FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Wang, H Smith, RN Spooner, AE Isselbacher, EM Cambria, RP MacGillivray, TE Stone, JH Stone, JR AF Wang, He Smith, R. Neal Spooner, Amy E. Isselbacher, Eric M. Cambria, Richard P. MacGillivray, Thomas E. Stone, John H. Stone, James R. TI Giant cell aortitis of the ascending aorta without signs or symptoms of systemic vasculitis is associated with elevated risk of distal aortic events SO ARTHRITIS AND RHEUMATISM LA English DT Editorial Material C1 [Wang, He; Smith, R. Neal; Spooner, Amy E.; Isselbacher, Eric M.; Cambria, Richard P.; MacGillivray, Thomas E.; Stone, John H.; Stone, James R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Wang, H (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 5 TC 9 Z9 9 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD JAN PY 2012 VL 64 IS 1 BP 317 EP 319 DI 10.1002/art.33343 PG 3 WC Rheumatology SC Rheumatology GA 869KZ UT WOS:000298598100039 PM 21953530 ER PT J AU Bashyal, RK Malchau, H Nimkin, K Holmes, LB AF Bashyal, Ravi K. Malchau, Henrik Nimkin, Katherine Holmes, Lewis B. TI The association of a dysmorphic pelvis, absence of pubic rami, hip dysplasia, and genitourinary anomalies SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Article DE absent pubic rami; absent uterus; genitourinary; anomalies; dysmorphic ID SUPPLY DISRUPTION SEQUENCE; POLAND; HYPOPLASIA AB BACKGROUND There have been reports of children who had absence of the pubic rami, hip dysplasia, and genitourinary anomalies. CASE REPORT: We describe a 44-year-old woman with severe hip dysplasia, bilateral chronic congenital hip dislocations, abnormal development of the entire pelvis, and absence of the pubic rami in association with absence of the uterus. CONCLUSION: We present an individual who has abnormal development of the entire pelvis, including absence of the pubic rami, and genitourinary anomalies. We suggest that this is a rare pattern of associated anomalies confined to a localized region of the body. Potential underlying developmental abnormalities include somatic mutations which affected the mesodermal cells from which the pelvis and mullerian structures develop. Birth Defects Research (Part A) 94:57-60, 2012. (C) 2011 Wiley Periodicals, Inc. C1 [Bashyal, Ravi K.; Malchau, Henrik] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed, Boston, MA USA. [Nimkin, Katherine] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Holmes, Lewis B.] Harvard Univ, Sch Med, Dept Pediat, Genet Unit,MassGen Hosp Children, Boston, MA 02115 USA. RP Holmes, LB (reprint author), Mass Gen Hosp Children, Genet Unit, 175 Cambridge St, Boston, MA 02114 USA. EM lewis@mgh.harvard.edu NR 24 TC 2 Z9 2 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 JAN PY 2012 VL 94 IS 1 BP 57 EP 60 DI 10.1002/bdra.22873 PG 4 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 874JE UT WOS:000298951600010 PM 22183795 ER PT J AU Xu, HS Yi, BA Wu, H Bock, C Gu, HC Lui, KO Park, JHC Shao, Y Riley, AK Domian, IJ Hu, E Willette, R Lepore, J Meissner, A Wang, Z Chien, KR AF Xu, Huansheng Yi, B. Alexander Wu, Hao Bock, Christoph Gu, Hongcang Lui, Kathy O. Park, Joo-Hye C. Shao, Ying Riley, Alyssa K. Domian, Ibrahim J. Hu, Erding Willette, Robert Lepore, John Meissner, Alexander Wang, Zhong Chien, Kenneth R. TI Highly efficient derivation of ventricular cardiomyocytes from induced pluripotent stem cells with a distinct epigenetic signature SO CELL RESEARCH LA English DT Article DE induced pluripotent stem cells; ventricular cardiomyocyte; regenerative medicine; epigenetic memory ID CARDIOVASCULAR PROGENITORS; CARDIAC MYOCYTES; HEART-MUSCLE; DIFFERENTIATION; MOUSE; MEMORY; REGENERATION; FIBROBLASTS; EXPRESSION; GENERATION AB Cardiomyocytes derived from pluripotent stem cells can be applied in drug testing, disease modeling and cell-based therapy. However, without procardiogenic growth factors, the efficiency of cardiomyogenesis from pluripotent stem cells is usually low and the resulting cardiomyocyte population is heterogeneous. Here, we demonstrate that induced pluripotent stem cells (iPSCs) can be derived from murine ventricular myocytes (VMs), and consistent with other reports of iPSCs derived from various somatic cell types, VM-derived iPSCs (ViPSCs) exhibit a markedly higher propensity to spontaneously differentiate into beating cardiomyocytes as compared to genetically matched embryonic stem cells (ESCs) or iPSCs derived from tail-tip fibroblasts. Strikingly, the majority of ViPSC-derived cardiomyocytes display a ventricular phenotype. The enhanced ventricular myogenesis in ViPSCs is mediated via increased numbers of cardiovascular progenitors at early stages of differentiation. In order to investigate the mechanism of enhanced ventricular myogenesis from ViPSCs, we performed global gene expression and DNA methylation analysis, which revealed a distinct epigenetic signature that may be involved in specifying the VM fate in pluripotent stem cells. C1 [Xu, Huansheng; Yi, B. Alexander; Wu, Hao; Lui, Kathy O.; Park, Joo-Hye C.; Shao, Ying; Riley, Alyssa K.; Domian, Ibrahim J.; Wang, Zhong; Chien, Kenneth R.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Xu, Huansheng; Yi, B. Alexander; Wu, Hao; Bock, Christoph; Gu, Hongcang; Lui, Kathy O.; Domian, Ibrahim J.; Meissner, Alexander; Wang, Zhong; Chien, Kenneth R.] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Xu, Huansheng; Yi, B. Alexander; Wu, Hao; Bock, Christoph; Gu, Hongcang; Lui, Kathy O.; Meissner, Alexander; Chien, Kenneth R.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Bock, Christoph; Gu, Hongcang; Meissner, Alexander] Broad Inst, Cambridge, MA 02142 USA. [Hu, Erding; Willette, Robert; Lepore, John] GlaxoSmithKline, Cardiac Biol, HF Discovery Performance Unit, Metab & Cardiovasc Therapeut Area Unit, King Of Prussia, PA 19406 USA. RP Chien, KR (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charles River Plaza CPZN 3208,185 Cambridge St, Boston, MA 02114 USA. EM krchien@partners.org RI Wu, Hao/G-4145-2013; Lui, Kathy O./E-4883-2015; OI Wu, Hao/0000-0002-1256-6891; Lui, Kathy O./0000-0002-1616-3643; Bock, Christoph/0000-0001-6091-3088 FU Massachusetts General Hospital Executive Committee; NIH [5T32HL007208-32]; MGH ECOR; Jane Coffin Childs postdoctoral fellowship; Croucher Foundation; GlaxoSmithKline Pharmaceuticals FX We would like to thank Laura Prickett-Rice, Kat Folz-Donahue, and Sutanuka Lahiri of the Harvard Stem Cell Institute Flow Cytometry Core Facility for assistance with FACS analysis, Chuang Du of the Tufts Electrophysiology Core for assistance with electrophysiology recordings, Jie Zhao and members of the Wellman Photopathology Core for assistance with histology, Patricia Follett for assistance with blastocyst injections, and Elizabeth Bearrick for assistance with experiments. We would like to thank Konrad Hochedlinger (Massachusetts General Hospital, Harvard University, USA) for sharing the Rosa26rtTA/rtTA mouse line as well as the lentiviral constructs for iPSC derivation. We would like to thank Lei Bu, Emil Hansson, members of the Chien laboratory, and Konrad Hochedlinger for helpful discussion. HX is supported by Massachusetts General Hospital Executive Committee of Research Fund for Medical Discovery. BAY has received support under NIH Training Grant (5T32HL007208-32) and the MGH ECOR Fund for Medical Discovery. HW is supported by a Jane Coffin Childs postdoctoral fellowship. KOL holds a Croucher Foundation Fellowship. This work is partially funded by GlaxoSmithKline Pharmaceuticals. NR 38 TC 40 Z9 43 U1 2 U2 15 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYANG ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 EI 1748-7838 J9 CELL RES JI Cell Res. PD JAN PY 2012 VL 22 IS 1 BP 142 EP 154 DI 10.1038/cr.2011.171 PG 13 WC Cell Biology SC Cell Biology GA 879EQ UT WOS:000299312900015 PM 22064699 ER PT J AU Roger, VL O'Donnell, CJ AF Roger, Veronique L. O'Donnell, Christopher J. TI Population Health, Outcomes Research, and Prevention Example of the American Heart Association 2020 Goals SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Editorial Material DE prevention; delivery of health care; outcomes assessment ID CLINICAL-PRACTICE GUIDELINES; NEW-YORK-CITY; CARDIOVASCULAR-DISEASE; CARE; BEHAVIOR; ERA C1 [Roger, Veronique L.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA. [Roger, Veronique L.] Mayo Clin, Div Cardiovasc Dis, Dept Internal Med, Rochester, MN 55905 USA. [O'Donnell, Christopher J.] NHLBI, Framingham, MA USA. [O'Donnell, Christopher J.] NHLBI Framingham Heart Study, Framingham, MA USA. [O'Donnell, Christopher J.] Massachusetts Gen Hosp, Div Cardiol, Dept Internal Med, Boston, MA 02114 USA. RP Roger, VL (reprint author), Mayo Clin, Dept Hlth Sci Res, 200 First St SW, Rochester, MN 55905 USA. EM roger.veronique@mayo.edu FU Intramural NIH HHS [Z99 HL999999]; NHLBI NIH HHS [R01 HL059205-13, R01 HL072435, R01 HL072435-08, R01 HL59205, R01 HL059205, R01 HL72435] NR 25 TC 5 Z9 5 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7705 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD JAN PY 2012 VL 5 IS 1 BP 6 EP 8 DI 10.1161/CIRCOUTCOMES.111.964734 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 880ML UT WOS:000299411100002 PM 22253367 ER PT J AU Arling, G Reeves, M Ross, J Williams, LS Keyhani, S Chumbler, N Phipps, MS Roumie, C Myers, LJ Salanitro, AH Ordin, DL Myers, J Bravata, DM AF Arling, Greg Reeves, Mathew Ross, Joseph Williams, Linda S. Keyhani, Salomeh Chumbler, Neale Phipps, Michael S. Roumie, Christianne Myers, Laura J. Salanitro, Amanda H. Ordin, Diana L. Myers, Jennifer Bravata, Dawn M. TI Estimating and Reporting on the Quality of Inpatient Stroke Care by Veterans Health Administration Medical Centers SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE acute stroke; performance measurement; quality indicators; stroke management; statistics ID ACUTE ISCHEMIC-STROKE; PLASMINOGEN-ACTIVATOR; PERFORMANCE-MEASURES; OF-CARE; OUTCOMES; MORTALITY; MODELS; IMPACT; INTERVENTION; IMPROVEMENT AB Background-Reporting of quality indicators (QIs) in Veterans Health Administration Medical Centers is complicated by estimation error caused by small numbers of eligible patients per facility. We applied multilevel modeling and empirical Bayes (EB) estimation in addressing this issue in performance reporting of stroke care quality in the Medical Centers. Methods and Results-We studied a retrospective cohort of 3812 veterans admitted to 106 Medical Centers with ischemic stroke during fiscal year 2007. The median number of study patients per facility was 34 (range, 12-105). Inpatient stroke care quality was measured with 13 evidence-based QIs. Eligible patients could either pass or fail each indicator. Multilevel modeling of a patient's pass/fail on individual QIs was used to produce facility-level EB-estimated QI pass rates and confidence intervals. The EB estimation reduced interfacility variation in QI rates. Small facilities and those with exceptionally high or low rates were most affected. We recommended 8 of the 13 QIs for performance reporting: dysphagia screening, National Institutes of Health Stroke Scale documentation, early ambulation, fall risk assessment, pressure ulcer risk assessment, Functional Independence Measure documentation, lipid management, and deep vein thrombosis prophylaxis. These QIs displayed sufficient variation across facilities, had room for improvement, and identified sites with performance that was significantly above or below the population average. The remaining 5 QIs were not recommended because of too few eligible patients or high pass rates with little variation. Conclusions-Considerations of statistical uncertainty should inform the choice of QIs and their application to performance reporting. (Circ Cardiovasc Qual Outcomes. 2012;5:44-51.) C1 [Arling, Greg; Williams, Linda S.; Chumbler, Neale; Bravata, Dawn M.] Regenstrief Inst Hlth Care, Indianapolis, IN 46202 USA. [Arling, Greg; Reeves, Mathew; Williams, Linda S.; Chumbler, Neale; Myers, Laura J.; Ordin, Diana L.; Myers, Jennifer; Bravata, Dawn M.] Stroke Qual Enhancement Res Initiat QUERI, VHA Hlth Serv Res & Dev HSR& D, Indianapolis, IN USA. [Ordin, Diana L.] VHA, Off Informat & Analyt, Washington, DC USA. [Arling, Greg; Myers, Laura J.; Bravata, Dawn M.] Indiana Univ Sch Med, Dept Med, Indianapolis, IN USA. [Reeves, Mathew] Michigan State Univ, Dept Epidemiol, E Lansing, MI 48824 USA. [Ross, Joseph] Yale Univ, Sch Med, Dept Med, Gen Internal Med Sect, New Haven, CT 06510 USA. [Ross, Joseph] Yale New Haven Med Ctr, Ctr Outcomes Res & Evaluat, New Haven, CT 06504 USA. [Williams, Linda S.; Chumbler, Neale; Myers, Laura J.; Myers, Jennifer; Bravata, Dawn M.] Richard L Roudebush VHA Med Ctr, VHA HSR&D Ctr Excellence Implementing Evidence Ba, Indianapolis, IN USA. [Williams, Linda S.] Indiana Univ Sch Med, Dept Neurol, Indianapolis, IN USA. [Keyhani, Salomeh] Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94143 USA. [Keyhani, Salomeh] San Francisco VA Med Ctr, HSR&D Res Enhancement Award Program, San Francisco, CA USA. [Chumbler, Neale] Indiana Univ Purdue Univ, Indiana Univ, Sch Liberal Arts, Dept Sociol, Indianapolis, IN 46202 USA. [Phipps, Michael S.] Yale Univ, Sch Med, Robert Wood Johnson Fdn, Clin Scholars Program, New Haven, CT USA. [Phipps, Michael S.] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA. [Roumie, Christianne] Vet Affairs Tennessee Valley Healthcare Syst, HSR&D Targeted Res Enhancement Program Ctr, GRECC, Nashville, TN USA. [Roumie, Christianne] Vet Affairs Tennessee Valley Healthcare Syst, Clin Res Training Ctr Excellence, Nashville, TN USA. [Roumie, Christianne; Salanitro, Amanda H.] Vanderbilt Univ, Med Ctr, Inst Med & Publ Hlth, Nashville, TN USA. [Salanitro, Amanda H.] Vanderbilt Univ, Med Ctr, Sect Hosp Med, Nashville, TN USA. RP Arling, G (reprint author), Regenstrief Inst Hlth Care, 410 W 10th St,Suite 2000, Indianapolis, IN 46202 USA. EM GArling@IUPUI.edu OI Phipps, Michael/0000-0001-8398-5404 FU Department of Veterans Affairs, Veterans Health Administration (VHA), Office of Quality and Performance and Health Services Research, and Development Service Quality Enhancement Research Initiative [RRP 09-184]; National Institute on Aging; American Federation of Aging Research [K08 AG032886]; VA HSRD FX The Department of Veterans Affairs, Veterans Health Administration (VHA), Office of Quality and Performance and Health Services Research, and Development Service Quality Enhancement Research Initiative (RRP 09-184) supported this project. Dr Ross is supported by the National Institute on Aging and by the American Federation of Aging Research through the Paul B. Beason Career Development Award Program (K08 AG032886). Dr Keyhani is supported by a VA HSR&D Career Development Award. NR 42 TC 18 Z9 19 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7705 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD JAN PY 2012 VL 5 IS 1 BP 44 EP U102 DI 10.1161/CIRCOUTCOMES.111.961474 PG 23 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 880ML UT WOS:000299411100009 PM 22147888 ER PT J AU Qian, F Ling, FS Deedwania, P Hernandez, AF Fonarow, GC Cannon, CP Peterson, ED Peacock, WF Kaltenbach, LA Laskey, WK Schwamm, LH Bhatt, DL AF Qian, Feng Ling, Frederick S. Deedwania, Prakash Hernandez, Adrian F. Fonarow, Gregg C. Cannon, Christopher P. Peterson, Eric D. Peacock, W. Frank Kaltenbach, Lisa A. Laskey, Warren K. Schwamm, Lee H. Bhatt, Deepak L. CA Get Guidelines Steering Comm TI Care and Outcomes of Asian-American Acute Myocardial Infarction Patients: Findings From the American Heart Association Get With The Guidelines-Coronary Artery Disease Program SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE Asian-Americans; acute myocardial infarction; quality of care; outcomes ID CARDIOVASCULAR RISK-FACTORS; RACIAL-DIFFERENCES; PERFORMANCE-MEASURES; ETHNIC-DIFFERENCES; PACIFIC ISLANDERS; CARDIAC PATIENTS; CLINICAL-TRIALS; UNSTABLE ANGINA; ST-ELEVATION; EVENT RATES AB Background-Asian-Americans represent an important United States minority population, yet there are limited data regarding the clinical care and outcomes of Asian-Americans following acute myocardial infarction (AMI). Using data from the American Heart Association Get With The Guidelines-Coronary Artery Disease (GWTG-CAD) program, we compared use of and trends in evidence-based care AMI processes and outcome in Asian-American versus white patients. Methods and Results-We analyzed 107 403 AMI patients (4412 Asian-Americans, 4.1%) from 382 United States centers participating in the Get With The Guidelines-Coronary Artery Disease program between 2003 and 2008. Use of 6 AMI performance measures, composite "defect-free" care (proportion receiving all eligible performance measures), door-to-balloon time, and in-hospital mortality were examined. Trends in care over this time period were explored. Compared with whites, Asian-American AMI patients were significantly older, more likely to be covered by Medicaid and recruited in the west region, and had a higher prevalence of diabetes, hypertension, heart failure, and smoking. In-hospital unadjusted mortality was higher among Asian-American patients. Overall, Asian-Americans were comparable with whites regarding the baseline quality of care, except that Asian-Americans were less likely to get smoking cessation counseling (65.6% versus 81.5%). Asian-American AMI patients experienced improvement in the 6 individual measures (P <= 0.048), defect-free care (P<0.001), and door-to-balloon time (P<0.001). The improvement rates were similar for both Asian-Americans and whites. Compared with whites, the adjusted in-hospital mortality rate was higher for Asian-Americans (adjusted relative risk: 1.16; 95% confidence interval: 1.00-1.35; P=0.04). Conclusions-Evidence-based care for AMI processes improved significantly over the period of 2003 to 2008 for Asian-American and white patients in the Get With The Guidelines-Coronary Artery Disease program. Differences in care between Asian-Americans and whites, when present, were reduced over time. (Circ Cardiovasc Qual Outcomes. 2012;5:126-133.) C1 [Qian, Feng] Univ Rochester, Med Ctr, Dept Anesthesiol, Rochester, NY 14642 USA. [Deedwania, Prakash] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Hernandez, Adrian F.; Peterson, Eric D.; Kaltenbach, Lisa A.] Duke Univ, Durham, NC USA. [Fonarow, Gregg C.] Ronald Reagan UCLA Med Ctr, Los Angeles, CA USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Fonarow, Gregg C.; Schwamm, Lee H.; Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. [Peacock, W. Frank] Cleveland Clin, Cleveland, OH 44106 USA. [Laskey, Warren K.] Univ New Mexico, Albuquerque, NM 87131 USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Qian, F (reprint author), Univ Rochester, Med Ctr, Dept Anesthesiol, 601 Elmwood Ave,Box 604, Rochester, NY 14642 USA. EM feng_qian@urmc.rochester.edu RI Hernandez, Adrian F./A-7818-2016 OI Schwamm, Lee/0000-0003-0592-9145; Hernandez, Adrian F./0000-0003-3387-9616 FU American Heart Association; Council on Clinical Cardiology of the American Heart Association; NHLBI; Novartis; Pfizer; Accumetrics; AstraZeneca; GlaxoSmithKline; Intekrin Therapeutics; Merck; Takeda; Bristol-Myers Squibb/Sanofi; Alnylam; Abbott; BAS; Brahms; Beckman-Coulter; Alere; Nanosphere; EKR; Medicines company; Amarin; Bristol-Myers Squibb; Eisai; Sanofi Aventis; Medtronic FX Dr Qian has received the American Heart Association Young Investigator Database Seed Grant, which is sponsored by the Council on Clinical Cardiology of the American Heart Association.; Dr Fonarow receives research funding from the NHLBI (significant), and consulting fees from Novartis (significant) and Pfizer (modest).; Dr Cannon receives research grants/support from Accumetrics, AstraZeneca, GlaxoSmithKline, Intekrin Therapeutics, Merck, and Takeda, and is on the advisory board (but funds donated to charity) for Bristol-Myers Squibb/Sanofi, Novartis, and Alnylam. He also receives an honorarium for development of independent educational symposia for Pfizer and AstraZeneca, and is clinical advisor for Automedics Medical Systems.; Dr Peacock has received research funding from Abbott, BAS, Brahms, Beckman-Coulter, Alere, Nanosphere, EKR, and The Medicines company. He has also served as a consultant for these companies and Lily.; Dr Bhatt receives research funding from Amarin, Astra Zeneca, Bristol-Myers Squibb, Eisai, Sanofi Aventis, Medtronic, and The Medicines Company. NR 43 TC 12 Z9 14 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7705 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD JAN PY 2012 VL 5 IS 1 BP 126 EP 133 DI 10.1161/CIRCOUTCOMES.111.961987 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 880ML UT WOS:000299411100019 PM 22235068 ER PT J AU Brennan, JM Peterson, ED Messenger, JC Rumsfeld, JS Weintraub, WS Anstrom, KJ Eisenstein, EL Milford-Beland, S Grau-Sepulveda, MV Booth, ME Dokholyan, RS Douglas, PS AF Brennan, J. Matthew Peterson, Eric D. Messenger, John C. Rumsfeld, John S. Weintraub, William S. Anstrom, Kevin J. Eisenstein, Eric L. Milford-Beland, Sarah Grau-Sepulveda, Maria V. Booth, Michael E. Dokholyan, Rachel S. Douglas, Pamela S. CA Duke Clinical Res Inst DEcIDE Team TI Linking the National Cardiovascular Data Registry CathPCI Registry With Medicare Claims Data Validation of a Longitudinal Cohort of Elderly Patients Undergoing Cardiac Catheterization SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE catheterization; data linkage; outcomes AB Background-The National Cardiovascular Data Registry CathPCI Registry was recently linked with longitudinal Centers for Medicare & Medicaid (CMS) claims data. The degree to which this linked cohort is representative of the overall CathPCI Registry and CMS PCI populations is unknown. Methods and Results-CathPCI Registry records were linked to CMS inpatient claims using indirect identifiers. We examined the degree to which hospitals and patients in the linked cohort are representative of the elderly (>= 65 years) CathPCI Registry and CMS populations. From 2004 to 2006, 1492 hospitals filed CMS PCI claims and 663 contributed CathPCI Registry data. Of these hospitals, 643 (97%) were linked across data sources. Compared with all CMS PCI hospitals, the linked data set contained fewer governmental, northeastern, southern, and low-volume (<200 beds) sites. Among CMS beneficiaries, 993 351 PCI procedures were performed, including 398 508 (40.1%) at centers in the linked database. Of these, 341 916 (86%) were linked to CathPCI Registry records. Linked and unlinked CMS patients had similar demographic and clinical features. In the CathPCI Registry database, 477 456 elderly patients underwent PCI, with 359 077 (75%) linked to CMS claims. Linked and unlinked National Cardiovascular Data Registry patients were similar, except for less commercial or health maintenance organization insurance in the linked cohort. Conclusions-By using deterministic matching strategies, a large and representative cohort with detailed clinical data from the CathPCI Registry and longitudinal follow-up from CMS claims has been created. (Circ Cardiovasc Qual Outcomes. 2012;5:134-140.) C1 [Brennan, J. Matthew; Peterson, Eric D.; Eisenstein, Eric L.; Milford-Beland, Sarah; Grau-Sepulveda, Maria V.; Booth, Michael E.; Dokholyan, Rachel S.; Douglas, Pamela S.] Duke Univ, Duke Clin Res Inst, Med Ctr, Durham, NC 27705 USA. [Messenger, John C.; Rumsfeld, John S.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Weintraub, William S.] Christiana Care Hlth Syst, Newark, DE USA. RP Brennan, JM (reprint author), Duke Univ, Duke Clin Res Inst, Med Ctr, 2400 Pratt St, Durham, NC 27705 USA. EM brenn009@mc.duke.edu FU Agency for Healthcare Research and Quality, US Department of Health and Human Services, Rockville, MD [24-EHC-1, HHSAA290-2005, 0032-TO4-WA2]; National Cardiovascular Data Registry, American College of Cardiology, Washington, DC; BMS/Sanofi; Merck; Lilly; JJ; Society of Thoracic Surgeons; ACC; Alexion; AstraZeneca; Bristol Myers Squibb; Innocoll Pharmaceuticals; Medtronic; Pfizer; Proctor Gamble; Eli Lilly FX This project was sponsored by the Agency for Healthcare Research and Quality, US Department of Health and Human Services, Rockville, MD, as part of the Cardiovascular Consortium and funded under Project ID: 24-EHC-1 and Work Assignment No. HHSAA290-2005 to 0032-TO4-WA2 as part of the Developing Evidence to Inform Decisions about Effectiveness (DEcIDE) program. Additional support was obtained from the National Cardiovascular Data Registry, American College of Cardiology, Washington, DC.; Dr Peterson reports receiving research funding from BMS/Sanofi, Merck, Lilly, J&J, Society of Thoracic Surgeons, and ACC (significant). Dr Messenger reports serving as the site principal investigator for the Resolute Study and the EDUCATE study: Medtronic, Inc (modest). Dr Rumsfeld is the Chief Science Officer for National Cardiovascular Data Registry. Dr Anstrom reports receiving research and salary support from Alexion, AstraZeneca, Bristol Myers Squibb, Lilly, Innocoll Pharmaceuticals, Medtronic, Pfizer, and Proctor & Gamble (modest); being on the data safety monitoring boards of Pfizer and Vertex (modest); and providing consulting services to Pacific Therapeutics, Bristol Myers Squibb, and AstraZeneca (modest). Dr Eisenstein reports receiving research funding from Medtronic and Eli Lilly (significant). NR 6 TC 26 Z9 26 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7705 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD JAN PY 2012 VL 5 IS 1 BP 134 EP 140 DI 10.1161/CIRCOUTCOMES.111.963280 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 880ML UT WOS:000299411100020 PM 22253370 ER PT J AU Hashash, JG Refaat, M Abdulbaki, A Aoun, EG Baidoo, L AF Hashash, Jana G. Refaat, Marwan Abdulbaki, Abdulrahman Aoun, Elie G. Baidoo, Leonard TI The Clinical Picture Cytomegalovirus colitis SO CLEVELAND CLINIC JOURNAL OF MEDICINE LA English DT Editorial Material ID INFLAMMATORY-BOWEL-DISEASE; PREVALENCE; INFECTION C1 [Hashash, Jana G.; Aoun, Elie G.] Univ Pittsburgh, Div Gastroenterol Hepatol & Nutr, Dept Med, Pittsburgh, PA 15213 USA. [Refaat, Marwan] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Refaat, Marwan] Harvard Univ, Sch Med, Boston, MA USA. [Abdulbaki, Abdulrahman] Louisiana State Univ, Shreveport, LA 71105 USA. [Abdulbaki, Abdulrahman] Hlth Sci Ctr, Shreveport, LA USA. RP Hashash, JG (reprint author), Univ Pittsburgh, Div Gastroenterol Hepatol & Nutr, Dept Med, 200 Lothrop St, Pittsburgh, PA 15213 USA. EM alhashashj@upmc.edu NR 5 TC 3 Z9 3 U1 0 U2 2 PU CLEVELAND CLINIC PI CLEVELAND PA 9500 EUCLID AVE, CLEVELAND, OH 44106 USA SN 0891-1150 J9 CLEV CLIN J MED JI Clevel. Clin. J. Med. PD JAN PY 2012 VL 79 IS 1 BP 12 EP 13 DI 10.3949/ccjm.78a.11028 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 880XQ UT WOS:000299444300002 PM 22219228 ER PT J AU Patil, SU Shreffler, WG AF Patil, S. U. Shreffler, W. G. TI Immunology in the Clinic Review Series; focus on allergies: basophils as biomarkers for assessing immune modulation SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Review DE basophil; desensitization; immunotherapy ID FC-EPSILON-RI; GRASS-POLLEN IMMUNOTHERAPY; WASP VENOM ALLERGY; HUMAN BLOOD BASOPHILS; HISTAMINE-RELEASE; IMMUNOGLOBULIN-G; GAMMA-RIIB; BEE VENOM; ACTIVATION MARKERS; RUSH IMMUNOTHERAPY AB Allergen-specific immunotherapy is an effective clinical treatment for hypersensitivity to many allergens. Studies of basophils during immunotherapy have provided insight into underlying immune mechanisms and support the potential use of basophil activation as a biomarker of clinical outcomes. This review examines the evidence for different pathways of basophil modulation associated with various forms of immunotherapy. Better understanding the molecular mechanisms of basophil activation and desensitization and the relationship between suppression of these effector cells to clinical outcomes holds promise for further development and improvement in potential therapies for allergic diseases. C1 [Patil, S. U.; Shreffler, W. G.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. RP Patil, SU (reprint author), 55 Fruit St,Cox 201, Boston, MA 02441 USA. EM spatil35@partners.org FU NIAID [R01 AI081845] FX Studies on basophil activation by mouse allergen are supported by funding from NIAID R01 AI081845. NR 65 TC 10 Z9 12 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD JAN PY 2012 VL 167 IS 1 BP 59 EP 66 DI 10.1111/j.1365-2249.2011.04503.x PG 8 WC Immunology SC Immunology GA 855GL UT WOS:000297551800008 PM 22132885 ER PT J AU Wesseling-Perry, K Pereira, RC Tseng, CH Elashoff, R Zaritsky, JJ Yadin, O Sahney, S Gales, B Juppner, H Salusky, IB AF Wesseling-Perry, Katherine Pereira, Renata C. Tseng, Chi-Hong Elashoff, Robert Zaritsky, Joshua J. Yadin, Ora Sahney, Shobha Gales, Barbara Jueppner, Harald Salusky, Isidro B. TI Early Skeletal and Biochemical Alterations in Pediatric Chronic Kidney Disease SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID GROWTH-FACTOR 23; CHRONIC-RENAL-FAILURE; GLOMERULAR-FILTRATION-RATE; PARATHYROID-HORMONE; LANTHANUM CARBONATE; HEALTHY-MEN; OSTEODYSTROPHY; PHOSPHATE; CHILDREN; FGF23 AB Background and objectives The relationship between parathyroid hormone, fibroblast growth factor 23 (FGF-23), and indices of bone turnover and mineralization in children with early CKD is unknown; thus, this study characterizes the features of renal osteodystrophy and their relationship to biochemical markers of mineral metabolism. Design, setting, participants, & measurements Fifty-two patients 2-21 years of age with predialysis CKD underwent tetracycline-labeled bone biopsy. Anthropomorphic measurements and biochemical values were obtained at the time of biopsy. Results Serum phosphorus levels were increased in 4% of patients with stage 3 CKD and 43% of those with stage 4/5 CKD. Parathyroid hormone concentrations were elevated in 36% of patients with stage 2, 71% with stage 3, and 93% with stage 4/5 CKD, whereas FGF-23 values were elevated in 81% of all patients, regardless of CKD stage. Bone turnover was normal in all patients with stage 2, but was increased in 13% with stage 3 and 29% with stage 4/5 CKD. Defective mineralization was present in 29% of patients with stage 2, 42% with stage 3, and 79% with stage 4/5 CKD. Defective skeletal mineralization was associated with lower serum calcium levels and increased parathyroid hormone concentrations. Conclusions Elevated circulating FGF-23 levels and defects in skeletal mineralization early in the course of CKD suggest that factors other than the traditional markers of mineral deficiency play a crucial role in the development of renal bone disease. Clin J Am Soc Nephrol 7: 146-152, 2012. doi: 10.2215/CJN.05940611 C1 [Wesseling-Perry, Katherine; Pereira, Renata C.; Zaritsky, Joshua J.; Yadin, Ora; Gales, Barbara; Salusky, Isidro B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Los Angeles, CA 90095 USA. [Tseng, Chi-Hong; Elashoff, Robert] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biomath, Los Angeles, CA 90095 USA. [Sahney, Shobha] Loma Linda Univ, Dept Pediat, Loma Linda, CA 92350 USA. [Jueppner, Harald] Harvard Univ, Sch Med, Boston, MA USA. [Jueppner, Harald] Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA. [Jueppner, Harald] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Wesseling-Perry, K (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, A2-383 MDCC,650 Charles Young Dr, Los Angeles, CA 90095 USA. EM kwesseling@mednet.ucla.edu FU US Public Health Service [DK-67563, DK-35423, DK-51081, DK-073039, RR-00865]; Casey Lee Ball Foundation FX This work was supported in part by grants from US Public Health Service (DK-67563, DK-35423, DK-51081, DK-073039, and RR-00865) and funds from the Casey Lee Ball Foundation. NR 36 TC 47 Z9 47 U1 0 U2 14 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 JAN PY 2012 VL 7 IS 1 BP 146 EP 152 DI 10.2215/CJN.05940611 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 877RD UT WOS:000299198700023 PM 22052943 ER PT J AU Hashash, JG Zakhary, L Aoun, EG Refaat, M AF Hashash, J. G. Zakhary, L. Aoun, E. G. Refaat, M. TI Heterotopic mesenteric ossification SO COLORECTAL DISEASE LA English DT Article ID INTRAABDOMINAL MYOSITIS-OSSIFICANS C1 [Hashash, J. G.] Univ Pittsburgh, Med Ctr, Div Gastroenterol Hepatol & Nutr, PUH, Pittsburgh, PA 15213 USA. [Zakhary, L.; Refaat, M.] Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. RP Hashash, JG (reprint author), Univ Pittsburgh, Med Ctr, Div Gastroenterol Hepatol & Nutr, PUH, 200 Lothrop St,M2, Pittsburgh, PA 15213 USA. EM alhashashj@upmc.edu NR 5 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1462-8910 J9 COLORECTAL DIS JI Colorectal Dis. PD JAN PY 2012 VL 14 IS 1 BP e29 EP e30 DI 10.1111/j.1463-1318.2011.02750.x PG 2 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 857SM UT WOS:000297739500006 PM 21819525 ER PT J AU DeFronzo, RA Davidson, JA Del Prato, S AF DeFronzo, R. A. Davidson, J. A. Del Prato, S. TI The role of the kidneys in glucose homeostasis: a new path towards normalizing glycaemia SO DIABETES OBESITY & METABOLISM LA English DT Review DE clinical trials; diabetes; glucose homeostasis; glycosuria; hyperglycaemia; kidneys; renal glucose transport; SGLT2; SGLT2 inhibitors; sodium-glucose cotransporters ID TYPE-2 DIABETES-MELLITUS; SELECTIVE SGLT2 INHIBITOR; JAPANESE HEALTHY-VOLUNTEERS; RENAL PROXIMAL TUBULES; BETA-CELL DYSFUNCTION; FREE FATTY-ACIDS; INSULIN-RESISTANCE; BLOOD-GLUCOSE; DOUBLE-BLIND; BODY-WEIGHT AB The maintenance of normal glucose homeostasis requires a complex, highly integrated interaction among the liver, muscle, adipocytes, pancreas and neuroendocrine system. Recent studies have showed that the kidneys also play a central role in glucose homeostasis by reabsorbing all the filtered glucose, an adaptive mechanism that ensures sufficient energy is available during fasting periods. This mechanism becomes maladaptive in diabetes, however, as hyperglycaemia augments the expression and activity of the sodiumglucose cotransporter (SGLT) 2 in the proximal tubule of the kidney. As a result, glucose reabsorption may be increased by as much as 20% in individuals with poorly controlled diabetes. SGLT2 is a low-affinity, high-capacity glucose transport protein that reabsorbs 90% of filtered glucose, while the high-affinity, low-capacity SGLT1 transporter reabsorbs the remaining 10%. SGLT2 represents a novel target for the treatment of diabetes. In animal studies, SGLT2 inhibition reduces plasma glucose levels, resulting in improved beta-cell function and enhanced insulin sensitivity in liver and muscle. Human studies have confirmed the efficacy of SLGT2 inhibitors in improving glucose control and reducing the A1c. Because the mechanism of SGLT2 inhibition is independent of circulating insulin levels or insulin sensitivity, these agents can be combined with all other antidiabetic classes, including exogenous insulin. Although the long-term efficacy and safety of SGLT2 inhibitors remain under study, the class represents a novel therapeutic approach with potential for the treatment of both type 2 and 1 diabetes. C1 [DeFronzo, R. A.] Univ Texas Hlth Sci Ctr San Antonio, Diabet Div, Dept Med, San Antonio, TX 78229 USA. [DeFronzo, R. A.] Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 USA. [Davidson, J. A.] Univ Texas SW Med Sch, Diabet Div, Dallas, TX USA. [Del Prato, S.] Univ Pisa, Diabet Div, Pisa, Italy. RP DeFronzo, RA (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Diabet Div, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM albarado@uthscsa.edu; davidsonmd@sbcglobal.net RI Del Prato, Stefano/K-3405-2016 OI Del Prato, Stefano/0000-0002-5388-0270 FU AstraZeneca; Bayer Healthcare; Bristol-Myers Squibb; GlaxoSmithKline; Johnson Johnson; Merck Sharp Dohme; Novartis; Novo Nordisk; Pfizer Inc; Sanofi-Aventis FX The authors have drafted this article on behalf of the Worldwide Initiative for Diabetes Education (WorldWIDE). WorldWIDE had no input into writing the initial version of the manuscript or into any revisions of the manuscript. WorldWIDE is a charitable foundation that provides training, education and information to healthcare providers. The mission of WorldWIDE is to challenge and shape the future management of diabetes in order to provide optimal treatment for all patients and to enhance professional education for physicians and other diabetes professionals. Publication of the article would help to achieve this goal. WorldWIDE receives financial support from AstraZeneca, Bayer Healthcare, Bristol-Myers Squibb, GlaxoSmithKline, Johnson & Johnson, Merck Sharp &Dohme, Novartis, Novo Nordisk, Pfizer Inc and Sanofi-Aventis. The authors acknowledge the editorial assistance of IntraMed Educational Group in the styling of this manuscript. NR 76 TC 151 Z9 163 U1 8 U2 36 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1462-8902 EI 1463-1326 J9 DIABETES OBES METAB JI Diabetes Obes. Metab. PD JAN PY 2012 VL 14 IS 1 BP 5 EP 14 DI 10.1111/j.1463-1326.2011.01511.x PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 862AW UT WOS:000298063200002 PM 21955459 ER PT J AU Henry, RR Aroda, VR Mudaliar, S Garvey, WT Chou, HS Jones, MR AF Henry, R. R. Aroda, V. R. Mudaliar, S. Garvey, W. T. Chou, H. S. Jones, M. R. TI Effects of colesevelam on glucose absorption and hepatic/peripheral insulin sensitivity in patients with type 2 diabetes mellitus SO DIABETES OBESITY & METABOLISM LA English DT Article DE bile acid sequestrant; colesevelam; glucose; insulin sensitivity; type 2 diabetes mellitus ID GLYCEMIC CONTROL; SECRETION; THERAPY; HYDROCHLORIDE AB Aim: Colesevelam lowers glucose and low-density lipoprotein cholesterol levels in patients with type 2 diabetes mellitus. This study examined the mechanisms by which colesevelam might affect glucose control. Methods: In this 12-week, randomized, double-blind, placebo-controlled study, subjects with type 2 diabetes and haemoglobin A(1c)(HbA(1c)) >= 7.5% on either stable diet and exercise or sulphonylurea therapy were randomized to colesevelam 3.75 g/day (n = 16) or placebo (n = 14). Hepatic/peripheral insulin sensitivity was evaluated at baseline and at week 12 by infusion of (3)H-labelled glucose followed by a 2-step hyperinsulinemic-euglycemic clamp. Two 75-g oral glucose tolerance tests (OGTTs) were conducted at baseline, one with and one without co-administration of colesevelam. A final OGTT was conducted at week 12. HbA(1c) and fasting plasma glucose (FPG) levels were evaluated pre- and post-treatment. Results: Treatment with colesevelam, compared to placebo, had no significant effects on basal endogenous glucose output, response to insulin or on maximal steady-state glucose disposal rate. At baseline, co-administration of colesevelam with oral glucose reduced total area under the glucose curve (AUCg) but not incremental AUCg. At week 12, neither total AUCg nor incremental AUCg were changed from pre-treatment values in either group. Post-load insulin levels increased with colesevelam at 30 and 120 min, but these changes in total area under the insulin curve (AUCi) and incremental AUCi did not differ between groups. Both HbA(1c) and FPG improved with colesevelam, but treatment differences were not significant. Conclusions: Colesevelam does not affect hepatic or peripheral insulin sensitivity and does not directly affect glucose absorption. C1 [Henry, R. R.; Mudaliar, S.] VA San Diego Healthcare Syst, Sect Diabet Endocrinol & Metab, San Diego, CA 92161 USA. [Henry, R. R.; Mudaliar, S.] Univ Calif San Diego, San Diego, CA 92161 USA. [Aroda, V. R.] MedStar Hlth Res Inst, Hyattsville, MD USA. [Garvey, W. T.] Univ Alabama, Dept Nutr Sci, Birmingham, AL 35294 USA. [Garvey, W. T.] Birmingham VA Med Ctr, Birmingham, AL USA. [Chou, H. S.] Daiichi Sankyo Prod Dev, Edison, NJ USA. [Jones, M. R.] Daiichi Sankyo Inc, Parsippany, NJ USA. RP Henry, RR (reprint author), VA San Diego Healthcare Syst, Sect Diabet Endocrinol & Metab, 3350 La Jolla Village Dr,111G, San Diego, CA 92161 USA. EM rrhenry@vapop.ucsd.edu FU Daiichi Sankyo Inc.; VA San Diego Healthcare System; Department of Veteran Affairs; Veterans Medical Research Foundation; Diabetes Education and Research Center [DK 063491]; General Clinical Research Center [MO1 RR-00827]; University of Alabama Birmingham from the Center for Clinical and Translational Science [UL1 RR02577]; Diabetes Research and Training Center [P60 DK079626] FX This study was sponsored by Daiichi Sankyo Inc. Editorial assistance was provided by Karen Stauffer, PhD, of inScience Communications, a Wolters Kluwer business. This assistance was performed in compliance with Good Publication Practices outlined by the International Committee of Medical Journal Editors and was funded by Daiichi Sankyo Inc. Support is acknowledged in San Diego from the VA San Diego Healthcare System, Department of Veteran Affairs, Veterans Medical Research Foundation, the Diabetes Education and Research Center DK 063491, and the General Clinical Research Center MO1 RR-00827. Support is acknowledged from the University of Alabama Birmingham from the Center for Clinical and Translational Science (UL1 RR02577) and the Diabetes Research and Training Center (P60 DK079626). NR 13 TC 12 Z9 12 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1462-8902 J9 DIABETES OBES METAB JI Diabetes Obes. Metab. PD JAN PY 2012 VL 14 IS 1 BP 40 EP 46 DI 10.1111/j.1463-1326.2011.01486.x PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 862AW UT WOS:000298063200006 PM 21831167 ER PT J AU Fang, JL Wang, XL Liu, HS Wang, Y Zhou, KH Hong, Y Liu, J Wang, L Xue, C Song, M Liu, BY Zhu, B AF Fang, Jiliang Wang, Xiaoling Liu, Hesheng Wang, Yin Zhou, Kehua Hong, Yang Liu, Jun Wang, Lei Xue, Chao Song, Ming Liu, Baoyan Zhu, Bing TI The Limbic-Prefrontal Network Modulated by Electroacupuncture at CV4 and CV12 SO EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE LA English DT Article ID INTRINSIC FUNCTIONAL CONNECTIVITY; HUMAN BRAIN; ACUPUNCTURE STIMULATION; IMPLICATED ACUPOINTS; CINGULATE CORTEX; HEALTHY-SUBJECTS; FMRI; MRI; ACTIVATION; MECHANISM AB fMRI studies showed that acupuncture could induce hemodynamic changes in brain networks. Many of these studies focused on whether specific acupoints could activate specific brain regions and were often limited to manual acupuncture at acupoints on the limbs. In this fMRI study, we investigated acupuncture's modulation effects on brain functional networks by electroacupuncture (EA) at acupoints on the midline of abdomen. Acupoints Guanyuan (CV4) and Zhongwan (CV12) were stimulated in 21 healthy volunteers. The needling sensations, brain activation, and functional connectivity were studied. We found that the limbic-prefrontal functional network was deactivated by EA at CV4 and CV12. More importantly, the local functional connectivity was significantly changed during EA stimulation, and the change persisted during the period after the stimulation. Although minor differences existed, both acupoints similarly modulated the limbic-prefrontal functional network, which is overlapped with the functional circuits associated with emotional and cognitive regulation. C1 [Fang, Jiliang; Wang, Xiaoling; Zhou, Kehua; Hong, Yang; Wang, Lei; Xue, Chao] China Acad Chinese Med Sci, Funct Brain Imaging Lab, Dept Radiol, Guang An Men Hosp, Beijing 100053, Peoples R China. [Fang, Jiliang; Liu, Hesheng] Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Wang, Yin; Liu, Jun] China Acad Chinese Med Sci, Dept Acupuncture & Moxibust, Guang An Men Hosp, Beijing 100053, Peoples R China. [Zhou, Kehua] Daemen Coll, Dept Phys Therapy, Amherst, NY 14226 USA. [Song, Ming] Chinese Acad Sci, Inst Automat, Beijing 100190, Peoples R China. [Zhu, Bing] China Acad Chinese Med Sci, Inst Acupuncture & Moxibust, Beijing 100700, Peoples R China. RP Fang, JL (reprint author), China Acad Chinese Med Sci, Funct Brain Imaging Lab, Dept Radiol, Guang An Men Hosp, Beijing 100053, Peoples R China. EM fangjiliang@sohu.com OI Liu, Hesheng/0000-0002-7233-1509 FU National Natural Science Foundation of China [30870668]; National Institutes of Health, National Center for Complementary and Alternative Medicine (NIH/NCCAM), USA [F05 AT003022-01-04] FX This study was funded by the National Natural Science Foundation of China (Grant Code no. 30870668) and National Institutes of Health, National Center for Complementary and Alternative Medicine (NIH/NCCAM) (F05 AT003022-01-04), USA. NR 51 TC 10 Z9 11 U1 0 U2 7 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1741-427X J9 EVID-BASED COMPL ALT JI Evid.-based Complement Altern. Med. PY 2012 AR 515893 DI 10.1155/2012/515893 PG 11 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 882AG UT WOS:000299532900001 ER PT J AU Rajasuriar, R Booth, DR Gouillou, M Spelman, T James, I Solomon, A Chua, K Stewart, G Deeks, S Bangsberg, DR Muzoora, C Cameron, PU Hunt, P Martin, J Lewin, SR AF Rajasuriar, R. Booth, D. R. Gouillou, M. Spelman, T. James, I. Solomon, A. Chua, K. Stewart, G. Deeks, S. Bangsberg, D. R. Muzoora, C. Cameron, P. U. Hunt, P. Martin, J. Lewin, S. R. TI The role of SNPs in the alpha-chain of the IL-7R gene in CD4+T-cell recovery in HIV-infected African patients receiving suppressive cART SO GENES AND IMMUNITY LA English DT Article DE HIV; IL-7R alpha; T cells; cART; Caucasian; African ID POTENT ANTIRETROVIRAL THERAPY; INTERLEUKIN-7 RECEPTOR-ALPHA; T-CELL-ACTIVATION; IMMUNE ACTIVATION; MULTIPLE-SCLEROSIS; MICROBIAL TRANSLOCATION; PARKINSONS-DISEASE; VIRAL SUPPRESSION; DOWN-REGULATION; CD4 AB We previously found an association between faster CD4+ T-cell recovery in HIV-infected patients receiving combination antiretroviral therapy (cART) and interleukin-7 receptor-alpha (IL-7R alpha) haplotype-2 in a predominantly Caucasian cohort. This study aims to determine whether this association was also significant in Africans. Patients were recruited from the Uganda AIDS Rural Treatment Outcomes (UARTO) cohort (n = 352). We used survival analysis and linear mixed modelling (LMM) to determine factors associated with CD4 T-cell recovery. Eight IL-7R alpha single-nucleotide polymorphisms (SNPs) were genotyped in both Africans and Caucasians (n = 57). Soluble (s)IL-7R alpha levels were measured by ELISA. In UARTO, IL-7R alpha haplotype-2 was associated with slower CD4 T-cell recovery following cART by using survival analysis (P = 0.020) and no association was found with LMM (P = 0.958). The tagging-SNP for IL-7R alpha haplotype-2 (rs6897932) was associated with decreased sIL-7R alpha (P < 0.001). The haplotypes for the IL-7R alpha. were significantly different in Africans and Caucasians. Using IL-7R alpha genotypes we found slower CD4 T-cell recovery in UARTO patients was still associated with rs6897932 (P = 0.009) and rs3194051 was associated with faster CD4 T-cell recovery (P = 0.006). Unlike Caucasians, we did not demonstrate a significant association between IL-7R alpha haplotype 2 and faster CD4 T-cell recovery in Africans. The IL-7R alpha SNPs associated with CD4 T-cell recovery following cART differ in African and Caucasian cohorts. Genes and Immunity (2012) 13, 83-93; doi:10.1038/gene.2011.65; published online 22 September 2011 C1 [Lewin, S. R.] Monash Univ, Infect Dis Unit, Dept Med, Floor Burnet Inst 2, Melbourne, Vic 3004, Australia. [Rajasuriar, R.] Univ Malaya, Fac Med, Kuala Lumpur, Malaysia. [Booth, D. R.; Stewart, G.] Univ Sydney, Westmead Millennium Inst, Sydney, NSW 2006, Australia. [Gouillou, M.; Spelman, T.] Burnet Inst, Ctr Populat Hlth, Melbourne, Vic, Australia. [James, I.] Murdoch Univ, Ctr Clin Immunol & Biomed Stat, Perth, WA, Australia. [Deeks, S.; Hunt, P.; Martin, J.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Bangsberg, D. R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Global Hlth,Ragon Inst MGH MIT & Harvard, Boston, MA USA. [Bangsberg, D. R.; Muzoora, C.] Mbarara Univ Sci & Technol, Mbarara, Uganda. [Cameron, P. U.; Lewin, S. R.] Burnet Inst, Ctr Virol, Melbourne, Vic, Australia. [Cameron, P. U.; Lewin, S. R.] The Alfred, Infect Dis Unit, Melbourne, Vic, Australia. RP Lewin, SR (reprint author), Monash Univ, Infect Dis Unit, Dept Med, Floor Burnet Inst 2, 85 Commercial Rd, Melbourne, Vic 3004, Australia. EM Sharon.Lewin@med.monash.edu.au RI Rajasuriar, Reena/B-9569-2010 FU Malaysian Government; NHMRC; Alfred Foundation; Mark and Lisa Schwartz Family Foundation; [MH54907]; [MH K-24 87227] FX RR is a recipient of the Kings Scholarship from the Malaysian Government and acknowledges the University of Malaya and the Ministry of Higher Education. SRL is an Australian National Health and Medical Research Council (NHMRC) practitioner fellow. SRL receives funding from the NHMRC and the Alfred Foundation. The UARTO cohort was funded by MH54907 and the Mark and Lisa Schwartz Family Foundation. DRB received additional funding from MH K-24 87227. NR 62 TC 8 Z9 8 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4879 J9 GENES IMMUN JI Genes Immun. PD JAN PY 2012 VL 13 IS 1 BP 83 EP 93 DI 10.1038/gene.2011.65 PG 11 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 882XJ UT WOS:000299596900010 PM 21938017 ER PT J AU Lapointe, J Bouchard, K Patenaude, AF Maunsell, E Simard, J Dorval, M AF Lapointe, Julie Bouchard, Karine Patenaude, Andrea Farkas Maunsell, Elizabeth Simard, Jacques Dorval, Michel CA INHERIT BRCAs Res Program TI Incidence and predictors of positive and negative effects of BRCA1/2 genetic testing on familial relationships: a 3-year follow-up study SO GENETICS IN MEDICINE LA English DT Article DE BRCA genes; family communication; prospective study; psychosocial issues ID OVARIAN-CANCER FAMILIES; AT-RISK RELATIVES; HEREDITARY BREAST; PSYCHOLOGICAL IMPACT; MUTATION CARRIERS; SUSCEPTIBILITY; COMMUNICATION; INFORMATION; DISTRESS; MODEL AB Purpose: Little is known about the long-term impact of BRCA1/2 testing on the relationships between family members. We assessed the incidence of positive and negative family relationship effects of BRCA1/2 testing in the 3 years after result disclosure and identified predictors of these effects. Methods: A total of 485 women and 67 men who had undergone BRCA1/2 testing were asked 3 years later whether having been tested had improved and/or disrupted relationships with their relatives. The associations with sociodemographic, medical, and psychosocial characteristics were assessed. Results: Globally, 85.1% did not report any positive or negative effects of genetic testing on family relationships. Positive and negative effects were reported by 13.2% and 3.7% of participants, respectively. Reporting positive relationship effects was associated with older age, intolerance for uncertainty, cancer-specific distress, and more social support. Low education, positive attitude toward prophylactic mastectomy, and low social support increased the likelihood of negative effects. Conclusion: Our findings do not support the belief that family relationships are frequently disrupted by BRCA1/2 testing. Understanding that most family relationships are unchanged long term by genetic testing may help genetic service providers encourage those considering testing to overcome hesitancy related to potential difficulties of communicating results to relatives. C1 [Lapointe, Julie; Dorval, Michel] Univ Laval, Fac Pharm, Quebec City, PQ, Canada. [Lapointe, Julie; Bouchard, Karine; Maunsell, Elizabeth; Dorval, Michel] Ctr Hosp Affilie Univ Quebec, Ctr Rech FRSQ, URESP, Quebec City, PQ, Canada. [Patenaude, Andrea Farkas] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. [Patenaude, Andrea Farkas] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Maunsell, Elizabeth; Simard, Jacques] Univ Laval, Fac Med, Quebec City, PQ G1K 7P4, Canada. [Maunsell, Elizabeth; Dorval, Michel] Hop St Sacrement, Ctr Malad Sein Deschenes Fabia, Quebec City, PQ, Canada. [Simard, Jacques] CHUQ CHUL, Ctr Rech, Lab Genom Canc, Quebec City, PQ, Canada. RP Dorval, M (reprint author), Univ Laval, Fac Pharm, Quebec City, PQ, Canada. EM mdorval@uresp.ulaval.ca FU Canadian Institutes of Health Research [CRT-43822, CRN-87521, TGF-63285]; Canadian Breast Cancer Research Alliance [11383]; Fonds d'Enseignement et de Recherche de la Faculte de Pharmacie de l'Universite Laval; Fonds de la Recherche en Sante du Quebec FX The INHERIT BRCAs research program was supported by the Canadian Institutes of Health Research (grant nos. CRT-43822 and CRN-87521) and the Canadian Breast Cancer Research Alliance (grant no. 11383). Julie Lapointe is a CIHR Fellow in Psychosocial Oncology Research and Training (PORT) and is funded through a CIHR Training Grant (no. TGF-63285) and the Fonds d'Enseignement et de Recherche de la Faculte de Pharmacie de l'Universite Laval; Jacques Simard is Chairholder of the Canada Research Chair in Oncogenetics; and Michel Dorval holds a Fonds de la Recherche en Sante du Quebec Investigator Award. The authors thank all the women and their families who agreed to participate for their time and effort. They also thank Claudia Cote for data management and quality insurance and Richard Poulin for linguistic revision. Parts of these results were presented in an oral session at the 12th World Congress of Psycho-oncology of the International Psycho-oncology Society (IPOS) and the Canadian Association of Psychosocial Oncology (CAPO) (25-29 May 2010). NR 60 TC 4 Z9 4 U1 3 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD JAN PY 2012 VL 14 IS 1 BP 60 EP 68 DI 10.1038/gim.0b013e3182310a7f PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 873NI UT WOS:000298889600006 PM 22237432 ER PT J AU Salvaris, M Cinel, C Citi, L Poli, R AF Salvaris, Mathew Cinel, Caterina Citi, Luca Poli, Riccardo TI Novel Protocols for P300-Based Brain-Computer Interfaces SO IEEE TRANSACTIONS ON NEURAL SYSTEMS AND REHABILITATION ENGINEERING LA English DT Article DE Brain-computer interfaces (BCIs); BCI mouse; event-related potentials; oddball paradigm; P300 ID EVENT-RELATED POTENTIALS; P300; BCI; SPELLER AB The oddball protocol is often used in brain-computer interfaces (BCIs) to induce P300 ERPs, although, recently, some issues have been shown to detrimentally effect its performance. In this paper, we study a new periodic protocol and explore whether it can compete with the standard oddball protocol within the context of a BCI mouse. We found that the new protocol consistently and significantly outperforms the standard oddball protocol in relation to information transfer rates (33 bits/min for the former and 22 bits/min for the latter, measured at 90% accuracy) as well as P300 amplitudes. Furthermore, we performed a comparison of two periodic protocols with two less conventional oddball-like protocols that reveals the importance of the interactions between task and sequence in determining the success of a protocol. C1 [Salvaris, Mathew; Cinel, Caterina; Poli, Riccardo] Univ Essex, Brain Comp Interfaces Lab, Sch Comp Sci & Elect Engn, Colchester CO4 3SQ, Essex, England. [Citi, Luca] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02117 USA. [Citi, Luca] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. RP Salvaris, M (reprint author), Univ Essex, Brain Comp Interfaces Lab, Sch Comp Sci & Elect Engn, Colchester CO4 3SQ, Essex, England. EM mssalv@essex.ac.uk; ccinel@essex.ac.uk; lciti@neurostat.mit.edu; rpoli@essex.ac.uk RI Citi, Luca/G-2270-2011; OI Citi, Luca/0000-0001-8702-5654; Poli, Riccardo/0000-0003-4612-0780 FU U.K. Engineering and Physical Sciences Research Council [EP/F033818/1] FX Manuscript received July 22, 2011; revised October 02, 2011; accepted October 04, 2011. Date of publication December 12, 2011; date of current version January 25, 2012. This work was supported by the U.K. Engineering and Physical Sciences Research Council under Grant EP/F033818/1. NR 37 TC 13 Z9 14 U1 0 U2 7 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1534-4320 EI 1558-0210 J9 IEEE T NEUR SYS REH JI IEEE Trans. Neural Syst. Rehabil. Eng. PD JAN PY 2012 VL 20 IS 1 BP 8 EP 17 DI 10.1109/TNSRE.2011.2174463 PG 10 WC Engineering, Biomedical; Rehabilitation SC Engineering; Rehabilitation GA 881TN UT WOS:000299512300003 PM 22180513 ER PT J AU Nicolau, DP Carmeli, Y Crank, CW Goff, DA Graber, CJ Lima, ALL Goldstein, EJC AF Nicolau, David P. Carmeli, Yehuda Crank, Christopher W. Goff, Debra A. Graber, Christopher J. Lima, Ana Lucia L. Goldstein, Ellie J. C. TI Carbapenem stewardship: does ertapenem affect Pseudomonas susceptibility to other carbapenems? A review of the evidence SO INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS LA English DT Review DE Carbapenem; Ecology; Ertapenem; Pseudomonas; Stewardship; Susceptibility ID 25 HOSPITALS; AERUGINOSA; IMIPENEM; THERAPY; IMPACT AB The group 2 carbapenems (imipenem, meropenem and, more recently, doripenem) have been a mainstay of treatment for patients with serious hospital infections caused by Pseudomonas aeruginosa, Enterobacteriaceae and other difficult-to-treat Gram-negative pathogens as well as mixed aerobic/anaerobic infections. When ertapenem, a group 1 carbapenem, was introduced, questions were raised about the potential for ertapenem to select for imipenem-and meropenem-resistant Pseudomonas. Results from ten clinical studies evaluating the effect of ertapenem use on the susceptibility of Pseudomonas to carbapenems have uniformly shown that ertapenem use does not result in decreased Pseudomonas susceptibility to these antipseudomonal carbapenems. Here we review these studies evaluating the evidence of how ertapenem use affects P. aeruginosa as well as provide considerations for ertapenem use in the context of institutional stewardship initiatives. (C) 2011 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved. C1 [Nicolau, David P.] Hartford Hosp, Ctr Anti Infect Res & Dev, Hartford, CT 06102 USA. [Carmeli, Yehuda] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Div Epidemiol, IL-69978 Tel Aviv, Israel. [Crank, Christopher W.] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Goff, Debra A.] Ohio State Univ, Med Ctr, Dept Pharm, Coll Pharm, Columbus, OH 43210 USA. [Graber, Christopher J.; Goldstein, Ellie J. C.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Graber, Christopher J.] VA Greater Los Angeles Healthcare Syst, Infect Dis Sect, Los Angeles, CA USA. [Lima, Ana Lucia L.] Univ Sao Paulo, Sch Med, Hosp Clin, Inst Orthopaed & Traumatol, Sao Paulo, Brazil. [Goldstein, Ellie J. C.] St Johns Hlth Ctr, Dept Infect Dis, Santa Monica, CA USA. RP Nicolau, DP (reprint author), Hartford Hosp, Ctr Anti Infect Res & Dev, 80 Seymour St, Hartford, CT 06102 USA. EM dnicola@harthosp.org OI Lima, Ana/0000-0002-1055-0554; Lima, Ana Lucia Munhoz/0000-0002-2396-9880 FU Achaogen Inc.; Basilea Pharmaceutica; BioLine Therapeutics; Cempra Pharmaceuticals Inc.; Intercell AG; Johnson and Johnson Pharmaceuticals; Merck; Cubist; Ortho Pharmaceuticals; Schering-Plough Pharmaceuticals; Optimer Pharmaceuticals; Theravance Inc.; Pfizer Inc.; Astellas Inc.; Cerexa Inc.; Impex Pharmaceuticals; Novexel; Novartis; Clinical Microbiology Institute; Genzyme; NanoPacific Holdings Inc.; Romark Laboratories LC; ViroXis Corp.; Warner Chilcott; Avid-Biotics Corp.; GLSynthesis Inc.; Immunome Inc.; Toltec Pharma LLC.; Ortho-McNeil-Janssen; Sanofi-Aventis; Bayer-Schering Pharma; AstraZeneca; Cerexa; Forest; Johnson Johnson; Pfizer FX Competing interests: YC has served on speaker bureaus, scientific advisory boards and/or received research grants from Achaogen Inc., Basilea Pharmaceutica, BioLine Therapeutics, Cempra Pharmaceuticals Inc., Intercell AG, Johnson and Johnson Pharmaceuticals and Merck. DAG has served on speaker bureaus and/or received research grants from Cubist, Merck and Ortho Pharmaceuticals. EJCG has served on advisory boards for Merck, Optimer Pharmaceuticals, Bayer Pharmaceuticals, Theravance Inc., BioK+, ViroPharma and Kindred Healthcare Corp., on speaker bureaus for Bayer Inc., Merck, Sanofi Pasteur and Forest Labs, and has received research grants from Merck, Schering-Plough Pharmaceuticals, Optimer Pharmaceuticals, Theravance Inc., Cubist, Pfizer Inc., Astellas Inc., Cerexa Inc., Impex Pharmaceuticals, Novexel, Novartis, Clinical Microbiology Institute, Genzyme, NanoPacific Holdings Inc., Romark Laboratories LC, ViroXis Corp., Warner Chilcott, Avid-Biotics Corp., GLSynthesis Inc., Immunome Inc. and Toltec Pharma LLC. CJG has received a research grant from Merck and an unrestricted educational grant from Ortho-McNeil-Janssen, and has served on an advisory board for Pfizer. ALLL has served on speaker bureaus and/or received research grants from Merck, Sanofi-Aventis and Bayer-Schering Pharma. DPN has served on speaker bureaus and/or received research grants from AstraZeneca, Cerexa, Cubist, Forest, Johnson & Johnson, Merck and Pfizer. CWC declares no competing interests. NR 19 TC 22 Z9 25 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-8579 J9 INT J ANTIMICROB AG JI Int. J. Antimicrob. Agents PD JAN PY 2012 VL 39 IS 1 BP 11 EP 15 DI 10.1016/j.ijantimicag.2011.08.018 PG 5 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 863DO UT WOS:000298143200002 PM 22047702 ER PT J AU Farr, SA Price, TO Dominguez, LJ Motisi, A Saiano, F Niehoff, ML Morley, JE Banks, WA Ercal, N Barbagallo, M AF Farr, Susan A. Price, Tulin O. Dominguez, Ligia J. Motisi, Antonio Saiano, Filippo Niehoff, Michael L. Morley, John E. Banks, William A. Ercal, Nuran Barbagallo, Mario TI Extra Virgin Olive Oil Improves Learning and Memory in SAMP8 Mice SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Extra virgin olive oil; learning; memory; object recognition; oxidative stress; SAMP8; T-maze ID SENESCENCE-ACCELERATED MICE; ALPHA-LIPOIC ACID; ALZHEIMERS-DISEASE; MEDITERRANEAN DIET; AMYLOID-BETA; GLUTATHIONE DISULFIDE; SENSORY PROPERTIES; OXIDATIVE STRESS; FATTY-ACIDS; MOUSE MODEL AB Polyphenols are potent antioxidants found in extra virgin olive oil (EVOO); antioxidants have been shown to reverse age-and disease-related learning and memory deficits. We examined the effects of EVOO on learning and memory in SAMP8 mice, an age-related learning/memory impairment model associated with increased amyloid-beta protein and brain oxidative damage. We administered EVOO, coconut oil, or butter to 11 month old SAMP8 mice for 6 weeks. Mice were tested in T-maze foot shock avoidance and one-trial novel object recognition with a 24 h delay. Mice which received EVOO had improved acquisition in the T-maze and spent more time with the novel object in one-trial novel object recognition versus mice which received coconut oil or butter. Mice that received EVOO had improve T-maze retention compared to the mice that received butter. EVOO increased brain glutathione levels suggesting reduced oxidative stress as a possible mechanism. These effects plus increased glutathione reductase activity, superoxide dismutase activity, and decreased tissue levels of 4-hydroxynoneal and 3-nitrotyrosine were enhanced with enriched EVOO (3x and 5x polyphenols concentration). Our findings suggest that EVOO has beneficial effects on learning and memory deficits found in aging and diseases, such as those related to the overproduction of amyloid-beta protein, by reversing oxidative damage in the brain, effects that are augmented with increasing concentrations of polyphenols in EVOO. C1 [Farr, Susan A.] St Louis Univ, Sch Med, VA Med Ctr, Dept Internal Med,Div Geriatr Med, St Louis, MO 63106 USA. [Farr, Susan A.; Morley, John E.] VA Med Ctr, GRECC, St Louis, MO USA. [Price, Tulin O.] St Louis Univ, Sch Med, Div Endocrinol, Dept Internal Med, St Louis, MO 63106 USA. [Dominguez, Ligia J.; Motisi, Antonio; Barbagallo, Mario] Univ Palermo, Div Geriatr Med, Palermo, Italy. [Saiano, Filippo] Univ Palermo, Fac Agron, Dept DEMETRA, Palermo, Italy. Univ Palermo, Dept Agroenvironm Syst, Palermo, Italy. [Banks, William A.] Vet Affairs Puget Sound Hlth Care Syst, GRECC, Seattle, WA USA. [Banks, William A.] Univ Washington, Sch Med, Div Gerontol & Geriatr Med, Dept Internal Med, Seattle, WA USA. [Ercal, Nuran] Missouri Univ Sci & Technol, Dept Chem, Rolla, MO USA. RP Farr, SA (reprint author), St Louis Univ, Sch Med, VA Med Ctr, Dept Internal Med,Div Geriatr Med, 915 N Grand Blvd,151-JC, St Louis, MO 63106 USA. EM farrsa@slu.edu OI BARBAGALLO, MARIO/0000-0002-1349-6530; dominguez, ligia j/0000-0003-1466-8610 FU VA Medical Center, St. Louis, MO FX This work was supported by VA Medical Center, St. Louis, MO. NR 54 TC 51 Z9 52 U1 2 U2 14 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2012 VL 28 IS 1 BP 81 EP 92 DI 10.3233/JAD-2011-110662 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 879EG UT WOS:000299311900007 PM 21955812 ER PT J AU Baker, LD Bayer-Carter, JL Skinner, J Montine, TJ Cholerton, BA Callaghan, M Leverenz, JB Walter, BK Tsai, E Postupna, N Lampe, J Craft, S AF Baker, Laura D. Bayer-Carter, Jennifer L. Skinner, Jeannine Montine, Thomas J. Cholerton, Brenna A. Callaghan, Maureen Leverenz, James B. Walter, Brooke K. Tsai, Elaine Postupna, Nadia Lampe, Johanna Craft, Suzanne TI High-Intensity Physical Activity Modulates Diet Effects on Cerebrospinal Amyloid-beta Levels in Normal Aging and Mild Cognitive Impairment SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Aging; Alzheimer's disease; amyloid; biomarker; brain; diet; exercise; interleukin; mild cognitive impairment; tau ID TRANSGENIC MOUSE MODEL; ALZHEIMERS-DISEASE; OLDER-ADULTS; CALORIC RESTRICTION; VOLUNTARY EXERCISE; MEDITERRANEAN DIET; RISK; BRAIN; MICE; AGE AB We previously showed that amyloid-beta 1-42 (A beta(42)) levels in cerebrospinal fluid (CSF) were markedly altered in response to a 4-week dietary intervention in normal aging and mild cognitive impairment (MCI). Here, we re-examined the data to assess whether diet-induced effects on CSF A beta(42) were modulated by high intensity physical activity (hi-PA). Normal older adults (n = 18, mean age = 68.6 +/- 7.4 y) and adults with amnestic MCI (n = 23, mean age = 68.0 +/- 6.5 y) received a low saturated fat/low glycemic index (LOW) diet or a high saturated fat/high glycemic index (HIGH) diet, and CSF levels of A beta(42), tau, and IL-8 were measured at baseline and week 4. Pre-study activity levels were assessed using a 7-d questionnaire, and weekly duration of hi-PA was quantified. At baseline, increased hi-PA in normals predicted lower CSF levels of tau (r = -0.54, p = 0.020) and IL-8 (r = -0.70, p = 0.025). Diet-induced effects on CSF A beta(42) during the intervention study were modulated by hi-PA, and the nature of this effect differed for normals and MCI (ANOVA, p = 0.039). That is, for normal adults, increased hi-PA attenuated the effects of the HIGH diet on CSF A beta(42) whereas in MCI, increased hi-PA potentiated the effects of the LOW diet. Our results suggest that normal adults who engage in hi-PA are less vulnerable to the pathological effects of an unhealthy diet, while in MCI, the benefit of a healthy diet on A beta modulation is greatest when paired with hi-PA. Exercise may thus interact with diet to alter pathological processes that ultimately modify risk of Alzheimer's disease. C1 [Baker, Laura D.; Bayer-Carter, Jennifer L.; Skinner, Jeannine; Cholerton, Brenna A.; Callaghan, Maureen; Craft, Suzanne] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Leverenz, James B.] Vet Affairs Puget Sound Hlth Care Syst, Mental Illness & Parkinson Dis Res Ctr, Seattle, WA USA. [Baker, Laura D.; Skinner, Jeannine; Cholerton, Brenna A.; Walter, Brooke K.; Tsai, Elaine; Craft, Suzanne] Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Seattle, WA USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Montine, Thomas J.; Postupna, Nadia] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. [Leverenz, James B.; Walter, Brooke K.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98195 USA. [Lampe, Johanna] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Leverenz, James B.] Vet Affairs Puget Sound Hlth Care Syst, Mental Illness & Parkinson Educ Ctr, Seattle, WA USA. [Leverenz, James B.] Vet Affairs Puget Sound Hlth Care Syst, Mental Illness & Parkinson Clin Ctr, Seattle, WA USA. RP Baker, LD (reprint author), S-182-GRECC,VAPSHCS 1660 S Columbian Way, Seattle, WA 98108 USA. EM ldbaker@uw.edu FU NIA [R37 AG-10880, P50 AG05136, 5T32 AG000258]; Nancy and Buster Alvord Endowment; Office of Research and Development Medical Research Service; Geriatric Research, Education and Clinical Center of the Department of Veterans Affairs FX This research was supported by NIA R37 AG-10880 (Craft), NIA P50 AG05136 Project 1 (Montine), NIA 5T32 AG000258 (Postupna), the Nancy and Buster Alvord Endowment, and the Office of Research and Development Medical Research Service and the Geriatric Research, Education and Clinical Center of the Department of Veterans Affairs. Dr. Baker had full access to all data and takes responsibility for its integrity and the accuracy of the data analysis which was conducted without input from the funding agencies. NR 60 TC 13 Z9 13 U1 3 U2 24 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2012 VL 28 IS 1 BP 137 EP 146 DI 10.3233/JAD-2011-111076 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 879EG UT WOS:000299311900012 PM 21971406 ER PT J AU Nielson, CM Zmuda, JM Carlos, AS Wagoner, WJ Larson, EA Orwoll, ES Klein, RF AF Nielson, Carrie M. Zmuda, Joseph M. Carlos, Amy S. Wagoner, Wendy J. Larson, Emily A. Orwoll, Eric S. Klein, Robert F. TI Rare coding variants in ALPL are associated with low serum alkaline phosphatase and low bone mineral density SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE OSTEOPOROSIS; HEREDITY; GENETICS; ALKALINE PHOSPHATASE ID QUANTITATIVE TRAIT LOCI; GENOME-WIDE ASSOCIATION; INFANTILE HYPOPHOSPHATASIA; OSTEOPOROTIC FRACTURES; LINKAGE ANALYSIS; INBRED STRAINS; PLASMA-LEVELS; MICE; C57BL/6J; GENES AB Alkaline phosphatase (ALP) plays an essential role in the regulation of tissue mineralization, and its activity is highly heritable. Guided by genetic associations discovered in a murine model, we hypothesized a role for rare coding variants in determining serum ALP level and bone mineral density (BMD) in humans. We sequenced the coding regions of the ALP gene (ALPL) in men with low and normal serum ALP activity levels. Single-nucleotide ALPL variants, including 19 rare nonsynonymous variants (minor allele frequency <1%), were much more frequent among the low ALP group (33.8%) than the normal group (1.4%, p=1 x 10(-11)). Within the low ALP group, men with a rare, nonsynonymous variant had 11.2% lower mean serum ALP (p=3.9x 10(-4)), 6.7% lower BMD (p=0.03), and 11.1% higher serum phosphate (p=0.002) than those without. In contrast, common nonsynonymous variants had no association with serum ALP, phosphate, or BMD. Multiple rare ALPL coding variants are present in the general population, and nonsynonymous coding variants may be responsible for heritable differences in mineralization and thus BMD. (C) 2012 American Society for Bone and Mineral Research C1 [Nielson, Carrie M.; Carlos, Amy S.; Wagoner, Wendy J.; Larson, Emily A.; Orwoll, Eric S.; Klein, Robert F.] Oregon Hlth & Sci Univ, Bone & Mineral Res Unit, Dept Med, Portland, OR 97239 USA. [Zmuda, Joseph M.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Zmuda, Joseph M.] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA USA. [Klein, Robert F.] Portland VA Med Ctr, Portland, OR USA. RP Klein, RF (reprint author), Oregon Hlth & Sci Univ, Bone & Mineral Unit CR113, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM Kleinro@ohsu.edu OI Orwoll, Eric/0000-0002-8520-7355 FU National Institutes of Health; National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) [AR44659, R01-AR051124]; National Institute on Aging (NIA) [R01-AG033618]; National Center for Research Resources (NCRR); NIH Roadmap for Medical Research [U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01 AG18197, U01-AG027810, UL1 RR024140]; Office of Research on Women's Health; National Institute of Child Health and Human Development, Building Interdisciplinary Research Careers in Women's Health (BIRCWH) [HD043488-08]; VA Medical Research Service FX The Osteoporotic Fractures in Men (MrOS) Study is supported by National Institutes of Health funding; the following institutes provide support: the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Institute on Aging (NIA), the National Center for Research Resources (NCRR), and NIH Roadmap for Medical Research under the following grant numbers: U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01 AG18197, U01-AG027810, and UL1 RR024140. Dr. Nielson is also supported by the Office of Research on Women's Health and the National Institute of Child Health and Human Development, Building Interdisciplinary Research Careers in Women's Health (BIRCWH) grant number HD043488-08. Dr. Klein's research effort is supported by the National Institute of Arthritis, Musculoskeletal and Skin Diseases (AR44659) and the VA Medical Research Service. Dr. Zmuda's research effort is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01-AR051124) and by the National Institute on Aging (R01-AG033618). NR 61 TC 10 Z9 10 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD JAN PY 2012 VL 27 IS 1 BP 93 EP 103 DI 10.1002/jbmr.527 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 867UA UT WOS:000298479000009 PM 21956185 ER PT J AU Greendale, GA Sowers, M Han, WJ Huang, MH Finkelstein, JS Crandall, CJ Lee, JS Karlamangla, AS AF Greendale, Gail A. Sowers, MaryFran Han, Weijuan Huang, Mei-Hua Finkelstein, Joel S. Crandall, Carolyn J. Lee, Jennifer S. Karlamangla, Arun S. TI Bone mineral density loss in relation to the final menstrual period in a multiethnic cohort: Results from the Study of Women's Health Across the Nation (SWAN) SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE MENOPAUSE; PERIMENOPAUSE; BONE MINERAL DENSITY; ETHNIC DIFFERENCES; LONGITUDINAL COHORT ID HIP FRACTURE INCIDENCE; ESTROGEN DEFICIENCY; SEX-DIFFERENCES; SKELETAL SITES; UNITARY MODEL; WHITE WOMEN; OSTEOPOROSIS; MENOPAUSE; GEOMETRY; RISK AB The objective of this study was to describe the time of onset and offset of bone mineral density (BMD) loss relative to the date of the final menstrual period (FMP); the rate and amount of BMD decline during the 5 years before and the 5 years after the FMP; and the independent associations between age at FMP, body mass index (BMI), and race/ethnicity with rates of BMD loss during this time interval. The sample included 242 African American, 384 white, 117 Chinese, and 119 Japanese women, pre- or early perimenopausal at baseline, who had experienced their FMP and for whom an FMP date could be determined. Loess-smoothed curves showed that BMD loss began 1 year before the FMP and decelerated (but did not cease) 2 years after the FMP, at both the lumbar spine (LS) and femoral neck (FN) sites. Piecewise, linear, mixed-effects regression models demonstrated that during the 10-year observation period, at each bone site, the rates and cumulative amounts of bone loss were greatest from 1 year before through 2 years after the FMP, termed the transmenopause. Postmenopausal loss rates, those occurring between 2 and 5 years after the FMP, were less than those observed during transmenopause. Cumulative, 10-year LS BMD loss was 10.6%; 7.38% was lost during the transmenopause. Cumulative FN loss was 9.1%; 5.8% was lost during the transmenopause. Greater BMI and African American heritage were related to slower loss rates, whereas the opposite was true of Japanese and Chinese ancestry. (C) 2012 American Society for Bone and Mineral Research C1 [Greendale, Gail A.; Han, Weijuan; Huang, Mei-Hua; Karlamangla, Arun S.] Univ Calif Los Angeles, David Geffen Sch Med, Div Geriatr, Los Angeles, CA 90095 USA. [Sowers, MaryFran] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Finkelstein, Joel S.] Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. [Crandall, Carolyn J.] Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med, Los Angeles, CA 90095 USA. [Lee, Jennifer S.] Univ Calif Davis, Dept Internal Med, Div Endocrinol, Davis, CA 95616 USA. RP Greendale, GA (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Geriatr, 10945 Le Conte Ave,Suite 2339, Los Angeles, CA 90095 USA. EM ggreenda@mednet.ucla.edu FU National Institutes of Health (NIH); DHHS through National Institute on Aging (NIA); National Institute of Nursing Research (NINR); NIH Office of Research on Women's Health (ORWH) [NR004061, AG012505, AG012535, AG012531, AG012539, AG012546, AG012553, AG012554, AG012495] FX The Study of Women's Health Across the Nation (SWAN) has grant support from the National Institutes of Health (NIH), DHHS, through the National Institute on Aging (NIA), the National Institute of Nursing Research (NINR), and the NIH Office of Research on Women's Health (ORWH) (grants NR004061; AG012505, AG012535, AG012531, AG012539, AG012546, AG012553, AG012554, AG012495). The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the NIA, NINR, ORWH, or the NIH. NR 21 TC 42 Z9 44 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD JAN PY 2012 VL 27 IS 1 BP 111 EP 118 DI 10.1002/jbmr.534 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 867UA UT WOS:000298479000011 PM 21976317 ER PT J AU Yu, EW Thomas, BJ Brown, JK Finkelstein, JS AF Yu, Elaine W. Thomas, Bijoy J. Brown, J. Keenan Finkelstein, Joel S. TI Simulated increases in body fat and errors in bone mineral density measurements by DXA and QCT SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE BONE DENSITOMETRY; BONE QCT; BODY COMPOSITION ID X-RAY ABSORPTIOMETRY; COMPUTED-TOMOGRAPHY QCT; GASTRIC BYPASS-SURGERY; WEIGHT-LOSS; ACCURATE ASSESSMENT; MORBID-OBESITY; SOFT-TISSUE; SPINE; PRECISION; MASS AB Major alterations in body composition, such as with obesity and weight loss, have complex effects on the measurement of bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA). The effects of altered body fat on quantitative computed tomography (QCT) measurements are unknown. We scanned a spine phantom by DXA and QCT before and after surrounding with sequential fat layers (up to 12kg). In addition, we measured lumbar spine and proximal femur BMD by DXA and trabecular spine BMD by QCT in 13 adult volunteers before and after a simulated 7.5kg increase in body fat. With the spine phantom, DXA BMD increased linearly with sequential fat layering at the normal (P<0.01) and osteopenic (p<0.01) levels, but QCT BMD did not change significantly. In humans, fat layering significantly reduced DXA spine BMD values (mean +/- SD: -2.2 +/- 3.7%, p=0.05) and increased the variability of measurements. In contrast, fat layering increased QCT spine BMD in humans (mean +/- SD: 1.5 +/- 2.5%, p=0.05). Fat layering did not change mean DXA BMD of the femoral neck or total hip in humans significantly, but measurements became less precise. Associations between baseline and fat-simulation scans were stronger for QCT of the spine (r2=0.97) than for DXA of the spine (r2=0.87), total hip (r2=0.80), or femoral neck (r2=0.75). Bland-Altman plots revealed that fat-associated errors were greater for DXA spine and hip BMD than for QCT trabecular spine BMD. Fat layering introduces error and decreases the reproducibility of DXA spine and hip BMD measurements in human volunteers. Although overlying fat also affects QCT BMD measurements, the error is smaller and more uniform than with DXA BMD. Caution must be used when interpreting BMD changes in humans whose body composition is changing. (C) 2012 American Society for Bone and Mineral Research C1 [Yu, Elaine W.; Finkelstein, Joel S.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Thomas, Bijoy J.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Brown, J. Keenan] Mindways Software, Austin, TX USA. RP Yu, EW (reprint author), MGH Endocrine Unit, 50 Blossom St,Their 1051, Boston, MA 02114 USA. EM ewyu@partners.org FU NIDDK NIH HHS [T32 DK007028, K23 DK093713] NR 27 TC 57 Z9 58 U1 0 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD JAN PY 2012 VL 27 IS 1 BP 119 EP 124 DI 10.1002/jbmr.506 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 867UA UT WOS:000298479000012 PM 21915902 ER PT J AU Cooper, LT Mather, PJ Alexis, JD Pauly, DF Torre-Amione, G Wittstein, IS Dec, GW Zucker, M Narula, J Kip, K McNamara, DM AF Cooper, Leslie T. Mather, Paul J. Alexis, Jeffrey D. Pauly, Daniel F. Torre-Amione, Guillermo Wittstein, Ilan S. Dec, G. William Zucker, Mark Narula, Jagat Kip, Kevin McNamara, Dennis M. CA IMAC2 Investigators TI Myocardial Recovery in Peripartum Cardiomyopathy: Prospective Comparison With Recent Onset Cardiomyopathy in Men and Nonperipartum Women SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE Heart failure; pregnancy; dilated cardiomyopathy; myocardial recovery; outcomes ID POSTPARTUM CARDIOMYOPATHY; EUROPEAN-SOCIETY; PROLACTIN; HEART; BROMOCRIPTINE; ASSOCIATION; MANAGEMENT; CARDIOLOGY; STATEMENT; DIAGNOSIS AB Background: Whether myocardial recovery occurs more frequently in peripartum cardiomyopathy (PPCM) than in recent onset cardiomyopathies in men and nonperipartum women has not been prospectively evaluated. This was examined through an analysis of outcomes in the Intervention in Myocarditis and Acute Cardiomyopathy 2 (IMAC2) registry. Methods and Results: IMAC2 enrolled 373 subjects with recent onset nonischemic dilated cardiomyopathy. Left ventricular ejection fraction (LVEF) was assessed at entry and 6 months, and subjects followed for up to 4 years. Myocardial recovery was compared between men (group 1), nonperipartum women (group 2) and subjects with PPCM (group 3). The cohort included 230 subjects in group 1, 104 in group 2, and 39 in group 3. The mean LVEF at baseline in groups 1, 2, and 3 was 0.23 +/- 0.08, 0.24 +/- 0.08, and 0.27 +/- 0.07 (P = .04), and at 6 months was 0.39 +/- 0.12, 0.42 +/- 0.11, and 0.45 +/- 0.14 (P = .007). Subjects in group 3 had a much greater likelihood of achieving an LVEF >0.50 at 6 months than groups 1 or 2 (19 %, 34%, and 48% respectively, P = .002). Conclusions: Prospective evaluation confirms myocardial recovery is greatest in women with PPCM, poorest in men, and intermediate in nonperipartum women. On contemporary therapy, nearly half of women with PPCM normalize cardiac function by 6 months. (J Cardiac Fail 2012;18:28-33) C1 [Cooper, Leslie T.] Mayo Clin, Rochester, MN USA. [Mather, Paul J.] Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA. [Alexis, Jeffrey D.] Univ Rochester, Rochester, NY USA. [Pauly, Daniel F.] Univ Florida, Coll Med, Gainesville, FL USA. [Torre-Amione, Guillermo] Methodist Hosp, Houston, TX 77030 USA. [Wittstein, Ilan S.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Dec, G. William] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Zucker, Mark] Beth Israel Hosp, Newark, NJ USA. [Narula, Jagat] Mt Sinai Sch Med, New York, NY USA. [Kip, Kevin] Univ S Florida, Tampa, FL USA. [McNamara, Dennis M.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. RP McNamara, DM (reprint author), Cardiovasc Inst, 200 Lothrop St, Pittsburgh, PA 15213 USA. EM mcnamaradm@upmc.edu FU NIH [HL75038, HL086918, HL102429, HL69912] FX Supported by NIH contracts HL75038, HL086918, HL102429, HL69912. NR 23 TC 26 Z9 27 U1 0 U2 5 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD JAN PY 2012 VL 18 IS 1 BP 28 EP 33 DI 10.1016/j.cardfail.2011.09.009 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 878GE UT WOS:000299242700004 PM 22196838 ER PT J AU Barber, JP Barrett, MS Gallop, R Rynn, MA Rickels, K AF Barber, Jacques P. Barrett, Marna S. Gallop, Robert Rynn, Moira A. Rickels, Karl TI Short-Term Dynamic Psychotherapy Versus Pharmacotherapy for Major Depressive Disorder: A Randomized, Placebo-Controlled Trial SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID COLLABORATIVE RESEARCH-PROGRAM; MENTAL-HEALTH TREATMENT; STAR-ASTERISK-D; CLINICAL-TRIALS; COGNITIVE THERAPY; PSYCHODYNAMIC PSYCHOTHERAPY; NATIONAL-INSTITUTE; RATING-SCALE; CARE; CITALOPRAM AB Objective: To determine whether supportive-expressive psychotherapy (SET), a form of dynamic psychotherapy, and pharmacotherapy + clinical management (MED) for major depressive disorder (MDD) are more effective than pill-placebo + clinical management (PBO). Method:This National Institute of Mental Health (NIMH)-sponsored randomized controlled trial was conducted (from November 2001 through June 2007) at the University of Pennsylvania Medical School. The sample included 156 patients diagnosed with MDD (DSM-IV) and having a 17-item Hamilton Rating Scale for Depression (HRSD17) score >= 14 for at least 2 consecutive weeks. This was an underserved sample in which 41% were male, 52% were self-designated minorities, and 76% had an annual income under $30,000. Treatment lasted 16 weeks. Medication patients not responsive by week 8 (maximum dose 200 mg/d of sertraline) were switched to venlafaxine (maximum dose 375 mg/d). Nonresponsive placebo patients at week 8 were switched to a different placebo. Results: Patients' depression improved over the 16 weeks (P<.0001), with no between-group differences (P=.95), even among severely (HRSD17 score >= 20) depressed patients (P=.45). Response rates did not differ between groups (P=.73). Gender and minority status moderated outcome (P=.014), with psychotherapy more efficacious for minority men than MED (P=.027, Cohen d=1.02) and PBO (P=.019, d=1.09). PBO was more efficacious for white men than MED (P=.03, d=0.62) and SET (P=.003, d=1.07). For white women, MED (P=.005, d=0.77) and SET (P=.033, d=0.71) were more efficacious than placebo. No differences among treatments were found for minority women. Conclusions:This trial of urban MDD patients failed to confirm that either active treatment was better than placebo. Minority status and gender had significant and differential effects on outcome that warrant replication in future studies. C1 [Barber, Jacques P.; Barrett, Marna S.; Gallop, Robert] Univ Penn, Sch Med, Dept Psychiat, Ctr Psychotherapy Res, Philadelphia, PA 19104 USA. [Barber, Jacques P.] Philadelphia VA Med Ctr, CESATE, Philadelphia, PA USA. [Barber, Jacques P.] Philadelphia VA Med Ctr, MIRECC, Philadelphia, PA USA. [Barrett, Marna S.; Rynn, Moira A.; Rickels, Karl] Univ Penn, Sch Med, Dept Psychiat, Mood & Anxiety Disorders Sect, Philadelphia, PA 19104 USA. [Rynn, Moira A.] Columbia Univ, Div Child & Adolescent Psychiat, New York, NY USA. [Rynn, Moira A.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. RP Barber, JP (reprint author), Adelphi Univ, Hy Weinberg Ctr, Derner Inst Adv Psychol Studies, Rm 301,1 South Ave,POB 701, Garden City, NY 11530 USA. EM jbarber@adelphi.edu FU National Institute of Mental Health (NIMH) [R01 MH 061410]; National Institute on Drug Abuse (NIDA); Guilford Press; Basic Books; Cambridge University Press; Boehringer Ingelheim Pharmaceuticals; Wyeth Pharmaceuticals; Neuropharm; Astra Zeneca; Pfizer Pharmaceuticals; Eli Lilly and Company; Forest Laboratories; Bristol-Myers Squibb; Organon; Cephalon; Johnson & Johnson Pharmaceutical Research Development; AstraZeneca; Bristol-Meyers Squibb; Epix Pharmaceuticals; Genaissance Pharmaceuticals (PGxHealth); GlaxoSmithkline; Merck Co; Pamlab; Pfizer; Somerset Pharmaceuticals; Wyeth Laboratory; Pfizer Corp. FX Dr Barber has received funding from the National Institute of Mental Health (NIMH) and the National Institute on Drug Abuse (NIDA); authors' fees from Guilford Press, Basic Books, and Cambridge University Press; and honoraria from Lundbeck. Dr Rynn has received research support from NIMH, Boehringer Ingelheim Pharmaceuticals, Wyeth Pharmaceuticals, Neuropharm, Astra Zeneca, Pfizer Pharmaceuticals, Eli Lilly and Company, Forest Laboratories, Bristol-Myers Squibb, Organon, Cephalon, and Johnson & Johnson Pharmaceutical Research & Development; has served as a consultant for Wyeth Pharmaceuticals, Pfizer Pharmaceuticals, Astra Zeneca, Pharmastar, Eli Lilly and Company, and Pepper Hamilton; has been on speakers' bureaus for Pfizer Pharmaceuticals and Wyeth Pharmaceuticals; has received royalties from APPI Press; and has received honoraria from Post Graduate Institute for Medicine, American Psychiatric Association, American Education Services, Oxford University Press, Case Western Reserve University, and Pennsylvania Medical Society. Please note that during this time period there are Grand Rounds for which she does not have the documentation of the funding source. Dr Rickels (from 2002 to 2009) has received honoraria and served as a consultant or on advisory boards to Cephalon, DOV Pharmaceuticals, Eli Lilly & Co, Hoffman-La Roche, Jazz Pharmaceuticals, Johnson & Johnson, Novartis Pharmaceuticals, Pfizer Inc, Epix (PreDix) Pharmaceuticals, PGxHealth, and Sanofi-Synthelabo Research; and has received research grants (issued to the University of Pennsylvania) from AstraZeneca, Bristol-Meyers Squibb, Cephalon, Epix Pharmaceuticals, Genaissance Pharmaceuticals (PGxHealth), GlaxoSmithkline, Merck & Co, NIMH, Pamlab, Pfizer, Somerset Pharmaceuticals, and Wyeth Laboratory. Drs Barrett and Gallops have no potential conflict of interest to disclose.; Written with support from NIMH grant R01 MH 061410 (Jacques P. Barber, PI). The sertraline and placebo pills were provided by a grant from Pfizer Corp. Neither sponsor had any role in the study besides funding the study (NIMH) or supplying the sertraline and placebo pills (Pfizer). NR 47 TC 57 Z9 57 U1 1 U2 19 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 JAN PY 2012 VL 73 IS 1 BP 66 EP 73 DI 10.4088/JCP.11m06831 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 880LK UT WOS:000299408400010 PM 22152401 ER PT J AU Sarris, J Mischoulon, D Schweitzer, I AF Sarris, Jerome Mischoulon, David Schweitzer, Isaac TI Omega-3 for Bipolar Disorder: Meta-Analyses of Use in Mania and Bipolar Depression SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID FATTY-ACID SUPPLEMENTATION; PLACEBO-CONTROLLED TRIALS; DOUBLE-BLIND; RATING-SCALE; OPEN-LABEL; MOOD DISORDERS; OMEGA-3-FATTY-ACIDS; EFFICACY; BRAIN; ASSOCIATION AB Objective: Studies using augmentation of pharmacotherapies with omega-3 in bipolar disorder have been conducted; however, to date a specific meta-analysis in this area has not been published. Thus, we present the significant findings from meta-analyses of omega-3 in the treatment of bipolar depression and bipolar mania. Data Sources: Pub Med, CINAHL, Web of Science, and Cochrane Library databases were searched for clinical trials up to September 1, 2010, using the search terms bipolar disorder OR bipolar depression OR bipolar mania OR mania OR hypomania OR cyclothymia with the search terms omega 3 OR essential fatty acids OR polyunsaturated fatty acids OR DHA OR EPA OR fish oil OR flax oil. Clinical trial registries and gray literature (published or unpublished data not readily accessible via main databases) were also searched. Data Selection: The analysis included randomized controlled studies 4 weeks or longer, with a sample size >10, written in English, using omega-3 for diagnosed bipolar depression or mania. No criteria were set for age, gender, or ethnicity. Data Extraction: A random-effects model was used. The model analyzed the standard mean difference between treatment and placebo between baseline and endpoint, combining the effect size (Hedges g) data. Funnel plot and heterogeneity analyses (I-2) were also performed. Data Synthesis:The findings of 5 pooled datasets (n=291) on the outcome of bipolar depression revealed a significant effect in favor of omega-3 (P=.029), with a moderate effect size of 0.34. On the outcome of mania, 5 pooled datasets (n=291) revealed a nonsignificant effect in favor of omega-3 (P=.099), with an effect size of 0.20. Minor heterogeneity between studies on the outcome of bipolar depression was found (I-2=30%; P=.213), which was not present on the outcome of bipolar mania (I-2=0%; P=.98). Funnel plot symmetry suggested no significant likelihood of publication bias. Meta-regression analysis between sample size and effect size, however, revealed that studies with smaller sample sizes had larger effect sizes (P=.05). Conclusions: The meta-analytic findings provide strong evidence that bipolar depressive symptoms may be improved by adjunctive use of omega-3. The evidence, however, does not support its adjunctive use in attenuating mania. J an Psychiatry 2012;73(1):81-86 (C) Copyright 2011 Physicians Postgraduate Press, Inc. C1 [Sarris, Jerome] Univ Melbourne, Melbourne Clin, Dept Psychiat, Fac Med, Richmond, Vic 3121, Australia. [Sarris, Jerome] Swinburne Univ Technol, Ctr Human Psychopharmacol, Melbourne, Vic, Australia. [Mischoulon, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, Boston, MA USA. RP Sarris, J (reprint author), Univ Melbourne, Melbourne Clin, Dept Psychiat, Fac Med, 2 Salisbury St, Richmond, Vic 3121, Australia. EM jsarris@unimelb.edu.au FU Integria Health and Society for Medicinal Plant; Natural Product Research; Nordic Naturals; Fisher Wallace Laboratories; Ganeden; MGH Psychiatry Academy; AstraZeneca; Eli Lilly; Lundbeck; Wyeth; Pfizer; Bristol-Myers Squibb FX Dr Sarris has received travel grant funding from Integria Health and Society for Medicinal Plant and Natural Product Research and speaking honoraria Dr Mischoulon has received research support from Nordic Naturals, Fisher Wallace Laboratories, and Ganeden; been a consultant to Bristol-Myers Squibb; has received writing honoraria from Pamlab; has received royalties from Back Bay Scientific for PMS Escape and from Lippincott Wilkins & Williams for the textbook Natural Medications for Psychiatric Disorders: Considering the Alternatives; and has received honoraria from Reed Medical Education (which is a logistics collaborator for the MGH Psychiatry Academy). The education programs conducted by the MGH Psychiatry Academy were supported through independent medical education 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 Web site, www.mghcme.org. Dr Schweitzer has received speaking honoraria from AstraZeneca, Eli Lilly, Lundbeck, Wyeth, Pfizer, Servier, and Janssen-Cilag; consultancy fees from AstraZeneca, Eli Lilly, Lundbeck, Wyeth, and Pfizer; and educational or research grants, sponsorships, or donations from Wyeth, Lundbeck, and Bristol-Myers Squibb. NR 42 TC 76 Z9 77 U1 1 U2 22 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 JAN PY 2012 VL 73 IS 1 BP 81 EP 86 DI 10.4088/JCP.10r06710 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 880LK UT WOS:000299408400012 PM 21903025 ER PT J AU Weiner, E Ball, MP Buchholz, AS Gold, JM Evins, AE McMahon, RP Buchanan, RW AF Weiner, Elaine Ball, M. Patricia Buchholz, Alison S. Gold, James M. Evins, A. Eden McMahon, Robert P. Buchanan, Robert W. TI Bupropion Sustained Release Added to Group Support for Smoking Cessation in Schizophrenia: A New Randomized Trial and a Meta-Analysis SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID PLACEBO-CONTROLLED TRIAL; MENTAL-HEALTH; DOUBLE-BLIND; NICOTINE; CLOZAPINE; PHARMACOTHERAPIES; INTERVENTION; DISORDERS; ADDICTION; BEHAVIORS AB Objective: To clarify the efficacy and tolerability of bupropion sustained release (SR) for the treatment of cigarette smoking in people with schizophrenia. Method:The first study is a double-blind, placebo-controlled clinical trial with 32 outpatients from the Maryland Psychiatric Research Center. From May 2003 to July 2007, clinically stable people with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder who smoked at least 10 cigarettes per day and who were interested in quitting smoking or cutting down were recruited for participation. All participated in a 9-week support group and were randomly assigned to receive 12 weeks of bupropion SR or placebo. The primary outcome measure was 4 weeks' sustained abstinence over the last 4 study weeks. Secondary outcome measures included decrease in smoking behavior and change in symptoms, neuropsychological performance, and side effects. In the second study, we performed an electronic literature search of MEDLINE in September 2008. Articles in English published between 2003 and 2008 were searched for the terms schizophrenia, bupropion SR, and smoking. Bibliographies of studies identified through the MEDLINE search were also examined. Case reports, open-label studies, crossover studies, and studies using nonstandard dosing of bupropion SR were excluded. In this way, 4 studies similar in methodology to the currently presented clinical trial were identified and the individual data combined in a meta-analysis. A random effects meta-analysis using Comprehensive Meta-Analysis software was used to obtain a pooled estimate of the odds ratio for 4-week smoking abstinence between bupropion SR and placebo. Results: There were no significant results on the primary or secondary smoking measures for the clinical trial, although a numeric advantage favored the bupropion SR group. There were no significant findings for secondary symptom or side effect measures and no significant change in neuropsychological performance. For the meta-analysis totaling 226 subjects, there were significant findings in favor of bupropion SR. The pooled estimate of the odds ratio for 4-week abstinence was 2.7 (95% Cl, 1.3 to 5.7; P=.009), and clinically significant greater smoking reduction in the bupropion SR group, with pooled difference estimates increasing over time between groups, became statistically significant by week 5 of study medication (P<.02). Conclusions: New clinical trial data and a meta-analysis strongly support the tolerability and efficacy of bupropion SR for the treatment of cigarette smoking in people with schizophrenia. C1 [Weiner, Elaine; Ball, M. Patricia; Buchholz, Alison S.; Gold, James M.; McMahon, Robert P.; Buchanan, Robert W.] Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Dept Psychiat, Baltimore, MD 21228 USA. [Evins, A. Eden] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Addict Res Program, Boston, MA USA. RP Weiner, E (reprint author), Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Dept Psychiat, POB 21247, Baltimore, MD 21228 USA. EM eweiner@mprc.umaryland.edu RI McMahon, Robert/C-5462-2009 FU GlaxoSmthKline; Pfizer; Novartis; Janssen; Bristol-Myers Squibb; Otsuka; Cephalon; Veterans Affairs Capitol Network (VISN 5) Mental Illness Research, Education, and Clinical Center; National Institute of Mental Health, Advance Center for Intervention Services Research [MH068580-01] FX Ms Ball has served as a consultant to ePharmaSolutions and Pfizer; Dr Gold has served as a consultant to Merck, AstraZeneca, Solvay, Pfizer, and GlaxoSmithKline. Dr Evins has served as a consultant to Pfizer, Boehringer, and Schering Plough and has received grant/research support from GlaxoSmthKline and Pfizer. Dr Buchanan has served as a consultant to Abbott and GlaxoSmithKline; has received grant/research support from Novartis and Janssen; has served on advisory boards for AstraZeneca, Wyeth, Schering Plough, Solvay, and Pfizer; and has received other material or financial support from Bristol-Myers Squibb, Otsuka, Pfizer, and Cephalon. Drs Weiner and McMahon and Ms Buchholz report no financial or other relationship relevant to the subject of this article.; Funded in part by the Veterans Affairs Capitol Network (VISN 5) Mental Illness Research, Education, and Clinical Center and National Institute of Mental Health Grant MH068580-01, Advance Center for Intervention Services Research. NR 53 TC 19 Z9 19 U1 2 U2 11 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JAN PY 2012 VL 73 IS 1 BP 95 EP 102 DI 10.4088/JCP.10m06143gre PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 880LK UT WOS:000299408400014 PM 21535998 ER PT J AU Mohamed, S Rosenheck, R Lyketsos, CG Kaczynski, R Sultzer, DL Schneider, LS AF Mohamed, Somaia Rosenheck, Robert Lyketsos, Constantine G. Kaczynski, Richard Sultzer, David L. Schneider, Lon S. TI Effect of Second-Generation Antipsychotics on Caregiver Burden in Alzheimer's Disease SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID RATING-SCALE BPRS; FAMILY CAREGIVERS; BEHAVIORAL DISTURBANCES; DEMENTIA VICTIMS; OLDER-ADULTS; CATIE-AD; HEALTH; PREDICTORS; TRIAL; DEPRESSION AB Background: Alzheimer's disease (AD) imposes a severe burden upon patients and their caregivers. Severity of psychiatric symptoms and behavioral disturbances is an important determinant of caregivers' experience of burden. These symptoms may be improved with atypical antipsychotic treatment. Objective: Data from the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease (CATIE-AD) trial were used to evaluate the effect of atypical antipsychotics versus placebo on the experiences of caregivers of outpatients with AD. Method: We compared the effect of atypical antipsychotic drugs (olanzapine, risperidone, or quetiapine considered together as a group) versus placebo on the experiences of caregivers of AD outpatients (diagnosed according to DSM-IV-TR). We also evaluated whether improvement in patients' psychiatric and behavioral symptoms mediated the relationship between drug treatment and caregiver burden. The CATIE-AD trial, conducted from April 2001 through November 2004, included outpatients (mean age = 77.9 years [SD = 7.5 years]) in usual care settings and assessed treatment effectiveness over a 9-month period at 42 US sites. In a set of secondary analyses, data from CATIE-AD participants who had at least 1 postbaseline outcome assessment and data from their caregivers were examined in an intention-to-treat (ITT) analysis (N = 361). A phase 1-only analysis was conducted including only observations while patients were receiving the initially randomized drug (N = 153). The Burden Interview, the Beck Depression Inventory, and the Neuropsychiatric Inventory (NPI) Caregiver Distress Scale were used to evaluate caregiver burden. Results: In both ITT and phase 1-only analyses, caregivers of patients treated with second-generation antipsychotics scored significantly lower than caregivers of patients receiving placebo on both the Burden Interview (P = .0090) and the NPI Caregiver Distress Scale (P = .0209). These differences appeared to have been mediated by lower levels of agitation, hostility, and psychotic distortions. Conclusion: In AD patients with symptoms of psychosis, agitation, or aggressive behavior, medications can have a small but significant impact on caregiver burden. J Clin Psychiatry 2012;73(1):121-128 (C) Copyright 2011 Physicians Postgraduate Press, Inc. C1 [Mohamed, Somaia; Rosenheck, Robert; Kaczynski, Richard] Vet Affairs New England Mental Illness Res Educ &, West Haven, CT USA. [Mohamed, Somaia; Rosenheck, Robert; Kaczynski, Richard] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Lyketsos, Constantine G.] Johns Hopkins Univ, Dept Psychiat & Behav Sci, Baltimore, MD USA. [Lyketsos, Constantine G.] Johns Hopkins Bayview Med Ctr, Baltimore, MD USA. [Sultzer, David L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Sultzer, David L.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Schneider, Lon S.] Univ So Calif, Keck Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90033 USA. RP Mohamed, S (reprint author), Vet Affairs Connecticut Hlth Care Syst, 950 Campbell Ave,182, West Haven, CT 06516 USA. EM Somaia.Mohamed@yale.edu FU Eli Lilly; Janssen; AstraZeneca; Pfizer; National Institute of Mental Health (NIMH) [N01 MH9001]; National Institute on Aging; Associated Jewish Federation of Baltimore; Harry and Jeanette Weinberg Foundation; Forest; GlaxoSmithKline; Eisai; Ortho-McNeil; Bristol-Myers Squibb; Novartis; National Football League (NFL); Elan; Supernus; Adlyfe; Takeda; Lundbeck; Merz; Genentech; NFL Players Association; Forest Research Institute; Johnson Johnson; National Institutes of Health (NIH) [P50 AG05142, P01 AG05146]; Pfizer, Madison, New Jersey; Department of Veterans Affairs FX Dr Rosenheck has received research support from Eli Lilly, Janssen, AstraZeneca, and Wyeth (currently Pfizer); has been a consultant to GlaxoSmithKline, Bristol-Myers Squibb, Organon, and Janssen; and has provided expert testimony in matters pertaining to Eli Lilly, Eli Lilly Canada, Novapharm, Janssen-Ortho, and Janssen. Dr Lyketsos has received grant support (for research or CME) from the National Institute of Mental Health (NIMH), the National Institute on Aging, The Associated Jewish Federation of Baltimore, The Harry and Jeanette Weinberg Foundation, Forest, GlaxoSmithKline, Eisai, Pfizer, AstraZeneca, Eli Lilly, Ortho-McNeil, Bristol-Myers Squibb, Novartis, National Football League (NFL), and Elan; has received consulting fees from AstraZeneca, GlaxoSmithKline, Eisai, Elan, Novartis, Forest, Supernus, Adlyfe, Takeda, Wyeth (currently Pfizer), Lundbeck, Merz, Eli Lilly, Genentech, Pfizer, NFL Players Association, and the NFL; and has received speaking honoraria or travel support from Pfizer, Forest, GlaxoSmithKline, and Health Monitor. Dr Sultzer has received research support from Eli Lilly and Forest Research Institute. Dr Schneider has received consulting fees from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Forest, GlaxoSmithKline, Novartis, Johnson & Johnson, and Pfizer and has received research grant support from Novartis, Eli Lilly, and Pfizer. Drs Mohamed and Kaczynski have no potential conflicts of interest with regard to the subject of this article.; Conduct of the study was supported by grant N01 MH9001 from NIMH, the National Institutes of Health (NIH) (to Dr Schneider). Dr Schneider's efforts in writing the manuscript were partially supported by grant P50 AG05142 from NIH to the University of Southern California Alzheimer Disease Research Center, Los Angeles, California. Dr Mohamed's efforts in writing the manuscript were partially supported by a contract with Wyeth Pharmaceuticals (currently Pfizer), Madison, New Jersey. Dr Lyketsos' efforts in writing the manuscript were supported by grant P01 AG05146 from NIH to the Johns Hopkins University Alzheimer's Disease Research Center, Baltimore, Maryland. Dr Sultzer's efforts in writing the manuscript were partially supported by the Department of Veterans Affairs (Merit Review Program). NR 47 TC 7 Z9 7 U1 3 U2 8 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 JAN PY 2012 VL 73 IS 1 BP 121 EP 128 DI 10.4088/JCP.10m06574 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 880LK UT WOS:000299408400018 PM 21939611 ER PT J AU Hoang, M Mahalingam, M AF Hoang, Mai Mahalingam, Meera TI Methodology matters, but... SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Letter DE stem cell marker; nestin; scarring alopecia C1 [Hoang, Mai] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Mahalingam, Meera] Harvard Univ, Sch Med, Dept Dermatol, Dermatopathol Sect, Boston, MA 02115 USA. RP Hoang, M (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. EM mmahalin@bu.edu OI Mahalingam, Meera/0000-0002-2800-9985 NR 2 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD JAN PY 2012 VL 39 IS 1 BP 78 EP 79 DI 10.1111/j.1600-0560.2011.01750.x PG 2 WC Dermatology; Pathology SC Dermatology; Pathology GA 869HF UT WOS:000298588100018 PM 21752058 ER PT J AU Ghandour, RM Kogan, MD Blumberg, SJ Jones, JR Perrin, JM AF Ghandour, Reem M. Kogan, Michael D. Blumberg, Stephen J. Jones, Jessica R. Perrin, James M. TI Mental Health Conditions Among School-Aged Children: Geographic and Sociodemographic Patterns in Prevalence and Treatment SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Article DE mood disorders; conduct disorders; children; treatment; geographic variation ID COMORBIDITY SURVEY REPLICATION; SUPPLEMENT NCS-A; US CHILDREN; PSYCHIATRIC-DISORDERS; LIFETIME PREVALENCE; SERVICE UTILIZATION; CONDUCT PROBLEMS; RISK BEHAVIORS; ADOLESCENTS; STATE AB Objective: To explore geographic differences in diagnosed emotional and behavioral mental health conditions and receipt of treatment. Methods: Data are from the 2007 National Survey of Children's Health, a nationally representative, parent-reported, cross-sectional survey. Pediatric mental health conditions were identified using parents' responses to 3 questions regarding whether a health care provider had ever told them that their child had depression, anxiety problems, or behavioral or conduct problems. Parents also reported on past-year treatment or counseling by a mental health professional. State-level differences in condition prevalence were identified using unadjusted and adjusted prevalence estimates. Multivariate logistic regression assessed the odds of not receiving treatment by state and diagnoses. Results: Nearly 8% of children aged 6 to 17 years have ever been diagnosed with depression or anxiety, and 5.4% have ever been diagnosed with behavioral or conduct problems. State-level estimates of parent-reported depression or anxiety varied from 4.8% in Georgia to 14.4% in Vermont, while prevalence of behavioral problems ranged from 3.2% in California to 9.2% in Louisiana. Nearly 10% of all school-aged children and 53.1% of those ever diagnosed with either condition type received past-year treatment. The odds of receiving past-year parent-reported treatment did not differ by state of residence with the exception of Louisiana and Nevada: children ever diagnosed had approximately 2.5 times the odds of not receiving past-year treatment in these states. Conclusion: The prevalence of parent-reported mental health disorders among children varies by geographic and sociodemographic factors, while receipt of treatment is generally dependent on sociodemographic and health-related factors. C1 [Ghandour, Reem M.] US Hlth Resources & Serv Adm, Off Epidemiol Policy & Evaluat, Maternal & Child Hlth Bur, Rockville, MD 20857 USA. [Blumberg, Stephen J.] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. [Perrin, James M.] Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA. RP Ghandour, RM (reprint author), US Hlth Resources & Serv Adm, Off Epidemiol Policy & Evaluat, Maternal & Child Hlth Bur, 5600 Fishers Lane,Room 18-41, Rockville, MD 20857 USA. EM rghandour@hrsa.gov NR 48 TC 13 Z9 13 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-206X J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD JAN PY 2012 VL 33 IS 1 BP 42 EP 54 DI 10.1097/DBP.0b013e31823e18fd PG 13 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA 880FY UT WOS:000299391700012 PM 22218014 ER PT J AU Carlson, KF Meis, LA Jensen, AC Simon, AB Gravely, AA Taylor, BC Bangerter, A Schaaf, KW Griffin, JM AF Carlson, Kathleen F. Meis, Laura A. Jensen, Agnes C. Simon, Alisha Baines Gravely, Amy A. Taylor, Brent C. Bangerter, Ann Schaaf, Katy Wilder Griffin, Joan M. TI Caregiver Reports of Subsequent Injuries Among Veterans With Traumatic Brain Injury After Discharge From Inpatient Polytrauma Rehabilitation Programs SO JOURNAL OF HEAD TRAUMA REHABILITATION LA English DT Article DE caregivers; health services; rehabilitation; traumatic brain injury; trauma; injury ID SPINAL-CORD-INJURY; RISK; MORTALITY; POPULATION; BEHAVIOR; DEATH; CARE; INDIVIDUALS; POSTINJURY; CHILDREN AB Objective: We examined prevalence of, and potential risk factors for, nonfatal injuries among Veterans with traumatic brain injury (TBI) postdischarge from Veterans Affairs inpatient polytrauma rehabilitation programs. Methods: We surveyed caregivers of patients who had military service anytime from 2001 to 2009, sustained polytrauma including TBI, received Veterans Affairs inpatient care from 2001 to 2009, were discharged at least 3 months before the study, and were alive when the study was fielded about caregiver and patient health, including patients' medically treated "accidents/new injuries" since discharge. We examined prevalence and source(s) of subsequent injuries and estimated patients' injury risk in reference to hypothesized risk factors. Odds ratios and 95% confidence intervals were calculated using multivariate logistic regression. Results: Caregivers reported that nearly one-third (32%) of patients incurred medically treated injuries after discharge; most were associated with falls (49%) and motor vehicles (37%). Odds of subsequent injury were associated with select demographics, initial injury characteristics, and postdischarge health and functioning. Characteristics of caregivers, including physical and mental health, were also associated with patients' odds of subsequent injury. Conclusions: A significant number of caregivers reported subsequent nonfatal injuries among patients treated for TBI/polytrauma in inpatient rehabilitation settings. Enhanced injury prevention efforts may be beneficial for this population. C1 [Carlson, Kathleen F.] Portland VA Med Ctr, Portland Ctr Study Chron Comorbid Mental & Phys D, Portland, OR USA. [Carlson, Kathleen F.] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. [Meis, Laura A.; Jensen, Agnes C.; Simon, Alisha Baines; Gravely, Amy A.; Taylor, Brent C.; Bangerter, Ann; Griffin, Joan M.] Minneapolis VA Hlth Care Syst, Ctr Chron Dis Outcomes Res, Minneapolis, MN USA. [Taylor, Brent C.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Meis, Laura A.; Taylor, Brent C.; Griffin, Joan M.] Univ Minnesota, Sch Med, Dept Med, Minneapolis, MN 55455 USA. [Schaaf, Katy Wilder] Virginia Commonwealth Univ, Dept Phys Med & Rehabil, Sch Med, Neuropsychol & Rehabil Psychol Serv, Richmond, VA USA. [Schaaf, Katy Wilder] Hunter Holmes McGuire VA Med Ctr, Richmond, VA USA. RP Carlson, KF (reprint author), Portland VA Med Ctr R&D 66, Portland Ctr Study Chron Comorbid Mental & Phys D, 3715 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM kathleen.carlson@va.gov RI Taylor, Brent/A-8069-2009 OI Taylor, Brent/0000-0002-2140-8377 FU Veterans Health Administration Health Services Research and Development Service [SDR 07-044, CDA 08-025] FX This work was supported by grants from the Veterans Health Administration Health Services Research and Development Service (SDR 07-044; CDA 08-025). The opinions 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 United States government. NR 50 TC 10 Z9 10 U1 3 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-9701 J9 J HEAD TRAUMA REHAB JI J. Head Trauma Rehabil. PD JAN-FEB PY 2012 VL 27 IS 1 BP 14 EP 25 DI 10.1097/HTR.0b013e318236bd86 PG 12 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 879JV UT WOS:000299326400002 PM 22218200 ER PT J AU Meterko, M Baker, E Stolzmann, KL Hendricks, AM Cicerone, KD Lew, HL AF Meterko, Mark Baker, Errol Stolzmann, Kelly L. Hendricks, Ann M. Cicerone, Keith D. Lew, Henry L. TI Psychometric Assessment of the Neurobehavioral Symptom Inventory-22: The Structure of Persistent Postconcussive Symptoms Following Deployment-Related Mild Traumatic Brain Injury Among Veterans SO JOURNAL OF HEAD TRAUMA REHABILITATION LA English DT Article ID POST-CONCUSSION SYNDROME; CONSTRUCT-VALIDITY C1 [Meterko, Mark; Baker, Errol; Stolzmann, Kelly L.; Hendricks, Ann M.] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Meterko, Mark; Baker, Errol; Stolzmann, Kelly L.] VA Ctr Org Leadership & Management Res, Boston, MA USA. [Meterko, Mark; Hendricks, Ann M.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Cicerone, Keith D.] JFK Johnson Rehabil Inst, Edison, NJ USA. [Lew, Henry L.] Univ Hawaii Manoa, Def & Vet Brain Injury Ctr, Honolulu, HI 96822 USA. [Lew, Henry L.] Univ Hawaii Manoa, John A Burns Sch Med, Honolulu, HI 96822 USA. RP Meterko, M (reprint author), VA Boston Healthcare Syst, Mail Stop 152M,150 S Huntington Ave, Boston, MA 02130 USA. EM mark.meterko@va.gov FU VHA HSRD [SDR 08-405] FX This research was supported by VHA HSR&D grant SDR 08-405. 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. NR 21 TC 35 Z9 35 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-9701 J9 J HEAD TRAUMA REHAB JI J. Head Trauma Rehabil. PD JAN-FEB PY 2012 VL 27 IS 1 BP 55 EP 62 DI 10.1097/HTR.0b013e318230fb17 PG 8 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 879JV UT WOS:000299326400006 PM 22190009 ER PT J AU Brill, A Fuchs, TA Savchenko, AS Thomas, GM Martinod, K De Meyer, SF Bhandari, AA Wagner, DD AF Brill, A. Fuchs, T. A. Savchenko, A. S. Thomas, G. M. Martinod, K. De Meyer, S. F. Bhandari, A. A. Wagner, D. D. TI Neutrophil extracellular traps promote deep vein thrombosis in mice SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Article DE citrullination; deep vein thrombosis; histones; neutrophil extracellular traps; von Willebrand factor ID ACTIVATED PROTEIN-C; HISTONE DEIMINATION; INNATE IMMUNITY; P-SELECTIN; CELL-DEATH; IN-VIVO; BLOOD; DNA; MICROPARTICLES; COAGULATION AB . Background: Upon activation, neutrophils can release nuclear material known as neutrophil extracellular traps (NETs), which were initially described as a part of antimicrobial defense. Extracellular chromatin was recently reported to be prothrombotic in vitro and to accumulate in plasma and thrombi of baboons with experimental deep vein thrombosis (DVT). Objective: To explore the source and role of extracellular chromatin in DVT. Methods: We used an established murine model of DVT induced by flow restriction (stenosis) in the inferior vena cava (IVC). Results: We demonstrate that the levels of extracellular DNA increase in plasma after 6 h IVC stenosis, compared with sham-operated mice. Immunohistochemical staining revealed the presence of Gr-1-positive neutrophils in both red (RBC-rich) and white (platelet-rich) parts of thrombi. Citrullinated histone H3 (CitH3), an element of NETs structure, was present only in the red part of thrombi and was frequently associated with the Gr-1 antigen. Immunofluorescent staining of thrombi showed proximity of extracellular CitH3 and von Willebrand factor (VWF), a platelet adhesion molecule crucial for thrombus development in this model. Infusion of Deoxyribonuclease 1 (DNase 1) protected mice from DVT after 6 h and also 48 h IVC stenosis. Infusion of an unfractionated mixture of calf thymus histones increased plasma VWF and promoted DVT early after stenosis application. Conclusions: Extracellular chromatin, likely originating from neutrophils, is a structural part of a venous thrombus and both the DNA scaffold and histones appear to contribute to the pathogenesis of DVT in mice. NETs may provide new targets for DVT drug development. C1 [Wagner, D. D.] Childrens Hosp, Immune Dis Inst, Program Cellular & Mol Med, Boston, MA 02115 USA. [Brill, A.; Fuchs, T. A.; Savchenko, A. S.; Thomas, G. M.; De Meyer, S. F.; Wagner, D. D.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Martinod, K.] Harvard Univ, Sch Med, Grad Program Immunol, Div Med Sci, Boston, MA USA. [De Meyer, S. F.] KULeuven Campus Kortrijk, Lab Thrombosis Res, Kortrijk, Belgium. RP Wagner, DD (reprint author), Childrens Hosp, Immune Dis Inst, Program Cellular & Mol Med, 3 Blackfan Circle,3rd floor, Boston, MA 02115 USA. EM wagner@idi.harvard.edu RI Thomas, Grace/G-1020-2011; Fuchs, Tobias/F-1189-2013; OI Thomas, Grace/0000-0003-4502-7154; Martinod, Kimberly/0000-0002-1026-6107 FU National Heart, Lung, and Blood Institute of the National Institutes of Health [R01 HL041002, R01 HL095091, R01 HL102101] FX This work was supported by National Heart, Lung, and Blood Institute of the National Institutes of Health grants R01 HL041002, R01 HL095091 and R01 HL102101 (to D.D.W.). S. F. De Meyer is a postdoctoral fellow of the 'Fond voor Wetenschappelijk Onderzoek Vlaanderen' (FWO). We thank L. Cowan for help in preparing the manuscript. NR 42 TC 204 Z9 217 U1 7 U2 31 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1538-7933 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD JAN PY 2012 VL 10 IS 1 BP 136 EP 144 DI 10.1111/j.1538-7836.2011.04544.x PG 9 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 872XD UT WOS:000298843500018 PM 22044575 ER PT J AU Kloverpris, HN Stryhn, A Harndahl, M van der Stok, M Payne, RP Matthews, PC Chen, FB Riddell, L Walker, BD Ndung'u, T Buus, S Goulder, P AF Kloverpris, Henrik N. Stryhn, Anette Harndahl, Mikkel van der Stok, Mary Payne, Rebecca P. Matthews, Philippa C. Chen, Fabian Riddell, Lynn Walker, Bruce D. Ndung'u, Thumbi Buus, Soren Goulder, Philip TI HLA-B(star)57 Micropolymorphism Shapes HLA Allele-Specific Epitope Immunogenicity, Selection Pressure, and HIV Immune Control SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; T-LYMPHOCYTE EPITOPES; DISEASE PROGRESSION; CELL RESPONSES; INFECTED-CELLS; GAG; TRANSMISSION; ASSOCIATIONS; REPERTOIRE; PROTEIN AB The genetic polymorphism that has the greatest impact on immune control of human immunodeficiency virus (HIV) infection is expression of HLA-B(star)57. Understanding of the mechanism for this strong effect remains incomplete. HLA-B(star)57 alleles and the closely related HLA-B(star)5801 are often grouped together because of their similar peptide-binding motifs and HIV disease outcome associations. However, we show here that the apparently small differences between HLA-B(star)57 alleles, termed HLA-B(star)57 micropolymorphisms, have a significant impact on immune control of HIV. In a study cohort of >2,000 HIV C-clade-infected subjects from southern Africa, HLA-B(star)5703 is associated with a lower viral-load set point than HLA-B(star)5702 and HLA-B(star)5801 (medians, 5,980, 15,190, and 19,000 HIV copies/ml plasma; P = 0.24 and P = 0.0005). In order to better understand these observed differences in HLA-B(star)57/5801-mediated immune control of HIV, we undertook, in a study of >1,000 C-clade-infected subjects, a comprehensive analysis of the epitopes presented by these 3 alleles and of the selection pressure imposed on HIV by each response. In contrast to previous studies, we show that each of these three HLA alleles is characterized both by unique CD8(+) T-cell specificities and by clear-cut differences in selection pressure imposed on the virus by those responses. These studies comprehensively define for the first time the CD8(+) T-cell responses and immune selection pressures for which these protective alleles are responsible. These findings are consistent with HLA class I alleles mediating effective immune control of HIV through the number of p24 Gag-specific CD8(+) T-cell responses generated that can drive significant selection pressure on the virus. C1 [Kloverpris, Henrik N.; Payne, Rebecca P.; Matthews, Philippa C.; Goulder, Philip] Univ Oxford, Dept Paediat, Oxford, England. [Stryhn, Anette; Harndahl, Mikkel; Buus, Soren] Univ Copenhagen, Dept Int Hlth Immunol & Microbiol, Copenhagen, Denmark. [van der Stok, Mary; Walker, Bruce D.; Ndung'u, Thumbi; Goulder, Philip] Univ KwaZulu Natal, Doris Duke Med Res Inst, HIV Pathogenesis Programme, Durban, South Africa. [Walker, Bruce D.; Goulder, Philip] MIT, Ragon Inst Massachusetts Gen Hosp, Boston, MA USA. [Chen, Fabian] Royal Berkshire Hosp, Dept Sexual Hlth, Reading RG1 5AN, Berks, England. [Riddell, Lynn] Northhamptonshire Healthcare Natl Hlth Serv Trust, Northhampton Gen Hosp, Dept Genitourinary Med, Cliftonville, Northants, England. [Walker, Bruce D.; Goulder, Philip] Harvard Univ, Boston, MA 02115 USA. RP Kloverpris, HN (reprint author), Univ Oxford, Dept Paediat, Peter Medawar Bldg, Oxford, England. EM henrik.kloverpris@paediatrics.ox.ac.uk RI Buus, Soren/F-5446-2010; OI Matthews, Philippa/0000-0002-4036-4269; Buus, Soren/0000-0001-8363-1999; Ndung'u, Thumbi/0000-0003-2962-3992 FU Wellcome Trust; National Institutes of Health [RO1 AI46995] FX This work was supported by the Wellcome Trust (P.G.) and the National Institutes of Health, grant RO1 AI46995. NR 59 TC 39 Z9 40 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2012 VL 86 IS 2 BP 919 EP 929 DI 10.1128/JVI.06150-11 PG 11 WC Virology SC Virology GA 870MW UT WOS:000298674600025 PM 22090105 ER PT J AU Ruhl, M Chhatwal, P Strathmann, H Kuntzen, T Bankwitz, D Skibbe, K Walker, A Heinemann, FM Horn, PA Allen, TM Hoffmann, D Pietschmann, T Timm, J AF Ruhl, Marianne Chhatwal, Patrick Strathmann, Heiko Kuntzen, Thomas Bankwitz, Dorothea Skibbe, Kathrin Walker, Andreas Heinemann, Falko M. Horn, Peter A. Allen, Todd M. Hoffmann, Daniel Pietschmann, Thomas Timm, Joerg TI Escape from a Dominant HLA-B*15-Restricted CD8(+) T Cell Response against Hepatitis C Virus Requires Compensatory Mutations outside the Epitope SO JOURNAL OF VIROLOGY LA English DT Article ID REPLICATION CAPACITY; LYMPHOCYTE ESCAPE; CLASS-I; IMMUNE-RESPONSES; INFECTION; EVOLUTION; HCV; TRANSMISSION; EXPRESSION; SELECTION AB Antiviral CD8(+) T cells are a key component of the adaptive immune system against hepatitis C virus (HCV). For the development of immune therapies, it is essential to understand how CD8(+) T cells contribute to clearance of infection and why they fail so often. A mechanism for secondary failure is mutational escape of the virus. However, some substitutions in viral epitopes are associated with fitness costs and often require compensatory mutations. We hypothesized that compensatory mutations may point toward epitopes under particularly strong selection pressure that may be beneficial for vaccine design because of a higher genetic barrier to escape. We previously identified two HLA-B*15-restricted CD8(+) epitopes in NS5B (LLRHHNMVY2450-2458 and SQRQKKVTF(2466-2474)), based on sequence analysis of a large HCV genotype 1b outbreak. Both epitopes are targeted in about 70% of HLA-B*15-positive individuals exposed to HCV. Reproducible selection of escape mutations was confirmed in an independent multicenter cohort in the present study. Interestingly, mutations were also selected in the epitope flanking region, suggesting that compensatory evolution may play a role. Covariation analysis of sequences from the database confirmed a significant association between escape mutations inside one of the epitopes (H2454R and M2456L) and substitutions in the epitope flanking region (S2439T and K2440Q). Functional analysis with the subgenomic replicon Con1 confirmed that the primary escape mutations impaired viral replication, while fitness was restored by the additional substitutions in the epitope flanking region. We concluded that selection of escape mutations inside an HLA-B*15 epitope requires secondary substitutions in the epitope flanking region that compensate for fitness costs. C1 [Ruhl, Marianne; Skibbe, Kathrin; Walker, Andreas; Timm, Joerg] Univ Duisburg Essen, Univ Hosp Essen, Inst Virol, Essen, Germany. [Chhatwal, Patrick; Bankwitz, Dorothea; Pietschmann, Thomas] Ctr Expt & Clin Infect Res, Div Expt Virol, TWINCORE, Hannover, Germany. [Strathmann, Heiko; Hoffmann, Daniel] Univ Duisburg Essen, Ctr Med Biotechnol, Essen, Germany. [Kuntzen, Thomas] Univ Zurich Hosp, Dept Gastroenterol & Hepatol, CH-8091 Zurich, Switzerland. [Heinemann, Falko M.; Horn, Peter A.] Univ Hosp Essen, Inst Transfus Med, Essen, Germany. [Allen, Todd M.] Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, Charlestown, MA USA. RP Timm, J (reprint author), Univ Duisburg Essen, Univ Hosp Essen, Inst Virol, Essen, Germany. EM joerg.timm@uni-due.de RI Allen, Todd/F-5473-2011; Pietschmann, Thomas/E-9241-2015; OI Pietschmann, Thomas/0000-0001-5138-6239; Walker, Andreas/0000-0002-8736-0863; Hoffmann, Daniel/0000-0003-2973-7869 FU Deutsche Forschungsgemeinschaft [DFG-TRR60, GK 1045]; National Institute of Allergy and Infectious Diseases (NIAID) [R01-AI067926, U19-AI082630] FX This work was supported by the Deutsche Forschungsgemeinschaft (DFG-TRR60 and GK 1045) and by federal funds from the National Institute of Allergy and Infectious Diseases (NIAID) under grants R01-AI067926 (T.M.A.) and U19-AI082630 (T.M.A.). NR 55 TC 9 Z9 9 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2012 VL 86 IS 2 BP 991 EP 1000 DI 10.1128/JVI.05603-11 PG 10 WC Virology SC Virology GA 870MW UT WOS:000298674600031 PM 22072759 ER PT J AU Wright, JK Brumme, ZL Julg, B van der Stok, M Mncube, Z Gao, XJ Carlson, JM Goulder, PJR Walker, BD Brockman, MA Ndung'u, T AF Wright, Jaclyn K. Brumme, Zabrina L. Julg, Boris van der Stok, Mary Mncube, Zenele Gao, Xiaojiang Carlson, Jonathan M. Goulder, Philip J. R. Walker, Bruce D. Brockman, Mark A. Ndung'u, Thumbi TI Lack of Association between HLA Class II Alleles and In Vitro Replication Capacities of Recombinant Viruses Encoding HIV-1 Subtype C Gag-Protease from Chronically Infected Individuals SO JOURNAL OF VIROLOGY LA English DT Article ID T-CELL RESPONSES; TYPE-1; MUTATIONS; CONTROLLERS; SELECTION; PRESSURE; IMMUNITY; FITNESS; ESCAPE; AIDS AB It is unknown whether favorable HLA class II alleles may attenuate HIV-1 through selection pressure in a manner similar to that of protective HLA class I alleles. We investigated the relationship between HLA class II alleles and in vitro replication capacities of recombinant viruses encoding HIV-1 subtype C Gag-protease from chronically infected individuals. No associations were found between individual alleles and lower replication capacity, suggesting no significant HIV-1 attenuation by HLA class II-restricted Gag-specific CD4(+) T cell immune pressure. C1 [Wright, Jaclyn K.; Julg, Boris; van der Stok, Mary; Mncube, Zenele; Goulder, Philip J. R.; Walker, Bruce D.; Ndung'u, Thumbi] Univ KwaZulu Natal, Doris Duke Med Res Inst, Nelson R Mandela Sch Med, HIV Pathogenesis Programme, Durban, South Africa. [Brumme, Zabrina L.; Brockman, Mark A.] Simon Fraser Univ, Burnaby, BC V5A 1S6, Canada. [Brumme, Zabrina L.; Brockman, Mark A.] BC Ctr Excellence HIV AIDS, Vancouver, BC, Canada. [Julg, Boris; Goulder, Philip J. R.; Walker, Bruce D.; Ndung'u, Thumbi] MIT, Ragon Inst Massachusetts Gen Hosp, Boston, MA USA. [Julg, Boris; Goulder, Philip J. R.; Walker, Bruce D.; Ndung'u, Thumbi] Harvard Univ, Boston, MA 02115 USA. [Gao, Xiaojiang] NCI Frederick, SAIC Frederick, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MA USA. [Carlson, Jonathan M.] Microsoft Res, eSci Grp, Redmond, WA USA. [Goulder, Philip J. R.] Univ Oxford, Nuffield Dept Med, Dept Paediat, Oxford, England. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Ndung'u, T (reprint author), Univ KwaZulu Natal, Doris Duke Med Res Inst, Nelson R Mandela Sch Med, HIV Pathogenesis Programme, Durban, South Africa. EM ndungu@ukzn.ac OI Ndung'u, Thumbi/0000-0003-2962-3992; Brockman, Mark/0000-0001-6432-1426 FU NIH [ROI-AI067073, NOI-AI-15422]; South African AIDS Vaccine Initiative; Howard Hughes Medical Institute; Ragon Institute Fund for Innovation and New International Initiatives; National Research Foundation; Ragon Institute of Massachusetts General Hospital; Massachusetts Institute of Technology; Harvard University; Canadian Institutes for Health Research (CIHR); National Cancer Institute, National Institutes of Health [HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer Research FX This research was funded by NIH (grant ROI-AI067073, contract NOI-AI-15422), the South African AIDS Vaccine Initiative, the Howard Hughes Medical Institute International Program, and the Ragon Institute Fund for Innovation and New International Initiatives. J.K.W. is funded by the National Research Foundation and the Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University. Z.L.B. is supported by a New Investigator Award from the Canadian Institutes for Health Research (CIHR). M. A. B. holds a Canada Research Chair, Tier 2 in Viral Pathogenesis and Immunity. T.N. holds the South African Department of Science and Technology/National Research Foundation Research Chair in Systems Biology of HIV/AIDS. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract no. HHSN261200800001E. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 31 TC 4 Z9 4 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2012 VL 86 IS 2 BP 1273 EP 1276 DI 10.1128/JVI.06533-11 PG 4 WC Virology SC Virology GA 870MW UT WOS:000298674600060 PM 22090116 ER PT J AU Afzali, A Berry, K Ioannou, GN AF Afzali, Anita Berry, Kristin Ioannou, George N. TI Excellent posttransplant survival for patients with nonalcoholic steatohepatitis in the United States SO LIVER TRANSPLANTATION LA English DT Article ID FATTY LIVER-DISEASE; CRYPTOGENIC CIRRHOSIS; NATURAL-HISTORY; TRANSPLANTATION; POPULATION; PREVALENCE AB Because of the ongoing epidemics of obesity and diabetes, nonalcoholic steatohepatitis (NASH) may become a leading indication for liver transplantation. There are concerns about the posttransplant survival of patients with NASH because of associated cardiovascular and metabolic risk factors. We aimed to determine recent trends in the proportion of patients undergoing transplantation for NASH-related cirrhosis in the United States and to estimate their posttransplant survival. We used data provided by the United Network for Organ Sharing for first-time adult cadaveric liver transplants performed in the United States between January 1, 1997 and October 31, 2010 (n = 53,738). The proportion of liver transplants performed for NASH-related cirrhosis increased dramatically from 1.2% in 1997-2003 to 7.4% in 2010 when NASH was the fourth most common indication for transplantation. The posttransplant survival of patients with NASH (n = 1810) at 1 (87.6%), 3 (82.2%), and 5 years (76.7%) was superior to the survival of patients with hepatocellular carcinoma, hepatitis C virus, alcoholic liver disease, acute hepatic necrosis, hemochromatosis, or cryptogenic liver disease and was inferior to the survival of only 4 groups of patients (those with primary biliary cirrhosis, primary sclerosing cholangitis, autoimmune hepatitis, or hepatitis B virus). In conclusion, NASH-related cirrhosis is increasing rapidly as an indication for liver transplantation in the United States and is associated with excellent posttransplant survival. Liver Transpl 18:2937, 2012. (C) 2011 AASLD. C1 [Afzali, Anita; Ioannou, George N.] Univ Washington, Div Gastroenterol, Dept Med, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Berry, Kristin] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Afzali, Anita; Ioannou, George N.] Vet Affairs Puget Sound Hlth Care Syst, Res Enhancement Award Program, Seattle, WA USA. RP Afzali, A (reprint author), Univ Washington, Div Gastroenterol, Dept Med, Vet Affairs Puget Sound Hlth Care Syst, 1959 NE Pacific St,Suite AA103,Box 356424, Seattle, WA 98195 USA. EM anitaa@medicine.washington.edu FU Health Resources and Services Administration [234-2005-370011C] FX This work was supported in part by the Health Resources and Services Administration (contract 234-2005-370011C). The content is the responsibility of the authors alone and does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. NR 21 TC 49 Z9 50 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1527-6465 J9 LIVER TRANSPLANT JI Liver Transplant. PD JAN PY 2012 VL 18 IS 1 BP 29 EP 37 DI 10.1002/lt.22435 PG 9 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA 867VO UT WOS:000298483100005 PM 21932374 ER PT J AU Kontos, N Querques, J Freudenreich, O AF Kontos, Nicholas Querques, John Freudenreich, Oliver TI Fighting the Good Fight: Responsibility and Rationale in the Confrontation of Patients SO MAYO CLINIC PROCEEDINGS LA English DT Editorial Material ID MEDICAL-ETHICS; CARE; CONSULTATION; DECISIONS; AUTONOMY; MODEL C1 [Kontos, Nicholas] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Kontos, N (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 55 Fruit St, Boston, MA 02114 USA. EM nkontos@partners.org NR 29 TC 3 Z9 3 U1 0 U2 3 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 JAN PY 2012 VL 87 IS 1 BP 63 EP 66 DI 10.1016/j.mayocp.2011.07.002 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 883XD UT WOS:000299667300010 PM 22212970 ER PT J AU Tsai, A Caprioli, J Shen, LQ AF Tsai, Andy Caprioli, Joseph Shen, Lucy Q. TI Coupled parametric model for estimation of visual field tests based on OCT macular thickness maps, and vice versa, in glaucoma care SO MEDICAL IMAGE ANALYSIS LA English DT Article DE OCT; Visual field testing; Glaucoma; PCA ID OPTICAL COHERENCE TOMOGRAPHY; NERVE-FIBER LAYER; COMPONENT ANALYSIS; REPRODUCIBILITY; PERIMETRY; EYES; PCA AB The current standard of care for glaucoma patients consists of functional assessment of vision via visual field (VF) testing, which is sensitive but subjective, time-consuming, and often unreliable. A new imaging technology, Fourier domain optical coherence tomography (OCT), is being introduced to assess the structural characteristics of the macula. This new complementary exam is efficient, objective, and reliable. A complex, but consistent, relationship exists between the structural information provided by macular OCT and the functional information gathered by VF maps. We propose a learning-based framework with the ability to estimate the VF map based on OCT macular thickness measurements as input (and vice versa). Central to this algorithmic framework is a coupled parametric model that captures not only the individual variabilities of the OCT macular thickness measurements and the VF maps, but also their co-dependencies. This model is derived by applying principal component analysis (PCA) to a library consisting of various pairs of OCT and VF maps. The parameters of this coupled model are obtained by solving a linear least squares problem. Next, these estimated parameters are used, in conjunction with the eigenvectors derived from PCA, to compute the estimate. The accuracy of this coupled parametric estimation model was evaluated by performing multiple leave-one-out cross validation experiments. (C) 2011 Elsevier B.V. All rights reserved. C1 [Tsai, Andy] Childrens Hosp Boston, Dept Radiol, Boston, MA 02115 USA. [Caprioli, Joseph] Jules Stein Eye Inst, Glaucoma Div, Los Angeles, CA 90095 USA. [Shen, Lucy Q.] Massachusetts Eye & Ear Infirm, Glaucoma Serv, Boston, MA 02114 USA. RP Tsai, A (reprint author), Childrens Hosp Boston, Dept Radiol, 300 Longwood Ave, Boston, MA 02115 USA. EM andy.tsai@childrens.harvard.edu OI Caprioli, Joseph/0000-0002-2383-7263 FU Department of Radiology, Children's Hospital Boston; American Glaucoma Society; Research to Prevent Blindness; Pfizer Inc.; Harvard Catalyst/the Harvard Clinical and Translational Science Center FX This work was supported in part by Department of Radiology, Children's Hospital Boston, American Glaucoma Society, unrestricted grants from Research to Prevent Blindness and Pfizer Inc., and Harvard Catalyst/the Harvard Clinical and Translational Science Center. The authors would like to thank Optovue, Inc. for providing technical assistance with RTVue, Dennis Mock for his role in data collection and processing, and Nancy Drinan for her help in the preparation of this manuscript. Finally, the authors would like to thank the anonymous reviewers for their valuable comments and thoughtful suggestions. NR 24 TC 3 Z9 3 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1361-8415 EI 1361-8423 J9 MED IMAGE ANAL JI Med. Image Anal. PD JAN PY 2012 VL 16 IS 1 BP 101 EP 113 DI 10.1016/j.media.2011.05.012 PG 13 WC Computer Science, Artificial Intelligence; Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 880KH UT WOS:000299405500009 PM 21723180 ER PT J AU Ueno, K Hirata, H Majid, S Yamamura, S Shahryari, V Tabatabai, ZL Hinoda, Y Dahiya, R AF Ueno, Koji Hirata, Hiroshi Majid, Shahana Yamamura, Soichiro Shahryari, Varahram Tabatabai, Z. Laura Hinoda, Yuji Dahiya, Rajvir TI Tumor Suppressor MicroRNA-493 Decreases Cell Motility and Migration Ability in Human Bladder Cancer Cells by Downregulating RhoC and FZD4 SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID IN-VITRO; HEPATOCELLULAR-CARCINOMA; GENOMIC ANALYSIS; METASTASIS; INVASION; PATHWAY; PROGRESSION; INHIBITION; BIOMARKERS; ACTIVATION AB The purpose of this study was to identify new tumor suppressor microRNAs (miRNA; miR) in bladder cancer, conduct functional analysis of their suppressive role, and identify their specific target genes. To explore tumor suppressor miRs in bladder cancer, miR microarray was conducted using SV-HUC-1, T24, J82, and TCCSUP cells. Expression of miR-493 in bladder cancer (T24, J82, and TCCSUP) cells was downregulated compared with normal SV-HUC-1 cells. Also, the expression of miR-493 was significantly lower in bladder cancer tissues than in their corresponding noncancerous tissues. Transfection of miR-493 into T24 or J82 cells decreased their cell growth andmigration abilities. On the basis of this result, to identify potential miR-493 target genes, we used target scan algorithms to identify target oncogenes related to invasion and migration. miR-493 decreased 30-untranslated region luciferase activity and protein expression of FZD4 and RhoC. miR-493 also decreased binding of RhoC and Rock-1. miR-493 is a new tumor suppressor miRNA in bladder cancer and inhibits cell motility through downregulation of RhoC and FZD4. Mol Cancer Ther; 11(1); 244-53. (C) 2011 AACR. C1 [Ueno, Koji; Hirata, Hiroshi; Majid, Shahana; Yamamura, Soichiro; Shahryari, Varahram; Dahiya, Rajvir] San Francisco VA Med Ctr, Dept Urol, San Francisco, CA USA. [Tabatabai, Z. Laura] San Francisco VA Med Ctr, Dept Pathol, San Francisco, CA USA. [Dahiya, Rajvir] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Hinoda, Yuji] Yamaguchi Univ, Grad Sch Med, Dept Oncol & Lab Med, Ube, Yamaguchi 755, Japan. RP Dahiya, R (reprint author), Vet Affairs Med Ctr, Urol Res Ctr 112F, 4150 Clement St, San Francisco, CA 94121 USA. EM rdahiya@urology.ucsf.edu FU NIH [R01CA130860, R01CA138642, R01CA111470, T32DK007790]; VA FX This study was supported by grants R01CA130860, R01CA138642, R01CA111470, T32DK007790 from the NIH, VA Research Enhancement Award Program (REAP), and Merit Review grants. NR 30 TC 40 Z9 43 U1 2 U2 5 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 JAN PY 2012 VL 11 IS 1 BP 244 EP 253 DI 10.1158/1535-7163.MCT-11-0592 PG 10 WC Oncology SC Oncology GA 879CV UT WOS:000299308200024 PM 22057916 ER PT J AU Yildirim, E Sadreyev, RI Pinter, SF Lee, JT AF Yildirim, Eda Sadreyev, Ruslan I. Pinter, Stefan F. Lee, Jeannie T. TI X-chromosome hyperactivation in mammals via nonlinear relationships between chromatin states and transcription SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID DROSOPHILA DOSAGE COMPENSATION; EMBRYONIC STEM-CELLS; LINKED GENES; PROXIMAL CHROMOSOME-7; ACETYL TRANSFERASE; UP-REGULATION; HISTONE H4; RNA-SEQ; MOUSE; INACTIVATION AB Dosage compensation in mammals occurs at two levels. In addition to balancing X-chromosome dosage between males and females via X inactivation, mammals also balance dosage of Xs and autosomes. It has been proposed that X-autosome equalization occurs by upregulation of Xa (active X). To investigate mechanism, we perform allele-specific ChIP-seq for chromatin epitopes and analyze RNA-seq data. The hypertranscribed Xa demonstrates enrichment of active chromatin marks relative to autosomes. We derive predictive models for relationships among Pol II occupancy, active mark densities and gene expression, and we suggest that Xa upregulation involves increased transcription initiation and elongation. Enrichment of active marks on Xa does not scale proportionally with transcription output, a disparity explained by nonlinear quantitative dependencies among active histone marks, Pol II occupancy and transcription. Notably, the trend of nonlinear upregulation also occurs on autosomes. Thus, Xa upregulation involves combined increases of active histone marks and Pol II occupancy, without invoking X-specific dependencies between chromatin states and transcription. C1 [Yildirim, Eda; Sadreyev, Ruslan I.; Pinter, Stefan F.; Lee, Jeannie T.] Howard Hughes Med Inst, Boston, MA 02115 USA. [Yildirim, Eda; Sadreyev, Ruslan I.; Pinter, Stefan F.; Lee, Jeannie T.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Yildirim, Eda; Sadreyev, Ruslan I.; Pinter, Stefan F.; Lee, Jeannie T.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. RP Lee, JT (reprint author), Howard Hughes Med Inst, Boston, MA 02115 USA. EM lee@molbio.mgh.harvard.edu OI Yildirim, Eda/0000-0002-4796-3854; Pinter, Stefan/0000-0003-4750-1403 FU MGH ECOR; Deutsche Forschungsgemeinschaft; US National Institutes of Health [RO1-GM090278] FX We are thankful to members of Lee laboratory for valuable discussions, to Y. Jeon for F1 mus/cast female MEFs and to B. Chapman, M. Borowsky and T. Ohsumi of the Bioinformatics Core Facility (Department of Molecular Biology, Massachusetts General Hospital (MGH)) for their suggestions for ChIP-Seq analysis. This work was supported by the MGH ECOR Medical Discovery Fund (E.Y.), the Deutsche Forschungsgemeinschaft (S.F.P.) and the US National Institutes of Health (RO1-GM090278, J.T.L.). J.T.L. is an investigator of the Howard Hughes Medical Institute. NR 53 TC 22 Z9 23 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1545-9993 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD JAN PY 2012 VL 19 IS 1 BP 56 EP U72 DI 10.1038/nsmb.2195 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 875PW UT WOS:000299046000010 ER PT J AU Liu, WR Xu, J Wang, H Xu, CS Ji, C Wang, Y Feng, CS Zhang, XN Xu, ZP Wu, AS Xie, ZC Yue, Y AF Liu, Weiran Xu, Jie Wang, Hui Xu, Chengshi Ji, Chao Wang, Yun Feng, Chunsheng Zhang, Xuena Xu, Zhipeng Wu, Anshi Xie, Zhongcong Yue, Yun TI Isoflurane-induced spatial memory impairment by a mechanism independent of amyloid-beta levels and tau protein phosphorylation changes in aged rats SO NEUROLOGICAL RESEARCH LA English DT Article DE Amyloid-beta; Hippocampus; Isoflurane; Morris water maze; Tau ID POSTOPERATIVE COGNITIVE DYSFUNCTION; NITROUS OXIDE ANESTHESIA; GENERAL-ANESTHETICS; ALZHEIMERS-DISEASE; BRAIN; OLIGOMERIZATION; ACQUISITION; APOPTOSIS AB Objectives: The molecular mechanism of postoperative cognitive dysfunction is largely unknown. Isoflurane has been shown to promote Alzheimer's disease neuropathogenesis. We set out to determine whether the effect of isoflurane on spatial memory is associated with amyloid-beta (A-beta) levels and tau phosphorylation in aged rats. Methods: Eighteen-month-old male Sprague-Dawley rats were randomly assigned as anesthesia group (n=31, received 1.4% isoflurane for 2 hours and had behavioral testing), training group (n=20, received no anesthesia but had behavioral testing), and control group (n=10, received no anesthesia and had no behavioral testing). Spatial memory was measured before and 2 days after the anesthesia by the Morris water maze. We divided the anesthesia group into an isoflurane-induced severe memory impairment group (SIG, n=6) and a no severe memory impairment group (NSIG, n=25), according to whether the escape latency was more than 1.96 stand deviation of that from the training group. Levels of A-beta and tau in the hippocampus were determined by enzyme-linked immunosorbent assay and quantitative western blot at the end of behavioral testing. Results: We found that isoflurane increased the escape latency in the SIG as compared to that in the training group and NSIG without affecting swimming speed. However, there were no differences in the levels of A-beta and tau among SIG, NSIG, training, and control groups. Conclusions: Isoflurane may induce spatial memory impairment through non-A-beta or tau neuropathogenesis mechanisms in aged rats. C1 [Liu, Weiran; Xu, Jie; Wang, Hui; Xu, Chengshi; Wang, Yun; Feng, Chunsheng; Zhang, Xuena; Wu, Anshi; Yue, Yun] Capital Med Univ, Dept Anesthesia, Chaoyang Hosp, Beijing 100020, Peoples R China. [Ji, Chao] Chinese Acad Med Sci, Dept Pharmacol, Sch Basic Med, Peking Union Med Coll, Beijing 100730, Peoples R China. [Ji, Chao] Chinese Acad Med Sci, Inst Basic Med Sci, Beijing 100730, Peoples R China. [Xu, Zhipeng; Xie, Zhongcong] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Charlestown, MA USA. RP Yue, Y (reprint author), Capital Med Univ, Dept Anesthesia, Chaoyang Hosp, 8 Gongtinan Rd, Beijing 100020, Peoples R China. EM yueyun@hotmail.com FU National Nature Science Foundation of China [30872425] FX Our study was supported by National Nature Science Foundation of China (grant no. 30872425). NR 25 TC 11 Z9 15 U1 0 U2 5 PU MANEY PUBLISHING PI LEEDS PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND SN 0161-6412 J9 NEUROL RES JI Neurol. Res. PD JAN PY 2012 VL 34 IS 1 BP 3 EP 10 DI 10.1179/1743132811Y.0000000047 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 870KK UT WOS:000298667900001 PM 22196855 ER PT J AU Li, YX Berenji, GR Shaba, WF Tafti, B Yevdayev, E Dadparvar, S AF Li, Yuxin Berenji, Gholam R. Shaba, Wisam F. Tafti, Bashir Yevdayev, Ella Dadparvar, Simin TI Association of vascular fluoride uptake with vascular calcification and coronary artery disease SO NUCLEAR MEDICINE COMMUNICATIONS LA English DT Article DE atherosclerosis; bone scan; sodium [(18)F] fluoride; positron emission tomography; vascular calcification ID BEAM COMPUTED-TOMOGRAPHY; ATHEROSCLEROTIC PLAQUE; CARDIOVASCULAR EVENTS; PET; CALCIUM; FEASIBILITY; RISK; FLUORODEOXYGLUCOSE; F-18-FLUORIDE; INFLAMMATION AB Objective The feasibility of a fluoride positron emission tomography/computed tomography (PET/CT) scan for imaging atherosclerosis has not been well documented. The purpose of this study was to assess fluoride uptake of vascular calcification in various major arteries, including coronary arteries. Methods We retrospectively reviewed the imaging data and cardiovascular history of 61 patients who received whole-body sodium [(18)F] fluoride PET/CT studies at our institution from 2009 to 2010. Fluoride uptake and calcification in major arteries, including coronary arteries, were analyzed by both visual assessment and standardized uptake value measurement. Results Fluoride uptake in vascular walls was demonstrated in 361 sites of 54 (96%) patients, whereas calcification was observed in 317 sites of 49 (88%) patients. Significant correlation between fluoride uptake and calcification was observed in most of the arterial walls, except in those of the abdominal aorta. Fluoride uptake in coronary arteries was demonstrated in 28 (46%) patients and coronary calcifications were observed in 34 (56%) patients. There was significant correlation between history of cardiovascular events and presence of fluoride uptake in coronary arteries. The coronary fluoride uptake value in patients with cardiovascular events was significantly higher than in patients without cardiovascular events. Conclusion sodium [(18)F] fluoride PET/CT might be useful in the evaluation of the atherosclerotic process in major arteries, including coronary arteries. An increased fluoride uptake in coronary arteries may be associated with an increased cardiovascular risk. Nucl Med Commun 33:14-20 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Berenji, Gholam R.] VA Greater Los Angeles Healthcare Syst, Nucl Med Serv 115, Los Angeles, CA 90073 USA. [Dadparvar, Simin] Univ PA Hlth Syst, Philadelphia, PA USA. RP Berenji, GR (reprint author), VA Greater Los Angeles Healthcare Syst, Nucl Med Serv 115, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM Gholam.Berenji@va.gov NR 33 TC 29 Z9 29 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0143-3636 J9 NUCL MED COMMUN JI Nucl. Med. Commun. PD JAN PY 2012 VL 33 IS 1 BP 14 EP 20 DI 10.1097/MNM.0b013e32834c187e PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 872ZL UT WOS:000298850000003 PM 21946616 ER PT J AU Pemberton, JD Fay, A AF Pemberton, John D. Fay, Aaron TI Idiopathic Sclerosing Orbital Inflammation: A Review of Demographics, Clinical Presentation, Imaging, Pathology, Treatment, and Outcome SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Review ID MULTIFOCAL FIBROSCLEROSIS; RETROPERITONEAL FIBROSIS; RIEDELS THYROIDITIS; CASE SERIES; PSEUDOTUMOR; DISEASE; RITUXIMAB; PATIENT; ENTITY AB Purpose: To characterize clinical features, diagnostics studies, treatments, and outcomes of patients with histologically proven idiopathic sclerosing orbital inflammation (ISOI), to define optimal management for this recalcitrant disease, and to determine changes in characterization and management by comparing our results with the last significant literature review. Methods: A search of the U. S. National Library of Medicine: National Institutes of Health's electronic database for cases and case series in the English literature of biopsy-proven ISOI published between March 1994 and September 2010 was conducted. A cross-literature review was performed to tabulate demographics, clinical findings, studies, treatments, and outcomes, which were compared with the ISOI data published by Rootman et al. (1994). Results: Sixty-one cases, 71 eyes from 17 published reports, met inclusion criteria. No ethnic, sex, or comorbidity predilection was established. Patients typically presented in the fourth decade with proptosis (73%), pain (49%), and normal vision (44%). Orbital imaging and histopathology were sparsely reported. Most common treatments involved systemic corticosteroids either alone (34%) or combined with other modalities (51%). Conclusions: Characteristics of the disease remain unchanged, and best management was not determined due to inconsistent reporting methods across the literature. Collaboration with established groups (i.e., European Group On Graves Orbitopathy (EUGOGO), International Thyroid Eye Disease Society (ITEDS)) or the formation of a new group of physicians and scientists to help develop a systematic approach for future reporting and evaluation was proposed. (Ophthal Plast Reconstr Surg 2012;28:79-83) C1 [Pemberton, John D.; Fay, Aaron] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Pemberton, John D.; Fay, Aaron] Harvard Univ, Sch Med, Dept Ophthalmol, Cambridge, MA 02138 USA. RP Fay, A (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM aaron_fay@meei.harvard.edu OI Pemberton, John/0000-0001-6305-4653 NR 33 TC 15 Z9 16 U1 0 U2 2 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 JAN-FEB PY 2012 VL 28 IS 1 BP 79 EP 83 DI 10.1097/IOP.0b013e318238ecf7 PG 5 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 880EO UT WOS:000299387800042 PM 22262301 ER PT J AU Theodossiadis, PG Theodoropoulou, S Neamonitou, G Grigoropoulo, V Liarakos, V Triantou, E Theodossiadis, GP Vlahakos, DV AF Theodossiadis, Panagiotis G. Theodoropoulou, Sofia Neamonitou, Georgia Grigoropoulo, Vlassis Liarakos, Vasilios Triantou, Eleni Theodossiadis, George P. Vlahakos, Demetrios V. TI Hemodialysis-Induced Alterations in Macular Thickness Measured by Optical Coherence Tomography in Diabetic Patients with End-Stage Renal Disease SO OPHTHALMOLOGICA LA English DT Article DE Macular thickness; Hemodialysis; Optical coherence tomography; Retina ID VISUAL-ACUITY; EDEMA; NEPHROPATHY; RETINOPATHY AB Background/Aims: To evaluate changes in macular thickness measured by optical coherence tomography (OCT) during a hemodialysis (HD) session in diabetic patients with end-stage renal disease. Methods: 72 eyes of 36 diabetic patients with and without macular edema were evaluated before and immediately after an HD session. Average and maximum macular thicknesses in the central disk (6 mm in diameter) and total macular volume were measured. Results: In the eyes with diabetic macular edema, maximum macular thickness within the central disk of 6 mm, and mainly in its peripheral parts, was significantly reduced by 31.18 +/- 4.18 mu m after HD (p < 0.001). Average macular thickness and total macular volume were also significantly reduced (p = 0.003 and 0.015, respectively). In diabetic eyes without edema, maximum macular thickness decreased significantly by 11.21 +/- 1.98 mu m after HD (p < 0.001), while average macular thickness and total macular volume decreased slightly (p = 0.034, p = 0.043). Best-corrected visual acuity failed to change. We found a significant association of macular thickness changes with osmolality reduction and the presence of macular edema. Conclusion: HD decreases macular thickness in diabetic patients with macular edema, while there exists a less-pronounced effect in diabetic eyes without edema. Copyright (C) 2011 S. Karger AG, Basel C1 [Theodossiadis, Panagiotis G.; Neamonitou, Georgia; Liarakos, Vasilios] Univ Athens, Attikon Univ Hosp, Dept Ophthalmol 2, GR-12462 Athens, Greece. [Vlahakos, Demetrios V.] Univ Athens, Attikon Univ Hosp, Renal Unit, GR-12462 Athens, Greece. [Grigoropoulo, Vlassis; Theodossiadis, George P.] Henry Dunant Hosp, Dept Ophthalmol 2, Athens, Greece. [Triantou, Eleni] Henry Dunant Hosp, Renal Unit, Athens, Greece. [Theodoropoulou, Sofia] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. RP Theodossiadis, PG (reprint author), Univ Athens, Attikon Univ Hosp, Dept Ophthalmol 2, 1 Rimini Str, GR-12462 Athens, Greece. EM patheo@med.uoa.gr NR 19 TC 11 Z9 11 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0030-3755 J9 OPHTHALMOLOGICA JI Ophthalmologica PY 2012 VL 227 IS 2 BP 90 EP 94 DI 10.1159/000331321 PG 5 WC Ophthalmology SC Ophthalmology GA 883WH UT WOS:000299665100005 PM 21921588 ER PT J AU Celano, CM Mastromauro, CA Lenihan, EC Januzzi, JL Rollman, BL Huffman, JC AF Celano, Christopher M. Mastromauro, Carol A. Lenihan, Emma C. Januzzi, James L. Rollman, Bruce L. Huffman, Jeff C. TI Association of Baseline Anxiety With Depression Persistence at 6 Months in Patients With Acute Cardiac Illness SO PSYCHOSOMATIC MEDICINE LA English DT Article DE anxiety; cardiac disease; heart failure; depression; myocardial infarction ID ACUTE MYOCARDIAL-INFARCTION; CORONARY-HEART-DISEASE; RANDOMIZED-CONTROLLED-TRIAL; COMORBID MEDICAL ILLNESS; MAJOR DEPRESSION; COLLABORATIVE CARE; ARTERY-DISEASE; ANTIDEPRESSANT TREATMENT; PROGNOSTIC ASSOCIATION; ENHANCING RECOVERY AB Objective: To assess the association of baseline anxiety with depression persistence and change in depressive symptoms 6 months after cardiac hospitalization. Methods: Data were analyzed from 137 depressed patients hospitalized on inpatient cardiac units for acute coronary syndrome, decompensated heart failure, or arrhythmia and who were enrolled in a randomized trial of collaborative care depression management. Subjects' demographic, medical, and psychiatric information at baseline was compiled. Measures of health-related quality of life, cardiac symptoms, and psychiatric symptoms, including the Hospital Anxiety and Depression Scale-anxiety subscale (HADS-A) for anxiety, were obtained at baseline and serially during a 6-month follow-up period. The association between baseline HADS-A score and depression persistence (<50% reduction in depressive symptoms on the Patient Health Questionnaire-9) at 6 months was assessed by multivariate logistic regression accounting for the effects of multiple relevant medical and psychological covariates. The association between baseline HADS-A score and improvement in depressive symptoms (Patient Health Questionnaire-9) from baseline at 6 months was assessed by linear regression accounting for the same covariates. Results: Baseline HADS-A score was independently associated with depression persistence at 6 months (odds ratio = 1.11, 95% confidence interval = 1.01-1.22, p = .03). Likewise, higher baseline HADS-A score was associated with less improvement in depressive symptoms at 6 months (A = -0.34, p = .01). Conclusions: Among a cohort of depressed cardiac patients, higher baseline anxiety score was linked with lesser improvement in depressive symptoms and increased likelihood of depression persistence at 6 months, independent of multiple relevant covariates. Trial Registration: clinicaltrials.gov Identifier: NCT00847132. C1 [Celano, Christopher M.; Mastromauro, Carol A.; Lenihan, Emma C.; Huffman, Jeff C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Celano, Christopher M.; Mastromauro, Carol A.; Lenihan, Emma C.; Januzzi, James L.; Huffman, Jeff C.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Januzzi, James L.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Rollman, Bruce L.] Univ Pittsburgh, Dept Med, Div Gen Internal Med, Pittsburgh, PA USA. RP Celano, CM (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Warren 605,55 Fruit St, Boston, MA 02114 USA. EM ccelano@partners.org FU American Heart Association [0735530T] FX This study was supported by the American Heart Association Scientist Development Grant 0735530T (Dr. Huffman). NR 55 TC 14 Z9 14 U1 2 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD JAN PY 2012 VL 74 IS 1 BP 93 EP 99 DI 10.1097/PSY.0b013e31823d3d38bc PG 7 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 880UW UT WOS:000299434400013 PM 22210240 ER PT J AU Robertson, SM Stanley, MA Cully, JA Naik, AD AF Robertson, Suzanne M. Stanley, Melinda A. Cully, Jeffrey A. Naik, Aanand D. TI Positive Emotional Health and Diabetes Care: Concepts, Measurement, and Clinical Implications SO PSYCHOSOMATICS LA English DT Review ID QUALITY-OF-LIFE; TREATMENT SATISFACTION; GLYCEMIC CONTROL; PSYCHOLOGICAL ADJUSTMENT; CONTROLLED TRIAL; SELF-MANAGEMENT; NEGATIVE AFFECT; MOOD; RESILIENCE; PEOPLE AB Background: Numerous studies describe the effect of emotional problems, including diabetes-related distress and depression, on diabetes outcomes. Little attention has been devoted to positive emotional health and its potential role in facilitating patients' self-management and improved outcomes. Objective: This review describes the conceptualization and measurement of three empirically-tested aspects of positive emotional health (well-being, positive affect, resilience) in the diabetes literature and their relationship to diabetes outcomes. Method: A literature review was conducted using PubMed and the Cochrane Library databases from 1970 to January 2011 to identify studies focused on well-being, positive affect, and resilience in diabetes patients. Results: Twenty-two studies were identified based on our inclusion criteria. Well-being studies were least. likely to include conceptualizations and relied on two primary measurement instruments compared to more heterogeneous presentations found in positive affect and resilience studies. All three aspects of positive emotional health were linked to health-related outcomes and self-management. Conclusion: Positive emotional health may facilitate chronic care self-management and improved health outcomes. We present a model to guide future research and intervention development efforts designed to enhance positive emotional health. (Psychosomatics 2012; 53:1-12) C1 [Robertson, Suzanne M.; Stanley, Melinda A.; Cully, Jeffrey A.; Naik, Aanand D.] Houston Hlth Serv Res & Dev Ctr Excellence, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. [Stanley, Melinda A.; Cully, Jeffrey A.; Naik, Aanand D.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Stanley, Melinda A.; Cully, Jeffrey A.; Naik, Aanand D.] VA S Cent Mental Illness Res Educ & Clin Ctr, Houston, TX USA. RP Robertson, SM (reprint author), Houston VA Hlth Serv Res & Dev Ctr Excellence, Michael E DeBakey VA Med Ctr, 2002 Holcombe Blvd,MEDVAMC 152, Houston, TX 77030 USA. EM smr1@bcm.tmc.edu FU Houston VA Health Services Research and Development Center of Excellence [HFP90-020]; VA Office of Academic Affiliations; National Institute of Aging [5K23AG027144]; Doris Duke Charitable Foundation FX This review is supported with resources and the use of facilities at the Houston VA Health Services Research and Development Center of Excellence (HFP90-020) at the Michael E. DeBakey VA Medical Center, Houston, TX Suzanne M. Robertson is a VA HSR post-doctoral fellow supported by VA Office of Academic Affiliations. Aanand D. Naik receives support from a National Institute of Aging Career Development Award (5K23AG027144) and a Doris Duke Charitable Foundation Clinical Scientist Development Award. The views expressed reflect those of the authors and not necessarily those of the Department of Veterans Affairs or Baylor College of Medicine. NR 47 TC 9 Z9 9 U1 2 U2 10 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 JAN-FEB PY 2012 VL 53 IS 1 BP 1 EP 12 PG 12 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 882TB UT WOS:000299585700001 PM 22221716 ER PT J AU Silverman, BC Stern, TW Gross, AF Rosenstein, DL Stern, TA AF Silverman, Benjamin C. Stern, Thomas W. Gross, Anne F. Rosenstein, Donald L. Stern, Theodore A. TI Lewd, Crude, and Rude Behavior: The Impact of Manners and Etiquette in the General Hospital SO PSYCHOSOMATICS LA English DT Article ID MEDICAL ETIQUETTE; DOCTORS; PSYCHIATRISTS; APPEARANCE; ATTITUDES; PATIENT; ATTIRE; ETHICS; CARE AB Background: Lewd, crude, and rude behaviors of patients and stall members have the potential to complicate care; unfortunately, the medical literature on manners and etiquette is sparse. Objective: We sought to understand the impact of lewd, crude, and rude behaviors in the general hospital and to provide a context in which to educate clinicians about the management of troublesome behaviors of patients and staff members. Method: We reviewed the history of etiquette in the general hospital, and discuss the ethical ramifications and clinical management of inappropriate behaviors. Results: Lewd, crude, and rude language and behaviors are often heard and seen in the general hospital: such behaviors can be understood in a biopsychosocial context. Conclusions: Teaching trainees about manners and etiquette can help them identify and manage offensive behaviors and can facilitate the provision of effective and ethical care. (Psychosomatics 2012; 53:13-20) C1 [Silverman, Benjamin C.; Stern, Thomas W.; Gross, Anne F.; Stern, Theodore A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Rosenstein, Donald L.] Univ N Carolina, Sch Med, Dept Psychiat, Chapel Hill, NC USA. RP Silverman, BC (reprint author), Adm Bldg,Rm G12D,115 Mill St, Boston, MA 02478 USA. EM bcsilverman@partners.org NR 43 TC 1 Z9 1 U1 1 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 JAN-FEB PY 2012 VL 53 IS 1 BP 13 EP 20 PG 8 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 882TB UT WOS:000299585700002 PM 22221717 ER PT J AU Coleman, SM Blashill, AJ Gandhi, RT Safren, SA Freudenreich, O AF Coleman, Shane M. Blashill, Aaron J. Gandhi, Rajesh T. Safren, Steven A. Freudenreich, Oliver TI Impact of Integrated and Measurement-Based Depression Care: Clinical Experience in an HIV Clinic SO PSYCHOSOMATICS LA English DT Article ID STAR-ASTERISK-D; ACTIVE ANTIRETROVIRAL THERAPY; CORONARY-HEART-DISEASE; INFECTED PATIENTS; HEALTH-CARE; METAANALYSIS; OUTCOMES; EPIDEMIOLOGY; OUTPATIENTS; DISORDERS AB Background: Just as in heart disease and diabetes, depression in HIV/AIDS is associated with negative outcomes. While randomized trials have shown the efficacy of treatment for depression in HIV/AIDS, the implementation of evidence-based treatments in real-world settings remains a challenge. Objective: The objective of this study was to assess the effectiveness of a collaborative, measurement-based approach to depression care, including psychopharmacologic and ancillary psychological therapies in patients with HIV/AIDS and to examine whether or not effective depression treatment would also improve virologic and immunologic outcomes. Methods: This was a retrospective chart review of patients referred for depression to a co-located psychiatry consultation service embedded within an infectious diseases outpatient clinic at an urban tertiary hospital. Data extracted at initial assessment and at last appointment included: axis 1 diagnosis, whether the patient was on an antidepressant, whether the patient was on a stimulant, BDI-II score, HIV RNA level, and CD4 cell count. Results: One hundred twenty-four patient charts were included. Pre- vs. post-treatment analyses revealed significant reductions in depression (average BDI-II score of 23 to 15.7, p = 0.00001) and HIV RNA (14.1 K to 4 K copies/mL, p = 0.003), and significant increases in CD4 count (518 to 592 cells/mu L, p = 0.001). Additionally, more participants were prescribed antidepressants and stimulants at post- vs. pre-treatment. Conclusion: Taking a collaborative, measurement-based approach to depression care appears to be an effective method for improving depression, virologic, and immunologic outcomes in depressed patients with HIV/AIDS illness. (Psychosomatics 2012; 53:51-57) C1 [Coleman, Shane M.] Univ Washington, Sch Med, Dept Psychiat, Seattle, WA 98195 USA. [Coleman, Shane M.; Blashill, Aaron J.; Gandhi, Rajesh T.; Safren, Steven A.; Freudenreich, Oliver] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Coleman, Shane M.; Blashill, Aaron J.; Gandhi, Rajesh T.; Safren, Steven A.; Freudenreich, Oliver] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Coleman, SM (reprint author), Univ Washington, Sch Med, Dept Psychiat, 1959 NE Pacific St,Box 356560, Seattle, WA 98195 USA. EM smc9@u.washington.edu NR 33 TC 5 Z9 6 U1 0 U2 6 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 JAN-FEB PY 2012 VL 53 IS 1 BP 51 EP 57 PG 7 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 882TB UT WOS:000299585700007 PM 22221721 ER PT J AU Braun, IM Rao, SR Pirl, WF AF Braun, Ilana M. Rao, Sowmya R. Pirl, William F. TI Comparison of Self-reported Cognitive Difficulties in a National Sample of Long-Term Cancer Survivors and Cancer-Naive Controls SO PSYCHOSOMATICS LA English DT Article ID COMORBIDITY SURVEY REPLICATION; MAJOR DEPRESSIVE DISORDER; BREAST-CANCER; ADJUVANT CHEMOTHERAPY; MENOPAUSAL SYMPTOMS; NCS-R; FATIGUE; WOMEN; DEFICITS AB Background: Evidence that long-term cancer survivors (LTCS) experience greater cognitive dysfunction than individuals without cancer is mixed. This analysis of a population-based sample of United States residents compares self-reported cognitive difficulties in LTCS and cancer naive controls (CNC), controlling for psychiatric disorders. Methods: National Comorbidity Survey-Replication (NCS-R) interviews were conducted in a nationally-representative sample of 9282 people, of whom 5692 were assessed for cancer history. Long-term survivors of adult cancers were defined as individuals who were at least 18 years old at time of diagnosis; greater than 5 years following diagnosis; and with cancer reportedly in remission or cured. Cognitive dysfunction queries included two screening questions and five items drawn than the World Health Organization (WHO) Disability Assessment Schedule 2.0. Psychiatric disorders were identified using the WHO's Composite International Diagnostic Interview. Odds ratios and 95% confidence intervals were obtained from multi-variable logistic regression models fit to evaluate the relationship between cancer status (LTCS versus CNC) and cognitive symptoms. Results: Of NCS-R participants, 225 met criteria for LTCS and 3953 for CNC. Long-term cancer survivors and CNC screened positive for cognitive symptoms at a rate of 19.5% and 20.8%, respectively, for the first screen and 16.0% and 16.4%, respectively, for the second. Adjusting for demographic and psychiatric variables, LTCS did not carry increased odds of experiencing cognitive symptoms [(OR) 1.00 (95% CI, .59 to 1.68); (OR) .95 (95 %CI, .57 to 1.59)] Conclusions: Self-reported cognitive symptoms are common among LTCS and CNC. LTCS do not report cognitive symptoms with greater frequency. (Psychosomatics 2012; 53:68-74) C1 [Braun, Ilana M.] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02215 USA. [Rao, Sowmya R.] Univ Massachusetts, Sch Med, Worcester, MA USA. [Rao, Sowmya R.] Vet Adm, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Pirl, William F.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Braun, IM (reprint author), Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Shields Warren 442B,450 Brookline Ave, Boston, MA 02215 USA. EM ibraun@partners.org NR 18 TC 3 Z9 3 U1 0 U2 2 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 JAN-FEB PY 2012 VL 53 IS 1 BP 68 EP 74 PG 7 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 882TB UT WOS:000299585700009 PM 22221723 ER PT J AU Pichurko Ruppel Kaminsky Busse Coates Rundell, KW Hess, DR Hnatiuk Enright Salzman AF Pichurko Ruppel Kaminsky Busse Coates Rundell, Kenneth W. Hess, Dean R. Hnatiuk Enright Salzman TI What Does Airway Resistance Tell Us About Lung Function? Discussion SO RESPIRATORY CARE LA English DT Editorial Material C1 [Rundell, Kenneth W.] Pharmaxis, Exton, PA USA. [Hess, Dean R.] Massachusetts Gen Hosp, Resp Care Serv, Boston, MA 02114 USA. NR 2 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 JAN PY 2012 VL 57 IS 1 SI SI BP 96 EP 99 PG 4 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 880IA UT WOS:000299399600015 ER PT J AU Saperstein, AM Thysen, J Medalia, A AF Saperstein, Alice M. Thysen, Julie Medalia, Alice TI The Measure of Insight into Cognition: Reliability and validity of clinician-rated and self-report scales of neurocognitive insight for schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Neurocognition; Insight ID PSYCHOSIS; ILLNESS; CONSEQUENCES; PERFORMANCE; DEPRESSION; AWARENESS; SYMPTOMS; DEFICITS AB Poor insight into the neurocognitive deficits in schizophrenia-spectrum disorders may have significant clinical implications for treatment. The purpose of this study was to replicate and extend the psychometric findings initially reported on the Measure of Insight into Cognition Clinician-Rated (MIC-CR) and Self-Report (MIC-SR) which assess awareness, attribution, and frequency of neurocognitive deficits. Assessments conducted one week apart allowed for internal consistency, test-retest reliability, concurrent validity, and administration order effects to be determined. In this study sample (N = 80), 73 demonstrated significant neurocognitive impairment, yet on the MIC-CR, the average awareness and attribution scores indicated only partial awareness and attribution of neurocognitive deficits. The average MIC-SR score indicated rare frequency of cognitive difficulty in everyday life. Cronbach's alphas for the MIC-CR (0.83) and MIC-SR (0.93) were consistent with the initial validation study; test-retest reliability for both MIC assessments was significant (p < 0.001). In new analyses, concurrent validity was demonstrated by significant correlations between the MIC-CR and MIC-SR in the first validation sample: r=-0.75 (p < 0.001) and the current replication sample: r=-0.70 (p < 0.001). Effect sizes were large when frequencies of neurocognitive complaints (MIC-SR) were compared between subjects with good versus poor awareness on the MIC-CR. Reliability and concurrent validity results were similar and significant regardless of order of MIC-CR and MIC-SR administration. The MIC-CR and MIC-SR are thus reliable and valid complementary instruments to assess neurocognitive insight in people with schizophrenia spectrum disorders. (C) 2011 Elsevier B.V. All rights reserved. C1 [Saperstein, Alice M.; Medalia, Alice] Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. [Thysen, Julie] James J Peters VA Med Ctr, Mt Sinai Sch Med, Bronx, NY 10468 USA. RP Saperstein, AM (reprint author), Columbia Univ Coll Phys & Surg, Dept Psychiat, 1051 Riverside Dr, New York, NY 10032 USA. EM saperst@nyspi.columbia.edu; am2938@columbia.edu FU Eli Lilly [F1D-US-X310] FX This research was supported by an Eli Lilly Investigator Initiated Trial, Grant # F1D-US-X310, PI: Alice Medalia, PhD. This institution had no further role in the study design, in the collection, analysis or interpretation of data, in writing the report, or in the decision to submit the paper for publication. NR 24 TC 5 Z9 5 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JAN PY 2012 VL 134 IS 1 BP 54 EP 58 DI 10.1016/j.schres.2011.10.002 PG 5 WC Psychiatry SC Psychiatry GA 881NH UT WOS:000299492900009 PM 22036020 ER PT J AU Kwiatkowski, N Deng, XM Wang, JH Tan, L Villa, F Santaguida, S Huang, HC Mitchison, T Musacchio, A Gray, N AF Kwiatkowski, Nicholas Deng, Xianming Wang, Jinhua Tan, Li Villa, Fabrizio Santaguida, Stefano Huang, Hsiao-Chun Mitchison, Tim Musacchio, Andrea Gray, Nathanael TI Selective Aurora Kinase Inhibitors Identified Using a Taxol-Induced Checkpoint Sensitivity Screen SO ACS CHEMICAL BIOLOGY LA English DT Article ID SMALL-MOLECULE INHIBITOR; A KINASE; B KINASE; HUMAN-CELLS; SPINDLE CHECKPOINT; PROTEIN-KINASE; TUMOR-GROWTH; IN-VIVO; ACTIVATION; COMPLEX AB The members of the Aurora kinase family play critical roles in the regulation of the cell cycle and mitotic spindle assembly and have been intensively investigated as potential targets for a new class of anticancer drugs. We describe a new highly potent and selective class of Aurora kinase inhibitors discovered using a phenotypic cellular screen. Optimized inhibitors display many of the hallmarks of Aurora inhibition including endoreduplication, polyploidy, and loss of cell viability in cancer cells. Structure activity relationships with respect to kinome-wide selectivity and guided by an Aurora B co-crystal structure resulted in the identification of key selectivity determinants and discovery of a subseries with selectivity toward Aurora A. A direct comparison of biochemical and cellular profiles with respect to published Aurora inhibitors including VX-680, AZD1152, MLN8054, and a pyrimidine-based compound from Genentech demonstrates that compounds 1 and 3 will become valuable additional pharmacological probes of Aurora-dependent functions. C1 [Kwiatkowski, Nicholas; Deng, Xianming; Wang, Jinhua; Tan, Li; Gray, Nathanael] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Kwiatkowski, Nicholas; Deng, Xianming; Wang, Jinhua; Tan, Li; Gray, Nathanael] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Huang, Hsiao-Chun; Mitchison, Tim] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Villa, Fabrizio; Santaguida, Stefano; Musacchio, Andrea] European Inst Oncol, Dept Expt Oncol, I-20139 Milan, Italy. [Musacchio, Andrea] Max Planck Inst Mol Physiol, D-44227 Dortmund, Germany. RP Gray, N (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA. EM nathanael_gray@dfci.harvard.edu RI villa, fabrizio/G-5757-2012; OI Santaguida, Stefano/0000-0002-1501-6190; Musacchio, Andrea/0000-0003-2362-8784 FU NIH [CA130876-03, HG005693-02, U54 HG006097-01, U54 HG006097, IRC2HG005693]; Italian Association for Cancer Research; Italian Foundation for Cancer Research FX We thank DiscoveRx (Ambit Biosciences) for performing KINOMEscan, Life Technologies Corporation for performing SelectScreen Kinase Profiling and ActivX for performing KiNativ analysis, as well as the Nikon Imaging Facility (HMS) and the Dana Farber Flow Cytometry Lab (DFCI) for technical help and instrument use. Funding was provided by NIH grants CA130876-03, HG005693-02, U54 HG006097-01. The HMS LINCS Center is funded by NIH U54 HG006097, and NIH Grand Opportunities grant IRC2HG005693. A.M. acknowledges generous funding from the Italian Association for Cancer Research. S.S. is supported by a fellowship from the Italian Foundation for Cancer Research. NR 49 TC 11 Z9 11 U1 0 U2 15 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1554-8929 J9 ACS CHEM BIOL JI ACS Chem. Biol. PD JAN PY 2012 VL 7 IS 1 BP 185 EP 196 DI 10.1021/cb200305u PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 878FQ UT WOS:000299241300020 PM 21992004 ER PT J AU Vendelbo, MH Clasen, BFF Treebak, JT Moller, L Krusenstjerna-Hafstrom, T Madsen, M Nielsen, TS Stodkilde-Jorgensen, H Pedersen, SB Jorgensen, JOL Goodyear, LJ Wojtaszewski, JFP Moller, N Jessen, N AF Vendelbo, M. H. Clasen, B. F. F. Treebak, J. T. Moller, L. Krusenstjerna-Hafstrom, T. Madsen, M. Nielsen, T. S. Stodkilde-Jorgensen, H. Pedersen, S. B. Jorgensen, J. O. L. Goodyear, L. J. Wojtaszewski, J. F. P. Moller, N. Jessen, N. TI Insulin resistance after a 72-h fast is associated with impaired AS160 phosphorylation and accumulation of lipid and glycogen in human skeletal muscle SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE Akt substrate of 160 kDa; skeletal muscle metabolism; fasting; insulin resistance in vivo; insulin signaling; TBC1D4 ID ACTIVATED PROTEIN-KINASE; FREE FATTY-ACIDS; SITE-SPECIFIC PHOSPHORYLATION; GLUCOSE-TRANSPORT; TBC1D1 PHOSPHORYLATION; GENE-EXPRESSION; POTENTIAL ROLE; 14-3-3 BINDING; EXERCISE; METABOLISM AB Vendelbo MH, Clasen BF, Treebak JT, Moller L, Krusenstjerna-Hafstrom T, Madsen M, Nielsen TS, Stodkilde-Jorgensen H, Pedersen SB, Jorgensen JO, Goodyear LJ, Wojtaszewski JF, Moller N, Jessen N. Insulin resistance after a 72-h fast is associated with impaired AS160 phosphorylation and accumulation of lipid and glycogen in human skeletal muscle. Am J Physiol Endocrinol Metab 302: E190-E200, 2012. First published October 25, 2011; doi: 10.1152/ajpendo.00207.2011.-During fasting, human skeletal muscle depends on lipid oxidation for its energy substrate metabolism. This is associated with the development of insulin resistance and a subsequent reduction of insulin-stimulated glucose uptake. The underlying mechanisms controlling insulin action on skeletal muscle under these conditions are unresolved. In a randomized design, we investigated eight healthy subjects after a 72-h fast compared with a 10-h overnight fast. Insulin action on skeletal muscle was assessed by a hyperinsulinemic euglycemic clamp and by determining insulin signaling to glucose transport. In addition, substrate oxidation, skeletal muscle lipid content, regulation of glycogen synthesis, and AMPK signaling were assessed. Skeletal muscle insulin sensitivity was reduced profoundly in response to a 72-h fast and substrate oxidation shifted to predominantly lipid oxidation. This was associated with accumulation of both lipid and glycogen in skeletal muscle. Intracellular insulin signaling to glucose transport was impaired by regulation of phosphorylation at specific sites on AS160 but not TBC1D1, both key regulators of glucose uptake. In contrast, fasting did not impact phosphorylation of AMPK or insulin regulation of Akt, both of which are established upstream kinases of AS160. These findings show that insulin resistance in muscles from healthy individuals is associated with suppression of site-specific phosphorylation of AS160, without Akt or AMPK being affected. This impairment of AS160 phosphorylation, in combination with glycogen accumulation and increased intramuscular lipid content, may provide the underlying mechanisms for resistance to insulin in skeletal muscle after a prolonged fast. C1 [Vendelbo, M. H.; Clasen, B. F. F.; Moller, L.; Krusenstjerna-Hafstrom, T.; Madsen, M.; Nielsen, T. S.; Pedersen, S. B.; Jorgensen, J. O. L.; Moller, N.; Jessen, N.] Aarhus Univ Hosp, Dept Internal Med & Endocrinol, DK-8000 Aarhus, Denmark. [Clasen, B. F. F.; Nielsen, T. S.; Jessen, N.] Aarhus Univ Hosp, Dept Clin Pharmacol, DK-8000 Aarhus, Denmark. [Treebak, J. T.; Wojtaszewski, J. F. P.] Univ Copenhagen, Dept Exercise & Sport Sci, Mol Physiol Grp, Copenhagen, Denmark. [Stodkilde-Jorgensen, H.] Aarhus Univ Hosp, Magnet Resonance Res Ctr, DK-8000 Aarhus, Denmark. [Goodyear, L. J.] Brigham & Womens Hosp, Joslin Diabet Ctr, Boston, MA 02115 USA. [Goodyear, L. J.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Goodyear, L. J.] Harvard Univ, Sch Med, Boston, MA USA. RP Jessen, N (reprint author), Aarhus Univ Hosp NBG, Dept Clin Pharmacol, DK-8000 Aarhus C, Denmark. EM Niels.Jessen@farm.au.dk RI Wojtaszewski, Jorgen /P-6583-2014; Moller, Niels/E-5091-2011; Treebak, Jonas/B-4521-2017; OI Wojtaszewski, Jorgen /0000-0001-9785-6830; Moller, Niels/0000-0001-5627-7322; Treebak, Jonas/0000-0003-1488-7012; Stodkilde-Jorgensen, Hans/0000-0002-8649-4173; Pedersen, Steen B./0000-0002-7838-8063; Jorgensen, Jens Otto Lunde/0000-0001-7408-1526; Jessen, Niels/0000-0001-5613-7274 FU Danish Agency for Science Technology and Innovation [271-07-0719]; Lundbeck Foundation; Danish Medical Research Council; Danish Ministry of Science, Technology, and Innovation; FOOD Study Group/Danish Ministry of Food, Agriculture, and Fisheries; Ministry of Family and Consumer Affairs [2101-05-0044] FX This work was supported by Danish Agency for Science Technology and Innovation Grant 271-07-0719 (to N. Jessen), the Lundbeck Foundation, and the Danish Medical Research Council. The Molecular Physiology Group, Department of Exercise and Sport Sciences, is part of the UNIK Project: Food, Fitness, and Pharma for Health and Disease, which is supported by the Danish Ministry of Science, Technology, and Innovation (to J. F. P. Wojtaszewski); the FOOD Study Group/Danish Ministry of Food, Agriculture, and Fisheries; and Ministry of Family and Consumer Affairs Grant 2101-05-0044 (to N. Moller). NR 55 TC 24 Z9 24 U1 3 U2 13 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD JAN PY 2012 VL 302 IS 2 BP E190 EP E200 DI 10.1152/ajpendo.00207.2011 PG 11 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 876MX UT WOS:000299112700004 PM 22028408 ER PT J AU Smith, GE Camp, C Cooley, S Gonzalez, HM Hartman-Stein, P LaRue, A Pachana, NA Zeiss, A AF Smith, Glenn E. Camp, Cameron Cooley, Susan Gonzalez, Hector M. Hartman-Stein, Paula LaRue, Asenath Pachana, Nancy A. Zeiss, Antonette CA Amer Psychological Assoc TI Guidelines for the Evaluation of Dementia and Age-Related Cognitive Change SO AMERICAN PSYCHOLOGIST LA English DT Article ID DIAGNOSTIC-CRITERIA; ALZHEIMERS-DISEASE; INFORMANT INTERVIEW; IMPAIRMENT; PREVALENCE; MANAGEMENT; AGITATION; CONSENSUS C1 [Smith, Glenn E.] Mayo Clin, Coll Med, Dept Psychiat & Psychol, Rochester, MN USA. [Camp, Cameron] Hearthstone Alzheimer Care, Res & Prod Dev, Woburn, MA USA. [Cooley, Susan] US Dept Vet Affairs, Off Geriatr & Extended Care, Geriatr Res & Dev & Dementia Initiat, Washington, DC USA. [Gonzalez, Hector M.] Wayne State Univ, Inst Gerontol, Detroit, MI 48202 USA. [Gonzalez, Hector M.] Wayne State Univ, Dept Family Med & Publ Hlth Sci, Detroit, MI 48202 USA. [Hartman-Stein, Paula] Ctr Hlth Aging, Kent, OH USA. [Hartman-Stein, Paula] Kent State Univ, E Liverpool, OH USA. [LaRue, Asenath] Univ Wisconsin, Wisconsin Alzheimers Inst, Madison, WI 53706 USA. [Pachana, Nancy A.] Univ Queensland, Sch Psychol, Brisbane, Qld 4072, Australia. [Pachana, Nancy A.] Univ Queensland, Ageing Mind Initiat, Brisbane, Qld 4072, Australia. [Zeiss, Antonette] US Dept Vet Affairs, Off Patient Care Serv, Off Mental Hlth Serv, Washington, DC USA. RP Smith, GE (reprint author), Amer Psychol Assoc, Publ Interest Directorate, Off Aging, 750 1st St,NE, Washington, DC 20002 USA. NR 41 TC 13 Z9 13 U1 2 U2 7 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0003-066X J9 AM PSYCHOL JI Am. Psychol. PD JAN PY 2012 VL 67 IS 1 BP 1 EP 9 DI 10.1037/a0024643 PG 9 WC Psychology, Multidisciplinary SC Psychology GA 878BP UT WOS:000299226800001 ER PT J AU Teixido, M Kung, B Rosowski, JJ Merchant, SN AF Teixido, Michael Kung, Brian Rosowski, John J. Merchant, Saumil N. TI Histopathology of the Temporal Bone in a Case of Superior Canal Dehiscence Syndrome SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE aural fullness; otopathology; superior canal dehiscence; temporal bone histopathology; tinnitus ID TULLIO PHENOMENON; HEARING; VERTIGO; SOUND AB Objectives: We describe the histopathologic findings in the temporal bones of a patient who had, during life, received a diagnosis of superior canal dehiscence (SCD) syndrome. Methods: The patient was found to have SCD syndrome at 59 years of age. She became a temporal bone donor, and died of unrelated causes at 62 years of age. Both temporal bones were prepared in celloidin and examined by light microscopy. Results: The patient developed bilateral aural fullness, pulsatile tinnitus, and difficulty tolerating loud noises after minor head trauma at 53 years of age. The symptoms were worse on the right. She also had Valsalva-induced dizziness and eye movements, as well as sound-induced dizziness (more prominent on the right). Audiometry showed a small air-bone gap of 10 dB in the right ear. Vestibular evoked myogenic potential testing showed an abnormally low threshold of 66 dB on the right, and a computed tomography scan showed dehiscence of the superior canal on the right. Histopathologic examination of the right ear showed a 1.4 x 0.6-mm dehiscence of bone covering the superior canal. Dura was in direct contact with the endosteum and the membranous duct at the level of the dehiscence. No osteoclastic process was evident within the otic capsule bone surrounding the dehiscence. The left ear showed thin but intact bone over the superior canal. Both ears showed focal microdehiscences of the tegmen tympani and tegmen mastoideum. The auditory and vestibular sense organs on both sides appeared normal. No endolymphatic hydrops was observed. Conclusions: The findings were consistent with the hypothesis put forth by Carey and colleagues that SCD may arise from a failure of postnatal bone development, and that minor trauma may disrupt thin bone or stable dura over the superior canal. C1 [Rosowski, John J.; Merchant, Saumil N.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Rosowski, John J.; Merchant, Saumil N.] Harvard Univ, Sch Med, Boston, MA USA. [Teixido, Michael; Kung, Brian] Christiana Care Hlth Syst, Dept Otolaryngol, Wilmington, DE USA. RP Merchant, SN (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. FU NIH [U24 DC011943] FX From the Department of Otolaryngology, Christiana Care Health System, Wilmington, Delaware (Teixido, Kung), and the Department of Otolaryngology, Massachusetts Eye and Ear Infirmary and Harvard Medical School, Boston, Massachusetts (Rosowski, Merchant). This work was supported by NIH grant U24 DC011943. NR 14 TC 8 Z9 8 U1 0 U2 1 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD JAN PY 2012 VL 121 IS 1 BP 7 EP 12 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA 879TS UT WOS:000299355700002 PM 22312921 ER PT J AU Friedmann, DR Eubig, J Winata, LS Pramanik, BK Merchant, SN Lalwani, AK AF Friedmann, David R. Eubig, Jan Winata, Leon S. Pramanik, Bidyut K. Merchant, Saumil N. Lalwani, Anil K. TI A Clinical and Histopathologic Study of Jugular Bulb Abnormalities SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID SEMICIRCULAR CANAL DEHISCENCE AB Objective: To further define the spectrum of clinical presentation and explore the histologic sequelae of jugular bulb abnormalities (JBAs). Design: Retrospective review. Setting: Academic medical center. Patients: Thirty patients with radiologic evidence of inner ear dehiscence by JBA. Main Outcome Measure: Thirty patients with radiologic inner ear dehiscence by JBA and 1579 temporal bone specimens were evaluated for consequences from JBA. Results: We found that JBA-associated inner ear dehiscence could be identified on computed tomography of the temporal bone but not on magnetic resonance imaging scan. Jugular bulb abnormalities eroded the vestibular aqueduct most often (in 25 patients), followed by the facial nerve (5 patients) and the posterior semicircular canal (4 patients). Half of the patients (15) were asymptomatic. Results from vestibular evoked myogenic potential (VEMP) tests were positive in 8 of 12 patients with inner ear dehiscence. Histologically, only 2 of 41 temporal bones with dehiscence of the vestibular aqueduct demonstrated endolymphatic hydrops. Conclusions: Jugular bulb abnormalities can erode into the vestibular aqueduct, facial nerve, and the posterior semicircular canal. While symptoms may include pulsatile tinnitus, vertigo, or conductive hearing loss, in contrast to earlier reports, half of the patients were asymptomatic. Dehiscence of vestibular aqueduct rarely leads to clinical or histologic hydrops. The VEMP testing was useful in confirming the presence of inner ear dehiscence due to JBAs. Because the natural history of JBAs is unknown, these patients should be followed closely to evaluate for progression of the JBA or development of symptoms. C1 [Friedmann, David R.; Lalwani, Anil K.] NYU, Sch Med, Dept Otolaryngol, New York, NY 10016 USA. [Eubig, Jan; Pramanik, Bidyut K.] NYU, Sch Med, Dept Radiol, New York, NY 10016 USA. [Lalwani, Anil K.] NYU, Sch Med, Dept Pediat, New York, NY 10016 USA. [Lalwani, Anil K.] NYU, Sch Med, Dept Physiol & Neurosci, New York, NY 10016 USA. [Winata, Leon S.; Merchant, Saumil N.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. RP Lalwani, AK (reprint author), NYU, Sch Med, Dept Otolaryngol, 550 1st Ave,7Q, New York, NY 10016 USA. EM anil.lalwani@nyumc.org FU National Institutes of Health [U24DC011943] FX This work was supported in part by National Institutes of Health grant U24DC011943 to Dr Merchant. NR 11 TC 16 Z9 16 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD JAN PY 2012 VL 138 IS 1 BP 66 EP 71 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 876TT UT WOS:000299131300012 PM 22249632 ER PT J AU Hill, CA Gallagher, TQ Maturo, S Sadow, PM Curtin, HD Hartnick, CJ AF Hill, Courtney A. Gallagher, Thomas Q. Maturo, Stephen Sadow, Peter M. Curtin, Hugh D. Hartnick, Christopher J. TI Radiology Quiz Case 1 Congenital cyst of the newborn SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Editorial Material ID LARYNGEAL CYSTS; CANCER C1 [Hill, Courtney A.; Gallagher, Thomas Q.; Maturo, Stephen; Sadow, Peter M.; Curtin, Hugh D.; Hartnick, Christopher J.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02115 USA. RP Hill, CA (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02115 USA. NR 9 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 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD JAN PY 2012 VL 138 IS 1 BP 87 EP 89 PG 3 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 876TT UT WOS:000299131300017 PM 22249637 ER PT J AU Dwojak, SM Hunt, JL Cunningham, MJ AF Dwojak, Sunshine M. Hunt, Jennifer L. Cunningham, Michael J. TI Pathology Quiz Case 3: Neuroblastoma with cervical metastases SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Editorial Material ID PROGNOSIS; TUMORS C1 [Dwojak, Sunshine M.; Cunningham, Michael J.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Hunt, Jennifer L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Dwojak, Sunshine M.; Hunt, Jennifer L.; Cunningham, Michael J.] Harvard Univ, Sch Med, Boston, MA USA. RP Dwojak, SM (reprint author), Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 10 TC 0 Z9 0 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD JAN PY 2012 VL 138 IS 1 BP 99 EP 101 PG 3 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 876TT UT WOS:000299131300022 PM 22249642 ER PT J AU Naeser, MA Martin, PI Ho, M Treglia, E Kaplan, E Bashir, S Pascual-Leone, A AF Naeser, Margaret A. Martin, Paula I. Ho, Michael Treglia, Ethan Kaplan, Elina Bashir, Shahid Pascual-Leone, Alvaro TI Transcranial Magnetic Stimulation and Aphasia Rehabilitation SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Aphasia; Rehabilitation; Stroke; Transcranial magnetic stimulation ID HUMAN MOTOR CORTEX; PARADOXICAL FUNCTIONAL FACILITATION; INFERIOR PREFRONTAL CORTEX; NONFLUENT APHASIA; POSTSTROKE APHASIA; IMPROVED LANGUAGE; RIGHT-HEMISPHERE; PARS TRIANGULARIS; BRAIN PLASTICITY; PREMOTOR CORTEX AB Repetitive transcranial magnetic stimulation (rTMS) has been reported to improve naming in chronic stroke patients with nonfluent aphasia since 2005. In part 1, we review the rationale for applying slow, 1-Hz, rTMS to the undamaged right hemisphere in chronic nonfluent aphasia patients after a left hemisphere stroke; and we present a transcranial magnetic stimulation (TMS) protocol used with these patients that is associated with long-term, improved naming post-TMS. In part 2, we present results from a case study with chronic nonfluent aphasia where TMS treatments were followed immediately by speech therapy (constraint-induced language therapy). In part 3, some possible mechanisms associated with improvement after a series of TMS treatments in stroke patients with aphasia are discussed. C1 [Naeser, Margaret A.; Martin, Paula I.; Ho, Michael; Treglia, Ethan; Kaplan, Elina] Boston Univ, Sch Med, Harold Goodglass Boston Univ, Aphasia Res Ctr,Dept Neurol, Boston, MA 02118 USA. [Bashir, Shahid; Pascual-Leone, Alvaro] Harvard Univ, Sch Med, Berenson Allen Ctr Noninvas Brain Stimulat, Dept Neurol, Boston, MA USA. [Bashir, Shahid; Pascual-Leone, Alvaro] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Pascual-Leone, Alvaro] Univ Autonoma Barcelona, Inst Guttman Neurorehabil, Inst Univ, Badalona, Spain. RP Naeser, MA (reprint author), VA Boston Healthcare Syst, Aphasia Res Ctr 12 A, 150 S Huntington Ave, Boston, MA 02130 USA. EM mnaeser@bu.edu RI Bashir, Shahid/B-4203-2012; Bashir, Shahid/E-7212-2014 FU National Institutes of Health [ROI DC05672, RRO18875]; National Institute on Deafness and Other Communication Disorders (NIDCD), Bethesda, MD; Medical Research Service, Department of Veterans Affairs, Washington, DC; Harvard-Thorndike General Clinical Research Center [NCRR MO1 RR01032]; Harvard Clinical and Translational Science Center [UL1 RR025758]; NIDCD; Harold Goodglass BU Aphasia Research Center [P30 DC05207] FX Supported by the National Institutes of Health (grant no. ROI DC05672) from the National Institute on Deafness and Other Communication Disorders (NIDCD), Bethesda, MD, and a grant from the Medical Research Service, Department of Veterans Affairs, Washington, DC; a K24 National Institutes of Health award (award no. RRO18875); the Harvard-Thorndike General Clinical Research Center (grant no. NCRR MO1 RR01032); the Harvard Clinical and Translational Science Center (grant no. UL1 RR025758); and a NIDCD grant to the Harold Goodglass BU Aphasia Research Center (grant no. P30 DC05207). NR 75 TC 24 Z9 27 U1 6 U2 27 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD JAN PY 2012 VL 93 IS 1 SU 1 BP S26 EP S34 DI 10.1016/j.apmr.2011.04.026 PG 9 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 873SY UT WOS:000298904500004 PM 22202188 ER PT J AU Rhee, EJ Nallamshetty, S Plutzky, J AF Rhee, Eun-Jung Nallamshetty, Shriram Plutzky, Jorge TI Retinoid metabolism and its effects on the vasculature SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS LA English DT Review DE Retinoid; Vascular smooth muscle cell; RXR; RAR; Inflammation; Atherosclerosis ID SMOOTH-MUSCLE-CELLS; VITAMIN-A-DEFICIENCY; C-REACTIVE PROTEIN; MICROVASCULAR ENDOTHELIAL-CELLS; TRANSCRIPTION FACTOR KLF5/BTEB2; NITRIC-OXIDE PRODUCTION; ACID RECEPTORS RARS; ALL-TRANS; X-RECEPTOR; BETA-CAROTENE AB Retinoids, the metabolically-active structural derivatives of vitamin A, are critical signaling molecules in many fundamental biological processes including cell survival, proliferation and differentiation. Emerging evidence, both clinical and molecular, implicates retinoids in atherosclerosis and other vasculoproliferative disorders such as restenosis. Although the data from clinical trials examining effect of vitamin A and vitamin precursors on cardiac events have been contradictory, this data does suggest that retinoids do influence fundamental processes relevant to atherosclerosis. Preclinical animal model and cellular studies support these concepts. Retinoids exhibit complex effects on proliferation, growth, differentiation and migration of vascular smooth muscle cells (VSMC), including responses to injury and atherosclerosis. Retinoids also appear to exert important inhibitory effects on thrombosis and inflammatory responses relevant to atherogenesis. Recent studies suggest retinoids may also be involved in vascular calcification and endothelial function, for example, by modulating nitric oxide pathways. In addition, established retinoid effects on lipid metabolism and adipogenesis may indirectly influence inflammation and atherosclerosis. Collectively, these observations underscore the scope and complexity of retinoid effects relevant to vascular disease. Additional studies are needed to elucidate how context and metabolite-specific retinoid effects affect atherosclerosis. This article is part of a Special Issue entitled: Retinoid and Lipid Metabolism. (C) 2011 Elsevier B.V. All rights reserved. C1 [Rhee, Eun-Jung; Nallamshetty, Shriram; Plutzky, Jorge] Harvard Univ, Brigham & Womens Hosp, Sch Med, Cardiovasc Div, Boston, MA 02115 USA. [Nallamshetty, Shriram] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Div, Boston, MA USA. [Rhee, Eun-Jung] Sungkyunkwan Univ, Sch Med, Kangbuk Samsung Hosp, Dept Endocrinol & Metab, Seoul, South Korea. RP Plutzky, J (reprint author), 77 Ave Louis Pasteur,NRB 742, Boston, MA 02115 USA. EM jplutzky@rics.bwh.harvard.edu OI Rhee, Eun-Jung/0000-0002-6108-7758 NR 163 TC 17 Z9 17 U1 1 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1388-1981 J9 BBA-MOL CELL BIOL L JI Biochim. Biophys. Acta Mol. Cell Biol. Lipids PD JAN PY 2012 VL 1821 IS 1 SI SI BP 230 EP 240 DI 10.1016/j.bbalip.2011.07.001 PG 11 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 877NX UT WOS:000299190300021 PM 21810483 ER PT J AU Hook, V Funkelstein, L Wegrzyn, J Bark, S Kindy, M Hook, G AF Hook, Vivian Funkelstein, Lydiane Wegrzyn, Jill Bark, Steven Kindy, Mark Hook, Gregory TI Cysteine Cathepsins in the secretory vesicle produce active peptides: Cathepsin L generates peptide neurotransmitters and cathepsin B produces beta-amyloid of Alzheimer's disease SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS LA English DT Review DE Cathepsin L; Cathepsin B; Secretory vesicle; Peptide neurotransmitters; beta-amyloid; Alzheimer's disease ID PRECURSOR PROTEIN; TRANSGENIC MICE; IN-VIVO; CHROMOGRANIN-A; WILD-TYPE; SELECTIVE INHIBITOR; CHROMAFFIN GRANULES; NEUROPEPTIDE-Y; FULL-LENGTH; MOUSE-BRAIN AB Recent new findings indicate significant biological roles of cysteine cathepsin proteases in secretory vesicles for production of biologically active peptides. Notably, cathepsin L in secretory vesicles functions as a key protease for proteolytic processing of proneuropeptides (and prohormones) into active neuropeptides that are released to mediate cell-cell communication in the nervous system for neurotransmission. Moreover, cathepsin B in secretory vesicles has been recently identified as a beta-secretase for production of neurotoxic beta-amyloid (A beta) peptides that accumulate in Alzheimer's disease (AD), participating as a notable factor in the severe memory loss in AD. These secretory vesicle functions of cathepsins L and B for production of biologically active peptides contrast with the well-known role of cathepsin proteases in lysosomes for the degradation of proteins to result in their inactivation. The unique secretory vesicle proteome indicates proteins of distinct functional categories that provide the intravesicular environment for support of cysteine cathepsin functions. Features of the secretory vesicle protein systems insure optimized intravesicular conditions that support the proteolytic activity of cathepsins. These new findings of recently discovered biological roles of cathepsins L and B indicate their significance in human health and disease. This article is part of a Special Issue entitled: Proteolysis 50 years after the discovery of lysosome. (C) 2011 Elsevier B.V. All rights reserved. C1 [Hook, Vivian; Funkelstein, Lydiane; Wegrzyn, Jill; Bark, Steven] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, Dept Neurosci, La Jolla, CA 92093 USA. [Hook, Vivian; Funkelstein, Lydiane; Wegrzyn, Jill; Bark, Steven] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, Dept Pharmacol, La Jolla, CA 92093 USA. [Hook, Vivian; Funkelstein, Lydiane; Wegrzyn, Jill; Bark, Steven] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, Dept Med, La Jolla, CA 92093 USA. [Kindy, Mark] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. [Kindy, Mark] Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA. [Hook, Gregory] Amer Life Sci Pharmaceut Inc, San Diego, CA 92109 USA. RP Hook, V (reprint author), Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, Dept Neurosci, 9500 Gilman Dr,MC 0744, La Jolla, CA 92093 USA. EM vhook@ucsd.edu OI Wegrzyn, Jill/0000-0001-5923-0888 FU National Institutes of Health [R01DA04271, R01NS24553, R01MH077305, P01HL58120, K01DA023065]; Alzheimer's Association; NIA/NIH [AG027446, 1R44AG032784]; [P30NS047101] FX The cathepsin L and proteomics research was supported by grants from the National Institutes of Health to V. Hook consisting of R01DA04271, R01NS24553, R01MH077305, P01HL58120 from the NIH, a grant from the Alzheimer's Association, and a grant to J. Gleeson, P30NS047101, for the microscopy core. S. Bark was supported by a NIH Mentored Scientist Award (K01DA023065). The authors also appreciate scientific advice by Dr. Shin-Rong Hwang, and technical assistance by Mr. Thomas Toneff, at the Skaggs School of Pharmacy and Pharmaceutical Sciences, Univ. of Calif., San Diego, La Jolla, CA. The authors appreciate collaboration of these studies with Dr. Thomas Reinheckel and Dr. Christoph Peters at the Albert-Ludwigs University, Freiburg, Germany.; The cathepsin B and Alzheimer's research was supported by the NIA/NIH R21 Grant AG027446 and 1R44AG032784 (to American Life Science Pharmaceuticals (ALSP)), and by an award from the Alzheimer's Association to V. Hook. V.H. holds equity in ALSP and serves on the Scientific Advisory Board of ALSP. The terms of this agreement have been reviewed by the University of California, San Diego, in accordance with its conflict of interest policies. G.H. holds equity in and is employed by ALSP. NR 121 TC 22 Z9 23 U1 0 U2 23 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-9639 J9 BBA-PROTEINS PROTEOM JI BBA-Proteins Proteomics PD JAN PY 2012 VL 1824 IS 1 SI SI BP 89 EP 104 DI 10.1016/j.bbapap.2011.08.015 PG 16 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 871CS UT WOS:000298715900010 PM 21925292 ER PT J AU Li, Y Schiepers, C Lake, R Dadparvar, S Berenji, GR AF Li, Yuxin Schiepers, Christiaan Lake, Ralph Dadparvar, Simin Berenji, Gholam R. TI Clinical utility of F-18-fluoride PET/CT in benign and malignant bone diseases SO BONE LA English DT Review DE F-18-sodium fluoride; Positron emission tomography, computed tomography, PET-CT; Bone scan ID POSITRON-EMISSION-TOMOGRAPHY; F-18 FLUORIDE-ION; BRAIN TRANSFER CONSTANTS; CELL LUNG-CANCER; TIME UPTAKE DATA; WHOLE-BODY PET; BREAST-CANCER; PROSTATE-CANCER; METABOLIC-ACTIVITY; SODIUM-FLUORIDE AB F-18 labeled sodium fluoride is a positron-emitting, bone seeking agent with more favorable skeletal kinetics than conventional phosphate and diphosphonate compounds. With the expanding clinical usage of PET/CT', there is renewed interest in using F-18-fluoride PET/CT for imaging bone diseases. Growing evidence indicates that F-18 fluoride PET/CT offers increased sensitivity, specificity, and diagnostic accuracy in evaluating metastatic bone disease compared to Tc-99m based bone scintigraphy. National Oncologic PET Registry (NOPR) has expanded coverage for F-18 sodium fluoride PET scans since February 2011 for the evaluation of osseous metastatic disease. In this article, we reviewed the pharmacological characteristics of sodium fluoride, as well as the clinical utility of PET/CT' using F-18-fluoride in both benign and malignant bone disorders. Published by Elsevier Inc. C1 [Berenji, Gholam R.] VA Greater Los Angeles Healthcare Syst, Nucl Med Serv 115, Los Angeles, CA 90073 USA. [Schiepers, Christiaan] Univ Calif Los Angeles, Dept Mol & Med Pharmacol, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Dadparvar, Simin] Univ PA Hlth Syst, Philadelphia, PA USA. RP Berenji, GR (reprint author), VA Greater Los Angeles Healthcare Syst, Nucl Med Serv 115, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM Gholam.Berenji@va.gov NR 75 TC 33 Z9 33 U1 1 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD JAN PY 2012 VL 50 IS 1 BP 128 EP 139 DI 10.1016/j.bone.2011.09.053 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 875VV UT WOS:000299064200017 PM 22001678 ER PT J AU Reardon, DA Cloughesy, T Rich, J Yung, WKA Yung, LT DiLea, C Huang, JR Dugan, M Mietlowski, W Maes, A Conrad, C AF Reardon, David A. Cloughesy, Timothy Rich, Jeremy Yung, W. K. Alfred Yung, Lotus DiLea, Clifford Huang, Jerry Dugan, Margaret Mietlowski, William Maes, Andrea Conrad, Charles TI Pharmacokinetic drug interaction between AEE788 and RAD001 causing thrombocytopenia in patients with glioblastoma SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE Glioblastoma; AEE788; Tyrosine kinase inhibitor; RAD001; mTOR ID PHASE-I; MAMMALIAN TARGET; INHIBITOR EVEROLIMUS; TUMOR-CELLS; CANCER; COMBINATION; RESISTANCE; PATHWAY; TRIALS; GLIOMA AB Treating glioblastoma through the simultaneous inhibition of multiple transduction pathways may prove more effective than single-pathway inhibition. We evaluated the safety, biologic activity, and pharmacokinetic profile of oral AEE788, a selective inhibitor of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF), plus oral RAD001, a mammalian target of rapamycin inhibitor, in glioblastoma patients. This phase IB/II, open-label, multicenter, 2-arm, dose-escalation study enrolled adult glioblastoma patients at first or second recurrence/relapse. Primary objective was to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of AEE788 combined with RAD001. Secondary objectives included determining the safety/tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of the combination. Sixteen patients were enrolled (AEE788 200 mg/day + RAD001 5 mg/day, 2 patients; AEE788 150 mg/day + RAD001 5 mg every other day [qod], 14); all patients discontinued the study most commonly because of disease progression. Four patients experienced DLT (AEE788 200 mg/day + RAD001 5 mg/day, 1 patient; AEE788 150 mg/day + RAD001 5 mg qod, 3). Both patients receiving AEE788 (200 mg/day) plus RAD001 (5 mg/day) experienced clinically significant thrombocytopenia requiring a dose reduction/interruption. AEE788 appeared to inhibit the metabolism of RAD001. The study was terminated prematurely before an MTD was determined because of safety findings in other studies evaluating AEE788 monotherapy. The coadministration of AEE788 and RAD001 in glioblastoma patients caused a clinically significant thrombocytopenia and a higher-than-expected RAD001 area under the curve concentration when dosed at 200 and 5 mg/day, respectively. After a dose reduction to AEE788 (150 mg/day) and RAD001 (5 mg qod), the combination appeared to be better tolerated. C1 [Reardon, David A.] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02215 USA. [Cloughesy, Timothy] Univ Calif Los Angeles, Los Angeles, CA USA. [Rich, Jeremy] Cleveland Clin, Lerner Res Inst, Cleveland, OH 44106 USA. [Mietlowski, William; Conrad, Charles] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Yung, Lotus] Celgene Corp, Summit, NJ USA. [DiLea, Clifford; Huang, Jerry; Dugan, Margaret; Mietlowski, William; Maes, Andrea] Novartis Pharmaceutical Corp, E Hanover, NJ USA. RP Reardon, DA (reprint author), Dana Farber Canc Inst, Ctr Neurooncol, 450 Brookline Ave,SW 460F, Boston, MA 02215 USA. EM David_Reardon@DFCI.harvard.edu FU Novartis Pharmaceuticals Corporation, East Hanover, NJ FX We are indebted to the patients who participated in this study and study coordinators. We thank Syntaxx Communications, Inc. for assistance with manuscript development and editing. Research support by Novartis Pharmaceuticals Corporation, East Hanover, NJ. NR 21 TC 5 Z9 5 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD JAN PY 2012 VL 69 IS 1 BP 281 EP 287 DI 10.1007/s00280-011-1754-1 PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 870EO UT WOS:000298652100032 PM 21984222 ER PT J AU Wolpin, BM Ng, K Bao, Y Kraft, P Stampfer, MJ Michaud, DS Ma, J Buring, JE Sesso, HD Lee, IM Rifai, N Cochrane, BB Wactawski-Wende, J Chlebowski, RT Willett, WC Manson, JE Giovannucci, EL Fuchs, CS AF Wolpin, Brian M. Ng, Kimmie Bao, Ying Kraft, Peter Stampfer, Meir J. Michaud, Dominique S. Ma, Jing Buring, Julie E. Sesso, Howard D. Lee, I-Min Rifai, Nader Cochrane, Barbara B. Wactawski-Wende, Jean Chlebowski, Rowan T. Willett, Walter C. Manson, JoAnn E. Giovannucci, Edward L. Fuchs, Charles S. TI Plasma 25-Hydroxyvitamin D and Risk of Pancreatic Cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID VITAMIN-D STATUS; FOOD FREQUENCY QUESTIONNAIRE; PHYSICAL-ACTIVITY QUESTIONNAIRE; MALE HEALTH-PROFESSIONALS; WOMENS HEALTH; PRIMARY PREVENTION; REPRODUCIBILITY; VALIDITY; METAANALYSIS; ASPIRIN AB Background: Laboratory studies suggest that vitamin D may inhibit pancreatic cancer cell growth. However, epidemiologic studies of vitamin D and pancreatic cancer risk have been conflicting. Methods: To determine whether prediagnostic levels of plasma 25-hydroxyvitamin D (25[OH]D; IDS Inc.; enzyme immunoassay) were associated with risk of pancreatic cancer, we conducted a pooled analysis of nested case-control studies with 451 cases and 1,167 controls from five cohorts through 2008. Median follow-up among controls was 14.1 years in Health Professionals Follow-Up Study (HPFS), 18.3 years in Nurses' Health Study (NHS), 25.3 years in Physicians' Health Study (PHS), 12.2 years in Women's Health Initiative-Observational Study (WHI), and 14.4 years in Women's Health Study (WHS). Logistic regression was used to compare the odds of pancreatic cancer by plasma level of 25(OH) D. Results: Mean plasma 25(OH) D was lower in cases versus controls (61.3 vs. 64.5 nmol/L, P = 0.005). In logistic regression models, plasma 25(OH) D was inversely associated with odds of pancreatic cancer. Participants in quintiles two through five had multivariable-adjusted ORs (95% confidence intervals) of 0.79 (0.56-1.10), 0.75 (0.53-1.06), 0.68 (0.48-0.97), and 0.67 (0.46-0.97; P(trend) = 0.03), respectively, compared with the bottom quintile. Compared with those with insufficient levels [25[OH] D, < 50 nmol/L], ORs were 0.75 (0.58-0.98) for subjects with relative insufficiency [25[OH] D, 50 to <75 nmol/L] and 0.71 (0.52-0.97) for those with sufficient levels [25[OH] D, >= 75 nmol/L]. No increased risk was noted in subjects with 25(OH) D >= 100 nmol/L, as suggested in a prior study. In subgroup analyses, ORs for the top versus bottom quartile of 25(OH) D were 0.72 (0.48-1.08) for women, 0.73 (0.40-1.31) for men, and 0.73 (0.51-1.03) for Whites. Conclusions: Among participants in five large prospective cohorts, higher plasma levels of 25(OH) D were associated with a lower risk for pancreatic cancer. Impact: Low circulating 25(OH) D may predispose individuals to the development of pancreatic cancer. Cancer Epidemiol Biomarkers Prev; 21(1); 82-91. (C) 2011 AACR. C1 [Wolpin, Brian M.; Ng, Kimmie; Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Bao, Ying; Stampfer, Meir J.; Ma, Jing; Willett, Walter C.; Manson, JoAnn E.; Giovannucci, Edward L.; Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. [Buring, Julie E.; Sesso, Howard D.] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA. [Buring, Julie E.; Sesso, Howard D.; Lee, I-Min; Manson, JoAnn E.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Buring, Julie E.] Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Cambridge, MA 02138 USA. [Kraft, Peter; Stampfer, Meir J.; Michaud, Dominique S.; Ma, Jing; Sesso, Howard D.; Lee, I-Min; Willett, Walter C.; Manson, JoAnn E.; Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Cambridge, MA 02138 USA. [Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Biostat, Cambridge, MA 02138 USA. [Stampfer, Meir J.; Willett, Walter C.; Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Cambridge, MA 02138 USA. [Rifai, Nader] Childrens Hosp Boston, Dept Lab Med, Boston, MA USA. [Michaud, Dominique S.] Brown Univ, Dept Publ Hlth Epidemiol, Providence, RI 02912 USA. [Cochrane, Barbara B.] Univ Washington, Sch Nursing, Seattle, WA 98195 USA. [Wactawski-Wende, Jean] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA. [Chlebowski, Rowan T.] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA. RP Wolpin, BM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM bwolpin@partners.org RI Michaud, Dominique/I-5231-2014 FU National Cancer Institute, NIH [P01 CA87969, P01 CA55075, P50 CA127003, R01 CA124908]; NCI [K07 CA140790]; American Society of Clinical Oncology; Howard Hughes Medical Institute; NIH (Bethesda, MD) [CA97193, CA34944, CA40360, HL26490, HL34595, CA047988, HL043851, HL080467]; National Heart, Lung, and Blood Institute, NIH; U.S. Department of Health and Human Services [N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, 44221] FX The NHS and HPFS are supported by the National Cancer Institute, NIH (grants no. P01 CA87969, P01 CA55075, P50 CA127003, and R01 CA124908). B. M. Wolpin, MD, MPH, is supported by NCI K07 CA140790, an American Society of Clinical Oncology Career Development award, and a Howard Hughes Medical Institute Early Career Physician-Scientist award. The PHS is supported by grants CA97193, CA34944, CA40360, HL26490, and HL34595 from the NIH (Bethesda, MD). The WHI program is funded by the National Heart, Lung, and Blood Institute, NIH, U.S. Department of Health and Human Services through contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, and 44221. The WHS is supported by grants CA047988, HL043851, and HL080467 from the NIH (Bethesda, MD). NR 49 TC 48 Z9 48 U1 2 U2 12 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 JAN PY 2012 VL 21 IS 1 BP 82 EP 91 DI 10.1158/1055-9965.EPI-11-0836 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 875RH UT WOS:000299051500009 PM 22086883 ER PT J AU Mavaddat, N Barrowdale, D Andrulis, IL Domchek, SM Eccles, D Nevanlinna, H Ramus, SJ Spurdle, A Robson, M Sherman, M Mulligan, AM Couch, FJ Engel, C McGuffog, L Healey, S Sinilnikova, OM Southey, MC Terry, MB Goldgar, D O'Malley, F John, EM Janavicius, R Tihomirova, L Hansen, TVO Nielsen, FC Osorio, A Stavropoulou, A Benitez, J Manoukian, S Peissel, B Barile, M Volorio, S Pasini, B Dolcetti, R Putignano, AL Ottini, L Radice, P Hamann, U Rashid, MU Hogervorst, FB Kriege, M van der Luijt, RB Peock, S Frost, D Evans, DG Brewer, C Walker, L Rogers, MT Side, LE Houghton, C Weaver, J Godwin, AK Schmutzler, RK Wappenschmidt, B Meindl, A Kast, K Arnold, N Niederacher, D Sutter, C Deissler, H Gadzicki, D Preisler-Adams, S Varon-Mateeva, R Schonbuchner, I Gevensleben, H Stoppa-Lyonnet, D Belotti, M Barjhoux, L Isaacs, C Peshkin, BN Caldes, T de la Hoya, M Canadas, C Heikkinen, T Heikkila, P Aittomaki, K Blanco, I Lazaro, C Brunet, J Agnarsson, BA Arason, A Barkardottir, RB Dumont, M Simard, J Montagna, M Agata, S D'Andrea, E Yan, M Fox, S Rebbeck, TR Rubinstein, W Tung, N Garber, JE Wang, XS Fredericksen, Z Pankratz, VS Lindor, NM Szabo, C Offit, K Sakr, R Gaudet, MM Singer, CF Tea, MK Rappaport, C Mai, PL Greene, MH Sokolenko, A Imyanitov, E Toland, AE Senter, L Sweet, K Thomassen, M Gerdes, AM Kruse, T Caligo, M Aretini, P Rantala, J von Wachenfeld, A Henriksson, K Steele, L Neuhausen, SL Nussbaum, R Beattie, M Odunsi, K Sucheston, L Gayther, SA Nathanson, K Gross, J Walsh, C Karlan, B Chenevix-Trench, G Easton, DF Antoniou, AC AF Mavaddat, Nasim Barrowdale, Daniel Andrulis, Irene L. Domchek, Susan M. Eccles, Diana Nevanlinna, Heli Ramus, Susan J. Spurdle, Amanda Robson, Mark Sherman, Mark Mulligan, Anna Marie Couch, Fergus J. Engel, Christoph McGuffog, Lesley Healey, Sue Sinilnikova, Olga M. Southey, Melissa C. Terry, Mary Beth Goldgar, David O'Malley, Frances John, Esther M. Janavicius, Ramunas Tihomirova, Laima Hansen, Thomas V. O. Nielsen, Finn C. Osorio, Ana Stavropoulou, Alexandra Benitez, Javier Manoukian, Siranoush Peissel, Bernard Barile, Monica Volorio, Sara Pasini, Barbara Dolcetti, Riccardo Putignano, Anna Laura Ottini, Laura Radice, Paolo Hamann, Ute Rashid, Muhammad U. Hogervorst, Frans B. Kriege, Mieke van der Luijt, Rob B. Peock, Susan Frost, Debra Evans, D. Gareth Brewer, Carole Walker, Lisa Rogers, Mark T. Side, Lucy E. Houghton, Catherine Weaver, JoEllen Godwin, Andrew K. Schmutzler, Rita K. Wappenschmidt, Barbara Meindl, Alfons Kast, Karin Arnold, Norbert Niederacher, Dieter Sutter, Christian Deissler, Helmut Gadzicki, Doroteha Preisler-Adams, Sabine Varon-Mateeva, Raymonda Schoenbuchner, Ines Gevensleben, Heidrun Stoppa-Lyonnet, Dominique Belotti, Muriel Barjhoux, Laure Isaacs, Claudine Peshkin, Beth N. Caldes, Trinidad de la Hoya, Miguel Canadas, Carmen Heikkinen, Tuomas Heikkila, Paivi Aittomaki, Kristiina Blanco, Ignacio Lazaro, Conxi Brunet, Joan Agnarsson, Bjarni A. Arason, Adalgeir Barkardottir, Rosa B. Dumont, Martine Simard, Jacques Montagna, Marco Agata, Simona D'Andrea, Emma Yan, Max Fox, Stephen Rebbeck, Timothy R. Rubinstein, Wendy Tung, Nadine Garber, Judy E. Wang, Xianshu Fredericksen, Zachary Pankratz, Vernon S. Lindor, Noralane M. Szabo, Csilla Offit, Kenneth Sakr, Rita Gaudet, Mia M. Singer, Christian F. Tea, Muy-Kheng Rappaport, Christine Mai, Phuong L. Greene, Mark H. Sokolenko, Anna Imyanitov, Evgeny Toland, Amanda Ewart Senter, Leigha Sweet, Kevin Thomassen, Mads Gerdes, Anne-Marie Kruse, Torben Caligo, Maria Aretini, Paolo Rantala, Johanna von Wachenfeld, Anna Henriksson, Karin Steele, Linda Neuhausen, Susan L. Nussbaum, Robert Beattie, Mary Odunsi, Kunle Sucheston, Lara Gayther, Simon A. Nathanson, Kate Gross, Jenny Walsh, Christine Karlan, Beth Chenevix-Trench, Georgia Easton, Douglas F. Antoniou, Antonis C. CA HEBON EMBRACE GEMO Study Collaborators kConFab Investigators SWE-BRCA Collaborators Consortium Investigators Modifiers TI Pathology of Breast and Ovarian Cancers among BRCA1 and BRCA2 Mutation Carriers: Results from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID ESTROGEN-RECEPTOR STATUS; IMMUNOHISTOCHEMICAL MARKERS; GERMLINE MUTATIONS; TUMOR SUBTYPES; FEATURES; RISK; PHENOTYPE; WOMEN; PREDICTION; CARCINOMA AB Background: Previously, small studies have found that BRCA1 and BRCA2 breast tumors differ in their pathology. Analysis of larger datasets of mutation carriers should allow further tumor characterization. Methods: We used data from 4,325 BRCA1 and 2,568 BRCA2 mutation carriers to analyze the pathology of invasive breast, ovarian, and contralateral breast cancers. Results: There was strong evidence that the proportion of estrogen receptor (ER)-negative breast tumors decreased with age at diagnosis among BRCA1 (P-trend = 1.2 x 10(-5)), but increased with age at diagnosis among BRCA2, carriers (P-trend 6.8 x 10(-6)). The proportion of triple-negative tumors decreased with age at diagnosis in BRCA1 carriers but increased with age at diagnosis of BRCA2 carriers. In both BRCA1 and BRCA2 carriers, ER-negative tumors were of higher histologic grade than ER-positive tumors (grade 3 vs. grade 1; P = 1.2 x 10(-13) for BRCA1 and P = 0.001 for BRCA2). ER and progesterone receptor (PR) expression were independently associated with mutation carrier status [ER-positive odds ratio (OR) for BRCA2 = 9.4, 95% CI: 7.0-12.6 and PR-positive OR = 1.7, 95% CI: 1.3-2.3, under joint analysis]. Lobular tumors were more likely to be BRCA2-related (OR for BRCA2 = 3.3, 95% CI: 2.4-4.4; P = 4.4 x 10(-14)), and medullary tumors BRCA1-related (OR for BRCA2 = 0.25, 95% CI: 0.18-0.35; P = 2.3 x 10(-15)). ER-status of the first breast cancer was predictive of ER-status of asynchronous contralateral breast cancer (P = 0.0004 for BRCA1; P = 0.002 for BRCA2). There were no significant differences in ovarian cancer morphology between BRCA1 and BRCA2 carriers (serous: 67%; mucinous: 1%; endometrioid: 12%; clear-cell: 2%). Conclusions/Impact: Pathologic characteristics of BRCA1 and BRCA2 tumors may be useful for improving risk-prediction algorithms and informing clinical strategies for screening and prophylaxis. Cancer Epidemiol Biomarkers Prev; 21(1); 134-47. (C) 2011 AACR. C1 [Mavaddat, Nasim; Barrowdale, Daniel; McGuffog, Lesley; Peock, Susan; Frost, Debra; Easton, Douglas F.; Antoniou, Antonis C.; EMBRACE] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge, England. [Andrulis, Irene L.; O'Malley, Frances] Mt Sinai Hosp, Fred A Litwin Ctr Canc Genet, Samuel Lunenfeld Res Inst, Toronto, ON, Canada. [Robson, Mark; Offit, Kenneth; Sakr, Rita] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY USA. [Robson, Mark; Offit, Kenneth; Sakr, Rita] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY USA. [Robson, Mark; Offit, Kenneth; Sakr, Rita] Mem Sloan Kettering Canc Ctr, Dept Epidemiol Biostat, New York, NY USA. [Terry, Mary Beth] Columbia Univ, Dept Epidemiol, New York, NY USA. [Andrulis, Irene L.; O'Malley, Frances] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A1, Canada. [Mulligan, Anna Marie] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5S 1A1, Canada. [Mulligan, Anna Marie] St Michaels Hosp, Toronto, ON M5B 1W8, Canada. [Rebbeck, Timothy R.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Rebbeck, Timothy R.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Weaver, JoEllen] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Eccles, Diana] Univ Southampton, Fac Med, Southampton Univ Hosp, NHS Trust, Southampton SO9 5NH, Hants, England. [Nevanlinna, Heli; Heikkinen, Tuomas] Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, FIN-00290 Helsinki, Finland. [Heikkila, Paivi] Univ Helsinki, Cent Hosp, Dept Pathol, Helsinki, Finland. [Aittomaki, Kristiina] Univ Helsinki, Cent Hosp, Dept Clin Genet, Helsinki, Finland. [Ramus, Susan J.; Gayther, Simon A.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90089 USA. [Gross, Jenny; Walsh, Christine; Karlan, Beth] Cedars Sinai Med Ctr, Samuel Oschin Canc Inst, Womens Canc Program, Los Angeles, CA 90048 USA. [Gross, Jenny; Walsh, Christine; Karlan, Beth] Cedars Sinai Med Ctr, Dept Obstet & Gynecol, Div Gynecol Oncol, Los Angeles, CA 90048 USA. [Spurdle, Amanda; Healey, Sue; Chenevix-Trench, Georgia] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Sherman, Mark] NCI, Hormonal & Reprod Epidemiol Branch, Rockville, MD USA. [Mai, Phuong L.; Greene, Mark H.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. [Couch, Fergus J.; Fredericksen, Zachary; Pankratz, Vernon S.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Lindor, Noralane M.] Mayo Clin, Dept Med Genet, Rochester, MN USA. [Engel, Christoph] Univ Leipzig, Inst Med Informat Stat & Epidemiol, Leipzig, Germany. [Sinilnikova, Olga M.] Ctr Hosp Univ Lyon, Ctr Leon Berard, Unite Mixte Genet Constitut Canc Frequents, Lyon, France. [Sinilnikova, Olga M.; Barjhoux, Laure] Univ Lyon 1, Canc Res Ctr Lyon, CNRS, INSERM,U1052,UMR5286, F-69622 Villeurbanne, France. [GEMO Study Collaborators] Federat Natl Ctr Lutte Canc, Canc Genet Network Grp Genet & Canc, Lyon, France. [Southey, Melissa C.] Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Melbourne, Vic 3010, Australia. [Fox, Stephen; kConFab Investigators] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Goldgar, David] Univ Utah, Sch Med, Dept Dermatol, Salt Lake City, UT USA. [John, Esther M.] Canc Prevent Inst Calif, Dept Epidemiol, Fremont, CA USA. [Janavicius, Ramunas] Vilnius Univ Hosp Santariskiu Clin, Dept Mol & Regenerat Med, Hematol Oncol & Transfus Med Ctr, Vilnius, Lithuania. [Tihomirova, Laima] Latvian Biomed Res & Study Ctr, Riga, Latvia. [Hansen, Thomas V. O.; Nielsen, Finn C.] Copenhagen Univ Hosp, Rigshosp, Dept Clin Biochem, Copenhagen, Denmark. [Gerdes, Anne-Marie] Univ Copenhagen, Rigshosp, Dept Clin Genet, DK-1168 Copenhagen, Denmark. [Caldes, Trinidad; de la Hoya, Miguel; Canadas, Carmen] Hosp Clin San Carlos, Mol Oncol Lab, Madrid, Spain. [Stavropoulou, Alexandra] Natl Ctr Sci Res Demokritos, Mol Diagnost Lab, IRRP, Athens, Greece. [Manoukian, Siranoush; Peissel, Bernard] Fdn IRCCS Ist Nazl Tumori INT, Dept Prevent & Predict Med, Unit Med Genet, San Giovanni Rotondo, Italy. [Radice, Paolo] Fdn IRCCS Ist Nazl Tumori INT, Dept Prevent & Predict Med, Unit Mol Bases Genet Risk & Genet Testing, San Giovanni Rotondo, Italy. [Volorio, Sara; Radice, Paolo] Fdn Ist FIRC Oncol Mol, IFOM, Milan, Italy. [Pasini, Barbara] Univ Turin, Dept Genet Biol & Biochem, Turin, Italy. [Dolcetti, Riccardo] IRCCS, Ctr Riferimento Oncol, Canc Bioimmunotherapy Unit, Aviano, PN, Italy. [Putignano, Anna Laura] Univ Florence, Dept Clin Physiopathol, I-50121 Florence, Italy. [Ottini, Laura] Univ Roma La Sapienza, Dept Mol Med, Rome, Italy. [Sutter, Christian] Univ Heidelberg Hosp, Dept Human Genet, Inst Human Genet, Heidelberg, Germany. [Rashid, Muhammad U.] Shaukat Khanum Mem Canc Hosp & Res Ctr, Dept Basic Sci, Lahore, Pakistan. [Hogervorst, Frans B.] Family Canc Clin, Amsterdam, Netherlands. [HEBON] Netherlands Canc Inst, Amsterdam, Netherlands. [Kriege, Mieke] Erasmus Univ, Med Ctr, Family Canc Clin, Dept Med Oncol, Rotterdam, Netherlands. [van der Luijt, Rob B.] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands. [Evans, D. Gareth] Cent Manchester Univ Hosp NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England. [Brewer, Carole] Royal Devon & Exeter Hosp, Dept Clin Genet, Exeter EX2 5DW, Devon, England. [Walker, Lisa] Churchill Hosp, Oxford Reg Genet Serv, Oxford OX3 7LJ, England. [Rogers, Mark T.] Univ Wales Hosp, All Wales Med Genet Serv, Cardiff CF4 4XW, S Glam, Wales. [Side, Lucy E.] Great Ormond St Hosp Sick Children, NE Thames Reg Genet Serv, London WC1N 3JH, England. [Houghton, Catherine] Liverpool Womens NHS Fdn Trust, Cheshire & Merseyside Clin Genet Serv, Liverpool, Merseyside, England. [Godwin, Andrew K.] Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Kansas City, KS 66103 USA. [Schmutzler, Rita K.; Wappenschmidt, Barbara] Univ Hosp Cologne, Ctr Familial Breast & Ovarian Canc, Dept Obstet & Gynaecol, Cologne, Germany. [Schmutzler, Rita K.; Wappenschmidt, Barbara] Univ Hosp Cologne, Ctr Integrated Oncol, Cologne, Germany. [Meindl, Alfons] Tech Univ Munich, Klinikum Rechts Isar, Dept Obstet & Gynaecol, Div Tumor Genet, D-8000 Munich, Germany. [Kast, Karin] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dept Obstet & Gynaecol, D-01062 Dresden, Germany. [Arnold, Norbert] Univ Kiel, Inst Human Genet, Univ Hosp Schleswig Holstein, Kiel, Germany. [Niederacher, Dieter] Univ Dusseldorf, Dept Obstet & Gynaecol, Univ Hosp Dusseldorf, D-40225 Dusseldorf, Germany. [Deissler, Helmut] Univ Hosp Ulm, Dept Obstet & Gynaecol, Ulm, Germany. [Gadzicki, Doroteha] Hannover Med Sch, Inst Cell & Mol Pathol, D-3000 Hannover, Germany. [Preisler-Adams, Sabine] Univ Munster, Inst Human Genet, D-4400 Munster, Germany. [Varon-Mateeva, Raymonda] Charite, Inst Human Genet, Campus Virchov Klinikum, Berlin, Germany. Univ Wurzburg, Dept Med Genet, Inst Human Genet, Ctr Familial Breast & Ovarian Canc, Wurzburg, Germany. [Stoppa-Lyonnet, Dominique; Belotti, Muriel] Inst Curie, Serv Genet Oncol, F-75231 Paris, France. [Stoppa-Lyonnet, Dominique] Inst Curie, INSERM, Unite U830, F-75231 Paris, France. [Stoppa-Lyonnet, Dominique] Univ Paris 05, Fac Med, Paris, France. [Isaacs, Claudine; Peshkin, Beth N.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. Germans Trias & Pujol Biopmed Res Inst IGTP, Inst Catala Oncol, Hereditary Canc Program, Badalona, Spain. [Blanco, Ignacio; Lazaro, Conxi] Hosp Duran i Reynals, Inst Catala Oncol, Hereditary Canc Program, Bellvitge Biomed Res Inst IDIBELL, Barcelona, Spain. [Brunet, Joan] Hosp Josp Trueta, Inst Catala Oncol, Hereditary Canc Program, Girona Biomed Res Inst IdiBGi, Girona, Spain. [Agnarsson, Bjarni A.; Arason, Adalgeir; Barkardottir, Rosa B.] Univ Iceland, Univ Hosp, Dept Pathol, Reykjavik, Iceland. [Agnarsson, Bjarni A.; Arason, Adalgeir; Barkardottir, Rosa B.] Univ Iceland, Fac Med, Reykjavik, Iceland. [Simard, Jacques] Ctr Hosp Univ Quebec, Canc Genom Lab, Canada Res Chair Oncogenet, Quebec City, PQ, Canada. [Simard, Jacques] Univ Laval, Quebec City, PQ, Canada. [Montagna, Marco; Agata, Simona] IRCCS, Ist Oncol Veneto, Immunol & Mol Oncol Unit, Padua, Italy. [D'Andrea, Emma] Univ Padua, Dept Oncol & Surg Sci, Padua, Italy. [Yan, Max] Prince Wales Hosp, Dept Anat Pathol, Randwick, NSW 2031, Australia. [Rubinstein, Wendy] N Shore Univ Hlth Syst, Ctr Med Genet, Evanston, IL USA. [Tung, Nadine] Beth Israel Deaconess Med Ctr, Boston, MA USA. [Garber, Judy E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Szabo, Csilla] Univ Delaware, Newark, DE USA. [Gaudet, Mia M.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Singer, Christian F.; Tea, Muy-Kheng; Rappaport, Christine] Med Univ Vienna, Dept OB GYN, Vienna, Austria. [Singer, Christian F.; Tea, Muy-Kheng; Rappaport, Christine] Med Univ Vienna, Ctr Comprehens Canc, Vienna, Austria. [Sokolenko, Anna; Imyanitov, Evgeny] St Petersburg Pediat Med Acad, Mol Oncol Lab, NN Petrov Inst Oncol, St Petersburg, Russia. [Sokolenko, Anna; Imyanitov, Evgeny] St Petersburg Pediat Med Acad, Dept Med Genet, St Petersburg, Russia. [Toland, Amanda Ewart] Ohio State Univ, Med Ctr, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA. [Senter, Leigha; Sweet, Kevin] Ohio State Univ, Med Ctr, Dept Internal Med, Div Human Genet,Comprehens Canc Ctr, Columbus, OH 43210 USA. [Thomassen, Mads; Kruse, Torben] Odense Univ Hosp, Dept Clin Genet, DK-5000 Odense, Denmark. [Caligo, Maria; Aretini, Paolo] Univ Pisa, Sect Genet Oncol, Dept Lab Med, Pisa, Italy. [Caligo, Maria; Aretini, Paolo] Univ Hosp Pisa, Pisa, Italy. [Rantala, Johanna] Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden. [von Wachenfeld, Anna] Karolinska Univ Hosp, Dept Oncol, Stockholm, Sweden. [SWE-BRCA Collaborators] Karolinska Univ, Stockholm, Sweden. [Henriksson, Karin] Univ Lund Hosp, Ctr Oncol, S-22185 Lund, Sweden. [Steele, Linda; Neuhausen, Susan L.] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Duarte, CA USA. [Nussbaum, Robert] Univ Calif San Francisco, Dept Med, Div Med Genet, San Francisco, CA USA. [Beattie, Mary] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. [Beattie, Mary] Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA. [Odunsi, Kunle] Roswell Pk Canc Inst, Dept Gynecol Oncol, Buffalo, NY 14263 USA. [Sucheston, Lara] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA. RP Antoniou, AC (reprint author), Strangeways Res Lab, Worts Causeway, Cambridge CB1 8RN, England. EM antonis@srl.cam.ac.uk RI Spurdle, Amanda/A-4978-2011; Ligtenberg, Marjolijn/N-9666-2013; Sokolenko, Anna/G-3123-2013; manoukian, siranoush/E-7132-2017; Peissel, Bernard/E-8187-2017; D'Andrea, Emma/B-4374-2013; Sweet, Kevin/E-4172-2011; Andrulis, Irene/E-7267-2013; Hoogerbrugge, Nicoline/O-1016-2013; Radice, Paolo/O-3119-2013; Oosterwijk, Jan C./G-5770-2011; Osorio, Ana/I-4324-2014; GLADIEFF, Laurence/O-5129-2014; Dolcetti, Riccardo/O-3832-2015; Lester, Jenny/B-5933-2012; Toland, Amanda/E-4202-2011; Arnold, Norbert/E-3012-2010; montagna, marco/E-2225-2012; OI Blanco, Ignacio/0000-0002-7414-7481; Ramus, Susan/0000-0003-0005-7798; Spurdle, Amanda/0000-0003-1337-7897; Barrowdale, Daniel/0000-0003-1661-3939; PUTIGNANO, Anna Laura/0000-0001-9434-1612; Brunet, Joan/0000-0003-1945-3512; Nevanlinna, Heli/0000-0002-0916-2976; Fox, Stephen/0000-0002-7648-8896; Ligtenberg, Marjolijn/0000-0003-1290-1474; manoukian, siranoush/0000-0002-6034-7562; Peissel, Bernard/0000-0001-9233-3571; Janavicius, Ramunas/0000-0002-3773-8485; Rappaport-Fuerhauser, Christine/0000-0002-6820-0020; Robson, Mark/0000-0002-3109-1692; Eeles, Rosalind/0000-0002-3698-6241; Nathanson, Katherine/0000-0002-6740-0901; Osorio, Ana/0000-0001-8124-3984; GLADIEFF, Laurence/0000-0002-6980-9719; Dolcetti, Riccardo/0000-0003-1625-9853; Arnold, Norbert/0000-0003-4523-8808; montagna, marco/0000-0002-4929-2150; Jacobs, Chris/0000-0002-9557-9080; Evans, Gareth/0000-0002-8482-5784 FU University of Kansas Cancer Center; Kansas Bioscience Authority Eminent Scholar Program; Cancer Research UK [C12292/A11174, C1287/A10118, C1287/A11990, C5047/A8385]; European Community [223175, HEALTH-F2-2009-223175]; Medical Research Council; National Cancer Institute, NIH, [RFA-CA-06-503]; Breast Cancer Family Registry and Principal Investigators, including Cancer Care Ontario [U01 CA69467]; Columbia University [U01 CA69398]; Fox Chase Cancer Center [U01 CA69631]; Huntsman Cancer Institute [U01 CA69446]; Cancer Prevention Institute of California [U01 CA69417]; University of Melbourne [U01 CA69638]; Research Triangle Institute Informatics Support Center (RFP) [N02PC45022-46]; Cancer Care Ontario; U.S. National Cancer Institute, NIH under RFA [CA-06-503]; Research Council of Lithuania [LIG-19/2010]; LSC [05.0023.04., 10.0010.08]; NEYE Foundation; Fundacion Mutua Madrilena; Asociacion Espanola Contra el Cancer; Spanish Ministry of Science and Innovation [FIS PI08 1120]; Basque Foundation for Health Innovation and Research (BIOEF) [BIO07/CA/006]; DKFZ; Dutch Cancer Society [NKI1998-1854, NKI2004-3088, NKI2007-3756]; ZonMW [91109024]; NIHR; Royal Marsden NHS Foundation Trust; Eileen Stein Jacoby Fund [U01CA69631, 5U01CA113916]; Centre of Molecular Medicine Cologne (CMMC) [109076]; Ligue National Contre le Cancer and The Association; National Cancer Institute [NCI P30 CA51008-12]; Fisher Center for Familial Cancer Research; Helsinki University Central Hospital; Academy of Finland [132473]; Finnish Cancer Society; Sigrid Juselius Foundation; Icelandic Association "Walking for Breast Cancer Research"; Landspitali University Hospital; Canadian Breast Cancer Research [019511]; Ministero della Salute [RFPS 2006-5-341353, ACC2/R6.9]; Progetto Tumori Femminili; National Breast Cancer Foundation; National Health and Medical Research Council (NHMRC) [145684, 288704, 454508]; Queensland Cancer Fund; Cancer Councils of New South Wales, Victoria, Tasmania and South Australia; Cancer Foundation of Western Australia; NIH [CA116167, CA128978, CA74415]; Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201]; Komen Foundation for the Cure; Breast Cancer Research Foundation; U.S. National Cancer Institute; Westat, Inc. [NO2-CP-11019-50, N02-CP-65504]; Russian Federation for Basic Research [10-04-92601, 11-04-00250, 11-04-00227]; Federal Agency for Science and Innovations [02.740.11.0780]; Commission of the European Communities [PITN-GA-2009-238132]; OSU Comprehensive Cancer Center; ITT (Tuscany Institute for Tumors) [2010-2012]; NCI Bay Area Breast Cancer SPORE [P50-CA058207]; Avon Foundation; UCSF Helen Diller Family Comprehensive Cancer Center; CRUK; Cancer Genetics Network and Marjorie Cohen Foundation; American Cancer Society [SIOP-06-258-01-CCE] FX The author, A.K. Godwin, thanks the support from The University of Kansas Cancer Center and the Kansas Bioscience Authority Eminent Scholar Program. A.K. Godwin is the Chancellors Distinguished Chair in Biomedical Sciences-endowed Professor.; This work was supported by Cancer Research UK grants C12292/A11174 and C1287/A10118. The research leading to these results has received funding from the European Community's Seventh Framework Programme under grant agreement no 223175 (HEALTH-F2-2009-223175). NM was funded by a scholarship from the Medical Research Council. ACA is a CR-UK Senior Cancer Research Fellow. DFE is a CR-UK Principal Research Fellow.; This work was supported by the National Cancer Institute, NIH, under RFA-CA-06-503 and through cooperative agreements with members of the Breast Cancer Family Registry and Principal Investigators, including Cancer Care Ontario (U01 CA69467), Columbia University (U01 CA69398), Fox Chase Cancer Center (U01 CA69631), Huntsman Cancer Institute (U01 CA69446), Cancer Prevention Institute of California (U01 CA69417), University of Melbourne (U01 CA69638), and Research Triangle Institute Informatics Support Center (RFP No. N02PC45022-46).; This work was supported by Cancer Care Ontario and the U.S. National Cancer Institute, NIH, under RFA # CA-06-503 and through cooperative agreements with members of the Breast Cancer Family Registry (BCFR) and principal investigators.; Lithuania: This work is financially supported by the Research Council of Lithuania grant LIG-19/2010 to R. Janavicius.; Latvia: L. Tihomirova was financially supported by LSC grants 05.0023.04. and 10.0010.08.; The authors thank NEYE Foundation for financial support; This study was partially supported financially by the Fundacion Mutua Madrilena, Asociacion Espanola Contra el Cancer and the Spanish Ministry of Science and Innovation (FIS PI08 1120). This was funded, in part, by the Basque Foundation for Health Innovation and Research (BIOEF): BIO07/CA/006.; The DKFZ study was supported by the DKFZ.; The HEBON study is supported by the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, and NKI2007-3756 and the ZonMW grant 91109024.; EMBRACE is financially supported by Cancer Research UK Grants C1287/A10118 and C1287/A11990. D. G. Evans and F. Lalloo are financially supported by an NIHR grant to the Biomedical Research Centre, Manchester, UK. The investigators at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust are financially 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, E. Bancroft, and L. D'Mello are also financially supported by a Cancer Research UK grant C5047/A8385.; A.K. Godwinwas funded by U01CA69631, 5U01CA113916, and the Eileen Stein Jacoby Fund.; GC-HBOC is financially supported by a grant of the German Cancer Aid (grant 109076) the Centre of Molecular Medicine Cologne (CMMC).; This study was supported by The Ligue National Contre le Cancer and The Association "Le cancer du sein, parlons-en!" Award.; C. Isaacs and B.N. Peshkin are supported by National Cancer Institute Grant (NCI P30 CA51008-12) and by the Fisher Center for Familial Cancer Research.; The HEBCS study has been financially supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (132473), the Finnish Cancer Society, and the Sigrid Juselius Foundation.; The ILUH group was supported by the Icelandic Association "Walking for Breast Cancer Research" and by the Landspitali University Hospital Research Fund.; This work was supported by the Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program and by the Canadian Breast Cancer Research Alliance-grant #019511.; This study was supported by "Ministero della Salute" (grant numbers RFPS 2006-5-341353, ACC2/R6.9 and "Progetto Tumori Femminili").; 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 (funded by NHMRC grants 145684, 288704, and 454508).; The MAYO study was supported by NIH grants CA116167, CA128978, a Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), and awards from the Komen Foundation for the Cure and the Breast Cancer Research Foundation.; The research of Drs. P. L. Mai and M. H. Greene was supported by the Intramural Research Program of the U.S. National Cancer Institute and by support services contracts NO2-CP-11019-50 and N02-CP-65504 with Westat, Inc.; This work has been supported by the Russian Federation for Basic Research (grants 10-04-92601, 11-04-00250, 11-04-00227), the Federal Agency for Science and Innovations (contract 02.740.11.0780), and the Commission of the European Communities (grant PITN-GA-2009-238132).; This work was supported by the OSU Comprehensive Cancer Center. Caroline Craven and Michelle O'Connor were responsible for patient accrual and data management.; M. Caligo was supported by an ITT (Tuscany Institute for Tumors) grant 2010-2012.; S. L. Neuhausen was partially supported by NIH CA74415 and the Morris and Horowitz Families Endowed Professorship.; The grant funding was obtained from the NIH, NCI Bay Area Breast Cancer SPORE (P50-CA058207), and the Avon Foundation. Support was also provided from the UCSF Helen Diller Family Comprehensive Cancer Center.; UKFOCR was supported by a project grant from CRUK to Paul Pharoah.; The funding was obtained from Breast Cancer Research Foundation (to K.L. Nathanson); and Cancer Genetics Network and Marjorie Cohen Foundation (to S.M. Domchek).; WCRI acknowledges support from the American Cancer Society, SIOP-06-258-01-CCE. NR 47 TC 110 Z9 112 U1 6 U2 43 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 JAN PY 2012 VL 21 IS 1 BP 134 EP 147 DI 10.1158/1055-9965.EPI-11-0775 PG 14 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 875RH UT WOS:000299051500014 PM 22144499 ER PT J AU Chan, AT Hsu, M Zauber, AG Hawk, ET Bertagnolli, MM AF Chan, Andrew T. Hsu, Meier Zauber, Ann G. Hawk, Ernest T. Bertagnolli, Monica M. TI The Influence of UGT1A6 Variants and Aspirin Use in a Randomized Trial of Celecoxib for Prevention of Colorectal Adenoma SO CANCER PREVENTION RESEARCH LA English DT Article ID GENETIC-VARIANTS; RISK; CANCER; POLYMORPHISMS; RECURRENCE; POLYPS; ENZYME; CYP2C9 AB Aspirin and celecoxib prevent colorectal adenoma recurrence. Genetic variants in the UGT1A6 enzyme are associated with delayed aspirin metabolism and greater chemopreventive efficacy. We examined the effect of combining aspirin and celecoxib in relation to UGT1A6 T181A and R184S variants among 1,647 patients in the Adenoma Prevention with Celecoxib (APC) trial who were stratified according to the use of low-dose aspirin after removal of adenomas and randomized to placebo, 200-mg twice daily, or 400-mg twice daily celecoxib for 3 years. Patients underwent follow-up colonoscopies at 1 and 3 years to assess on-treatment efficacy. At 5 years, 538 patients underwent a colonoscopy to assess risk of recurrence after treatment was discontinued for at least 1 year. During treatment, the relative risk (RR) of recurrent adenoma was 0.68 [95% confidence interval (CI), 0.59-0.79] for 200-mg twice daily celecoxib and 0.54 (95% CI, 0.46-0.64) for 400-mg twice daily celecoxib compared with placebo. Aspirin use was not independently associated with recurrent adenoma (RR, 0.98, 95% CI, 0.86-1.15). These results did not vary according to UGT1A6 genotype. However, among those with a variant UGT1A6 genotype on aspirin, the RR of adenoma was 1.60 (95% CI, 0.81-3.15) after withdrawal of 200-mg twice daily and 1.98 (95% CI, 1.06-3.70) after withdrawal of 400-mg twice daily celecoxib compared with withdrawal of placebo. In contrast, there was no increased risk associated with discontinuing celecoxib among any other groups. Concurrent use of low-dose aspirin does not influence the efficacy of celecoxib in adenoma prevention. However, discontinuing celecoxib among aspirin-using individuals who initially developed adenoma despite a UGT1A6 variant genotype resulted in rapid reemergence of disease. Cancer Prev Res; 5(1); 61-72. (C)2011 AACR. C1 [Chan, Andrew T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Chan, Andrew T.; Bertagnolli, Monica M.] Harvard Univ, Sch Med, Boston, MA USA. [Chan, Andrew T.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Bertagnolli, Monica M.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Hsu, Meier; Zauber, Ann G.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Hawk, Ernest T.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Chan, AT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St,GRJ-728A, Boston, MA 02114 USA. EM achan@partners.org FU Pfizer Inc.; National Cancer Institute at the NIH [R01 CA137178, N01 CN95015] FX A. T. Chan has served as a consultant to Bayer HealthCare and Millennium Pharmaceuticals. M. M. Bertagnolli is the recipient of research funding from Pfizer Inc. E. T. Hawk has served as a consultant for Pozen Pharmaceutical Development Company. The statistical analysis of the entire data sets pertaining to efficacy and safety has been independently confirmed by A. G. Zauber, who is not employed by any corporate entity. A. T. Chan had full access to all of the data and takes full responsibility for the veracity of the data and analysis. No potential conflicts of interest were disclosed by other authors.; This work was supported by the National Cancer Institute at the NIH (grant number R01 CA137178 to A. T. Chan and N01 CN95015 to M. M. Bertagnolli). A. T. Chan is a Damon Runyon Cancer Research Foundation Clinical Investigator. NR 21 TC 6 Z9 6 U1 0 U2 1 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 JAN PY 2012 VL 5 IS 1 BP 61 EP 72 DI 10.1158/1940-6207.CAPR-11-0337 PG 12 WC Oncology SC Oncology GA 877RT UT WOS:000299200500010 PM 22030088 ER PT J AU Joshu, CE Parmigiani, G Colditz, GA Platz, EA AF Joshu, Corinne E. Parmigiani, Giovanni Colditz, Graham A. Platz, Elizabeth A. TI Opportunities for the Primary Prevention of Colorectal Cancer in the United States SO CANCER PREVENTION RESEARCH LA English DT Article ID CIGARETTE-SMOKING; BEHAVIOR-CHANGE; COLON-CANCER; RISK; INTERVENTIONS; SOCIETY; HEALTH; TRENDS; MEN AB Several studies indicate that screening in combination with lifestyle modification may produce a greater reduction in colorectal cancer rates than screening alone. To identify national opportunities for the primary prevention of colorectal cancer, we assessed the prevalence of modifiable lifestyle risk factors in the United States. We used nationally representative, cross-sectional data from 5 NHANES cycles (1999-2000, n = 2,753; 2001-2002, n = 3,169; 2003-2004, n = 2,872; 2005-2006, n = 2,993; 2007-2008, n = 3,438). We evaluated the 5 colorectal cancer risk factors deemed "convincing" by the World Cancer Research Fund (obesity, physical inactivity, intake of red meat, processed meat, alcohol), and cigarette smoking, a "suggestive" risk factor in the Surgeon General's report. We estimated the prevalence of each risk factor separately and jointly, and report it overall, and by sex, race/ethnicity, age, and year. In 2007 to 2008, 81% percent of U.S. adults, aged 20 to 69 years, had at least one modifiable risk factor for colorectal cancer. More than 15% of those younger than 50 years had 3 or more risk factors. There was no change in the prevalence of risk factors between 1999 and 2008. The most common risk factors were risk factors for other chronic diseases. Our findings provide additional support for the prioritization of preventive services in health care reform. Increasing awareness, especially among young adults, that lifestyle factors influence colorectal cancer risk, and other chronic diseases, may encourage lifestyle changes and adherence to screening guidelines. Complementary approaches of screening and lifestyle modification will likely provide the greatest reduction of colorectal cancer. Cancer Prev Res; 5(1); 138-45. (C)2011 AACR. C1 [Joshu, Corinne E.; Platz, Elizabeth A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. [Platz, Elizabeth A.] Johns Hopkins Med Inst, James Buchanan Brady Urol Inst, Baltimore, MD 21205 USA. [Platz, Elizabeth A.] Johns Hopkins Med Inst, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21205 USA. [Parmigiani, Giovanni] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Parmigiani, Giovanni] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Colditz, Graham A.] