth C. Wright, PhD; University of Washington, Seattle, WA (contract N01-DK-9-2318): Chihiro Morishima, MD, David R. Gretch, MD, PhD, Minjun Chung Apodaca, BS, ASCP, Rohit Shankar, BC, ASCP, Natalia Antonov, MEd; New England Research Institutes, Watertown, MA (contract N01-DK-9-2328): Kristin K. Snow, MSc, ScD, Anne M. Stoddard, ScD, Linda Massey; Armed Forces Institute of Pathology, Washington, DC: Zachary D. Goodman, MD, PhD, Fanny Monge, Michelle Parks; Data and Safety Monitoring Board Members: (Chair) Gary L. Davis, MD, Guadalupe Garcia-Tsao, MD, Michael Kutner, PhD, Stanley M. Lemon, MD, Robert P. Perrillo, MD. NR 27 TC 2 Z9 2 U1 1 U2 5 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 MAY PY 2011 VL 106 IS 5 BP 884 EP 893 DI 10.1038/ajg.2010.456 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 759MP UT WOS:000290250100011 PM 21139575 ER PT J AU Powe, CE Ecker, J Rana, S Wang, A Ankers, E Ye, J Levine, RJ Karumanchi, A Thadhani, R AF Powe, Camille E. Ecker, Jeffrey Rana, Sarosh Wang, Alice Ankers, Elizabeth Ye, Jun Levine, Richard J. Karumanchi, Ananth Thadhani, Ravi TI Preeclampsia and the risk of large-for-gestational-age infants SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE fetal growth; gestational diabetes; large for gestational age; preeclampsia ID HEALTHY NULLIPAROUS WOMEN; FETAL GROWTH-RETARDATION; GLUCOSE-TOLERANCE; BIRTH-WEIGHT; PREGNANCY; OBESITY; CYTOTROPHOBLASTS; HYPERGLYCEMIA; HYPERTENSION; OUTCOMES AB OBJECTIVE: We sought to compare the risk of giving birth to large-for-gestational-age (LGA) infants in women with and without preeclampsia, after adjustment for obesity and glucose intolerance. STUDY DESIGN: We conducted secondary analysis of a prospective database of pregnant women with and without preeclampsia who delivered infants from 1998 through 2006 at Massachusetts General Hospital (n = 17,465). RESULTS: The risk of LGA was similar in women with and without preeclampsia (odds ratio, 0.81; 95% confidence interval, 0.59-1.14). After adjustment for body mass index, glucose intolerance, and other factors, the risk of LGA was significantly lower in women with preeclampsia compared to those without preeclampsia (odds ratio, 0.69; 95% confidence interval, 0.49-0.96). Stratified analysis in groups with a higher risk of LGA revealed that preeclampsia has a similar effect on the risk of LGA regardless of maternal obesity, glucose intolerance, parity, and race. CONCLUSION: Preeclampsia appears to be characterized by reduced, and not increased, fetal growth. C1 [Powe, Camille E.; Ankers, Elizabeth; Ye, Jun; Thadhani, Ravi] Massachusetts Gen Hosp, Div Nephrol, Dept Med, Boston, MA 02114 USA. [Ecker, Jeffrey] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Rana, Sarosh; Karumanchi, Ananth] Beth Israel Deaconess Med Ctr, Dept Obstet Gynecol, Boston, MA USA. [Karumanchi, Ananth] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA USA. [Wang, Alice] Boston Univ, Med Ctr, Dept Pediat, Boston, MA USA. [Levine, Richard J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Dept Hlth & Human Serv, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA. RP Thadhani, R (reprint author), Massachusetts Gen Hosp, Div Nephrol, Dept Med, 55 Fruit St,Bullfinch 127, Boston, MA 02114 USA. EM rthadhani@partners.org FU Eunice Kennedy Shriver National Institute of Child Health and Human Development FX Ms Powe is a Howard Hughes Medical Institute Medical Research Training Fellow. Dr Levine receives salary support from the intramural research program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr Karumanchi is an investigator of the Howard Hughes Medical Institute. NR 34 TC 2 Z9 2 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD MAY PY 2011 VL 204 IS 5 AR 425.e1 DI 10.1016/j.ajog.2010.12.030 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 758YZ UT WOS:000290206200033 PM 21371687 ER PT J AU Harston, RK McKillop, JC Moschella, PC Van Laer, A Quinones, LS Baicu, CF Balasubramanian, S Zile, MR Kuppuswamy, D AF Harston, Rebecca K. McKillop, John C. Moschella, Phillip C. Van Laer, An Quinones, Lakeya S. Baicu, Catalin F. Balasubramanian, Sundaravadivel Zile, Michael R. Kuppuswamy, Dhandapani TI Rapamycin treatment augments both protein ubiquitination and Akt activation in pressure-overloaded rat myocardium SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE hypertrophy; mammalian target of rapamycin; signal transduction; cell survival ID NF-KAPPA-B; CARDIAC-HYPERTROPHY; IN-VIVO; VENTRICULAR HYPERTROPHY; LIFE-SPAN; MTOR; MICE; PROTEASOME; PATHWAY; GROWTH AB Harston RK, McKillop JC, Moschella PC, Van Laer A, Quinones LS, Baicu CF, Balasubramanian S, Zile MR, Kuppuswamy D. Rapamycin treatment augments both protein ubiquitination and Akt activation in pressure-overloaded rat myocardium. Am J Physiol Heart Circ Physiol 300: H1696-H1706, 2011. First published February 25, 2011; doi:10.1152/ajpheart.00545.2010.-Ubiquitin-mediated protein degradation is necessary for both increased ventricular mass and survival signaling for compensated hypertrophy in pressure-overloaded (PO) myocardium. Another molecular keystone involved in the hypertrophic growth process is the mammalian target of rapamycin (mTOR), which forms two distinct functional complexes: mTORC1 that activates p70S6 kinase-1 to enhance protein synthesis and mTORC2 that activates Akt to promote cell survival. Independent studies in animal models show that rapamycin treatment that alters mTOR complexes also reduces hypertrophic growth and increases lifespan by an unknown mechanism. We tested whether the ubiquitin-mediated regulation of growth and survival in hypertrophic myocardium is linked to the mTOR pathway. For in vivo studies, right ventricle PO in rats was conducted by pulmonary artery banding; the normally loaded left ventricle served as an internal control. Rapamycin (0.75 mg/kg per day) or vehicle alone was administered intraperitoneally for 3 days or 2 wk. Immunoblot and immunofluorescence imaging showed that the level of ubiquitylated proteins in cardiomyocytes that increased following 48 h of PO was enhanced by rapamycin. Rapamycin pretreatment also significantly increased PO-induced Akt phosphorylation at S473, a finding confirmed in cardiomyocytes in vitro to be downstream of mTORC2. Analysis of prosurvival signaling in vivo showed that rapamycin increased PO-induced degradation of phosphorylated inhibitor of kappa B, enhanced expression of cellular inhibitor of apoptosis protein 1, and decreased active caspase-3. Long-term rapamycin treatment in 2-wk PO myocardium blunted hypertrophy, Unproved contractile function, and reduced caspase-3 and calpain activation. These data indicate potential cardioprotective benefits of rapamycin in PO hypertrophy. C1 [Harston, Rebecca K.; McKillop, John C.; Moschella, Phillip C.; Van Laer, An; Quinones, Lakeya S.; Baicu, Catalin F.; Balasubramanian, Sundaravadivel; Zile, Michael R.; Kuppuswamy, Dhandapani] Med Univ S Carolina, Gazes Cardiac Res Inst, Div Cardiol, Dept Med, Charleston, SC 29425 USA. [Zile, Michael R.; Kuppuswamy, Dhandapani] Vet Affairs Med Ctr, Ralph H Johnson Dept, Charleston, SC 29403 USA. RP Kuppuswamy, D (reprint author), Med Univ S Carolina, Gazes Cardiac Res Inst, Div Cardiol, Dept Med, 114 Doughty St, Charleston, SC 29425 USA. EM kuppusd@musc.edu FU National Institutes of Health [RHL092124A, T32HL07260]; Research Service of the Department of Veterans Affairs; AHA [061546811] FX This study was supported by the National Institutes of Health (RHL092124A to D. Kuppuswamy), and by Merit Award from the Research Service of the Department of Veterans Affairs (to M. Zile), by AHA predoctoral fellowship 061546811 (to R. K. Harston), and by NIH predoctoral fellowship NIH T32HL07260 (to R. K. Harston). NR 42 TC 13 Z9 13 U1 1 U2 7 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD MAY PY 2011 VL 300 IS 5 BP H1696 EP H1706 DI 10.1152/ajpheart.00545.2010 PG 11 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 757NA UT WOS:000290092800016 PM 21357504 ER PT J AU Sas, KM Janech, MG Favre, E Arthur, JM Bell, PD AF Sas, Kelli M. Janech, Michael G. Favre, Elizabeth Arthur, John M. Bell, P. Darwin TI Cilia movement regulates expression of the Raf-1 kinase inhibitor protein SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE polycystic kidney disease; renal epithelial cells; renal cysts ID POLYCYSTIC KIDNEY-DISEASE; PROSTATE-CANCER METASTASIS; AUTOSOMAL-DOMINANT; CYST FORMATION; EPITHELIAL-CELLS; COLLECTING DUCT; B-RAF; FLUID; MICE; ACTIVATION AB Sas KM, Janech MG, Favre E, Arthur JM, Bell PD. Cilia movement regulates expression of the Raf-1 kinase inhibitor protein. Am J Physiol Renal Physiol 300: F1163-F1170, 2011. First published February 23, 2011; doi:10.1152/ajprenal.00602.2010.-Renal epithelial cell primary cilia act as mechanosensors in response to changes in luminal fluid flow. To determine the role of cilia bending in the mechanosensory function of cilia, we performed proteomic analysis of collecting duct cell lines with or without cilia that were kept stationary or rotated to stimulate cilia bending. Expression of the Raf-1 kinase inhibitor protein (RKIP), an inhibitor of the MAPK pathway, was significantly elevated in rotated cilia (+) cells. This was compared with RKIP levels in cilia (-) cells that were stationary or rotated as well as in cilia (+) cells that were stationary. This result was confirmed in cilia knockout adult mice that had lower renal RKIP levels compared with adult mice with cilia. Downstream of RKIP, expression of phosphorylated ERK was decreased only in cells that had cilia and were subjected to constant cilia bending. Furthermore, elevated RKIP levels were associated with reduced cell proliferation. Blockade of PKC abrogated ciliary bending-induced increases in RKIP. In summary, we found that ciliary movement may help control the expression of the Raf-1 kinase inhibitor protein and thus maintain cell differentiation. In terms of polycystic kidney disease, loss of cilia and therefore sensitivity to flow may lead to reduced RKIP levels, activation of the MAPK pathway, and contribute to the formation of cysts. C1 [Janech, Michael G.; Arthur, John M.; Bell, P. Darwin] MUSC, Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. [Sas, Kelli M.; Janech, Michael G.; Favre, Elizabeth; Arthur, John M.; Bell, P. Darwin] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. RP Bell, PD (reprint author), MUSC, Ralph H Johnson Vet Affairs Med Ctr, 173 Ashley Ave,CRI 211, Charleston, SC 29425 USA. EM bellpd@musc.edu OI Janech, Michael/0000-0002-3202-4811 FU Veterans Affairs (VA); National Institutes of Health (NIH) [DK32032, P30 DK074038, T32 DK007752]; Dialysis Clinic, Inc.; Nephcure Foundation; Foundation Young Investigator Award; NIH, National Center for Research Resources [C06 RR015455] FX This work was supported by Veterans Affairs (VA) Merit Awards (P. D. Bell, J. M. Arthur), a VA Career Development Award (M. G. Janech), National Institutes of Health (NIH) Grants DK32032 (P. D. Bell), P30 DK074038 (P. D. Bell; UAB Core Center, Lisa Guay-Woodford, PI) and T32 DK007752 (K. M. Sas; P. D. Bell, PI). Support was also provided by Dialysis Clinic, Inc., and a Nephcure Foundation Young Investigator Award (M. G. Janech). Foundation Young Investigator Award (M. G. Janech). This work was conducted in a facility constructed with support from NIH Grant C06 RR015455 from the Extramural Research Facilities Program of the National Center for Research Resources. NR 54 TC 5 Z9 5 U1 1 U2 3 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 MAY PY 2011 VL 300 IS 5 BP F1163 EP F1170 DI 10.1152/ajprenal.00602.2010 PG 8 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 758YY UT WOS:000290206100014 PM 21345975 ER PT J AU Smoller, JW AF Smoller, Jordan W. TI Do Antidepressants Raise the Risk of Stroke? SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Editorial Material ID CASE-CROSSOVER C1 [Smoller, Jordan W.] Herman Dana Trust, Newton, MA 02459 USA. RP Smoller, JW (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA. EM jsmoller@hms.harvard.edu NR 6 TC 4 Z9 4 U1 0 U2 2 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 MAY PY 2011 VL 168 IS 5 BP 457 EP 459 DI 10.1176/appi.ajp.2011.11020336 PG 3 WC Psychiatry SC Psychiatry GA 757MG UT WOS:000290089000004 PM 21536699 ER PT J AU Dodrill, CL Helmer, DA Kosten, TR AF Dodrill, Carrie L. Helmer, Drew A. Kosten, Thomas R. TI Prescription Pain Medication Dependence SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Editorial Material ID CHRONIC NONMALIGNANT PAIN; OPIOID DEPENDENCE; ADDICTION TREATMENT; DRUG-ABUSE; BACK-PAIN; BUPRENORPHINE; METHADONE; THERAPY; DETOXIFICATION; PREVALENCE C1 [Dodrill, Carrie L.] Baylor Coll Med, Dept Psychiat, Michael E Debakey Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Dodrill, CL (reprint author), Baylor Coll Med, Dept Psychiat, Michael E Debakey Vet Affairs Med Ctr, 2002 Holcombe Blvd,Bldg 110,Rm 223, Houston, TX 77030 USA. EM dodrill@bcm.edu FU NIDA NIH HHS [K05-DA0454] NR 44 TC 16 Z9 16 U1 2 U2 9 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 MAY PY 2011 VL 168 IS 5 BP 466 EP 471 DI 10.1176/appi.ajp.2010.10020260 PG 6 WC Psychiatry SC Psychiatry GA 757MG UT WOS:000290089000007 PM 21536702 ER PT J AU Foland-Ross, LC Thompson, PM Sugar, CA Madsen, SK Shen, JK Penfold, C Ahlf, K Rasser, PE Fischer, J Yang, YL Townsend, J Bookheimer, SY Altshuler, LL AF Foland-Ross, Lara C. Thompson, Paul M. Sugar, Catherine A. Madsen, Sarah K. Shen, Jim K. Penfold, Conor Ahlf, Kyle Rasser, Paul E. Fischer, Jeffrey Yang, Yilan Townsend, Jennifer Bookheimer, Susan Y. Altshuler, Lori L. TI Investigation of Cortical Thickness Abnormalities in Lithium-Free Adults With Bipolar I Disorder Using Cortical Pattern Matching SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID VOXEL-BASED MORPHOMETRY; GRAY-MATTER DENSITY; CINGULATE CORTEX VOLUME; PREFRONTAL CORTEX; ORBITOFRONTAL CORTEX; RATING-SCALE; GREY-MATTER; HUMAN BRAIN; AMYGDALA; SCHIZOPHRENIA AB Objective: Although several lines of evidence implicate gray matter abnormalities in the prefrontal cortex and anterior cingulate cortex in patients with bipolar disorder, findings have been largely inconsistent across studies. Differences in patients' medication status or mood state or the application of traditional volumetric methods that are insensitive to subtle neuroanatomical differences may have contributed to variations in findings. The authors used MRI in conjunction with cortical pattern matching methods to assess cortical thickness abnormalities in euthymic bipolar patients who were not receiving lithium treatment. Method: Thirty-four lithium-free euthymic patients with bipolar I disorder and 31 healthy comparison subjects under-went MRI scanning. Data were processed to measure cortical gray matter thickness. Thickness maps were spatially normalized using cortical pattern matching and were analyzed to assess illness effects and associations with clinical variables. Results: Relative to healthy comparison subjects, euthymic bipolar patients had significantly thinner gray matter in the left and right prefrontal cortex (Brodmann's areas 11, 10, 8, and 44) and the left anterior cingulate cortex (Brodmann's areas 24/32). Thinning in these regions was more pronounced in patients with a history of psychosis. No areas of thicker cortex were detected in bipolar patients relative to healthy comparison subjects. Conclusions: Using a technique that is highly sensitive to subtle neuroanatomical differences, significant regional cortical thinning was found in lithium-free euthymic patients with bipolar disorder. C1 Univ Calif Los Angeles, Sch Med, Dept Neurol, Lab NeuroImaging, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Ahmanson Lovelace Brain Mapping Ctr, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Biostat, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Schizophrenia Res Inst, Darlinghurst, NSW, Australia. Univ Newcastle, Prior Ctr Brain & Mental Hlth Res, Callaghan, NSW 2308, Australia. VA Greater Los Angeles Healthcare Syst, Dept Psychiat, Los Angeles, CA USA. W Los Angeles Healthcare Ctr, Los Angeles, CA USA. RP Altshuler, LL (reprint author), 300 UCLA Med Plaza,Suite 1544,Box 957057, Los Angeles, CA 90095 USA. EM laltshuler@mednet.ucla.edu FU NIMH [MH078556, MH075944, MH01848]; NARSAD; National Center for Research Resources [AG016570, EB01651, RR019771, RR12169, RR13642, RR00865]; National Institute on Aging; National Institute of Biomedical Imaging and Bioengineering; Brain Mapping Medical Research Organization; Brain Mapping Support Foundation; Pierson-Lovelace Foundation; Ahmanson Foundation; William M. and Linda R. Dietel Philanthropic Fund at the Northern Piedmont Community Foundation; Tamkin Foundation; Jennifer Jones-Simon Foundation; Capital Group Companies Charitable Foundation; Robson Family; Northstar Fund FX Supported by NIMH grants MH078556, MH075944, and MH01848; NARSAD; National Center for Research Resources grants AG016570, EB01651, RR019771, RR12169, RR13642, and RR00865; and the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, the Brain Mapping Medical Research Organization, the Brain Mapping Support Foundation, the Pierson-Lovelace Foundation, the Ahmanson Foundation, the William M. and Linda R. Dietel Philanthropic Fund at the Northern Piedmont Community Foundation, the Tamkin Foundation, the Jennifer Jones-Simon Foundation, the Capital Group Companies Charitable Foundation, the Robson Family, and the Northstar Fund. NR 59 TC 36 Z9 37 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 MAY PY 2011 VL 168 IS 5 BP 530 EP 539 DI 10.1176/appi.ajp.2010.10060896 PG 10 WC Psychiatry SC Psychiatry GA 757MG UT WOS:000290089000014 PM 21285139 ER PT J AU Didier, JP Villet, R Huggler, E Lew, DP Hooper, DC Kelley, WL Vaudaux, P AF Didier, Jean-Philippe Villet, Regis Huggler, Elzbieta Lew, Daniel P. Hooper, David C. Kelley, William L. Vaudaux, Pierre TI Impact of Ciprofloxacin Exposure on Staphylococcus aureus Genomic Alterations Linked with Emergence of Rifampin Resistance SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID STALLED REPLICATION FORKS; TOPOISOMERASE-IV; RNA-POLYMERASE; MUTATION FREQUENCIES; PRIMARY TARGET; SOS RESPONSE; DNA GYRASE; BACTERIA; REPAIR; MUTANTS AB Intensive use of antimicrobial agents in health care settings not only leads to the selection of multiresistant nosocomial isolates of Staphylococcus aureus but may also promote endogenous, resistance-conferring mutations in bacterial genes that encode drug targets. We evaluated the spectrum of rifampin resistance-conferring mutations in cultures of methicillin-susceptible S. aureus (MSSA) or methicillin-resistant S. aureus (MRSA) strains exposed in vitro to sub-MICs of ciprofloxacin. Growth of ciprofloxacin-susceptible MRSA strain MRGR3 and ciprofloxacin-resistant MSSA strain RA1 (a NCTC 8325 derivative) in the presence of 1/2x or 1/4x MIC of ciprofloxacin led to higher frequencies of rifampin-resistant mutants on agar supplemented with rifampin (0.25 mg/liter) than under ciprofloxacin-free conditions. While rifampin-resistant mutants from ciprofloxacin-free cultures essentially showed single-amino-acid substitutions, a significant proportion of rifampin-resistant mutants from ciprofloxacin-exposed cultures displayed in-frame deletions or insertions in the rpoB gene at several positions of the rifampin resistance cluster I. In-frame deletions or insertions were also recorded in rpoB cluster I of rifampin-resistant mutants from ciprofloxacin-exposed cultures of mutS and mutL DNA repair mutants of ciprofloxacin-resistant S. aureus strain RA1. Frequencies of rifampin-resistant mutants grown under ciprofloxacin-free medium were higher for mutant strains RA1 mutS2 and RA1 mutL, but not RA1 recA, than for their parent RA1. In conclusion, ciprofloxacin-mediated DNA damage in S. aureus, as exemplified by the wide diversity of deletions or insertions in rpoB, suggests the occurrence of major, quinolone-mediated disturbances in DNA fork progression and replication repair. Besides promoting antibiotic resistance, accumulation of unrepaired DNA replication errors, including insertions and deletions, may also contribute to potentially lethal mutations. C1 [Didier, Jean-Philippe; Villet, Regis; Huggler, Elzbieta; Lew, Daniel P.; Kelley, William L.; Vaudaux, Pierre] Univ Hosp Geneva, Infect Dis Serv, CH-1211 Geneva 14, Switzerland. [Hooper, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA. RP Vaudaux, P (reprint author), Univ Hosp Geneva, Infect Dis Serv, 4 Rue Gabrielle Perret Gentil, CH-1211 Geneva 14, Switzerland. EM Pierrevaudaux@yahoo.fr FU Swiss National Science Foundation [320000-116518, 31003A-120428, 3200B0-108401]; U.S. Public Health Service, National Institutes of Health [R37-AI023988-20] FX This study was supported by research grants 320000-116518 (to P.V.), 31003A-120428 (to W.K.), and 3200B0-108401 (to D.P.L.) from the Swiss National Science Foundation and by research grant R37-AI023988-20 (to D.C.H.) from the U.S. Public Health Service, National Institutes of Health. NR 45 TC 12 Z9 12 U1 2 U2 6 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 MAY PY 2011 VL 55 IS 5 BP 1946 EP 1952 DI 10.1128/AAC.01407-10 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 756NM UT WOS:000290019200016 PM 21357297 ER PT J AU Sandweiss, DA Slymen, DJ LeardMann, CA Smith, B White, MR Boyko, EJ Hooper, TI Gackstetter, GD Amoroso, PJ Smith, TC AF Sandweiss, Donald A. Slymen, Donald J. LeardMann, Cynthia A. Smith, Besa White, Martin R. Boyko, Edward J. Hooper, Tomoko I. Gackstetter, Gary D. Amoroso, Paul J. Smith, Tyler C. CA Millennium Cohort Study Team TI Preinjury Psychiatric Status, Injury Severity, and Postdeployment Posttraumatic Stress Disorder SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID MOTOR-VEHICLE ACCIDENTS; READJUSTMENT RATING-SCALE; COMBAT TRAUMA REGISTRY; MENTAL-HEALTH PROBLEMS; MILLENNIUM COHORT; PRIMARY-CARE; MILITARY SERVICE; RISK-FACTORS; US MILITARY; PERCEIVED THREAT AB Context: Physical injury has been associated with the development of posttraumatic stress disorder (PTSD). Previous studies have retrospectively examined the relationship of preinjury psychiatric status and postinjury PTSD with conflicting results, but no prospective studies regarding this subject have been conducted, to our knowledge. Objective: To prospectively assess the relationship of predeployment psychiatric status and injury severity with postdeployment PTSD. Design: Prospective, longitudinal study. Setting: United States military personnel deployed in support of the conflicts in Iraq and Afghanistan. Participants: United States service member participants in the Millennium Cohort Study who completed a baseline questionnaire (from July 1, 2001, through June 30, 2003) and at least 1 follow-up questionnaire (from June 1, 2004, through February 14, 2006, and from May 15, 2007, through December 31, 2008) and who were deployed in the intervening period. Self-reported health information was used to prospectively examine the relationship between baseline psychiatric status and follow-up PTSD in injured and uninjured deployed individuals. Main Outcome Measures: A positive screening result using the PTSD Checklist-Civilian Version. Results: Of 22 630 eligible participants, 1840 (8.1%) screened positive for PTSD at follow-up, and 183 (0.8%) sustained a deployment-related physical injury that was documented in the Joint Theater Trauma Registry or the Navy-Marine Corps Combat Trauma Registry Expeditionary Medical Encounter Database. The odds of screening positive for PTSD symptoms were 2.52 (95% confidence interval, 2.01-3.16) times greater in those with 1 or more defined baseline mental health disorder and 16.1% (odds ratio, 1.16; 95% confidence interval, 1.01-1.34) greater for every 3-unit increase in the Injury Severity Score. Irrespective of injury severity, self-reported preinjury psychiatric status was significantly associated with PTSD at follow-up. Conclusions: Baseline psychiatric status and deployment-related physical injuries were associated with screening positive for postdeployment PTSD. More vulnerable members of the deployed population might be identified and benefit from interventions targeted to prevent or to ensure early identification and treatment of postdeployment PTSD. C1 [Sandweiss, Donald A.; LeardMann, Cynthia A.; Smith, Besa; White, Martin R.; Smith, Tyler C.] USN, Hlth Res Ctr, Dept Deployment Hlth Res, San Diego, CA 92106 USA. [Slymen, Donald J.] San Diego State Univ, Grad Sch Publ Hlth, San Diego, CA 92182 USA. [Boyko, Edward J.] Vet Affairs Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. [Hooper, Tomoko I.] Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA. [Gackstetter, Gary D.] Analyt Serv Inc, Arlington, VA USA. [Amoroso, Paul J.] Madigan Army Med Ctr, Dept Clin Invest, Tacoma, WA 98431 USA. RP LeardMann, CA (reprint author), USN, Hlth Res Ctr, Dept Deployment Hlth Res, 140 Sylvester Rd, San Diego, CA 92106 USA. EM cynthia.leardmann@med.navy.mil FU US Department of Defense; Veterans Affairs Puget Sound Health Care System FX This work represents report 10-03, supported by the US Department of Defense, within work unit 60002. The work of Dr Boyko in this project was supported by the Veterans Affairs Puget Sound Health Care System. NR 75 TC 19 Z9 19 U1 1 U2 7 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 MAY PY 2011 VL 68 IS 5 BP 496 EP 504 PG 9 WC Psychiatry SC Psychiatry GA 757UY UT WOS:000290114500010 PM 21536979 ER PT J AU Culbertson, CS Bramen, J Cohen, MS London, ED Olmstead, RE Gan, JJ Costello, MR Shulenberger, S Mandelkern, MA Brody, AL AF Culbertson, Christopher S. Bramen, Jennifer Cohen, Mark S. London, Edythe D. Olmstead, Richard E. Gan, Joanna J. Costello, Matthew R. Shulenberger, Stephanie Mandelkern, Mark A. Brody, Arthur L. TI Effect of Bupropion Treatment on Brain Activation Induced by Cigarette-Related Cues in Smokers SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID SUSTAINED-RELEASE BUPROPION; ANTERIOR CINGULATE CORTEX; SMOKING-CESSATION; NICOTINE DEPENDENCE; TOBACCO DEPENDENCE; CONTROLLED-TRIAL; RECEPTOR SUBTYPES; RANDOMIZED-TRIAL; DRUG-ADDICTION; FMRI AB Context: Nicotine-dependent smokers exhibit craving and brain activation in the prefrontal and limbic regions when presented with cigarette-related cues. Bupropion hydrochloride treatment reduces cue-induced craving in cigarette smokers; however, the mechanism by which bupropion exerts this effect has not yet been described. Objective: To assess changes in regional brain activation in response to cigarette-related cues from before to after treatment with bupropion (vs placebo). Design: Randomized, double-blind, before-after controlled trial. Setting: Academic brain imaging center. Participants: Thirty nicotine-dependent smokers (paid volunteers). Interventions: Participants were randomly assigned to receive 8 weeks of treatment with either bupropion or a matching placebo pill (double-blind). Main Outcome Measures: Subjective cigarette craving ratings and regional brain activations (blood oxygen level-dependent response) in response to viewing cue videos. Results: Bupropion-treated participants reported less craving and exhibited reduced activation in the left ventral striatum, right medial orbitofrontal cortex, and bilateral anterior cingulate cortex from before to after treatment when actively resisting craving compared with placebo-treated participants. When resisting craving, reduction in self-reported craving correlated with reduced regional brain activation in the bilateral medial orbitofrontal and left anterior cingulate cortices in all participants. Conclusions: Treatment with bupropion is associated with improved ability to resist cue-induced craving and a reduction in cue-induced activation of limbic and prefrontal brain regions, while a reduction in craving, regardless of treatment type, is associated with reduced activation in prefrontal brain regions. C1 [Culbertson, Christopher S.; Bramen, Jennifer; Cohen, Mark S.; London, Edythe D.; Gan, Joanna J.; Costello, Matthew R.; Brody, Arthur L.] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA. [London, Edythe D.] Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA USA. [London, Edythe D.; Brody, Arthur L.] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90024 USA. [Olmstead, Richard E.; Shulenberger, Stephanie; Mandelkern, Mark A.; Brody, Arthur L.] Greater Los Angeles Vet Affairs Healthcare Syst, Dept Nucl Med, Los Angeles, CA USA. [Mandelkern, Mark A.] Univ Calif Irvine, Dept Phys, Irvine, CA 92717 USA. RP Brody, AL (reprint author), 300 UCLA Med Plaza,Ste 2200, Los Angeles, CA 90095 USA. EM abrody@ucla.edu RI Cohen, Mark/C-6610-2011 OI Cohen, Mark/0000-0001-6731-4053 FU National Institute on Drug Abuse [R01 DA20872, DA245482]; Tobacco-Related Disease Research Program, a Veterans Affairs Type I Merit Review Award [16RT-0098]; Richard Metzner Chair in Clinical Neuropharmacology; Thomas P. and Katherine K. Pike Chair in Addiction Studies; Marjorie M. Greene Trust FX This study was supported by grants R01 DA20872 (Dr Brody) and DA245482 (Mr Culbertson) from the National Institute on Drug Abuse; grant 16RT-0098 from the Tobacco-Related Disease Research Program, a Veterans Affairs Type I Merit Review Award, and endowments from the Richard Metzner Chair in Clinical Neuropharmacology (Dr Brody); and endowments from the Thomas P. and Katherine K. Pike Chair in Addiction Studies and the Marjorie M. Greene Trust (Dr London). NR 92 TC 32 Z9 33 U1 1 U2 9 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 MAY PY 2011 VL 68 IS 5 BP 505 EP 515 DI 10.1001/archgenpsychiatry.2010.193 PG 11 WC Psychiatry SC Psychiatry GA 757UY UT WOS:000290114500012 PM 21199957 ER PT J AU Hunt, JL AF Hunt, Jennifer L. TI An Update on Molecular Diagnostics of Squamous and Salivary Gland Tumors of the Head and Neck SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID ADENOID CYSTIC CARCINOMA; GROWTH-FACTOR RECEPTOR; IN-SITU HYBRIDIZATION; UPPER AERODIGESTIVE TRACT; LOW-GRADE ADENOCARCINOMA; ETV6-NTRK3 FUSION GENE; CELL LUNG-CANCER; MUCOEPIDERMOID CARCINOMA; HUMAN-PAPILLOMAVIRUS; C-KIT AB Context.-Molecular testing in anatomic pathology is becoming standardized and can contribute valuable diagnostic, therapeutic, and prognostic information for the clinical management of patients. In head and neck pathology, recent advances in molecular testing have provided important targets in several different diagnostic areas, with particular emerging clinical applications in squamous and salivary gland pathology. In squamous mucosal-derived lesions, human papilloma virus has emerged as an important pathogenic etiology in a subset of oropharyngeal squamous cell carcinomas. Within the category of salivary gland tumors, 3 tumors have recently been recognized that contain oncogenic translocations. Objective.-To describe the current state of information about the molecular alterations in squamous lesions and in salivary gland tumors of the head and neck. Data Sources.-Published literature on squamous and salivary gland tumors of the head and neck. Conclusions.-The different approaches to identification of viral-associated tumors include assays using polymerase chain reaction, in situ hybridization, and immunohistochemistry. Most mucoepidermoid carcinomas harbor MECT1-MAML2 gene rearrangement. The MYB-NFIB translocations have recently been identified in adenoid cystic carcinomas. Finally, a newly described tumor of salivary gland, mammary analogue secretory carcinoma, harbors the ETV6-NTRK3 translocation. Although these translocations are just emerging as diagnostic targets, future roles may evolve as potential therapeutic targets. (Arch Pathol Lab Med. 2011;135:602-609) C1 [Hunt, Jennifer L.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Hunt, Jennifer L.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Hunt, JL (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren Bldg 202,55 Fruit St, Boston, MA 02114 USA. EM jhunt5@partners.org NR 118 TC 13 Z9 16 U1 0 U2 4 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 MAY PY 2011 VL 135 IS 5 BP 602 EP 609 PG 8 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 759DU UT WOS:000290221700011 PM 21526958 ER PT J AU Mino-Kenudson, M Mark, EJ AF Mino-Kenudson, Mari Mark, Eugene J. TI Reflex Testing for Epidermal Growth Factor Receptor Mutation and Anaplastic Lymphoma Kinase Fluorescence In Situ Hybridization in Non-Small Cell Lung Cancer SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Review ID EML4-ALK FUSION GENE; BRONCHIOLOALVEOLAR PATHOLOGICAL SUBTYPE; EGFR MUTATIONS; TYROSINE KINASE; CLINICAL-TRIALS; ADJUVANT CHEMOTHERAPY; MOLECULAR PREDICTORS; SOMATIC MUTATIONS; GEFITINIB; ADENOCARCINOMA AB Context.-Non-small cell lung cancer (NSCLC) is a poor-prognosis malignancy for which more effective treatments are needed, with accumulating clinical experiences supporting benefits of receptor tyrosine kinase inhibitors for patients with tumors harboring an epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) rearrangement. Objective.-To review completed and ongoing clinical trials of EGFR tyrosine kinase inhibitors for EGFR mutation-positive NSCLC and an ALK inhibitor for those with ALK rearrangement, while also exploring practical issues surrounding the implementation of molecular testing as a routine component of the diagnostic workup of NSCLC in the United States. Data Sources.-Published biomedical literature, abstracts presented at recent major oncology meetings, and ClinicalTrials.gov. Conclusions.-Continually evolving evidence indicates the possible efficacy of molecularly targeted agents for the treatment of advanced NSCLC, especially adenocarcinoma. To identify patients who will most likely benefit from the targeted therapy, routine determination of the corresponding genetic alterations after histologic diagnosis of NSCLC (reflex molecular testing for EGFR mutations and ALK rearrangement) should be considered. (Arch Pathol Lab Med. 2011;135:655-664) C1 [Mino-Kenudson, Mari; Mark, Eugene J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Mino-Kenudson, M (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren 122, Boston, MA 02114 USA. EM mminokenudson@partners.org FU Boehringer Ingelheim Pharmaceuticals, Inc (BIPI; Ridgefield, Connecticut) FX This work is supported by Boehringer Ingelheim Pharmaceuticals, Inc (BIPI; Ridgefield, Connecticut). Editorial assistance is provided by Alyssa Tippens, PhD, of MedErgy (Yardley, Pennsylvania), which is contracted by BIPI for these services. The authors report the payment of $483 by BIPI to the Nature Publishing Company for permission to publish Figure 1, A through F. The authors have received no compensation related to the development of the manuscript. The authors have no relevant financial interest in the products or companies described in this article. NR 74 TC 20 Z9 20 U1 2 U2 5 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 MAY PY 2011 VL 135 IS 5 BP 655 EP 664 PG 10 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 759DU UT WOS:000290221700017 PM 21526964 ER PT J AU Shon, SM Park, JH Nahrendorf, M Schellingerhout, D Kim, JY Kang, BT Jeong, SW Kim, EJ Ryu, JH Kim, K Kwon, IC Lee, DK Lee, MM Kim, DE AF Shon, Soo-Min Park, Jong-Ho Nahrendorf, Matthias Schellingerhout, Dawid Kim, Jeong-Yeon Kang, Byeong-Teck Jeong, Sang-Wuk Kim, Eo-Jin Ryu, Ju Hee Kim, Kwangmeyung Kwon, Ick Chan Lee, Dong Kun Lee, Myoung Mook Kim, Dong-Eog TI Exercise attenuates matrix metalloproteinase activity in preexisting atherosclerotic plaque SO ATHEROSCLEROSIS LA English DT Article DE Exercise; Atherosclerosis; Matrix metalloproteinase; Preexisting plaque; Molecular imaging ID E-DEFICIENT MICE; LIPID-ACCUMULATION; ENZYME-ACTIVITY; PLASMA-PROTEIN; FOAM CELLS; ADIPONECTIN; EXPRESSION; HEART; ATHEROGENESIS; MACROPHAGES AB Objective: Few studies have investigated if exercise by itself has anti-atherosclerotic effects, without combining interventions with a low-fat diet. We studied the effects of exercise as a stand-alone intervention on preexisting atheromata by measuring not only plaque size but also the levels of plaque-destabilizing matrix-metalloproteinase (MMP) activity in vivo. Methods and results: We used near-infrared fluorescent (NIRF) molecular imaging with an MMP-2/9 activatable NIRF probe to visualize the inflammatory protease activity within preexisting atheromata of 17-week-old ApoE(-/-) mice on: (a) normal chow diet (NCD), (b) Western diet (WD), and (c) WD with treadmill exercise for 10 weeks. We also measured tissue levels of aortic lipid peroxidation (LPO) and plasma levels of glucose/lipid/cytokine profiles. Exercise did not attenuate growth of preexisting atheromatous plaques. However, exercise strongly decreased proteolytic activity in plaques for animals on WD, with levels decreasing almost to NCD levels. Exercise was associated with decreased aortic LPO levels and increased blood adiponectin/leptin levels; however, exercise did not affect WD-consumption/weight-gain or improve blood glucose/lipid profiles. Conclusions: Exercise training reduced aortic MMP activity in mice with preexisting atheromata, even though they remained on a high fat diet and plaque-growth was not attenuated. (C) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Kim, Dong-Eog] Dongguk Univ, Ilsan Hosp, Dept Neurol, Div Stroke Med,Mol Imaging & Neurovasc Res MINER, Goyang, South Korea. [Park, Jong-Ho] Kwandong Univ, Myongji Hosp, Neurovasc Ctr, Goyang, South Korea. [Nahrendorf, Matthias] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Nahrendorf, Matthias] Harvard Univ, Sch Med, Boston, MA USA. [Schellingerhout, Dawid] Univ Texas MD Anderson Canc Ctr, Dept Radiol, Houston, TX 77030 USA. [Schellingerhout, Dawid] Univ Texas MD Anderson Canc Ctr, Dept Expt Diagnost Imaging, Houston, TX 77030 USA. [Kim, Eo-Jin] Dongguk Univ, Ilsan Hosp, Dept Pathol, Goyang, South Korea. [Ryu, Ju Hee; Kim, Kwangmeyung; Kwon, Ick Chan] Korea Inst Sci & Technol, Biomed Res Ctr, Seoul, South Korea. [Lee, Myoung Mook] Dongguk Univ, Ilsan Hosp, Div Cardiol, Goyang, South Korea. RP Kim, DE (reprint author), Dongguk Univ, Ilsan Hosp, Dept Neurol, Div Stroke Med,Mol Imaging & Neurovasc Res MINER, 814 Siksa Dong, Goyang, South Korea. EM kdongeog@duih.org FU Translational Stroke Research Center, Ministry of Health & Welfare, Republic of Korea [A08020] FX This work was supported by a grant (A08020, Translational Stroke Research Center Grant to Dr. Dong-Eog Kim) of the Korea Healthcare Technology R&D Project, Ministry of Health & Welfare, Republic of Korea. NR 23 TC 14 Z9 15 U1 0 U2 10 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 MAY PY 2011 VL 216 IS 1 BP 67 EP 73 DI 10.1016/j.atherosclerosis.2011.01.036 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 758YV UT WOS:000290205800011 PM 21334624 ER PT J AU Sharma, R Prudente, S Andreozzi, F Powers, C Mannino, G Bacci, S Gervino, EV Hauser, TH Succurro, E Mercuri, L Goheen, EH Shah, H Trischitta, V Sesti, G Doria, A AF Sharma, Rajani Prudente, Sabrina Andreozzi, Francesco Powers, Christine Mannino, Gaia Bacci, Simonetta Gervino, Ernest V. Hauser, Thomas H. Succurro, Elena Mercuri, Luana Goheen, Elizabeth H. Shah, Hetal Trischitta, Vincenzo Sesti, Giorgio Doria, Alessandro TI The type 2 diabetes and insulin-resistance locus near IRS1 is a determinant of HDL cholesterol and triglycerides levels among diabetic subjects SO ATHEROSCLEROSIS LA English DT Article DE Coronary artery disease; Polymorphisms; Insulin-resistance; Type 2 diabetes ID CORONARY-ARTERY-DISEASE; HEART-DISEASE; RISK; HERITABILITY; ASSOCIATION; RECEPTOR; EVENTS AB Objective: SNP rs2943641 near the insulin receptor substrate 1 (IRS1) gene has been found to be associated with type 2 diabetes (T2D) and insulin-resistance in genome-wide association studies. We investigated whether this SNP is associated with cardiovascular risk factors and coronary artery disease (CAD) among diabetic individuals. Methods: SNP rs2943641 was typed in 2133 White T2D subjects and tested for association with BMI, serum HDL cholesterol and triglycerides, hypertension history, and CAD risk. Results: HDL cholesterol decreased by 1 mg/dl (p = 0.004) and serum triglycerides increased by 6 mg/dl (p = 0.016) for each copy of the insulin-resistance allele. Despite these effects, no association was found with increased CAD risk (OR = 1.00, 95% CI 0.88-1.13). Conclusions: The insulin-resistance and T2D locus near the IRS1 gene is a determinant of lower HDL cholesterol among T2D subjects. However, this effect is small and does not translate into a detectable increase in CAD risk in this population. (C) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Doria, Alessandro] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Genet & Epidemiol,Div Res, Boston, MA 02115 USA. [Prudente, Sabrina; Mercuri, Luana; Trischitta, Vincenzo] IRCCS Casa Sollievo Sofferenza, Mendel Lab, San Giovanni Rotondo, Italy. [Andreozzi, Francesco; Mannino, Gaia; Succurro, Elena; Sesti, Giorgio] Magna Graecia Univ Catanzaro, Dept Expt & Clin Med, Catanzaro, Italy. [Bacci, Simonetta] IRCCS Casa Sollievo Sofferenza, Unit Endocrinol, San Giovanni Rotondo, Italy. [Gervino, Ernest V.; Hauser, Thomas H.] Beth Israel Deaconess Med Ctr, Div Cardiovasc, Boston, MA 02215 USA. [Gervino, Ernest V.; Hauser, Thomas H.; Shah, Hetal; Doria, Alessandro] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Trischitta, Vincenzo] IRCCS Casa Sollievo Sofferenza, Res Unit Diabet & Endocrine Dis, San Giovanni Rotondo, Italy. [Trischitta, Vincenzo] Univ Roma La Sapienza, Dept Expt Med, Rome, Italy. [Doria, Alessandro] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Doria, A (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Genet & Epidemiol,Div Res, 1 Joslin Pl, Boston, MA 02115 USA. EM alessandro.doria@joslin.harvard.edu RI Sesti, Giorgio/B-1509-2012; Prudente, Sabrina/H-2886-2016; Mannino, Gaia/K-1580-2016; Trischitta, Vincenzo/K-1487-2016; OI Prudente, Sabrina/0000-0001-9220-8981; Mannino, Gaia/0000-0002-6341-4572; Trischitta, Vincenzo/0000-0003-1174-127X; Andreozzi, Francesco/0000-0001-9375-1513; Sesti, Giorgio/0000-0002-1618-7688; Succurro, Elena/0000-0003-2578-692X FU National Institutes of Health [HL73168, DK36836]; Italian Ministry of Health; Fondazione Roma; European Union [LSHM-CT-2004-512013]; NIDDK [T32 DK007260] FX This research was supported by grants from the National Institutes of Health (HL73168 to A. D. and DK36836 to the Genetics Core of the Diabetes & Endocrinology Research Center at the Joslin Diabetes Center), the Italian Ministry of Health ("Ricerca Corrente 2009 and 2010" to S. P and V. T), the Fondazione Roma ("Sostegno alla ricerca scientifica biomedica 2008" to V. T), and the European Union (FP6 EUGENE2 no LSHM-CT-2004-512013 to G. S.). R. S. was supported by the 2010 NIDDK Medical Student Research Program in Diabetes through grant T32 DK007260 to the Joslin Diabetes Center. The content of the paper is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies. We are grateful to Erin Murphy and Alyssa Kanagaki for assistance with the recruitment of study subjects. We acknowledge the invaluable contribution by the individuals who participated in this study. NR 16 TC 12 Z9 12 U1 0 U2 5 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 MAY PY 2011 VL 216 IS 1 BP 157 EP 160 DI 10.1016/j.atherosclerosis.2011.01.022 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 758YV UT WOS:000290205800025 PM 21353221 ER PT J AU Jegga, AG Schneider, L Ouyang, XS Zhang, J AF Jegga, Anil G. Schneider, Lonnie Ouyang, Xiaosen Zhang, Jianhua TI Systems biology of the autophagy-lysosomal pathway SO AUTOPHAGY LA English DT Article DE systems biology; autophagy; lysosome; transcription factors; microRNA ID CATHEPSIN-D DEFICIENCY; ALZHEIMERS-DISEASE; LIPID-METABOLISM; TRANSCRIPTION FACTORS; MICRORNA EXPRESSION; MUSCLE-CELLS; NEURONS; ACCUMULATION; KINASE; GENES AB The mechanisms of the control and activity of the autophagy-lysosomal protein degradation machinery are emerging as an important theme for neurodevelopment and neurodegeneration. However, the underlying regulatory and functional networks of known genes controlling autophagy and lysosoma I function and their role in disease are relatively unexplored. We performed a systems biology-based integrative computational analysis to study the interactions between molecular components and to develop models for regulation and function of genes involved in autophagy and lysosomal function. Specifically, we analyzed transcriptional and microRNA-based post-transcriptional regulation of these genes and performed functional enrichment analyses to understand their involvement in nervous system-related diseases and phenotypes. Transcriptional regulatory network analysis showed that binding sites for transcription factors, SREBP1, USF, AP-1 and NFE2, are common among autophagy and lysosomal genes. MicroRNA enrichment analysis revealed miR-130, 98, 124, 204 and 142 as the putative post-transcriptional regulators of the autophagy-lysosomal pathway genes. Pathway enrichment analyses revealed that the mTOR and insulin signaling pathways are important in the regulation of genes involved in autophagy. In addition, we found that glycosaminoglycan and glycosphingolipid pathways also make a major contribution to lysosoma I gene regulation. The analysis confirmed the known contribution of the autophagy-lysosomal genes to Alzheimer and Parkinson diseases and also revealed potential involvement in tuberous sclerosis, neuronal ceroid-lipofuscinoses, sepsis and lung, liver and prostatic neoplasms. To further probe the impact of autophagy-lysosomal gene deficits on neurologically-linked phenotypes, we also mined the mouse knockout phenotype data for the autophagy-lysosomal genes and found them to be highly predictive of nervous system dysfunction. Overall this study demonstrates the utility of systems biology-based approaches for understanding the autophagy-lysosomal pathways and gaining additional insights into the potential impact of defects in these complex biological processes. C1 [Schneider, Lonnie; Ouyang, Xiaosen; Zhang, Jianhua] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Jegga, Anil G.] Cincinnati Childrens Hosp, Med Ctr, Div Biomed Informat, Cincinnati, OH USA. [Zhang, Jianhua] Univ Alabama Birmingham, Ctr Free Radical Biol, Birmingham, AL 35294 USA. [Ouyang, Xiaosen; Zhang, Jianhua] Birmingham VA Med Ctr, Dept Vet Affairs, Birmingham, AL USA. RP Zhang, J (reprint author), Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. EM zhanja@uab.edu RI zhang, jianhua/D-3404-2009; Jegga, Anil/H-6140-2011; di Ronza, Alberto/H-7674-2016; OI Jegga, Anil/0000-0002-4881-7752; di Ronza, Alberto/0000-0002-9813-5143; Zhang, Jianhua/0000-0002-2128-9574 FU National Institutes of Health [DK078392]; University of Alabama at Birmingham [NIHR01-NS064090]; VA FX We thank Dr. Victor Darley-Usmar for critical discussions and for editing the manuscript. We acknowledge the help of Ron Bryson, Technical Writer, Division of Biomedical Informatics, CCHMC, OH USA, in editing the article. This work was partially supported by the grants from National Institutes of Health DK078392 (Gene Expression and Sequencing Core and Bioinformatics Core, Digestive Disease Research Core Center in Cincinnati) (A.J.), and University of Alabama at Birmingham start-up support, NIHR01-NS064090 and a VA merit award (J.Z.). NR 71 TC 58 Z9 60 U1 1 U2 17 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1554-8627 J9 AUTOPHAGY JI Autophagy PD MAY PY 2011 VL 7 IS 5 BP 477 EP 489 DI 10.4161/auto.7.5.14811 PG 13 WC Cell Biology SC Cell Biology GA 757LW UT WOS:000290087600004 PM 21293178 ER PT J AU Huang, J Johnson, AD O'Donnell, CJ AF Huang, Jie Johnson, Andrew D. O'Donnell, Christopher J. TI PRIMe: a method for characterization and evaluation of pleiotropic regions from multiple genome-wide association studies SO BIOINFORMATICS LA English DT Article ID GENERALIZED ESTIMATING EQUATIONS; GENETIC ASSOCIATION; CHARGE CONSORTIUM; LOCI; PHENOTYPES; TRAITS; VARIANTS; TESTS; RISK AB Motivation: The concept of pleiotropy was proposed a century ago, though up to now there have been insufficient efforts to design robust statistics and software aimed at visualizing and evaluating pleiotropy at a regional level. The Pleiotropic Region Identification Method (PRIMe) was developed to evaluate potentially pleiotropic loci based upon data from multiple genome-wide association studies (GWAS). Methods: We first provide a software tool to systematically identify and characterize genomic regions where low association P-values are observed with multiple traits. We use the term Pleiotropy Index to denote the number of traits with low association P-values at a particular genomic region. For GWAS assumed to be uncorrelated, we adopted the binomial distribution to approximate the statistical significance of the Pleiotropy Index. For GWAS conducted on traits with known correlation coefficients, simulations are performed to derive the statistical distribution of the Pleiotropy Index under the null hypothesis of no genotype-phenotype association. For six hematologic and three blood pressure traits where full GWAS results were available from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, we estimated the trait correlations and applied the simulation approach to examine genomic regions with statistical evidence of pleiotropy. We then applied the approximation approach to explore GWAS summarized in the National Human Genome Research Institute (NHGRI) GWAS Catalog. Results: By simulation, we identified pleiotropic regions including SH2B3 and BRAP (12q24.12) for hematologic and blood pressure traits. By approximation, we confirmed the genome-wide significant pleiotropy of these two regions based on the GWAS Catalog data, together with an exploration on other regions which highlights the FTO, GCKR and ABO regions. C1 [Huang, Jie; Johnson, Andrew D.; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Huang, Jie; Johnson, Andrew D.; O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Bethesda, MD 20824 USA. [O'Donnell, Christopher J.] Harvard Univ, Div Cardiol, Sch Med, Dept Med,Massachusetts Gen Hosp, Boston, MA 02114 USA. RP O'Donnell, CJ (reprint author), NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. EM odonnellc@nhlbi.nih.gov RI Johnson, Andrew/G-6520-2013 FU National Heart, Lung and Blood Institute, Division of Intramural Research FX This project is supported by the National Heart, Lung and Blood Institute, Division of Intramural Research. NR 32 TC 33 Z9 36 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD MAY 1 PY 2011 VL 27 IS 9 BP 1201 EP 1206 DI 10.1093/bioinformatics/btr116 PG 6 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 760NS UT WOS:000290331600002 PM 21398673 ER PT J AU Ma, HS Schadt, EE Kaplan, LM Zhao, HY AF Ma, Haisu Schadt, Eric E. Kaplan, Lee M. Zhao, Hongyu TI COSINE: COndition-SpecIfic sub-NEtwork identification using a global optimization method SO BIOINFORMATICS LA English DT Article ID PROTEIN REFERENCE DATABASE; SET ENRICHMENT ANALYSIS; GENE-EXPRESSION; RACIAL-DIFFERENCES; PROSTATE-CANCER; CANDIDATE GENES; DISEASE; PATHWAYS; POPULATIONS; PROFILES AB Motivation: The identification of condition specific sub-networks from gene expression profiles has important biological applications, ranging from the selection of disease-related biomarkers to the discovery of pathway alterations across different phenotypes. Although many methods exist for extracting these sub-networks, very few existing approaches simultaneously consider both the differential expression of individual genes and the differential correlation of gene pairs, losing potentially valuable information in the data. Results: In this article, we propose a new method, COSINE (COndition SpecIfic sub-NEtwork), which employs a scoring function that jointly measures the condition-specific changes of both 'nodes' (individual genes) and 'edges' (gene-gene co-expression). It uses the genetic algorithm to search for the single optimal sub-network which maximizes the scoring function. We applied COSINE to both simulated datasets with various differential expression patterns, and three real datasets, one prostate cancer dataset, a second one from the across-tissue comparison of morbidly obese patients and the other from the across-population comparison of the HapMap samples. Compared with previous methods, COSINE is more powerful in identifying truly significant sub-networks of appropriate size and meaningful biological relevance. C1 [Zhao, Hongyu] Yale Univ, Dept Epidemiol & Publ Hlth, Dept Genet, New Haven, CT 06520 USA. [Ma, Haisu] Yale Univ, Program Computat Biol & Bioinformat, New Haven, CT 06511 USA. [Schadt, Eric E.] Sage Bionetworks, Seattle, WA USA. [Schadt, Eric E.] Pacific Biosci, Menlo Pk, CA 94025 USA. [Kaplan, Lee M.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Kaplan, Lee M.] Massachusetts Gen Hosp, MGH Weight Ctr, Boston, MA 02114 USA. [Kaplan, Lee M.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. RP Zhao, HY (reprint author), Yale Univ, Dept Epidemiol & Publ Hlth, Dept Genet, New Haven, CT 06520 USA. EM hongyu.zhao@yale.edu FU National Institutes of Health [GM59507]; Chinese Scholarship Council FX The authors are grateful to funding support from National Institutes of Health (GM59507 to H.Z.) and a graduate student fellowship from the Chinese Scholarship Council to H. M. NR 47 TC 31 Z9 32 U1 2 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD MAY 1 PY 2011 VL 27 IS 9 BP 1290 EP 1298 DI 10.1093/bioinformatics/btr136 PG 9 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 760NS UT WOS:000290331600014 PM 21414987 ER PT J AU Coen, JJ Feldman, AS Smith, MR Zietman, AL AF Coen, John J. Feldman, Adam S. Smith, Matthew R. Zietman, Anthony L. TI Watchful waiting for localized prostate cancer in the PSA era: what have been the triggers for intervention? SO BJU INTERNATIONAL LA English DT Article DE prostate cancer; watchful waiting; active surveillance; PSA ID ACTIVE SURVEILLANCE; CONSERVATIVE MANAGEMENT; PATIENTS PERCEPTIONS; ANTIGEN ERA; OUTCOMES; LIFE; MEN AB Circulating tumour cells (CTC) have prognostic relevance for patients with different metastatic carcinomas. Detection of CTC using the CellSearch system has also been reported in bladder cancer, but mainly in patients with metastatic disease. This is the largest report demonstrating that detection of CTC in non-metastatic bladder cancer patients is feasible using the CellSearch system. Presence of CTC may be predictive for early systemic disease. OBJECTIVE To prospectively detect and evaluate the biological significance of circulating tumour cells (CTC) in patients with bladder cancer, especially in those patients with non-metastatic, advanced bladder cancer (NMABC). PATIENTS AND METHODS Between July 2007 and January 2009, blood samples of 50 consecutive patients with localized bladder cancer and five patients with metastatic disease scheduled for cystectomy were prospectively investigated for CTC. Peripheral blood (7.5 ml) was drawn before cystectomy. Detection of CTC was performed using the USA Food and Drug Administration-approved CellSearchTM system. Data were compared with the clinical and histopathological findings. RESULTS CTC were detected in 15 of 50 patients (30%) with non-metastatic disease and five of five patients with metastatic disease. The overall mean number of CTC was 33.7 (range: 1-372; median: 2). In non-metastatic patients, the mean number of CTC was 3.1 (range: 1-11; median: 1). Except for a univariate association between CTC with vessel infiltration (P = 0.047), all other common clinical and histopathological parameters did not reveal a significant correlation with CTC detection. A median 1-year follow up was available for 53 patients (96.4%). Ten out of 19 preoperatively CTC-positive patients died as a result of cancer progression. CTC-positive patients showed significantly worse overall (P = 0.001), progression-free (P < 0.001) and cancer specific survival (P < 0.001) compared to preoperatively CTC-negative patients. CONCLUSION This is the largest study demonstrating that detection of CTC in NMABC patients is feasible using the CellSearchTM system. Our findings suggest that the presence of CTC may be predictive for early systemic disease. C1 [Coen, John J.; Zietman, Anthony L.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Feldman, Adam S.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Smith, Matthew R.] Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02114 USA. RP Coen, JJ (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM jcoen@partners.org FU NCI NIH HHS [K24 CA121990, K24 CA121990-05] NR 18 TC 6 Z9 6 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1464-4096 J9 BJU INT JI BJU Int. PD MAY PY 2011 VL 107 IS 10 BP 1582 EP 1586 DI 10.1111/j.1464-410X.2010.09652.x PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 755AN UT WOS:000289899100009 PM 20860650 ER PT J AU Mirman, D Yee, E Blumstein, SE Magnuson, JS AF Mirman, Daniel Yee, Eiling Blumstein, Sheila E. Magnuson, James S. TI Theories of spoken word recognition deficits in Aphasia: Evidence from eye-tracking and computational modeling SO BRAIN AND LANGUAGE LA English DT Article DE Spoken word recognition; Aphasia; Eye-tracking; Computational models; Growth curve analysis ID SHORT-TERM-MEMORY; SPEECH-PERCEPTION; LEXICAL ACCESS; TIME-COURSE; AUDITORY COMPREHENSION; TRACE MODEL; COMPETITION; ACTIVATION; MOVEMENTS; FMRI AB We used eye-tracking to investigate lexical processing in aphasic participants by examining the fixation time course for rhyme (e.g., carrot-parrot) and cohort (e.g., beaker-beetle) competitors. Broca's aphasic participants exhibited larger rhyme competition effects than age-matched controls. A re-analysis of previously reported data (Yee, Blumstein, & Sedivy, 2008) confirmed that Wernicke's aphasic participants exhibited larger cohort competition effects. Individual-level analyses revealed a negative correlation between rhyme and cohort competition effect size across both groups of aphasic participants. Computational model simulations were performed to examine which of several accounts of lexical processing deficits in aphasia might account for the observed effects. Simulation results revealed that slower deactivation of lexical competitors could account for increased cohort competition in Wernicke's aphasic participants; auditory perceptual impairment could account for increased rhyme competition in Broca's aphasic participants; and a perturbation of a parameter controlling selection among competing alternatives could account for both patterns, as well as the correlation between the effects. In light of these simulation results, we discuss theoretical accounts that have the potential to explain the dynamics of spoken word recognition in aphasia and the possible roles of anterior and posterior brain regions in lexical processing and cognitive control. (C) 2011 Elsevier Inc. All rights reserved. C1 [Mirman, Daniel] Moss Rehabil Res Inst, Elkins Pk, PA 19027 USA. [Yee, Eiling] Univ Penn, Dept Psychol, Philadelphia, PA 19104 USA. [Blumstein, Sheila E.] Brown Univ, Dept Cognit Linguist & Psychol Sci, Providence, RI 02912 USA. [Blumstein, Sheila E.] Res Serv, Dept Vet Affairs Med Ctr, Providence, RI 02908 USA. [Blumstein, Sheila E.] Boston Univ, Harold Goodglass Aphasia Res Ctr, VA Boston Healthcare Syst, Boston, MA 02130 USA. [Blumstein, Sheila E.] Res Serv, VA Boston Healthcare Syst, Boston, MA 02130 USA. [Magnuson, James S.] Univ Connecticut, Dept Psychol, Storrs, CT 06269 USA. [Magnuson, James S.] Haskins Labs Inc, New Haven, CT 06511 USA. RP Mirman, D (reprint author), Moss Rehabil Res Inst, 50 Township Line Rd, Elkins Pk, PA 19027 USA. EM mirmand@einstein.edu RI Magnuson, James/E-5046-2011; Mirman, Daniel/A-2113-2012; Yee, Eiling/F-2161-2010 FU Jacob K. Javits Fellowship; NSF [0748684]; National Institutes of Health [DC005765, HD001994, HD40353, DC00314, DC0081]; Moss Rehabilitation Research Institute; [F32HD052364] FX A preliminary report on this work was presented at the 2008 Meeting of the Cognitive Neuroscience Society (April, 2008, San Francisco, CA). This research was supported by F32HD052364 to DM, a Jacob K. Javits Fellowship to EY, NSF CAREER 0748684 to JSM, National Institutes of Health grants DC005765 to JSM, HD001994 and HD40353 to Haskins Labs, DC00314 to Brown University, and DC0081 to the Boston University School of Medicine, and the Moss Rehabilitation Research Institute. This material is the result of work supported with resources and the use of facilities at the Department of Veterans Affairs Medical Centers in Boston, MA and Providence, RI. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the NIH. We thank Kathy Kurowski and Cara Misiurski for assistance with participant testing, James Dixon for helpful suggestions regarding the growth curve analyses, and Ted Strauss for assistance with the simulations. NR 71 TC 27 Z9 28 U1 1 U2 15 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 MAY PY 2011 VL 117 IS 2 BP 53 EP 68 DI 10.1016/j.bandl.2011.01.004 PG 16 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA 754OM UT WOS:000289864800001 PM 21371743 ER PT J AU Khalili, H Wolpin, BM Huang, ES Giovannucci, EL Kraft, P Fuchs, CS Chan, AT AF Khalili, Hamed Wolpin, Brian M. Huang, Edward S. Giovannucci, Edward L. Kraft, Peter Fuchs, Charles S. Chan, Andrew T. TI ABO Blood Group and Risk of Colorectal Cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID PANCREATIC-CANCER AB Background: Recent studies have shown an association between non-O blood group and risk of pancreatic cancer. It is unclear whether this association is observed with other gastrointestinal malignancies, including colorectal cancers. Methods: We examined the relationship between ABO blood group and the risk of incident colorectal cancer in two large prospective cohorts. We calculated HR using Cox proportional hazard modeling while adjusting for known risk factors of colorectal cancer. Results: During 996,779 person-years of follow-up, we documented 1,025 incident cases of colorectal cancers. Compared to individuals with blood group O, the multivariate-adjusted HR were 1.08 (95% CI, 0.94-1.24) for blood group A, 1.20 (95% CI, 1.00-1.45) for blood group B, and 1.08 (95% CI, 0.85-1.36) for blood group AB. Conclusion: In two large prospective cohorts, we did not observe a statistically significant association between ABO blood group and risk of colorectal cancer. Impact: These results do not support an association between ABO blood group and risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev; 20(5); 1017-20. (C) 2011 AACR. C1 [Chan, Andrew T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Div Gastroenterol, Boston, MA 02114 USA. [Giovannucci, Edward L.; Fuchs, Charles S.; Chan, Andrew T.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA 02115 USA. [Wolpin, Brian M.; Fuchs, Charles S.] Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. [Giovannucci, Edward L.; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Chan, AT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Div Gastroenterol, 55 Fruit St,GRJ-728A, Boston, MA 02114 USA. EM achan@partners.org FU IBD Working Group; [R01 CA137178]; [P01 CA55075]; [P01 CA87969] FX Funded by R01 CA137178, P01 CA55075, P01 CA87969. Dr. Chan is a Damon Runyon Cancer Research Foundation Clinical Investigator. Dr. Khalili is supported by a career development award from the IBD Working Group. NR 12 TC 23 Z9 23 U1 0 U2 4 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 MAY PY 2011 VL 20 IS 5 BP 1017 EP 1020 DI 10.1158/1055-9965.EPI-10-1250 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 759MU UT WOS:000290251000034 PM 21415359 ER PT J AU Spurdle, AB Marquart, L McGuffog, L Healey, S Sinilnikova, O Wan, F Chen, XQ Beesley, J Singer, CF Dressler, AC Gschwantler-Kaulich, D Blum, JL Tung, N Weitzel, J Lynch, H Garber, J Easton, DF Peock, S Cook, M Oliver, CT Frost, D Conroy, D Evans, DG Lalloo, F Eeles, R Izatt, L Davidson, R Chu, C Eccles, D Selkirk, CG Daly, M Isaacs, C Stoppa-Lyonnet, D Sinilnikova, OM Buecher, B Belotti, M Mazoyer, S Barjhoux, L Verny-Pierre, C Lasset, C Dreyfus, H Pujol, P Collonge-Rame, MA Rookus, MA Verhoef, S Kriege, M Hoogerbrugge, N Ausems, MGEM van Os, TA Wijnen, J Devilee, P Meijers-Heijboer, HEJ Blok, MJ Heikkinen, T Nevanlinna, H Jakubowska, A Lubinski, J Huzarski, T Byrski, T Durocher, F Couch, FJ Lindor, NM Wang, XS Thomassen, M Domchek, S Nathanson, K Caligo, MA Jernstrom, H Liljegren, A Ehrencrona, H For, PK Ganz, PA Olopade, OI Tomlinson, G Neuhausen, S Antoniou, AC Chenevix-Trench, G Rebbeck, TR AF Spurdle, Amanda B. Marquart, Louise McGuffog, Lesley Healey, Sue Sinilnikova, Olga Wan, Fei Chen, Xiaoqing Beesley, Jonathan Singer, Christian F. Dressler, Anne-Catharine Gschwantler-Kaulich, Daphne Blum, Joanne L. Tung, Nadine Weitzel, Jeff Lynch, Henry Garber, Judy Easton, Douglas F. Peock, Susan Cook, Margaret Oliver, Clare T. Frost, Debra Conroy, Don Evans, D. Gareth Lalloo, Fiona Eeles, Ros Izatt, Louise Davidson, Rosemarie Chu, Carol Eccles, Diana Selkirk, Christina G. Daly, Mary Isaacs, Claudine Stoppa-Lyonnet, Dominique Sinilnikova, Olga M. Buecher, Bruno Belotti, Muriel Mazoyer, Sylvie Barjhoux, Laure Verny-Pierre, Carole Lasset, Christine Dreyfus, Helene Pujol, Pascal Collonge-Rame, Marie-Agnes Rookus, Matti A. Verhoef, Senno Kriege, Mieke Hoogerbrugge, Nicoline Ausems, Margreet G. E. M. van Os, Theo A. Wijnen, Juul Devilee, Peter Meijers-Heijboer, Hanne E. J. Blok, Marinus J. Heikkinen, Tuomas Nevanlinna, Heli Jakubowska, Anna Lubinski, Jan Huzarski, Tomasz Byrski, Tomasz Durocher, Francine Couch, Fergus J. Lindor, Noralane M. Wang, Xianshu Thomassen, Mads Domchek, Susan Nathanson, Kate Caligo, M. A. Jernstrom, Helena Liljegren, Annelie Ehrencrona, Hans Karlsson, Per Ganz, Patricia A. Olopade, Olufunmilayo I. Tomlinson, Gail Neuhausen, Susan Antoniou, Antonis C. Chenevix-Trench, Georgia Rebbeck, Timothy R. CA GEMO Study Collaborators SWE-BRCA TI Common Genetic Variation at BARD1 Is Not Associated with Breast Cancer Risk in BRCA1 or BRCA2 Mutation Carriers SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID UNKNOWN CLINICAL-SIGNIFICANCE; DNA-SEQUENCE VARIANTS; OVARIAN-CANCER; HAPLOTYPE FREQUENCIES; CYS557SER ALLELE; SUSCEPTIBILITY; IDENTIFICATION; POPULATION; DISEASE; COHORT AB Background: Inherited BRCA1 and BRCA2 (BRCA1/2) mutations confer elevated breast cancer risk. Knowledge of factors that can improve breast cancer risk assessment in BRCA1/2 mutation carriers may improve personalized cancer prevention strategies. Methods: A cohort of 5,546 BRCA1 and 2,865 BRCA2 mutation carriers was used to evaluate risk of breast cancer associated with BARD1 Cys557Ser. In a second nonindependent cohort of 1,537 of BRCA1 and 839 BRCA2 mutation carriers, BARD1 haplotypes were also evaluated. Results: The BARD1 Cys557Ser variant was not significantly associated with risk of breast cancer from single SNP analysis, with a pooled effect estimate of 0.90 (95% CI: 0.71-1.15) in BRCA1 carriers and 0.87 (95% CI: 0.59-1.29) in BRCA2 carriers. Further analysis of haplotypes at BARD1 also revealed no evidence that additional common genetic variation not captured by Cys557Ser was associated with breast cancer risk. Conclusion: Evidence to date does not support a role for BARD1 variation, including the Cy557Ser variant, as a modifier of risk in BRCA1/2 mutation carriers. Impact: Interactors of BRCA1/2 have been implicated as modifiers of BRCA1/2-associated cancer risk. Our finding that BARD1 does not contribute to this risk modification may focus research on other genes that do modify BRCA1/2-associated cancer risk. Cancer Epidemiol Biomarkers Prev; 20(5); 1032-38. (C) 2011 AACR. C1 [Rebbeck, Timothy R.] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Spurdle, Amanda B.; Marquart, Louise; Healey, Sue; Chen, Xiaoqing; Beesley, Jonathan; Chenevix-Trench, Georgia] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [McGuffog, Lesley; Easton, Douglas F.; Peock, Susan; Cook, Margaret; Antoniou, Antonis C.] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England. [Oliver, Clare T.; Frost, Debra; Conroy, Don] Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge, England. [Sinilnikova, Olga] IARC, Lyon, France. [Daly, Mary] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Singer, Christian F.; Dressler, Anne-Catharine; Gschwantler-Kaulich, Daphne] Med Univ Vienna, Vienna, Austria. [Blum, Joanne L.] Baylor Sammons Canc Ctr, Hereditary Canc Risk Program, Dallas, TX USA. [Tomlinson, Gail] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Tung, Nadine] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Garber, Judy; Neuhausen, Susan] Dana Farber Canc Inst, Boston, MA 02115 USA. [Weitzel, Jeff] City Hope Natl Med Ctr, Duarte, CA USA. [Ganz, Patricia A.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. [Ganz, Patricia A.] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. [Ganz, Patricia A.] Jonsson Comprehens Canc Ctr, Los Angeles, CA 90034 USA. [Lynch, Henry] Creighton Univ, Omaha, NE 68178 USA. [Evans, D. Gareth; Lalloo, Fiona] Cent Manchester Univ Hosp NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England. [Eeles, Ros] Inst Canc Res, Oncogenet Team, London SW3 6JB, England. [Eeles, Ros] Royal Marsden NHS Fdn Trust, London, England. [Izatt, Louise] Guys & St Thomas NHS Fdn Trust, London, England. [Davidson, Rosemarie] Yorkhill Hosp, Ferguson Smith Ctr Clin Genet, Glasgow, Lanark, Scotland. [Chu, Carol] Yorkshire Reg Genet Serv, Leeds, W Yorkshire, England. [Eccles, Diana] Princess Anne Hosp, Wessex Clin Genet Serv, Southampton, Hants, England. [Selkirk, Christina G.] Northshore Univ Hlth Syst, Evanston, IL USA. [Olopade, Olufunmilayo I.] Univ Chicago, Chicago, IL 60637 USA. [Isaacs, Claudine] Georgetown Univ, Lombardi Canc Ctr, Washington, DC USA. [Stoppa-Lyonnet, Dominique; Buecher, Bruno; Belotti, Muriel] Univ Paris 05, INSERM, Inst Curie, Serv Genet Oncol,U509, Paris, France. [Sinilnikova, Olga M.; Barjhoux, Laure; Verny-Pierre, Carole] Ctr Hosp Univ Lyon, Ctr Leon Berard, Unite Mixte Genet Constitut Canc Frequents, Lyon, France. [Sinilnikova, Olga M.; Mazoyer, Sylvie; Barjhoux, Laure; Verny-Pierre, Carole] Univ Lyon, CNRS, Ctr Leon Berard, Equipe Labellisee,LIGUE 2008,UMR5201, Lyon, France. [Lasset, Christine] Univ Lyon 1, CNRS, UMR5558, F-69365 Lyon, France. [Lasset, Christine] Ctr Leon Berard, Unite Prevent & Epidemiol Genet, F-69373 Lyon, France. [Dreyfus, Helene] CHU Grenoble, Dept Genet, F-38043 Grenoble, France. [Dreyfus, Helene] Univ Grenoble, Inst Albert Bonniot, Grenoble, France. [Pujol, Pascal] Ctr Hosp Univ Arnaud de Villeneuve, Unite Oncogenet, Montpellier, France. [Pujol, Pascal] CRCM Val dAurelle, INSERM 896, Montpellier, France. CHU Besancon, Serv Genet Histol Biol Dev & Reprod, F-25030 Besancon, France. [GEMO Study Collaborators] Federat Natl Ctr Lutte Canc, GEMO Study Canc Genet Network Grp Genet & Canc, Lyon, France. [Rookus, Matti A.; Verhoef, Senno] Netherlands Canc Inst, Amsterdam, Netherlands. [Meijers-Heijboer, Hanne E. J.] Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands. [Collonge-Rame, Marie-Agnes; Kriege, Mieke] Erasmus MC, Rotterdam, Netherlands. [Hoogerbrugge, Nicoline] Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands. [Ausems, Margreet G. E. M.] Univ Med Ctr Utrecht, Utrecht, Netherlands. [van Os, Theo A.] Amsterdam Med Ctr, Leiden, Netherlands. [Wijnen, Juul; Devilee, Peter] Leiden Univ, Med Ctr, Leiden, Netherlands. [Blok, Marinus J.] Univ Hosp Maastricht, Maastricht, Netherlands. [Heikkinen, Tuomas; Nevanlinna, Heli] Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, FIN-00290 Helsinki, Finland. [Jakubowska, Anna; Lubinski, Jan; Huzarski, Tomasz; Byrski, Tomasz] Pomeranian Med Univ, Int Hereditary Canc Ctr, Dept Genet & Pathol, Szczecin, Poland. [Durocher, Francine] Ctr Hosp Univ Quebec, Quebec City, PQ, Canada. [Durocher, Francine] Univ Laval, Quebec City, PQ, Canada. [Couch, Fergus J.; Lindor, Noralane M.; Wang, Xianshu] Mayo Clin, Rochester, MN USA. [Thomassen, Mads] Odense Univ Hosp, Dept Clin Genet, Odense, Denmark. [Caligo, M. A.] Univ Hosp Pisa, Pisa, Italy. [Jernstrom, Helena] Univ Lund Hosp, S-22185 Lund, Sweden. [Liljegren, Annelie; SWE-BRCA] Karolinska Inst, Karolinska Univ Hosp, Stockholm, Sweden. [Ehrencrona, Hans] Uppsala Univ, Rudbeck Lab, Uppsala, Sweden. [Karlsson, Per] Sahlgrens Univ Hosp, Gothenburg, Sweden. RP Rebbeck, TR (reprint author), Univ Penn, Sch Med, Dept Biostat & Epidemiol, Abramson Canc Ctr, 217 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM rebbeck@mail.med.upenn.edu RI Hoogerbrugge, Nicoline/O-1016-2013; BYRSKI, Tomasz/I-2844-2014; Spurdle, Amanda/A-4978-2011; Ehrencrona, Hans/M-5619-2014; Jakubowska, Anna/O-8050-2014; GLADIEFF, Laurence/O-5129-2014 OI Nordling, Margareta/0000-0002-4047-4994; Eeles, Rosalind/0000-0002-3698-6241; Nathanson, Katherine/0000-0002-6740-0901; Spurdle, Amanda/0000-0003-1337-7897; Nevanlinna, Heli/0000-0002-0916-2976; Evans, Gareth/0000-0002-8482-5784; Ehrencrona, Hans/0000-0002-5589-3622; GLADIEFF, Laurence/0000-0002-6980-9719 FU Nebraska Department of Health and Human Services; NIH [5UO1 CA86389, R01-CA74415, R01-CA102776, R01-CA083855, CA128978]; MUV Comprensive Cancer Center; Austrian Society for Endocrinological Oncology; Cancer Research, UK [C1287/A10118, C1287/A8874, C8197/A10123, C5047/A8385]; NIHR; Royal Marsden NHS Foundation Trust; Ligue National Contre le Cancer; Association for International Cancer Research [AICR-07-0454]; Association "Le cancer du sein, parlons-en!" Award; Dutch Cancer Society [NKI 1998-1854, NKI 2004-3088, NKI 2007-3756]; Helsinki University Central Hospital; Academy of Finland [132473]; Finnish Cancer Society; Sigrid Juselius Foundation; Canadian Institutes of Health Research (CIHR); Fonds de la Recherche en Sante du Quebec (FRSQ)/Reseau de Medecine Genetique Appliquee (RMGA); CURE Foundation; Canadian Breast Cancer Research Alliance (CBCRA); Fonds de la Recherche en Sante du Quebec (FRSQ); CIHR/R&D Health Research Foundation; NHMRC [145684, 288704, 454508]; National Breast Cancer Foundation; Queensland Cancer Fund; Cancer Councils of New South Wales, Victoria; Cancer Councils of New South Wales, Tasmania; Cancer Councils of New South Wales, South Australia; Cancer Foundation of Western Australia; NCI [CA116201]; breast Cancer Research Foundation; Komen Foundation for the cure; [PBZ_KBN_122/P05/2004]; [HHSN21620074400C] FX MAGIC: The MAGIC Consortium includes the following centers and individuals: Baylor-Charles A. Sammons Cancer Center (J.L. Blum, M. D. Ph.D., Estelle Brothers, RN, Gaby Ethington), Baylor College of Medicine (Claire Noll, Sharon Plon, M. D., Ph.D.), Beth Israel Deaconess Medical Center (N. Tung, M. D.), City of Hope National Medical Center (Veronica Lagos, Jeffery Weitzel, M. D.), Creighton University (Carrie Snyder, B. A., H. T. Lynch, M. D., Patrice Watson, Ph.D.), Dana Farber Cancer Institute (Kathryn Stoeckert, J.E. Garber, M. D., M. P. H.), Duke University (Sydnee Crankshaw, Joellen Schildkraut, Ph.D.), NorthShore University Health-System Center for Medical Genetics (Wendy S. Rubinstein, M. D., Ph.D., C. G. Selkirk, M. S. C. G. C.), Fox Chase Cancer Center (M. B. Daly, M. D., Ph.D., Andrew Godwin, Ph.D.), Queensland Institute of Medical Research (G. Chenevix-Trench), Georgetown University (C. Isaacs, M. D.), Jonsson Comprehensive Cancer Center at the University of California, Los Angeles (Joyce Seldon, M. S. C. G. C., P. A. Ganz, M. D.), Mayo Clinic College of Medicine (Linda Wadum, F.J. Couch, Ph.D.), University of Chicago (Shelly Cummings, O.I. Olopade, M. D.), University of California, Irvine (S. L. Neuhausen, Ph.D., Linda Steele), University of Pennsylvania Health System: (S. Domchek, M. D., K. Nathanson M. D., Tara Friebel, M. P. H., T. R. Rebbeck, Ph.D.), University of Texas, Southwestern (G. Tomlinson, M. D.), University of Vienna (C. F. Singer, M. D.), Women's College Hospital (Steven A. Narod, M. D.). This publication was supported in part by revenue from Nebraska cigarette taxes awarded to Creighton University by the Nebraska Department of Health and Human Services. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the State of Nebraska or the Nebraska Department of Health and Human Services. Support was also received from NIH grants 5UO1 CA86389 (to HTL) and R01-CA083855, R01-CA74415 (to SLN) and R01-CA102776 and R01-CA083855 (to T. R. Rebbeck).; Austria MUV: The authors thank Daniela Muhr, Christine Fuerhauser-Rappaport, all the Hereditary Breast and Ovarian Cancer counselling clinics in Austria, and the many families who contributed to this study. This study was supported by the MUV Comprensive Cancer Center (Cluster Genetics and Epigenetics) and by the Austrian Society for Endocrinological Oncology.; EMBRACE: Epidemiologic study of BRCA1 and BRCA2 mutation carriers (EMBRACE): D. F. Easton is the PI of the study. EMBRACE Collaborating Centers are: Coordinating Center, Cambridge: S. Peock, M. Cook, C. T. Oliver, D. Frost. North of Scotland Regional Genetics Service, Aberdeen: Helen Gregory, Zosia Miedzybrodzka. Northern Ireland Regional Genetics Service, Belfast: Patrick Morrison, Lisa Jeffers. West Midlands Regional Clinical Genetics Service, Birmingham: Trevor Cole, Carole McKeown, Kai-Ren Ong, Laura Boyes. South West Regional Genetics Service, Bristol: Alan Donaldson. East Anglian Regional Genetics Service, Cambridge: Joan Paterson. Medical Genetics Services for Wales, Cardiff: Alexandra Murray, Mark T. Rogers, Emma McCann. St James's Hospital, Dublin & National Centre for Medical Genetics, Dublin: M. John Kennedy, David Barton. South East of Scotland Regional Genetics Service, Edinburgh: Mary Porteous. Peninsula Clinical Genetics Service, Exeter: Carole Brewer, Emma Kivuva, Anne Searle, Selina Goodman. West of Scotland Regional Genetics Service, Glasgow: R. Davidson, Victoria Murday, Nicola Bradshaw, Lesley Snadden, Mark Longmuir, Catherine Watt, Sarah Gibson. South East Thames Regional Genetics Service, Guys Hospital London: Louise Izatt, Gabriella Pichert, Chris Jacobs, Caroline Langman. North West Thames Regional Genetics Service, Kennedy-Galton Centre, Harrow: Huw Dorkins. Leicestershire Clinical Genetics Service, Leicester: Julian Barwell. Yorkshire Regional Genetics Service, Leeds: C. Chu, Tim Bishop, Julie Miller. Merseyside & Cheshire Clinical Genetics Service, Liverpool: Ian Ellis, Catherine Houghton. Manchester Regional Genetics Service, Manchester: D. G. Evans, F. Lalloo, Felicity Holt. North East Thames Regional Genetics Service, NE Thames: Alison Male, Lucy Side, Cheryl Berlin. Nottingham Centre for Medical Genetics, Nottingham: Jacqueline Eason, Rebecca Collier. Northern Clinical Genetics Service, Newcastle: Fiona Douglas, Oonagh Claber. Oxford Regional Genetics Service, Oxford: Lisa Walker, Diane McLeod, Dorothy Halliday, Sarah Durrell, Barbara Stayner. The Institute of Cancer Research and Royal Marsden NHS Foundation Trust: R. Eeles, Susan Shanley, Nazneen Rahman, Richard Houlston, Elizabeth Bancroft, Lucia D'Mello, Elizabeth Page, Audrey Ardern-Jones, Kelly Kohut, Jennifer Wiggins. Elena Castro, Anita Mitra, Lisa Robertson. North Trent Clinical Genetics Service, Sheffield: Jackie Cook, Oliver Quarrell, Cathryn Bardsley. South Essex Cancer Research Network, Southend: Anne Robinson. South West Thames Regional Genetics Service, London: Shirley Hodgson, Sheila Goff, Glen Brice, Lizzie Winchester. Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton: D. Eccles, Anneke Lucassen, Gillian Crawford, Emma Tyler, Donna McBride. EMBRACE is funded by Cancer Research, UK grants C1287/A10118 and C1287/A8874. D. Conroy is supported by Cancer Research UK grant C8197/A10123. D. G. Evans and F. Lalloo are supported by an NIHR grant to the Biomedical Research Centre, Manchester. The Investigators at The Institute of Cancer Research and The RoyalMarsden NHS Foundation Trust are supported by an NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. R. Eeles, Elizabeth Bancroft, and Lucia D'Mello are also supported by Cancer Research UK grant C5047/A8385.; GEMO: The GEMO study (Cancer Genetics Network "Groupe Genetique et Cancer,"Federation Nationale des Centres de Lutte Contre le Cancer, France) is supported by the Ligue National Contre le Cancer; Association for International Cancer Research grant (AICR-07-0454); and the Association "Le cancer du sein, parlons-en!" Award.; HEBON: The Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON) Collaborating Centers: Coordinating center: Netherlands Cancer Institute, Amsterdam: Frans B. L. Hogervorst, S. Verhoef, Martijn Verheus, Laura J. van't Veer, Flora E. van Leeuwen, M. A. Rookus; Erasmus Medical Center, Rotterdam: Margriet Collee, Ans M. W. van den Ouweland, Agnes Jager, Maartje J. Hooning, Madeleine M. A. Tilanus-Linthorst, Caroline Seynaeve; Leiden University Medical Center, Leiden: Christi J. van Asperen, J. T. Wijnen, Maaike P. Vreeswijk, Rob A. Tollenaar, P. Devilee; Radboud University Nijmegen Medical Center, Nijmegen: Marjolijn J. Ligtenberg, N. Hoogerbrugge; University Medical Center Utrecht, Utrecht: M. G. E. M. Ausems, Rob B. van der Luijt; Amsterdam Medical Center: Cora M. Aalfs, T. A. van Os; VU University Medical Center, Amsterdam: Johan J. P. Gille, Quinten Waisfisz, H. E. J. Meijers-Heijboer; University Hospital Maastricht, Maastricht: Encarna B. Gomez-Garcia, Cees E. van Roozendaal, M. J. Blok; University Medical Center Groningen University: Jan C. Oosterwijk, Annemarie H. van der Hout, Marian J. Mourits; The Netherlands Foundation for the detection of hereditary tumors, Leiden, the Netherlands: Hans F. Vasen. The HEBON study is supported by the Dutch Cancer Society grants NKI 1998-1854, NKI 2004-3088, and NKI 2007-3756.; HEBCS study was supported by Helsinki University Central Hospital Research Fund, Academy of Finland (132473), the Finnish Cancer Society and the Sigrid Juselius Foundation. The authors thank Drs. Kristiina Aittomaki, Carl Blomqvist, and Kirsimari Aaltonen for their help with patient data and samples.; IHCC: Support was provided by grant PBZ_KBN_122/P05/2004.; INHERIT: The authors thank Dr. Martine Dumont for sample management, Martine Tranchant for skillful technical assistance, and Dr. Frederic Guenard for genotyping. They also thank Dr. Jacques Simard, Director of the INHERIT BRCAs research program, which is supported by the Canadian Institutes of Health Research (CIHR). This work was also supported by the Fonds de la Recherche en Sante du Quebec (FRSQ)/Reseau de Medecine Genetique Appliquee (RMGA), the CURE Foundation, and the Canadian Breast Cancer Research Alliance (CBCRA). F. Durocher is a recipient of a chercheur-boursier from the Fonds de la Recherche en Sante du Quebec (FRSQ) and a Research Career Award in the Health Sciences from CIHR/R&D Health Research Foundation.; kConFab: The authors thank Heather Thorne, Eveline Niedermayr, all the kConFab research nurses and staff, the heads and staff of the Family Cancer Clinics, and the Clinical Follow Up Study (funded by NHMRC grants 145684, 288704, and 454508) for their contributions to this resource, and the many families who contribute to kConFab. kConFab is supported by grants from the National Breast Cancer Foundation, the National Health and Medical Research Council (NHMRC) and by the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. A. B. Spurdle and G. Chenevix-Trench are supported by a NHMRC Senior Research and Principal Research Fellowships, respectively.; Mayo: This research was supported by NIH grant CA128978, and NCI breast cancer specialized program of research excellence (SPORE) CA116201, and grants from the breast Cancer Research Foundation and the Komen Foundation for the cure. The authors thank Zachary Fredericksen, Robert Tarrell, and Vernon S. Pankratz for their assistance.; Penn: This work was supported by HHSN21620074400C (to SMD), the Breast Cancer Research Foundation (to KLN), and R01-CA102776 and R01-CA083855 (to T. R. Rebbeck). NR 21 TC 4 Z9 5 U1 0 U2 7 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 MAY PY 2011 VL 20 IS 5 BP 1032 EP 1038 DI 10.1158/1055-9965.EPI-10-0909 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 759MU UT WOS:000290251000037 PM 21393566 ER PT J AU Chan, AT AF Chan, Andrew T. TI Aspirin and Familial Adenomatous Polyposis: Coming Full Circle SO CANCER PREVENTION RESEARCH LA English DT Article ID SPORADIC COLORECTAL ADENOMAS; DIFLUOROMETHYLORNITHINE PLUS SULINDAC; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; SPONTANEOUS INTESTINAL ADENOMAS; RANDOMIZED CONTROLLED-TRIAL; DOUBLE-BLIND TRIAL; LOW-DOSE ASPIRIN; MIN MOUSE MODEL; CARDIOVASCULAR RISK; SODIUM-SALICYLATE AB This perspective discusses the clinical trial reported by Burn and colleagues in this issue of the journal (beginning on page 655), which assessed aspirin and resistant starch for the prevention of colorectal adenomas in patients with familial adenomatous polyposis (FAP). The findings are examined in the context of previous clinical trials of aspirin in patients with sporadic adenomas and of sulindac or celecoxib in patients with FAP. This newly reported work raises important considerations of a role for aspirin in the clinical management of FAP patients and adds to considerations of a role for aspirin in the chemoprevention of colorectal cancer among broader populations. Cancer Prev Res; 4(5); 623-7. (c) 2011 AACR. C1 [Chan, Andrew T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit,Dep Med, Boston, MA 02114 USA. [Chan, Andrew T.