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. [Colditz, Graham A.] Washington Univ, Sch Med, Alvin J Siteman Canc Ctr, St Louis, MO USA. RP Joshu, CE (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St,Rm E6137, Baltimore, MD 21205 USA. EM cjoshu@jhsph.edu RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU National Cancer Institute at the NIH [T32 CA009314]; Seraph Foundation; American Cancer Society FX C. E. Joshu was supported by the National Cancer Institute at the NIH (grant number T32 CA009314) and the Seraph Foundation. G. A. Colditz is supported by the American Cancer Society (Clinical Research Professorship). NR 22 TC 8 Z9 8 U1 0 U2 5 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 JAN PY 2012 VL 5 IS 1 BP 138 EP 145 DI 10.1158/1940-6207.CAPR-11-0322 PG 8 WC Oncology SC Oncology GA 877RT UT WOS:000299200500017 PM 21955521 ER PT J AU Pang, PS Hoffmann, U Shah, SJ AF Pang, Peter S. Hoffmann, Udo Shah, Sanjiv J. TI Classification of Patients With Acute Heart Failure Syndromes in the Emergency Department SO CIRCULATION-HEART FAILURE LA English DT Editorial Material DE Editorials; coronary artery disease; heart failure; ischemia; troponin ID CORONARY-ARTERY-DISEASE; CLINICAL-TRIALS; MANAGEMENT; TROPONIN; OUTCOMES; ASSOCIATION; GUIDELINES; DIAGNOSIS; SOCIETY; TRENDS C1 [Pang, Peter S.] Northwestern Univ, Feinberg Sch Med, Dept Emergency Med, Chicago, IL 60611 USA. [Pang, Peter S.] Northwestern Univ, Feinberg Sch Med, Ctr Cardiovasc Innovat, Chicago, IL 60611 USA. [Shah, Sanjiv J.] Northwestern Univ, Feinberg Sch Med, Div Cardiol, Dept Med, Chicago, IL 60611 USA. [Hoffmann, Udo] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Pang, PS (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Emergency Med, 211 E Ontario St,Ste 300, Chicago, IL 60611 USA. EM ppang@northwestern.edu NR 27 TC 1 Z9 1 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD JAN PY 2012 VL 5 IS 1 BP 2 EP 5 DI 10.1161/CIRCHEARTFAILURE.111.965830 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 879IY UT WOS:000299324100007 PM 22253405 ER PT J AU Luke, JJ Hodi, FS AF Luke, Jason J. Hodi, F. Stephen TI Vemurafenib and BRAF Inhibition: A New Class of Treatment for Metastatic Melanoma SO CLINICAL CANCER RESEARCH LA English DT Article ID PHASE-III; RAF; KINASE; PATHWAY; TRIAL; DACARBAZINE; RESISTANCE; SORAFENIB; PLX4032; PLACEBO AB The U.S. Food and Drug Administration recently approved vemurafenib for the treatment of BRAF valine in exon 15, at codon 600 (V600E) mutant metastatic melanoma. Vemurafenib is a competitive small-molecule serine-threonine kinase inhibitor that functions by binding to the ATP-binding domain of mutant BRAF. Compared with dacarbazine chemotherapy, vemurafenib significantly improved the 6-month overall survival of patients from 64% to 84% and exhibited a response rate of approximately 50%. Median progression-free survival was also significantly improved with vemurafenib as compared with dacarbazine (5.3 versus 1.6 months, respectively), and this was consistent among groups analyzed, including age, sex, geography, Eastern Cooperative Oncology Group status, disease stage, and serum lactate dehydrogenase. The success of targeting melanoma genomics has created a paradigm shift for future drug development. Currently, the elucidation of resistant mechanisms to vemurafenib therapy remains an important area of active investigation that will shape rational drug treatments for melanoma. The development of vemurafenib, the role of BRAF targeting, and the changing landscape of treatment for melanoma provide a new foundation for clinical investigation. Clin Cancer Res; 18(1); 9-14. (C) 2011 AACR. C1 [Hodi, F. Stephen] Dana Farber Canc Inst, Melanoma Dis Ctr, Boston, MA 02215 USA. [Hodi, F. Stephen] Harvard Univ, Sch Med, Boston, MA USA. [Luke, Jason J.] Mem Sloan Kettering Canc Ctr, Melanoma & Sarcoma Serv, New York, NY 10021 USA. [Luke, Jason J.] Weill Cornell Med Coll, New York, NY USA. RP Hodi, FS (reprint author), Dana Farber Canc Inst, Melanoma Dis Ctr, 450 Brookline Ave, Boston, MA 02215 USA. EM Stephen_hodi@dfci.harvard.edu FU Genentech/Roche; Bristol-Myers Squibb; Novartis; Pfizer; Synta FX F.S. Hodi, clinical trial research support, Genentech/Roche, Bristol-Myers Squibb, Novartis, Pfizer, and Synta; nonpaid consultant, Genentech, Roche, Novartis, and Bristol-Myers Squibb. J.J. Luke disclosed no potential conflicts of interest. NR 29 TC 34 Z9 37 U1 1 U2 7 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 JAN 1 PY 2012 VL 18 IS 1 BP 9 EP 14 DI 10.1158/1078-0432.CCR-11-2197 PG 6 WC Oncology SC Oncology GA 871SV UT WOS:000298758900003 PM 22083257 ER PT J AU Alcala, AM Flaherty, KT AF Alcala, Alexander Marzuka Flaherty, Keith T. TI BRAF Inhibitors for the Treatment of Metastatic Melanoma: Clinical Trials and Mechanisms of Resistance SO CLINICAL CANCER RESEARCH LA English DT Article ID MUTATIONS; SURVIVAL; EFFICACY; THERAPY; CRAF AB The efficacy of selective BRAF inhibitors has now been established in the 50% of patients with metastatic melanoma whose tumors harbor activating mutations. However, for the vast majority of patients, responses persist for less than a year. In extensive preclinical investigations, researchers have focused on potential resistance mechanisms with the hope of identifying treatment strategies that can overcome resistance. Preliminary results suggest that reactivation of the mitogen-activated protein kinase (MAPK) pathway by several BRAF-independent mechanisms is the predominant pattern. However, MAPK pathway-independent mechanisms also seem to play a potential role. More definitive cataloging of resistance mechanisms in patients' tumor samples is needed as combination regimens are being readied for clinical evaluation. Clin Cancer Res; 18(1); 33-9. (C) 2012 AACR. C1 [Flaherty, Keith T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA. [Alcala, Alexander Marzuka] Yale Univ, Sch Med, New Haven, CT USA. RP Flaherty, KT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, 55 Fruit St,Yawkey 9E, Boston, MA 02114 USA. EM kflaherty@partners.org NR 28 TC 56 Z9 57 U1 0 U2 5 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 JAN 1 PY 2012 VL 18 IS 1 BP 33 EP 39 DI 10.1158/1078-0432.CCR-11-0997 PG 7 WC Oncology SC Oncology GA 871SV UT WOS:000298758900007 PM 22215904 ER PT J AU Azab, F Azab, AK Maiso, P Calimeri, T Flores, L Liu, Y Quang, P Roccaro, AM Sacco, A Ngo, HT Zhang, Y Morgan, BL Carrasco, RD Ghobrial, IM AF Azab, Feda Azab, Abdel Kareem Maiso, Patricia Calimeri, Teresa Flores, Ludmila Liu, Yang Phong Quang Roccaro, Aldo M. Sacco, Antonio Ngo, Hai T. Zhang, Yong Morgan, Brittany L. Carrasco, Ruben D. Ghobrial, Irene M. TI Eph-B2/Ephrin-B2 Interaction Plays a Major Role in the Adhesion and Proliferation of Waldenstrom's Macroglobulinemia SO CLINICAL CANCER RESEARCH LA English DT Article ID MULTIPLE-MYELOMA; TYROSINE KINASE; EPH RECEPTORS; TUMOR ANGIOGENESIS; CELL-MIGRATION; CANCER; CHEMOTAXIS; REQUIRES; DISEASE; TARGET AB Purpose: The ephrin receptors (Eph) are found in a wide range of cancers and correlate with metastasis. In this study, we characterized the role of Eph-B2 receptor in the interaction of Waldenstrom's macroglobulinemia (WM) cells with the bone marrow microenvironment. Experimental Design: We screened the activity of different receptor tyrosine kinases in WM patients and found that Eph-B2 was overexpressed compared with control. Also, we tested the expression of ephrin-B2 ligand on endothelial cells and bone marrow stromal cells (BMSC) isolated from WM patients. We then tested the role of Eph-B2/Ephrin-B2 interaction in the adhesion of WM cells to endothelial cells and BMSCs; the cell signaling induced by the coculture in both the WM cells and the endothelial cells; WM cell proliferation, apoptosis, and cell cycle in vitro and tumor progression in vivo; and in angiogenesis. Results: Eph-B2 receptor was found to be activated in WM patients compared with control, with a 5-fold increase in CD19(+) WM cells, and activated cell adhesion signaling, including focal adhesion kinase, Src, P130, paxillin, and cofilin, but decreased WM cell chemotaxis. Ephrin-B2 ligand was highly expressed on endothelial cells and BMSCs isolated from WM patients and on human umbilical vein endothelial cells and induced signaling in the endothelial cells promoting adhesion and angiogenesis. Blocking of ephrin-B2 or Eph-B2 inhibited adhesion, cytoskeletal signaling, proliferation, and cell cycle in WM cells, which was induced by coculture with endothelial cells and decreased WM tumor progression in vivo. Conclusion: Ephrin-B2/Eph-B2 axis regulates adhesion, proliferation, cell cycle, and tumor progression in vivo through the interaction of WM with the cells in the bone marrow microenvironment. Clin Cancer Res; 18(1); 91-104. (C) 2011 AACR. C1 [Azab, Feda; Azab, Abdel Kareem; Maiso, Patricia; Calimeri, Teresa; Flores, Ludmila; Liu, Yang; Phong Quang; Roccaro, Aldo M.; Sacco, Antonio; Ngo, Hai T.; Zhang, Yong; Morgan, Brittany L.; Carrasco, Ruben D.; Ghobrial, Irene M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ghobrial, IM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St,Mayer 548A, Boston, MA 02115 USA. EM irene_ghobrial@dfci.harvard.edu RI Sacco, Antonio/K-4681-2016; OI Sacco, Antonio/0000-0003-2945-9416; Maiso, Patricia/0000-0003-3745-1924; Roccaro, Aldo/0000-0002-1872-5128 FU Kirsch Laboratory for Waldenstrom's Macroglobulinemia; Heje fellowship; International Waldenstrom's Macroglobulinemia Foundation (IWMF) FX The work was supported by the Kirsch Laboratory for Waldenstrom's Macroglobulinemia, the Heje fellowship for WM, and the International Waldenstrom's Macroglobulinemia Foundation (IWMF). NR 33 TC 12 Z9 13 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 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 1 PY 2012 VL 18 IS 1 BP 91 EP 104 DI 10.1158/1078-0432.CCR-11-0111 PG 14 WC Oncology SC Oncology GA 871SV UT WOS:000298758900012 PM 22010211 ER PT J AU Schroen, AT Petroni, GR Wang, HK Thielen, MJ Gray, R Benedetti, J Wang, XFF Sargent, DJ Wickerham, DL Cronin, W Djulbegovic, B Slingluff, CL AF Schroen, Anneke T. Petroni, Gina R. Wang, Hongkun Thielen, Monika J. Gray, Robert Benedetti, Jacqueline Wang, Xiaofei F. Sargent, Daniel J. Wickerham, Donald L. Cronin, Walter Djulbegovic, Benjamin Slingluff, Craig L., Jr. TI Achieving Sufficient Accrual to Address the Primary Endpoint in Phase III Clinical Trials from US Cooperative Oncology Groups SO CLINICAL CANCER RESEARCH LA English DT Article ID RANDOMIZED CONTROLLED-TRIALS; THERAPY EVALUATION PROGRAM; TIME; RECRUITMENT AB Purpose: Assessing impact of poor accrual on premature trial closure requires a relevant metric. We propose defining accrual sufficiency on apparent ability to address primary endpoints (PE) rather than attaining accrual targets. Experimental Design: All phase III trials open January 1, 1993, to December 31, 2002, by five U.S. oncology Clinical Trials Cooperative Groups (CTCG) were evaluated for accrual sufficiency and scientific results. Sufficient accrual included meeting accrual target, CTCGs documentation attesting adequate accrual, or conclusive results at interim analysis; insufficient accrual included poor accrual as cited closure reason or other reasons rendering a trial unable to address its primary endpoints. Closure rates based on our accrual sufficiency definition are compared with rates of meeting accrual targets and addressing the primary endpoints. A percentage of target accrual above which trials commonly answer the intended scientific question was identified to serve as an alternative to meeting full target accrual in designating accrual success. Results: Of 238 eligible trials, 158 (66%) closed with sufficient accrual. Among 80 trials with insufficient accrual, 70 (29%) closed specifically because of poor accrual. Inadequate accrual rates are overemphasized when defining accrual success solely by meeting accrual targets. Nearly 75% of trials conclusively addressed the primary endpoints with positive results in 39% of trials. Exceeding 80% of target accrual serves as a reliable proxy for answering the intended scientific question. Conclusions: Approximately one third of phase III trials closed with insufficient accrual to address the primary endpoints, primarily due to poor accrual. Defining accrual sufficiency broader than meeting accrual targets represents a fairer account of trial closures. Clin Cancer Res; 18(1); 256-62. (C)2011 AACR. C1 [Schroen, Anneke T.; Thielen, Monika J.; Slingluff, Craig L., Jr.] Univ Virginia, Dept Surg, Charlottesville, VA 22908 USA. [Schroen, Anneke T.; Petroni, Gina R.; Wang, Hongkun] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA 22908 USA. [Gray, Robert] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. [Benedetti, Jacqueline] SW Oncol Grp Stat Ctr, Seattle, WA USA. [Wang, Xiaofei F.] Duke Univ, Dept Biostat & Bioinformat, Durham, NC USA. [Sargent, Daniel J.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Wickerham, Donald L.; Cronin, Walter] Natl Surg Adjuvant Breast & Bowel Project Operati, Pittsburgh, PA USA. [Djulbegovic, Benjamin] Univ S Florida, Dept Med, Tampa, FL USA. RP Schroen, AT (reprint author), Univ Virginia, Dept Surg, POB 800709, Charlottesville, VA 22908 USA. EM ats2x@virginia.edu RI Djulbegovic, Benjamin/I-3661-2012; OI Djulbegovic, Benjamin/0000-0003-0671-1447; Sargent, Daniel/0000-0002-2684-4741 FU NIH [R01 CA118232]; Public Health Service from the National Cancer Institute, Department of Health and Human Services [U10CA-12027, U10CA-69974, U10CA-37377, U10CA-69651, U10CA-25224, U24CA-114732] FX This work was supported by a grant from the NIH (R01 CA118232) to A.T. Schroen and, in part, by Public Health Service grants U10CA-12027, U10CA-69974, U10CA-37377, U10CA-69651, U10CA-25224, and U24CA-114732 from the National Cancer Institute, Department of Health and Human Services. NR 19 TC 17 Z9 17 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 1 PY 2012 VL 18 IS 1 BP 256 EP 262 DI 10.1158/1078-0432.CCR-11-1633 PG 7 WC Oncology SC Oncology GA 871SV UT WOS:000298758900027 PM 21976533 ER PT J AU Desai, NR Giugliano, RP AF Desai, Nihar R. Giugliano, Robert P. TI Can We Predict Outcomes in Atrial Fibrillation? SO CLINICAL CARDIOLOGY LA English DT Review ID ACUTE MYOCARDIAL-INFARCTION; CONGESTIVE-HEART-FAILURE; SICK SINUS SYNDROME; VENTRICULAR SYSTOLIC DYSFUNCTION; PARKINSON-WHITE SYNDROME; PROGNOSTIC-SIGNIFICANCE; CARDIOVASCULAR EVENTS; RHYTHM CONTROL; UNITED-STATES; RISK AB Atrial fibrillation (AF) is the most common arrhythmia encountered by generalists and cardiologists alike. Much of the attendant morbidity from AF arises from systemic embolic complications which are effectively reduced with utilization of anti-platelet and/or anticoagulant therapy. The systemic embolic complications of AF and the medical therapy to attenuate these risks are very well established. Through the course of this review, we aim to highlight the complex relationship between AF and other, non-embolic outcomes. The presence of AF has been demonstrated to be associated with a 1.5 to 2-fold increase in mortality across numerous observational cohorts. Still further, AF frequently coexists with heart failure, whether as a causative factor or a consequence of underlying structural heart disease or neurohumoral derangement, where its presence is associated with worse clinical outcomes. Whether AF is an independent risk factor for acute coronary syndromes (ACS) remains controversial, though its occurrence in patients with ACS has been shown to be associated with adverse outcomes both in observational cohorts as well as clinical trial populations. Individuals with AF have a 1.5 to 3-fold increase in the rate of hospitalization and are at elevated risk for other arrhythmic disorders including both bradyarrhythmias as well as tachyarrhythmias. AF leads to considerable morbidity and mortality for patients and exacts a tremendous financial toll on the healthcare systemestimated to range from $6.0 to $26.0 billion. Given the current demographic transition in developed countries, the prevalence of AF will continue to increase and the need for refined approaches to risk stratification and pharmacotherapeutic interventions to attenuate the burden on patients will only become more important. C1 [Desai, Nihar R.; Giugliano, Robert P.] Harvard Univ, Brigham & Womens Hosp, Div Cardiovasc Med, Dept Med,Med Sch, Boston, MA 02115 USA. RP Giugliano, RP (reprint author), TIMI Study Grp, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM rgiugliano@partners.org FU Sanofi Aventis; Daiichi-Sankyo, Merck FX N.R. Desai and R. P. Giugliano received an honorarium through an educational grant from Sanofi Aventis for their time and expertise spent writing this article. R. P. Giugliano has also received research grant support and honoraria for CME lectures/consulting services from Daiichi-Sankyo, Merck. He has also received honoraria for CME lectures from Bristol Myers Squibb. NR 36 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0160-9289 J9 CLIN CARDIOL JI Clin. Cardiol. PD JAN PY 2012 VL 35 SU 1 BP S10 EP S14 DI 10.1002/clc.20989 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 875ZU UT WOS:000299076800003 ER PT J AU Apple, FS Blankenberg, S Morrow, DA AF Apple, Fred S. Blankenberg, Stefan Morrow, David A. TI Impact of Biomarkers, Proteomics, and Genomics in Cardiovascular Disease Introduction SO CLINICAL CHEMISTRY LA English DT Editorial Material C1 [Apple, Fred S.] Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA. [Apple, Fred S.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. [Blankenberg, Stefan] Univ Med Ctr Hamburg Eppendorf, Univ Heart Ctr, Dept Gen & Intervent Cardiol, Hamburg, Germany. [Morrow, David A.] Brigham & Womens Hosp, Dept Med, TIMI Study Grp, Boston, MA 02115 USA. [Morrow, David A.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. RP Apple, FS (reprint author), Hennepin Cty Med Ctr, Clin Labs P4,701 Pk Ave, Minneapolis, MN 55415 USA. EM apple004@umn.edu NR 28 TC 3 Z9 3 U1 0 U2 6 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JAN PY 2012 VL 58 IS 1 BP 1 EP 2 DI 10.1373/clinchem.2011.175919 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 875RQ UT WOS:000299052700001 PM 22125299 ER PT J AU Ho, JE Wang, TJ AF Ho, Jennifer E. Wang, Thomas J. TI Growth Differentiation Factor 15: A Canary in a Coal Mine? SO CLINICAL CHEMISTRY LA English DT Editorial Material ID CARDIOVASCULAR DYSFUNCTION; BETA SUPERFAMILY; DISEASE; ACTIVATION; MARKER; MEMBER; HEART; RISK C1 [Ho, Jennifer E.; Wang, Thomas J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Wang, TJ (reprint author), Massachusetts Gen Hosp, Div Cardiol, GRB 800,55 Fruit St, Boston, MA 02114 USA. EM tjwang@partners.org OI Ho, Jennifer/0000-0002-7987-4768 FU NHLBI NIH HHS [R01-HL083197, R01-HL086875, R01-HL098283, R01-HL102780, R01 HL102780, R01 HL083197, R01 HL086875, R01 HL098283]; NIDDK NIH HHS [R01 DK081572, R01-DK081572] NR 17 TC 6 Z9 6 U1 0 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JAN PY 2012 VL 58 IS 1 BP 3 EP 5 DI 10.1373/clinchem.2011.175406 PG 3 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 875RQ UT WOS:000299052700002 PM 22065154 ER PT J AU Apple, FS Morrow, DA AF Apple, Fred S. Morrow, David A. TI Delta Cardiac Troponin Values in Practice: Are We Ready to Move Absolutely Forward to Clinical Routine? SO CLINICAL CHEMISTRY LA English DT Editorial Material ID ACUTE MYOCARDIAL-INFARCTION; I ASSAY; CORONARY SYNDROME; EARLY-DIAGNOSIS; DEFINITION; ISCHEMIA; OUTCOMES; RISK C1 [Apple, Fred S.] Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA. [Apple, Fred S.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. [Morrow, David A.] Brigham & Womens Hosp, Dept Med, TIMI Study Grp, Boston, MA 02115 USA. [Morrow, David A.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. RP Apple, FS (reprint author), Hennepin Cty Med Ctr, Clinical Labs P4,701 Pk Ave, Minneapolis, MN 55415 USA. EM apple004@umn.edu NR 14 TC 14 Z9 14 U1 0 U2 2 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JAN PY 2012 VL 58 IS 1 BP 8 EP 10 DI 10.1373/clinchem.2011.175414 PG 3 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 875RQ UT WOS:000299052700004 PM 22125300 ER PT J AU Apple, FS Morrow, D Zaugg, C Hickey, D Zaharik, M Blackwood, JJ Jakobsen, K AF Apple, Fred S. Morrow, David Zaugg, Christian Hickey, David Zaharik, Michelle Blackwood, John J. Jakobsen, Kirsten TI The Challenges and Concerns Companies Face Pertaining to the US Food and Drug Administration 510(k) Process for Cardiac Biomarkers SO CLINICAL CHEMISTRY LA English DT Editorial Material C1 [Apple, Fred S.] Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA. [Apple, Fred S.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. [Morrow, David] Brigham & Womens Hosp, Dept Med, TIMI Study Grp, Boston, MA 02115 USA. [Morrow, David] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. [Hickey, David] Roche Diagnost, Med & Sci Affairs, Rotkreuz, Switzerland. [Hickey, David] Siemens Healthcare Diagnost, Chem Immunoassay & Automat Business Unit, Tarrytown, NY USA. [Zaharik, Michelle] Response Biomed, Prod Dev, Vancouver, BC, Canada. [Blackwood, John J.] Beckman Coulter, Prod Management, Chaska, MN USA. [Jakobsen, Kirsten] Radiometer Med, Copenhagen, Denmark. RP Apple, FS (reprint author), Hennepin Cty Med Ctr, Clinical Labs P4,701 Pk Ave, S Minneapolis, MN 55415 USA. EM apple004@umn.edu NR 0 TC 4 Z9 4 U1 0 U2 2 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JAN PY 2012 VL 58 IS 1 BP 31 EP 38 DI 10.1373/clinchem.2011.165860 PG 8 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 875RQ UT WOS:000299052700009 PM 22096032 ER PT J AU Gilstrap, LG Wang, TJ AF Gilstrap, Lauren G. Wang, Thomas J. TI Biomarkers and Cardiovascular Risk Assessment for Primary Prevention: An Update SO CLINICAL CHEMISTRY LA English DT Review ID C-REACTIVE PROTEIN; CORONARY-HEART-DISEASE; NATRIURETIC PEPTIDE LEVELS; HIGHLY SENSITIVE ASSAY; PHOSPHOLIPASE A(2); ARTERY-DISEASE; INDEPENDENT PREDICTOR; ATHEROSCLEROSIS RISK; MULTIPLE BIOMARKERS; ROC CURVE AB BACKGROUND: Interest in cardiovascular biomarkers in primary prevention has increased dramatically in the past decade. This increase has been fueled by an improved understanding of cardiovascular pathophysiology, as well as novel technologies for biomarker identification. CONTENT: In this review we provide a brief overview of recent concepts in the evaluation of screening biomarkers, because biomarkers may behave differently when used for screening as opposed to diagnosis or disease staging. The following specific biomarker examples are then discussed, with a focus on data from primary prevention studies: high-sensitivity C-reactive protein, B-type natriuretic peptide, lipoprotein-associated phospholipase A2, and high-sensitivity troponin T. The article concludes by addressing novel platforms for biomarker discovery, reviewing recent examples from the field of metabolomics. SUMMARY: An ongoing challenge is to develop screening strategies that can identify individuals at risk for cardiovascular events well before symptoms appear. For this purpose, the measurement of soluble biomarkers could be an important adjunct to traditional cardiovascular risk assessment. Recent studies highlight both the strengths and limitations of "novel" circulating biomarkers, and suggest that substantial work is still needed to identify biomarkers that are sufficiently accurate and cost-effective for routine use in primary prevention. (C) 2011 American Association for Clinical Chemistry C1 [Gilstrap, Lauren G.; Wang, Thomas J.] Harvard Univ, Div Cardiol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Gilstrap, Lauren G.; Wang, Thomas J.] Harvard Univ, Dept Med, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Wang, TJ (reprint author), Harvard Univ, Div Cardiol, Massachusetts Gen Hosp, Sch Med, GRB 800, Boston, MA 02114 USA. EM tjwang@partners.org FU NIH [R01-HL086875, R01-HL102780, R01-DK081572, R01-HL098283, R01-HL083197]; Diasorin; Brahms; Critical Diagnostics; Singulex; Siemens Healthcare Diagnostics; Roche Diagnostics FX T.J. Wang, NIH R01-HL086875, R01-HL102780, R01-DK081572, R01-HL098283, and R01-HL083197; Diasorin; Brahms; Critical Diagnostics; Singulex; Siemens Healthcare Diagnostics; and Roche Diagnostics. NR 77 TC 38 Z9 39 U1 2 U2 16 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JAN PY 2012 VL 58 IS 1 BP 72 EP 82 DI 10.1373/clinchem.2011.165712 PG 11 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 875RQ UT WOS:000299052700016 PM 22125305 ER PT J AU Schnabel, RB Baccarelli, A Lin, HH Ellinor, PT Benjamin, EJ AF Schnabel, Renate B. Baccarelli, Andrea Lin, Honghuang Ellinor, Patrick T. Benjamin, Emelia J. TI Next Steps in Cardiovascular Disease Genomic Research-Sequencing, Epigenetics, and Transcriptomics SO CLINICAL CHEMISTRY LA English DT Review ID CORONARY-ARTERY-DISEASE; SINGLE-NUCLEOTIDE POLYMORPHISMS; COPY NUMBER VARIANTS; DNA METHYLATION; GENE-EXPRESSION; MYOCARDIAL-INFARCTION; WIDE ASSOCIATION; HEART-FAILURE; CHROMATIN MODIFICATIONS; CARDIAC-HYPERTROPHY AB BACKGROUND: Genomic research in cardiovascular disease (CVD) has progressed rapidly over the last 5 years. In most cases, however, these groundbreaking observations have not yet been accompanied by clinically applicable tools for risk prediction, diagnosis, or therapeutic interventions. CONTENT: We reviewed the scientific literature published in English for novel methods and promising genomic targets that would permit large-scale screening and follow-up of recent genomic findings for CVD. We anticipate that advances in 3 key areas will be critical for the success of these projects. First, exome-centered and whole-genome next-generation sequencing will identify rare and novel genetic variants associated with CVD and its risk factors. Improvements in methods will also greatly advance the field of epigenetics and gene expression in humans. Second, research is increasingly acknowledging that static DNA sequence variation explains only a fraction of the inherited phenotype. Therefore, we expect that multiple epigenetic and gene expression signatures will be related to CVD in experimental and clinical settings. Lever-aging existing large-scale consortia and clinical biobanks in combination with electronic health records holds promise for integrating epidemiological and clinical genomics data. Finally, a systems biology approach will be needed to integrate the accumulated multidimensional data. SUMMARY: Novel methods in sequencing, epigenetics, and transcriptomics, plus unprecedented large-scale cooperative efforts, promise to generate insights into the complexity of CVD. The rapid accumulation and integration of knowledge will shed light on a considerable proportion of the missing heritability for CVD. (C) 2011 American Association for Clinical Chemistry C1 [Schnabel, Renate B.] Univ Heart Ctr Hamburg, Dept Gen & Intervent Cardiol, Hamburg, Germany. [Baccarelli, Andrea] Harvard Univ, Sch Publ Hlth, Lab Environm Epigenet, Exposure Epidemiol & Risk Program, Boston, MA 02115 USA. [Lin, Honghuang; Benjamin, Emelia J.] NHLBI, Framingham, MA USA. [Lin, Honghuang; Benjamin, Emelia J.] Boston Univ Framingham Heart Study, Framingham, MA USA. [Lin, Honghuang] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Cardiol Sect, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Prevent Med Sect, Boston, MA 02118 USA. RP Schnabel, RB (reprint author), Univ Heart Ctr Hamburg, Dept Gen & Intervent Cardiol, Hamburg, Germany. EM schnabelr@gmx.de RI Schnabel, Renate/F-6527-2014; OI Lin, Honghuang/0000-0003-3043-3942; Baccarelli, Andrea/0000-0002-3436-0640; Benjamin, Emelia/0000-0003-4076-2336 FU Evans Center for Interdisciplinary Biomedical Research ARC on "Atrial Fibrillation at Boston University"; Deutsche Forschungsgemeinschaft (German Research Foundation) [SCHN 1149/3-1]; National Institute of Environmental Health Sciences [P30ES000002, R21ES019773, R01ES015172]; NIH [1R01HL092577, 5R21DA027021, 5R01HL104156, 1K24HL105780, 1RC1HL101056, 1R01HL102214, 1R01AG028321] FX Evans Center for Interdisciplinary Biomedical Research ARC on "Atrial Fibrillation at Boston University" (http://www.bumc.bu.edu/evanscenteribr/). R. Schnabel, Deutsche Forschungsgemeinschaft (German Research Foundation) Emmy Noether Program SCHN 1149/3-1; A. Baccarelli, National Institute of Environmental Health Sciences grants P30ES000002, R21ES019773, and R01ES015172; P. Ellinor, NIH grants 1R01HL092577, 5R21DA027021, 5R01HL104156, and 1K24HL105780; E. Benjamin, NIH grants 1R01HL092577, 1RC1HL101056, 1R01HL102214, and 1R01AG028321. NR 100 TC 28 Z9 29 U1 1 U2 18 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JAN PY 2012 VL 58 IS 1 BP 113 EP 126 DI 10.1373/clinchem.2011.170423 PG 14 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 875RQ UT WOS:000299052700020 PM 22100807 ER PT J AU van Kimmenade, RRJ Januzzi, JL AF van Kimmenade, Roland R. J. Januzzi, James L., Jr. TI Emerging Biomarkers in Heart Failure SO CLINICAL CHEMISTRY LA English DT Review ID BRAIN NATRIURETIC PEPTIDE; CELL DISTRIBUTION WIDTH; GELATINASE-ASSOCIATED LIPOCALIN; GROWTH-DIFFERENTIATION FACTOR-15; EXTRACELLULAR-MATRIX TURNOVER; ACUTE MYOCARDIAL-INFARCTION; HIGH-SENSITIVITY TROPONIN; LONG PENTRAXIN PTX3; FAMILY-MEMBER ST2; RISK STRATIFICATION AB BACKGROUND: Until recently, biomarker testing in heart failure (HF) syndromes has been viewed as an elective supplement to diagnostic evaluation of patients suspected to suffer from this condition. This approach to the use of biomarker testing contrasts with other cardiovascular diagnoses such as acute myocardial infarction, for which biomarkers are integral to disease process definition, risk stratification, and in some cases treatment decision making. CONTENT: In this review we consider various perspectives on the evaluation of biomarkers in HF. In addition, we examine recent advances in the understanding of established biomarkers in HF (such as the natriuretic peptides), the elucidation of novel biomarkers potentially useful for the evaluation and management of patients with HF, and the growing understanding of important and relevant comorbidities in HF. We also review candidate biomarkers from a number of classes: (a) myocyte stretch, (b) myocyte necrosis, (c) systemic inflammation, (d) oxidative stress, (e) extracellular matrix turnover, (f) neurohormones, and (g) biomarkers of extracardiac processes, such as renal function. SUMMARY: Novel applications of established biomarkers of HF as well as elucidation and validation of emerging assays for HF syndromes have collectively led to a growing interest in the more widespread use of such testing in patients affected by the diagnosis. (C) 2011 American Association for Clinical Chemistry C1 [Januzzi, James L., Jr.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [van Kimmenade, Roland R. J.] Maastricht Univ Med Ctr, Dept Cardiol, Maastricht, Netherlands. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Div Cardiol, Yawkey 5984,55 Fruit St, Boston, MA 02114 USA. EM JJanuzzi@Partners.org RI Kimmenade, R.R.J./L-4432-2015 FU Roche; Critical Diagnostics; Siemens FX J.L. Januzzi, Roche, Critical Diagnostics, and Siemens. NR 88 TC 96 Z9 96 U1 4 U2 16 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JAN PY 2012 VL 58 IS 1 BP 127 EP 138 DI 10.1373/clinchem.2011.165720 PG 12 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 875RQ UT WOS:000299052700021 PM 22086968 ER PT J AU Rhee, EP Gerszten, RE AF Rhee, Eugene P. Gerszten, Robert E. TI Metabolomics and Cardiovascular Biomarker Discovery SO CLINICAL CHEMISTRY LA English DT Review ID CORONARY-ARTERY-DISEASE; HEART-DISEASE; RISK; REVEALS; MARKERS; METABOLISM; EVENTS; PLASMA; BLOOD; TECHNOLOGIES AB BACKGROUND: Metabolomics, the systematic analysis of low molecular weight biochemical compounds in a biological specimen, has been increasingly applied to biomarker discovery. CONTENT: Because no single analytical method can accommodate the chemical diversity of the entire metabolome, various methods such as nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS) have been employed, with the latter coupled to an array of separation techniques including gas and liquid chromatography. Whereas NMR can provide structural information and absolute quantification for select metabolites without the use of exogenous standards, MS tends to have much higher analytical sensitivity, enabling broader surveys of the metabolome. Both NMR and MS can be used to characterize metabolite data either in a targeted manner or in a nontargeted, pattern-recognition manner. In addition to technical considerations, careful sample selection and study design are important to minimize potential confounding influences on the metabolome, including diet, medications, and comorbitidies. To this end, metabolite profiling has been applied to human biomarker discovery in small-scale interventions, in which individuals are extremely well phenotyped and able to serve as their own biological controls, as well as in larger epidemiological cohorts. Understanding how metabolites relate to each other and to established risk markers for diseases such as diabetes and renal failure will be important in evaluating the potential value of these metabolites as clinically useful biomarkers. SUMMARY: Applied to both experimental and epidemiological study designs, metabolite profiling has begun to highlight the breadth metabolic disturbances that accompany human disease. Experimental work in model systems and integration with other functional genomic approaches will be required to establish a causal link between select biomarkers and disease pathogenesis. (C) 2011 American Association for Clinical Chemistry C1 [Gerszten, Robert E.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Gerszten, Robert E.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Rhee, Eugene P.] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [Rhee, Eugene P.; Gerszten, Robert E.] Broad Inst, Cambridge, MA USA. RP Gerszten, RE (reprint author), Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. EM rgerszten@partners.org FU NIDDK NIH HHS [K08 DK090142, K08 DK090142-02] NR 36 TC 82 Z9 86 U1 6 U2 58 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JAN PY 2012 VL 58 IS 1 BP 139 EP 147 DI 10.1373/clinchem.2011.169573 PG 9 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 875RQ UT WOS:000299052700022 PM 22110018 ER PT J AU Kohli, P Bonaca, MP Kakkar, R Kudinova, AY Scirica, BM Sabatine, MS Murphy, SA Braunwald, E Lee, RT Morrow, DA AF Kohli, Payal Bonaca, Marc P. Kakkar, Rahul Kudinova, Anastacia Y. Scirica, Benjamin M. Sabatine, Marc S. Murphy, Sabina A. Braunwald, Eugene Lee, Richard T. Morrow, David A. TI Role of ST2 in Non-ST-Elevation Acute Coronary Syndrome in the MERLIN-TIMI 36 Trial SO CLINICAL CHEMISTRY LA English DT Article ID FAMILY-MEMBER ST2; ACUTE MYOCARDIAL-INFARCTION; SERUM-SOLUBLE ST2; HEART-FAILURE; NATRIURETIC PEPTIDE; BIOMARKER ST2; ACUTE DYSPNEA; RECEPTOR; MORTALITY; PROTEIN AB OBJECTIVE: We investigated the prognostic performance of ST2 with respect to cardiovascular death (CVD) and heart failure (HF) in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) in a large multinational trial. BACKGROUND: Myocytes that are subjected to mechanical stress secrete ST2, a soluble interleukin-1 receptor family member that is associated with HF after STE-ACS. METHODS: We measured ST2 with a high-sensitivity assay in all available baseline samples (N = 4426) in patients enrolled in the Metabolic Efficiency With Ranolazine for Less Ischemia in the Non-ST-Elevation Acute Coronary Syndrome Thrombolysis in Myocardial Infarction 36 (MERLIN-TIMI 36), a placebo-controlled trial of ranolazine in NSTE-ACS. All events, including cardiovascular death and new or worsening HF, were adjudicated by an independent events committee. RESULTS: Patients with ST2 concentrations in the top quartile (> 35 mu g/L) were more likely to be older and male and have diabetes and renal dysfunction. ST2 was only weakly correlated with troponin and B-type natriuretic peptide. High ST2 was associated with increased risk for CVD/HF at 30 days (6.6% vs 1.6%, P < 0.0001) and 1 year (12.2% vs 5.2%, P < 0.0001). The risk associated with ST2 was significant after adjustment for clinical covariates and biomarkers (adjusted hazard ratio CVD/HF 1.90, 95% CI 1.15-3.13 at 30 days, P = 0.012; 1.51, 95% CI 1.15-1.98 at 1 year, P = 0.003), with a significant integrated discrimination improvement (P < 0.0001). No significant interaction was found between ST2 and ranolazine (P(interaction) = 0.15). CONCLUSIONS: ST2 correlates weakly with biomarkers of acute injury and hemodynamic stress but is strongly associated with the risk of HF after NSTE-ACS. This biomarker and related pathway merit further investigation as potential therapeutic targets for patients with ACS at risk for cardiac remodeling. (C) 2011 American Association for Clinical Chemistry C1 [Kohli, Payal] Harvard Univ, Brigham & Womens Hosp, TIMI Study Grp, Cardiovasc Div,Sch Med, Boston, MA 02115 USA. [Kohli, Payal; Bonaca, Marc P.; Kudinova, Anastacia Y.; Scirica, Benjamin M.; Sabatine, Marc S.; Braunwald, Eugene; Lee, Richard T.; Morrow, David A.] Harvard Univ, Brigham & Womens Hosp, Dept Med, Cardiovasc Div,Sch Med, Boston, MA 02115 USA. [Kakkar, Rahul] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kakkar, Rahul] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Kohli, P (reprint author), Harvard Univ, Brigham & Womens Hosp, TIMI Study Grp, Cardiovasc Div,Sch Med, 75 Francis St, Boston, MA 02115 USA. EM pkohli@partners.org FU CV Therapeutics; NIH; Critical Diagnostics; National Heart, Lung, and Blood Institute [RC1HL099692] FX CV Therapeutics (acquired by Gilead Pharmaceuticals) provided research grant support for the MERLIN-TIMI 36 trial. R.T. Lee, NIH; D.A. Morrow, Critical Diagnostics and National Heart, Lung, and Blood Institute (award number RC1HL099692); M.S. Sabatine, National Heart, Lung, and Blood Institute (award number RC1HL099692). Critical Diagnostics provided reagent for measurement of ST2. NR 36 TC 46 Z9 53 U1 2 U2 6 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JAN PY 2012 VL 58 IS 1 BP 257 EP 266 DI 10.1373/clinchem.2011.173369 PG 10 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 875RQ UT WOS:000299052700039 PM 22096031 ER PT J AU Grandin, EW Jarolim, P Murphy, SA Ritterova, L Cannon, CP Braunwald, E Morrow, DA AF Grandin, E. Wilson Jarolim, Petr Murphy, Sabina A. Ritterova, Lea Cannon, Christopher P. Braunwald, Eugene Morrow, David A. TI Galectin-3 and the Development of Heart Failure after Acute Coronary Syndrome: Pilot Experience from PROVE IT-TIMI 22 SO CLINICAL CHEMISTRY LA English DT Article ID MYOCARDIAL-INFARCTION; PROGNOSTIC VALUE; FIBROSIS; MACROPHAGES; DYSFUNCTION; PREDICTORS; EXPRESSION; MORTALITY; HF AB BACKGROUND: Galectin-3 is a beta-galactoside-binding lectin that has been implicated in cardiac fibrosis and remodeling, is increased in models of failure-prone hearts, and has prognostic value in patients with heart failure (HF). The relationship between galectin-3 and the development of HF after acute coronary syndrome (ACS) is unknown. METHODS: In a nested case-control study among patients with ACS in PROVE IT-TIMI 22, we identified 100 cases with a hospitalization for new or worsening HF. Controls were matched (1:1) for age, sex, ACS type, and randomized treatment. Serum galectin-3 was measured at baseline (within 7 days post-ACS). RESULTS: Patients who developed HF had higher baseline galectin-3 [median 16.7 mu g/L (25th, 75th percentile 14.0, 20.6) vs 14.6 mu g/L (12.0, 17.6), P = 0.004]. Patients with baseline galectin-3 above the median had an odds ratio of 2.1 (95% CI 1.2-3.6) for developing HF, P = 0.010. Galectin-3 showed a graded relationship with risk of HF. Cases were more likely to have hypertension, diabetes, prior MI, and prior HF; after adjustment for these factors, this graded relationship with galectin-3 quartile and HF remained significant [adjusted OR 1.4 (95% CI 1.1-1.9), P = 0.020]. When BNP was added to the model, the relationship between galectin-3 and HF was attenuated [adjusted OR 1.3 (95% CI: 0.96 -1.9), P = 0.08]. CONCLUSIONS: The finding that galectin-3 is associated with the risk of developing HF following ACS adds to emerging evidence supporting galectin-3 as a biomarker of adverse remodeling contributing to HF as well as a potential therapeutic target. (C) 2011 American Association for Clinical Chemistry C1 [Grandin, E. Wilson] Brigham & Womens Hosp, Dept Med, TIMI Study Grp, Boston, MA 02115 USA. [Cannon, Christopher P.; Braunwald, Eugene; Morrow, David A.] Brigham & Womens Hosp, Dept Med, Cardiovasc Div, Boston, MA 02115 USA. [Jarolim, Petr; Ritterova, Lea] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Grandin, EW (reprint author), Brigham & Womens Hosp, Dept Med, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM wgrandin1@partners.org FU Bristol-Myers Squibb/Sankyo FX The PROVE IT-TIMI 22 trial was supported by Bristol-Myers Squibb/Sankyo. D.A. Morrow (principal investigator), BG Medicine. NR 25 TC 52 Z9 56 U1 0 U2 5 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JAN PY 2012 VL 58 IS 1 BP 267 EP 273 DI 10.1373/clinchem.2011.174359 PG 7 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 875RQ UT WOS:000299052700040 PM 22110019 ER PT J AU Karakas, M Januzzi, JL Hoffmann, U Koenig, W AF Karakas, Mahir Januzzi, James L., Jr. Hoffmann, Udo Koenig, Wolfgang TI Copeptin-A Novel Marker in Acute Myocardial Infarction In Reply SO CLINICAL CHEMISTRY LA English DT Letter ID SENSITIVITY TROPONIN-T; CHEST-PAIN; RAPID RULE; ELEVATION; ISCHEMIA C1 [Karakas, Mahir; Koenig, Wolfgang] Univ Ulm, Med Ctr, Dept Internal Med Cardiol 3, D-89081 Ulm, Germany. [Januzzi, James L., Jr.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Koenig, W (reprint author), Univ Ulm, Med Ctr, Dept Internal Med Cardiol 3, Albert Einstein Allee 23, D-89081 Ulm, Germany. EM wolfgang.koenig@uniklinik-ulm.de NR 10 TC 0 Z9 0 U1 1 U2 3 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JAN PY 2012 VL 58 IS 1 BP 309 EP 311 DI 10.1373/clinchem.2011.175422 PG 4 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 875RQ UT WOS:000299052700049 ER PT J AU Hendrickson, RG McKeown, NJ AF Hendrickson, Robert G. McKeown, Nathanael J. TI Is maternal opioid use hazardous to breast-fed infants? SO CLINICAL TOXICOLOGY LA English DT Editorial Material DE Opioids; Breast milk; Human milk; Breastfeeding; Analgesics ID PATIENT-CONTROLLED ANALGESIA; HUMAN-MILK; HUMAN LIVER; CODEINE USE; METHADONE-MAINTENANCE; NEONATAL-PERIOD; PREGNANT-WOMEN; DRUG-THERAPY; IN-VITRO; MORPHINE AB Over the last few decades, the rate of breastfeeding has increased steadily in the developed countries of the world. During this time, opioid use in the general population has steadily increased as well. Despite this, clinicians remain unclear whether opioid use is safe during breastfeeding. While the vast majority of medications used during breastfeeding occur without incident, case reports and studies have reported possible opioid toxicity in breast-fed infants. Multiple enzymes are involved in the metabolism of opioids. CYP2D6 catabolizes O-demethylation of codeine, tramadol, oxycodone, and hydrocodone to more potent metabolites. CYP3A4 inactivates methadone, meperidine, and buprenorphine. Glucoronide conjugation by the UGT enzyme family inactivates morphine and hydromorphone. Genetic polymorphisms and interfering medications affect the maternal metabolism, which in turn determines the exposure and risk to the breast-fed neonate. We review the production of breast milk, the transfer of xenobiotics from blood to milk, the characteristics that alter xenobiotic breast-milk concentrations, and we review the evidence of specific common opioids and infant toxicity. The short-term maternal use of prescription opioids is usually safe and infrequently presents a hazard to the newborn. C1 [Hendrickson, Robert G.; McKeown, Nathanael J.] Oregon Hlth & Sci Univ, Portland, OR 97219 USA. [Hendrickson, Robert G.; McKeown, Nathanael J.] Oregon Poison Ctr, Portland, OR USA. [McKeown, Nathanael J.] Portland VA Med Ctr, Portland, OR USA. RP Hendrickson, RG (reprint author), Oregon Hlth & Sci Univ, 3181 SW Sam Jackson Pk Rd,Mail Code CB550, Portland, OR 97219 USA. EM hendriro@ohsu.edu NR 110 TC 17 Z9 18 U1 3 U2 14 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 1556-3650 J9 CLIN TOXICOL JI Clin. Toxicol. PD JAN PY 2012 VL 50 IS 1 BP 1 EP 14 DI 10.3109/15563650.2011.635147 PG 14 WC Toxicology SC Toxicology GA 876RZ UT WOS:000299126700001 PM 22148986 ER PT J AU Marchiori, EJ Torrente, J del Blanco, A Moreno-Ger, P Sancho, P Fernandez-Manjon, B AF Marchiori, Eugenio J. Torrente, Javier del Blanco, Angel Moreno-Ger, Pablo Sancho, Pilar Fernandez-Manjon, Baltasar TI A narrative metaphor to facilitate educational game authoring SO COMPUTERS & EDUCATION LA English DT Article DE Authoring tools and methods; Serious games; Improving classroom teaching ID END-USER DEVELOPMENT; DESIGN; COMPUTER AB In this paper we present WEEV (Writing Environment for Educational Video games), a methodology for educational point-and-click adventure game authoring. Our approach aims to allow educators to actively collaborate in the educational game development process, using a narrative-based representation. WEEV is based on a pragmatic reinterpretation of previous works on narrativity and video games, enhanced by the use of a novel visual language to represent the flow of the story or narrative. The WEEV methodology has been implemented into an actual tool based on the already established < e-Adventure > platform for educational games. This tool was improved with feedback gathered from formative evaluation, end-users testing (i.e. educators), and actual use in the development of an educational game. The system, still under development, presents some user-interaction problems along with a need for the educational effectiveness of the resulting games to be further analyzed. However, this paper highlights that, according to the qualitative results of evaluations, WEEV can indeed be successfully applied to simplify the game creation process and that by using representations of games that educators can understand, WEEV can help provide educational value to games. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Marchiori, Eugenio J.; Torrente, Javier; del Blanco, Angel; Moreno-Ger, Pablo; Sancho, Pilar; Fernandez-Manjon, Baltasar] Univ Complutense, Dept Software Engn & Artificial Intelligence, E-28040 Madrid, Spain. [Fernandez-Manjon, Baltasar] Harvard Univ, Massachusetts Gen Hosp, Comp Sci Lab, Boston, MA USA. RP Marchiori, EJ (reprint author), Univ Complutense, Dept Software Engn & Artificial Intelligence, E-28040 Madrid, Spain. EM emarchiori@fdi.ucm.es; jtorrente@fdi.ucm.es; angel.dba@fdi.ucm.es; pablom@fdi.ucm.es; pilar@sip.ucm.es; balta@fdi.ucm.es RI Fernandez-Manjon, Baltasar/A-5281-2011; Moreno-Ger, Pablo/B-5419-2009 OI Fernandez-Manjon, Baltasar/0000-0002-8200-6216; Moreno-Ger, Pablo/0000-0003-4817-8150 FU Ministry of Education [Movilidad I-D+i PR2010-0070, TIN2010-21735-C02-02]; Ministry of Industry [TSI-020110-2009-170, TSI-020312-2009-27]; Complutense University of Madrid; Regional Government of Madrid [GR35/10-A, S2009/TIC-1650]; PROACTIVE EU [505469-2009-LLP-ES-KA3-KA3MP]; GALA EU Network of Excellence in serious games [FP7-ICT-2009-5- 258169] FX The Ministry of Education (grants Movilidad I-D+i PR2010-0070 and TIN2010-21735-C02-02) and the Ministry of Industry (grants TSI-020110-2009-170, TSI-020312-2009-27) have partially supported this work, as well as the Complutense University of Madrid and the Regional Government of Madrid (research group GR35/10-A and project e-Madrid S2009/TIC-1650), and the PROACTIVE EU project (505469-2009-LLP-ES-KA3-KA3MP) and the GALA EU Network of Excellence in serious games (FP7-ICT-2009-5- 258169). NR 36 TC 13 Z9 14 U1 5 U2 25 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0360-1315 J9 COMPUT EDUC JI Comput. Educ. PD JAN PY 2012 VL 58 IS 1 BP 590 EP 599 DI 10.1016/j.compedu.2011.09.017 PG 10 WC Computer Science, Interdisciplinary Applications; Education & Educational Research SC Computer Science; Education & Educational Research GA 868LH UT WOS:000298524300052 ER PT J AU Fiedler, SE Sisson, JH Wyatt, TA Pavlik, JA Gambling, TM Carson, JL Carr, DW AF Fiedler, Sarah E. Sisson, Joseph H. Wyatt, Todd A. Pavlik, Jacqueline A. Gambling, Todd M. Carson, Johnny L. Carr, Daniel W. TI Loss of ASP but not ROPN1 reduces mammalian ciliary motility SO CYTOSKELETON LA English DT Article DE ROPN1L; ropporin; A-kinase anchoring protein; OmniBank (R) ID KINASE ANCHORING PROTEIN; RADIAL SPOKE PROTEIN-3; AIRWAY EPITHELIAL-CELLS; BEAT FREQUENCY; DEPENDENT PHOSPHORYLATION; FLAGELLAR MOTILITY; REGULATORY SUBUNIT; BINDING-PROTEIN; FIBROUS SHEATH; CAMP AB Protein kinase A (PKA) signaling is targeted by interactions with A-kinase anchoring proteins (AKAPs) via a dimerization/docking domain on the regulatory (R) subunit of PKA. Four other mammalian proteins [AKAP-associated sperm protein (ASP), ropporin (ROPN1), sperm protein 17 (SP17) and calcium binding tyrosine-(Y)-phosphorylation regulated protein (CABYR)] share this highly conserved RII dimerization/docking (R2D2) domain. ASP and ROPN1 are 41% identical in sequence, interact with a variety of AKAPs in a manner similar to PKA, and are expressed in ciliated and flagellated human cells. To test the hypothesis that these proteins regulate motility, we developed mutant mouse lines lacking ASP or ROPN1. Both mutant lines produced normal numbers of cilia with intact ciliary ultrastructure. Lack of ROPN1 had no effect on ciliary motility. However, the beat frequency of cilia from mice lacking ASP is significantly slower than wild type, indicating that ASP signaling may regulate ciliary motility. This is the first demonstration of in vivo function for ASP. Similar localization of ASP in mice and humans indicates that these findings may translate to human physiology, and that these mice will be an excellent model for future studies related to the pathogenesis of human disease. (C) 2011 Wiley Periodicals, Inc. C1 [Fiedler, Sarah E.; Carr, Daniel W.] VA Med Ctr, Portland, OR USA. [Fiedler, Sarah E.; Carr, Daniel W.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Sisson, Joseph H.; Wyatt, Todd A.; Pavlik, Jacqueline A.] Univ Nebraska Med Ctr, Dept Internal Med, Pulm Crit Care Sleep & Allergy Div, Durham Res Ctr 2 1046, Omaha, NE USA. [Gambling, Todd M.; Carson, Johnny L.] Univ N Carolina, Ctr Environm Med Asthma & Lung Biol, Chapel Hill, NC USA. [Carson, Johnny L.] Univ N Carolina, Dept Pediat, Chapel Hill, NC USA. RP Carr, DW (reprint author), Portland VA Med Ctr, Mail Code R&D8,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM carrd@ohsu.edu FU NIH [HD 36408, 5 R37AA008769-18]; VA Merit Award; Flight Attendant Medical Research Institute; US Environmental Protection Agency [CR833463-01]; Center for Environmental Medicine, Asthma, and Lung Biology at the University of North Carolina at Chapel Hill FX Funding for this project is provided by NIH Grant HD 36408 (DWC), VA Merit Award (DWC), NIH Grant 5 R37AA008769-18 (JHS), a Clinical Innovator Award (JLC) from the Flight Attendant Medical Research Institute, and the US Environmental Protection Agency (JLC). Although the research described in this article has been funded wholly or in part by the US Environmental Protection Agency through cooperative agreement CR833463-01 with the Center for Environmental Medicine, Asthma, and Lung Biology at the University of North Carolina at Chapel Hill, it has not been subjected to the agency's required peer and policy review, and therefore does not necessarily reflect the views of the agency and no official endorsement should be inferred. Mention of trade names or commercial products does not constitute endorsement or recommendation for use. NR 39 TC 8 Z9 8 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1949-3584 J9 CYTOSKELETON JI Cytoskeleton PD JAN PY 2012 VL 69 IS 1 BP 22 EP 32 DI 10.1002/cm.20539 PG 11 WC Cell Biology SC Cell Biology GA 877DG UT WOS:000299156500002 PM 22021175 ER PT J AU Liu, E McKeown, NM Pittas, AG Meigs, JB Economos, CD Booth, SL Jacques, PF AF Liu, E. McKeown, N. M. Pittas, A. G. Meigs, J. B. Economos, C. D. Booth, S. L. Jacques, P. F. TI Predicted 25-hydroxyvitamin D score and change in fasting plasma glucose in the Framingham offspring study SO EUROPEAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE vitamin D; fasting plasma glucose; Framingham offspring cohort ID VITAMIN-D SUPPLEMENTATION; PLACEBO-CONTROLLED TRIAL; SERUM 25-HYDROXYVITAMIN-D; INSULIN SENSITIVITY; WOMEN; CALCIUM; EXPRESSION; RESISTANCE; RECEPTOR; ADULTS AB Data on the association between vitamin D status and actual change in glycemic measures are limited. We examined the prospective association between a predicted 25-hydroxyvitamin D (25(OH)D) score and change in fasting plasma glucose concentration over a mean follow-up of 7 years, in 2571 men and women (mean age 54 years) without diabetes in the Framingham Offspring Study cohort. After adjustment for age, sex, body mass index and fasting plasma glucose at baseline, higher predicted 25(OH)D score at baseline was associated with a smaller 7-year increase in fasting plasma glucose concentrations (0.23 mmol/l versus 0.35 mmol/l for highest versus lowest tertile of 25(OH)D score, respectively, P-trend = 0.002). Vitamin D status may be an important determinant for change in fasting plasma glucose concentration among middle-aged and older adults without diabetes. European Journal of Clinical Nutrition (2012) 66, 139-141; doi:10.1038/ejcn.2011.181; published online 19 October 2011 C1 [Liu, E.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [McKeown, N. M.; Booth, S. L.; Jacques, P. F.] Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [McKeown, N. M.; Economos, C. D.; Booth, S. L.; Jacques, P. F.] Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA. [Pittas, A. G.] Tufts Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA USA. [Meigs, J. B.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Meigs, J. B.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Meigs, J. B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. RP Liu, E (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 1633 Tremont St, Boston, MA 02115 USA. EM eliu@hsph.harvard.edu FU US Department of Agriculture [58-1950-7-707]; National Heart Lung and Blood Institute of the National Institutes of Health [N01-HC-25195]; American Diabetes Association; Career Development Award [NIDDK K24 DK080140, R01DK076092, R21DK078867, NIA AG14759]; Beverage Institute for Health and Wellness FX We are grateful to the Framingham Study participants and staff. We thank Gail Rogers, from Jean Mayer USDA Human Nutrition Research Center, for data management and statistical guidance. The present study was supported in part by the US Department of Agriculture, under agreement No. 58-1950-7-707, and the Framingham Heart Study of the National Heart Lung and Blood Institute of the National Institutes of Health (Contract No. N01-HC-25195), and by an American Diabetes Association Career Development Award (JBM), NIDDK K24 DK080140 (JBM), R01DK076092 and R21DK078867 (AGP), NIA AG14759 (SLB), and the Beverage Institute for Health and Wellness (CDE). NR 19 TC 10 Z9 10 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0954-3007 J9 EUR J CLIN NUTR JI Eur. J. Clin. Nutr. PD JAN PY 2012 VL 66 IS 1 BP 139 EP 141 DI 10.1038/ejcn.2011.181 PG 3 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 876GE UT WOS:000299094800021 PM 22009071 ER PT J AU Hu, D Liu, X Zeng, WY Weiner, HL Ritz, J AF Hu, Dan Liu, Xia Zeng, Wanyong Weiner, Howard L. Ritz, Jerome TI A clonal model for human CD8(+) regulatory T cells: Unrestricted contact-dependent killing of activated CD4(+) T cells SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE CD8+Treg cells; Suppression and cytotoxicity ID IMMUNOLOGICAL SELF-TOLERANCE; MEDIATED APOPTOSIS; IMMUNE-RESPONSES; SUPPRESSOR; FOXP3; ANTIGEN; LYMPHOCYTES; MECHANISMS; DISTINCT; DISEASE AB Previous studies in murine systems have demonstrated that CD8+ Treg cells down-regulate immune responses in vivo through suppressing activated CD4+ T cells. Here we describe novel regulatory CD8+ T-cell clones isolated from healthy human peripheral blood following in vitro stimulation with autologous EpsteinBarr virus (EBV)-specific CD4+ T cells. TCR activation of CD4+ target T cells was required for CD8+ Treg cells to exert suppressive activity, which was mediated through lysis of CD4+ targets in a cell contact-dependent manner. Suppression was independent of Foxp3 expression in CD8+ Treg cells, HLA compatibility between CD8+ Treg cells and CD4+ target cells and antigen-specificity of CD4+ target T cells. CD8+ Treg clones expressed CD3 and a variety of TCR V beta chains as well as CD56, CD69, CD62L and CD95 but did not express CD16, CD161, CXCR4 and CCR7. When used together, antibodies specific for CD11a/CD18 and CD8 inhibited suppressive activity of CD8+ Treg clones. The ability to establish clonal CD8+ T cells that maintain regulatory function in vitro will facilitate further studies to define this population in vivo and to identify the mechanisms used for recognition and suppression of activated target cells. C1 [Hu, Dan; Liu, Xia; Zeng, Wanyong; Ritz, Jerome] Dana Farber Canc Inst, Div Hematol Malignancies, Canc Vaccine Ctr, Boston, MA 02115 USA. [Hu, Dan; Weiner, Howard L.; Ritz, Jerome] Harvard Univ, Sch Med, Boston, MA USA. [Hu, Dan; Weiner, Howard L.] Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. RP Ritz, J (reprint author), Dana Farber Canc Inst, Div Hematol Malignancies, Canc Vaccine Ctr, 44 Binney St, Boston, MA 02115 USA. EM Jerome_Ritz@dfci.harvard.edu RI Hu, Dan/D-9642-2015; OI Ritz, Jerome/0000-0001-5526-4669 FU National Institutes of Health [AI29530, CA142106] FX The authors thank G. Freeman, G. Dranoff, U. von Andrian and H. von Boehmer for helpful discussions; G. Freeman for reagents; D. Sese for technical assistance; E. Zorn for technical advice. This research was supported by grants from the National Institutes of Health (AI29530 and CA142106 to J. R.). NR 38 TC 4 Z9 4 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JAN PY 2012 VL 42 IS 1 BP 69 EP 79 DI 10.1002/eji.201141618 PG 11 WC Immunology SC Immunology GA 869KK UT WOS:000298596600009 PM 22002875 ER PT J AU Feuchtner, G Loureiro, R Bezerra, H Rocha-Filho, JA Sarwar, A Pflederer, T Marwan, M Petranovic, M Raffel, CO Brady, TB Jang, IK Achenbach, S Cury, RC AF Feuchtner, Gudrun Loureiro, Ricardo Bezerra, Hiram Rocha-Filho, Jose A. Sarwar, Ammar Pflederer, Tobias Marwan, Mohamed Petranovic, Milena Raffel, Christopher O. Brady, Thomas B. Jang, Ik-Kyung Achenbach, Stephan Cury, Ricardo C. TI Quantification of coronary stenosis by dual source computed tomography in patients: A comparative study with intravascular ultrasound and invasive angiography SO EUROPEAN JOURNAL OF RADIOLOGY LA English DT Article DE Computed tomography; Coronary stenosis; Quantification; Intravascular ultrasound; Invasive coronary angiography ID DIAGNOSTIC-ACCURACY; ARTERY STENOSIS; MULTIDETECTOR CT; DISEASE; PERFORMANCE; NARROWINGS; LESIONS AB Objective: To determine the accuracy of dual-source CT (DSCT) to quantify coronary stenosis compared to intravascular ultrasound (IVUS) and quantitative coronary angiography (QCA). Methods: 21 patients (23 vessels) were examined with DSCT, IVUS and invasive coronary angiography. Coronary minimal luminal diameter (MLD) and area (MLA) were measured in cross-sectional multiplanar reformatted images perpendicular to the vessel long-axis. The vessel cross-sectional area stenosis (MLA/CSA ratio) was calculated. DSCT results were compared with IVUS and QCA. Results: A good correlation between DSCT and IVUS was noted for diameter and area stenosis (r = 0.69 and r = 0.73), with an overestimation of MLD stenosis by DSCT (+9.1%) and an underestimation of MLA stenosis (-5.8%). For MLD and MLA, high correlation coefficients (r = 0.78 and r = 0.90, respectively) were found between DSCT and IVUS; and the bias was almost zero (-0.41 mm and +0.1 mm(2), respectively). The correlation between DSCT and QCA was moderate (r = 0.60) for MLD stenosis with minor overestimation by DSCT (+4.0%) and moderate (r = 0.59) for MLD (bias, +0.01 mm). The cross-sectional area stenosis showed a moderate correlation (r = 0.59) between DSCT and IVUS (+0.00). Conclusions: DSCT allows accurate quantification of coronary stenosis as compared to IVUS. An excellent correlation was found for the MLA between DSCT and IVUS. (C) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Feuchtner, Gudrun; Loureiro, Ricardo; Bezerra, Hiram; Rocha-Filho, Jose A.; Sarwar, Ammar; Petranovic, Milena; Brady, Thomas B.; Cury, Ricardo C.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Feuchtner, Gudrun] Innsbruck Med Univ, Dept Radiol 2, Innsbruck, Austria. [Pflederer, Tobias; Marwan, Mohamed; Achenbach, Stephan] Univ Erlangen Nurnberg, Div Cardiol, Erlangen, Germany. [Raffel, Christopher O.; Jang, Ik-Kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02115 USA. [Feuchtner, Gudrun; Cury, Ricardo C.] Baptist Cardiac & Vasc Inst, Cardiovasc MR & CT Program, Miami, FL USA. RP Cury, RC (reprint author), Baptist Cardiac Vasc Inst, Miami, FL 33156 USA. EM rcury@baptisthealth.net FU Pfizer Inc.; New York Cardiac Center FX This research was partly supported from Pfizer Inc. and the New York Cardiac Center. NR 26 TC 15 Z9 18 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0720-048X J9 EUR J RADIOL JI Eur. J. Radiol. PD JAN PY 2012 VL 81 IS 1 BP 83 EP 88 DI 10.1016/j.ejrad.2010.12.008 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 876LU UT WOS:000299109800027 PM 21227613 ER PT J AU Lampiris, HW AF Lampiris, Harry W. TI Elvitegravir: a once-daily, boosted, HIV-1 integrase inhibitor SO EXPERT REVIEW OF ANTI-INFECTIVE THERAPY LA English DT Article DE cobicistat; elvitegravir; HIV-1 integrase; integrase drug interactions; integrase inhibitor; integrase pharmacokinetics; integrase resistance ID ANTIRETROVIRAL THERAPY; EXPERIENCED PATIENTS; STRAND TRANSFER; IN-VITRO; RESISTANCE; RALTEGRAVIR; PHARMACOKINETICS; INFECTION; FAILURE; EVOLUTION AB The development of HIV-1 integrase strand transfer inhibitors (INSTIs) has been a major therapeutic breakthrough in the management of HIV-1 infection. The first HIV-1 integrase inhibitor, raltegravir, was licensed in 2007 and was subsequently approved for use in treatment-naive patients. Since then, newer members of the INSTI class have been developed, including elvitegravir (EVG), which is in advanced clinical development and is being developed for use in both treatment-naive and treatment-experienced patients. EVG utilizes pharmacokinetic boosting to achieve adequate serum levels with once-daily dosing. Boosting agents with which it is being studied include ritonavir and cobicistat. In addition, EVG is being studied as a once-daily INSTI in a coformulated fixed-dose combination pill with the agents tenofovir disoproxil fumarate, emtricitabine and cobicistat (QUAD pill), which has the additional potential benefit of convenient once-daily dosing. The in vitro activity, pharmacokinetic and pharmacodynamic properties, results of Phase I-III clinical trials, resistance profile and drug-drug interactions of EVG will be reviewed in this article. C1 [Lampiris, Harry W.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Lampiris, Harry W.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Lampiris, HW (reprint author), Univ Calif San Francisco, San Francisco, CA 94143 USA. EM harry.lampiris@va.gov NR 40 TC 11 Z9 12 U1 1 U2 2 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1478-7210 J9 EXPERT REV ANTI-INFE JI Expert Rev. Anti-Infect. Ther. PD JAN PY 2012 VL 10 IS 1 BP 13 EP 20 DI 10.1586/ERI.11.157 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 875ES UT WOS:000299013800007 PM 22149610 ER PT J AU Kang, K Schmahl, J Lee, JM Garcia, K Patil, K Chen, A Keene, M Murphy, A Sleeman, MW AF Kang, Kihwa Schmahl, Jennifer Lee, Jong-Min Garcia, Karen Patil, Ketan Chen, Amelia Keene, Michelle Murphy, Andrew Sleeman, Mark W. TI Mouse ghrelin-O-acyltransferase (GOAT) plays a critical role in bile acid reabsorption SO FASEB JOURNAL LA English DT Article DE intestine; ISBT; metabolomics ID STIMULATES INSULIN-SECRETION; DES-ACYL GHRELIN; BETA-CELLS; FOOD-INTAKE; RAT ISLETS; ENDOCRINE; GLUCOSE; HORMONE; MICE; PANCREAS AB Ghrelin is a unique peptide gut hormone that requires post-translational modification to stimulate both feeding and growth hormone release. Ghrelin O-acyltransferase (GOAT) was identified as a specific acyl-transferase for ghrelin, and recent genetic deletion studies of the Goat gene (Goat(-/-)) uncovered the role of ghrelin in the regulation of glucose homeostasis. To further understand the physiological functions of the GOAT/ghrelin system, we have conducted a metabolomic and microarray profile of Goat-null mice, as well as determined Goat expression in different tissues using the lacZ reporter gene. Serum metabolite profile analysis revealed that Goat(-/-) mice exhibited increased secondary bile acids > 2.5-fold. This was attributed to increased mRNA and protein expression of the ileal sodium-dependent bile acid transporter (ISBT) in the intestinal and biliary tract. Increased expression of additional solute carrier proteins, including Slc5a12 (> 10-fold) were also detected in the small intestine and bile duct. Goat staining was consistently observed in the pituitary glands, stomach, and intestines, and to a lesser extent in the gallbladder and pancreatic duct. This is the first report that the GOAT/ghrelin system regulates bile acid metabolism, and these findings suggest a novel function of GOAT in the regulation of intestinal bile acid reabsorption.-Kang, K., Schmahl, J., Lee, J. -M., Garcia, K., Patil, K., Chen, A., Keene, M., Murphy, A., Sleeman, M. W. Mouse ghrelin-O-acyltransferase (GOAT) plays a critical role in bile acid reabsorption. FASEB J. 26, 259-271 (2012). www.fasebj.org C1 [Kang, Kihwa; Schmahl, Jennifer; Garcia, Karen; Patil, Ketan; Chen, Amelia; Keene, Michelle; Murphy, Andrew; Sleeman, Mark W.] Regeneron Pharmaceut, Tarrytown, NY USA. [Lee, Jong-Min] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Kang, K (reprint author), Regeneron Pharmaceut Inc, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA. EM kihwa.kang@regeneron.com; mark.sleeman@regeneron.com NR 43 TC 16 Z9 18 U1 0 U2 7 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JAN PY 2012 VL 26 IS 1 BP 259 EP 271 DI 10.1096/fj.11-191460 PG 13 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 877SF UT WOS:000299202200027 PM 21965605 ER PT J AU Chattergoon, NN Giraud, GD Louey, S Stork, P Fowden, AL Thornburg, KL AF Chattergoon, Natasha N. Giraud, George D. Louey, Samantha Stork, Philip Fowden, Abigail L. Thornburg, Kent L. TI Thyroid hormone drives fetal cardiomyocyte maturation SO FASEB JOURNAL LA English DT Article DE proliferation; sheep fetus; p21 ID SIGNAL-REGULATED KINASE; CELL-CYCLE ACTIVITY; INTRAUTERINE GROWTH RESTRICTION; ATRIAL-NATRIURETIC-FACTOR; ACTIVATED PROTEIN-KINASE; CARDIAC-MUSCLE-CELLS; MEK-ERK PATHWAY; SARCOPLASMIC-RETICULUM; POSTNATAL-DEVELOPMENT; SHEEP CARDIOMYOCYTES AB Tri-iodo-L-thyronine (T-3) suppresses the proliferation of near-term serum-stimulated fetal ovine cardiomyocytes in vitro. Thus, we hypothesized that T-3 is a major stimulant of cardiomyocyte maturation in vivo. We studied 3 groups of sheep fetuses on gestational days 125-130 (term similar to 145 d): a T-3-infusion group, to mimic fetal term levels (plasma T-3 levels increased from similar to 0.1 to similar to 1.0 ng/ml; t(1/2) similar to 24 h); a thyroidectomized group, to produce low thyroid hormone levels; and a vehicle-infusion group, to serve as intact controls. At 130 d of gestation, sections of left ventricular freewall were harvested, and the remaining myocardium was enzymatically dissociated. Proteins involved in cell cycle regulation (p21, cyclin D1), proliferation (ERK), and hypertrophy (mTOR) were measured in left ventricular tissue. Evidence that elevated T-3 augmented the maturation rate of cardiomyocytes included 14% increased width, 31% increase in binucleation, 39% reduction in proliferation, 150% reduction in cyclin D1 protein, and 500% increase in p21 protein. Increased expression of phospho-mTOR, ANP, and SERCA2a also suggests that T-3 promotes maturation and hypertrophy of fetal cardiomyocytes. Thyroidectomized fetuses had reduced cell cycle activity and binucleation. These findings support the hypothesis that T-3 is a prime driver of prenatal cardiomyocyte maturation.-Chattergoon, N. N., Giraud, G. D., Louey, S., Stork, P., Fowden, A. L., Thornburg, K. L. Thyroid hormone drives fetal cardiomyocyte maturation FASEB J. 26, 397-408 (2012). www.fasebj.org C1 [Chattergoon, Natasha N.; Giraud, George D.; Louey, Samantha; Thornburg, Kent L.] Oregon Hlth & Sci Univ, Heart Res Ctr, Portland, OR 97239 USA. [Giraud, George D.; Thornburg, Kent L.] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97239 USA. [Giraud, George D.; Louey, Samantha; Thornburg, Kent L.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97239 USA. [Stork, Philip] Oregon Hlth & Sci Univ, Vollum Inst, Portland, OR 97239 USA. [Giraud, George D.] Portland VA Med Ctr, Portland, OR USA. [Fowden, Abigail L.] Univ Cambridge, Physiol Lab, Dept Physiol Dev & Neurosci, Cambridge CB2 3EG, England. RP Thornburg, KL (reprint author), Oregon Hlth & Sci Univ, Heart Res Ctr, 3303 SW Bond Ave,CH15H, Portland, OR 97239 USA. EM thornbur@ohsu.edu FU U.S. National Institute of Child Health and Human Development [P01 HD 34430]; National Heart, Lung, and Blood Institute (NHLBI) [R21 HL093617, T32HL094294]; National Institutes of Health [R01 HL102763] FX The authors thank Mr. Robert Webber and Ms. Loni Socha for excellent technical assistance. The authors appreciate support from the M. Lowell Edwards Endowment. This study was supported by funds from U.S. National Institute of Child Health and Human Development grant P01 HD 34430, National Heart, Lung, and Blood Institute (NHLBI) grant R21 HL093617, and National Institutes of Health grant R01 HL102763. N.N.C. was supported by NHLBI training grant T32HL094294. NR 91 TC 37 Z9 38 U1 1 U2 10 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JAN PY 2012 VL 26 IS 1 BP 397 EP 408 DI 10.1096/fj.10-179895 PG 12 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 877SF UT WOS:000299202200039 PM 21974928 ER PT J AU He, AB Shen, XH Ma, Q Cao, JJ von Gise, A Zhou, PZ Wang, G Marquez, VE Orkin, SH Pu, WT AF He, Aibin Shen, Xiaohua Ma, Qing Cao, Jingjing von Gise, Alexander Zhou, Pingzhu Wang, Gang Marquez, Victor E. Orkin, Stuart H. Pu, William T. TI PRC2 directly methylates GATA4 and represses its transcriptional activity SO GENES & DEVELOPMENT LA English DT Article DE epigenetics; heart development; polycomb complex; transcriptional regulation ID HISTONE METHYLTRANSFERASE ACTIVITY; H3 LYSINE-27 METHYLATION; STEM-CELLS; POLYCOMB; EZH2; DIFFERENTIATION; ACETYLATION; PROTEIN; GENOME; HEART AB Polycomb-repressive complex 2 (PRC2) promotes tissue-specific differentiation by depositing trimethylated histone H3 Lys 27 (H3K27me3) epigenetic marks to silence ectopic gene expression programs. Here, we show that EZH2, the catalytic subunit of PRC2, is required for cardiac morphogenesis. Both in vitro and in fetal hearts, EZH2 interacted with cardiac transcription factor GATA4 and directly methylated it at Lys 299. PRC2 methylation of GATA4 attenuated its transcriptional activity by reducing its interaction with and acetylation by p300. Our results reveal a new mechanism of PRC2-mediated transcriptional repression in which PRC2 methylates a transcription factor to inhibit its transcriptional activity. C1 [He, Aibin; Ma, Qing; Cao, Jingjing; von Gise, Alexander; Zhou, Pingzhu; Wang, Gang; Pu, William T.] Harvard Univ, Sch Med, Dept Cardiol, Childrens Hosp Boston, Boston, MA 02115 USA. [He, Aibin; Shen, Xiaohua; Ma, Qing; Cao, Jingjing; von Gise, Alexander; Zhou, Pingzhu; Wang, Gang; Orkin, Stuart H.; Pu, William T.] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Shen, Xiaohua; Orkin, Stuart H.] Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst,Childrens Hosp Boston, Boston, MA 02115 USA. [Marquez, Victor E.] NCI, Biol Chem Lab, Ctr Canc Res, Frederick, MD 21702 USA. [Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02115 USA. RP Pu, WT (reprint author), Harvard Univ, Sch Med, Dept Cardiol, Childrens Hosp Boston, Boston, MA 02115 USA. EM wpu@enders.tch.harvard.edu RI Zhou, Pingzhu/J-2809-2014 FU National Institutes of Health (NIH) [U01HL098166, R01HL095712]; American Heart Association; NIDDK; NIH, National Cancer Institute, and Center for Cancer Research FX This work was supported by funding from the National Institutes of Health (NIH) (U01HL098166 and R01HL095712 to W.T.P.) and the American Heart Association (post-doctoral fellowship to A. H.); by charitable donations from Edward Marram, Karen Carpenter, and Gail Federici Smith; and by a Center of Excellence Award in Molecular Hematology from the NIDDK to S.H.O., an Investigator of the HHMI. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, and Center for Cancer Research. Mass spectrometry analysis was performed by the Proteomics Center at Children's Hospital Boston. NR 34 TC 72 Z9 78 U1 3 U2 23 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD JAN 1 PY 2012 VL 26 IS 1 BP 37 EP 42 DI 10.1101/gad.173930.111 PG 6 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 877RI UT WOS:000299199200006 PM 22215809 ER PT J AU Calderwood, MS Ma, A Khan, YM Olsen, MA Bratzler, DW Yokoe, DS Hooper, DC Stevenson, K Fraser, VJ Platt, R Huang, SS AF Calderwood, Michael S. Ma, Allen Khan, Yosef M. Olsen, Margaret A. Bratzler, Dale W. Yokoe, Deborah S. Hooper, David C. Stevenson, Kurt Fraser, Victoria J. Platt, Richard Huang, Susan S. CA CDC Prevention Epictr Program TI Use of Medicare Diagnosis and Procedure Codes to Improve Detection of Surgical Site Infections following Hip Arthroplasty, Knee Arthroplasty, and Vascular Surgery SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID CARE-ASSOCIATED INFECTIONS; POSTOPERATIVE INFECTIONS; ENHANCED IDENTIFICATION; ANTIBIOTIC EXPOSURE; SURVEILLANCE; INDICATORS; HOSPITALS; DISCHARGE; CRITERIA; CLAIMS AB OBJECTIVE. To evaluate the use of routinely collected electronic health data in Medicare claims to identify surgical site infections (SSIs) following hip arthroplasty, knee arthroplasty, and vascular surgery. DESIGN. Retrospective cohort study. SETTING. Four academic hospitals that perform prospective SSI surveillance. METHODS. We developed lists of International Classification of Diseases, Ninth Revision, and Current Procedural Terminology diagnosis and procedure codes to identify potential SSIs. We then screened for these codes in Medicare claims submitted by each hospital on patients older than 65 years of age who had undergone 1 of the study procedures during 2007. Each site reviewed medical records of patients identified by either claims codes or traditional infection control surveillance to confirm SSI using Centers for Disease Control and Prevention/National Healthcare Safety Network criteria. We assessed the performance of both methods against all chart-confirmed SSIs identified by either method. RESULTS. Claims-based surveillance detected 1.8-4.7-fold more SSIs than traditional surveillance, including detection of all previously identified cases. For hip and vascular surgery, there was a 5-fold and 1.6-fold increase in detection of deep and organ/space infections, respectively, with no increased detection of deep and organ/space infections following knee surgery. Use of claims to trigger chart review led to confirmation of SSI in 1 out of 3 charts for hip arthroplasty, 1 out of 5 charts for knee arthroplasty, and 1 out of 2 charts for vascular surgery. CONCLUSION. Claims-based SSI surveillance markedly increased the number of SSIs detected following hip arthroplasty, knee arthroplasty, and vascular surgery. It deserves consideration as a more effective approach to target chart reviews for identifying SSIs. Infect Control Hosp Epidemiol 2012; 33(1):40-49 C1 [Calderwood, Michael S.] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA 02115 USA. [Calderwood, Michael S.; Platt, Richard] Harvard Pilgrim Healthcare Inst, Boston, MA 02115 USA. [Ma, Allen; Bratzler, Dale W.] Oklahoma Fdn Med Qual, Oklahoma City, OK USA. [Khan, Yosef M.; Stevenson, Kurt] Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. [Khan, Yosef M.; Stevenson, Kurt] Ohio State Univ, Coll Med, Columbus, OH 43210 USA. [Olsen, Margaret A.; Fraser, Victoria J.] Washington Univ, Sch Med, St Louis, MO USA. [Bratzler, Dale W.] Univ Oklahoma, Hlth Sci Ctr, Coll Publ Hlth, Oklahoma City, OK USA. [Yokoe, Deborah S.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Hooper, David C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Huang, Susan S.] Univ Calif Irvine, Sch Med, Irvine, CA 92717 USA. RP Calderwood, MS (reprint author), Harvard Univ, Sch Med, Dept Populat Med, 133 Brookline Ave,6th Floor, Boston, MA 02115 USA. EM mcalderwood@partners.org FU Centers for Disease Control and Prevention [1U01CI000344]; Agency for Healthcare Research and Quality [F32HS018878] FX Financial support. This study was funded in part by the Centers for Disease Control and Prevention (Prevention Epicenter Program, 1U01CI000344 [R.P.]). This project was supported by grant F32HS018878 from the Agency for Healthcare Research and Quality (M.S.C.). NR 23 TC 30 Z9 30 U1 2 U2 8 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD JAN PY 2012 VL 33 IS 1 BP 40 EP 49 DI 10.1086/663207 PG 10 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 876CP UT WOS:000299085100008 PM 22173521 ER PT J AU Tan, WH Goldstein, R Gerrard, P Ryan, CM Niewczyk, P Kowalske, K Zafonte, R Schneider, JC AF Tan, Wei-Han Goldstein, Richard Gerrard, Paul Ryan, Colleen M. Niewczyk, Paulette Kowalske, Karen Zafonte, Ross Schneider, Jeffrey C. TI Outcomes and Predictors in Burn Rehabilitation SO JOURNAL OF BURN CARE & RESEARCH LA English DT Article; Proceedings Paper CT Canadian-Special-Interest-Group Meeting at the 43rd Annual Meeting of the American-Burn-Association (ABA) CY MAR 28-APR 01, 2011 CL Chicago, IL SP Amer Burn Assoc (ABA), Canadian Special Interest Grp ID SPINAL-CORD-INJURY; FUNCTIONAL INDEPENDENCE MEASURE; LENGTH-OF-STAY; INPATIENT REHABILITATION; ENVIRONMENTAL-FACTORS; MULTIPLE IMPUTATION; LIFE SATISFACTION; CLINICAL-RESEARCH; BRAIN-INJURY; HAND BURNS AB Advances in burn care in recent decades have resulted in a growing population of burn survivors and an increased need for inpatient rehabilitation. Burn survivors who require inpatient rehabilitation typically experience severe and complicated injuries. The purpose of this study is to examine burn rehabilitation outcomes and their predictor variables. Data are obtained from the Uniform Data System for Medical Rehabilitation from 2002 to 2007. Inclusion criterion is primary diagnosis of burn injury. Predictor variables include demographic, medical, and facility data. Outcome measures are length of stay efficiency, FIM (R) gain, community discharge, and FIM (R) discharge of at least 78. Linear and logistic regression analyses are used to determine significant predictors of outcomes. There are 2920 patients who meet inclusion criteria. The mean age of the population is 51 years, 33% of the population is female, 73% is Caucasian, and 40% are married. The median TBSA decile is 20 to 29%. The population exhibits a mean FIM (R) gain of 28 and length of stay efficiency of 2.1. A majority of the population is discharged to the community (76%) and has a FIM (R) discharge of at least 78 (81%). Significant predictors of outcomes in burn rehabilitation include age, FIM (R) admission, onset days, employment status, and marital status. Inpatient rehabilitation is critical to community reintegration of burn survivors. Survivors who are young, married, employed, and higher functioning at the time of admission to rehabilitation demonstrate the best outcomes. This research will help assess the rehabilitation potential of burn survivors and inform resource allocation. (J Burn Care Res 2012;33:110-117) C1 [Tan, Wei-Han; Goldstein, Richard; Gerrard, Paul; Zafonte, Ross; Schneider, Jeffrey C.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Spaulding Rehabil Hosp, Boston, MA 02114 USA. [Ryan, Colleen M.] Harvard Univ, Sch Med, Sumner Redstone Burn Ctr, Surg Serv,Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ryan, Colleen M.] Shriners Hosp Children, Boston, MA USA. [Niewczyk, Paulette] Uniform Data Syst Med Rehabil, Amherst, NY USA. [Niewczyk, Paulette] Daemen Coll, Hlth Care Studies Dept, Amherst, NY USA. [Kowalske, Karen] Univ Texas SW Med Ctr Dallas, Dept Phys Med & Rehabil, Dallas, TX 75390 USA. RP Schneider, JC (reprint author), Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Spaulding Rehabil Hosp, 125 Nashua St, Boston, MA 02114 USA. OI Gerrard, Paul/0000-0003-0654-5354 NR 31 TC 19 Z9 19 U1 1 U2 7 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 JAN-FEB PY 2012 VL 33 IS 1 BP 110 EP 117 DI 10.1097/BCR.0b013e318234d91a PG 8 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA 877BQ UT WOS:000299151900022 PM 21941195 ER PT J AU Li, WM Rong, R Zhao, S Zhu, XM Zhang, K Xiong, X Yu, XQ Cui, QH Li, SQ Chen, L Cai, J Du, J AF Li, Weiming Rong, Rong Zhao, Sheng Zhu, Xiaoming Zhang, Ke Xiong, Xin Yu, Xueqing Cui, Qinghua Li, Shuqiang Chen, Li Cai, Jun Du, Jie TI Proteomic analysis of metabolic, cytoskeletal and stress response proteins in human heart failure SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE LA English DT Article DE heart failure; proteomics; metabolism; cytoskeleton; heat shock protein ID ALPHA-B-CRYSTALLIN; SPONTANEOUSLY HYPERTENSIVE-RATS; FAILING HUMAN HEARTS; NF-KAPPA-B; DILATED CARDIOMYOPATHY; LIGHT-CHAIN; HYPERTROPHIC CARDIOMYOPATHY; ISCHEMIA/REPERFUSION INJURY; SHOCK PROTEINS; BCL-2 HOMOLOG AB Human heart failure is a complex syndrome and a primary cause of morbidity and mortality in the world. However, the molecular pathways involved in the remodelling process are poorly understood. In this study, we performed exhaustive global proteomic surveys of cardiac ventricle isolated from failing and non-failing human hearts, and determined the regulatory pathway to uncover the mechanism underlying heart failure. Two-dimensional gel electrophoresis (2-DE) coupled with tandem mass spectrometry was used to identify differentially expressed proteins in specimens from failing (n = 9) and non-failing (n = 6) human hearts. A total of 25 proteins with at least 1.5-fold change in the failing heart were identified; 15 proteins were up-regulated and 10 proteins were down-regulated. The altered proteins belong to three broad functional categories: (i) metabolic [e.g. NADH dehydrogenase (ubiquinone), dihydrolipoamide dehydrogenase, and the cytochrome c oxidase subunit]; (ii) cytoskeletal (e.g. myosin light chain proteins, troponin I type 3 and transthyretin) and (iii) stress response (e.g. aB-crystallin, HSP27 and HSP20). The marked differences in the expression of selected proteins, including HSP27 and HSP20, were further confirmed by Western blot. Thus, we carried out full-scale screening of the protein changes in human heart failure and profiled proteins that may be critical in cardiac dysfunction for future mapping. C1 [Li, Weiming; Zhu, Xiaoming; Cai, Jun] Capital Med Univ, Chaoyang Hosp, Dept Cardiol, Minist Educ,Key Lab Remodelling Related Cardiovas, Beijing 100020, Peoples R China. [Rong, Rong; Yu, Xueqing] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Nephrol, Guangzhou 510275, Guangdong, Peoples R China. [Zhao, Sheng] Nanjing Med Univ, Affiliated Hosp 1, Dept Cardiac Surg, Nanjing, Peoples R China. [Zhang, Ke] Tech Univ Munich, German Res Ctr Environm Hlth, Munich, Germany. [Xiong, Xin] Chongqing Med Univ, Affiliated Hosp 1, Chongqing, Peoples R China. [Cui, Qinghua] Peking Univ, Hlth Sci Ctr, Dept Biomed Informat, Beijing 100871, Peoples R China. [Li, Shuqiang] Harvard Univ, Sch Med, Dept Canc Immunol, Boston, MA 02115 USA. [Li, Shuqiang] Harvard Univ, Sch Med, AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA. [Chen, Li] Texas Heart Inst, Houston, TX 77025 USA. [Du, Jie] Capital Med Univ, Beijing Anzhen Hosp, Key Lab Remodelling Related Cardiovasc Dis, Minist Educ, Beijing, Peoples R China. RP Cai, J (reprint author), Capital Med Univ, Chaoyang Hosp, Dept Cardiol, Minist Educ,Key Lab Remodelling Related Cardiovas, Beijing 100020, Peoples R China. EM caijun7879@yahoo.com.cn FU National Science Foundation of China [81050012, 30888004, 30900590]; Beijing Nova Program [2009B39]; Beijing Natural Science Foundation [7102057]; Scientific Research Foundation for the Returned Overseas Chinese Scholars, Education Ministry of China FX This work is supported by grants from the National Science Foundation of China (Nos. 81050012, 30888004 and 30900590), Beijing Nova Program (No. 2009B39), Beijing Natural Science Foundation (No. 7102057) and the Scientific Research Foundation for the Returned Overseas Chinese Scholars, Education Ministry of China. NR 46 TC 14 Z9 14 U1 0 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1582-1838 J9 J CELL MOL MED JI J. Cell. Mol. Med. PD JAN PY 2012 VL 16 IS 1 BP 59 EP 71 DI 10.1111/j.1582-4934.2011.01336.x PG 13 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 869GT UT WOS:000298586600006 PM 21545686 ER PT J AU DePaola, DP AF DePaola, Dominick P. TI The Evolution of Dental Education as a Profession, 1936-2011, and the Role of the Journal of Dental Education SO JOURNAL OF DENTAL EDUCATION LA English DT Article DE dental education; research; access to care; educational milestones; future of dental education as a profession; vision; assessment and outcomes; transformational change AB This article describes selected changes in dental education from 1936 to 2011 and describes how the Journal of Dental Education (JDE) has assisted in both reporting and, at times, championing change. The review provides a series of selective contextual milestones as a backdrop and running commentary for the changing profession of dental education. An assessment of the current state of knowledge in this field is articulated, as are some of the drivers of change. The article poses a series of questions in seven categories that define the extraordinary opportunities ahead. A vision of the future of the JDE and dental education is described including the use of the journal as a futurist forum to educate, cajole, and advocate for continuous movement toward realizing an enlightened destiny. C1 [DePaola, Dominick P.] Nova SE Univ, Coll Dent Med, Ft Lauderdale, FL 33328 USA. [DePaola, Dominick P.] Forsyth Inst, Cambridge, MA USA. RP DePaola, DP (reprint author), Nova SE Univ, Coll Dent Med, 3200 S Univ Dr, Ft Lauderdale, FL 33328 USA. EM ddominic@nova.edu NR 33 TC 4 Z9 4 U1 1 U2 2 PU AMER DENTAL EDUCATION ASSOC PI WASHINGTON PA 1400 K STREET, NW, STE 1100, WASHINGTON, DC 20005 USA SN 0022-0337 J9 J DENT EDUC JI J. Dent. Educ. PD JAN PY 2012 VL 76 IS 1 SI SI BP 14 EP 27 PG 14 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 876YS UT WOS:000299144300003 PM 22262546 ER PT J AU Ibrahimi, OA Campbell, T Youker, S Eisen, DB AF Ibrahimi, Omar A. Campbell, Tracy Youker, Summer Eisen, Daniel B. TI Nonanatomic Free Cartilage Batten Grafting With Second Intention Healing for Defects on the Distal Nose SO JOURNAL OF DRUGS IN DERMATOLOGY LA English DT Article ID NASAL ALA; SECONDARY INTENTION; TRANSPOSITION FLAP; RECONSTRUCTION; REPAIR AB Background: Defects of the distal nose, particularly the nasal ala, pose a reconstructive challenge due to the lack of loose adjacent tissue and proximity to a free margin. Objective: We report our experience using nonanatomic free cartilage batten grafts in combination with second intention healing for nasal ala defects. Methods: A retrospective study of distal nose defects repaired using nonanatomic free cartilage batten grafting with second intention healing was performed. Detailed data on the quality of the scar, post-operative complications, free margin distortion, functional impairments, and patient satisfaction were recorded. Digital images were also shown to an experienced fellowship-trained Mohs surgeon to assess the overall aesthetic outcome using a 5-point score ranging from poor to excellent. Results: Sixteen subjects were included in the study. Complications were common, but minor. Five (similar to 31%) subjects had subtle contour depressions, three (similar to 18%) subjects had excessive granulation tissue, two (similar to 12%) subjects had post-operative ear pain at the donor site lasting up to 10 days, and one (similar to 6%) subject had a hypertrophic scar at the recipient site. There were two occurrences (similar to 12%) of mild alar notching but no occurrences of significant alar margin distortion or nasal valve dysfunction. In terms of aesthetic outcome, seven (similar to 43%) were assessed by an independent fellowship-trained Mohs surgeon as having excellent aesthetic outcomes, six (similar to 38%) were very good, and three (similar to 19%) were good. All sixteen subjects reported satisfaction on follow-up evaluation. Conclusions: Nonanatomic free cartilage grafting with second intention healing allows for facile, single-step repair of nasal ala defects with high patient satisfaction and aesthetically pleasing results. This provides an attractive alternative to other flap techniques, skin grafting, and healing via secondary intention. C1 [Ibrahimi, Omar A.] Univ Connecticut, Dept Dermatol, Farmington, CT USA. [Ibrahimi, Omar A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. [Eisen, Daniel B.] Univ Calif Davis, Dept Dermatol, Sacramento, CA 95817 USA. RP Ibrahimi, OA (reprint author), 21 South Rd,2nd Floor, Farmington, CT 06032 USA. EM omar.ibrahimi@gmail.com OI Eisen, Daniel/0000-0001-6741-3182 NR 21 TC 5 Z9 5 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 JAN PY 2012 VL 11 IS 1 BP 46 EP 50 PG 5 WC Dermatology SC Dermatology GA 875VE UT WOS:000299062500006 PM 22206076 ER PT J AU Lenehan, G AF Lenehan, Gail TI ENA, SUPPORTING EMERGENCY NURSES ON THE FRONT LINES IN 2012 SO JOURNAL OF EMERGENCY NURSING LA English DT Editorial Material C1 [Lenehan, Gail] Emergency Nurses Assoc, Boston, MA USA. [Lenehan, Gail] Massachusetts Gen Hosp, Emergency Dept, Boston, MA 02114 USA. RP Lenehan, G (reprint author), Emergency Nurses Assoc, Boston, MA USA. EM gail.lenehan@gmail.com 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 0099-1767 J9 J EMERG NURS JI J. Emerg. Nurs. PD JAN PY 2012 VL 38 IS 1 BP 1 EP 2 DI 10.1016/j.jen.2011.12.003 PG 2 WC Emergency Medicine; Nursing SC Emergency Medicine; Nursing GA 878NJ UT WOS:000299263500001 PM 22226130 ER PT J AU Rattner, DW AF Rattner, David W. TI Happy Mother's Day SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Editorial Material DE Women surgeons; SSAT presidential address; Gender and surgery ID SURGERY; WOMEN C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Rattner, DW (reprint author), Massachusetts Gen Hosp, Dept Surg, 15 Parkman St, Boston, MA 02114 USA. EM drattner@partners.org NR 7 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD JAN PY 2012 VL 16 IS 1 BP 1 EP 6 DI 10.1007/s11605-011-1656-x PG 6 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 873LJ UT WOS:000298884500001 PM 22065314 ER PT J AU Cecchini, S Correa-Gallego, C Desphande, V Ligorio, M Dursun, A Wargo, J Fernandez-del Castillo, C Warshaw, AL Ferrone, CR AF Cecchini, Stefano Correa-Gallego, Camilo Desphande, Vikram Ligorio, Matteo Dursun, Abdulmetin Wargo, Jennifer Fernandez-del Castillo, Carlos Warshaw, Andrew Louis Ferrone, Cristina Rosa TI Superior Prognostic Importance of Perineural Invasion vs. Lymph Node Involvement After Curative Resection of Duodenal Adenocarcinoma SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article DE Duodenal adenocarcinoma; Duodenal cancer; Nodal metastases; Perineural invasion; Prognosis; Survival; Predictor; Lymph node ID INTERNATIONAL STUDY-GROUP; PERIAMPULLARY ADENOCARCINOMA; GASTRIC-CANCER; AXON GUIDANCE; SURVIVAL; DEFINITION; MECHANISMS; CARCINOMA; AMPULLA; GROWTH AB Unlike other gastrointestinal tumors, lymph node involvement has not consistently been a negative prognostic factor for survival in patients with duodenal adenocarcinoma. Our aim is to examine prognostic factors in patients who underwent a curative resection of their duodenal adenocarcinoma. A retrospective review of 169 patients diagnosed with primary duodenal lesions between 1982 and 2010 was performed, of whom 103 were treated with curative intent. Clinico-pathologic factors were evaluated. A potentially curative resection was performed in 103 patients with a median age of 67 years (range, 22-91). Perineural and lympho-vascular invasion were identified in 30 (29.1%) and 39 patients (37.9%), respectively. Median follow-up was 26.5 months. The 5-year overall survival was 62% vs. 25% for patients with or without nodal metastases (p < 0.001) and 56% vs. 19% for patients with or without perineural invasion (p < 0.001), respectively. Lymph node ratio, type of resection, and size of tumor failed to stratify prognosis. By multivariate analysis, perineural invasion was the most powerful independent predictor of survival (HR, 2.520; CI, 1.361-4.664). Perineural invasion is a stronger predictor for recurrence and survival than tumor size, depth of infiltration, lymph node involvement, and type of resection in patients with duodenal adenocarcinoma. C1 [Ferrone, Cristina Rosa] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Gen Surg, Boston, MA 02114 USA. [Cecchini, Stefano; Correa-Gallego, Camilo; Ligorio, Matteo; Dursun, Abdulmetin; Wargo, Jennifer; Fernandez-del Castillo, Carlos; Warshaw, Andrew Louis; Ferrone, Cristina Rosa] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Desphande, Vikram] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Ferrone, CR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Gen Surg, 15 Parkman St,WAC 470F, Boston, MA 02114 USA. EM cferrone@partners.org RI Cecchini, Stefano/A-3084-2013 OI Cecchini, Stefano/0000-0002-7144-3154 NR 33 TC 13 Z9 14 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD JAN PY 2012 VL 16 IS 1 BP 113 EP 120 DI 10.1007/s11605-011-1704-6 PG 8 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 873LJ UT WOS:000298884500024 PM 22005894 ER PT J AU Cowan, J Makanji, H Mudgal, C Jupiter, J Ring, D AF Cowan, James Makanji, Heeren Mudgal, Chaitanya Jupiter, Jesse Ring, David TI Determinants of Return to Work After Carpal Tunnel Release SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Carpal tunnel release; disability; pain anxiety; patient expectations; work status ID SURGERY; VALIDATION; PREDICTORS; SINCERITY; INCISION; TRIAL; SCALE; PAIN AB Purpose The determinants of time to return to work a common measure of treatment effectiveness are incompletely defined. Our primary hypothesis was that employment circumstances are the strongest determinant of earlier return to work. Our secondary hypothesis was that return to work in patients with desk-based jobs is predicted by patient expectations and other psychosocial factors. Methods We enrolled 65 employed patients with limited incision open carpal tunnel release in a prospective cohort study. Patients completed validated measures of depression, coping strategies, pain anxiety, and job burnout. Heavy lifting was not allowed for I month after surgery. Return to modified and full work duty was recorded in days. Although not specifically an exclusion criterion, none of the patients had a workers' compensation claim or other source of secondary gain. Results Patients returned to modified duty an average of 11.8 days and full duty at an average of 18.9 days after surgery. Predictors of earlier return to modified duty in multivariate analyses included desk-based work and both the number of days patients expected to take off and the numbers of days they wanted to take off for the entire cohort, with an additional influence from catastrophic thinking in desk-based workers. Predictors of earlier return to full duty in multivariate analyses included desk-based work and number of days patients expected to take off before for the entire cohort, fewer days off desired in non-desk-based workers, fewer days off desired and change in work role in desk-based workers, and lower pain anxiety in part-time workers. Conclusions The most important determinant of return to full duty work after limited incision open carpal tunnel release is job type, but psychological factors such as patient expectations, catastrophic wthinking, and anxiety in response to pain also have a role. (J Hand Surg 2012;37A:18-27. Copyright (C) 2012 by the American Society for Surgery of the Hand. All rights reserved.) C1 [Ring, David] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Yawkey Ctr, Hand & Upper Extrem Serv,Dept Orthopaed Surg, Boston, MA 02114 USA. RP Ring, D (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Yawkey Ctr, Hand & Upper Extrem Serv,Dept Orthopaed Surg, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org FU Wright Medical; AO Foundation; Smith and Nephew; Small Bone Innovations; Joint Active Systems; Biomet FX D.R. received support from Wright Medical, the AO Foundation, Smith and Nephew, Small Bone Innovations, Joint Active Systems, and Biomet. NR 23 TC 15 Z9 15 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD JAN PY 2012 VL 37A IS 1 BP 18 EP 27 DI 10.1016/j.jhsa.2011.10.033 PG 10 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 874OI UT WOS:000298967500005 PM 22137062 ER PT J AU ten Berg, PWL Ring, D AF ten Berg, Paul W. L. Ring, David TI Patients Lost to Follow-Up After Metacarpal Fractures SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Metacarpal fracture; non-attendance; follow-up; outpatient clinic ID SOCIAL DEPRIVATION; NON-ATTENDANCE; HAND AB Purpose To determine factors associated with non-attendance at scheduled follow-up visits for treatment of metacarpal fractures, to improve subject retention in prospective investigations. Methods This study included adult patients with metacarpal fractures seen in an outpatient hand clinic between 2004 and 2009. We assessed a number of variables (demographic, social, and injury-specific) that might be associated with failure to return for follow-up. The statistical analysis included both bivariate and multivariable models. Results In a cohort of 335 patients (228 men and 107 women) with a mean age of 40 years (range, 18-88 y), independent factors associated with non-attendance were unmarried status (single or divorced), having no insurance, having an unemployed or disabled status, having an unknown work status, and having a small finger metacarpal neck fracture. Conclusions Patients who do not attend a scheduled 1-month follow-up after a single isolated metacarpal fracture are sociologically distinct from those who do attend. (J Hand Surg 2012;37A: 42-46. Copyright (C) 2012 by the American Society for Surgery of the Hand. All rights reserved.) C1 [Ring, David] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv,Yawkey Ctr, Boston, MA 02114 USA. RP Ring, D (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv,Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 15 TC 8 Z9 8 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD JAN PY 2012 VL 37A IS 1 BP 42 EP 46 DI 10.1016/j.jhsa.2011.08.003 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 874OI UT WOS:000298967500008 PM 22015075 ER PT J AU Lichterfeld, M Yu, XG AF Lichterfeld, Mathias Yu, Xu G. TI The emerging role of leukocyte immunoglobulin-like receptors (LILRs) in HIV-1 infection SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Review DE regulatory cell surface molecules; innate cell-mediated immunity; dendritic cell; immunodeficiency; retroviral/AIDS ID CLASS-I MOLECULES; PLASMACYTOID DENDRITIC CELLS; INHIBITORY RECEPTOR; MYELOMONOCYTIC CELLS; CUTTING EDGE; HLA-G; CRYSTAL-STRUCTURE; T-LYMPHOCYTES; MYELOID CELLS; CTL ESCAPE AB LILRs represent a group of immunomodulatory molecules that regulate the functional properties of professional APCs and influence immune activation in a variety of disease contexts. Many members of the LILR family recognize peptide/MHC class I complexes as their physiological ligands, and increasing evidence suggests that such interactions are prominently influenced by polymorphisms in HLA class I alleles or sequence variations in the presented antigenic peptides. Emerging data show that LILRs are involved in multiple, different aspects of HIV-1 disease pathogenesis and may critically influence spontaneous HIV-1 disease progression. Here, we review recent progress in understanding the role of LILR during HIV-1 infection by focusing on the dynamic interplay between LILR and HLA class I molecules in determining HIV-1 disease progression, the effects of HIV-1 mutational escape on LILR-mediated immune recognition, the contribution of LILR to HIV-1-associated immune dysfunction, and the unique expression patterns of LILR on circulating myeloid DCs from elite controllers, a small subset of HIV-1-infected patients with natural control of HIV-1 replication. Obtaining a more complete understanding of LILR-mediated immune regulation during HIV-1 infection may ultimately allow for improved strategies to treat or prevent HIV-1-associated disease manifestations. J. Leukoc. Biol. 91: 27-33; 2012. C1 [Yu, Xu G.] Ragon Inst MGH MIT & Harvard, Boston, MA 02129 USA. [Lichterfeld, Mathias] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Yu, XG (reprint author), Ragon Inst MGH MIT & Harvard, 149 13th St, Boston, MA 02129 USA. EM xyu@partners.org FU Doris Duke Charitable Foundation; NIH [AI078799, AI089339, AI093203]; DDCF [2009034] FX X.G.Y. and M.L. are recipients of the Clinical Scientist Development Award from the Doris Duke Charitable Foundation. X.G.Y. is supported by NIH grants AI078799 and AI089339, and M.L. is supported by NIH grant AI093203 and DDCF grant 2009034. The authors thank Dr. Arman Bashirova (NCI Frederick, Maryland, USA) and Mr. Jerome Rogich (Ragon Institute, Boston, MA, USA) for helping with the preparation of the included table and figure. NR 66 TC 16 Z9 16 U1 0 U2 3 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 JAN PY 2012 VL 91 IS 1 BP 27 EP 33 DI 10.1189/jlb.0811442 PG 7 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 877HO UT WOS:000299168600005 PM 22028331 ER PT J AU Penjweini, R Loew, HG Hamblin, MR Kratky, KW AF Penjweini, Rozhin Loew, Hans G. Hamblin, Michael R. Kratky, Karl W. TI Long-term monitoring of live cell proliferation in presence of PVP-Hypericin: a new strategy using ms pulses of LED and the fluorescent dye CFSE SO JOURNAL OF MICROSCOPY LA English DT Article DE CFSE; fluorescence; live cell imaging; photobleaching; phototoxicity; pulsed LED excitation; PVP-Hypericin ID LIGHT-EMITTING-DIODES; MICROSCOPY; PHOTOTOXICITY; ILLUMINATION AB During fluorescent live cell imaging it is critical to keep excitation light dose as low as possible, especially in the presence of photosensitizer drugs, which generate free radicals upon photobleaching. During fluorescent imaging, stress by excitation and free radicals induces serious cell damages that may arrest the cell cycle. This limits the usefulness of the technique for drug discovery, when prolonged live cell imaging is necessary. This paper presents a strategy to provide gentle experimental conditions for dynamic monitoring of the proliferation of human lung epithelial carcinoma cells (A549) in the presence of the photosensitizer Polyvinylpyrrolidone-Hypericin. The distinctive strategy of this paper is based on the stringent environmental control and optimizing the excitation light dose by (i) using a low-power pulsed blue light-emitting diode with short pulse duration of 1.29 ms and (ii) adding a nontoxic fluorescent dye called carboxyfluorescein-diacetate-succinimidyl-ester (CFSE) to improve the fluorescence signals. To demonstrate the usefulness of the strategy, fluorescence signals and proliferation of dual-marked cells, during 5-h fluorescence imaging under pulsed excitation, were compared with those kept under continuous excitation and nonmarked reference cells. The results demonstrated 3% cell division and 2% apoptosis due to pulsed excitation compared to no division and 85% apoptosis under the continuous irradiation. Therefore, our strategy allows live cell imaging to be performed over longer time scales than with conventional continuous excitation. C1 [Penjweini, Rozhin; Loew, Hans G.; Kratky, Karl W.] Univ Vienna, Fac Phys, A-1090 Vienna, Austria. [Loew, Hans G.] Med Univ Vienna, Dept Therapeut Radiol, Vienna, Austria. [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.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Kratky, KW (reprint author), Univ Vienna, Fac Phys, Boltzmanng 5, A-1090 Vienna, Austria. EM karl.kratky@univie.ac.at RI Loew, Hans Gunter/L-2548-2013; OI Hamblin, Michael/0000-0001-6431-4605 FU Austrian Economy Chamber; Hochschuljubilaumsfond [H1971-2006] FX The new strategy and imaging setup used in this paper was supported by the Austrian Economy Chamber (http://www.i2b.at) and developed by RISCREEN, granted with First place i2B-Businessplan-2009 AWARD (15.12.2009) and Hochschuljubilaumsfond-project H1971-2006. Authors would like to thank Gottfried Koehler, Martin Knapp, Maria Eisenbauer and Paul Breit for useful discussion. NR 27 TC 9 Z9 10 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-2720 J9 J MICROSC-OXFORD JI J. Microsc.. PD JAN PY 2012 VL 245 IS 1 BP 100 EP 108 DI 10.1111/j.1365-2818.2011.03555.x PG 9 WC Microscopy SC Microscopy GA 860LW UT WOS:000297950800011 PM 21974829 ER PT J AU Osborne, C Ecker, JL Gauvreau, K Lieberman, E AF Osborne, Cara Ecker, Jeffrey L. Gauvreau, Kimberlee Lieberman, Ellice TI First Birth Cesarean and Risk of Antepartum Fetal Death in a Subsequent Pregnancy SO JOURNAL OF MIDWIFERY & WOMENS HEALTH LA English DT Article DE antepartum care; cesarean birth; obstetric complications; primary cesarean birth; quantitative research; stillbirth ID UTERINE RUPTURE; STILLBIRTH; DELIVERY; WOMEN; OUTCOMES; WEIGHT; LABOR; POPULATION; MORTALITY; SECTION AB Introduction: To examine the relationship between first birth by cesarean and antepartum fetal death in a subsequent pregnancy in a large, hospital-based population. Methods: Data for this retrospective cohort study were taken from a database of all women who gave birth at Brigham and Women's Hospital during 4 waves of data collection beginning in 1994 and ending in 2002. We calculated the risk of antepartum fetal death in the subsequent pregnancy for women whose first birth was by cesarean compared to women with a vaginal first birth. Survival analysis was used to examine the influence of gestational age at birth. Results: Of 10,996 women who met inclusion criteria, 22% (n = 2450) had first births by cesarean, and 78% (n = 8546) had vaginal first births. The risk of antepartum fetal death in the subsequent pregnancy for women whose first birth was by cesarean was significantly greater than the risk for women whose first birth was vaginal (odds ratio 2.6; 95% confidence interval, 1.1-6.2). The relationship between first birth cesarean and antepartum fetal death in a subsequent pregnancy differed by gestational age at birth, with no excess risk among women with a previous cesarean birth who gave birth before 34 weeks' gestation but with a substantially increased risk for women who gave birth at 34 or more weeks' gestation (unadjusted hazard ratio = 5.6; 95% confidence interval, 1.6-19.8). Hazard ratio estimates for the association remained significant in bivariate models when adjusted for maternal height, weight, age, hypertension, and diabetes. Discussion: In these data, first birth by cesarean was associated with an increased risk of antepartum fetal death in a subsequent pregnancy. Our findings suggest that antepartum fetal deaths in subsequent pregnancies might be prevented by avoiding primary cesarean birth. J MidwiferyWomens Health 2012; 57: 12-17 (C) 2011 by the American College of Nurse-Midwives. C1 [Osborne, Cara] Univ Arkansas, Elenor Mann Sch Nursing, Fayetteville, AR 72701 USA. [Ecker, Jeffrey L.; Gauvreau, Kimberlee; Lieberman, Ellice] Harvard Univ, Sch Med, Boston, MA USA. [Ecker, Jeffrey L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lieberman, Ellice] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Gauvreau, Kimberlee] Childrens Hosp Boston, Dept Cardiol, Boston, MA USA. [Lieberman, Ellice] Brigham & Womens Hosp, Div Clin & Epidemiol Res, Boston, MA 02115 USA. RP Osborne, C (reprint author), Univ Arkansas, Elenor Mann Sch Nursing, 216 F Ozark Hall, Fayetteville, AR 72701 USA. EM cxo004@uark.edu NR 24 TC 3 Z9 3 U1 0 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 JAN-FEB PY 2012 VL 57 IS 1 BP 12 EP 17 DI 10.1111/j.1542-2011.2011.00142.x PG 6 WC Nursing SC Nursing GA 877CZ UT WOS:000299155800003 PM 22251907 ER PT J AU Spencer, R Schorge, J Del Carmen, M Goodman, A Growdon, W Boruta, D AF Spencer, Ryan Schorge, John Del Carmen, Marcela Goodman, Annekathryn Growdon, Whitfield Boruta, David TI Laparoscopic Surgery for Endometrial Cancer: Why Don't All Patients Go Home the Day After Surgery? SO JOURNAL OF MINIMALLY INVASIVE GYNECOLOGY LA English DT Article DE Endometrial cancer; Hospital length of stay; Laparoscopy ID CONTROLLED-TRIALS; HYSTERECTOMY; LYMPHADENECTOMY; SURVIVAL; COST AB Study Objective: To identify risk factors for hospital length of stay (LOS) longer than 1 postoperative day in patients undergoing laparoscopic hysterectomy because of endometrial cancer. Design: Retrospective observational study (Canadian Task Force classification II-2). Setting: Tertiary-care university hospital. Patients: One hundred thirty-three patients undergoing laparoscopic hysterectomy because of endometrial cancer between August 2006 and August 2010. Interventions: One hundred thirty-three women underwent traditional laparoscopy. In 101 of these patients, lymph node sampling was performed. Measurements and Main Outcomes: Seventy-four women (55%) were discharged on postoperative day 1. The percentage of women discharged on postoperative day 1 (POD1) vs after POD1 did not differ by extent of staging. Risk of perioperative complications was associated with hospital LOS longer than POD1 (odds ratio [OR], 11.45; 95% confidence interval [CI], 1.40-94.39). Procedure start time after 3:00 PM (OR, 3.20; 95% CI, 1.14-9.04) and procedure end time after 5:00 pm (OR, 2.47; 95% CI, 1.17-5.20) were independent factors associated with hospital LOS beyond POD1. There was a nonsignificant tendency toward later hospital discharge with administration of intravenous narcotic agents. Conclusions: Laparoscopic surgery to treat endometrial cancer should be preferentially scheduled early in the day to facilitate discharge on POD1. The extent of staging lymphadenectomy performed does not increase hospital stay beyond POD1. Journal of Minimally Invasive Gynecology (2012) 19, 95-100 (C) 2012 AAGL. All rights reserved. C1 [Spencer, Ryan] Harvard Univ, Div Gynecol Oncol, Dept Obstet & Gynecol, Massachusetts Gen Hosp,Med Sch,Yawkey Ctr, Boston, MA 02114 USA. RP Spencer, R (reprint author), Harvard Univ, Div Gynecol Oncol, Dept Obstet & Gynecol, Massachusetts Gen Hosp,Med Sch,Yawkey Ctr, 32 Fruit St,Ste 4F, Boston, MA 02114 USA. EM rjspencer@partners.org NR 27 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1553-4650 J9 J MINIM INVAS GYN JI J. Mimim. Invasive Gynecol. PD JAN-FEB PY 2012 VL 19 IS 1 BP 95 EP 100 DI 10.1016/j.jmig.2011.10.007 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 879BQ UT WOS:000299305100017 PM 22196258 ER PT J AU Tuncel, N Korkmaz, OT Tekin, N Sener, E Akyuz, F Inal, M AF Tuncel, Nese Korkmaz, Orhan Tansel Tekin, Neslihan Sener, Erol Akyuz, Fahrettin Inal, Mine TI Antioxidant and Anti-Apoptotic Activity of Vasoactive Intestinal Peptide (VIP) Against 6-Hydroxy Dopamine Toxicity in the Rat Corpus Striatum SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE Vasoactive intestinal peptide; Parkinson's disease; DNA fragmentation; Oxidative damage; 6-OHDA; Nitric oxide ID NITRIC-OXIDE SYNTHASE; PARKINSONS-DISEASE; OXIDATIVE STRESS; MAST-CELLS; NEURODEGENERATIVE DISEASES; SUPEROXIDE-DISMUTASE; ISCHEMIA-REPERFUSION; LIPID-PEROXIDATION; LUNG INJURY; PATHOGENESIS AB 6-Hydroxydopamine (6-OHDA) is an oxidative stress neurotoxin, which is oxidized in neurons, causes respiratory inhibition, and induces free radical formation and oxidative stress. Therefore, a 6-OHDA-induced Parkinson's disease (PD) experimental model can be used to test a candidate molecule for use as an antioxidant that could be a promising therapeutic for treating Parkinson's disease. Recent studies have shown that vasoactive intestinal peptide (VIP) might be a good candidate agent for the treatment of PD. In this study, the anti-apoptotic and antioxidant actions of VIP were investigated using the 6-OHDA-lesioned rat model for PD. Twenty-four young adult Sprague-Dawley rats were used. The rats were separated into the following groups: group I (n = 8), sham operated; group II (n = 8), 6-OHDA lesioned; group III (n = 8), 6-OHDA lesioned + i.p. VIP-injected (25 ng/kg) every 2 days for 15 days. The first i.p. injection of VIP was made 1 h after the intrastriatal 6-OHDA microinjection. Antioxidant enzymatic activity [super oxide dismutase (SOD) and catalase (CAT)], lipid peroxidation, nitric oxide and DNA fragmentation were measured from homogenates isolated from the corpus striatum. SOD, CAT, malondialdehyde, and DNA fragmentation were measured using a spectrophotometer, and nitric oxide (NO) levels were measured by capillary electrophoresis. 6-OHDA significantly induced oxidative stress, lipid peroxidation, and DNA fragmentation in the corpus striatum of rats. VIP significantly protected neuronal tissue from oxidative stress and apoptosis by reducing lipid peroxidation and DNA fragmentation. 6-OHDA toxicity did not cause significant changes in NO production in the corpus striatum. However, VIP treatment significantly reduced NO levels in brain tissue. C1 [Korkmaz, Orhan Tansel] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Korkmaz, Orhan Tansel] VA Boston Healthcare Syst, Dept Vet Affairs, Boston, MA 02130 USA. [Korkmaz, Orhan Tansel; Tekin, Neslihan] Eskisehir Osmangazi Univ, Fac Med, Dept Physiol, TR-26480 Eskisehir, Turkey. [Tekin, Neslihan; Akyuz, Fahrettin; Inal, Mine] Eskisehir Osmangazi Univ, Fac Med, Dept Biochem, TR-26480 Eskisehir, Turkey. [Sener, Erol] Anadolu Univ, Fac Pharm, Dept Analyt Chem, TR-26470 Eskisehir, Turkey. RP Korkmaz, OT (reprint author), Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. EM otk@bu.edu NR 58 TC 18 Z9 19 U1 1 U2 16 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD JAN PY 2012 VL 46 IS 1 BP 51 EP 57 DI 10.1007/s12031-011-9618-z PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 879MA UT WOS:000299332200006 PM 21850490 ER PT J AU Schmidt, HD Sangrey, GR Darnell, SB Schassburger, RL Cha, JHJ Pierce, RC Sadri-Vakili, G AF Schmidt, Heath D. Sangrey, Gavin R. Darnell, Shayna B. Schassburger, Rachel L. Cha, Jang-Ho J. Pierce, R. Christopher Sadri-Vakili, Ghazeleh TI Increased brain-derived neurotrophic factor (BDNF) expression in the ventral tegmental area during cocaine abstinence is associated with increased histone acetylation at BDNF exon I-containing promoters SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE addiction; chromatin remodeling; neurotrophic factor; psychostimulant; self-administration; transcription ID GLUTAMATE-RECEPTOR SUBUNITS; MESOLIMBIC DOPAMINE SYSTEM; MEDIAL PREFRONTAL CORTEX; GENE-EXPRESSION; NUCLEUS-ACCUMBENS; PROTEIN-LEVELS; D-3 RECEPTOR; TRANSCRIPTION; ADDICTION; INFUSION AB Recent evidence suggests that the persistence of cocaine seeking during periods of protracted drug abstinence following chronic cocaine exposure is mediated, in part, by neuroadaptations in the mesolimbic dopamine system. Specifically, incubation of cocaine-seeking behavior coincides with increased brain-derived neurotrophic factor (BDNF) protein expression in the ventral tegmental area (VTA). However, the molecular mechanisms that regulate time-dependent changes in VTA BDNF protein expression during cocaine abstinence are unclear. The goal of these experiments was to determine whether VTA BDNF transcript levels are altered following cocaine abstinence and identify the molecular mechanisms regulating cocaine-induced changes in VTA BDNF transcription. Rats were allowed to self-administer cocaine (0.25 mg/infusion, i.v.) for 14 days on a fixed-ratio schedule of reinforcement followed by 7 days of forced drug abstinence. BDNF protein and exon I-containing transcripts were significantly increased in the VTA of cocaine-experienced rats following 7 days of forced drug abstinence compared to yoked saline controls. Cocaine-induced changes in BDNF mRNA were associated with increased acetylation of histone 3 and binding of CREB-binding protein to exon I-containing promoters in the VTA. Taken together, these results suggest that drug abstinence following cocaine self-administration remodels chromatin in the VTA resulting in increased expression of BDNF, which may contribute to neuroadaptations underlying cocaine craving and relapse. C1 [Sangrey, Gavin R.; Darnell, Shayna B.; Cha, Jang-Ho J.; Sadri-Vakili, Ghazeleh] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Boston, MA 02114 USA. [Schmidt, Heath D.; Schassburger, Rachel L.; Pierce, R. Christopher] Univ Pennsylvania Sch, Perelman Sch Med, Dept Psychiat, Ctr Neurobiol & Behav, Philadelphia, PA USA. RP Sadri-Vakili, G (reprint author), Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, 114 16th St, Charlestown, MA 02129 USA. EM gsadrivakili@partners.org FU NIDA [DA22339, DA18678]; K01 award [DA030445] FX This work was supported by NIDA grants DA22339 (RCP and GSV) and DA18678 (RCP). HDS was supported by an individual K01 award (DA030445). The authors declare no conflicts of interest. NR 48 TC 34 Z9 37 U1 2 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JAN PY 2012 VL 120 IS 2 BP 202 EP 209 DI 10.1111/j.1471-4159.2011.07571.x PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 869ME UT WOS:000298601400002 PM 22043863 ER PT J AU Pinna, G Rasmusson, AM AF Pinna, Graziano Rasmusson, Ann M. TI Up-Regulation of Neurosteroid Biosynthesis as a Pharmacological Strategy to Improve Behavioural Deficits in a Putative Mouse Model of Post-Traumatic Stress Disorder SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Review DE allopregnanolone; 5a-reductase type I; selective brain steroidogenic stimulants; aggressive behaviour; GABAA receptors; social isolation; anxiety; post-traumatic stress disorder ID GABA-A RECEPTOR; GAMMA-AMINOBUTYRIC-ACID; GENERALIZED ANXIETY DISORDER; PROTRACTED SOCIAL-ISOLATION; RANDOMIZED CONTROLLED-TRIAL; NEURAL PROGENITOR CELLS; VENTRAL TEGMENTAL AREA; PROTEIN 18 KDA; PREFRONTAL CORTEX; NEUROACTIVE STEROIDS AB Benzodiazepines remain the most frequently used psychotropic drugs for the treatment of anxiety spectrum disorders; however, their use is associated with the development of tolerance and dependence. Another major hindrance is represented by their lack of efficacy in many patients, including patients with post-traumatic stress disorder (PTSD). For these nonresponders, the use of selective serotonin reuptake inhibitors (SSRIs) has been the therapy of choice. In the past decade, clinical studies have suggested that the pharmacological action of SSRIs may include the ability of these drugs to normalise decreased brain levels of neurosteroids in patients with depression and PTSD; in particular, the progesterone derivative allopregnanolone, which potently, positively and allosterically modulates the action of GABA at GABAA receptors. Preclinical studies using the socially-isolated mouse as an animal model of PTSD have demonstrated that fluoxetine and congeners ameliorate anxiety-like behaviour, fear responses and aggressive behaviour expressed by such mice by increasing corticolimbic levels of allopregnanolone. This is a novel and more selective mechanism than serotonin reuptake inhibition, which, for half a century, has been considered to be the main molecular mechanism for the therapeutic action of SSRIs. Importantly, this finding may shed light on the high rates of SSRI resistance among patients with PTSD and depression, comprising disorders in which there appears to be a block in allopregnanolone synthesis. There are several different mechanisms by which such a block may occur, and SSRIs may only be corrective under some conditions. Thus, the up-regulation of allopregnanolone biosynthesis in corticolimbic neurones may offer a novel nontraditional pharmacological target for a new generation of potent nonsedating, anxiolytic medications for the treatment of anxiety, depression, and PTSD: selective brain steroidogenic stimulants. C1 [Pinna, Graziano] Univ Illinois, Dept Psychiat, Inst Psychiat, Coll Med, Chicago, IL 60612 USA. [Rasmusson, Ann M.] Boston Univ, Sch Med, Womens Hlth Sci Div,VA Boston Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, Boston, MA 02118 USA. RP Pinna, G (reprint author), Univ Illinois, Dept Psychiat, Inst Psychiat, Coll Med, 1601 W Taylor St, Chicago, IL 60612 USA. EM gpinna@psych.uic.edu FU National Institute of Mental Health [MH 085999, MH31113]; VA Boston Healthcare System FX This review was supported by the National Institute of Mental Health Grant MH 085999 (to G. Pinna) and VA Boston Healthcare System and National Institute of Mental Health Grant MH31113 (to A. Rasmusson). NR 187 TC 32 Z9 34 U1 1 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0953-8194 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD JAN PY 2012 VL 24 IS 1 BP 102 EP 116 DI 10.1111/j.1365-2826.2011.02234.x PG 15 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 869MI UT WOS:000298601800010 PM 21981145 ER PT J AU Chen, M Lee, G Kwong, LN Lamont, S Chaves, C AF Chen, Merry Lee, Grace Kwong, Lawrence N. Lamont, Sharon Chaves, Claudia TI Cerebral White Matter Lesions in Patients with Crohn's Disease SO JOURNAL OF NEUROIMAGING LA English DT Article DE White matter abnormalities; Crohn's disease; MRI of the brain ID INFLAMMATORY-BOWEL-DISEASE; DEFINITE MULTIPLE-SCLEROSIS; NEUROLOGICAL COMPLICATIONS; PREDICT CONVERSION; BRAIN; ABNORMALITIES; CRITERIA; MR AB BACKGROUND To investigate the incidence, characteristics, and predisposing factors for cerebral white matter lesions in patients with Crohn's disease. METHODS We retrospectively evaluated the incidence and characteristics of cerebral T2 white matter abnormalities in 54 patients with Crohn's disease and compared to 100 age-matched controls. We also investigated potential co-morbidities known to be associated with white matter abnormalities in Crohn's patients with normal and abnormal Magnetic Resonance Imaging (MRI). RESULTS Seventy-two percent of patients with Crohn's disease had T2 white matter abnormalities, as compared with 34% of the age-matched controls (P < .001). Lesion severity and size were not significantly different between the two groups; however, periventricular distribution and fulfillment of the Barkhof MRI criteria were overrepresented in Crohn's population. History of hypertension, diabetes, and migraine; gender, duration of disease and prior exposure to anti-tumor necrosis factor were not significantly different between Crohn's patients with and without white matter abnormalities; however, patients with lesions were significantly older than those without. CONCLUSIONS Patients with Crohn's disease have a higher incidence of white matter T2 hyperintensities as compared with controls. Age was the only significant factor for the abnormalities within Crohn's group. White matter T2 hyperintensities are likely another extra-intestinal manifestation of Crohn's disease. C1 [Chen, Merry; Lamont, Sharon; Chaves, Claudia] Lahey Clin Fdn, Dept Neurol, Lexington, MA 02421 USA. [Lee, Grace] Lahey Clin Fdn, Dept Radiol, Burlington, MA USA. [Kwong, Lawrence N.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Chaves, C (reprint author), Lahey Clin Fdn, Dept Neurol, 16 Hayden Ave, Lexington, MA 02421 USA. EM Claudia.j.chaves@lahey.org NR 17 TC 10 Z9 10 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1051-2284 J9 J NEUROIMAGING JI J. Neuroimaging PD JAN PY 2012 VL 22 IS 1 BP 38 EP 41 DI 10.1111/j.1552-6569.2010.00538.x PG 4 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 877DZ UT WOS:000299158500007 PM 21091817 ER PT J AU Johnson, KA Hartwell, K LeMatty, T Borckardt, J Morgan, PS Govindarajan, K Brady, K George, MS AF Johnson, Kevin A. Hartwell, Karen LeMatty, Todd Borckardt, Jeffrey Morgan, Paul S. Govindarajan, Koushik Brady, Kathleen George, Mark S. TI Intermittent "Real-time" fMRI Feedback Is Superior to Continuous Presentation for a Motor Imagery Task: A Pilot Study SO JOURNAL OF NEUROIMAGING LA English DT Article DE fMRI; neurofeedback; real-time fMRI; motor imagery ID RESONANCE-IMAGING FMRI; CORTICAL ACTIVITY; BRAIN ACTIVATION; SELF-REGULATION; FUNCTIONAL MRI; NEUROFEEDBACK AB BACKGROUND Real-time functional MRI feedback (RTfMRIf) is a developing technique, with unanswered methodological questions. Given a delay of seconds between neural activity and the measurable hemodynamic response, one issue is the optimal method for presentation of neurofeedback to subjects. The primary objective of this preliminary study was to compare the methods of continuous and intermittent presentation of neural feedback on targeted brain activity. METHODS Thirteen participants performed a motor imagery task and were instructed to increase activation in an individually defined region of left premotor cortex using RTfMRIf. The fMRI signal change was compared between real and false feedback for scans with either continuous or intermittent feedback presentation. RESULTS More individuals were able to increase their fMRI signal with intermittent feedback, while some individuals had decreased signal with continuous feedback. The evaluation of feedback itself activated an extensive amount of brain regions, and false feedback resulted in brain activation outside of the individually defined region of interest. CONCLUSIONS As implemented in this study, intermittent presentation of feedback is more effective than continuous presentation in promoting self-modulation of brain activity. Furthermore, it appears that the process of evaluating feedback involves many brain regions that can be isolated using intermittent presentation. C1 [Johnson, Kevin A.] Stanford Univ, Dept Anesthesiol, Syst Neurosci & Pain Lab, Palo Alto, CA 94304 USA. [Hartwell, Karen; LeMatty, Todd; Brady, Kathleen] Med Univ S Carolina, Dept Psychiat, CNS Div, Charleston, SC 29425 USA. [Johnson, Kevin A.; Borckardt, Jeffrey; George, Mark S.] Med Univ S Carolina, Dept Psychiat, Brain Stimulat Lab, Charleston, SC 29425 USA. [Johnson, Kevin A.; Morgan, Paul S.; Govindarajan, Koushik; George, Mark S.] Med Univ S Carolina, Ctr Adv Imaging Res, Charleston, SC 29425 USA. [Morgan, Paul S.] Med Univ S Carolina, Dept Radiol, Charleston, SC 29425 USA. [Hartwell, Karen; Brady, Kathleen; George, Mark S.