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab,Dept Med, Boston, MA 02114 USA. RP Chan, AT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit,Dep Med, 55 Fruit St, Boston, MA 02114 USA. EM achan@partners.org FU NCI NIH HHS [R01 CA137178-03, R01 CA137178] NR 59 TC 5 Z9 5 U1 0 U2 3 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 MAY PY 2011 VL 4 IS 5 BP 623 EP 627 DI 10.1158/1940-6207.CAPR-11-0157 PG 5 WC Oncology SC Oncology GA 758XP UT WOS:000290201100001 PM 21543340 ER PT J AU Pomerantz, MM Werner, L Xie, WL Regan, MM Lee, GSM Sun, T Evan, C Petrozziello, G Nakabayashi, M Oh, WK Kantoff, PW Freedman, ML AF Pomerantz, Mark M. Werner, Lillian Xie, Wanling Regan, Meredith M. Lee, Gwo-Shu Mary Sun, Tong Evan, Carolyn Petrozziello, Gillian Nakabayashi, Mari Oh, William K. Kantoff, Philip W. Freedman, Matthew L. TI Association of Prostate Cancer Risk Loci with Disease Aggressiveness and Prostate Cancer-Specific Mortality SO CANCER PREVENTION RESEARCH LA English DT Article ID GENOME-WIDE ASSOCIATION; RADICAL PROSTATECTOMY; SUSCEPTIBILITY LOCI; CHROMOSOME 8Q24; MULTIPLE LOCI; VARIANTS; ANTIGEN; IDENTIFICATION; POLYMORPHISMS; PROMOTER AB Genome-wide association studies have detected more than 30 inherited prostate cancer risk variants. While clearly associated with risk, their relationship with clinical outcome, particularly prostate cancer-specific mortality, is less well known. We investigated whether the risk variants are associated with various measures of disease aggressiveness and prostate cancer-specific mortality. In a cohort of 3,945 men of European ancestry with prostate cancer, we genotyped 36 single nucleotide polymorphisms (SNP): 35 known prostate cancer risk variants and one SNP (rs4054823) that was recently reported to be associated with prostate cancer aggressiveness. The majority of subjects had a diagnosis of prostate cancer between 1995 and 2004, and the cohort included a total of 580 prostate cancer-specific deaths. We evaluated associations between the 36 polymorphisms and prostate cancer survival, as well as other clinical parameters including age at diagnosis, prostate-specific antigen (PSA) at diagnosis, and Gleason score. Two SNPs, rs2735839 at chromosome 19(413 and rs7679673 at 4q24, were associated with prostate cancer-specific survival (P = 7 x 10(-4) and 0,014, respectively). A total of 12 SNPs were associated with other variables (P < 0.05): age at diagnosis, PSA at diagnosis, Gleason score, and/or disease aggressiveness based on D'Amico criteria, Genotype status at rs4054823 was not associated with aggressiveness or outcome. Our results identify two common polymorphisms associated with prostate cancer-specific mortality. Cancer Prey Res; 4(5); 719-28. (c) 2011 AACR. C1 [Pomerantz, Mark M.; Lee, Gwo-Shu Mary; Sun, Tong; Evan, Carolyn; Petrozziello, Gillian; Nakabayashi, Mari; Kantoff, Philip W.; Freedman, Matthew L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Werner, Lillian; Xie, Wanling; Regan, Meredith M.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Werner, Lillian; Xie, Wanling; Regan, Meredith M.] Harvard Univ, Sch Med, Boston, MA USA. [Oh, William K.] Mt Sinai Sch Med, Dept Med Oncol, New York, NY USA. RP Freedman, ML (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Dana Bldg Rm 710A,44 Binney St, Boston, MA 02115 USA. EM freedman@broadinstitute.org RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 FU William L. Edwards Prostate Cancer Foundation; Howard Hughes Medical Institute Physician Scientist Early Career Awardee; Doris Duke Clinical Scientist Development Award; NIH [R01 CA129435]; Mayer Foundation; H.L. Snyder Medical Foundation; Emerald Foundation, Inc.; Dana-Farber/Harvard Cancer Center Prostate Cancer SPORE (National Cancer Institute) [5P50CA90381] FX M. Pomerantz is the recipient of the William L. Edwards Prostate Cancer Foundation Young Investigator Award. M.L. Freedman is a Howard Hughes Medical Institute Physician Scientist Early Career Awardee and is a recipient of a 2006 Doris Duke Clinical Scientist Development Award. This is was supported by grants from the NIH (R01 CA129435 to M.L. Freedman), the Mayer Foundation (to M.L. Freedman), the H.L. Snyder Medical Foundation (to M.L. Freedman), the Emerald Foundation, Inc. (to M.L. Freedman), and the Dana-Farber/Harvard Cancer Center Prostate Cancer SPORE (National Cancer Institute Grant 5P50CA90381). NR 40 TC 22 Z9 24 U1 0 U2 3 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 MAY PY 2011 VL 4 IS 5 BP 719 EP 728 DI 10.1158/1940-6207.CAPR-10-0292 PG 10 WC Oncology SC Oncology GA 758XP UT WOS:000290201100012 PM 21367958 ER PT J AU Lee, JE Li, HJ Chan, AT Hollis, BW Lee, IM Stampfer, MJ Wu, K Giovannucci, E Ma, J AF Lee, Jung Eun Li, Haojie Chan, Andrew T. Hollis, Bruce W. Lee, I-Min Stampfer, Meir J. Wu, Kana Giovannucci, Edward Ma, Jing TI Circulating Levels of Vitamin D and Colon and Rectal Cancer: The Physicians' Health Study and a Meta-analysis of Prospective Studies SO CANCER PREVENTION RESEARCH LA English DT Article ID COLORECTAL-CANCER; SUBSEQUENT RISK; VDR GENOTYPES; CALCIUM; PLASMA; 25-HYDROXYVITAMIN-D; CARCINOGENESIS; INHIBITION; PROSTATE; D-3 AB It remains unknown whether increased risk with low levels of vitamin D is present for colon and/or rectal cancer. To investigate the association between circulating vitamin D levels and colon and rectal cancer, we examined the associations between plasma levels of 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] and colon and rectal cancer in the Physicians' Health Study and then conducted a meta-analysis of eight prospective studies of circulating levels of 25(OH)D and colon and rectal cancers, including the Physicians' Health Study. Study-specific ORs and 95% CIs were pooled by using a random-effects model. A total of 1,822 colon and 868 rectal cancers were included in the meta-analysis. We observed a significant inverse association for colorectal cancer (OR = 0.66; 95% Cl, 0.54-0.81), comparing top versus bottom quantiles of circulating 25(OH)D levels. The inverse association stronger for rectal cancer (OR = 0.50 for top versus bottom quantiles; 95% CI, 0.28-0.88) than colon cancer (OR = 0.77; 95% CI, 0.56-1.07; P value for difference between colon and rectal cancer = 0.20). These data suggest an inverse association between circulating 25(OH)D levels and colorectal cancer, with a stronger association for rectal cancer. Cancer Pier Res; 4(5); 735-43. (c) 2011 AACR. C1 [Ma, Jing] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. [Lee, I-Min] Brigham & Womens Hosp, Div Prevent Med, Dept Med, Boston, MA 02115 USA. [Chan, Andrew T.; Lee, I-Min] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Lee, Jung Eun] Sookmyung Womens Univ, Dept Food & Nutr, Seoul, South Korea. [Chan, Andrew T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Stampfer, Meir J.; Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Li, Haojie] GlaxoSmithKline R&D, Worldwide Epidemiol, Collegeville, PA USA. [Hollis, Bruce W.] Med Univ S Carolina, Dept Pediat, Darby Childrens Res Inst, Charleston, SC 29425 USA. RP Ma, J (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. EM jing.ma@channing.harvard.edu OI Lee, Jung Eun/0000-0003-1141-878X FU National Cancer Institute [CA42182, CA90598, CA58684, CA34944, CA40360, CA137178, CA097193]; National Heart, Lung, and Blood Institute [HL26490, HL34595]; Damon Runyon clinical investigator award; National Cancer Institute of Canada [019894]; Prevent Cancer Foundation FX This study was supported by grant CA42182, CA90598, CA58684, CA34944, CA40360, CA137178, and CA097193 from the National Cancer Institute; by grant HL26490 and HL34595 from the National Heart, Lung, and Blood Institute; by Damon Runyon clinical investigator award (ATC); by the National Cancer Institute of Canada (019894) and by Prevent Cancer Foundation fellowship grant (JEL) A.T. Chan is a Damon Runs on Clinical Investigator. NR 33 TC 88 Z9 91 U1 2 U2 10 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 MAY PY 2011 VL 4 IS 5 BP 735 EP 743 DI 10.1158/1940-6207.CAPR-10-0289 PG 9 WC Oncology SC Oncology GA 758XP UT WOS:000290201100014 PM 21430073 ER PT J AU Alam, MM Riyadh, MA Fatema, K Rahman, MA Akhtar, N Ahmed, T Chowdhury, MI Chowdhury, F Calderwood, SB Harris, JB Ryan, ET Qadri, F AF Alam, Mohammad Murshid Riyadh, M. Asrafuzzaman Fatema, Kaniz Rahman, Mohammad Arif Akhtar, Nayeema Ahmed, Tanvir Chowdhury, Mohiul Islam Chowdhury, Fahima Calderwood, Stephen B. Harris, Jason B. Ryan, Edward T. Qadri, Firdausi TI Antigen-Specific Memory B-Cell Responses in Bangladeshi Adults after One- or Two-Dose Oral Killed Cholera Vaccination and Comparison with Responses in Patients with Naturally Acquired Cholera SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID IMMUNOLOGICAL MEMORY; SWEDISH VOLUNTEERS; IMMUNE-RESPONSES; TOXIN ADJUVANT; FIELD TRIAL; IMMUNIZATION; VACCINES; INFECTION; O1; LIPOPOLYSACCHARIDE AB The mediators of protective immunity against cholera are currently unknown, but memory B-cell responses may play a central role in facilitating long-term and anamnestic responses against Vibrio cholerae, the cause of cholera. We compared memory B-cell responses in adults with natural cholera in Bangladesh (n = 70) to responses in Bangladeshi adults after one-dose (n = 30) or two-dose (n = 30) administration of an oral killed cholera vaccine, WC-rBS (Dukoral; Crucell), assessing the responses at the acute stage of disease or prevaccination and then on days 3, 30, 90, 180, 270, and 360. Individuals with natural cholera developed prominent vibriocidal and plasma anti-cholera toxin B subunit (CtxB) and lipopolysaccharide (LPS) IgG and IgA responses, but these responses returned to baseline by 1 year of follow-up. Vaccinees developed plasma anti-CtxB and anti-LPS IgG and IgA responses that were generally comparable to those in individuals recovering from natural disease, but vibriocidal responses were lower in vaccinees than in infected patients. Individuals recovering from natural disease developed memory B-cell IgG and IgA anti-CtxB and anti-LPS responses by day 30, and these responses were detectable through at least days 180 to 360. In contrast, we detected no IgA or IgG memory B-cell responses to LPS in vaccinees; anti-CtxB IgA responses were only detectable on day 30, and anti-CtxB IgG responses were detectable until days 90 to 180, compared to days 270 to 360 in patients. These findings may explain in part the relatively short-term protection afforded by oral cholera vaccination compared to natural disease. C1 [Qadri, Firdausi] Int Ctr Diarrhoeal Dis Res, Div Sci Lab, Immunol Unit, Dhaka 1212, Bangladesh. [Calderwood, Stephen B.; Harris, Jason B.; Ryan, Edward T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Harris, Jason B.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Calderwood, Stephen B.; Ryan, Edward T.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. [Ryan, Edward T.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Qadri, F (reprint author), Int Ctr Diarrhoeal Dis Res, Div Sci Lab, Immunol Unit, 68 Shaheed Tajuddin Ahmed Sarani, Dhaka 1212, Bangladesh. EM fqadri@icddrb.org FU ICDDR,B; National Institutes of Health, including the National Institute of Allergy and Infectious Diseases [AI058935, AI077883]; Fogarty International Center [TW05572, K01]; Swedish Sida FX This study was supported by the ICDDR,B and by grants from the National Institutes of Health, including the National Institute of Allergy and Infectious Diseases (AI058935 [S.B.C., E.T.R., and F.Q.] and AI077883 [E.T.R. and F.Q.]), a training grant in vaccine development from the Fogarty International Center (TW05572 [M.M.A. and F.Q.], and a career development award (K01) from the Fogarty International Center (TW007409 [J.B.H.]). This study was also supported by the Swedish Sida (F.Q.). NR 42 TC 36 Z9 36 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD MAY PY 2011 VL 18 IS 5 BP 844 EP 850 DI 10.1128/CVI.00562-10 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 758IB UT WOS:000290156600021 PM 21346055 ER PT J AU Porwancher, RB Hagerty, CG Fan, JQ Landsberg, L Johnson, BJB Kopnitsky, M Steere, AC Kulas, K Wong, SJ AF Porwancher, Richard B. Hagerty, C. Greg Fan, Jianqing Landsberg, Lisa Johnson, Barbara J. B. Kopnitsky, Mark Steere, Allen C. Kulas, Karen Wong, Susan J. TI Multiplex Immunoassay for Lyme Disease Using VlsE1-IgG and pepC10-IgM Antibodies: Improving Test Performance through Bioinformatics SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID LINKED-IMMUNOSORBENT-ASSAY; BORRELIA-BURGDORFERI; SERODIAGNOSIS; CLASSIFICATION; DIAGNOSIS; PEPTIDE; VLSE; REGRESSION; ACCURACY; CRITERIA AB The Centers for Disease Control and Prevention currently recommends a 2-tier serologic approach to Lyme disease laboratory diagnosis, comprised of an initial serum enzyme immunoassay (EIA) for antibody to Borrelia burgdorferi followed by supplementary IgG and IgM Western blotting of EIA-positive or -equivocal samples. Western blot accuracy is limited by subjective interpretation of weakly positive bands, false-positive IgM immunoblots, and low sensitivity for detection of early disease. We developed an objective alternative second-tier immunoassay using a multiplex microsphere system that measures VlsE1-IgG and pepC10-IgM antibodies simultaneously in the same sample. Our study population comprised 79 patients with early acute Lyme disease, 82 patients with early-convalescent-phase disease, 47 patients with stage II and III disease, 34 patients post-antibiotic treatment, and 794 controls. A bioinformatic technique called partial receiver-operator characteristic (ROC) regression was used to combine individual antibody levels into a single diagnostic score with a single cutoff; this technique enhances test performance when a high specificity is required (e. g., >= 95%). Compared to Western blotting, the multiplex assay was equally specific (95.6%) but 20.7% more sensitive for early-convalescent-phase disease (89.0% versus 68.3%, respectively; 95% confidence interval [95% CI] for difference, 12.1% to 30.9%) and 12.5% more sensitive overall (75.0% versus 62.5%, respectively; 95% CI for difference, 8.1% to 17.1%). As a second-tier test, a multiplex assay for VlsE1-IgG and pepC10-IgM antibodies performed as well as or better than Western blotting for Lyme disease diagnosis. Prospective validation studies appear to be warranted. C1 [Porwancher, Richard B.; Landsberg, Lisa] Infect Dis Consultants PC, Mercerville, NJ 08619 USA. [Porwancher, Richard B.; Hagerty, C. Greg] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Med, Piscataway, NJ 08854 USA. [Fan, Jianqing] Princeton Univ, Dept Operat Res & Financial Engn, Princeton, NJ 08544 USA. [Johnson, Barbara J. B.] Ctr Dis Control & Prevent, Div Vector Borne Dis, Ft Collins, CO USA. [Kopnitsky, Mark] Zeus Sci Inc, Branchburg, NJ USA. [Steere, Allen C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol, Boston, MA USA. [Kulas, Karen; Wong, Susan J.] New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA. RP Porwancher, RB (reprint author), Infect Dis Consultants PC, 1245 Whitehorse Mercerville Rd,Suite 411, Mercerville, NJ 08619 USA. EM porwancher@aol.com FU SBIR-AT-NIAID [1R43AI069564-01, -01S1]; National Institute of Allergy and Infectious Diseases, National Institutes of Health; Zeus Scientific, Inc., to Health Research, Inc., Menands, NY FX Financial support was provided by SBIR-AT-NIAID grants 1R43AI069564-01 and -01S1 to Infectious Disease Consultants, PC, from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, and by a grant from Zeus Scientific, Inc., to Health Research, Inc., Menands, NY, a nonprofit organization which supported the work performed by S.J.W. and K.K. at the NYSDOH, Albany, NY, for this study. NR 41 TC 18 Z9 19 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD MAY PY 2011 VL 18 IS 5 BP 851 EP 859 DI 10.1128/CVI.00409-10 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 758IB UT WOS:000290156600022 PM 21367982 ER PT J AU Chawla, A Sterns, RH Nigwekar, SU Cappuccio, JD AF Chawla, Arun Sterns, Richard H. Nigwekar, Sagar U. Cappuccio, Joseph D. TI Mortality and Serum Sodium: Do Patients Die from or with Hyponatremia? SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID SEVERE SYMPTOMATIC HYPONATREMIA; CENTRAL PONTINE MYELINOLYSIS; CHARLSON COMORBIDITY INDEX; IN-HOSPITAL MORTALITY; RISK-FACTOR; POPULATION; MANAGEMENT; OSTEOPOROSIS; MORBIDITY; FRACTURE AB Background and objectives Severe hyponatremia (<120 mEq/L) in hospitalized patients has a high mortality rate. We hypothesized that underlying diseases causing hyponatremia attribute to mortality rather than hyponatremia itself. Design, setting, participants, & measurements The relationship between mortality and serum sodium (sNa) was examined in 45,693 patients admitted to a single community teaching hospital between January 1996 and December 2007. We conducted a comprehensive retrospective review of the medical records of 53 patients who died after developing sNa <120 mEq/L before or after admission and of 32 patients who survived after developing sNa <110 mEq/L. Results Mortality rates tended to increase as the sNa fell from 134 to 120 mEq/L, rising above 10% for patients with sNa of 120 to 124 mEq/L. However, below sNa of 120 mEq/L, the trend reversed, such that the mortality rate progressively decreased as sNa fell. More than two thirds of patients who died after sNa <120mEq/L had at least two additional acute severe progressive illnesses, most commonly sepsis and multiorgan failure. Three deaths (5.6%) in 12 years could plausibly be related to adverse consequences of hyponatremia, and one (1.8% of the fatal cases and 0.15% of all patients with sNa <120 mEq/L) was from cerebral edema. Most patients who survived with sNa <110 mEq/L had medication-induced hyponatremia. Severe underlying illnesses were uncommon in this group. Conclusions The nature of underlying illness rather than the severity of hyponatremia best explains mortality associated with hyponatremia. Neurologic complications from hyponatremia are uncommon among patients who die with hyponatremia. C1 [Sterns, Richard H.; Nigwekar, Sagar U.; Cappuccio, Joseph D.] Univ Rochester, Rochester Gen Hosp, Sch Med, Rochester, NY 14621 USA. [Chawla, Arun] Hofstra N Shore LIJ Sch Med, Div Nephrol & Hypertens, Great Neck, NY USA. [Nigwekar, Sagar U.] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [Nigwekar, Sagar U.] Brigham & Womens Hosp, Div Nephrol, Boston, MA 02115 USA. RP Sterns, RH (reprint author), Univ Rochester, Rochester Gen Hosp, Sch Med, Rochester, NY 14621 USA. EM richard.sterns@rochestergeneral.org NR 27 TC 76 Z9 78 U1 0 U2 5 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 MAY PY 2011 VL 6 IS 5 BP 960 EP 965 DI 10.2215/CJN.10101110 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 761CK UT WOS:000290372600004 PM 21441132 ER PT J AU Lachin, JM Viberti, G Zinman, B Haffner, SM Aftring, RP Paul, G Kravitz, BG Herman, WH Holman, RR Kahn, SE AF Lachin, John M. Viberti, Giancarlo Zinman, Bernard Haffner, Steven M. Aftring, R. Paul Paul, Gitanjali Kravitz, Barbara G. Herman, William H. Holman, Rury R. Kahn, Steven E. CA ADOPT Study Grp TI Renal Function in Type 2 Diabetes with Rosiglitazone, Metformin, and Glyburide Monotherapy SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID AMBULATORY BLOOD-PRESSURE; GLUCOSE CONTROL; FOLLOW-UP; MICROALBUMINURIA; NEPHROPATHY; COMPLICATIONS; MELLITUS; METAANALYSIS; PROGRESSION; PREVENTION AB Background and objectives In ADOPT (A Diabetes Outcomes Prevention Trial), initial monotherapy with rosiglitazone provided more durable glycemic control than metformin or glyburide in patients with recently diagnosed type 2 diabetes. Herein, we examine differences in albumin excretion, renal function (estimated GFR), and BP over 5 years between treatment groups. Design, setting, participants, & measurements A total of 4351 recently diagnosed, drug-naive patients with type 2 diabetes were treated and followed for up to 5 years with rosiglitazone, metformin, or glyburide and were examined with periodic assessments of albumin/creatinine ratio (ACR), modification of diet in renal disease (MDRD)-estimated GFR, and BP. Results The ACR rose slowly with metformin. It fell with rosiglitazone and less so with glyburide over the first 2 years, and then rose slowly over time. Estimated GFR (eGFR) with all therapies rose into the high normal range over the first 3 to 4 years, more so with rosiglitazone, and then declined, more so with glyburide. Systolic BP was stable over time, values with rosiglitazone being lower, and diastolic BP declined over time, more so with rosiglitazone than with metformin or glyburide. There was no difference among groups in the incidence of emergent albuminuria (ACR >= 30 mg/g), hypertension, or impaired eGFR (<60 ml/min per 1.73 m(2)). Conclusions Over a 5-year period, initial monotherapy with rosiglitazone retards the rise of ACR compared with metformin, preserves eGFR compared with glyburide, and lowers BP relative to both comparators. Clin J Ant Sac Nephrol 6: 1032-1040, 2011. doi: 10.2215/CJN.09291010 C1 [Lachin, John M.] George Washington Univ, Ctr Biostat, Rockville, MD 20852 USA. [Viberti, Giancarlo] Kings Coll London, Kings Coll London Sch Med, London WC2R 2LS, England. [Zinman, Bernard] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Zinman, Bernard] Univ Toronto, Toronto, ON, Canada. [Aftring, R. Paul; Paul, Gitanjali; Kravitz, Barbara G.] GlaxoSmithKline, King Of Prussia, PA USA. [Herman, William H.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Herman, William H.] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Holman, Rury R.] Univ Oxford, Diabet Trials Unit, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. [Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA USA. [Kahn, Steven E.] Univ Washington, Seattle, WA 98195 USA. RP Lachin, JM (reprint author), George Washington Univ, Ctr Biostat, 6110 Execut Blvd, Rockville, MD 20852 USA. EM jml@bsc.gwu.edu RI Zinman, Bernard/E-7266-2013; OI Lachin, John/0000-0001-9838-2841; Kahn, Steven/0000-0001-7307-9002 NR 34 TC 20 Z9 22 U1 0 U2 1 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD MAY PY 2011 VL 6 IS 5 BP 1032 EP 1040 DI 10.2215/CJN.09291010 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 761CK UT WOS:000290372600013 PM 21454723 ER PT J AU Delucchi, KL Katerberg, H Stewart, SE Denys, DAJP Lochner, C Stack, DE den Boer, JA van Balkom, AJLM Jenike, MA Stein, DJ Cath, DC Mathews, CA AF Delucchi, Kevin L. Katerberg, Hilga Stewart, S. Evelyn Denys, Damiaan A. J. P. Lochner, Christine Stack, Denise E. den Boer, Johan A. van Balkom, Anton J. L. M. Jenike, Michael A. Stein, Dan J. Cath, Danielle C. Mathews, Carol A. TI Latent class analysis of the Yale-Brown Obsessive-Compulsive Scale symptoms in obsessive-compulsive disorder SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; COMPLEX SEGREGATION ANALYSIS; FACTOR-ANALYZED SYMPTOM; DSM-IV ADHD; SPECTRUM DISORDERS; DIMENSIONS; SUBTYPES; ADOLESCENTS; HETEROGENEITY; POLYMORPHISM AB Objective: Obsessive-compulsive disorder (OCD) is phenomenologically heterogeneous, and findings of underlying structure classification based on symptom grouping have been ambiguous to date. Variable-centered approaches, primarily factor analysis, have been used to identify homogeneous groups of symptoms; but person-centered latent methods have seen little use. This study was designed to uncover sets of homogeneous groupings within 1611 individuals with OCD based on symptoms. Method: Latent class analysis models using 61 obsessive-compulsive symptoms collected from the Yale-Brown Obsessive-Compulsive Scale were fit. Relationships between latent class membership and treatment response, sex, symptom severity, and comorbid tic disorders were tested for relationship to class membership. Results: Latent class analysis models of best fit yielded 3 classes. Classes differed only in frequency of symptom endorsement. Classes with higher symptom endorsement were associated with earlier age of onset, being male, higher Yale-Brown Obsessive-Compulsive Scale symptom severity scores, and comorbid tic disorders. There were no differences in treatment response between classes. Conclusions: These results provide support for the validity of a single underlying latent OCD construct, in addition to the distinct symptom factors identified previously via factor analyses. (C) 2011 Elsevier Inc. All rights reserved. C1 [Delucchi, Kevin L.; Mathews, Carol A.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Katerberg, Hilga; den Boer, Johan A.] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, Groningen, Netherlands. [Stewart, S. Evelyn; Jenike, Michael A.] Massachusetts Gen Hosp, Obsess Compuls Disorder Clin Adult & Pediat, Boston, MA 02114 USA. [Stewart, S. Evelyn] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Psychiat & Neurodev Genet Unit, Boston, MA USA. [Stewart, S. Evelyn; Stack, Denise E.; Jenike, Michael A.] McLean Hosp, Obsess Compuls Disorder Inst, Belmont, MA 02178 USA. [Denys, Damiaan A. J. P.] Univ Amsterdam, Acad Med Ctr, Dept Psychiat, NL-1105 AZ Amsterdam, Netherlands. [Denys, Damiaan A. J. P.] Netherlands Inst Neurosci, Amsterdam, Netherlands. [Katerberg, Hilga; Lochner, Christine; Stein, Dan J.] Univ Stellenbosch, Dept Psychiat, MRC Unit Anxiety & Stress Disorders, ZA-7600 Stellenbosch, South Africa. [Cath, Danielle C.] Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, GGZ Buitenamstel, Amsterdam, Netherlands. [Stein, Dan J.] Univ Cape Town, Dept Psychiat, ZA-7700 Rondebosch, South Africa. [van Balkom, Anton J. L. M.; Cath, Danielle C.] Univ Utrecht, Dept Clin & Hlth Psychol, Utrecht, Netherlands. [van Balkom, Anton J. L. M.; Cath, Danielle C.] Altrecht Anxiety Outpatient Program, Utrecht, Netherlands. RP Delucchi, KL (reprint author), Univ Calif San Francisco, Dept Psychiat, Box 0984-TRC, San Francisco, CA 94143 USA. EM kdelucchi@lppi.ucsf.edu RI Stewart, Evelyn/K-6961-2014; Stein, Dan/A-1752-2008; OI Stein, Dan/0000-0001-7218-7810; Stewart, S. Evelyn/0000-0002-0994-6383 FU NARSAD; Obsessive Compulsive Foundation; Harvard Scholar in Medicine Program; Canadian Institutes of Health Research FX The authors are grateful to the families with OCD in all of the participating centers who generously agreed to be part of this study. This work was partially supported by funds from NARSAD (CAM), the Obsessive Compulsive Foundation (CAM, SES), the Harvard Scholar in Medicine Program (SES), and the Canadian Institutes of Health Research (SES). NR 63 TC 6 Z9 6 U1 1 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 0010-440X J9 COMPR PSYCHIAT JI Compr. Psychiat. PD MAY-JUN PY 2011 VL 52 IS 3 BP 334 EP 341 DI 10.1016/j.comppsych.2010.06.007 PG 8 WC Psychiatry SC Psychiatry GA 754TS UT WOS:000289880900015 PM 21145539 ER PT J AU Kahn, SE Lachin, JM Zinman, B Haffner, SM Aftring, RP Pau, G Kravitz, BG Herman, WH Viberti, G Holman, RR AF Kahn, Steven E. Lachin, John M. Zinman, Bernard Haffner, Steven M. Aftring, R. Paul Pau, Gitanjali Kravitz, Barbara G. Herman, William H. Viberti, Giancarlo Holman, Rury R. CA ADOPT Study Grp TI Effects of Rosiglitazone, Glyburide, and Meiformin on beta-Cell Function and Insulin Sensitivity in ADOPT SO DIABETES LA English DT Article ID HUMAN PANCREATIC-ISLETS; GLUCOSE-TOLERANCE; DIABETES-MELLITUS; RESISTANCE; SECRETION; METFORMIN; DYSFUNCTION; THERAPY; INDEX AB OBJECTIVE-ADOPT (A Diabetes Outcome Progression Trial) demonstrated that initial monotherapy with rosiglitazone provided superior durability of glycemic control compared with metformin and glyburide in patients with recently diagnosed type 2 diabetes. Herein, we examine measures of beta-cell function and insulin sensitivity from an oral glucose tolerance test (OGTT) over a 4-year period among the three treatments. RESEARCH DESIGN AND METHODS-Recently diagnosed, drug-naive patients with type 2 diabetes (4,360 total) were treated for a median of 4.0 years with rosiglitazone, metformin, or glyburide and were examined with periodic metabolic testing using an OGTT. RESULTS-Measures of beta-cell function and insulin sensitivity from an OGTT showed more favorable changes over time with rosiglitazone versus metformin or glyburide. Persistent improvements were seen in those who completed 4 years of monotherapy and marked deterioration of beta-cell function in those who failed to maintain adequate glucose control with initial monotherapy. CONCLUSIONS-The favorable combined changes in beta-cell function and insulin sensitivity over time with rosiglitazone appear to be responsible for its superior glycemic durability over metformin and glyburide as initial monotherapy in type 2 diabetes. Diabetes 60:1552-1560, 2011 C1 [Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. [Kahn, Steven E.] Univ Washington, Seattle, WA 98195 USA. [Lachin, John M.] George Washington Univ, Ctr Biostat, Rockville, MD USA. [Zinman, Bernard] Univ Toronto, Toronto, ON M5S 1A1, Canada. [Zinman, Bernard] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON, Canada. [Aftring, R. Paul; Pau, Gitanjali; Kravitz, Barbara G.] GlaxoSmithKline Inc, King Of Prussia, PA USA. [Herman, William H.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Herman, William H.] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Viberti, Giancarlo] Kings Coll London, Kings Coll London Sch Med, London WC2R 2LS, England. [Holman, Rury R.] Univ Oxford, Diabet Trials Unit, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. RP Kahn, SE (reprint author), VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. EM skahn@u.washington.edu RI Zinman, Bernard/E-7266-2013; OI Kahn, Steven/0000-0001-7307-9002 FU GlaxoSmithKline FX The study was supported by GlaxoSmithKline. Academic members of the ADOPT Steering Committee have received honoraria, consulting fees, and/or grant/research support from GlaxoSmithKline. R.P.A., G.P., and B.G.K are employees of the company. No other potential conflicts of interest relevant to this article were reported. NR 21 TC 60 Z9 62 U1 0 U2 6 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 2011 VL 60 IS 5 BP 1552 EP 1560 DI 10.2337/db10-1392 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 760UP UT WOS:000290349700023 PM 21415383 ER PT J AU Clermont, A Chilcote, TJ Kita, T Liu, J Riva, P Sinha, S Feener, EP AF Clermont, Allen Chilcote, Tamie J. Kita, Takeshi Liu, Jia Riva, Priscilla Sinha, Sukanto Feener, Edward P. TI Plasma Kallikrein Mediates Retinal Vascular Dysfunction and Induces Retinal Thickening in Diabetic Rats SO DIABETES LA English DT Article ID B-1 RECEPTOR ANTAGONIST; MACULAR EDEMA; KININ SYSTEM; BLOOD-FLOW; FACTOR-XII; DEFICIENT MICE; IN-VIVO; RETINOPATHY; BRADYKININ; PERMEABILITY AB OBJECTIVE Plasma kallikrein (PK) has been identified in vitreous fluid obtained from individuals with diabetic retinopathy and has been implicated in contributing to retinal vascular dysfunction. In this report, we examined the effects of PK on retinal vascular functions and thickness in diabetic rats. RESEARCH DESIGN AND METHODS We investigated the effects of a selective PK inhibitor, ASP-440, and Cl inhibitor (C1-INH), the primary physiological inhibitor of PK, on retinal vascular permeability (RVP) and hemodynamics in rats with streptozotocin-induced diabetes. The effect of intravitreal PK injection on retinal thickness was examined by spectral domain optical coherence tomography. RESULTS Systemic continuous administration of ASP-440 for 4 weeks initiated at the time of diabetes onset inhibited RVP by 42% (P = 0.013) and 83% (P < 0.001) at doses of 0.25 and 0.6 mg/kg per day, respectively. Administration of ASP-440 initiated 2 weeks after the onset of diabetes ameliorated both RVP and retinal blood flow abnormalities in diabetic rats measured at 4 weeks' diabetes duration. Intravitreal injection of C1-INH similarly decreased impaired RVP in rats with 2 weeks' diabetes duration. Intravitreal injection of PK increased both acute RVP and sustained focal RVP (24 h postinjection) to a greater extent in diabetic rats compared with nondiabetic control rats. Intravitreal injection of PK increased retinal thickness compared with baseline to a greater extent (P = 0.017) in diabetic rats (from 193 +/- 10 mu m to 223 +/- 13 mu m) compared with nondiabetic rats (from 182 +/- 8 mu m to 193 +/- 9 mu m). CONCLUSIONS These results show that PK contributes to retinal vascular dysfunctions in diabetic rats and that the combination of diabetes and intravitreal injection of PK in rats induces retinal thickening. Diabetes 60:1590-1598, 2011 C1 [Clermont, Allen; Kita, Takeshi; Liu, Jia; Riva, Priscilla; Feener, Edward P.] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Clermont, Allen; Kita, Takeshi; Liu, Jia; Feener, Edward P.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Chilcote, Tamie J.; Sinha, Sukanto] ActiveSite Pharmaceut, Berkeley, CA USA. RP Feener, EP (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM edward.feener@joslin.harvard.edu FU Juvenile Diabetes Foundation International; National Institutes of Health [EY-19029, DK-36836, HL-090132] FX This work was supported in part by the Juvenile Diabetes Foundation International and the National Institutes of Health (grants EY-19029, DK-36836, and HL-090132). NR 39 TC 30 Z9 30 U1 0 U2 9 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 2011 VL 60 IS 5 BP 1590 EP 1598 DI 10.2337/db10-1260 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 760UP UT WOS:000290349700028 PM 21444925 ER PT J AU Cooper, JD Smyth, DJ Walker, NM Stevens, H Burren, OS Wallace, C Greissl, C Ramos-Lopez, E Hypponen, E Dunger, DB Spector, TD Ouwehand, WH Wang, TJ Badenhoop, K Todd, JA AF Cooper, Jason D. Smyth, Deborah J. Walker, Neil M. Stevens, Helen Burren, Oliver S. Wallace, Chris Greissl, Christopher Ramos-Lopez, Elizabeth Hyppoenen, Elina Dunger, David B. Spector, Timothy D. Ouwehand, Willem H. Wang, Thomas J. Badenhoop, Klaus Todd, John A. TI Inherited Variation in Vitamin D Genes Is Associated With Predisposition to Autoimmune Disease Type 1 Diabetes SO DIABETES LA English DT Article ID GENOME-WIDE ASSOCIATION; MULTIPLE-SCLEROSIS; D DEFICIENCY; 25-HYDROXYVITAMIN-D LEVELS; RHEUMATOID-ARTHRITIS; YOUNG-ADULTS; RISK; CHILDHOOD; CYP27B1; SERUM AB OBJECTIVE Vitamin D deficiency (25-hydroxyvitamin D [25(OH)D] < 50 nmol/L) is commonly reported in both children and adults worldwide, and growing evidence indicates that vitamin D deficiency is associated with many extraskeletal chronic disorders, including the autoimmune diseases type 1 diabetes and multiple sclerosis. RESEARCH DESIGN AND METHODS We measured 25(OH)D concentrations in 720 case and 2,610 control plasma samples and genotyped single nucleotide polymorphisms from seven vitamin D metabolism genes in 8,517 case, 10,438 control, and 1,933 family samples. We tested genetic variants influencing 25(OH)D metabolism for an association with both circulating 25(OH)D concentrations and disease status. RESULTS Type 1 diabetic patients have lower circulating levels of 25(OH)D than similarly aged subjects from the British population. Only 4.3 and 18.6% of type 1 diabetic patients reached optimal levels (>= 75 nmol/L) of 25(OH)D for bone health in the winter and summer, respectively. We replicated the associations of four vitamin D metabolism genes (GC, DHCR7, CYP2R1, and CYP24A1) with 25(OH)D in control subjects. In addition to the previously reported association between type 1 diabetes and CYP27B1 (P = 1.4 x 10(-4)), we obtained consistent evidence of type 1 diabetes being associated with DHCR7 (P = 1.2 x 10(-3)) and CYP2R1 (P = 3.0 x 10(-3)). CONCLUSIONS Circulating levels of 25(OH)D in children and adolescents with type 1 diabetes vary seasonally and are under the same genetic control as in the general population but are much lower. Three key 25(OH)D metabolism genes show consistent evidence of association with type 1 diabetes risk, indicating a genetic etiological role for vitamin D deficiency in type 1 diabetes. Diabetes 60:1624-1631, 2011 C1 [Cooper, Jason D.; Smyth, Deborah J.; Walker, Neil M.; Stevens, Helen; Burren, Oliver S.; Wallace, Chris; Todd, John A.] Univ Cambridge, Addenbrookes Hosp, Cambridge Inst Med Res,Dept Med Genet, Juvenile Diabet Res Fdn,Wellcome Trust Diabet & I, Cambridge CB2 2QQ, England. [Greissl, Christopher; Ramos-Lopez, Elizabeth; Badenhoop, Klaus] Univ Hosp Frankfurt, Div Endocrinol Diabet & Metab, Dept Internal Med 1, Frankfurt, Germany. [Hyppoenen, Elina] UCL, Inst Child Hlth, Ctr Epidemiol Child Hlth, MRC, London, England. [Hyppoenen, Elina] UCL, Inst Child Hlth, Ctr Paediat Epidemiol & Biostat, London, England. [Dunger, David B.] Univ Cambridge, Addenbrookes Hosp, Dept Paediat, Cambridge CB2 2QQ, England. [Spector, Timothy D.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England. [Ouwehand, Willem H.] Univ Cambridge, Dept Haematol, Cambridge, England. [Ouwehand, Willem H.] Wellcome Trust Sanger Inst, Hinxton, England. [Ouwehand, Willem H.] Natl Hlth Serv Blood & Transplant, Cambridge, England. [Wang, Thomas J.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Wang, Thomas J.] Harvard Univ, Sch Med, Boston, MA USA. [Wang, Thomas J.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. RP Todd, JA (reprint author), Univ Cambridge, Addenbrookes Hosp, Cambridge Inst Med Res,Dept Med Genet, Juvenile Diabet Res Fdn,Wellcome Trust Diabet & I, Cambridge CB2 2QQ, England. EM john.todd@cimr.cam.ac.uk RI Hypponen, Elina/B-2596-2014; OI Hypponen, Elina/0000-0003-3670-9399; Walker, Neil/0000-0001-9796-7688; Burren, Oliver/0000-0002-3388-5760; smyth, deborah/0000-0002-6330-2669; Dunger, Professor David/0000-0002-2566-9304; Wallace, Chris/0000-0001-9755-1703; Ouwehand, Willem/0000-0002-7744-1790 FU U.K. Medical Research Council (MRC) [G0000934]; Wellcome Trust [068545/Z/02, 076113/C/04/Z, 076113, 079895]; Wellcome Trust/Juvenile Diabetes Research Foundation [061858]; National Institutes of Health Research of England; Department of Health's National Institute for Health Research (Biomedical Research Centre); Medical Research Council [G0601653]; Food Standards Agency; Department of Health [4243]; Juvenile Diabetes Research Foundation International; National Institute for Health Research Cambridge Biomedical Centre; European Union [241447, 201167]; American Heart Association FX The authors thank the U.K. Medical Research Council (MRC) (grant no. G0000934) and the Wellcome Trust (grant no. 068545/Z/02) for funding the collection of DNA for the British 1958 Birth Cohort. The authors acknowledge use of DNA from the UKBS-CC, funded by the Wellcome Trust (grant 076113/C/04/Z), the Wellcome Trust/Juvenile Diabetes Research Foundation (grant 061858), and the National Institutes of Health Research of England. The collection was established as part of the Wellcome Trust Case-Control Consortium. The authors acknowledge use of DNA from the Human Biological Data Interchange and Diabetes U.K. for the U.S. and U.K. multiplex families, respectively; the Norwegian Study Group for Childhood Diabetes (D. Undlien, University of Oslo, and K. Ronningen, Norwegian Institute of Public Health, Norway) for the Norwegian families; D. Savage of the Belfast Health and Social Care Trust; C. Patterson and D. Carson of Queen's University Belfast; P. Maxwell of Belfast City Hospital for the Northern Irish families; and C. Guja and C. Ionescu-Tirgoviste of the Institute of Diabetes "N Paulescu", Romania, for the Romanian families. Funding for the project was provided by the Wellcome Trust (award no. 076113). The Cambridge Institute for Medical Research is in receipt of a Wellcome Trust Strategic Award (079895). The Great Ormond Street Hospital/University College London, Institute of Child Health receives a proportion of funding from the Department of Health's National Institute for Health Research (Biomedical Research Centre Funding). The Medical Research Council provides funds for the MRC Centre of Epidemiology for Child Health and for the vitamin D genetics project (G0601653). The National Diet and Nutrition Survey was funded by the Food Standards Agency and Department of Health and was accessed through the U.K. Data Archive (study no. 4243). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. J.D.C. was funded by the Juvenile Diabetes Research Foundation International and the Wellcome Trust, the National Institute for Health Research Cambridge Biomedical Centre, and the European Union (FP7-NAIMIT; grant agreement no. 241447). D.J.S., N.M.W., H.S., and J.A.T. were funded by the Juvenile Diabetes Research Foundation International, the Wellcome Trust, and the National Institute for Health Research Cambridge Biomedical Centre. J.A.T. is a Senior Investigator of the National Institute for Health Research. K.B. is funded by the European Union (FP7-NAIMIT and FP7-EURADRENAL; grant agreement no. 241447 and 201167) and T.J.W. by the American Heart Association. E.H. is funded by the Department of Health (U.K.) Public Health Career Scientist Award. NR 50 TC 113 Z9 114 U1 0 U2 10 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 2011 VL 60 IS 5 BP 1624 EP 1631 DI 10.2337/db10-1656 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 760UP UT WOS:000290349700032 PM 21441443 ER PT J AU Beverly, EA Hultgren, BA Brooks, KM Ritholz, MD Abrahamson, MJ Weinger, K AF Beverly, Elizabeth A. Hultgren, Brittney A. Brooks, Kelly M. Ritholz, Marilyn D. Abrahamson, Martin J. Weinger, Katie TI Understanding Physicians' Challenges When Treating Type 2 Diabetic Patients' Social and Emotional Difficulties A qualitative study SO DIABETES CARE LA English DT Article ID GLYCEMIC CONTROL; NEEDS DAWN; DEPRESSION; CARE; METAANALYSIS; PREVALENCE; ATTITUDES; ADHERENCE; SYMPTOMS; BURNOUT AB OBJECTIVE-To explore physicians' awareness of and responses to type 2 diabetic patients' social and emotional difficulties. RESEARCH DESIGN AND METHODS-We conducted semistructured interviews with 19 physicians. Interviews were transcribed, coded, and analyzed using thematic analysis. RESULTS-Three themes emerged: 1) physicians' awareness of patients' social and emotional difficulties: physicians recognized the frequency and seriousness of patients' social and emotional difficulties; 2) physicians' responses to patients' social and emotional difficulties: many reported that intervening with these difficulties was challenging with few treatment options beyond making referrals, individualizing care, and recommending more frequent follow-up visits; and 3) the impact of patients' social and emotional difficulties on physicians: few available patient treatment options, time constraints, and a perceived lack of psychological expertise contributed to physicians' feeling frustrated, inadequate, and overwhelmed. CONCLUSIONS-Recognition and understanding of physicians' challenges when treating diabetes patients' social and emotional difficulties are important for developing programmatic interventions. C1 [Beverly, Elizabeth A.; Hultgren, Brittney A.; Brooks, Kelly M.; Ritholz, Marilyn D.; Abrahamson, Martin J.; Weinger, Katie] Joslin Diabet Ctr, Boston, MA 02215 USA. [Beverly, Elizabeth A.; Ritholz, Marilyn D.; Abrahamson, Martin J.; Weinger, Katie] Harvard Univ, Sch Med, Boston, MA USA. [Ritholz, Marilyn D.] Childrens Hosp, Boston, MA 02115 USA. RP Weinger, K (reprint author), Joslin Diabet Ctr, Boston, MA 02215 USA. EM katie.weinger@joslin.harvard.edu FU The Kathleen P. Welsh Fund; Pfizer FX The Kathleen P. Welsh Fund supported this study. M.J.A. has received research funding from Pfizer and has provided consulting services to Novo Nordisk, sanofi-aventis, Halozyme, and Merck. No other potential conflicts of interest relevant to this article were reported. NR 15 TC 17 Z9 17 U1 3 U2 10 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 MAY PY 2011 VL 34 IS 5 BP 1086 EP 1088 DI 10.2337/dc10-2298 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 761RV UT WOS:000290419200004 PM 21411508 ER PT J AU Becker, JR Deo, RC Werdich, AA Panakova, D Coy, S MacRae, CA AF Becker, Jason R. Deo, Rahul C. Werdich, Andreas A. Panakova, Daniela Coy, Shannon MacRae, Calum A. TI Human cardiomyopathy mutations induce myocyte hyperplasia and activate hypertrophic pathways during cardiogenesis in zebrafish SO DISEASE MODELS & MECHANISMS LA English DT Article ID CARDIAC TROPONIN-T; VENTRICULAR-TACHYCARDIA; GENE-EXPRESSION; MOUSE MODEL; HEART; GROWTH; MICE; MECHANISMS; PHENOTYPES; ARRHYTHMIA AB To assess the effects during cardiac development of mutations that cause human cardiomyopathy, we modeled a sarcomeric gene mutation in the embryonic zebrafish. We designed morpholino antisense oligonucleotides targeting the exon 13 splice donor site in the zebrafish cardiac troponin T (tnnt2) gene, in order to precisely recapitulate a human TNNT2 mutation that causes hypertrophic cardiomyopathy (HCM). HCM is a disease characterized by myocardial hypertrophy, myocyte and myofibrillar disarray, as well as an increased risk of sudden death. Similar to humans with HCM, the morphant zebrafish embryos displayed sarcomere disarray and there was a robust induction of myocardial hypertrophic pathways. Microarray analysis uncovered a number of shared transcriptional responses between this zebrafish model and a well-characterized mouse model of HCM. However, in contrast to adult hearts, these embryonic hearts developed cardiomyocyte hyperplasia in response to this genetic perturbation. The re-creation of a human disease-causing TNNT2 splice variant demonstrates that sarcomeric mutations can alter cardiomyocyte biology at the earliest stages of heart development with distinct effects from those observed in adult hearts despite shared transcriptional responses. C1 [Becker, Jason R.; Deo, Rahul C.; Werdich, Andreas A.; Panakova, Daniela; Coy, Shannon; MacRae, Calum A.] Harvard Univ, Sch Med, Div Cardiol, Massachusetts Gen Hosp, Boston, MA 02129 USA. [Becker, Jason R.] Vanderbilt Univ, Med Ctr, Nashville, TN 37232 USA. [Panakova, Daniela; MacRae, Calum A.] Harvard Univ, Sch Med, Div Cardiol, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Becker, JR (reprint author), Harvard Univ, Sch Med, Div Cardiol, Massachusetts Gen Hosp, Boston, MA 02129 USA. EM jason.r.becker@vanderbilt.edu FU Hypertrophic Cardiomyopathy Center at Massachusetts General Hospital; [T32HL007208] FX We would like to thank Mary McKee for the electron microscopy technical assistance and Jennifer Love for the microarray technical assistance. We would also like to thank Michael Fifer and Barry London for their advice and encouragement. This work was supported by an institutional grant from the Hypertrophic Cardiomyopathy Center at Massachusetts General Hospital (C.A.M.) and T32HL007208 (J.R.B., R.C.D.). NR 36 TC 23 Z9 23 U1 0 U2 10 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 1754-8403 J9 DIS MODEL MECH JI Dis. Model. Mech. PD MAY PY 2011 VL 4 IS 3 BP 400 EP 410 DI 10.1242/dmm.006148 PG 11 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 761EG UT WOS:000290377900016 PM 21245263 ER PT J AU Choma, MA Suter, MJ Vakoc, BJ Bouma, BE Tearney, GJ AF Choma, Michael A. Suter, Melissa J. Vakoc, Benjamin J. Bouma, Brett E. Tearney, Guillermo J. TI Physiological homology between Drosophila melanogaster and vertebrate cardiovascular systems SO DISEASE MODELS & MECHANISMS LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; CARDIAC-OUTPUT; DORSAL VESSEL; HEART; ZEBRAFISH; QUANTIFICATION; IDENTIFICATION; PERFORMANCE; DISEASE; MODEL AB The physiology of the Drosophila melanogaster cardiovascular system remains poorly characterized compared with its vertebrate counterparts. Basic measures of physiological performance remain unknown. It also is unclear whether subtle physiological defects observed in the human cardiovascular system can be reproduced in D. melanogaster. Here we characterize the cardiovascular physiology of D. melanogaster in its pre-pupal stage by using high-speed dye angiography and optical coherence tomography. The heart has vigorous pulsatile contractions that drive intracardiac, aortic and extracellular-extravascular hemolymph flow. Several physiological measures, including weight-adjusted cardiac output, body-length-adjusted aortic velocities and intracardiac shear forces, are similar to those in the closed vertebrate cardiovascular systems, including that of humans. Extracellular-extravascular flow in the pre-pupal D. melanogaster circulation drives convection-limited fluid transport. To demonstrate homology in heart dysfunction, we showed that, at the pre-pupal stage, a troponin I mutant, held-up2 (hdp2), has impaired systolic and diastolic heart wall velocities. Impaired heart wall velocities occur in the context of a non-dilated phenotype with a mildly depressed fractional shortening. We additionally derive receiver operating characteristic curves showing that heart wall velocity is a potentially powerful discriminator of systolic heart dysfunction. Our results demonstrate physiological homology and support the use of D. melanogaster as an animal model of complex cardiovascular disease. C1 [Choma, Michael A.] Yale Univ, Sch Med, Dept Diagnost Radiol, New Haven, CT 06520 USA. [Choma, Michael A.] Childrens Hosp Boston, Boston, MA 02115 USA. [Choma, Michael A.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Suter, Melissa J.; Vakoc, Benjamin J.; Bouma, Brett E.; Tearney, Guillermo J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Suter, Melissa J.; Vakoc, Benjamin J.; Bouma, Brett E.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Vakoc, Benjamin J.; Bouma, Brett E.; Tearney, Guillermo J.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Tearney, Guillermo J.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Choma, MA (reprint author), Yale Univ, Sch Med, Dept Diagnost Radiol, 333 Cedar St, New Haven, CT 06520 USA. EM michael.choma@yale.edu FU NIH [R01HL076398, R01CA103769]; Department of Defense Air Force Office of Scientific Research [FA9550-04-1-0079] FX This work was generously supported by the Frederick H. Lovejoy Fund, Children's Hospital Boston (M. A. C.) and by an American Medical Association Foundation Seed Grant (M. A. C.). We additionally acknowledge funding support from NIH R01HL076398 and NIH R01CA103769 (development of the imaging system) and from the Department of Defense Air Force Office of Scientific Research, Medical Free Electron Laser Program FA9550-04-1-0079. We thank Thorlabs their loan of an OCT system. We thank James Vigoreaux for supplying hdp2 D. melanogaster. NR 46 TC 19 Z9 19 U1 0 U2 6 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 1754-8403 J9 DIS MODEL MECH JI Dis. Model. Mech. PD MAY PY 2011 VL 4 IS 3 BP 411 EP 420 DI 10.1242/dmm.005231 PG 10 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 761EG UT WOS:000290377900017 PM 21183476 ER PT J AU Obstein, KL Estepar, RSJ Jayender, J Patil, VD Spofford, IS Ryan, MB Lengyel, BI Shams, R Vosburgh, KG Thompson, CC AF Obstein, K. L. Estepar, R. S. J. Jayender, J. Patil, V. D. Spofford, I. S. Ryan, M. B. Lengyel, B. I. Shams, R. Vosburgh, K. G. Thompson, C. C. TI Image Registered Gastroscopic Ultrasound (IRGUS) in human subjects: a pilot study to assess feasibility SO ENDOSCOPY LA English DT Article ID NEEDLE ASPIRATION; PANCREATIC MASSES; MENTAL WORKLOAD; COLONOSCOPY; ULTRASONOGRAPHY; NAVIGATION; EFFICIENCY; THERAPY; IMPACT; TASK AB Background and study aims: Endoscopic ultrasound (EUS) is a complex procedure due to the subtleties of ultrasound interpretation, the small field of observation, and the uncertainty of probe position and orientation. Animal studies demonstrated that Image Registered Gastroscopic Ultrasound (IRGUS) is feasible and may be superior to conventional EUS in efficiency and image interpretation. This study explores whether these attributes of IRGUS will be evident in human subjects, with the aim of assessing the feasibility, effectiveness, and efficiency of IRGUS in patients with suspected pancreatic lesions. Patients and methods: This was a prospective feasibility study at a tertiary care academic medical center in human patients with pancreatic lesions on computed tomography (CT) scan. Patients who were scheduled to undergo conventional EUS were randomly chosen to undergo their procedure with IRGUS. Main outcome measures included feasibility, ease of use, system function, validated task load (TLX) assessment instrument, and IRGUS experience questionnaire. Results: Five patients underwent IRGUS without complication. Localization of pancreatic lesions was accomplished efficiently and accurately (TLX temporal demand 3.7 %; TLX effort 8.6 %). Image synchronization and registration was accomplished in real time without procedure delay. The mean assessment score for endoscopist experience with IRGUS was positive (66.6 +/- 29.4). Real-time display of CT images in the EUS plane and echoendoscope orientation were the most beneficial characteristics. Conclusions: IRGUS appears feasible and safe in human subjects, and efficient and accurate at identification of probe position and image interpretation. IRGUS has the potential to broaden the adoption of EUS techniques and shorten EUS learning curves. Clinical studies comparing IRGUS with conventional EUS are ongoing. C1 [Ryan, M. B.; Thompson, C. C.] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. [Obstein, K. L.] Vanderbilt Univ, Med Ctr, Div Gastroenterol, Nashville, TN USA. [Estepar, R. S. J.; Lengyel, B. I.; Vosburgh, K. G.] Brigham & Womens Hosp, Surg Planning Lab, Boston, MA 02115 USA. [Jayender, J.; Patil, V. D.; Vosburgh, K. G.] Massachusetts Gen Hosp, Ctr Integrat Med, Boston, MA 02114 USA. [Jayender, J.; Patil, V. D.; Vosburgh, K. G.] Massachusetts Gen Hosp, Innovat Technol Image Guidance Lab, Boston, MA 02114 USA. [Spofford, I. S.] Massachusetts Gen Hosp, Div Pediat Gastroenterol, Boston, MA 02114 USA. [Shams, R.] Australian Natl Univ, Coll Engn & Comp Sci, Canberra, ACT, Australia. RP Thompson, CC (reprint author), Brigham & Womens Hosp, Div Gastroenterol, 75 Francis St, Boston, MA 02115 USA. EM ccthompson@partners.org FU NCI NIH HHS [R42 CA115112, R25 CA089017]; NCRR NIH HHS [U41 RR019703, P41 RR019703]; NIBIB NIH HHS [P41 EB015898] NR 29 TC 4 Z9 4 U1 2 U2 3 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0013-726X J9 ENDOSCOPY JI Endoscopy PD MAY PY 2011 VL 43 IS 5 BP 394 EP 399 DI 10.1055/s-0030-1256241 PG 6 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 759MM UT WOS:000290249700003 PM 21425041 ER PT J AU Jeffries, MA Dozmorov, M Tang, YH Merrill, JT Wren, JD Sawalha, AH AF Jeffries, Matlock A. Dozmorov, Mikhail Tang, Yuhong Merrill, Joan T. Wren, Jonathan D. Sawalha, Amr H. TI Genome-wide DNA methylation patterns in CD4(+) T cells from patients with systemic lupus erythematosus SO EPIGENETICS LA English DT Article DE lupus; T cells; CD4(+) T cells; methylation; methylome ID MATRIX METALLOPROTEINASES; RHEUMATOID-ARTHRITIS; AUTOIMMUNE-DISEASE; GENE-EXPRESSION; IN-VITRO; OVEREXPRESSION; DEMETHYLATION; LYMPHOCYTES; INFECTION; CD11A AB Systemic lupus erythematosus is a chronic-relapsing autoimmune disease of incompletely understood etiology. Recent evidence strongly supports an epigenetic contribution to the pathogenesis of lupus. To understand the extent and nature of dysregulated DNA methylation in lupus T cells, we performed a genome-wide DNA methylation study in CD4(+) T cells in lupus patients compared to normal healthy controls. Cytosine methylation was quantified in 27,578 CG sites located within the promoter regions of 14,495 genes. We identified 236 hypomethylated and 105 hypermethylated CG sites in lupus CD4(+) T cells compared to normal controls, consistent with widespread DNA methylation changes in lupus T cells. Of interest, hypomethylated genes in lupus T cells include CD9, which is known to provide potent T-cell co-stimulation signals. Other genes with known involvement in autoimmunity such as MMP9 and PDGFRA were also hypomethylated. The BST2 gene, an interferon-inducible membrane-bound protein that helps restrict the release of retroviral particles was also hypomethylated in lupus patients. Genes involved in folate biosynthesis, which plays a role in DNA methylation, were overrepresented among hypermethylated genes. In addition, the transcription factor RUNX3 was hypermethylated in patients, suggesting an impact on T-cell maturation. Protein-protein interaction maps identified a transcription factor, HNF4a, as a regulatory hub affecting a number of differentially methylated genes. Apoptosis was also an overrepresented ontology in these interaction maps. Further, our data suggest that the methylation status of RAB22A, STX1B2, LGALS3BP, DNASE1L1 and PREX1 correlates with disease activity in lupus patients. C1 [Jeffries, Matlock A.; Sawalha, Amr H.] Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA. [Jeffries, Matlock A.; Dozmorov, Mikhail; Wren, Jonathan D.; Sawalha, Amr H.] Oklahoma Med Res Fdn, Arthrit & Clin Immunol Program, Oklahoma City, OK 73104 USA. [Tang, Yuhong] Samuel Roberts Noble Fdn Inc, Oklahoma City, OK USA. [Merrill, Joan T.] Oklahoma Med Res Fdn, Clin Pharmacol Program, Oklahoma City, OK 73104 USA. [Sawalha, Amr H.] US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. RP Sawalha, AH (reprint author), Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA. EM amr-sawalha@omrf.ouhsc.edu RI Wren, Jonathan/E-5611-2011; Dozmorov, Mikhail/B-1374-2009; OI Wren, Jonathan/0000-0003-2776-3545; Dozmorov, Mikhail/0000-0002-0086-8358; Jeffries, Matlock/0000-0001-9516-4312 FU NIH from the National Institute of Allergy and Infectious Diseases [R03AI076729]; NIH [P20RR020143, P30AR053483]; Lupus Research Institute FX This work was made possible by NIH Grant Number R03AI076729 from the National Institute of Allergy and Infectious Diseases and NIH Grants Number P20RR020143 and P30AR053483 and the Lupus Research Institute. We are thankful to the genotyping core at OMRF and in particular to Adam Adler and Kenneth Kaufman, Ph.D., for their help with this study. NR 53 TC 81 Z9 81 U1 0 U2 6 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1559-2294 J9 EPIGENETICS-US JI Epigenetics PD MAY PY 2011 VL 6 IS 5 BP 593 EP 601 DI 10.4161/epi.6.5.15374 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 758YH UT WOS:000290203600009 PM 21436623 ER PT J AU Fifer, MA Sigwart, U AF Fifer, Michael A. Sigwart, Ulrich TI Controversies in cardiovascular medicine Hypertrophic obstructive cardiomyopathy: alcohol septal ablation SO EUROPEAN HEART JOURNAL LA English DT Review DE Alcohol septal ablation; Hypertrophic cardiomyopathy; Hypertrophic obstructive cardiomyopathy ID MYOCARDIAL CONTRAST ECHOCARDIOGRAPHY; VENTRICULAR OUTFLOW TRACT; COMPLETE HEART-BLOCK; REDUCTION THERAPY; TRANSCORONARY ABLATION; FOLLOW-UP; DIASTOLIC FUNCTION; TIME-COURSE; MYECTOMY; EXPERIENCE AB Alcohol septal ablation (ASA) was introduced in 1994 as an alternative to septal myectomy for patients with hypertrophic obstructive cardiomyopathy and symptoms refractory to medical therapy. This procedure alleviates symptoms by producing a targeted, limited infarction of the upper interventricular septum, resulting in an increase in left ventricular outflow tract (LVOT) diameter, a decrease in LVOT gradient, and regression of the component of LV hypertrophy that is due to pressure overload. Clinical success, with improvement in symptoms and reduction in gradient, is achieved in the great majority of patients with either resting or provocable LVOT obstruction. The principal morbidity of the procedure is complete heart block, resulting in some patients in the requirement for a permanent pacemaker. The introduction of myocardial contrast echocardiography as a component of the ASA procedure has contributed to the induction of smaller myocardial infarctions with lower dosages of alcohol and, in turn, fewer complications. Non-randomized comparisons of septal ablation and septal myectomy have shown similar mortality rates and post-procedure New York Heart Association class for the two procedures. C1 [Sigwart, Ulrich] Univ Geneva, Ctr Cardiol, Geneva, Switzerland. [Fifer, Michael A.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Fifer, Michael A.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Sigwart, U (reprint author), Univ Geneva, Ctr Cardiol, Geneva, Switzerland. EM ulrich.sigwart@unige.ch NR 88 TC 26 Z9 27 U1 1 U2 7 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 MAY PY 2011 VL 32 IS 9 BP 1059 EP U44 DI 10.1093/eurheartj/ehr013 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 760HR UT WOS:000290315900010 PM 21447511 ER PT J AU Cooley, J Sontag, MK Accurso, FJ Remold-O'Donnell, E AF Cooley, J. Sontag, M. K. Accurso, F. J. Remold-O'Donnell, E. TI SerpinB1 in cystic fibrosis airway fluids: quantity, molecular form and mechanism of elastase inhibition SO EUROPEAN RESPIRATORY JOURNAL LA English DT Article DE Cystic fibrosis; elastase; neutrophil serine proteases; protease inhibitors; Serpin ID NEUTROPHIL ELASTASE; LUNG-DISEASE; SERINE PROTEASES; ACTIVE-SITE; PROTEINS; MNEI; PSEUDOMONAS; SPUTUM; EXPRESSION; INFECTION AB Neutrophil serine proteases (NSPs), especially elastase, are major agents of lung destruction in cystic fibrosis (CF) patients. This study investigated SerpinB1, a highly efficient inhibitor of NSPs, in CF lung disease. Bronchoalveolar lavage fluid (BALF) from 31 children with CF and 24 control children was examined for amount and molecular species of SerpinB1, and its mechanism of action was studied. CF BALF had more SerpinB1 than control BALF (geometric mean 3.9 (95% CI 2.60-5.62) versus 1.37 (1.20-1.55) mu g.mL(-1); p < 0.001). BALF levels of SerpinB1 were higher for infected versus uninfected CF subjects (5.5 versus 2.7 mu g.mL(-1); p < 0.04) and substantially higher for elastase-positive versus -negative CF subjects (8.41 versus 1.89 mu g.mL(-1); p < 0.001). Most SerpinB1 in CF BALF had been cleaved. Adding recombinant SerpinB1 to CF BALF stoichiometrically inhibited endogenous elastase, indicating that the inhibitor functions in the CF microenvironment. In vitro simulations comparing SerpinB1 and alpha(1)-antitrypsin (SerpinA1) showed that both rapidly form irreversible inhibitory covalent complexes with elastase and that these differed in survival time. The SerpinB1-elastase complex survived only briefly due to fragmentation of bound elastase, releasing cleaved SerpinB1, the molecular form in CF BALF. The findings define an innate role for SerpinB1 in CF airways. C1 [Cooley, J.; Remold-O'Donnell, E.] Childrens Hosp Boston, Immune Dis Inst, Boston, MA 02115 USA. [Cooley, J.; Remold-O'Donnell, E.] Childrens Hosp Boston, Program Cellular & Mol Med, Boston, MA 02115 USA. [Remold-O'Donnell, E.] Harvard Univ, Sch Med, Dept Paediat, Boston, MA USA. [Sontag, M. K.] Univ Colorado, Colorado Sch Publ Hlth, Dept Epidemiol, Aurora, CO USA. [Accurso, F. J.] Childrens Hosp, Dept Paediat, Aurora, CO USA. [Accurso, F. J.] Univ Colorado Denver, Sch Med, Aurora, CO USA. RP Remold-O'Donnell, E (reprint author), Childrens Hosp Boston, Immune Dis Inst, 3 Blackfan Circle,3rd Floor, Boston, MA 02115 USA. EM remold@idi.harvard.edu FU National Institutes of Health [HL066548, HL41579, HL081335, RR0069]; Cystic Fibrosis Foundation FX The study was supported by National Institutes of Health (grants HL066548, HL41579, HL081335 and RR0069) and the Cystic Fibrosis Foundation. NR 33 TC 11 Z9 11 U1 0 U2 3 PU EUROPEAN RESPIRATORY SOC JOURNALS LTD PI SHEFFIELD PA 442 GLOSSOP RD, SHEFFIELD S10 2PX, ENGLAND SN 0903-1936 J9 EUR RESPIR J JI Eur. Resp. J. PD MAY PY 2011 VL 37 IS 5 BP 1083 EP 1090 DI 10.1183/09031936.00073710 PG 8 WC Respiratory System SC Respiratory System GA 757MI UT WOS:000290089200016 PM 20817705 ER PT J AU Kwon, JY Myerson, MS AF Kwon, John Y. Myerson, Mark S. TI Talar Neck Fracture After Tibiotalar Arthrodesis: Case Report SO FOOT & ANKLE INTERNATIONAL LA English DT Article DE Tatar Neck Fracture; Tibiotalar Arthrodesis ID TALUS FRACTURES; ANKLE ARTHRODESIS; INTRAMEDULLARY NAIL; FOLLOW-UP; FIXATION; HINDFOOT C1 [Kwon, John Y.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Kwon, JY (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, 55 Fruit St, Boston, MA 02114 USA. EM jkwon@partners.org NR 27 TC 0 Z9 0 U1 0 U2 0 PU AMER ORTHOPAEDIC FOOT & ANKLE SOC, INC PI SEATTLE PA 2517 EASTLAKE AVE EAST, STE 200, SEATTLE, WA 98102 USA SN 1071-1007 J9 FOOT ANKLE INT JI Foot Ankle Int. PD MAY PY 2011 VL 32 IS 5 BP 560 EP 563 DI 10.3113/FAI.2011.0560 PG 4 WC Orthopedics SC Orthopedics GA 758DC UT WOS:000290139700016 ER PT J AU Nguyen, DM El-Serag, HB Shub, M Integlia, M Henderson, L Richardson, P Fairly, K Gager, MA AF Nguyen, Dang M. El-Serag, Hashem B. Shub, Mitchell Integlia, Mark Henderson, Louise Richardson, Peter Fairly, Kenneth Gager, Mark A. TI Barrett's esophagus in children and adolescents without neurodevelopmental or tracheoesophageal abnormalities: a prospective study SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID GASTROESOPHAGEAL-REFLUX DISEASE; NATURAL-HISTORY; PREVALENCE; CHILDHOOD; SYMPTOMS; POPULATION; DEFINITION; METAPLASIA; VALIDATION; GERD AB Background: Barrett's esophagus (BE) in children has been examined in retrospective studies, consisting of case series and cross-sectional studies. Objective: To evaluate the prevalence and determinants of BE in children who are free from neurodevelopmental disorders and tracheoesophageal abnormalities. Design: A prospective, cross-sectional study. Setting: Three pediatric GI Centers in Houston, Texas; Phoenix, Arizona; and Portland, Maine between February 2006 and December 2007. Patients: This study involved children and adolescents consecutively presenting for elective upper endoscopy. Patients with neurodevelopmental and tracheoesophageal disorders were excluded. Intervention: Endoscopic pictures of all cases with suspected BE were independently reviewed and verified by two experienced investigators. Esophageal biopsy specimens were obtained in all patients, and targeted biopsy specimens also were obtained from suspected BE. Main Outcome Measurements: Endoscopically suspected BE and histologically confirmed BE. Results: A total of 840 patients (mean age 9.5 years) were enrolled and had complete questionnaire and endoscopic data. Twelve patients were suspected of having BE (prevalence of 1.43%; 95% confidence interval [CI], 0.73-2.45), and only 1 patient had intestinal metaplasia, for a prevalence of 0.12% (95% Cl, 0-0.65), whereas the rest had gastric oxyntic glands (n = 6) or squamous esophageal epithelium (n = 5). Patients with suspected BE had a higher mean body mass index (23.0 vs 19.1, P =.05) and more chest pain (50% vs 13%, P < .01.) than patients without BE or reflux esophagitis. There was a trend toward a higher frequency of dysphagia, heartburn, and regurgitation in patients with suspected BE. Limitations: The accuracy of BE prevalence estimates is limited by the small number of cases. Conclusion: BE is rare in children without neurodevelopmental delay or tracheoesophageal anomalies presenting for elective upper endoscopy. (Gastrointest Enclose 201:1;73:875-80.) C1 [El-Serag, Hashem B.; Richardson, Peter] Michael E DeBakey Vet Affairs Med Ctr 152, Houston, TX 77030 USA. [Nguyen, Dang M.; El-Serag, Hashem B.; Richardson, Peter; Fairly, Kenneth; Gager, Mark A.] Baylor Coll Med, Houston, TX 77030 USA. [Fairly, Kenneth; Gager, Mark A.] Texas Childrens Hosp, Houston, TX 77030 USA. [Integlia, Mark] Barbara Bush Childrens Hosp, Portland, ME USA. [Shub, Mitchell] Phoenix Childrens Hosp, Phoenix, AZ USA. [Henderson, Louise] Univ N Carolina, Chapel Hill, NC USA. RP El-Serag, HB (reprint author), Michael E DeBakey Vet Affairs Med Ctr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. FU NIH [1-R03-DK068148-01]; Texas Gulf Coast Digestive Diseases Center [NIH P50 DK56338]; Houston Veterans Affairs HSR&D center of Excellence [HFP90-020] FX M. Gilger and H. El-Serag are supported by grants R03 (NIH 1-R03-DK068148-01). H. El-Serag also is supported in part by grants from the Texas Gulf Coast Digestive Diseases Center (NIH P50 DK56338) and the Houston Veterans Affairs HSR&D center of Excellence (HFP90-020). No other financial relationships relevant to this publication were disclosed. NR 22 TC 7 Z9 7 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 EI 1097-6779 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD MAY PY 2011 VL 73 IS 5 BP 875 EP 880 DI 10.1016/j.gie.2011.01.017 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 760AK UT WOS:000290292800004 PM 21354565 ER PT J AU Koh, H Hayashi, T Sato, KK Harita, N Maeda, I Nishizawa, Y Endo, G Fujimoto, WY Boyko, EJ Hikita, Y AF Koh, Hideo Hayashi, Tomoshige Sato, Kyoko Kogawa Harita, Nobuko Maeda, Isseki Nishizawa, Yoshiki Endo, Ginji Fujimoto, Wilfred Y. Boyko, Edward J. Hikita, Yonezo TI Visceral adiposity, not abdominal subcutaneous fat area, is associated with high blood pressure in Japanese men: the Ohtori study SO HYPERTENSION RESEARCH LA English DT Article DE computed tomography; epidemiology; high normal blood pressure; visceral adiposity ID CORONARY-HEART-DISEASE; BODY-FAT; RISK-FACTORS; FOLLOW-UP; WAIST CIRCUMFERENCE; INSULIN-RESISTANCE; METABOLIC SYNDROME; DIABETES-MELLITUS; VASCULAR-DISEASE; HYPERTENSION AB Visceral adiposity is considered to have a key role in cardiometabolic diseases. The purpose of this study is to investigate cross-sectionally the association between intra-abdominal fat area (IAFA) measured by computed tomography (CT) and high blood pressure independent of abdominal subcutaneous fat area (ASFA) and insulin resistance. Study participants included 624 Japanese men not taking oral hypoglycemic medications or insulin. Abdominal, thoracic and thigh fat areas were measured by CT. Total fat area (TFA) was calculated as the sum of abdominal, thoracic and thigh fat area. Total subcutaneous fat area (TSFA) was defined as TFA minus IAFA. Hypertension and high normal blood pressure were defined using the 1999 criteria of the World Health Organization. Multiple-adjusted odds ratios of hypertension for tertiles of IAFA were 2.64 (95% confidence interval, 1.35-5.16) for tertile 2, and 5.08 (2.48-10.39) for tertile 3, compared with tertile 1 after adjusting for age, fasting immunoreactive insulin, diabetes status, ASFA, alcohol consumption, regular physical exercise and smoking habit. IAFA remained significantly associated with hypertension even after adjustment for ASFA, TSFA, TFA, body mass index or waist circumference, and no other measure of regional or total adiposity was associated with the odds of hypertension in models, which included IAFA. Similar results were obtained for the association between IAFA and the prevalence of high normal blood pressure or hypertension. In conclusion, greater visceral adiposity was associated with a higher odds of high blood pressure in Japanese men. Hypertension Research (2011) 34, 565-572; doi:10.1038/hr.2010.271; published online 13 January 2011 C1 [Hayashi, Tomoshige] Osaka City Univ, Grad Sch Med, Dept Prevent Med & Environm Hlth, Abeno Ku, Osaka 5458585, Japan. [Hayashi, Tomoshige; Boyko, Edward J.] Vet Affairs Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA USA. [Nishizawa, Yoshiki] Osaka City Univ, Grad Sch Med, Dept Metab Endocrinol & Mol Med, Osaka 5458585, Japan. [Fujimoto, Wilfred Y.; Boyko, Edward J.] Univ Washington, Dept Med, Seattle, WA USA. [Hikita, Yonezo] Ohtori Hlth Promot Ctr, Sakai, Osaka, Japan. RP Hayashi, T (reprint author), Osaka City Univ, Grad Sch Med, Dept Prevent Med & Environm Hlth, Abeno Ku, 1-4-3 Asahi Machi, Osaka 5458585, Japan. EM thayashi@med.osaka-cu.ac.jp RI Hayashi, Tomoshige/N-8508-2015 FU Ministry of Education, Culture, Sports, Science and Technology [17390177, 20390187] FX This work was supported by a Grant-in-Aid for Scientific Research (17390177, 20390187) from the Ministry of Education, Culture, Sports, Science and Technology, as well as by the facilities and services provided by the Ohtori Health Promotion Center. The funding sources had no role in the decision to submit the paper for publication. We thank the participants in the Ohtori Study for their dedication. NR 43 TC 10 Z9 11 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0916-9636 J9 HYPERTENS RES JI Hypertens. Res. PD MAY PY 2011 VL 34 IS 5 BP 565 EP 572 DI 10.1038/hr.2010.271 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 759MQ UT WOS:000290250200006 PM 21228782 ER PT J AU Bhan, I Camargo, CA Wenger, J Ricciardi, C Ye, J Borregaard, N Thadhani, R AF Bhan, Ishir Camargo, Carlos A., Jr. Wenger, Julia Ricciardi, Catherine Ye, Jun Borregaard, Niels Thadhani, Ravi TI Circulating levels of 25-hydroxyvitamin D and human cathelicidin in healthy adults SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter ID VITAMIN-D; ANTIMICROBIAL PEPTIDE; PLASMA; HCAP18 C1 [Bhan, Ishir; Ye, Jun; Thadhani, Ravi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nephrol,Dept Med, Boston, MA 02115 USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol,Dept Med, Boston, MA USA. [Ricciardi, Catherine] MIT, Clin Res Ctr, Cambridge, MA 02139 USA. [Borregaard, Niels] Univ Copenhagen, Dept Hematol, Rigshosp, DK-1168 Copenhagen, Denmark. RP Bhan, I (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nephrol,Dept Med, Boston, MA 02115 USA. EM ibhan@partners.org FU NIDDK NIH HHS [K23 1K23DK081677, K23 DK081677, K23 DK081677-02] NR 9 TC 39 Z9 42 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 MAY PY 2011 VL 127 IS 5 BP 1302 EP 1304 DI 10.1016/j.jaci.2010.12.1097 PG 4 WC Allergy; Immunology SC Allergy; Immunology GA 756NG UT WOS:000290018600030 PM 21310475 ER PT J AU Klingman, KM Marsh, EE Klerman, EB Anderson, EJ Hall, JE AF Klingman, Kara M. Marsh, Erica E. Klerman, Elizabeth B. Anderson, Ellen J. Hall, Janet E. TI Absence of Circadian Rhythms of Gonadotropin Secretion in Women SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID LUTEINIZING-HORMONE SECRETION; FREE ALPHA-SUBUNIT; FOLLICLE-STIMULATING-HORMONE; POSTMENOPAUSAL WOMEN; INHIBIN-B; PULSE FREQUENCY; MENSTRUAL-CYCLE; SLEEP; PHASE; MEN AB Context: Diurnal rhythms of LH and FSH have been reported in normal women, but it is unclear whether these reflect underlying circadian control from the suprachiasmatic nucleus and/or external influences. Objective: The aim of this study was to determine whether endogenous circadian rhythms of LH, FSH, and the glycoprotein free alpha-subunit (FAS) are present in reproductive-aged women. Design and Setting: Subjects were studied in the early follicular phase using a constant routine protocol in a Clinical Research Center at an academic medical center. Subjects: Subjects were healthy, normal-cycling women aged 23-29 yr (n = 11). Main Outcome Measures: Temperature data were collected, and blood samples were assayed for LH, FSH, FAS, and TSH. Results: Core body temperature and TSH were best fit by a sinusoid model, indicating that known circadian rhythms were present in this population. However, the patterns of FSH, LH, and FAS over 24 h were best fit by a linear model. Furthermore, there were no differences in LH and FAS interpulse intervals or pulse amplitudes between evening, night, and morning. Conclusions: Under conditions that control for sleep/wake, light/dark, activity, position, and nutritional cues, there is no circadian rhythm of LH, FSH, or FAS in women during the early follicular phase despite the presence of endogenous rhythms of TSH and core body temperature. These studies indicate that endogenous circadian control does not contribute to previously reported diurnal rhythms in reproductive-aged women and emphasizes the importance of environmental cues in controlling normal reproductive function. (J Clin Endocrinol Metab 96: 1456-1461, 2011) C1 [Klingman, Kara M.; Marsh, Erica E.; Hall, Janet E.] Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. [Marsh, Erica E.] Northwestern Univ, Div Reprod Endocrinol & Infertil, Dept Obstet & Gynecol, Feinberg Sch Med, Chicago, IL 60611 USA. [Klerman, Elizabeth B.] Brigham & Womens Hosp, Div Sleep Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. [Anderson, Ellen J.] Massachusetts Gen Hosp, Mallinkrodt Clin Res Ctr, Boston, MA 02114 USA. RP Hall, JE (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, BHX-5,55 Fruit St, Boston, MA 02114 USA. EM jehall@partners.org FU National Institutes of Health (NIH) [R01-AG-13241, M01 RR 01066, NIH P01-AG009975, NIH K02-HD045459, NIH R01-HD40291] FX This work was supported by National Institutes of Health (NIH) Grant R01-AG-13241, M01 RR 01066, and NIH P01-AG009975, NIH K02-HD045459, and NIH R01-HD40291 (to E.B.K.). NR 44 TC 10 Z9 10 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 2011 VL 96 IS 5 BP 1456 EP 1461 DI 10.1210/jc.2010-2739 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 759AE UT WOS:000290210600050 PM 21346063 ER PT J AU Tritos, NA Greenspan, SL King, D Hamrahian, A Cook, DM Jonsson, PJ Wajnrajch, MP Koltowska-Haggstrom, M Biller, BMK AF Tritos, Nicholas A. Greenspan, Susan L. King, Donna Hamrahian, Amir Cook, David M. Jonsson, Peter J. Wajnrajch, Michael P. Koltowska-Haggstrom, Maria Biller, Beverly M. K. TI Unreplaced Sex Steroid Deficiency, Corticotropin Deficiency, and Lower IGF-I Are Associated with Lower Bone Mineral Density in Adults with Growth Hormone Deficiency: A KIMS Database Analysis SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID RADIOLOGICAL SPINAL DEFORMITIES; GH REPLACEMENT THERAPY; HYPOPITUITARISM; STANDARDIZATION; PROLIFERATION; MULTICENTER; CHILDHOOD; ONSET; MICE; MASS AB Context: GH deficiency (GHD) is associated with low bone mineral density (BMD). Risk factors for lower BMD in this GHD population have not been fully elucidated. In particular, there are limited published data in GH-naive subjects. Objective: The objective of the study was to identify endocrine correlates of low BMD in treatment naive adult GHD subjects. Design: This was a retrospective analysis of data extracted from the (Pfizer International Metabolic Study) KIMS database. Setting: The study was an international epidemiological survey of more than 15,000 adult GHD patients from 31 countries. Patients: A total of 1218 subjects with stringently defined GHD of adult onset (641 women and 577 men) who were GH naive and had BMD measured in the posterior anterior lumbar spine and femoral neck by dual-energy X-ray absorptiometry. Main Outcome Measures: Variables associated with standardized BMD(sBMD) in adult-onset GHD were examined. Results: In the LS, body mass index (r = 0.13, P < 0.01), unreplaced sex steroid deficiency (r = -0.17, P < 0.0001), and corticotropin deficiency (r = -0.11, P < 0.01) were independently associated with sBMD. In the FN, age (r = -0.19, P < 0.0001), female gender (r = -0.18, P < 0.0001), body mass index (r = 0.21, P < 0.0001), and decreased IGF-I SD scores (r = 0.10, P < 0.001) were independently associated with sBMD. Conclusions: Hormone variables associated with lower sBMD in patients with adult-onset GHD include unreplaced sex steroid deficiency and corticotropin deficiency in the LS and lower IGF-I SDS in the FN. (J Clin Endocrinol Metab 96: 1516-1523, 2011) C1 [Tritos, Nicholas A.; Biller, Beverly M. K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. [Greenspan, Susan L.] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA. [Hamrahian, Amir] Cleveland Clin, Dept Endocrinol Diabet & Metab, Cleveland, OH 44195 USA. [Cook, David M.] Oregon Hlth & Sci Univ, Dept Endocrinol, Portland, OR 97239 USA. [Jonsson, Peter J.; Koltowska-Haggstrom, Maria] Pfizer Endocrine Care, KIMS Med Outcomes, S-19190 Sollentuna, Sweden. [King, Donna; Wajnrajch, Michael P.] Pfizer Inc, New York, NY 10017 USA. RP Tritos, NA (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Zero Emerson Pl,Suite 112, Boston, MA 02114 USA. EM ntritos@partners.org OI Wajnrajch, Michael/0000-0002-8211-9237 FU Pfizer Inc.; Eli Lilly; Warner Chilcott; Tarsa; Serono; Indevus; Novo Nordisk FX KIMS is sponsored by Pfizer Inc. D. K. and M. P. W. are full-time employees of Pfizer Inc. P.J.J. and M. K.-H. are employed by Pfizer Health AB. N.A.T., S. L. G., A. H., D. M. C., and B. M. K. B. were not compensated for their contributions to this manuscript.; N.A.T., A. H., D. M. C., and B. M. K. B. are KIMS Investigators. N.A.T. has been a recipient of lecture fees from Pfizer Inc., and his spouse is an employee of Pfizer Inc. S. L. G. has been a recipient of research funding from Eli Lilly, Warner Chilcott, and Tarsa and has consulted and served on an advisory board for Amgen and Merck. A. H. has been a recipient of lecture fees from Pfizer Inc. and has consulted for Novo Nordisk. D. M. C. has received lecture fees from Pfizer, has received research funding from Serono, Eli Lilly, and Indevus, and served on an advisory board for Novo Nordisk. D. K. and M. P. W. are full-time employees of Pfizer Inc. P.J.J. and M. K.