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Johnson, KA (reprint author), Stanford Univ, Dept Anesthesiol, Syst Neurosci & Pain Lab, 780 Welch Rd 208, Palo Alto, CA 94304 USA. EM johnsk@stanford.edu OI Morgan, Paul/0000-0002-5870-1446 FU NIH/NIDA (Brady, George) [1R21DA026085-01] FX The authors have no conflicts of interest to disclose. This study is supported in part by NIH/NIDA 1R21DA026085-01 (Brady, George). NR 17 TC 37 Z9 39 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1051-2284 J9 J NEUROIMAGING JI J. Neuroimaging PD JAN PY 2012 VL 22 IS 1 BP 58 EP 66 DI 10.1111/j.1552-6569.2010.00529.x PG 9 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 877DZ UT WOS:000299158500011 PM 20977537 ER PT J AU Pantilat, SZ Kerr, KM Billings, JA Bruno, KA O'Riordan, DL AF Pantilat, Steven Z. Kerr, Kathleen M. Billings, J. Andrew Bruno, Kelly A. O'Riordan, David L. TI Palliative Care Services in California Hospitals: Program Prevalence and Hospital Characteristics SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Prevalence; structure; palliative care services; hospital AB Context. In 2000, 17% of California hospitals offered palliative care (PC) services. Since then, hospital-based PC programs have become increasingly common, and preferred practices for these services have been proposed by expert consensus. Objectives. We sought to examine the prevalence of PC programs in California, their structure, and the hospital characteristics associated with having a program. Methods. A total of 351 acute care hospitals in California completed a survey that determined the presence of and described the structure of PC services. Logistic regression identified hospital characteristics associated with having a PC program. Results. A total of 324 hospitals (92%) responded, of which 44% (n = 141) reported having a PC program. Hospitals most likely to have PC programs were large nonprofit facilities that belonged to a health system, had teaching programs, and had participated in a training program designed to promote development of PC services. Investor-owned sites (odds ratio [OR] = 0.08; 95% confidence interval [CI] = 0.03, 0.2) and city/county facilities (OR = 0.06; 95% CI = 0.01, 0.3) were less likely to have a PC program. The most common type of PC service was an inpatient consultation service (88%), staffed by a physician (87%), social worker (81%), chaplain (76%), and registered nurse (74%). Most programs (71%, n = 86) received funding from the hospital and were expected to meet goals set by the hospital or health system. Conclusion. Although the number of hospital-based PC services in California has doubled since 2000, more than half of the acute care hospitals still do not provide PC services. Developing initiatives that target small, public, and investor-owned hospitals may lead to wider availability of PC services. J Pain Symptom Manage 2012; 43: 39-46. (C) 2012 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved. C1 [Pantilat, Steven Z.; Kerr, Kathleen M.; O'Riordan, David L.] Univ Calif San Francisco, Palliat Care Program, Div Hosp Med, Dept Med, San Francisco, CA 94143 USA. [Billings, J. Andrew] Massachusetts Gen Hosp, Palliat Care Serv, Boston, MA 02114 USA. [Billings, J. Andrew] Harvard Univ, Sch Med, Ctr Palliat Care, Boston, MA USA. [Bruno, Kelly A.] Natl Hlth Fdn, Los Angeles, CA USA. RP Pantilat, SZ (reprint author), Univ Calif San Francisco, Palliat Care Program, Div Hosp Med, Dept Med, 521 Parnassus Ave,Suite C-126, San Francisco, CA 94143 USA. EM stevep@medicine.ucsf.edu FU California HealthCare Foundation; Hospital Council of Northern and Central California; Hospital Council of Southern California; Hospital Council of San Diego and Imperial Counties FX The California HealthCare Foundation provided funding to support the administration of the survey and analysis of findings, as well as limited dissemination of results through the Foundation's communication venues. The authors declare no competing interests.; The authors thank the members of the advisory board for their input on the survey: Judy Citko, Richard Della Penna, Betty Ferrell, James Hallenbeck, Andrew Halpert, Karl Lorenz, Anna Schenck, Bradley Stuart, Mary Carol Todd, and Charles von Gunten. They also thank the Hospital Council of Northern and Central California, the Hospital Council of Southern California, and the Hospital Council of San Diego and Imperial Counties for their support in encouraging their members to participate. Finally, they thank all the respondents for their diligence and care in responding to the survey. NR 7 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 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD JAN PY 2012 VL 43 IS 1 BP 39 EP 46 DI 10.1016/j.jpainsymman.2011.03.021 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 877WH UT WOS:000299212900005 PM 21802898 ER PT J AU Lee, CN Chang, YC Adimorah, N Belkora, JK Moy, B Partridge, AH Ollila, DW Sepucha, KR AF Lee, Clara N. Chang, Yuchiao Adimorah, Nesochi Belkora, Jeff K. Moy, Beverly Partridge, Ann H. Ollila, David W. Sepucha, Karen R. TI Decision Making about Surgery for Early-Stage Breast Cancer SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID PATIENT PARTICIPATION; SURGICAL-TREATMENT; INFORMED DECISION; RANDOMIZED-TRIAL; LOCAL THERAPY; WOMEN; QUALITY; KNOWLEDGE; MASTECTOMY; CARCINOMA AB BACKGROUND: Practice variation in breast cancer surgery has raised concerns about the quality of treatment decisions. We sought to evaluate the quality of decisions about surgery for early-stage breast cancer by measuring patient knowledge, concordance between goals and treatments, and involvement in decisions. STUDY DESIGN: A mailed survey of stage I/II breast cancer survivors was conducted at 4 sites. The Decision Quality Instrument measured knowledge, goals, and involvement in decisions. A multivariable logistic regression model of treatment was developed. The model-predicted probability of mastectomy was compared with treatment received for each patient. Concordance was defined as having mastectomy and predicted probability >0.5 or partial mastectomy and predicted probability <0.5. Frequency of discussion about partial mastectomy was compared with discussion about mastectomy using chi-square tests. RESULTS: Four hundred and forty patients participated (59% response rate). Mean overall knowledge was 52.7%; 45.9% knew that local recurrence risk is higher after breast conservation and 55.7% knew that survival is equivalent for the 2 options. Most participants (89.0%) had treatment concordant with their goals. Participants preferring mastectomy had lower concordance (80.5%) than those preferring partial mastectomy (92.6%; p = 0.001). Participants reported more frequent discussion of partial mastectomy and its advantages than of mastectomy, and 48.6% reported being asked their preference. CONCLUSIONS: Breast cancer survivors had major knowledge deficits, and those preferring mastectomy were less likely to have treatment concordant with goals. Patients perceived that discussions focused on partial mastectomy, and many were not asked their preference. Improvements in the quality of decisions about breast cancer surgery are needed. (J Am Coll Surg 2012; 214: 1-11. (C) 2012 by the American College of Surgeons) C1 [Lee, Clara N.] Univ N Carolina, Div Plast & Reconstruct Surg, Lineberger Comprehens Canc Ctr, Sheps Ctr Hlth Serv Res, Chapel Hill, NC 27599 USA. [Adimorah, Nesochi; Ollila, David W.] Univ N Carolina, Dept Surg, Chapel Hill, NC 27599 USA. [Belkora, Jeff K.] Univ Calif San Francisco, Inst Hlth Policy Studies, San Francisco, CA 94143 USA. [Chang, Yuchiao] Harvard Univ, Massachusetts Gen Hosp, Dept Gen Med, Sch Med, Boston, MA 02114 USA. [Moy, Beverly] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. [Partridge, Ann H.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Sch Med, Boston, MA 02114 USA. [Sepucha, Karen R.] Harvard Univ, Sch Med, Hlth Decis Sci Ctr, Boston, MA 02114 USA. RP Lee, CN (reprint author), Univ N Carolina, Div Plast & Reconstruct Surg, Lineberger Comprehens Canc Ctr, Sheps Ctr Hlth Serv Res, CB 7195, Chapel Hill, NC 27599 USA. EM cnlee@med.unc.edu FU not-for-profit Foundation for Informed Medical Decision Making; NIH/National Center for Resesarch Resources [1KL2RR025746] FX Drs Belkora, Lee, and Sepucha were supported by a grant from the not-for-profit Foundation for Informed Medical Decision Making. Dr Lee was supported by NIH/National Center for Resesarch Resources 1KL2RR025746. NR 38 TC 24 Z9 24 U1 2 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 JAN PY 2012 VL 214 IS 1 BP 1 EP 10 DI 10.1016/j.jamcollsurg.2011.09.017 PG 10 WC Surgery SC Surgery GA 875SF UT WOS:000299054400003 PM 22056355 ER PT J AU Marcum, ZA Amuan, ME Hanlon, JT Aspinall, SL Handler, SM Ruby, CM Pugh, MJV AF Marcum, Zachary A. Amuan, Megan E. Hanlon, Joseph T. Aspinall, Sherrie L. Handler, Steven M. Ruby, Christine M. Pugh, Mary Jo V. TI Prevalence of Unplanned Hospitalizations Caused by Adverse Drug Reactions in Older Veterans SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE adverse drug reactions; veterans; aged; pharmacoepidemiology ID MEDICATION-USE; ELDERLY-PATIENTS; AMBULATORY-CARE; ADULTS; EVENTS; ADMISSION; GUIDELINES; POLYPHARMACY; PATIENT; RATES AB OBJECTIVES: To describe the prevalence of unplanned hospitalizations caused by adverse drug reactions (ADRs) in older veterans and to examine the association between this outcome and polypharmacy after controlling for comorbidities and other patient characteristics. DESIGN: Retrospective cohort. SETTING: Veterans Affairs Medical Centers. PARTICIPANTS: Six hundred seventy-eight randomly selected unplanned hospitalizations of older (aged >= 65) veterans between October 1, 2003, and September 30, 2006. MEASUREMENTS: Naranjo ADR algorithm, ADR preventability, and polypharmacy (0-4, 5-8, and >= 9 scheduled medications). RESULTS: Seventy ADRs involving 113 drugs were found in 68 (10%) hospitalizations of older veterans, of which 25 (36.8%) were preventable. Extrapolating to the population of more than 2.4 million older veterans receiving care during the study period, 8,000 hospitalizations may have been unnecessary. The most common ADRs that occurred were bradycardia (n = 6; beta-blockers, digoxin), hypoglycemia (n = 6; sulfonylureas, insulin), falls (n = 6; antidepressants, angiotensin-converting enzyme inhibitors), and mental status changes (n = 6; anticonvulsants, benzodiazepines). Overall, 44.8% of veterans took nine or more outpatient medications and 35.4% took five to eight. Using multivariable logistic regression and controlling for demographic, health-status, and access-to-care variables, polypharmacy (>= 9 and 5-8) was associated with greater risk of ADR-related hospitalization (adjusted odds ratio (AOR) = 3.90, 95% confidence interval (CI) = 1.43-10.61 and AOR = 2.85, 95% CI = 1.03-7.85, respectively). CONCLUSION: ADRs, determined using a validated causality algorithm, are a common cause of unplanned hospitalization in older veterans, are frequently preventable, and are associated with polypharmacy. J Am Geriatr Soc 60:34-41, 2012. C1 [Marcum, Zachary A.; Hanlon, Joseph T.; Handler, Steven M.; Ruby, Christine M.] Univ Pittsburgh, Sch Med, Dept Geriatr, Pittsburgh, PA 15213 USA. [Handler, Steven M.] Univ Pittsburgh, Sch Med, Dept Biomed Informat, Pittsburgh, PA 15213 USA. [Hanlon, Joseph T.; Aspinall, Sherrie L.; Ruby, Christine M.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15213 USA. [Amuan, Megan E.] Bedford Vet Affairs Med Ctr, Bedford, MA USA. [Hanlon, Joseph T.; Handler, Steven M.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. [Hanlon, Joseph T.; Aspinall, Sherrie L.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Aspinall, Sherrie L.] Vet Affairs Ctr Medicat Safety, Hines, IL USA. [Pugh, Mary Jo V.] S Texas Vet Hlth Care Syst, Vet Evidence Based Res Disseminat & Implementat C, San Antonio, TX USA. [Pugh, Mary Jo V.] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA. [Pugh, Mary Jo V.] Univ Texas Hlth Sci Ctr San Antonio, Div Geriatr & Gerontol, Dept Med, San Antonio, TX 78229 USA. RP Marcum, ZA (reprint author), Univ Pittsburgh, Dept Geriatr Med, Kaufmann Med Bldg,Suite 500,3471 5th Ave, Pittsburgh, PA 15213 USA. EM zam12@pitt.edu OI Handler, Steven/0000-0002-3940-3224; Pugh, Mary Jo/0000-0003-4196-7763 FU National Institute on Aging (NIA) [R01AG027017, P30AG024827, T32AG021885, K07AG033174, R01AG034056]; National Institute of Mental Health [R34 MH082682]; National Institute of Nursing Research [R01NR010135]; Agency for Healthcare Research and Quality [R01HS017695, R01HS018721, R18HS018151, K12HS019461]; VA Health Services Research and Development Service (HSR D) [IIR-06-062, DHI 09-237, IIR 02274, IIR 08-274, SDR-07-042, IIR-05-121, IAF-06-080, IIR-09335]; NIA [K07AG033174, U01 AG012553]; Pennsylvania Department of Aging; Epilepsy Foundation; SHP [08-140] FX Dr. Hanlon has received research funding from National Institute on Aging (NIA) Grants R01AG027017, P30AG024827, T32AG021885, K07AG033174, and R01AG034056; National Institute of Mental Health Grant R34 MH082682, National Institute of Nursing Research Grant R01NR010135, Agency for Healthcare Research and Quality Grant R01HS017695, and VA Health Services Research and Development Service (HSR& D) IIR-06-062. Dr. Handler has received research funding from Agency for Healthcare Research and Quality Grants R01HS018721 and R18HS018151; NIA Grant K07AG033174, a Pennsylvania Department of Aging grant, and from VA HSR& D IIR-06-062. Dr. Pugh has received research funding from VA HSR& D DHI 09-237 (PI); VA HSR& D IIR-06-062 (PI), Epilepsy Foundation (PI), VA HSR& D PPO 09-295 PI, VA HSR& D IIR 02274 PI. Pugh as co-I: VA HSR& D IIR 08-274, VA HSR& D SDR-07-042, IIR-05-121, IAF-06-080, IIR-09335, SHP 08-140, TRX 01-091 Department of Defense CDMRP 09090014, NIH R01-NR010828, Pugh Speaker Honoraria: 2009 Kelsey Seybold Research Foundation. The investigators received support from NIA Grant U01 AG012553 and Agency for Healthcare Research and Quality Grant K12HS019461. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. NR 50 TC 45 Z9 47 U1 1 U2 7 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 JAN PY 2012 VL 60 IS 1 BP 34 EP 41 DI 10.1111/j.1532-5415.2011.03772.x PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 875PN UT WOS:000299044100005 PM 22150441 ER PT J AU Shega, JW Dale, W Andrew, M Paice, J Rockwood, K Weiner, DK AF Shega, Joseph W. Dale, William Andrew, Melissa Paice, Judith Rockwood, Kenneth Weiner, Debra K. TI Persistent Pain and Frailty: A Case for Homeostenosis SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE pain; frailty; older adults; homeostenosis ID LOW-BACK-PAIN; OLDER-ADULTS; MORTALITY; PEOPLE; PREVALENCE; MANAGEMENT; DEMENTIA; IMPACT; CARE; 3MS AB OBJECTIVES: To compare the association between self-reported moderate to severe pain and frailty. DESIGN: Cross-sectional analysis of the Canadian Study of Health and Aging Wave 2. SETTING: Community. PARTICIPANTS: Representative sample of persons aged 65 and older in Canada. MEASUREMENTS: Pain (exposure) was categorized as no or very mild pain versus moderate or greater pain. Frailty (outcome) was operationalized as the accumulation of 33 possible self-reported health attitudes, illnesses, and functional abilities, subsequently divided into tertiles (not frail, prefrail, and frail). Multivariable logistic regression assessed for the association between pain and frailty. RESULTS: Of participants who reported moderate or greater pain (35.5%, 1,765/4,968), 16.2% were not frail, 34.1% were prefrail, and 49.8% were frail. For persons with moderate or greater pain, the odds of being prefrail rather than not frail were higher by a factor of 2.52 (95% confidence interval (CI) = 2.13-2.99; P < .001). For persons with moderate or greater pain, the odds of being frail rather than not frail were higher by a factor of 5.52 (95% CI = 4.49-6.64 P < .001). CONCLUSION: Moderate or higher pain was independently associated with frailty. Although causality cannot be ascertained in a cross-sectional analysis, interventions to improve pain management may help prevent or ameliorate frailty. J Am Geriatr Soc 60:113-117, 2012. C1 [Shega, Joseph W.; Dale, William] Univ Chicago, Sect Geriatr & Palliat Med, Chicago, IL 60637 USA. [Shega, Joseph W.] Univ Chicago, Sect Hematol & Oncol, Chicago, IL 60637 USA. [Andrew, Melissa; Rockwood, Kenneth] Dalhousie Univ, Div Geriatr Med, Halifax, NS, Canada. [Paice, Judith] Northwestern Univ, Feinberg Sch Med, Div Hematol Oncol, Chicago, IL 60611 USA. [Weiner, Debra K.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. [Weiner, Debra K.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Weiner, Debra K.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Weiner, Debra K.] Univ Pittsburgh, Dept Anesthesiol, Pittsburgh, PA USA. RP Shega, JW (reprint author), Univ Chicago, Sect Geriatr & Palliat Med, MC 6098,5841 S Maryland Ave, Chicago, IL 60637 USA. EM jshega@gmail.com FU National Health Research Development Program; Seniors' Independence Research program [6606-3954-MC(S)]; National Institute on Aging [K23AG029815]; Canadian Institutes of Health Research [MOP-62823]; Dalhousie Medical Research Foundation; QEII Research Foundation FX All the data reported here were gathered using public funding from the National Health Research Development Program, which administrated a grant from the Seniors' Independence Research program (6606-3954-MC(S)). Funding for these analyses came from a career development award K23AG029815 from the National Institute on Aging and from the Canadian Institutes of Health Research through operating grant MOP-62823. Additional support came from the Dalhousie Medical Research Foundation (career support to KR as Kathryn Allen Weldon Professor of Alzheimer Research) and the Fountain Innovation Fund of the QEII Research Foundation. NR 29 TC 22 Z9 22 U1 2 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JAN PY 2012 VL 60 IS 1 BP 113 EP 117 DI 10.1111/j.1532-5415.2011.03769.x PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 875PN UT WOS:000299044100015 PM 22150394 ER PT J AU O'Hare, AM AF O'Hare, Ann M. TI Age and Access to Kidney Transplantation SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Editorial Material ID OLDER-ADULTS; PROGNOSTIC INDEX; MORTALITY; VALIDATION C1 [O'Hare, Ann M.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [O'Hare, Ann M.] Vet Affairs Puget Sound Healthcare Syst, Dept Med, Seattle, WA USA. [O'Hare, Ann M.] Grp Hlth Res Inst Seattle, Seattle, WA USA. RP O'Hare, AM (reprint author), Univ Washington, Dept Med, Seattle, WA 98195 USA. NR 15 TC 1 Z9 1 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JAN PY 2012 VL 60 IS 1 BP 151 EP 153 DI 10.1111/j.1532-5415.2011.03790.x PG 3 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 875PN UT WOS:000299044100022 PM 22239294 ER PT J AU Jackson, ML Wallis, J Williams, K Schoessow, K Drohan, B AF Jackson, Mary Lou Wallis, Jennifer Williams, Kristina Schoessow, Kimberly Drohan, Brian TI Visual Function in the 'Oldest-Old' 1 Year After Comprehensive Vision Rehabilitation SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Letter ID QUALITY-OF-LIFE; IMPAIRMENT; OUTCOMES; ADULTS; IMPACT C1 [Jackson, Mary Lou; Wallis, Jennifer; Williams, Kristina] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. [Schoessow, Kimberly] San Francisco Vet Affairs Hlth Care Syst, Frank Stein & Paul S May Ctr Low Vis Rehabil, Palo Alto, CA USA. [Drohan, Brian] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Jackson, ML (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. NR 10 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JAN PY 2012 VL 60 IS 1 BP 183 EP 185 DI 10.1111/j.1532-5415.2011.03742.x PG 3 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 875PN UT WOS:000299044100043 PM 22239315 ER PT J AU Oklu, R Habito, R Mayr, M Deipolyi, AR Albadawi, H Hesketh, R Walker, TG Linskey, KR Long, CA Wicky, S Stoughton, J Watkins, MT AF Oklu, Rahmi Habito, Roy Mayr, Manuel Deipolyi, Amy R. Albadawi, Hassan Hesketh, Robin Walker, T. Gregory Linskey, Katy R. Long, Chandler A. Wicky, Stephan Stoughton, Julianne Watkins, Michael T. TI Pathogenesis of Varicose Veins SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Review ID CHRONIC VENOUS INSUFFICIENCY; BETA BINDING PROTEIN-1; EXTRACELLULAR-MATRIX; GENERAL-POPULATION; EDINBURGH VEIN; DISEASE; WALL; PROTEOMICS; DISORDERS; MUTATIONS AB Despite the high prevalence of varicose veins and the recent surge in research on the condition, the precise mechanisms underlying their development remain uncertain. In the past decade, there has been a shift from initial theories based on purely mechanical factors to hypotheses pointing to complex molecular changes causing histologic alterations in the vessel wall and extracellular matrix. Despite progress in understanding the molecular aspects of venous insufficiency, therapies for symptomatic varicose veins are directed toward anatomic and physical interventions. The present report reviews current evidence identifying the underlying biochemical alterations in the pathogenesis of varicose veins. C1 [Oklu, Rahmi; Habito, Roy; Deipolyi, Amy R.; Walker, T. Gregory; Wicky, Stephan] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Vasc Imaging & Intervent, Boston, MA 02114 USA. [Albadawi, Hassan; Long, Chandler A.; Stoughton, Julianne; Watkins, Michael T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Vasc Surg, Boston, MA 02114 USA. [Linskey, Katy R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Hesketh, Robin] Univ Cambridge, Dept Biochem, Cambridge CB2 1QW, England. [Mayr, Manuel] Kings Coll London, Dept Cardiol, London WC2R 2LS, England. RP Oklu, R (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Vasc Imaging & Intervent, 55 Fruit St,290 Gray Bigelow, Boston, MA 02114 USA. EM roklu@partners.org OI Mayr, Manuel/0000-0002-0597-829X; Deipolyi, Amy/0000-0003-3144-386X FU American College of Phlebology FX R.O. is the recipient of the American College of Phlebology Investigator Award. M.M. is a British Heart Foundation Senior Fellow. M.T.W. is the Isenberg Scholar in Academic Surgery at Massachusetts General Hospital. None of the authors have identified a conflict of interest. NR 74 TC 15 Z9 17 U1 3 U2 10 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 JAN PY 2012 VL 23 IS 1 BP 33 EP 39 DI 10.1016/j.jvir.2011.09.010 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 877BL UT WOS:000299151400005 PM 22030459 ER PT J AU Gervais, DA AF Gervais, Debra A. TI Preexisting Chronic Kidney Disease and Renal Tumor Ablation: Preliminary Answers and Persistent Questions SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Gervais, DA (reprint author), Massachusetts Gen Hosp, Dept Radiol, White 270,55 Fruit St, Boston, MA 02114 USA. EM dgervais@partners.org NR 2 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 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD JAN PY 2012 VL 23 IS 1 BP 46 EP 47 DI 10.1016/j.jvir.2011.10.011 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 877BL UT WOS:000299151400007 PM 22221472 ER PT J AU Krop, I Winer, EP AF Krop, Ian Winer, Eric P. TI Further progress in HER2-directed therapy SO LANCET ONCOLOGY LA English DT Editorial Material ID HER2-POSITIVE BREAST-CANCER; TRASTUZUMAB C1 [Krop, Ian; Winer, Eric P.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Krop, I (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM ikrop@partners.org NR 9 TC 2 Z9 4 U1 1 U2 2 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 JAN PY 2012 VL 13 IS 1 BP 2 EP 3 PG 2 WC Oncology SC Oncology GA 875EZ UT WOS:000299014500025 PM 22225715 ER PT J AU Kumar, SK Lee, JH Lahuerta, JJ Morgan, G Richardson, PG Crowley, J Haessler, J Feather, J Hoering, A Moreau, P Leleu, X Hulin, C Klein, SK Sonneveld, P Siegel, D Blade, J Goldschmidt, H Jagannath, S Miguel, JS Orlowski, R Palumbo, A Sezer, O Rajkumar, SV Durie, BGM AF Kumar, S. K. Lee, J. H. Lahuerta, J. J. Morgan, G. Richardson, P. G. Crowley, J. Haessler, J. Feather, J. Hoering, A. Moreau, P. LeLeu, X. Hulin, C. Klein, S. K. Sonneveld, P. Siegel, D. Blade, J. Goldschmidt, H. Jagannath, S. Miguel, J. S. Orlowski, R. Palumbo, A. Sezer, O. Rajkumar, S. V. Durie, B. G. M. CA Int Myeloma Working Grp TI Risk of progression and survival in multiple myeloma relapsing after therapy with IMiDs and bortezomib: A multicenter international myeloma working group study SO LEUKEMIA LA English DT Article DE multiple myeloma; relapse; natural history; survival ID LENALIDOMIDE PLUS DEXAMETHASONE; NEWLY-DIAGNOSED MYELOMA; COMBINATION THERAPY; THALIDOMIDE; RETREATMENT; EXPERIENCE; IMPACT; TRIALS AB Promising new drugs are being evaluated for treatment of multiple myeloma (MM), but their impact should be measured against the expected outcome in patients failing current therapies. However, the natural history of relapsed disease in the current era remains unclear. We studied 286 patients with relapsed MM, who were refractory to bortezomib and were relapsed following, refractory to or ineligible to receive, an IMiD (immunomodulatory drug), had measurable disease, and ECOG PS of 0, 1 or 2. The date patients satisfied the entry criteria was defined as time zero (T-0). The median age at diagnosis was 58 years, and time from diagnosis to T-0 was 3.3 years. Following T-0, 213 (74%) patients had a treatment recorded with one or more regimens (median = 1; range 0-8). The first regimen contained bortezomib in 55 (26%) patients and an IMiD in 70 (33%). A minor response or better was seen to at least one therapy after T0 in 94 patients (44%) including >= partial response in 69 (32%). The median overall survival and event-free survival from T-0 were 9 and 5 months, respectively. This study confirms the poor outcome, once patients become refractory to current treatments. The results provide context for interpreting ongoing trials of new drugs. Leukemia (2012) 26, 149-157; doi:10.1038/leu.2011.196; published online 29 July 2011 C1 [Kumar, S. K.; Rajkumar, S. V.] Mayo Clin, Div Hematol, Rochester, MN 55905 USA. [Lee, J. H.] Gachon Univ, Gil Hosp, Div Hematooncol, Inchon, South Korea. [Lahuerta, J. J.] Hosp Univ 12 Octubre, Dept Hematol, Madrid, Spain. [Morgan, G.] Royal Marsden Hosp, Dept Hematol, Sutton, Surrey, England. [Richardson, P. G.; Feather, J.] Dana Farber Canc Inst, Div Hematol Malignancies, Dept Med Oncol, Boston, MA 02115 USA. [Crowley, J.; Haessler, J.; Hoering, A.] Canc Res & Biostat, Seattle, WA USA. [Moreau, P.] Univ Hosp, Hotel Dieu, Div Hematol, Nantes, France. [LeLeu, X.] CHU Lille, Hop Claude Huriez, Serv Malad Sang, Lille, France. [Hulin, C.] CHU Nancy, Serv Dhematol, Nancy, France. [Klein, S. K.; Sonneveld, P.] Erasmus MC, Dept Hematol, Rotterdam, Netherlands. [Siegel, D.] Hackensack Univ Med Ctr, Ctr Canc, Hackensack, NJ USA. [Blade, J.] Hosp Clin Barcelona, Barcelona, Spain. [Goldschmidt, H.] Univ Heidelberg, Heidelberg, Germany. [Jagannath, S.] Mt Sinai Canc Inst, New York, NY USA. [Miguel, J. S.] Hosp Univ Salamanca, Serv Hematol, Salamanca, Spain. [Orlowski, R.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Palumbo, A.] Univ Turin, Dept Hematol, Turin, Italy. [Sezer, O.] Univ Hamburg, Dept Hematol, Hamburg, Germany. [Durie, B. G. M.] Samuel Oschin Comprehens Canc Inst, Cedars Sinai Outpatient Canc Ctr, Los Angeles, CA USA. RP Kumar, SK (reprint author), Mayo Clin, Div Hematol & Blood & Marrow Transplant, 200 1st St SW, Rochester, MN 55905 USA. EM kumar.shaji@mayo.edu RI Waage, Anders/D-7705-2013; Sangue, Inct/I-1919-2013; FACON, THIERRY/M-9736-2014; Kumar, Shaji/A-9853-2008; richard, chrystelle/K-8595-2015; Garcia-Sanz, Ramon/B-7986-2017; OI FACON, THIERRY/0000-0001-7705-8460; Kumar, Shaji/0000-0001-5392-9284; Garcia-Sanz, Ramon/0000-0003-4120-2787; Rajkumar, S. Vincent/0000-0002-5862-1833; nahi, hareth/0000-0003-4711-5094 FU Celgene; Jansen-Cilag FX JJL is on the Scientific advisory boards of Celgene and Janssen-Cilag. PGR and JSM are Advisory board participants for Celgene, Millenium, Johnson and Johnson. DS is on the Speakers Bureau and BD is an Advisory board participant for Celgene and Millenium. AP is an Advisory Board participant for Celgene, Johnson and Johnson. JB has received Honoraria for lectures and advisory boards from Celgene, Jansen Cilag and Grant support from Celgene and Jansen-Cilag. The remaining authors declare no conflict of interest. NR 31 TC 256 Z9 261 U1 3 U2 29 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD JAN PY 2012 VL 26 IS 1 BP 149 EP 157 DI 10.1038/leu.2011.196 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA 879GJ UT WOS:000299317400015 PM 21799510 ER PT J AU Nelson, BD Saltzman, A Lee, PT AF Nelson, Brett D. Saltzman, Amy Lee, Patrick T. TI Bridging the global health training gap: Design and evaluation of a new clinical global health course at Harvard Medical School SO MEDICAL TEACHER LA English DT Article ID NEGLECTED TROPICAL DISEASES; NEONATAL SURVIVAL; CHILD HEALTH; MATERNAL MORTALITY; EXPERIENCES; ELECTIVES; DEATHS; CARE; INTERVENTIONS; OPPORTUNITIES AB Background: Medical student and resident interest in global health has been growing rapidly. Meanwhile, educational opportunities for trainees remain limited, and many trainees participate in global health experiences abroad without adequate preparation. Medical institutions are attempting to respond to this training gap by developing global health curricula. Aims: We describe a novel clinical skills-based curriculum recently established among Harvard medical students and residents with the primary objective of providing essential clinical knowledge and skills to work effectively in resource-limited settings. Methods: The course consisted of 10 evening sessions taught by a multidisciplinary faculty and focusing on practical management of the leading causes of the global burden of disease. Didactic discussions were reinforced by case studies and practical skills sessions, such as tropical microscopy, basic bedside ultrasound, simple dental extraction, and newborn resuscitation. Results: Student mean knowledge scores increased significantly, from 64.5% (SD 8.9) before the course to 79.5% (SD 8.6) after the course (p < 0.001). Students also gave strongly positive evaluations and particularly valued the course's practical skills-building and the horizontal and vertical mentorship that developed among the diverse student, resident, and faculty participants. Conclusions: This clinical course in global health may serve as one model for more effectively preparing trainees to work in developing countries. C1 [Nelson, Brett D.; Lee, Patrick T.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Nelson, Brett D.; Saltzman, Amy; Lee, Patrick T.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Nelson, BD (reprint author), Massachusetts Gen Hosp, Dept Pediat, 55 Fruit St, Boston, MA 02114 USA. EM brett.d.nelson@gmail.com RI yan, liu/A-1822-2015; OI yan, liu/0000-0001-8517-1084; Nelson, Brett/0000-0002-5049-1798 NR 64 TC 9 Z9 9 U1 0 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0142-159X J9 MED TEACH JI Med. Teach. PY 2012 VL 34 IS 1 BP 45 EP 51 DI 10.3109/0142159X.2011.577122 PG 7 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 877IQ UT WOS:000299171600015 PM 21592020 ER PT J AU Zhan, W Kang, GA Glass, GA Zhang, Y Shirley, C Millin, R Possin, KL Nezamzadeh, M Weiner, MW Marks, WJ Schuff, N AF Zhan, Wang Kang, Gail A. Glass, Graham A. Zhang, Yu Shirley, Cheryl Millin, Rachel Possin, Katherine L. Nezamzadeh, Marzieh Weiner, Michael W. Marks, William J., Jr. Schuff, Norbert TI Regional Alterations of Brain Microstructure in Parkinson's Disease Using Diffusion Tensor Imaging SO MOVEMENT DISORDERS LA English DT Article DE diffusion tensor imaging; magnetic resonance imaging; Parkinson's disease; subtypes ID SUBSTANTIA-NIGRA; BASAL GANGLIA; RAT MODEL; TRACT; SENSORIMOTOR; DISORDERS; DEMENTIA; MRI AB This study tested the hypothesis that diffusion tensor imaging can detect alteration in microscopic integrity of white matter and basal ganglia regions known to be involved in Parkinson's disease (PD) pathology. It was also hypothesized that there is an association between diffusion abnormality and PD severity and subtype. Diffusion tensor imaging at 4 Tesla was obtained in 12 PD and 20 control subjects, and measures of fractional anisotropy and mean diffusivity were evaluated using both region-of-interest and voxel-based methods. Movement deficits and subtypes in PD subjects were assessed using the Motor Subscale (Part III) of the Unified Parkinson's Disease Rating Scale. Reduced fractional anisotropy (P < .05, corrected) was found in PD subjects in regions related to the precentral gyrus, substantia nigra, putamen, posterior striatum, frontal lobe, and the supplementary motor areas. Reduced fractional anisotropy in the substantia nigra correlated (P < .05, corrected) with the increased rating scale motor scores. Significant spatial correlations between fractional anisotropy alterations in the putamen and other PD-affected regions were also found in the context of PD subtypes index analysis. Our data suggest that microstructural alterations detected with diffusion tensor might serve as a potential biomarker for PD. (C) 2011 Movement Disorder Society C1 [Zhan, Wang; Zhang, Yu; Shirley, Cheryl; Millin, Rachel; Nezamzadeh, Marzieh; Weiner, Michael W.; Schuff, Norbert] Univ Calif San Francisco, Dept Radiol & Med Imaging, Ctr Imaging Neurodegenerat Dis, San Francisco, CA 94121 USA. [Kang, Gail A.; Glass, Graham A.; Marks, William J., Jr.] San Francisco VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, San Francisco, CA USA. [Kang, Gail A.; Glass, Graham A.; Possin, Katherine L.; Marks, William J., Jr.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. RP Zhan, W (reprint author), Univ Calif San Francisco, Dept Radiol, VA Med Ctr 114M, 4150 Clement St, San Francisco, CA 94121 USA. EM Wang.Zhan@gmail.com FU Michael J. Fox Foundation [MJJF-BM2007]; NIH/NIRR "Research Resource for MRI of Neurodegenerative Disorders" [1 P41RR023953]; Larry L. Hillblom Foundation [2008-A-020-FEL] FX This work was supported in part by the Michael J. Fox Foundation for Parkinson's Research, "Multimodal MRI Markers for Parkinson's Disease" (MJJF-BM2007); NIH/NIRR "Research Resource for MRI of Neurodegenerative Disorders" (1 P41RR023953); and the Larry L. Hillblom Foundation, "Early markers and brain bases of spatial impairment in alpha-synuclein disorders" (2008-A-020-FEL). NR 47 TC 59 Z9 61 U1 2 U2 13 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD JAN PY 2012 VL 27 IS 1 BP 90 EP 97 DI 10.1002/mds.23917 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 877DA UT WOS:000299155900015 PM 21850668 ER PT J AU Chitnis, T Tenembaum, S Banwell, B Krupp, L Pohl, D Rostasy, K Yeh, EA Bykova, O Wassmer, E Tardieu, M Kornberg, A Ghezzi, A AF Chitnis, T. Tenembaum, S. Banwell, B. Krupp, L. Pohl, D. Rostasy, K. Yeh, E. A. Bykova, O. Wassmer, E. Tardieu, M. Kornberg, A. Ghezzi, A. CA Int Pediat Multiple Sclerosis TI Consensus statement: evaluation of new and existing therapeutics for pediatric multiple sclerosis SO MULTIPLE SCLEROSIS JOURNAL LA English DT Article DE disease-modifying therapies; multiple sclerosis ID TECHNOLOGY-ASSESSMENT SUBCOMMITTEE; EARLY-ONSET MS; INTERFERON-BETA; PSYCHOSOCIAL FEATURES; CLINICAL-FEATURES; AMERICAN-ACADEMY; CHILDHOOD-ONSET; CELL REPERTOIRE; UNITED-STATES; JUVENILE MS AB New therapies are being evaluated by clinical trials and, if efficacious, introduced for the treatment of adult MS. The role of these new and existing agents in the management of pediatric MS has yet to be defined. Pediatric investigation plans are now required by the Food and Drug Administration and European Medicines Agency for approval of new biological agents, providing an important opportunity to gather much-needed data for clinicians caring for children and adolescents with MS. However, challenges include the small number of patients, and the need for efficient yet comprehensive study designs incorporating factors necessary to inform the clinical care of children with MS. The elected Steering committee of the International Pediatric MS Study Group (IPMSSG) conducted a structured review of existing data on the disease-modifying therapies in pediatric MS and developed a consensus statement, which was further modified by the IPMSSG general membership, using an online survey tool. Fifty-one IPMSSG members from 21 countries responded to the survey, and 50 approved the final statement. Consensus recommendations regarding use of existing first-and second-line therapies, as well as a proposed definition for inadequate treatment response, are presented. Recommendations for the use and evaluation of emerging therapies (currently in phase III clinical trials or recently approved for adult MS) are discussed. The IPMSSG endorses the inclusion of pediatric MS patients in trials evaluating appropriate new and emerging therapies. Mechanisms for conducting high-impact, multicenter studies, including long-term follow-up in pediatric MS, are required to ensure that all MS patients, irrespective of age, benefit from advances in MS therapeutics. C1 [Chitnis, T.] Massachusetts Gen Hosp, Partners Pediat Multiple Sclerosis Ctr, Boston, MA 02114 USA. [Tenembaum, S.] Natl Pediat Hosp, Buenos Aires, DF, Argentina. [Banwell, B.] Univ Toronto, Hosp Sick Children, Toronto, ON M5S 1A1, Canada. [Krupp, L.] SUNY Stony Brook, Med Ctr, Stony Brook, NY USA. [Pohl, D.] Univ Ottawa, Childrens Hosp Eastern Ontario, Ottawa, ON K1N 6N5, Canada. [Rostasy, K.] Innsbruck Med Univ, Div Pediat Neurol & Inborn Errors Metab, Dept Pediat 4, Innsbruck, Austria. [Yeh, E. A.] SUNY Buffalo, Dept Neurol, Buffalo, NY 14260 USA. [Bykova, O.] Moscow Pediat Psychoneurol Hosp, Moscow, Russia. [Wassmer, E.] Birmingham Childrens Hosp, Birmingham, W Midlands, England. [Tardieu, M.] Hop Bicetre, AP HP, Paris, France. [Tardieu, M.] Univ Paris 11, Paris, France. [Kornberg, A.] Royal Childrens Hosp, Melbourne, Vic, Australia. [Ghezzi, A.] Hosp Gallarate, Multiple Sclerosis Study Ctr, Gallarate, Italy. RP Chitnis, T (reprint author), Massachusetts Gen Hosp, Partners Pediat Multiple Sclerosis Ctr, ACC-708,55 Fruit St, Boston, MA 02114 USA. EM tchitnis@partners.org OI amato, Maria Pia/0000-0003-3325-3760; Simone, Isabella Laura/0000-0002-7429-3091; Jan, Mohammed/0000-0002-5188-8922 FU MS International Federation; National MS Society; Canadian MS Society FX We would like to thank Professor Giancarlo Comi for valuable input during the inaugural meeting. We would like to thank Professor Alan Thompson and Professor Christopher Polman for critical reviewing of this manuscript. The meeting of the IPMSSG Steering committee and invited speakers on September 26, 2010 was funded by the MS International Federation, National MS Society, and the Canadian MS Society. NR 78 TC 61 Z9 63 U1 2 U2 16 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 J9 MULT SCLER J JI Mult. Scler. J. PD JAN PY 2012 VL 18 IS 1 BP 116 EP 127 DI 10.1177/1352458511430704 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 876CL UT WOS:000299084600020 PM 22146610 ER PT J AU Hersher, R DePinho, R AF Hersher, Rebecca DePinho, Ronald TI Straight talk with ... Ronald DePinho SO NATURE MEDICINE LA English DT Editorial Material C1 [DePinho, Ronald] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [DePinho, Ronald] Dana Farber Canc Inst, Renowned Belfer Ctr Appl Canc Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JAN PY 2012 VL 18 IS 1 BP 9 EP 9 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 875GO UT WOS:000299018600011 ER PT J AU Garofalo, M Romano, G Di Leva, G Nuovo, G Jeon, YJ Ngankeu, A Sun, J Lovat, F Alder, H Condorelli, G Engelman, JA Ono, M Rho, JK Cascione, L Volinia, S Nephew, KP Croce, CM AF Garofalo, Michela Romano, Giulia Di Leva, Gianpiero Nuovo, Gerard Jeon, Young-Jun Ngankeu, Apollinaire Sun, Jin Lovat, Francesca Alder, Hansjuerg Condorelli, Gerolama Engelman, Jeffrey A. Ono, Mayumi Rho, Jin Kyung Cascione, Luciano Volinia, Stefano Nephew, Kenneth P. Croce, Carlo M. TI EGFR and MET receptor tyrosine kinase-altered microRNA expression induces tumorigenesis and gefitinib resistance in lung cancers SO NATURE MEDICINE LA English DT Article ID GROWTH-FACTOR RECEPTOR; MESENCHYMAL TRANSITION; CELLS; AMPLIFICATION; INHIBITORS; ADENOCARCINOMA; SENSITIVITY; METASTASIS; ACTIVATION; PTEN AB The involvement of the MET oncogene in de novo and acquired resistance of non-small cell lung cancers (NSCLCs) to tyrosine kinase inhibitors (TKIs) has previously been reported, but the precise mechanism by which MET overexpression contributes to TKI-resistant NSCLC remains unclear. MicroRNAs (miRNAs) negatively regulate gene expression, and their dysregulation has been implicated in tumorigenesis. To understand their role in TKI-resistant NSCLCs, we examined changes in miRNA that are mediated by tyrosine kinase receptors. Here we report that miR-30b, miR-30c, miR-221 and miR-222 are modulated by both epidermal growth factor (EGF) and MET receptors, whereas miR-103 and miR-203 are controlled only by MET. We showed that these miRNAs have important roles in gefitinib-induced apoptosis and epithelial-mesenchymal transition of NSCLC cells in vitro and in vivo by inhibiting the expression of the genes encoding BCL2-like 11 (BIM), apoptotic peptidase activating factor 1 (APAF-1), protein kinase C epsilon (PKC-epsilon) and sarcoma viral oncogene homolog (SRC). These findings suggest that modulation of specific miRNAs may provide a therapeutic approach for the treatment of NSCLCs. C1 [Garofalo, Michela; Di Leva, Gianpiero; Nuovo, Gerard; Jeon, Young-Jun; Ngankeu, Apollinaire; Sun, Jin; Lovat, Francesca; Alder, Hansjuerg; Cascione, Luciano; Volinia, Stefano; Croce, Carlo M.] Ohio State Univ, Ctr Comprehens Canc, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA. [Romano, Giulia] Ist Ricovero & Cura Carattere Sci, Studio Diagnost Nucl SDN, Naples, Italy. [Condorelli, Gerolama] Univ Naples Federico 2, Fac Biotechnol Sci, Inst Expt Endocrinol & Oncol, Dept Cellular & Mol Biol & Pathol,Consiglio Nazl, Naples, Italy. [Engelman, Jeffrey A.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Engelman, Jeffrey A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Ono, Mayumi] Kyushu Univ, Grad Sch Pharmaceut Sci, Dept Pharmaceut Sci, Fukuoka 812, Japan. [Rho, Jin Kyung] Univ Ulsan, Dept Pulm & Crit Care Med, Seoul, South Korea. [Cascione, Luciano] Univ Catania, Dept Clin & Mol Biomed, Catania, Italy. [Nephew, Kenneth P.] Indiana Univ, Simon Canc Ctr, Bloomington, IN USA. [Nephew, Kenneth P.] Indiana Univ Sch Med, Med Sci Program, Dept Cellular & Integrated Physiol, Bloomington, IN USA. RP Croce, CM (reprint author), Ohio State Univ, Ctr Comprehens Canc, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA. EM carlo.croce@osumc.edu RI Volinia, Stefano/A-3029-2010; Ngankeu, Apollinaire/J-8188-2012; OI Volinia, Stefano/0000-0003-0910-3893; Cascione, Luciano/0000-0002-4606-0637 FU Ohio State University; US National Institutes of Health [CA113001]; Kimmel Scholar Award FX We thank K. Huebner and S. Lutz for revisions to the paper and P. Fadda and S. Miller for qRT-PCR assistance. We also thank K. Sergott and Ventana Medical Systems for supplying the immunohistochemistry reagents used in this study. M. Nuovo (The Ohio State University Medical Center) kindly provided the photomicroscopy work. We are grateful for research support from The Ohio State University Targeted Investment in Excellence Award, the US National Institutes of Health grant CA113001 and the Kimmel Scholar Award (M.G.). NR 31 TC 175 Z9 184 U1 5 U2 56 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 JAN PY 2012 VL 18 IS 1 BP 74 EP 82 DI 10.1038/nm.2577 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 875GO UT WOS:000299018600032 PM 22157681 ER PT J AU Jeong, H Cohen, DE Cui, LB Supinski, A Savas, JN Mazzulli, JR Yates, JR Bordone, L Guarente, L Krainc, D AF Jeong, Hyunkyung Cohen, Dena E. Cui, Libin Supinski, Andrea Savas, Jeffrey N. Mazzulli, Joseph R. Yates, John R., III Bordone, Laura Guarente, Leonard Krainc, Dimitri TI Sirt1 mediates neuroprotection from mutant huntingtin by activation of the TORC1 and CREB transcriptional pathway SO NATURE MEDICINE LA English DT Article ID DISEASE TRANSGENIC MICE; CALORIE RESTRICTION; GENE-TRANSCRIPTION; NEURODEGENERATION; PGC-1-ALPHA; EXPRESSION; PROTEINS; NEURONS; REPEAT AB Sirt1, a NAD-dependent protein deacetylase, has emerged as a key regulator of mammalian transcription in response to cellular metabolic status and stressl. Here we show that Sirt1 has a neuroprotective role in models of Huntington's disease, an inherited neurodegenerative disorder caused by a glutamine repeat expansion in huntingtin protein (HIT)2. Brain-specific knockout of Sirt1 results in exacerbation of brain pathology in a mouse model of Huntington's disease, whereas overexpression of Sirt1 improves survival, neuropathology and the expression of brain-derived neurotrophic factor (BDNF) in Huntington's disease mice. We show that Sirt1 deacetylase activity directly targets neurons to mediate neuroprotection from mutant HTT. The neuroprotective effect of Sirt1 requires the presence of CREB-regulated transcription coactivator 1 (TORC1), a brain-specific modulator of CREB activity3. We show that under normal conditions, Sirt1 deacetylates and activates TORC1 by promoting its dephosphorylation and its interaction with CREB. We identified BDNF as a key target of Sirt1 and TORC1 transcriptional activity in both normal and Huntington's disease neurons. Mutant HTT interferes with the TORC1-CREB interaction to repress BDNF transcription, and Sirt1 rescues this defect in vitro and in vivo. These studies suggest a key role for Sirt1 in transcriptional networks in both the normal and Huntington's disease brain and offer an opportunity for therapeutic development. C1 [Jeong, Hyunkyung; Cui, Libin; Mazzulli, Joseph R.; Krainc, Dimitri] Harvard Univ, MassGen Inst Neurodegenerat Dis, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. [Cohen, Dena E.; Supinski, Andrea; Guarente, Leonard] MIT, Dept Biol, Paul F Glenn Lab, Cambridge, MA USA. [Savas, Jeffrey N.; Yates, John R., III] Scripps Res Inst, Dept Physiol Chem, La Jolla, CA 92037 USA. [Bordone, Laura] Novartis Inst BioMed Res, Cardiovasc & Metab Dis Area, Cambridge, MA USA. RP Krainc, D (reprint author), Harvard Univ, MassGen Inst Neurodegenerat Dis, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. EM leng@mit.edu; krainc@helix.mgh.harvard.edu FU US National Institutes of Health [R01NS051303, R01MH067880-08, P41RR011823-15]; Cure Huntington's Disease Initiative (CHDI); Hereditary Disease Foundation (FIDE); Glenn Foundation for Medical Research FX We thank M. Montminy (Peptide Biology Laboratories (PBL), Salk Institute) for the Flag-CREB, Flag-TORC1 and Flag-TORC1 S151A plasmids and for antibody to TORC1 (#6937, PBL, Salk Institute) and helpful discussions; M.E. Greenberg (Harvard Medical School) for the pIII(170)Luc plasmid 15; T. Kouzarides (University of Cambridge) for Sirt1 and Sift1 HY plasmids; Z. Wu (Novartis Institutes for Biomedical Research) for the TORC1 plasmid; M. Difiglia (Massachusetts General Hospital) for antibody to HTT (Ab1); E. Regulier (Novartis Institutes for Biomedical Research) for lentiviral vectors expressing HTTEx1-25Q, HTTEx1-72Q and Sirt1; and J.M. Park (Massachusetts General Hospital) for the lentiviral vector used for CREB knockdown. We also acknowledge C. Whitaker (Massachusetts Institute of Technology) for analysis of the microarray data. This work was supported by grant R01NS051303 from the US National Institutes of Health (D.K.); the Cure Huntington's Disease Initiative (CHDI), Hereditary Disease Foundation (FIDE) (D.E.C.); US National Institutes of Health, Glenn Foundation for Medical Research (L.G.) and grants R01MH067880-08 and P41RR011823-15 from the US National Institutes of Health (J.R.Y.). NR 31 TC 127 Z9 133 U1 6 U2 18 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 JAN PY 2012 VL 18 IS 1 BP 159 EP 165 DI 10.1038/nm.2559 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 875GO UT WOS:000299018600043 PM 22179316 ER PT J AU Dickerson, BC Wolk, DA AF Dickerson, Bradford C. Wolk, David A. CA Alzheimers Dis Neuroimaging Initi TI MRI cortical thickness biomarker predicts AD-like CSF and cognitive decline in normal adults SO NEUROLOGY LA English DT Article ID PRECLINICAL ALZHEIMER-DISEASE; BRAIN ATROPHY RATES; TEMPORAL-LOBE; DEMENTIA; MILD; IMPAIRMENT; SIGNATURE; NEUROPATHOLOGY; INDIVIDUALS; PROGRESSION AB Objective: New preclinical Alzheimer disease (AD) diagnostic criteria have been developed using biomarkers in cognitively normal (CN) adults. We implemented these criteria using an MRI biomarker previously associated with AD dementia, testing the hypothesis that individuals at high risk for preclinical AD would be at elevated risk for cognitive decline. Methods: The Alzheimer's Disease Neuroimaging Initiative database was interrogated for CN individuals. MRI data were processed using a published set of a priori regions of interest to derive a single measure known as the AD signature (ADsig). Each individual was classified as ADsig-low (>= 1 SD below the mean: high risk for preclinical AD), ADsig-average (within 1 SD of mean), or ADsig-high (>= 1 SD above mean). A 3-year cognitive decline outcome was defined a priori using change in Clinical Dementia Rating sum of boxes and selected neuropsychological measures. Results: Individuals at high risk for preclinical AD were more likely to experience cognitive decline, which developed in 21% compared with 7% of ADsig-average and 0% of ADsig-high groups (p = 0.03). Logistic regression demonstrated that every 1 SD of cortical thinning was associated with a nearly tripled risk of cognitive decline (p = 0.02). Of those for whom baseline CSF data were available, 60% of the high risk for preclinical AD group had CSF characteristics consistent with AD while 36% of the ADsig-average and 19% of the ADsig-high groups had such CSF characteristics (p = 0.1). Conclusions: This approach to the detection of individuals at high risk for preclinical AD-identified in single CN individuals using this quantitative ADsig MRI biomarker-may provide investigators with a population enriched for AD pathobiology and with a relatively high likelihood of imminent cognitive decline consistent with prodromal AD. Neurology (R) 2012;78:84-90 C1 [Dickerson, Bradford C.] Massachusetts Gen Hosp, Dept Neurol, Frontotemporal Dementia Unit, Massachusetts Alzheimers Dis Res Ctr, Boston, MA 02114 USA. [Dickerson, Bradford C.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Wolk, David A.] Univ Penn, Dept Neurol, Alzheimers Dis Core Ctr, Philadelphia, PA 19104 USA. [Wolk, David A.] Univ Penn, Penn Memory Ctr, Philadelphia, PA 19104 USA. RP Dickerson, BC (reprint author), Massachusetts Gen Hosp, Dept Neurol, Frontotemporal Dementia Unit, Massachusetts Alzheimers Dis Res Ctr, Boston, MA 02114 USA. EM bradd@nmr.mgh.harvard.edu RI Saykin, Andrew/A-1318-2007 OI Saykin, Andrew/0000-0002-1376-8532 FU Alzheimer's Disease Neuroimaging Initiative (ADNI) (NIH) [U01 AG024904]; National Institute on Aging; National Institute of Biomedical Imaging and Bioengineering; Abbott; AstraZeneca AB; Bayer Schering Pharma AG; Bristol-Myers Squibb; Eisai Global Clinical Development; Elan Corporation; Genentech; GE Healthcare; GlaxoSmithKline; Innogenetics; Johnson and Johnson; Eli Lilly and Co.; Medpace, Inc.; Merck and Co., Inc.; Novartis AG; Pfizer Inc; F. Hoffman-La Roche; Schering-Plough; Synarc, Inc.; NIH [P30 AG010129, K01 AG030514]; Dana Foundation; NIA [R01-AG29411, R21-AG29840, P50-AG005134, K23-AG028018, P30AG010124]; Alzheimer's Association; PA Department of Health FX Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (NIH Grant U01 AG024904). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through contributions from the following: Abbott, AstraZeneca AB, Bayer Schering Pharma AG, Bristol-Myers Squibb, Eisai Global Clinical Development, Elan Corporation, Genentech, GE Healthcare, GlaxoSmithKline, Innogenetics, Johnson and Johnson, Eli Lilly and Co., Medpace, Inc., Merck and Co., Inc., Novartis AG, Pfizer Inc, F. Hoffman-La Roche, Schering-Plough, Synarc, Inc., as well as nonprofit partners the Alzheimer's Association and Alzheimer's Drug Discovery Foundation, with participation from the U. S. Food and Drug Administration. Private sector contributions to ADNI are facilitated by the Foundation for the NIH (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of California, Los Angeles. This research was also supported by NIH grants P30 AG010129, K01 AG030514, and the Dana Foundation. This analysis was also supported by grants from the NIA R01-AG29411, R21-AG29840, P50-AG005134, K23-AG028018, P30AG010124 and the Alzheimer's Association.; Dr. Dickerson serves on the editorial board of Hippocampus; serves as a consultant for Pfizer Inc; and receives research support from the NIH and the Alzheimer's Association. Dr. Wolk serves as a consultant for GE Healthcare and receives research support from GE Healthcare, Pfizer Inc, the NIH, and the PA Department of Health. NR 33 TC 66 Z9 70 U1 2 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JAN PY 2012 VL 78 IS 2 BP 84 EP 90 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 877EL UT WOS:000299159700007 PM 22189451 ER PT J AU Culhane, AC Schroder, MS Sultana, R Picard, SC Martinelli, EN Kelly, C Haibe-Kains, B Kapushesky, M St Pierre, AA Flahive, W Picard, KC Gusenleitner, D Papenhausen, G O'Connor, N Correll, M Quackenbush, J AF Culhane, Aedin C. Schroeder, Markus S. Sultana, Razvan Picard, Shaita C. Martinelli, Enzo N. Kelly, Caroline Haibe-Kains, Benjamin Kapushesky, Misha St Pierre, Anne-Alyssa Flahive, William Picard, Kermshlise C. Gusenleitner, Daniel Papenhausen, Gerald O'Connor, Niall Correll, Mick Quackenbush, John TI GeneSigDB: a manually curated database and resource for analysis of gene expression signatures SO NUCLEIC ACIDS RESEARCH LA English DT Article ID CANCER; BIOINFORMATICS; ATLAS AB GeneSigDB (http://www.genesigdb.org or http://compbio.dfci.harvard.edu/genesigdb/) is a database of gene signatures that have been extracted and manually curated from the published literature. It provides a standardized resource of published prognostic, diagnostic and other gene signatures of cancer and related disease to the community so they can compare the predictive power of gene signatures or use these in gene set enrichment analysis. Since GeneSigDB release 1.0, we have expanded from 575 to 3515 gene signatures, which were collected and transcribed from 1604 published articles largely focused on gene expression in cancer, stem cells, immune cells, development and lung disease. We have made substantial upgrades to the GeneSigDB website to improve accessibility and usability, including adding a tag cloud browse function, facetted navigation and a 'basket' feature to store genes or gene signatures of interest. Users can analyze GeneSigDB gene signatures, or upload their own gene list, to identify gene signatures with significant gene overlap and results can be viewed on a dynamic editable heatmap that can be downloaded as a publication quality image. All data in GeneSigDB can be downloaded in numerous formats including .gmt file format for gene set enrichment analysis or as a R/Bioconductor data file. GeneSigDB is available from http://www.genesigdb.org. C1 [Culhane, Aedin C.; Schroeder, Markus S.; Sultana, Razvan; Picard, Shaita C.; Martinelli, Enzo N.; Kelly, Caroline; Haibe-Kains, Benjamin; St Pierre, Anne-Alyssa; Flahive, William; Picard, Kermshlise C.; Gusenleitner, Daniel; Papenhausen, Gerald; O'Connor, Niall; Correll, Mick; Quackenbush, John] Dana Farber Canc Inst, Boston, MA 02215 USA. [Culhane, Aedin C.; Haibe-Kains, Benjamin] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Kapushesky, Misha; Quackenbush, John] European Bioinformat Inst, EMBL Outstn Hinxton, Cambridge CB10 1SD, England. RP Culhane, AC (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM aedin@jimmy.harvard.edu; johnq@jimmy.harvard.edu RI Haibe-Kains, Benjamin/D-3702-2011 OI Haibe-Kains, Benjamin/0000-0002-7684-0079 FU National Institutes for Health National Library of Medicine [1R01 LM010129]; National Cancer Institute [1U19 CA148065]; Genome Research Institute [1P50 HG004233]; Dana-Farber Cancer Institute Women; Claudia Adams Barr foundation FX This work was supported by National Institutes for Health National Library of Medicine (1R01 LM010129), National Cancer Institute (1U19 CA148065), Genome Research Institute (1P50 HG004233); Dana-Farber Cancer Institute Women's Cancers Program (to A. C. C); Claudia Adams Barr foundation. NR 24 TC 42 Z9 43 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2012 VL 40 IS D1 BP D1060 EP D1066 DI 10.1093/nar/gkr901 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 869MD UT WOS:000298601300159 PM 22110038 ER PT J AU Haibe-Kains, B Olsen, C Djebbari, A Bontempi, G Correll, M Bouton, C Quackenbush, J AF Haibe-Kains, Benjamin Olsen, Catharina Djebbari, Amira Bontempi, Gianluca Correll, Mick Bouton, Christopher Quackenbush, John TI Predictive networks: a flexible, open source, web application for integration and analysis of human gene networks SO NUCLEIC ACIDS RESEARCH LA English DT Article ID POSITIVE BREAST-CANCER; SOFTWARE ENVIRONMENT; INFERENCE; VISUALIZATION; BIOCURATION; CYTOSCAPE; ALGORITHM; MODELS; SCALE; TOOL AB Genomics provided us with an unprecedented quantity of data on the genes that are activated or repressed in a wide range of phenotypes. We have increasingly come to recognize that defining the networks and pathways underlying these phenotypes requires both the integration of multiple data types and the development of advanced computational methods to infer relationships between the genes and to estimate the predictive power of the networks through which they interact. To address these issues we have developed Predictive Networks (PN), a flexible, open-source, web-based application and data services framework that enables the integration, navigation, visualization and analysis of gene interaction networks. The primary goal of PN is to allow biomedical researchers to evaluate experimentally derived gene lists in the context of large-scale gene interaction networks. The PN analytical pipeline involves two key steps. The first is the collection of a comprehensive set of known gene interactions derived from a variety of publicly available sources. The second is to use these 'known' interactions together with gene expression data to infer robust gene networks. The PN web application is accessible from http://predictivenetworks.org. The PN code base is freely available at https://sourceforge.net/projects/predictivenets/. C1 [Haibe-Kains, Benjamin; Quackenbush, John] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Haibe-Kains, Benjamin; Quackenbush, John] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. [Olsen, Catharina; Bontempi, Gianluca] Univ Libre Bruxelles, Machine Learning Grp, Brussels, Belgium. [Djebbari, Amira] Univ Toronto, Ontario Canc Inst, Princess Margaret Hosp UHN, Toronto, ON M5G 1L7, Canada. [Djebbari, Amira] Univ Toronto, Campbell Family Inst Canc Res, Toronto, ON M5G 1L7, Canada. [Correll, Mick; Quackenbush, John] Dana Farber Canc Inst, Ctr Canc Computat Biol, Boston, MA 02215 USA. [Bouton, Christopher] Entagen, Newburyport, MA 01950 USA. RP Haibe-Kains, B (reprint author), Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. EM bhaibeka@jimmy.harvard.edu; johnq@jimmy.harvard.edu RI Haibe-Kains, Benjamin/D-3702-2011 OI Haibe-Kains, Benjamin/0000-0002-7684-0079 FU National Library of Medicine of the US National Institutes of Health [1R01LM010129] FX Funding for open access charge: National Library of Medicine of the US National Institutes of Health (grant 1R01LM010129). NR 49 TC 17 Z9 18 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2012 VL 40 IS D1 BP D866 EP D875 DI 10.1093/nar/gkr1050 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 869MD UT WOS:000298601300130 PM 22096235 ER PT J AU Kapushesky, M Adamusiak, T Burdett, T Culhane, A Farne, A Filippov, A Holloway, E Klebanov, A Kryvych, N Kurbatova, N Kurnosov, P Malone, J Melnichuk, O Petryszak, R Pultsin, N Rustici, G Tikhonov, A Travillian, RS Williams, E Zorin, A Parkinson, H Brazma, A AF Kapushesky, Misha Adamusiak, Tomasz Burdett, Tony Culhane, Aedin Farne, Anna Filippov, Alexey Holloway, Ele Klebanov, Andrey Kryvych, Nataliya Kurbatova, Natalja Kurnosov, Pavel Malone, James Melnichuk, Olga Petryszak, Robert Pultsin, Nikolay Rustici, Gabriella Tikhonov, Andrew Travillian, Ravensara S. Williams, Eleanor Zorin, Andrey Parkinson, Helen Brazma, Alvis TI Gene Expression Atlas update-a value-added database of microarray and sequencing-based functional genomics experiments SO NUCLEIC ACIDS RESEARCH LA English DT Article ID RNA-SEQ; ONTOLOGY; BIOINFORMATICS AB Gene Expression Atlas (http://www.ebi.ac.uk/gxa) is an added-value database providing information about gene expression in different cell types, organism parts, developmental stages, disease states, sample treatments and other biological/experimental conditions. The content of this database derives from curation, re-annotation and statistical analysis of selected data from the ArrayExpress Archive and the European Nucleotide Archive. A simple interface allows the user to query for differential gene expression either by gene names or attributes or by biological conditions, e.g. diseases, organism parts or cell types. Since our previous report we made 20 monthly releases and, as of Release 11.08 (August 2011), the database supports 19 species, which contains expression data measured for 19 014 biological conditions in 136 551 assays from 5598 independent studies. C1 [Kapushesky, Misha; Adamusiak, Tomasz; Burdett, Tony; Farne, Anna; Filippov, Alexey; Holloway, Ele; Klebanov, Andrey; Kryvych, Nataliya; Kurbatova, Natalja; Kurnosov, Pavel; Malone, James; Melnichuk, Olga; Petryszak, Robert; Pultsin, Nikolay; Rustici, Gabriella; Tikhonov, Andrew; Travillian, Ravensara S.; Williams, Eleanor; Zorin, Andrey; Parkinson, Helen; Brazma, Alvis] EMBL, European Bioinformat Inst, Hinxton, England. [Culhane, Aedin] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kapushesky, M (reprint author), EMBL, European Bioinformat Inst, Hinxton, England. EM ostolop@ebi.ac.uk OI Brazma, Alvis/0000-0001-5988-7409; Adamusiak, Tomasz/0000-0002-0746-2916; Petryszak, Robert/0000-0001-6333-2182; Burdett, Anthony/0000-0002-2513-5396; Parkinson, Helen/0000-0003-3035-4195; Rustici, Gabriella/0000-0003-3085-1271; Williams, Eleanor/0000-0002-0851-7990 FU European Molecular Biology Laboratory (EMBL); SLING; SYBARIS; GEUVADIS; European Commission from the BBSRC [BB/G022755/1]; NHGRI; EMBL FX The project was funded by the European Molecular Biology Laboratory (EMBL), SLING, SYBARIS, GEUVADIS and GEN2PHEN grants from the European Commission, grant #BB/G022755/1 from the BBSRC, and the MAGE grant from the NHGRI. Funding for open access charge: EMBL. NR 20 TC 74 Z9 77 U1 1 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2012 VL 40 IS D1 BP D1077 EP D1081 DI 10.1093/nar/gkr913 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 869MD UT WOS:000298601300161 PM 22064864 ER PT J AU Sui, SJH Begley, K Reilly, D Chapman, B McGovern, R Rocca-Sera, P Maguire, E Altschuler, GM Hansen, TAA Sompallae, R Krivtsov, A Shivdasani, RA Armstrong, SA Culhane, AC Correll, M Sansone, SA Hofmann, O Hide, W AF Sui, Shannan J. Ho Begley, Kimberly Reilly, Dorothy Chapman, Brad McGovern, Ray Rocca-Sera, Philippe Maguire, Eamonn Altschuler, Gabriel M. Hansen, Terah A. A. Sompallae, Ramakrishna Krivtsov, Andrei Shivdasani, Ramesh A. Armstrong, Scott A. Culhane, Aedin C. Correll, Mick Sansone, Susanna-Assunta Hofmann, Oliver Hide, Winston TI The Stem Cell Discovery Engine: an integrated repository and analysis system for cancer stem cell comparisons SO NUCLEIC ACIDS RESEARCH LA English DT Article ID GENE-EXPRESSION; SIGNATURES; SURVIVAL; ONTOLOGY; DATABASE AB Mounting evidence suggests that malignant tumors are initiated and maintained by a subpopulation of cancerous cells with biological properties similar to those of normal stem cells. However, descriptions of stem-like gene and pathway signatures in cancers are inconsistent across experimental systems. Driven by a need to improve our understanding of molecular processes that are common and unique across cancer stem cells (CSCs), we have developed the Stem Cell Discovery Engine (SCDE)-an online database of curated CSC experiments coupled to the Galaxy analytical framework. The SCDE allows users to consistently describe, share and compare CSC data at the gene and pathway level. Our initial focus has been on carefully curating tissue and cancer stem cell-related experiments from blood, intestine and brain to create a high quality resource containing 53 public studies and 1098 assays. The experimental information is captured and stored in the multi-omics Investigation/Study/Assay (ISA-Tab) format and can be queried in the data repository. A linked Galaxy framework provides a comprehensive, flexible environment populated with novel tools for gene list comparisons against molecular signatures in GeneSigDB and MSigDB, curated experiments in the SCDE and pathways in WikiPathways. The SCDE is available at http://discovery.hsci.harvard.edu. C1 [Sui, Shannan J. Ho; Begley, Kimberly; Reilly, Dorothy; Chapman, Brad; McGovern, Ray; Altschuler, Gabriel M.; Hansen, Terah A. A.; Sompallae, Ramakrishna; Culhane, Aedin C.; Hofmann, Oliver; Hide, Winston] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Sui, Shannan J. Ho; Begley, Kimberly; Reilly, Dorothy; Chapman, Brad; McGovern, Ray; Hansen, Terah A. A.; Hofmann, Oliver; Hide, Winston] Harvard Univ, Sch Publ Hlth, HSPH Bioinformat Core, Boston, MA 02115 USA. [Reilly, Dorothy; Sansone, Susanna-Assunta] Novartis Inst BioMed Res, Cambridge, MA USA. [Rocca-Sera, Philippe; Maguire, Eamonn] Univ Oxford, Oxford E Res Ctr, Oxford OX1 2JD, England. [Krivtsov, Andrei; Armstrong, Scott A.] Childrens Hosp, Dept Pediat Oncol, Boston, MA 02115 USA. [Culhane, Aedin C.; Correll, Mick] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. [Krivtsov, Andrei; Shivdasani, Ramesh A.; Armstrong, Scott A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Shivdasani, Ramesh A.; Armstrong, Scott A.; Hide, Winston] Harvard Stem Cell Inst, Cambridge, MA USA. [Correll, Mick] Dana Farber Canc Inst, Ctr Canc Computat Biol, Boston, MA 02115 USA. RP Hide, W (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. EM shosui@hsph.harvard.edu; whide@hsph.harvard.edu RI Hofmann, Oliver/F-1800-2013; OI Hofmann, Oliver/0000-0002-7738-1513; Chapman, Brad/0000-0002-3026-1856; Hide, Winston/0000-0002-8621-3271 FU National Institutes of Health [1RC2CA148222-01]; Harvard Stem Cell Institute; Harvard School of Public Health FX National Institutes of Health (1RC2CA148222-01 to R.S., S.A. and W.H.); Harvard Stem Cell Institute. Funding for open access charge: Harvard School of Public Health Dean's Fund; National Institutes of Health Stimulus awards. NR 25 TC 7 Z9 7 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2012 VL 40 IS D1 BP D984 EP D991 DI 10.1093/nar/gkr1051 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 869MD UT WOS:000298601300148 ER PT J AU Wang, XW Spandidos, A Wang, HJ Seed, B AF Wang, Xiaowei Spandidos, Athanasia Wang, Huajun Seed, Brian TI PrimerBank: a PCR primer database for quantitative gene expression analysis, 2012 update SO NUCLEIC ACIDS RESEARCH LA English DT Article ID REAL-TIME PCR; POLYMERASE-CHAIN-REACTION; CROSS-PLATFORM; QUANTIFICATION; AMPLIFICATION; SEQUENCES; SELECTION; DESIGN; PROBES; PAIRS AB Optimization of primer sequences for polymerase chain reaction (PCR) and quantitative PCR (qPCR) and reaction conditions remains an experimental challenge. We have developed a resource, PrimerBank, which contains primers that can be used for PCR and qPCR under stringent and allele-invariant amplification conditions. A distinguishing feature of PrimerBank is the experimental validation of primer pairs covering most known mouse genes. Here, we describe a major update of PrimerBank that includes the design of new primers covering 17 076 and 18 086 genes for the human and mouse species, respectively. As a result of this update, PrimerBank contains 497 156 primers (an increase of 62% from the previous version) that cover 36 928 human and mouse genes, corresponding to around 94% of all known protein-coding gene sequences. An updated algorithm based on our previous approach was used to design new primers using current genomic information available from the National Center for Biotechnology Information (NCBI). PrimerBank primers work under uniform PCR conditions, and can be used for high-throughput or genome-wide qPCR. Because of their broader linear dynamic range and greater sensitivity, qPCR approaches are used to reanalyze changes in expression suggested by exploratory technologies such as microarrays and RNA-Seq. The primers and all experimental validation data can be freely accessed from the PrimerBank website, http://pga.mgh.harvard.edu/primerbank/. C1 [Spandidos, Athanasia; Wang, Huajun; Seed, Brian] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Spandidos, Athanasia; Wang, Huajun; Seed, Brian] Harvard Univ, Dept Genet, Sch Med, Boston, MA 02115 USA. [Wang, Xiaowei] Washington Univ, Sch Med, Dept Radiat Oncol, St Louis, MO 63108 USA. RP Seed, B (reprint author), Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, 185 Cambridge St, Boston, MA 02114 USA. EM bseed@ccib.mgh.harvard.edu FU National Institutes of Health [U01 HL066678, R01 GM089784]; Center for Computational and Integrative Biology, Massachusetts General Hospital FX National Institutes of Health (U01 HL066678 and R01 GM089784). Funding for open access charge: Center for Computational and Integrative Biology, Massachusetts General Hospital. NR 26 TC 115 Z9 119 U1 2 U2 14 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2012 VL 40 IS D1 BP D1144 EP D1149 DI 10.1093/nar/gkr1013 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 869MD UT WOS:000298601300171 PM 22086960 ER PT J AU Flaherty, P Natsoulis, G Muralidharan, O Winters, M Buenrostro, J Bell, J Brown, S Holodniy, M Zhang, N Ji, HP AF Flaherty, Patrick Natsoulis, Georges Muralidharan, Omkar Winters, Mark Buenrostro, Jason Bell, John Brown, Sheldon Holodniy, Mark Zhang, Nancy Ji, Hanlee P. TI Ultrasensitive detection of rare mutations using next-generation targeted resequencing SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DNA; VARIANTS; PERFORMANCE; CANCER AB With next-generation DNA sequencing technologies, one can interrogate a specific genomic region of interest at very high depth of coverage and identify less prevalent, rare mutations in heterogeneous clinical samples. However, the mutation detection levels are limited by the error rate of the sequencing technology as well as by the availability of variant-calling algorithms with high statistical power and low false positive rates. We demonstrate that we can robustly detect mutations at 0.1% fractional representation. This represents accurate detection of one mutant per every 1000 wild-type alleles. To achieve this sensitive level of mutation detection, we integrate a high accuracy indexing strategy and reference replication for estimating sequencing error variance. We employ a statistical model to estimate the error rate at each position of the reference and to quantify the fraction of variant base in the sample. Our method is highly specific (99%) and sensitive (100%) when applied to a known 0.1% sample fraction admixture of two synthetic DNA samples to validate our method. As a clinical application of this method, we analyzed nine clinical samples of H1N1 influenza A and detected an oseltamivir (antiviral therapy) resistance mutation in the H1N1 neuraminidase gene at a sample fraction of 0.18%. C1 [Flaherty, Patrick; Natsoulis, Georges; Buenrostro, Jason; Bell, John; Ji, Hanlee P.] Stanford Univ, Stanford Genome Technol Ctr, Palo Alto, CA 94304 USA. [Flaherty, Patrick] Stanford Univ, Dept Biochem, Stanford, CA 94305 USA. [Muralidharan, Omkar; Zhang, Nancy] Stanford Univ, Dept Stat, Stanford, CA 94305 USA. [Winters, Mark; Holodniy, Mark] Stanford Univ, Div Infect Dis, Dept Med, Stanford, CA 94305 USA. [Brown, Sheldon] James J Peters VA Med Ctr, Bronx, NY 10468 USA. [Holodniy, Mark] VA Palo Alto Hlth Care Syst, Palo Alto, CA 94304 USA. [Ji, Hanlee P.] Stanford Univ, Div Oncol, Dept Med, Sch Med, Stanford, CA 94305 USA. RP Ji, HP (reprint author), Stanford Univ, Stanford Genome Technol Ctr, Palo Alto, CA 94304 USA. EM genomics_ji@stanford.edu FU National Science Foundation, Division of Mathematical Sciences (NSF DMS) DMS [1043204]; Department of Veterans Affairs; National Institutes of Health (NIH) [5K08CA96879-6, DK56339, 2P01HG000205, R21CA140089]; Doris Duke Clinical Foundation; Reddere Foundation; Liu Bie Ju Cha and Family Fellowship in Cancer; Wang Family Foundation; Howard Hughes Medical Foundation FX National Science Foundation, Division of Mathematical Sciences (NSF DMS) DMS (Grant #1043204 to N.Z. and H.P.J.); Department of Veterans Affairs (in part, to M. H.); National Institutes of Health (NIH) (grants 5K08CA96879-6 to H.P.J., DK56339 to H.P.J, 2P01HG000205 to J.B., J.M.B., H.P.J. and P. F. and R21CA140089 to G.N. and H.P.J.); Doris Duke Clinical Foundation (to H.P.J.); Reddere Foundation (to H.P.J.); Liu Bie Ju Cha and Family Fellowship in Cancer (to H.P.J.); Wang Family Foundation (to H.P.J.); Howard Hughes Medical Foundation (to H.P.J.). Funding for open access charge: NIH (grant 2P01HG000205) and NSF DMS (grant 1043204). NR 21 TC 53 Z9 53 U1 1 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2012 VL 40 IS 1 AR e2 DI 10.1093/nar/gkr861 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 871JG UT WOS:000298733500002 PM 22013163 ER PT J AU Livhits, M Mercado, C Yermilov, I Parikh, JA Dutson, E Mehran, A Ko, CY Gibbons, MM AF Livhits, Masha Mercado, Cheryl Yermilov, Irina Parikh, Janak A. Dutson, Erik Mehran, Amir Ko, Clifford Y. Gibbons, Melinda Maggard TI Preoperative Predictors of Weight Loss Following Bariatric Surgery: Systematic Review SO OBESITY SURGERY LA English DT Review DE Bariatric surgery; Predictors; Weight loss; Preoperative; Outcomes ID Y GASTRIC BYPASS; VERTICAL BANDED GASTROPLASTY; QUALITY-OF-LIFE; MORBIDLY OBESE-PATIENTS; BODY-MASS INDEX; 12-MONTH POSTOPERATIVE OUTCOMES; DUODENAL SWITCH OPERATION; CHILDHOOD SEXUAL-ABUSE; BINGE-EATING DISORDER; RISKS VS. BENEFITS AB Obesity affects 32% of adults in the USA. Surgery generates substantial weight loss, but 20-30% fails to achieve successful weight loss. Our objective was to identify preoperative psychosocial factors associated with weight loss following bariatric surgery. We performed a literature search of PubMedA (R) and the Cochrane Database of Reviews of Effectiveness between 1988 and April 2010. Articles were screened for bariatric surgery and weight loss if they included a preoperative predictor of weight loss: body mass index (BMI), preoperative weight loss, eating disorders, or psychiatric disorder/substance abuse. One thousand seven titles were reviewed, 534 articles screened, and 115 included in the review. Factors that may be positively associated with weight loss after surgery include mandatory preoperative weight loss (7 of 14 studies with positive association). Factors that may be negatively associated with weight loss include preoperative BMI (37 out of 62 studies with negative association), super-obesity (24 out of 33 studies), and personality disorders (7 out of 14 studies). Meta-analysis revealed a decrease of 10.1% excess weight loss (EWL) for super-obese patients (95% confidence interval (CI) [3.7-16.5%]), though there was significant heterogeneity in the meta-analysis, and an increase of 5.9% EWL for patients with binge eating at 12 months after surgery (95% CI [1.9-9.8%]). Further studies are necessary to investigate whether preoperative factors can predict a clinically meaningful difference in weight loss after bariatric surgery. The identification of predictive factors may improve patient selection and help develop interventions targeting specific needs of patients. C1 [Livhits, Masha; Yermilov, Irina; Parikh, Janak A.; Ko, Clifford Y.; Gibbons, Melinda Maggard] VA Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA 90073 USA. [Livhits, Masha; Mercado, Cheryl; Yermilov, Irina; Parikh, Janak A.; Dutson, Erik; Mehran, Amir; Ko, Clifford Y.; Gibbons, Melinda Maggard] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Gibbons, Melinda Maggard] Olive View UCLA, Dept Surg, Los Angeles, CA 91342 USA. RP Livhits, M (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Surg, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM mlivhits@mednet.ucla.edu FU VA Department of Surgery; Robert Wood Johnson Physician Faculty FX We would like to acknowledge the generous contribution of Paul G. Shekelle to the design of our project and critical review of the analysis. The VA Department of Surgery provided support for Dr. Livhits and Dr. Gibbons. Dr. Gibbons's time was supported in part by a grant from the Robert Wood Johnson Physician Faculty Scholars program. NR 145 TC 153 Z9 153 U1 5 U2 44 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0960-8923 EI 1708-0428 J9 OBES SURG JI Obes. Surg. PD JAN PY 2012 VL 22 IS 1 BP 70 EP 89 DI 10.1007/s11695-011-0472-4 PG 20 WC Surgery SC Surgery GA 876PU UT WOS:000299120700013 PM 21833817 ER PT J AU Bourguignon, LYW Earle, C Wong, G Spevak, CC Krueger, K AF Bourguignon, L. Y. W. Earle, C. Wong, G. Spevak, C. C. Krueger, K. TI Stem cell marker (Nanog) and Stat-3 signaling promote MicroRNA-21 expression and chemoresistance in hyaluronan/CD44-activated head and neck squamous cell carcinoma cells SO ONCOGENE LA English DT Article DE nanog; Stat-3; miR-21; hyaluronan; CD44; head & neck cancer ID NF-KAPPA-B; CANCER STATISTICS; GENE-EXPRESSION; TUMOR-CELLS; RHO-KINASE; HYALURONAN; BREAST; PROGRESSION; ACTIVATION; TRANSCRIPTION AB MicroRNAs are often associated with the pathogenesis of many cancers, including head and neck squamous cell carcinoma (HNSCC). In particular, microRNA-21 (miR-21) appears to have a critical role in tumor cell survival, chemoresistance and HNSCC progression. In this study, we investigated matrix hyaluronan (HA)-induced CD44 (a primary HA receptor) interaction with the stem cell markers, Nanog and Stat-3, in HNSCC cells (HSC-3 cells). Our results indicate that HA binding to CD44 promotes Nanog-Stat-3 (also tyrosine phosphorylated Stat-3) complex formation, nuclear translocation and transcriptional activation. Further analyses reveal that miR-21 is controlled by an upstream promoter containing Stat-3 binding site(s), while chromatin immunoprecipitation assays demonstrate that stimulation of miR-21 expression by HA/CD44 signaling is Nanog/Stat-3-dependent in HNSCC cells. This process results in a decrease of a tumor suppressor protein (PDCD4), and an upregulation of i nhibitors of the apoptosis family of proteins (IAPs) as well as chemoresistance in HSC-3 cells. Treatment of HSC-3 cells with Nanog- and/or Stat-3-specific small interfering RNAs effectively blocks HA-mediated Nanog-Stat-3 signaling events, abrogates miR-21 production and increases PDCD4 expression. Subsequently, this Nanog-Stat-3 signaling inhibition causes downregulation of survival protein (IAP) expression and enhancement of chemosensitivity. To further evaluate the role of miR-21 in tumor cell-specific functions, HSC-3 cells were also transfected with a specific anti-miR-21 inhibitor in order to silence miR-21 expression and block its target functions. Our results demonstrate that anti-miR-21 inhibitor not only upregulates PDCD4 expression but also decreases IAP expression and enhances chemosensitivity in HA-treated HNSCC cells. Together, these findings indicate that the HA-induced CD44 interaction with Nanog and Stat-3 has a pivotal role in miR-21 production leading to PDCD4 reduction, IAP upregulation and chemoresistance in HNSCC cells. This novel Nanog/Stat-3 signaling pathway-specific mechanism involved in miR-21 production is significant for the formation of future intervention strategies in the treatment of HA/CD44-activated HNSCC. Oncogene (2012) 31, 149-160; doi:10.1038/onc.2011.222; published online 20 June 2011 C1 [Bourguignon, L. Y. W.] Univ Calif San Francisco, Dept Med, Endocrine Unit 111N, San Francisco, CA 94121 USA. San Francisco VA Med Ctr, San Francisco, CA USA. RP Bourguignon, LYW (reprint author), Univ Calif San Francisco, Dept Med, Endocrine Unit 111N, 4150 Clement St, San Francisco, CA 94121 USA. EM lilly.bourguignon@ucsf.edu FU Veterans Affairs (VA) Merit Review grant; United States Public Health grants [R01 CA66163, R01 CA78633, P01 AR39448] FX We gratefully acknowledge the assistance of Drs Gerard J Bourguignon and Walter M Holleran in the preparation and review of this manuscript. We are grateful for Ms Christina Camacho for her assistance in preparing graphs and illustrations. We would also like to thank for Dr Shaomeng Wang from the University of Michigan for providing us an IAP inhibitor, SM164. This work was supported by Veterans Affairs (VA) Merit Review grant and United States Public Health grants (R01 CA66163, R01 CA78633 and P01 AR39448). LYWB is a VA Senior Research Career Scientist. NR 30 TC 89 Z9 93 U1 2 U2 12 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN PY 2012 VL 31 IS 2 BP 149 EP 160 DI 10.1038/onc.2011.222 PG 12 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 879CN UT WOS:000299307400002 PM 21685938 ER PT J AU Uslan, DZ Gleva, MJ Warren, DK Mela, T Chung, MK Gottipaty, V Borge, R Dan, D Shinn, T Mitchell, K Holcomb, RG Poole, JE AF Uslan, Daniel Z. Gleva, Marye J. Warren, David K. Mela, Theofanie Chung, Mina K. Gottipaty, Venkateshwar Borge, Richard Dan, Dan Shinn, Timothy Mitchell, Kevin Holcomb, Richard G. Poole, Jeanne E. TI Cardiovascular Implantable Electronic Device Replacement Infections and Prevention: Results from the REPLACE Registry SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Article DE pacemaker; defibrillator; infection ID PERMANENT PACEMAKER IMPLANTATION; ANTIBIOTIC-PROPHYLAXIS; RISK-FACTORS; CARDIOVERTER-DEFIBRILLATORS; TEMPORAL TRENDS; RATES; MANAGEMENT; SURGERY; HEART AB Background: Infection following cardiovascular implantable electronic device (CIED) replacement is a serious complication, and rates of infection have increased. Analysis of procedural and clinical data from device replacement procedures collected by the REPLACE Registry may provide insights into infection prevention strategies and outcomes. Methods: We prospectively evaluated procedural complications in patients undergoing CIED replacement over 6 months from 72 U. S. sites. Major and minor infections were predefined and adjudicated by an independent blinded clinical events committee. Data regarding infection prevention strategies and infectious outcomes were analyzed for their potential relationships. Results: A total of 1,744 patients were included in REPLACE. All patients received preoperative intravenous antibiotics and 68.7% received postoperative systemic antibiotic therapy. CIED infection developed in 22 patients (1.3%), of which 14 cases were major (0.8%, 95% confidence interval [CI] 0.4%-1.3%) and eight were minor (0.5%, 95% CI 0.2%-0.9%). Patients with infections were more likely to have had postoperative hematomas (five of 22 [22.7%] vs 17 of 1,722 [0.98%], P = 0.002). Participating sites experiencing infection rates >5% were more likely to use povidone-iodine for topical antisepsis, had lower implantation volume, and had patients with higher Charlson Comorbidity Index (2.79 vs 2.32, 95% CI for difference 0.08-0.86, P = 0.019). Conclusions: In this multicenter prospective study with 6 months of follow-up, infections associated with CIED replacements were surprisingly infrequent, possibly due to the use of preoperative antibiotics. Patients with infections were more likely to have had a postoperative hematoma, and sites with higher infection rates had sicker patients and lower overall procedural volume. (PACE 2012; 35:81-87) C1 [Uslan, Daniel Z.] Univ Calif Los Angeles, David Geffen Sch Med, Div Infect Dis, Los Angeles, CA 90095 USA. [Gleva, Marye J.; Warren, David K.] Washington Univ, Sch Med, St Louis, MO USA. [Mela, Theofanie] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chung, Mina K.] Cleveland Clin, Inst Heart & Vasc, Cleveland, OH 44106 USA. [Gottipaty, Venkateshwar] S Carolina Heart Ctr, Columbia, SC USA. [Borge, Richard] Abington Med Specialists, Abington, PA USA. [Dan, Dan] Piedmont Heart Inst, Atlanta, GA USA. [Shinn, Timothy] Michigan Heart, Ypsilanti, MI USA. [Mitchell, Kevin] Biotronik Inc, Lake Oswego, OR USA. [Poole, Jeanne E.] Univ Washington, Seattle, WA 98195 USA. RP Uslan, DZ (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Infect Dis, 10833 LeConte Ave,37-121 CHS, Los Angeles, CA 90095 USA. EM duslan@mednet.ucla.edu OI Warren, David/0000-0001-8679-8241 FU BIOTRONIK, Inc., Lake Oswego, Oregon; Biotronik FX This study was supported by BIOTRONIK, Inc., Lake Oswego, Oregon.; Disclosures have been made by all the authors, and details are on file. All have received direct or indirect support from Biotronik. Most have also received support from other CIED manufacturers and/or technology companies and/ or pharmacologic companies. NR 20 TC 43 Z9 44 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0147-8389 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD JAN PY 2012 VL 35 IS 1 BP 81 EP 87 DI 10.1111/j.1540-8159.2011.03257.x PG 7 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA 875MK UT WOS:000299034400019 PM 22077194 ER PT J AU Meghani, SH Polomano, RC Tait, RC Vallerand, AH Anderson, KO Gallagher, RM AF Meghani, Salimah H. Polomano, Rosemary C. Tait, Raymond C. Vallerand, April H. Anderson, Karen O. Gallagher, Rollin M. TI Advancing a National Agenda to Eliminate Disparities in Pain Care: Directions for Health Policy, Education, Practice, and Research SO PAIN MEDICINE LA English DT Article DE Pain; Disparities-Ethnic; Disparities-Racial; Pain Management; Pain Treatment; Policy; Advocacy; Legislation; Ethnic Disparities; Opioids; Analgesics; United States ID LIMITED ENGLISH PROFICIENCY; PATIENT-PHYSICIAN RELATIONSHIP; RANDOMIZED CONTROLLED-TRIAL; EMERGENCY-DEPARTMENT; UNITED-STATES; CULTURAL COMPETENCE; ETHNIC DISPARITIES; WHITE AMERICANS; CANCER-PATIENTS; MUSCULOSKELETAL PAIN AB Background. Pain is strongly associated with significant personal and societal costs. A crucial element of any initiative on pain must focus on eliminating pain care disparities that are pervasive throughout the United States health care settings. Objectives. This report focuses on macro-level factors related to pain care disparities in the United States that may be amenable to policy interventions. Methods. We identify concrete opportunities for achieving equity in pain care, especially those occasioned by recent legislative changes in the United States health care system. An aggressive policy, advocacy, and research agenda is synthesized in five domains: 1) structural/system; 2) policy and advocacy; 3) workforce; 4) provider; and 5) research. Results. Inequities in pain care remain an important and neglected health policy concern. Many direct and indirect provisions within the Affordable Care Act (ACA) and other national initiatives that leverage on ACA offer opportunities to achieve equity in pain care. These include changes in insurance, in public, provider, and legislative education, in primary care and pain specialist training, improving workforce diversity, achieving uniformity in race/ethnicity data collection, emphasizing patient-centered outcomes research, and encouraging focus on pain care disparities within the comparative effectiveness research paradigm. Conclusions. Recent national legislative initiatives within ACA are expected to generate multilevel efforts that will impact the flow of funding to address the pervasive issue of disparities. It is an opportune time for the pain community to take a lead in implementing a concerted agenda on pain care disparities in order to leverage these national initiatives. C1 [Meghani, Salimah H.] Univ Penn, Ctr Bioeth, NewCourtland Ctr Transit & Hlth, Dept Biobehav Hlth Sci,Sch Nursing, Philadelphia, PA 19104 USA. [Tait, Raymond C.] St Louis Univ, St Louis, MO 63103 USA. [Vallerand, April H.] Wayne State Univ, Detroit, MI USA. [Anderson, Karen O.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Gallagher, Rollin M.] Univ Penn, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. RP Meghani, SH (reprint author), Univ Penn, Ctr Bioeth, NewCourtland Ctr Transit & Hlth, Dept Biobehav Hlth Sci,Sch Nursing, Claire M Fagin Hall,418 Curie Blvd,Room 337, Philadelphia, PA 19104 USA. EM meghanis@nursing.upenn.edu RI Vallerand, April/I-8150-2012 FU Pricara, Unit of Ortho-McNeil, Inc. FX This work was supported by an unrestricted educational grant to the Philadelphia Research and Education Foundation, Philadelphia VA Medical Center, from Pricara, Unit of Ortho-McNeil, Inc., administered by Ortho-McNeil Janssen Scientific Affairs. NR 152 TC 34 Z9 34 U1 7 U2 22 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1526-2375 J9 PAIN MED JI Pain Med. PD JAN PY 2012 VL 13 IS 1 BP 5 EP 28 DI 10.1111/j.1526-4637.2011.01289.x PG 24 WC Medicine, General & Internal SC General & Internal Medicine GA 874KB UT WOS:000298954200002 PM 22142450 ER PT J AU Ellenbogen, JM Pace-Schott, EF AF Ellenbogen, Jeffrey M. Pace-Schott, Edward F. TI Drug-induced sleep: theoretical and practical considerations SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY LA English DT Review DE Sleep; Sleep disorders; Slow-wave sleep; Sleep-inducing drug; Pharmacology; Sleep apnea; Receptor ID SLOW-WAVE SLEEP; RESTLESS LEGS SYNDROME; DEPENDENT CORTICAL PLASTICITY; SHORT-ACTING BENZODIAZEPINE; OREXIN RECEPTOR ANTAGONIST; GABA(A) RECEPTOR; PRIMARY INSOMNIA; SODIUM OXYBATE; DOUBLE-BLIND; EXOGENOUS MELATONIN AB Faithful replication of normal sleep through medications-can it be achieved? Departure from normal sleep with the use of drugs-when is it desired? Answers to these questions depend on accurate understanding of sleep and on concrete criteria upon which to define it. Since these elements are evolving sciences, as yet incompletely known, one might take a nihilistic approach that we simply cannot judge whether we have successfully replicated sleep, since we do not fully grasp what sleep is or what it does. To address these potential obstacles, our article is written in two sections. The first addresses theoretical considerations for how medications might be seen in the larger framework of sleep. The purpose of this section is to inform readers about key issues in evaluating whether a drug has sufficient data to persuasively argue it is re-creating sleep. (We hope that researchers interested in conducting studies, or critical readers of the drug-study literature, might find this section particularly useful.) The second section of this article approaches exemplary, current concepts of pharmacologic manipulation of sleep, organized by disorders as articulated by the International Classification of Sleep Disorders (2005). This second section will combine practical knowledge of clinical sleep medicine, with emphasis on contemporary knowledge about molecular mechanisms that are felt to underlie some of these phenomena. We recognize that our collective knowledge about sleep will advance in the coming years. We hope that this article serves to facilitate that advance. C1 [Ellenbogen, Jeffrey M.] Massachusetts Gen Hosp, Dept Neurol, Sleep Div, Boston, MA 02114 USA. [Ellenbogen, Jeffrey M.] Harvard Univ, Sch Med, Boston, MA USA. [Pace-Schott, Edward F.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Pace-Schott, Edward F.] Univ Massachusetts, Dept Psychol, Amherst, MA 01003 USA. RP Ellenbogen, JM (reprint author), Massachusetts Gen Hosp, Dept Neurol, Sleep Div, 15 Blossom St,Wang 720, Boston, MA 02114 USA. EM jeffrey_ellenbogen@hms.harvard.edu NR 118 TC 1 Z9 1 U1 0 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0031-6768 J9 PFLUG ARCH EUR J PHY JI Pflugers Arch. PD JAN PY 2012 VL 463 IS 1 SI SI BP 177 EP 186 DI 10.1007/s00424-011-1033-3 PG 10 WC Physiology SC Physiology GA 877BX UT WOS:000299152600016 PM 21953011 ER PT J AU Zucker, DM Choi, J Gallagher, ER AF Zucker, Donna M. Choi, Jeungok Gallagher, Emily R. TI Mobile Outreach Strategies for Screening Hepatitis and HIV in High-Risk Populations SO PUBLIC HEALTH NURSING LA English DT Article DE hepatitis; HIV; mobile strategies; risk factors ID C VIRUS-INFECTION; HOMELESS ADULTS; PREDICTORS; PRISONERS; BEHAVIOR AB Objectives: To screen, counsel and offer hepatitis A and B vaccination for subjects at high risk for hepatitis C virus (HCV) and HIV, and determine any relationship between risk factors and HCV positivity. C1 [Zucker, Donna M.; Choi, Jeungok] Univ Massachusetts, Sch Nursing, Amherst, MA 01003 USA. [Gallagher, Emily R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Zucker, DM (reprint author), Univ Massachusetts, Sch Nursing, 651 Pleasant St, Amherst, MA 01003 USA. EM donna@acad.umass.edu NR 17 TC 3 Z9 3 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0737-1209 J9 PUBLIC HEALTH NURS JI Public Health Nurs. PD JAN-FEB PY 2012 VL 29 IS 1 BP 27 EP 35 DI 10.1111/j.1525-1446.2011.00970.x PG 9 WC Public, Environmental & Occupational Health; Nursing SC Public, Environmental & Occupational Health; Nursing GA 869IF UT WOS:000298590900005 PM 22211749 ER PT J AU Martinez, F Chung, JH Digumarthy, SR Kanne, JP Abbott, GF Shepard, JAO Mark, EJ Sharma, A AF Martinez, Felipe Chung, Jonathan H. Digumarthy, Subba R. Kanne, Jeffrey P. Abbott, Gerald F. Shepard, Jo-Anne O. Mark, Eugene J. Sharma, Amita TI Common and Uncommon Manifestations of Wegener Granulomatosis at Chest CT: Radiologic-Pathologic Correlation SO RADIOGRAPHICS LA English DT Article ID ANCA-ASSOCIATED VASCULITIDES; COMPLETE HEART-BLOCK; OPEN LUNG BIOPSIES; THORACIC MANIFESTATIONS; COMPUTED-TOMOGRAPHY; PATHERGIC GRANULOMATOSIS; PULMONARY VASCULITIS; SYSTEMIC VASCULITIS; EARLY DIAGNOSIS; DISEASE AB Wegener granulomatosis is an uncommon necrotizing vasculitis that classically manifests as a clinical triad consisting of upper and lower airway involvement and glomerulonephritis. Other less frequently involved organ systems include the central and peripheral nervous system and large joints. The diagnosis is based on a combination of clinical and laboratory findings. Because thoracic involvement often predominates, chest radiographic findings are often the first to suggest the diagnosis. However, chest computed tomography (CT) has superior sensitivity and specificity for evaluation of the airways, lung parenchyma, and mediastinum, particularly with the use of multiplanar reformatted and three-dimensional images. Common pulmonary radiologic findings include waxing and waning nodules, masses, ground-glass opacities, and consolidation. Airway involvement is usually characterized by circumferential tracheobronchial thickening, which can be smooth or nodular. Pleural effusions are the most common manifestation of pleural disease and can result from primary involvement or be secondary to renal failure. Mediastinal lymphadenopathy is a nonspecific finding and is usually reactive. Uncommon thoracic radiologic manifestations include involvement of the heart and great vessels. CT is the imaging modality of choice for diagnosis, surveillance, and follow-up in patients with Wegener granulomatosis. C1 [Martinez, Felipe; Chung, Jonathan H.; Digumarthy, Subba R.; Abbott, Gerald F.; Shepard, Jo-Anne O.; Sharma, Amita] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Mark, Eugene J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Kanne, Jeffrey P.] Univ Wisconsin, Dept Radiol, Sch Med & Publ Hlth, Madison, WI 53706 USA. RP Sharma, A (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,Founders 202, Boston, MA 02114 USA. EM asharma2@partners.org FU Amirsys; Norman; Hanson; DeTroy; Yale Cancer Center webinar; Wolter Klewer FX E.J.M.: Related financial activities: none. Other financial activities: received payment for expert testimony in asbestos litigation. J.H.C.: Related financial activities: none. Other financial activities: received royalties from Amirsys. J.O.S.: Related financial activities: none. Other financial activities: received payment for expert testimony from Norman, Hanson, and DeTroy; received payment for lectures (including service on speakers bureaus) from Yale Cancer Center webinar. J.P.K.: Related financial activities: none. Other financial activities: consultant for PTC Therapeutics and Perceptive Informatics, received royalties from Wolter Klewer. NR 68 TC 17 Z9 22 U1 0 U2 2 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 JAN-FEB PY 2012 VL 32 IS 1 BP 51 EP 69 DI 10.1148/rg.321115060 PG 19 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 875TX UT WOS:000299059200007 PM 22236893 ER PT J AU Drukteinis, JS Gombos, EC Raza, S Chikarmane, SA Swami, A Birdwell, RL AF Drukteinis, Jennifer S. Gombos, Eva C. Raza, Sughra Chikarmane, Sona A. Swami, Arpita Birdwell, Robyn L. TI MR Imaging Assessment of the Breast after Breast Conservation Therapy: Distinguishing Benign from Malignant Lesions SO RADIOGRAPHICS LA English DT Article ID 20-YEAR FOLLOW-UP; COMPARING TOTAL MASTECTOMY; CONTRAST-ENHANCED MRI; LOCAL RECURRENCE; CONSERVING SURGERY; FAT NECROSIS; RADICAL-MASTECTOMY; RADIATION-THERAPY; TIME-COURSE; STAGE-I AB Dynamic contrast material-enhanced magnetic resonance (MR) imaging has emerged as a valuable tool in evaluation of women who have undergone lumpectomy and whole-breast radiation therapy for breast cancer. Early diagnosis of local recurrence by means of close clinical and imaging follow-up is an important component of a breast-conserving strategy, as it may improve survival. In the post-breast conservation therapy (BCT) breast, resolving edema, fat necrosis, a small focal area of non-masslike enhancement (NMLE), and thin linear NMLE at the lumpectomy site can all be expected findings. In contrast, masslike enhancement or NMLE of ductal or segmental distribution can indicate recurrence. Therefore, at MR imaging of the post-BCT breast, it is important to identify lesions that are benign or appropriate for short-interval imaging surveillance to minimize unnecessary intervention, as well as to discern suspicious lesions and optimize the diagnosis of recurrence. C1 [Drukteinis, Jennifer S.; Gombos, Eva C.; Raza, Sughra; Chikarmane, Sona A.; Swami, Arpita; Birdwell, Robyn L.] Brigham & Womens Hosp, Dept Radiol, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Drukteinis, JS (reprint author), Brigham & Womens Hosp, Dept Radiol, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. EM jendruk@yahoo.com FU GE Healthcare; Amirsys FX E.C.G.: Related financial activities: grant from GE Healthcare. Other financial activities: royalties from Amirsys. R. L. B.: Related financial activities: none. Other financial activities: royalties from Amirsys. NR 33 TC 10 Z9 11 U1 0 U2 4 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 JAN-FEB PY 2012 VL 32 IS 1 BP 219 EP 234 DI 10.1148/rg.321115016 PG 16 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 875TX UT WOS:000299059200019 PM 22236903 ER PT J AU Thabet, A Kalva, SP Liu, B Mueller, PR Lee, SI AF Thabet, Ashraf Kalva, Sanjeeva P. Liu, Bob Mueller, Peter R. Lee, Susanna I. TI Interventional Radiology in Pregnancy Complications: Indications, Technique, and Methods for Minimizing Radiation Exposure SO RADIOGRAPHICS LA English DT Article ID UTERINE ARTERY EMBOLIZATION; PRIMARY POSTPARTUM HEMORRHAGE; TERM-FOLLOW-UP; ECTOPIC PREGNANCY; CESAREAN-SECTION; PLACENTA-ACCRETA; PERCUTANEOUS NEPHROSTOMY; TRANSVAGINAL ASPIRATION; CERVICAL PREGNANCY; FLUID COLLECTIONS AB Complications of pregnancy, whether they occur during gestation or postpartum, often pose complex challenges because they affect two patients ( mother and fetus or infant) and because both short- and long-term outcomes must be considered in management decision making. Interventional radiologists play a critical role in treating complications such as ectopic implantation, postpartum hemorrhage, symptomatic ovarian cyst, post-cesarean section fluid collection, obstructive uropathy, and vesicouterine fistula. Interventional radiology offers therapeutic options that obviate surgery, thereby minimizing morbidity and mortality and maximizing the potential for fertility preservation. Such options include chemical injection of an ectopic gestational sac, uterine artery embolization, aspiration and drainage, percutaneous nephrostomy, and suprapubic cystostomy catheter placement. All these procedures are performed with the use of radiologic imaging for guidance. The levels of radiation to which the mother and fetus may be exposed during such procedures are of concern because of potential negative effects on long-term health. However, various methods can be used to lower maternal and fetal radiation dose levels to the minimum needed to accomplish the clinical objective. C1 [Thabet, Ashraf; Liu, Bob; Mueller, Peter R.; Lee, Susanna I.] Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent, Dept Radiol, Boston, MA 02114 USA. [Kalva, Sanjeeva P.] Massachusetts Gen Hosp, Div Vasc Imaging & Intervent, Dept Radiol, Boston, MA 02114 USA. RP Thabet, A (reprint author), Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent, Dept Radiol, 55 Fruit St,White 270, Boston, MA 02114 USA. EM athabet@partners.org FU Amirsys FX S.P.K.: Related financial activities: none. Other financial activities: speaker for KMH Labs; royalties from Amirsys. NR 73 TC 15 Z9 20 U1 0 U2 2 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 JAN-FEB PY 2012 VL 32 IS 1 BP 255 EP 274 DI 10.1148/rg.321115064 PG 20 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 875TX UT WOS:000299059200022 PM 22236906 ER PT J AU Wu, Y Collier, L Pan, J Qin, W Bauman, WA Cardozo, CP AF Wu, Y. Collier, L. Pan, J. Qin, W. Bauman, W. A. Cardozo, C. P. TI Testosterone reduced methylprednisolone-induced muscle atrophy in spinal cord-injured rats SO SPINAL CORD LA English DT Article DE Spinal cord injury; methylprednisolone; muscle atrophy; atrogenes; testosterone ID HIGH-DOSE METHYLPREDNISOLONE; GROWTH-FACTOR-I; SKELETAL-MUSCLE; SERUM TESTOSTERONE; CONTROLLED-TRIAL; GENE-EXPRESSION; UP-REGULATION; MYOSTATIN; DIAPHRAGM; PROTEIN AB Study design: Male rats with complete transections of the spinal cord were administered vehicle or methylprednisolone (MP) for 24 h, with or without infusion, for 7 days, of testosterone at either a replacement or low pharmacological doses. Muscles were collected at 7 days after SCI. Objective: The objective of this study is to determine, in a rat model of complete spinal cord transection, whether testosterone reduces muscle atrophy or upregulates muscle atrophy-linked genes, induced by 24 h of MP administration at doses comparable to those prescribed in man during the period immediately following acute spinal cord injury (SCI) in an attempt to preserve neurological function. Results: MP significantly reduced the mass of triceps, soleus and plantaris, and significantly increased expression of genes that promote atrophy. Testosterone significantly reduced muscle atrophy induced by MP, but did not prevent it; there was no difference between low-or high-dose testosterone in reducing MP-induced muscle loss. High-dose testosterone reduced expression of muscle atrophy genes more than did low dose. Testosterone-induced declines in mRNA levels for these atrophy-associated genes did not correlate well with protection against MP-induced muscle atrophy. Conclusions: MP induces marked and lasting changes in the biology of muscle that persisted for at least 7 days, or 6 days after MP has been eliminated from the body. Testosterone partially protected against muscle atrophy and gene expression changes caused by 1 day of MP. Spinal Cord (2012) 50, 57-62; doi:10.1038/sc.2011.91; published online 20 September 2011 C1 [Wu, Y.; Collier, L.; Pan, J.; Qin, W.; Bauman, W. A.; Cardozo, C. P.] James J Peters VA Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Dept Vet Affairs, Bronx, NY 10468 USA. [Qin, W.; Bauman, W. A.; Cardozo, C. P.] Mt Sinai Sch Med, Dept Med, New York, NY USA. [Bauman, W. A.; Cardozo, C. P.] Mt Sinai Sch Med, Dept Rehabil Med, New York, NY USA. RP Cardozo, CP (reprint author), James J Peters VA Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Dept Vet Affairs, Room 7A-13,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM Chris.Cardozo@mssm.edu FU Veterans Health Administration, Rehabilitation Research and Development Service [B4162C, B3347 K] FX This research was supported by the Veterans Health Administration, Rehabilitation Research and Development Service (B4162C and B3347 K). NR 33 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1362-4393 EI 1476-5624 J9 SPINAL CORD JI Spinal Cord PD JAN PY 2012 VL 50 IS 1 BP 57 EP 62 DI 10.1038/sc.2011.91 PG 6 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 879FB UT WOS:000299314000011 PM 21931329 ER PT J AU Williams, RE Bauman, WA Spungen, AM Vinnakota, RR Farid, RZ Galea, M Korsten, MA AF Williams, R. E., III Bauman, W. A. Spungen, A. M. Vinnakota, R. R. Farid, R. Z. Galea, M. Korsten, M. A. TI SmartPill technology provides safe and effective assessment of gastrointestinal function in persons with spinal cord injury SO SPINAL CORD LA English DT Article DE spinal cord injury; gastric emptying time; colonic transit time; whole gut transit time; gastroesophageal reflux disease ID CAPSULE AB Study design: Spinal cord injury (SCI) results in gastrointestinal (GI) complications, including gastroesophageal reflux disease and constipation, but much of the data is based on older technology. Objective: GI transit times were determined in subjects with SCI using a new device called a SmartPill. Our principal goal was to assess whether this new technology can be applied in persons with SCI. Methods: SCI and age-and gender-matched able-bodied (AB) control subjects not taking proton pump inhibitors were studied. Following an 8-h overnight fast, subjects consumed 120 g EggBeaters (60 kcal), two slices of white bread (120 kcal) and 30g strawberry jam (74 kcal). A pH calibrated SmartPill capsule was swallowed with 8 ounces of water, after which subjects fasted for an additional 6 h prior to consuming an Ensure Plus nutrition shake (350kcal). Subjects remained fasted for an additional 2 h, after which time they resumed their regular diets. Results: Twenty subjects with SCI and 10 AB control subjects were studied. Data are expressed as mean +/- s.d. Comparing the group with SCI to the AB control group, gastric emptying time (GET), colonic transit time (CTT) and whole gut transit time (WGTT) were prolonged (GET: 10.6 +/- 7.2 vs 3.5 +/- 1.0h, P < 0.01; CTT: 52.3 +/- 42.9 vs 14.2 +/- 7.6 h, P = 0.01; WGTT: 3.3 +/- 2.5 vs 1.0 +/- 0.7 days, P < 0.01). No complications or side effects were reported. Conclusion: Our results indicate that the SmartPill technology is a safe, non-invasive assessment technique that provides valid diagnostic information in persons with SCI. Spinal Cord (2012) 50, 81-84; doi:10.1038/sc.2011.92; published online 30 August 2011 C1 [Korsten, M. A.] James J Peters Vet Affairs Med Ctr, Gastroenterol Serv, VA RR&D Ctr Excellence Med Consequences Spinal Co, Bronx, NY 10468 USA. [Bauman, W. A.; Spungen, A. M.; Korsten, M. A.] James J Peters Vet Affairs Med Ctr, Med Serv, Bronx, NY 10468 USA. [Bauman, W. A.; Spungen, A. M.; Korsten, M. A.] Mt Sinai Med Ctr, Dept Med, New York, NY 10029 USA. [Bauman, W. A.; Spungen, A. M.; Korsten, M. A.] Mt Sinai Med Ctr, Dept Rehabil Med, New York, NY 10029 USA. [Galea, M.] James J Peters Vet Affairs Med Ctr, Spinal Cord Injury Serv, Bronx, NY 10468 USA. RP Korsten, MA (reprint author), James J Peters Vet Affairs Med Ctr, Gastroenterol Serv, VA RR&D Ctr Excellence Med Consequences Spinal Co, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM mark.korsten@va.gov FU Department of Veteran Affairs Rehabilitation Research and Development Service Center of Excellence for the Medical Consequences of Spinal Cord Injury [B4162-C]; James J Peters VA Medical Center FX The Department of Veteran Affairs Rehabilitation Research and Development Service Center of Excellence for the Medical Consequences of Spinal Cord Injury (#B4162-C) and the James J Peters VA Medical Center have provided the support that made this work possible. NR 11 TC 8 Z9 8 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1362-4393 J9 SPINAL CORD JI Spinal Cord PD JAN PY 2012 VL 50 IS 1 BP 81 EP 84 DI 10.1038/sc.2011.92 PG 4 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 879FB UT WOS:000299314000016 PM 21876549 ER PT J AU Tomedi, LE Bogen, DL Hanusa, BH Wisner, KL Bodnar, LM AF Tomedi, Laura Elizabeth Bogen, Debra L. Hanusa, Barbara H. Wisner, Katherine L. Bodnar, Lisa M. TI A Pilot Study of the Nutritional Status of Opiate-Using Pregnant Women on Methadone Maintenance Therapy SO SUBSTANCE USE & MISUSE LA English DT Article DE methadone; pregnancy; nutrition; obesity; dietary intake; nutritional biomarkers ID POSTNATAL DEPRESSION SCALE; NEURAL-TUBE DEFECTS; ILLICIT DRUG-USE; HISTORY QUESTIONNAIRE; SUBSTANCE USE; BIRTH-WEIGHT; LIFE-STYLE; VITAMIN; PREVALENCE; VALIDATION AB Pregnant women in methadone maintenance therapy may have poor nutrition during pregnancy. In 2006-2008, methadone-treated pregnant women (n = 22) were recruited at an urban academic medical center and compared with nondrug-using pregnant women (n = 119) at 20-35 weeks' gestation. We measured adiposity using prepregnancy body mass index (BMI), dietary intake using a food frequency questionnaire, and micronutrient and essential fatty acid status using biomarkers. Methadone-treated women had lower BMI, consumed more calories, had lower serum carotenoid concentrations, and higher plasma homocysteine concentrations than controls. The study's limitations and implications for future research are discussed. C1 [Tomedi, Laura Elizabeth; Wisner, Katherine L.; Bodnar, Lisa M.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA. [Bogen, Debra L.] Univ Pittsburgh, Childrens Hosp Pittsburgh, Sch Med, Div Gen Acad Pediat, Pittsburgh, PA USA. [Hanusa, Barbara H.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Wisner, Katherine L.] Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Pittsburgh, PA USA. [Wisner, Katherine L.] Univ Pittsburgh, Dept Obstet Gynecol & Reprod Sci, Sch Med, Pittsburgh, PA USA. RP Tomedi, LE (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA. EM let20@pitt.edu FU Children's Hospital of Pittsburgh Research Advisory Committee; Gerber Foundation; National Institutes of Health (NIH) [MO1RR00056]; Building Interdisciplinary Research Careers in Women's Health (BIRCWH) Award [K12 HD043441]; NIH/NIMH (National Institute of Mental Health) [R01 MH060335, K01 MH074092]; National Institute of Child Health and Human Development (NICHD) [HD 055 162-03 NIH NRSA T32] FX This study was funded by the Children's Hospital of Pittsburgh Research Advisory Committee and the Gerber Foundation. Study visits were conducted in the Magee-Womens Hospital Clinical and Translational Research Center, which is funded by National Institutes of Health (NIH; grant MO1RR00056). The authors' contributions to this work were supported by K12 HD043441 [Building Interdisciplinary Research Careers in Women's Health (BIRCWH) Award], NIH/NIMH (National Institute of Mental Health) grants R01 MH060335 and K01 MH074092, and the Reproductive, Perinatal and Pediatric Epidemiology grant HD 055 162-03 NIH NRSA T32 [National Institute of Child Health and Human Development (NICHD)]. NR 52 TC 2 Z9 2 U1 4 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1082-6084 EI 1532-2491 J9 SUBST USE MISUSE JI Subst. Use Misuse PY 2012 VL 47 IS 3 BP 286 EP 295 DI 10.3109/10826084.2011.635324 PG 10 WC Substance Abuse; Psychiatry; Psychology SC Substance Abuse; Psychiatry; Psychology GA 873BT UT WOS:000298856500008 PM 22217127 ER PT J AU Shao, HL Min, C Issadore, D Liong, M Yoon, TJ Weissleder, R Lee, H AF Shao, Huilin Min, Changwook Issadore, David Liong, Monty Yoon, Tae-Jong Weissleder, Ralph Lee, Hakho TI Magnetic Nanoparticles and microNMR for Diagnostic Applications SO THERANOSTICS LA English DT Review DE biosensor; diagnostics; magnetic nanoparticle; microfluidics; nuclear magnetic resonance ID CORE-SHELL NANOPARTICLES; CANCER-CELLS; RELAXATION; RESONANCE; BIOSENSOR; ASSAYS; PROTEIN; PROBES; ARRAYS; NANOCRYSTALS AB Sensitive and quantitative measurements of clinically relevant protein biomarkers, pathogens and cells in biological samples would be invaluable for disease diagnosis, monitoring of malignancy, and for evaluating therapy efficacy. Biosensing strategies using magnetic nanoparticles (MNPs) have recently received considerable attention, since they offer unique advantages over traditional detection methods. Specifically, because biological samples have negligible magnetic background, MNPs can be used to obtain highly sensitive measurements in minimally processed samples. This review focuses on the use of MNPs for in vitro detection of cellular biomarkers based on nuclear magnetic resonance (NMR) effects. This detection platform, termed diagnostic magnetic resonance (DMR), exploits MNPs as proximity sensors to modulate the spin-spin relaxation time of water molecules surrounding the molecularly-targeted nanoparticles. With new developments such as more effective MNP biosensors, advanced conjugational strategies, and highly sensitive miniaturized NMR systems, the DMR detection capabilities have been considerably improved. These developments have also enabled parallel and rapid measurements from small sample volumes and on a wide range of targets, including whole cells, proteins, DNA/mRNA, metabolites, drugs, viruses and bacteria. The DMR platform thus makes a robust and easy-to-use sensor system with broad applications in biomedicine, as well as clinical utility in point-of-care settings. C1 [Shao, Huilin; Min, Changwook; Issadore, David; Liong, Monty; Yoon, Tae-Jong; Weissleder, Ralph; Lee, Hakho] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St,CPZN 5206, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu; hlee@mgh.harvard.edu RI Issadore, David/L-8451-2014 FU Agency for Science, Technology and Research, Singapore; NIH [2RO1EB004626, U01-HL080731, HHSN 268201000044C, U54-CA119349, T32-CA79443] FX The authors thank N. Sergeyev for providing cross-linked dextran-coated iron oxide nanoparticles. H. Shao acknowledges financial support from the B.S.-Ph.D. National Science Scholarship awarded by the Agency for Science, Technology and Research, Singapore. This work was supported in part by NIH Grants (2RO1EB004626, U01-HL080731, HHSN 268201000044C, U54-CA119349 and T32-CA79443). NR 59 TC 67 Z9 70 U1 15 U2 108 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1838-7640 J9 THERANOSTICS JI Theranostics PY 2012 VL 2 IS 1 BP 55 EP 65 DI 10.7150/thno.3465 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 876PZ UT WOS:000299121200004 PM 22272219 ER PT J AU Perlstein, TS Goldhaber, SZ Nelson, K Joshi, V Morgan, TV Lesko, LJ Lee, JY Gobburu, J Schoenfeld, D Kucherlapati, R Freeman, MW Creager, MA AF Perlstein, Todd S. Goldhaber, Samuel Z. Nelson, Kerrie Joshi, Victoria Morgan, T. Vance Lesko, Lawrence J. Lee, Joo-Yeon Gobburu, Jogarao Schoenfeld, David Kucherlapati, Raju Freeman, Mason W. Creager, Mark A. TI The Creating an Optimal Warfarin Nomogram (CROWN) Study SO THROMBOSIS AND HAEMOSTASIS LA English DT Article DE Pharmacogenetics; warfarin; clinical trial ID ORAL ANTICOAGULATION; ATRIAL-FIBRILLATION; LABELING DECISIONS; VKORC1 HAPLOTYPES; DRUG APPLICATIONS; CLINICAL FACTORS; CHINESE PATIENTS; CYP2C9 VARIANTS; IMPACT; GENOTYPE AB A significant proportion of warfarin dose variability is explained by variation in the genotypes of the cytochrome P450 CYP2C9 and the vitamin K epoxide reductase complex, VKORC1, enzymes that influence warfarin metabolism and sensitivity, respectively. We sought to develop an optimal pharmacogenetic warfarin dosing algorithm that incorporated clinical and genetic information. We enroled patients initiating warfarin therapy. Genotyping was performed of the VKORC1, -1639G>A, the CYP2C9*2, 430C>T, and the CYP2C9*3,1075C>A genotypes. The initial warfarin dosing algorithm (Algorithm A) was based upon established clinical practice and published warfarin pharmacogenetic information. Subsequent dosing algorithms (Algorithms B and Algorithm C) were derived from pharmacokinetic / pharmacodynamic (PK/PD) modelling of warfarin dose, international normalised ratio (INR), clinical and genetic factors from patients treated by the preceding algorithm(s). The primary outcome was the time in the therapeutic range, considered an INR of 1.8 to 3.2.A total of 344 subjects are included in the study analyses. The mean percentage time within the therapeutic range for each subject increased progressively from Algorithm A toAlgorithm C from 58.9 (22.0), to 59.7 (23.0), to 65.8 (16.9) percent (p = 0.04). Improvement also occurred in most secondary endpoints, which included the per-patient percentage of INRs outside of the therapeutic range (p = 0.004), the time to the first therapeutic INR (p = 0.07), and the time to achieve stable therapeutic anticoagulation (p < 0.001). In conclusion, warfarin pharmacogenetic dosing can be optimised in real time utilising observed PK/PD information in an adaptive fashion. C1 [Perlstein, Todd S.; Goldhaber, Samuel Z.; Creager, Mark A.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Nelson, Kerrie; Schoenfeld, David] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Schoenfeld, David] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Freeman, Mason W.] Massachusetts Gen Hosp, Lipid Metab Unit, Boston, MA 02114 USA. [Freeman, Mason W.] Massachusetts Gen Hosp, Div Endocrine, Boston, MA 02114 USA. [Joshi, Victoria] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Joshi, Victoria] Brigham & Womens Hosp, Partners Ctr Personalized Genet Med, Boston, MA 02115 USA. [Morgan, T. Vance; Kucherlapati, Raju] Harvard Univ, Sch Med, Ctr Personalized Genet Med, Boston, MA USA. [Lesko, Lawrence J.; Lee, Joo-Yeon; Gobburu, Jogarao] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Creager, MA (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. EM mcreager@partners.org FU Partners HealthCare; National Heart, Lung, and Blood Institute [K12-HL083786] FX This work was funded by Partners HealthCare through a grant to the Harvard Partners Center for Personalized Genetic Medicine. Dr Perlstein received support from the National Heart, Lung, and Blood Institute Research Career Development Award K12-HL083786. Dr. Creager is the Simon C. Fireman Scholar in Cardiovascular Medicine at Brigham and Women's Hospital. NR 37 TC 7 Z9 7 U1 0 U2 8 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 JAN PY 2012 VL 107 IS 1 BP 59 EP 68 DI 10.1160/TH11-08-0568 PG 10 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 879UO UT WOS:000299357900012 PM 22116191 ER PT J AU Biederman, J Petty, CR Bhide, PG Woodworth, KY Faraone, S AF Biederman, Joseph Petty, Carter R. Bhide, Pradeep G. Woodworth, K. Yvonne Faraone, Stephen TI Does exposure to maternal smoking during pregnancy affect the clinical features of ADHD? Results from a controlled study SO WORLD JOURNAL OF BIOLOGICAL PSYCHIATRY LA English DT Article DE ADHD; smoking; children; brain development; childhood ADHD ID DEFICIT HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DSM-III-R; FOLLOW-UP; RISK; GIRLS AB Objectives. Exposure to maternal smoking during pregnancy may be a signifi cant risk factor for attention-deficit/hyperactivity disorder (ADHD) independently of family history of ADHD. The main aim of this study was to examine whether the clinical profile of ADHD differs between children with and without exposure to maternal smoking during pregnancy. Methods. This was a case-control study of boys and girls with and without ADHD ascertained from psychiatric and paediatric sources. Maternal smoking during pregnancy was defined by interviews with subjects' mothers. Main outcome measures were ADHD symptoms and associated clinical features in children with and without exposure to maternal smoking during pregnancy. Results. No signifi cant differences were found between ADHD children with and without exposure to maternal smoking during pregnancy on clinical characteristics. When these analyses were repeated in the subgroup of subjects without parental history of ADHD, there were also no statistically signifi cant differences found. Conclusions. Despite adequate statistical power, no signifi cant differences were found between ADHD children with and without exposure in the clinical features of ADHD and associated disorders. Results provide support for the notion that ADHD cases resulting from exposure to maternal smoking during pregnancy have similar clinical profiles as other ADHD cases. C1 [Biederman, Joseph; Petty, Carter R.; Woodworth, K. Yvonne] Massachusetts Gen Hosp, Dept Psychiat, Clin Program Pediat Psychiat & Adult ADHD, Boston, MA 02114 USA. [Biederman, Joseph; Petty, Carter R.; Woodworth, K. Yvonne] Massachusetts Gen Hosp, Dept Psychiat, Res Program Pediat Psychiat & Adult ADHD, Boston, MA 02114 USA. [Biederman, Joseph; Bhide, Pradeep G.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Bhide, Pradeep G.] Massachusetts Gen Hosp, Neurosci Ctr, Boston, MA 02114 USA. [Faraone, Stephen] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Clin Program Pediat Psychiat & Adult ADHD, 55 Fruit St,Warren 705, Boston, MA 02114 USA. EM jbiederman@partners.org OI Bhide, Pradeep/0000-0003-4236-9415; Faraone, Stephen/0000-0002-9217-3982 FU Pediatric Psychopharmacology Philanthropy Fund; Elminda; Janssen; McNeil; Shire; Fundacion Areces, Medice Pharmaceuticals; Spanish Child Psychiatry Association; Abbott; Alza; AstraZeneca; Bristol Myers Squibb; Celltech; Cephalon; Eli Lilly and Co.; Esai; Forest; Glaxo; Gliatech; Merck; NARSAD; NIDA; New River; NICHD; NIMH; Novartis; Noven; Neurosearch; Organon; Otsuka; Pfizer; Pharmacia; Prechter Foundation; Stanley Foundation; UCB Pharma, Inc.; Wyeth.; National Institutes of Health FX This work was supported by the Pediatric Psychopharmacology Philanthropy Fund. The funding organization did not play any role in the design and conduct of the study, the collection, management analysis and interpretation of the data, or in the preparation, review or approval of the manuscript.; Dr Joseph Biederman is currently receiving research support from the following sources: Elminda, Janssen, McNeil, and Shire. In 2010, Dr Biederman did not receive any outside income. In 2009, Dr Biederman received a speaker's fee from the following sources: Fundacion Areces, Medice Pharmaceuticals, and the Spanish Child Psychiatry Association. In previous years, Dr Biederman received research support, consultation fees, or speaker's fees for/from the following additional sources: Abbott, Alza, AstraZeneca, Bristol Myers Squibb, Celltech, Cephalon, Eli Lilly and Co., Esai, Forest, Glaxo, Gliatech, Janssen, McNeil, Merck, NARSAD, NIDA, New River, NICHD, NIMH, Novartis, Noven, Neurosearch, Organon, Otsuka, Pfizer, Pharmacia, The Prechter Foundation, Shire, The Stanley Foundation, UCB Pharma, Inc. and Wyeth. In the past year, Dr Stephen Faraone has received consulting fees and has been on Advisory Boards for Eli Lilly, Ortho-McNeil and Shire Development and has received research support from Eli Lilly, Pfizer, Shire and the National Institutes of Health. In previous years, Dr Faraone has received consulting fees or has been on Advisory Boards or has been a speaker for the following sources: Shire, McNeil, Janssen, Novartis, Pfizer and Eli Lilly. In previous years he has received research support from Eli Lilly, Shire, Pfi zer and the National Institutes of Health. Dr Bhide, Mr Petty and Ms Woodworth have nothing to disclose. NR 21 TC 8 Z9 9 U1 0 U2 8 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1562-2975 J9 WORLD J BIOL PSYCHIA JI World J. Biol. Psychiatry PD JAN PY 2012 VL 13 IS 1 BP 60 EP 64 DI 10.3109/15622975.2011.562243 PG 5 WC Psychiatry SC Psychiatry GA 878ZF UT WOS:000299296100008 PM 21545244 ER PT J AU Mirzakhani, H Welch, CA Eikermann, M Nozari, A AF Mirzakhani, H. Welch, C. A. Eikermann, M. Nozari, A. TI Neuromuscular blocking agents for electroconvulsive therapy: a systematic review SO ACTA ANAESTHESIOLOGICA SCANDINAVICA LA English DT Review ID NEUROLEPTIC MALIGNANT SYNDROME; POSTOPERATIVE RESIDUAL CURARIZATION; POSTANESTHESIA CARE-UNIT; RELAXANT BINDING-AGENT; CONVULSIVE SHOCK THERAPY; ANESTHETIC CONSIDERATIONS; SEVOFLURANE ANESTHESIA; ELDERLY-PATIENTS; DOSE-RESPONSE; TRAUMATIC COMPLICATIONS AB Electroconvulsive therapy (ECT) is the transcutaneous application of small electrical stimuli to the brain to induce generalised seizures for the treatment of selected psychiatric disorders. The clinical indications for ECT as an effective therapeutic modality have been considerably expanded since its introduction. Anaesthesia and neuromuscular blocking agents (NMBAs) are required to ensure patients safety during ECT. The optimal dose of muscle relaxant for ECT reduces muscle contractions without inducing complete paralysis. Slight residual motor convulsive activity is helpful in ascertaining that a seizure has occurred, while total paralysis prolongs the procedure unnecessarily. Suxamethonium is commonly used, but nondepolarising NMBAs are indicated in patients with certain comorbidities. In this review, we summarise current concepts of NMBA management for ECT. C1 [Mirzakhani, H.; Eikermann, M.; Nozari, A.] Harvard Univ, Dept Anaesthesia Crit Care & Pain Med, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Welch, C. A.] Harvard Univ, Dept Psychiat, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Nozari, A (reprint author), Harvard Univ, Dept Anaesthesia Crit Care & Pain Med, Sch Med, Massachusetts Gen Hosp, GRJ 416, Boston, MA 02114 USA. EM anozari@partners.org NR 151 TC 14 Z9 14 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0001-5172 J9 ACTA ANAESTH SCAND JI Acta Anaesthesiol. Scand. PD JAN PY 2012 VL 56 IS 1 BP 3 EP 16 DI 10.1111/j.1399-6576.2011.02520.x PG 14 WC Anesthesiology SC Anesthesiology GA 860AS UT WOS:000297918400002 PM 22092267 ER PT J AU Vallaster, M Vallaster, CD Wu, SM AF Vallaster, Marcus Vallaster, Caroline Dacwag Wu, Sean M. TI Epigenetic mechanisms in cardiac development and disease SO ACTA BIOCHIMICA ET BIOPHYSICA SINICA LA English DT Review DE epigenetics; histone modifications; DNA methylation; congenital heart disease ID HOLT-ORAM-SYNDROME; CONGENITAL HEART-DISEASE; EMBRYONIC STEM-CELLS; CHROMATIN-REMODELING COMPLEX; TRANSCRIPTION FACTOR TBX5; DIGEORGE-SYNDROME; SMOOTH-MUSCLE; PROGENITOR SPECIFICATION; HISTONE ACETYLATION; MYOCARDIAL-CELLS AB During mammalian development, cardiac specification and ultimately lineage commitment to a specific cardiac cell type is accomplished by the action of specific transcription factors (TFs) and their meticulous control on an epigenetic level. In this review, we detail how cardiac-specific TFs function in concert with nucleosome remodeling and histone-modifying enzymes to regulate a diverse network of genes required for processes such as cell growth and proliferation, or epithelial to mesenchymal transition (EMT), for instance. We provide examples of how several cardiac TFs, such as Nkx2.5, WHSC1, Tbx5, and Tbx1, which are associated with developmental and congenital heart defects, are required for the recruitment of histone modifiers, such as Jarid2, p300, and Ash2l, and components of ATP-dependent remodeling enzymes like Brg1, Baf60c, and Baf180. Binding of these TFs to their respective sites at cardiac genes coincides with a distinct pattern of histone marks, indicating that the precise regulation of cardiac gene networks is orchestrated by interactions between TFs and epigenetic modifiers. Furthermore, we speculate that an epigenetic signature, comprised of TF occupancy, histone modifications, and overall chromatin organization, is an underlying mechanism that governs cardiac morphogenesis and disease. C1 [Vallaster, Marcus; Vallaster, Caroline Dacwag; Wu, Sean M.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Vallaster, Caroline Dacwag; Wu, Sean M.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Wu, Sean M.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Wu, SM (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. EM SMWU@partners.org FU NIH [OD004411, HL081086, HL100408, 5T32HL007208] FX This work was supported by grants from the NIH (OD004411, HL081086, HL100408 to S.M.W.; 5T32HL007208 to C.D.V.). NR 103 TC 28 Z9 32 U1 2 U2 14 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1672-9145 J9 ACTA BIOCH BIOPH SIN JI Acta Biochim. Biophys. Sin. PD JAN PY 2012 VL 44 IS 1 SI SI BP 92 EP 102 DI 10.1093/abbs/gmr090 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 866NB UT WOS:000298386700010 PM 22194017 ER PT J AU Montine, TJ Phelps, CH Beach, TG Bigio, EH Cairns, NJ Dickson, DW Duyckaerts, C Frosch, MP Masliah, E Mirra, SS Nelson, PT Schneider, JA Thal, DR Trojanowski, JQ Vinters, HV Hyman, BT AF Montine, Thomas J. Phelps, Creighton H. Beach, Thomas G. Bigio, Eileen H. Cairns, Nigel J. Dickson, Dennis W. Duyckaerts, Charles Frosch, Matthew P. Masliah, Eliezer Mirra, Suzanne S. Nelson, Peter T. Schneider, Julie A. Thal, Dietmar Rudolf Trojanowski, John Q. Vinters, Harry V. Hyman, Bradley T. TI National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease: a practical approach SO ACTA NEUROPATHOLOGICA LA English DT Article ID BRAINNET EUROPE CONSORTIUM; LEWY BODY DISEASE; FRONTOTEMPORAL LOBAR DEGENERATION; VASCULAR COGNITIVE IMPAIRMENT; CEREBRAL AMYLOID ANGIOPATHY; HIPPOCAMPAL SCLEROSIS; DIAGNOSTIC GUIDELINES; SYNAPSE LOSS; NEUROFIBRILLARY PATHOLOGY; CONSENSUS RECOMMENDATIONS AB We present a practical guide for the implementation of recently revised National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease (AD). Major revisions from previous consensus criteria are: (1) recognition that AD neuropathologic changes may occur in the apparent absence of cognitive impairment, (2) an "ABC" score for AD neuropathologic change that incorporates histopathologic assessments of amyloid beta deposits (A), staging of neurofibrillary tangles (B), and scoring of neuritic plaques (C), and (3) more detailed approaches for assessing commonly co-morbid conditions such as Lewy body disease, vascular brain injury, hippocampal sclerosis, and TAR DNA binding protein (TDP)-43 immunoreactive inclusions. Recommendations also are made for the minimum sampling of brain, preferred staining methods with acceptable alternatives, reporting of results, and clinico-pathologic correlations. C1 [Montine, Thomas J.] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98104 USA. [Phelps, Creighton H.] NIA, Bethesda, MD 20892 USA. [Beach, Thomas G.] Banner Sun Hlth Res Inst, Civin Lab Neuropathol, Sun City, AZ USA. [Bigio, Eileen H.] Northwestern Univ, Dept Pathol, Feinberg Sch Med, Chicago, IL 60611 USA. [Bigio, Eileen H.] Northwestern Univ, NW Alzheimer Dis Ctr, Feinberg Sch Med, Chicago, IL 60611 USA. [Cairns, Nigel J.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [Cairns, Nigel J.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA. [Dickson, Dennis W.] Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA. [Duyckaerts, Charles] Hop La Pitie Salpetriere, Serv Neuropathol Raymond Escourolle, Paris, France. [Frosch, Matthew P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, CS Kubik Lab Neuropathol, Boston, MA USA. [Masliah, Eliezer] Univ Calif San Diego, Sch Med, Dept Neurosci, La Jolla, CA 92093 USA. [Masliah, Eliezer] Univ Calif San Diego, Sch Med, Dept Pathol, La Jolla, CA 92093 USA. [Mirra, Suzanne S.] Suny Downstate Med Ctr, Dept Pathol, Brooklyn, NY 11203 USA. [Nelson, Peter T.] Univ Kentucky, Sanders Brown Ctr Aging, Lexington, KY 40536 USA. [Schneider, Julie A.] Rush Univ, Rush Alzheimers Dis Ctr, Med Ctr, Dept Pathol, Chicago, IL 60612 USA. [Schneider, Julie A.] Rush Univ, Rush Alzheimers Dis Ctr, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA. [Thal, Dietmar Rudolf] Univ Ulm, Neuropathol Lab, Inst Pathol, Ulm, Germany. [Trojanowski, John Q.] Univ Penn, Sch Med, Dept Pathol & Lab Med, Inst Aging,Ctr Neurodegenerat Dis Res, Philadelphia, PA 19104 USA. [Vinters, Harry V.] Univ Calif Los Angeles, Dept Pathol & Lab Med Neuropathol, Los Angeles, CA USA. [Vinters, Harry V.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Hyman, Bradley T.] Harvard Univ, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Montine, TJ (reprint author), Univ Washington, Sch Med, Dept Pathol, Box 359791, Seattle, WA 98104 USA. EM tmontine@uw.edu OI Dickson, Dennis W/0000-0001-7189-7917 FU National Institute on Aging [AG05134, AG05136, AG03991, AG05681, AG24904, AG28383, AG10161, AG17917, AG10124, AG13854, AG19610, NS62684, AG15819, AG12435, AG05131, AG016976, AG16570, AG15866, AG18840]; Alzheimer's Association; Arizona Department of Health Services [211002]; Deutsche Forschungsgemeinschaft (DFG) [TH-624-4-1]; Alzheimer Forschung Initiative (AFI) [10810]; Nancy and Buster Alvord Endowment; Charles and Joanne Knight Alzheimer Research Initiative FX Support was provided by the National Institute on Aging (AG05134, AG05136, AG03991, AG05681, AG24904, AG28383, AG10161, AG17917, AG10124, AG13854, AG19610, NS62684, AG16570, AG15819, AG12435, AG05131, AG016976, AG16570, AG15866 and AG18840) as well as the Alzheimer's Association, Arizona Department of Health Services (contract 211002, Arizona Alzheimer's Consortium), Deutsche Forschungsgemeinschaft (DFG TH-624-4-1) and Alzheimer Forschung Initiative (AFI #10810), the Nancy and Buster Alvord Endowment, and the Charles and Joanne Knight Alzheimer Research Initiative. We thank Dr. Joshua Sonnen for providing some photomicrographs. The authors extend their deepest thanks to Dr. Heiko Braak, Dr. Kelly Del Tredici, Dr. Nina Silverberg, Dr. Walter Kukull, Dr. Kathleen Montine, Dr. Cerise Elliott, Dr. Bill Thies, Dr. Maria C. Carrillo, and Ms. Sarah Monsell for their valuable input. NR 64 TC 420 Z9 422 U1 6 U2 38 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD JAN PY 2012 VL 123 IS 1 BP 1 EP 11 DI 10.1007/s00401-011-0910-3 PG 11 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 870BF UT WOS:000298643400001 PM 22101365 ER PT J AU Mufson, EJ Binder, L Counts, SE DeKosky, ST deToledo-Morrell, L Ginsberg, SD Ikonomovic, MD Perez, SE Scheff, SW AF Mufson, Elliott J. Binder, Lester Counts, Scott E. DeKosky, Steven T. deToledo-Morrell, Leyla Ginsberg, Stephen D. Ikonomovic, Milos D. Perez, Sylvia E. Scheff, Stephen W. TI Mild cognitive impairment: pathology and mechanisms SO ACTA NEUROPATHOLOGICA LA English DT Review DE Alzheimer's disease; Amyloid; Cholinergic; Dementia; MCI; Neurofibrillary tangles; Neuropathology; Molecular; Neurotrophins; Synapses ID EARLY ALZHEIMERS-DISEASE; CHOLINERGIC BASAL FOREBRAIN; AMYLOID PRECURSOR PROTEIN; NICOTINIC ACETYLCHOLINE-RECEPTOR; ENTORHINAL CORTEX NEURONS; CENTRAL-NERVOUS-SYSTEM; PRIMARY VISUAL-CORTEX; E TYPE-4 ALLELE; SUBSTANTIA INNOMINATA; NUCLEUS BASALIS AB Mild cognitive impairment (MCI) is rapidly becoming one of the most common clinical manifestations affecting the elderly. The pathologic and molecular substrate of people diagnosed with MCI is not well established. Since MCI is a human specific disorder and neither the clinical nor the neuropathological course appears to follow a direct linear path, it is imperative to characterize neuropathology changes in the brains of people who came to autopsy with a well-characterized clinical diagnosis of MCI. Herein, we discuss findings derived from clinical pathologic studies of autopsy cases who died with a clinical diagnosis of MCI. The heterogeneity of clinical MCI imparts significant challenges to any review of this subject. The pathologic substrate of MCI is equally complex and must take into account not only conventional plaque and tangle pathology but also a wide range of cellular, biochemical and molecular deficits, many of which relate to cognitive decline as well as compensatory responses to the progressive disease process. The multifaceted nature of the neuronal disconnection syndrome associated with MCI suggests that there is no single event which precipitates this prodromal stage of AD. In fact, it can be argued that neuronal degeneration initiated at different levels of the central nervous system drives cognitive decline as a final common pathway at this stage of the dementing disease process. C1 [Mufson, Elliott J.; Counts, Scott E.; deToledo-Morrell, Leyla; Perez, Sylvia E.] Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA. [Binder, Lester] Northwestern Univ, Dept Cell & Mol Biol, Feinberg Sch Med, Chicago, IL 60611 USA. [DeKosky, Steven T.] Univ Virginia, Sch Med, Charlottesville, VA 22908 USA. [Ginsberg, Stephen D.] NYU, Langone Med Ctr, Ctr Dementia Res, Nathan Kline Inst,Dept Psychiat, Orangeburg, NY 10962 USA. [Ginsberg, Stephen D.] NYU, Langone Med Ctr, Ctr Dementia Res, Nathan Kline Inst,Dept Physiol, Orangeburg, NY 10962 USA. [Ginsberg, Stephen D.] NYU, Langone Med Ctr, Ctr Dementia Res, Nathan Kline Inst,Dept Neurosci, Orangeburg, NY 10962 USA. [Ikonomovic, Milos D.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Ikonomovic, Milos D.] Univ Pittsburgh, Dept Neurol, Educ & Clin Ctr, Pittsburgh, PA 15260 USA. [Ikonomovic, Milos D.] Univ Pittsburgh, Dept Psychiat, Educ & Clin Ctr, Pittsburgh, PA USA. [Ikonomovic, Milos D.] Univ Pittsburgh, Dept Geriatr Res, Educ & Clin Ctr, Pittsburgh, PA USA. [Scheff, Stephen W.] Univ Kentucky, Sanders Brown Ctr Aging, Lexington, KY 40536 USA. RP Mufson, EJ (reprint author), Rush Univ, Med Ctr, Dept Neurol Sci, 1735 W Harrison St,Suite 300, Chicago, IL 60612 USA. EM emufson@rush.edu OI Ginsberg, Stephen/0000-0002-1797-4288 FU NIA [PO1 AG14999, PO1 AG09466, AG10688, AG025204] FX This study was supported by NIA grants PO1 AG14999, PO1 AG09466, AG10688 and AG025204. We thank all our collaborators and the participants in each Alzheimer's Disease Center, institute and organization without whom the information reviewed would not have been possible. NR 188 TC 61 Z9 61 U1 5 U2 17 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD JAN PY 2012 VL 123 IS 1 BP 13 EP 30 DI 10.1007/s00401-011-0884-1 PG 18 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 870BF UT WOS:000298643400002 PM 22101321 ER PT J AU Augustinack, JC Huber, KE Postelnicu, GM Kakunoori, S Wang, RP van der Kouwe, AJW Wald, LL Stein, TD Frosch, MP Fischl, B AF Augustinack, Jean C. Huber, Kristen E. Postelnicu, Gheorghe M. Kakunoori, Sita Wang, Ruopeng van der Kouwe, Andre J. W. Wald, Lawrence L. Stein, Thor D. Frosch, Matthew P. Fischl, Bruce TI Entorhinal verrucae geometry is coincident and correlates with Alzheimer's lesions: a combined neuropathology and high-resolution ex vivo MRI analysis SO ACTA NEUROPATHOLOGICA LA English DT Article DE Neuroimaging; Modularity; Cortex; Ex vivo; Surface reconstruction ID MILD COGNITIVE IMPAIRMENT; PROTEIN SYNTHETIC CAPABILITY; AGE-RELATED-CHANGES; NEUROFIBRILLARY TANGLES; LAYER-II; PARAHIPPOCAMPAL GYRUS; HIPPOCAMPAL-FORMATION; PATHOLOGICAL-CHANGES; CORTEX NEURONS; SENILE PLAQUES AB Entorhinal cortex displays a distinctive organization in layer II and forms small elevations on its surface called entorhinal verrucae. In Alzheimer's disease, the verrucae disappear due to neurofibrillary tangle formation and neuronal death. Isosurface models were reconstructed from high-resolution ex vivo MRI volumes scanned at 7.0 T and individual verruca were measured quantitatively for height, width, volume, and surface area on control and mild Alzheimer's cases. Mean verruca height was 0.13 +/- A 0.04 mm for our cognitively normal (controls) sample set whereas for mild AD samples mean height was 0.11 mm +/- A 0.05 mm (p < 0.001) in entorhinal cortex (n = 10 cases). These quantitative methods were validated by a significant correlation of verrucae height and volume with qualitative verrucae ratings (n = 36 cases). Entorhinal surfaces were significantly different from other cortical heights such as, cingulate, frontal, occipital, parietal and temporal cortices. Colocalization of verrucae with entorhinal islands was confirmed in ex vivo MRI and, moreover, verrucae ratings were negatively correlated to Braak and Braak pathological stage. This study characterizes novel methods to measure individual entorhinal verruca size, and shows that verrucae size correlates to Alzheimer's pathology. Taken together, these results suggest that verrucae may have the potential to serve as an early and specific morphological marker for mild cognitive impairment and Alzheimer's disease. C1 [Augustinack, Jean C.; Huber, Kristen E.; Kakunoori, Sita; Wang, Ruopeng; van der Kouwe, Andre J. W.; Wald, Lawrence L.; Fischl, Bruce] Massachusetts Gen Hosp, Dept Pathol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Postelnicu, Gheorghe M.] Google Inc, CH-8002 Zurich, Switzerland. [Stein, Thor D.; Frosch, Matthew P.] Massachusetts Gen Hosp, Dept Neuropathol, Boston, MA 02115 USA. [Fischl, Bruce] MIT, CSAIL, Cambridge, MA 02139 USA. RP Augustinack, JC (reprint author), Massachusetts Gen Hosp, Dept Pathol, Athinoula A Martinos Ctr Biomed Imaging, Bldg 149,13th St,Room 2301, Charlestown, MA 02129 USA. EM jean@nmr.mgh.harvard.edu RI Wald, Lawrence/D-4151-2009; OI Stein, Thor/0000-0001-6954-4477 FU National Center for Research Resources [P41-RR14075]; NCRR BIRN [BIRN002, U24 RR021382]; National Institute for Biomedical Imaging and Bioengineering [R01EB006758]; National Institute on Aging [AG022381, AG028521]; National Center for Alternative Medicine [RC1AT005728-01]; National Institute for Neurological Disorders and Stroke [R01 NS052585-01, 1R21NS072652-01, 1R01NS070963]; Autism and Dyslexia Project; Ellison Medical Foundation; NIH Blueprint for Neuro-science Research [U01-MH093765]; [1S10RR023401]; [1S10RR019307]; [1S10RR023043] FX We would like to thank those who donated tissue; their generous donation made this work possible. We also thank David Salat for comments and discussion. Support for this research was provided in part by the National Center for Research Resources (P41-RR14075, and the NCRR BIRN Morphometric Project BIRN002, U24 RR021382), the National Institute for Biomedical Imaging and Bioengineering (R01EB006758), the National Institute on Aging (AG022381) and (AG028521), the National Center for Alternative Medicine (RC1AT005728-01), the National Institute for Neurological Disorders and Stroke (R01 NS052585-01, 1R21NS072652-01, 1R01NS070963), and was made possible by the resources provided by Shared Instrumentation Grants 1S10RR023401, 1S10RR019307, and 1S10RR023043. Additional support was provided by The Autism and Dyslexia Project funded by the Ellison Medical Foundation and by the NIH Blueprint for Neuro-science Research (U01-MH093765, part of the multi-institutional Human Connectome Project). NR 56 TC 9 Z9 9 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD JAN PY 2012 VL 123 IS 1 BP 85 EP 96 DI 10.1007/s00401-011-0929-5 PG 12 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 870BF UT WOS:000298643400007 PM 22160360 ER PT J AU Counter, SA Buchanan, LH Ortega, F AF Counter, S. Allen Buchanan, Leo H. Ortega, Fernando TI Acoustic stapedius muscle reflex in mercury-exposed Andean children and adults SO ACTA OTO-LARYNGOLOGICA LA English DT Article DE Middle ear muscles; brainstem; facial nerve; methylmercury; elemental mercury; neurotoxicity; environmental ID BLOOD MERCURY; HEARING-LOSS; URINE; NEUROTOXICITY; TRANSPORT; RESPONSES; HAIR; LEAD; AGE AB Conclusion: The results suggested mercury (Hg)-induced anomalies in the brainstem-mediated acoustic stapedius muscle reflex in children. Objectives: Hg exposure has been associated with hearing impairment and brainstem anomalies. Acoustic stapedius reflex (ASR) thresholds, growth functions, decay/adaptation times, and behavioral auditory thresholds were used to screen Andean children and adults for Hg-induced auditory brainstem and facial nerve impairment. Methods: Fifty-one participants, which included 22 children (aged 6-17 years) and 29 adults (aged 19-83 years) living in gold mining areas of Ecuador where Hg is widely used in amalgamation, were screened using ASR immittance procedures. Results: Mean blood mercury (HgB) level in the children was 15.6 mu g/L (SD, 21.3; median, 7 mu g/L; range, 2.0-89 mu g/L), and in the adults 8.5 mu g/L (SD, 7.1; median, 6 mu g/L; range, 2.0-32 mu g/L). Mean contralateral ASR thresholds (ASRT) for the screening frequency of 2000 Hz in the children (39 ears) was 92.9 dB HL (SD, 6.1; range, 80-105 dB HL), and in the adults (53 ears) 90.0 dB HL (SD, 6.4; range, 65-105 dB HL). The ASRT in the children increased significantly with HgB level (rho = 0.433; p = 0.008). C1 [Counter, S. Allen] Harvard Univ, Sch Med, Harvard Biol Labs, Dept Neurol, Cambridge, MA 02138 USA. [Counter, S. Allen] Massachusetts Gen Hosp, Dept Neurophysiol, Boston, MA 02114 USA. [Buchanan, Leo H.] Univ Massachusetts, Sch Med, Eunice Kennedy Shriver Ctr, Dept Pediat, Waltham, MA USA. [Buchanan, Leo H.] Harvard Univ Hlth Serv, Dept Otolaryngol, Cambridge, MA USA. [Ortega, Fernando] Univ San Francisco Quito, Coll Hlth Sci, Integrated Community Dev Dept, Quito, Ecuador. RP Counter, SA (reprint author), Harvard Univ, Sch Med, Biol Labs, Dept Neurol, 16 Divin Ave, Cambridge, MA 02138 USA. EM allen_counter@harvard.edu FU Administration of Universidad San Francisco de Quito; Fundacion Capacitar of Ecuador; Harvard Biological Laboratories; Harvard David Rockefeller Center for Latin American Studies; Shriver Center/University of Massachusetts Medical School; Harvard University FX The authors thank the Administration of Universidad San Francisco de Quito and the Fundacion Capacitar of Ecuador for support of this project. The authors thank Anthony Bruce Jacobs for excellent technical assistance, and the Mayo Medical Laboratories for laboratory support. We are grateful to the Harvard Biological Laboratories, the Harvard David Rockefeller Center for Latin American Studies, the Shriver Center/University of Massachusetts Medical School, and Dr Jeremy Bloxham of Harvard University for support. NR 20 TC 4 Z9 5 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0001-6489 J9 ACTA OTO-LARYNGOL JI Acta Oto-Laryngol. PD JAN PY 2012 VL 132 IS 1 BP 51 EP 63 DI 10.3109/00016489.2011.617778 PG 13 WC Otorhinolaryngology SC Otorhinolaryngology GA 865FM UT WOS:000298296400009 PM 22175530 ER PT J AU Rajasingham, R Mimiaga, MJ White, JM Pinkston, MM Baden, RP Mitty, JA AF Rajasingham, Radha Mimiaga, Matthew J. White, Jaclyn M. Pinkston, Megan M. Baden, Rachel P. Mitty, Jennifer A. TI A Systematic Review of Behavioral and Treatment Outcome Studies Among HIV-Infected Men Who Have Sex with Men Who Abuse Crystal Methamphetamine SO AIDS PATIENT CARE AND STDS LA English DT Review ID ACTIVE ANTIRETROVIRAL THERAPY; PLACEBO-CONTROLLED TRIAL; LOS-ANGELES-COUNTY; ILLICIT DRUG-USE; BISEXUAL MEN; RISK BEHAVIORS; CONTINGENCY MANAGEMENT; POSITIVE MEN; SAN-FRANCISCO; MEDICATION ADHERENCE AB Men who have sex with men (MSM) have the highest incidence of HIV infection in the United States. One of the contributing factors to HIV spread among this group is the use of crystal methamphetamine ("meth''). The objective was to review the behavioral impact of crystal meth use in HIV-infected MSM and potential treatment options. A systematic review of MEDLINE identified studies that evaluated the clinical effects of crystal meth on the HIV-infected MSM population. Search terms included HIV, methamphetamine, MSM, antiretroviral therapy, adherence, resistance, and treatment. U. S. citations in the English language in peer-reviewed journals until December 2010 were included. The primary author reviewed eligible articles, and relevant data including study design, sample, and outcomes were entered into an electronic data table. The 61 included studies highlight that HIV-infected MSM who use crystal meth are more likely to report high-risk sexual behaviors, incident sexually transmitted infections, and serodiscordant unprotected anal intercourse, compared to HIV-infected MSM who do not use crystal meth. Medication adherence in this population is notably low, which may contribute to transmission of resistant virus. No medications have proven effective in the treatment of crystal meth addiction, and the role of behavioral therapies, such as contingency management are still in question. HIV-infected MSM who abuse crystal meth have worse HIV-related health outcomes. Behavioral interventions have shown variable results in treating crystal meth addiction, and more investigation into rehabilitation options are needed. The results presented support efforts to develop and implement novel interventions to reduce crystal meth use in HIV-infected MSM. C1 [Rajasingham, Radha; Baden, Rachel P.; Mitty, Jennifer A.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Mimiaga, Matthew J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02215 USA. [Mimiaga, Matthew J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. [Pinkston, Megan M.] Brown Med Sch, Dept Psychiat & Human Behav, Providence, RI USA. [Mimiaga, Matthew J.; White, Jaclyn M.] Fenway Inst, Boston, MA USA. RP Rajasingham, R (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Deaconess 311,330 Brookline Ave, Boston, MA 02215 USA. EM radha.rajasingham@gmail.com FU NIH [P30 AI060354]; NIAID; NCI; NICHD; NHLBI; NIDA; NIMH; NIA; NCCAM; FIC; National Institute On Drug Abuse [R34DA031028]; National Institutes of Mental Health [R01 (5R01MH084757-03)]; TNC-CDAAR [P30DA013868] FX No competing financial interests exist. This publication was made possible with help from the Harvard University Center for AIDS Research (CFAR), an NIH funded program (P30 AI060354), which is supported by the following NIH Co-Funding and Participating Institutes and Centers: NIAID, NCI, NICHD, NHLBI, NIDA, NIMH, NIA, NCCAM, and FIC. This publication was also supported in part by Award Number R34DA031028 (PI:Mimiaga) from the National Institute On Drug Abuse. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute On Drug Abuse or the National Institutes of Health. MP was supported by National Institutes of Mental Health R01 (5R01MH084757-03) and TNC-CDAAR (P30DA013868). NR 75 TC 28 Z9 30 U1 2 U2 17 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1087-2914 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD JAN PY 2012 VL 26 IS 1 BP 36 EP 52 DI 10.1089/apc.2011.0153 PG 17 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 866SL UT WOS:000298402800006 PM 22070609 ER PT J AU Milloy, MJ Kerr, T Bangsberg, DR Buxton, J Parashar, S Guillemi, S Montaner, J Wood, E AF Milloy, M. -J. Kerr, Thomas Bangsberg, David R. Buxton, Jane Parashar, Surita Guillemi, Silvia Montaner, Julio Wood, Evan TI Homelessness as a Structural Barrier to Effective Antiretroviral Therapy Among HIV-Seropositive Illicit Drug Users in a Canadian Setting SO AIDS PATIENT CARE AND STDS LA English DT Article ID MARGINALLY HOUSED ADULTS; SAN-FRANCISCO; MEDICATION ADHERENCE; VIRAL LOAD; INFECTED INDIVIDUALS; PROTEASE INHIBITORS; FOOD INSECURITY; HOUSING STATUS; LOS-ANGELES; CELL COUNT AB Despite the advent of effective antiretroviral therapy (ART), HIV-seropositive injection drug users (IDU) continue to suffer from elevated levels of morbidity and mortality. Evidence is needed to identify social- and structural-level barriers to effective ART. We investigated the impact of homelessness on plasma HIV RNA response among illicit drug users initiating ART in a setting with free and universal access to HIV care. We accessed data from a long-running prospective cohort of community-recruited IDU linked to comprehensive HIV clinical monitoring and ART dispensation records. Using Cox proportional hazards with recurrent events modeling, we estimated the independent effect of homelessness on time to plasma HIV viral load suppression. Between May 1996 and September 2009, 247 antiretroviral naive individuals initiated ART and contributed 1755 person-years of follow-up. Among these individuals, the incidence density of plasma HIV RNA suppression less than 500 copies/mm(3) was 56.7 (95% confidence interval [CI]: 46.9-66.0) per 100 person-years. In unadjusted analyses, homelessness was strongly associated with lower rates suppression (hazard ratio = 0.56, 95% CI: 0.40-0.78, p = 0.001), however, after adjustment for adherence this association was no longer significant (adjusted hazard ratio = 0.79, 95% CI: 0.56-1.11, p = 0.177). Homelessness poses a significant structural barrier to effective HIV treatment. However, since this relationship appears to be mediated by lower levels of ART adherence, interventions to improve adherence among members of this vulnerable population are needed. C1 [Milloy, M. -J.; Kerr, Thomas; Parashar, Surita; Guillemi, Silvia; Montaner, Julio; Wood, Evan] St Pauls Hosp, BC Ctr Excellence HIV AIDS, Vancouver, BC V6Z 1Y6, Canada. [Kerr, Thomas; Montaner, Julio; Wood, Evan] Univ British Columbia, Dept Med, Vancouver, BC, Canada. [Milloy, M. -J.; Buxton, Jane] Univ British Columbia, Sch Populat & Publ Hlth, Vancouver, BC V5Z 1M9, Canada. [Bangsberg, David R.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Bangsberg, David R.] Harvard Univ, Sch Med, Boston, MA USA. [Buxton, Jane] British Columbia Ctr Dis Control, Vancouver, BC, Canada. RP Wood, E (reprint author), St Pauls Hosp, BC Ctr Excellence HIV AIDS, 608-1081 Burrard St, Vancouver, BC V6Z 1Y6, Canada. EM uhri-ew@cfenet.ubc.ca FU US National Institutes of Health [R01DA021525]; Canadian Institutes of Health Research (CHIR) [MOP-79297, RAA-79918]; Michael Smith Foundation for Health Research; Abbott Laboratories; Agouron Pharmaceuticals Inc.; Boehringer Ingelheim Pharmaceuticals Inc.; Borean Pharma AS; Bristol-Myers Squibb; DuPont Pharma; Gilead Sciences; GlaxoSmithKline; Hoffmann-La Roche; Immune Response Corporation; Incyte; Janssen-Ortho Inc.; Kucera Pharmaceutical Company; Merck Frosst Laboratories; Pfizer Canada Inc.; Sanofi Pasteur; Shire Biochem Inc.; Tibotec Pharmaceuticals Ltd.; Trimeris Inc. FX The authors thank the study participants for their contribution to the research as well as current and past researchers and staff. We would specifically like to thank Deborah Graham, Tricia Collingham, Caitlin Johnston, Steve Kain, and Calvin Lai for their research and administrative assistance. The study was supported by the US National Institutes of Health (R01DA021525) and the Canadian Institutes of Health Research (MOP-79297, RAA-79918). Thomas Kerr is supported by the Michael Smith Foundation for Health Research and the Canadian Institutes of Health Research (CIHR). M.-J. Milloy is supported by a doctoral research award from CIHR.; Dr. Montaner has received educational grants from, served as an ad hoc adviser to or spoken at various events sponsored by Abbott Laboratories, Agouron Pharmaceuticals Inc., Boehringer Ingelheim Pharmaceuticals Inc., Borean Pharma AS, Bristol-Myers Squibb, DuPont Pharma, Gilead Sciences, GlaxoSmithKline, Hoffmann-La Roche, Immune Response Corporation, Incyte, Janssen-Ortho Inc., Kucera Pharmaceutical Company, Merck Frosst Laboratories, Pfizer Canada Inc., Sanofi Pasteur, Shire Biochem Inc., Tibotec Pharmaceuticals Ltd., and Trimeris Inc. Dr. Bangsbergh receives research support from Abbott Laboratories, Gilead Sciences, and Bristol-Myers Squibb. NR 58 TC 41 Z9 41 U1 3 U2 8 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1087-2914 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD JAN PY 2012 VL 26 IS 1 BP 60 EP 67 DI 10.1089/apc.2011.0169 PG 8 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 866SL UT WOS:000298402800008 PM 22107040 ER PT J AU Cullen, G Kroshinsky, D Cheifetz, AS Korzenik, JR AF Cullen, G. Kroshinsky, D. Cheifetz, A. S. Korzenik, J. R. TI Anti-TNF associated psoriasis: authors' reply SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material C1 [Cullen, G.; Korzenik, J. R.] Massachusetts Gen Hosp, Crohns & Colitis Ctr, Boston, MA 02114 USA. [Kroshinsky, D.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Cullen, G.; Cheifetz, A. S.] Beth Israel Deaconess Med Ctr, Div Gastroenterol, Boston, MA 02215 USA. [Cullen, G.; Kroshinsky, D.; Cheifetz, A. S.; Korzenik, J. R.] Harvard Univ, Sch Med, Boston, MA USA. RP Cullen, G (reprint author), Massachusetts Gen Hosp, Crohns & Colitis Ctr, Boston, MA 02114 USA. EM gcullen@bidmc.harvard.edu NR 2 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0269-2813 J9 ALIMENT PHARM THER JI Aliment. Pharmacol. Ther. PD JAN PY 2012 VL 35 IS 2 BP 309 EP 310 DI 10.1111/j.1365-2036.2011.04945.x PG 2 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 862JI UT WOS:000298086600012 ER PT J AU White, WB Grady, D Giudice, LC Berry, SM Zborowski, J Snabes, MC AF White, William B. Grady, Deborah Giudice, Linda C. Berry, Scott M. Zborowski, Joanne Snabes, Michael C. TI A cardiovascular safety study of LibiGel (testosterone gel) in postmenopausal women with elevated cardiovascular risk and hypoactive sexual desire disordera SO AMERICAN HEART JOURNAL LA English DT Article ID SURGICALLY MENOPAUSAL WOMEN; METABOLIC SYNDROME; BREAST-CANCER; UNITED-STATES; HEALTH; DYSFUNCTION; PREVALENCE; EVENTS; MEN; ESTROGEN AB Evaluation of the safety of hormonal preparations for the treatment of female sexual dysfunction is important to assess the benefit-to-risk profile of these drugs and has been strongly encouraged by the Food and Drug Administration. LibiGel (Biosante Pharmaceuticals, Inc., Lincolnshire, IL), a low-dose testosterone gel, is under development for the treatment of hypoactive sexual desire disorder (HSDD) in oophorectomized women. To evaluate the long-term effects of LibiGel on risk for cardiovascular (CV) events, breast cancer, and general safety, a randomized, placebo-controlled clinical study using a novel adaptive design to optimize sample size and power is being conducted. The primary end point of the BioSante LibiGel Safety Study (BLISS) is a composite of CV events including death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, hospitalized unstable angina, and venous thromboembolic events. Breast cancer is a coprimary end point. Postmenopausal women (both surgically and naturally) with HSDD and increased risk for CV events will be followed up for up to 5 years postrandomization with an interim data analysis for regulatory approval after the last woman enrolled has been on therapy for at least 12 months. Determination of the number of subjects to enroll is based on an adaptive design that uses interim data to estimate the predictive probability of study success. In agreement with the Food and Drug Administration, LibiGel will be declared safe if the upper limit of the 97.2% CI of the hazard ratio is <= 2.0 or the upper bound of the 97.2% CI for the absolute difference between CV event rates per 100 person-years is <= 1% and the observed hazard ratio is <= 2.0. The BLISS study will define the CV safety profile of low-dose testosterone therapy in the formulation of LibiGel for postmenopausal women with HSDD, and the trial design may provide a paradigm for studies that aim to document long-term safety when the proposed outcome under study is an uncommon adverse event. (Am Heart J 2012;163:27-32.) C1 [White, William B.] Univ Connecticut, Sch Med, Calhoun Cardiol Ctr, Div Hypertens & Clin Pharmacol, Farmington, CT 06030 USA. [Grady, Deborah] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Grady, Deborah] Univ Calif San Francisco, San Francisco Vet Adm Med Ctr, San Francisco, CA 94143 USA. [Giudice, Linda C.] Univ Calif San Francisco, Dept Obstet & Gynecol & Reprod Sci, San Francisco, CA 94143 USA. [Berry, Scott M.] Berry Consultants, Austin, TX USA. [Zborowski, Joanne; Snabes, Michael C.] Biosante Pharmaceut Inc, Lincolnshire, IL USA. RP White, WB (reprint author), Univ Connecticut, Sch Med, Calhoun Cardiol Ctr, Div Hypertens & Clin Pharmacol, 263 Farmington Ave, Farmington, CT 06030 USA. EM wwhite@nso1.uchc.edu FU BioSante Pharmaceuticals, Inc, Lincolnshire, IL FX The sponsor of this study is BioSante Pharmaceuticals, Inc, Lincolnshire, IL. NR 26 TC 23 Z9 25 U1 0 U2 3 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 JAN PY 2012 VL 163 IS 1 BP 27 EP 32 DI 10.1016/j.ahj.2011.09.021 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 863HI UT WOS:000298153000007 PM 22172433 ER PT J AU Diercks, DB Peacock, WF Hollander, JE Singer, AJ Birkhahn, R Shapiro, N Glynn, T Nowack, R Safdar, B Miller, CD Lewandrowski, E Nagurney, JT AF Diercks, Deborah B. Peacock, W. Frank Hollander, Judd E. Singer, Adam J. Birkhahn, Robert Shapiro, Nathan Glynn, Ted Nowack, Richard Safdar, Basmah Miller, Chadwick D. Lewandrowski, Elizabeth Nagurney, John T. CA MIDAS Investigators TI Diagnostic accuracy of a point-of-care troponin I assay for acute myocardial infarction within 3 hours after presentation in early presenters to the emergency department with chest pain SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE CORONARY SYNDROME; SYMPTOMS; BIOMARKERS; PROTOCOL; RISK AB Background Guidelines recommend that serial cardiac marker testing to rule out acute myocardial infarction (AMI) be performed for 8 to 12 hours after symptom onset. We aim to determine the diagnostic accuracy of a contemporary point-of-care (POC) troponin I (TnI) assay within 3 hours for patients presenting within 8 hours of symptom onset. Methods The MIDAS study collected blood from patients presenting with suspected acute coronary syndrome at presentation and at 90 minutes, 3 hours, and 6 hours in whom the emergency physician planned an objective cardiac ischemia evaluation. Criterion standard diagnoses were adjudicated by experienced clinicians using all available medical records per American Heart Association/American College of Cardiology criteria. Reviewers were blinded to the investigational marker, Cardio3 TnI POC. The Cardio3 TnI reference value was defined as >0.05 ng/mL. Measures of diagnostic accuracy are presented with 95% CI. Results A total of 858 of 1107 patients met the inclusion criteria. The study cohort had 476 men (55.5%) with median age of 57.0 years (interquartile range 48.0-67.0 years). Median time from symptom onset to initial blood draw was 3.9 hours (interquartile range 2.7-5.2 hours). Acute myocardial infarction was diagnosed in 82 patients (9.6%). The sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio over 3 hours were 84.1, 93.4, 12.8, and 0.17, respectively. There was no significant improvement in diagnostic accuracy associated with adding 6-hour serial testing to the 3-hour sample. Conclusion In suspected patients with acute coronary syndrome presenting to the emergency department within 8 hours of symptom onset, 3 hours of serial testing with the Cardio3 TnI POC platform provides similar diagnostic accuracy for AMI as longer periods. (Am Heart J 2012;163:74-80.e4.) C1 [Diercks, Deborah B.] Univ Calif Davis, Sacramento, CA 95817 USA. [Peacock, W. Frank] Cleveland Clin, Cleveland, OH 44106 USA. [Hollander, Judd E.] Univ Penn, Philadelphia, PA 19104 USA. [Singer, Adam J.] Stony Brook Univ & Med Ctr, Stony Brook, NY USA. [Birkhahn, Robert] New York Methodist Hosp, Brooklyn, NY USA. [Shapiro, Nathan] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Glynn, Ted] Ingham Reg Med Ctr, Lansing, MT USA. [Diercks, Deborah B.; Peacock, W. Frank; Hollander, Judd E.; Singer, Adam J.; Birkhahn, Robert; Shapiro, Nathan; Glynn, Ted; Nowack, Richard; Safdar, Basmah; Miller, Chadwick D.; Lewandrowski, Elizabeth; Nagurney, John T.] Henry Ford Med Ctr, Detroit, MI USA. [Nowack, Richard; Safdar, Basmah] Yale Univ, New Haven, CT USA. [Miller, Chadwick D.] Wake Forest Univ Hlth Sci, Winston Salem, NC USA. [Lewandrowski, Elizabeth; Nagurney, John T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Diercks, DB (reprint author), UCMDC, 2315 Stockton Blvd,PSSB 2100, Sacramento, CA 95817 USA. EM dbdiercks@ucdavis.edu RI Shapiro, Nathan/F-1718-2016; OI Hollander, Judd/0000-0002-1318-2785 FU Inverness Medical FX This study was funded by Inverness Medical. NR 17 TC 23 Z9 26 U1 0 U2 6 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 JAN PY 2012 VL 163 IS 1 BP 74 EP U102 DI 10.1016/j.ahj.2011.09.028 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 863HI UT WOS:000298153000013 PM 22172439 ER PT J AU Rienstra, M Sun, JX Lubitz, SA Frankel, DS Vasan, RS Levy, D Magnani, JW Sullivan, LM Meigs, JB Ellinor, PT Benjamin, EJ AF Rienstra, Michiel Sun, Jenny X. Lubitz, Steven A. Frankel, David S. Vasan, Ramachandran S. Levy, Daniel Magnani, Jared W. Sullivan, Lisa M. Meigs, James B. Ellinor, Patrick T. Benjamin, Emelia J. TI Plasma resistin, adiponectin, and risk of incident atrial fibrillation: The Framingham Offspring Study SO AMERICAN HEART JOURNAL LA English DT Article ID CONGESTIVE-HEART-FAILURE; C-REACTIVE PROTEIN; MYOCARDIAL-INFARCTION; OBESITY; ONSET; PIOGLITAZONE; HYPERTENSION; INFLAMMATION; INDIVIDUALS; POPULATION AB Background We sought to investigate whether higher concentrations of resistin and lower concentrations of adiponectin relate to incident atrial fibrillation (AF) and whether this association is mediated by AF risk factors and inflammation. Resistin and adiponectin are adipokines that have been associated with multiple known risk factors for AF including diabetes, obesity, inflammation, and heart failure. Methods We studied the relations between circulating concentrations of both adipokines and incident AF in participants of the Framingham Offspring Study. Results Participants (n = 2,487) had a mean age of 61 +/- 10 years, and 54% were women. During a mean follow-up of 7.6 +/- 2.0 years, 206 (8.3%) individuals (96 women) developed incident AF. Plasma resistin concentration was significantly associated with incident AF (multivariable-adjusted hazard ratio [HR] 1.17 per SD [0.41 ng/mL] of natural logarithmically transformed resistin, 95% CI 1.02-1.34, P =.028). The resistin-AF association was attenuated after further adjustment for C-reactive protein (HR per SD increase resistin 1.14, 95% CI 0.99-1.31, P =.073). Adiponectin concentrations were not significantly associated with incident AF (multivariable-adjusted HR of 0.95 per SD [0.62 mu g/mL] of logarithmically transformed adiponectin, 95% CI 0.81-1.10, P =.478). Conclusion In our community-based longitudinal study, higher mean concentrations of resistin were associated with incident AF, but the relation was attenuated by adjustment for C-reactive protein. We did not detect a statistically significant association between adiponectin and incident AF. Additional studies are needed to clarify the potential role of adipokines in AF and mechanisms linking adiposity to AF. (Am Heart J 2012; 163: 119-124. e1.) C1 [Rienstra, Michiel; Vasan, Ramachandran S.; Levy, Daniel; Magnani, Jared W.; Meigs, James B.; Ellinor, Patrick T.; Benjamin, Emelia J.] Boston Univ, Framingham Heart Study, Framingham, MA 01702 USA. [Rienstra, Michiel] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands. [Rienstra, Michiel; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [Rienstra, Michiel; Vasan, Ramachandran S.; Levy, Daniel; Magnani, Jared W.; Meigs, James B.; Benjamin, Emelia J.] NHLBI, Framingham, MA USA. [Sun, Jenny X.; Sullivan, Lisa M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Lubitz, Steven A.; Ellinor, Patrick T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, Boston, MA USA. [Frankel, David S.] Hosp Univ Penn, Dept Med, Div Cardiovasc, Philadelphia, PA 19104 USA. [Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Prevent Med Sect, Framingham, MA 01702 USA. [Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Framingham, MA 01702 USA. [Vasan, Ramachandran S.; Magnani, Jared W.; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Cardiol Sect, Framingham, MA 01702 USA. [Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [Meigs, James B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med,Dept Med, Boston, MA USA. RP Benjamin, EJ (reprint author), Boston Univ, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM emelia@bu.edu OI Ramachandran, Vasan/0000-0001-7357-5970; Sullivan, Lisa/0000-0003-0726-7149; Benjamin, Emelia/0000-0003-4076-2336; Rienstra, Michiel/0000-0002-2581-070X FU National Heart, Lung, and Blood Institute; NHLBI/NIH [N01-HC-25195]; Boston University School of Medicine; Netherlands Organization for Scientific Research [825.09.020]; National Institutes of Health [1R01HL092577, 1RC1HL101056, 1R01HL102214, R01AG028321, 6R01-NS17950, 5R21DA027021, 5RO1HL104156, 1K24HL105780, R01-DK-080739]; American Heart Association [09FTF2190028]; Evans Center for Interdisciplinary Biomedical Research ARC on "Atrial Fibrillation" at Boston University FX The Framingham Heart Study is supported by National Heart, Lung, and Blood Institute; Framingham Heart Study (NHLBI/NIH contract N01-HC-25195); and the Boston University School of Medicine. Dr Rienstra is supported by a grant from the Netherlands Organization for Scientific Research (Rubicon grant 825.09.020). This work was supported by grants from the National Institutes of Health to Drs Benjamin and Ellinor (1R01HL092577); Dr Benjamin (1RC1HL101056, 1R01HL102214, R01AG028321; and support via 6R01-NS17950) and Dr Ellinor (5R21DA027021, 5RO1HL104156, 1K24HL105780); and Dr Vasan (R01-DK-080739). Dr Magnani is supported by American Heart Association Award 09FTF2190028. This work was partially supported by the Evans Center for Interdisciplinary Biomedical Research ARC on "Atrial Fibrillation" at Boston University (http://www.bumc.bu.edu/evanscenteribr/). NR 37 TC 26 Z9 26 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JAN PY 2012 VL 163 IS 1 BP 119 EP U151 DI 10.1016/j.ahj.2011.09.029 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 863HI UT WOS:000298153000019 PM 22172445 ER PT J AU Steinhaus, DA Vittinghoff, E Moffatt, E Hart, AP Ursell, P Tseng, ZH AF Steinhaus, Daniel A. Vittinghoff, Eric Moffatt, Ellen Hart, Amy P. Ursell, Philip Tseng, Zian H. TI Characteristics of sudden arrhythmic death in a diverse, urban community SO AMERICAN HEART JOURNAL LA English DT Article ID MULTIPLE SOURCE SURVEILLANCE; CARDIAC DEATH; MYOCARDIAL-INFARCTION; TEMPORAL TRENDS; CORONARY DEATH; POPULATION; RISK; EPIDEMIOLOGY; PREVENTION; ETIOLOGY AB Background Sudden cardiac death (SCD) remains a major public health problem; however, its true burden remains unknown with widely variable estimates of its incidence. We aimed to examine the contemporary epidemiology and autopsy characteristics of SCD in an ethnically diverse community. Methods Three physicians reviewed all deaths of individuals aged >= 20 years reported to the San Francisco medical examiner in 2007 for presentations fitting World Health Organization (WHO) SCD criteria-within 1 hour of symptom onset (witnessed) or within 24 hours of being observed alive and symptom free (unwitnessed). After comprehensive review of medical examiner investigation, WHO SCDs were classified as sudden arrhythmic death (SAD) or nonarrhythmic death. Coronary artery disease (CAD) and cardiac mass were evaluated in all SADs undergoing autopsy and compared with demographically similar accidental trauma control deaths. Results We identified 252 WHO SCDs; 145 were SADs. Men had a 2.2-fold higher SAD rate (P < .0005). Blacks had a 3.15-fold higher SAD rate compared with whites (P = .003). Significant CAD was present in 38.9% of SADs and associated with higher SAD risk compared with control deaths (OR 2.58, 95% CI 1.12-5.97, P = .026). Mean cardiac mass was linearly associated with risk for SAD in cases without significant CAD (OR 2.06 per 100 g, 95% CI 1.43-2.98, P < .0005). Conclusions In a diverse, urban population, SAD incidence varied substantially by gender and race. Significant CAD accounted for far fewer SADs than previous studies but remained associated with a 2.6-fold higher risk as compared with control deaths. These findings may reflect the evolving contemporary epidemiology of SCD. (Am Heart J 2012;163:125-31.) C1 [Tseng, Zian H.] Univ Calif San Francisco, Sect Cardiac Electrophysiol, Dept Med, Div Cardiol, San Francisco, CA 94143 USA. [Steinhaus, Daniel A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Vittinghoff, Eric] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Moffatt, Ellen; Hart, Amy P.] City & Cty San Francisco, Office Chief Med Examiner, San Francisco, CA USA. [Ursell, Philip] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA. RP Tseng, ZH (reprint author), Univ Calif San Francisco, Sect Cardiac Electrophysiol, Dept Med, Div Cardiol, 500 Parnassus Ave,Box 1354, San Francisco, CA 94143 USA. EM zhtseng@medicine.ucsf.edu FU National Center for Research Resources, a component of the National Institutes of Health (NIH); NIH Roadmap for Medical Research [KL2 RR024130]; National Heart, Lung, and Blood Institute [R01 HL102090-01A1] FX This research was funded by grants from the National Center for Research Resources, a component of the National Institutes of Health (NIH) and NIH Roadmap for Medical Research (KL2 RR024130) and the National Heart, Lung, and Blood Institute (R01 HL102090-01A1), both to ZHT. There are no relationships with industry. NR 27 TC 13 Z9 13 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD JAN PY 2012 VL 163 IS 1 BP 125 EP 131 DI 10.1016/j.ahj.2011.09.016 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 863HI UT WOS:000298153000020 PM 22172446 ER PT J AU Berger, JS Bhatt, DL AF Berger, Jeffery S. Bhatt, Deepak L. TI Reply to the letter by Chatterjee et al "Bleeding, mortality, and antiplatelet therapy: Results from the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) trial" SO AMERICAN HEART JOURNAL LA English DT Letter C1 [Berger, Jeffery S.] NYU, Sch Med, New York, NY 10016 USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Berger, JS (reprint author), NYU, Sch Med, 530 1st Ave,Skirball 9R, New York, NY 10016 USA. EM Jeffrey.berger@nyumc.org; DLBHATTMD@post.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JAN PY 2012 VL 163 IS 1 BP E3 EP E3 DI 10.1016/j.ahj.2011.10.005 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 863HI UT WOS:000298153000002 ER PT J AU Rosenblum, JL Castro, VM Moore, CE Kaplan, LM AF Rosenblum, Jennifer L. Castro, Victor M. Moore, Carolyn E. Kaplan, Lee M. TI Calcium and vitamin D supplementation is associated with decreased abdominal visceral adipose tissue in overweight and obese adults SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID PLACEBO-CONTROLLED TRIAL; WEIGHT-LOSS; BODY-WEIGHT; FAT LOSS; DIETARY CALCIUM; DAIRY; WOMEN; HEALTHY; RISK; ADOLESCENTS AB Background: Several studies suggest that calcium and vitamin D (CaD) may play a role in the regulation of abdominal fat mass. Objective: This study investigated the effect of CaD-supplemented orange juice (OJ) on weight loss and reduction of visceral adipose tissue (VAT) in overweight and obese adults (mean +/- SD age: 40.0 +/- 12.9 y). Design: Two parallel, double-blind, placebo-controlled trials were conducted with either regular or reduced-energy (lite) orange juice. For each 16-wk trial, 171 participants were randomly assigned to 1 of 2 groups. The treatment groups consumed three 240-mL glasses of OJ (regular or lite) fortified with 350 mg Ca and 100 IU vitamin D per serving, and the control groups consumed either unfortified regular or lite OJ. Computed tomography scans of VAT and subcutaneous adipose tissue were performed by imaging a single cut at the lumbar 4 level. Results: After 16 wk, the average weight loss (similar to 2.45 kg) did not differ significantly between groups. In the regular OJ trial, the reduction of VAT was significantly greater (P = 0.024) in the CaD group (-12.7 +/- 25.0 cm(2)) than in the control group (-1.3 +/- 13.6 cm(2)). In the lite OJ trial, the reduction of VAT was significantly greater (P = 0.039) in the CaD group (-13.1 +/- 18.4 cm(2)) than in the control group (-6.4 +/- 17.5 cm(2)) after control for baseline VAT. The effect of calcium and vitamin D on VAT remained highly significant when the results of the 2 trials were combined (P = 0.007). Conclusions: The findings suggest that calcium and/or vitamin D supplementation contributes to a beneficial reduction of VAT. This trial is registered at clinicaltrial.gov as NCT00386672, NCT01363115. Am J Clin Nutr 2012;95:101-8. C1 [Rosenblum, Jennifer L.; Castro, Victor M.; Kaplan, Lee M.] Massachusetts Gen Hosp, Weight Ctr, Boston, MA 02114 USA. [Rosenblum, Jennifer L.; Castro, Victor M.; Kaplan, Lee M.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Kaplan, LM (reprint author), Massachusetts Gen Hosp, Weight Ctr, 50 Staniford St,4th Floor, Boston, MA 02114 USA. EM lmkaplan@partners.org FU National Institute of Diabetes and Digestive and Kidney Diseases [DK046200]; Beverage Institute for Health & Wellness of The Coca-Cola Company; Massachusetts General Hospital Weight Center FX Supported by the National Institute of Diabetes and Digestive and Kidney Diseases (DK046200), Beverage Institute for Health & Wellness of The Coca-Cola Company, and the Massachusetts General Hospital Weight Center. NR 42 TC 47 Z9 50 U1 5 U2 24 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JAN PY 2012 VL 95 IS 1 BP 101 EP 108 DI 10.3945/ajcn.111.019489 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 866SF UT WOS:000298402100014 PM 22170363 ER PT J AU Ryan, RJH Sloan, JM Collins, AB Mansouri, J Raje, NS Zukerberg, LR Ferry, JA AF Ryan, Russell J. H. Sloan, J. Mark Collins, A. Bernard Mansouri, Jaleh Raje, Noopur S. Zukerberg, Lawrence R. Ferry, Judith A. TI Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue With Amyloid Deposition A Clinicopathologic Case Series SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE Lymphoma; MALT lymphoma; Marginal zone lymphoma; Amyloid ID B-CELL LYMPHOMA; OF-THE-LITERATURE; LOCALIZED PULMONARY AMYLOIDOSIS; PRIMARY SJOGRENS-SYNDROME; ABDOMINAL FAT PAD; SYSTEMIC AMYLOIDOSIS; MALT-LYMPHOMA; MALIGNANT-LYMPHOMA; PREDICTIVE-VALUE; NERVOUS-SYSTEM AB Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) lymphoma is a mature B-cell neoplasm that typically/follows an indolent clinical course. Amyloid deposition associated with MALT lymphoma is uncommon. We describe the clinical and pathologic features of 20 cases of MALT lymphoma and associated amyloid deposition across diverse primary sites. Frozen section immunofluorescence performed on 4 cases suggests that these deposits are a localized form of AL amyloid. Clinical follow-up was available for 15 patients. Amyloid deposits distant from the initial site occurred in 5 cases, always at sites also involved by the underlying lymphoma. No definitive evidence of systemic amyloidosis affecting the heart, kidneys, or liver was present in any patient. Given the generally indolent clinical behavior of MALT lymphomas with associated amyloid, we do not recommend extensive follow-up testing for systemic amyloidosis or more aggressive therapy than would be indicated for other MALT lymphomas of similar clinical stage. C1 [Ryan, Russell J. H.; Collins, A. Bernard; Zukerberg, Lawrence R.; Ferry, Judith A.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Raje, Noopur S.] Massachusetts Gen Hosp, Dept Med, Hematol Oncol Unit, Boston, MA 02114 USA. [Sloan, J. Mark] Boston Univ, Amyloid Res & Treatment Program, Boston, MA 02215 USA. [Mansouri, Jaleh] Lowell Gen Hosp, Dept Pathol, Lowell, MA USA. RP Ryan, RJH (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren 2, Boston, MA 02114 USA. OI Sloan, John/0000-0001-7069-4528 FU Pathology Department, Massachusetts General Hospital FX Supported by the Pathology Department, Massachusetts General Hospital. NR 38 TC 12 Z9 12 U1 0 U2 5 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD JAN PY 2012 VL 137 IS 1 BP 51 EP 64 DI 10.1309/AJCPI08WAKYVLHHA PG 14 WC Pathology SC Pathology GA 865WC UT WOS:000298340600008 PM 22180478 ER PT J AU Kim, JY Dzik, WH Dighe, AS Lewandrowski, KB AF Kim, Ji Yeon Dzik, Walter H. Dighe, Anand S. Lewandrowski, Kent B. TI Laboratory Test Utilization Reply SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Letter C1 [Kim, Ji Yeon; Dzik, Walter H.; Dighe, Anand S.; Lewandrowski, Kent B.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Kim, JY (reprint author), Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD JAN PY 2012 VL 137 IS 1 BP 166 EP 166 PG 1 WC Pathology SC Pathology GA 865WC UT WOS:000298340600025 ER PT J AU Ujkaj, M Davidoff, DA Seiner, SJ Ellison, JM Harper, DG Forester, BP AF Ujkaj, Manjola Davidoff, Donald A. Seiner, Stephen J. Ellison, James M. Harper, David G. Forester, Brent P. TI Safety and Efficacy of Electroconvulsive Therapy for the Treatment of Agitation and Aggression in Patients With Dementia SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE agitation; aggression; BPSD; dementia; ECT; elderly; electroconvulsive therapy ID ILLNESS RATING-SCALE; DEPRESSED OLDER-ADULTS; ELDERLY-PATIENTS; ALZHEIMERS-DISEASE; NEUROPSYCHIATRIC SYMPTOMS; CASE SERIES; ECT; SCHIZOPHRENIA; PROPOFOL; DISORDER AB Objectives: Noncognitive behavioral disturbances including agitation and aggression frequently accompany the cognitive symptoms of dementia accounting for much of dementia's morbidity, yet treatment options are currently limited. The authors examine the safety and efficacy of Electroconvulsive Therapy (ECT) for agitation and aggression in dementia patients. Design: Retrospective systematic chart review. Setting: McLean Hospital's geriatric neuropsychiatry unit. Participants: Sixteen patients with a diagnosis of dementia treated with ECT for agitation/aggression during 2004-2007. Measurements: Clinical charts were rated on the Pittsburgh Agitation Scale as the primary outcome, the Clinical Global Impression scale and the Global Assessment of Functioning pre- and post-ECT. Results: 16 patients of mean age 66.6 +/- 8.3 years were studied. Their average overall and pre-ECT lengths of stay were 59.7 +/- 39.7 days and 23 +/- 15.7 days, respectively. Patients received a mean of 9 ECT treatments, mostly bilateral. Patients showed significant reductions in their total Pittsburgh Agitation Scale scores from baseline after ECT (from 11.0 +/- 5.0 to 3.9 +/- 4.3 [F = 30.33, df = 1, 15, p < 0.001]). Clinical Global Impression scale decreased significantly (from 6.0 +/- 0.6 pre-ECT to 2.1 +/- 1.6 post-ECT [F = 112.97, df = 1, 15, p < 0.001]). Global Assessment of Functioning change was not significant (from 23.0 +/- 4.9 to 26.9 +/- 6.9 [F = 5.73, df = 1, 13, p = 0.32]). Only one patient, in whom ECT was discontinued following 11 bilateral treatments, showed no improvement. Eight patients showed transient postictal confusion, which typically resolved within 48 hours. Two patients showed more severe postictal confusion that required modification of treatment. Conclusions: These results suggest that ECT is an effective and safe treatment for agitation and aggression in dementia. Further prospective studies are warranted. (Am J Geriatr Psychiatry 2012; 20: 61-72) C1 [Ujkaj, Manjola] Harvard Univ, VA Boston Healthcare Syst, Harvard S Shore Psychiat Residency Training Progr, Dept Psychiat,Sch Med,Brockton Div, Brockton, MA 02301 USA. [Davidoff, Donald A.] Harvard Univ, McLean Hosp, Sch Med, Dept Neuropsychol, Belmont, MA 02178 USA. [Davidoff, Donald A.; Seiner, Stephen J.; Ellison, James M.; Harper, David G.; Forester, Brent P.] Harvard Univ, McLean Hosp, Sch Med, Dept Psychiat, Belmont, MA 02178 USA. RP Ujkaj, M (reprint author), Harvard Univ, VA Boston Healthcare Syst, Harvard S Shore Psychiat Residency Training Progr, Dept Psychiat,Sch Med,Brockton Div, Bldg 5,940 Belmont St, Brockton, MA 02301 USA. EM manjola_ujkaj@hms.harvard.edu NR 49 TC 14 Z9 14 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 EI 1545-7214 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD JAN PY 2012 VL 20 IS 1 BP 61 EP 72 DI 10.1097/JGP.0b013e3182051bbc PG 12 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 869ZQ UT WOS:000298639300007 PM 22143072 ER PT J AU Goodfriend, T AF Goodfriend, Theodore TI Molecular Trafficking of Angiotensin Receptors SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Editorial Material C1 William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. RP Goodfriend, T (reprint author), William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. EM tgoodfri@facstaff.wisc.edu NR 2 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD JAN PY 2012 VL 25 IS 1 BP 23 EP 23 DI 10.1038/ajh.2011.222 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 864UE UT WOS:000298264800008 PM 22170076 ER PT J AU O'Seaghdha, CM Yang, Q Wu, HS Hwang, SJ Fox, CS AF O'Seaghdha, Conall M. Yang, Qiong Wu, Hongsheng Hwang, Shih-Jen Fox, Caroline S. TI Performance of a Genetic Risk Score for CKD Stage 3 in the General Population SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Chronic kidney disease; genetics; risk prediction ID CHRONIC KIDNEY-DISEASE; CORONARY-HEART-DISEASE; GLOMERULAR-FILTRATION-RATE; DIABETIC-NEPHROPATHY; RENAL-INSUFFICIENCY; UNITED-STATES; PREVALENCE; ADULTS; PREDICTION; FRAMINGHAM AB Background: Recent genome-wide association studies have identified multiple genetic loci that increase the risk of chronic kidney disease (CKD) in the general population. We hypothesized that knowledge of these loci might permit improved CKD risk prediction beyond that provided by traditional phenotypic risk factors. Study Design: Observational cohort study. Setting & Participants: Participants who attended the 15th (1977-1979) and 24th (1995-1998) examination cycles of the original cohort or the 6th (1995-1998) and 8th cycles (2005-2008) of the offspring cohort of the Framingham Heart Study (n = 2,489). Predictors: Single-nucleotide polymorphisms at 16 stage 3 CKD loci were genotyped and used to construct a genetic risk score. Standard clinical predictors of incident stage 3 CKD also were used. Outcomes & Measurements: Incident stage 3 CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m(2) at follow-up. Participants with baseline stage 3 CKD were excluded. Logistic regression was used to generate C statistics, which measured the power of the genetic risk score to discriminate risk of incident CKD stage 3 with and without traditional risk factors. Results: There were 270 new stage 3 CKD cases during an average of 10.8 years of follow-up. Mean genetic risk score was 17.5 +/- 2.8 (SD) for those who developed stage 3 CKD and 17.3 +/- 2.6 for those who did not (P for genotype score difference = 0.2). The OR for stage 3 CKD was 1.06 (95% CI, 1.01-1.11; P = 0.03) per additional risk allele, adjusting for age and sex. In the age-and sex-adjusted model, the C statistic was 0.748 without the genotype score and 0.751 with the score (P difference = 0.3). The risk score was not statistically significant in a multivariable model adjusted for standard stage 3 CKD risk factors (P = 0.07). Limitations: All participants were of European ancestry; the genotype score may not be valid in different ancestral groups. Conclusions: A genetic score generated from 16 known CKD risk alleles did not predict new cases of stage 3 CKD in the community beyond knowledge of common clinical risk factors alone. Am J Kidney Dis. 59(1): 19-24. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is a US Government Work. There are no restrictions on its use. C1 [O'Seaghdha, Conall M.; Hwang, Shih-Jen; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [O'Seaghdha, Conall M.; Hwang, Shih-Jen; Fox, Caroline S.] Ctr Populat Studies, Framingham, MA USA. [O'Seaghdha, Conall M.] Massachusetts Gen Hosp, Div Renal, Brigham & Womens Hosp, Boston, MA 02114 USA. [O'Seaghdha, Conall M.; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA. [Yang, Qiong; Wu, Hongsheng] Boston Univ, Dept Biostat, Boston, MA 02215 USA. [Wu, Hongsheng] Wentworth Inst Technol, Dept Comp Sci, Boston, MA USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA. RP Fox, CS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Ste 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov RI Yang, Qiong/G-5438-2014 FU NHLBI's FHS [N01-HC-25195] FX This research was conducted in part using data and resources from the FHS of the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health and Boston University School of Medicine. This work was partially supported by the NHLBI's FHS (Contract No. N01-HC-25195). The sponsors had no role in the conduct or interpretation of the study. The corresponding author had full access to all data in the study and had final responsibility for the decision to submit for publication. NR 41 TC 12 Z9 12 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 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD JAN PY 2012 VL 59 IS 1 BP 19 EP 24 DI 10.1053/j.ajkd.2011.08.030 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 863HO UT WOS:000298153600008 PM 21995970 ER PT J AU Peralta, CA Jacobs, DR Katz, R Ix, JH Madero, M Duprez, DA Sarnak, MJ Criqui, MH Kramer, HJ Palmas, W Herrington, D Shlipak, MG AF Peralta, Carmen A. Jacobs, David R., Jr. Katz, Ronit Ix, Joachim H. Madero, Magdalena Duprez, Daniel A. Sarnak, Mark J. Criqui, Michael H. Kramer, Holly J. Palmas, Walter Herrington, David Shlipak, Michael G. TI Association of Pulse Pressure, Arterial Elasticity, and Endothelial Function With Kidney Function Decline Among Adults With Estimated GFR > 60 mL/min/1.73 m(2): The Multi-Ethnic Study of Atherosclerosis (MESA) SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Kidney function; arterial elasticity; chronic kidney disease; atherosclerosis ID GLOMERULAR-FILTRATION-RATE; BLOOD-PRESSURE; HYPERTENSIVE PATIENTS; CARDIOVASCULAR-DISEASE; RENAL-FUNCTION; WAVE VELOCITY; STIFFNESS; RISK; DYSFUNCTION; POPULATION AB Background: The association of subclinical vascular disease and early declines in kidney function has not been well studied. Study Design: Prospective cohort study. Setting & Participants: Multi-Ethnic Study of Atherosclerosis (MESA) participants with estimated glomerular filtration rate (eGFR) >= 60 mL/min/1.73 m(2) with follow-up of 5 years. Predictors: Pulse pressure, small (SAE) and large arterial elasticity (LAE), and flow-mediated dilation. Outcomes: Kidney function decline. Measurements: SAE and LAE were measured by pulse contour analysis of the radial artery. Kidney function was assessed by eGFR based on serum creatinine (eGFR(SCr)) and cystatin C (eGFR(SCysC)). Results: For 4,853 adults, higher pulse pressure and lower SAE and LAE had independent and linear associations with faster rates of kidney function decline. Compared with persons with pulse pressure of 40-50 mm Hg, eGFR(SCysC) declines were 0.29 (P = 0.006), 0.56 (P < 0.001), and 0.91 (P < 0.001) mL/min/1.73 m(2)/y faster in persons with pulse pressure of 50-60, 60-70, and >70 mm Hg, respectively. Compared with the highest quartile of SAE (most elastic), eGFR(SCysC) declines were 0.26 (P = 0.009), 0.35 (P = 0.001), and 0.70 (P < 0.001) mL/min/1.73 m(2)/y faster for the second, third, and fourth quartiles, respectively. For LAE, compared with the highest quartile, eGFR(SCysC) declines were 0.28 (P = 0.004), 0.58 (P < 0.001), and 0.83 (P < 0.001) mL/min/1.73 m(2)/y faster for each decreasing quartile of LAE. Findings were similar for eGFR(SCr). In contrast, for 2,997 adults with flow-mediated dilation and kidney function measures, flow-mediated dilation was not associated significantly with kidney function decline. For every 1-standard deviation greater flow-mediated dilation, eGFR(SCysC) and eGFR(SCr) changed by 0.05 (P = 0.3) and 0.06 mL/min/1.73 m(2)/y (P = 0.04), respectively. Limitations: We had no direct measure of GFR, in common with nearly all large population-based studies. Conclusions: Higher pulse pressure and lower arterial elasticity, but not flow-mediated dilation, were associated linearly and independently with faster kidney function decline in persons with eGFR >= 60 mL/min/1.73 m(2). Future studies should investigate whether treatments to decrease the stiffness of large and small arteries may slow the rate of kidney function loss. Am J Kidney Dis. 59(1):41-49. (C) 2011 by the National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved. C1 [Peralta, Carmen A.; Shlipak, Michael G.] San Francisco VA Med Ctr, San Francisco, CA USA. [Peralta, Carmen A.; Shlipak, Michael G.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Jacobs, David R., Jr.] Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA. [Katz, Ronit] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Ix, Joachim H.] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. [Madero, Magdalena] Inst Nacl Cardiol Ignacio Chavez, Div Nephrol, Mexico City, DF, Mexico. [Duprez, Daniel A.] Univ Minnesota, Div Cardiovasc, Sch Med, Minneapolis, MN 55455 USA. [Sarnak, Mark J.] Tufts Med Ctr, Div Nephrol, Boston, MA USA. [Criqui, Michael H.] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. [Kramer, Holly J.] Loyola Univ, Med Ctr, Div Nephrol, Maywood, IL 60153 USA. [Palmas, Walter] Columbia Univ Coll Phys & Surg, Dept Med, New York, NY 10032 USA. [Herrington, David] Wake Forest Univ, Sch Med, Internal Med Sect Cardiol, Winston Salem, NC 27109 USA. RP Peralta, CA (reprint author), 4150 Clement St,111A1, San Francisco, CA 94121 USA. EM carmenalicia.peralta@ucsf.edu OI Kramer, Holly/0000-0002-6374-837X FU National Heart, Lung, and Blood Institute [N01-HC-95159, N01-HC-95169]; National Institute of Diabetes and Digestive and Kidney Disease [1K23DK082793-01] FX This research was supported by contracts N01-HC-95159 through N01-HC-95169 from the National Heart, Lung, and Blood Institute and by the National Institute of Diabetes and Digestive and Kidney Disease (grant 1K23DK082793-01, Dr Peralta). These funding sources had no involvement in the design or execution of this study. NR 44 TC 40 Z9 41 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 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD JAN PY 2012 VL 59 IS 1 BP 41 EP 49 DI 10.1053/j.ajkd.2011.08.015 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 863HO UT WOS:000298153600011 PM 22000727 ER PT J AU Johansen, KL Painter, P AF Johansen, Kirsten L. Painter, Patricia TI Exercise in Individuals With CKD SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Review DE Exercise; physical activity; chronic kidney disease ID CHRONIC KIDNEY-DISEASE; CHRONIC-RENAL-FAILURE; AMERICAN-HEART-ASSOCIATION; QUALITY-OF-LIFE; PHYSICAL-ACTIVITY; CARDIOVASCULAR OUTCOMES; PREDIALYSIS PATIENTS; SPORTS-MEDICINE; RISK-FACTOR; CAPACITY AB There are few studies evaluating exercise in the nondialysis chronic kidney disease (CKD) population. This review covers the rationale for exercise in patients with CKD not requiring dialysis and the effects of exercise training on physical functioning, progression of kidney disease, and cardiovascular risk factors. In addition, we address the issue of the risk of exercise and make recommendations for implementation of exercise in this population. Evidence from uncontrolled studies and small randomized controlled trials shows that exercise training results in improved physical performance and functioning in patients with CKD. In addition, although there are no studies examining cardiovascular outcomes, several studies suggest that cardiovascular risk factors such as hypertension, inflammation, and oxidative stress may be improved with exercise training in this population. Although the current literature does not allow for definitive conclusions about whether exercise training slows the progression of kidney disease, no study has reported worsening of kidney function as a result of exercise training. In the absence of guidelines specific to the CKD population, recent guidelines developed for older individuals and patients with chronic disease should be applied to the CKD population. In sum, exercise appears to be safe in this patient population if begun at moderate intensity and increased gradually. The evidence suggests that the risk of remaining inactive is higher. Patients should be advised to increase their physical activity when possible and be referred to physical therapy or cardiac rehabilitation programs when appropriate. Am J Kidney Dis. 59(1):126-134. (C) 2011 by the National Kidney Foundation, Inc. C1 [Johansen, Kirsten L.] San Francisco VA Med Ctr, Nephrol Sect, San Francisco, CA 94121 USA. [Johansen, Kirsten L.] Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94143 USA. [Painter, Patricia] Univ Minnesota, Sch Nursing, Div Hypertens & Renal Dis, Minneapolis, MN 55455 USA. RP Johansen, KL (reprint author), San Francisco VA Med Ctr, Nephrol Sect, 4150 Clement St,111J, San Francisco, CA 94121 USA. EM kirsten.johansen@ucsf.edu FU NIDDK NIH HHS [K24 DK085153-02, K24 DK085153, K24 DK085153-03, K24 DK085153-01A1] NR 52 TC 63 Z9 67 U1 1 U2 23 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD JAN PY 2012 VL 59 IS 1 BP 126 EP 134 DI 10.1053/j.ajkd.2011.10.008 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 863HO UT WOS:000298153600022 PM 22113127 ER PT J AU Weinberg, I Jaff, MR AF Weinberg, Ido Jaff, Michael R. TI Spontaneous Blue Finger Syndrome: A Benign Process SO AMERICAN JOURNAL OF MEDICINE LA English DT Letter C1 [Weinberg, Ido; Jaff, Michael R.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Weinberg, I (reprint author), Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. NR 3 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD JAN PY 2012 VL 125 IS 1 BP E1 EP E2 DI 10.1016/j.amjmed.2011.05.007 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 866IF UT WOS:000298373300001 PM 22195537 ER PT J AU Boatin, A Wylie, B Singh, MP Singh, N Yeboah-Antwi, K Hamer, D AF Boatin, Adeline Wylie, Blair Singh, Mrigendra Pal Singh, Neeru Yeboah-Antwi, Kojo Hamer, Davidson TI Prevalence of and risk factors for pica among pregnant women in Chhattisgarh, India SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 32nd Annual Scientific Meeting/Pregnancy Meeting of Society-for-Maternal-Fetal-Medicine CY FEB 06-11, 2012 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Boatin, Adeline] Massachusetts Gen Hosp, OB GYN, Boston, MA 02114 USA. [Wylie, Blair] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. [Yeboah-Antwi, Kojo; Hamer, Davidson] Ctr Global Hlth & Dev, Boston, MA USA. NR 0 TC 3 Z9 3 U1 2 U2 4 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 JAN PY 2012 VL 206 IS 1 SU S MA 671 BP S299 EP S299 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 873NL UT WOS:000298889900668 ER PT J AU Bryant, A Madden, E AF Bryant, Allison Madden, Erin TI Short interpregnancy intervals and maternal well-being: the association with placental abruption SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 32nd Annual Scientific Meeting/Pregnancy Meeting of Society-for-Maternal-Fetal-Medicine CY FEB 06-11, 2012 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Bryant, Allison] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Madden, Erin] NCIRE, Vet Hlth Res Inst, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2012 VL 206 IS 1 SU S MA 540 BP S245 EP S245 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 873NL UT WOS:000298889900538 ER PT J AU Bryant, A Madden, E AF Bryant, Allison Madden, Erin TI Short interpregnancy intervals and health services utilization: is neonatal hospital readmission associated with short intervals? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 32nd Annual Scientific Meeting/Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 06-11, 2012 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Bryant, Allison] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Madden, Erin] NCIRE, Vet Res Inst, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2012 VL 206 IS 1 SU S MA 541 BP S246 EP S246 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 873NL UT WOS:000298889900539 ER PT J AU Bryant, A Madden, E AF Bryant, Allison Madden, Erin TI Short interpregnancy intervals and health services utilization: is maternal antepartum admission associated with short intervals? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 32nd Annual Scientific Meeting/Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 06-11, 2012 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Bryant, Allison] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Madden, Erin] NCIRE, Vet Hlth Res Inst, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2012 VL 206 IS 1 SU S MA 542 BP S246 EP S246 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 873NL UT WOS:000298889900540 ER PT J AU Caughey, AB Nicholson, J Kaimal, A Dublin, S Getahun, D Cheng, YW AF Caughey, Aaron B. Nicholson, James Kaimal, Anjali Dublin, Sascha Getahun, Darios Cheng, Yvonne W. TI Elective induction of labor and outcomes by gestational age SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 32nd Annual Scientific Meeting/Pregnancy Meeting of Society-for-Maternal-Fetal-Medicine CY FEB 06-11, 2012 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Caughey, Aaron B.] Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Portland, OR 97201 USA. [Nicholson, James] Univ Penn, Dept Family Med & Community Hlth, Philadelphia, PA 19104 USA. [Kaimal, Anjali] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kaimal, Anjali] Harvard Univ, Sch Med, Div Maternal Fetal Med, Boston, MA USA. [Dublin, Sascha] Grp Hlth Res Inst, Grp Hlth, Seattle, WA USA. [Getahun, Darios] Kaiser Permanente So Calif, Dept Res & Evaluat, Pasadena, CA USA. [Cheng, Yvonne W.] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2012 VL 206 IS 1 SU S MA 276 BP S134 EP S134 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 873NL UT WOS:000298889900276 ER PT J AU Fuchs, K Spitz, J Toland, G Bromley, B Benacerraf, B Platt, L D'Alton, M AF Fuchs, Karin Spitz, Jean Toland, Gregory Bromley, Bryann Benacerraf, Beryl Platt, Lawrence D'Alton, Mary TI Impact of a required remediation program on nuchal translucency measurements: experience of the Nuchal Translucency Quality Review (NTQR) Program SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 32nd Annual Scientific Meeting/Pregnancy Meeting of Society-for-Maternal-Fetal-Medicine CY FEB 06-11, 2012 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Fuchs, Karin; D'Alton, Mary] Columbia Univ, Med Ctr, Div Maternal Fetal Med, New York, NY USA. [Spitz, Jean; Toland, Gregory] Maternal Fetal Med Fdn, Nuchal Translucency Qual Review Program, Washington, DC USA. [Bromley, Bryann] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Benacerraf, Beryl] Harvard Univ, Dept Obstet Gynecol, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Benacerraf, Beryl] Harvard Univ, Dept Radiol, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Platt, Lawrence] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Platt, Lawrence] Ctr Fetal Med & Womens Ultrasound, Dept Obstet Gynecol, Los Angeles, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2012 VL 206 IS 1 SU S MA 353 BP S166 EP S166 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 873NL UT WOS:000298889900352 ER PT J AU Kaimal, A Newman, K Croft, D Ecker, J AF Kaimal, Anjali Newman, Katharine Croft, Damien Ecker, Jeffrey TI Cesarean birth after vaginal: risk factors for primary cesarean delivery in multiparous women SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 32nd Annual Scientific Meeting/Pregnancy Meeting of Society-for-Maternal-Fetal-Medicine CY FEB 06-11, 2012 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Kaimal, Anjali; Newman, Katharine; Croft, Damien; Ecker, Jeffrey] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 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 JAN PY 2012 VL 206 IS 1 SU S MA 660 BP S295 EP S295 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 873NL UT WOS:000298889900658 ER PT J AU Kaimal, A Little, S Caughey, AB AF Kaimal, Anjali Little, Sarah Caughey, Aaron B. TI Induction of labor for nulliparous women > 40: what is the optimal gestational age? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 32nd Annual Scientific Meeting/Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 06-11, 2012 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Kaimal, Anjali] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Little, Sarah] Brigham & Womens Hosp, Boston, MA 02115 USA. [Caughey, Aaron B.] Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Portland, OR 97201 USA. [Little, Sarah] Harvard Univ, Sch Med, Div Maternal Fetal Med, Dept Ob Gyn, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2012 VL 206 IS 1 SU S MA 93 BP S56 EP S57 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 873NL UT WOS:000298889900094 ER PT J AU Little, S Sparks, TN Pilliod, R Shaffer, B Caughey, AB Kaimal, A AF Little, Sarah Sparks, Teresa N. Pilliod, Rachel Shaffer, Brian Caughey, Aaron B. Kaimal, Anjali TI When is the optimal time to deliver dichorionic diamniotic twins? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 32nd Annual Scientific Meeting/Pregnancy Meeting of Society-for-Maternal-Fetal-Medicine CY FEB 06-11, 2012 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Little, Sarah] Brigham & Womens Hosp, Boston, MA 02115 USA. [Little, Sarah] Harvard Univ, Sch Med, Div Maternal Fetal Med, Dept Ob Gyn, Boston, MA USA. [Sparks, Teresa N.] Brigham & Womens Massachusetts Gen Hosp, Boston, MA USA. [Pilliod, Rachel; Shaffer, Brian; Caughey, Aaron B.] Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Portland, OR 97201 USA. [Kaimal, Anjali] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2012 VL 206 IS 1 SU S MA 150 BP S78 EP S79 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 873NL UT WOS:000298889900151 ER PT J AU Mohta, VJ Caceres, I Smith, L Cohen, B Declercq, G Subramanian, SV Ecker, J AF Mohta, Vanitha Janakiraman Caceres, Isabel Smith, Lauren Cohen, Bruce Declercq, Gene Subramanian, S. V. Ecker, Jeffrey TI Hospital variation in cesarean delivery rates among a very low risk population in Massachusetts: an opportunity for quality improvement? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 32nd Annual Scientific Meeting/Pregnancy Meeting of Society-for-Maternal-Fetal-Medicine CY FEB 06-11, 2012 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Mohta, Vanitha Janakiraman; Ecker, Jeffrey] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Caceres, Isabel; Smith, Lauren; Cohen, Bruce] DPH, Massachusetts Dept Publ Hlth, Boston, MA USA. [Declercq, Gene] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Subramanian, S. V.] Harvard Univ, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2012 VL 206 IS 1 SU S MA 638 BP S285 EP S286 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 873NL UT WOS:000298889900636 ER PT J AU Panda, B Panda, A Abrahams, VM Norwitz, E Stanic, AK Ecker, JL Rueda, BR AF Panda, Britta Panda, Alexander Abrahams, Vikki M. Norwitz, Errol Stanic, Aleksandar K. Ecker, Jeffrey L. Rueda, Bo R. TI Increase in TLR protein in preeclamptic patients does not correlate with a corresponding increase in TLR gene expression SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 32nd Annual Scientific Meeting/Pregnancy Meeting of Society-for-Maternal-Fetal-Medicine CY FEB 06-11, 2012 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Panda, Britta; Stanic, Aleksandar K.; Ecker, Jeffrey L.; Rueda, Bo R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Panda, Alexander; Abrahams, Vikki M.] Yale Univ, New Haven, CT USA. [Norwitz, Errol] Tufts Univ, Sch Med, Boston, MA 02111 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2012 VL 206 IS 1 SU S MA 745 BP S330 EP S330 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 873NL UT WOS:000298889901011 ER PT J AU Panda, B Young, B Madden, E Bryant, A AF Panda, Britta Young, Brett Madden, Erin Bryant, Allison TI What happens after the puerperium? Analysis of late postpartum admissions in California SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 32nd Annual Scientific Meeting/Pregnancy Meeting of Society-for-Maternal-Fetal-Medicine CY FEB 06-11, 2012 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Panda, Britta; Young, Brett; Bryant, Allison] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Madden, Erin] NCIRE, Vet Res Inst, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2012 VL 206 IS 1 SU S MA 546 BP S248 EP S248 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 873NL UT WOS:000298889900544 ER PT J AU Riley, L Hutchings, Y Lieberman, E AF Riley, Laura Hutchings, Yalonda Lieberman, Ellice TI The effect of doula support on epidural use among nulliparous women in tertiary care centers SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 32nd Annual Scientific Meeting/Pregnancy Meeting of Society-for-Maternal-Fetal-Medicine CY FEB 06-11, 2012 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Riley, Laura] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Maternal Fetal Med, Boston, MA USA. [Hutchings, Yalonda; Lieberman, Ellice] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2012 VL 206 IS 1 SU S MA 132 BP S70 EP S71 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 873NL UT WOS:000298889900133 ER PT J AU Saxena, A Seely, E Rich-Edwards, J Wilkins-Haug, L Karumanchi, A McElrath, T AF Saxena, Aditi Seely, Ellen Rich-Edwards, Janet Wilkins-Haug, Louise Karumanchi, Ananth McElrath, Thomas TI First trimester PAPP-A levels correlate with sFlt-1 levels longitudinally in pregnant women with and without preeclampsia SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 32nd Annual Scientific Meeting/Pregnancy Meeting of Society-for-Maternal-Fetal-Medicine CY FEB 06-11, 2012 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Seely, Ellen] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Rich-Edwards, Janet] Brigham & Womens Hosp, Dept Dev Epidemiol, Boston, MA 02115 USA. [Karumanchi, Ananth] Harvard Univ, Sch Med, BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2012 VL 206 IS 1 SU S MA 732 BP S325 EP S325 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 873NL UT WOS:000298889900727 ER PT J AU Sparks, TN Burwick, R Feinberg, B AF Sparks, Teresa N. Burwick, Richard Feinberg, Bruce TI Vitamin D deficiency is associated with increased mean arterial pressure at term SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 32nd Annual Scientific Meeting/Pregnancy Meeting of Society-for-Maternal-Fetal-Medicine CY FEB 06-11, 2012 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Sparks, Teresa N.; Burwick, Richard; Feinberg, Bruce] Brigham & Womens Hosp, Boston, MA 02115 USA. [Sparks, Teresa N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. OI Sparks, Teresa/0000-0002-8593-2186 NR 0 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 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2012 VL 206 IS 1 SU S MA 801 BP S352 EP S353 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 873NL UT WOS:000298889901067 ER PT J AU Sparks, TN Little, S Pilliod, R Shaffer, B Kaimal, A Caughey, AB AF Sparks, Teresa N. Little, Sarah Pilliod, Rachel Shaffer, Brian Kaimal, Anjali Caughey, Aaron B. TI When is the optimal time to deliver monochorionic diamniotic twins? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 32nd Annual Scientific Meeting/Pregnancy Meeting of Society-for-Maternal-Fetal-Medicine CY FEB 06-11, 2012 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Sparks, Teresa N.] Brigham & Womens Massachusetts Gen Hosp, Boston, MA USA. [Little, Sarah] Brigham & Womens Hosp, Boston, MA 02115 USA. [Little, Sarah] Harvard Univ, Sch Med, Div Maternal Fetal Med, Dept Ob Gyn, Boston, MA USA. [Pilliod, Rachel; Caughey, Aaron B.] Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Portland, OR 97201 USA. [Kaimal, Anjali] Massachusetts Gen Hosp, Boston, MA 02114 USA. OI Sparks, Teresa/0000-0002-8593-2186 NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2012 VL 206 IS 1 SU S MA 155 BP S81 EP S82 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 873NL UT WOS:000298889900156 ER PT J AU Yee, L Nakagawa, S Kaimal, A Kuppermann, M AF Yee, Lynn Nakagawa, Sanae Kaimal, Anjali Kuppermann, Miriam TI Postpartum sexual functioning and mode of delivery in a diverse population of women SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 32nd Annual Scientific Meeting/Pregnancy Meeting of Society-for-Maternal-Fetal-Medicine CY FEB 06-11, 2012 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Yee, Lynn; Nakagawa, Sanae; Kuppermann, Miriam] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA USA. [Kaimal, Anjali] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2012 VL 206 IS 1 SU S MA 329 BP S155 EP S155 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 873NL UT WOS:000298889900328 ER PT J AU New, DD Block, K Bhandhari, B Gorin, Y Abboud, HE AF New, David D. Block, Karen Bhandhari, Basant Gorin, Yves Abboud, Hanna E. TI IGF-I increases the expression of fibronectin by Nox4-dependent Akt phosphorylation in renal tubular epithelial cells SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE extracellular matrix; growth factor signaling; kidney; reactive oxygen species; redox signaling; NADPH oxidase 4; insulin-like growth factor ID GROWTH-FACTOR-I; MESSENGER-RNA TRANSLATION; SMOOTH-MUSCLE-CELLS; NAD(P)H OXIDASE; DIABETIC-NEPHROPATHY; NADPH OXIDASES; HIGH GLUCOSE; PROTEIN-SYNTHESIS; MESANGIAL CELLS; ANGIOTENSIN-II AB New DD, Block K, Bhandhari B, Gorin Y, Abboud HE. IGF-I increases the expression of fibronectin by Nox4-dependent Akt phosphorylation in renal tubular epithelial cells. Am J Physiol Cell Physiol 302: C122-C130, 2012. First published September 21, 2011; doi:10.1152/ajpcell.00141.2011.-Extracellular matrix accumulation contributes to the progression of chronic kidney disease. Many growth factors including insulin-like growth factor-I (IGF-I) enhance matrix protein accumulation. Proximal tubular epithelial cells (PTCs) synthesize matrix proteins. NADPH oxidases are major sources of reactive oxygen species (ROS), important signaling molecules that mediate biological responses in a variety of cells and tissue. We investigated the mechanism by which IGF-I regulates fibronectin accumulation in PTCs and the role of a potential redox-dependent signaling pathway. IGF-I induces an increase in NADPH-dependent superoxide generation, enhances the release of hydrogen peroxide, and increases the expression of NADPH oxidase 4 (Nox4) in PTCs. IGF-I also stimulates phosphorylation of Akt, and inhibition of Akt or its upstream activator phosphatidylinositol 3-kinase attenuates IGF-I-induced fibronectin accumulation. Expression of dominant negative Akt also inhibits IGF-I-induced expression of fibronectin, indicating a role for this kinase in fibronectin accumulation. Expression of dominant negative adenovirus Nox4 inhibits IGF-I-induced NADPH oxidase activity, Akt phosphorylation, and fibronectin protein expression. Moreover, transfection of small interfering RNA targeting Nox4 decreases Nox4 protein expression and blocks IGF-I-induced Akt phosphorylation and the increase in fibronectin, placing Nox4 and ROS upstream of Akt signaling pathway. To confirm the role of Nox4, PTCs were infected with adenovirus construct expressing wild-type Nox4. Ad-Nox4, but not control Ad-green fluorescent protein, upregulated Nox4 expression and increased NADPH oxidase activity as well as fibronectin expression. Taken together, these results provide the first evidence for a role of Nox4 in IGF-I-induced Akt phosphorylation and fibronectin expression in tubular epithelial cells. C1 [Abboud, Hanna E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Nephrol, San Antonio, TX 78229 USA. [Block, Karen] Audie L Murphy Mem Hosp, S Texas Vet Healthcare Syst, San Antonio, TX USA. RP Abboud, HE (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Nephrol, MC 7882,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM abboud@uthscsa.edu OI Gorin, Yves/0000-0003-4048-6925 FU Veterans Administration; National Institutes of Health [DK-R01-078971, CA131272, DK-079996]; Juvenile Diabetes Research Foundation; Career Development Award FX Support for these studies was provided by the following sources: Veterans Administration Merit Review grant and National Institutes of Health Grant DK-R01-078971 (H. E. Abboud) and Career Development Award and National Institutes of Health Grant CA131272 (K. Block), Juvenile Diabetes Research Foundation regular research grant, and National Institutes of Health Grant DK-079996 (Y. Gorin). NR 51 TC 28 Z9 28 U1 1 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD JAN PY 2012 VL 302 IS 1 BP C122 EP C130 DI 10.1152/ajpcell.00141.2011 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 866IN UT WOS:000298374100015 PM 21940672 ER PT J AU Morton, GJ Thatcher, BS Reidelberger, RD Ogimoto, K Wolden-Hanson, T Baskin, DG Schwartz, MW Blevins, JE AF Morton, Gregory J. Thatcher, Brendan S. Reidelberger, Roger D. Ogimoto, Kayoko Wolden-Hanson, Tami Baskin, Denis G. Schwartz, Michael W. Blevins, James E. TI Peripheral oxytocin suppresses food intake and causes weight loss in diet-induced obese rats SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE leptin; food intake ID BRAIN-STEM NUCLEI; CENTRALLY ADMINISTERED OXYTOCIN; DEFICIENT MICE; PARAVENTRICULAR NUCLEUS; ENERGY-EXPENDITURE; LEPTIN RESISTANCE; SPINAL-CORD; SIM1 GENE; HYPERPHAGIC OBESITY; SOLITARY TRACT AB Morton GJ, Thatcher BS, Reidelberger RD, Ogimoto K, Wolden-Hanson T, Baskin DG, Schwartz MW, Blevins JE. Peripheral oxytocin suppresses food intake and causes weight loss in diet-induced obese rats. Am J Physiol Endocrinol Metab 302: E134-E144, 2012. First published October 18, 2011; doi:10.1152/ajpendo.00296.2011.-Growing evidence suggests that oxytocin plays an important role in the regulation of energy balance and that central oxytocin administration induces weight loss in diet-induced obese (DIO) animals. To gain a better understanding of how oxytocin mediates these effects, we examined feeding and neuronal responses to oxytocin in animals rendered obese following exposure to either a high-fat (HFD) or low-fat diet (LFD). Our findings demonstrate that peripheral administration of oxytocin dose-dependently reduces food intake and body weight to a similar extent in rats maintained on either diet. Moreover, the effect of oxytocin to induce weight loss remained intact in leptin receptor-deficient Koletsky (fak/fak) rats relative to their lean littermates. To determine whether systemically administered oxytocin activates hindbrain areas that regulate meal size, we measured neuronal c-Fos induction in the nucleus of the solitary tract (NTS) and area postrema (AP). We observed a robust neuronal response to oxytocin in these hindbrain areas that was unexpectedly increased in rats rendered obese on a HFD relative to lean, LFD-fed controls. Finally, we report that repeated daily peripheral administration of oxytocin in DIO animals elicited a sustained reduction of food intake and body weight while preventing the reduction of energy expenditure characteristic of weight-reduced animals. These findings extend recent evidence suggesting that oxytocin circumvents leptin resistance and induces weight-loss in DIO animals through a mechanism involving activation of neurons in the NTS and AP, key hindbrain areas for processing satiety-related inputs. C1 [Morton, Gregory J.; Ogimoto, Kayoko; Schwartz, Michael W.] Univ Washington, Dept Med, Diabet & Obes Ctr Excellence, Seattle, WA USA. [Morton, Gregory J.; Baskin, Denis G.; Schwartz, Michael W.; Blevins, James E.] Univ Washington, Sch Med, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. [Thatcher, Brendan S.; Wolden-Hanson, Tami; Baskin, Denis G.; Blevins, James E.] Vet Affairs Puget Sound Hlth Care Syst, Dept Vet Affairs Med Ctr, Off Res & Dev, Med Res Serv, Seattle, WA USA. [Reidelberger, Roger D.] Nebraska Western Iowa Hlth Care Syst, Dept Vet Affairs, Omaha, NE USA. [Reidelberger, Roger D.] Creighton Univ, Dept Biomed Sci, Omaha, NE 68178 USA. RP Morton, GJ (reprint author), Univ Washington S Lake Union, Dept Med, 815 Mercer St,N334,Box 358055, Seattle, WA 98109 USA. EM gjmorton@u.washington.edu RI Schwartz, Michael/H-9950-2012 FU Office of Research and Development, Medical Research Service, Department of Veterans Affairs; Veterans Affairs Puget Sound Health Care System; Department of Veterans Affairs; Department of Veterans Affairs Nebraska Western Iowa Health Care System; NIH [DK-068304, DK-083042, DK-052989, DK-089056]; American Heart Association; Cellular and Molecular Imaging Core of the National Institutes of Health (NIH) Diabetes Endocrinology Research Center (DERC) [P30 DK-17047]; NIH Nutrition Obesity Research Unit Animal Studies Physiology Core at the University of Washington (NORC) [P30 DK-035816]; NIH Mouse Metabolic Phenotyping Center Diabetes and Energy Balance Core (MMPC) [U24 DK-076126] FX This work was supported by resources from the Office of Research and Development, Medical Research Service, Department of Veterans Affairs, including the Department of Veterans Affairs Career Development Program, Merit Review Research Program, and the Career Scientist Program. D. G. Baskin is the recipient of a Department of Veterans Affairs Senior Research Career Scientist Award at the Veterans Affairs Puget Sound Health Care System. R. D. Reidelberger is the recipient of a Department of Veterans Affairs Research Career Scientist Award at the Department of Veterans Affairs Nebraska Western Iowa Health Care System. M. W. Schwartz is supported by NIH grants (DK-068304, DK-083042, DK-052989). G. J. Morton is supported by an NIH grant (DK-089056) and a Scientist Development Grant from the American Heart Association. This research was also supported by the Cellular and Molecular Imaging Core of the National Institutes of Health (NIH) Diabetes Endocrinology Research Center (DERC, P30 DK-17047), the NIH Nutrition Obesity Research Unit Animal Studies Physiology Core at the University of Washington (NORC, P30 DK-035816), and the NIH Mouse Metabolic Phenotyping Center Diabetes and Energy Balance Core (MMPC, U24 DK-076126). NR 64 TC 63 Z9 64 U1 1 U2 15 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD JAN PY 2012 VL 302 IS 1 BP E134 EP E144 DI 10.1152/ajpendo.00296.2011 PG 11 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 866JU UT WOS:000298377600015 PM 22008455 ER PT J AU Haegens, A Schols, AM Gorissen, SH van Essen, AL Snepvangers, F Gray, DA Shoelson, SE Langen, RC AF Haegens, Astrid Schols, Annemie M. Gorissen, Stefan H. van Essen, Anon L. Snepvangers, Frank Gray, Douglas A. Shoelson, Steven E. Langen, Ramon C. TI NF-kappa B activation and polyubiquitin conjugation are required for pulmonary inflammation-induced diaphragm atrophy SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE inspiratory muscle; inflammation; protein degradation ID SKELETAL-MUSCLE ATROPHY; SYSTEMIC INFLAMMATION; MUTANT UBIQUITIN; DISEASE; DYSFUNCTION; MICE; LIPOPOLYSACCHARIDE; VENTILATION; EXPRESSION; MORTALITY AB Haegens A, Schols AM, Gorissen SH, van Essen AL, Snepvangers F, Gray DA, Shoelson SE, Langen RC. NF-kappa B activation and polyubiquitin conjugation are required for pulmonary inflammation-induced diaphragm atrophy. Am J Physiol Lung Cell Mol Physiol 302: L103-L110, 2012. First published October 14, 2011; doi: 10.1152/ajplung.00084.2011.-Loss of diaphragm muscle strength in inflammatory lung disease contributes to mortality and is associated with diaphragm fiber atrophy. Ubiquitin (Ub) 26S-proteasome system (UPS)-dependent protein breakdown, which mediates muscle atrophy in a number of physiological and pathological conditions, is elevated in diaphragm muscle of patients with chronic obstructive pulmonary disease. Nuclear factor kappa B (NF-kappa B), an essential regulator of many inflammatory processes, has been implicated in the regulation of poly-Ub conjugation of muscle proteins targeted for proteolysis by the UPS. Here, we test if NF-kappa B activation in diaphragm muscle and subsequent protein degradation by the UPS are required for pulmonary inflammation-induced diaphragm atrophy. Acute pulmonary inflammation was induced in mice by intratracheal lipopolysaccharide instillation. Fiber cross-sectional area, ex vivo tyrosine release, protein poly-Ub conjugation, and inflammatory signaling were determined in diaphragm muscle. The contribution of NF-kappa B or the UPS to diaphragm atrophy was assessed in mice with intact or genetically repressed NF-kappa B signaling or attenuated poly-Ub conjugation, respectively. Acute pulmonary inflammation resulted in diaphragm atrophy measured by reduced muscle fiber cross-sectional area. This was accompanied by diaphragm NF-kappa B activation, and proteolysis, measured by tyrosine release from the diaphragm. Poly-Ub conjugation was increased in diaphragm, as was the expression of muscle-specific E3 Ub ligases. Genetic suppression of poly-Ub conjugation prevented inflammation-induced diaphragm muscle atrophy, as did muscle-specific inhibition of NF-kappa B signaling. In conclusion, the present study is the first to demonstrate that diaphragm muscle atrophy, resulting from acute pulmonary inflammation, requires NF-kappa B activation and UPS-mediated protein degradation. C1 [Haegens, Astrid; Schols, Annemie M.; Gorissen, Stefan H.; van Essen, Anon L.; Snepvangers, Frank; Langen, Ramon C.] Maastricht Univ Med Ctr, Dept Resp Med, NUTRIM Sch Nutr Toxicol & Metab, NL-6202 AZ Maastricht, Netherlands. [Gray, Douglas A.] Ottawa Hosp Res Inst, Ottawa, ON, Canada. [Shoelson, Steven E.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Shoelson, Steven E.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Schols, AM (reprint author), Maastricht Univ Med Ctr, Dept Resp Med, NUTRIM Sch Nutr Toxicol & Metab, POB 5800, NL-6202 AZ Maastricht, Netherlands. EM a.schols@maastrichtuniv.nl RI Gorissen, Stefan/H-5341-2016 OI Gorissen, Stefan/0000-0003-3737-9053 FU Dutch Top Institute Pharma [T1-201]; Organization for Scientific Research NWO [VENI 91656112] FX This work was supported by the Dutch Top Institute Pharma (project no. T1-201) and the Organization for Scientific Research NWO (VENI 91656112). NR 37 TC 20 Z9 23 U1 2 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD JAN PY 2012 VL 302 IS 1 BP L103 EP L110 DI 10.1152/ajplung.00084.2011 PG 8 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 866VC UT WOS:000298413000011 PM 22003096 ER PT J AU Zhao, KQ Xiong, GX Wilber, M Cohen, NA Kreindler, JL AF Zhao, Ke-Qing Xiong, Guoxiang Wilber, Morgan Cohen, Noam A. Kreindler, James L. TI A role for two-pore K+ channels in modulating Na+ absorption and Cl- secretion in normal human bronchial epithelial cells SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE chloride secretion; cystic fibrosis; ion transport ID CHLORIDE SECRETION; ANION SECRETION; POTASSIUM CHANNELS; AIRWAY EPITHELIA; ION-TRANSPORT; LUNG-DISEASE; LINE CALU-3; CONDUCTANCE; MEMBRANE; LIQUID AB Zhao KQ, Xiong G, Wilber M, Cohen NA, Kreindler JL. A role for two-pore K+ channels in modulating Na+ absorption and Cl- secretion in normal human bronchial epithelial cells. Am J Physiol Lung Cell Mol Physiol 302: L4-L12, 2012. First published September 30, 2011; doi: 10.1152/ajplung.00102.2011.-Mucociliary clearance is the primary innate physical defense mechanism against inhaled pathogens and toxins. Vectorial ion transport, primarily sodium absorption and anion secretion, by airway epithelial cells supports mucociliary clearance. This is evidenced by diseases of abnormal ion transport such as cystic fibrosis and pseudohypoaldosteronism that are characterized by changes in mucociliary clearance. Sodium absorption and chloride secretion in human bronchial epithelial cells depend on potassium channel activity, which creates a favorable electrochemical gradient for both by hyperpolarizing the apical plasma membrane. Although the role of basolateral membrane potassium channels is firmly established and extensively studied, a role for apical membrane potassium channels has also been described. Here, we demonstrate that bupivacaine and quinidine, blockers of four-transmembrane domain, two-pore potassium (K2P) channels, inhibit both amiloride-sensitive sodium absorption and forskolin-stimulated anion secretion in polarized, normal human bronchial epithelial cells at lower concentrations when applied to the mucosal surface than when applied to the serosal surface. Transcripts from four genes, KCNK1 (TWIK-1), KCNK2 (TREK-1), KCNK5 (TASK-2), and KCNK6 (TWIK-2), encoding K2P channels were identified by RT-PCR. Protein expression at the apical membrane was confirmed by immunofluorescence. Our data provide further evidence that potassium channels, in particular K2P channels, are expressed and functional in the apical membrane of airway epithelial cells where they may be targets for therapeutic manipulation. C1 [Zhao, Ke-Qing] Fudan Univ, Sch Shanghai Med, Dept Otorhinolaryngol Head & Neck Surg, Eye & Ear Nose & Throat Hosp, Shanghai 200433, Peoples R China. [Zhao, Ke-Qing; Cohen, Noam A.] Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, Philadelphia, PA 19104 USA. [Xiong, Guoxiang] Childrens Hosp Philadelphia, Div Neurol, Philadelphia, PA 19104 USA. [Cohen, Noam A.] Philadelphia Vet Affairs Med Ctr, Surg Serv, Philadelphia, PA USA. [Kreindler, James L.] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. RP Kreindler, JL (reprint author), Abramson Res Ctr, 3615 Civ Ctr Blvd,Rm 1016-D, Philadelphia, PA 19104 USA. EM kreindler@email.chop.edu OI Cohen, Noam/0000-0002-9462-3932 FU National Heart, Lung, and Blood Institute [K08-HL-081080]; Children's Hospital of Philadelphia FX This work was funded by National Heart, Lung, and Blood Institute Grant K08-HL-081080 (to J. L. Kreindler) and by institutional funds from the Children's Hospital of Philadelphia. NR 33 TC 19 Z9 20 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD JAN PY 2012 VL 302 IS 1 BP L4 EP L12 DI 10.1152/ajplung.00102.2011 PG 9 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 866VC UT WOS:000298413000002 PM 21964404 ER PT J AU Thomas, JJ Weigel, TJ Lawton, RK Levendusky, PG Becker, AE AF Thomas, Jennifer J. Weigel, Thomas J. Lawton, Robert K. Levendusky, Philip G. Becker, Anne E. TI Cognitive-Behavioral Treatment of Body Image Disturbance in a Congenitally Blind Patient With Anorexia Nervosa SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Editorial Material ID WOMAN TOTALLY BLIND; EATING-DISORDERS; DSM-V; AGE C1 [Thomas, Jennifer J.] McLean Hosp, Klarman Eating Disorders Ctr, Belmont, MA 02178 USA. Massachusetts Gen Hosp, Eating Disorders Clin & Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA 02115 USA. RP Thomas, JJ (reprint author), McLean Hosp, Klarman Eating Disorders Ctr, 115 Mill St, Belmont, MA 02178 USA. EM jjthomas@partners.org NR 19 TC 4 Z9 4 U1 2 U2 5 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 JAN PY 2012 VL 169 IS 1 BP 16 EP 20 DI 10.1176/appi.ajp.2010.10040555 PG 5 WC Psychiatry SC Psychiatry GA 875UQ UT WOS:000299061100006 PM 22223010 ER PT J AU Cannuscio, C Bugos, E Hersh, S Asch, DA Weiss, EE AF Cannuscio, Carolyn Bugos, Eva Hersh, Shari Asch, David A. Weiss, Eve E. TI Using ART to AMPLIFY Youth Voices on Housing Insecurity SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material C1 [Cannuscio, Carolyn; Asch, David A.] Univ Penn, Ctr Hlth Equi Res & Promot, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Cannuscio, Carolyn; Asch, David A.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Cannuscio, Carolyn] Univ Penn, Perelman Sch Med, Dept Family Med & Community Hlth, Philadelphia, PA 19104 USA. [Cannuscio, Carolyn; Bugos, Eva; Weiss, Eve E.] Univ Penn, Mixed Methods Res Lab, Philadelphia, PA 19104 USA. [Cannuscio, Carolyn; Bugos, Eva; Weiss, Eve E.] Univ Penn, Ctr Publ Hlth Initiat, Philadelphia, PA 19104 USA. [Hersh, Shari] Mural Arts Program, Philadelphia, PA USA. RP Cannuscio, C (reprint author), Univ Penn, Ctr Hlth Equi Res & Promot, Philadelphia VA Med Ctr, 3620 Hamilton Walk,Anat & Chem Bldg,Room 145, Philadelphia, PA 19104 USA. EM carolyncannu@gmail.com OI Asch, David/0000-0002-7970-286X NR 4 TC 2 Z9 2 U1 2 U2 14 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JAN PY 2012 VL 102 IS 1 BP 10 EP 12 DI 10.2105/AJPH.2011.300494 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 867IZ UT WOS:000298449400005 PM 22095365 ER PT J AU Okechukwu, CA El Ayadi, AM Tamers, SL Sabbath, EL Berkman, L AF Okechukwu, Cassandra A. El Ayadi, Alison M. Tamers, Sara L. Sabbath, Erika L. Berkman, Lisa TI Household Food Insufficiency, Financial Strain, Work-Family Spillover, and Depressive Symptoms in the Working Class: The Work, Family, and Health Network Study SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID COMMON MENTAL-DISORDERS; JOB STRAIN; WELFARE RECIPIENTS; STAFF TURNOVER; NURSING-HOMES; WOMEN; INCOME; INSECURITY; OVERWEIGHT; QUALITY AB Objectives. We evaluated the association of household-level stressors with depressive symptoms among low-wage nursing home employees. Methods. Data were collected in 2006 and 2007 from 452 multiethnic primary and nonprimary wage earners in 4 facilities in Massachusetts. We used logistic regression to estimate the association of depressive symptoms with household financial strain, food insufficiency, and work-family spillover (preoccupation with work-related concerns while at home and vice versa). Results. Depressive symptoms were significantly associated with household financial strain (odds ratio [OR]=1.82; 95% confidence interval [CI]=1.03, 3.21) and food insufficiency (OR=2.10; 95% CI=1.10, 4.18). Among primary earners, stratified analyses showed that food insufficiency was associated with depressive symptoms (OR=3.60; 95% CI=1.42, 9.11) but financial strain was not. Among nonprimary wage earners, depressive symptoms correlated with financial strain (OR=3.65; 95% CI=1.48, 9.01) and work-family spillover (OR=3.22; 95% CI=1.11, 9.35). Conclusions. Household financial strain, food insufficiency, and work-family spillover are pervasive problems for working populations, but associations vary by primary wage earner status. The prevalence of food insufficiency among full-time employees was striking and might have a detrimental influence on depressive symptoms and the health of working-class families. (Am J Public Health. 2012;102:126-133. doi:10.2105/AJPH.2011.300323) C1 [Okechukwu, Cassandra A.; El Ayadi, Alison M.; Tamers, Sara L.; Sabbath, Erika L.; Berkman, Lisa] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Tamers, Sara L.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Berkman, Lisa] Harvard Univ, Ctr Populat & Dev Studies, Boston, MA USA. RP Okechukwu, CA (reprint author), Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, 677 Huntington Ave,Kresge 7th Floor, Boston, MA 02115 USA. EM cokechuk@hsph.harvard.edu FU National Institute of Aging [3U01AG027669-06S1]; National Institute of Child Health and Human Development [U01 5186989]; Maternal Child Health (MCH) Bureau; MCH/School of Public Health Institute [5T76 MC 00001J, T03MCO7648]; National Cancer Institute [5R25CA057711] FX This study was conducted as part of the Work, Family, and Health Network, which is funded by the National Institute of Aging and the National Institute of Child Health and Human Development (grant U01 5186989). Cassandra A. Okechukwu was supported by a National Institute of Aging supplement (grant 3U01AG027669-06S1). Alison M. El Ayadi was supported by the Maternal Child Health (MCH) Bureau training grant and an epidemiological MCH/School of Public Health Institute grant (5T76 MC 00001J [formerly MCJ201] and T03MCO7648). Sara L. Tamers was supported by the National Cancer Institute Harvard Education Program in Cancer Prevention Control (grant 5R25CA057711). NR 52 TC 22 Z9 22 U1 1 U2 20 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JAN PY 2012 VL 102 IS 1 BP 126 EP 133 DI 10.2105/AJPH.2011.300323 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 867IZ UT WOS:000298449400024 PM 22095360 ER PT J AU Walker, TG Kalva, SP Ganguli, S Oklu, R Salazar, GM Waltman, AC Wicky, S AF Walker, T. Gregory Kalva, Sanjeeva P. Ganguli, Suvranu Oeklue, Rahmi Salazar, Gloria M. Waltman, Arthur C. Wicky, Stephan TI Image Optimization During Endovascular Aneurysm Repair SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE endovascular aneurysm repair; image geometry; radiation safety ID ABDOMINAL-AORTIC-ANEURYSM; RADIATION-EXPOSURE; PATIENT; RADIOLOGY; INJURY; NEPHROTOXICITY; SUITABILITY; STRATEGIES; GUIDELINES; MANAGEMENT AB OBJECTIVE. The purposes of this review are to examine various properties of the fluoroscopic imaging equipment used during endovascular aneurysm repair (EVAR) that can be modified to reduce radiation dose while optimizing image acquisition and display, to detail geometric aspects of EVAR intraprocedural imaging used to achieve consistently optimal EVAR results, and to describe acquisition parameters and strategies for minimizing contrast-induced nephropathy. CONCLUSION. The outcome of EVAR is strongly linked to image acquisition and interpretation, including the preprocedural, intraprocedural, and postprocedural display of relevant vascular anatomy, positions and configurations of the endograft components, and documentation of successful aneurysm exclusion. Operator familiarity with the imaging equipment, radiation and contrast dose reduction strategies, and image optimization techniques strongly influence the outcome of EVAR. C1 [Walker, T. Gregory; Kalva, Sanjeeva P.; Ganguli, Suvranu; Oeklue, Rahmi; Salazar, Gloria M.; Waltman, Arthur C.; Wicky, Stephan] Massachusetts Gen Hosp, Div Vasc Imaging & Intervent, Boston, MA 02116 USA. RP Walker, TG (reprint author), Massachusetts Gen Hosp, Div Vasc Imaging & Intervent, 55 Fruit St,GRB 290A, Boston, MA 02116 USA. EM TGWalker@partners.org NR 34 TC 6 Z9 6 U1 0 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JAN PY 2012 VL 198 IS 1 BP 200 EP 206 DI 10.2214/AJR.11.6608 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 873LF UT WOS:000298884100057 PM 22194498 ER PT J AU Mc Auley, G Jagannathan, J O'Regan, K Krajewski, KM Hornick, JL Butrynski, J Ramaiya, N AF Mc Auley, Grainne Jagannathan, Jyothi O'Regan, Kevin Krajewski, Katherine M. Hornick, Jason L. Butrynski, James Ramaiya, Nikhil TI Extraskeletal Osteosarcoma: Spectrum of Imaging Findings SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE extraskeletal osteosarcoma; osteogenic osteosarcoma; soft-tissue sarcoma ID OSTEOGENIC SARCOMA; SOFT TISSUES AB OBJECTIVE. The purpose of this article is to present the spectrum of imaging findings of primary and metastatic extraskeletal osteosarcoma and highlight the differences from primary osteogenic osteosarcoma in bone. CONCLUSION. Extraskeletal osteosarcoma is a rare mesenchymal malignancy of soft tissue, histologically indistinguishable from primary osteosarcoma of bone. However, there are distinct differences in demographics, imaging features, prognosis, and management compared with osteogenic osteosarcoma. Imaging characteristics reflect tumor morphology, with only 50% of primary tumors showing mineralization. Metastases may or may not show mineralization, even if present in the primary tumor. The overall prognosis is poor. C1 [Mc Auley, Grainne; Jagannathan, Jyothi; O'Regan, Kevin; Krajewski, Katherine M.; Ramaiya, Nikhil] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiol, Boston, MA 02215 USA. [Hornick, Jason L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Butrynski, James] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. RP Mc Auley, G (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiol, 450 Brookline Ave, Boston, MA 02215 USA. EM grainnemcauley@mac.com NR 13 TC 13 Z9 14 U1 0 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JAN PY 2012 VL 198 IS 1 BP W31 EP W37 DI 10.2214/AJR.11.6927 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 873LF UT WOS:000298884100006 PM 22194512 ER PT J AU Dick, AA Mercer, LD Smith, JM McDonald, RA Young, B Healey, PJ AF Dick, Andre A. Mercer, Laina D. Smith, Jodi M. McDonald, Ruth A. Young, Bessie Healey, Patrick J. TI Living Donor Kidney Transplantation in Adolescents: Does Size Matter? SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American-Society-of-Transplant-Surgeons (ASTS) 12th Annual State of the Art Winter Symposium/North-American-Transplant-Coordinators-Organization (NATCO) Symposium for Advanced Transplant Professionals CY JAN 12-15, 2012 CL Miami, FL SP Amer Soc Transplant Surg (ASTS), N Amer Transplant Coordinators Org (NATCO) C1 [Dick, Andre A.; Healey, Patrick J.] Seattle Childrens Hosp, Div Pediat Transplantat, Seattle, WA USA. [Mercer, Laina D.] Seattle Childrens Hosp, Seattle Childrens Res Inst, Seattle, WA USA. [Smith, Jodi M.; McDonald, Ruth A.] Seattle Childrens Hosp, Div Nephrol, Dept Pediat, Seattle, WA USA. [Young, Bessie] VA Puget Sound Hlth Care Syst, Div Nephrol, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2012 VL 12 SU 2 SI SI BP 70 EP 70 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 867UW UT WOS:000298481300050 ER PT J AU Yeh, HD Dong, N Elizabeth, S Schoenfeld, D Markmann, J AF Yeh, Heidi Dong, Ning Elizabeth, Smoot Schoenfeld, David Markmann, James TI Listing Rates for Liver Transplantation Influence Mortality from Liver Disease SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American-Society-of-Transplant-Surgeons (ASTS) 12th Annual State of the Art Winter Symposium/North-American-Transplant-Coordinators-Organization (NATCO) Symposium for Advanced Transplant Professionals CY JAN 12-15, 2012 CL Miami, FL SP Amer Soc Transplant Surg (ASTS), N Amer Transplant Coordinators Org (NATCO) C1 [Yeh, Heidi; Markmann, James] Massachusetts Gen Hosp, Dept Surg, Div Transplantat, Boston, MA 02114 USA. [Dong, Ning; Elizabeth, Smoot; Schoenfeld, David] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2012 VL 12 SU 2 SI SI BP 90 EP 90 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 867UW UT WOS:000298481300114 ER PT J AU Chunara, R Andrews, JR Brownstein, JS AF Chunara, Rumi Andrews, Jason R. Brownstein, John S. TI Social and News Media Enable Estimation of Epidemiological Patterns Early in the 2010 Haitian Cholera Outbreak SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID WEB SEARCH; SURVEILLANCE; INFLUENZA; CONTACTS; NUMBER; MODEL; SARS AB During infectious disease outbreaks, data collected through health institutions and official reporting structures may not be available for weeks, hindering early epidemiologic assessment. By contrast, data from informal media are typically available in near real-time and could provide earlier estimates of epidemic dynamics. We assessed correlation of volume of cholera-related HealthMap news media reports, Twitter postings, and government cholera cases reported in the first 100 days of the 2010 Haitian cholera outbreak. Trends in volume of informal sources significantly correlated in time with official case data and was available up to 2 weeks earlier. Estimates of the reproductive number ranged from 1..54 to 6.89 (informal sources) and 1.27 to 3.72 (official sources) during the initial outbreak growth period, and 1.04 to 1.51 (informal) and 1.06 to 1.73 (official) when Hurricane Tomas afflicted Haiti. Informal data can be used complementarily with official data in an outbreak setting to get timely estimates of disease dynamics. C1 Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Childrens Hosp Boston, Childrens Hosp Informat Program, Div Emergency Med, Boston, MA USA. [Andrews, Jason R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA USA. McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ, Canada. RP Chunara, R (reprint author), 1 Autumn St,Suite 433, Boston, MA 02215 USA. EM rumi@alum.mit.edu; jandrews6@partners.org; john.brownstein@childrens.harvard.edu OI Andrews, Jason/0000-0002-5967-251X FU Google.org; National Library of Medicine [5G08LM9776-2]; National Institutes of Health [1R01LM01812-01]; National institute of Allergy and Infectious Diseases [T32AI007433-20] FX Financial support for this study was provided by research grants from Google.org, the National Library of Medicine (5G08LM9776-2), and National Institutes of Health (1R01LM01812-01) to RC and JSB, and National institute of Allergy and Infectious Diseases training grant (T32AI007433-20) to JRA. NR 29 TC 99 Z9 103 U1 7 U2 48 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD JAN PY 2012 VL 86 IS 1 BP 39 EP 45 DI 10.4269/ajtmh.2012.11-0597 PG 7 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 875WF UT WOS:000299065200013 PM 22232449 ER PT J AU Otto, M Bowser, R Turner, M Berry, J Brettschneider, J Connor, J Costa, J Cudkowicz, M Glass, J Jahn, O Lehnert, S Malaspina, A Parnetti, L Petzold, A Shaw, P Sherman, A Steinacker, P Sussmuth, S Teunissen, C Tumani, H Wuolikainen, A Ludolph, A AF Otto, Markus Bowser, Robert Turner, Martin Berry, James Brettschneider, Johannes Connor, James Costa, Julia Cudkowicz, Merit Glass, Jonathan Jahn, Olaf Lehnert, Stefan Malaspina, Andrea Parnetti, Lucilla Petzold, Axel Shaw, Pamela Sherman, Alexander Steinacker, Petra Suessmuth, Sigurd Teunissen, Charlotte Tumani, Hayrettin Wuolikainen, Anna Ludolph, Albert CA Volcano Grp TI Roadmap and standard operating procedures for biobanking and discovery of neurochemical markers in ALS SO AMYOTROPHIC LATERAL SCLEROSIS LA English DT Review DE Biomarker; biobank; proteomics; cerebrospinal fluid; brain bank ID AMYOTROPHIC-LATERAL-SCLEROSIS; CREUTZFELDT-JAKOB-DISEASE; CEREBROSPINAL-FLUID; QUANTITATIVE PROTEOMICS; MASS-SPECTROMETRY; BRAINNET EUROPE; LIGAND LIBRARY; BIOMARKERS; DIAGNOSIS; BLOOD AB Despite major advances in deciphering the neuropathological hallmarks of amyotrophic lateral sclerosis (ALS), validated neurochemical biomarkers for monitoring disease activity, earlier diagnosis, defining prognosis and unlocking key pathophysiological pathways are lacking. Although several candidate biomarkers exist, translation into clinical application is hindered by small sample numbers, especially longitudinal, for independent verification. This review considers the potential routes to the discovery of neurochemical markers in ALS, and provides a consensus statement on standard operating procedures that will facilitate multicenter collaboration, validation and ultimately clinical translation. C1 [Otto, Markus; Brettschneider, Johannes; Lehnert, Stefan; Steinacker, Petra; Suessmuth, Sigurd; Tumani, Hayrettin; Ludolph, Albert] Univ Ulm, Dept Neurol, D-89081 Ulm, Germany. [Bowser, Robert] St Josephs Hosp, Barrow Neurol Inst, Div Neurol, Phoenix, AZ USA. [Turner, Martin] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Clin Neurosci, Oxford OX3 9DU, England. [Berry, James; Cudkowicz, Merit; Sherman, Alexander] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Connor, James] Penn State Univ, Coll Med, Dept Neurosurg, George M Leader Family Lab, Hershey, PA USA. [Costa, Julia] Univ Nova Lisboa, Inst Tecnol Quim & Biol, Lab Glycobiol, Oeiras, Portugal. [Glass, Jonathan] Emory Univ, Sch Med, Atlanta, GA USA. [Jahn, Olaf] Max Planck Inst Expt Med, Gottingen, Germany. [Malaspina, Andrea] Univ London, Queen Mary Hosp, Ctr Neurosci & Trauma, Blizard Inst Cell & Mol Sci, London WC1E 7HU, England. [Parnetti, Lucilla] Univ Perugia, Neurol Sect, Lab Clin Neurochem, Ctr Memory Disturbances, I-06100 Perugia, Italy. [Petzold, Axel] Natl Hosp Neurol & Neurosurg, UCL Inst Neurol, Dept Neuroimmunol, London WC1N 3BG, England. [Petzold, Axel] Vrije Univ Amsterdam, Med Ctr, Dept Neurol, Amsterdam, Netherlands. [Shaw, Pamela] Univ Sheffield, Sch Med, Acad Unit Neurol, Sheffield, S Yorkshire, England. [Teunissen, Charlotte] Vrije Univ Amsterdam, Med Ctr, Dept Clin Chem, Neurol Lab, Amsterdam, Netherlands. [Wuolikainen, Anna] Umea Univ, Dept Chem, Umea, Sweden. RP Otto, M (reprint author), Univ Ulm, Dept Neurol, Oberer Eselsberg 34, D-89081 Ulm, Germany. EM markus.otto@uni-ulm.de RI Costa, Julia/B-7131-2008; Petzold, Axel/C-1090-2009; Otto, Markus/F-4304-2015; OI Costa, Julia/0000-0001-7782-6319; Petzold, Axel/0000-0002-0344-9749; Otto, Markus/0000-0003-4273-4267; Turner, Martin/0000-0003-0267-3180; Wuolikainen, Anna/0000-0003-0838-5526 FU World Federation of Neurology FX This work was supported by World Federation of Neurology. The name Volcano Group was chosen because the first meeting of the group had to be postponed as several group members were stranded somewhere in the world because of the eruption of the Eyjafjallajokull in Iceland in April 2010. NR 42 TC 40 Z9 40 U1 1 U2 11 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1748-2968 J9 AMYOTROPH LATERAL SC JI Amyotroph. Lateral. Scler. PD JAN PY 2012 VL 13 IS 1 BP 1 EP 10 DI 10.3109/17482968.2011.627589 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 871OF UT WOS:000298746800001 PM 22214350 ER PT J AU Lawton, KA Cudkowicz, ME Brown, MV Alexander, D Caffrey, R Wulff, JE Bowser, R Lawson, R Jaffa, M Milburn, MV Ryals, JA Berry, JD AF Lawton, Kay A. Cudkowicz, Merit E. Brown, Meredith V. Alexander, Danny Caffrey, Rebecca Wulff, Jacob E. Bowser, Robert Lawson, Robert Jaffa, Matt Milburn, Michael V. Ryals, John A. Berry, James D. TI Biochemical alterations associated with ALS SO AMYOTROPHIC LATERAL SCLEROSIS LA English DT Article DE ALS; biomarker; metabolomics; pathophysiology ID AMYOTROPHIC-LATERAL-SCLEROSIS; CREATINE; CANCER; TRIAL; DEGENERATION; METABOLOME; MUTATIONS; NEURONS; MOUSE; DEATH AB Our objective was to identify metabolic pathways affected by ALS using non-targeted metabolomics in plasma, comparing samples from healthy volunteers to those from ALS patients. This discovery could become the basis for the identification of therapeutic targets and diagnostic biomarkers of ALS. Two distinct cross-sectional studies were conducted. Plasma was collected from 62 (Study 1) and 99 (Study 2) participants meeting El Escorial criteria for possible, probable, or definite ALS; 69 (Study 1) and 48 (Study 2) healthy controls samples were collected. Global metabolic profiling was used to detect and evaluate biochemical signatures of ALS. Twenty-three metabolites were significantly altered in plasma from ALS patients in both studies. These metabolites include biochemicals in pathways associated with neuronal change, hypermetabolism, oxidative damage, and mitochondrial dysfunction, all of which are proposed disease mechanisms in ALS. The data also suggest possible hepatic dysfunction associated with ALS. In conclusion, the data presented here provide insight into the pathophysiology of ALS while suggesting promising areas of focus for future studies. The metabolomics approach can generate novel hypotheses regarding ALS disease mechanisms with the potential to identify therapeutic targets and novel diagnostic biomarkers. C1 [Berry, James D.] Massachusetts Gen Hosp, Dept Neurol, Neurol Clin Trials Unit, Charlestown, MA 02129 USA. [Lawton, Kay A.; Brown, Meredith V.; Alexander, Danny; Caffrey, Rebecca; Wulff, Jacob E.; Milburn, Michael V.; Ryals, John A.] Metabolon Inc, Durham, NC USA. [Bowser, Robert] Univ Pittsburgh, Pittsburgh, PA 15260 USA. RP Berry, JD (reprint author), Massachusetts Gen Hosp, Dept Neurol, Neurol Clin Trials Unit, 149 13th St,Suite 2-2274, Charlestown, MA 02129 USA. EM jdberry@partners.org FU ALS Association; National Institutes of Health; National Institute of Neurological Disorders and Stroke; National Institutes of Health/National Center for Research Resources/General Clinical Research Centers Program; North Carolina Biotechnology Center; Neuralstem Inc; ISIS Pharmaceuticals Inc; Knopp Biosciences; Biogen Idec; NIH FX The project was supported, in part, by support from the following: ALS Association, National Institutes of Health, National Institute of Neurological Disorders and Stroke, and National Institutes of Health/National Center for Research Resources/General Clinical Research Centers Program. The content of this publication is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Neurological Disorders and Stroke, National Institutes of Health, or ALS Association. Support for MVB was received from the North Carolina Biotechnology Center Industrial Fellowship program. The authors would also like to acknowledge project input and support from David Lacomis at the University of Pittsburgh School of Medicine, the North-East ALS Consortium (NEALS), the NEALS Biofluid Repository Committee and the committee co-Chairs, Robert Bowser and Carol Milligan. The authors thank Lucie Bruijn and ALSA for guidance; the NEALS Consortium for sample collection; Darlene Sawicki for overseeing protocol development, informed consent design, supervising clinical operations, and research coordination; Lisa Paige, Bruce McCreedy and Jeff Shuster for contributions to preliminary studies; and Matthew Mitchell, and the Metabolon Analytical Team for contributing to statistical analyses and data acquisition. The analysis for this paper was generated using Array Studio software. Array Studio, Array Viewer and Array Server and all other Omicsoft products or service names are registered trademarks or trademarks of Omicsoft Corporation., Research Triangle Park, NC, USA.; Kay Lawton, Meredith Brown, Danny Alexander, Jacob Wulff, Rebecca Caffrey, Mike Milburn, and John Ryals are employees of Metabolon, Inc. Merit Cudkowicz has worked as a consultant for Shire, Trophos, and GlaxoSmithKline. She has received industry-sponsored grants from Neuralstem Inc, ISIS Pharmaceuticals Inc, Knopp Biosciences, and Biogen Idec. She has also received funding from NIH grants. Robert Bowser is a cofounder of Knopp Neurosciences and consultant to Cytonics Corporation. Robert Lawson and Matt Jaffa have no disclosures. James Berry is on the editorial board of the Neurology Resident and Fellow Section and is supported by an NIH training grant. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript. NR 35 TC 33 Z9 33 U1 2 U2 13 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1748-2968 J9 AMYOTROPH LATERAL SC JI Amyotroph. Lateral. Scler. PD JAN PY 2012 VL 13 IS 1 BP 110 EP 118 DI 10.3109/17482968.2011.619197 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 871OF UT WOS:000298746800015 PM 22117131 ER PT J AU Karam, C AF Karam, Chafic TI IBP is a form of PLS and should be distinguished from PBP SO AMYOTROPHIC LATERAL SCLEROSIS LA English DT Letter ID AMYOTROPHIC-LATERAL-SCLEROSIS C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuromuscular Div, Boston, MA 02215 USA. RP Karam, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuromuscular Div, Boston, MA 02215 USA. NR 5 TC 0 Z9 0 U1 2 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1748-2968 J9 AMYOTROPH LATERAL SC JI Amyotroph. Lateral. Scler. PD JAN PY 2012 VL 13 IS 1 BP 158 EP 158 DI 10.3109/17482968.2011.610465 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 871OF UT WOS:000298746800023 PM 22214358 ER PT J AU Troianos, CA Hartman, GS Glas, KE Skubas, NJ Eberhardt, RT Walker, JD Reeves, ST AF Troianos, Christopher A. Hartman, Gregg S. Glas, Kathryn E. Skubas, Nikolaos J. Eberhardt, Robert T. Walker, Jennifer D. Reeves, Scott T. CA Amer Soc Echocardiography TI Guidelines for Performing Ultrasound Guided Vascular Cannulation: Recommendations of the American Society of Echocardiography and the Society of Cardiovascular Anesthesiologists SO ANESTHESIA AND ANALGESIA LA English DT Article ID INTERNAL JUGULAR-VEIN; CENTRAL VENOUS CATHETERIZATION; RADIAL ARTERY CANNULATION; PERIPHERAL INTRAVENOUS ACCESS; RANDOMIZED CONTROLLED-TRIAL; CONTROLLED CLINICAL-TRIAL; COMMON FEMORAL-ARTERY; CROSS-SECTIONAL AREA; ANATOMIC RELATIONSHIP; HEAD ROTATION C1 [Troianos, Christopher A.] W Penn Allegheny Hlth Syst, Dept Anesthesiol, Pittsburgh, PA USA. [Hartman, Gregg S.] Dartmouth Hitchcock Med Ctr, Dept Anesthesiol, Lebanon, NH 03766 USA. [Glas, Kathryn E.] Emory Univ, Dept Anesthesiol, Atlanta, GA 30322 USA. [Skubas, Nikolaos J.] Weill Cornell Med Coll, Dept Anesthesiol, New York, NY USA. [Eberhardt, Robert T.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Walker, Jennifer D.] Massachusetts Gen Hosp, Dept Cardiothorac Surg, Boston, MA 02114 USA. [Reeves, Scott T.] Med Univ S Carolina, Dept Anesthesiol, Charleston, SC 29425 USA. RP Troianos, CA (reprint author), W Penn Allegheny Hlth Syst, Dept Anesthesiol, Pittsburgh, PA USA. NR 96 TC 88 Z9 95 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD JAN PY 2012 VL 114 IS 1 BP 46 EP 72 DI 10.1213/ANE.0b013e3182407cd8 PG 27 WC Anesthesiology SC Anesthesiology GA 866UM UT WOS:000298410400005 PM 22127816 ER PT J AU Frick, CG Fink, H Blobner, M Martyn, J AF Frick, Christiane G. Fink, Heidrun Blobner, Manfred Martyn, Jeevendra TI A Single Injection of Botulinum Toxin Decreases the Margin of Safety of Neurotransmission at Local and Distant Sites SO ANESTHESIA AND ANALGESIA LA English DT Article ID MUSCULOSKELETAL-TISSUE ALLOGRAFTS; ACETYLCHOLINE-RECEPTORS; D-TUBOCURARINE; RESISTANCE; NEUROTOXINS; MECHANISMS; MUSCLES AB BACKGROUND: We tested the hypothesis that a single injection of botulinum toxin not only has local, but also distant effects on muscle function, biochemistry, and pharmacodynamics of atracurium. METHODS: Botulinum toxin (2.5 U) was injected into the tibialis muscle of anesthetized rats (n = 26). The contralateral side with no injection served to study distant effects. Control animals (n = 25) received a saline injection. Neuromuscular function, pharmacology, and expression of acetylcholine receptors (nAChRs) were evaluated in the tibialis at 0, 4, and 16 days after injection and in comparison with saline-injected controls. RESULTS: On day 4, botulinum toxin caused complete paralysis of the tibialis, while its contralateral side showed a decrease in absolute twitch tension (1.8 N [1.6; 1.9] vs 3.0 N [2.8; 3.1], Newton, P < 0.05). On day 16, muscle weakness was only present on the toxin-injected side where absolute twitch tension was decreased (0.6 N [0.6, 0.7] vs 3.4 N [3.1, 3.7], P < 0.05). Tibialis mass was decreased on the toxin-injected side at day 4 (1.46 mg/g [1.43, 1.48] vs 1.74 mg/g [1.72; 1.75], P < 0.05) and on day 16 (0.78 mg/g [0.76, 0.79] vs 1.73 mg/g [1.69; 1.77], P < 0.05). Effects distant from the site of injection were seen on day 16, when muscle atrophy was also present in the adjacent gastrocnemius and soleus muscles. Normalized to tibialis mass, specific twitch tension (tension/g muscle) was reduced on the contralateral side at day 4 and on the toxin-injected side at day 16 in relation to saline controls. At day 16, an increased sensitivity to atracurium was seen on the toxin-injected side, evidenced as a decreased ED(50) (0.23 mg/kg [0.13, 0.33] vs 0.72 mg/kg [0.63, 0.82], P < 0.05) and a lower infusion rate (38 mu L/kg/min [32, 43] vs135 mu L/kg/min [126, 144], P < 0.05), together with a reduced plasma concentration requirement of atracurium (0.5 mu g/mL [0.4, 0.7] vs 4.5 mu g/mL [3.8, 5.2], P < 0.05) to achieve a steady state 50% reduction in baseline (absolute) twitch tension. ED50 of atracurium was also decreased on the contralateral side at day 16 in relation to saline controls. The nAChRs in the tibialis were increased on the toxin-injected side to 123 fmol/mg [115, 131] vs 28 fmol/mg [25, 29] (P < 0.05) in time-matched saline-injected controls at day 4 and to 378 [341, 413] vs 27 fmol/mg [25, 29] (P < 0.05) at day 16. CONCLUSIONS: Botulinum toxin has local and distant effects on muscle. The decrease in specific twitch tension indicates that the muscle atrophy alone cannot explain the functional changes; neuromuscular transmission is also impaired. An increased sensitivity to atracurium on the toxin-injected side, despite up-regulation of nAChRs, seems unique to botulinum toxin. (Anesth Analg 2012; 114: 102-9) C1 [Frick, Christiane G.] TU Muenchen, Dept Anesthesia & Crit Care, Klin Anesthesiol, D-81675 Munich, Germany. [Frick, Christiane G.; Martyn, Jeevendra] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Frick, Christiane G.; Martyn, Jeevendra] Harvard Univ, Sch Med, Shriners Hosp Children, Boston, MA USA. RP Frick, CG (reprint author), TU Muenchen, Dept Anesthesia & Crit Care, Klin Anesthesiol, Ismaningerstr 22, D-81675 Munich, Germany. EM c.frick@lrz.tu-muenchen.de OI Lewald, Heidrun/0000-0002-5192-425X FU National Institutes of Health, Bethesda, MD [GM 031569, GM 055082, GM 21500]; Shriners Hospital Research Philantrophy, Tampa, FL FX Supported by grants (GM 031569, GM 055082, GM 21500-Project IV) from the National Institutes of Health, Bethesda, MD, and Shriners Hospital Research Philantrophy, Tampa, FL, to J.A.J. Martyn. NR 22 TC 6 Z9 6 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD JAN PY 2012 VL 114 IS 1 BP 102 EP 109 DI 10.1213/ANE.0b013e31823526bf PG 8 WC Anesthesiology SC Anesthesiology GA 866UM UT WOS:000298410400011 PM 22003222 ER PT J AU Lee, LA Roth, S Todd, MM Posner, KL Polissar, NL Neradilek, MB Torner, J Newman, NJ Domino, KB Lauer, KK Buddithi, R Gollapudy, S Pajewski, TN Scalzo, DC Avitsian, R Brown, MJ Buenvenida, S Mashour, GA Moore, LE Samra, SK Lieberman, J Lane, RK Ramani, R Wagner, J Tempelhoff, R Monsey, CM Robicsek, SA Vu, MM Weeks, J Manninen, PH Fu, ES Sanchez-Yanes, GC Peterfreund, RA Albrecht, MA Sapire, KJ Baughman, VL Caplan, RA Cheney, FW Metzner, J AF Lee, Lorri A. Roth, Steven Todd, Michael M. Posner, Karen L. Polissar, Nayak L. Neradilek, Moni B. Torner, James Newman, Nancy J. Domino, Karen B. Lauer, Kathryn K. Buddithi, Rachel Gollapudy, Suneeta Pajewski, Thomas N. Scalzo, David C. Avitsian, Rafi Brown, Michael J. Buenvenida, Shonie Mashour, George A. Moore, Laurel E. Samra, Satwant K. Lieberman, Jeremy Lane, Rondall K. Ramani, Ramachandran Wagner, Jessica Tempelhoff, Rene Monsey, Cynthia M. Robicsek, Steven A. Vu, Melissa M. Weeks, Julie Manninen, Pirjo H. Fu, Eugene S. Sanchez-Yanes, Greys C. Peterfreund, Robert A. Albrecht, Meredith A. Sapire, Kenneth J. Baughman, Verna L. Caplan, Robert A. Cheney, Frederick W. Metzner, Julia CA Postoperative Visual Loss Study Gr TI Risk Factors Associated with Ischemic Optic Neuropathy after Spinal Fusion Surgery SO ANESTHESIOLOGY LA English DT Article ID POSTOPERATIVE VISUAL-LOSS; RESUSCITATION; COMPLICATIONS AB Background: Perioperative visual loss, a rare but dreaded complication of spinal fusion surgery, is most commonly caused by ischemic optic neuropathy (ION). The authors sought to determine risk factors for ION in this setting. Methods: Using a multicenter case-control design, the authors compared 80 adult patients with ION from the American Society of Anesthesiologists Postoperative Visual Loss Registry with 315 adult control subjects without ION after spinal fusion surgery, randomly selected from 17 institutions, and matched by year of surgery. Preexisting medical conditions and perioperative factors were compared between patients and control subjects using stepwise multivariate analysis to assess factors that might predict ION. Results: After multivariate analysis, risk factors for ION after spinal fusion surgery included male sex (odds ratio [OR] 2.53, 95% CI 1.35-4.91, P = 0.005), obesity (OR 2.83, 95% CI 1.52-5.39, P = 0.001), Wilson frame use (OR 4.30, 95% CI 2.13-8.75, P < 0.001), anesthesia duration (OR per 1 h = 1.39, 95% CI 1.22-1.58, P < 0.001), estimated blood loss (OR per 1 l = 1.34, 95% CI 1.13-1.61, P = 0.001), and colloid as percent of nonblood replacement (OR per 5% = 0.67, 95% CI 0.52-0.82, P < 0.001). After cross-validation, area under the curve = 0.85, sensitivity = 0.79, and specificity = 0.82. Conclusions: This is the first study to assess ION risk factors in a large, multicenter case-control fashion with detailed perioperative data. Obesity, male sex, Wilson frame use, longer anesthetic duration, greater estimated blood loss, and decreased percent colloid administration were significantly and independently associated with ION after spinal fusion surgery. C1 [Lee, Lorri A.; Posner, Karen L.; Domino, Karen B.] Univ Washington, Dept Anesthesiol & Pain Med, Sch Med, Seattle, WA 98195 USA. [Roth, Steven] Univ Chicago, Dept Anesthesia & Crit Care, Chicago, IL 60637 USA. [Todd, Michael M.; Weeks, Julie] Univ Iowa, Dept Anesthesia, Carver Coll Med, Iowa City, IA 52242 USA. [Polissar, Nayak L.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Polissar, Nayak L.; Neradilek, Moni B.] Mt Whisper Light Stat, Seattle, WA USA. [Torner, James] Univ Iowa, Dept Epidemiol, Carver Coll Med, Iowa City, IA USA. [Newman, Nancy J.] Emory Univ, Dept Ophthalmol, Atlanta, GA 30322 USA. [Newman, Nancy J.] Emory Univ, Dept Neurol, Atlanta, GA 30322 USA. [Lauer, Kathryn K.; Buddithi, Rachel; Gollapudy, Suneeta] Med Coll Wisconsin, Dept Anesthesiol, Milwaukee, WI 53226 USA. [Pajewski, Thomas N.; Scalzo, David C.] Univ Virginia Hlth Syst, Dept Anesthesiol & Neurol Surg, Charlottesville, VA USA. [Avitsian, Rafi] Cleveland Clin, Inst Anesthesiol, Cleveland, OH 44106 USA. [Brown, Michael J.] Mayo Clin, Coll Med, Dept Anesthesiol, Rochester, MN USA. [Buenvenida, Shonie] Mayo Clin, Coll Med, Dept Anesthesiol, Rochester, MN USA. [Mashour, George A.; Moore, Laurel E.; Samra, Satwant K.] Univ Michigan, Dept Anesthesiol, Sch Med, Ann Arbor, MI 48109 USA. [Mashour, George A.] Univ Michigan, Sch Med, Dept Neurosurg, Ann Arbor, MI 48109 USA. [Lieberman, Jeremy; Lane, Rondall K.] Univ Calif San Francisco, Dept Anesthesia & Perioperat Care, San Francisco, CA 94143 USA. [Ramani, Ramachandran; Wagner, Jessica] Yale Univ, Sch Med, Dept Anesthesiol, New Haven, CT 06510 USA. [Tempelhoff, Rene; Monsey, Cynthia M.] Washington Univ, Dept Anesthesiol, St Louis, MO USA. [Robicsek, Steven A.; Vu, Melissa M.] Univ Florida, Dept Anesthesiol, Gainesville, FL USA. [Manninen, Pirjo H.] Univ Toronto, Toronto Western Hosp, Dept Anesthesia, Univ Hlth Network, Toronto, ON M5T 2S8, Canada. [Fu, Eugene S.; Sanchez-Yanes, Greys C.] Univ Miami, Sch Med, Dept Anesthesiol, Miami, FL USA. [Peterfreund, Robert A.; Albrecht, Meredith A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. [Sapire, Kenneth J.] Univ Texas MD Anderson Canc Ctr, Dept Anesthesiol & Perioperat Med, Houston, TX 77030 USA. [Baughman, Verna L.] Univ Illinois, Coll Med Chicago, Dept Anesthesiol, Chicago, IL USA. [Caplan, Robert A.] Virginia Mason Med Ctr, Seattle, WA 98101 USA. [Cheney, Frederick W.; Metzner, Julia] Univ Washington, Sch Med, Dept Anesthesiol & Pain Med, Seattle, WA USA. RP Lee, LA (reprint author), Univ Washington, Dept Anesthesiol & Pain Med, Sch Med, Box 356540,1959 NE Pacific Ave, Seattle, WA 98195 USA. EM lorlee@u.washington.edu FU American Society of Anesthesiologists (ASA); ASA Closed Claims Project, Park Ridge, Illinois; Washington State Society; Department of Anesthesiology and Pain Medicine seed; University of Washington School of Medicine, Seattle, Washington; Research to Prevent Blindness, Inc, New York, New York; Lew Wasserman Award FX Received from the Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, Washington. Submitted for publication June 8, 2011. Accepted for publication September 27, 2011. Supported in part by the American Society of Anesthesiologists (ASA) as part of the ASA Closed Claims Project, Park Ridge, Illinois; the Washington State Society of Anesthesiologists Seafair Grant; and the Department of Anesthesiology and Pain Medicine seed funding grant, University of Washington School of Medicine, Seattle, Washington. Dr. Newman reports receiving partial research support from Research to Prevent Blindness, Inc, New York, New York, via an unrestricted grant and the Lew Wasserman Award to the Department of Ophthalmology, Emory University, Atlanta, Georgia. The funding organizations had no role in the design and conduct of the study; in the collection, analysis, and interpretation of the data; or in the preparation, review, or approval of the manuscript. Information on previous presentation of the information reported in this manuscript: An abstract with preliminary data from a subset of the control cases only (100 out of 315 controls) regarding range of anesthetic management in spine surgery was presented at the American Society of Anesthesiologists (ASA) annual meeting, on October 19, 2009, in New Orleans, Louisiana, as Abstract #A1013. An abstract on the predictive model for ischemic optic neuropathy was submitted to the ASA annual meeting, held October 15-19, 2011, in Chicago, Illinois, for the Late-Breaking Scientific Abstracts Session. No other presentations or publications from this study have been made.The authors gratefully acknowledge the following individuals for acquisition of data: Robin A. Bruchas, M. S. W., Research Study Coordinator, and John Campos, M. A., Research Consultant, Department of Anesthesiology and Pain Medicine, University of Washington School of Medicine, Seattle, Washington; Melissa Passe, R. R. T., Study Coordinator, Department of Anesthesiology, Mayo Clinic College of Medicine, Rochester, Minnesota; Xing Fu, M. D., Resident in Anesthesiology, Department of Anesthesiology, Yale University School of Medicine, New Haven, Connecticut; Aki Honda, M. D., Research Assistant, Department of Anesthesiology, Washington University, St. Louis, Missouri; Elaine Hrinyo, B. S., C. P. C., Professional Fee Billing Manager, and Sharon Jakubczyk, B.S.N., Research Nurse, Department of Anesthesia and Critical Care, University of Chicago, Chicago, Illinois; Stephanie Davis, M. D., Resident, and John Klein, M. D., Resident, Department of Anesthesia, University of Iowa Carver School of Medicine, Iowa City, Iowa; Yiqing Yin, M. D., Anesthesia Fellow, and Qanwei Luo, M. D., Research Assistant, Department of Anesthesia, Toronto Western Hospital, University of Toronto, University Health Network University of Toronto, Toronto, Ontario, Canada; Theresa A. Morris, R.N., Quality Assurance Coordinator, Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Sonya Meyers, M. D., Medical Student ( at time of data collection), Department of Anesthesiology, University of Illinois College of Medicine at Chicago, Chicago, Illinois. The authors acknowledge Lynn Akerlund, Research Coordinator, Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, Washington, for contributions to the project coordination and expert secretarial assistance. NR 23 TC 40 Z9 41 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 JAN PY 2012 VL 116 IS 1 BP 15 EP 24 DI 10.1097/ALN.0b013e31823d012a PG 10 WC Anesthesiology SC Anesthesiology GA 869OU UT WOS:000298608400006 ER PT J AU Eikermann, M Grosse-Sundrup, M Zaremba, S Henry, ME Bittner, EA Hoffmann, U Chamberlin, NL AF Eikermann, Matthias Grosse-Sundrup, Martina Zaremba, Sebastian Henry, Mark E. Bittner, Edward A. Hoffmann, Ulrike Chamberlin, Nancy L. TI Ketamine Activates Breathing and Abolishes the Coupling between Loss of Consciousness and Upper Airway Dilator Muscle Dysfunction SO ANESTHESIOLOGY LA English DT Article ID GENIOGLOSSUS MUSCLE; NMDA RECEPTORS; NERVE ACTIVITY; SLEEP-WAKE; IN-VIVO; ANESTHESIA; PROPOFOL; SEDATION; COLLAPSIBILITY; HYPOGLOSSAL AB Background: Procedural sedation is frequently performed in spontaneously breathing patients, but hypnotics and opioids decrease respiratory drive and place the upper airway at risk for collapse. Methods: In a randomized, controlled, cross-over, pharmaco-physiologic study in 12 rats, we conducted acute experiments to compare breathing and genioglossus electromyogram activity at equianesthetic concentrations of ketamine, a noncompetitive N-methyl-D-aspartate receptor antagonist that combines potent analgesic with hypnotic action effects, versus propofol. In 10 chronically instrumented rats resting in a plethysmograph, we measured these variables as well as electroencephalography during five conditions: quiet wakefulness, nonrapid-eye-movement sleep, rapid eye movement sleep, and low-dose (60 mg/kg intraperitoneally) and high-dose ketamine anesthesia (125 mg/kg intraperitoneally). Results: Ketamine anesthesia was associated with markedly increased genioglossus activity (1.5 to fivefold higher values of genioglossus electromyogram) compared with sleep-and propofol-induced unconsciousness. Plethysmography revealed a respiratory stimulating effect: higher values of flow rate, respiratory rate, and duty-cycle (effective inspiratory time, 1.5-to-2-fold higher values). During wakefulness and normal sleep, the delta (f = 6.51, P = 0.04) electroencephalogram power spectrum was an independent predictor of genioglossus activity, indicating an association between electroencephalographic determinants of consciousness and genioglossus activity. Following ketamine administration, electroencephalogram power spectrum and genioglossus electroencephalogram was dissociated (P = 0.9 for the relationship between delta/theta power spectrum and genioglossus electromyogram). Conclusions: Ketamine is a respiratory stimulant that abolishes the coupling between loss-of-consciousness and upper airway dilator muscle dysfunction in a wide dose-range. Ketamine compared with propofol might help stabilize airway patency during sedation and anesthesia. C1 [Eikermann, Matthias] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Crit Care Div,Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Chamberlin, Nancy L.] Harvard Univ, Sch Med, Div Sleep Med, Boston, MA USA. [Eikermann, Matthias] Univ Klinikum Essen, Klin Anasthesie & Intens Med, Essen, Germany. [Grosse-Sundrup, Martina; Zaremba, Sebastian; Henry, Mark E.; Chamberlin, Nancy L.] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. [Hoffmann, Ulrike] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Eikermann, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Crit Care Div,Dept Anesthesia & Crit Care, Boston, MA 02114 USA. EM meikermann@partners.org FU National Institutes of Health, Bethesda, Maryland [HL095491, HL060292] FX Received from the Department of Anesthesia and Critical Care, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts. Submitted for publication April 5, 2011. Accepted for publication August 4, 2011. This work was performed by members of the Respiratory and Anesthesia Translation Group, an interdisciplinary cooperation between the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, and the Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts. Supported by grant Nos. HL095491 and HL060292 from the National Institutes of Health, Bethesda, Maryland. NR 56 TC 26 Z9 27 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD JAN PY 2012 VL 116 IS 1 BP 35 EP 46 DI 10.1097/ALN.0b013e31823d010a PG 12 WC Anesthesiology SC Anesthesiology GA 869OU UT WOS:000298608400008 PM 22108392 ER PT J AU Ruesch, D Neumann, E Wulf, H Forman, SA AF Ruesch, Dirk Neumann, Elena Wulf, Hinnerk Forman, Stuart A. TI An Allosteric Coagonist Model for Propofol Effects on alpha 1 beta 2 gamma 2L gamma-Aminobutyric Acid Type A Receptors SO ANESTHESIOLOGY LA English DT Article ID OPEN-CLOSE EQUILIBRIUM; GATED ION CHANNELS; GABA(A) RECEPTORS; GENERAL-ANESTHETICS; AZI-ETOMIDATE; MODULATION; SUBUNIT; SITES; EFFICACY; BINDING AB Background: Propofol produces its major actions via gamma-aminobutyric acid type A (GABA(A)) receptors. At low concentrations, propofol enhances agonist-stimulated GABA(A) receptor activity, and high propofol concentrations directly activate receptors. Etomidate produces similar effects, and there is convincing evidence that a single class of etomidate sites mediate both agonist modulation and direct GABA(A) receptor activation. It is unknown if the propofol binding site(s) on GABA(A) receptors that modulate agonist-induced activity also mediate direct activation. Methods: GABA(A) alpha 1 beta 2 gamma 2L receptors were heterologously expressed in Xenopus oocytes and activity was quantified using voltage clamp electrophysiology. We tested whether propofol and etomidate display the same linkage between agonist modulation and direct activation of GABA(A) receptors by identifying equiefficacious drug solutions for direct activation. We then determined whether these drug solutions produce equal modulation of GABA-induced receptor activity. We also measured propofol-dependent direct activation and modulation of low GABA responses. Allosteric coagonist models similar to that established for etomidate, but with variable numbers of propofol sites, were fitted to combined data. Results: Solutions of 19 mu M propofol and 10 mu M etomidate were found to equally activate GABA(A) receptors. These two drug solutions also produced indistinguishable modulation of GABA-induced receptor activity. Combined electrophysiological data behaved in a manner consistent with allosteric coagonist models with more than one propofol site. The best fit was observed when the model assumed three equivalent propofol sites. Conclusions: Our results support the hypothesis that propofol, like etomidate, acts at GABA(A) receptor sites mediating both GABA modulation and direct activation. C1 [Forman, Stuart A.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Forman, Stuart A.] Harvard Univ, Sch Med, Boston, MA USA. [Ruesch, Dirk; Wulf, Hinnerk] Univ Hosp Giessen Marburg, Dept Anesthesia & Intens Care, Marburg, Germany. [Neumann, Elena] Univ Tubingen, Dept Anesthesiol, Sect Expt Anesthesiol, Tubingen, Germany. RP Forman, SA (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Jackson 4,55 Fruit St, Boston, MA 02114 USA. EM saforman@partners.org FU National Institutes of Health, Bethesda, Maryland [P01 GM58448, R01 GM089745]; Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital; Department of Anesthesia and Intensive Care, University Hospital Giessen-Marburg, Marburg, Germany FX Received from the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts. Submitted for publication May 12, 2011. Accepted for publication August 24, 2011. Supported by grant nos. P01 GM58448 and R01 GM089745 from the National Institutes of Health, Bethesda, Maryland; the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital; and the Department of Anesthesia and Intensive Care, University Hospital Giessen-Marburg, Marburg, Germany. NR 35 TC 11 Z9 11 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD JAN PY 2012 VL 116 IS 1 BP 47 EP 55 DI 10.1097/ALN.0b013e31823d0c36 PG 9 WC Anesthesiology SC Anesthesiology GA 869OU UT WOS:000298608400009 PM 22104494 ER PT J AU Agasti, SS Liong, M Tassa, C Chung, HJ Shaw, SY Lee, H Weissleder, R AF Agasti, Sarit S. Liong, Monty Tassa, Carlos Chung, Hyun Jung Shaw, Stanley Y. Lee, Hakho Weissleder, Ralph TI Supramolecular Host-Guest Interaction for Labeling and Detection of Cellular Biomarkers SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE antibodies; bioorthogonal labeling; host-guest systems; nanoparticles; supramolecular chemistry ID MESOPOROUS SILICA NANOPARTICLES; CIRCULATING TUMOR-CELLS; CHEMISTRY; BINDING; SURFACE; RECOGNITION; COMPLEXES; PLATFORM; TARGETS; ASSAYS C1 [Agasti, Sarit S.; Liong, Monty; Tassa, Carlos; Chung, Hyun Jung; Shaw, Stanley Y.; Lee, Hakho; Weissleder, Ralph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Lee, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, 185 Cambridge St, Boston, MA 02114 USA. EM hlee@mgh.harvard.edu; rweissleder@mgh.harvard.edu RI Chung, Hyun Jung/J-3205-2014 FU National Institutes of Health [R01-EB0044626, R01-EB010011, T32A79443, P50A86355]; CCNE [U54A151884]; TPEN [HHSN268201000044C] FX We thank M. Fernandez-Suarez, R. Mazitschek, T. Reiner, K. S. Yang, and K. Tran for helpful discussions; I. Bagayev and E. Tiglao for assistance in cell experiments; N. Sergeyev for providing the crosslinked iron oxide particles; Y. Fisher-Jeffes for reviewing the manuscript. This work was supported in part by National Institutes of Health Grants R01-EB0044626, R01-EB010011, T32 grant T32A79443, P50 grant P50A86355, CCNE contract U54A151884, and TPEN contract HHSN268201000044C. NR 42 TC 29 Z9 29 U1 9 U2 80 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1433-7851 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PY 2012 VL 51 IS 2 BP 450 EP 454 DI 10.1002/anie.201105670 PG 5 WC Chemistry, Multidisciplinary SC Chemistry GA 872ER UT WOS:000298792100019 PM 22113923 ER PT J AU Stone, MB Nagdev, A Tayal, VS Noble, VE AF Stone, Michael B. Nagdev, Arun Tayal, Vivek S. Noble, Vicki E. TI Ultrasonographic Infection Control Practices in the Emergency Department: A Call for Evidence-Based Practice SO ANNALS OF EMERGENCY MEDICINE LA English DT Letter C1 [Stone, Michael B.; Nagdev, Arun] Highland Hosp, Dept Emergency Med, Alameda Cty Med Ctr, Oakland, CA USA. [Tayal, Vivek S.] Carolinas Med Ctr, Dept Emergency Med, Charlotte, NC 28203 USA. [Noble, Vicki E.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Stone, MB (reprint author), Highland Hosp, Dept Emergency Med, Alameda Cty Med Ctr, Oakland, CA USA. NR 3 TC 1 Z9 1 U1 0 U2 4 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 JAN PY 2012 VL 59 IS 1 BP 83 EP 84 DI 10.1016/j.annemergmed.2011.07.040 PG 2 WC Emergency Medicine SC Emergency Medicine GA 873OX UT WOS:000298893800026 PM 22177685 ER PT J AU Sebro, R Lange, C Laird, NM Rogus, JJ Risch, NJ AF Sebro, Ronnie Lange, Christoph Laird, Nan M. Rogus, John J. Risch, Neil J. TI Differentiating Population Stratification from Genotyping Error Using Family Data SO ANNALS OF HUMAN GENETICS LA English DT Article DE Genotyping error; population stratification; nonrandom mating ID SINGLE NUCLEOTIDE POLYMORPHISMS; HARDY-WEINBERG EQUILIBRIUM; TRANSMISSION/DISEQUILIBRIUM TEST; ASSOCIATION; DISEQUILIBRIUM AB Identifying population stratification and genotyping error are important for candidate gene association studies using the Transmission Disequilibrium Test (TDT). Although the TDT retains the prespecified Type I error in the presence of population stratification, the test may have decreased power in the presence of population stratification. Genotyping error can also cause the TDT to have an elevated Type I error. Differentiating population stratification from genotyping error remains a challenge for geneticists. Both genotyping error and population stratification can result in an increase in the observed homozygosity of a sample relative to that expected assuming Hardy-Weinberg Equilibrium (HWE). We show that when family data are available, even if a limited number of markers are genotyped, evaluating the markers that show statistically significant deviation from HWE with the Mating Type Distortion Test (MTDT) a test based on the mating type distribution can reliably differentiate genotyping error from population stratification. We simulate data based on several models of genotyping error in previously published literature, and show how this method could be used in practice to assist in differentiating population stratification from systematic genotyping error. C1 [Sebro, Ronnie; Risch, Neil J.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA. [Sebro, Ronnie] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Lange, Christoph; Laird, Nan M.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Lange, Christoph] Univ Bonn, Inst Genom Math, Bonn, Germany. [Lange, Christoph] German Ctr Neurodegenerat Dis DZNE, Bonn, Germany. [Rogus, John J.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02115 USA. [Risch, Neil J.] Kaiser Permanente, Div Res, Oakland, CA 94612 USA. [Risch, Neil J.] Univ Calif San Francisco, Dept Biostat & Epidemiol, San Francisco, CA 94143 USA. RP Sebro, R (reprint author), Univ Calif San Francisco, Inst Human Genet, 513 Parnassus Ave,Suite S965, San Francisco, CA 94143 USA. EM ronnie.sebro@radiology.ucsf.edu FU Howard Hughes Medical Institute FX Ronnie Sebro was supported by a Howard Hughes Medical Institute Pre-Doctoral Fellowship. The authors thank Solandra Craig and the two anonymous reviewers for their insightful comments that lead to improvement of the manuscript. NR 25 TC 4 Z9 4 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0003-4800 J9 ANN HUM GENET JI Ann. Hum. Genet. PD JAN PY 2012 VL 76 BP 42 EP 52 DI 10.1111/j.1469-1809.2011.00689.x PN 1 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 864QJ UT WOS:000298254600006 PM 22111716 ER PT J AU Olson, EM Lin, NU DiPiro, PJ Najita, JS Krop, IE Winer, EP Burstein, HJ AF Olson, E. M. Lin, N. U. DiPiro, P. J. Najita, J. S. Krop, I. E. Winer, E. P. Burstein, H. J. TI Responses to subsequent anti-HER2 therapy after treatment with trastuzumab-DM1 in women with HER2-positive metastatic breast cancer SO ANNALS OF ONCOLOGY LA English DT Article DE HER2/neu; lapatinib; metastatic breast cancer; trastuzumab; trastuzumab-DM1 ID LAPATINIB AB Background: Women with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) can respond to multiple lines of anti-HER2 therapy. It is unknown whether these patients will derive further clinical benefit following treatment with trastuzumab-MCC-DM1 (T-DM1). Patients and methods: We retrospectively identified HER2-positive MBC patients treated with T-DM1 and characterized outcomes during subsequent lines of anti-HER2 therapy. Response was determined by a blinded radiology review. Time-dependent analyses were carried out using Kaplan-Meier estimates. Results: We identified 23 patients treated with single-agent T-DM1 and report on the 20 patients who discontinued protocol therapy. All patients received trastuzumab-based metastatic therapy before initiation of T-DM1 [median 7 regimens (range 3-14)]. Of these 20 patients, 75% (15 of 20) received further therapy with or without anti-HER2 agents after discontinuing T-DM1. Partial response to either first-or second-subsequent line(s) of therapy was seen in 5 of 15 (33%) treated patients, including 33% (4 of 12) who received a regimen containing trastuzumab and/or lapatinib. Median durations of therapy to first- and second-subsequent regimens after T-DM1 were 5.5 and 6.4 months, respectively. Conclusions: In heavily pretreated HER2-positive MBC patients, prior exposure to T-DM1 does not exhaust the potential benefit of ongoing anti-HER2 therapy with trastuzumab-and/or lapatinib-based regimens. C1 [Olson, E. M.; Lin, N. U.; Krop, I. E.; Winer, E. P.; Burstein, H. J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [DiPiro, P. J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiol, Boston, MA 02215 USA. [Najita, J. S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. RP Burstein, HJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave,Yawkey 12, Boston, MA 02215 USA. EM hburstein@partners.org FU Canadian Cancer Society; Ontario Cancer Research Network; Ligue Nationale Contre le Cancer; Sanofi-Aventis; USA National Cancer Institute [CA 31946, 33601]; Alberta Heritage Foundation for Medical Research; Alberta Cancer Foundation; Genentech Inc. FX Canadian Cancer Society; Ontario Cancer Research Network; Ligue Nationale Contre le Cancer; Sanofi-Aventis (unrestricted grants); USA National Cancer Institute (CA 31946 and 33601); Alberta Heritage Foundation for Medical Research; Alberta Cancer Foundation.; This work was not supported by an outside source and thus there was no involvement from an outside source in any part of this study. EMO, NUL, IEK, and EPW receive research support for clinical trials from Genentech Inc. The other authors declare no conflict of interest. NR 12 TC 14 Z9 14 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JAN PY 2012 VL 23 IS 1 BP 93 EP 97 DI 10.1093/annonc/mdr061 PG 5 WC Oncology SC Oncology GA 866MO UT WOS:000298385300014 PM 21531783 ER PT J AU Prescott, JD Parangi, S AF Prescott, Jason D. Parangi, Sareh TI Bilaterality in Papillary Thyroid Carcinoma: Does It Influence Prognosis? SO ANNALS OF SURGICAL ONCOLOGY LA English DT Editorial Material ID CANCER DATA REGISTRY; RISING INCIDENCE; SURVEILLANCE; EPIDEMIOLOGY; MUTATION C1 [Prescott, Jason D.; Parangi, Sareh] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Thyroid Canc Res Lab,Dept Surg, Boston, MA 02114 USA. RP Prescott, JD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Thyroid Canc Res Lab,Dept Surg, Boston, MA 02114 USA. EM sparangi@partners.org FU NCI NIH HHS [R01 CA149738] NR 10 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD JAN PY 2012 VL 19 IS 1 BP 1 EP 2 DI 10.1245/s10434-011-2098-0 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA 873AL UT WOS:000298852700001 PM 21956610 ER PT J AU Liu, R Wolinsky, JB Catalano, PJ Chirieac, LR Wagner, AJ Grinstaff, MW Colson, YL Raut, CP AF Liu, Rong Wolinsky, Jesse B. Catalano, Paul J. Chirieac, Lucian R. Wagner, Andrew J. Grinstaff, Mark W. Colson, Yolonda L. Raut, Chandrajit P. TI Paclitaxel-Eluting Polymer Film Reduces Locoregional Recurrence and Improves Survival in a Recurrent Sarcoma Model: A Novel Investigational Therapy SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 63rd Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 03-07, 2010 CL St Louis, MO SP Soc Surg Oncol ID SOFT-TISSUE SARCOMA; ELECTRON-BEAM RADIOTHERAPY; PLACEBO-CONTROLLED TRIAL; RETROPERITONEAL SARCOMAS; RADIATION-THERAPY; PROGNOSTIC-FACTORS; DRUG-DELIVERY; INTRAPERITONEAL CHEMOTHERAPY; CISPLATIN; RESECTION AB Locoregional recurrences occur in up to 50% of patients after macroscopically complete (R0/R1) resections of abdominal, pelvic, and retroperitoneal sarcomas. Efficacy of a drug-eluting polymer film in reducing locoregional recurrence rates was assessed in a murine recurrent sarcoma model. Poly(glycerol monostearate-co-caprolactone) polymer films were synthesized with and without 300 mu g paclitaxel (Pax-film and unloaded film). Cytotoxicity was assessed against CS-1 (human chondrosarcoma) cells in vitro and in vivo in nude mice. Following R0/R1 resection of primary subcutaneous tumors, mice were blindly randomized to: (1) Pax-film implant, (2) unloaded film implant, (3) paclitaxel 300 mu g IV (Pax IV), or (4) no other therapy ("untreated"). Locoregional recurrence, overall survival (OS), and tumor mitotic index were evaluated. Pax-films, but not unloaded films, reduced CS-1 viability in vitro for > 50 days (P < 0.001). In vivo, locoregional recurrence was observed in 2 of 12 Pax-film mice (17%), 9 of 13 unloaded film mice (69%), 8 of 9 Pax IV mice (89%), and 7 of 8 untreated mice (88%) (P < 0.01). Median OS was 81, 64, 48, and 56 days, respectively. Paclitaxel levels in local tissues were 50- to 300-fold greater in Pax-film mice compared with Pax IV mice. Tumor mitotic index adjacent to Pax-films was significantly lower than adjacent to unloaded films. Tumor bed implantation of Pax-films after R0/R1 resection is superior to Pax IV as evidenced by reduced locoregional recurrence and improved OS in a murine recurrent sarcoma model. Continuous local drug exposure via polymer films represents a potentially novel approach for treatment of locally aggressive sarcomas. C1 [Liu, Rong; Colson, Yolonda L.; Raut, Chandrajit P.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Wolinsky, Jesse B.; Grinstaff, Mark W.] Boston Univ, Dept Chem, Boston, MA 02215 USA. [Wolinsky, Jesse B.; Grinstaff, Mark W.] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Catalano, Paul J.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Chirieac, Lucian R.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Wagner, Andrew J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Liu, R (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. EM mgrin@bu.edu; ycolson@partners.org; craut@partners.org OI Grinstaff, Mark/0000-0002-5453-3668 NR 42 TC 15 Z9 15 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD JAN PY 2012 VL 19 IS 1 BP 199 EP 206 DI 10.1245/s10434-011-1871-4 PG 8 WC Oncology; Surgery SC Oncology; Surgery GA 873AL UT WOS:000298852700034 PM 21769471 ER PT J AU Azadani, AN Chitsaz, S Matthews, PB Jaussaud, N Leung, J Tsinman, T Ge, L Tseng, EE AF Azadani, Ali N. Chitsaz, Sam Matthews, Peter B. Jaussaud, Nicolas Leung, James Tsinman, Tonia Ge, Liang Tseng, Elaine E. TI Comparison of Mechanical Properties of Human Ascending Aorta and Aortic Sinuses SO ANNALS OF THORACIC SURGERY LA English DT Article ID FINITE-ELEMENT; VALVE INCOMPETENCE; ROOT; ANEURYSM; ARTERIES; MODEL; AGE AB Background. Computational finite element models of the aortic root have previously used material properties of the ascending aorta to describe both aortic sinuses and ascending aorta. We have previously demonstrated significant material property differences between ascending aorta and sinuses in pigs. However, it is unknown whether these regional material property differences exist in humans. The main objective of this study was to investigate biomechanics of fresh human ascending aorta and aortic sinuses and compare nonlinear material properties of these regions. Methods. Fresh human aortic root specimens obtained from the California Transplant Donor Network (Oakland, CA) were subjected to displacement-controlled equibiaxial stretch testing within 24 hours of harvest. Stress-strain data recorded were used to derive strain energy functions for each region. Tissue behavior was quantified by tissue stiffness and a direct comparison was made between different regions of aortic root at physiologic stress levels. Results. All regions demonstrated a nonlinear response to strain during stretch testing in both circumferential and longitudinal directions. No significant difference in tissue stiffness was found between anterior and posterior regions of the ascending aorta or among the three sinuses in both directions. However, our results demonstrated that human ascending aorta is significantly more compliant than aortic sinuses in both circumferential and longitudinal directions within the physiologic stress range. Conclusions. Significant material and structural differences were observed between human ascending aorta and aortic sinuses. Regionally specific material properties should be employed in computational models used to assess treatments of structural aortic root disease. (Ann Thorac Surg 2012;93:87-94) (C) 2012 by The Society of Thoracic Surgeons C1 [Tseng, Elaine E.] Univ Calif San Francisco, Med Ctr, Div Cardiothorac Surg, Dept Surg, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, San Francisco, CA USA. RP Tseng, EE (reprint author), Univ Calif San Francisco, Med Ctr, Div Cardiothorac Surg, Dept Surg, 500 Parnassus Ave,Ste 405W,Box 0118, San Francisco, CA 94143 USA. EM elaine.tseng@ucsfmedctr.org RI Chitsaz, Sam/C-4586-2008 FU American Heart Association FX We thank Dr Philip Ursell for his histologic characterization and the California Transplant Donor Network for the hearts. This work was supported by an American Heart Association Grant-in-Aid, which was administered by the Northern California Institute for Research and Education with resources of the Veterans Affairs Medical Center, San Francisco, California. NR 18 TC 19 Z9 19 U1 2 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JAN PY 2012 VL 93 IS 1 BP 87 EP 94 DI 10.1016/j.athoracsur.2011.08.002 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 864QR UT WOS:000298255400019 PM 22075218 ER PT J AU Hynes, BG Margey, RJ Ruggiero, N Kiernan, TJ Rosenfield, K Jaff, MR AF Hynes, Brian G. Margey, Ronan J. Ruggiero, Nicholas, II Kiernan, Thomas J. Rosenfield, Kenneth Jaff, Michael R. TI Endovascular Management of Acute Limb Ischemia SO ANNALS OF VASCULAR SURGERY LA English DT Review ID TISSUE-PLASMINOGEN-ACTIVATOR; PROSPECTIVE RANDOMIZED TRIAL; PERIPHERAL ARTERIAL-DISEASE; DIRECTED THROMBOLYTIC THERAPY; LOWER-EXTREMITY ISCHEMIA; INTER-SOCIETY CONSENSUS; ACUTE LEG ISCHEMIA; SURGICAL REVASCULARIZATION; INTRAOPERATIVE ANGIOGRAPHY; ANTITHROMBOTIC THERAPY AB Despite major advances in pharmacologic and endovascular therapies, acute limb ischemia (ALI) continues to result in significant morbidity and mortality. The incidence of ALI may be as high as 13-17 cases per 100,000 people per year, with mortality rates approaching 18% in some series. This review will address the contemporary endovascular management of ALI encompassing pharmacologic and percutaneous interventional treatment strategies. C1 [Hynes, Brian G.; Margey, Ronan J.; Rosenfield, Kenneth; Jaff, Michael R.] Massachusetts Gen Hosp, Div Cardiol, Sect Vasc Med, Boston, MA 02114 USA. [Ruggiero, Nicholas, II] Thomas Jefferson Univ Hosp, Div Cardiol, Philadelphia, PA 19107 USA. [Kiernan, Thomas J.] Cork Univ Hosp, Dept Cardiol, Cork, Ireland. RP Jaff, MR (reprint author), Massachusetts Gen Hosp, Div Cardiol, Sect Vasc Med, 55 Fruit St, Boston, MA 02114 USA. EM mrjaff@partners.org NR 80 TC 6 Z9 9 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0890-5096 J9 ANN VASC SURG JI Ann. Vasc. Surg. PD JAN PY 2012 VL 26 IS 1 BP 110 EP 124 DI 10.1016/j.avsg.2011.05.017 PG 15 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 865QR UT WOS:000298325900020 PM 21920700 ER PT J AU Sizova, MV Hohmann, T Hazen, A Paster, BJ Halem, SR Murphy, CM Panikov, NS Epstein, SS AF Sizova, M. V. Hohmann, T. Hazen, A. Paster, B. J. Halem, S. R. Murphy, C. M. Panikov, N. S. Epstein, S. S. TI New Approaches for Isolation of Previously Uncultivated Oral Bacteria SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID IN-SITU CULTIVATION; SP-NOV.; UNCULTURABLE BACTERIA; DENTAL PLAQUE; DIVERSITY; MICROORGANISMS; MICROBIOLOGY; CULTURE; METAGENOMICS; CLOSTRIDIUM AB A significant number of microorganisms from the human oral cavity remain uncultivated. This is a major impediment to the study of human health since some of the uncultivated species may be involved in a variety of systemic diseases. We used a range of innovations previously developed to cultivate microorganisms from the human oral cavity, focusing on anaerobic species. These innovations include (i) in vivo cultivation to specifically enrich for species actively growing in the oral cavity (the "minitrap" method), (ii) single-cell long-term cultivation to minimize the effect of fast-growing microorganisms, and (iii) modifications of conventional enrichment techniques, using media that did not contain sugar, including glucose. To enable cultivation of obligate anaerobes, we maintained strict anaerobic conditions in most of our cultivation experiments. We report that, on a per cell basis, the most successful recovery was achieved using minitrap enrichment (11%), followed by single-cell cultivation (3%) and conventional plating (1%). Taxonomically, the richest collection was obtained using the single-cell cultivation method, followed by minitrap and conventional enrichment, comprising representatives of 13, 9, and 4 genera, respectively. Interestingly, no single species was isolated by all three methods, indicating method complementarity. An important result is the isolation and maintenance in pure culture of 10 strains previously only known by their molecular signatures, as well as representatives of what are likely to be three new microbial genera. We conclude that the ensemble of new methods we introduced will likely help close the gap between cultivated and uncultivated species from the human oral cavity. C1 [Sizova, M. V.; Hohmann, T.; Hazen, A.; Panikov, N. S.; Epstein, S. S.] Northeastern Univ, Dept Biol, Boston, MA 02115 USA. [Paster, B. J.; Halem, S. R.; Murphy, C. M.] Forsyth Inst, Cambridge, MA USA. [Paster, B. J.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. RP Epstein, SS (reprint author), Northeastern Univ, Dept Biol, Boston, MA 02115 USA. EM s.epstein@neu.edu FU NIH [1RC1DE020707-01, 3 R21 DE018026-02S1] FX This work was supported by NIH grants 1RC1DE020707-01 and 3 R21 DE018026-02S1 to S.S.E. NR 60 TC 31 Z9 31 U1 2 U2 36 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD JAN PY 2012 VL 78 IS 1 BP 194 EP 203 DI 10.1128/AEM.06813-11 PG 10 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 866QR UT WOS:000298396700025 PM 22057871 ER PT J AU Nakamura, Y He, XJ Kato, H Wakitani, S Kobayashi, T Watanabe, S Iida, A Tahara, H Warman, ML Watanapokasin, R Postlethwait, JH AF Nakamura, Yukio He, Xinjun Kato, Hiroyuki Wakitani, Shigeyuki Kobayashi, Tatsuya Watanabe, Sumiko Iida, Atsumi Tahara, Hideaki Warman, Matthew L. Watanapokasin, Ramida Postlethwait, John H. TI Sox9 Is Upstream of MicroRNA-140 in Cartilage SO APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY LA English DT Article DE MicroRNA-140 (miR-140); Sox9; Cartilage; Zebrafish; T/C-28; siRNA; In situ hybridization; RT-PCR ID SRY-RELATED GENE; AUTOSOMAL SEX REVERSAL; TRANSCRIPTIONAL REGULATION; EMBRYONIC-DEVELOPMENT; CAMPOMELIC DYSPLASIA; EXPRESSION; ZEBRAFISH; CHONDROGENESIS; PROTEIN; MUTATIONS AB MicroRNA-140 (miR-140) is specifically expressed in developing cartilage tissues. We have previously reported that miR-140 plays an important role during palatal cartilage development by modulating platelet-derived growth factor receptor alpha (pdgfra) in zebrafish. However, the regulatory mechanism of miR-140 in cartilage is still unknown. Using developing zebrafish, sox9a mutant (sox9a-/-) and sox9b mutant (sox9b-/-) zebrafish and SOX9 small interfering RNA in human chondrocytes, T/C-28 cells, we found that miR-140 is regulated by the cartilage master transcription regulator Sox9 in zebrafish and mammalian cells. C1 [Watanapokasin, Ramida] Srinakharinwirot Univ, Dept Biochem, Fac Med, Bangkok, Thailand. [Warman, Matthew L.] Childrens Hosp Boston, Howard Hughes Med Inst, Dept Orthopaed Surg, Boston, MA 02115 USA. [Warman, Matthew L.] Childrens Hosp Boston, Howard Hughes Med Inst, Dept Genet, Boston, MA 02115 USA. [Warman, Matthew L.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Tahara, Hideaki] Univ Tokyo, Inst Med Sci, Adv Clin Res Ctr, Dept Surg & Bioengn, Tokyo 1088639, Japan. [Watanabe, Sumiko; Iida, Atsumi] Univ Tokyo, Inst Med Sci, Dept Mol & Dev Biol, Tokyo 1088639, Japan. [Kobayashi, Tatsuya] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Kobayashi, Tatsuya] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Wakitani, Shigeyuki] Osaka City Univ, Grad Sch Med, Dept Orthopaed Surg, Osaka 5458585, Japan. [He, Xinjun; Postlethwait, John H.] Univ Oregon, Inst Neurosci, Eugene, OR 97403 USA. [Nakamura, Yukio; Kato, Hiroyuki] Shinshu Univ, Sch Med, Dept Orthopaed Surg, Matsumoto, Nagano 3908621, Japan. RP Watanapokasin, R (reprint author), Srinakharinwirot Univ, Dept Biochem, Fac Med, Bangkok, Thailand. EM ramidawa@yahoo.com RI He, Xinjun/F-9797-2011 FU NIH [HD22486, RR020833] FX We thank Dr. Keiko Tamai at Case Western Reserve University, Cleveland, OH for her valuable discussions and to NIH grants HD22486 and RR020833 to JHP. NR 29 TC 26 Z9 32 U1 2 U2 7 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0273-2289 J9 APPL BIOCHEM BIOTECH JI Appl. Biochem. Biotechnol. PD JAN PY 2012 VL 166 IS 1 BP 64 EP 71 DI 10.1007/s12010-011-9404-y PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 874XZ UT WOS:000298992900007 PM 22052544 ER PT J AU Tanpowpong, P Ingham, TR Lampshire, PK Kirchberg, FF Epton, MJ Crane, J Camargo, CA AF Tanpowpong, Pornthep Ingham, Tristram R. Lampshire, Phillipa K. Kirchberg, Franca F. Epton, Michael J. Crane, Julian Camargo, Carlos A., Jr. CA New Zealand Asthma & Allergy Cohor TI Coeliac disease and gluten avoidance in New Zealand children SO ARCHIVES OF DISEASE IN CHILDHOOD LA English DT Article ID IRRITABLE-BOWEL-SYNDROME; QUALITY-OF-LIFE; LACTOSE-INTOLERANCE; FREE DIET; PREVALENCE; SYMPTOMS; DIAGNOSIS; RISK AB Objectives Although gluten avoidance is thought to be common among New Zealanders, the prevalence of gluten avoidance and of actual coeliac disease (CD) in children is uncertain. Our aims were: (1) to determine the prevalence of doctor-diagnosed CD and of gluten avoidance in New Zealand children; and (2) among children without CD, to identify independent predictors of gluten avoidance. Design The New Zealand Asthma and Allergy Cohort Study has detailed information on participants' demographic, pregnancy-related and neonatal factors. The authors surveyed parents regarding their child's history of lactose intolerance and gluten-related issues (eg, gluten avoidance, history of wheat or gluten allergy in first degree relatives, testing and doctor diagnosis of CD). After excluding children with doctor-diagnosed CD, the authors identified independent predictors of gluten avoidance. Results Among 916 children, most (78%) were of European ethnicity. The authors identified nine (1.0%, 95% CI 0.5% to 1.9%) who had doctor-diagnosed CD, while 48 (5.2%, 95% CI 4.0% to 6.9%) avoided gluten. Among children without diagnosed CD, significant independent predictors for gluten avoidance were Christchurch site (OR 2.2, 95% CI 1.02 to 4.7), prior testing for CD (OR 9.0, 95% CI 4.1 to 19.5) and doctor-diagnosed lactose intolerance (OR 5.2, 95% CI 2.0 to 13.9). Conclusions CD affected 1% of these New Zealand children, but 5% reported gluten avoidance. The predictors of gluten avoidance in children without doctor-diagnosed CD suggest important regional differences in community belief or medical practice regarding implementation of gluten avoidance and the contributory role of non-specific subjective abdominal complaints. C1 [Kirchberg, Franca F.; Camargo, Carlos A., Jr.] Harvard Univ, Dept Emergency Med, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Tanpowpong, Pornthep] Harvard Univ, Div Pediat Gastroenterol Hepatol & Nutr, Sch Med, Massachusetts Gen Hosp Children,Dept Pediat, Boston, MA 02114 USA. [Ingham, Tristram R.; Lampshire, Phillipa K.; Crane, Julian] Univ Otago, Wellington Asthma Res Grp, Dept Med, Wellington Sch Med & Hlth Sci, Wellington, New Zealand. [Epton, Michael J.] Christchurch Hosp, Dept Resp Med, Christchurch, New Zealand. RP Camargo, CA (reprint author), Harvard Univ, Dept Emergency Med, Massachusetts Gen Hosp, Sch Med, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM ccamargo@partners.org OI Siebers, Robert/0000-0002-6359-3144; Kirchberg, Franca Fabiana/0000-0001-6863-1202 FU Health Research Council of New Zealand; David and Cassie Anderson Bequest (Wellington, New Zealand); Food Allergy & Anaphylaxis Network (Fairfax, Virginia, USA) FX This work was supported by grants from the Health Research Council of New Zealand, the David and Cassie Anderson Bequest (Wellington, New Zealand) and the Food Allergy & Anaphylaxis Network (Fairfax, Virginia, USA). NR 32 TC 38 Z9 39 U1 0 U2 14 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-9888 EI 1468-2044 J9 ARCH DIS CHILD JI Arch. Dis. Child. PD JAN PY 2012 VL 97 IS 1 BP 12 EP 16 DI 10.1136/archdischild-2011-300248 PG 5 WC Pediatrics SC Pediatrics GA 865ZS UT WOS:000298350000005 PM 22075107 ER PT J AU Roussos, P Katsel, P Davis, KL Bitsios, P Giakoumaki, SG Jogia, J Rozsnyai, K Collier, D Frangou, S Siever, LJ Haroutunian, V AF Roussos, Panos Katsel, Pavel Davis, Kenneth L. Bitsios, Panos Giakoumaki, Stella G. Jogia, Jigar Rozsnyai, Kinga Collier, David Frangou, Sophia Siever, Larry J. Haroutunian, Vahram TI Molecular and Genetic Evidence for Abnormalities in the Nodes of Ranvier in Schizophrenia SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID MULTIPLE BRAIN-REGIONS; ANTERIOR CINGULATE CORTEX; GENOME-WIDE ASSOCIATION; MILD ALZHEIMER-DISEASE; BIPOLAR DISORDER; EXPRESSION; MYELIN; HIPPOCAMPUS; DYSFUNCTION; PHENOTYPE AB Context: Genetic, neuroimaging, and molecular neurobiological evidence support the hypothesis that the disconnectivity syndrome in schizophrenia (SZ) could arise from failures of saltatory conduction and abnormalities at the nodes of Ranvier (NOR) interface where myelin and axons interact. Objective: To identify abnormalities in the expression of oligodendroglial genes and proteins that participate in the formation, maintenance, and integrity of the NOR in SZ. Design: The messenger RNA (mRNA) expression levels of multiple NOR genes were quantified in 2 independent postmortem brain cohorts of individuals with SZ, and generalizability to protein expression was confirmed. The effect of the ANK3 genotype on the mRNA expression level was tested in postmortem human brain. Case-control analysis tested the association of the ANK3 genotype with SZ. The ANK3 genotype's influence on cognitive task performance and functional magnetic resonance imaging activation was tested in 2 independent cohorts of healthy individuals. Setting: Research hospital. Patients: Postmortem samples from patients with SZ and healthy controls were used for the brain expression study (n=46) and the case-control analysis (n=272). Healthy white men and women participated in the cognitive (n=513) and neuroimaging (n=52) studies. Main Outcome Measures: The mRNA and protein levels in postmortem brain samples, genetic association with schizophrenia, cognitive performance, and blood oxygenation level-dependent functional magnetic resonance imaging. Results: The mRNA expression of multiple NOR genes was decreased in schizophrenia. The ANK3 rs9804190 C allele was associated with lower ANK3 mRNA expression levels, higher risk for SZ in the case-control cohort, and poorer working memory and executive function performance and increased prefrontal activation during a working memory task in healthy individuals. Conclusions: These results point to abnormalities in the expression of genes and protein associated with the integrity of the NOR and suggest them as substrates for the disconnectivity syndrome in SZ. The association of ANK3 with lower brain mRNA expression levels implicates a molecular mechanism for its genetic, clinical, and cognitive associations with SZ. C1 [Roussos, Panos; Katsel, Pavel; Davis, Kenneth L.; Siever, Larry J.; Haroutunian, Vahram] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Roussos, Panos; Siever, Larry J.; Haroutunian, Vahram] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. [Roussos, Panos; Bitsios, Panos; Giakoumaki, Stella G.] Univ Crete, Dept Psychiat & Behav Sci, Fac Med, Iraklion, Crete, Greece. [Jogia, Jigar; Frangou, Sophia] Kings Coll London, Sect Neurobiol Psychosis, Inst Psychiat, London, England. [Rozsnyai, Kinga; Collier, David] Kings Coll London, Social Genet & Dev Psychiat Res Ctr, Inst Psychiat, London, England. RP Haroutunian, V (reprint author), Mt Sinai Sch Med, Dept Psychiat, Room 4F-33,130 Kingsbridge Rd, Bronx, NY 10468 USA. EM vahram.haroutunian@mssm.edu RI Frangou, Sophia/A-2672-2013; Collier, David/D-1649-2011; Roussos, Panos/J-7090-2013; OI Collier, David/0000-0003-4087-1559; Roussos, Panos/0000-0002-4640-6239; Jogia, Jigar/0000-0003-1799-1245 FU National Institutes of Health [MH066392, MH064673]; Veterans Affairs Mental Illness Research Education and Clinical Center; Veterans Affairs FX This work was supported by grants MH066392 and MH064673 from the National Institutes of Health (Dr Haroutunian), a Veterans Affairs Mental Illness Research Education and Clinical Center award (Dr Siever), and a Veterans Affairs merit award (Dr Haroutunian). NR 39 TC 45 Z9 48 U1 0 U2 12 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 JAN PY 2012 VL 69 IS 1 BP 7 EP 15 DI 10.1001/archgenpsychiatry.2011.110 PG 9 WC Psychiatry SC Psychiatry GA 870NH UT WOS:000298675700002 PM 21893642 ER PT J AU Olfson, M Marcus, SC Bridge, JA AF Olfson, Mark Marcus, Steven C. Bridge, Jeffrey A. TI Emergency Treatment of Deliberate Self-harm SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID BORDERLINE PERSONALITY-DISORDER; ATTEMPTED-SUICIDE; FOLLOW-UP; COMPLETED SUICIDE; DEPARTMENT VISITS; HEALTH-CARE; COHORT; ADULTS; RISK; DEPRESSION AB Context: Although concern exists over the quality of emergency mental health services, little is known about the mental health care of adults who are admitted to emergency departments for deliberately harming themselves and then discharged to the community. Objective: To describe the predictors of emergency department discharge, the emergency mental health assessments, and the follow-up outpatient mental health care of adult Medicaid beneficiaries treated for deliberate self-harm. Design: A retrospective longitudinal cohort analysis. Setting: National Medicaid claims data supplemented with county-level sociodemographic variables and Medicaid state policy survey data. Participants: Adults aged 21 to 64 years who were treated in emergency departments for 7355 episodes of deliberate self-harm, focusing on those who were discharged to the community (4595 episodes). Main Outcome Measures: Rates and adjusted risk ratios (ARRs) of discharge to the community, mental health assessments in the emergency department, and outpatient mental health visits during the 30 days following the emergency department visit. Results: Most patients (62.5%) were discharged to the community. Emergency department discharge was directly related to younger patient age (21-31 years vs 45-64 years) (ARR, 1.18 [99% confidence interval {CI}, 1.10-1.25]) and self-harm by cutting (ARR, 1.18 [99% CI, 1.12-1.24]) and inversely related to poisoning (ARR, 0.84 [99% CI, 0.80-0.89]) and recent psychiatric hospitalization (ARR, 0.74 [99% CI, 0.67-0.81]). Approximately one-half of discharged patients (47.5%) received a mental health assessment in the emergency department, and a similar percentage of discharged patients (52.4%) received a follow-up outpatient mental health visit within 30 days. Follow-up mental health care was directly related to recent outpatient mental health care (ARR, 2.30 [99% CI, 2.11-2.50]) and treatment in a state with Medicaid coverage of mental health clinic services (ARR, 1.13 [99% CI, 1.05-1.22]) and inversely related to African American (ARR, 0.86 [99% CI, 0.75-0.96]) and Hispanic (ARR, 0.86 [99% CI, 0.75-0.99]) race/ethnicity. Conclusion: Most adult Medicaid beneficiaries who present for emergency care for deliberate self-harm are discharged to the community, and many do not receive emergency mental health assessments or follow-up outpatient mental health care. C1 [Olfson, Mark] Columbia Univ, New York State Psychiat Inst, Dept Psychiat, Coll Phys & Surg, New York, NY 10032 USA. [Marcus, Steven C.] Univ Penn, Ctr Hlth Equ Res & Promot, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Marcus, Steven C.] Univ Penn, Sch Social Policy & Practice, Philadelphia, PA 19104 USA. [Bridge, Jeffrey A.] Ohio State Univ, Res Inst, Nationwide Childrens Hosp, Ctr Innovat Pediat Practice, Columbus, OH USA. [Bridge, Jeffrey A.] Ohio State Univ, Dept Pediat, Columbus, OH USA. RP Olfson, M (reprint author), Columbia Univ, New York State Psychiat Inst, Dept Psychiat, Coll Phys & Surg, 1051 Riverside Dr, New York, NY 10032 USA. EM mo49@columbia.edu FU Eli Lilly; Bristol-Myers Squibb; AstraZeneca; Dainippon Sumitomo; Forest Research Institute; Ortho-McNeil-Janssen; Pfizer Inc; Roche Pharmaceuticals; sanofi-aventis; Schering-Plough; Sepracor; United BioSource; Lundbeck; American Foundation for Suicide Prevention FX Dr Olfson has received a research grant to Columbia University from Eli Lilly and Bristol-Myers Squibb. Dr Bridge has received honoraria for participation in a suicidality consensus conference supported by independent educational or other unrestricted grant support from AstraZeneca, Dainippon Sumitomo, Eli Lilly, Forest Research Institute, Ortho-McNeil-Janssen, Pfizer Inc, Roche Pharmaceuticals, sanofi-aventis, Schering-Plough, Sepracor, and United BioSource; and he has presented on suicide prevention in children and adolescents at a conference supported in part by Eli Lilly and Lundbeck.; This research was funded by a grant to Columbia University from the American Foundation for Suicide Prevention. NR 60 TC 24 Z9 24 U1 4 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 JAN PY 2012 VL 69 IS 1 BP 80 EP 88 DI 10.1001/archgenpsychiatry.2011.108 PG 9 WC Psychiatry SC Psychiatry GA 870NH UT WOS:000298675700010 PM 21893643 ER PT J AU Craft, S Baker, LD Montine, TJ Minoshima, S Watson, GS Claxton, A Arbuckle, M Callaghan, M Tsai, E Plymate, SR Green, PS Leverenz, J Cross, D Gerton, B AF Craft, Suzanne Baker, Laura D. Montine, Thomas J. Minoshima, Satoshi Watson, G. Stennis Claxton, Amy Arbuckle, Matthew Callaghan, Maureen Tsai, Elaine Plymate, Stephen R. Green, Pattie S. Leverenz, James Cross, Donna Gerton, Brooke TI Intranasal Insulin Therapy for Alzheimer Disease and Amnestic Mild Cognitive Impairment A Pilot Clinical Trial SO ARCHIVES OF NEUROLOGY LA English DT Article ID AMYLOID-BETA; RATING-SCALE; OLDER-ADULTS; HUMAN BRAIN; IN-VIVO; MECHANISMS; PLASTICITY; INCREASES; OLIGOMERS; SEVERITY AB Objective: To examine the effects of intranasal insulin administration on cognition, function, cerebral glucose metabolism, and cerebrospinal fluid biomarkers in adults with amnestic mild cognitive impairment or Alzheimer disease (AD). Design: Randomized, double-blind, placebo-controlled trial. Setting: Clinical research unit of a Veterans Affairs medical center. Participants: The intent-to-treat sample consisted of 104 adults with amnestic mild cognitive impairment (n=64) or mild to moderate AD (n=40). Intervention: Participants received placebo (n=30), 20 IU of insulin (n=36), or 40 IU of insulin (n=38) for 4 months, administered with a nasal drug delivery device (Kurve Technology, Bothell, Washington). Main Outcome Measures: Primary measures consisted of delayed story recall score and the Dementia Severity Rating Scale score, and secondary measures included the Alzheimer Disease's Assessment Scale-cognitive subscale (ADAS-cog) score and the Alzheimer's Disease Cooperative Study-activities of daily living (ADCS-ADL) scale. A subset of participants underwent lumbar puncture (n=23) and positron emission tomography with fludeoxyglucose F 18 (n=40) before and after treatment. Results: Outcome measures were analyzed using repeated-measures analysis of covariance. Treatment with 20 IU of insulin improved delayedmemory(P <.05), and both doses of insulin (20 and 40 IU) preserved caregiver-rated functional ability (P <.01). Both insulin doses also preserved general cognition as assessed by the ADAS-cog score for younger participants and functional abilities as assessed by the ADCS-ADL scale for adults with AD (P <.05). Cerebrospinal fluid biomarkers did not change for insulin-treated participants as a group, but, in exploratory analyses, changes in memory and function were associated with changes in the A beta 42 level and in the tau protein-to-A beta 42 ratio in cerebrospinal fluid. Placebo-assigned participants showed decreased fludeoxyglucose F 18 uptake in the parietotemporal, frontal, precuneus, and cuneus regions and insulin-minimized progression. No treatment-related severe adverse events occurred. Conclusions: These results support longer trials of intranasal insulin therapy for patients with amnestic mild cognitive impairment and patients with AD. C1 [Craft, Suzanne; Baker, Laura D.; Watson, G. Stennis; Claxton, Amy; Arbuckle, Matthew; Callaghan, Maureen; Plymate, Stephen R.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Leverenz, James; Gerton, Brooke] Vet Affairs Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Craft, Suzanne; Baker, Laura D.; Watson, G. Stennis; Claxton, Amy; Leverenz, James] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Montine, Thomas J.] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. [Minoshima, Satoshi; Cross, Donna] Univ Washington, Sch Med, Dept Radiol, Seattle, WA 98195 USA. [Tsai, Elaine; Plymate, Stephen R.; Green, Pattie S.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Leverenz, James; Gerton, Brooke] Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA. RP Craft, S (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, S-182,1660 S Columbian Way, Seattle, WA 98108 USA. EM scraft@uw.edu FU National Institute of Aging [AG027415, P50 AG05136, T32 AG000258]; Nancy and Buster Alvord Endowment; Department of Veterans Affairs FX This research was supported by National Institute of Aging grants AG027415 (to Dr Craft), P50 AG05136 (to Dr Montine), and T32 AG000258 (to Dr Claxton), the Nancy and Buster Alvord Endowment, and the Department of Veterans Affairs. This material is the result of work supported in part by resources from the Veterans Affairs Puget Sound Health Care System, Seattle, Washington. NR 31 TC 390 Z9 397 U1 17 U2 82 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 JAN PY 2012 VL 69 IS 1 BP 29 EP 38 DI 10.1001/archneurol.2011.233 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 874GX UT WOS:000298944500004 PM 21911655 ER PT J AU Gorman, MP Tillema, JM Ciliax, AM Guttmann, CRG Chitnis, T AF Gorman, Mark P. Tillema, Jan-Mendelt Ciliax, Annika M. Guttmann, Charles R. G. Chitnis, Tanuja TI Daclizumab Use in Patients With Pediatric Multiple Sclerosis SO ARCHIVES OF NEUROLOGY LA English DT Article ID ANTIBODY; THERAPY; NATALIZUMAB AB Background: Daclizumab, a humanized monoclonal antibody specific for the interleukin 2 receptor alpha chain, reduces clinical and magnetic resonance imaging disease activity in patients with adult-onset multiple sclerosis (MS) as monotherapy or add-on therapy with interferon. Objective: To report the use of daclizumab in pediatric-onset MS. Design: Case series. Setting: Two comprehensive pediatric MS centers. Patients: Seven patients with pediatric-onset MS with clinical and magnetic resonance imaging disease activity despite first-line disease-modifying therapy. Intervention: Intravenous daclizumab, 1 mg/kg monthly. Main Outcome Measures: Annualized relapse rates, Expanded Disability Status Scale scores, contrast-enhancing lesions, and adverse effects. Results: Treatment with daclizumab, primarily combined with interferon, was associated with reductions in annualized relapse rates and contrast-enhancing lesions and with reduction or stabilization of Expanded Disability Status Scale scores in each patient. However, 4 patients had relapses and new contrast-enhancing lesions during daclizumab treatment. No significant adverse effects occurred. Conclusion: Daclizumab may be a safe and at least partially effective treatment option for patients with pediatric-onset MS with disease activity despite first-line disease-modifying therapy. C1 [Gorman, Mark P.; Chitnis, Tanuja] Massachusetts Gen Hosp, Partners Pediat Multiple Sclerosis Ctr, Boston, MA 02114 USA. [Gorman, Mark P.] Childrens Hosp Boston, Pediat Multiple Sclerosis & Related Disorders Pro, Boston, MA USA. [Ciliax, Annika M.; Guttmann, Charles R. G.] Brigham & Womens Hosp, Ctr Neurol Imaging, Boston, MA 02115 USA. [Tillema, Jan-Mendelt] Cincinnati Childrens Hosp Med Ctr, Div Neurol, Cincinnati, OH USA. RP Chitnis, T (reprint author), Massachusetts Gen Hosp, Partners Pediat Multiple Sclerosis Ctr, ACC 708,55 Fruit St, Boston, MA 02114 USA. EM tchitnis@partners.org FU Teva Neuroscience; Merck-Serono; EMD-Serono; Pediatric Multiple Sclerosis Centers of Excellence from the National Multiple Sclerosis Society FX Dr Guttman has served as a consultant for Tibotec Therapeutics/Johnson & Johnson and has received research support from Teva Neuroscience. Dr Chitnis has served as a consultant for Biogen-Idec, EMD-Serono, Teva Neuroscience, and Novartis and has received salary support from Merck-Serono and EMD-Serono.; This work was supported by the Pediatric Multiple Sclerosis Centers of Excellence Grant from the National Multiple Sclerosis Society. NR 18 TC 17 Z9 17 U1 0 U2 3 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 JAN PY 2012 VL 69 IS 1 BP 78 EP 81 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 874GX UT WOS:000298944500011 PM 22232346 ER PT J AU Sperling, R Johnson, K AF Sperling, Reisa Johnson, Keith TI To Sleep, Perchance to Delay Dementia SO ARCHIVES OF NEUROLOGY LA English DT Editorial Material ID ALZHEIMERS-DISEASE; APNEA; HYPOXIA C1 [Sperling, Reisa; Johnson, Keith] Brigham & Womens Hosp, Dept Neurol, Ctr Alzheimer Res & Treatment, Boston, MA 02115 USA. [Sperling, Reisa; Johnson, Keith] Harvard Univ, Sch Med, Boston, MA USA. [Sperling, Reisa; Johnson, Keith] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Johnson, Keith] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Sperling, R (reprint author), Brigham & Womens Hosp, Dept Neurol, Ctr Alzheimer Res & Treatment, 221 Longwood Ave, Boston, MA 02115 USA. EM reisa@.rics.bwh.harvard.edu NR 10 TC 5 Z9 5 U1 2 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JAN PY 2012 VL 69 IS 1 BP 118 EP 120 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 874GX UT WOS:000298944500018 PM 22232352 ER PT J AU Goyal, S Chauhan, SK Dana, R AF Goyal, Sunali Chauhan, Sunil K. Dana, Reza TI Blockade of Prolymphangiogenic Vascular Endothelial Growth Factor C in Dry Eye Disease SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID SJOGRENS-SYNDROME; INFLAMMATORY LYMPHANGIOGENESIS; ANGIOGENESIS; CELLS; KERATOCONJUNCTIVITIS; HEMANGIOGENESIS; MACROPHAGES; TH17 AB Objective: To determine whether blocking prolymphangiogenic factors such as vascular endothelial growth factor C (VEGF-C) would suppress alloimmunity in dry eye disease using a murine model. Methods: The effects of intraperitoneal injections of 400 mu g of anti-VEGF-C antibody (treated group) and intraperitoneal normal saline (untreated group) were studied in murine dry eyes induced by exposing mice to high-flow desiccated air in a controlled-environment chamber. Growth of lymphatic vessels and infiltration of macrophages were evaluated by immunohistochemistry using CD31 (panendothelial marker), lymphatic vessel endothelial receptor 1 (lymphatic endothelial marker), and CD11b (monocyte and macrophage marker). Real-time polymerase chain reaction was performed to quantify expression of different inflammatory cytokine transcripts in the conjunctiva and lymph nodes as well as vascular endothelial growth factors and their receptors (VEGF-A, VEGF-C, VEGF-D, VEGFR-2, and VEGFR-3) in the cornea. Results: Blocking VEGF-C led to significant reductions in lymphatic caliber (P=.02) and lymphatic area (P=.006) in the corneas of mice with dry eye disease. In addition to significantly decreasing CD11b(+) cells (P=.005), anti-VEGF-C treatment significantly decreased transcript levels of VEGF-C (P=.002), VEGF-D (P=.01), and VEGFR-3 (P=.02) in the corneas of the treated group. A significant decrease in expression of inflammatory cytokines in the conjunctiva (interleukin 1 alpha, P=.003; interleukin 1 beta, P=.02; interleukin 6, P=.005) and lymph nodes (interferon gamma, P=.008; interleukin 17, P=.003) was also seen with anti-VEGF-C treatment. Conclusion: Treatment with anti-VEGF-C led to significant improvement in dry eye disease, reflected by a decrease in inflammation at the clinical, molecular, and cellular levels. Clinical Relevance: Targeting prolymphangiogenic growth factors or their receptors could inhibit the trafficking of antigen-presenting cells to the draining lymph nodes and hence prove to be a potential therapeutic target for dry eye disease. C1 [Dana, Reza] Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Dana, R (reprint author), Harvard Univ, Sch Med, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM reza.dana@schepens.harvard.edu FU National Institutes of Health [EY20889]; Vegenics (Circadian Technologies); Research to Prevent Blindness; Sjogren's Syndrome Foundation FX This work was supported in part by grant EY20889 from the National Institutes of Health and by grants from Vegenics (Circadian Technologies), the Lew R. Wasserman Research Award of Research to Prevent Blindness (Dr Dana), and Sjogren's Syndrome Foundation (Dr Chauhan). NR 33 TC 20 Z9 21 U1 1 U2 3 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 JAN PY 2012 VL 130 IS 1 BP 84 EP 89 DI 10.1001/archophthalmol.2011.266 PG 6 WC Ophthalmology SC Ophthalmology GA 874LE UT WOS:000298957900009 PM 21911653 ER PT J AU Stevenson, W Chauhan, SK Dana, R AF Stevenson, William Chauhan, Sunil K. Dana, Reza TI Dry Eye Disease An Immune-Mediated Ocular Surface Disorder SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID PRIMARY SJOGRENS-SYNDROME; FLOW-CYTOMETRIC ANALYSIS; NONPRESERVED METHYLPREDNISOLONE THERAPY; CYCLOSPORINE OPHTHALMIC EMULSION; INFLAMMATORY CYTOKINE EXPRESSION; DYSFUNCTIONAL TEAR SYNDROME; CORNEAL EPITHELIAL-CELLS; TUMOR-NECROSIS-FACTOR; VERSUS-HOST-DISEASE; DESICCATING STRESS AB Dry eye disease is a multifactorial disorder of the tears and ocular surface characterized by symptoms of dryness and irritation. Although the pathogenesis of dry eye disease is not fully understood, it is recognized that inflammation has a prominent role in the development and propagation of this debilitating condition. Factors that adversely affect tear film stability and osmolarity can induce ocular surface damage and initiate an inflammatory cascade that generates innate and adaptive immune responses. These immunoinflammatory responses lead to further ocular surface damage and the development of a self-perpetuating inflammatory cycle. Herein, we review the fundamental links between inflammation and dry eye disease and discuss the clinical implications of inflammation in disease management. Arch Ophthalmol. 2012; 130(1):90-100 C1 [Dana, Reza] Harvard Univ, Sch Med, Dept Ophthalmol, Schepens Eye Res Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Dana, R (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM reza.dana@schepens.harvard.edu FU Sjogren's Syndrome Foundation; National Institutes of Health [EY20889] FX This work was supported in part by the Sjogren's Syndrome Foundation (Dr Chauhan) and by grant EY20889 from the National Institutes of Health (Dr Dana). NR 133 TC 120 Z9 123 U1 3 U2 18 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 JAN PY 2012 VL 130 IS 1 BP 90 EP 100 PG 11 WC Ophthalmology SC Ophthalmology GA 874LE UT WOS:000298957900010 PM 22232476 ER PT J AU Takusagawa, HL Hunter, RS Jue, A Pasquale, LR Chen, TC AF Takusagawa, Hana L. Hunter, Rebecca S. Jue, Andrea Pasquale, Louis R. Chen, Teresa C. TI Bilateral Uveal Effusion and Angle-Closure Glaucoma Associated With Bupropion Use SO ARCHIVES OF OPHTHALMOLOGY LA English DT Letter ID VENLAFAXINE C1 [Chen, Teresa C.] Massachusetts Eye & Ear Infirm, Glaucoma Serv, Boston, MA 02114 USA. [Jue, Andrea] New York Eye & Ear Infirm, New York, NY 10003 USA. RP Chen, TC (reprint author), Massachusetts Eye & Ear Infirm, Glaucoma Serv, 243 Charles St, Boston, MA 02114 USA. EM teresa_chen@meei.harvard.edu NR 6 TC 6 Z9 6 U1 0 U2 2 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 JAN PY 2012 VL 130 IS 1 BP 120 EP 122 PG 4 WC Ophthalmology SC Ophthalmology GA 874LE UT WOS:000298957900019 PM 22232485 ER PT J AU Grossman, JM Ranganath, VK Chen, WL Furst, DE McMahon, M Volkmann, E Gordon, R Deal, C Caplan, L Curtis, JR Patkar, NM Saag, KG AF Grossman, Jennifer M. Ranganath, Veena K. Chen, Weiling Furst, Daniel E. McMahon, Maureen Volkmann, Elizabeth Gordon, Rebecca Deal, Chad Caplan, Liron Curtis, Jeffrey R. Patkar, Nivedita M. Saag, Kenneth G. TI Fracture risk in glucocorticoid-induced osteoporosis: comment on the article by Grossman et al SO ARTHRITIS CARE & RESEARCH LA English DT Letter C1 [Grossman, Jennifer M.; Ranganath, Veena K.; Chen, Weiling; Furst, Daniel E.; McMahon, Maureen; Volkmann, Elizabeth; Gordon, Rebecca] Univ Calif Los Angeles, Los Angeles, CA 90024 USA. [Gordon, Rebecca] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Deal, Chad] Cleveland Clin, Cleveland, OH 44106 USA. [Caplan, Liron] Univ Colorado, Denver, CO 80202 USA. [Curtis, Jeffrey R.; Patkar, Nivedita M.; Saag, Kenneth G.] Univ Alabama, Birmingham, AL USA. RP Grossman, JM (reprint author), Univ Calif Los Angeles, Los Angeles, CA 90024 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 JAN PY 2012 VL 64 IS 1 BP 157 EP 158 DI 10.1002/acr.20650 PG 2 WC Rheumatology SC Rheumatology GA 868QB UT WOS:000298536700025 ER PT J AU Cheng, S Wang, N Larson, MG Palmisano, JN Mitchell, GF Benjamin, EJ Vasan, RS Levy, D McCabe, EL Vita, JA Wang, TJ Shaw, SY Cohen, KS Hamburg, NM AF Cheng, Susan Wang, Na Larson, Martin G. Palmisano, Joseph N. Mitchell, Gary F. Benjamin, Emelia J. Vasan, Ramachandran S. Levy, Daniel McCabe, Elizabeth L. Vita, Joseph A. Wang, Thomas J. Shaw, Stanley Y. Cohen, Kenneth S. Hamburg, Naomi M. TI Circulating angiogenic cell populations, vascular function, and arterial stiffness SO ATHEROSCLEROSIS LA English DT Article DE Angiogenesis; Vascular function; Risk factors; Endothelium; Epidemiology ID ENDOTHELIAL PROGENITOR CELLS; CORONARY-HEART-DISEASE; COLONY-FORMING-UNITS; BONE-MARROW; CARDIOVASCULAR RISK; MONONUCLEAR-CELLS; AORTIC STIFFNESS; ADVANCING AGE; DYSFUNCTION; NUMBER AB Objective: Several bone marrow-derived cell populations have been identified that may possess angiogenic activity and contribute to vascular homeostasis in experimental studies. We examined the extent to which lower quantities of these circulating angiogenic cell phenotypes may be related to impaired vascular function and greater arterial stiffness. Methods: We studied 1948 Framingham Heart Study participants (mean age, 66 +/- 9 years; 54% women) who were phenotyped for circulating angiogenic cells: CD34+, CD34+/KDR+, and early outgrowth colony forming units (CFU). Participants underwent non-invasive assessments of vascular function including peripheral arterial tone (PAT), arterial tonometry, and brachial reactivity testing. Results: In unadjusted analyses, higher CD34+ and CD34+/KDR+ concentrations were modestly associated with lower PAT ratio (beta = -0.052 +/- 0.011, P < 0.001 and beta = -0.030 +/- 0.011, P = 0.008, respectively) and with higher carotid-brachial pulse wave velocity (beta = 0.144 +/- 0.043, P = 0.001 and beta = 0.112 +/- 0.043, P = 0.009), but not with flow-mediated dilation; higher CD34+ was also associated with lower carotid-femoral pulse wave velocity (beta = -0.229 +/- 0.094, P = 0.015). However, only the association of lower CD34+ concentration with higher PAT ratio persisted in multivariable analyses that adjusted for standard cardiovascular risk factors. In all analyses, CFU was not associated with measures of vascular function or arterial stiffness. Conclusions: In our large, community-based sample of men and women, circulating angiogenic cell phenotypes largely were not associated with measures of vascular function or arterial stiffness in analyses adjusting for traditional risk factors. (c) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Hamburg, Naomi M.] Boston Univ, Sch Med, Dept Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. [Cheng, Susan; Larson, Martin G.; Benjamin, Emelia J.; Vasan, Ramachandran S.; Levy, Daniel; Wang, Thomas J.; Hamburg, Naomi M.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Cheng, Susan] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Mitchell, Gary F.] Cardiovasc Engn Inc, Norwood, MA USA. [Wang, Na; Palmisano, Joseph N.; Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA. [Wang, Na; Palmisano, Joseph N.; Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Data Coordinating Ctr, Boston, MA 02118 USA. [Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02118 USA. [Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [Benjamin, Emelia J.; Vasan, Ramachandran S.; Vita, Joseph A.; Hamburg, Naomi M.] Boston Univ, Sch Med, Evans Dept Med, Boston, MA 02118 USA. [Benjamin, Emelia J.; Vasan, Ramachandran S.; Vita, Joseph A.; Hamburg, Naomi M.] Boston Univ, Sch Med, Prevent Med Sect, Boston, MA 02118 USA. [Benjamin, Emelia J.; Vasan, Ramachandran S.; Vita, Joseph A.; Hamburg, Naomi M.] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA. [McCabe, Elizabeth L.; Wang, Thomas J.; Shaw, Stanley Y.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Shaw, Stanley Y.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Cohen, Kenneth S.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Cohen, Kenneth S.] Univ Chicago, Med Ctr, Hematol Oncol Sect, Chicago, IL 60637 USA. RP Hamburg, NM (reprint author), Boston Univ, Sch Med, Dept Med, Whitaker Cardiovasc Inst, 88 E Newton St C818, Boston, MA 02118 USA. EM naomi.hamburg@bmc.org OI Benjamin, Emelia/0000-0003-4076-2336; Hamburg, Naomi/0000-0001-5504-5589; Vita, Joseph/0000-0001-5607-1797; Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970 FU NIH/NHLBI [N01-HC25195]; NIH [1R01HL60040, 1R01HL70100, R01AG028321, HL083197, HL083781, HL102299]; Ellison Foundation; Itamar Medical FX The Framingham Heart Study is funded by NIH/NHLBI contract N01-HC25195. The project was supported NIH grants 1R01HL60040 (EJB), 1R01HL70100 (EJB), R01AG028321 (EJB), and HL083197 (TJW). Dr. Hamburg is supported by NIH grants HL083781 and HL102299. Dr. Cheng is supported by a grant from the Ellison Foundation. The work was supported by an unrestricted research grant to Dr. Benjamin from Itamar Medical. The grant was used to conduct statistical analyses following guidelines established by the National Heart, Lung, and Blood Institute: http://www.nhlbi.nih.gov/funding/policies/thirdparty.htm. NR 36 TC 3 Z9 3 U1 0 U2 6 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 JAN PY 2012 VL 220 IS 1 BP 145 EP 150 DI 10.1016/j.atherosclerosis.2011.10.015 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866IU UT WOS:000298374800024 PM 22093724 ER PT J AU Ueland, T Smedbakken, LM Hallen, J Atar, D Januzzi, JL Halvorsen, B Jensen, JK Aukrust, P AF Ueland, T. Smedbakken, L. M. Hallen, J. Atar, D. Januzzi, J. L. Halvorsen, B. Jensen, J. K. Aukrust, P. TI Soluble CXCL16 and long-term outcome in acute ischemic stroke SO ATHEROSCLEROSIS LA English DT Article DE CXCL16; Acute ischemic stroke; Long-term prognosis; Mortality ID CORONARY-ARTERY-DISEASE; SCAVENGER RECEPTOR; SR-PSOX; INFLAMMATION; ATHEROSCLEROSIS; CHEMOKINE; CXCL16/SR-PSOX; LIPOPROTEIN; MARKER; RISK AB Objective: CXCL16 is a chemokine involved in atherosclerosis by promoting inflammation, lipid accumulation and matrix degradation. The level of circulating CXCL16 has been proposed as a predictor of long-term mortality in acute coronary syndromes. We studied plasma CXCL16 in acute ischemic stroke and examined associations with long-term mortality following the acute event. Methods: CXCL16 samples were obtained from 244 patients with acute ischemic stroke (age: 69 +/- 13 years) daily from presentation to day 5 and at half a year after the stroke. Patients with overt ischemic heart disease and atrial fibrillation were excluded. The patients were followed for 47 months, with all-cause and cardiovascular (CV) mortality as end-points. Results: At follow-up, 72 patients had died with 43 due to CV causes. Plasma CXCL16 was stably elevated in the first days after the acute event followed by a marked decrease after 6 months. In patients who subsequently suffered an adverse outcome, CXCL16 levels at 4 days after the initial event were elevated and were moderately associated with mortality. The increase in CXCL16 from day 1 to 4 was a predictor for all-cause and, in particular, CV mortality even after adjustment in the multivariate analysis for established risk factors such as age, the presence of heart/renal failure, troponin, C-reactive protein and stroke severity. Conclusions: An increase in plasma CXCL16 during the first days after the initial event is associated with an adverse outcome in patients with acute ischemic stroke, supporting the potential pathogenic role of CXCL16 in atherosclerosis and vascular remodelling as well as their major clinical consequences. (C) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Ueland, T.; Smedbakken, L. M.; Halvorsen, B.; Aukrust, P.] Univ Oslo, Rikshosp, Internal Med Res Inst, Oslo Univ Hosp, N-0027 Oslo, Norway. [Aukrust, P.] Univ Oslo, Rikshosp, Oslo Univ Hosp, Sect Clin Immunol & Infect Dis, N-0027 Oslo, Norway. [Hallen, J.; Atar, D.] Univ Oslo, Ulleval Hosp, Div Cardiol, Oslo, Norway. [Ueland, T.; Atar, D.; Aukrust, P.] Univ Oslo, Fac Med, N-0027 Oslo, Norway. [Jensen, J. K.] Odense Univ Hosp, Dept Cardiol, DK-5000 Odense, Denmark. [Januzzi, J. L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Ueland, T (reprint author), Univ Oslo, Rikshosp, Internal Med Res Inst, Oslo Univ Hosp, Room D1-2017,Sognsvannsveien 20, N-0027 Oslo, Norway. EM thor.ueland@medisin.uio.no NR 23 TC 11 Z9 12 U1 2 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 EI 1879-1484 J9 ATHEROSCLEROSIS JI Atherosclerosis PD JAN PY 2012 VL 220 IS 1 BP 244 EP 249 DI 10.1016/j.atherosclerosis.2011.10.004 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866IU UT WOS:000298374800041 PM 22055341 ER PT J AU Smolderen, KG Spertus, JA Reid, KJ Buchanan, DM Vaccarino, V Lichtman, JH Bekelman, DB Chan, PS AF Smolderen, Kim G. Spertus, John A. Reid, Kimberly J. Buchanan, Donna M. Vaccarino, Viola Lichtman, Judith H. Bekelman, David B. Chan, Paul S. TI Association of Somatic and Cognitive Depressive Symptoms and Biomarkers in Acute Myocardial Infarction: Insights from the Translational Research Investigating Underlying Disparities in Acute Myocardial Infarction Patients' Health Status Registry SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Coagulation; depressive symptoms; inflammation; mechanisms; myocardial infarction; neurohormones ID C-REACTIVE PROTEIN; ACUTE CORONARY SYNDROMES; BRAIN NATRIURETIC PEPTIDE; HEART-RATE-VARIABILITY; N-TERMINAL PROATRIAL; CARDIOVASCULAR-DISEASE; INFLAMMATORY BIOMARKERS; SICKNESS BEHAVIOR; NATIONAL-HEART; PROGNOSIS AB Background: Somatic depressive symptoms and certain biomarkers are each associated with worse acute myocardial infarction (AMI) prognosis, but the relationship between depressive symptom domains and inflammatory, neurohormonal, and coagulation markers is unknown. Methods: We examined the relationship between depressive symptoms and 1-month biomarker levels (high-sensitivity C-reactive protein [hs-CRP], N-terminal pro-brain natriuretic peptide [NT-proBNP], white blood cell [WBC], platelet counts) in 1265 AMI patients. Depressive symptoms (9-item Patient Health Questionnaire) were assessed during index hospitalization and categorized as somatic or cognitive. Using median regression models, the upper quartile of somatic and cognitive depression scores and each biomarker were compared with the lower three quartiles, adjusting for site, demographics, and clinical characteristics. Results: Although hs-CRP values were higher in patients with somatic symptoms, this association was attenuated after adjustment (B(per SD increase) = .02, 95% confidence interval: .00; .05, p = .07). WBC count was independently associated with somatic depressive symptoms (B(per SD increase) = .28, 95% confidence interval: .12; .44, p = .001). Cognitive depressive symptoms were not associated with hs-CRP or WBC count. Neither dimension was associated with NT-proBNP or platelet levels. For each biomarker, the depression dimensions explained <1% of their variation. Conclusions: Neither somatic nor cognitive depressive symptoms were meaningfully associated with hs-CRP, NT-proBNP, WBC, or platelet counts 1 month after AMI, suggesting that the association between depression and long-term outcomes may be unrelated to these biomarkers. Future research should explore other biomarkers to better illuminate pathways by which depression adversely impacts AMI prognosis. C1 [Smolderen, Kim G.; Spertus, John A.; Reid, Kimberly J.; Buchanan, Donna M.; Chan, Paul S.] St Lukes Mid Amer Heart & Vasc Inst, Kansas City, MO 64111 USA. [Smolderen, Kim G.] Tilburg Univ, Dept Med Psychol, Ctr Res Psychol Somat Dis, NL-5000 LE Tilburg, Netherlands. [Spertus, John A.; Chan, Paul S.] Univ Missouri, Dept Med, Kansas City, MO 64110 USA. [Spertus, John A.; Chan, Paul S.] Univ Missouri, Dept Biomed & Hlth Informat, Kansas City, MO 64110 USA. [Vaccarino, Viola] Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA. [Lichtman, Judith H.] Yale Univ, Sch Publ Hlth, Div Chron Dis Epidemiol, New Haven, CT USA. [Bekelman, David B.] Denver Vet Affairs Med Ctr, Res Sect, Denver, CO USA. [Bekelman, David B.] Denver Vet Affairs Med Ctr, Geriatr Sect, Denver, CO USA. [Vaccarino, Viola] Emory Univ, Sch Med, Div Cardiol, Atlanta, GA 30322 USA. RP Smolderen, KG (reprint author), St Lukes Mid Amer Heart & Vasc Inst, 4401 Wornall Rd, Kansas City, MO 64111 USA. EM k.g.e.smolderen@gmail.com RI Smolderen, Kim/B-8078-2015 FU National Heart, Lung, and Blood Institute Specialized Center of Clinically Oriented Research in Cardiac Dysfunction and Disease [P50 HL077113]; CV Therapeutics, Palo Alto, California; American Heart Association [AHA: 0875149N]; Netherlands Organization for Scientific Research [916.11.179] FX Grant support was received from the National Heart, Lung, and Blood Institute Specialized Center of Clinically Oriented Research in Cardiac Dysfunction and Disease (Grant number P50 HL077113) and CV Therapeutics, Palo Alto, California. Dr. Smolderen was supported by the Outcomes Research postdoctoral fellowship awarded by the American Heart Association Pharmaceutical Roundtable and David and Stevie Spina (Grant number AHA: 0875149N) and by The Netherlands Organization for Scientific Research (Veni Grant number: 916.11.179). NR 50 TC 8 Z9 9 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JAN 1 PY 2012 VL 71 IS 1 BP 22 EP 29 DI 10.1016/j.biopsych.2011.07.029 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 863BI UT WOS:000298137400007 PM 21903199 ER PT J AU Roosen, A Woodhouse, CRJ Wood, DN Stief, CG McDougal, WS Gerharz, EW AF Roosen, Alexander Woodhouse, Christopher R. J. Wood, Daniel N. Stief, Christian G. McDougal, W. Scott Gerharz, Elmar W. TI Animal models in urinary diversion SO BJU INTERNATIONAL LA English DT Review DE urinary diversion; urinary reservoirs; continent; models; animal; rat; dog ID ANTIREFLUX URETEROILEAL ANASTOMOSIS; SEROSALIZED MUSCLE LAYER; FETAL SHEEP BLADDER; CHRONIC UREMIC RATS; INTESTINAL SEGMENTS; AUGMENTATION CYSTOPLASTY; PORCINE MODEL; ILEAL VALVE; URETEROINTESTINAL ANASTOMOSIS; METABOLIC-ACIDOSIS AB We set out to critically assess the value of animal experimentation in urinary diversion through intestinal segments, as some authors question the effectiveness of animal research, criticising the methodological quality, lack of standardization, inadequate reporting and the few systematic reviews in this fi eld. Based on a comprehensive MEDLINE literature search ( MeSH database; search terms: urinary diversion, urinary reservoirs, continent, rat, dog, animal models) we retrieved and evaluated all full- length papers published in English, German, French, and Spanish languages from 1966 to 2011 reporting the use of animal models in the setting of urinary diversion. Studies were stratifi ed according to the addressed research question. Within each category species, gender, number of animals, age at procedure, type of diversion, mortality, length of follow- up, experimental procedure and outcome were recorded and tabulated. In all, 159 articles were judged to be relevant and while there are numerous animal models only a few have been used in more than one study. Animals were used for the systematic study of new surgical techniques ( 93 articles) or metabolic and functional consequences of urinary reconstruction ( 66 articles). For the latter purpose, the most often used animal is the rat, whereas the dog model is preferred for technical experimentation. In many studies, the validity of the model is at least questionable. Animal experiments have repeatedly been conducted addressing the same question, often with striking discrepancies in outcome. Animal studies were even performed after a surgical technique had been pioneered in humans. The use of animal models in urinary diversion is far from standardized rendering the results less than ideal for comparison across studies. Due to differences in anatomy and physiology, the applicability of fi ndings in animal experiments to clinical urology is limited. Continued effort is needed to optimise the use of animal models in experimental urology. C1 [Roosen, Alexander; Stief, Christian G.] Univ Munich, Dept Urol, Sch Med, D-81377 Munich, Germany. [Woodhouse, Christopher R. J.; Wood, Daniel N.] UCL, Ctr Urol, London, England. [McDougal, W. Scott] Massachusetts Gen Hosp, Urol Serv, Boston, MA 02114 USA. [Gerharz, Elmar W.] Frankfurt Urol Associates, Frankfurt, Germany. RP Roosen, A (reprint author), Univ Munich, Dept Urol, Sch Med, Marchioninistr 15, D-81377 Munich, Germany. EM a_roosen@hotmail.com NR 163 TC 3 Z9 3 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 J9 BJU INT JI BJU Int. PD JAN PY 2012 VL 109 IS 1 BP 6 EP 23 DI 10.1111/j.1464-410X.2011.10494.x PG 18 WC Urology & Nephrology SC Urology & Nephrology GA 862AU UT WOS:000298063000005 PM 21917109 ER PT J AU Singh, H Giardina, TD Petersen, LA Smith, MW Paul, LW Dismukes, K Bhagwath, G Thomas, EJ AF Singh, Hardeep Giardina, Traber Davis Petersen, Laura A. Smith, Michael W. Paul, Lindsey Wilson Dismukes, Key Bhagwath, Gayathri Thomas, Eric J. TI Exploring situational awareness in diagnostic errors in primary care SO BMJ QUALITY & SAFETY LA English DT Article ID PATIENT SAFETY; MALPRACTICE CLAIMS; DECISION-MAKING; MISSED OPPORTUNITIES; CANCER DIAGNOSIS; DYNAMIC-SYSTEMS; ADVERSE EVENTS; MEDICINE; STRATEGIES; COGNITION AB Objective: Diagnostic errors in primary care are harmful but poorly studied. To facilitate the understanding of diagnostic errors in real-world primary care settings that use electronic health records (EHRs), this study explored the use of the situational awareness (SA) framework from aviation human factors research. Methods: A mixed-methods study was conducted involving reviews of EHR data followed by semi-structured interviews of selected providers from two institutions in the USA. The study population included 380 consecutive patients with colorectal and lung cancers diagnosed between February 2008 and January 2009. Using a pre-tested data collection instrument, trained physicians identified diagnostic errors, defined as lack of timely action on one or more established indications for diagnostic work-up for lung and colorectal cancers. Twenty-six providers involved in cases with and without errors were interviewed. Interviews probed for providers' lack of SA and how this may have influenced the diagnostic process. Results: Of 254 cases meeting inclusion criteria, errors were found in 30 of 92 (32.6%) lung cancer cases and 56 of 167 (33.5%) colorectal cancer cases. Analysis of interviews related to error cases revealed evidence of lack of one of four levels of SA applicable to primary care practice: information perception, information comprehension, forecasting future events, and choosing appropriate action based on the first three levels. In cases without error, application of the SA framework provided insight into processes involved in attention management. Conclusions: A framework of SA can help analyse and understand diagnostic errors in primary care settings that use EHRs. C1 [Singh, Hardeep; Giardina, Traber Davis; Petersen, Laura A.; Smith, Michael W.] Baylor Coll Med, Houston VA HSR&D Ctr Excellence, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Singh, Hardeep; Giardina, Traber Davis; Petersen, Laura A.; Smith, Michael W.] Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. [Paul, Lindsey Wilson] Univ Texas Austin, Sch Social Work, Austin, TX 78712 USA. [Dismukes, Key] NASA, Ames Res Ctr, Moffett Field, CA 94035 USA. [Bhagwath, Gayathri] Univ Texas Galveston, Med Branch, Dept Internal Med, Div Hematol Oncol, Galveston, TX 77550 USA. [Thomas, Eric J.] Univ Texas Houston, Sch Med, Dept Med, Div Gen Med, Houston, TX 77030 USA. [Thomas, Eric J.] Univ Texas Houston, Sch Med, Mem Hermann Ctr Healthcare Qual, Houston, TX USA. RP Singh, H (reprint author), Med Ctr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM hardeeps@bcm.edu OI Davis Giardina, Traber/0000-0002-9184-6524 FU NIH [K23CA125585]; Houston VA HSR&D Center of Excellence [HFP90-020] FX This study was supported by an NIH K23 career development award (K23CA125585) to Dr Singh, and in part by the Houston VA HSR&D Center of Excellence (HFP90-020). These sources 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 77 TC 19 Z9 20 U1 4 U2 14 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-5415 J9 BMJ QUAL SAF JI BMJ Qual. Saf. PD JAN PY 2012 VL 21 IS 1 BP 30 EP 38 DI 10.1136/bmjqs-2011-000310 PG 9 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 862ZZ UT WOS:000298133900005 PM 21890757 ER PT J AU Chirgwin, J Sun, ZX Smith, I Price, KN Thurlimann, B Ejlertsen, B Bonnefoi, H Regan, MM Goldhirsch, A Coates, AS AF Chirgwin, Jacquie Sun, Zhuoxin Smith, Ian Price, Karen N. Thuerlimann, Beat Ejlertsen, Bent Bonnefoi, Herve Regan, Meredith M. Goldhirsch, Aron Coates, Alan S. CA BIG 1-98 Collaborative Int Breast TI The advantage of letrozole over tamoxifen in the BIG 1-98 trial is consistent in younger postmenopausal women and in those with chemotherapy-induced menopause SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Aromatase inhibitor; Menopause; Hormonal therapy; Letrozole; Tamoxifen; Chemotherapy-induced amenorrhea ID BREAST-CANCER PATIENTS; AROMATASE INHIBITORS; PREMENOPAUSAL WOMEN; ADJUVANT CHEMOTHERAPY; INDUCED AMENORRHEA; THERAPY; DOCETAXEL; CAUTION; TAXANE; IMPACT AB Letrozole, an aromatase inhibitor, is ineffective in the presence of ovarian estrogen production. Two subpopulations of apparently postmenopausal women might derive reduced benefit from letrozole due to residual or returning ovarian activity: younger women (who have the potential for residual subclinical ovarian estrogen production), and those with chemotherapy-induced menopause who may experience return of ovarian function. In these situations tamoxifen may be preferable to an aromatase inhibitor. Among 4,922 patients allocated to the monotherapy arms (5 years of letrozole or tamoxifen) in the BIG 1-98 trial we identified two relevant subpopulations: patients with potential residual ovarian function, defined as having natural menopause, treated without adjuvant or neoadjuvant chemotherapy and age acurrency sign55 years (n = 641); and those with chemotherapy-induced menopause (n = 105). Neither of the subpopulations examined showed treatment effects differing from the trial population as a whole (interaction P values are 0.23 and 0.62, respectively). Indeed, both among the 641 patients aged acurrency sign55 years with natural menopause and no chemotherapy (HR 0.77 [0.51, 1.16]) and among the 105 patients with chemotherapy-induced menopause (HR 0.51 [0.19, 1.39]), the disease-free survival (DFS) point estimate favoring letrozole was marginally more beneficial than in the trial as a whole (HR 0.84 [0.74, 0.95]). Contrary to our initial concern, DFS results for young postmenopausal patients who did not receive chemotherapy and patients with chemotherapy-induced menopause parallel the letrozole benefit seen in the BIG 1-98 population as a whole. These data support the use of letrozole even in such patients. C1 [Chirgwin, Jacquie] Australian New Zealand Breast Canc Trials Grp, Newcastle, NSW, Australia. [Chirgwin, Jacquie] Monash Univ, Box Hill & Maroondah Hosp, Melbourne, Vic 3004, Australia. [Sun, Zhuoxin] Dana Farber Canc Inst, Ctr Stat, Int Breast Canc Study Grp, Boston, MA 02115 USA. [Smith, Ian] Royal Marsden Hosp, Inst Canc Res, London SW3 6JJ, England. [Price, Karen N.] Frontier Sci & Technol Res Fdn Inc, Ctr Stat, Int Breast Canc Study Grp, Boston, MA USA. [Thuerlimann, Beat] Kantonsspital St Gallen, Breast Ctr, St Gallen, Switzerland. [Thuerlimann, Beat] Swiss Grp Clin Canc Res SAKK, Bern, Switzerland. [Ejlertsen, Bent] Rigshosp, Danish Breast Canc Cooperat Grp DBCG, DK-2100 Copenhagen, Denmark. [Bonnefoi, Herve] Univ Bordeaux, FNCLCC Unicancer, INSERM, Inst Bergonie,U916, Bordeaux, France. [Regan, Meredith M.] Harvard Univ, Sch Med, Boston, MA USA. [Regan, Meredith M.] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Int Breast Canc Study Grp IBCSG,Stat Ctr,Dept Bio, Boston, MA 02115 USA. RP Chirgwin, J (reprint author), Australian New Zealand Breast Canc Trials Grp, Newcastle, NSW, Australia. EM chirgwin@tpg.com.au; zhuoxin@jimmy.harvard.edu; Ian.Smith@rmh.nhs.uk; price@jimmy.harvard.edu; beat.thuerlimann@kssg.ch; bent.ejlertsen@rh.regionh.dk; bonnefoi@bergonie.org; mregan@jimmy.harvard.edu; aron.goldhirsch@ibcsg.org; alan.coates@ibcsg.org RI Munzone, Elisabetta/G-8848-2011; Cheuk, Robyn/H-1944-2013; Rimassa, Lorenza/N-4884-2016; Sedlackova, Eva/B-9959-2017; GLADIEFF, Laurence/O-5129-2014; Wardley, ANdrew/N-8135-2015; Wyld, David/B-8893-2015; Gonzalez Larriba, Jose Luis/G-6177-2016; Petruzelka, Lubos/A-2750-2017 OI Segelov, Eva/0000-0002-4410-6144; Cheuk, Robyn/0000-0001-9516-5526; Rimassa, Lorenza/0000-0001-9957-3615; Sedlackova, Eva/0000-0002-0089-1611; GLADIEFF, Laurence/0000-0002-6980-9719; Wardley, ANdrew/0000-0002-9639-0888; Wyld, David/0000-0001-9523-4333; Walpole, Euan/0000-0001-6105-9039; Gonzalez Larriba, Jose Luis/0000-0003-2631-0309; Petruzelka, Lubos/0000-0002-4397-0635 FU Novartis; IBCSG: Swedish Cancer Society; Cancer Council Australia; Australian New Zealand Breast Cancer Trials Group; Frontier Science and Technology Research Foundation; Swiss Group for Clinical Cancer Research (SAKK; National Cancer Institute [CA-75362]; Cancer Research Switzerland/Oncosuisse; Foundation for Clinical Cancer Research of Eastern Switzerland (OSKK) FX We thank the patients, physicians, nurses, and data managers who participated in the BIG 1-98 clinical trial. The BIG 1-98 trial was financed by Novartis and coordinated by IBCSG. Support for the IBCSG: Swedish Cancer Society, The Cancer Council Australia, Australian New Zealand Breast Cancer Trials Group, Frontier Science and Technology Research Foundation, Swiss Group for Clinical Cancer Research (SAKK), National Cancer Institute Grant CA-75362, Cancer Research Switzerland/Oncosuisse, and the Foundation for Clinical Cancer Research of Eastern Switzerland (OSKK). Clinicaltrials.gov ID = NCT00004205. NR 26 TC 7 Z9 7 U1 3 U2 14 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JAN PY 2012 VL 131 IS 1 BP 295 EP 306 DI 10.1007/s10549-011-1741-6 PG 12 WC Oncology SC Oncology GA 861GB UT WOS:000298006300030 PM 21892704 ER PT J AU Ligibel, JA O'Malley, AJ Fisher, M Daniel, GW Winer, EP Keating, NL AF Ligibel, Jennifer A. O'Malley, A. James Fisher, Maxine Daniel, Gregory W. Winer, Eric P. Keating, Nancy L. TI Risk of myocardial infarction, stroke, and fracture in a cohort of community-based breast cancer patients SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Aromatase inhibitor; Breast cancer; Fracture; Myocardial infarction; Stroke; Tamoxifen ID POSTMENOPAUSAL WOMEN; TAMOXIFEN THERAPY; RANDOMIZED-TRIAL; ADHERENCE; ANASTROZOLE; MORTALITY; OUTCOMES; PROJECT; CARE AB Clinical trials suggest that increased risk of osteoporosis and fracture are the only serious side effects of adjuvant aromatase inhibitors (AIs), but little is known regarding toxicities of AIs in non-trial populations. We evaluated whether use of AIs was associated with myocardial infarction, stroke, and fracture in a community-based population. Using data from the HealthCore Integrated Research Database, 44,463 women aged a parts per thousand yen50 years with a parts per thousand yen2 breast cancer diagnosis codes between 2001 and 2007 were followed through 2008. Of these, 44,026 were matched using propensity score methods to women aged a parts per thousand yen50 years with no breast cancer codes. We assessed whether treatment with AIs was associated with myocardial infarction, stroke, and fracture using Cox proportional hazards models with time-varying treatment variables. Among breast cancer patients, 68.7% received no hormonal therapy, 20.6% received AIs (15.8% received only AIs, 4.8% were also treated with tamoxifen), and 10.7% received tamoxifen only. Breast cancer patients on AIs had a higher risk of any fracture (AHR = 1.13, 95% CI = 1.02-1.25) than breast cancer patients not receiving hormonal therapy. Patients on tamoxifen had a lower risk of hip fracture (AHR = 0.51, 95% CI = 0.32-0.81) than breast cancer patients not receiving hormonal therapy. Rates of myocardial infarction and stroke for patients on AIs or tamoxifen did not differ significantly from breast cancer patients not on therapy. The side effect profile of AIs in this community-based population was similar to that seen in clinical trials. These findings provide reassurance that AIs appear to be associated with few serious side effects. C1 [O'Malley, A. James; Keating, Nancy L.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Ligibel, Jennifer A.; Winer, Eric P.] Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. [Fisher, Maxine; Daniel, Gregory W.] HealthCore Inc, Wilmington, DE USA. [Keating, Nancy L.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. RP Keating, NL (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. EM keating@hcp.med.harvard.edu FU National Institutes of Health [R01 CA127652] FX This study was funded by the National Institutes of Health (R01 CA127652 to Dr. Keating). NR 28 TC 8 Z9 8 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JAN PY 2012 VL 131 IS 2 BP 589 EP 597 DI 10.1007/s10549-011-1754-1 PG 9 WC Oncology SC Oncology GA 871QG UT WOS:000298752200023 PM 21881937 ER PT J AU Beasley, JM Kwan, ML Chen, WY Weltzien, EK Kroenke, CH Lu, W Nechuta, SJ Cadmus-Bertram, L Patterson, RE Sternfeld, B Shu, XO Pierce, JP Caan, BJ AF Beasley, Jeannette M. Kwan, Marilyn L. Chen, Wendy Y. Weltzien, Erin K. Kroenke, Candyce H. Lu, Wei Nechuta, Sarah J. Cadmus-Bertram, Lisa Patterson, Ruth E. Sternfeld, Barbara Shu, Xiao-Ou Pierce, John P. Caan, Bette J. TI Meeting the physical activity guidelines and survival after breast cancer: findings from the after breast cancer pooling project SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Physical activity guidelines; Breast cancer survival; Mortality; Epidemiology ID ACTIVITY QUESTIONNAIRE; WOMENS HEALTH; REPRODUCIBILITY; VALIDATION; DIAGNOSIS; MORTALITY; VALIDITY; COHORT; DIET; LIFE AB The 2008 Physical Activity (PA) Guidelines recommend engaging in at least 2.5 h (10 MET-hours/week) of moderate intensity PA per week (defined as 4 METs) to reduce risk of morbidity and mortality. This analysis was conducted to investigate whether this recommendation can be extended to breast cancer survivors. Data from four studies of breast cancer survivors measuring recreational PA from semi-quantitative questionnaires a median of 23 months post-diagnosis (interquartile range 18-32 months) were pooled in the After Breast Cancer Pooling Project (n = 13,302). Delayed entry Cox proportional hazards models were applied in data analysis with adjustment for age, post-diagnosis body mass index, race/ethnicity, menopausal status, TNM stage, cancer treatment, and smoking history. Engaging in at least 10 MET-hours/week of PA was associated with a 27% reduction in all-cause mortality (n = 1,468 events, Hazard Ratio (HR) = 0.73, 95% CI, 0.66-0.82) and a 25% reduction in breast cancer mortality (n = 971 events, HR = 0.75, 95% CI 0.65-0.85) compared with women who did not meet the PA Guidelines (< 10 MET-hours/week). Risk of breast cancer recurrence (n = 1,421 events) was not associated with meeting the PA Guidelines (HR = 0.96, 95% CI, 0.86-1.06). These data suggest that adhering to the PA guidelines may be an important intervention target for reducing mortality among breast cancer survivors. C1 [Beasley, Jeannette M.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Kwan, Marilyn L.; Weltzien, Erin K.; Kroenke, Candyce H.; Sternfeld, Barbara; Caan, Bette J.] Kaiser Permanente Div Res, Oakland, CA 94612 USA. [Chen, Wendy Y.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. [Chen, Wendy Y.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Lu, Wei] Shanghai Ctr Dis Control & Prevent, Shanghai, Peoples R China. [Nechuta, Sarah J.; Shu, Xiao-Ou] Vanderbilt Univ, Nashville, TN 37203 USA. [Cadmus-Bertram, Lisa; Patterson, Ruth E.; Pierce, John P.] Univ Calif San Diego, Moores UCSD Canc Ctr, Canc Prevent & Control Program, San Diego, CA 92093 USA. RP Beasley, JM (reprint author), Fred Hutchinson Canc Res Ctr, 1000 Fairview Ave,N M3-A410, Seattle, WA 98109 USA. EM jbeasley@whi.org OI Beasley, Jeannette/0000-0002-9343-6895 FU National Cancer Institute [3R01CA118229-03S1] FX Joan Schwalbe contributed substantively to the data analysis. This study was supported by the National Cancer Institute (Grant number 3R01CA118229-03S1). The parent grants for each individual cohort included in the After Breast Cancer Pooling Project are: LACE (National Cancer Institute, R01 CA129059), NHS (P01 CA87969), SBCSS (Department of Defense, DAMD 17-02-1-0607 and National Cancer Institute, R01 CA118229), and WHEL (Susan G. Komen Foundation, #KG100988). NR 28 TC 51 Z9 51 U1 0 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JAN PY 2012 VL 131 IS 2 BP 637 EP 643 DI 10.1007/s10549-011-1770-1 PG 7 WC Oncology SC Oncology GA 871QG UT WOS:000298752200028 PM 21935600 ER PT J AU Panageas, KS Sima, CS Liberman, L Schrag, D AF Panageas, K. S. Sima, C. S. Liberman, L. Schrag, D. TI Use of high technology imaging for surveillance of early stage breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast cancer surveillance; High technology imaging; SEER-Medicare ID FOLLOW-UP; RANDOMIZED-TRIAL; SURVIVAL; UPDATE AB Guidelines do not support utilization of high technology radiologic imaging (HTRI) for surveillance after curative treatment for early stage breast cancer. Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data were used to identify 25,555 women diagnosed with stage I-II breast cancer between 1998 and 2003 who survived a parts per thousand yen48 months from diagnosis without evidence of second primary or recurrent cancer in this interval. HTRI utilization (computerized tomography scanning (CT), bone scan (BS), breast magnetic resonance imaging, and positron emission tomography scans) was measured in months 13-48 post-diagnosis. Cases were individually matched to 75,669 female Medicare enrollees without cancer. Factors associated with HTRI utilization were evaluated. Forty percent of women with stage I-II breast cancer and 25% of controls had a parts per thousand yen1 HTRI during the surveillance interval (P < 0.001). High utilization rates were observed for CT (30%) and BSs (19%). The proportion of women who had a CT during the surveillance period increased in both cancer survivors and controls. Among breast cancer cases age < 80, higher comorbidity index, stage II disease, and more recent diagnosis were independently associated with receipt of HTRI. Paralleling patterns observed in controls, HTRI utilization for surveillance following diagnosis of early stage breast cancer has steadily increased among Medicare beneficiaries. Strategies to foster judicious utilization of HTRI should be a priority. C1 [Panageas, K. S.; Sima, C. S.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Liberman, L.] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10021 USA. [Schrag, D.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Panageas, KS (reprint author), Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, 307 E 63rd St,3rd Floor, New York, NY 10021 USA. EM panageak@mskcc.org NR 28 TC 11 Z9 13 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JAN PY 2012 VL 131 IS 2 BP 663 EP 670 DI 10.1007/s10549-011-1773-y PG 8 WC Oncology SC Oncology GA 871QG UT WOS:000298752200031 PM 21947679 ER PT J AU Moran, MS Bai, HX Harris, EER Arthur, DW Bailey, L Bellon, JR Carey, L Goyal, S Halyard, MY Horst, KC MacDonald, SM Haffty, BG AF Moran, Meena S. Bai, Harrison X. Harris, Eleanor E. R. Arthur, Douglas W. Bailey, Lisa Bellon, Jennifer R. Carey, Lisa Goyal, Sharad Halyard, Michele Y. Horst, Kathleen C. MacDonald, Shannon M. Haffty, Bruce G. TI ACR Appropriateness Criteria (R) Ductal Carcinoma in Situ SO BREAST JOURNAL LA English DT Article DE ACR appropriateness criteria; breast conservation therapy; ductal carcinoma in situ; guidelines; radiation therapy ID SURGICAL ADJUVANT BREAST; RADIOTHERAPY; TRIAL; CANCER; WOMEN AB Ductal carcinoma in situ (DCIS) describes a wide spectrum of non-invasive tumors which carry a significant risk of invasive relapse, thus prevention of local recurrence is vital. For appropriate patients with limited disease, management with breast conserving surgery (BCS) followed by whole-breast radiation (RT) is supported by multiple Phase III studies, but mastectomy may be appropriate in selected patients. Omission of RT may also be reasonable in some patients, though which criteria are to be utilized remain unclear, and the existing data are contradictory with limited follow-up. Various RT techniques such as boost to the tumor bed, partial breast radiation or hypofractionated, whole-breast RT are increasingly utilized but the data to support their use specifically in DCIS is limited. Tamoxifen also increases local control for ER + DCIS, adding to the complexity of the local treatment management. This article reviews the existing scientific evidence, the controversies surrounding local management, and clinical guidelines for DCIS based on the group consensus by the ACR Breast Expert Panel. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. C1 [Moran, Meena S.; Bai, Harrison X.] Yale Univ, Sch Med, New Haven, CT USA. [Harris, Eleanor E. R.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Arthur, Douglas W.] Virginia Commonwealth Univ, Med Coll Virginia, Richmond, VA 23298 USA. [Bailey, Lisa] Alta Bates Summit Med Ctr, Oakland, CA USA. [Bellon, Jennifer R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Carey, Lisa] Univ N Carolina Hlth Care Syst, Chapel Hill, NC USA. [Goyal, Sharad; Haffty, Bruce G.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, New Brunswick, NJ USA. [Halyard, Michele Y.] Mayo Clin, Scottsdale, AZ USA. [Horst, Kathleen C.] Stanford Univ, Sch Med, Stanford, CA USA. [MacDonald, Shannon M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Moran, MS (reprint author), Amer Coll Radiol, 1891 Preston White Dr, Reston, VA 20191 USA. EM meena.moran@yale.edu OI Harris, Eleanor/0000-0002-7529-7473 NR 11 TC 10 Z9 10 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1075-122X J9 BREAST J JI Breast J. PD JAN-FEB PY 2012 VL 18 IS 1 BP 8 EP 15 DI 10.1111/j.1524-4741.2011.01197.x PG 8 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 873WX UT WOS:000298916200003 PM 22107336 ER PT J AU Barkley, C Burstein, H Smith, B Bellon, J Wong, J Gadd, M Taghian, A Winer, E Iglehart, JD Harris, J Golshan, M AF Barkley, Christina Burstein, Harold Smith, Barbara Bellon, Jennifer Wong, Julia Gadd, Michele Taghian, Alphonse Winer, Eric Iglehart, James Dirk Harris, Jay Golshan, Mehra TI Can Axillary Node Dissection Be Omitted in a Subset of Patients with Low Local and Regional Failure Rates? SO BREAST JOURNAL LA English DT Article DE axillary node dissection; breast cancer; sentinel node biopsy ID SENTINEL LYMPH-NODE; BREAST-CANCER PATIENTS; BIOPSY; METASTASES; RECURRENCE; NOMOGRAM; MICROMETASTASES; PREDICTION; LIKELIHOOD; SURGERY AB Axillary node dissection (ALND) is the standard of care for patients who have a positive sentinel lymph node (SLN) on sentinel lymph node biopsy (SLNB). We sought to identify a low-risk patient population with positive SLN that may not need cALND. We analyzed SLNB for breast cancer at our institutions between 1999 and 2007. We identified 130 patients who had a positive SLN but did not undergo completion ALND. We evaluated clinical data, adjuvant treatment patterns and intermediate locoregional and distant events. The median patient age was 50; 19% had N0(i+) disease, 53% had micrometastatic (N1mi) disease, and 28% had macrometastasis. Eighty-eight percent of patients underwent radiation therapy; 66 patients (51%) had documented nodal radiation (of these 50 were treated with three fields and 14 with high tangents. Local recurrence in the breast occurred in two patients (2%) and nine patients (7%) developed distant metastases; there were no axillary/nodal recurrences. In this highly selected group of patients who had a positive SLNB but did not undergo cALND, we observed no axillary recurrences. C1 [Barkley, Christina; Iglehart, James Dirk; Golshan, Mehra] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Burstein, Harold; Winer, Eric] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Smith, Barbara; Gadd, Michele] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Bellon, Jennifer; Wong, Julia; Harris, Jay] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Taghian, Alphonse] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Golshan, M (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. EM mgolshan@partners.org NR 34 TC 5 Z9 5 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1075-122X J9 BREAST J JI Breast J. PD JAN-FEB PY 2012 VL 18 IS 1 BP 23 EP 27 DI 10.1111/j.1524-4741.2011.01178.x PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 873WX UT WOS:000298916200005 PM 22017599 ER PT J AU Warren, LE Mendlinger, SE Corso, KA Greenberg, CC AF Warren, Laura E. Mendlinger, Sheryl E. Corso, Katherine A. Greenberg, Caprice C. TI A Model of Knowledge Acquisition in Early Stage Breast Cancer Patients SO BREAST JOURNAL LA English DT Article DE breast cancer; decision-making; knowledge acquisition ID DECISION-MAKING; RECONSTRUCTION; MASTECTOMY; SURGERY; WOMEN; POSTMASTECTOMY; CONSERVATION; CHOICE; IMPACT AB To meaningfully participate in the decision-making regarding a newly diagnosed breast cancer, a patient must acquire new knowledge. We describe a model of knowledge acquisition that can provide a framework for exploring the process and types of knowledge that breast cancer patients gain following their diagnosis. The four types of knowledge presented in this modelauthoritative, technical, embodied, and traditionalare described and potential sources discussed. An understanding of knowledge acquisition in early stage breast cancer patients can provide healthcare practitioners with an important framework for optimizing decision-making in this population. C1 [Warren, Laura E.] Harvard Univ, Sch Med, Boston, MA USA. [Mendlinger, Sheryl E.] Northeastern Univ, Inst Urban Hlth Res, Boston, MA 02115 USA. [Corso, Katherine A.; Greenberg, Caprice C.] Brigham & Womens Hosp, Dept Surg, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Greenberg, Caprice C.] Dana Farber Canc Inst, Dept Med Oncol, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. RP Greenberg, CC (reprint author), Univ Wisconsin, Dept Surg, Wisconsin Surg Outcomes Res Program, Ctr Clin Sci, 600 Highland Ave H4-742, Madison, WI 53792 USA. EM greenberg@sur-gery.wisc.edu FU NCI NIH HHS [L30 CA123695] NR 23 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1075-122X J9 BREAST J JI Breast J. PD JAN-FEB PY 2012 VL 18 IS 1 BP 69 EP 72 DI 10.1111/j.1524-4741.2011.01183.x PG 4 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 873WX UT WOS:000298916200012 PM 22226068 ER PT J AU Rudge, C Matesanz, R Delmonico, FL Chapman, J AF Rudge, C. Matesanz, R. Delmonico, F. L. Chapman, J. TI International practices of organ donation SO BRITISH JOURNAL OF ANAESTHESIA LA English DT Review DE living donors; organ transplantation; tissue and organ procurement; transplantation ID MEDICAL GUIDELINES; DONOR; FORUM; LIVER; CARE AB Organ donation and transplant rates vary widely across the globe, but there remains an almost universal shortage of deceased donors. The unmet need for transplants has resulted in many systematic approaches to increase donor rates, but there have also been practices that have crossed the boundaries of legal and ethical acceptability. Recent years have seen intense interest from international political organizations, led by the World Health Organization, and professional bodies, led by The Transplantation Society. Their efforts have focused on the development of a series of legal and ethical frameworks, designed to encourage all countries to eradicate unacceptable practices while introducing programmes that strive to achieve national or regional self-sufficiency in meeting the need for organ transplants. These programmes should seek to reduce both the need for transplantation and also develop deceased donation to its maximum potential. Living donation remains the mainstay of transplantation in many parts of the world, and many of the controversial-and unacceptable-areas of practice are found in the exploitation of living donors. However, until lessons are learnt, and applied, from countries with highly developed deceased donor programmes, these abuses of human rights will be difficult to eradicate. A clear international framework is now in place to achieve this. C1 [Rudge, C.] Dept Hlth, London SE1 8UG, England. [Matesanz, R.] Natl Transplant Org ONT, Madrid 28029, Spain. [Delmonico, F. L.] Massachusetts Gen Hosp, Transplantat Soc, Boston, MA 02114 USA. [Delmonico, F. L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA USA. [Delmonico, F. L.] New England Organ Bank Inc, Waltham, MA USA. [Chapman, J.] Univ Sydney, Westmead Hosp, Ctr Transplant & Renal Res, Westmead, NSW 2145, Australia. RP Rudge, C (reprint author), Dept Hlth, Wellington House,Waterloo Rd, London SE1 8UG, England. EM cjrudge@btinternet.com NR 16 TC 37 Z9 38 U1 1 U2 8 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 JAN PY 2012 VL 108 SU 1 BP I48 EP I55 DI 10.1093/bja/aer399 PG 8 WC Anesthesiology SC Anesthesiology GA 866MG UT WOS:000298384500008 PM 22194431 ER PT J AU Colpo, A Boyer, D Fathi, AT AF Colpo, Anna Boyer, Daniel Fathi, Amir T. TI Hypereosinophilia in relapsed acute myeloid leukaemia SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Editorial Material C1 [Colpo, Anna] Univ Padua, Sch Med, Dept Clin & Expt Med Hematol & Clin Immunol, Padua, Italy. [Boyer, Daniel] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. [Fathi, Amir T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Div Hematol Oncol, Boston, MA USA. RP Colpo, A (reprint author), Univ Padua, Sch Med, Dept Clin & Expt Med Hematol & Clin Immunol, Padua, Italy. EM afathi@partners.org NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JAN PY 2012 VL 156 IS 1 BP 2 EP 2 DI 10.1111/j.1365-2141.2011.08804.x PG 1 WC Hematology SC Hematology GA 861YX UT WOS:000298058100002 PM 21810088 ER PT J AU Cursiefen, C Colin, J Dana, R Diaz-Llopis, M Faraj, LA Garcia-Delpech, S Geerling, G Price, FW Remeijer, L Rouse, BT Seitz, B Udaondo, P Meller, D Dua, H AF Cursiefen, Claus Colin, Joseph Dana, Reza Diaz-Llopis, Manuel Faraj, Lana A. Garcia-Delpech, Salvador Geerling, Gerd Price, Francis W. Remeijer, Lies Rouse, Barry T. Seitz, Berthold Udaondo, Patricia Meller, Daniel Dua, Harminder TI Consensus statement on indications for anti-angiogenic therapy in the management of corneal diseases associated with neovascularisation: outcome of an expert roundtable SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Review ID ENDOTHELIAL GROWTH-FACTOR; STEM-CELL DEFICIENCY; HERPETIC STROMAL KERATITIS; GRAFT-SURVIVAL; TOPICAL BEVACIZUMAB; RISK-FACTORS; ARGON-LASER; PENETRATING KERATOPLASTY; ACANTHAMOEBA-KERATITIS; LYMPHATIC VESSELS AB The cornea is the clear window at the front of the eye and is the eye's main refractive medium. Its transparency is essential for vision. Corneal neovascularisation is a common clinical problem with serious consequences for vision; it can compromise corneal transparency and plays a major role in corneal graft rejection by breaching corneal immune privilege. In this review, we formulate a consensus on the unmet medical needs in the management of corneal neovascularisation and outline a framework for the clinical research that is needed to identify suitable agents to meet these needs. C1 [Cursiefen, Claus] Univ Cologne, Dept Ophthalmol, Erlangen, Germany. [Colin, Joseph] Ctr Hosp Univ Pellegrin, Bordeaux, France. [Dana, Reza] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst, Boston, MA USA. [Diaz-Llopis, Manuel; Garcia-Delpech, Salvador; Udaondo, Patricia] La Fe Univ Hosp, Dept Ophthalmol, Valencia, Spain. [Diaz-Llopis, Manuel; Garcia-Delpech, Salvador] Univ Valencia, Valencia, Spain. [Diaz-Llopis, Manuel; Garcia-Delpech, Salvador; Udaondo, Patricia] Biomed Network Res Ctr Rare Dis CIBERER, Valencia, Spain. [Faraj, Lana A.; Dua, Harminder] Univ Nottingham, Div Ophthalmol & Visual Sci, Nottingham NG7 2RD, England. [Geerling, Gerd] Univ Wurzburg, Dept Ophthalmol, Wurzburg, Germany. [Price, Francis W.] Price Vis Grp, Indianapolis, IN USA. [Price, Francis W.] Cornea Res Fdn Amer, Indianapolis, IN USA. [Remeijer, Lies] Rotterdam Eye Hosp, Cornea & External Dis Serv, Rotterdam, Netherlands. [Rouse, Barry T.] Univ Tennessee, Coll Vet Med, Dept Pathobiol, Knoxville, TN 37901 USA. [Seitz, Berthold] Univ Saarland, Dept Ophthalmol, D-6650 Homburg, Germany. [Meller, Daniel] Univ Essen Gesamthsch, Dept Ophthalmol, Essen, Germany. RP Cursiefen, C (reprint author), Univ Cologne, Dept Ophthalmol, Joseph Stelzmann Str 9, D-50924 Cologne, Germany. EM claus.cursiefen@uk-koeln.de OI Faraj, Lana/0000-0001-7060-166X FU IZKF Erlangen (A9); Voisin Consulting Life Sciences, France FX IZKF Erlangen (A9) and Voisin Consulting Life Sciences, France. The planning of this study, interpretation of findings, writing and conclusions of manuscript were undertaken entirely independently of the company interests. NR 84 TC 32 Z9 33 U1 0 U2 5 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD JAN PY 2012 VL 96 IS 1 BP 3 EP 9 DI 10.1136/bjo.2011.204701 PG 7 WC Ophthalmology SC Ophthalmology GA 866EZ UT WOS:000298364600002 PM 21712359 ER PT J AU Gasperini, JL Fawzi, AA Khondkaryan, A Lam, L Chong, LP Eliott, D Walsh, AC Hwang, J Sadda, SR AF Gasperini, Julie L. Fawzi, Amani A. Khondkaryan, Ani Lam, Linda Chong, Lawrence P. Eliott, Dean Walsh, Alexander C. Hwang, John Sadda, SriniVas R. TI Bevacizumab and ranibizumab tachyphylaxis in the treatment of choroidal neovascularisation SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; RETINAL VEIN OCCLUSION; MACULAR DEGENERATION; INTRAVITREAL BEVACIZUMAB; AVASTIN TREATMENT; ANTIBODIES; REGRESSION; DISEASE; EDEMA AB Aims To evaluate the effect of switching to bevacizumab or ranibizumab after developing tachyphylaxis during anti-vascular endothelial growth factor (VEGF) therapy for choroidal neovascularisation (CNV). Methods The authors reviewed the records of all patients who received both ranibizumab and bevacizumab for treatment of CNV to identify those who developed tachyphylaxis, defined as optical coherence tomography evidence of initial decreased exudation followed by lack of further reduction or an increase in exudation. Signs of exudation included subreitnal fluid (SRF), pigment epithelial detachment (PED) and/or cystoid macular oedema (CMO). Results 26 eyes were included. 