-H. are employed by Pfizer Health AB. B. M. K. B. has been a recipient of research funding from Eli Lilly and Novo Nordisk and has served on an advisory board and received consulting fees from Pfizer and Novo Nordisk. NR 28 TC 12 Z9 12 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 MAY PY 2011 VL 96 IS 5 BP 1516 EP 1523 DI 10.1210/jc.2010-2662 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 759AE UT WOS:000290210600058 PM 21367928 ER PT J AU Elmariah, SB Kundu, RV AF Elmariah, Sarina B. Kundu, Roopal V. TI Progressive Macular Hypomelanosis SO JOURNAL OF DRUGS IN DERMATOLOGY LA English DT Article ID BAND ULTRAVIOLET-B; UVB AB Progressive macular hypomelanosis is an under-recognized disorder characterized by the presence of numerous ill-defined hypopigmented macules and patches on the trunk of young adults. Although common, particularly in Fitzpatrick skin types IV-VI, this condition is frequently misdiagnosed and treated inadequately with antifungals or topical steroids resulting in patient frustration. The exact pathogenesis of progressive macular hypomelanosis is unknown; however, recent studies suggest hypopigmentation results from decreased melanin formation and altered melanosome distribution in response to Proprionibacterium. While there are no well-established or consistently effective therapies for progressive macular hypomelanosis, our growing understanding of its pathogenesis urges consideration of alternative treatment strategies. Here, we report five patients with progressive macular hypomelanosis who benefitted from topical and systemic antimicrobial therapy and summarize the current clinical, pathological and treatment paradigms of this disorder. C1 [Kundu, Roopal V.] Northwestern Univ, Feinberg Sch Med, Dept Dermatol, Chicago, IL 60611 USA. [Elmariah, Sarina B.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. RP Kundu, RV (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Dermatol, 676 N St Clair St,Suite 1600, Chicago, IL 60611 USA. EM rkundu@nmff.org NR 21 TC 3 Z9 3 U1 0 U2 0 PU JOURNAL OF DRUGS IN DERMATOLOGY PI NEW YORK PA 377 PARK AVE SOUTH, 6TH FLOOR, NEW YORK, NY 10016 USA SN 1545-9616 J9 J DRUGS DERMATOL JI J. Drugs Dermatol. PD MAY PY 2011 VL 10 IS 5 BP 502 EP 506 PG 5 WC Dermatology SC Dermatology GA 760YR UT WOS:000290361700007 PM 21533296 ER PT J AU Davis, LL Gilliss, CL Deshefy-Longhi, T Chestnutt, DH Molloy, M AF Davis, Linda Lindsey Gilliss, Catherine L. Deshefy-Longhi, Tess Chestnutt, Deborah H. Molloy, Margory TI The Nature and Scope of Stressful Spousal Caregiving Relationships SO JOURNAL OF FAMILY NURSING LA English DT Article DE spousal caregivers; spousal relationships; relationship quality; relational stress; caregiving burden; Alzheimer's disease; Parkinson's disease ID PARKINSONS-DISEASE; DEPRESSIVE SYMPTOMS; FAMILY CAREGIVERS; PHYSICAL HEALTH; DEMENTIA; BURDEN; MUTUALITY; GENDER; INTERVENTION; METAANALYSIS AB The caregiving literature provides compelling evidence that caregiving burden and depressive symptoms are linked with stressful care relationships, however, relational difficulties around caregiving are seldom described in the literature. This article presents findings from content analysis of baseline interviews with 40 Alzheimer's disease (AD) and Parkinson's disease (PD) spousal caregivers enrolled in a home care skill-training trial who identified their care relationship as a source of care burden. Disappointment and sadness about the loss of the relationship; tension within the relationship; and care decision conflicts within the relationship were recurrent themes of relational stress in caregiving. These spousal caregivers had relationship quality scores below the mean and burden and depressive symptom scores above the means of other caregivers in the study. These findings provide support for developing dyadic interventions that help spouses manage relational losses, care-related tensions, and care decision-making conflicts. C1 [Davis, Linda Lindsey; Molloy, Margory] Duke Univ, Sch Nursing, Ctr Nursing Discovery, Durham, NC 27710 USA. [Deshefy-Longhi, Tess] Fairfield Univ, Sch Nursing, Fairfield, CT 06430 USA. [Chestnutt, Deborah H.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Davis, LL (reprint author), Duke Univ, Sch Nursing, Ctr Nursing Discovery, 307 Trent Dr,DUMC 3322, Durham, NC 27710 USA. EM davis317@mc.duke.edu FU National Institute for Nursing Research [RO1 NR008285]; Duke University Center for the Study of Aging and Human Development [AG00029] FX Project ASSIST for Chronic Illness Caregivers was funded by the National Institute for Nursing Research: Grant number: RO1 NR008285. (L. Davis, Principal Investigator). Dr. Deshefy-Longhi's work with the ASSIST study was supported by the Duke University Center for the Study of Aging and Human Development, where she completed postdoctoral training under T-32 Grant number: AG00029. NR 40 TC 20 Z9 21 U1 4 U2 20 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1074-8407 J9 J FAM NURS JI J. Fam. Nurs. PD MAY PY 2011 VL 17 IS 2 BP 224 EP 240 DI 10.1177/1074840711405666 PG 17 WC Family Studies; Nursing SC Family Studies; Nursing GA 756PS UT WOS:000290027300006 PM 21531858 ER PT J AU Brouwer, KM Jupiter, JB Ring, D AF Brouwer, Kim M. Jupiter, Jesse B. Ring, David TI Nonunion of Operatively Treated Capitellum and Trochlear Fractures SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Osteonecrosis; open reduction internal fixation; capitellum; trochlea; fracture ID INTERNAL-FIXATION; OPEN REDUCTION; HUMERUS AB Purpose To test the hypothesis that comminuted fractures of the capitellum and trochlea with posterior comminution (Dubberley type 3B) have a greater risk of nonunion than other types of capitellum and trochlea fractures. Methods We observed 30 patients with operatively treated fractures of the capitellum and trochlea for an average of 34 months (range, 12-75 mo). We compared 18 fractures with comminution of the capitellum and trochlea and posterior comminution (type 3B according to Dubberley and colleagues) with 12 fractures consisting of single large anterior fracture fragments with (6 patients; Dubberley type 2B) or without (6 patients; Dubberley type 2A) posterior comminution. Results Of 18 patients, 8 with type 3B fractures were noted to have nonunion. No patients with type 2 fractures had a nonunion. Conclusions Fractures of the capitellum and trochlea are prone to nonunion when they create multiple articular fragments and there is posterior comminution (Dubberley type 3B). (J Hand Surg 2011;36A:804-807. Copyright (C) 2011 by the American Society for Surgery of the Hand. All rights reserved.) C1 [Ring, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Ring, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand & Upper Extrem Serv, Yawkey Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org FU Wright Medical FX D.R. receives royalities from and is a consultant with Wright Medical, and he is a consultant with Acumed and Tomier. NR 9 TC 3 Z9 4 U1 0 U2 3 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 MAY PY 2011 VL 36A IS 5 BP 804 EP 807 DI 10.1016/j.jhsa.2011.01.022 PG 4 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 758SC UT WOS:000290185700006 PM 21435800 ER PT J AU Peterson, SL Rayan, GM AF Peterson, Steven L. Rayan, Ghazi M. TI Shoulder and Upper Arm Muscle Architecture SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Muscle architecture; musculotendinous transfer; shoulder muscles ID TENDON TRANSFER; POTENTIAL EXCURSION; RELATIVE TENSION; HAND; TRANSFERS; RELEVANCE; FOREARM AB Purpose To examine the architecture of the shoulder and upper arm muscles and generate data that could serve as a guide for comparison, compatibility, and relative performance among these muscles for use in transfer. Method Eleven shoulder and arm muscles were dissected bilaterally in 5 fresh cadavers. Of these 110 potentially available muscles, 107 were suitable for evaluation and were grouped according to similarities in architecture. Resting muscle length, required excursion, muscle fiber length, pennation angle, and mass were determined. Physiologic cross-sectional area (PCSA) was then calculated from these parameters using a standard formula. Results Based on the gross appearance of muscle fiber orientation, the 11 muscles were subdivided into 3 groups. Required excursion was found to be less than fiber length in all muscles except for the teres major and middle deltoid with abduction. The middle deltoid muscle was found to have a short fiber length, complex multipennate structure, and high PCSA. Comparison showed the biceps and posterior deltoid to have fiber lengths greater than any portion of the triceps; however, neither demonstrated architectural features that would generate the force (represented by PCSA) determined for the combined triceps. Conclusions Data presented in this study offer the opportunity for direct comparison of architectural features of select shoulder and arm musculature. Clinical relevance This information might help in the evaluation of compatibility of various musculotendinous transfers around the shoulder and elbow. (J Hand Surg 2011;36A:881-889. Copyright (C) 2011 by the American Society for Surgery of the Hand. All rights reserved.) C1 [Rayan, Ghazi M.] Univ Oklahoma, Hlth Sci Ctr, Dept Orthoped & Rehabil, Oklahoma City, OK 73112 USA. [Rayan, Ghazi M.] Integris Baptist Hosp, Dept Orthoped & Rehabil, Oklahoma City, OK 73112 USA. Portland VA Med Ctr, Hand & Plast Surg Sect, Operat Care Div, Portland, OR USA. RP Rayan, GM (reprint author), Univ Oklahoma, Hlth Sci Ctr, Dept Orthoped & Rehabil, 3366 NW Expressway,Bldg D 700, Oklahoma City, OK 73112 USA. EM ouhsgmr@aol.com NR 26 TC 7 Z9 7 U1 0 U2 9 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD MAY PY 2011 VL 36A IS 5 BP 881 EP 889 DI 10.1016/j.jhsa.2011.01.008 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 758SC UT WOS:000290185700019 PM 21527142 ER PT J AU Ulvila, J Vanha-aho, LM Kleino, A Vaha-Makila, M Vuoksio, M Eskelinen, S Hultmark, D Kocks, C Hallman, M Parikka, M Ramet, M AF Ulvila, Johanna Vanha-aho, Leena-Maija Kleino, Anni Vaha-Makila, Mari Vuoksio, Milka Eskelinen, Sinikka Hultmark, Dan Kocks, Christine Hallman, Mikko Parikka, Mataleena Ramet, Mika TI Cofilin regulator 14-3-3 zeta is an evolutionarily conserved protein required for phagocytosis and microbial resistance SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE Drosophila; zebrafish; plasmatocyte; macrophage; immunity ID DROSOPHILA IMD PATHWAY; SCAVENGER RECEPTOR; RNAI SCREEN; BACTERIAL-INFECTION; IMMUNE-RESPONSE; ACTIN DYNAMICS; S2 CELLS; REVEALS; EXPRESSION; ZEBRAFISH AB Phagocytosis is an ancient cellular process that plays an important role in host defense. In Drosophila melanogaster phagocytic, macrophage-like hemocytes recognize and ingest microbes. We performed an RNAi-based in vitro screen in the Drosophila hemocyte cell line S2 and identified Abi, cpa, cofilin regulator 14-3-3 zeta, tlk, CG2765, and CG15609 as mediators of bacterial phagocytosis. Of these identified genes, 14-3-3 zeta had an evolutionarily conserved role in phagocytosis: bacterial phagocytosis was compromised when 14-3-3 zeta was targeted with RNAi in primary Drosophila hemocytes and when the orthologous genes Ywhab and Ywhaz were silenced in zebrafish and mouse RAW 264.7 cells, respectively. In Drosophila and zebrafish infection models, 14-3-3 zeta was required for resistance against Staphylococcus aureus. We conclude that 14-3-3 zeta is essential for phagocytosis and microbial resistance in insects and vertebrates. J. Leukoc. Biol. 89: 649-659; 2011. C1 [Ulvila, Johanna; Vaha-Makila, Mari; Hallman, Mikko] Univ Oulu, Bioctr Oulu, Dept Pediat, Oulu, Finland. [Eskelinen, Sinikka] Univ Oulu, Bioctr Oulu, Dept Pathol, Oulu, Finland. [Vanha-aho, Leena-Maija; Kleino, Anni; Vuoksio, Milka; Hultmark, Dan; Parikka, Mataleena; Ramet, Mika] Univ Tampere, Inst Biomed Technol, Tampere 33014, Finland. [Ramet, Mika] Univ Tampere, Dept Pediat, Tampere 33014, Finland. [Kleino, Anni; Hultmark, Dan] Umea Univ, Dept Mol Biol, Umea, Sweden. [Kocks, Christine] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kocks, Christine] Harvard Univ, Sch Med, Boston, MA USA. RP Ramet, M (reprint author), Univ Tampere, Inst Med Technol, Tampere 33014, Finland. EM mika.ramet@uta.fi RI Parikka, Mataleena/D-4364-2014; Hultmark, Dan/C-5058-2013; Hammaren, Milka/C-6990-2016; OI Hultmark, Dan/0000-0002-6506-5855; Hammaren, Milka/0000-0001-9076-8782; Parikka, Mataleena/0000-0001-5555-3815 FU Sigrid Juselius Foundation; Academy of Finland; Foundation for Pediatric Research; Tampere Tuberculosis Foundation; Emil Aaltonen Foundation; Swedish Research Council; Swedish Cancer Society; Pirkanmaa Hospital District; Biocenter Finland FX This work was supported by grants from the Sigrid Juselius Foundation (M. H. and M. R.), the Academy of Finland (M. R., D. H., and M. P.), the Foundation for Pediatric Research (M. R.), Tampere Tuberculosis Foundation (M. R.), the Emil Aaltonen Foundation (M. R.), the Swedish Research Council and the Swedish Cancer Society (D. H.), and Competitive Research Funding of the Pirkanmaa Hospital District (M. R. and M. P.). The zebrafish work was done at University of Tampere Zebrafish Core Facility, funded by Biocenter Finland. The fly work was done at University of Tampere Drosophila Core Facility, funded by Biocenter Finland. We thank Heidi Enwald, Tapio Kotipelto, Mirkka Ovaska, and Dr. Samuli Rounioja for technical assistance and members of the M. H. and M. R. labs for stimulating discussions. In addition, we thank NIG-Fly and VDRC for RNAi fly lines. NR 54 TC 22 Z9 23 U1 1 U2 7 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD MAY PY 2011 VL 89 IS 5 BP 649 EP 659 DI 10.1189/jlb.0410195 PG 11 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 757PL UT WOS:000290100100003 PM 21208897 ER PT J AU Goodman, D AF Goodman, Daisy TI Buprenorphine for the Treatment of Perinatal Opioid Dependence: Pharmacology and Implications for Antepartum, Intrapartum, and Postpartum Care SO JOURNAL OF MIDWIFERY & WOMENS HEALTH LA English DT Review DE buprenorphine; neonatal abstinence; perinatal opioid dependence; pregnancy ID NEONATAL ABSTINENCE SYNDROME; SUBSTANCE USE DISORDERS; ACUTE PAIN MANAGEMENT; PREGNANT-WOMEN; PSYCHOSOCIAL CHARACTERISTICS; METHADONE; MAINTENANCE; METABOLISM; EXPOSURE; OUTCOMES AB Opioid dependence during pregnancy is associated with significant health risks for both the mother and her fetus. Opioid maintenance therapy with methadone (Dolophine) is the current standard of care, reduces medical and social risks associated with illicit drug use, and decreases rates of prematurity and low birth weight. However, treatment with methadone is frequently associated with neonatal abstinence syndrome. Buprenorphine is an alternative to methadone that preliminary data indicates is equivalent in safety and efficacy to methadone and significantly increases access to treatment. The pharmacology of buprenorphine and its implications for the care of pregnant women with opioid dependence are described. C1 [Goodman, Daisy] Franklin Mem Hosp, Farmington, ME USA. [Goodman, Daisy] Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. RP Goodman, D (reprint author), 111 Franklin Hlth Commons, Farmington, ME 04938 USA. EM dgood-man@fchn.org NR 51 TC 2 Z9 2 U1 1 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1526-9523 J9 J MIDWIFERY WOM HEAL JI J. Midwifery Women Health PD MAY-JUN PY 2011 VL 56 IS 3 BP 240 EP 247 DI 10.1111/j.1542-2011.2011.00049.x PG 8 WC Nursing SC Nursing GA 756DR UT WOS:000289992400007 PM 21535372 ER PT J AU Horky, LL Hsiao, EM Weiss, SE Drappatz, J Gerbaudo, VH AF Horky, Laura L. Hsiao, Edward M. Weiss, Stephanie E. Drappatz, Jan Gerbaudo, Victor H. TI Dual phase FDG-PET imaging of brain metastases provides superior assessment of recurrence versus post-treatment necrosis SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Brain; Metastasis; Tumor; Recurrence; Necrosis; Radiation; FDG; PET; PET/CT; FDG-PET; Dual phase imaging; Dual time point ID POSITRON-EMISSION-TOMOGRAPHY; RADIATION NECROSIS; F-18 FLUORODEOXYGLUCOSE; TUMOR; TISSUE; TIME; DIFFERENTIATION; METABOLISM; INDEX AB To study the ability of dual phase FDG-PET/CT imaging to accurately distinguish tumor versus necrosis in patients treated for brain metastases. 32 (22 female, 10 male) consecutive patients with treated brain metastases, lesion size greater than 0.5 cm(3) and suspected recurrence on MRI underwent dual-phase FDG-PET/CT. Clinical outcome was assessed by biopsy or by MRI. SUVmax and SUVmean values of the lesion (L) and gray matter (GM) at the level of the thalamus were measured on early (1) and delayed (2) imaging. L1/GM1 and L2/GM2 and the change of L/GM ratios as a function of time were calculated [(L2/GM2 - L1/GM1)/(L1/GM1)]. Cut-off values were obtained by ROC analysis. P < 0.05 defined statistical significance. Seven patients were excluded due to indeterminate outcomes. 25 patients (16 female, 9 male; 27 lesions; 28 scan sessions) had clear outcomes, proven by either biopsy (n = 16 patients) or serial follow-up MRI (n = 9 patients). Primary subtypes included breast (n = 9), lung (n = 7), melanoma (n = 3), squamous cell cancer of the head and neck (n = 2) and other (n = 4). Twenty-two patients underwent prior radiation (2-113 months) and three received only prior chemotherapy (5 months to 3 years). A change > 0.19 of L/GM ratios as a function of time was 95% sensitive, 100% specific, and 96.4% accurate (P = 0.0001; AUC = 0.97) for distinguishing tumor versus radiation necrosis. The ratio of the change of the lesion to WM ratios over time was the second best indicator of outcome when compared to all indices used (ROC cut-off = 0.25, sensitivity 89.5% and specificity 90.9%, and accuracy 89.2%; P = 0.0001; AUC = 0.95), Early or late SUVs of the lesion alone did not differentiate between tumor and necrosis. Regardless of histological type, differentiation of necrosis from metastatic brain lesions was improved by using the change of lesion to gray matter SUVmax ratios as a function of time. C1 [Horky, Laura L.; Hsiao, Edward M.; Gerbaudo, Victor H.] Harvard Univ, Brigham & Womens Hosp, Dept Radiol, Div Nucl Med & Mol Imaging,Med Sch, Boston, MA 02115 USA. [Weiss, Stephanie E.] Harvard Univ, Brigham & Womens Hosp, Dept Radiat Oncol, Sch Med, Boston, MA 02115 USA. [Drappatz, Jan] Harvard Univ, Dana Farber Canc Inst, Sch Med, Ctr Neurooncol, Boston, MA 02115 USA. [Drappatz, Jan] Harvard Univ, Brigham & Womens Hosp, Dept Neurol, Sch Med, Boston, MA 02115 USA. RP Horky, LL (reprint author), Harvard Univ, Brigham & Womens Hosp, Dept Radiol, Div Nucl Med & Mol Imaging,Med Sch, 75 Francis St, Boston, MA 02115 USA. EM lhorky@partners.org NR 26 TC 30 Z9 30 U1 0 U2 3 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 MAY PY 2011 VL 103 IS 1 BP 137 EP 146 DI 10.1007/s11060-010-0365-8 PG 10 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 760KL UT WOS:000290323100012 PM 20838854 ER PT J AU Kelly, PJ Dinkin, MJ Drappatz, J O'Regan, KN Weiss, SE AF Kelly, Paul J. Dinkin, Marc J. Drappatz, Jan O'Regan, Kevin N. Weiss, Stephanie E. TI Unexpected late radiation neurotoxicity following bevacizumab use: a case series SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Optic neuropathy; Bevacizumab; Radiation; Neurotoxicity; Glioblastoma ID ENDOTHELIAL GROWTH-FACTOR; OPTIC NEUROPATHY; TUMOR-GROWTH; SPINAL-CORD; ANGIOGENESIS AB The purpose of this case series is to report the unexpected occurrence of four cases of late radiation-induced neurotoxicity with bevacizumab use following radiotherapy to the CNS. We retrospectively reviewed the case records of four patients, three with glioblastoma and one with bone metastases secondary to metastatic breast cancer, who were treated with radiotherapy and developed late radiation-induced neurotoxicity following bevacizumab use. Three cases of optic neuropathy in glioblastoma patients and a single case of Brown-S,quard syndrome in the thoracic spine of a patient with metastatic breast cancer are reported. We hypothesize that bevacizumab use following radiotherapy to the CNS may inhibit vascular endothelial growth factor-dependent repair of normal neural tissue, and thus may increase the risk of late radiation neurotoxicity. Phase III data on the safety and efficacy of bevacizumab use with radiation in the setting of glioblastoma is awaited. C1 [Kelly, Paul J.; Weiss, Stephanie E.] Harvard Univ, Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst,Med Sch, Boston, MA 02115 USA. [Dinkin, Marc J.] New York Presbyterian Hosp, Dept Ophthalmol, Weill Cornell Med Coll, New York, NY USA. [Drappatz, Jan] Harvard Univ, Brigham & Womens Hosp, Dept Neurol, Ctr Neurooncol,Dana Farber Canc Inst,Med Sch, Boston, MA 02115 USA. [O'Regan, Kevin N.] Harvard Univ, Dana Farber Canc Inst, Dept Radiol, Sch Med, Boston, MA 02115 USA. RP Kelly, PJ (reprint author), Harvard Univ, Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst,Med Sch, 75 Francis St ASB1,L2, Boston, MA 02115 USA. EM pkelly@lroc.harvard.edu NR 17 TC 6 Z9 7 U1 1 U2 3 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 MAY PY 2011 VL 102 IS 3 BP 485 EP 490 DI 10.1007/s11060-010-0336-0 PG 6 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 760KE UT WOS:000290322400016 PM 20680396 ER PT J AU Adams, JM AF Adams, Jeffrey M. TI The Development of Nurse Executive Leadership An Interview With Marjorie Beyers SO JOURNAL OF NURSING ADMINISTRATION LA English DT Editorial Material C1 Massachusetts Gen Hosp, Yvonne L Munn Ctr Nursing Res, Boston, MA 02114 USA. RP Adams, JM (reprint author), Massachusetts Gen Hosp, Yvonne L Munn Ctr Nursing Res, 275 Cambridge St,POB 4, Boston, MA 02114 USA. EM jadams9@partners.org NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-0443 J9 J NURS ADMIN JI J. Nurs. Adm. PD MAY PY 2011 VL 41 IS 5 BP 194 EP 196 DI 10.1097/NNA.0b013e3182171b5e PG 3 WC Nursing SC Nursing GA 754WD UT WOS:000289887500002 ER PT J AU Bienstock, DA Dodson, TB Perrott, DH Chuang, SK AF Bienstock, Daniel A. Dodson, Thomas B. Perrott, David H. Chuang, Sung-Kiang TI Prognostic Factors Affecting the Duration of Disability After Third Molar Removal SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID QUALITY-OF-LIFE; ALVEOLAR OSTEITIS; 3RD-MOLAR SURGERY; RISK-FACTORS; RECOVERY; COMPLICATIONS; CHLORHEXIDINE; OUTCOMES; AGE AB Purpose: The purposes of this investigation were 1) to estimate the duration of disability after third molar removal and 2) to identify factors associated with prolonged recovery. Materials and Methods: This was a prospective cohort study composed of subjects enrolled in the American Association of Oral and Maxillofacial Surgeons Age-Related Third Molar Study. The predictor variables were grouped as follows: demographic, health status, anatomic, pathologic, medications, and complications. The outcome variable was the duration of postoperative disability measured as the number of days the subject reported inability to perform normal daily activities after third molar removal. Bivariate and multiple linear regression analyses were used. The level of statistical significance was P < .05. Results: The study sample included 4,004 subjects who had 8,748 third molars removed. The mean duration of postoperative disability was 1.4 +/- 1.8 days (range, 0-26; median, 1 day). In the multiple linear regression model, age, female gender, number of third molars removed, mandibular third molar removal, full-bony impaction, sum of antibiotics or pain medications, and complications were associated with prolonged recovery (P < .05). Erupted third molars, periodontal disease or other preoperative pathology, and use of chlorhexidine were associated with earlier return to normal daily activities (P < .05). Conclusion: The study results suggest that third molar removal is associated with a mean delay in returning to normal activities of less than 2 days. Several factors were statistically associated with time to return to normal activities. (C) 2011 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 69:1272-1277, 2011 C1 [Dodson, Thomas B.; Chuang, Sung-Kiang] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Dodson, Thomas B.; Chuang, Sung-Kiang] Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. [Perrott, David H.] Salinas Valley Mem Healthcare Syst, Salinas, CA USA. [Dodson, Thomas B.] Massachusetts Gen Hosp, Ctr Appl Clin Invest, Boston, MA 02114 USA. RP Chuang, SK (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, 55 Fruit St,Warren 1201, Boston, MA 02114 USA. EM sungkiangchuang@gmail.com FU Oral and Maxillofacial Surgery Foundation; Massachusetts General Hospital Department of Oral and Maxillofacial Surgery's Center; Harvard Medical School Office; Massachusetts General Physicians Organization FX This investigation was supported by 1) the Student Research Training Award from the Oral and Maxillofacial Surgery Foundation, 2) Massachusetts General Hospital Department of Oral and Maxillofacial Surgery's Center for Applied Clinical Investigation and Education and Research Fund, 3) Harvard Medical School Office of Enrichment Programs Student Research Fund, and 4) Massachusetts General Physicians Organization. NR 12 TC 11 Z9 11 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 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD MAY PY 2011 VL 69 IS 5 BP 1272 EP 1277 DI 10.1016/j.joms.2010.06.211 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 759KS UT WOS:000290242300013 PM 21256646 ER PT J AU Marcus, SC Durkin, M AF Marcus, Steven C. Durkin, Michael TI Stimulant Adherence and Academic Performance in Urban Youth With Attention-Deficit/Hyperactivity Disorder SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE stimulant; adherence; academic performance; school; ADHD ID DEFICIT HYPERACTIVITY DISORDER; TERM SCHOOL OUTCOMES; AFRICAN-AMERICAN; CHILDREN; ADHD; METHYLPHENIDATE; MEDICATION; ADOLESCENTS; ACHIEVEMENT; CHILDHOOD AB Objective: This analysis assessed whether stimulant adherence was associated with improvement in academic grade point average (GPA) among children diagnosed with and treated for attention-deficit/hyperactivity disorder (ADHD). Method: Medicaid claims were merged with academic records from Philadelphia public schools of Medicaid-eligible children in first through eighth grades who were diagnosed with ADHD and who had filled one or more stimulant prescription. Students diagnosed with mental retardation, autism, or speech, hearing, visual, or language impairments were excluded. Marking periods were scored for GPA (range: 0-4.0) based on English, mathematics, social studies, and science grades and for stimulant adherence (medication possession ratio >= 0.70). Random and fixed-effects models estimated the effects of stimulant adherence on GPA, between all adherent and nonadherent marking periods in aggregate and within individual student's marking periods, respectively. Results: A total of 3,543 students contributed 29,992 marking periods, of which 18.6% were adherent. Mean GPA was significantly higher during stimulant-adherent (2.18) than stimulant-nonadherent (1.99) marking periods in aggregate (p < .0001). The regression coefficient representing within-student association between stimulant adherence and GPA over time was 0.108 (p < .0001), indicating that adherence was associated with a 0.108 increase in GPA. In stratified analyses, analogous coefficients were 0.106 for boys, 0.111 for girls, 0.078 for elementary students, and 0.118 for middle school students (all p < .0001). The association was stronger among students with (0.139) than without (0.088) comorbid disruptive behavior disorders (both p < .0001). Conclusions: Stimulant adherence, although found to be low among urban elementary and middle school students diagnosed with ADHD, was associated with a marginal improvement in GPA. J. Am. Acad. Child Adolesc. Psychiatry, 2011;50(5):480-489. C1 [Marcus, Steven C.] Univ Penn, Sch Social Policy & Practice, Philadelphia, PA 19103 USA. [Marcus, Steven C.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Durkin, Michael] Ortho McNeil Janssen Sci Affairs LLC, Titusville, NJ USA. RP Marcus, SC (reprint author), Univ Penn, Sch Social Policy & Practice, 3701 Locust Walk, Philadelphia, PA 19103 USA. EM marcuss@sp2.upenn.edu FU Ortho-McNeil Janssen Scientific Affairs, LLC; Eli Lilly and Co., Bristol-Myers Squibb; Johnson and Johnson FX This project was funded by Ortho-McNeil Janssen Scientific Affairs, LLC.; Dr. Marcus has received grant support from Ortho-McNeil Janssen, and has served as a consultant to Eli Lilly and Co., Bristol-Myers Squibb, and AstraZeneca. Mr. Durkin holds stock in Johnson and Johnson. NR 35 TC 18 Z9 18 U1 0 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAY PY 2011 VL 50 IS 5 BP 480 EP 489 DI 10.1016/j.jaac.2011.02.007 PG 10 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 757GH UT WOS:000290073000009 PM 21515197 ER PT J AU Rao, SR DesRoches, CM Donelan, K Campbe, EG Miralles, PD Jha, AK AF Rao, Sowmya R. DesRoches, Catherine M. Donelan, Karen Campbe, Eric G. Miralles, Paola D. Jha, Ashish K. TI Electronic health records in small physician practices: availability, use, and perceived benefits SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID ADOPTION; CARE AB Objective To examine variation in the adoption of electronic health record (EHR) functionalities and their use patterns, barriers to adoption, and perceived benefits by physician practice size. Design Mailed survey of a nationally representative random sample of practicing physicians identified from the Physician Masterfile of the American Medical Association. Measurements We measured, stratified by practice size: (1) availability of EHR functionalities, (2) functionality use, (3) barriers to the adoption and use of EHR, and (4) impact of the EHR on the practice and quality of patient care. Results With a response rate of 62%, we found that <2% of physicians in solo or two-physician (small) practices reported a fully functional EHR and 5% reported a basic EHR compared with 13% of physicians from 11+ group (largest group) practices with a fully functional system and 26% with a basic system. Between groups, a 21-46% difference in specific functionalities available was reported. Among adopters there were moderate to large differences in the use of the EHR systems. Financial barriers were more likely to be reported by smaller practices, along with concerns about future obsolescence. These differences were sizable (13-16%) and statistically significant (p<0.001). All adopters reported similar benefits. Limitations Although we have adjusted for response bias, influences may still exist. Conclusion Our study found that physicians in small practices have lower levels of EHR adoption and that these providers were less likely to use these systems. Ensuring that unique barriers are addressed will be critical to the widespread meaningful use of EHR systems among small practices. C1 [Jha, Ashish K.] Harvard Univ, Dept Hlth Policy & Management, Sch Publ Hlth, Boston, MA 02115 USA. [Rao, Sowmya R.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Ctr Biostat, Boston, MA 02114 USA. RP Jha, AK (reprint author), Harvard Univ, Dept Hlth Policy & Management, Vet Affairs Boston Healthcare Syst, Brigham & Womens Hosp,Div Gen Med,Sch Publ Hlth, 677 Huntington Ave, Boston, MA 02115 USA. EM ajha@hsph.harvard.edu FU Office of the National Coordinator for Health Information Technology; Robert Wood Johnson Foundation; GE Corporation Healthcare; UpToDate FX This study was supported by the Office of the National Coordinator for Health Information Technology and a grant from the Robert Wood Johnson Foundation. Drs Rao and Donelan report receiving grant support from GE Corporation Healthcare, and Dr Jha reports receiving consulting fees from UpToDate. NR 12 TC 46 Z9 46 U1 7 U2 15 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD MAY PY 2011 VL 18 IS 3 BP 271 EP 275 DI 10.1136/amiajnl-2010-000010 PG 5 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 755TT UT WOS:000289960600010 PM 21486885 ER PT J AU Schnipper, JL Liang, CL Hamann, C Karson, AS Palchuk, MB McCarthy, PC Sherlock, M Turchin, A Bates', DW AF Schnipper, Jeffrey L. Liang, Catherine L. Hamann, Claus Karson, Andrew S. Palchuk, Matvey B. McCarthy, Patricia C. Sherlock, Melanie Turchin, Alexander Bates', David W. TI Development of a tool within the electronic medical record to facilitate medication reconciliation after hospital discharge SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article AB Serious medication errors occur commonly in the period after hospital discharge. Medication reconciliation in the postdischarge ambulatory setting may be one way to reduce the frequency of these errors. The authors describe the design and implementation of a novel tool built into an ambulatory electronic medical record ([MA) to facilitate postdischarge medication reconciliation. The tool compares the preadmission medication list within the ambulatory EMR to the hospital discharge medication list, highlights all changes, and allows the EMR medication list to be easily updated. As might be expected for a novel tool intended for use in a minority of visits, use of the tool was low at first: 20% of applicable patient visits within 30 days of discharge. Clinician outreach, education, and a pop-up reminder succeeded in increasing use to 41% of applicable visits. Review of feedback identified several usability issues that will inform subsequent versions of the tool and provide generalizable lessons for how best to design medication reconciliation tools for this setting. C1 [Schnipper, Jeffrey L.] Brigham & Womens Hosp, Div Gen Med, Brigham & Womens Hosp Hospitalist Serv, Boston, MA 02120 USA. [Schnipper, Jeffrey L.; Liang, Catherine L.; Bates', David W.] Brigham & Womens Hosp, Div Gen Med & Primary Care, Boston, MA 02120 USA. [Hamann, Claus; Karson, Andrew S.; McCarthy, Patricia C.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Hamann, Claus] Massachusetts Gen Hosp, Geriatr Med Unit, Boston, MA 02114 USA. [Karson, Andrew S.; McCarthy, Patricia C.] Massachusetts Gen Hosp, Ctr Qual & Safety, Boston, MA 02114 USA. [Palchuk, Matvey B.; Sherlock, Melanie; Turchin, Alexander] Partners Informat Syst Clin Informat Res & Dev, Wellesley, MA USA. [Turchin, Alexander] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02120 USA. [Bates', David W.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Schnipper, JL (reprint author), Brigham & Womens Hosp, Div Gen Med, Brigham & Womens Hosp Hospitalist Serv, 1620 Tremont St,BC3-2Y, Boston, MA 02120 USA. EM jschnipper@partners.org FU Agency for Healthcare Research and Quality [1 U18 HS016970-01]; National Heart Lung and Blood Institute [1 K08 HL072806-01] FX This study was supported by a grant from the Agency for Healthcare Research and Quality (1 U18 HS016970-01). JLS was supported by a mentored career development award from the National Heart Lung and Blood Institute (1 K08 HL072806-01). NR 11 TC 30 Z9 30 U1 0 U2 7 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD MAY PY 2011 VL 18 IS 3 BP 309 EP 313 DI 10.1136/amiajnl-2010-000040 PG 5 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 755TT UT WOS:000289960600016 PM 21486889 ER PT J AU Kozora, E Filley, CM AF Kozora, Elizabeth Filley, Christopher M. TI Cognitive Dysfunction and White Matter Abnormalities in Systemic Lupus Erythematosus SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Review DE Lupus; Neuropsychology; Magnetic resonance imaging; Magnetic resonance spectroscopy; Mechanisms; Methodology ID MAGNETIC-RESONANCE SPECTROSCOPY; CENTRAL-NERVOUS-SYSTEM; PROTON MR SPECTROSCOPY; BRAIN-LESIONS; ACUTE ONSET; DEFICITS; INJURY; SLE; MANIFESTATIONS; IMPAIRMENT AB Brain abnormalities have been documented by neuropsychological assessment as well as a variety of neuroimaging techniques in patients with systemic lupus erythematosus (SLE). Conventional neuroimaging in patients with neuropsychiatric disease (NPSLE) typically discloses periventricular white matter (WM) hyperintensities, infarcts, hemorrhages, and cerebral atrophy. In SLE patients with none of these findings, sophisticated neuroimaging techniques have recently supported associations between microstructural WM abnormalities and abnormal attention, executive function, and processing speed. This mild cognitive dysfunction in SLE (MCD-SLE), which may result from early myelinopathy, precedes the more severe cognitive dysfunction of NPSLE, related to more obvious WM and neuronal damage. (JINS, 2011, 17, 385-392) C1 [Kozora, Elizabeth] Natl Jewish Hlth, Denver, CO 80206 USA. [Kozora, Elizabeth; Filley, Christopher M.] Univ Colorado, Sch Med, Dept Neurol, Denver, CO USA. [Kozora, Elizabeth; Filley, Christopher M.] Univ Colorado, Sch Med, Dept Psychiat, Denver, CO 80262 USA. [Filley, Christopher M.] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Kozora, E (reprint author), Natl Jewish Hlth, 1400 Jackson St, Denver, CO 80206 USA. EM kozorae@njhealth.org RI Burleson, Andrew/B-5609-2016 OI Burleson, Andrew/0000-0002-4857-3583 FU National Institute of Musculoskeletal and Skin Diseases [RO1 AR049152] FX The authors report no conflicts of interest. This manuscript has not been published previously either electronically or in print. Supported in part by the National Institute of Musculoskeletal and Skin Diseases, (Grant RO1 AR049152). NR 40 TC 20 Z9 20 U1 1 U2 12 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1355-6177 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD MAY PY 2011 VL 17 IS 3 BP 385 EP 392 DI 10.1017/S1355617711000191 PG 8 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 757QU UT WOS:000290103600001 PM 21338548 ER PT J AU Burstein, HJ AF Burstein, Harold J. TI Texting the Doctor SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Editorial Material C1 [Burstein, Harold J.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Burstein, Harold J.] Dana Farber Canc Inst, Boston, MA USA. [Burstein, Harold J.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Burstein, Harold J.] Massachusetts Gen Hosp, Boston, MA 02114 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 HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD MAY PY 2011 VL 9 IS 5 BP 459 EP 459 PG 1 WC Oncology SC Oncology GA 760AG UT WOS:000290292400002 PM 21550965 ER PT J AU Zelenetz, AD Abramson, JS Advani, RH Andreadis, CB Bartlett, N Bellam, N Byrd, JC Czuczman, MS Fayad, LE Glenn, MJ Gockerman, JP Gordon, LI Harris, NL Hoppe, RT Horwitz, SM Kelsey, CR Kim, YH LaCasce, AS Nademanee, A Porcu, P Press, O Pro, B Reddy, N Sokol, L Swinnen, LJ Tsien, C Vose, JM Wierda, WG Yahalom, J Zafar, N AF Zelenetz, Andrew D. Abramson, Jeremy S. Advani, Ranjana H. Andreadis, C. Babis Bartlett, Nancy Bellam, Naresh Byrd, John C. Czuczman, Myron S. Fayad, Luis E. Glenn, Martha J. Gockerman, Jon P. Gordon, Leo I. Harris, Nancy Lee Hoppe, Richard T. Horwitz, Steven M. Kelsey, Christopher R. Kim, Youn H. LaCasce, Ann S. Nademanee, Auayporn Porcu, Pierluigi Press, Oliver Pro, Barbara Reddy, Nashitha Sokol, Lubomir Swinnen, Lode J. Tsien, Christina Vose, Julie M. Wierda, William G. Yahalom, Joachim Zafar, Nadeem TI Non-Hodgkin's Lymphomas SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review DE NCCN Clinical Practice Guidelines; NCCN Guidelines; chronic lymphocytic leukemia; follicular lymphoma; diffuse large B-cell lymphoma; mantle cell lymphoma; peripheral T-cell lymphoma; cutaneous T-cell lymphoma; mycosis fungoides; Sezary syndrome; marginal zone lymphoma; mucosaassociated lymphoid tissue lymphoma; diagnosis; treatment; hematopathology; immunohistochemistry; treatment guidelines; staging evaluation; lymphoma pathology; lymphoma therapy ID CHRONIC LYMPHOCYTIC-LEUKEMIA; B-CELL LYMPHOMA; TERM-FOLLOW-UP; RANDOMIZED CONTROLLED-TRIAL; PHASE-II TRIAL; ANTI-CD20 MONOCLONAL-ANTIBODY; PREVIOUSLY UNTREATED PATIENTS; POSITRON-EMISSION-TOMOGRAPHY; INVOLVED-FIELD RADIOTHERAPY; PROGRESSION-FREE SURVIVAL C1 [Zelenetz, Andrew D.; Horwitz, Steven M.; Yahalom, Joachim] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Abramson, Jeremy S.; Harris, Nancy Lee] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Advani, Ranjana H.; Hoppe, Richard T.; Kim, Youn H.] Stanford Comprehens Canc Ctr, Stanford, CA USA. [Andreadis, C. Babis] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Bartlett, Nancy] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Bartlett, Nancy] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Bellam, Naresh] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL USA. [Byrd, John C.; Porcu, Pierluigi] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Czuczman, Myron S.] Roswell Pk Canc Inst, Buffalo, NY USA. [Fayad, Luis E.; Wierda, William G.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Glenn, Martha J.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Gordon, Leo I.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [LaCasce, Ann S.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Nademanee, Auayporn] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Press, Oliver] Seattle Canc Care Alliance, Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [Pro, Barbara] Fox Chase Canc Ctr, Philadelphia, PA USA. [Sokol, Lubomir] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Swinnen, Lode J.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Tsien, Christina] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Vose, Julie M.] Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE USA. [Zafar, Nadeem] Univ Tennessee, Inst Canc, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. RP Zelenetz, AD (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. FU NCI NIH HHS [P30 CA016672] NR 387 TC 33 Z9 37 U1 0 U2 11 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 MAY PY 2011 VL 9 IS 5 BP 484 EP 560 PG 77 WC Oncology SC Oncology GA 760AG UT WOS:000290292400005 PM 21550968 ER PT J AU Arellano, RS Gervais, DA Mueller, PR AF Arellano, Ronald S. Gervais, Debra A. Mueller, Peter R. TI Computed Tomography-guided Drainage of Mediastinal Abscesses: Clinical Experience with 23 Patients SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID DESCENDING NECROTIZING MEDIASTINITIS; ESOPHAGOGASTRIC ANASTOMOTIC LEAK; PERCUTANEOUS DRAINAGE; ESOPHAGECTOMY; MANAGEMENT; CANCER AB Purpose: To evaluate the technical and clinical success rates of computed tomography (CT) guided percutaneous drainage of mediastinal abscesses. Materials and Methods: An interventional radiology database was used to identify patients who underwent CT-guided percutaneous drainage of mediastinal abscesses. Medical records were reviewed to evaluate abscess etiology, drainage technique, clinical outcome, and complications. Results: Over a 10-year period, 23 patients (20 men; average age, 54 y; range, 34-77 y) with 24 mediastinal abscesses underwent 25 CT-guided drainage procedures. Abscess etiologies included esophageal leak after esophagectomy (n = 6), perforated esophageal cancer (n = 4), Nissen fundoplication (n = 3), emetogenic esophageal rupture (n = 3), infectious (n = 2), cardiac surgery (n = 1), iatrogenic (n = 1), gastric strangulation (n = 1), Whipple procedure (n = 1), and thoracotomy for lung cancer (n = I). Drainages were performed with tandem trocar (n = 14) or Seldinger (n = 11) technique. A total of 25 catheters were used: 8.5 F (n = 9), 10 (n = 8), 12 F (n = 6), 14 F (n = 1), and 16 F (n = 1). The mean time of catheter drainage was 13.6 days. Technical success was achieved in all 25 attempts (100%). Twenty-two of the 23 patients had complete resolution of the abscess without the need for surgical debridement, for a clinical success rate of 95.6%. One patient underwent technically and clinically successful abscess drainage but required surgical exploration for repair of an anastomotic leak after esophagogastrectomy. There was one complication. One patient had inadvertent placement of a catheter within a pulmonary vein. The catheter was removed after 24 hours without hemodynamic consequences. Conclusions: Percutaneous CT-guided drainage of mediastinal abscesses is an uncommon procedure, but the results of this study suggest that it is associated with high technical and clinical success rates. C1 [Arellano, Ronald S.; Gervais, Debra A.; Mueller, Peter R.] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Arellano, RS (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, 55 Fruit St,White 270, Boston, MA 02114 USA. EM rarellano@partners.org NR 23 TC 9 Z9 9 U1 0 U2 2 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 MAY PY 2011 VL 22 IS 5 BP 673 EP 677 DI 10.1016/j.jvir.2011.01.427 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 760XT UT WOS:000290358700013 PM 21439848 ER PT J AU Levenson, RB Pearson, KM Saokar, A Lee, SI Mueller, PR Hahn, PF AF Levenson, Robin B. Pearson, Kara M. Saokar, Anuradha Lee, Susanna I. Mueller, Peter R. Hahn, Peter F. TI Image-guided Drainage of Tuboovarian Abscesses of Gastrointestinal or Genitourinary Origin: A Retrospective Analysis SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID TRANSVAGINAL DRAINAGE; PERCUTANEOUS DRAINAGE; FLUID COLLECTIONS; ASPIRATION AB Purpose: To analyze the authors' success with image-guided drainage of tuboovarian abscesses (TOAs). Materials and Methods: Retrospective analysis of patients with image-guided TOA drainage from 1999 to 2008 was performed. Patient recovery without salpingo-oophorectomy was considered clinical success. A total of 57 TOAs were drained in 49 female patients (mean age, 43; range, 12 to > 89). Results: Thirty-three (58%) TOAs were drained percutaneously using computed tomography guidance and 24 were ultrasound guided (21 transvaginally, three transabdominally). Fifty-three TOAs were drained with catheter placement, and four were drained with aspiration alone. Abscess etiologies include pelvic inflammatory disease (n = 21, 37%), gastrointestinal conditions related (n = 21, 37%), gynecologic surgery (n = 8, 14%), and other (12%). Image-guided drainage resolved TOAs without salpingo-oophorectomy in 74% of cases overall (42 of 57) and 88% (29 of 33) of gynecologic-related cases, including 95% (20 of 21) of pelvic inflammatory disease cases. Salpingo-oophorectomy was performed more often in gastrointestinal-related cases (10 of 21, 48%) than for all other causes (five of 36, 14%; P < .001), with concurrent bowel surgery performed in the majority of the gastrointestinal-related cases. Mean follow-up after image-guided drainage was 48 months (range, 1-113) in patients who did not have related surgery. In patients who underwent salpingo-oophorectomy, it was performed on average 2.2 months (range, 0.5-5) after initial drainage. Two minor complications occurred; both involved catheter transgression of the urinary bladder in patients with transvaginal ultrasound-guided drainages. The patients were successfully treated conservatively with Foley catheter bladder decompression, without prolonged hospitalization. Conclusions: TOAs, especially of gynecologic origin, can often be managed successfully with image-guided drainage. After image-guided drainage, patients with gynecologic-related TOA were less likely to undergo salpingo-oophorectomy than patients with gastrointestinal-related TOAs. C1 [Levenson, Robin B.] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. [Levenson, Robin B.; Pearson, Kara M.; Saokar, Anuradha; Lee, Susanna I.; Mueller, Peter R.; Hahn, Peter F.] Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent, Dept Radiol, Boston, MA 02114 USA. RP Levenson, RB (reprint author), Beth Israel Deaconess Med Ctr, Dept Radiol, 1 Deaconess Rd, Boston, MA 02215 USA. EM rlevenso@bidmc.harvard.edu NR 20 TC 5 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 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD MAY PY 2011 VL 22 IS 5 BP 678 EP 686 DI 10.1016/j.jvir.2010.10.032 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 760XT UT WOS:000290358700014 PM 21419651 ER PT J AU Gloviczki, P Comerota, AJ Dalsing, MC Eklof, BG Gillespie, DL Gloviczki, ML Lohr, JM McLafferty, RB Meissner, MH Murad, MH Padberg, FT Pappas, PJ Passman, MA Raffetto, JD Vasquez, MA Wakefield, TW AF Gloviczki, Peter Comerota, Anthony J. Dalsing, Michael C. Eklof, Bo G. Gillespie, David L. Gloviczki, Monika L. Lohr, Joann M. McLafferty, Robert B. Meissner, Mark H. Murad, M. Hassan Padberg, Frank T. Pappas, Peter J. Passman, Marc A. Raffetto, Joseph D. Vasquez, Michael A. Wakefield, Thomas W. TI The care of patients with varicose veins and associated chronic venous diseases: Clinical practice guidelines of the Society for Vascular Surgery and the American Venous Forum SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID GREAT SAPHENOUS-VEIN; QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; ENDOVENOUS LASER-ABLATION; TRANSILLUMINATED POWERED PHLEBECTOMY; GUIDED FOAM SCLEROTHERAPY; ENDOSCOPIC PERFORATOR SURGERY; RADIOFREQUENCY OBLITERATION CLOSURE; TELANGIECTATIC LEG VEINS; PLACEBO-CONTROLLED TRIAL AB The Society for Vascular Surgery (SVS) and the American Venous Forum (AVF) have developed clinical practice guidelines for the care of patients with varicose veins of the lower limbs and pelvis. The document also includes recommendations on the management of superficial and perforating vein incompetence in patients with associated, more advanced chronic venous diseases (CVDs), including edema, skin changes, or venous ulcers. Recommendations of the Venous Guideline Committee are based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system as strong (GRADE I) if the benefits clearly outweigh the risks, burden, and costs. The suggestions are weak (GRADE 2) if the benefits are closely balanced with risks and burden. The level of available evidence to support the evaluation or treatment can be of high (A), medium (B), or low or very low (C) quality. The key recommendations of these guidelines are: We recommend that in patients with varicose veins or more severe CVD, a complete history and detailed physical examination are complemented by duplex ultrasound scanning of the deep and superficial veins (GRADE 1A). We recommend that the CEAP classification is used for patients with CVD (GRADE 1A) and that the revised Venous Clinical Severity Score is used to assess treatment outcome (GRADE 1B). We suggest compression therapy for patients with symptomatic varicose veins (GRADE 2C) but recommend against compression therapy as the primary treatment if the patient is a candidate for saphenous vein ablation (GRADE 1B). We recommend compression therapy as the primary treatment to aid healing of venous ulceration (GRADE 1B). To decrease the recurrence of venous ulcers, we recommend ablation of the incompetent superficial veins in addition to compression therapy (GRADE 1A). For treatment of the incompetent great saphenous vein (GSV), we recommend endovenous thermal ablation (radiofrequency or laser) rather than high ligation and inversion stripping of the saphenous vein to the level of the knee (GRADE 1B). We recommend phlebectomy or sclerotherapy to treat varicose tributaries (GRADE 1B) and suggest foam sclerotherapy as an option for the treatment of the incompetent saphenous vein (GRADE 2C). We recommend against selective treatment of perforating vein incompetence in patients with simple varicose veins (CEAP class C-2; GRADE 1B), but we suggest treatment of pathologic perforating veins (outward flow duration >= 500 ms, vein diameter >= 3.5 mm) located underneath healed or active ulcers (CEAP class C-5-C-6; GRADE 2B). We suggest treatment of pelvic congestion syndrome and pelvic varices with coil embolization, plugs, or transcatheter sclerotherapy, used alone or together (GRADE 2B). ( J Vase Surg 2011;53:2S-48S.) C1 [Gloviczki, Peter] Mayo Clin, Div Vasc & Endovasc Surg, Rochester, MN 55905 USA. [Gloviczki, Monika L.] Mayo Clin, Div Nephrol & Hypertens, Rochester, MN 55905 USA. [Murad, M. Hassan] Mayo Clin, Div Prevent Occupat & Aerosp Med, Rochester, MN 55905 USA. [Comerota, Anthony J.] Jobst Vasc Ctr, Toledo, OH USA. [Dalsing, Michael C.] Indiana Univ Sch Med, Indianapolis, IN USA. [Eklof, Bo G.] Lund Univ, Helsingborg, Sweden. [Gillespie, David L.] Univ Rochester, Sch Med & Dent, Rochester, NY USA. [Lohr, Joann M.] Lohr Surg Specialists, Cincinnati, OH USA. [McLafferty, Robert B.] So Illinois Univ, Springfield, IL USA. [Meissner, Mark H.] Univ Washington, Sch Med, Seattle, WA USA. [Padberg, Frank T.; Pappas, Peter J.] Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. [Passman, Marc A.] Univ Alabama Birmingham, Birmingham, AL USA. [Raffetto, Joseph D.] VA Boston Healthcare Syst, W Roxbury, MA USA. [Vasquez, Michael A.] Venous Inst Buffalo, N Tonawanda, NY USA. [Wakefield, Thomas W.] Univ Michigan, Sch Med, Ann Arbor, MI USA. RP Gloviczki, P (reprint author), Mayo Clin, Div Vasc & Endovasc Surg, 200 1st St SW, Rochester, MN 55905 USA. EM gloviczki.peter@mayo.edu OI Gillespie, David/0000-0002-4378-9465; Murad, Mohammad Hassan/0000-0001-5502-5975 NR 374 TC 206 Z9 231 U1 5 U2 30 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 MAY PY 2011 VL 53 SU S BP 2S EP 48S DI 10.1016/j.jvs.2011.01.079 PG 47 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 760YZ UT WOS:000290362600002 PM 21536172 ER PT J AU Conrad, MF Ergul, EA Patel, VI Cambria, MR LaMuraglia, GM Simon, M Cambria, RP AF Conrad, Mark F. Ergul, Emel A. Patel, Virendra I. Cambria, Matthew R. LaMuraglia, Glenn M. Simon, Mirela Cambria, Richard P. TI Evolution of operative strategies in open thoracoabdominal aneurysm repair SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT Vascular Annual Meeting/Society-for-Vascular Surgery CY JUN 10-13, 2010 CL Boston, MA SP Soc Vasc Surg ID HYPOTHERMIC CARDIOPULMONARY BYPASS; INTERCOSTAL ARTERY REATTACHMENT; MOTOR-EVOKED POTENTIALS; AORTIC-ANEURYSM; SPINAL-CORD; CIRCULATORY ARREST; NEUROLOGIC DEFICIT; FLUID DRAINAGE; SURGERY; RISK AB Objective: During a 24-year interval, we managed >90% of thoracoabdominal aortic aneurysm (TAA) repairs with a clamp-and-sew (clamp/sew) approach supplemented with protective adjuncts, including renal hypothermia and epidural cooling with aggressive intercostal reconstruction for spinal cord protection. A finite paraplegia rate led to operative modifications using distal aortic perfusion (DAP) through atriofemoral bypass to support cord collateral circulation and selective intercostal reconstruction based on motor evoked potential (MEP) monitoring. This study evaluated the effect of DAP/MEP on perioperative outcomes. Methods: Consecutive patients undergoing repair of nonruptured Crawford extent I-III TAA using DAP/MEP were compared with propensity-matched patients treated with the clamp/sew technique. Outcomes included 30-day mortality and paraplegia. Results: There were 52 patients in the DAP cohort vs 127 undergoing clamp/sew. The DAP and clamp/sew cohorts differed in age (62.6 vs 69.5 years, P = .0003), presence of Marfan disease (10% vs 2%, P = .01), and chronic dissection (37% vs 8%, P = .001). Operative mortality was low (DAP, 2%; clamp/sew, 5%; P = .38). Postoperative renal insufficiency, although doubled in clamp/sew (17%) vs DAP (8%; P = .10), was not significant. DAP patients had a significantly lower incidence of intercostal reconstruction than the clamp/sew group (1.0% vs 34%, P < .0001), yet there was no paraplegia in the DAP cohort vs 5% in clamp/sew (P = .11). The composite death/paraplegia rate was decreased with DAP at 1 of 52 (2%) vs clamp/sew at 11 of 127 (9%; P = .01). Paraparesis with complete recovery occurred in 5 of 52 (10%) of the DAP group. Conclusions: Elective TAA repair was accomplished with a low mortality in the DAP and clamp/sew cohorts. The use of MEP in the DAP cohort (despite a higher spinal cord ischemic risk due to the number of chronic dissection patients) decreased the need for intercostal reconstruction, with no paraplegia to date. DAP with MEP is the preferred operative strategy for extent I to III TAA repair. (J Vasc Surg 2011;53:1195-201.) C1 Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Conrad, MF (reprint author), 15 Parkman St,WAC 440, Boston, MA 02114 USA. EM mconrad@partners.org NR 45 TC 29 Z9 34 U1 0 U2 3 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 MAY PY 2011 VL 53 IS 5 BP 1195 EP 1201 DI 10.1016/j.jvs.2010.11.055 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 760YU UT WOS:000290362100006 PM 21315544 ER PT J AU Zhao, GF Shaik, RS Zhao, H Beagle, J Kuo, S Hales, CA AF Zhao, Gaofeng Shaik, Rahamthulla S. Zhao, Hang Beagle, John Kuo, Shuennwen Hales, Charles A. TI Low molecular weight (LMW) heparin inhibits injury-induced femoral artery remodeling in mouse via upregulating CD44 expression SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID SMOOTH-MUSCLE-CELLS; PULMONARY-HYPERTENSION; NEOINTIMAL HYPERPLASIA; HYALURONAN RECEPTOR; PROLIFERATION; MECHANISMS; MODEL; ATHEROSCLEROSIS; RESTENOSIS; APOPTOSIS AB Objective: The mechanism of postangioplasty restenosis remains poorly understood. Low molecular weight (LMW) heparin has been shown to inhibit the proliferation of vascular smooth muscle cells (VSMCs), which is the principal characteristic of restenosis. Studies have shown that LMW heparin could bind to CD44. We hypothesized that LMW heparin might modulate CD44 expression thereby decreasing vascular remodeling. Methods: Vascular remodeling was induced in CD44(+/+) and CD44(-/-) mice and treated with LMW heparin. The arteries were harvested for histologic assessment and determination of CD44 expression. Bone marrow transplantation was introduced to further explore the role and functional sites of CD44. Effects of LMW heparin on growth capacity, CD44 expression were further studied using the cultured mouse VSMCs. Results: Transluminal injury induced remarkable remodeling in mouse femoral artery (sham wall thickness percentage [WT%]: 3.4 +/- 1.2% vs injury WT%: 31.8 +/- 4.7%; P < .001). LMW heparin reduced the remodeling significantly (WT%: 17.8 +/- 3.5%, P < .005). CD44(-/-) mice demonstrated considerably thicker arterial wall remodeling (WT%: 46.2 +/- 7.6%, P = .0035), and CD44-chimeric mice exhibited equal contributions of the local and circulating CD44 signal to the neointima formation. LMW heparin markedly upregulated CD44 expression in the injured femoral arteries. In vitro, LMW heparin decreased mouse VSMC growth capacity and upregulated its CD44 expression simultaneously in a dose-dependent and time-dependent manner, which could be partially blocked by CD44 inhibitor. Conclusions: LMW heparin inhibits injury-induced femoral artery remodeling, at least partially, by upregulating CD44 expression. (J Vase Surg 2011;53:1359-67.) C1 [Zhao, Gaofeng; Shaik, Rahamthulla S.; Zhao, Hang; Beagle, John; Kuo, Shuennwen; Hales, Charles A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm Crit Care Unit,Dept Med, Boston, MA 02114 USA. [Zhao, Gaofeng] Zhengzhou Univ, Affiliated Hosp 1, Dept Surg, Zhengzhou, Peoples R China. [Kuo, Shuennwen] Natl Taiwan Univ, Dept Surg & Traumatol, Taipei 10764, Taiwan. RP Hales, CA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm Crit Care Unit,Dept Med, 55 Fruit St,Bulfinch 148, Boston, MA 02114 USA. EM chales@partners.org OI KUO, SHUENN-WEN/0000-0001-5026-5582 FU National Institutes of Health (NIH) [HL039150] FX Supported by National Institutes of Health (NIH) grant HL039150 (C.A.H) NR 28 TC 3 Z9 3 U1 1 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 MAY PY 2011 VL 53 IS 5 BP 1359 EP 1367 DI 10.1016/j.jvs.2010.11.048 PG 9 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 760YU UT WOS:000290362100027 PM 21276692 ER PT J AU Ye, Q Yan, Z Liao, XD Li, Y Yang, J Sun, JN Kawano, T Wang, XJ Cao, Z Wang, ZG Huang, L AF Ye, Qing Yan, Zheng Liao, Xiaodong Li, Yuan Yang, Jie Sun, Jiening Kawano, Takeshi Wang, Xiaojin Cao, Ziang Wang, Zhugang Huang, Lei TI MUC1 induces metastasis in esophageal squamous cell carcinoma by upregulating matrix metalloproteinase 13 SO LABORATORY INVESTIGATION LA English DT Article DE ESCC; metastasis; MMP13; MUC1; transcription ID INHIBITS TUMOR INVASION; GENE-TRANSCRIPTION; IN-VITRO; EXPRESSION; PROGNOSIS; CANCER; STRESS; RNA AB Esophagus squamous cell carcinoma (ESCC) is one of the most deadly malignances because of its high frequency of metastasis. Given the associations of MUC1 with ESCC and tumor metastasis, we explored a potential role of MUC1 in ESCC metastasis. Among 40 ESCC and 20 paired normal tissue specimens examined, we found a significant increase of MUC1 expression in ESCC and more importantly, that expression of MUC1 and MMP13 are strongly correlated in patients who had lymph node metastasis. Studies with cell models indicated that overexpression of MUC1 upregulates the expression of MMP13, leading to increased cell migration. In support of a mode of transcriptional regulation, promoter analysis revealed that MUC1 stimulates MMP13 expression through the Runx-2-binding site. The link of MUC1 to cell motility was further confirmed by the finding that depletion of MUC1 resulted in reduced expression of MMP13 and cell migration, invasion and adhesion. Moreover, the loss of cell metastatic potential was rescued by overexpression of MMP13 completely. Collectively, our findings indicate that MUC1 contributes to ESCC metastasis by stimulating MMP13 expression, suggesting MUC1 as a novel diagnostic biomarker and therapeutic target in ESCC. Laboratory Investigation (2011) 91, 778-787; doi:10.1038/labinvest.2011.12; published online 21 February 2011 C1 [Yan, Zheng; Liao, Xiaodong; Li, Yuan; Yang, Jie; Sun, Jiening; Wang, Zhugang; Huang, Lei] Shanghai Jiao Tong Univ, Dept Med Genet, Sch Med, Shanghai Univ,E Inst, Shanghai 200025, Peoples R China. [Ye, Qing; Cao, Ziang] Shanghai Jiao Tong Univ, Renji Hosp, Sch Med, Dept Cardiothorac Surg, Shanghai 200025, Peoples R China. [Wang, Xiaojin] Shanghai Jiao Tong Univ, Dept Biostat, Sch Med, Shanghai 200025, Peoples R China. [Kawano, Takeshi] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Huang, L (reprint author), Shanghai Jiao Tong Univ, Dept Med Genet, Sch Med, Shanghai Univ,E Inst, 280 S Chongqing Rd, Shanghai 200025, Peoples R China. EM zhugangw@shsmu.edu.cn; leihuang@shsmu.edu.cn FU NNSF of China [30871363, 81071666]; State Education Ministry; Science and Technology Commission of Shanghai Municipality [07pj14065, 06ZR14067]; Shanghai Municipal Education Commission [E03003, J50201]; [NCET-08-0349] FX This work was supported by program 30871363, 81071666 by NNSF of China, program NCET-08-0349 and the SRF for ROCS by State Education Ministry, the program 07pj14065 and 06ZR14067 by Science and Technology Commission of Shanghai Municipality and program E03003 and J50201 by the Shanghai Municipal Education Commission. The authors are very grateful to Dr Donald Kufe (Dana-Farber Cancer Institute, Harvard Medical School) for expert advice and to Dr Zhimin Yuan (UT Health Science Center) for critical comments on the manuscript. NR 25 TC 22 Z9 22 U1 2 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD MAY PY 2011 VL 91 IS 5 BP 778 EP 787 DI 10.1038/labinvest.2011.12 PG 10 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 755WT UT WOS:000289971200013 PM 21339746 ER PT J AU Zinman, L Cudkowicz, M AF Zinman, Lorne Cudkowicz, Merit TI Emerging targets and treatments in amyotrophic lateral sclerosis SO LANCET NEUROLOGY LA English DT Review ID STEM-CELL TRANSPLANTATION; PLACEBO-CONTROLLED TRIAL; FRONTOTEMPORAL LOBAR DEGENERATION; RANDOMIZED SEQUENTIAL TRIAL; GROWTH-FACTOR-I; MOUSE MODEL; WILD-TYPE; SUPEROXIDE-DISMUTASE; CLINICAL-TRIAL; SKELETAL-MUSCLE AB Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease that is currently untreatable. Many compounds have been tested in laboratory-based models and in patients with ALS, but so far only one drug, riluzole, has shown efficacy, yet it only slightly slows disease progression. Several new insights into the causes of motor neuron death have led to the identification of some important novel targets for intervention. At no time have studies involved such a wide range of innovations and such advanced technologies. Many promising studies are underway to test potential targets that will hopefully translate into meaningful therapeutics for patients with ALS. C1 [Zinman, Lorne] Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. [Cudkowicz, Merit] Massachusetts Gen Hosp, Neurol Clin Trials Unit, Charlestown, MA USA. RP Zinman, L (reprint author), Sunnybrook Hlth Sci Ctr, 2075 Bayview Ave,UG-26, Toronto, ON M4N 3M5, Canada. EM lorne.zinman@sunnybrook.ca FU Neuralstem; ISIS; Knopp Neuroscience FX MC has received research grants from Neuralstem, ISIS, and Knopp Neuroscience, and has consulted for Trophos and Synapse, serving as chairperson of the data and safety monitoring board. LZ declares that he has no conflicts of interest. NR 106 TC 46 Z9 50 U1 0 U2 18 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1474-4422 EI 1474-4465 J9 LANCET NEUROL JI Lancet Neurol. PD MAY PY 2011 VL 10 IS 5 BP 481 EP 490 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 761TV UT WOS:000290424800017 PM 21511200 ER PT J AU Askenazi, M Webber, JT Marto, JA AF Askenazi, Manor Webber, James T. Marto, Jarrod A. TI mzServer: Web-based Programmatic Access for Mass Spectrometry Data Analysis SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID PROTEOMIC MS REPOSITORIES; PIPELINES; WORLD AB Continued progress toward systematic generation of large-scale and comprehensive proteomics data in the context of biomedical research will create project-level data sets of unprecedented size and ultimately overwhelm current practices for results validation that are based on distribution of native or surrogate mass spectrometry files. Moreover, the majority of proteomics studies leverage discovery-mode MS/MS analyses, rendering associated data-reduction efforts incomplete at best, and essentially ensuring future demand for re-analysis of data as new biological and technical information become available. Based on these observations, we propose to move beyond the sharing of interpreted spectra, or even the distribution of data at the individual file or project level, to a system much like that used in high-energy physics and astronomy, whereby raw data are made programmatically accessible at the site of acquisition. Toward this end we have developed a web-based server (mzServer), which exposes our common API (mzAPI) through very intuitive (RESTful) uniform resource locators (URL) and provides remote data access and analysis capabilities to the research community. Our prototype mzServer provides a model for lab-based and community-wide data access and analysis. Molecular & Cellular Proteomics 10: 10.1074/mcp.M110.003988, 1-7, 2011. C1 [Webber, James T.; Marto, Jarrod A.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Webber, James T.; Marto, Jarrod A.] Dana Farber Canc Inst, Blais Prote Ctr, Boston, MA 02115 USA. [Askenazi, Manor; Marto, Jarrod A.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Askenazi, Manor] Hebrew Univ Jerusalem, Dept Biol Chem, IL-91904 Jerusalem, Israel. 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 OI Webber, James/0000-0001-8594-9888 FU Dana-Farber Cancer Institute; National Institutes of Health, NHGRI [P50HG004233]; National Institutes of Health, NINDS [P01NS047572] FX Generous support for this work was provided by the Dana-Farber Cancer Institute and the National Institutes of Health, NHGRI (P50HG004233), and NINDS (P01NS047572). NR 15 TC 5 Z9 5 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD MAY PY 2011 VL 10 IS 5 SI SI DI 10.1074/mcp.M110.003988 PG 7 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 759CC UT WOS:000290216700008 ER PT J AU Webber, JT Askenazi, M Marto, JA AF Webber, James T. Askenazi, Manor Marto, Jarrod A. TI mzResults: An Interactive Viewer for Interrogation and Distribution of Proteomics Results SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID MASS-SPECTROMETRY; MS REPOSITORIES; PROTEIN; GUIDELINES; MS/MS; QUANTITATION; PIPELINES; STRATEGY; TANDEM; TOOLS AB The growing use of mass spectrometry in the context of biomedical research has been accompanied by an increased demand for distribution of results in a format that facilitates rapid and efficient validation of claims by reviewers and other interested parties. However, the continued evolution of mass spectrometry hardware, sample preparation methods, and peptide identification algorithms complicates standardization and creates hurdles related to compliance with journal submission requirements. Moreover, the recently announced Philadelphia Guidelines (1, 2) suggest that authors provide native mass spectrometry data files in support of their peer-reviewed research articles. These trends highlight the need for data viewers and other tools that work independently of manufacturers' proprietary data systems and seamlessly connect proteomics results with original data files to support user-driven data validation and review. Based upon our recently described API1-based framework for mass spectrometry data analysis (3, 4), we created an interactive viewer (mzResults) that is built on established database standards and enables efficient distribution and interrogation of results associated with proteomics experiments, while also providing a convenient mechanism for authors to comply with data submission standards as described in the Philadelphia Guidelines. In addition, the architecture of mzResults supports in-depth queries of the native mass spectrometry files through our multiplierz software environment. We use phosphoproteomics data to illustrate the features and capabilities of mzResults. Molecular & Cellular Proteomics 10: 10.1074/mcp.M110.003970, 1-7, 2011. C1 [Webber, James T.; Marto, Jarrod A.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Webber, James T.; Marto, Jarrod A.] Dana Farber Canc Inst, Blais Prote Ctr, Boston, MA 02115 USA. [Askenazi, Manor; Marto, Jarrod A.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Askenazi, Manor] Hebrew Univ Jerusalem, Dept Biol Chem, IL-91905 Jerusalem, Israel. 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 OI Webber, James/0000-0001-8594-9888 FU Dana-Farber Cancer Institute; National Institutes of Health, NHGRI [P50HG004233]; National Institutes of Health, NINDS [P01NS047572] FX Generous support for this work was provided by the Dana-Farber Cancer Institute and the National Institutes of Health, NHGRI (P50HG004233), and NINDS (P01NS047572). NR 28 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD MAY PY 2011 VL 10 IS 5 SI SI DI 10.1074/mcp.M110.003970 PG 7 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 759CC UT WOS:000290216700007 ER PT J AU Kure, M Pezzolesi, MG Poznik, GD Katavetin, P Skupien, J Dunn, JS Mychaleckyj, JC Warram, JH Krolewski, AS AF Kure, Masahiko Pezzolesi, Marcus G. Poznik, G. David Katavetin, Pisut Skupien, Jan Dunn, Jonathon S. Mychaleckyj, Josyf C. Warram, James H. Krolewski, Andrzej S. TI Genetic variation in the matrix metalloproteinase genes and diabetic nephropathy in type 1 diabetes SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE Diabetic nephropathy; Type 1 diabetes; End-stage renal disease; Matrix metalloproteinase; Genetic association ID ALLELE-SPECIFIC REGULATION; ARTERY LUMINAL DIMENSIONS; GENOME-WIDE ASSOCIATION; PROMOTER ACTIVITY; SUSCEPTIBILITY; DISEASE; EXPRESSION; MELLITUS; GLOMERULOSCLEROSIS; ATHEROSCLEROSIS AB Genetic data support the notion that polymorphisms in members of the matrix metalloproteinase (MMP) family of genes play an important role in extracellular matrix remodeling and contribute to the pathogenesis of vascular disease. To identify novel genetic markers for diabetic nephropathy (DN), we examined the relationship between MMP gene polymorphisms and DN in the Genetics of Kidneys in Diabetes (GoKinD) population. Genotypic data from the Genetic Association Information Network (GAIN) type 1 DN project were analyzed for associations across 21 MMP genes in 1705 individual with type 1 diabetes, including 885 normoalbuminuric control subjects and 820 advanced DN case subjects. In total, we investigated the role of 1283 SNPs (198 genotyped SNPs and 1085 imputed SNPs) mapping to the MMP genes. We identified associations at several correlated SNPs across a 29.2 kb interval on chromosome 11q at the MMP-3/MMP-12 locus. The strongest associations occurred at 2 highly-correlated SNPs, rs610950 (OR=0.50, P=1.6x10(-5)) and rs1277718 (OR = 0.50, P = 2.1 x 10(-5)). Further examination of this locus identified 17 SNPs (2 genotyped SNPs and 15 imputed SNPs) in complete linkage disequilibrium associated with ON (P-values < 2.5 x 10(-4)), including a non-synonymous SNP (rs652438, Asn357Ser) located in exon 8 of MMP-12 that significantly reduced the risk of DN among carriers of the serine substitution relative to homozygous carriers of asparagine (OR = 0.51; 95% CI = 0.37-0.71, P=62 x 10(-5)). Taken together, our study suggests that genetic variations within the MMP-3/MMP-12 locus influence susceptibility of ON in type 1 diabetes. (C) 2011 Elsevier Inc. All rights reserved. C1 [Krolewski, Andrzej S.] Joslin Diabet Ctr, Div Res, Sect Genet & Epidemiol, Boston, MA 02215 USA. [Kure, Masahiko; Pezzolesi, Marcus G.; Poznik, G. David; Katavetin, Pisut; Skupien, Jan; Dunn, Jonathon S.; Warram, James H.; Krolewski, Andrzej S.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Mychaleckyj, Josyf C.] Univ Virginia, Sch Med, Ctr Publ Hlth Genom, Charlottesville, VA 22908 USA. [Katavetin, Pisut] Chulalongkorn Univ, Fac Med, Dept Med, Div Nephrol, Bangkok 10330, Thailand. RP Krolewski, AS (reprint author), Joslin Diabet Ctr, Div Res, Sect Genet & Epidemiol, 1 Joslin Pl, Boston, MA 02215 USA. EM Andrzej.Krolewski@joslin.harvard.edu FU Juvenile Diabetes Research Foundation (JDRF) [3-2009-397]; Centers for Disease Control (CDC) [PL 105-33, 106-554, 107-360]; National Institutes of Health (NIH) [DK58549, DK77532, DK36836]; Joslin Diabetes Center's NIH [DK007260-31] FX Funding support for the GAIN Search for Susceptibility Genes for Diabetic Nephropathy in Type 1 Diabetes (GoKinD study participants) study was provided by the Juvenile Diabetes Research Foundation (JDRF), and the Centers for Disease Control (CDC) (PL 105-33, 106-554, and 107-360 administered by the National Institute of Diabetes and Digestive and Kidney Diseases, NIDDK) and the genotyping of samples was provided through the Genetic Association Information Network (GAIN). The dataset(s) used for the analyses described in this manuscript were obtained from the database of Genotype and Phenotype (dbGaP) found at http://www.ncbi.nlm.nih.gov/gap through dbGaP accession number phs000018.v1.p1.; We acknowledge grant support from the National Institutes of Health (NIH) (DK58549 and DK77532 to ASK and DK36836 to the Genetics Core of the Diabetes and Endocrinology Research Center at the Joslin Diabetes Center). We also acknowledge the Joslin Diabetes Center's NIH T32 Training Grant (DK007260-31 to MGP) and support from the Juvenile Diabetes Research Foundation (JDRF) (3-2009-397 to JS). NR 36 TC 3 Z9 3 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 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD MAY PY 2011 VL 103 IS 1 BP 60 EP 65 DI 10.1016/j.ymgme.2011.01.001 PG 6 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 758WW UT WOS:000290199100009 PM 21277817 ER PT J AU Nathwani, AC Rosales, C McIntosh, J Rastegarlari, G Nathwani, D Raj, D Nawathe, S Waddington, SN Bronson, R Jackson, S Donahue, RE High, KA Mingozzi, F Ng, CYC Zhou, JF Spence, Y McCarville, MB Valentine, M Allay, J Coleman, J Sleep, S Gray, JT Nienhuis, AW Davidoff, AM AF Nathwani, Amit C. Rosales, Cecilia McIntosh, Jenny Rastegarlari, Ghasem Nathwani, Devhrut Raj, Deepak Nawathe, Sushmita Waddington, Simon N. Bronson, Roderick Jackson, Scott Donahue, Robert E. High, Katherine A. Mingozzi, Federico Ng, Catherine Y. C. Zhou, Junfang Spence, Yunyu McCarville, M. Beth Valentine, Marc Allay, James Coleman, John Sleep, Susan Gray, John T. Nienhuis, Arthur W. Davidoff, Andrew M. TI Long-term Safety and Efficacy Following Systemic Administration of a Self-complementary AAV Vector Encoding Human FIX Pseudotyped With Serotype 5 and 8 Capsid Proteins SO MOLECULAR THERAPY LA English DT Article ID ADENOASSOCIATED VIRAL VECTORS; HUMAN-FACTOR-IX; NONHUMAN PRIMATE MODEL; HEMOPHILIA-B; GENE-THERAPY; EFFICIENT TRANSDUCTION; LIVER TRANSDUCTION; SKELETAL-MUSCLE; VIRUS VECTORS; LARGE-SCALE AB Adeno-associated virus vectors (AAV) show promise for liver-targeted gene therapy. In this study, we examined the long-term consequences of a single intravenous administration of a self-complementary AAV vector (scAAV2/8-LP1-hFIXco) encoding a codon optimized human factor IX (hFIX) gene in 24 nonhuman primates (NHPs). A dose-response relationship between vector titer and transgene expression was observed. Peak hFIX expression following the highest dose of vector (2 x 10(12) pcr-vector genomes (vg)/kg) was 21 +/- 3 mu g/ml (similar to 420% of normal). Fluorescent in-situ hybridization demonstrated scAAV provirus in almost 100% of hepatocytes at that dose. No perturbations of clinical or laboratory parameters were noted and vector genomes were cleared from bodily fluids by 10 days. Macaques transduced with 2 x 10(11) pcr-vg/kg were followed for the longest period (similar to 5 years), during which time expression of hFIX remained > 10% of normal level, despite a gradual decline in transgene copy number and the proportion of transduced hepatocytes. All macaques developed serotype-specific antibodies but no capsid-specific cytotoxic T lymphocytes were detected. The liver was preferentially transduced with 300-fold more proviral copies than extrahepatic tissues. Long-term biochemical, ultrasound imaging, and histologic follow-up of this large cohort of NHP revealed no toxicity. These data support further evaluation of this vector in hemophilia B patients. C1 [Nathwani, Amit C.; Rosales, Cecilia; McIntosh, Jenny; Rastegarlari, Ghasem; Nathwani, Devhrut; Raj, Deepak; Nawathe, Sushmita] UCL, UCL Canc Inst, Dept Hematol, London WC1E 6BT, England. [Nathwani, Amit C.] NHS Blood & Transplant, London, England. [Waddington, Simon N.] UCL, Inst Womens Hlth, London WC1E 6BT, England. [Bronson, Roderick; Davidoff, Andrew M.] Dana Farber Harvard Canc Ctr, Boston, MA USA. [Jackson, Scott] Univ Tennessee, Hlth Sci Ctr, Dept Comparat Med, Memphis, TN USA. [Donahue, Robert E.] NHLBI, Hematol Branch, Washington, DC USA. [High, Katherine A.; Mingozzi, Federico] Childrens Hosp Philadelphia, Ctr Cellular & Mol Therapeut, Philadelphia, PA 19104 USA. [High, Katherine A.] Childrens Hosp Philadelphia, Howard Hughes Med Inst, Philadelphia, PA 19104 USA. [Ng, Catherine Y. C.; Zhou, Junfang; Spence, Yunyu] St Jude Childrens Hosp, Dept Surg, Memphis, TN 38105 USA. [McCarville, M. Beth] St Jude Childrens Hosp, Dept Radiol Sci, Memphis, TN 38105 USA. [Valentine, Marc] St Jude Childrens Hosp, Dept Genet & Tumor Cell Biol, Memphis, TN 38105 USA. [Allay, James; Coleman, John; Sleep, Susan] St Jude Childrens Hosp, Childrens GMP, Memphis, TN 38105 USA. [Gray, John T.; Nienhuis, Arthur W.] St Jude Childrens Hosp, Div Expt Hematol, Memphis, TN 38105 USA. RP Nathwani, AC (reprint author), UCL, UCL Canc Inst, Dept Hematol, Paul OGorman Bldg,72 Huntley St, London WC1E 6BT, England. EM a.nathwani@ucl.ac.uk RI Waddington, Simon/G-3778-2011; mingozzi, federico/I-2332-2013 OI Waddington, Simon/0000-0003-4970-4730; FU Katharine Dormandy Trust, U.K., Medical Research Council, UK, Department of Health's NIHR Biomedical Research Centers; National Heart, Lung, and Blood Institute [HL073838]; National Cancer Institute Cancer Center [CA027165] FX This work was supported by The Katharine Dormandy Trust, U.K., Medical Research Council, UK, Department of Health's NIHR Biomedical Research Centers funding award to UCLH/UCL, UK, The ASSISI Foundation of Memphis, the American Lebanese Syrian Associated Charities (ALSAC), the National Heart, Lung, and Blood Institute grant HL073838 and the National Cancer Institute Cancer Center Support Grant CA027165. This report/article presents independent research commissioned by the National Institute for Health Research (NIHR), UK under its Programme Grants for Applied Research scheme (RP-PG-0310-1001). The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health. The authors declared no conflict of interest. NR 45 TC 107 Z9 109 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2011 VL 19 IS 5 BP 876 EP 885 DI 10.1038/mt.2010.274 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 758FE UT WOS:000290146200012 PM 21245849 ER PT J AU Kostic, AD Ojesina, AI Pedamallu, CS Jung, J Verhaak, RGW Getz, G Meyerson, M AF Kostic, Aleksandar D. Ojesina, Akinyemi I. Pedamallu, Chandra Sekhar Jung, Joonil Verhaak, Roel G. W. Getz, Gad Meyerson, Matthew TI PathSeq: software to identify or discover microbes by deep sequencing of human tissue SO NATURE BIOTECHNOLOGY LA English DT Letter ID HUMAN GENOME; SUBTRACTION; CARCINOMA; SEARCH C1 [Kostic, Aleksandar D.; Ojesina, Akinyemi I.; Pedamallu, Chandra Sekhar; Jung, Joonil; Verhaak, Roel G. W.; Getz, Gad; Meyerson, Matthew] Massachusetts Inst Technol & Harvard, Broad Inst, Cambridge, MA USA. [Kostic, Aleksandar D.; Meyerson, Matthew] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Ojesina, Akinyemi I.; Pedamallu, Chandra Sekhar; Jung, Joonil; Verhaak, Roel G. W.; Meyerson, Matthew] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Ojesina, Akinyemi I.; Pedamallu, Chandra Sekhar; Jung, Joonil; Verhaak, Roel G. W.; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Kostic, AD (reprint author), Massachusetts Inst Technol & Harvard, Broad Inst, Cambridge, MA USA. EM matthew_meyerson@dfci.harvard.edu RI Meyerson, Matthew/E-7123-2012; OI Ojesina, Akinyemi/0000-0003-0755-3639; Kostic, Aleksandar/0000-0002-0837-4360 FU NCI NIH HHS [RC2 CA148317, RC2CA148317] NR 15 TC 108 Z9 113 U1 0 U2 14 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD MAY PY 2011 VL 29 IS 5 BP 393 EP 396 DI 10.1038/nbt.1868 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 760CX UT WOS:000290301700013 PM 21552235 ER PT J AU Lupberger, J Zeisel, MB Xiao, F Thumann, C Fofana, I Zona, L Davis, C Mee, CJ Turek, M Gorke, S Royer, C Fischer, B Zahid, MN Lavillette, D Fresquet, J Cosset, FL Rothenberg, SM Pietschmann, T Patel, AH Pessaux, P Doffoel, M Raffelsberger, W Poch, O McKeating, JA Brino, L Baumert, TF AF Lupberger, Joachim Zeisel, Mirjam B. Xiao, Fei Thumann, Christine Fofana, Isabel Zona, Laetitia Davis, Christopher Mee, Christopher J. Turek, Marine Gorke, Sebastian Royer, Cathy Fischer, Benoit Zahid, Muhammad N. Lavillette, Dimitri Fresquet, Judith Cosset, Francois-Loic Rothenberg, S. Michael Pietschmann, Thomas Patel, Arvind H. Pessaux, Patrick Doffoel, Michel Raffelsberger, Wolfgang Poch, Olivier McKeating, Jane A. Brino, Laurent Baumert, Thomas F. TI EGFR and EphA2 are host factors for hepatitis C virus entry and possible targets for antiviral therapy SO NATURE MEDICINE LA English DT Article ID EPIDERMAL-GROWTH-FACTOR; CELL LUNG-CANCER; B TYPE-I; FACTOR RECEPTOR; NEUTRALIZING ANTIBODIES; HEPATOMA-CELLS; TRANSFORMING-GROWTH; HUMAN LIVER; INFECTION; CD81 AB Hepatitis C virus (HCV) is a major cause of liver disease, but therapeutic options are limited and there are no prevention strategies. Viral entry is the first step of infection and requires the cooperative interaction of several host cell factors. Using a functional RNAi kinase screen, we identified epidermal growth factor receptor and ephrin receptor A2 as host cofactors for HCV entry. Blocking receptor kinase activity by approved inhibitors broadly impaired infection by all major HCV genotypes and viral escape variants in cell culture and in a human liver chimeric mouse model in vivo. The identified receptor tyrosine kinases (RTKs) mediate HCV entry by regulating CD81-claudin-1 co-receptor associations and viral glycoprotein-dependent membrane fusion. These results identify RTKs as previously unknown HCV entry cofactors and show that tyrosine kinase inhibitors have substantial antiviral activity. Inhibition of RTK function may constitute a new approach for prevention and treatment of HCV infection. C1 [Lupberger, Joachim; Zeisel, Mirjam B.; Xiao, Fei; Thumann, Christine; Fofana, Isabel; Zona, Laetitia; Turek, Marine; Royer, Cathy; Zahid, Muhammad N.; Baumert, Thomas F.] INSERM, U748, Strasbourg, France. [Lupberger, Joachim; Zeisel, Mirjam B.; Xiao, Fei; Thumann, Christine; Fofana, Isabel; Zona, Laetitia; Turek, Marine; Royer, Cathy; Zahid, Muhammad N.; Baumert, Thomas F.] Univ Strasbourg, Strasbourg, France. [Davis, Christopher; Mee, Christopher J.; McKeating, Jane A.] Univ Birmingham, Div Immun & Infect, Hepatitis C Res Grp, Birmingham, W Midlands, England. [Gorke, Sebastian] Univ Freiburg, Dept Med 2, Freiburg, Germany. [Fischer, Benoit; Raffelsberger, Wolfgang; Poch, Olivier; Brino, Laurent; Baumert, Thomas F.] Univ Strasbourg, INSERM, CNRS, Inst Genet & Biol Mol & Cellulaire,U964,UMR1704, Illkirch Graffenstaden, France. [Lavillette, Dimitri; Fresquet, Judith; Cosset, Francois-Loic] Univ Lyon 1, INSERM, Ecole Normale Super, Inst Fed Rech 128,U758, F-69365 Lyon, France. [Rothenberg, S. Michael] Massachusetts Gen Hosp, Ctr Canc, Howard Hughes Med Inst, Charlestown, MA USA. [Rothenberg, S. Michael] Harvard Univ, Sch Med, Charlestown, MA USA. [Pietschmann, Thomas] Ctr Expt & Clin Infect Res, TWINCORE, Div Expt Virol, Hannover, Germany. [Patel, Arvind H.] Univ Glasgow, MRC, Ctr Virus Res, Glasgow, Lanark, Scotland. [Pessaux, Patrick; Doffoel, Michel; Baumert, Thomas F.] Hop Univ Strasbourg, Strasbourg, France. RP Baumert, TF (reprint author), INSERM, U748, Strasbourg, France. EM thomas.baumert@unistra.fr RI Xiao, Fei/E-7133-2013; zahid, Muhammad Nauman/F-8793-2013; Pietschmann, Thomas/E-9241-2015; Zeisel, Mirjam/E-9205-2016; OI Xiao, Fei/0000-0001-7353-2700; Pietschmann, Thomas/0000-0001-5138-6239; Zeisel, Mirjam/0000-0003-1606-0131; Mee, Christopher/0000-0002-6359-2694; McKeating, Jane/0000-0002-7229-5886 FU European Research Council [ERC-2008-AdG-233130-HEPCENT]; INTERREG-IV-Rhin Superieur-FEDER-Hepato-Regio-Net; Agence Nationale de la Recherche [ANR-05-CEXC-008]; Agence Nationale de Recherche sur le Sida [2008/354]; Region Alsace; Institut National du Cancer; Institut de Genetique et de Biologie Moleculaire et Cellulaire; Institut National de la Sante et de la Recherche Medicale; Centre National de la Recherche Scientifique; Universite de Strasbourg; US National Insititutes of Health [1K08DE020139-01A1]; UK Medical Research Council; Wellcome Trust FX This work was supported by the European Research Council (ERC-2008-AdG-233130-HEPCENT), INTERREG-IV-Rhin Superieur-FEDER-Hepato-Regio-Net 2009, Agence Nationale de la Recherche (ANR-05-CEXC-008), Agence Nationale de Recherche sur le Sida 2008/354, Region Alsace, Institut National du Cancer, the Institut de Genetique et de Biologie Moleculaire et Cellulaire, Institut National de la Sante et de la Recherche Medicale, Centre National de la Recherche Scientifique, Universite de Strasbourg, the US National Insititutes of Health (1K08DE020139-01A1), the UK Medical Research Council and the Wellcome Trust. We acknowledge A.