10 were initially treated with bevacizumab and then changed to ranibizumab for persistent SRF, PED and/or CMO. Of these, seven had occult CNV and three had predominantly classic CNV. One eye in the occult CNV group did not respond after being switched to ranibizumab. Six eyes had a positive therapeutic response, after one injection in four eyes, and after two or three injections in one eye each. In the classic group, two responded to ranibizumab and one did not. Sixteen eyes were initially treated with ranibizumab before changing to bevacizumab. Of these, 15 had occult CNV and 1 was predominantly classic. Three of the 16 eyes failed to respond to bevacizumab; 6 improved after one injection and 5 after two injections. Conclusions Patients with CNV who develop tachyphylaxis to ranibizumab or bevacizumab may respond to another anti-VEGF drug. The majority of cases (81%) in this series demonstrated at least some response after switching therapies. C1 [Fawzi, Amani A.; Khondkaryan, Ani; Lam, Linda; Walsh, Alexander C.; Hwang, John; Sadda, SriniVas R.] Univ So Calif, Doheny Eye Inst, Doheny Retina Inst, Keck Sch Med,Dept Ophthalmol, Los Angeles, CA 90033 USA. [Gasperini, Julie L.] S Coast Retina Ctr, Torrance, CA USA. [Chong, Lawrence P.] VMR Inst, Huntington Beach, CA USA. [Eliott, Dean] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Sadda, SR (reprint author), Univ So Calif, Doheny Eye Inst, Doheny Retina Inst, Keck Sch Med,Dept Ophthalmol, 1450 San Pablo St,DEI 3623, Los Angeles, CA 90033 USA. EM sadda@usc.edu OI fawzi, amani/0000-0002-9568-3558 FU Research to Prevent Blindness Inc., New York, NY; Fletcher Jones Foundation; Carl Zeiss Meditec; Optovue, Inc. FX Supported in part by an unrestricted grant to the Department of Ophthalmology from Research to Prevent Blindness Inc., New York, NY, and a grant from the Fletcher Jones Foundation.; LPC: Allergan Consultant; DE: Genentech Speaker; ACW: co-inventor of Doheny intellectual property related to optical coherence tomography that has been licensed by Topcon Medical Systems and receives research support from Carl Zeiss Meditec and Optovue, Inc.; SVRS: co-inventor of Doheny intellectual property related to optical coherence tomography that has been licensed by Topcon Medical Systems, consultant for Heidelberg Engineering, Genentech and Allergan, and receives research support from Carl Zeiss Meditec and Optovue, Inc. NR 26 TC 61 Z9 64 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD JAN PY 2012 VL 96 IS 1 BP 14 EP 20 DI 10.1136/bjo.2011.204685 PG 7 WC Ophthalmology SC Ophthalmology GA 866EZ UT WOS:000298364600004 PM 21791509 ER PT J AU Lobo, AM Rhee, DJ AF Lobo, A-M Rhee, D. J. TI Delayed interval of involvement of the second eye in a male patient with bilateral Chandler's syndrome SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID IRIDOCORNEAL ENDOTHELIAL SYNDROME; COGAN-REESE C1 [Lobo, A-M; Rhee, D. J.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Rhee, DJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM dougrhee@aol.com NR 16 TC 1 Z9 2 U1 1 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD JAN PY 2012 VL 96 IS 1 BP 134 EP 147 DI 10.1136/bjo.2009.177931 PG 4 WC Ophthalmology SC Ophthalmology GA 866EZ UT WOS:000298364600030 PM 20710048 ER PT J AU Saboo, SS Krajewski, KM O'Regan, KN Giardino, A Brown, JR Ramaiya, N Jagannathan, JP AF Saboo, S. S. Krajewski, K. M. O'Regan, K. N. Giardino, A. Brown, J. R. Ramaiya, N. Jagannathan, J. P. TI Spleen in haematological malignancies: spectrum of imaging findings SO BRITISH JOURNAL OF RADIOLOGY LA English DT Review ID NON-HODGKIN-LYMPHOMA; EXTRANODAL INVOLVEMENT; DIAGNOSTIC-ACCURACY; F-18-FDG PET; DISEASE; CT; FEATURES; LEUKEMIA; MYELOMA AB Imaging morphology and metabolic activity of splenic lesions is of paramount importance in patients with haematological malignancies; it can alter tumour staging, treatment protocols and overall prognosis. CT, MRI and positron emission tomography (PET)/CT have been shown to be powerful tools for the non-invasive assessment of splenic involvement in various haematological malignancies. Since many haematological malignancies and non-neoplastic conditions can involve the spleen and imaging manifestations can overlap, imaging and clinical findings outside of the spleen should be looked for to narrow the differential diagnosis; confirmation can be obtained by pathological findings. Radiologists should be familiar with the cross-sectional imaging patterns of haematological malignancies involving the spleen as well as non-neoplastic splenic findings common in these patients to facilitate their care and follow-up. This pictorial review provides the common and uncommon imaging appearances and complications of various haematological malignancies involving the spleen on CT, MRI and PET/CT, and common pitfalls in diagnosis. C1 [Saboo, S. S.; Krajewski, K. M.; O'Regan, K. N.; Giardino, A.; Ramaiya, N.; Jagannathan, J. P.] Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. [Brown, J. R.] Dana Farber Canc Inst, Dept Hematol Oncol, Boston, MA 02115 USA. [Saboo, S. S.; Brown, J. R.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Saboo, SS (reprint author), Dana Farber Canc Inst, Dept Radiol, 44 Binney St, Boston, MA 02115 USA. EM ssaboo@partners.org NR 26 TC 15 Z9 15 U1 0 U2 4 PU BRITISH INST RADIOLOGY PI LONDON PA 36 PORTLAND PLACE, LONDON W1N 4AT, ENGLAND SN 0007-1285 J9 BRIT J RADIOL JI Br. J. Radiol. PD JAN PY 2012 VL 85 IS 1009 BP 81 EP 92 DI 10.1259/bjr/31542964 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 866RH UT WOS:000298398900017 PM 22096219 ER PT J AU Rahbar, H Tavakkol, Z Bhargava, P AF Rahbar, H. Tavakkol, Z. Bhargava, P. TI Characteristic CT appearance of lung cysts prompting the diagnosis of a rare genodermatosis SO BRITISH JOURNAL OF RADIOLOGY LA English DT Editorial Material ID HOGG-DUBE-SYNDROME; HEREDITARY C1 [Rahbar, H.; Bhargava, P.] Univ Washington, Sch Med, Dept Radiol, Seattle, WA 98195 USA. [Rahbar, H.; Bhargava, P.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Tavakkol, Z.] Univ Washington, Div Dermatol, Sch Med, Dept Med, Seattle, WA 98195 USA. RP Bhargava, P (reprint author), VA Puget Sound Hlth Care Ctr, Mail Box 358280,1660 S Columbian Way, Seattle, WA 98108 USA. EM bhargp@u.washington.edu OI Bhargava, Puneet/0000-0002-3849-9666 NR 6 TC 0 Z9 0 U1 0 U2 0 PU BRITISH INST RADIOLOGY PI LONDON PA 36 PORTLAND PLACE, LONDON W1N 4AT, ENGLAND SN 0007-1285 J9 BRIT J RADIOL JI Br. J. Radiol. PD JAN PY 2012 VL 85 IS 1009 BP 93 EP 95 DI 10.1259/bjr/13687494 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 866RH UT WOS:000298398900018 PM 22190751 ER PT J AU Hoffman, KE Neville, BA Mamon, HJ Kachnic, LA Katz, MS Earle, CC Punglia, RS AF Hoffman, Karen E. Neville, Bridget A. Mamon, Harvey J. Kachnic, Lisa A. Katz, Matthew S. Earle, Craig C. Punglia, Rinaa S. TI Adjuvant therapy for elderly patients with resected gastric adenocarcinoma Population-Based Practices and Treatment Effectiveness SO CANCER LA English DT Article DE gastric cancer; aged; SEER-Medicare; chemotherapy; radiotherapy ID SEER-MEDICARE DATA; FEE-FOR-SERVICE; RADIATION-THERAPY; POSTOPERATIVE CHEMORADIATION; INTERGROUP-0116 TRIAL; COMORBIDITY INDEX; CHEMOTHERAPY USE; PROSTATE-CANCER; BREAST-CANCER; PATTERNS AB BACKGROUND: A study was undertaken to determine the survival benefit of postoperative chemoradiation therapy for elderly patients with resected gastric adenocarcinoma. METHODS: The authors identified 1023 individuals aged 65 years and older (median 76) who underwent gastrectomy for nonmetastatic stage IB-IV gastric adenocarcinoma diagnosed between 2000 and 2002 in the linked Surveillance, Epidemiology, and End Results-Medicare database. They examined factors associated with receiving postoperative chemoradiation and analyzed the survival benefit associated with receiving postoperative chemoradiation. RESULTS: Thirty percent of patients received adjuvant chemoradiation. On multivariate analysis, younger age (P < .0001), lymph node involvement (P < .0001), and more recent diagnosis (P = .0284) were associated with receiving chemoradiation. There was a trend toward increased use among patients with less comorbidity (P = .0515). The median follow-up was 25.5 months, and 62% died. On multivariate survival analysis, older patients (P < .0001) and those with lymph node involvement (P < .0001), T3 or T4 disease (P = .0472), higher grade disease (P = .0355), and more comorbidity (P = .0411) were more likely to die. After adjustment for other factors, receipt of adjuvant chemoradiation therapy did not significantly increase survival (hazard ratio, 0.90; 95% confidence interval, 0.72-1.12; P = .3453) and did not increase survival in a multivariate analysis that included propensity scores (P = .2090). CONCLUSIONS: The authors did not detect a survival benefit, suggesting that some elderly patients with resected gastric adenocarcinoma may not gain a survival benefit from the administration of adjuvant chemoradiation. The analysis had limitations, and the results are hypothesis generating. Future gastric cancer trials should enroll more elderly patients and stratify patients by age to better understand the impact of treatment regimens on older patients. Cancer 2012;118:248-57. (C) 2011 American Cancer Society. C1 [Hoffman, Karen E.; Mamon, Harvey J.; Punglia, Rinaa S.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [Hoffman, Karen E.; Mamon, Harvey J.; Punglia, Rinaa S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hoffman, Karen E.] Harvard Univ, Sch Med, Harvard Radiat Oncol Program, Boston, MA USA. [Neville, Bridget A.; Punglia, Rinaa S.] Dana Farber Canc Inst, Dept Med Oncol, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. [Kachnic, Lisa A.] Boston Med Ctr, Dept Radiat Oncol, Boston, MA USA. [Katz, Matthew S.] Radiat Oncol Associates PA, Manchester, NH USA. [Earle, Craig C.] Inst Clin Evaluat Sci, Toronto, ON, Canada. RP Hoffman, KE (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, 1515 Holcombe Blvd,Unit 1202, Houston, TX 77030 USA. EM khoffman1@mdanderson.org FU National Institutes of Health [1K07CA118629]; J C R T Foundation FX This work was supported by a National Institutes of Health grant (1K07CA118629, R. S. P.) and a J C R T Foundation grant (K.E.H.). NR 33 TC 9 Z9 9 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD JAN 1 PY 2012 VL 118 IS 1 BP 248 EP 257 DI 10.1002/cncr.26248 PG 10 WC Oncology SC Oncology GA 868TW UT WOS:000298549700031 PM 21692071 ER PT J AU Parikh, R Sher, DJ AF Parikh, Ravi Sher, David J. TI Primary radiotherapy versus radical prostatectomy for high-risk prostate cancer A Decision Analysis SO CANCER LA English DT Article DE decision analysis; radical prostatectomy; external beam radiation; prostate cancer; high risk ID QUALITY-OF-LIFE; ANDROGEN-DEPRIVATION THERAPY; 3-DIMENSIONAL CONFORMAL RADIOTHERAPY; INTENSITY-MODULATED RADIOTHERAPY; GROUP PROTOCOL 92-02; PHASE-III TRIAL; RADIATION-THERAPY; FOLLOW-UP; EUROPEAN-ORGANIZATION; ONCOLOGY AB BACKGROUND: Two evidence-based therapies exist for the treatment of high-risk prostate cancer (PCA): external-beam radiotherapy (RT) with hormone therapy (H) (RT + H) and radical prostatectomy (S) with adjuvant radiotherapy (S + RT). Each of these strategies is associated with different rates of local control, distant metastasis (DM), and toxicity. By using decision analysis, the authors of this report compared the quality-adjusted life expectancy (QALE) between men with high-risk PCA who received RT + H versus S + RT versus a hypothetical trimodality therapy (S + RT + H). METHODS: The authors developed a Markov model to describe lifetime health states after treatment for high-risk PCA. Probabilities and utilities were extrapolated from the literature. Toxicities after radiotherapy were based on intensity-modulated radiotherapy series, and patients were exposed to risks of diabetes, cardiovascular disease, and fracture for 5 years after completing H. Deterministic and probabilistic sensitivity analyses were performed to model uncertainty in outcome rates, toxicities, and utilities. RESULTS: RT + H resulted in a higher QALE compared with S + RT over a wide range of assumptions, nearly always resulting in an increase of >1 quality-adjusted life year with outcomes highly sensitive to the risk of increased all-cause mortality from H. S + RT + H typically was superior to RT + H, albeit by small margins (<0.5 quality-adjusted life year), with results sensitive to assumptions about toxicity and radiotherapy efficacy. CONCLUSIONS: For men with high-risk PCA, RT + H was superior to S + RT, and the result was sensitive to the risk of all-cause mortality from H. Moreover, trimodality therapy may offer local and distant control benefits that lead to optimal outcomes in a meaningful population of men. Cancer 2012;118:258-67. (C) 2011 American Cancer Society. C1 [Sher, David J.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Sher, David J.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Parikh, Ravi] Harvard Univ, Sch Med, Boston, MA USA. [Sher, David J.] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. RP Sher, DJ (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. EM dsher@lroc.harvard.edu NR 37 TC 3 Z9 3 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD JAN 1 PY 2012 VL 118 IS 1 BP 258 EP 267 DI 10.1002/cncr.26272 PG 10 WC Oncology SC Oncology GA 868TW UT WOS:000298549700032 PM 21720990 ER PT J AU Dunn, JH Ellis, LZ Fujita, M AF Dunn, Jeffrey H. Ellis, Lixia Z. Fujita, Mayumi TI Inflammasomes as molecular mediators of inflammation and cancer: Potential role in melanoma SO CANCER LETTERS LA English DT Review DE Inflammasome; Inflammation; Cancer; Melanoma; IL-1 beta; ASC ID INTERLEUKIN-1 INDUCES INTERLEUKIN-1; CASPASE RECRUITMENT DOMAIN; INNATE IMMUNE-RESPONSE; FAMILIAL MEDITERRANEAN FEVER; TUMOR-HOST INTERACTIONS; TOLL-LIKE RECEPTORS; SPECK-LIKE PROTEIN; NF-KAPPA-B; NALP3 INFLAMMASOME; IN-VITRO AB The inflammasome is a multi-protein complex that mediates immune responses to microbial, host, and environmental signals. When active, inflammasomes regulate caspase-1 activation and IL-1 beta secretion. There is a strong link between inflammation and cancer, and IL-1 beta is one of the major molecules involved in both of these disease processes. Here we review the role of inflammasomes in regulating IL-1 beta secretion, and the impact of this pathway on cancer pathogenesis, with a focus on melanoma. This represents an exciting new area of research, and could potentially result in new targets for melanoma therapeutics in the future. Published by Elsevier Ireland Ltd. C1 [Dunn, Jeffrey H.; Ellis, Lixia Z.; Fujita, Mayumi] Univ Colorado Denver, Dept Dermatol, Sch Med, Aurora, CO 80045 USA. [Fujita, Mayumi] Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. RP Fujita, M (reprint author), Univ Colorado Denver, Dept Dermatol, Sch Med, Mail Stop 8127,12801 E 17th Ave,RC-1 S,Rm 4124, Aurora, CO 80045 USA. EM mayumi.fujita@ucdenver.edu FU Dermatology Foundation; Wendy Will Case Cancer Fund grant; Cancer League of Colorado; Tadamitsu Cancer Research Fund FX The authors thank Charles A Dinarello, MD, Miyako Okamoto, MD, PhD and Weimin Liu, MD (University of Colorado Denver) for helpful discussions. This work was supported, in whole or in part, by Dermatology Foundation (to M.F.), Wendy Will Case Cancer Fund grant (to M.F.), Cancer League of Colorado (to M.F.) and Tadamitsu Cancer Research Fund (to M.F.). The funders had no role in study design, data collection, analysis and interpretation, manuscript preparation and decision to submit the manuscript. NR 163 TC 28 Z9 28 U1 2 U2 9 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD JAN 1 PY 2012 VL 314 IS 1 BP 24 EP 33 DI 10.1016/j.canlet.2011.10.001 PG 10 WC Oncology SC Oncology GA 868OF UT WOS:000298531900003 PM 22050907 ER PT J AU Judd, NP Winkler, AE Murillo-Sauca, O Brotman, JJ Law, JH Lewis, JS Dunn, GP Bui, JD Sunwoo, JB Uppaluri, R AF Judd, Nancy P. Winkler, Ashley E. Murillo-Sauca, Oihana Brotman, Joshua J. Law, Jonathan H. Lewis, James S., Jr. Dunn, Gavin P. Bui, Jack D. Sunwoo, John B. Uppaluri, Ravindra TI ERK1/2 Regulation of CD44 Modulates Oral Cancer Aggressiveness SO CANCER RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMA; EPITHELIAL-MESENCHYMAL TRANSITION; NECK-CANCER; RAS ACTIVATION; STEM-CELLS; HEAD; EXPRESSION; MODELS; GROWTH; CARCINOGENESIS AB Carcinogen-induced oral cavity squamous cell carcinoma (OSCC) incurs significant morbidity and mortality and constitutes a global health challenge. To gain further insight into this disease, we generated cell line models from 7,12-dimethylbenz(a) anthracene-induced murine primary OSCC capable of tumor formation upon transplantation into immunocompetent wild-type mice. Whereas several cell lines grew rapidly and were capable of metastasis, some grew slowly and did not metastasize. Aggressively growing cell lines displayed ERK1/2 activation, which stimulated expression of CD44, a marker associated with epithelial to mesenchymal transition and putative cancer stem cells. MEK (MAP/ERK kinase) inhibition upstream of ERK1/2 decreased CD44 expression and promoter activity and reduced cell migration and invasion. Conversely, MEK1 activation enhanced CD44 expression and promoter activity, whereas CD44 attenuation reduced in vitro migration and in vivo tumor formation. Extending these findings to freshly resected human OSCC, we confirmed a strict relationship between ERK1/2 phosphorylation and CD44 expression. In summary, our findings identify CD44 as a critical target of ERK1/2 in promoting tumor aggressiveness and offer a preclinical proof-of-concept to target this pathway as a strategy to treat head and neck cancer. Cancer Res; 72(1); 365-74. (C) 2011 AACR. C1 [Judd, Nancy P.; Winkler, Ashley E.; Brotman, Joshua J.; Law, Jonathan H.; Lewis, James S., Jr.; Uppaluri, Ravindra] Washington Univ, Sch Med, Dept Otolaryngol, St Louis, MO 63110 USA. [Uppaluri, Ravindra] Washington Univ, Sch Med, John Cochran VA Med Ctr, St Louis, MO 63110 USA. [Lewis, James S., Jr.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. [Murillo-Sauca, Oihana; Sunwoo, John B.] Stanford Univ, Dept Otolaryngol, Stanford, CA 94305 USA. [Dunn, Gavin P.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Bui, Jack D.] UCSD, Dept Pathol, La Jolla, CA USA. RP Uppaluri, R (reprint author), Washington Univ, Sch Med, Dept Otolaryngol, 660 S Euclid Ave,Campus Box 8115, St Louis, MO 63110 USA. EM uppalurr@wustl.edu FU NCI [K08CA090403]; Veteran's Affairs Research Service; NIH [T32DC00022] FX R. Uppaluri was supported by the NCI (K08CA090403) and the Veteran's Affairs Research Service. N.P. Judd and J.H. Law were supported by NIH-T32DC00022. NR 50 TC 39 Z9 39 U1 1 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2012 VL 72 IS 1 BP 365 EP 374 DI 10.1158/0008-5472.CAN-11-1831 PG 10 WC Oncology SC Oncology GA 871RO UT WOS:000298755600036 PM 22086849 ER PT J AU Hirata, H Hinoda, Y Ueno, K Shahryari, V Tabatabai, ZL Dahiya, R AF Hirata, Hiroshi Hinoda, Yuji Ueno, Koji Shahryari, Varahram Tabatabai, Z. Laura Dahiya, Rajvir TI MicroRNA-1826 targets VEGFC, beta-catenin (CTNNB1) and MEK1 (MAP2K1) in human bladder cancer SO CARCINOGENESIS LA English DT Article ID LYMPH-NODE METASTASIS; FACTOR-C EXPRESSION; SIGNAL-TRANSDUCTION; KINASE CASCADE; CELL-LINES; TUMORS; LYMPHANGIOGENESIS; ACTIVATION; BIOMARKERS; CARCINOMA AB The Wnt/beta-catenin (CTNNB1) and Ras-Raf-MEK-ERK signaling pathway play an important role in bladder cancer (BC) progression. Tumor-suppressive microRNAs (miRNAs) targeting these cancer pathways may provide a new therapeutic approach for BC. We initially identified miRNA-1826 potentially targeting CTNNB1, VEGFC and MEK1 using several target scan algorithms. Also 3' untranslated region luciferase activity and protein expression of these target genes were significantly downregulated in miR-1826-transfected BC cells (J82 and T24). The expression of miR-1826 was lower in BC tissues and inverse correlation of miR-1826 with several clinical parameters (pT, grade) was observed. Also the expression of miR-1826 was much lower in three BC cell lines (J82, T24 and TCCSUP) compared with a normal bladder cell line (SV-HUC-1). We then performed analyses to look at miR-1826 function and found that miR-1826 inhibited BC cell viability, invasion and migration. We also found increased apoptosis and G(1) cell cycle arrest in miR-1826-transfected BC cells. To examine whether the effect of miR-1826 was through CTNNB1 (beta-catenin) or MEK1 knockdown, we knocked down CTNNB1/MEK1 messenger RNA using a small interfering RNA (siRNA) technique. We observed that CTNNB1 or MEK1 siRNA knockdown resulted in effects similar to those with miR-1826 in BC cells. In conclusion, our data suggest that the miR-1826 plays an important role as tumor suppressor via CTNNB1/MEK1/VEGFC downregulation in BC. C1 [Hirata, Hiroshi; Ueno, Koji; Shahryari, Varahram; Dahiya, Rajvir] San Francisco VA Med Ctr, Dept Urol, San Francisco, CA 94121 USA. [Hinoda, Yuji; Tabatabai, Z. Laura] Univ Calif San Francisco, San Francisco, CA 94121 USA. [Hinoda, Yuji; Tabatabai, Z. Laura] Yamaguchi Univ, Grad Sch Med, Dept Oncol AnLab Med, Yamaguchi 7558505, Japan. [Tabatabai, Z. Laura] San Francisco VA Med Ctr, Dept Pathol, San Francisco, CA 94121 USA. RP Dahiya, R (reprint author), Vet Affairs Med Ctr, Urol Res Ctr 112F, San Francisco, CA 94121 USA. EM rdahiya@urology.ucsf.edu FU National Institutes of Health [RO1CA130860, RO1CA111470, RO1CA138642, T32-DK07790]; VA Research Enhancement Award Program; Merit Review grants; Yamada Science Foundation FX RO1CA130860, RO1CA111470, RO1CA138642, T32-DK07790 from the National Institutes of Health, VA Research Enhancement Award Program, Merit Review grants and Yamada Science Foundation. NR 36 TC 39 Z9 42 U1 2 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JAN PY 2012 VL 33 IS 1 BP 41 EP 48 DI 10.1093/carcin/bgr239 PG 8 WC Oncology SC Oncology GA 870HF UT WOS:000298659200006 PM 22049531 ER PT J AU Stone, JR Basso, C Baandrup, UT Bruneval, P Butany, J Gallagher, PJ Halushka, MK Miller, DV Padera, RF Radio, SJ Sheppard, MN Suvarna, K Tan, CD Thiene, G van der Wal, AC Veinot, JP AF Stone, James R. Basso, Cristina Baandrup, Ulrik T. Bruneval, Patrick Butany, Jagdish Gallagher, Patrick J. Halushka, Marc K. Miller, Dylan V. Padera, Robert F. Radio, Stanley J. Sheppard, Mary N. Suvarna, Kim Tan, Carmela D. Thiene, Gaetano van der Wal, Allard C. Veinot, John P. TI Recommendations for processing cardiovascular surgical pathology specimens: a consensus statement from the Standards and Definitions Committee of the Society for Cardiovascular Pathology and the Association for European Cardiovascular Pathology SO CARDIOVASCULAR PATHOLOGY LA English DT Article DE Cardiovascular disease; Cardiovascular surgical pathology specimens; Patient care; Pathology standards ID AMERICAN-HEART-ASSOCIATION; BIOPSY-PROVEN MYOCARDITIS; SUBAORTIC SEPTAL MYECTOMY; HUMAN CARDIAC ALLOGRAFTS; TEMPORAL ARTERY BIOPSY; ENDOMYOCARDIAL BIOPSY; HYPERTROPHIC CARDIOMYOPATHY; DILATED CARDIOMYOPATHY; SCIENTIFIC STATEMENT; ATRIAL-FIBRILLATION AB With the advent of molecular subclassification of diseases, much consideration should be given to the proper processing of cardiovascular surgical pathology specimens to maximize patient care. Such specimens include endomyocardial biopsies, cardiac myectomy specimens, cardiac apical core segments, resected cardiac valves, pericardial biopsies, resected segments of aorta, cardiac tumors, vascular stents, vascular grafts, cardiac devices, resected veins, arterial biopsies including temporal artery biopsies and hearts removed during cardiac transplantation. In this report, the Standards and Definitions Committee of the Society for Cardiovascular Pathology and the Association for European Cardiovascular Pathology present consensus guidelines for the gross description, sectioning, processing, and staining of these specimens. This report is presented to aid pathologists, pathology assistants, and clinicians in maximizing the diagnostic utility of cardiovascular surgical pathology specimens for enhanced patient care. (C) 2012 Elsevier Inc. All rights reserved. C1 [Stone, James R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Basso, Cristina] Univ Padua, Sch Med, Dept Med Diagnost Sci & Special Therapies, I-35121 Padua, Italy. [Baandrup, Ulrik T.] Aalborg Univ, Vendsyssel Hosp, Aalborg, Denmark. [Bruneval, Patrick] Univ Paris 05, Paris, France. [Butany, Jagdish] Toronto Gen Hosp, Toronto, ON, Canada. [Gallagher, Patrick J.] Southhampton Univ Hosp, Southampton, England. [Halushka, Marc K.] Johns Hopkins Univ, Baltimore, MD USA. [Miller, Dylan V.] Univ Utah, Salt Lake City, UT 84112 USA. [Padera, Robert F.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Radio, Stanley J.] Univ Nebraska, Lincoln, NE 68583 USA. [Sheppard, Mary N.] Univ London Imperial Coll Sci Technol & Med, London, England. [Suvarna, Kim] No Gen Hosp, Sheffield, England. [Tan, Carmela D.] Cleveland Clin, Cleveland, OH 44106 USA. [van der Wal, Allard C.] Univ Amsterdam, Amsterdam, Netherlands. [Veinot, John P.] Univ Ottawa, Ottawa, ON, Canada. RP Stone, JR (reprint author), Massachusetts Gen Hosp, Simches Bldg,Room 8236, Boston, MA 02114 USA. EM jrstone@partners.org; cristina.basso@unipd.it OI Halushka, Marc/0000-0002-7112-7389 NR 85 TC 20 Z9 20 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-8807 EI 1879-1336 J9 CARDIOVASC PATHOL JI Cardiovasc. Pathol. PD JAN-FEB PY 2012 VL 21 IS 1 BP 2 EP 16 DI 10.1016/j.carpath.2011.01.001 PG 15 WC Cardiac & Cardiovascular Systems; Pathology SC Cardiovascular System & Cardiology; Pathology GA 867GT UT WOS:000298443600002 PM 21353600 ER PT J AU Gordon, JA AF Gordon, James A. TI As Accessible as a Book on a Library Shelf The Imperative of Routine Simulation in Modern Health Care SO CHEST LA English DT Editorial Material ID DELIBERATE PRACTICE; EXPERT PERFORMANCE; HOSPITAL LIBRARIES; MEDICAL-EDUCATION; ACQUISITION; RESIDENTS AB Technology-enhanced patient simulation has emerged as an important new modality for teaching and learning in medicine. In particular, immersive simulation platforms that replicate the clinical environment promise to revolutionize medical education by enabling an enhanced level of safety, standardization, and efficiency across health-care training. Such an experiential approach seems unique in reliably catalyzing a level of emotional engagement that fosters immediate and indelible learning and allows for increasingly reliable levels of performance evaluation-all in a completely risk-free environment. As such, medical simulation is poised to emerge as a critical component of training and certification throughout health care, promising to fundamentally enhance quality and safety across disciplines. To encourage routine simulation-based practice as part of its core quality and safety mission, Massachusetts General Hospital now incorporates simulation resources within its historic medical library (est. 1847), located at the center of the campus. In this new model, learners go to the library not only to read about a patient's illness, but also to take care of their "patient." Such an approach redefines and advances the central role of the library on the campus and ensures that simulation-based practice is centrally available as part of everyday hospital operations. This article describes the reasons for identifying simulation as an institutional priority leading up to the Massachusetts General Hospital Bicentennial Celebration (1811-2011) and for creating a simulation-based learning laboratory within a hospital library. CHEST 2012; 141(1):12-16 C1 Massachusetts Gen Hosp, MGH Learning Lab, Boston, MA 02114 USA. [Gordon, James A.] Massachusetts Gen Hosp, Dept Emergency Med, Div Med Simulat, Boston, MA 02114 USA. [Gordon, James A.] Harvard Univ, Sch Med, Gilbert Program Med Simulat, Boston, MA 02138 USA. [Gordon, James A.] Ctr Integrat Med & Innovat Technol CIMIT, Boston, MA USA. RP Gordon, JA (reprint author), Massachusetts Gen Hosp, MGH Learning Lab, 0 Emerson Pl,Ste 3B, Boston, MA 02114 USA. EM jgordon3@partners.org NR 27 TC 10 Z9 10 U1 0 U2 3 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JAN PY 2012 VL 141 IS 1 BP 12 EP 16 DI 10.1378/chest.11-0571 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 874FW UT WOS:000298941800006 PM 22215825 ER PT J AU Kerr, KM Auger, WR Marsh, JJ Devendra, G Spragg, RG Kim, NH Channick, RN Jamieson, SW Madani, MM Manecke, GR Roth, DM Shragg, GP Fedullo, PF AF Kerr, Kim M. Auger, William R. Marsh, James J. Devendra, Gehan Spragg, Roger G. Kim, Nick H. Channick, Richard N. Jamieson, Stuart W. Madani, Michael M. Manecke, Gerard R. Roth, David M. Shragg, Gordon P. Fedullo, Peter F. TI Efficacy of Methylprednisolone in Preventing Lung Injury Following Pulmonary Thromboendarterectomy SO CHEST LA English DT Article ID CARDIOPULMONARY BYPASS; ENDARTERECTOMY; APROTININ; SURGERY AB Background: We sought to determine the efficacy and safety of perioperative treatment with methylprednisolone on the development of lung injury after pulmonary thromboendarterectomy. Methods: This was a randomized, prospective, double-blind, placebo-controlled study of 98 adult patients with chronic thromboembolic pulmonary hypertension who were undergoing pulmonary thromboendarterectomy at a single institution. The patients received either placebo (n = 47) or methylprednisolone (n = 51) (30 mg/kg in the cardiopulmonary bypass prime, 500 mg IV bolus following the final circulatory arrest, and 250 mg IV bolus 36 h after surgery). The primary end point was the presence of lung injury as determined by two independent, blinded physicians using prospectively defined criteria. The secondary end points included ventilator-free, ICU-free, and hospital-free days and selected levels of cytokines in the blood and in BAL fluid. Results: The incidence of lung injury was similar in both treatment groups (45% placebo, 41% steroid; P = .72). There were no statistical differences in the secondary clinical end points between treatment groups. Treatment with methylprednisolone, compared with placebo, was associated with a statistically significant reduction in plasma IL-6 and IL-8, a significant increase in plasma IL-10, and a significant reduction in postoperative IL-Ira and IL-6, but not IL-8 in BAL fluid obtained 1 day after surgery. Conclusions: Perioperative methylprednisolone does not reduce the incidence of lung injury following pulmonary thromboendarterectomy surgery despite having an antiinflammatory effect on plasma and lavage cytokine levels. CHEST 2012; 141(1):27-35 C1 [Kerr, Kim M.; Auger, William R.; Marsh, James J.; Spragg, Roger G.; Kim, Nick H.; Fedullo, Peter F.] Univ Calif San Diego, Div Pulm & Crit Care Med, San Diego, CA 92103 USA. [Jamieson, Stuart W.; Madani, Michael M.] Univ Calif San Diego, Div Cardiothorac Surg, San Diego, CA 92103 USA. [Manecke, Gerard R.; Roth, David M.] Univ Calif San Diego, Dept Anesthesiol, San Diego, CA 92103 USA. [Shragg, Gordon P.] Univ Calif San Diego, Gen Clin Res Ctr, San Diego, CA 92103 USA. [Devendra, Gehan] Kaiser Permanente, Sacramento, CA USA. [Channick, Richard N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kerr, KM (reprint author), Univ Calif San Diego, Med Ctr, Pulm & Crit Care Med Div, 9300 Campus Point Dr,M-C 7381, La Jolla, CA 92037 USA. EM kmkerr@ucsd.edu FU National Institutes of Health, National Center for Research Resources for the University of California, San Diego, General Clinical Research Center [NHLBI HL23584, MO1-RR0827] FX This study was supported by the National Institutes of Health [Grants NHLBI HL23584 and MO1-RR0827 from the National Center for Research Resources for the University of California, San Diego, General Clinical Research Center]. NR 20 TC 9 Z9 10 U1 0 U2 5 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 EI 1931-3543 J9 CHEST JI Chest PD JAN PY 2012 VL 141 IS 1 BP 27 EP 35 DI 10.1378/chest.10-2639 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 874FW UT WOS:000298941800009 PM 21835900 ER PT J AU Zemans, RL Stream, AR Musani, AI Dhaliwal, G AF Zemans, Rachel L. Stream, Amanda R. Musani, Ali I. Dhaliwal, Gurpreet TI A 46-Year-Old Man With Seizures, Brain Lesions, and Pulmonary Infiltrates SO CHEST LA English DT Editorial Material ID ALVEOLAR PROTEINOSIS; THERAPY C1 [Zemans, Rachel L.; Musani, Ali I.] Natl Jewish Hlth, Dept Med, Denver, CO 80206 USA. [Zemans, Rachel L.; Stream, Amanda R.; Musani, Ali I.] Univ Colorado Denver, Dept Med, Aurora, CO USA. [Dhaliwal, Gurpreet] San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA. [Dhaliwal, Gurpreet] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. RP Zemans, RL (reprint author), Natl Jewish Hlth, Dept Med, 1400 Jackson St,A555, Denver, CO 80206 USA. EM ZemansR@NJHealth.org FU NHLBI NIH HHS [K08 HL103772, HL103772] NR 10 TC 0 Z9 0 U1 1 U2 2 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JAN PY 2012 VL 141 IS 1 BP 265 EP 269 DI 10.1378/chest.11-1397 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 874FW UT WOS:000298941800041 PM 22215837 ER PT J AU Mavros, MN Velmahos, GC Falagas, ME AF Mavros, Michael N. Velmahos, George C. Falagas, Matthew E. TI Edict of Postoperative Fever and Atelectasis Response SO CHEST LA English DT Letter C1 [Mavros, Michael N.; Falagas, Matthew E.] Alfa Inst Biomed Sci, Athens 15123, Greece. [Velmahos, George C.] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. [Velmahos, George C.] Harvard Univ, Sch Med, Boston, MA USA. [Falagas, Matthew E.] Henry Dunant Hosp, Dept Med, Athens, Greece. [Falagas, Matthew E.] Tufts Univ, Sch Med, Dept Med, Athens, Greece. RP Falagas, ME (reprint author), Alfa Inst Biomed Sci, 9 Neapoleos St, Athens 15123, Greece. EM m.falagas@aibs.gr NR 4 TC 0 Z9 0 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JAN PY 2012 VL 141 IS 1 BP 275 EP 275 DI 10.1378/chest.11-2206 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 874FW UT WOS:000298941800046 ER PT J AU Bostic, JQ Bagnell, AL AF Bostic, Jeffrey Q. Bagnell, Alexa L. TI Evidence-Based School Psychiatry Preface SO CHILD AND ADOLESCENT PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 [Bostic, Jeffrey Q.] Massachusetts Gen Hosp, Sch Psychiat, Boston, MA 02114 USA. [Bagnell, Alexa L.] Dalhousie Univ, Dept Psychiat, IWK Maritime Psychiat, Halifax, NS B3K 6R8, Canada. RP Bostic, JQ (reprint author), Massachusetts Gen Hosp, Sch Psychiat, 55 Fruit St, Boston, MA 02114 USA. EM JBOSTIC@PARTNERS.ORG; Alexa.Bagnell@iwk.nshealth.ca NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1056-4993 J9 CHILD ADOL PSYCH CL JI Child Adolesc. Psychiatr. N. Am. PD JAN PY 2012 VL 21 IS 1 BP XIII EP XVI DI 10.1016/j.chc.2011.10.001 PG 4 WC Psychiatry SC Psychiatry GA 865JY UT WOS:000298308400001 PM 22137822 ER PT J AU Brunt, C Bostic, JQ AF Brunt, Colby Bostic, Jeffrey Q. TI School Law for the Child Psychiatrist: Legal Principles and Case Implications SO CHILD AND ADOLESCENT PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article DE School; Mental health; Legal; School law psychiatry; Special education AB Schools are evolving to support all students, including those with mental health issues. Clinicians can help patients and schools by providing diagnostic clarity about a child's condition, how that condition interferes with school progress, and what interventions are needed in the school setting. State and Federal legislation supports timely response by schools to mental health issues emerging in students through special education laws and general education accommodations, such as Response To Intervention (RTI), which encourages schools to implement evidence-based interventions for students exhibiting mental health conditions. Case examples illuminate important legal considerations when clinicians are faced with issues such as therapeutic placements, home hospital forms, and substance abuse, and student misconduct. C1 [Bostic, Jeffrey Q.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02114 USA. [Bostic, Jeffrey Q.] Massachusetts Gen Hosp, Sch Psychiat, Boston, MA 02114 USA. RP Bostic, JQ (reprint author), Harvard Univ, Sch Med, Dept Psychiat, 6900 Yawkey Bldg,55 Fruit St, Boston, MA 02114 USA. EM jbostic@partners.org NR 4 TC 0 Z9 0 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 1056-4993 J9 CHILD ADOL PSYCH CL JI Child Adolesc. Psychiatr. N. Am. PD JAN PY 2012 VL 21 IS 1 BP 29 EP + DI 10.1016/j.chc.2011.09.001 PG 15 WC Psychiatry SC Psychiatry GA 865JY UT WOS:000298308400005 PM 22137809 ER PT J AU Jellinek, MS Okoli, UD AF Jellinek, Mike S. Okoli, Uchenwa D. TI When a Student Dies: Organizing the School's Response SO CHILD AND ADOLESCENT PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article DE Crisis counseling; Death; Grief; School ID SHOOTINGS; SUICIDE AB Principals, teachers, and guidance counselors feel ill-prepared to address a student's death. Often the death is not anticipated, comes as a shock, and has many reverberations in the school itself and in the broader community. The principal and others in the school may be called upon to serve as leaders in this sudden crisis and have broad responsibilities to their school community that may seem overwhelming in the face of their own grief and reactions to the loss. These guidelines present a meaningful response to an event that can profoundly affect the school and community. C1 [Jellinek, Mike S.; Okoli, Uchenwa D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Newton, MA USA. RP Jellinek, MS (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Newton, MA USA. EM mjellinek@partners.org NR 21 TC 1 Z9 1 U1 2 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1056-4993 J9 CHILD ADOL PSYCH CL JI Child Adolesc. Psychiatr. N. Am. PD JAN PY 2012 VL 21 IS 1 BP 57 EP + DI 10.1016/j.chc.2011.08.008 PG 12 WC Psychiatry SC Psychiatry GA 865JY UT WOS:000298308400007 PM 22137811 ER PT J AU Bostic, JQ Hart, LJ AF Bostic, Jeffrey Q. Hart, Lauren J. TI Building Better Brains: Evidence-Based Interventions to Enhance Contemporary Schooling SO CHILD AND ADOLESCENT PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article DE School; Mental health; Academic success ID PHYSICAL-ACTIVITY; ADOLESCENT SLEEP; START TIME; CHILDREN; FITNESS; IMPACT; YOUTH; CONSUMPTION; EFFICACY; BEHAVIOR AB School is a rich environment for cultivating academic skills, but also for developing metacognitive skills such as executive functioning and emotional regulation. However, the hours students spend in school are often guided by familiar practices rather than contemporary findings about how the brain best learns and grows. This article describes biological conditions favorable to brain development, psychological skills associated with effective school functioning, and school practices associated with academic and interpersonal success. The aim is that schooling might be shaped with regard to children's and adolescents' brain development needs rather than social custom. C1 [Bostic, Jeffrey Q.; Hart, Lauren J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02114 USA. [Bostic, Jeffrey Q.] Massachusetts Gen Hosp, Sch Psychiat, Boston, MA 02114 USA. [Hart, Lauren J.] Northeastern Univ, Dept Publ Hlth, Boston, MA USA. RP Bostic, JQ (reprint author), Dept Child Psychiat, 6900 Yawkey Bldg,55 Fruit St, Boston, MA 02114 USA. EM jbostic@partners.org NR 34 TC 0 Z9 0 U1 0 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1056-4993 EI 1558-0490 J9 CHILD ADOL PSYCH CL JI Child Adolesc. Psychiatr. N. Am. PD JAN PY 2012 VL 21 IS 1 BP 69 EP + DI 10.1016/j.chc.2011.09.006 PG 14 WC Psychiatry SC Psychiatry GA 865JY UT WOS:000298308400008 PM 22137812 ER PT J AU Yule, AM Prince, JB AF Yule, Amy M. Prince, Jefferson B. TI Adolescent Substance Use Disorders in the School Setting SO CHILD AND ADOLESCENT PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article DE Substance abuse; Adolescents; Prevention programs; School; Treatment ID ABUSE RESISTANCE EDUCATION; CLUSTER-RANDOMIZED-TRIAL; DRUG-ABUSE; PROJECT ALERT; FOLLOW-UP; ALCOHOL-USE; PREVENTION; TOBACCO; MIDDLE; DARE AB Adolescent substance use is a major public health problem that concerns parents, schools, clinicians, and policy makers. The authors review school-based prevention programs, school drug policies, clinical signs and symptoms of substance impairment, recommendations for referral and engaging adolescents who are using substances, and treatment interventions for adolescent substance use disorders. C1 [Yule, Amy M.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Prince, Jefferson B.] MassGen Children N Shore Med Ctr, Salem, MA 01970 USA. [Prince, Jefferson B.] Massachusetts Gen Hosp, Pediat Psychopharmacol Clin, Boston, MA 02114 USA. [Prince, Jefferson B.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Yule, AM (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 55 Fruit St, Boston, MA 02114 USA. EM ayule@partners.org NR 63 TC 0 Z9 0 U1 1 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1056-4993 EI 1558-0490 J9 CHILD ADOL PSYCH CL JI Child Adolesc. Psychiatr. N. Am. PD JAN PY 2012 VL 21 IS 1 BP 175 EP + DI 10.1016/j.chc.2011.09.003 PG 13 WC Psychiatry SC Psychiatry GA 865JY UT WOS:000298308400016 PM 22137820 ER PT J AU Stevens, JR Prince, JB AF Stevens, Jonathan R. Prince, Jefferson B. TI Schooling Students with Psychotic Disorders SO CHILD AND ADOLESCENT PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article DE Psychosis; Childhood-onset schizophrenia; Hallucinations; School interventions ID CHILDHOOD-ONSET SCHIZOPHRENIA; SYMPTOMS; THERAPY AB The term psychosis is generally used to describe the abnormal behaviors of children and adolescents with grossly impaired reality testing. This article discusses evaluation of psychotic symptoms in students and psychosocial school interventions for students with psychosis, including the roles of teachers and school administrators. Psychoeducation provided by clinicians and school staff to enhance coping and cognitive strategies is described. C1 [Stevens, Jonathan R.] Med Ctr, Pediat Inpatient Psychiat Unit, Lynn, MA 01904 USA. [Prince, Jefferson B.] MassGen Children N Shore Med Ctr, Salem, MA USA. [Prince, Jefferson B.] Massachusetts Gen Hosp, Pediat Psychopharmacol Clin, Boston, MA 02114 USA. RP Stevens, JR (reprint author), Med Ctr, Pediat Inpatient Psychiat Unit, 500 Lynnfield St, Lynn, MA 01904 USA. EM jstevens@partners.org NR 18 TC 1 Z9 1 U1 2 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1056-4993 EI 1558-0490 J9 CHILD ADOL PSYCH CL JI Child Adolesc. Psychiatr. N. Am. PD JAN PY 2012 VL 21 IS 1 BP 187 EP + DI 10.1016/j.chc.2011.09.008 PG 15 WC Psychiatry SC Psychiatry GA 865JY UT WOS:000298308400017 PM 22137821 ER PT J AU Gray, SW Hornik, RC Schwartz, JS Armstrong, K AF Gray, S. W. Hornik, R. C. Schwartz, J. S. Armstrong, K. TI The impact of risk information exposure on women's beliefs about direct-to-consumer genetic testing for BRCA mutations SO CLINICAL GENETICS LA English DT Article DE BRCA; cancer; communication; direct-to-consumer; informed consent ID POLICY STATEMENT UPDATE; CANCER SUSCEPTIBILITY; GENOMIC MEDICINE; AMERICAN-SOCIETY; OVARIAN-CANCER; UNITED-STATES; INTERNET; SERVICES; BREAST; VIEWS AB Despite an increase in direct-to-consumer (DTC) genetic testing, little is known about how variations in website content might alter consumer behavior. We evaluated the impact of risk information provision on women's attitudes about DTC BRCA testing. We conducted a randomized experiment; women viewed a 'mock' BRCA testing website without [control group (CG)] or with information on the potential risks of DTC testing [RG; framed two ways: unattributed risk (UR) information and risk information presented by experts (ER)]. Seven hundred and sixty-seven women participated; mean age was 37 years, mean education was 15 years, and 79% of subjects were white. Women in the RG had less positive beliefs about DTC testing (mean RG = 23.8, CG = 25.2; p = 0.001), lower intentions to get tested (RG = 2.8, CG = 3.1; p = 0.03), were more likely to prefer clinic-based testing (RG = 5.1, CG = 4.8; p = 0.03) and to report that they had seen enough risk information (RG = 5.3, CG = 4.7; p < 0.001). UR and ER exposure produced similar effects. Effects did not differ for women with or without a personal/family history of breast/ovarian cancer. Exposing women to the potential risks of DTC BRCA testing altered their beliefs, preferences, and intentions. Risk messages appear to be salient to women irrespective of their chance of having a BRCA mutation. C1 [Gray, S. W.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Gray, S. W.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Hornik, R. C.] Univ Penn, Annenberg Sch Commun, Ctr Excellence Canc Commun Res, Philadelphia, PA 19104 USA. [Schwartz, J. S.; Armstrong, K.] Univ Penn, Sect Gen Internal Med, Philadelphia, PA 19104 USA. [Schwartz, J. S.] Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. [Armstrong, K.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. RP Gray, SW (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,LW 633, Boston, MA 02215 USA. EM stacyw_gray@dfci.harvard.edu OI Hornik, Robert/0000-0002-2148-8805 FU Robert Wood Johnson Foundation; NCI [5P50CA095856-05, R25 CA092203]; American Society for Clinical Oncology FX Funding/Support for this study was provided by Robert Wood Johnson Foundation, NCI 5P50CA095856-05, The American Society for Clinical Oncology, and NCI R25 CA092203. NR 57 TC 4 Z9 4 U1 2 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD JAN PY 2012 VL 81 IS 1 BP 29 EP 37 DI 10.1111/j.1399-0004.2011.01797.x PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 860CP UT WOS:000297925600005 PM 21992449 ER PT J AU Hermos, JA Young, MM Fonda, JR Gagnon, DR Fiore, LD Lawler, EV AF Hermos, John A. Young, Melissa M. Fonda, Jennifer R. Gagnon, David R. Fiore, Louis D. Lawler, Elizabeth V. TI Risk of Community-Acquired Pneumonia in Veteran Patients to Whom Proton Pump Inhibitors Were Dispensed SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID SPONTANEOUS BACTERIAL PERITONITIS; ACID SUPPRESSION; GASTROESOPHAGEAL-REFLUX; ASSOCIATION; DISEASE; INFECTIONS; OVERGROWTH; THERAPY; ADULTS; OLDER AB Background. Observational studies linking proton pump inhibitor (PPI) exposure with community-acquired pneumonia (CAP) have reported either modest or no associations. Accordingly, we studied PPI exposure and CAP in veteran patients, using a retrospective, nested case-control design. Methods. From linked pharmacy and administrative databases of the New England Veterans Healthcare System, we identified 71 985 outpatients newly prescribed PPIs between 1998 and 2007; 1544 patients met criteria for CAP subsequent to PPI initiation; 15 440 controls were matched through risk-set sampling by age and time under observation. Crude and adjusted odds ratios comparing current with past PPI exposures, as well as tests for interactions, were conducted for the entire and stratified samples. Results. Current PPI use associated with CAP (adjusted odds ratio [OR], 1.29 [95% confidence interval {CI}, 1.15-1.45]). Risks were not substantially altered by age or year of diagnosis. Dementia (n = 85; P = .062 for interaction) and sedative/tranquilizer use (n = 224; P = .049 for interaction) were likely effect modifiers increasing a PPI-CAP association; conversely, for some chronic medical conditions, PPI-associated CAP risks were reversed. PPI exposures between 1 and 15 days increased CAP risks, compared with longer exposures, but PPI initiation also frequently occurred shortly after CAP diagnoses. Prescribed PPI doses.1 dose/day also increased PPI-associated CAP risks. Conclusions. Among the veterans studied, current compared with past PPI exposures associated modestly with increased risks of CAP. However, our observations that recent treatment initiation and higher PPI doses were associated with greater risks, and the inconsistent PPI-CAP associations between patient subgroups, indicate that further inquiries are needed to separate out coincidental patterns of associations. C1 [Hermos, John A.; Young, Melissa M.; Fonda, Jennifer R.; Gagnon, David R.; Fiore, Louis D.; Lawler, Elizabeth V.] VA Boston Healthcare Syst, VA Cooperat Studies Program, Massachusetts Vet Epidemiol Res & Informat Ctr, Pharmacoepidemiol Grp, Boston, MA USA. [Hermos, John A.; Fiore, Louis D.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Gagnon, David R.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Lawler, Elizabeth V.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Hermos, JA (reprint author), VA Boston Healthcare Syst 151MAV, 150 S Huntington Ave, Boston, MA 02130 USA. EM john.hermos@va.gov OI Gagnon, David/0000-0002-6367-3179 FU Core Funds Massachusetts Veterans Epidemiology Research and Information Center; VA Cooperative Studies Program, VA Boston Healthcare System FX This work was supported by Core Funds Massachusetts Veterans Epidemiology Research and Information Center, VA Cooperative Studies Program, VA Boston Healthcare System. NR 34 TC 25 Z9 28 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JAN 1 PY 2012 VL 54 IS 1 BP 33 EP 42 DI 10.1093/cid/cir767 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 866LX UT WOS:000298383500008 PM 22100573 ER PT J AU Butt, AA Kanwal, F AF Butt, Adeel A. Kanwal, Fasiha TI Boceprevir and Telaprevir in the Management of Hepatitis C Virus-Infected Patients SO CLINICAL INFECTIOUS DISEASES LA English DT Review ID GENOTYPE 1 INFECTION; PROTEASE INHIBITOR; ANTIVIRAL THERAPY; PLUS RIBAVIRIN; INTERFERON; RESISTANCE AB Recent approval of direct-acting antiviral agents (DAAs) against hepatitis C virus (HCV) offers a major advance in the management of HCV infection. These DAAs, boceprevir and telaprevir, when given with pegylated interferon alfa (Peg-IFN) and ribavirin (RBV), result in a much higher sustained virologic response rate compared with Peg-IFN and RBV. The DAA-containing regimens are approved for HCV genotype 1 infection in HCV treatment-naive and HCV treatment-experienced patients. In this review, we present an overview of pharmacology, efficacy, adverse events, and emergence of resistance-associated variants with the use of these agents. As with all drugs, especially newly approved drugs, clinicians must consult the package insert for detailed prescribing information, list of all reported adverse events, contraindications, and drug interactions. C1 [Butt, Adeel A.] Univ Pittsburgh, Sch Med, Div Infect Dis, Dept Med, Pittsburgh, PA 15213 USA. [Butt, Adeel A.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Butt, Adeel A.] Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Kanwal, Fasiha] St Louis Univ, Sch Med, St Louis Vet Affairs Med Ctr, St Louis, MO 63103 USA. [Kanwal, Fasiha] St Louis Univ, Sch Med, Dept Med, Div Gastroenterol & Hepatol, St Louis, MO 63103 USA. RP Butt, AA (reprint author), Univ Pittsburgh, Sch Med, Dept Med & Infect Dis, 3601 5th Ave,Ste 3A, Pittsburgh, PA 15213 USA. EM aabutt@pitt.edu FU Merck Sharp Dohme Corp. FX A. A. B. has received investigator-initiated grant support (to University of Pittsburgh) from Merck Sharp & Dohme Corp. NR 21 TC 45 Z9 48 U1 1 U2 10 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JAN 1 PY 2012 VL 54 IS 1 BP 96 EP 104 DI 10.1093/cid/cir774 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 866LX UT WOS:000298383500020 PM 22156853 ER PT J AU Vorhies, JS Wang, Y Herndon, JH Maloney, WJ Huddleston, JI AF Vorhies, John S. Wang, Yun Herndon, James H. Maloney, William J. Huddleston, James I. TI Decreased Length of Stay After TKA Is Not Associated With Increased Readmission Rates in a National Medicare Sample SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID KNEE REPLACEMENT SURGERY; TOTAL HIP-REPLACEMENT; UNITED-STATES; SURGICAL CARE; ARTHROPLASTY; OUTCOMES; QUALITY AB Background There is a trend toward decreasing length of hospital stay (LOS) after TKA although it is unclear whether this trend is detrimental to the overall postoperative course. Such information is important for future decisions related to cost containment. Questions/purposes We determined whether decreases in LOS after TKA are associated with increases in readmission rates. Patients and Methods We retrospectively reviewed the rates and reasons for readmission and LOS for 4057 Medicare TKA patients from 2002 to 2007. We abstracted data from the Medicare Patient Safety Monitoring System. Hierarchical generalized linear modeling was used to assess the odds of changing readmission rates and LOS over time, controlling for changes in patient demographic and clinical variables. Results The overall readmission rate in the 30 days after discharge was 228/4057 (5.6%). The 10 most common reasons for readmission were congestive heart failure (20.4%), chronic ischemic heart disease (13.9%), cardiac dysrhythmias (12.5%), pneumonia (10.8%), osteoarthrosis (9.4%), general symptoms (7.4%), acute myocardial infarction (7.0%), care involving other specified rehabilitation procedure (6.3%), diabetes mellitus (6.3%), and disorders of fluid, electrolyte, and acid-base balance (5.9%); the top 10 causes did not include venous thromboembolism syndromes. We found no difference in the readmission rate between the periods 2002-2004 (5.5%) and 2005-2007 (5.8%) but a reduction in LOS between the periods 2002-2004 (4.1 +/- A 2.0 days) and 2005-2007 (3.8 +/- A 1.7 days). Conclusions The most common causes for readmission were cardiac-related. A reduction in LOS was not associated with an increase in the readmission rate in this sample. Optimization of cardiac status before discharge and routine primary care physician followup may lead to lower readmission rates. C1 [Vorhies, John S.; Maloney, William J.; Huddleston, James I.] Stanford Med Outpatient Ctr, Dept Orthopaed Surg, Redwood City, CA 94063 USA. [Wang, Yun] Qualidigm Inc, Middletown, CT USA. [Wang, Yun] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Herndon, James H.] Harvard Univ, Sch Med, Dept Orthopaed Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Huddleston, JI (reprint author), Stanford Med Outpatient Ctr, Dept Orthopaed Surg, 450 Broadway St,Mailcode 6324, Redwood City, CA 94063 USA. EM jhuddleston@stanford.edu NR 22 TC 32 Z9 33 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD JAN PY 2012 VL 470 IS 1 BP 166 EP 171 DI 10.1007/s11999-011-1957-0 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 862OR UT WOS:000298103100021 PM 21720934 ER PT J AU Lambers, K Ootes, D Ring, D AF Lambers, Kaj Ootes, Daan Ring, David TI Incidence of Patients with Lower Extremity Injuries Presenting to US Emergency Departments by Anatomic Region, Disease Category, and Age SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID ANKLE INJURIES; HIP-FRACTURES; UNITED-STATES; EPIDEMIOLOGY; SPRAINS; POPULATION; PREDICTORS; ACCIDENT; RULES AB Background The incidence of patients with lower extremity injuries presenting to emergency departments in the United States with respect to specific anatomic regions and disease categories is unknown. Such information might be used for injury prevention, resource allocation, and training priorities. Questions/purposes We determined the anatomic regions, disease categories, and circumstances that account for the highest incidence of leg problems among patients presenting to emergency departments in the United States. Methods We used the National Electronic Injury Surveillance System (NEISS) to obtain a probability sample of all lower extremity injuries treated at emergency departments during 2009. A total of 119,815 patients who presented to emergency departments with lower extremity injuries in 2009 were entered in the NEISS database. Patient and injury characteristics were analyzed. Incidence rates for various regions, disease categories, injuries, and age groups were calculated using US census data. Results We identified 112 unique combinations of disease categories and anatomic regions. Strains and sprains accounted for 36% of all lower extremity injuries. The injury with the greatest incidence was an ankle sprain (206 per 100,000; 95% confidence interval, 181-230). Younger patients were more likely to have ankle sprains, foot contusions/abrasions, and foot strains/sprains. Older patients were more likely to have lower trunk fractures and lower trunk contusions/abrasions. The most common incidence for injury was at home (45%). Conclusions Given relatively low-acuity leg problems such as strains and sprains account for a substantial number of emergency department visits pertaining to leg problems, use of telephone triage, scheduled same or next-day urgent care appointments, and other alternatives to the traditional emergency room might result in better use of emergency healthcare resources. C1 [Ring, David] Yawkey Ctr, Boston, MA 02114 USA. [Lambers, Kaj; Ootes, Daan; Ring, David] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Ring, D (reprint author), Yawkey Ctr, 55 Fruit St,Suite 2100, Boston, MA 02114 USA. EM dring@partners.org NR 24 TC 27 Z9 28 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD JAN PY 2012 VL 470 IS 1 BP 284 EP 290 DI 10.1007/s11999-011-1982-z PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 862OR UT WOS:000298103100036 PM 21785896 ER PT J AU Isong, IA Luff, D Perrin, JM Winickoff, JP Ng, MW AF Isong, Inyang A. Luff, Donna Perrin, James M. Winickoff, Jonathan P. Man Wai Ng TI Parental Perspectives of Early Childhood Caries SO CLINICAL PEDIATRICS LA English DT Article DE children; parents; caries; qualitative interviews ID CHILDRENS ORAL-HEALTH; HEAD-START CHILDREN; YOUNG-CHILDREN; QUALITATIVE RESEARCH; MEDICAL LITERATURE; USERS GUIDES; CARE; IMPACT; LITERACY; OUTCOMES AB Background. Parental perspectives of children with early childhood caries may help inform the development and improvement of caries prevention strategies. Objectives. This study aimed to explore parents' experiences, perceptions, and expectations regarding prevention and management of early childhood caries. Methods. The authors conducted semistructured interviews with 25 parents of children aged 2 to 5 years, with a known history of caries. All interviews were transcribed and coded, and iterative analyses were conducted to identify key emergent themes within the data. Results. Parents had limited knowledge of behaviors contributing to early childhood caries and when to first seek regular dental care. Parents expected pediatricians to provide education on how to prevent childhood caries, conduct preliminary oral health assessments, and help establish early linkages between medical and dental care. Conclusion. The findings make a strong case for pediatricians to take responsibility for engaging and educating parents on fostering optimal oral health and helping to access early childhood dental care. C1 [Isong, Inyang A.] MassGen Hosp Children, Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA. [Luff, Donna] Harvard Pediat Hlth Serv Res Program, Boston, MA USA. [Man Wai Ng] Childrens Hosp Boston, Boston, MA USA. RP Isong, IA (reprint author), MassGen Hosp Children, Ctr Child & Adolescent Hlth Policy, 50 Staniford St,Suite 901, Boston, MA 02114 USA. EM iisong@partners.org FU DentaQuest Institute; Health Resources and Services Administration, Department of Health and Human Services [T32 HP10018] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was supported by DentaQuest Institute. Dr Isong's work is supported by a National Research Service Award (T32 HP10018) from the Health Resources and Services Administration, Department of Health and Human Services. We thank Odeviz Soto (OS), Gay Torresyap and Dr. Peter Maramaldi for support and contributions to the study. NR 31 TC 9 Z9 9 U1 1 U2 23 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0009-9228 J9 CLIN PEDIATR JI Clin. Pediatr. PD JAN PY 2012 VL 51 IS 1 BP 77 EP 85 DI 10.1177/0009922811417856 PG 9 WC Pediatrics SC Pediatrics GA 870GC UT WOS:000298656200010 PM 21903623 ER PT J AU Daniel, BS Hertl, M Werth, VP Eming, R Murrell, DF AF Daniel, Benjamin S. Hertl, Michael Werth, Victoria P. Eming, Ruediger Murrell, Dedee F. TI Severity score indexes for blistering diseases SO CLINICS IN DERMATOLOGY LA English DT Article ID PEMPHIGUS-VULGARIS; ORAL PEMPHIGUS; IMMUNOADSORPTION; AUTOANTIBODIES; PROGRESSION; ANTIBODIES; RITUXIMAB AB Scoring systems are used to assess the severity of a disease and the response to treatment. The main severity scoring indexes are the Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) and the Pemphigus Disease Area Index (PDAI). They have been validated and are already used in the evaluation of pemphigus and in clinical trials. They quantify disease severity by performing a global assessment of all lesions. In recent years, other severity scoring systems have been developed for pemphigus and other autoimmune blistering diseases. (C) 2012 Elsevier Inc. All rights reserved. C1 [Daniel, Benjamin S.; Murrell, Dedee F.] St George Hosp, Dept Dermatol, Sydney, NSW, Australia. [Daniel, Benjamin S.; Murrell, Dedee F.] Univ New S Wales, Dept Dermatol, Sydney, NSW, Australia. [Hertl, Michael; Eming, Ruediger] Univ Marburg, Dept Dermatol, Marburg, Germany. [Werth, Victoria P.] Philadelphia VA Med Ctr, Dept Dermatol, Philadelphia, PA USA. [Werth, Victoria P.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Murrell, DF (reprint author), St George Hosp, Dept Dermatol, Sydney, NSW, Australia. EM d.murrell@unsw.edu.au FU National Institutes of Health [NIH K24-AR 02207] FX This work was supported in part by the National Institutes of Health (grant number NIH K24-AR 02207) to VPW. NR 28 TC 26 Z9 28 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0738-081X J9 CLIN DERMATOL JI Clin. Dermatol. PD JAN-FEB PY 2012 VL 30 IS 1 BP 108 EP 113 DI 10.1016/j.clindermatol.2011.03.017 PG 6 WC Dermatology SC Dermatology GA 864BS UT WOS:000298212600014 PM 22137234 ER PT J AU Schalock, PC Menne, T Johansen, JD Taylor, JS Maibach, HI Liden, C Bruze, M Thyssen, JP AF Schalock, Peter C. Menne, Torkil Johansen, Jeanne D. Taylor, James S. Maibach, Howard I. Liden, Carola Bruze, Magnus Thyssen, Jacob P. TI Hypersensitivity reactions to metallic implants - diagnostic algorithm and suggested patch test series for clinical use SO CONTACT DERMATITIS LA English DT Review DE allergic contact dermatitis; implant reactions; metals; patch tests ID TOTAL JOINT REPLACEMENT; TOTAL HIP-ARTHROPLASTY; IN-STENT RESTENOSIS; ORTHOPEDIC IMPLANTS; CONTACT SENSITIVITY; BONE-CEMENT; T-CELL; HUMAN OSTEOCLASTS; ION RELEASE; ALLERGY AB Cutaneous and systemic hypersensitivity reactions to implanted metals are challenging to evaluate and treat. Although they are uncommon, they do exist, and require appropriate and complete evaluation. This review summarizes the evidence regarding evaluation tools, especially patch and lymphocyte transformation tests, for hypersensitivity reactions to implanted metal devices. Patch test evaluation is the gold standard for metal hypersensitivity, although the results may be subjective. Regarding pre-implant testing, those patients with a reported history of metal dermatitis should be evaluated by patch testing. Those without a history of dermatitis should not be tested unless considerable concern exists. Regarding post-implant testing, a subset of patients with metal hypersensitivity may develop cutaneous or systemic reactions to implanted metals following implant. For symptomatic patients, a diagnostic algorithm to guide the selection of screening allergen series for patch testing is provided. At a minimum, an extended baseline screening series and metal screening is necessary. Static and dynamic orthopaedic implants, intravascular stent devices, implanted defibrillators and dental and gynaecological devices are considered. Basic management suggestions are provided. Our goal is to provide a comprehensive reference for use by those evaluating suspected cutaneous and systemic metal hypersensitivity reactions. C1 [Schalock, Peter C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA 02114 USA. [Menne, Torkil; Johansen, Jeanne D.; Thyssen, Jacob P.] Univ Copenhagen, Gentofte Hosp, Dept Dermatoallergol, Natl Allergy Res Ctr, DK-2820 Copenhagen, Denmark. [Taylor, James S.] Cleveland Clin, Dept Dermatol, Cleveland, OH 44195 USA. [Maibach, Howard I.] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94115 USA. [Liden, Carola] Karolinska Inst, Inst Environm Med, S-10462 Stockholm, Sweden. [Bruze, Magnus] Lund Univ, Dept Occupat & Environm Dermatol, Skane Univ Hosp, S-20502 Malmo, Sweden. RP Schalock, PC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, 55 Fruit St, Boston, MA 02114 USA. EM schalock.prof@gmail.com OI Schalock, Peter/0000-0001-8953-4639; Liden, Carola/0000-0001-9951-5896 NR 91 TC 40 Z9 41 U1 2 U2 20 PU WILEY PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-1873 EI 1600-0536 J9 CONTACT DERMATITIS JI Contact Dermatitis PD JAN PY 2012 VL 66 IS 1 BP 4 EP 19 DI 10.1111/j.1600-0536.2011.01971.x PG 16 WC Allergy; Dermatology SC Allergy; Dermatology GA 860CX UT WOS:000297926500002 PM 21957996 ER PT J AU Braun, AB Gibbons, FK Litonjua, AA Giovannucci, E Christopher, KB AF Braun, Andrea B. Gibbons, Fiona K. Litonjua, Augusto A. Giovannucci, Edward Christopher, Kenneth B. TI Low serum 25-hydroxyvitamin D at critical care initiation is associated with increased mortality SO CRITICAL CARE MEDICINE LA English DT Article DE 25-hydroxyvitamin D; mortality; epidemiology; vitamin D ID CHRONIC KIDNEY-DISEASE; REGULATORY T-CELLS; DISPARITIES GEOCODING PROJECT; VITAMIN-D DEFICIENCY; NUTRITION EXAMINATION SURVEY; PROLONGED CRITICAL ILLNESS; 3RD NATIONAL-HEALTH; ILL PATIENTS; NEIGHBORHOOD POVERTY; INTENSIVE-CARE AB Objective: We hypothesized that deficiency in 25-hydroxyvitamin D at critical care initiation would be associated with all-cause mortalities. Design: Two-center observational study. Setting: Two teaching hospitals in Boston, MA. Patients: The study included 1,325 patients, age >= 18 yrs, in whom 25-hydroxyvitamin D was measured 7 days before or after critical care initiation between 1998 and 2009. Measurements: 25-hydroxyvitamin D was categorized as deficiency in 25-hydroxyvitamin D (<= 15 ng/mL), insufficiency (16-29 ng/mL), and sufficiency (>= 30 ng/mL). Logistic regression examined death by days 30, 90, and 365 postcritical care initiation and in-hospital mortality. Adjusted odds ratios were estimated by multivariable logistic regression models. Interventions: None. Key Results: 25-hydroxyvitamin D deficiency is predictive for short-term and long-term mortality. Thirty days following critical care initiation, patients with 25-hydroxyvitamin D deficiency have an odds ratio for mortality of 1.85 (95% confidence interval 1.15-2.98; p = .01) relative to patients with 25-hydroxyvitamin D sufficiency. 25-hydroxyvitamin D deficiency remains a significant predictor of mortality at 30 days following critical care initiation following multivariable adjustment for age, gender, race, Deyo-Charlson index, sepsis, season, and surgical vs. medical patient type (adjusted odds ratio 1.94; 95% confidence interval 1.18-3.20; p = .01). Results were similarly significant at 90 and 365 days following critical care initiation and for in-hospital mortality. The association between vitamin D and mortality was not modified by sepsis, race, or neighborhood poverty rate, a proxy for socioeconomic status. Conclusion: Deficiency of 25-hydroxyvitamin D at the time of critical care initiation is a significant predictor of all-cause patient mortality in a critically ill patient population. (Crit Care Med 2012; 40:63-72) C1 [Braun, Andrea B.; Christopher, Kenneth B.] Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. [Litonjua, Augusto A.] Brigham & Womens Hosp, Pulm & Crit Care Div, Boston, MA 02115 USA. [Christopher, Kenneth B.] Brigham & Womens Hosp, Nathan E Hellman Mem Lab, Boston, MA 02115 USA. [Gibbons, Fiona K.] Massachusetts Gen Hosp, Div Pulm, Boston, MA 02114 USA. [Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Christopher, KB (reprint author), Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. EM kbchristopher@partners.org OI Litonjua, Augusto/0000-0003-0422-5875 FU NIH [K08AI060881] FX Supported, in part, by NIH K08AI060881 (KBC). NR 105 TC 79 Z9 92 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JAN PY 2012 VL 40 IS 1 BP 63 EP 72 DI 10.1097/CCM.0b013e31822d74f3 PG 10 WC Critical Care Medicine SC General & Internal Medicine GA 866KO UT WOS:000298379800010 PM 21926604 ER PT J AU Berra, L Coppadoro, A Bittner, EA Kolobow, T Laquerriere, P Pohlmann, JR Bramati, S Moss, J Pesenti, A AF Berra, Lorenzo Coppadoro, Andrea Bittner, Edward A. Kolobow, Theodor Laquerriere, Patrice Pohlmann, Joshua R. Bramati, Simone Moss, Joel Pesenti, Antonio TI A clinical assessment of the Mucus Shaver: A device to keep the endotracheal tube free from secretions SO CRITICAL CARE MEDICINE LA English DT Article DE bacterial biofilm; endotracheal tube; endotracheal tube occlusion; endotracheal tube suctioning; mechanical ventilation; Mucus Shaver; secretion removal; ventilator-associated pneumonia ID VENTILATOR-ASSOCIATED PNEUMONIA; PSEUDOMONAS-AERUGINOSA BIOFILMS; MECHANICAL VENTILATION; BACTERIAL-COLONIZATION; TRACHEAL TUBE; INTUBATION; PREVENTION; RESISTANCE; INFECTION; DIAMETER AB Objective: We evaluated a new device designed to clean the endotracheal tube in mechanically ventilated patients, the Mucus Shaver. Design: Prospective, randomized trial. Setting: University hospital intensive care unit. Patients: We enrolled 24 patients expected to remain ventilated for >72 hrs. Interventions: The Mucus Shaver is a concentric inflatable catheter for the removal of mucus and secretions from the interior surface of the endotracheal tube. The Mucus Shaver is advanced to the distal endotracheal tube tip, inflated, and subsequently withdrawn over a period of 3-5 secs. Patients were prospectively randomized within 2 hrs of intubation to receive standard endotracheal tube suctioning treatment or standard suctioning plus Mucus Shaver use until extubation. Measurements and Main Results: During the study period, demographic data, recent medical history, adverse events, and staff evaluation of the Mucus Shaver were recorded. At extubation, each endotracheal tube was removed, cultured, and analyzed by scanning electron microscopy. Twelve patients were assigned to the study group and 12 were assigned to the control group. No adverse events related to the use of the Mucus Shaver were observed. At extubation, only one endotracheal tube from the Mucus Shaver group was colonized, whereas in the control group ten endotracheal tubes were colonized (8% vs. 83%; p < .001). Scanning electron microscopy showed little secretions on the endotracheal tubes from the study group, whereas thick bacterial deposits were present on all the endotracheal tubes from the control group (p < .001 by Fisher exact test, using a maximum biofilm thickness of 30 mu m as cut-off). The nursing staff was satisfied by the overall safety, feasibility, and efficacy of the Mucus Shaver. Conclusions: The Mucus Shaver is a safe, feasible, and efficient device for endotracheal tube cleaning in the clinical setting. The Mucus Shaver is helpful in preventing endotracheal tube colonization by potentially harmful microorganisms. (Crit Care Med 2012; 40:119-124) C1 [Berra, Lorenzo; Coppadoro, Andrea; Bittner, Edward A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02115 USA. [Coppadoro, Andrea; Pesenti, Antonio] Univ Milano Bicocca, Dept Expt Med, Milan, Italy. [Kolobow, Theodor] NHLBI, Sect Pulm & Cardiac Assist Devices, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. [Laquerriere, Patrice] Univ Reims, INSERM, Electron Microscopy Lab, Reims, France. [Pohlmann, Joshua R.] Univ Michigan, Dept Gen Surg, Ann Arbor, MI 48109 USA. [Bramati, Simone] San Gerardo Hosp, Microbiol & Virol Dept, Monza, Italy. [Moss, Joel] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA. [Pesenti, Antonio] San Gerardo Hosp, Dept Perioperat Med & Intens Care, Monza, Italy. RP Berra, L (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02115 USA. EM lberra@partners.org RI Pesenti, Antonio/H-7483-2012; Laquerriere, Patrice/P-1025-2016 OI Laquerriere, Patrice/0000-0001-7637-9094 FU National Heart, Lung, and Blood Institute, Division of International Research, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland; Department of Perioperative Medicine and Intensive Care, San Gerardo Hospital, Monza, Italy; National Institutes of Health, National Heart, Lung, and Blood Institute, Bethesda, Maryland FX Supported, in part, by the National Heart, Lung, and Blood Institute, Division of International Research, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, and by the Department of Perioperative Medicine and Intensive Care, San Gerardo Hospital, Monza, Italy. Dr. Moss and Dr. Kolobow were supported by the Intramural Research Program, National Institutes of Health, National Heart, Lung, and Blood Institute, Bethesda, Maryland. NR 30 TC 37 Z9 38 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JAN PY 2012 VL 40 IS 1 BP 119 EP 124 DI 10.1097/CCM.0b013e31822e9fe3 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA 866KO UT WOS:000298379800017 PM 21926595 ER PT J AU Pejo, E Feng, Y Chao, W Cotten, JF Ge, RL Raines, DE AF Pejo, Ervin Feng, Yan Chao, Wei Cotten, Joseph F. Ge, Ri Le Raines, Douglas E. TI Differential effects of etomidate and its pyrrole analogue carboetomidate on the adrenocortical and cytokine responses to endotoxemia SO CRITICAL CARE MEDICINE LA English DT Article DE anesthesia; corticosteroine; cytokines; endotoxemia; lipopolysaccharides; sepsis ID RAPID-SEQUENCE INTUBATION; LOW-DOSE HYDROCORTISONE; SEPTIC SHOCK; NITROUS-OXIDE; ADRENAL INSUFFICIENCY; EMERGENCY-DEPARTMENT; CRITICALLY-ILL; ANIMAL-MODELS; INDUCTION; SEPSIS AB Objective: We developed a novel pyrrole analog of etomidate, (R)-ethyl 1-(1-phenylethyl)-1H-pyrrole-2-carboxylate (carboetomidate), which retains etomidate's desirable anesthetic and hemodynamic properties but lacks its potent inhibitory affect on adrenocorticotropic hormone-stimulated steroid synthesis. The objective of this study was to test the hypothesis that in contrast to etomidate, carboetomidate neither suppresses the adrenocortical response to endotoxemia nor enhances the accompanying production of proinflammatory cytokines. Design: Animal study. Setting: University research laboratory. Subjects: Male Sprague-Dawley rats. Interventions: For both single and multiple anesthetic dose studies, rats were injected with Escherichia coli lipopolysaccharide immediately followed by a hypnotic dose of etomidate, carboetomidate, or vehicle alone (dimethyl sulfoxide) as a control. For single-dose studies, no additional anesthetic (or vehicle) was administered. For multiple anesthetic dose studies, additional doses of anesthetic (or vehicle) were administered every 15 mins for a total of eight anesthetic (or vehicle) doses. Measurements and Main Results: Plasma adrenocorticotropic hormone, corticosterone, and cytokine concentrations were measured before lipopolysaccharide administration and intermittently throughout the 5-hr experiment. In single anesthetic dose studies, plasma adrenocorticotropic hormone and cytokine concentrations were not different at any time point among the etomidate, carboetomidate, and vehicle groups, whereas plasma corticosterone concentrations were briefly (60-120 mins) reduced in the etomidate group. In multiple anesthetic dose studies, plasma corticosterone concentrations were persistently lower and peak plasma interleukin-1 beta and interleukin-6 concentrations were higher in the etomidate group vs. the carboetomidate and control groups. Peak plasma interleukin-10 concentrations were similarly elevated in the etomidate and carboetomidate groups vs. the control group. Conclusions: Compared with etomidate, carboetomidate produces less suppression of adrenocortical function and smaller increases in proinflammatory cytokine production in an endotoxemia model of sepsis. These findings suggest that carboetomidate could be a useful alternative to etomidate for maintaining anesthesia for a prolonged period of time in patients with sepsis. (Crit Care Med 2012; 40: 187-192) C1 [Pejo, Ervin; Feng, Yan; Chao, Wei; Cotten, Joseph F.; Ge, Ri Le; Raines, Douglas E.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Pejo, E (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM draines@partners.org RI Feng, Yan/H-5808-2012 FU National Institutes of Health, Bethesda, MD [R01-GM087316, R21-DA029253, K08-GM083216]; Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, MA; National Institutes of Health FX Supported by grants R01-GM087316, R21-DA029253, and K08-GM083216 from the National Institutes of Health, Bethesda, MD, and the Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, MA.; The Massachusetts General Hospital has submitted patent applications for carboetomidate and related analogues. Two authors (Drs. Raines and Cotten), and their respective laboratories, departments, and institutions, could receive compensation related to the development or sale of these drugs. Dr. Raines is the cofounder of Annovation Biopharma and has an equity interest in Annovation BioPharma, Inc., which has an option to license this technology for development. Dr. Raines is also the lead inventor of Carboetomidate and received royalties as an inventor. Dr. Cotten received patents and royalties from the National Institutes of Health. The remaining authors have not disclosed any potential conflicts of interest. NR 54 TC 10 Z9 12 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JAN PY 2012 VL 40 IS 1 BP 187 EP 192 DI 10.1097/CCM.0b013e31822d7924 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA 866KO UT WOS:000298379800027 PM 21926608 ER PT J AU Kabra, R Singh, JP AF Kabra, Rajesh Singh, Jagmeet P. TI Catheter ablation targeting complex fractionated atrial electrograms for the control of atrial fibrillation SO CURRENT OPINION IN CARDIOLOGY LA English DT Review DE ablation; atrial fibrillation; complex fractionated atrial electrograms ID MAGNETIC-RESONANCE; SUBSTRATE ABLATION; PERSISTENT; HUMANS; PREVALENCE; MECHANISMS; AF AB Purpose of review Catheter ablation of persistent atrial fibrillation has a lower success rate than for paroxysmal atrial fibrillation, due to structural, electrical and anatomical remodeling of the left atrium. Ablation strategies targeting complex fractionated atrial electrograms (CFAEs) are commonly employed to identify and eliminate the substrate responsible for atrial fibrillation maintenance in persistent cases. This review discusses the pathophysiology as well as the role of targeting CFAEs in catheter ablation of atrial fibrillation. Recent findings As our understanding regarding the origin and role of CFAEs in atrial fibrillation continues to evolve, there have been multiple recent studies looking at pathophysiology, distribution and significance of CFAEs in atrial fibrillation. In addition, different ablation strategies targeting CFAEs have been compared with the standard pulmonary vein isolation in persistent as well as paroxysmal atrial fibrillation. Recent meta-analysis studies have striven to identify atrial fibrillation patients who would benefit from CFAE ablation. Summary Whereas CFAE ablation in addition to standard pulmonary vein isolation improves outcomes in patients with persistent atrial fibrillation, there is no benefit of CFAE ablation in paroxysmal atrial fibrillation. Further studies are required to define and identify CFAEs more accurately, in a standardized manner, to enhance the success of catheter ablation and freedom from atrial fibrillation. C1 [Singh, Jagmeet P.] Harvard Univ, Sch Med, Cardiac Arrhythmia Serv, Massachusetts Gen Hosp,Heart Ctr, Boston, MA 02114 USA. [Singh, Jagmeet P.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Kabra, Rajesh] Univ Tennessee, Ctr Hlth Sci, Dept Med & Cardiac Electrophysiol, Memphis, TN 38163 USA. RP Singh, JP (reprint author), Harvard Univ, Sch Med, Cardiac Arrhythmia Serv, Massachusetts Gen Hosp,Heart Ctr, Boston, MA 02114 USA. EM jsingh@partners.org FU St Jude Medical; Medtronic, Inc.; Boston Scientific Corp.; Biotronik; Guidant Corp.; Sorin Group FX J.P.S. received grant supports from St Jude Medical, Medtronic, Inc., Boston Scientific Corp., and Biotronik; served on advisory boards or as a consultant for Boston Scientific Corp., St Jude Medical, and Medtronic; and received honoraria or speaker fees from Medtronic, Inc., Biotronik, Guidant Corp., St Jude Medical, and Sorin Group. NR 33 TC 5 Z9 5 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0268-4705 J9 CURR OPIN CARDIOL JI Curr. Opin. Cardiol. PD JAN PY 2012 VL 27 IS 1 BP 49 EP 54 DI 10.1097/HCO.0b013e32834dc3bc PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 863EF UT WOS:000298144900009 PM 22123605 ER PT J AU Haining, WN Barnitz, RA AF Haining, W. Nicholas Barnitz, R. Anthony TI Deconvolving heterogeneity in the CD8(+) T-cell response to HIV SO CURRENT OPINION IN HIV AND AIDS LA English DT Review DE genomics; heterogeneity; HIV; single-cell ID DISEASE PROGRESSION; LUNG ADENOCARCINOMA; MELANOMA PATIENTS; EXPRESSION; INFECTION; DIFFERENTIATION; EXHAUSTION; IMMUNE; DISCOVERY; ANTIGEN AB Purpose of review This review will discuss the use of systems biology approaches to dissect the heterogeneity of the HIV-specific CD8(+) T-cell response. Recent findings New experimental approaches have allowed complex phenotypes of individual cells present in the human antigen-specific CD8(+) T-cell response to be characterized. Genome-wide measurements of gene expression in antigen-specific T cells have created broad molecular phenotypes of the T-cell response to HIV. Pattern recognition algorithms to discover new subclasses of samples in microarray datasets are becoming increasingly sophisticated. Together, these advances now allow the heterogeneity of the T-cell response to HIV to be unraveled. Summary The phenotype of antigen-specific T cells responding to pathogens like HIV in humans is seen as much 'noisier' than in animal models of infection. However, applying new systems biology tools may provide an opportunity to identify the sources of this 'noise' as novel, biologically distinct subclasses of the CD8(+) T-cell response to HIV. C1 [Haining, W. Nicholas; Barnitz, R. Anthony] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Haining, W. Nicholas] Harvard Univ, Sch Med, Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. RP Haining, WN (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St,Dana 640, Boston, MA 02115 USA. EM nicholas_haining@dfci.harvard.edu OI Barnitz, Tony/0000-0002-9634-4558 FU National Institutes of Health [NIAID R01AI091493] FX The work was supported by the National Institutes of Health (NIAID R01AI091493 to W.N.H.). NR 48 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1746-630X J9 CURR OPIN HIV AIDS JI Curr. Opin. HIV AIDS PD JAN PY 2012 VL 7 IS 1 BP 38 EP 43 DI 10.1097/COH.0b013e32834dde1c PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 863GS UT WOS:000298151400007 PM 22156844 ER PT J AU Yonekawa, Y Kim, IK AF Yonekawa, Yoshihiro Kim, Ivana K. TI Pseudophakic cystoid macular edema SO CURRENT OPINION IN OPHTHALMOLOGY LA English DT Review DE anti-vascular endothelial growth factor; corticosteroids; Irvine-Gass syndrome; nonsteroidal anti-inflammatory drugs; pseudophakic cystoid macular edema ID OPTICAL COHERENCE TOMOGRAPHY; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; INTRAOCULAR-LENS IMPLANTATION; CATARACT-SURGERY; INTRAVITREAL BEVACIZUMAB; PHACOEMULSIFICATION SURGERY; TRIAMCINOLONE ACETONIDE; COMBINATION THERAPY; TOPICAL DICLOFENAC; EFFICACY AB Purpose of review Pseudophakic cystoid macular edema (PCME) is a common cause of visual impairment after cataract surgery. This article systematically reviews and discusses the epidemiology, risk factors, diagnosis, and treatment of PCME, with a focus on advances in the past 1-2 years. Recent findings The incidence of PCME has declined with the advent of modern surgical techniques. Optical coherence tomography (OCT) has become an important adjunct to biomicroscopy and fluorescein angiography. PCME prophylaxis with topical nonsteroidal anti-inflammatory drugs remains unproven because long-term visual outcomes and comparative effectiveness studies are lacking. Chronic, refractory CME remains a therapeutic challenge, but investigational therapies with potential include corticosteroid intravitreal injections and implants, and intravitreal anti-vascular endothelial growth factor treatments. Few studies have assessed surgical options. Summary There is currently a lack of well designed randomized clinical trials to guide the treatment of PCME. C1 [Yonekawa, Yoshihiro; Kim, Ivana K.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv,Dept Ophthalmol, Boston, MA 02114 USA. RP Kim, IK (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv,Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM ivana_kim@meei.harvard.edu FU Genentech, Inc. FX I.K.K. has received research support from Genentech, Inc. and has served as a consultant for Genentech and Novartis. NR 54 TC 36 Z9 39 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8738 J9 CURR OPIN OPHTHALMOL JI Curr. Opin. Ophthalmol. PD JAN PY 2012 VL 23 IS 1 BP 26 EP 32 DI 10.1097/ICU.0b013e32834cd5f8 PG 7 WC Ophthalmology SC Ophthalmology GA 863GL UT WOS:000298150700006 PM 22134362 ER PT J AU Sahin, A Hamrah, P AF Sahin, Afsun Hamrah, Pedram TI Clinically relevant biometry SO CURRENT OPINION IN OPHTHALMOLOGY LA English DT Review DE biometry; cataract surgery; intraocular lens calculation; keratometry; refractive surgery ID INTRAOCULAR-LENS POWER; PARTIAL COHERENCE INTERFEROMETRY; CORNEAL REFRACTIVE SURGERY; CHAMBER DEPTH MEASUREMENTS; CATARACT-SURGERY; OCULAR BIOMETRY; ORBSCAN II; EYES; FORMULA; ACCURACY AB Purpose of review Obtaining precise postoperative target refraction is of utmost importance in today's modern cataract and refractive surgery. Given the growing number of patients undergoing premium intraocular lens (IOL) implantations, patient expectation continues to rise. In order to meet heightened patient expectations, it is crucial to pay utmost attention to patient selection, accurate keratometry and biometry readings, as well as to the application of correct IOL power formula with optimized lens constants. This article reviews recent advances in the field of clinical biometry and IOL power calculations. Recent findings Recently developed low-coherence reflectometry optical biometry is comparable to older ultrasonic biometric and keratometric techniques. In addition, the new IOLMaster software upgrade has improved reproducibility and enhanced signal acquisition. Further, the modern lens power formulas currently determine the effective lens position and the shape of the intraocular lens power prediction curve more accurately. Summary In order to reach target refraction, precise biometric measurements are imperative. Understanding the strengths and limitations of the currently available biometry devices allows prevention of high variability and inaccuracy, ultimately determining the refractive outcomes. C1 [Sahin, Afsun; Hamrah, Pedram] Massachusetts Eye & Ear Infirm, Cornea & Refract Surg Serv, Ocular Surface Imaging Ctr, Boston, MA 02114 USA. [Sahin, Afsun; Hamrah, Pedram] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. [Sahin, Afsun] Eskisehir Osmangazi Univ, Sch Med, Dept Ophthalmol, Eskisehir, Turkey. RP Hamrah, P (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Cornea Serv, 243 Charles St, Boston, MA 02114 USA. EM pedram_hamrah@meei.harvard.edu FU National Institutes of Health, Bethesda, Maryland, USA [K08-EY020575]; Research to Prevent Blindness FX The research was supported by a career development grant K08-EY020575 (P.H.) from the National Institutes of Health, Bethesda, Maryland, USA. P. H. is also the recipient of a Career Development Award from Research to Prevent Blindness. NR 41 TC 14 Z9 14 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8738 J9 CURR OPIN OPHTHALMOL JI Curr. Opin. Ophthalmol. PD JAN PY 2012 VL 23 IS 1 BP 47 EP 53 DI 10.1097/ICU.0b013e32834cd63e PG 7 WC Ophthalmology SC Ophthalmology GA 863GL UT WOS:000298150700009 PM 22081032 ER PT J AU Ripoll, LH AF Ripoll, Luis H. TI Clinical psychopharmacology of borderline personality disorder: an update on the available evidence in light of the Diagnostic and Statistical Manual of Mental Disorders-5 SO CURRENT OPINION IN PSYCHIATRY LA English DT Review DE Borderline personality disorder; Diagnostic and Statistical Manual of Mental Disorders-5; psychopharmacology ID 18-MONTH FOLLOW-UP; POSITRON-EMISSION-TOMOGRAPHY; DIALECTICAL BEHAVIOR-THERAPY; SELF-INJURIOUS-BEHAVIOR; DOUBLE-BLIND; TOPIRAMATE TREATMENT; 10-YEAR COURSE; PART II; PHARMACOLOGICAL-TREATMENT; AFFECTIVE INSTABILITY AB Purpose of review Clinical considerations for evidence-based treatment of borderline personality disorder (BPD) are outlined in the context of the best available evidence, discussed with reference to BPD traits currently identified in the upcoming Diagnostic and Statistical Manual of Mental Disorders - 5 (DSM-5) revision. The DSM-5 will highlight refractory affective, interpersonal, and identity symptoms in BPD as potential treatment targets. In addition to providing a framework for clinical decision-making, future research strategies will also focus on neurotransmitter systems of greater relevance to understanding overall personality functioning. Recent findings Although only a few randomized controlled trials of psychopharmacological treatments for BPD have been published recently, several meta-analyses and systematic reviews converge on the consensus effectiveness of lamotrigine, topiramate, valproate, aripiprazole, olanzapine, and omega-3 fatty acid supplementation. Stronger evidence exists for treating disinhibition and antagonism than negative affectivity, particularly interpersonal facets of such traits. In addition, basic research suggests a future role for modifying glutamatergic, opioid, and oxytocinergic neurotransmitter systems to treat BPD. Summary Clinicians should utilize omega-3, anticonvulsants, and atypical antipsychotic agents in treating specific DSM-5 BPD traits, notably disinhibition, antagonism, and some aspects of negative affectivity. Future research will focus on normalizing opioid and oxytocin dysregulation, as an adjunct to evidence-based psychotherapy, in an effort to improve interpersonal functioning. C1 [Ripoll, Luis H.] MIRECC, James J Peters VA Med Ctr, Bronx, NY 10468 USA. [Ripoll, Luis H.] Mt Sinai Sch Med, Mood & Personal Res Program, New York, NY USA. RP Ripoll, LH (reprint author), MIRECC, James J Peters VA Med Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM luis.ripoll@mssm.edu FU US Department of Veteran Affairs via a MIRECC FX The author has nothing to disclose, in terms of private funding relevant to this research. At present, he is funded entirely through US Department of Veteran Affairs via a MIRECC Fellowship. NR 91 TC 7 Z9 7 U1 1 U2 25 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0951-7367 J9 CURR OPIN PSYCHIATR JI Curr. Opin. Psychiatr. PD JAN PY 2012 VL 25 IS 1 BP 52 EP 58 DI 10.1097/YCO.0b013e32834c3f19 PG 7 WC Psychiatry SC Psychiatry GA 863CS UT WOS:000298141000009 PM 22037092 ER PT J AU Carruthers, MN Stone, JH Khosroshahi, A AF Carruthers, Mollie N. Stone, John H. Khosroshahi, Arezou TI The latest on IgG4-RD: a rapidly emerging disease SO CURRENT OPINION IN RHEUMATOLOGY LA English DT Review DE autoimmune pancreatitis; IgG4; IgG4 related disease; IgG4 related systemic disease ID IGG4-RELATED SYSTEMIC-DISEASE; ANGIOMATOID-NODULAR-TRANSFORMATION; EOSINOPHILIC ANGIOCENTRIC FIBROSIS; INFLAMMATORY MYOFIBROBLASTIC TUMOR; PLASMA-CELLS; TUBULOINTERSTITIAL NEPHRITIS; AUTOIMMUNE PANCREATITIS; MEMBRANOUS NEPHROPATHY; SCLEROSING MESENTERITIS; MULTIFOCAL FIBROSCLEROSIS AB Purpose of review Provide an update of the developments in IgG4 related disease within the last year in terms of nomenclature, diagnostic criteria and clinical features. Recent findings The number of diseases associated with IgG4 related disease continues to grow. The entities of idiopathic orbital inflammation, idiopathic cervical fibrosis, eosinophilic angiocentric fibrosis, reactive nodular fibrous pseudotumor, sclerosing mesenteritis, and membranous glomerulonephritis should all be added to the list of diseases associated with the IgG4 related disease spectrum. The issues of nomenclature and diagnostic criteria for IgG4 related disease have important recent developments as well. Summary The diagnosis of IgG4 related disease continues to be challenging. Increasing recognition of IgG4 related disease has led to a large body of literature on organ sites of involvement. Understanding how the disease manifests itself is critical to diagnosis and ultimately treatment. C1 [Carruthers, Mollie N.; Stone, John H.; Khosroshahi, Arezou] Massachusetts Gen Hosp, Rheumatol Unit, Div Rheumatol, Dept Med, Boston, MA 02114 USA. RP Stone, JH (reprint author), Massachusetts Gen Hosp, Rheumatol Unit, Div Rheumatol, Dept Med, 55 Fruit St, Boston, MA 02114 USA. EM jhstone@partners.org NR 45 TC 57 Z9 68 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8711 J9 CURR OPIN RHEUMATOL JI Curr. Opin. Rheumatol. PD JAN PY 2012 VL 24 IS 1 BP 60 EP 69 DI 10.1097/BOR.0b013e32834ddb4a PG 10 WC Rheumatology SC Rheumatology GA 863DG UT WOS:000298142400009 PM 22157413 ER PT J AU Stathatos, N Daniels, GH AF Stathatos, Nikolaos Daniels, Gilbert H. TI Autoimmune thyroid disease SO CURRENT OPINION IN RHEUMATOLOGY LA English DT Review DE autoimmune; rheumatologic disorders; thyroid disorders ID GRAVES-DISEASE; RHEUMATOID-ARTHRITIS; HASHIMOTOS-THYROIDITIS; STIMULATING HORMONE; PRETIBIAL MYXEDEMA; NA+/I-SYMPORTER; THYROGLOBULIN; ANTIBODY; GENE; AUTOANTIBODIES AB Purpose of review Autoimmune thyroid disorders (AITDs) are the most common organ-specific autoimmune disorders. The genetics as well as clinical and laboratory manifestations of AITDs are reviewed. Recent findings We discuss the association between specific rheumatologic disorders and AITDs and manifestations of AITDs that mimic rheumatologic disorders. The recently discovered common molecular pathways involved in these processes are discussed. Summary AITDs and rheumatologic disorders have significant commonalities both clinically and etiologically. This information is important for rheumatologists and primary care physicians who care for patients with these disorders. C1 [Stathatos, Nikolaos; Daniels, Gilbert H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Stathatos, N (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 15 Parkman St,WACC 730S, Boston, MA 02114 USA. EM nstathatos@partners.org NR 64 TC 16 Z9 16 U1 3 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-8711 EI 1531-6963 J9 CURR OPIN RHEUMATOL JI Curr. Opin. Rheumatol. PD JAN PY 2012 VL 24 IS 1 BP 70 EP 75 DI 10.1097/BOR.0b013e32834ddb27 PG 6 WC Rheumatology SC Rheumatology GA 863DG UT WOS:000298142400010 PM 22157414 ER PT J AU Schaefer, EAK Pratt, DS AF Schaefer, Esperance A. K. Pratt, Daniel S. TI Autoimmune hepatitis: current challenges in diagnosis and management in a chronic progressive liver disease SO CURRENT OPINION IN RHEUMATOLOGY LA English DT Review DE autoimmune; hepatitis; iimunosuppression; liver disease; treatment ID EPIDEMIOLOGY AB Purpose of review The understanding of autoimmune hepatitis (AIH) has evolved in the past two decades since diagnostic criteria were developed. Now with long-term experience with well characterized cohorts, strides have been gained in understanding the true epidemiology and natural history of the disease. Therapeutic trials have also added new tools to the armamentarium in managing this challenging disease. Recent findings AIH has been demonstrated to be a disease of middle-aged women, with a disease course that frequently progresses to cirrhosis, transplant or death. Despite its rare prevalence, AIH is one of the most common indications for transplantation. Diagnosis remains challenging, and the most recently adopted criteria prove very specific but lack sensitivity in the diagnosis of AIH, particularly when presenting atypically. Recently, drug-induced AIH and IgG4(+)-associated AIH have been proposed as distinct clinicopathological entities. Clinical trials for alternate therapeutics have long been needed, and recently two agents, budesonide and mycophenolate mofeteil, show promise in treating AIH. Summary Increasing evidence has mounted to suggest that AIH is a disease that often requires long-term treatment, and frequently progresses to end-stage liver disease. Further research identifying predictors of poor outcome, optimal therapeutic regimens and duration of treatment is much needed. C1 [Schaefer, Esperance A. K.; Pratt, Daniel S.] Massachusetts Gen Hosp, Dept Med, Gastroenterol Unit, Boston, MA 02114 USA. RP Pratt, DS (reprint author), Massachusetts Gen Hosp, Dept Med, Gastroenterol Unit, Boston, MA 02114 USA. EM dspratt@partners.org NR 28 TC 0 Z9 1 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8711 J9 CURR OPIN RHEUMATOL JI Curr. Opin. Rheumatol. PD JAN PY 2012 VL 24 IS 1 BP 84 EP 89 DI 10.1097/BOR.0b013e32834de5d9 PG 6 WC Rheumatology SC Rheumatology GA 863DG UT WOS:000298142400012 PM 22089102 ER PT J AU Carvello, M Petrelli, A Vergani, A Lee, KM Tezza, S Chin, M Orsenigo, E Staudacher, C Secchi, A Dunussi-Joannopoulos, K Sayegh, MH Markmann, JF Fiorina, P AF Carvello, Michele Petrelli, Alessandra Vergani, Andrea Lee, Kang Mi Tezza, Sara Chin, Melissa Orsenigo, Elena Staudacher, Carlo Secchi, Antonio Dunussi-Joannopoulos, Kyri Sayegh, Mohamed H. Markmann, James F. Fiorina, Paolo TI Inotuzumab Ozogamicin Murine Analog Mediated B-Cell Depletion Reduces Anti-islet ABo- and Autoimmune Responses SO DIABETES LA English DT Article ID ISLET ALLOGRAFT SURVIVAL; COSTIMULATION BLOCKADE; NOD MICE; PHASE-I; REJECTION; TRANSPLANTATION; TOLERANCE; LYMPHOCYTES; RITUXIMAB; LYMPHOMA AB B cells participate in the priming of the allo- and autoimmune responses, and their depletion can thus be advantageous for islet transplantation. Herein, we provide an extensive study of the effect of B-cell depletion in murine models of islet transplantation. Islet transplantation was performed in hyperglycemic B-cell-deficient (mu MT) mice, in a purely alloimmune setting (BALB/c into hyperglycemic C57BL/6), in a purely autoimmune setting (NOD.SCID into hyperglycemic NOD), anti in a mixed allo-/autoimmune setting (BALB/c into hyperglycemic NOD). Inotuzumab ozogarnicin murine analog (anti-CD22 monoclonal antibody conjugated with calicheamicin [anti-CD22/cal]) efficiently depleted B cells in all three models of islet transplantation examined. Islet graft survival was significantly prolonged in B-cell-depleted mice compared with control groups in transplants of islets from BALB/c into C57BL/6 (mean survival time [MST]: 16.5 vs. 12.0 days; P = 0.004), from NOD.SCID into NOD (MST: 23.5 vs. 14.0 days; P = 0.03), and from BALB/c into NOD (MST: 12.0 vs. 5.5 days; P = 0.003). In the BALB/c into B-cell-deficient mice model, islet survival was prolonged as well (MST: mu MT = 32.5 vs. WT = 14 days; P = 0.002). Pathology revealed reduced CD3(+) cell islet infiltration and confirmed the absence of B cells in treated mice. Mechanistically, effector T cells were reduced in number, concomitant with a peripheral Th2 profile skewing and ex vivo recipient hyporesponsiveness toward donor-derived antigen as well as islet autoantigens. Finally, an anti-CD22/cal and CTLA4-Ig-based combination therapy displayed remarkable prolongation of graft survival in the stringent model of islet transplantation (BALB/c into NOD). And-CD22/cal-mediated B-cell depletion promotes the reduction of the anti-islet immune response in various models of islet transplantation. Diabetes 61:155-165,2012 C1 [Petrelli, Alessandra; Vergani, Andrea; Tezza, Sara; Chin, Melissa; Sayegh, Mohamed H.; Fiorina, Paolo] Harvard Univ, Childrens Hosp, Sch Med, Transplantat Res Ctr,Nephrol Div, Boston, MA 02115 USA. [Carvello, Michele; Lee, Kang Mi; Markmann, James F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. [Carvello, Michele; Orsenigo, Elena; Staudacher, Carlo] Ist Sci San Raffaele, Dept Surg, I-20132 Milan, Italy. [Petrelli, Alessandra; Secchi, Antonio; Fiorina, Paolo] Ist Sci San Raffaele, Dept Med, I-20132 Milan, Italy. [Dunussi-Joannopoulos, Kyri] Pfizer Res, Cambridge, MA USA. RP Fiorina, P (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Transplantat Res Ctr,Nephrol Div, Boston, MA 02115 USA. EM paolo.florina@childrens.harvard.edu RI Petrelli, Alessandra/M-7004-2015 OI Petrelli, Alessandra/0000-0002-5639-9415 FU Juvenile Diabetes Research Foundation; American Society of Nephrology; American Diabetes Association; Italian Ministero dell'Istruzione, dell'Universita e della Ricerca [Staminali RF-FSR-2008-1213704]; Pfizer FX P.F. is the recipient of a Juvenile Diabetes Research Foundation Career Development Award, an American Society of Nephrology Career Development Award, an American Diabetes Association mentor-based fellowship, and a grant from the Italian Ministero dell'Istruzione, dell'Universita e della Ricerca (Staminali RF-FSR-2008-1213704). K.D.J. is a paid employee of Pfizer. Pfizer provided anti-CD22/cal and control antibody compounds. No other potential conflicts of interest relevant to this article were reported. NR 42 TC 9 Z9 9 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JAN PY 2012 VL 61 IS 1 BP 155 EP 165 DI 10.2337/db11-0684 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 871XZ UT WOS:000298772300019 PM 22076927 ER PT J AU Nicolau, JC Serrano, CV Giraldez, RR Baracioli, LM Moreira, HG Lima, F Franken, M Kalil, R Ramires, JAF Giugliano, RP AF Nicolau, Jose Carlos Serrano, Carlos Vicente, Jr. Giraldez, Roberto Rocha Baracioli, Luciano Moreira Moreira, Humberto Graner Lima, Felipe Franken, Marcelo Kalil, Roberto Franchini Ramires, Jose Antonio Giugliano, Robert P. TI In Patients With Acute Myocardial Infarction, the Impact of Hyperglycemia as a Risk Factor for Mortality Is Not Homogeneous Across Age-Groups SO DIABETES CARE LA English DT Article ID ACUTE CORONARY SYNDROME; DIABETES-MELLITUS; GLYCEMIC CONTROL; INSULIN; INFLAMMATION; ASSOCIATION; THERAPY; GLUCOSE AB OBJECTIVE To assess the impact of hyperglycemia in different age-groups of patients with acute myocardial infarction (AM I). RESEARCH DESIGN AND METHODS A total of 2,027 patients with AMI were categorized into one of five age-groups: <50 years (n = 301), >= 50 and <60 (n = 477),>= 60 and <70 (n = 545), >= 70 and <80 (n = 495), and years (n = 209). Hyperglycemia was defined as initial glucose >= 115 mg/dL. RESULTS The adjusted odds ratios for hyperglycemia predicting hospital mortality in groups 1-5 were, respectively, 7.57 (P = 0.004), 3.21 (P 0.046), 3.50 (P = 0.003), 3.20 (P < 0.001.), and 2.16 (P = 0.021). The adjusted P values for correlation between glucose level (as a continuous variable) and mortality were 0.007, <0.001, 0.043, <0.001, and 0.064. The areas under the ROC curves (AUCs) were 0.785, 0.709, 0.657, 0.648, and 0.613. The AUC in group 1 was significantly higher than those in groups 3-5. CONCLUSIONS The impact of hyperglycemia as a risk factor for hospital mortality in AMI is more pronounced in younger patients. C1 [Nicolau, Jose Carlos; Serrano, Carlos Vicente, Jr.; Giraldez, Roberto Rocha; Baracioli, Luciano Moreira; Moreira, Humberto Graner; Lima, Felipe; Franken, Marcelo; Kalil, Roberto; Franchini Ramires, Jose Antonio] Univ Sao Paulo, Sch Med, Heart Inst InCor, Sao Paulo, Brazil. [Giugliano, Robert P.] Brigham & Womens Hosp, Thrombolysis Myocardial Infarct TIMI Study Grp, Boston, MA 02115 USA. RP Nicolau, JC (reprint author), Univ Sao Paulo, Sch Med, Heart Inst InCor, Sao Paulo, Brazil. EM corjnicolau@incor.usp.br RI Moreira, Humberto/D-2001-2012; Nicolau, Jose/E-1487-2012; Giraldez, Roberto/E-2498-2012; Serrano Junior, Carlos Vicente/I-2729-2013; Kalil Filho, Roberto/D-4994-2014 NR 15 TC 6 Z9 7 U1 0 U2 1 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 JAN PY 2012 VL 35 IS 1 BP 150 EP 152 DI 10.2337/dc11-1170 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 871XV UT WOS:000298771900026 PM 22028280 ER PT J AU Funnell, MM Brown, TL Childs, BP Haas, LB Hosey, GM Jensen, B Maryniuk, M Peyrot, M Piette, JD Reader, D Siminerio, LM Weinger, K Weiss, MA AF Funnell, Martha M. Brown, Tammy L. Childs, Belinda P. Haas, Linda B. Hosey, Gwen M. Jensen, Brian Maryniuk, Melinda Peyrot, Mark Piette, John D. Reader, Diane Siminerio, Linda M. Weinger, Katie Weiss, Michael A. TI National Standards for Diabetes Self-Management Education SO DIABETES CARE LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; CHRONIC DISEASE MANAGEMENT; IMPROVE GLYCEMIC CONTROL; PRIMARY-CARE PATIENTS; HEALTH-CARE; COMPLICATIONS TRIAL; PATIENT EDUCATION; AFRICAN-AMERICAN; COMMUNITY-HEALTH; CHRONIC ILLNESS C1 [Funnell, Martha M.] Univ Michigan, Dept Med Educ, Ctr Diabet Res & Training, Ann Arbor, MI 48109 USA. [Brown, Tammy L.] Indian Hlth Serv, Albuquerque, NM USA. [Childs, Belinda P.] MidAmer Diabet Associates, Wichita, KS USA. [Haas, Linda B.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Hosey, Gwen M.] Ctr Dis Control & Prevent, Div Diabet Translat, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA. [Jensen, Brian] Lakeshore Apothacare, Two Rivers, WI USA. [Maryniuk, Melinda; Weinger, Katie] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Peyrot, Mark] Loyola Coll, Baltimore, MD 21210 USA. [Piette, John D.] VA Ann Arbor Hlth Care Syst, Ann Arbor, MI USA. [Piette, John D.] Univ Michigan, Dept Internal Med, Ctr Diabet Res & Training, Ann Arbor, MI 48109 USA. [Reader, Diane] Int Diabet Ctr, Minneapolis, MN USA. [Siminerio, Linda M.] Univ Pittsburgh, Med Ctr, Inst Diabet, Pittsburgh, PA USA. [Weiss, Michael A.] Patient Ctr Solut, Pittsburgh, PA USA. RP Funnell, MM (reprint author), Univ Michigan, Dept Med Educ, Ctr Diabet Res & Training, Ann Arbor, MI 48109 USA. EM mfunnell@umich.edu FU National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health [NIH5P60 DK20572, 1 R18 0K062323]; American Diabetes Association; American Association of Diabetes Educators FX Work on this article was supported in part by grant nos. NIH5P60 DK20572 and 1 R18 0K062323 from the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health.; The Task Force gratefully acknowledges the assistance and support of Paulina Duker, MPH, APRN-BC, CDE, and Nathanial Clark, MD, CDE, of the American Diabetes Association; Lori Porter, MBA, RD, CAE, of the American Association of Diabetes Educators; and Karmeen Kulkami, MS, RD, BC-ADM, Past President, Health Care and Education of the American Diabetes Association; Malincla Peeples, MS, RN, CDE, Past President of the American Association of Diabetes Educators; and Carole' Mensing, RN, MA, CDE, for their insights and helpful suggestions. NR 164 TC 78 Z9 78 U1 3 U2 19 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD JAN PY 2012 VL 35 IS 1 SU 1 BP S101 EP S108 DI 10.2337/dc12-S089 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 871XY UT WOS:000298772200010 PM 22187467 ER PT J AU Fan, Y Liu, Y Oklu, R He, NS Li, P Wu, Q Deipolyi, A Wicky, S Song, HY AF Fan, Yong Liu, Yang Oklu, Rahmi He, Neng-Shu Li, Ping Wu, Qi Deipolyi, Amy Wicky, Stephan Song, Ho-Young TI Balloon occlusion of the right main bronchus in an ovine model provides sufficient time for emergent interventions in massive pulmonary embolism SO DIAGNOSTIC AND INTERVENTIONAL RADIOLOGY LA English DT Article DE pulmonary embolism; ventilation-perfusion ratio; balloon catheterization; animal experimentation ID AUTOLOGOUS BLOOD; PORCINE MODEL; THROMBOLYSIS AB PURPOSE Massive pulmonary embolism (PE) causes hemodynamic compromise and is associated with a high rate of mortality. We sought to create a model of massive PE and to determine whether occlusion of the right main bronchus could mitigate the physiological effects of massive PE in this model. MATERIALS AND METHODS We used 27 female sheep to generate a model of massive PE by either autologous blood clot injection (n=18) or detachable balloon release (n=9) into the right main pulmonary artery. Four sheep were excluded after blood clot injection, as they did not exhibit adequate declines in blood oxygen saturation (SaO(2)). Nine of the sheep that received autologous blood clot and nine that received detachable balloons went on to treatment with right main bronchus occlusion. The control group (n=5) received the autologous blood clot, but no occlusion of the right main bronchus. All sheep underwent continuous monitoring of pulmonary arterial mean pressure (PAMP), SaO(2), arterial partial pressure of oxygen (PaO(2)), and arterial partial pressure of carbon dioxide. RESULTS Twenty-three sheep (85%) subjected to PE demonstrated immediate tachycardia, tachypnea, and decline in SaO(2) of at least 25% within 30 min. After right main bronchus occlusion, 18 sheep (100%) survived for the length of the experiment and exhibited persistently higher SaO(2) and PaO(2) levels, as well as decreased PAMP compared with the controls. In the control group, two out of five sheep died within 30 min, and the three surviving subjects demonstrated significantly decreased SaO(2) and PaO(2) levels. CONCLUSION Occlusion of the right main bronchus in an ovine model of massive PE effectively extends life and provides favorable physiological parameters to allow emergent interventions. C1 [Oklu, Rahmi; Deipolyi, Amy; Wicky, Stephan] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Vasc Imaging & Intervent, Cambridge, MA 02138 USA. [Fan, Yong] Tianjin Med Univ, Grad Sch, Tianjin, Peoples R China. [Liu, Yang] Childrens Hosp, Dept Radiol, Tianjin, Peoples R China. [He, Neng-Shu] Tianjin Med Univ, Gen Hosp, Dept Radiol, Tianjin, Peoples R China. [Li, Ping] Haihe Hosp, Dept Radiol, Tianjin, Peoples R China. [Wu, Qi] Haihe Hosp, Dept Pulmonol, Tianjin, Peoples R China. [Song, Ho-Young] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Radiol, Seoul, South Korea. RP Oklu, R (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Vasc Imaging & Intervent, Cambridge, MA 02138 USA. EM rahmioklu@gmail.com OI Deipolyi, Amy/0000-0003-3144-386X NR 19 TC 0 Z9 0 U1 0 U2 1 PU TURKISH SOC RADIOLOGY PI ANKARA PA HOSDERE CAD, GUZELKENT SOK, CANKAYA EVLERI, F-2, ANKARA, 06540, TURKEY SN 1305-3825 J9 DIAGN INTERV RADIOL JI Diagn. Interv. Radiol. PD JAN-FEB PY 2012 VL 18 IS 1 BP 127 EP 131 DI 10.4261/1305-3825.DIR.4069-10.2 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 872RZ UT WOS:000298828300017 PM 22020948 ER PT J AU Deipolyi, A Karaosmanoglu, A Habito, C Brannan, S Wicky, S Hirsch, J Oklu, R AF Deipolyi, Amy Karaosmanoglu, Ali Habito, Cicero Brannan, Scott Wicky, Stephan Hirsch, Joshua Oklu, Rahmi TI The role of bilateral inferior petrosal sinus sampling in the diagnostic evaluation of Cushing syndrome SO DIAGNOSTIC AND INTERVENTIONAL RADIOLOGY LA English DT Review DE ACTH-secreting pituitary adenoma; inferior petrosal sinus sampling; Cushing syndrome ID CORTICOTROPIN-RELEASING-FACTOR; DIFFERENTIAL-DIAGNOSIS; ADRENOCORTICOTROPIC HORMONE; TRANSSPHENOIDAL SURGERY; VENOUS DRAINAGE; DISEASE; ADENOMAS; COMPLICATIONS; POPULATION; ACTH AB Bilateral inferior petrosal sinus sampling is the gold standard diagnostic assay in identifying the pituitary source of adrenocorticotropic hormone secretion in Cushing syndrome. The noninvasive assays used in the workup of Cushing syndrome are often misleading or ambiguous, yielding sensitivities of up to only 80%. Inferior petrosal sinus sampling, however, is highly accurate and safe when performed in experienced centers. We review here the historical and technical details of the procedure, with emphasis on the relevant anatomy and a discussion of possible rare complications. C1 [Deipolyi, Amy; Karaosmanoglu, Ali; Habito, Cicero; Brannan, Scott; Wicky, Stephan; Oklu, Rahmi] Massachusetts Gen Hosp, Dept Vasc Imaging & Intervent, Boston, MA 02114 USA. [Hirsch, Joshua] Massachusetts Gen Hosp, Dept Neurointervent Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Oklu, R (reprint author), Massachusetts Gen Hosp, Dept Vasc Imaging & Intervent, Boston, MA 02114 USA. EM roklu@partners.org RI Karaosmanoglu, Ali/D-8624-2015; OI Karaosmanoglu, Ali/0000-0003-0027-9593; Deipolyi, Amy/0000-0003-3144-386X FU American College of Phlebology FX Dr. Oklu is the recipient of the Junior Faculty Investigator Award from the American College of Phlebology. NR 55 TC 7 Z9 7 U1 0 U2 1 PU TURKISH SOC RADIOLOGY PI ANKARA PA HOSDERE CAD, GUZELKENT SOK, CANKAYA EVLERI, F-2, ANKARA, 06540, TURKEY SN 1305-3825 EI 1305-3612 J9 DIAGN INTERV RADIOL JI Diagn. Interv. Radiol. PD JAN-FEB PY 2012 VL 18 IS 1 BP 132 EP 138 DI 10.4261/1305-3825.DIR.4279-11.0 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 872RZ UT WOS:000298828300018 PM 21348009 ER PT J AU Sikanderkhel, S Luthra, M Chavalitdhamrong, D AF Sikanderkhel, Saad Luthra, Munish Chavalitdhamrong, Disaya TI SNAKESKIN-LIKE PATTERN MIMICKING PORTAL HYPERTENSIVE GASTROPATHY IN PATIENT WITH EOSINOPHILIC GASTRITIS SO DIGESTIVE ENDOSCOPY LA English DT Editorial Material C1 [Sikanderkhel, Saad; Luthra, Munish; Chavalitdhamrong, Disaya] Mt Sinai Sch Med, James J Peters Vet Affairs Med Ctr, Bronx, NY USA. RP Sikanderkhel, S (reprint author), Mt Sinai Sch Med, James J Peters Vet Affairs Med Ctr, Bronx, NY USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0915-5635 J9 DIGEST ENDOSC JI Dig. Endosc. PD JAN PY 2012 VL 24 IS 1 BP 53 EP 53 DI 10.1111/j.1443-1661.2011.01155.x PG 1 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 869KT UT WOS:000298597500013 PM 22211417 ER PT J AU Levack, MM Savitt, LR Berger, DL Shellito, PC Hodin, RA Rattner, DW Goldberg, SM Bordeianou, L AF Levack, Melissa M. Savitt, Lieba R. Berger, David L. Shellito, Paul C. Hodin, Richard A. Rattner, David W. Goldberg, Stanley M. Bordeianou, Liliana TI Sigmoidectomy Syndrome? Patients' Perspectives on the Functional Outcomes Following Surgery for Diverticulitis SO DISEASES OF THE COLON & RECTUM LA English DT Article DE Diverticulitis; Quality of life; Fecal incontinence; Colectomy ID QUALITY-OF-LIFE; FECAL INCONTINENCE; COMORBIDITY; PREVALENCE; INSTRUMENT; PARAMETERS; DIAGNOSIS; COLOSTOMY; RESECTION; SYMPTOMS AB BACKGROUND: Bowel function following surgery for diverticulitis has not previously been systematically described. OBJECTIVE: This study aimed to document the frequency, severity, and predictors of suboptimal bowel function in patients who have undergone sigmoid colectomy for diverticulitis. DESIGN: This study is a retrospective analysis. SETTING: This study was conducted at a large, academic medical center. PATIENTS: Three hundred twenty-five patients who underwent laparoscopic or open sigmoid colectomy with restoration of intestinal continuity for diverticulitis were included in the study population. Of these, 249 patients (76.6%) returned a 70-question survey incorporating the Fecal Incontinence Severity Index, the Fecal Incontinence Quality of Life Scale, and the Memorial Bowel Function Instrument. MAIN OUTCOME MEASURES: Survey responders and nonresponders were compared with the use of chi(2) and t tests. Responders with suboptimal bowel function (fecal incontinence, urgency and/or incomplete emptying) were then compared with those with good outcomes by the use of logistic regression analysis to determine the predictors of poor function. RESULTS: Of the responders, 24.8% reported clinically relevant fecal incontinence (Fecal Incontinence Severity Index >= 24), 19.6% reported fecal urgency (Memorial Bowel Function Instrument Urgency Subscale >= 4), and 20.8% reported incomplete emptying (Memorial Bowel Function Instrument Emptying Subscale >= 4). On logistic regression analysis, fecal incontinence was predicted by female sex (OR = 2.3, p = 0.008) and the presence of a preoperative abscess (OR = 1.4, p < 0.05). Fecal urgency was associated with female sex (OR = 1.3, p < 0.05) and a diverting ileostomy (OR = 2.1, p < 0.001). Incomplete emptying was associated with female sex (OR = 1.4, p < 0.05) and postoperative sepsis (OR = 1.9, p < 0.05). LIMITATIONS: This study was limited by the fact that we did not use a nondiverticulitis control group and we had limited preoperative data on the history of bowel impairment symptoms. CONCLUSION: One-fifth of patients reported fecal urgency, fecal incontinence, or incomplete emptying after surgery for diverticulitis. Despite the limitations of our study, these results are concerning and should be investigated further prospectively. C1 [Levack, Melissa M.; Savitt, Lieba R.; Berger, David L.; Shellito, Paul C.; Hodin, Richard A.; Rattner, David W.; Bordeianou, Liliana] Massachusetts Gen Hosp, Div Gastrointestinal Surg, Colon & Rectal Surg Program, Boston, MA 02114 USA. [Levack, Melissa M.; Savitt, Lieba R.; Berger, David L.; Shellito, Paul C.; Hodin, Richard A.; Rattner, David W.; Bordeianou, Liliana] Harvard Univ, Sch Med, Boston, MA USA. [Goldberg, Stanley M.] Univ Minnesota, Dept Colon & Rectal Surg, Minneapolis, MN USA. RP Bordeianou, L (reprint author), Massachusetts Gen Hosp, Div Gastrointestinal Surg, Colon & Rectal Surg Program, 15 Parkman St,ACC 460, Boston, MA 02114 USA. EM lbordeianou@partners.org NR 23 TC 22 Z9 22 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0012-3706 J9 DIS COLON RECTUM JI Dis. Colon Rectum PD JAN PY 2012 VL 55 IS 1 BP 10 EP 17 DI 10.1097/DCR.0b013e31823907a9 PG 8 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 863GK UT WOS:000298150600007 PM 22156862 ER PT J AU Rosowski, JJ Nakajima, HH Hamade, MA Mahfoud, L Merchant, GR Halpin, CF Merchant, SN AF Rosowski, John J. Nakajima, Hideko H. Hamade, Mohamad A. Mahfoud, Lorice Merchant, Gabrielle R. Halpin, Christopher F. Merchant, Saumil N. TI Ear-Canal Reflectance, Umbo Velocity, and Tympanometry in Normal-Hearing Adults SO EAR AND HEARING LA English DT Article ID HUMAN MIDDLE-EAR; LASER-DOPPLER VIBROMETRY; TYMPANIC MEMBRANE; ENERGY REFLECTANCE; MULTIFREQUENCY TYMPANOMETRY; ACOUSTIC-IMPEDANCE; OTOSCLEROTIC EARS; INPUT IMPEDANCE; SOUND PRESSURE; FREQUENCY AB Objective: This study compares measurements of ear-canal reflectance (ECR) to other objective measurements of middle ear function including audiometry, umbo velocity (V(U)), and tympanometry in a population of strictly defined normal-hearing ears. Design: Data were prospectively gathered from 58 ears of 29 normal-hearing subjects, 16 females and 13 males, aged 22 to 64 yr. Subjects met all of the following criteria to be considered as having normal hearing: (1) no history of significant middle ear disease; (2) no history of otologic surgery; (3) normal tympanic membrane on otoscopy; (4) pure-tone audiometric thresholds of 20 dB HL or better for 0.25 to 8 kHz; (5) air-bone gaps no greater than 15 dB at 0.25 kHz and 10 dB for 0.5 to 4 kHz; (6) normal, type-A peaked tympanograms; and (7) all subjects had two "normal" ears (as defined by these criteria). Measurements included pure-tone audiometry for 0.25 to 8 kHz, standard 226 Hz tympanometry, ECR for 0.2 to 6 kHz at 60 dB SPL using the Mimosa Acoustics HearID system, and umbo velocity (V(U)) for 0.3 to 6 kHz at 70 to 90 dB SPL using the HLV-1000 laser Doppler vibrometer (Polytec Inc). Results: Mean power reflectance (vertical bar ECR vertical bar(2)) was near 1.0 at 0.2 to 0.3 kHz, decreased to a broad minimum of 0.3 to 0.4 between 1 and 4 kHz, and then sharply increased to almost 0.8 by 6 kHz. The mean pressure reflectance phase angle (angle ECR) plotted on a linear frequency scale showed a group delay of approximately 0.1 msec for 0.2 to 6 kHz. Small significant differences were observed in vertical bar ECR vertical bar(2) at the lowest frequencies between right and left ears and between males and females at 4 kHz. vertical bar ECR vertical bar(2) decreased with age but reached significance only at 1 kHz. Our ECR measurements were generally similar to previous published reports. Highly significant negative correlations were found between vertical bar ECR vertical bar(2) and V(U) for frequencies below 1 kHz. Significant correlations were also found between the tympanometrically determined peak total compliance and vertical bar ECR vertical bar(2) and V(U) at frequencies below 1 kHz. The results suggest that middle ear compliance contributes significantly to the measured power reflectance and umbo velocity at frequencies below 1 kHz but not at higher frequencies. Conclusions: This study has established a database of objective measurements of middle ear function (ECR, umbo velocity, tympanometry) in a population of strictly defined normal-hearing ears. These data will promote our understanding of normal middle ear function and will serve as a control for comparison to similar measurements made in pathological ears. C1 [Rosowski, John J.; Nakajima, Hideko H.; Hamade, Mohamad A.; Mahfoud, Lorice; Merchant, Gabrielle R.; Merchant, Saumil N.