-L. Morand, L. Froidevaux, A. Weiss, L. Poidevin, S. Durand and E. Soulier for excellent technical work. We thank R. Bartenschlager (University of Heidelberg) for providing Jc1 and Luc-Jc1 expression vectors, J. Ball (University of Nottingham) for UKN2A.2.4, UKN3A1.28 and UKN4.21.16 expression vectors, T. Wakita (National Institute of Infectious Diseases, Japan) for JFH1 constructs, C. M. Rice (The Rockefeller University) for Huh7.5 cells, F. V. Chisari (The Scripps Research Institute) for Huh7.5.1 cells, E. Harlow (Harvard University) for CDC2 expression plasmids and M. Tanaka (Hamamatsu University) for EphA2 expression plasmids. NR 55 TC 318 Z9 328 U1 4 U2 52 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAY PY 2011 VL 17 IS 5 BP 589 EP U109 DI 10.1038/nm.2341 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 759MR UT WOS:000290250400035 PM 21516087 ER PT J AU Vemula, PK Anderson, RR Karp, JM AF Vemula, Praveen Kumar Anderson, R. Rox Karp, Jeffrey M. TI Nanoparticles reduce nickel allergy by capturing metal ions SO NATURE NANOTECHNOLOGY LA English DT Article ID CONTACT-DERMATITIS; ACETIC ACID; SOFT ACIDS; IN-VIVO; RELEASE; DISULFIRAM; CHELATION; BASES; HARD; EDTA AB Approximately 10% of the population in the USA(1,2) suffer from nickel allergy(3-5), and many are unable to wear jewellery or handle coins and other objects that contain nickel(6-10). Many agents have been developed to reduce the penetration of nickel through skin(11,12), but few formulations are safe and effective(13-15). Here, we show that applying a thin layer of glycerine emollient containing nanoparticles of either calcium carbonate or calcium phosphate on an isolated piece of pig skin (in vitro) and on the skin of mice (in vivo) prevents the penetration of nickel ions into the skin. The nanoparticles capture nickel ions by cation exchange, and remain on the surface of the skin, allowing them to be removed by simple washing with water. Approximately 11-fold fewer nanoparticles by mass are required to achieve the same efficacy as the chelating agent ethylenediamine tetraacetic acid. Using nanoparticles with diameters smaller than 500 nm in topical creams may be an effective way to limit the exposure to metal ions that can cause skin irritation. C1 [Vemula, Praveen Kumar; Karp, Jeffrey M.] Harvard Univ, Sch Med, Ctr Regenerat Therapeut, Boston, MA 02115 USA. [Vemula, Praveen Kumar; Karp, Jeffrey M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Vemula, Praveen Kumar; Karp, Jeffrey M.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Vemula, Praveen Kumar; Karp, Jeffrey M.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Anderson, R. Rox] Harvard Univ, Sch Med, Laser & Cosmet Dermatol Ctr, Boston, MA 02114 USA. [Anderson, R. Rox] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Vemula, PK (reprint author), Harvard Univ, Sch Med, Ctr Regenerat Therapeut, Boston, MA 02115 USA. EM jkarp@rics.bwh.harvard.edu FU Brigham and Women's Hospital; Ewing Marion Kauffman Foundation FX The authors thank A. Kimball from the Massachusetts General Hospital for helpful discussions. This work was funded by start-up funds from the Brigham and Women's Hospital (J.M.K.). P.K.V. acknowledges the Ewing Marion Kauffman Foundation for an entrepreneur postdoctoral fellowship. The authors also thank D. Blankschtein and B. Polat for the generous gift of pigskin, as well as the MIT Center for Material Science Engineering Imaging facility and P. Boisvert for assistance, and S. Sonis for valuable discussions. NR 30 TC 14 Z9 14 U1 1 U2 15 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1748-3387 J9 NAT NANOTECHNOL JI Nat. Nanotechnol. PD MAY PY 2011 VL 6 IS 5 BP 291 EP 295 DI 10.1038/NNANO.2011.37 PG 5 WC Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Science & Technology - Other Topics; Materials Science GA 760CV UT WOS:000290301300009 PM 21460828 ER PT J AU Laubach, J Richardson, PG Anderson, K AF Laubach, Jacob Richardson, Paul G. Anderson, Kenneth TI HEMATOLOGY Setting the standard for newly diagnosed multiple myeloma SO NATURE REVIEWS CLINICAL ONCOLOGY LA English DT Editorial Material ID STEM-CELL TRANSPLANTATION; THALIDOMIDE PLUS DEXAMETHASONE; BORTEZOMIB; THERAPY; TRIAL C1 [Laubach, Jacob; Richardson, Paul G.; Anderson, Kenneth] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Laubach, J (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM jacobp_laubach@dfci.harvard.edu NR 10 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4774 J9 NAT REV CLIN ONCOL JI Nat. Rev. Clin. Oncol. PD MAY PY 2011 VL 8 IS 5 BP 255 EP 256 DI 10.1038/nrclinonc.2011.43 PG 2 WC Oncology SC Oncology GA 758GG UT WOS:000290150100001 PM 21423257 ER PT J AU Zhu, AX Duda, DG Sahani, DV Jain, RK AF Zhu, Andrew X. Duda, Dan G. Sahani, Dushyant V. Jain, Rakesh K. TI HCC and angiogenesis: possible targets and future directions SO NATURE REVIEWS CLINICAL ONCOLOGY LA English DT Review ID ENDOTHELIAL-GROWTH-FACTOR; ADVANCED HEPATOCELLULAR-CARCINOMA; TYROSINE KINASE INHIBITOR; TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION; MESSENGER-RNA EXPRESSION; PHASE-II TRIAL; CANCER-RELATED INFLAMMATION; FACTOR-RECEPTOR; PROGNOSTIC-SIGNIFICANCE; VASCULAR NORMALIZATION AB Hepatocellular carcinoma (HCC), the most common primary liver tumor, is notoriously resistant to systemic therapies, and often recurs even after aggressive local therapies. HCCs rely on the formation of new blood vessels for growth, and VEGF is critical in this process. A hallmark of new vessel formation in tumors is their structural and functional abnormality. This leads to an abnormal tumor microenvironment characterized by low oxygen tension. The liver is perfused by both arterial and venous blood and the resulting abnormal microenvironment selects for more-aggressive malignancies. Anti-VEGF therapy with sorafenib was the first systemic therapy to demonstrate improved survival in patients with advanced-stage HCC. This important development in the treatment of HCC raises hope as well as critical questions on the future development of targeted agents including other antiangiogenic agents, which hold promise to further increase survival in this aggressive disease. C1 [Zhu, Andrew X.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA. [Duda, Dan G.; Jain, Rakesh K.] Harvard Univ, Steele Lab Tumor Biol, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. [Sahani, Dushyant V.] Harvard Univ, Dept Radiol, Sch Med, Boston, MA 02114 USA. RP Zhu, AX (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, 55 Fruit St, Boston, MA 02114 USA. EM azhu@partners.org FU National Institutes of Health [P01CA80124, R01CA115767, R21CA139168, M01RR01066]; Department of Defense [W81XWH-10-1-0016]; American Cancer Society [RSG-11-073-01-TBG] FX The authors acknowledge support by the National Institutes of Health (P01CA80124, R01CA115767, R21CA139168, M01RR01066, Federal Share/NCI Proton Beam Program Income Grants); by a Department of Defense Breast Cancer Research Innovator award (W81XWH-10-1-0016) and by an American Cancer Society Research Grant (RSG-11-073-01-TBG). NR 147 TC 156 Z9 166 U1 0 U2 23 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4774 EI 1759-4782 J9 NAT REV CLIN ONCOL JI Nat. Rev. Clin. Oncol. PD MAY PY 2011 VL 8 IS 5 BP 292 EP 301 DI 10.1038/nrclinonc.2011.30 PG 10 WC Oncology SC Oncology GA 758GG UT WOS:000290150100007 PM 21386818 ER PT J AU Tercyak, KP Alford, SH Emmons, KM Lipkus, IM Wilfond, BS McBride, CM AF Tercyak, Kenneth P. Alford, Sharon Hensley Emmons, Karen M. Lipkus, Isaac M. Wilfond, Benjamin S. McBride, Colleen M. TI Parents' Attitudes Toward Pediatric Genetic Testing for Common Disease Risk SO PEDIATRICS LA English DT Article DE genetic testing; chronic disease; risks and benefits; children; parents ID PERSONALIZED MEDICINE; PSYCHOLOGICAL-ASPECTS; CONFOUNDER-SELECTION; GENOMICS; CHILDREN; HEALTH; CANCER; BEHAVIORS; WILL; OPPORTUNITIES AB OBJECTIVE: To describe parents' attitudes toward pediatric genetic testing for common, adult-onset health conditions and to identify factors underlying these attitudes. PARTICIPANTS AND METHODS: Parents (n = 219) enrolled in a large, group-practice health plan were offered a "multiplex" genetic test for susceptibility to 8 common, adult-onset health conditions and completed an online survey assessing attitudes and beliefs about the risks and benefits of the test for their child, their willingness to consider having their child tested, and other psychosocial variables. RESULTS: Parents viewed the benefits of pediatric testing to outweigh its risks (positive decisional balance) and were moderately interested in pediatric testing. Variables associated with positive decisional balance included greater interest in knowing about gene-health associations in their child, anticipation of less difficulty understanding their child's genetic health risks, and more positive emotional reactions to learning about their child's decreased health risks (adjusted R-2 = 0.33, P < .0001). Similarly, variables associated with greater parental willingness to test were being a mother (versus being a father), greater perceived risk of diseases in their child, greater interest in knowing about gene-health relationships in their child, anticipating less difficulty learning about their child's genetic health risks, anticipating more positive emotional reactions to learning about their child's decreased health risks, and positive decisional balance (adjusted R-2 = 0.57, P < .0001). CONCLUSIONS: As genetic susceptibility testing for common, adult-onset health conditions proliferates, pediatricians should anticipate parents' interest in testing children and be prepared to facilitate informed decision making about such testing. Pediatrics 2011;127:e1288-e1295 C1 [Tercyak, Kenneth P.] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Div Hlth Outcomes & Hlth Behav,Dept Oncol, Washington, DC 20007 USA. [Tercyak, Kenneth P.] Georgetown Univ, Med Ctr, Dept Pediat, Washington, DC 20007 USA. [Alford, Sharon Hensley] Henry Ford Hlth Syst, Dept Biostat & Res Epidemiol, Detroit, MI USA. [Emmons, Karen M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Emmons, Karen M.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Lipkus, Isaac M.] Duke Univ, Sch Nursing, Durham, NC USA. [Wilfond, Benjamin S.] Univ Washington, Sch Med, Seattle Childrens Hosp, Treuman Katz Ctr Pediat Bioeth, Seattle, WA USA. [Wilfond, Benjamin S.] Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 USA. [McBride, Colleen M.] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA. RP Tercyak, KP (reprint author), Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Div Hlth Outcomes & Hlth Behav,Dept Oncol, 3300 Whitehaven St,NW,Suite 4100, Washington, DC 20007 USA. EM tercyakk@georgetown.edu FU National Institutes of Health (NIH) [HHSN268200782096C]; National Human Genome Research Institute at the National Institutes of Health; National Institutes of Health/National Cancer Institute [U19CA079689]; Group Health Research Institute; Henry Ford Hospital; Center for Inherited Disease Research; National Human Genome Research Institute [R01HG002686]; National Cancer Institute [R01CA137625] FX Funded by the National Institutes of Health (NIH).; This work was supported by the Intramural Research Program of the National Human Genome Research Institute at the National Institutes of Health. The research also was made possible by collaboration with the health management organization Cancer Research Network (CRN) funded by the National Institutes of Health/National Cancer Institute (U19CA079689). The overall goal of the CRN is to use a consortium of delivery systems to conduct cancer research. Additional resources were provided by the Group Health Research Institute and the Henry Ford Hospital. Genotyping services were provided by the Center for Inherited Disease Research, an entity fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University (HHSN268200782096C). Manuscript preparation was supported by grants from the Ethical, Legal, and Social Implication Research Program of the National Human Genome Research Institute (R01HG002686) and from the National Cancer Institute (R01CA137625 to Kenneth P. Tercyak). NR 35 TC 28 Z9 28 U1 1 U2 7 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD MAY PY 2011 VL 127 IS 5 BP E1288 EP E1295 DI 10.1542/peds.2010-0938 PG 8 WC Pediatrics SC Pediatrics GA 757OO UT WOS:000290097800024 PM 21502235 ER PT J AU Liu, AS Kao, HK Reish, RG Hergrueter, CA May, JW Guo, LF AF Liu, Allen S. Kao, Huang-Kai Reish, Richard G. Hergrueter, Charles A. May, James W., Jr. Guo, Lifei TI Postoperative Complications in Prosthesis-Based Breast Reconstruction Using Acellular Dermal Matrix SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID EXPANDER/IMPLANT RECONSTRUCTION; CAPSULE FORMATION; ALLODERM; IMPLANT; ALLOGRAFT; RADIATION AB Background: Acellular dermal matrix has become a common adjunct in prosthesis-based breast reconstruction. The authors' aim was to determine whether acellular dermal matrix use in immediate prosthesis-based breast reconstruction is associated with higher rate of complications. Methods: Over a 5 1/2-year period at the Brigham and Women's Hospital, 470 postmastectomy defects were reconstructed immediately using tissue expanders or implants. These were divided into two groups: reconstructions with or without acellular dermal matrix. Data were collected on patient comorbidities, radiation, intraoperative tumescent solution use, prosthesis size, initial fill volume, and complications. Results: The risk for major infections that required prosthesis removal was elevated in the acellular dermal matrix group (4.9 versus 2.5 percent), but this increase did not reach statistical significance (p = 0.172). There was a statistically significant increase in overall wound infection rate in the acellular dermal matrix group (6.8 versus 2.5 percent, p = 0.031), but in a multivariate analysis, the use of acellular dermal matrix did not materialize as a significant risk factor for overall wound infection. Overall surgical complication rate was significantly higher in the acellular dermal matrix group at 19.5 percent, compared with the non-acellular dermal matrix group at 12.3 percent (p = 0.001). Other significant risk factors for overall surgical complication included smoking, higher body mass index, higher initial volume, and larger implant size. Conclusions: Patient selection for prosthesis reconstruction involving acellular dermal matrix should be judicious, especially among smokers and patients with elevated body mass index. Even though the use of acellular dermal matrix allows higher initial volumes and reduced number of expansions, one should be careful about putting in too high of an initial volume. (Plast. Reconstr. Surg. 127: 1755, 2011.) C1 [Guo, Lifei] Brigham & Womens Hosp, Dept Surg, Div Plast Surg, Boston, MA 02115 USA. Chang Gung Mem Hosp, Dept Plast & Reconstruct Surg, Kaohsiung, Taiwan. Massachusetts Gen Hosp, Div Plast Surg, Boston, MA 02114 USA. RP Guo, LF (reprint author), Brigham & Womens Hosp, Dept Surg, Div Plast Surg, 75 Francis St, Boston, MA 02115 USA. EM lguo@partners.org NR 23 TC 102 Z9 107 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD MAY PY 2011 VL 127 IS 5 BP 1755 EP 1762 DI 10.1097/PRS.0b013e31820cf233 PG 8 WC Surgery SC Surgery GA 758FT UT WOS:000290148100002 PM 21228744 ER PT J AU Yaremchuk, MJ Doumit, G Thomas, MA AF Yaremchuk, Michael J. Doumit, Gabe Thomas, Matthew A. TI Alloplastic Augmentation of the Facial Skeleton: An Occasional Adjunct or Alternative to Orthognathic Surgery SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Editorial Material ID IMPLANTS AB Background: Alloplastic implants can be adjunctive to orthognathic surgery by correcting contour irregularities or disharmonies after skeletal movements. Implant augmentation can also simulate the visual effect of osteotomies in patients with skeletal deficiencies whose occlusion is normal or has been corrected. Although sometimes it is an adjunct or an alternative to facial skeletal rearrangements, facial skeleton augmentation is not a substitute for orthognathic surgery. Methods: Alloplastic implants designed specifically to augment the infraorbital rim can correct the residual upper midface deficiency remaining after Le Fort I maxillary advancement. When used with paranasal and malar implants, they can simulate the visual effect of the Le Fort III osteotomy with advancement. Paranasal implants can simulate the appearance after Le Fort I advancement. Mandible and extended chin implants can correct skeletal irregularities and deficiencies after sagittal and horizontal osteotomies. They can also simulate the visual effect of these osteotomies. Results: The application of these concepts has been effective, with low morbidity, in 294 patients. No implants extruded or migrated. Eight patients (3 percent) had early postoperative infections. There were no late infections. Ten of 108 patients (9 percent) with midface implants had implant visibility with time. Conclusion: Alloplastic augmentation of the facial skeleton can be a useful adjunct or an alternative to orthognathic surgical procedures in situations when the occlusion is normal or has been corrected. (Plast. Reconstr. Surg. 127: 2021, 2011.) C1 [Yaremchuk, Michael J.; Doumit, Gabe; Thomas, Matthew A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Yaremchuk, MJ (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM myaremchuk@partners.org NR 19 TC 11 Z9 11 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD MAY PY 2011 VL 127 IS 5 BP 2021 EP 2030 DI 10.1097/PRS.0b013e31820e9263 PG 10 WC Surgery SC Surgery GA 758FT UT WOS:000290148100034 PM 21532429 ER PT J AU Decanini-Mancera, A Lessell, S Lee, MS Subramanian, PS AF Decanini-Mancera, Alejandra Lessell, Simmons Lee, Michael S. Subramanian, Prem S. TI Syphilis and the Monk SO SURVEY OF OPHTHALMOLOGY LA English DT Review DE aritifungal therapy; Aspergillus infection; corticosteroids; primary orbital Aspergillosis ID ORBITAL APEX SYNDROME; ASPERGILLUS-FUMIGATUS; OPTIC NEUROPATHY; SINUS ASPERGILLOSIS; INFECTION; NEURITIS; NERVE AB Primary orbital aspergillus infection may occur in immunocompetent individuals. It frequently represents a diagnostic challenge for clinicians due to nonspecific clinical presentations and neuroimaging signs. We present a 47-year-old otherwise healthy man with an isolated unilateral optic neuropathy secondary to primary orbital aspergillosis. He had a remote history of tuberculosis and positive syphilis serologies. After he worsened despite intravenous penicillin therapy, a biopsy showed chronic inflammation. Corticosteroids treatment was followed by further deterioration of his clinical condition. Finally, a repeat biopsy revealed the aspergillus infection. Despite antifungal therapy, the outcome was unfavorable. A high index of suspicion should result in aggressive diagnostic testing and prompt institution of antifungal therapy in patients with primary orbital aspergillosis. (Surv Ophthalmol 56:267-273, 2011. (C) 2011 Elsevier Inc. All rights reserved.) C1 [Decanini-Mancera, Alejandra; Lee, Michael S.] Univ Minnesota, Dept Ophthalmol, Minneapolis, MN 55455 USA. [Lessell, Simmons] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Subramanian, Prem S.] Wilmer Eye Inst, Baltimore, MD 21287 USA. RP Lee, MS (reprint author), Univ Minnesota, Dept Ophthalmol, MMC 493,420 Delaware St SE, Minneapolis, MN 55455 USA. OI Subramanian, Prem/0000-0001-5824-8322 FU Research to Prevent Blindness, New York, NY; Lions Club of Minnesota FX The authors reported no proprietary or commercial interest in any product mentioned or concept discussed in this article. Publication of this article was supported by unrestricted grants from Research to Prevent Blindness, New York, NY, and the Lions Club of Minnesota. NR 23 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 0039-6257 J9 SURV OPHTHALMOL JI Surv. Ophthalmol. PD MAY-JUN PY 2011 VL 56 IS 3 BP 267 EP 273 DI 10.1016/j.survophthal.2010.08.004 PG 7 WC Ophthalmology SC Ophthalmology GA 758SU UT WOS:000290187600006 PM 21056446 ER PT J AU Ackerly, DC Sangvai, DG Udayakumar, K Shah, BR Kalman, NS Cho, AH Schulman, KA Fulkerson, WJ Dzau, VJ AF Ackerly, D. Clay Sangvai, Devdutta G. Udayakumar, Krishna Shah, Bimal R. Kalman, Noah S. Cho, Alex H. Schulman, Kevin A. Fulkerson, William J., Jr. Dzau, Victor J. TI Training the Next Generation of Physician-Executives: An Innovative Residency Pathway in Management and Leadership SO ACADEMIC MEDICINE LA English DT Article ID DUAL-DEGREE; MD-MBA; BUSINESS; MEDICINE AB The rapidly changing field of medicine demands that future physician-leaders excel not only in clinical medicine but also in the management of complex health care enterprises. However, many physicians have become leaders "by accident," and the active cultivation of future leaders is required. Addressing this need will require multiple approaches, targeting trainees at various stages of their careers, such as degree-granting programs, residency and fellowship training, and career and leadership development programs. Here, the authors describe a first-of-its-kind graduate medical education pathway at Duke Medicine, the Management and Leadership Pathway for Residents (MLPR). This program was developed for residents with both a medical degree and management training. Created in 2009, with its first cohort enrolled in the summer of 2010, the MLPR is intended to help catalyze the emergence of a new generation of physician-leaders. The program will provide physiciansin-training with rigorous clinical exposure along with mentorship and rotational opportunities in management to accelerate the development of critical leadership and management skills in all facets of medicine, including care delivery, research, and education. To achieve this, the MLPR includes 15 to 18 months of project-based rotations under the guidance of senior leaders in many disciplines including finance, patient safety, health system operations, strategy, and others. Developing both clinical and management skill sets during graduate medical education holds the promise of engaging future leaders of health care at an early career stage, keeping more MD-MBA graduates within health care, and creating a bench of talented future physician-executives. C1 [Dzau, Victor J.] Duke Univ, Off Chancellor, Durham, NC 27710 USA. [Fulkerson, William J., Jr.; Dzau, Victor J.] Duke Univ Hlth Syst, Durham, NC USA. [Ackerly, D. Clay; Schulman, Kevin A.] Duke Univ, Duke Clin Res Inst, Durham, NC 27710 USA. [Udayakumar, Krishna] Duke Natl Univ Singapore, Grad Sch Med, Singapore, Singapore. [Ackerly, D. Clay] Harvard Univ, Sch Med, Boston, MA USA. [Ackerly, D. Clay] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Dzau, VJ (reprint author), Duke Univ, Off Chancellor, Box 3701 Med Ctr, Durham, NC 27710 USA. EM victor.dzau@duke.edu FU Duke's Graduate Medical Education Endowment Innovation Fund FX The MLPR relies on a shared investment model, reflecting the broad support for the program across the institution. Funding support is provided by Duke's Graduate Medical Education Endowment Innovation Fund, participating clinical departments, the administrative units through which trainees will rotate, and the office of the chancellor for health affairs. Trainees will receive their regular salary stipend during their enrollment in the MLPR. The program will seek to obtain additional funding to enable future expansion and sustainability from multiple other sources such as grants, private-public partnerships, and philanthropy. NR 12 TC 30 Z9 31 U1 0 U2 17 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD MAY PY 2011 VL 86 IS 5 BP 575 EP 579 DI 10.1097/ACM.0b013e318212e51b PG 5 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 755WU UT WOS:000289971300016 PM 21436663 ER PT J AU Herrle, SR Corbett, EC Fagan, MJ Moore, CG Elnicki, DM AF Herrle, Scott R. Corbett, Eugene C., Jr. Fagan, Mark J. Moore, Charity G. Elnicki, D. Michael TI Bayes' Theorem and the Physical Examination: Probability Assessment and Diagnostic Decision Making SO ACADEMIC MEDICINE LA English DT Article ID CLINICAL EXAMINATION; INTERNAL-MEDICINE; AUSCULTATORY SKILLS; FAMILY-PRACTICE; PATIENT; CARE; HEURISTICS; JUDGMENT; HISTORY; ERRORS AB Purpose To determine how examination findings influence the probability assessment and diagnostic decision making of third-and fourth-year medical students, internal medicine residents, and academic general internists. Method In a 2008 cross-sectional, Web-based survey, participants from three medical schools were asked questions about their training and eight examination scenarios representing four conditions. Participants were given literature-derived preexamination probabilities for each condition and were asked to (1) estimate postexamination probabilities (post-EPs) and (2) select a diagnostic choice (report that condition is present, order more tests, or report that condition is absent). Participants' inverse transformed logit (ITL) mean post-EPs were compared with corresponding literature-derived post-EPs. Results Of 906 individuals invited to participate, 684 (75%) submitted a completed survey. In two of four scenarios with positive findings, the participants' ITL mean post-EPs were significantly less than corresponding literature-derived post-EP point estimates (P < .001 for each). In three of four scenarios with negative findings, ITL mean post-EPs were significantly greater than corresponding literature-derived post-EP point estimates (P < .001 for each). In the four scenarios with positive findings, 17% to 38% of participants ordered more diagnostic tests when the literature indicated a > 85% probability that the condition was present. In the four scenarios with largely negative findings, 70% to 85% chose to order diagnostic tests to further reduce diagnostic uncertainty. Conclusions All three groups tended to similarly underestimate the impact of examination findings on condition probability assessment, especially negative findings, and often ordered more tests when probabilities indicated that additional testing was unnecessary. C1 [Herrle, Scott R.] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Div Gen Internal Med, Dept Med,Sect Gen Internal Med, Pittsburgh, PA 15240 USA. [Corbett, Eugene C., Jr.] Univ Virginia, Dept Med, Div Gen Med Geriatr & Palliat Care, Charlottesville, VA USA. [Fagan, Mark J.] Brown Univ, Dept Med, Alpert Med Sch, Providence, RI 02912 USA. [Moore, Charity G.] Univ Pittsburgh, Dept Med, Div Gen Internal Med, Ctr Res Hlth Care Data Ctr, Pittsburgh, PA 15240 USA. RP Herrle, SR (reprint author), Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Div Gen Internal Med, Dept Med,Sect Gen Internal Med, 130-U,Univ Dr C, Pittsburgh, PA 15240 USA. EM herrles@pitt.edu RI liu, jing/D-9482-2012; OI Moore, Charity/0000-0002-0060-0124 FU National Center for Research Resources (NCRR), National Institutes of Health (NIH) [UL1 RR024153]; NIH Roadmap for Medical Research FX This study was made possible by Grant Number UL1 RR024153 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH. Additional funding for this study was provided by the Shadyside Hospital Foundation. The Shadyside Hospital Foundation had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. NR 41 TC 10 Z9 10 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD MAY PY 2011 VL 86 IS 5 BP 618 EP 627 DI 10.1097/ACM.0b013e318212eb00 PG 10 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 755WU UT WOS:000289971300025 PM 21436660 ER PT J AU Geithner, CA Scharpf, JA Delistraty, J AF Geithner, Christina A. Scharpf, Jean Ann Delistraty, Jema TI EXPERIENTIAL LEARNING AND COMMUNITY SERVICE ENHANCE PROFESSIONAL DEVELOPMENT A 2-and 4-Year Approach SO ACSMS HEALTH & FITNESS JOURNAL LA English DT Article DE Academic training programs; Exercise testing and prescription; Experiential learning; Client-based projects; Community service ID REVEALS FITNESS TRENDS; WORLDWIDE SURVEY C1 [Geithner, Christina A.] Gonzaga Univ, Dept Human Physiol, Spokane, WA 99258 USA. [Scharpf, Jean Ann] Suffolk CCC, Dept Phys Educ, New York, NY USA. [Scharpf, Jean Ann] Fitness Specialist Program, San Diego, CA USA. [Delistraty, Jema] Deaconess Med Ctr, Prevent Cardiol Dept, Boston, MA USA. RP Geithner, CA (reprint author), Gonzaga Univ, Dept Human Physiol, Spokane, WA 99258 USA. NR 11 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1091-5397 J9 ACSMS HEALTH FIT J JI ACSMS Health Fit. J. PD MAY-JUN PY 2011 VL 15 IS 3 BP 19 EP 28 DI 10.1249/FIT.0b013e3182160f67 PG 10 WC Sport Sciences SC Sport Sciences GA 755WR UT WOS:000289970900005 ER PT J AU Rodriguez, FJ Scheithauer, BW George, D Midha, R MacCollin, M Stemmer-Rachamimov, AO AF Rodriguez, Fausto J. Scheithauer, Bernd W. George, David Midha, Rajiv MacCollin, Mia Stemmer-Rachamimov, Anat O. TI Superficial neurofibromas in the setting of schwannomatosis: nosologic implications SO ACTA NEUROPATHOLOGICA LA English DT Article DE Schwannoma; Neurofibroma; Schwannomatosis; Neurofibromatosis; Peripheral nerve ID FAMILIAL SCHWANNOMATOSIS; DIAGNOSTIC-CRITERIA; NF2 LOCUS; TYPE-2; SMARCB1; TUMOR AB First described in the past decade, schwannomatosis is a syndrome distinct from neurofibromatosis 2 (NF2). It is characterized by the development of multiple schwannomas, sparing the vestibular division of cranial nerve VIII, and may also predispose to develop meningiomas. We report two female patients, a 27 and a 44 years old who developed multiple peripheral schwannomas, but without involvement of the vestibular nerves, satisfying clinical criteria for schwannomatosis. Lack of vestibular nerve involvement was confirmed with MRI using an internal auditory canal protocol with 3 mm thick slices in both patients after age 30. Both patients developed a small neurofibroma in axillary subcutaneous tissues and a diffuse cutaneous neurofibroma of the left buttock, respectively. This report highlights that superficial neurofibromas may arise in the setting of schwannomatosis, which may have implications for the diagnostic criteria of this unique syndrome. In particular, the presence of a cutaneous neurofibroma in a patient with multiple schwannomas should not lead to a diagnosis of NF2. C1 [Rodriguez, Fausto J.] Johns Hopkins Univ, Dept Pathol, Div Neuropathol, Baltimore, MD 21205 USA. [Rodriguez, Fausto J.; Scheithauer, Bernd W.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [George, David] Foothills Prov Gen Hosp, Dept Pathol & Neurosurg, Calgary, AB T2N 2T9, Canada. [Midha, Rajiv] Univ Calgary, Fac Med, Dept Clin Neurosci, Calgary, AB, Canada. [MacCollin, Mia] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Stemmer-Rachamimov, Anat O.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Rodriguez, FJ (reprint author), Johns Hopkins Univ, Dept Pathol, Div Neuropathol, 720 Rutland Ave,Ross Bldg 512B, Baltimore, MD 21205 USA. EM frodrig4@jhmi.edu FU NCI NIH HHS [P30 CA006973] NR 16 TC 3 Z9 3 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD MAY PY 2011 VL 121 IS 5 BP 663 EP 668 DI 10.1007/s00401-010-0793-8 PG 6 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 756RS UT WOS:000290033000010 PM 21191601 ER PT J AU Pisculli, ML Reichmann, WM Losina, E Donnell-Fink, LA Arbelaez, C Katz, JN Walensky, RP AF Pisculli, Mary L. Reichmann, William M. Losina, Elena Donnell-Fink, Laurel A. Arbelaez, Christian Katz, Jeffrey N. Walensky, Rochelle P. TI Factors Associated with Refusal of Rapid HIV Testing in an Emergency Department SO AIDS AND BEHAVIOR LA English DT Article DE Rapid HIV testing; HIV test refusal; HIV test acceptance; Routine HIV testing; Emergency department; Human immunodeficiency virus ID TRANSMITTED DISEASE CLINICS; UNITED-STATES; MISSED OPPORTUNITIES; ETHNIC DISPARITIES; INFECTION; ROUTINE; RISK; PERSPECTIVE; PERCEPTIONS; ACCEPTANCE AB HIV screening studies in the emergency department (ED) have demonstrated rates of HIV test refusal ranging from 40-67%. This study aimed to determine the factors associated with refusal to undergo routine rapid HIV testing in an academic ED in Boston. HIV counselors offered routine testing to 1,959 patients; almost one-third of patients (29%) refused. Data from a self-administered survey were used to determine independent correlates of HIV testing refusal. In multivariate analysis, women and patients with annual household incomes of $50,000 or more were more likely to refuse testing, as were those who reported not engaging in HIV risk behaviors, those previously HIV tested and those who did not perceive a need for testing. Enrollment during morning hours was also associated with an increased risk of refusal. Increased educational efforts to convey the rationale and benefits of universal screening may improve testing uptake among these groups. C1 [Walensky, Rochelle P.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Pisculli, Mary L.; Walensky, Rochelle P.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Reichmann, William M.; Losina, Elena; Donnell-Fink, Laurel A.; Katz, Jeffrey N.] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. [Reichmann, William M.; Losina, Elena] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Arbelaez, Christian] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Katz, Jeffrey N.] Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Katz, Jeffrey N.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Walensky, Rochelle P.] Harvard Univ, Sch Med, Ctr AIDS Res, Boston, MA USA. RP Walensky, RP (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM rwalensky@partners.org OI Walensky, Rochelle P./0000-0002-8795-379X FU NIAID NIH HHS [T32 AI007433]; NIMH NIH HHS [R01 MH065869, R01 MH073445, R01 MH65869] NR 38 TC 18 Z9 18 U1 2 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 MAY PY 2011 VL 15 IS 4 BP 734 EP 742 DI 10.1007/s10461-010-9837-2 PG 9 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 754YS UT WOS:000289894400007 PM 20978834 ER PT J AU Wanyenze, RK Hahn, JA Liechty, CA Ragland, K Ronald, A Mayanja-Kizza, H Coates, T Kamya, MR Bangsberg, DR AF Wanyenze, Rhoda K. Hahn, Judith A. Liechty, Cheryl A. Ragland, Kathie Ronald, Allan Mayanja-Kizza, Harriet Coates, Thomas Kamya, Moses R. Bangsberg, David R. TI Linkage to HIV Care and Survival Following Inpatient HIV Counseling and Testing SO AIDS AND BEHAVIOR LA English DT Article DE Provider Initiated HIV Testing and Counseling (PITC); Inpatient; Access to care; Survival; Africa ID ANTIRETROVIRAL THERAPY; INCOME COUNTRIES; UGANDA; PROGRAMS; COUPLES; SEROCONVERSION; POPULATION; PREVALENCE; SEROSTATUS; EXPERIENCE AB Linkage to HIV care and survival in sub-Saharan Africa is not well documented. In 2004 we conducted a randomized trial among medical inpatients in Mulago Hospital to assess the impact of HIV counseling and testing (HCT) on linkage to care and survival. Participants were randomized to inpatient HCT (intervention) or outpatient HCT 1 week post-discharge (control); inpatient HCT was not available at Mulago during the study. Among 590 eligible patients, 85% (500) agreed to participate; 98.8% (248) in the intervention arm received HCT compared to 68.7% (171) in the control arm. Within 6 months, 62.2% (92) of surviving HIV-infected participants received HIV care; 15.0% (20) received antiretroviral medications (ARVs). Overall mortality among HIV-infected participants was 34.6% (72). HCT had significant impact on linkage to care among surviving participants. Referral for HCT was a missed opportunity for diagnosis. There is need for earlier diagnosis and linkage to HIV care among inpatients. C1 [Wanyenze, Rhoda K.] Makerere Univ, Sch Publ Hlth, Kampala, Uganda. [Hahn, Judith A.; Ragland, Kathie] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Liechty, Cheryl A.] Glen Cove Internal Med, Rockport, ME USA. [Ronald, Allan] Infect Dis Inst, Kampala, Uganda. [Mayanja-Kizza, Harriet; Kamya, Moses R.] Makerere Univ, Sch Med, Kampala, Uganda. [Coates, Thomas] Univ Calif Los Angeles, Los Angeles, CA USA. [Bangsberg, David R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Global Hlth, Boston, MA USA. RP Wanyenze, RK (reprint author), Makerere Univ, Sch Publ Hlth, POB 7072, Kampala, Uganda. EM rwanyenze@hotmail.com OI Mayanja-Kizza, Harriet/0000-0002-9297-6208; Ronald, Allan/0000-0002-5746-3490 FU NIMH NIH HHS [K24-MH087227, R01 MH077512, R01 MH077512-01A1, R01 MH077512-02, R01 MH077512-03, K24 MH087227, R01 MH077512-04, R01 MH077512-05, R01 MH054907] NR 28 TC 27 Z9 28 U1 0 U2 1 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 MAY PY 2011 VL 15 IS 4 BP 751 EP 760 DI 10.1007/s10461-010-9704-1 PG 10 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 754YS UT WOS:000289894400009 PM 20431933 ER PT J AU Korthuis, PT Saha, S Chander, G McCarty, D Moore, RD Cohn, JA Sharp, VL Beach, MC AF Korthuis, P. Todd Saha, Somnath Chander, Geetanjali McCarty, Dennis Moore, Richard D. Cohn, Jonathan A. Sharp, Victoria L. Beach, Mary Catherine TI Substance Use and the Quality of Patient-Provider Communication in HIV Clinics SO AIDS AND BEHAVIOR LA English DT Article DE Alcoholism; Substance-related disorders; Communication; HIV; Quality of health care; Patient satisfaction ID ADDICTION SEVERITY INDEX; HUMAN-IMMUNODEFICIENCY-VIRUS; ANTIRETROVIRAL THERAPY; ABUSE TREATMENT; UNITED-STATES; DRUG-USERS; SERVICES UTILIZATION; MEDICAL INTERACTIONS; RELAPSE PREVENTION; INFECTED ADULTS AB The objective of this study was to estimate the influence of substance use on the quality of patient-provider communication during HIV clinic encounters. Patients were surveyed about unhealthy alcohol and illicit drug use and rated provider communication quality. Audio-recorded encounters were coded for specific communication behaviors. Patients with vs. without unhealthy alcohol use rated the quality of their provider's communication lower; illicit drug user ratings were comparable to non-users. Visit length was shorter, with fewer activating/engaging and psychosocial counseling statements for those with vs. without unhealthy alcohol use. Providers and patients exhibited favorable communication behaviors in encounters with illicit drug users vs. non-users, demonstrating greater evidence of patient-provider engagement. The quality of patient-provider communication was worse for HIV-infected patients with unhealthy alcohol use but similar or better for illicit drug users compared with non-users. Interventions should be developed that encourage providers to actively engage patients with unhealthy alcohol use. C1 [Korthuis, P. Todd; Saha, Somnath] Oregon Hlth & Sci Univ, Div Gen Internal Med & Geriatr, Portland, OR 97239 USA. [Korthuis, P. Todd; Saha, Somnath; McCarty, Dennis] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97239 USA. [Saha, Somnath] Portland VA Med Ctr, Gen Internal Med Sect, Portland, OR USA. [Chander, Geetanjali; Moore, Richard D.; Beach, Mary Catherine] Johns Hopkins Univ, Sch Med, Dept Med, Div Gen Internal Med, Baltimore, MD 21205 USA. [Cohn, Jonathan A.] Wayne State Univ, Sch Med, Dept Med, Div Infect Dis, Detroit, MI 48201 USA. [Sharp, Victoria L.] Columbia Univ, St Lukes Roosevelt Hosp Ctr, Ctr Comprehens Care, New York, NY USA. RP Korthuis, PT (reprint author), Oregon Hlth & Sci Univ, Div Gen Internal Med & Geriatr, 3181 SW Sam Jackson Pk Rd,Mail Code L-475, Portland, OR 97239 USA. EM korthuis@ohsu.edu FU AHRQ HHS [K08 HS013903-05, K08 HS013903]; NIAAA NIH HHS [K23 AA015313, K23AA015313, R01 AA016893, R01 AA016893-01A2, R01 AA16893]; NIAID NIH HHS [U01 AI069918, U01 AI069918-05]; NIDA NIH HHS [K23 DA019809, K23DA019809, K24 DA000432, K24 DA000432-10, R01 DA011602, R01 DA011602-13, R01 DA11602]; NIMH NIH HHS [R34 MH089279, R34 MH089279-01A1, R34 MH089279-02]; PHS HHS [AHRQ 290-01-0012] NR 51 TC 16 Z9 17 U1 3 U2 8 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 MAY PY 2011 VL 15 IS 4 BP 832 EP 841 DI 10.1007/s10461-010-9779-8 PG 10 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 754YS UT WOS:000289894400017 PM 20703792 ER PT J AU Oslin, D AF Oslin, David TI Personalized Addiction Treatment: How Close Are We? SO ALCOHOL AND ALCOHOLISM LA English DT Editorial Material ID OPIOID RECEPTOR GENE; NALTREXONE RESPONSE; ALCOHOL DEPENDENCE; OPRM1; CUES C1 [Oslin, David] Univ Penn, Philadelphia, PA 19104 USA. [Oslin, David] Philadelphia VA Med Ctr, Treatment Res Ctr, Philadelphia, PA 19104 USA. RP Oslin, D (reprint author), Univ Penn, 3600 Chestnut St, Philadelphia, PA 19104 USA. EM oslin@upenn.edu NR 10 TC 3 Z9 4 U1 2 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0735-0414 J9 ALCOHOL ALCOHOLISM JI Alcohol Alcohol. PD MAY-JUN PY 2011 VL 46 IS 3 BP 231 EP 232 DI 10.1093/alcalc/agr030 PG 2 WC Substance Abuse SC Substance Abuse GA 754ET UT WOS:000289837300003 PM 21508195 ER PT J AU Pandol, SJ Lugea, A Mareninova, OA Smoot, D Gorelick, FS Gukovskaya, AS Gukovsky, I AF Pandol, Stephen J. Lugea, Aurelia Mareninova, Olga A. Smoot, Duane Gorelick, Fred S. Gukovskaya, Anna S. Gukovsky, Ilya TI Investigating the Pathobiology of Alcoholic Pancreatitis SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Alcoholic Pancreatitis; Inflammation; Autophagy; Mitochondrial Permeabilization; Endoplasmic Reticulum Stress; Pancreatic Stellate Cell ID CERULEIN-INDUCED PANCREATITIS; ENDOPLASMIC-RETICULUM STRESS; PERMEABILITY TRANSITION PORE; KEY PATHOLOGICAL RESPONSES; UNFOLDED PROTEIN RESPONSE; KAPPA-B ACTIVATION; STELLATE CELLS; ACINAR-CELLS; ZYMOGEN ACTIVATION; BASOLATERAL EXOCYTOSIS AB Alcohol abuse is one of the most common causes of pancreatitis. The risk of developing alcohol-induced pancreatitis is related to the amount and duration of drinking. However, only a small portion of heavy drinkers develop disease, indicating that other factors (genetic, environmental, or dietary) contribute to disease initiation. Epidemiologic studies suggest roles for cigarette smoking and dietary factors in the development of alcoholic pancreatitis. The mechanisms underlying alcoholic pancreatitis are starting to be understood. Studies from animal models reveal that alcohol sensitizes the pancreas to key pathobiologic processes that are involved in pancreatitis. Current studies are focussed on the mechanisms responsible for the sensitizing effect of alcohol; recent findings reveal disordering of key cellular organelles including endoplasmic reticulum, mitochondria, and lysosomes. As our understanding of alcohol's effects continue to advance to the level of molecular mechanisms, insights into potential therapeutic strategies will emerge providing opportunities for clinical benefit. C1 [Pandol, Stephen J.; Lugea, Aurelia; Mareninova, Olga A.; Gukovskaya, Anna S.; Gukovsky, Ilya] Univ Calif Los Angeles, Pancreat Res Grp, Dept Vet Affairs Greater Los Angeles, Los Angeles, CA USA. So Calif Res Ctr Alcohol Liver & Pancreat Dis, Los Angeles, CA USA. [Smoot, Duane] Howard Univ, Washington, DC 20059 USA. [Gorelick, Fred S.] Yale Univ, New Haven, CT USA. RP Pandol, SJ (reprint author), UCLA VA Greater Los Angeles, Pancreat Res Grp, W Los Angeles VA Healthcare Ctr, 11301 Wilshire Blvd,Blg 258,Rm 340, Los Angeles, CA 90073 USA. EM stephen.pandol@va.gov; igukovsk@ucla.edu FU AGA Foundation FX Southern California Research Center for Alcoholic Liver and Pancreatic Diseases (P50AA11999); UCLA Center for Excellence in Pancreatic Diseases (P01AT003960); NIH/NIAAA (U56 AA0114643, R21AA016010, R21AA015781, R21AA017276); NIH/NCI (R01CA119025); NIH/NIDDK (R01DK059936, R01DK54021); and the AGA Foundation Designated Research Scholar Award in Pancreatitis. NR 88 TC 20 Z9 21 U1 0 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2011 VL 35 IS 5 BP 830 EP 837 DI 10.1111/j.1530-0277.2010.01408.x PG 8 WC Substance Abuse SC Substance Abuse GA 754ZK UT WOS:000289896200013 PM 21284675 ER PT J AU Arnedt, JT Rohsenow, DJ Almeida, AB Hunt, SK Gokhale, M Gottlieb, DJ Howland, J AF Arnedt, J. Todd Rohsenow, Damaris J. Almeida, Alissa B. Hunt, Sarah K. Gokhale, Manjusha Gottlieb, Daniel J. Howland, Jonathan TI Sleep Following Alcohol Intoxication in Healthy, Young Adults: Effects of Sex and Family History of Alcoholism SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Alcohol; Sleep; Polysomnography; Sex; Family History ID GENDER-DIFFERENCES; MENSTRUAL-CYCLE; PERFORMANCE; DRINKING; ETHANOL; EEG; HANGOVER; ELECTROENCEPHALOGRAM; DEPENDENCE; LEVEL AB Background: This study evaluated sex and family history of alcoholism as moderators of subjective ratings of sleepiness/sleep quality and polysomnography (PSG) following alcohol intoxication in healthy, young adults. Methods: Ninety-three healthy adults [mean age 24.4 +/- 2.7 years, 59 women, 29 subjects with a positive family history of alcoholism (FH+)] were recruited. After screening PSG, participants consumed alcohol (sex/weight adjusted dosing) to intoxication [peak breath alcohol concentration (BrAC) of 0.11 +/- 0.01 g% for men and women] or matching placebo between 20:30 and 22:00 hours. Sleep was monitored using PSG between 23:00 and 07:00 hours. Participants completed the Stanford Sleepiness Scale and Karolinska Sleepiness Scale at bedtime and on awakening and a validated post-sleep questionnaire. Results: Following alcohol, total sleep time, sleep efficiency, nighttime awakenings, and wake after sleep onset were more disrupted in women than men, with no differences by family history status. Alcohol reduced sleep onset latency, sleep efficiency, and rapid eye movement sleep while increasing wakefulness and slow wave sleep across the entire night compared with placebo. Alcohol also generally increased sleep consolidation in the first half of the night, but decreased it during the second half. Sleepiness ratings were higher following alcohol, particularly in women at bedtime. Morning sleep quality ratings were lower following alcohol than placebo. Conclusions: Alcohol intoxication increases subjective sleepiness and disrupts sleep objectively more in healthy women than in men, with no differences evident by family history of alcoholism status. Evaluating moderators of alcohol effects on sleep may provide insight into the role of sleep in problem drinking. C1 [Arnedt, J. Todd] Univ Michigan, Dept Psychiat, Sleep & Chronophysiol Lab, Ann Arbor, MI 48109 USA. [Rohsenow, Damaris J.] Brown Univ, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA. [Almeida, Alissa B.; Hunt, Sarah K.] Boston Univ, Sch Publ Hlth, Dept Community Hlth Sci, Boston, MA USA. [Howland, Jonathan] Boston Univ, Dept Emergency Med, Boston, MA 02215 USA. [Gokhale, Manjusha] Boston Univ, Sch Publ Hlth, Data Coordinating Ctr, Boston, MA 02215 USA. [Gottlieb, Daniel J.] Boston Univ, Sch Med, Dept Med, Boston, MA 02215 USA. [Gottlieb, Daniel J.] Boston Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02215 USA. RP Arnedt, JT (reprint author), Univ Michigan, Dept Psychiat, Sleep & Chronophysiol Lab, 4250 Plymouth Rd, Ann Arbor, MI 48109 USA. EM tarnedt@med.umich.edu OI Howland, Jonathan/0000-0001-8079-1188 FU National Institute on Alcohol Abuse and Alcoholism (NIAAA) [R01 AA12087]; National Center for Research Resources, General Clinical Research Center [M01 RR00533] FX This research was supported by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) Grant #R01 AA12087 to the Boston University School of Public Health and the National Center for Research Resources, General Clinical Research Center grant M01 RR00533. NR 47 TC 13 Z9 13 U1 2 U2 20 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2011 VL 35 IS 5 BP 870 EP 878 DI 10.1111/j.1530-0277.2010.01417.x PG 9 WC Substance Abuse SC Substance Abuse GA 754ZK UT WOS:000289896200022 PM 21323679 ER PT J AU Reinke, LF Griffith, RG Wolpin, S Donesky-Cuenco, D Carrieri-Kohlman, V Nguyen, HQ AF Reinke, Lynn F. Griffith, Randall G. Wolpin, Seth Donesky-Cuenco, DorAnne Carrieri-Kohlman, Virginia Nguyen, Huong Q. TI Feasibility of a Webinar for Coaching Patients With Chronic Obstructive Pulmonary Disease on End-of-Life Communication SO AMERICAN JOURNAL OF HOSPICE & PALLIATIVE MEDICINE LA English DT Article DE webinar; end-of-life communication; chronic obstructive pulmonary disease; patient education; advanced care planning; technology ID ADVANCE DIRECTIVE EDUCATION; CARE; REHABILITATION; BARRIERS; OUTCOMES; SUPPORT; CANCER; COPD AB Rationale: Previous research has shown that patients with chronic obstructive pulmonary disease (COPD) desire conversations about end-of-life wishes. However, most clinicians do not initiate these discussions. We explored whether educating patients via Web conferencing (webinar) would equip them with knowledge and skills to engage in conversations about end-of-life care. Results: Prewebinar, 6 of the 7 patients had completed advanced care planning forms but only half had shared these with their clinicians. Most patients felt confident about discussing end-of-life preferences. At 3 months, all participants had taken further action on end-of-life planning. Five felt the webinar was an acceptable option if unable to participate in person. All patients voiced that adding a video stream would have promoted interaction in the context of these sensitive conversations. Conclusions: This pilot project demonstrated that a webinar to educate patients on end-of-life communication was acceptable for the majority of patients. Improvements in audio and video bandwidth may facilitate more interaction among virtual participants. This may be particularly useful for patient education on sensitive topics. C1 [Reinke, Lynn F.] Univ Washington, VA Puget Sound Hlth Care Syst, Dept Vet Affairs, Seattle, WA 98101 USA. [Donesky-Cuenco, DorAnne; Carrieri-Kohlman, Virginia] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Reinke, LF (reprint author), Univ Washington, VA Puget Sound Hlth Care Syst, Dept Vet Affairs, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM reinkl@u.washington.edu FU [R01 NR008938]; [1KL2RR025015-01]; [TPP-61-021] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article:; R01 NR008938 (Carrieri-Kohlman); 1KL2RR025015-01 (Nguyen); TPP-61-021 (Reinke). NR 18 TC 7 Z9 7 U1 2 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1049-9091 J9 AM J HOSP PALLIAT ME JI Am. J. Hosp. Palliat. Med. PD MAY PY 2011 VL 28 IS 3 BP 147 EP 152 DI 10.1177/1049909110376807 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 756FQ UT WOS:000289997500002 PM 20834035 ER PT J AU Huang, ES Strate, LL Ho, WW Lee, SS Chan, AT AF Huang, Edward S. Strate, Lisa L. Ho, Wendy W. Lee, Salina S. Chan, Andrew T. TI Long-Term Use of Aspirin and the Risk of Gastrointestinal Bleeding SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Aspirin; Dose; Duration; Gastrointestinal bleeding; Long-term ID LOW-DOSE ASPIRIN; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; RANDOMIZED CONTROLLED-TRIALS; PRIMARY PREVENTION; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; COLORECTAL-CANCER; PHYSICAL-ACTIVITY; AMERICAN-COLLEGE; UNSTABLE ANGINA AB BACKGROUND: In short-term trials, aspirin is associated with gastrointestinal bleeding. However, the effect of dose and duration of aspirin use on risk remains unclear. METHODS: We conducted a prospective study of 87,680 women enrolled in the Nurses' Health Study in 1990 who provided biennial data on aspirin use. We examined the relative risk (RR) of major gastrointestinal bleeding requiring hospitalization or blood transfusion. RESULTS: During a 24-year follow-up, 1537 women reported a major gastrointestinal bleeding. Among women who used aspirin regularly (>= 2 standard [325 mg] tablets/week), the multivariate RR of gastrointestinal bleeding was 1.43 (95% confidence interval [CI], 1.29-1.59) when compared with nonregular users. Compared with women who denied any aspirin use, the multivariate RRs of gastrointestinal bleeding were 1.03 (95% CI, 0.85-1.24) for women who used 0.5 to 1.5 standard aspirin tablets/week, 1.30 (95% CI, 1.07-1.58) for women who used 2 to 5 tablets/week, 1.77 (95% CI, 1.44-2.18) for women who used 6 to 14 tablets/week, and 2.24 (95% CI, 1.66-3.03) for women who used more than 14 tablets/week (P(trend)<.001). Similar dose-response relationships were observed among short-term users (<= 5 years; P(trend)<.001) and long-term users (>5 years; P(trend)<.001). In contrast, after adjustments were made for dose, increasing duration of use did not confer a greater risk of bleeding (P(trend) = .28). CONCLUSION: Regular aspirin use is associated with gastrointestinal bleeding. Risk seems more strongly related to dose than duration of aspirin use. Efforts to minimize adverse effects of aspirin therapy should emphasize using the lowest effective dose among both short-and long-term users. (C) 2011 Elsevier Inc. All rights reserved. The American Journal of Medicine (2011) 124, 426-433 C1 [Huang, Edward S.; Chan, Andrew T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Huang, Edward S.; Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA USA. [Strate, Lisa L.] Univ Washington, Dept Med, Div Gastroenterol, Seattle, WA USA. [Ho, Wendy W.] Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Dept Med, Los Angeles, CA 90095 USA. [Lee, Salina S.] Northwestern Univ, Dept Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Chan, Andrew T.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. RP Chan, AT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St, Boston, MA 02114 USA. EM achan@partners.org FU National Cancer Institute, National Institutes of Health [CA 87969, CA 55075, CA 107412, CA 137178]; American Gastroenterological Association; American Gastroenterological Association/Foundation for Digestive Health and Nutrition FX Supported by grants (CA 87969, CA 55075, CA 107412, CA 137178) from the National Cancer Institute, National Institutes of Health. Dr. Chan was a recipient of the American Gastroenterological Association/Foundation for Digestive Health and Nutrition Pilot Research Award for this work. Dr. Chan is a Damon Runyon Clinical Investigator. Dr. Huang is supported by American Gastroenterological Association Fellow to Faculty Transition Award. No pharmaceutical industry funds were received for preparation of this manuscript. The National Cancer Institute, the National Institutes of Health, the American Gastroenterological Association, the Foundation for Digestive Health and Nutrition, and the Damon Runyon Cancer Research Foundation had no role in the collection, management, analysis, or interpretation of the data, and had no role in the preparation, review, or approval of the manuscript. NR 45 TC 53 Z9 59 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD MAY PY 2011 VL 124 IS 5 BP 426 EP 433 DI 10.1016/j.amjmed.2010.12.022 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 756NB UT WOS:000290017900014 PM 21531232 ER PT J AU Moss, M Au, DH AF Moss, Marc Au, David H. TI ATS International Conference Preview Where Today's Science Will Meet Tomorrow's Care SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Editorial Material C1 [Moss, Marc] Univ Colorado Denver, Div Pulm Sci & Crit Care Med, ATS Int Conf Comm 2010 2011, Aurora, CO USA. [Au, David H.] Univ Washington, VA Puget Sound Hlth Care Syst, ATS Int Conf Comm 2010 2011, Seattle, WA USA. RP Moss, M (reprint author), Univ Colorado Denver, Div Pulm Sci & Crit Care Med, ATS Int Conf Comm 2010 2011, Aurora, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAY 1 PY 2011 VL 183 IS 9 BP 1117 EP 1118 DI 10.1164/rccm.201103-0386ED PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 756IO UT WOS:000290005100001 PM 21531948 ER PT J AU Bellani, G Guerra, L Musch, G Zanella, A Patroniti, N Mauri, T Messa, C Pesenti, A AF Bellani, Giacomo Guerra, Luca Musch, Guido Zanella, Alberto Patroniti, Nicolo Mauri, Tommaso Messa, Cristina Pesenti, Antonio TI Lung Regional Metabolic Activity and Gas Volume Changes Induced by Tidal Ventilation in Patients with Acute Lung Injury SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE acute lung injury; respiration; artificial; tomography; X-ray computed; positron emission tomography ID RESPIRATORY-DISTRESS-SYNDROME; END-EXPIRATORY PRESSURE; POSITRON-EMISSION-TOMOGRAPHY; RANDOMIZED CONTROLLED-TRIAL; MECHANICAL VENTILATION; PULMONARY INFLAMMATION; BURST ACTIVITY; RECRUITMENT; ACTIVATION; STRATEGY AB Rationale: During acute lung injury (ALI), mechanical ventilation can aggravate inflammation by promoting alveolar distension and cyclic recruitment-derecruitment. As an estimate of the intensity of inflammation, metabolic activity can be measured by positron emission tomography imaging of [(18)F]fluoro-2-deoxy-D-glucose. Objectives: To assess the relationship between gas volume changes induced by tidal ventilation and pulmonary metabolic activity in patients with ALI. Methods: In 13 mechanically ventilated patients with ALI and relatively high positive end-expiratory pressure, we performed a positron emission tomography scan of the chest and three computed tomography scans: at mean airway pressure, end-expiration, and end-inspiration. Metabolic activity was measured from the [(18)F]fluoro-2-deoxy-D-glucose uptake rate. The computed tomography scans were used to classify lung regions as derecruited throughout the respiratory cycle, undergoing recruitment-derecruitment, and normally aerated. Measurements and Main Results: Metabolic activity of normally aerated lung was positively correlated both with plateau pressure, showing a pronounced increase above 26 to 27 cm H(2)O, and with regional V(T) normalized by end-expiratory lung gas volume. This relationship did not appear to be caused by a higher underlying parenchymal metabolic activity in patients with higher plateau pressure. Regions undergoing cyclic recruitment-derecruitment did not have higher metabolic activity than those collapsed throughout the respiratory cycle. Conclusions: In patients with ALI managed with relatively high end-expiratory pressure, metabolic activity of aerated regions was associated with both plateau pressure and regional VT normalized by end-expiratory lung gas volume, whereas no association was found between cyclic recruitment-derecruitment and increased metabolic activity. C1 [Bellani, Giacomo; Zanella, Alberto; Patroniti, Nicolo; Mauri, Tommaso; Pesenti, Antonio] Univ Milano Bicocca, Dept Expt Med, Monza, MI, Italy. [Bellani, Giacomo; Zanella, Alberto; Patroniti, Nicolo; Mauri, Tommaso; Pesenti, Antonio] San Gerardo Hosp, Dept Perioperat Med & Intens Care, Monza, MI, Italy. [Guerra, Luca; Messa, Cristina] San Gerardo Hosp, Nucl Med Unit, Monza, MI, Italy. [Guerra, Luca; Messa, Cristina] Univ Milano Bicocca, Ctr Bioimmagini Mol, I-20052 Monza, MB, Italy. [Musch, Guido] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. [Messa, Cristina] Natl Res Council CNR, Inst Mol Bioimaging & Physiol IBFM, Milan, Italy. RP Pesenti, A (reprint author), Univ Milano Bicocca, Dept Expt Med DIMS, Via Cadore 48, I-20052 Monza, MB, Italy. EM antonio.pesenti@unimib.it RI Bellani, Giacomo/D-2379-2010; Pesenti, Antonio/H-7483-2012; Patroniti, Nicolo/K-6347-2016; OI Bellani, Giacomo/0000-0002-3089-205X; Patroniti, Nicolo/0000-0003-3600-193X; zanella, Alberto/0000-0002-2967-2527 FU European Society of Intensive Care Medicine; National Institutes of Health [R01HL094639] FX Supported in part by a grant from the European Society of Intensive Care Medicine (ECCRN Young Investigator Award 2006), by departmental funding, and by National Institutes of Health grant R01HL094639 (G.M.). NR 50 TC 68 Z9 70 U1 0 U2 6 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAY 1 PY 2011 VL 183 IS 9 BP 1193 EP 1199 DI 10.1164/rccm.201008-1318OC PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 756IO UT WOS:000290005100014 PM 21257791 ER PT J AU Kuna, ST Gurubhagavatula, I Maislin, G Hin, S Hartwig, KC McCloskey, S Hachadoorian, R Hurley, S Gupta, R Staley, B Atwood, CW AF Kuna, Samuel T. Gurubhagavatula, Indira Maislin, Greg Hin, Sakhena Hartwig, Kathryn C. McCloskey, Sue Hachadoorian, Robert Hurley, Sharon Gupta, Rajesh Staley, Bethany Atwood, Charles W. TI Noninferiority of Functional Outcome in Ambulatory Management of Obstructive Sleep Apnea SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE polysomnogram; portable monitor testing; obstructive sleep apnea; continuous positive airway pressure ID POSITIVE AIRWAY PRESSURE; PRACTICE PARAMETERS; POLYSOMNOGRAPHY; DISORDERS; DIAGNOSIS AB Rationale: Home portable monitor testing is increasingly being used to diagnose patients with obstructive sleep apnea (OSA) and to initiate them on continuous positive airway pressure (CPAP) treatment. Objectives: To compare functional outcome and treatment adherence in patients who receive ambulatory versus in-laboratory testing for OSA. Methods: Veterans with suspected OSA were randomized to either home testing or standard in-laboratory testing. Home testing consisted of a type 3 portable monitor recording followed by at least three nights using an automatically adjusting positive airway pressure apparatus. Participants diagnosed with OSA were treated with (PAP for 3 months. Measurements and Main Results: We measured the change in Functional Outcomes of Sleep Questionnaire score, with an a priori noninferiority delta of -1, and the mean daily hours of objectively measured CPAP adherence, with an a priori noninferiority delta of -0.75 hour/day. Of the 296 subjects enrolled, 260 (88%) were diagnosed with OSA, and 213 (75%) were initiated on CPAP. Mean +/- SD functional outcome score improved 1.74 +/- 2.81 in the home group (P < 0.001) and 1.85 +/- 2.46 in the in-laboratory group (P < 0.0001). The lower bound of the one-sided 95% noninferiority confidence interval was -0.54. Mean +/- SD hours of daily (PAP adherence were 3.5 +/- 2.5 hours/day in the home group and 2.9 +/- 2.3 hours/day in the in-laboratory group (P = 0.08). The lower bound of the one-sided 95% noninferiority confidence interval was 0.03. Conclusions: Functional outcome and treatment adherence in patients evaluated according to a home testing algorithm is not clinically inferior to that in patients receiving standard in-laboratory polysomnography. C1 [Kuna, Samuel T.] Philadelphia Vet Affairs Med Ctr, VISN Eastern Reg Sleep Ctr 111P 4, Dept Med, Philadelphia, PA 19104 USA. [Kuna, Samuel T.; Gurubhagavatula, Indira; Staley, Bethany] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Maislin, Greg; Hachadoorian, Robert; Hurley, Sharon] Biomed Stat Consulting, Wynnewood, PA USA. [Hartwig, Kathryn C.; Atwood, Charles W.] Vet Affairs Pittsburgh Healthcare Syst, Dept Med, Pittsburgh, PA USA. [Atwood, Charles W.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. RP Kuna, ST (reprint author), Philadelphia Vet Affairs Med Ctr, VISN Eastern Reg Sleep Ctr 111P 4, Dept Med, 3900 Woodland Ave, Philadelphia, PA 19104 USA. EM Samuel.Kuna@va.gov FU Veterans Health Administration, Health Services Research and Development [IIR-04-021-2]; Center for Health Equity Research and Promotion at the Philadelphia VA Medical Center; Philips; Embla, Inc.; Philips-Respironics; NIH; Resmed; Vapotherm; Boston Scientific FX Supported by Veterans Health Administration, Health Services Research and Development grant IIR-04-021-2; the Center for Health Equity Research and Promotion at the Philadelphia VA Medical Center; Philips; and Embla, Inc.; S.T.K. received grant support from Philips-Respironics. I.G. received loaned portable monitoring equipment for use in an NIH-funded clinical research study from Embla Corp. G.M., S.H., K.C.H., S.M., R.H., S.H., R.G., and B.S. do not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. C.W.A. was on the Board or Advisory Board for Cephalon and received lecture fees from Embla. He received grant support from Philips-Respironics, Resmed, Vapotherm, Boston Scientific, and the VA HSR&D. NR 23 TC 83 Z9 87 U1 0 U2 3 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAY 1 PY 2011 VL 183 IS 9 BP 1238 EP 1244 DI 10.1164/rccm.201011-1770OC PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 756IO UT WOS:000290005100020 PM 21471093 ER PT J AU Zhang, Y Ren, YP Jiao, JJ Li, D Zhang, Y AF Zhang, Yu Ren, Yiping Jiao, Jingjing Li, Dong Zhang, Ying TI Ultra High-Performance Liquid Chromatography-Tandem Mass Spectrometry for the Simultaneous Analysis of Asparagine, Sugars, and Acrylamide in Maillard Reactions SO ANALYTICAL CHEMISTRY LA English DT Article ID ATMOSPHERIC AEROSOLS; FOOD; GLUCOSE; MS/MS; GENOTOXICITY; ATTACHMENT; STRATEGIES; REDUCTION; KNOWLEDGE; PRODUCTS AB We developed an automated microwave digestion labstation (MDL) combined with ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method under the control of positive-negative ion switching as a robust kinetic study tool for rapid and simultaneous quantification of asparagine, glucose, fructose, and acrylamide in Maillard reaction products. Maillard reactions were conducted in a potato model via MDL. The two-step simple pretreatment procedures included the addition of isotope internal standards (15)N(2)-asparagine, (13)C(6)-glucose, and D(3)-acrylamide, followed by appropriate dilution with the mobile phase and filtration. Analytes were separated on a Hypercarb column and monitored by MS/MS. Study of matrix effects indicated Maillard reaction products induce an ionization suppression of both positive and negative precursor ions, but quantitative results are corrected through the use of isotopically labeled internal standards. Using this method, the limit of detection (LOD) and limit of quantification (LOQ) ranges of all analytes were calculated as 0.04-0.6 and 0.1-1.1 mu M, respectively. Excellent repeatability (RSD < 9.6%) and acceptable within-laboratory reproducibility (RSD < 9.2%) substantially supported the use of this method for sample analysis. The present kinetic tools, with 10-50 min mimic of Maillard reactions and short instrumental run time (5.5 min per sample), were successfully validated and applied to simultaneous determination of acrylamide and its pre-cursors and intermediates during Maillard reactions and kinetic elucidation. Furthermore, current tools of MDL combined with simple sample treatment procedures and UHPLC-MS/MS analysis reduce sample analysis time and labor in the kinetic study. C1 [Zhang, Yu; Jiao, Jingjing; Li, Dong; Zhang, Ying] Zhejiang Univ, Sch Biosyst Engn & Food Sci, Dept Food Sci & Nutr, Hangzhou 310058, Zhejiang, Peoples R China. [Ren, Yiping] Zhejiang Prov Ctr Dis Control & Prevent, Hangzhou 310051, Zhejiang, Peoples R China. [Zhang, Yu; Jiao, Jingjing] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Zhang, Yu; Jiao, Jingjing] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Zhang, Y (reprint author), Zhejiang Univ, Sch Biosyst Engn & Food Sci, Dept Food Sci & Nutr, Hangzhou 310058, Zhejiang, Peoples R China. EM y_zhang@zju.edu.cn; y_zhang@zju.edu.cn FU National Natural Science Foundation of China [30972486]; Eleventh Five-Year National Key Technology R&D Program of China [2009BADB9B07-2a] FX This study was financially supported by the National Natural Science Foundation of China (Grant No. 30972486) and the Eleventh Five-Year National Key Technology R&D Program of China (Grant No. 2009BADB9B07-2a). NR 25 TC 31 Z9 33 U1 7 U2 65 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD MAY 1 PY 2011 VL 83 IS 9 BP 3297 EP 3304 DI 10.1021/ac1029538 PG 8 WC Chemistry, Analytical SC Chemistry GA 755SN UT WOS:000289956800014 PM 21462916 ER PT J AU Alfille, PH AF Alfille, Paul H. TI Using Recruitment Maneuvers to Decrease Tidal Volumes during One-lung Ventilation SO ANESTHESIOLOGY LA English DT Editorial Material ID END-EXPIRATORY PRESSURE; INJURY C1 [Alfille, Paul H.] Harvard Univ, Sch Med, Dept Anesthesiol, Boston, MA 02115 USA. [Alfille, Paul H.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Management, Boston, MA 02114 USA. RP Alfille, PH (reprint author), Harvard Univ, Sch Med, Dept Anesthesiol, Boston, MA 02115 USA. EM palfille@partners.org NR 9 TC 1 Z9 2 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD MAY PY 2011 VL 114 IS 5 BP 1009 EP 1010 DI 10.1097/ALN.0b013e318216469f PG 2 WC Anesthesiology SC Anesthesiology GA 755ZG UT WOS:000289980200001 PM 21521963 ER PT J AU Ng, JB Bittner, EA AF Ng, Joshua B. Bittner, Edward A. TI Tracheobronchomegaly A Rare Cause of Endotracheal Tube Cuff Leak SO ANESTHESIOLOGY LA English DT Editorial Material ID MOUNIER-KUHN-SYNDROME C1 [Ng, Joshua B.; Bittner, Edward A.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Ng, JB (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM jbng@partners.org NR 3 TC 2 Z9 2 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD MAY PY 2011 VL 114 IS 5 BP 1211 EP 1211 DI 10.1097/ALN.0b013e318206ff9a PG 1 WC Anesthesiology SC Anesthesiology GA 755ZG UT WOS:000289980200026 PM 21270631 ER PT J AU Posner, MR Lorch, JH Goloubeva, O Tan, M Schumaker, LM Sarlis, NJ Haddad, RI Cullen, KJ AF Posner, M. R. Lorch, J. H. Goloubeva, O. Tan, M. Schumaker, L. M. Sarlis, N. J. Haddad, R. I. Cullen, K. J. TI Survival and human papillomavirus in oropharynx cancer in TAX 324: a subset analysis from an international phase III trial SO ANNALS OF ONCOLOGY LA English DT Article DE chemoradiotherapy; chemotherapy; head and neck cancer; human papillomavirus; oropharynx cancer; randomized trials ID SQUAMOUS-CELL CARCINOMA; RANDOMIZED-TRIAL; NECK-CANCER; RADIATION-THERAPY; ORGAN PRESERVATION; TONSILLAR CANCER; HEAD; CHEMOTHERAPY; RADIOTHERAPY; LARYNX AB Background: The association between human papillomavirus (HPV) and overall survival (OS) in oropharynx cancer (OPC) was retrospectively examined in TAX 324, a phase III trial of sequential therapy for locally advanced head and neck cancer. Methods: Accrual for TAX 324 was completed in 2003 and data updated through 2008. Pretherapy tumor biopsies were studied by PCR for human papillomavirus type 16 and linked to OS, progression-free survival (PFS) and demographics. Results: Of 264 patients with OPC, 111 (42%) had evaluable biopsies; 56 (50%) were HPV+ and 55 (50%) were HPV-. HPV+ patients were significantly younger (54 versus 58 years, P = 0.02), had T1/T2 primary cancers (49% versus 20%, P = 0.001), and had a performance status of zero (77% versus 49%, P = 0.003). OS and PFS were better for HPV+ patients (OS, hazard ratio = 0.20, P < 0.0001). Local-regional failure was less in HPV+ patients (13% versus 42%, P = 0.0006); at 5 years, 82% of HPV+ patients were alive compared with 35% of HPV- patients (P < 0.0001). Conclusions: HPV+ OPC has a different biology compared with HPV- OPC; 5-year OS, PFS, and local-regional control are unprecedented. These results support the possibility of selectively reducing therapy and long-term morbidity in HPV+ OPC while preserving survival and approaching HPV- disease with more aggressive treatment. C1 [Posner, M. R.] Mt Sinai Sch Med, Tisch Canc Inst, Head & Neck Oncol Ctr, New York, NY 10029 USA. [Lorch, J. H.; Haddad, R. I.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Goloubeva, O.; Tan, M.; Schumaker, L. M.; Cullen, K. J.] Univ Maryland, Marlene & Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA. [Sarlis, N. J.] Sanofi Aventis US, Bridgewater, MA USA. RP Posner, MR (reprint author), Mt Sinai Sch Med, Tisch Canc Inst, Head & Neck Oncol Ctr, 1 Gustave L Levy Pl,Box 1128, New York, NY 10029 USA. EM marshall.posner@mssm.edu OI Schumaker, Lisa/0000-0002-8454-9660 FU Sanofi-Aventis; Steven Tendrich Fund FX Sanofi-Aventis; Steven Tendrich Fund to M.R.P. These Funds were used for HPV testing of tissues and the statistical analysis of the data. NR 27 TC 160 Z9 163 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 2011 VL 22 IS 5 BP 1071 EP 1077 DI 10.1093/annonc/mdr006 PG 7 WC Oncology SC Oncology GA 756YB UT WOS:000290049600011 PM 21317223 ER PT J AU Arriaga, AF Elbardissi, AW Regenbogen, SE Greenberg, CC Berry, WR Lipsitz, S Moorman, D Kasser, J Warshaw, AL Zinner, MJ Gawande, AA AF Arriaga, Alexander F. Elbardissi, Andrew W. Regenbogen, Scott E. Greenberg, Caprice C. Berry, William R. Lipsitz, Stuart Moorman, Donald Kasser, James Warshaw, Andrew L. Zinner, Michael J. Gawande, Atul A. TI A Policy-based Intervention for the Reduction of Communication Breakdowns in Inpatient Surgical Care Results From a Harvard Surgical Safety Collaborative SO ANNALS OF SURGERY LA English DT Article ID CLOSED MALPRACTICE CLAIMS; TEACHING HOSPITALS; PATIENT-CARE; ERRORS; MORTALITY; SURGERY; INSURERS; TEAMWORK AB Objective: To develop and evaluate an intervention to reduce breakdowns in communication during inpatient surgical care. Background: Communication breakdowns are the second most common cause of avoidable surgical adverse events after technical errors. Methods: In a pre- and postintervention study, a random selection of patients on the surgical services of 4 teaching hospitals were observed according to 3 measures: (1) resident-attending communication of critical patient events (eg, transfer into the intensive care unit, unplanned intubation, cardiac arrest); (2) resident-attending notification regarding routine weekend patient status; and (3) frequency of weekend patient visits by an attending. All departments then developed and adopted a set of policy and education initiatives designed to increase prompt and consistent resident-attending communication (especially in critical events) and to improve regular attending visits with surgical patients. Specific reinforcement of the policies included a pocket information card for residents, as well as periodic reminders. Repeat audits of the surgical services were then conducted. Results: We reviewed information for 211 critical events and 1360 patients for the nature of resident and attending communication practices. After the intervention, the proportion of critical events not conveyed to an attending decreased from 33% (26/80) to 2% (1/47), and gaps in the frequency of attending notification of patient status on weekends were virtually eliminated (P < 0.0001); the proportion of weekend patients not visited by an attending for greater than 24 hours decreased by half (from 61% to 33%; P = 0.0002). Contact resulted in attending-led changes in patient management in one-third of cases. Conclusions: An intervention to improve surgical communication practices at 4 teaching hospitals led to significant reductions in potentially harmful communication breakdowns during inpatient care; significant alterations in patient management were noted in one-third of cases in which there was an adherence to recommended communication practices. C1 [Arriaga, Alexander F.; Elbardissi, Andrew W.; Regenbogen, Scott E.; Greenberg, Caprice C.; Berry, William R.; Gawande, Atul A.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Arriaga, Alexander F.; Elbardissi, Andrew W.; Greenberg, Caprice C.; Lipsitz, Stuart; Zinner, Michael J.; Gawande, Atul A.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Regenbogen, Scott E.; Warshaw, Andrew L.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Moorman, Donald] Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA. [Kasser, James] Childrens Hosp, Dept Surg, Boston, MA 02115 USA. RP Arriaga, AF (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, 677 Huntington Ave, Boston, MA 02115 USA. EM aarriaga@partners.org OI Gawande, Atul/0000-0002-1824-9176 FU Harvard Risk Management Foundation (CRICO/RMF) FX Supported by a grant from the Harvard Risk Management Foundation (CRICO/RMF). NR 27 TC 19 Z9 19 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD MAY PY 2011 VL 253 IS 5 BP 849 EP 854 DI 10.1097/SLA.0b013e3181f4dfc8 PG 6 WC Surgery SC Surgery GA 749ZD UT WOS:000289510600001 PM 21173696 ER PT J AU Livhits, M Ko, CY Leonardi, MJ Zingmond, DS Gibbons, MM de Virgilio, C AF Livhits, Masha Ko, Clifford Y. Leonardi, Michael J. Zingmond, David S. Gibbons, Melinda Maggard de Virgilio, Christian TI Risk of Surgery Following Recent Myocardial Infarction SO ANNALS OF SURGERY LA English DT Article ID MAJOR NONCARDIAC SURGERY; RANDOMIZED CONTROLLED-TRIAL; BETA-BLOCKER THERAPY; VASCULAR-SURGERY; CARDIAC RISK; CARDIOVASCULAR EVENTS; ADMINISTRATIVE DATA; MORTALITY; ATORVASTATIN; ANESTHESIA AB Objective: We aimed to assess the impact of recentmyocardial infarction (MI) on outcomes after subsequent surgery in the contemporary clinical setting. Background: Prior work shows that a history of a recent MI is a risk factor for complications following noncardiac surgery. However, this data does not reflect current advances in clinical management. Methods: Using the California Patient Discharge Database, we retrospectively analyzed patients undergoing hip surgery, cholecystectomy, colectomy, elective abdominal aortic aneurysm repair, and lower extremity amputation from 1999 to 2004 (n = 563,842). Postoperative 30-day MI rate, 30-day mortality, and 1-year mortality were compared for patients with and without a recent MI using univariate analyses and multivariate logistic regression. Relative risks (RR) with 95% confidence intervals were estimated using bootstrapping with 1000 repetitions. Results: Postoperative MI rate for the recent MI cohort decreased substantially as the length of time from MI to operation increased (0-30 days = 32.8%, 31-60 days = 18.7%, 61-90 days = 8.4%, and 91-180 days = 5.9%), as did 30-day mortality (0-30 days = 14.2%, 31-60 days = 11.5%, 61-90 days = 10.5%, and 91-180 days = 9.9%). MI within 30 days of an operation was associated with a higher risk of postoperative MI (RR range = 9.98-44.29 for the 5 procedures), 30-day mortality (RR range, 1.83-3.84), and 1-year mortality (RR range, 1.56-3.14). Conclusions: A recent MI remains a significant risk factor for postoperative MI and mortality following surgery. Strategies such as delaying elective operations for at least 8 weeks and medical optimization should be considered. C1 [de Virgilio, Christian] Harbor UCLA Med Ctr, Dept Surg, Torrance, CA 90509 USA. [de Virgilio, Christian] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA. [Livhits, Masha; Ko, Clifford Y.; Leonardi, Michael J.; Gibbons, Melinda Maggard] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Livhits, Masha; Ko, Clifford Y.; Gibbons, Melinda Maggard] VA Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA USA. [Zingmond, David S.] Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA. [Gibbons, Melinda Maggard] Olive View UCLA, Dept Surg, Sylmar, CA USA. RP de Virgilio, C (reprint author), Harbor UCLA Med Ctr, Dept Surg, 1000 W Carson St, Torrance, CA 90509 USA. EM cdevirgilio@labiomed.org FU VA Department of Surgery; Robert Wood Johnson Physician Faculty FX Supported by VA Department of Surgery and Robert Wood Johnson Physician Faculty Scholars program. NR 31 TC 21 Z9 21 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD MAY PY 2011 VL 253 IS 5 BP 857 EP 864 DI 10.1097/SLA.0b013e3182125196 PG 8 WC Surgery SC Surgery GA 749ZD UT WOS:000289510600003 PM 21372685 ER PT J AU Funk, LM Gawande, AA Semel, ME Lipsitz, SR Berry, WR Zinner, MJ Jha, AK AF Funk, Luke M. Gawande, Atul A. Semel, Marcus E. Lipsitz, Stuart R. Berry, William R. Zinner, Michael J. Jha, Ashish K. TI Esophagectomy Outcomes at Low-Volume Hospitals The Association Between Systems Characteristics and Mortality SO ANNALS OF SURGERY LA English DT Article ID CANCER-SURGERY; UNITED-STATES; OPERATIVE MORTALITY; SURGICAL VOLUME; RESECTION; CENTERS; PATTERNS; IMPACT AB Objective: To evaluate the association between systems characteristics and esophagectomy mortality at low-volume hospitals Background: High-volume hospitals have lower esophagectomy mortality rates, but receiving care at such centers is not always feasible. We examined low-volume hospitals and sought to identify characteristics of those with better outcomes. Methods: Using national data from Medicare and the American Hospital Association, we studied 4498 elderly patients who underwent an esophagectomy from 2004 to 2007. We divided hospitals into terciles based on esophagectomy volume and examined characteristics of patients and hospitals (size, nurse ratios, and presence of advanced medical, surgical, and radiological services). Our primary outcome was mortality. We identified 5 potentially beneficial systems characteristics in our data set and used multi-variable logistic regression to determine whether these characteristics were associated with lower mortality rates at low-volume hospitals. Results: Of the 874 hospitals that performed esophagectomies, 83% (723) were low-volume hospitals whereas only 3% (25) were high-volume. Low-volume hospitals performed a median of 1 esophagectomy during the 4-year study period and cared for patients that were older, more likely to be minority, and more likely to have multiple comorbidities compared with high-volume centers. Low-volume hospitals that had at least 3 of 5 characteristics (high nurse ratios, lung transplantation services, complex medical oncology services, bariatric surgery services, and positron emission tomography scanners) had markedly lower mortality rates compared with low-volume hospitals with none of these characteristics (12.5% vs. 5.0%; P value = 0.042). Conclusions: Low-volume hospitals with certain system