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Rosowski, John J.; Nakajima, Hideko H.; Hamade, Mohamad A.; Mahfoud, Lorice; Merchant, Saumil N.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Rosowski, John J.; Nakajima, Hideko H.; Merchant, Gabrielle R.; Merchant, Saumil N.] MIT, Harvard Mit Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02139 USA. [Halpin, Christopher F.] Massachusetts Eye & Ear Infirm, Dept Audiol, Boston, MA 02114 USA. RP Rosowski, JJ (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM john_rosowski@meei.harvard.edu OI Merchant, Gabrielle/0000-0001-7251-1879 FU NIH/NIDCD [R01-DC004798] FX This work was supported by NIH/NIDCD Grant R01-DC004798. NR 70 TC 29 Z9 30 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-0202 J9 EAR HEARING JI Ear Hear. PD JAN-FEB PY 2012 VL 33 IS 1 BP 19 EP 34 DI 10.1097/AUD.0b013e31822ccb76 PG 16 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA 869WS UT WOS:000298630200003 PM 21857517 ER PT J AU Nakajima, HH Pisano, DV Roosli, C Hamade, MA Merchant, GR Mahfoud, L Halpin, CF Rosowski, JJ Merchant, SN AF Nakajima, Hideko H. Pisano, Dominic V. Roosli, Christof Hamade, Mohamad A. Merchant, Gabrielle R. Mahfoud, Lorice Halpin, Christopher F. Rosowski, John J. Merchant, Saumil N. TI Comparison of Ear-Canal Reflectance and Umbo Velocity in Patients With Conductive Hearing Loss: A Preliminary Study SO EAR AND HEARING LA English DT Article ID HUMAN MIDDLE-EAR; ENERGY REFLECTANCE; TYMPANIC MEMBRANE; OSSICULAR CHAIN; DEHISCENCE; ADULTS; ADMITTANCE; VIBROMETRY; IMPEDANCE; INFANTS AB Objective: The goal of the present study was to investigate the clinical utility of measurements of ear-canal reflectance (ECR) in a population of patients with conductive hearing loss in the presence of an intact, healthy tympanic membrane and an aerated middle ear. We also sought to compare the diagnostic accuracy of umbo velocity (V(U)) measurements and measurements of ECR in the same group of patients. Design: This prospective study comprised 31 adult patients with conductive hearing loss, of which 14 had surgically confirmed stapes fixation due to otosclerosis, 6 had surgically confirmed ossicular discontinuity, and 11 had computed tomography and vestibular evoked myogenic potential confirmed superior semicircular canal dehiscence (SCD). Measurements on all 31 ears included pure-tone audiometry for 0.25 to 8 kHz, ECR for 0.2 to 6 kHz using the Mimosa Acoustics HearID system, and V(U) for 0.3 to 6 kHz using the HLV-1000 laser Doppler vibrometer (Polytec Inc, Waldbronn, Germany). We analyzed power reflectance vertical bar ECR vertical bar(2) as well as the absorbance level = 10 x log(10)(1 - vertical bar ECR vertical bar(2)). All measurements were made before any surgical intervention. The V(U) and ECR data were plotted against normative data obtained in a companion study of 58 strictly defined normal ears (Rosowski et al., 2011). Results: Small increases in vertical bar ECR vertical bar(2) at low-to-mid frequencies (400-1000 Hz) were observed in cases with stapes fixation, while narrowband decreases were seen for both SCD and ossicular discontinuity. The SCD and ossicular discontinuity differed in that the SCD had smaller decreases at mid-frequency (similar to 1000 Hz), whereas ossicular discontinuity had larger decreases at lower frequencies (500-800 Hz). SCD tended to have less air-bone gap at high frequencies (1-4 kHz) compared with stapes fixation and ossicular discontinuity. The vertical bar ECR vertical bar(2) measurements, in conjunction with audiometry, could successfully separate 28 of the 31 cases into the three pathologies. By comparison, VU measurements, in conjunction with audiometry, could successfully separate various pathologies in 29 of 31 cases. Conclusions: The combination of vertical bar ECR vertical bar(2) with audiometry showed clinical utility in the differential diagnosis of conductive hearing loss in the presence of an intact tympanic membrane and an aerated middle ear and seems to be of similar sensitivity and specificity to measurements of V(U) plus audiometry. Additional research is needed to expand upon these promising preliminary results. C1 [Nakajima, Hideko H.; Pisano, Dominic V.; Roosli, Christof; Hamade, Mohamad A.; Merchant, Gabrielle R.; Mahfoud, Lorice; Rosowski, John J.; Merchant, Saumil N.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Nakajima, Hideko H.; Roosli, Christof; Hamade, Mohamad A.; Mahfoud, Lorice; Halpin, Christopher F.; Rosowski, John J.; Merchant, Saumil N.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Nakajima, Hideko H.; Merchant, Gabrielle R.; Rosowski, John J.; Merchant, Saumil N.] MIT, Harvard Mit Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02139 USA. [Halpin, Christopher F.] Massachusetts Eye & Ear Infirm, Dept Audiol, Boston, MA 02114 USA. RP Nakajima, HH (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM heidi_nakajima@meei.harvard.edu OI Merchant, Gabrielle/0000-0001-7251-1879 FU NIH [R01 DC004798] FX This work was supported by NIH Grant R01 DC004798 and a donation from Mr. Lakshmi Mittal. NR 34 TC 23 Z9 24 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-0202 J9 EAR HEARING JI Ear Hear. PD JAN-FEB PY 2012 VL 33 IS 1 BP 35 EP 43 DI 10.1097/AUD.0b013e31822ccba0 PG 9 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA 869WS UT WOS:000298630200004 PM 21857516 ER PT J AU Jones, JA Freyman, RL AF Jones, J. Ackland Freyman, Richard L. TI Effect of Priming on Energetic and Informational Masking in a Same-Different Task SO EAR AND HEARING LA English DT Article ID ON-SPEECH MASKING; IMPLICIT MEMORY; OLDER-ADULTS; WORD RECOGNITION; RELEASE; CONTEXT; YOUNGER; PERCEPTION; HEARING; RECALL AB Objectives: The primary goal of this study was to investigate how speech perception is altered by the provision of a preview or "prime" of a sample of speech just before it is presented in masking. A same-different test paradigm was developed which enabled the effect of priming to be measured with energetic maskers in addition to those that most likely produced both energetic and informational masking. Using this paradigm, the benefit of priming in overcoming energetic and informational masking was compared. Design: Twenty-four normal-hearing subjects listened to nonsense sentences presented in a background of competing speech (two-talker babble) or one of two types of speech-shaped noise. Both target and masker were presented via loudspeaker directly in front of the listeners. In the baseline condition, the listeners were then shown a sentence on a computer screen that either matched the auditory target sentence exactly or contained a replacement for one of the three target key words. Their task was to judge whether the printed sentence matched the auditory target and respond via computer keyboard. In the first experimental condition, the printed sentence preceded rather than followed the auditory presentation (the priming condition). In the second experimental condition, the perception of spatial separation was created between target and masker by presenting the masker from two loudspeakers (front and 60 to the right) and imposing a 4-msec delay in the masker coming from the front loudspeaker. This resulted in the target being heard from the front while, because of the precedence effect, the masker was heard well to the right (the spatial condition). In a third experimental condition, spatial separation and priming were combined. A total of five signal-to-noise ratios were tested for each masker. Results: The competing speech masker produced more masking than noise, consistent with previous findings. For the competing speech masker, the signal-to-noise ratio for 80% correct performance was approximately 6.7 dB lower when the listeners read the sentences first (the priming condition) than in the baseline condition. This priming effect was similar to the improvement obtained when the target and masker were separated spatially. Significant priming effects were also observed with speech-shaped noise maskers, and when there was perceived spatial separation between target and masker, conditions in which informational masking was believed to have been minimal. There seemed to be an additive effect of spatial separation and priming in the two-talker babble condition. Conclusions: (1) Priming was effective in improving speech perception in all conditions, including those consisting of primarily energetic masking. (2) It is not clear how much benefit from priming could be attributed to release from informational masking. (3) Performance on the same-different task was linearly related to performance on an open-set speech recognition task using the same target and masker. C1 [Jones, J. Ackland] Massachusetts Eye & Ear Infirm, Dept Audiol, Boston, MA 02114 USA. [Jones, J. Ackland; Freyman, Richard L.] Univ Massachusetts, Dept Commun Disorders, Amherst, MA 01003 USA. RP Jones, JA (reprint author), Massachusetts Eye & Ear Infirm, Dept Audiol, 243 Charles St,2nd Floor, Boston, MA 02114 USA. EM ackland_jones@meei.harvard.edu FU NIDCD [01625] FX This work was supported by NIDCD Grant No. 01625. NR 33 TC 3 Z9 3 U1 3 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-0202 J9 EAR HEARING JI Ear Hear. PD JAN-FEB PY 2012 VL 33 IS 1 BP 124 EP 133 DI 10.1097/AUD.0b013e31822b5bee PG 10 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA 869WS UT WOS:000298630200013 PM 21841488 ER PT J AU Tanaka, Y Park, JH Tanwar, PS Kaneko-Tarui, T Mittal, S Lee, HJ Teixeira, JM AF Tanaka, Yoshihiro Park, Joo Hyun Tanwar, Pradeep S. Kaneko-Tarui, Tomoko Mittal, Shilpi Lee, Ho-Joon Teixeira, Jose M. TI Deletion of Tuberous Sclerosis 1 in Somatic Cells of the Murine Reproductive Tract Causes Female Infertility SO ENDOCRINOLOGY LA English DT Article ID ANTI-MULLERIAN HORMONE; REGULATE MUC1 EXPRESSION; BABOON PAPIO-ANUBIS; UTERINE EPITHELIUM; PRIMORDIAL FOLLICLES; LIFE-SPAN; INHIBITING SUBSTANCE; ENDOMETRIAL CANCER; BETA-CATENIN; MOUSE UTERUS AB Tumors develop with dysregulated activation of mammalian target of rapamycin (mTOR), the kinase activity of which is kept in an inactive state by a tumor suppressor dimer containing tuberous sclerosis 1 (TSC1) and TSC2. We examined whether conditional deletion of TSC1 by a knock-in allele of the anti-Mullerian hormone type 2 receptor (Amhr2) driving Cre expression and subsequent activation of mTOR in granulosa cells and in oviductal and uterine stromal cells affects fertility in female mice. Increased phosphorylation of ribosomal protein S6, a downstream target of activated mTOR, was observed in all AMHR2-expressing tissues examined, indicating loss of TSC1 activity. TSC1 deletion in granulosa cells led to the detection of significantly fewer primordial follicles in mutant mice at 12 wk, suggesting premature ovarian insufficiency, which might be related to the significantly increased time mutant mice spent in estrus. Although the number of good-quality ovulated oocytes was not significantly different compared with controls, there was a significantly higher number of degenerated oocytes after normal and superovulation, suggesting compromised oocyte quality, as well. Natural mating also showed severalfold higher numbers of degenerate bodies in the mutants that collected in bilateral swellings resembling hydrosalpinges that formed in all mice examined because of occlusion of the proximal oviduct. Attempts to transfer control embryos into mutant uteri also failed, indicating that implantation was compromised. Endometrial epithelial cells continued to proliferate, and quantitative RT-PCR showed that mucin 1 expression persisted during the window of implantation in mutantuteri, without any changes in progesterone receptor mRNA expression, suggesting a mechanism that does not involve disrupted estradiol-regulated progesterone receptor expression. Homozygous deletion of TSC1 in reproductive tract somatic tissues of mice rendered females completely infertile, which is likely due to these pleiotropic effects on follicle recruitment, oviductal development, and blastocyst implantation. (Endocrinology 153: 404-416, 2012) C1 Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Teixeira, JM (reprint author), Massachusetts Gen Hosp, Vincent Ctr Reprod Biol Thier 931, 55 Fruit St, Boston, MA 02114 USA. EM teixeira@helix.mgh.harvard.edu OI Teixeira, Jose/0000-0002-6438-5064 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) [HD052701]; Vincent Memorial Research Funds; NICHD (Specialized Cooperative Centers) [U54-HD28934] FX This work was supported by funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (HD052701) and by Vincent Memorial Research Funds to J.M.T. The University of Virginia Center for Research in Reproduction Ligand Core Laboratory is supported by NICHD (Specialized Cooperative Centers Program in Reproduction and Infertility Research) Grant U54-HD28934. NR 61 TC 20 Z9 21 U1 0 U2 3 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JAN PY 2012 VL 153 IS 1 BP 404 EP 416 DI 10.1210/en.2011-1191 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 869XC UT WOS:000298631500038 PM 22128018 ER PT J AU Sonnenberg, A AF Sonnenberg, A. TI Test sequence in the management of gastrointestinal bleeding SO ENDOSCOPY LA English DT Article ID EPIDEMIOLOGY; DIAGNOSIS AB Background and study aim: A large variety of test procedures is available to diagnose and treat patients with suspected gastrointestinal bleeding. The aim of the study was to investigate which test sequence should be utilized in managing gastrointestinal bleeding. Methods: For each endoscopic, radiologic, or laboratory test procedure, professional fees and facility costs were estimated based on payments allowed by the US Centers for Medicare and Medicaid Services during the fiscal year 2010. A threshold analysis was used to compare the costs associated with different test sequences of varying clinical scenarios. Results: A threshold represents the lowest expected probability of success, for which a test would still be indicated. In a work-up including all possible management options, the threshold associated with laboratory tests and gastric lavage was 1%, esophagogastroduodenoscopy (EGD) 8%, colonoscopy 9%, nuclear scan 9%, enteroscopy 11%, computed tomography (CT) angiography 14%, capsule endoscopy 23%, and angiography with transcatheter embolization 25%. Varying sets of thresholds were calculated for different clinical scenarios. The thresholds of EGD and colonoscopy remained low in most scenarios. In sensitivity analysis, rising risk of complications or costs of a procedure also lead to rising threshold values for it, potentially rendering the particular procedure untenable. Conclusions: A low threshold indicated a preferred management option that should be used early rather than late in a sequence of multiple possible test procedures to work up instances of gastrointestinal bleeding. C1 [Sonnenberg, A.] Portland VA Med Ctr, Portland, OR 97239 USA. [Sonnenberg, A.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr, P3-GI 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 8 TC 5 Z9 5 U1 2 U2 2 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0013-726X J9 ENDOSCOPY JI Endoscopy PD JAN PY 2012 VL 44 IS 1 BP 43 EP 47 DI 10.1055/s-0031-1291536 PG 5 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 866TF UT WOS:000298405400008 PM 22198774 ER PT J AU Connorton, E Perry, MJ Hemenway, D Miller, M AF Connorton, Ellen Perry, Melissa J. Hemenway, David Miller, Matthew TI Humanitarian Relief Workers and Trauma-related Mental Illness SO EPIDEMIOLOGIC REVIEWS LA English DT Article DE anxiety; depression; mental health; relief work; stress disorders; post-traumatic; stress disorders; traumatic; acute; stress; psychological; substance-related disorders ID POSTTRAUMATIC-STRESS-DISORDER; NATIONAL COMORBIDITY SURVEY; RISK-FACTORS; AID WORKERS; VICARIOUS TRAUMA; UN-SOLDIERS; HEALTH; SYMPTOMS; PEACEKEEPERS; EXPOSURE AB Humanitarian relief work is a growing field characterized by ongoing exposure to primary and secondary trauma, which has implications for workers' occupational mental health. This paper reviews and summarizes research to date on mental health effects of relief work. Twelve studies on relief workers and 5 studies on organizations that employ relief workers are examined to determine whether relief work is a risk factor for trauma-related mental illness. Although studies are inconsistent regarding methods and outcomes documenting trauma-related mental illness among relief workers, it appears that relief workers, compared with the general population, experience elevated trauma rates and suffer from more posttraumatic stress disorder, depression, and anxiety. Organizations that employ relief workers have varying approaches to train for these risks, and more support in the field is needed. C1 [Connorton, Ellen; Hemenway, David; Miller, Matthew] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02215 USA. [Connorton, Ellen; Hemenway, David; Miller, Matthew] Dana Farber Canc Inst, Boston, MA 02215 USA. [Perry, Melissa J.] George Washington Univ, Univ Sch Publ Hlth & Hlth Serv, Dept Environm & Occupat Hlth, Washington, DC USA. RP Connorton, E (reprint author), Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, 450 Brookline Ave,LW 750, Boston, MA 02215 USA. EM econnort@hsph.harvard.edu NR 51 TC 14 Z9 14 U1 4 U2 23 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0193-936X J9 EPIDEMIOL REV JI Epidemiol. Rev. PD JAN PY 2012 VL 34 IS 1 BP 145 EP 155 DI 10.1093/epirev/mxr026 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 873NN UT WOS:000298890100013 PM 22180469 ER PT J AU Power, MC Weuve, J Gagne, JJ McQueen, MB Viswanathan, A Blacker, D AF Power, Melinda C. Weuve, Jennifer Gagne, Joshua J. McQueen, Matthew B. Viswanathan, Anand Blacker, Deborah TI Hypertension and Alzheimer Disease Is There a Link? response SO EPIDEMIOLOGY LA English DT Letter C1 [Power, Melinda C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Power, Melinda C.; Weuve, Jennifer] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Weuve, Jennifer] Rush Univ, Med Ctr, Inst Healthy Aging, Chicago, IL 60612 USA. [Weuve, Jennifer] Rush Univ, Med Ctr, Dept Internal Med, Chicago, IL 60612 USA. [Gagne, Joshua J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Gagne, Joshua J.] Harvard Univ, Sch Med, Boston, MA USA. [Gagne, Joshua J.] Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. [McQueen, Matthew B.] Univ Colorado, Dept Psychol, Boulder, CO 80309 USA. [McQueen, Matthew B.] Univ Colorado, Inst Behav Genet, Boulder, CO 80309 USA. [Viswanathan, Anand] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Hemorrhag Stroke Res Program, Boston, MA USA. [Blacker, Deborah] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Blacker, Deborah] Harvard Univ, Sch Med, Dept Psychiat, Gerontol Res Unit, Boston, MA 02115 USA. RP Power, MC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 665 Huntington Ave, Boston, MA 02115 USA. EM mcpower@hsph.harvard.edu 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 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JAN PY 2012 VL 23 IS 1 BP 177 EP 178 DI 10.1097/EDE.0b013e31823b6513 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 863IU UT WOS:000298156800029 ER PT J AU Graber, CJ Hutchings, C Dong, F Lee, W Chung, JK Tran, T AF Graber, C. J. Hutchings, C. Dong, F. Lee, W. Chung, J. K. Tran, T. TI Changes in antibiotic usage and susceptibility in nosocomial Enterobacteriaceae and Pseudomonas isolates following the introduction of ertapenem to hospital formulary SO EPIDEMIOLOGY AND INFECTION LA English DT Article DE Antibiotic resistance; antibiotics; hospital-acquired (nosocomial) infections; hospital microbiology; Pseudomonas ID TIME-SERIES ANALYSIS; RESISTANT; AERUGINOSA; IMIPENEM; THERAPY; RATES AB There is concern that widespread usage of ertapenem may promote cross-resistance to other carbapenems. To analyse the impact that adding ertapenem to our hospital formulary had on usage of other broad-spectrum agents and on susceptibilities of nosocomial Enterobacteriaceae and Pseudomonas isolates, we performed interrupted time-series analyses to determine the change in linear trend in antibiotic usage and change in mean proportion and linear trend of susceptibility pre-(March 2004-June 2005) and post-(July 2005-December 2008) ertapenem introduction. Usage of piperacillin-tazobactam (P = 0.0013) and ampicillin-sulbactam (P = 0.035) declined post-ertapenem introduction. For Enterobacteriaceae, the mean proportion susceptible to ciprofloxacin (P = 0.016) and piperacillin-tazobactam (P = 0.038) increased, while the linear trend in susceptibility significantly increased for cefepime (P = 0.012) but declined for ceftriaxone (P = 0.0032). For Pseudomonas, the mean proportion susceptible to cefepime (P = 0.011) and piperacillin-tazobactam (P = 0.028) increased, as did the linear trend in susceptibility to ciprofloxacin (P = 0.028). Notably, no significant changes in carbapenem susceptibility were observed. C1 [Graber, C. J.] Univ Calif Los Angeles, David Geffen Sch Med, UCLA Infect Dis Sect, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Graber, C. J.; Tran, T.] VA Greater Los Angeles Healthcare Syst, Infect Dis Sect, Los Angeles, CA USA. [Hutchings, C.; Dong, F.; Tran, T.] VA Greater Los Angeles Healthcare Syst, Serv Pharm, Los Angeles, CA USA. [Lee, W.] Univ So Calif, Keck Sch Med, Dept Biostat, Los Angeles, CA 90033 USA. [Chung, J. K.] Univ So Calif, Sch Pharm, Los Angeles, CA USA. RP Graber, CJ (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, UCLA Infect Dis Sect, VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,111-F, Los Angeles, CA 90073 USA. EM cgraber@ucla.edu FU Merck Pharmaceuticals; Ortho-McNeil-Janssen FX This project was supported by a grant from Merck Pharmaceuticals.; C.J.G. has received an unrestricted educational grant from Ortho-McNeil-Janssen and has served on an advisory board for Pfizer. NR 13 TC 3 Z9 3 U1 0 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0950-2688 J9 EPIDEMIOL INFECT JI Epidemiol. Infect. PD JAN PY 2012 VL 140 IS 1 BP 115 EP 125 DI 10.1017/S0950268811000082 PG 11 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 868TC UT WOS:000298547400015 PM 21303590 ER PT J AU Ahasic, AM Zhai, RH Su, L Zhao, Y Aronis, KN Thompson, BT Mantzoros, CS Christiani, DC AF Ahasic, Amy M. Zhai, Rihong Su, Li Zhao, Yang Aronis, Konstantinos N. Thompson, B. Taylor Mantzoros, Christos S. Christiani, David C. TI IGF1 and IGFBP3 in acute respiratory distress syndrome SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article ID GROWTH-FACTOR-I; IDIOPATHIC PULMONARY-FIBROSIS; FACTOR-BINDING PROTEIN-3; ACUTE LUNG INJURY; BRONCHOALVEOLAR LAVAGE FLUID; MORTALITY; ADULTS; PREDICTORS; HORMONE; DISEASE AB Objective: IGF1 and its most abundant binding protein, IGF-binding protein 3 (IGFBP3), have been implicated in fibrotic lung diseases and persistent acute respiratory distress syndrome (ARDS) due to profibrogenic and antiapoptotic activity. Whether circulating levels of IGF1 and IGFBP3 are altered in ARDS and whether they predict progression of and survival from ARDS remains unknown. This study aims to characterize the circulating levels of IGF1 and IGFBP3 in patients at risk for ARDS in relation to i) development of ARDS and ii) mortality among ARDS cases. Design: In this case-cohort study, consecutive patients with risk factors for ARDS admitted to the intensive care unit were enrolled and followed prospectively for the development of ARDS. Cases were followed for all-cause mortality through day 60. Of the 2397 patients enrolled in the parent study, plasma samples were available in 531 (22%) patients (356 controls and 175 cases) from early in presentation. Total plasma IGF1 and IGFBP3 levels were measured. Results: After adjusting for relevant clinical covariates including severity of illness, IGF1 and IGFBP3 levels were significantly lower in ARDS cases than in controls (odds ratio (OR), 0.58; P=0.006; OR, 0.57; P=0.0015 respectively). Among the ARDS cases, IGF1 and IGFBP3 levels were significantly lower in the 78 (45%) non-survivors (hazard ratio (HR), 0.70; P=0.024; HR, 0.69; P=0.021 respectively). Conclusions: Lower circulating levels of IGF1 and IGFBP3 were independently associated with ARDS case status. Furthermore, lower levels were associated with mortality among the ARDS cases. These data support the role of the IGF pathway in ARDS. C1 [Ahasic, Amy M.] Yale Univ, Sch Med, Dept Med, Sect Pulm & Crit Care Med, New Haven, CT 06520 USA. [Ahasic, Amy M.; Zhai, Rihong; Su, Li; Zhao, Yang; Mantzoros, Christos S.; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Aronis, Konstantinos N.; Mantzoros, Christos S.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab,Dept Med, Boston, MA 02215 USA. [Thompson, B. Taylor; Christiani, David C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pulm & Crit Care Unit,Dept Med, Boston, MA 02114 USA. RP Ahasic, AM (reprint author), Yale Univ, Sch Med, Dept Med, Sect Pulm & Crit Care Med, 300 Cedar St,POB 208057, New Haven, CT 06520 USA. EM amy.ahasic@yale.edu RI Aronis, Konstantinos/F-3586-2012; Aronis, Konstantinos/J-6582-2014 OI Aronis, Konstantinos/0000-0001-7189-8434; FU National Institutes of Health [R01-HL60710 (NHLBI), ES00002 (NIEHS), T32-HL07874 (NHLBI)]; American Heart Association [10FTF3440007] FX This work was supported by the National Institutes of Health (R01-HL60710 (NHLBI), ES00002 (NIEHS), T32-HL07874 (NHLBI)) and by the American Heart Association (10FTF3440007). NR 31 TC 7 Z9 8 U1 0 U2 3 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0804-4643 J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD JAN PY 2012 VL 166 IS 1 BP 121 EP 129 DI 10.1530/EJE-11-0778 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 865YX UT WOS:000298347900017 PM 22004906 ER PT J AU Richardson, PG Laubach, JP Schlossman, RL Ghobrial, IM Mitsiades, CS Rosenblatt, J Mahindra, A Raje, N Munshi, N Anderson, KC AF Richardson, Paul G. Laubach, Jacob P. Schlossman, Robert L. Ghobrial, Irene M. Mitsiades, Constantine S. Rosenblatt, Jacalyn Mahindra, Anuj Raje, Noopur Munshi, Nikhil Anderson, Kenneth C. TI The Medical Research Council Myeloma IX trial: the impact on treatment paradigms* SO EUROPEAN JOURNAL OF HAEMATOLOGY LA English DT Review DE bisphosphonate; clodronate; multiple myeloma; pamidronate; zoledronic acid ID BISPHOSPHONATE ZOLEDRONIC ACID; MULTIPLE-MYELOMA; STAGING SYSTEM; CELL-LINES; BONE-DISEASE; IN-VIVO; DEXAMETHASONE; SURVIVAL; STRATIFICATION; THALIDOMIDE AB Osteolytic bone disease is a hallmark of symptomatic multiple myeloma. Bisphosphonates have been the mainstay of treatment to preserve skeletal integrity and prevent skeletal-related events in patients with myeloma-related bone disease. Recently, the MRC Myeloma IX trial demonstrated for the first time improved survival and delayed disease progression with the use of an intravenous amino-bisphosphonate, zoledronic acid, vs. an oral agent, clodronate, with intensive and non-intensive anti-myeloma treatment regimens in patients with newly diagnosed multiple myeloma. These results validate a large body of preclinical, translational and other clinical data suggesting anti-myeloma effects of amino-bisphosphonates. In addition, this trial also provided the first head-to-head evidence for superiority of one bisphosphonate over another (zoledronic acid vs. clodronate) for reducing skeletal morbidity in patients with multiple myeloma, as well as a prospective comparison of toxicities. Despite the use of non-bortezomib containing anti-myeloma treatment regimens in the MRC Myeloma IX trial, these results are encouraging and provide an impetus to continue to evaluate current treatment guidelines for myeloma-associated bone disease. C1 [Richardson, Paul G.; Laubach, Jacob P.; Schlossman, Robert L.; Ghobrial, Irene M.; Mitsiades, Constantine S.; Munshi, Nikhil; Anderson, Kenneth C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Rosenblatt, Jacalyn] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Mahindra, Anuj; Raje, Noopur] Harvard Univ, Sch Med, Div Hematol Oncol, Boston, MA USA. RP Richardson, PG (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,Dana 1B02, Boston, MA 02115 USA. EM paul_richardson@dfci.harvard.edu FU Rick Corman Multiple Myeloma Research Fund; Novartis Pharmaceuticals; AstraZeneca; Acetylon; Celgene FX Funding for administrative assistance and for medical writing support was provided in part by the Rick Corman Multiple Myeloma Research Fund and Novartis Pharmaceuticals.; PGR - Advisory Board: Celgene, Millennium, Novartis, Johnson & Johnson, BMS. IMG - Advisory Board: Celgene, Millennium, Novartis, Onyx. NR - Advisory Board: Celgene, Novartis, Amgen, Research Funding: AstraZeneca, Acetylon, Celgene. KCA - Advisory Board: Novartis, Millennium, Celgene, Onyx, BMS, Merck. Founder of Acetylon. JR - Research Funding: Celgene, Millennium. AM - Advisory Board: Millennium. JPL, RLS - have no competing interests. NR 42 TC 4 Z9 4 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0902-4441 J9 EUR J HAEMATOL JI Eur. J. Haematol. PD JAN PY 2012 VL 88 IS 1 BP 1 EP 7 DI 10.1111/j.1600-0609.2011.01721.x PG 7 WC Hematology SC Hematology GA 862KM UT WOS:000298089600001 PM 21991938 ER PT J AU van der Pol, A Domian, I van der Meer, P AF van der Pol, Atze Domian, Ibrahim van der Meer, Peter TI Cardiac regeneration in left ventricular dysfunction: are we asking the right questions? SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Editorial Material ID ACUTE MYOCARDIAL-INFARCTION; PROGENITOR CELLS; PARACRINE MECHANISMS; HEART-FAILURE; STEM-CELLS; REPAIR; TRANSPLANTATION; CARDIOMYOCYTES; INSIGHTS; MUSCLE C1 [van der Pol, Atze; van der Meer, Peter] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, NL-9713 GZ Groningen, Netherlands. [Domian, Ibrahim] Massachusetts Gen Hosp, Div Cardiol, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP van der Meer, P (reprint author), Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Hanzepl 1, NL-9713 GZ Groningen, Netherlands. EM p.van.der.meer@umcg.nl FU NHLBI NIH HHS [K08 HL091209] NR 20 TC 2 Z9 2 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1388-9842 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD JAN PY 2012 VL 14 IS 1 BP 1 EP 4 DI 10.1093/eurjhf/hfr160 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 866LN UT WOS:000298382400001 PM 22147203 ER PT J AU Fagerness, JA Yu, Y Maller, JB Neale, BM Reynolds, RC Daly, MJ Seddon, JM AF Fagerness, Jesen A. Yu, Yi Maller, Julian B. Neale, Benjamin M. Reynolds, Robyn C. Daly, Mark J. Seddon, Johanna M. TI Reply to Cipriani et al SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Letter C1 [Fagerness, Jesen A.; Maller, Julian B.; Neale, Benjamin M.; Daly, Mark J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Fagerness, Jesen A.; Maller, Julian B.; Neale, Benjamin M.; Daly, Mark J.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. [Yu, Yi; Reynolds, Robyn C.; Seddon, Johanna M.] Tufts Med Ctr, New England Eye Ctr, Ophthalm Epidemiol & Genet Serv, Boston, MA USA. [Maller, Julian B.] Univ Oxford, Dept Stat, Oxford OX1 3TG, England. [Seddon, Johanna M.] Tufts Univ, Sch Med, Dept Ophthalmol, Boston, MA 02111 USA. RP Fagerness, JA (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. EM jseddon@tuftsmedicalcenter.org NR 3 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD JAN PY 2012 VL 20 IS 1 BP 3 EP 3 DI 10.1038/ejhg.2011.177 PG 1 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 863MF UT WOS:000298167700005 ER PT J AU Abusief, ME Missmer, SA Ginsburg, ES Weeks, JC Partridge, AH AF Abusief, Mary E. Missmer, Stacey A. Ginsburg, Elizabeth S. Weeks, Jane C. Partridge, Ann H. TI Relationship between reproductive history, anthropometrics, lifestyle factors, and the likelihood of persistent chemotherapy-related amenorrhea in women with premenopausal breast cancer SO FERTILITY AND STERILITY LA English DT Article DE Chemotherapy-related amenorrhea; breast cancer; gravidity; parity; lifestyle factors; premature menopause ID INDUCED OVARIAN FAILURE; NATURAL MENOPAUSE; ADJUVANT CHEMOTHERAPY; CIGARETTE-SMOKING; AGE; RISK; FERTILITY; MENARCHE; THERAPY; CYCLOPHOSPHAMIDE AB Objective: To determine the association between patient characteristics at diagnosis of premenopausal breast cancer, including gravidity, parity, age at menarche, age at first birth, alcohol use, smoking history, weight, height, and body mass index (BMI), with the development of persistent chemotherapy-related amenorrhea (CRA) in follow-up. Design: Retrospective cohort study. Setting: Dana Farber Cancer Institute and Brigham and Women's Hospital. Patient(s): Premenopausal women with breast cancer. Intervention(s): We identified all premenopausal women who received standard adjuvant chemotherapy during 1997-2005 for whom menstrual data were available. Multivariable logistic regression models evaluating persistent amenorrhea at >= 6 month after completion of chemotherapy were conducted. Main Outcome Measure(s): Persistent chemotherapy-related amenorrhea (CRA) at >= 6 months from completion of chemotherapy. Result(s): A total of 431 women met eligibility criteria and had >= 6-months' follow-up. Women with older (>13 years) vs. younger (12-13 years) age at menarche were more than twice as likely to remain amenorrheic. Current smokers had 2.4 greater odds of CRA vs. never smokers, although this association was not statistically significant (95% confidence interval, 0.86-6.75). Conclusion(s): Few identifiable factors contribute to the variability in CRA among premenopausal women after adjuvant chemotherapy for breast cancer. Further research to improve the prediction of CRA, premature menopause, and infertility in young breast cancer survivors is warranted. (Fertil Steril (R) 2012;97:154-9. (C) 2012 by American Society for Reproductive Medicine.) C1 [Abusief, Mary E.; Missmer, Stacey A.; Ginsburg, Elizabeth S.] Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. [Missmer, Stacey A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Weeks, Jane C.; Partridge, Ann H.] Harvard Univ, Sch Med, Boston, MA USA. [Missmer, Stacey A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Weeks, Jane C.; Partridge, Ann H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Abusief, ME (reprint author), Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, 75 Francis St, Boston, MA 02115 USA. EM maskelya@msn.com FU NCI NIH HHS [K05 CA166208]; NCRR NIH HHS [M01 RR002635] NR 52 TC 8 Z9 8 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD JAN PY 2012 VL 97 IS 1 BP 154 EP 159 DI 10.1016/j.fertnstert.2011.10.005 PG 6 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 866GD UT WOS:000298367600029 PM 22192139 ER PT J AU Styskal, J Van Remmen, H Richardson, A Salmon, AB AF Styskal, JennaLynn Van Remmen, Holly Richardson, Arlan Salmon, Adam B. TI Oxidative stress and diabetes: What can we learn about insulin resistance from antioxidant mutant mouse models? SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Review DE Oxidative stress; Diabetes; Obesity; Adipose; Insulin resistance ID EXTRACELLULAR-SUPEROXIDE-DISMUTASE; CELLULAR GLUTATHIONE-PEROXIDASE; METHIONINE SULFOXIDE REDUCTASE; MEMBRANE LIPID-PEROXIDATION; OXIDANT TISSUE-INJURY; RAT SKELETAL-MUSCLE; GENE-TARGETED MICE; ALPHA-LIPOIC ACID; RED-BLOOD-CELLS; NF-KAPPA-B AB The development of metabolic dysfunctions like diabetes and insulin resistance in mammals is regulated by a myriad of factors. Oxidative stress seems to play a central role in this process as recent evidence shows a general increase in oxidative damage and a decrease in oxidative defense associated with several metabolic diseases. These changes in oxidative stress can be directly correlated with increased fat accumulation, obesity, and consumption of high-calorie/high-fat diets. Modulation of oxidant protection through either genetic mutation or treatment with antioxidants can significantly alter oxidative stress resistance and accumulation of oxidative damage in laboratory rodents. Antioxidant mutant mice have previously been utilized to examine the role of oxidative stress in other disease models, but have been relatively unexplored as models to study the regulation of glucose metabolism. In this review, we will discuss the evidence for oxidative stress as a primary mechanism linking obesity and metabolic disorders and whether alteration of antioxidant status in laboratory rodents can significantly alter the development of insulin resistance or diabetes. (C) 2011 Elsevier Inc. All rights reserved. C1 [Styskal, JennaLynn; Van Remmen, Holly; Richardson, Arlan; Salmon, Adam B.] Univ Texas Hlth Sci Ctr San Antonio, Sam & Ann Barshop Inst Longev & Aging Studies, San Antonio, TX 78245 USA. [Styskal, JennaLynn; Van Remmen, Holly; Richardson, Arlan] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Van Remmen, Holly; Richardson, Arlan; Salmon, Adam B.] S Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA. [Salmon, Adam B.] Univ Texas Hlth Sci Ctr San Antonio, Dept Mol Med, San Antonio, TX 78245 USA. RP Salmon, AB (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Sam & Ann Barshop Inst Longev & Aging Studies, 15355 Lambda Dr,MSC 7755, San Antonio, TX 78245 USA. EM salmona@uthscsa.edu FU NIH [T32 AG021890-05, R01AG015908, R01AG023843, P01AG19316, P01AG020591, R37AG026557]; Department of Veterans Affairs; San Antonio Nathan Shock Center of Excellence in the Basic Biology of Aging FX This work was supported by NIH Training Grant T32 AG021890-05, NIH Grants R01AG015908, R01AG023843, P01AG19316, P01AG020591, and R37AG026557, the Department of Veterans Affairs (Merit Grants and a Research Enhancement Award Program), and the Mitocondrial Function and Oxidative Damage Core Facility of the San Antonio Nathan Shock Center of Excellence in the Basic Biology of Aging. NR 184 TC 90 Z9 91 U1 1 U2 25 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD JAN 1 PY 2012 VL 52 IS 1 BP 46 EP 58 DI 10.1016/j.freeradbiomed.2011.10.441 PG 13 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 874RJ UT WOS:000298975500005 PM 22056908 ER PT J AU Rungruang, B Miller, A Richard, SD Hamilton, CA Rodriguez, N Bookman, MA Maxwell, GL Krivak, TC Horowitz, NS AF Rungruang, Bunja Miller, Austin Richard, Scott D. Hamilton, Chad A. Rodriguez, Noah Bookman, Michael A. Maxwell, G. Larry Krivak, Thomas C. Horowitz, Neil S. TI Should stage IIIC ovarian cancer be further stratified by intraperitoneal vs. retroperitoneal only disease?: A Gynecologic Oncology Group study SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Ovarian cancer; Lymphadenopathy; FIGO staging ID PRIMARY CYTOREDUCTIVE SURGERY; NODE INVOLVEMENT; CARCINOMA; SURVIVAL; LYMPHADENECTOMY; METASTASIS; IMPACT; TRIAL AB Objective. To examine whether clinical outcomes varied with intraperitoneal (IP) and/or retroperitoneal (RP) involvement in stage IIIC epithelial ovarian cancer (EOC) patients with microscopic residual disease after cytoreduction. Methods. Retrospective review was performed for EOC patients enrolled in Gynecologic Oncology Group (GOG)-182 who underwent primary cytoreduction to microscopic residual disease. Patients were divided into 3 groups: stage IIIC by lymphadenopathy with <2 cm IF spread (RP): >2 cm IP spread and negative nodes (IP/RP-): and >2 cm IP dissemination and positive lymphadenopathy (IP/RP+). Product-limit and multivariate proportional hazards modeling were used. Results. Analyses included 417 stage IIIC women who underwent primary cytoreduction with lymphadenectomy to microscopic residual. There were 203, 123, and 91 in the RP, IP/RP-, and IP/RP+ groups, respectively. IP/RP+ and IP/RP- were associated with worse progression-free survival (PFS) (Hazard Ratio (HR) 1.68, 95% confidence interval (CI) 1.23-2.30: HR 1.38, 95% CI 1.04-1.84) vs. RP only. IP/RP+ was associated with worse overall survival (OS) (HR 1.79, 95% CI 1.24-2.57) while IP/RP- trended towards worse OS (HR 1.21, 95% CI 0.85-1.73) vs. RP only. Median PFS for IP/RP+ and IP/RP- groups was 21 and 29 months, respectively, vs. 48 months in the RP group (p = 0.0007) and median OS of 63 and 79 months vs. "not reached," respectively (p = 0.0038). Conclusions. Among EOC patients surgically cytoreduced to microscopic residual disease, those upstaged to IIIC by retroperitoneal involvement demonstrated significant improvement in PFS and OS compared to patients with intraperitoneal tumor, suggesting that these women may represent a unique subset of FIGO stage IIIC patients. (C) 2011 Elsevier Inc. All rights reserved. C1 [Rungruang, Bunja; Richard, Scott D.; Krivak, Thomas C.] UPMC, Magee Womens Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Pittsburgh, PA USA. [Miller, Austin] Roswell Pk Canc Inst, Stat & Data Ctr, Gynecol Oncol Grp, Buffalo, NY 14263 USA. [Hamilton, Chad A.; Maxwell, G. Larry] Walter Reed Army Med Ctr, Dept Obstet & Gynecol, Div Gynecol Oncol, Washington, DC 20307 USA. [Rodriguez, Noah; Horowitz, Neil S.] Brigham & Womens Hosp, Div Gynecol Oncol, Boston, MA 02115 USA. [Bookman, Michael A.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. RP Horowitz, NS (reprint author), Massachusetts Gen Hosp, 75 Francis St, Boston, MA 02115 USA. EM nhorowitz@partners.org FU National Cancer Institute [CA 27469, CA 37517] FX This study was supported by National Cancer Institute grants to the Gynecologic Oncology Group (COG) Administrative Office (CA 27469) and the Gynecologic Oncology Group Statistical Office (CA 37517). The following Gynecologic Oncology Group member institutions participated in the primary treatment studies: University of Alabama at Birmingham, Oregon Health Sciences University, Duke University Medical Center, Abington Memorial Hospital, University of Rochester Medical Center, Walter Reed Army Medical Center, Wayne State University, University of Minnesota Medical School, University of Southern California at Los Angeles, University of Mississippi Medical Center, Colorado Gynecologic Oncology Group P.C., University of California at Los Angeles, University of Washington. University of Pennsylvania Cancer Center, University of Miami School of Medicine, Milton S. Hershey Medical Center, Georgetown University Hospital, University of Cincinnati, University of North Carolina School of Medicine. University of Iowa Hospitals and Clinics. University of Texas Southwestern Medical Center at Dallas, Indiana University School of Medicine, Wake Forest University School of Medicine, Albany Medical College, University of California Medical Center at Irvine, Tufts-New England Medical Center, Rush-Presbyterian-St. Luke's Medical Center, University of Kentucky, Eastern Virginia Medical School, The Cleveland Clinic Foundation, Johns Hopkins Oncology Center, State University of New York at Stony Brook, Eastern Pennsylvania GYN/ONC Center, P.C., Southwestern Oncology Group, Washington University School of Medicine, Memorial Sloan-Kettering Cancer Center, Columbus Cancer Council, University of Massachusetts Medical School, Fox Chase Cancer Center, Medical University of South Carolina, Women's Cancer Center, University of Oklahoma. University of Virginia Health Sciences Center, University of Chicago, University of Arizona Health Science Center, Tacoma General Hospital, Eastern Collaborative Oncology Group, Thomas Jefferson University Hospital, Case Western Reserve University, and Tampa Bay Cancer Consortium. NR 25 TC 4 Z9 6 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JAN PY 2012 VL 124 IS 1 BP 53 EP 58 DI 10.1016/j.ygyno.2011.09.024 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 864BV UT WOS:000298212900012 PM 22032836 ER PT J AU van Hanegem, N Barroilhet, LM Nucci, MR Bernstein, M Feldman, S AF van Hanegem, Nehalennia Barroilhet, Lisa M. Nucci, Marisa R. Bernstein, Marilyn Feldman, Sarah TI Fertility-sparing treatment in younger women with adenocarcinoma in situ of the cervix SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Adenocarcinoma in situ; Cervix; Loop excision; Cold knife conization ID SQUAMOUS-CELL CARCINOMA; ELECTROSURGICAL EXCISION PROCEDURE; COLD-KNIFE CONIZATION; UTERINE CERVIX; INTRAEPITHELIAL NEOPLASIA; CONSERVATIVE TREATMENT; UNITED-STATES; CONE BIOPSY; MANAGEMENT; MARGINS AB Objective. For women who have completed childbearing, the treatment of choice for adenocarcinoma in situ (ACIS) of the cervix is hysterectomy. In women who desire future fertility, however, conservative therapy is an acceptable alternative. In this study we compare the outcomes for young women who underwent loop conization or were treated with cold knife conization. Methods. We performed a retrospective analysis in 112 patients with ACIS, age 30 or younger, treated with cold knife conization or loop conization between 1998 and 2010. Decision to perform office loop conization was based on the size of the cervix and the colposcopic lesion. Main outcomes were negative margins after the procedure and recurrence of ACIS. Results. Fifty-eight patients (52%) were treated with cold knife conization and 54 (48%) underwent loop conization. The odds ratio for cold knife conization to achieve negative cone margins compared with loop conization was 1.4 (95% CI 0.6-3.5). We observed no difference in residual or recurrent ACIS between patients treated with loop conization versus cold knife conization. Conclusions. In select young patients who desire future fertility, loop conization and cold knife conization have equivalent rates of negative margins and negative follow-up. For optimal results, patients must have a lesion which can be removed in one pass of a loop, confirmed by expert colposcopy. Loop excision should be considered the treatment of choice in this specific group of patients. (C) 2011 Published by Elsevier Inc. C1 [van Hanegem, Nehalennia; Barroilhet, Lisa M.; Bernstein, Marilyn; Feldman, Sarah] Harvard Univ, Brigham & Womens Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol,Dana Farber Canc Inst,Med Sch, Boston, MA 02115 USA. [van Hanegem, Nehalennia] Univ Amsterdam, Acad Med Ctr, Dept Obstet & Gynecol, NL-1105 AZ Amsterdam, Netherlands. [Nucci, Marisa R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Womens & Perinatal Pathol,Dept Pathol, Boston, MA 02115 USA. RP Feldman, S (reprint author), Harvard Univ, Brigham & Womens Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol,Dana Farber Canc Inst,Med Sch, 75 Francis St, Boston, MA 02115 USA. EM sfeldman@partners.org NR 33 TC 20 Z9 20 U1 0 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 JAN PY 2012 VL 124 IS 1 BP 72 EP 77 DI 10.1016/j.ygyno.2011.09.006 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 864BV UT WOS:000298212900016 PM 22030403 ER PT J AU Parshall, MB Carle, AC Ice, U Taylor, R Powers, J AF Parshall, Mark B. Carle, Adam C. Ice, Unchalee Taylor, Robert Powers, Joyce TI Validation of a three-factor measurement model of dyspnea in hospitalized adults with heart failure SO HEART & LUNG LA English DT Article DE Chronic obstructive pulmonary disease; Confirmatory factor analysis; Dyspnea; Respiratory sensation ID OBSTRUCTIVE PULMONARY-DISEASE; CO2-INDUCED AIR HUNGER; RESPIRATORY SENSATIONS; CARDIORESPIRATORY DISEASES; VENTILATED QUADRIPLEGICS; RESPONSE CHARACTERISTICS; QUALITATIVE ASPECTS; CLINICAL-TRIALS; FIT INDEXES; BREATHLESSNESS AB OBJECTIVE: The purpose of this study was to validate a 3-factor measurement model of dyspnea sensory quality (WORK-EFFORT, TIGHTNESS, SMOTHERING-AIR HUNGER) originally derived in patients with exacerbated chronic obstructive pulmonary disease. METHODS: In this validation study, adult patients with heart failure were enrolled after hospital admission (median hospital day 1) and asked to rate the intensity of dyspnea sensory quality descriptors on the day of enrollment (study day 1; N = 119) and in a recall version for the day of admission (study day 0; n = 97). RESULTS: Confirmatory factor analysis demonstrated good model fit for both days. Cronbach's alpha for each factor was greater than .87 for both study days. CONCLUSION: This is the first study to validate a previously specified measurement model of dyspnea sensory quality in an independent sample. Results indicate that measurement of dyspnea sensory quality in exacerbated cardiopulmonary disease does not necessarily require disease-specific questionnaires. Cite this article: Parshall, M. B., Carle, A. C., Ice, U., Taylor, R., & Powers, J. (2012, JANUARY/FEBRUARY). Validation of a three-factor measurement model of dyspnea in hospitalized adults with heart failure. Heart & Lung, 41(1), 44-56. doi:10.1016/j.hrtlng.2011.05.003. C1 [Parshall, Mark B.; Ice, Unchalee] Univ New Mexico, Coll Nursing, Hlth Sci Ctr, Albuquerque, NM 87131 USA. [Carle, Adam C.] Univ Cincinnati, Coll Med, James M Anderson Ctr Hlth Syst Excellence, Cincinnati, OH USA. [Taylor, Robert] Univ New Mexico, Sch Med, Dept Internal Med, Div Cardiol,Hlth Sci Ctr, Albuquerque, NM 87131 USA. [Powers, Joyce] US Dept Vet Affairs, Raymond G Murphy VA Med Ctr, Albuquerque, NM USA. RP Parshall, MB (reprint author), Univ New Mexico, Coll Nursing, Hlth Sci Ctr, MSC 09 5350,1 Univ New Mexico, Albuquerque, NM 87131 USA. EM mparshall@salud.unm.edu FU National Institute of Nursing Research [1 R15 NR008883] FX Funded by a grant from the National Institute of Nursing Research (1 R15 NR008883). The opinions expressed in this article are solely those, of the authors. NR 78 TC 6 Z9 6 U1 1 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0147-9563 J9 HEART LUNG JI Heart Lung PD JAN-FEB PY 2012 VL 41 IS 1 BP 44 EP 56 DI 10.1016/j.hrtlng.2011.05.003 PG 13 WC Cardiac & Cardiovascular Systems; Nursing; Respiratory System SC Cardiovascular System & Cardiology; Nursing; Respiratory System GA 875KE UT WOS:000299028000008 PM 21794918 ER PT J AU Maleki, N Becerra, L Upadhyay, J Burstein, R Borsook, D AF Maleki, Nasim Becerra, Lino Upadhyay, Jaymin Burstein, Rami Borsook, David TI Direct optic nerve pulvinar connections defined by diffusion MR tractography in humans: Implications for photophobia SO HUMAN BRAIN MAPPING LA English DT Article DE tractography; nonimage forming pathway; visual pathway; thalamus; central sensitization; migraine; pain ID MACAQUE MONKEY; MOTOR CORTEX; NUCLEUS; PROJECTIONS; THALAMUS; BRAIN; MIGRAINE; PATHWAY; SYSTEM; AREAS AB The pathway that underlies exacerbation of migraine headache by light has not been elucidated in the human brain but has recently been reported in a rodent model. We employ diffusion weighted imaging and probabilistic tractography to map connectivity of direct pathways from the optic nerve to the pulvinar implicated with whole-body allodynia during migraine. Nine healthy subjects were recruited to the study and underwent scanning on a 3T magnet. We were able to define well-known image-forming (optic nerve -> lateral geniculate -> visual cortex) as well as a less known nonimage forming visual pathway from the optic chiasm to the pulvinar, and from the pulvinar to several associative cortical brain regions. Such pathway may allow photic signals to converge on a thalamic region we described recently to be selectively activated during migraine headache. Consistent with physiological and anatomical studies in rats, the data provide an anatomical substrate for exacerbation of migraine headache by light in the human. Hum Brain Mapp, 2012. (C) 2011 Wiley Periodicals, Inc. C1 [Maleki, Nasim; Becerra, Lino; Upadhyay, Jaymin; Borsook, David] Harvard Univ, Sch Med, McLean Hosp, PAIN Grp,Brain Imaging Ctr, Belmont, MA 02478 USA. [Becerra, Lino] Massachusetts Gen Hosp, Martinos Ctr, Charlestown, MA USA. [Burstein, Rami] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Anesthesia & Crit Care, Belmont, MA 02478 USA. RP Borsook, D (reprint author), Harvard Univ, Sch Med, McLean Hosp, PAIN Grp,Brain Imaging Ctr, 115 Mill St, Belmont, MA 02478 USA. EM dborsook@partners.org FU NINDS [R01 NS056195, K24 NS064050] FX NINDS; Contract grant numbers: R01 NS056195, K24 NS064050. NR 60 TC 30 Z9 31 U1 1 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD JAN PY 2012 VL 33 IS 1 BP 75 EP 88 DI 10.1002/hbm.21194 PG 14 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 869IH UT WOS:000298591100007 PM 21337474 ER PT J AU Anderson, J Wagner, J Bessesen, M Williams, LC AF Anderson, Judith Wagner, Julia Bessesen, Mary Williams, Linda C. TI Usability testing in the hospital SO HUMAN FACTORS AND ERGONOMICS IN MANUFACTURING & SERVICE INDUSTRIES LA English DT Article DE Patient safety; Usability; Hospital; Healthcare; Human factors engineering ID CONSULTATION; IMPROVE AB It is not unusual for hospitals to purchase equipment, devices, and materials based on preferences expressed by staff, based on economics and the best offer, or based on the promise of improvement by a new version. However, routinely subjecting potential purchases to basic usability testing provides valuable information upon which to base the decisions. Responsible manufacturers are interested in knowing of needed improvements to their products. Usability testing will also guide training for implementation. Usability testing is included in an introductory human factors engineering (HFE) session as part of a patient safety training course for physicians. Clinicians equipped with this skill are able to build evidence to support purchase decisions, make demands for improved design, and encourage a more thorough HFE evaluation by experts. (c) 2011 Wiley Periodicals, Inc. C1 [Anderson, Judith] VA Natl Ctr Patient Safety, Denver, CO USA. [Wagner, Julia; Bessesen, Mary] Denver VAMC, Denver, CO USA. [Williams, Linda C.] VA Natl Ctr Patient Safety, Ann Arbor, MI USA. RP Williams, LC (reprint author), 24 Frank Lloyd Wright Dr,M2100, Ann Arbor, MI 48106 USA. EM linbywilliams@gmail.com OI Bessesen, Mary/0000-0001-9305-1293 NR 16 TC 1 Z9 1 U1 2 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1090-8471 J9 HUM FACTOR ERGON MAN JI Hum. Factors Ergonom. Manuf. Serv. Ind. PD JAN-FEB PY 2012 VL 22 IS 1 SI SI BP 52 EP 63 DI 10.1002/hfm.20277 PG 12 WC Engineering, Manufacturing; Ergonomics SC Engineering GA 869JG UT WOS:000298593600006 ER PT J AU Lesselroth, BJ Dorr, DA Adams, K Church, V Adams, S Mazur, D Russ, Y Felder, R Douglas, DM AF Lesselroth, Blake J. Dorr, David A. Adams, Kathleen Church, Victoria Adams, Shawn Mazur, Dennis Russ, Yelizaveta Felder, Robert Douglas, David M. TI Medication review software to improve the accuracy of outpatient medication histories: protocol for a randomized controlled trial SO HUMAN FACTORS AND ERGONOMICS IN MANUFACTURING & SERVICE INDUSTRIES LA English DT Review DE Medication reconciliation; Medication errors; Technology assessment; Biomedical; Adverse drug events; Medical records systems; Computerized; Consumer health information ID ADVERSE DRUG EVENTS; HOSPITAL DISCHARGE; CLINICAL IMPORTANCE; RECONCILIATION; DISCREPANCIES; ERRORS; CARE; IMPLEMENTATION; ADMISSION; DESIGN AB Medication-prescribing errors generated at interfaces-in-care are the most common cause of preventable health care errors and contribute substantially to adverse patient outcomes. For this reason, standardized medication reconciliation (MR) processes need to be inserted at these interfaces. However, MR is an inherently complex task, and little data exist to inform system-based operationalization. The Portland Informatics Center addressed this challenge by creating an electronic patient-directed multimedia survey to automate the medication history collection. This article describes a research protocol designed to compare the software's medication discrepancy detection rate with traditional history collection strategies. For this randomized, controlled, single-blind trial, participants are randomly allocated into one of two groups: the control group reviews a paper list printed from the electronic record, whereas the intervention group uses a computer-assisted reconciliation survey that includes display of visual data (i.e., medication pictures). (c) 2011 Wiley Periodicals, Inc. C1 [Lesselroth, Blake J.; Adams, Kathleen; Church, Victoria; Adams, Shawn; Mazur, Dennis; Russ, Yelizaveta; Felder, Robert; Douglas, David M.] Portland Oregon Vet Affairs Med Ctr, Portland, OR USA. [Lesselroth, Blake J.; Dorr, David A.; Mazur, Dennis] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Lesselroth, BJ (reprint author), Portland VA Med Ctr, P3 MED,3710 SW US Vet Hosp Dr, Portland, OR 97239 USA. EM blake.lesselroth@va.gov FU VA National Center for Patient Safety FX The authors thank the VA National Center for Patient Safety for support of this project. The authors also thank Ms. Kelly Finley for assistance preparing this manuscript for publication. NR 56 TC 4 Z9 4 U1 1 U2 12 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1090-8471 J9 HUM FACTOR ERGON MAN JI Hum. Factors Ergonom. Manuf. Serv. Ind. PD JAN-FEB PY 2012 VL 22 IS 1 SI SI BP 72 EP 86 DI 10.1002/hfm.20287 PG 15 WC Engineering, Manufacturing; Ergonomics SC Engineering GA 869JG UT WOS:000298593600008 ER PT J AU Gerhard-Herman, M Smoot, LB Wake, N Kieran, MW Kleinman, ME Miller, DT Schwartzman, A Giobbie-Hurder, A Neuberg, D Gordon, LB AF Gerhard-Herman, Marie Smoot, Leslie B. Wake, Nicole Kieran, Mark W. Kleinman, Monica E. Miller, David T. Schwartzman, Armin Giobbie-Hurder, Anita Neuberg, Donna Gordon, Leslie B. TI Mechanisms of Premature Vascular Aging in Children With Hutchinson-Gilford Progeria Syndrome SO HYPERTENSION LA English DT Article DE Hutchinson-Gilford progeria syndrome; atherosclerosis; arteriosclerosis; arterial stiffness; lamin; aging ID ARTERIAL STIFFNESS; INDEPENDENT PREDICTOR; AORTIC STIFFNESS; CARDIOVASCULAR-DISEASE; HYPERTENSIVE PATIENTS; SENESCENCE; PHENOTYPE; MORTALITY; VELOCITY; DEFECTS AB Hutchinson-Gilford progeria syndrome is a rare, segmental premature aging syndrome of accelerated atherosclerosis and early death from myocardial infarction or stroke. This study sought to establish comprehensive characterization of the fatal vasculopathy in Hutchinson-Gilford progeria syndrome and its relevance to normal aging. We performed cardiovascular assessments at a single clinical site on the largest prospectively studied cohort to date. Carotid-femoral pulse wave velocity was dramatically elevated (mean: 13.00 +/- 3.83 m/s). Carotid duplex ultrasound echobrightness, assessed in predefined tissue sites as a measure of arterial wall density, was significantly greater than age-and sex-matched controls in the intima-media (P < 0.02), near adventitia (P < 0.003), and deep adventitia (P < 0.01), as was internal carotid artery mean flow velocity (P < 0.0001). Ankle-brachial indices were abnormal in 78% of patients. Effective disease treatments may be heralded by normalizing trends of these noninvasive cardiovascular measures. The data demonstrate that, along with peripheral vascular occlusive disease, accelerated vascular stiffening is an early and pervasive mechanism of vascular disease in Hutchinson-Gilford progeria syndrome. There is considerable overlap with cardiovascular changes of normal aging, which reinforces the view that defining mechanisms of cardiovascular disease in Hutchinson-Gilford progeria syndrome provides a unique opportunity to isolate a subset of factors influencing cardiovascular disease in the general aging population. (Hypertension. 2012;59:92-97.). Online Data Supplement C1 [Gordon, Leslie B.] Brown Univ, Dept Pediat, Hasbro Childrens Hosp, Warren Alpert Med Sch, Providence, RI 02903 USA. [Gerhard-Herman, Marie; Wake, Nicole] Brigham & Womens Hosp, Div Cardiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. [Smoot, Leslie B.] Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. [Kleinman, Monica E.; Gordon, Leslie B.] Childrens Hosp, Dept Anesthesia, Boston, MA 02115 USA. [Miller, David T.] Childrens Hosp, Dept Genet, Boston, MA 02115 USA. [Kieran, Mark W.] Childrens Hosp, Dept Pediat Oncol, Boston, MA 02115 USA. [Kieran, Mark W.] Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. [Schwartzman, Armin; Giobbie-Hurder, Anita; Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Schwartzman, Armin; Neuberg, Donna] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Gordon, LB (reprint author), Brown Univ, Dept Pediat, Hasbro Childrens Hosp, Warren Alpert Med Sch, 593 Eddy St, Providence, RI 02903 USA. EM Leslie.Gordon@brown.edu OI Kieran, Mark/0000-0003-2184-7692; Schwartzman, Armin/0000-0001-5335-1611 FU Progeria Research Foundation, Peabody, MA [PRFCLIN2007-01]; National Institutes of Health [MO1-RR02172, UL1 RR025758-01] FX The study was funded by the Progeria Research Foundation (PRFCLIN2007-01), Peabody, MA and by National Institutes of Health grants to the Children's Hospital Boston General Clinical Research Center (MO1-RR02172) and to the Harvard Catalyst Clinical and Translational Study Unit (UL1 RR025758-01). NR 36 TC 33 Z9 36 U1 2 U2 16 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD JAN PY 2012 VL 59 IS 1 BP 92 EP U229 DI 10.1161/HYPERTENSIONAHA.111.180919 PG 11 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 866SS UT WOS:000298403800019 PM 22083160 ER PT J AU Young, B Hacker, MR Rana, S AF Young, Brett Hacker, Michele R. Rana, Sarosh TI Physicians' Knowledge of Future Vascular Disease in Women with Preeclampsia SO HYPERTENSION IN PREGNANCY LA English DT Article DE Preeclampsia; Cardiovascular disease; Ischemic heart disease; Stroke; Primary prevention ID LONG-TERM MORTALITY; RETROSPECTIVE COHORT; RISK; PREGNANCY; HEALTH AB Objective. Preeclampsia, a hypertensive disorder of pregnancy, affects 5-8% of women. Large studies demonstrate a strong association between preeclampsia and future cardiovascular disease (CVD). Despite CVD being the leading cause of mortality for women, there has been little education for internal medicine physicians or obstetrician-gynecologists (ob-gyns) about this association; published guidelines do not include preeclampsia as a risk factor for future CVD. Therefore, women with a history of preeclampsia may not receive adequate risk-reduction counseling for CVD. It is unclear whether primary care physicians are aware of the association; thus, we sought to determine whether primary care providers at our institution were aware of preeclampsia's association with future CVD and whether they were providing appropriate counseling. Methods. An anonymous online survey was sent to all internists and (ob-gyns) at our hospital. Results. Although most internists (95%) and (ob-gyns) (70%) provide routine cardiovascular risk-reduction counseling, a substantial proportion of them were unaware of any health risk associated with a history of preeclampsia. Many internists were unsure or did not know whether preeclampsia is associated with ischemic heart disease (56%), stroke (48%), and decreased life expectancy (79%). The corresponding proportions for (ob-gyns) were 23, 38, and 77%, respectively. Only 9% of internists and 38% of obstetrician-gynecologists were providing cardiovascular risk-reduction counseling to women with a history of preeclampsia. Conclusion. There is limited knowledge of the association between preeclampsia and future CVD; this deficiency may limit the application of this risk factor to clinical care. C1 [Rana, Sarosh] Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Div Maternal Fetal Med, Boston, MA 02215 USA. [Young, Brett] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Div Maternal Fetal Med, Boston, MA 02114 USA. [Hacker, Michele R.] Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Div Reprod Endocrinol, Boston, MA 02215 USA. RP Rana, S (reprint author), Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Div Maternal Fetal Med, Res N 363,99 Brookline Ave, Boston, MA 02215 USA. EM srana1@bidmc.harvard.edu OI Hacker, Michele/0000-0003-0217-9991 FU NICHD NIH HHS [K12 HD001255, K12 HD001255-10] NR 17 TC 24 Z9 26 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1064-1955 J9 HYPERTENS PREGNANCY JI Hypertens. Pregnancy PY 2012 VL 31 IS 1 BP 50 EP 58 DI 10.3109/10641955.2010.544955 PG 9 WC Obstetrics & Gynecology; Physiology; Peripheral Vascular Disease SC Obstetrics & Gynecology; Physiology; Cardiovascular System & Cardiology GA 865FG UT WOS:000298295800006 PM 21332326 ER PT J AU Wang, LJ Trebicka, E Fu, Y Ellenbogen, S Hong, CC Babitt, JL Lin, HY Cherayil, BJ AF Wang, Lijian Trebicka, Estela Fu, Ying Ellenbogen, Shiri Hong, Charles C. Babitt, Jodie L. Lin, Herbert Y. Cherayil, Bobby J. TI The bone morphogenetic protein-hepcidin axis as a therapeutic target in inflammatory bowel disease SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE inflammation; iron; bone morphogenetic protein; hepcidin ID HEREDITARY HEMOCHROMATOSIS; IRON-METABOLISM; IL-10-DEFICIENT MICE; MOUSE MODEL; EXPRESSION; COLITIS; HFE; BMP6; GENE; DEFICIENCY AB Background: A debilitating anemia associated with low serum iron often accompanies inflammatory bowel disease (IBD). Increased production of the iron regulatory hormone hepcidin is implicated in its pathogenesis and may also contribute to the inflammatory process itself. Hepcidin expression is dependent on bone morphogenetic proteins (BMPs) like BMP6, but the mechanisms that increase hepcidin levels during intestinal inflammation are not clear. Here we test the hypothesis that inhibiting hepcidin expression may have beneficial effects in IBD, and also shed light on the mechanism of colitis-induced hepcidin upregulation. C1 [Wang, Lijian; Trebicka, Estela; Fu, Ying; Ellenbogen, Shiri; Cherayil, Bobby J.] Massachusetts Gen Hosp, Mucosal Immunol Lab, Charlestown, MA USA. [Hong, Charles C.] Vanderbilt Univ, Med Ctr, Vet Affairs TVHS, Nashville, TN USA. [Hong, Charles C.] Vanderbilt Univ, Med Ctr, Div Cardiovasc Med, Nashville, TN USA. [Babitt, Jodie L.; Lin, Herbert Y.] Massachusetts Gen Hosp, Div Nephrol, Program Membrane Biol, Boston, MA 02114 USA. [Babitt, Jodie L.; Lin, Herbert Y.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Cherayil, Bobby J.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Cherayil, BJ (reprint author), MGH E, Pediat Gastroenterol Unit, Bldg 114,16th St, Boston, MA 02129 USA. EM cherayil@helix.mgh.harvard.edu RI Fu, Ying/G-2899-2015 FU Broad Medical Research Program [IBD-0253]; National Institutes of Health [R56 AI089700]; Wyeth Nutrition FX Supported by grants from the Broad Medical Research Program (IBD-0253) and the National Institutes of Health (R56 AI089700) to B.J.C., and by an unrestricted educational grant from Wyeth Nutrition to L.W. NR 41 TC 29 Z9 33 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD JAN PY 2012 VL 18 IS 1 BP 112 EP 119 DI 10.1002/ibd.21675 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 865TL UT WOS:000298333100018 PM 21351217 ER PT J AU Viswanathan, AN Moughan, J Small, W Levenback, C Iyer, R Hymes, S Dicker, AP Miller, B Erickson, B Gaffney, DK AF Viswanathan, Akila N. Moughan, Jennifer Small, William, Jr. Levenback, Charles Iyer, Revathy Hymes, Sharon Dicker, Adam P. Miller, Brigitte Erickson, Beth Gaffney, David K. TI The Quality of Cervical Cancer Brachytherapy Implantation and the Impact on Local Recurrence and Disease-Free Survival in Radiation Therapy Oncology Group Prospective Trials 0116 and 0128 SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Article DE Brachytherapy quality; Cervical cancer ID EXTENDED-FIELD IRRADIATION; SQUAMOUS-CELL CARCINOMA; ILIAC LYMPH-NODES; UTERINE CERVIX; CISPLATIN CHEMOTHERAPY; RADIOTHERAPY PRACTICE; PATTERNS; CARE; RTOG-0116; CELECOXIB AB Purpose: The objective of the study was to determine the impact of brachytherapy implant quality on outcome among cervical cancer patients treated on Radiation Therapy Oncology Group prospective trials 0116 and 0128. Methods: All enrolled patients received concurrent chemoradiation followed by brachytherapy. Individual brachytherapy parameters, including the symmetry of ovoids in relation to the tandem, displacement of ovoids in relation to the cervical os, tandem bisecting the ovoids, tandem in the midpelvis, and appropriateness of packing, were scored for each implant. Multivariate Cox proportional hazards models were constructed for each parameter for local recurrence (LR), regional recurrence, distant recurrence, disease-free survival (DFS), and overall survival. Results: Records for 103 patients were analyzed. The median follow-up time was 24.5 months. Patients with unacceptable symmetry of ovoids to the tandem had a significantly higher risk of LR than patients in the acceptable group (hazard ratio [HR], 2.67; 95% confidence interval [CI], 1.11-6.45; P = 0.03). Patients with displacement of ovoids in relation to the cervical os had a significantly increased risk of LR (HR, 2.50; 95% CI, 1.05-5.93; P = 0.04) and a lower DFS rate (HR, 2.28; 95% CI, 1.18-4.41; P = 0.01). Inappropriate placement of packing resulted in a lower DFS rate (HR, 2.06; 95% CI, 1.08-3.92; P = 0.03). Conclusions: Assessment of the quality of a brachytherapy implant is imperative, as proper placement has an impact on patient DFS. If feasible, inappropriate placements should be corrected before treatment initiation. Brachytherapy applicators for cervical cancer should preferably be placed and assessed by experienced practitioners. C1 [Viswanathan, Akila N.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Radiat Oncol, Boston, MA 02115 USA. [Moughan, Jennifer] Amer Coll Radiol, Ctr Stat, Radiat Therapy Oncol Grp, Philadelphia, PA 90034 USA. [Small, William, Jr.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [Levenback, Charles; Iyer, Revathy; Hymes, Sharon] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Dicker, Adam P.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Miller, Brigitte] Batte Canc Ctr, Concord, NC USA. [Erickson, Beth] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Gaffney, David K.] Univ Utah, Huntsman Canc Ctr, Salt Lake City, UT USA. RP Viswanathan, AN (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Radiat Oncol, 75 Francis St,L2, Boston, MA 02115 USA. EM aviswanathan@lroc.harvard.edu OI Dicker, Adam/0000-0003-0733-3337 FU NCI NIH HHS [U10 CA21661, U10 CA021661, U10 CA037422, U10 CA37422, K07 CA117979, K07 CA117979-05] NR 27 TC 24 Z9 24 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1048-891X J9 INT J GYNECOL CANCER JI Int. J. Gynecol. Cancer PD JAN PY 2012 VL 22 IS 1 BP 123 EP 131 DI 10.1097/IGC.0b013e31823ae3c9 PG 9 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 869WI UT WOS:000298628800022 PM 22193645 ER PT J AU Young, RH AF Young, Robert H. TI History of Gynecological Pathology XXIV. Dr Cuthbert Lockyer SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Biographical-Item DE Cuthbert Lockyer; Historical essay; Histopathology C1 Harvard Univ, James Homer Wright Pathol Labs, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Young, RH (reprint author), Harvard Univ, James Homer Wright Pathol Labs, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. EM rhyoung@partners.org NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD JAN PY 2012 VL 31 IS 1 BP 38 EP 47 DI 10.1097/PGP.0b013e31823bb0d9 PG 10 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA 863EW UT WOS:000298146600006 PM 22123722 ER PT J AU Zietman, AL AF Zietman, Anthony L. TI RECEIVING THE TORCH SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Zietman, AL (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Cox 302,100 Blossom St, Boston, MA 02114 USA. EM azietman@partners.org NR 0 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JAN PY 2012 VL 82 IS 1 BP 1 EP 2 DI 10.1016/j.ijrobp.2011.10.008 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 868LZ UT WOS:000298526100001 ER PT J AU Chen, WC Kim, J Kim, E Silverman, P Overmoyer, B Cooper, BW Anthony, S Shenk, R Leeming, R Hanks, SH Lyons, JA AF Chen, William C. Kim, Janice Kim, Edward Silverman, Paula Overmoyer, Beth Cooper, Brenda W. Anthony, Sue Shenk, Robert Leeming, Rosemary Hanks, Shelli H. Lyons, Janice A. TI A PHASE II STUDY OF RADIOTHERAPY AND CONCURRENT PACLITAXEL CHEMOTHERAPY IN BREAST-CONSERVING TREATMENT FOR NODE-POSITIVE BREAST CANCER SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Breast; Radiation; Chemoradiation ID CELL LUNG-CANCER; RADIATION-THERAPY; CONSERVATIVE SURGERY; ADJUVANT CHEMOTHERAPY; LOCAL-CONTROL; STAGE-II; RISK; CHEMORADIOTHERAPY; DOXORUBICIN; CYCLOPHOSPHAMIDE AB Purpose: Administering adjuvant chemotherapy before breast radiotherapy decreases the risk of systemic recurrence, but delays in radiotherapy could yield higher local failure. We assessed the feasibility and efficacy of placing radiotherapy earlier in the breast-conserving treatment course for lymph node positive breast cancer. Methods and Materials: Between June 2000 and December 2004, 44 women with node-positive Stage II and III breast cancer were entered into this trial. Breast-conserving surgery and 4 cycles of doxorubicin (60 mg/m(2))/cyclophosphamide (600 mg/m2) were followed by 4 cycles of paclitaxel (175 mg/m2) delivered every 3 weeks. Radiotherapy was concurrent with the first 2 cycles of paclitaxel. The breast received 39.6 Gy in 22 fractions with a tumor bed boost of 14 Gy in 7 fractions. Regional lymphatics were included when indicated. Functional lung volume was assessed by use of the diffusing capacity for carbon monoxide as a proxy. Breast cosmesis was evaluated with the Harvard criteria. Results: The 5-year actuarial rate of disease-free survival is 88%, and overall survival is 93%. There have been no local failures. Median follow-up is 75 months. No cases of radiation pneumonitis developed. There was no significant change in the diffusing capacity for carbon monoxide either immediately after radiotherapy (p = 0.51) or with extended follow-up (p = 0.63). Volume of irradiated breast tissue correlated with acute cosmesis, and acute Grade 3 skin toxicity developed in 2 patients. Late cosmesis was not adversely affected. Conclusions: Concurrent paclitaxel chemotherapy and radiotherapy after breast-conserving surgery shortened total treatment time, provided excellent local control, and was well tolerated. (C) 2012 Elsevier Inc. C1 [Chen, William C.; Anthony, Sue; Lyons, Janice A.] Univ Hosp Case Med Ctr, Dept Radiat Oncol, Cleveland, OH 44106 USA. [Silverman, Paula; Cooper, Brenda W.] Univ Hosp Case Med Ctr, Dept Med, Cleveland, OH 44106 USA. [Shenk, Robert; Leeming, Rosemary] Univ Hosp Case Med Ctr, Dept Surg, Cleveland, OH 44106 USA. [Kim, Janice] Univ Washington, Med Ctr, Dept Radiat Oncol, Seattle, WA 98195 USA. [Kim, Edward] Ohio State Univ, Med Ctr, Dept Radiat Oncol, Columbus, OH 43210 USA. [Overmoyer, Beth] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Hanks, Shelli H.] Arizona Inst Urol, Tucson, AZ USA. RP Lyons, JA (reprint author), Univ Hosp Case Med Ctr, Dept Radiat Oncol, 11100 Euclid Ave, Cleveland, OH 44106 USA. EM janice.lyons@uhhospitals.org NR 42 TC 4 Z9 5 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JAN PY 2012 VL 82 IS 1 BP 14 EP 20 DI 10.1016/j.ijrobp.2010.08.051 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 868LZ UT WOS:000298526100005 PM 21035961 ER PT J AU Kelly, PJ Lin, YIB Yu, AY Alexander, BM Hacker, F Marcus, KJ Weiss, SE AF Kelly, Paul J. Lin, Yijie Brittany Yu, Alvin Y. Alexander, Brian M. Hacker, Fred Marcus, Karen J. Weiss, Stephanie E. TI STEREOTACTIC IRRADIATION OF THE POSTOPERATIVE RESECTION CAVITY FOR BRAIN METASTASIS: A FRAMELESS LINEAR ACCELERATOR-BASED CASE SERIES AND REVIEW OF THE TECHNIQUE SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Stereotactic radiosurgery; Hypofractionated stereotactic radiotherapy; Brain metastasis; Resection cavity; Whole brain radiotherapy ID CEREBRAL METASTASES; RADIOSURGERY BOOST; SINGLE METASTASES; RANDOMIZED-TRIAL; RADIOTHERAPY; RADIATION; PROGRESSION; DISEASE AB Purpose: Whole-brain radiation therapy (WBRT) is the standard of care after resection of a brain metastasis. However, concern regarding possible neurocognitive effects and the lack of survival benefit with this approach has led to the use of stereotactic radiosurgery (SRS) to the resection cavity in place of WBRT. We report our initial experience using an image-guided linear accelerator-based frameless stereotactic system and review the technical issues in applying this technique. Methods and Materials: We retrospectively reviewed the setup accuracy, treatment outcome, and patterns of failure of the first 18 consecutive cases treated at Brigham and Women's Hospital. The target volume was the resection cavity without a margin excluding the surgical track. Results: The median number of brain metastases per patient was 1 (range; 1-3). The median planning target volume was 3.49 mL. The median prescribed dose was 18 Gy (range, 15-18 Gy) with normalization ranging from 68% to 85%. In all cases, 99% of the planning target volume was covered by the prescribed dose. The median conformity index was 1.6 (range, 1.41-1.92). The SRS was delivered with submillimeter accuracy. At a median follow-up of 12.7 months, local control was achieved in 16/18 cavities treated. True local recurrence occurred in 2 patients. No marginal failures occurred. Distant recurrence occurred in 6/17 patients. Median time to any failure was 7.4 months. No Grade 3 or higher toxicity was recorded. A long interval between initial cancer diagnosis and the development of brain metastasis was the only factor that trended toward a significant association with the absence of recurrence (local or distant) (log-rank p = 0.097). Conclusions: Frameless stereotactic irradiation of the resection cavity after surgery for a brain metastasis is a safe and accurate technique that offers durable local control and defers the use of WBRT in select patients. This technique should be tested in larger prospective studies. (C) 2012 Elsevier Inc. C1 [Kelly, Paul J.; Alexander, Brian M.; Hacker, Fred; Marcus, Karen J.; Weiss, Stephanie E.] Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA USA. [Lin, Yijie Brittany; Yu, Alvin Y.] Harvard Univ, Sch Med, Boston, MA USA. RP Kelly, PJ (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,ASB1,L2, Boston, MA 02115 USA. EM pkelly@lroc.harvard.edu OI Hacker, Fred/0000-0001-7535-7598 FU European Association of Neurooncology FX This abstract was presented as an oral presentation at the 9th Congress of the European Association of Neurooncology, Maastricht, Netherlands, September 16-19, 2010. A travel grant was awarded by the European Association of Neurooncology. NR 22 TC 35 Z9 36 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JAN PY 2012 VL 82 IS 1 BP 95 EP 101 DI 10.1016/j.ijrobp.2010.10.043 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 868LZ UT WOS:000298526100016 PM 21168282 ER PT J AU Kachnic, LA Tsai, HK Coen, JJ Blaszkowsky, LS Hartshorn, K Kwak, EL Willins, JD Ryan, DP Hong, TS AF Kachnic, Lisa A. Tsai, Henry K. Coen, John J. Blaszkowsky, Lawrence S. Hartshorn, Kevan Kwak, Eunice L. Willins, John D. Ryan, David P. Hong, Theodore S. TI DOSE-PAINTED INTENSITY-MODULATED RADIATION THERAPY FOR ANAL CANCER: A MULTI-INSTITUTIONAL REPORT OF ACUTE TOXICITY AND RESPONSE TO THERAPY SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Anal cancer; Chemoradiation; IMRT; Acute toxicity ID HIV-POSITIVE PATIENTS; SQUAMOUS-CELL CARCINOMA; RANDOMIZED-TRIAL; CONCURRENT CHEMOTHERAPY; TREATMENT TOLERANCE; CANAL CARCINOMA; PHASE-II; RADIOTHERAPY; IMRT; MITOMYCIN AB Purpose: Chemoradiation for anal cancer yields effective tumor control, but is associated with significant acute toxicity. We report our multi-institutional experience using dose-painted IMRT (DP-IMRT). Patients and Methods: Between August 2005 and May 2009,43 patients were treated with DP-IMRT and concurrent chemotherapy for biopsy-proven, squamous cell carcinoma of the anal canal at two academic medical centers. DP-IMRT was prescribed as follows: T2N0: 42 Gy, 1.5 Gy/fraction (fx) to elective nodal planning target volume (PTV) and 50.4 Gy, 1.8 Gy/fx to anal tumor PTV; T3-4N0-3: 45 Gy, 1.5 Gy/fx to elective nodal PTV, and 54 Gy, 1.8 Gy/fx to the anal tumor and metastatic nodal PTV >3 cm with 50.4 Gy, 1.68 Gy/fx to nodal PTVs <= 3 cm in size. Acute and late toxicity was reported by the treating physician. Actuarial analysis was performed using the Kaplan-Meier method. Results: Median age was 58 years; 67% female; 16% Stage I, 37% II; 42% III; 5% IV. Fourteen patients were immunocompromised: 21% HIV-positive and 12% on chronic immunosuppression. Median follow-up was 24 months (range, 0.6-43.5 months). Sixty percent completed chemoradiation without treatment interruption; median duration of treatment interruption was 2 days (range, 2-24 days). Acute Grade 3+ toxicity included: hematologic 51%, dermatologic 10%, gastrointestinal 7%, and genitourinary 7%. Two-year local control, overall survival, colostomy-free survival, and metastasis-free survival were 95%, 94%, 90%, and 92%, respectively. Conclusions: Dose-painted IMRT appears effective and well-tolerated as part of a chemoradiation therapy regimen for the treatment of anal canal cancer. (C) 2012 Elsevier Inc. C1 [Kachnic, Lisa A.; Willins, John D.] Boston Med Ctr, Dept Radiat Oncol, LL, Boston, MA 02118 USA. [Hartshorn, Kevan] Boston Med Ctr, Dept Med, Boston, MA 02118 USA. [Tsai, Henry K.] Harvard Univ, Sch Med, Harvard Radiat Oncol Program, Boston, MA USA. [Kachnic, Lisa A.; Coen, John J.; Willins, John D.; Hong, Theodore S.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Blaszkowsky, Lawrence S.; Kwak, Eunice L.; Ryan, David P.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Kachnic, LA (reprint author), Boston Med Ctr, Dept Radiat Oncol, LL, 830 Harrison Ave, Boston, MA 02118 USA. EM lisa.kachnic@bmc.org OI Hartshorn, Kevan/0000-0002-7196-7433 NR 25 TC 61 Z9 63 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JAN PY 2012 VL 82 IS 1 BP 153 EP 158 DI 10.1016/j.ijrobp.2010.09.030 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 868LZ UT WOS:000298526100024 PM 21095071 ER PT J AU Viswanathan, AN Creutzberg, CL Craighead, P McCormack, M Toita, T Narayan, K Reed, N Long, H Kim, HJ Marth, C Lindegaard, JC Cerrotta, A Small, W Trimble, E AF Viswanathan, Akila N. Creutzberg, Carien L. Craighead, Peter McCormack, Mary Toita, Takafumi Narayan, Kailash Reed, Nicholas Long, Harry Kim, Hak-Jae Marth, Christian Lindegaard, Jacob C. Cerrotta, Annmarie Small, William, Jr. Trimble, Edward TI INTERNATIONAL BRACHYTHERAPY PRACTICE PATTERNS: A SURVEY OF THE GYNECOLOGIC CANCER INTERGROUP (GCIG) SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Brachytherapy; Cervical cancer; Radiation dose ID HIGH-DOSE-RATE; CERVICAL-CANCER; INTRACAVITARY BRACHYTHERAPY; FRACTIONATION SCHEDULE; RADIOTHERAPY; RECOMMENDATIONS; CARCINOMA; TRIAL AB Purpose: To determine current practice patterns with regard to gynecologic high-dose-rate (HDR) brachytherapy among international members of the Gynecologic Cancer Intergroup (GCIG) in Japan/Korea (Asia), Australia/New Zealand (ANZ), Europe (E), and North America (NAm). Methods and Materials: A 32-item survey was developed requesting information on brachytherapy practice patterns and standard management for Stage IB-IVA cervical cancer. The chair of each GCIG member cooperative group selected radiation oncology members to receive the survey. Results: A total of 72 responses were analyzed; 61 respondents (85%) used HDR. The three most common HDR brachytherapy fractionation regimens for Stage IB-IIA patients were 6 Gy for five fractions (18%), 6 Gy for four fractions (15%), and 7 Gy for three fractions (11%); for Stage IIB-IVA patients they were 6 Gy for five fractions (19%), 7 Gy for four fractions (8%), and 7 Gy for three fractions (8%). Overall, the mean combined external-beam and brachytherapy equivalent dose (EQD2) was 81.1 (standard deviation [SD] 10.16). The mean EQD2 recommended for Stage IB-IIA patients was 78.9 Gy (SD 10.7) and for Stage IIB-IVA was 83.3 Gy (SD 11.2) (p = 0.02). By region, the mean combined EQD2 was as follows: Asia, 71.2 Gy (SD 12.65); ANZ, 81.18 (SD 4:96); E, 83.24 (SD 10.75); and NAm, 81.66 (SD, 6.05;p = 0.02 for Asia vs. other regions). The ratio of brachytherapy to total prescribed dose was significantly higher for Japan (p = 0.0002). Conclusion: Although fractionation patterns may vary, the overall mean doses administered for cervical cancer are similar in Australia/New Zealand, Europe, and North America, with practitioners in Japan administering a significantly lower external-beam dose but higher brachytherapy dose to the cervix. Given common goals, standardization should be possible in future clinical trials. (C) 2012 Elsevier Inc. C1 [Viswanathan, Akila N.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [Viswanathan, Akila N.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Creutzberg, Carien L.] Leiden Univ, Med Ctr, Dept Clin Oncol, Leiden, Netherlands. [Craighead, Peter] Tom Baker Canc Clin, Calgary, AB, Canada. [McCormack, Mary] Univ Coll London Hosp, Dept Oncol, London, England. [Toita, Takafumi] Univ Ryukyus, Grad Sch Med Sci, Dept Radiol, Okinawa, Japan. [Narayan, Kailash] Univ Melbourne, Peter MacCallum Canc Ctr, Div Radiat Oncol, Melbourne, Vic, Australia. [Narayan, Kailash] Univ Melbourne, Dept Obstet & Gynecol, Melbourne, Vic, Australia. [Reed, Nicholas] Western Infirm & Associated Hosp, Beatson Oncol Ctr, Glasgow G11 6NT, Lanark, Scotland. [Long, Harry] Mayo Clin, Coll Med, Dept Oncol, Div Med Oncol, Rochester, MN USA. [Kim, Hak-Jae] Seoul Natl Univ Hosp, Dept Oncol, Seoul 110744, South Korea. [Marth, Christian] Med Univ Innsbruck, Innsbruck, Austria. [Lindegaard, Jacob C.] Aarhus Univ Hosp, DK-8000 Aarhus, Denmark. [Cerrotta, Annmarie] Fdn IRCCS Ist Nazl Tumori, Dept Radiat Therapy, Milan, Italy. [Small, William, Jr.] Robert H Lurie Comprehens Canc NW Univ, Chicago, IL USA. [Trimble, Edward] NCI, Bethesda, MD 20892 USA. RP Viswanathan, AN (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St L2, Boston, MA 02115 USA. EM aviswanathan@lroc.harvard.edu RI Cerrotta, Annamaria/D-8063-2017; OI Cerrotta, Annamaria/0000-0001-7926-3716; Viswanathan, Akila/0000-0002-2003-0392 FU NCI NIH HHS [K07 CA117979] NR 20 TC 59 Z9 60 U1 2 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JAN PY 2012 VL 82 IS 1 BP 250 EP 255 DI 10.1016/j.ijrobp.2010.10.030 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 868LZ UT WOS:000298526100037 PM 21183288 ER PT J AU Schoenfeld, JD Sher, DJ Norris, CM Haddad, RI Posner, MR Balboni, TA Tishler, RB AF Schoenfeld, Jonathan D. Sher, David J. Norris, Charles M., Jr. Haddad, Robert I. Posner, Marshall R. Balboni, Tracy A. Tishler, Roy B. TI SALIVARY GLAND TUMORS TREATED WITH ADJUVANT INTENSITY-MODULATED RADIOTHERAPY WITH OR WITHOUT CONCURRENT CHEMOTHERAPY SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Chemoradiotherapy; Salivary gland cancers; Intensity-modulated radiotherapy; Adenoid cystic carcinoma; Mucoepidermoid carcinoma ID ADENOID CYSTIC CARCINOMA; COOPERATIVE-ONCOLOGY-GROUP; SQUAMOUS-CELL CARCINOMA; RADIATION-THERAPY; NECK-CANCER; PHASE-II; HEAD; SURGERY; CHEMORADIOTHERAPY; MALIGNANCIES AB Purpose: To analyze the recent single-institution experience of patients with salivary gland tumors who had undergone adjuvant intensity-modulated radiotherapy (IMRT), with or without concurrent chemotherapy. Patients and Methods: We performed a retrospective analysis of 35 salivary gland carcinoma patients treated primarily at the Dana-Farber Cancer Institute between 2005 and 2010 with surgery and adjuvant IMRT. The primary endpoints were local control, progression-free survival, and overall survival. The secondary endpoints were acute and chronic toxicity. The median follow-up was 2.3 years (interquartile range, 1.2-2.8) among the surviving patients. Results: The histologic types included adenoid cystic carcinoma in 15 (43%), mucoepidermoid carcinoma in 6 (17%), adenocarcinoma in 3 (9%), acinic cell carcinoma in 3 (9%), and other in 8 (23%). The primary sites were the parotid gland in 17 (49%), submandibular glands in 6 (17%), tongue in 4 (11%), palate in 4 (11%), and other in 4(11%). The median radiation dose was 66 Gy, and 22 patients (63%) received CRT. The most common chemotherapy regimen was carboplatin and paclitaxel (n = 14, 64%). A trend was seen for patients undergoing CRT to have more adverse prognostic factors, including Stage T3-T4 disease (CRT, n = 12, 55% vs. n = 4, 31%, p = .29), nodal positivity (CRT, n = 8, 36% vs. n = 1, 8%, p = .10), and positive margins (n = 13, 59% vs. n = 5, 38%, p = .30). One patient who had undergone CRT developed an in-field recurrence, resulting in an overall actuarial 3-year local control rate of 92%. Five patients (14%) developed distant metastases (1 who had undergone IMRT only and 4 who had undergone CRT). Acute Grade 3 mucositis, esophagitis, and dermatitis occurred in 8%, 8%, and 8% (1 each) of IMRT patients and in 18%, 5%, and 14% (4, 1, and 3 patients) of the CRT group, respectively. No acute Grade 4 toxicity occurred. The most common late toxicity was Grade 1 xerostomia (n = 8, 23%). Conclusions: Treatment of salivary gland malignancies with postoperative IMRT was well tolerated with a high rate of local control. Chemoradiotherapy resulted in excellent local control in a subgroup of patients with adverse prognostic factors and might be warranted in select patients. (C) 2012 Elsevier Inc. C1 [Schoenfeld, Jonathan D.] Harvard Radiat Oncol Program, Dept Radiat Oncol, Boston, MA 02114 USA. [Sher, David J.; Balboni, Tracy A.; Tishler, Roy B.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Norris, Charles M., Jr.] Brigham & Womens Hosp, Div Otolaryngol, Dept Surg, Boston, MA 02115 USA. [Haddad, Robert I.; Posner, Marshall R.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Haddad, Robert I.; Posner, Marshall R.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Schoenfeld, JD (reprint author), Harvard Radiat Oncol Program, Dept Radiat Oncol, 75 Francis St, Boston, MA 02114 USA. EM jdschoenfeld@partners.org NR 25 TC 32 Z9 33 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JAN PY 2012 VL 82 IS 1 BP 308 EP 314 DI 10.1016/j.ijrobp.2010.09.042 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 868LZ UT WOS:000298526100045 PM 21075557 ER PT J AU Haglund, KE Raut, CP Nascimento, AF Wang, Q George, S Baldini, EH AF Haglund, Karl E. Raut, Chandrajit P. Nascimento, Alessandra F. Wang, Qian George, Suzanne Baldini, Elizabeth H. TI RECURRENCE PATTERNS AND SURVIVAL FOR PATIENTS WITH INTERMEDIATE- AND HIGH-GRADE MYXOFIBROSARCOMA SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Myxofibrosarcoma; surgery; radiation therapy; amputalion; extremity sarcoma ID SOFT-TISSUE SARCOMAS; LIMB-SPARING SURGERY; PROGNOSTIC-FACTORS; SURGICAL MARGINS; RADIATION-THERAPY; RANDOMIZED-TRIAL; LOCAL RECURRENCE; CLINICOPATHOLOGICAL ANALYSIS; POSTOPERATIVE RADIOTHERAPY; ADJUVANT CHEMOTHERAPY AB Purpose: Myxofibrosarcoma (MFS) is a rare sarcoma with a predilection for multiple local recurrences (LR), for which optimal treatment has not been defined. We reviewed our experience to determine the impact of surgery and radiation therapy (RT) on pattern of recurrence, limb salvage, and overall survival (OS). Methods and Materials: Between 1995 and 2005, 36 patients with localized intermediate-or high-grade MFS were treated at our institution. Data on clinicopathologic features, treatments, and patient outcomes were reviewed and analyzed. Results: Median age was 72.5 years (range, 42-96 years). Median tumor size was 7.5 cm, and 34 tumors (94%) were high grade. All patients underwent surgery at our institution, including re-resections in 20 patients (56%) after initial surgery elsewhere. Margins were microscopically positive in 9 patients (25%). RT was given to 28 patients (78%) pre - and/or postoperatively. After a median follow-up of 3.5 years (range, 0.4-12.4 years), 11 patients (31%) developed LR. There were no significant predictors for L:R on univariate analysis, including margin status or use of RT. Limb salvage was ultimately achieved in only 5 of 11 LRs (45%) because of multiple subsequent LRs. Distant recurrence (DR) occurred in 6 patients (17%). Median and 4-year OS were 96 months and 65%, respectively. Seven patients (19%) died of tumor-related causes, 6 of whom had DRs. On univariate analysis, tumor size was associated with OS. Conclusions: Despite aggressive surgery and RT, intermediate-and high-grade MFS are associated with a high rate of LR that adversely affects limb preservation. More aggressive local treatment strategies are necessary. (C) 2012 Elsevier Inc. C1 [Baldini, Elizabeth H.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [Raut, Chandrajit P.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Nascimento, Alessandra F.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [George, Suzanne] Brigham & Womens Hosp, Dept Med Oncol, Boston, MA 02115 USA. [Haglund, Karl E.] Brigham & Womens Hosp, Harvard Radiat Oncol Program, Boston, MA 02115 USA. [Raut, Chandrajit P.; Wang, Qian; George, Suzanne; Baldini, Elizabeth H.] Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. RP Baldini, EH (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,ASB1-L2, Boston, MA 02115 USA. EM ebaldini@LROC.Harvard.edu NR 34 TC 19 Z9 19 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JAN PY 2012 VL 82 IS 1 BP 361 EP 367 DI 10.1016/j.ijrobp.2010.08.042 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 868LZ UT WOS:000298526100053 PM 20951504 ER PT J AU Bradley, J Bae, K Choi, N Forster, K Siegel, BA Brunetti, J Purdy, J Faria, S Vu, T Thorstad, W Choy, H AF Bradley, Jeffrey Bae, Kyounghwa Choi, Noah Forster, Ken Siegel, Barry A. Brunetti, Jacqueline Purdy, James Faria, Sergio Vu, Toni Thorstad, Wade Choy, Hak TI A PHASE II COMPARATIVE STUDY OF GROSS TUMOR VOLUME DEFINITION WITH OR WITHOUT PET/CT FUSION IN DOSIMETRIC PLANNING FOR NON-SMALL-CELL LUNG CANCER (NSCLC): PRIMARY ANALYSIS OF RADIATION THERAPY ONCOLOGY GROUP (RTOG) 0515 SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Lung cancer; FDG-PET; Mediastinal nodal staging; mediastinum AB Background: Radiation Therapy Oncology Group (RTOG) 0515 is a Phase II prospective trial designed to quantify the impact of positron emission tomography (PET)/computed tomography (CT) compared with CT alone on radiation treatment plans (RTPs) and to determine the rate of elective nodal failure for PET/CT-derived volumes. Methods: Each enrolled patient underwent definitive radiation therapy for non small-cell lung cancer (>= 60 Gy) and had two RTP datasets generated: gross tumor volume (GTV) derived with CTalone and with PET/CT. Patients received treatment using the PET/CT-derived plan. The primary end point, the impact of PET/CT fusion on treatment plans was measured by differences of the following variables for each patient: GTV, number of involved nodes, nodal station, mean lung dose (MLD), volume of lung exceeding 20 Gy (V20), and mean esophageal dose (MED). Regional failure rate was a secondary end point. The nonparametric Wilcoxon matched-pairs signed-ranks test was used with Bonferroni adjustment for an overall significance level of 0.05. Results: RTOG 0515 accrued 52 patients, 47 of whom are evaluable. The follow-up time for all patients is 12.9 months (2.7-22.2). Tumor staging was as follows: 11 = 6%; IIIA = 40%; and IIIB = 54%. The GTV was statistically significantly smaller for PET/CT-derived volumes (98.7 vs. 86.2 mL; p < 0.0001). MLDs for PET/CT plans were slightly lower (19 vs. 17.8 Gy; p = 0.06). There was no significant difference in the number of involved nodes (2.1 vs. 2.4), V20 (32% vs. 30.8%), or MED (28.7 vs. 27.1 Gy). Nodal contours were altered by PET/CT for 51% of patients. One patient (2%) has developed an elective nodal failure. Conclusions: PET/CT-derived tumor volumes were smaller than those derived by CT alone. PET/CT changed nodal GTV contours in 51% of patients. The elective nodal failure rate for GTVs derived by PET/CT is quite low, supporting the RTOG standard of limiting the target volume to the primary tumor and involved nodes. (C) 2012 Elsevier Inc. C1 [Bradley, Jeffrey] Washington Univ, Sch Med, Dept Radiat Oncol, Alvin J Siteman Comprehens Canc Ctr, Washington, DC USA. [Bae, Kyounghwa] RTOG, Dept Stat, Philadelphia, PA USA. [Choi, Noah] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Forster, Ken] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Brunetti, Jacqueline] Holy Name Med Ctr, Teaneck, NJ USA. [Purdy, James] Univ Calif Davis, Davis, CA 95616 USA. [Faria, Sergio] McGill Univ, Montreal, PQ, Canada. [Vu, Toni] Univ Montreal, Notre Dame Hosp, Ctr Hosp Univ Montreal, Montreal, PQ H3C 3J7, Canada. [Choy, Hak] Univ Texas SW, Dallas, TX USA. RP Bradley, J (reprint author), Washington Univ, Sch Med, Dept Radiat Oncol, Alvin J Siteman Comprehens Canc Ctr, 4921 Parkview Pl, Washington, DC USA. EM jbradley@wustl.edu FU RTOG [U10 CA21661]; CCOP [U10 CA37422]; National Cancer Institute (NCI) [U24 CA81647] FX This project was supported by RTOG grant U10 CA21661, CCOP grant U10 CA37422, and ATC grant U24 CA81647 from the National Cancer Institute (NCI). NR 6 TC 28 Z9 30 U1 1 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JAN PY 2012 VL 82 IS 1 BP 435 EP 441 DI 10.1016/j.ijrobp.2010.09.033 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 868LZ UT WOS:000298526100062 PM 21075551 ER PT J AU Gandhi, NR Andrews, JR Brust, JCM Montreuil, R Weissman, D Heo, M Moll, AP Friedland, GH Shah, NS AF Gandhi, N. R. Andrews, J. R. Brust, J. C. M. Montreuil, R. Weissman, D. Heo, M. Moll, A. P. Friedland, G. H. Shah, N. S. TI Risk factors for mortality among MDR- and XDR-TB patients in a high HIV prevalence setting SO INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE LA English DT Article DE MDR-TB; XDR-TB; risk factors; mortality; TB-HIV co-infection ID MULTIDRUG-RESISTANT TUBERCULOSIS; SOUTH-AFRICA; ANTIRETROVIRAL THERAPY; TREATMENT OUTCOMES AB SETTING : Recent studies suggest that the prevalence of drug-resistant tuberculosis (TB) in sub-Saharan Africa may be rising. This is of concern, as human immunodeficiency virus (HIV) co-infection in multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB has been associated with exceedingly high mortality rates. OBJECTIVE: To identify risk factors associated with mortality in MDR- and XDR-TB patients co-infected with HIV in South Africa. DESIGN: Case-control study of patients who died of all causes within 2 years of diagnosis with MDR- or XDR-TB. RESULTS: Among 123 MDR-TB patients, 78 (63%) died following diagnosis. CD4 count <= 50 (HR 4.64, P = 0.01) and 51-200 cells/mm(3) (HR 4.17, P = 0.008) were the strongest independent risk factors for mortality. Among 139 XDR-TB patients, 111 (80%) died. CD4 count <= 50 cells/mm(3) (HR 4.46, P = 0.01) and resistance to all six drugs tested (HR 2.54, P = 0.04) were the principal risk factors. Use of antiretroviral therapy (ART) was protective (HR 0.34, P = 0.009). CONCLUSIONS: Mortality due to MDR- and XDR-TB was associated with greater degree of immunosuppression and drug resistance. Efforts to reduce mortality must focus on preventing the amplification of resistance by strengthening TB treatment programs, as well as reducing the pool of immunosuppressed HIV-infected patients through aggressive HIV testing and ART initiation. C1 [Gandhi, N. R.] Montefiore Med Ctr, Div Gen Internal Med, Dept Med, Bronx, NY 10467 USA. [Gandhi, N. R.; Heo, M.; Shah, N. S.] Montefiore Med Ctr, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. [Andrews, J. R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA USA. [Moll, A. P.] Philanjalo & Church Scotland Hosp, Tugela Ferry, Kwazulu Natal, South Africa. [Friedland, G. H.] Yale Univ, Sch Med, New Haven, CT USA. RP Gandhi, NR (reprint author), Montefiore Med Ctr, Div Gen Internal Med, Dept Med, 111 E 210 St, Bronx, NY 10467 USA. EM neelgandhi@alumni.williams.edu OI Andrews, Jason/0000-0002-5967-251X FU Doris Duke Charitable Foundation [NRG 2007070, NSS 2007071, 2007018]; Gilead Foundation; Irene Diamond Fund [R05130] FX The authors are grateful to the dedicated, courageous, and inspiring staff of the Church of Scotland Hospital, the Umzinyathi District Department of Health, and the KwaZulu-Natal Province TB Control Program. They thank the National Health and Laboratory Services of the Inkosi Albert Luthuli Central Hospital for performing all TB culture and DST for patients from Tugela Ferry. This work would not have been possible without the medical students, residents, research assistants, and data capturers who contributed to data collection and data cleaning. The authors also thank X Li for his helpful comments during the analysis of these data. NRG and NSS are both recipients of the Doris Duke Charitable Foundation Clinical Scientist Development Award (NRG 2007070, NSS 2007071). GF is also supported by the Doris Duke Charitable Foundation (2007018), the Gilead Foundation, and The Irene Diamond Fund (R05130). Statistical support was provided by the Center for AIDS Research (CFAR) of Albert Einstein College of Medicine/Montefiore Medical Center. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. NR 26 TC 29 Z9 29 U1 0 U2 8 PU INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D) PI PARIS PA 68 BOULEVARD SAINT-MICHEL,, 75006 PARIS, FRANCE SN 1027-3719 J9 INT J TUBERC LUNG D JI Int. J. Tuberc. Lung Dis. PD JAN PY 2012 VL 16 IS 1 BP 90 EP 97 DI 10.5588/ijtld.11.0153 PG 8 WC Infectious Diseases; Respiratory System SC Infectious Diseases; Respiratory System GA 871GU UT WOS:000298726700017 PM 22236852 ER PT J AU Jiang, T Kambadakone, A Kulkarni, NM Zhu, AX Sahani, DV AF Jiang, Tao Kambadakone, Avinash Kulkarni, Naveen M. Zhu, Andrew X. Sahani, Dushyant V. TI Monitoring Response to Antiangiogenic Treatment and Predicting Outcomes in Advanced Hepatocellular Carcinoma Using Image Biomarkers, CT Perfusion, Tumor Density, and Tumor Size (RECIST) SO INVESTIGATIVE RADIOLOGY LA English DT Article DE hepatocellular carcinoma; antiangiogenic treatment; image biomarker; CT perfusion; RECIST ID GUIDELINE VERSION 1.1; COMPUTED-TOMOGRAPHY; SOLID TUMORS; EVALUATION CRITERIA; INITIAL-EXPERIENCE; COLORECTAL-CANCER; FUNCTIONAL-CT; RAT MODEL; LIVER; ANGIOGENESIS AB Purpose: Our aim was to investigate the hypothesis that the CT perfusion (CTP) is a more sensitive image biomarker when compared with tumor burden (Response Evaluation Criteria in Solid Tumors [RECIST]) and tumor density (HU) for monitoring treatment changes and for predicting long-term outcome in advanced hepatocellular carcinoma (HCC) treated with a combination of antiangiogenic treatment and chemotherapy. Material and Methods: In this phase II clinical trial, 33 patients with advanced HCC were enrolled and 23 were included in the current study. A diagnostic dual-phase contrast-enhanced CT and perfusion CT was performed at baseline and days 10 to 12 after initiation of antiangiogenic treatment (Bevacizumab). The patients subsequently received bevacizumab in combination with gemcitabine and oxaliplatin (GEMOX-B) and contrast-enhanced CT was performed at the end of treatment (after completing 3 cycles of GEMOX-B chemotherapy) and after every 8 week until there was evidence of disease progression or intolerable toxicity. The CTP protocol included a targeted dynamic cine acquisition for 25 to 30 seconds after 50 to 70 mL of iodinated contrast media injection at 5 to 7 mL/s. The CTP parameters were compared with tumor size (according to Response Evaluation Criteria in Solid Tumors, RECIST 1.1) and density measurements (HU) before and after treatment and correlated with patient's outcome in groups with and without tumor thrombus. A one-sided P value was calculated and the Bonferroni correction was used to address the issue of multiple comparisons. Results: On days 10 to 12 after initiation of bevacizumab, significant decrease in CTP parameters was noted (P < 0.005). There was a mild reduction in mean tumor density (P = 0.016) without any significant change in mean tumor size. Tumors with higher baseline mean transit time values on CTP correlated with favorable clinical outcome (partial response and stable disease) and had better 6 months progression-free survival (P = 0.002 and P = 0.005, respectively). The baseline transfer constant (Ktrans) of responders (1425.19 +/- 609.47 mL/1000mL/min) was significantly higher than that of nonresponders (935.96 +/- 189.47 mL/1000 mL/min). The tumor thrombus in the portal vein demonstrated baseline perfusion values and post-treatment change values similar to the HCC. Conclusion: In advanced HCC, CTP is a more sensitive image biomarker for monitoring early antiangiogenic treatment effects as well as in predicting outcome at the end of treatment and progression-free survival as compared with RECIST and tumor density. C1 [Jiang, Tao; Kambadakone, Avinash; Kulkarni, Naveen M.; Sahani, Dushyant V.] Harvard Univ, Sch Med, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. [Zhu, Andrew X.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Jiang, Tao] Second Mil Med Univ, ChangZheng Hosp, Dept Radiol, Shanghai, Peoples R China. RP Sahani, DV (reprint author), Harvard Univ, Sch Med, Div Abdominal Imaging & Intervent, 55 Fruit St,White 270, Boston, MA 02114 USA. EM dsahani@partners.org NR 37 TC 76 Z9 79 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-9996 EI 1536-0210 J9 INVEST RADIOL JI Invest. Radiol. PD JAN PY 2012 VL 47 IS 1 BP 11 EP 17 DI 10.1097/RLI.0b013e3182199bb5 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 866RR UT WOS:000298400100004 PM 21512396 ER PT J AU Lichterfeld, M Gandhi, RT Simmons, RP Flynn, T Sbrolla, A Yu, XG Basgoz, N Mui, S Williams, K Streeck, H Burgett-Yandow, N Roy, G Janssens, M Pedneault, L Vandepapeliere, P Koutsoukos, M Demoitie, MA Bourguignon, P McNally, L Voss, G Altfeld, M AF Lichterfeld, Mathias Gandhi, Rajesh T. Simmons, Rachel P. Flynn, Theresa Sbrolla, Amy Yu, Xu G. Basgoz, Nesli Mui, Stanley Williams, Katie Streeck, Hendrik Burgett-Yandow, Nicole Roy, Gilbert Janssens, Michel Pedneault, Louise Vandepapeliere, Pierre Koutsoukos, Marguerite Demoitie, Marie-Ange Bourguignon, Patricia McNally, Lisa Voss, Gerald Altfeld, Marcus TI Induction of Strong HIV-1-Specific CD4(+) T-Cell Responses Using an HIV-1 gp120/NefTat Vaccine Adjuvanted With AS02(A) in Antiretroviral-Treated HIV-1-Infected Individuals SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV-1; HIV-1-specific CD4(+) cells; therapeutic vaccination; vaccination ID VIRUS TYPE-1 HIV-1; TREATMENT INTERRUPTION; INFECTED PATIENTS; VIRAL REPLICATION; IMMUNE CONTROL; FOLLOW-UP; THERAPY; IMMUNODEFICIENCY; AIDS; MEMORY AB Background: Induction of HIV-1-specific CD4(+) T-cell responses by therapeutic vaccination represents an attractive intervention to potentially increase immune control of HIV-1. Methods: We performed a double-blinded, randomized, placebo-controlled clinical trial to determine the safety and immunogenicity of GlaxoSmithKline Biologicals' HIV-1 gp120/NefTat subunit protein vaccine formulated with the AS02(A) Adjuvant System in subjects with well-controlled chronic HIV-1 infection on highly active antiretroviral therapy. Ten individuals received the vaccine; whereas adjuvant alone or placebo was given to 5 subjects each. Immunogenicity was monitored by intracellular cytokine flow cytometry and carboxyfluorescein succinimidyl ester-based proliferation assays. Results: The vaccine was well tolerated with no related serious adverse events. Vaccine recipients had significantly stronger gp120-specific CD4(+) T-cell responses which persisted until week 48 and greater gp120-specific CD4(+) T-cell proliferation activity as compared with controls. In the vaccine group, the number of participants who demonstrated positive responses for both gp120-specific CD4(+) T-cell interleukin-2 production and gp120-specific CD8(+) T-cell proliferation were significantly higher at week 6. Conclusions: The gp120/NefTat/AS02(A) vaccine induced strong gp120-specific CD4(+) T-cell responses and a higher number of vaccinees developed both HIV-1-specific CD4(+) T-cell responses and CD8(+) T-cell proliferation. The induction of these responses may be important in enhancing immune-mediated viral control. C1 [Lichterfeld, Mathias; Gandhi, Rajesh T.; Simmons, Rachel P.; Flynn, Theresa; Sbrolla, Amy; Yu, Xu G.; Basgoz, Nesli; Mui, Stanley; Williams, Katie; Streeck, Hendrik; Burgett-Yandow, Nicole; Roy, Gilbert; Altfeld, Marcus] Massachusetts Gen Hosp, Ragon Inst, MIT, Boston, MA USA. [Lichterfeld, Mathias; Gandhi, Rajesh T.; Simmons, Rachel P.; Flynn, Theresa; Sbrolla, Amy; Yu, Xu G.; Basgoz, Nesli; Mui, Stanley; Williams, Katie; Streeck, Hendrik; Burgett-Yandow, Nicole; Roy, Gilbert; Altfeld, Marcus] Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA USA. [Janssens, Michel; Koutsoukos, Marguerite; Demoitie, Marie-Ange; Bourguignon, Patricia; McNally, Lisa; Voss, Gerald] GlaxoSmithKline Biol, Rixensart, Belgium. [Pedneault, Louise] Populat Council, New York, NY 10021 USA. [Vandepapeliere, Pierre] Neovacs SA, Paris, France. RP Altfeld, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ragon Inst,MIT, 149 13th St, Charlestown, MA 02129 USA. EM maltfeld@partners.org OI Simmons, Rachel/0000-0003-2498-7965 FU National Institutes of Health [RO1 AI50429]; Doris Duke Charitable Foundation; GlaxoSmithKline Biologicals FX Supported by the National Institutes of Health (M.A., RO1 AI50429), the Doris Duke Charitable Foundation (M.A., M.L., R.S.), and GlaxoSmithKline Biologicals. NR 49 TC 10 Z9 10 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD JAN 1 PY 2012 VL 59 IS 1 BP 1 EP 9 DI 10.1097/QAI.0b013e3182373b77 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 865DW UT WOS:000298292000005 PM 21963936 ER PT J AU Bassett, IV Chetty, S Wang, BX Mazibuko, M Giddy, J Lu, ZG Walensky, RP Freedberg, KA Losina, E AF Bassett, Ingrid V. Chetty, Senica Wang, Bingxia Mazibuko, Matilda Giddy, Janet Lu, Zhigang Walensky, Rochelle P. Freedberg, Kenneth A. Losina, Elena TI Loss to Follow-Up and Mortality Among HIV-Infected People Co-Infected With TB at ART Initiation in Durban, South Africa SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV; long-term outcomes; mortality; South Africa; tuberculosis ID ANTIRETROVIRAL THERAPY; SCALE-UP; TUBERCULOSIS; OUTCOMES; PROGRAM; CARE AB Objective: To quantify the impact of tuberculosis (TB) co-infection on death and loss to follow-up (LTFU) 12 months after entry into an ART program. Design: Prospective intervention study. Methods: From May 2007 to 2008, patients undergoing pre-ART training in Durban, South Africa, were screened for pulmonary TB using mycobacterial culture. Subjects missing appointments for >3 months were phoned. Patients who could not be reached were considered LTFU. Deaths were ascertained by report from family members. We used the Kaplan-Meier method to estimate time to LTFU or death for 3 groups at enrollment as follows: (1) newly diagnosed with TB by sputum culture; (2) on TB treatment (ie, previously diagnosed); and (3) TB free. We evaluated the role of TB on mortality and LTFU using Cox proportional hazards models. Results: Nine hundred fifty-one HIV-infected subjects were enrolled; 59% were female, and median baseline CD4 count was 90 cells per microliter (IQR: 41-148 cells/mL). One hundred forty-four (15%) were newly diagnosed with TB by sputum culture; an additional 199 (21%) were already on TB treatment. By 12 months, 26% newly diagnosed with TB at enrollment died or were LTFU, compared with 19% already on TB treatment, and 14% who were TB free (P = 0.001). Controlling for age, sex, smoking, CD4, and opportunistic infection history, subjects newly diagnosed with pulmonary TB were 76% more likely to die or be LTFU (hazard ratio: 1.76, 95% confidence interval: 1.20 to 2.60) than those without TB. Conclusions: HIV/TB co-infected individuals are more likely to die or be LTFU within 12 months of ART clinic entry in South Africa. These patients require intensive follow-up during ART initiation. C1 [Bassett, Ingrid V.; Walensky, Rochelle P.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Bassett, Ingrid V.; Wang, Bingxia; Lu, Zhigang; Walensky, Rochelle P.; Freedberg, Kenneth A.; Losina, Elena] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Chetty, Senica; Mazibuko, Matilda; Giddy, Janet] McCord Hosp, Durban, South Africa. [Wang, Bingxia; Walensky, Rochelle P.; Freedberg, Kenneth A.; Losina, Elena] Harvard Univ, Harvard Ctr AIDS Res CFAR, Boston, MA 02115 USA. [Walensky, Rochelle P.] Boston Univ, Sch Publ Hlth, Div Infect Dis, Boston, MA USA. [Freedberg, Kenneth A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Losina, Elena] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Losina, Elena] Brigham & Womens Hosp, Dept Orthoped, Boston, MA 02115 USA. RP Bassett, IV (reprint author), 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM ibassett@partners.org OI Walensky, Rochelle P./0000-0002-8795-379X FU National Institute of Allergy and Infectious Disease [K23 AI 068458]; PEPFAR supplement [R01 AI058736]; Harvard University Center for AIDS Research [P30 AI060354]; National Institute of Mental Health [R01 MH090326, R01 MH073445]; National Institute of Arthritis and Musculoskeletal and Skin Diseases [K24AR057827]; Doris Duke Charitable Foundation; Operations Research on AIDS Care and Treatment in Africa; [K24 AI062476] FX Supported in part by the National Institute of Allergy and Infectious Disease: K23 AI 068458 (I.V.B.); a PEPFAR supplement to R01 AI058736 (K.A.F.); K24 AI062476 (K.A.F.); the Harvard University Center for AIDS Research P30 AI060354; the National Institute of Mental Health: R01 MH090326 (I.V.B.); R01 MH073445 (R.P.W.); the National Institute of Arthritis and Musculoskeletal and Skin Diseases: K24AR057827 (E.L.); the Doris Duke Charitable Foundation, Clinical Scientist Development Award (R.P.W.) and Operations Research on AIDS Care and Treatment in Africa (K.A.F.). NR 21 TC 22 Z9 22 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD JAN 1 PY 2012 VL 59 IS 1 BP 25 EP 30 DI 10.1097/QAI.0b013e31823d3aba PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 865DW UT WOS:000298292000008 PM 22027877 ER PT J AU Izadi, N Goetz, MB Graber, CJ AF Izadi, Neema Goetz, Matthew Bidwell Graber, Christopher J. TI Inverse Correlation of Initial CD8 Lymphocyte Count and CD4 Lymphocyte Response to Combination Antiretroviral Therapy in Treatment-Naive HIV-Infected Patients SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Letter ID T-CELL-ACTIVATION; HIV-1-INFECTED PATIENTS; COLLABORATIVE ANALYSIS; IMMUNE ACTIVATION; PREDICT; COHORT; SUPPRESSION; RECOVERY; MARKER; DEATH C1 [Izadi, Neema; Goetz, Matthew Bidwell; Graber, Christopher J.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Goetz, Matthew Bidwell; Graber, Christopher J.] VA Greater Los Angeles Healthcare Syst, Dept Med, Infect Dis Sect, Los Angeles, CA USA. RP Izadi, N (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. OI Goetz, Matthew/0000-0003-4542-992X NR 19 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD JAN 1 PY 2012 VL 59 IS 1 BP E1 EP E3 DI 10.1097/QAI.0b013e31823d3277 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 865DW UT WOS:000298292000001 PM 22156822 ER PT J AU Hattangadi, JA Taback, N Neville, BA Harris, JR Punglia, RS AF Hattangadi, Jona A. Taback, Nathan Neville, Bridget A. Harris, Jay R. Punglia, Rinaa S. TI Accelerated Partial Breast Irradiation Using Brachytherapy for Breast Cancer: Patterns in Utilization and Guideline Concordance SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID RADIATION-THERAPY SYSTEM; MAMMOSITE REGISTRY TRIAL; 20-YEAR FOLLOW-UP; CONSERVING THERAPY; AMERICAN SOCIETY; RANDOMIZED-TRIALS; STAGE-I; CONSENSUS STATEMENT; REGIONAL-VARIATIONS; ONCOLOGY ASTRO AB Accelerated partial breast irradiation using brachytherapy (APBIb) is an alternative to whole-breast irradiation (WBI) after breast-conserving surgery. We evaluated patterns of APBIb use with respect to 2009 American Society for Radiation Oncology consensus guidelines (ASTRO-G) in a population-based cohort. From Surveillance, Epidemiology, and End Results data, we identified 138 815 American women with breast cancer diagnosed between January 1, 2000, and December 31, 2007, who underwent WBI or APBIb after breast-conserving surgery and classified them as suitable, cautionary, or unsuitable for APBIb according to ASTRO-G criteria. Logistic regression was applied to study APBIb use overall and within each guideline category. All P values are from two-sided tests. Overall, 2.6% of patients received APBIb, and 65.8% of them were classified as cautionary or unsuitable. APBIb was used by 5% of suitable, 3.4% of cautionary, and 1.6% of unsuitable patients by ASTRO-G criteria (P < .001). APBIb use increased from 0.4% in 2000 to 6.6% in 2007 and varied widely (0%-7%) between localities. Variables associated with APBIb use among suitable patients included other vs white race (odds ratio [OR] = 0.51, P < .001), region (OR = 2.60-8.62, P < .001), and more recent year (OR = 20.3, P < .001). Among cautionary patients, variables associated with APBIb use included black vs white race (OR = 0.76, P = .027), other vs white race (OR = 0.57, P < .001), Hispanic ethnicity (OR = 0.75, P = .036), region (OR = 3.10-10.2, P < .001), nonmetropolitan or rural location (OR = 0.53, P = .012), and more recent year (OR = 17.6, P < .001). Among unsuitable patients, black vs white race (OR = 0.77, P = .008), other vs white race (OR = 0.46, P < .001), region (OR = 3.33-21.6, P < .001), and more recent year (OR = 12.7, P < .001) were associated with APBIb use. APBIb after breast-conserving surgery has been rapidly adopted in the United States. Use varied by race, ethnicity, and widely by region, especially among patients who may not be suitable for this radiation technique. C1 [Hattangadi, Jona A.] Harvard Radiat Oncol Program, Boston, MA USA. [Taback, Nathan; Neville, Bridget A.] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. [Hattangadi, Jona A.; Harris, Jay R.; Punglia, Rinaa S.] Harvard Univ, Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst,Sch Med, Boston, MA 02115 USA. RP Hattangadi, JA (reprint author), Harvard Univ, Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst,Sch Med, 75 Francis St,L-2 Level, Boston, MA 02115 USA. EM jhattangadi@partners.org FU Joint Center for Radiation Therapy Foundation, Boston, MA FX This study was supported by a grant from the Joint Center for Radiation Therapy Foundation (JAH), Boston, MA. NR 57 TC 37 Z9 37 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 JNCI-J NATL CANCER I JI JNCI-. Natl. Cancer Inst. PD JAN PY 2012 VL 104 IS 1 BP 29 EP 41 DI 10.1093/jnci/djr495 PG 13 WC Oncology SC Oncology GA 873OH UT WOS:000298892200008 PM 22180643 ER PT J AU Baldessarini, RJ Salvatore, P Khalsa, HMK Imaz-Etxeberria, H Gonzalez-Pinto, A Tohen, M AF Baldessarini, R. J. Salvatore, P. Khalsa, H. -M. K. Imaz-Etxeberria, H. Gonzalez-Pinto, A. Tohen, M. TI Episode cycles with increasing recurrences in first-episode bipolar-I disorder patients SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Bipolar disorder; Cycle-length; First-episodes; Progression; Recurrences; Wellness-intervals ID PROSPECTIVE FOLLOW-UP; MANIC-DEPRESSIVE PSYCHOSIS; MAJOR AFFECTIVE-DISORDER; MOOD DISORDERS; CASE REGISTER; PROGNOSIS; INSANITY; RECOVERY; ILLNESS; PERIODICITY AB Background: Preliminary review of a century of studies of the course of manic-depressive syndromes produced 40 reports, of which approximately one-third report evidence of shortening wellness intervals or cycle-lengths with more recurrences, and two-thirds did not. Methods: We evaluated inter-episode intervals (cycle-length) in 128 clinically-treated, DSM-IV bipolar-I disorder patients followed prospectively and systematically over 5.7 years, with 6.5 episodes/person. Results: As expected, cycle-length varied inversely with total cycle-count/person: however, multivariate linear regression found only longer initial hospitalization and fewer total cycles to be associated with cycle-length, whereas cycle-number (1, 2, 3, etc.), sex, intake-age, and first-episode polarity were not. Regression of within-subject cycle-length versus cycle-number yielded individual slope-functions with pseudo-random distribution (28% fell within +/- 1 month/cycle of the null [zero-slope]). Mean duration of early and late euthymic intervals (cycles 2 vs. 5) in patients with matched recurrence-counts was nearly identical. Conclusions: The course of bipolar-I disorder from onset was largely random or chaotic over nearly 6 years from onset. Only a minority of patients showed either cycle-acceleration or slowing, without changes in wellness intervals. The findings may be influenced by treatment-effects, but seem to indicate that most current bipolar-I disorder patients are unlikely to show progressive shortening of recurrence-cycles. (C) 2011 Elsevier B.V. All rights reserved. C1 [Baldessarini, R. J.; Salvatore, P.; Khalsa, H. -M. K.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp,McLean Div,Int Consortium, Boston, MA 02115 USA. [Salvatore, P.] Univ Parma, Dept Neurosci, Sect Psychiat, I-43100 Parma, Italy. [Imaz-Etxeberria, H.; Gonzalez-Pinto, A.] Vittoria Med Ctr, Dept Psychiat, Vittoria, Spain. [Tohen, M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. RP Baldessarini, RJ (reprint author), McLean Hosp, Mailman Res Ctr 312, 115 Mill St, Belmont, MA 02478 USA. EM rbaldessarini@mclean.harvard.edu FU Bruce J. Anderson Foundation; McLean Private Donors Bipolar Disorder Research Fund; NARSAD; Atlas Foundation FX Supported in part by a grant from the Bruce J. Anderson Foundation and the McLean Private Donors Bipolar Disorder Research Fund (to RJB), by a grant from NARSAD (to PS), and by the Atlas Foundation (to MT). These funding sources had no influence on the design, analysis, or reporting of this study. NR 52 TC 20 Z9 20 U1 0 U2 1 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 JAN PY 2012 VL 136 IS 1-2 BP 149 EP 154 DI 10.1016/j.jad.2011.08.037 PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 867JW UT WOS:000298451700019 PM 21943930 ER PT J AU Watson, KE Dovi, WF Conhaim, RL AF Watson, Kal E. Dovi, William F. Conhaim, Robert L. TI Evidence for active control of perfusion within lung microvessels SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE pulmonary circulation; microcirculation; vasoconstriction; circulatory control; vasoreactivity ID ESTIMATED FUNCTIONAL DIAMETER; ALVEOLAR SEPTAL MICROVESSELS; ISOLATED RAT LUNGS; PULMONARY-HYPERTENSION; VASCULAR-RESISTANCE; THROMBOXANE; CONTRACTILE; CIRCULATION; HYPOXIA; MUSCLE AB Watson KE, Dovi WF, Conhaim RL. Evidence for active control of perfusion within lung microvessels. J Appl Physiol 112: 48-53, 2012. First published October 13, 2011; doi:10.1152/japplphysiol.00820.2011.-Vasoconstrictors cause contraction of pulmonary microvascular endothelial cells in culture. We wondered if this meant that contraction of these cells in situ caused active control of microvascular perfusion. If true, it would mean that pulmonary microvessels were not simply passive tubes and that control of pulmonary microvascular perfusion was not mainly due to the contraction and dilation of arterioles. To test this idea, we vasoconstricted isolated perfused rat lungs with angiotensin II, bradykinin, serotonin, or U46619 (a thromboxane analog) at concentrations that produced equal flows. We also perfused matched-flow controls. We then infused a bolus of 3 mu m diameter particles into each lung and measured the rate of appearance of the particles in the venous effluent. We also measured microscopic trapping patterns of particles retained within each lung. Thirty seconds after particle infusion, venous particle concentrations were significantly lower (P <= 0.05) for lungs perfused with angiotensin II or bradykinin than for those perfused with U46619, but not significantly different from serotonin perfused lungs or matched flow controls. Microscopic clustering of particles retained within the lungs was significantly greater (P <= 0.05) for lungs perfused with angiotensin II, bradykinin, or serotonin, than for lungs perfused with U46619 or for matched flow controls. Our results suggest that these agents did not produce vasoconstriction by a common mechanism and support the idea that pulmonary microvessels possess a level of active control and are not simply passive exchange vessels. C1 [Dovi, William F.; Conhaim, Robert L.] Univ Wisconsin, Sch Med & Publ Hlth, William S Middleton Mem Vet Hosp, Madison, WI USA. [Watson, Kal E.; Conhaim, Robert L.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Surg, Madison, WI USA. RP Conhaim, RL (reprint author), H5-301 BX3236,600 Highland Ave, Madison, WI 53792 USA. EM conhaim@surgery.wisc.edu FU Veterans Health Administration, Office of Research and Development, Department of Veterans Affairs, Biomedical Laboratory Research and Development Service FX This work was supported by the Veterans Health Administration, Office of Research and Development, Department of Veterans Affairs, Biomedical Laboratory Research and Development Service. NR 23 TC 3 Z9 3 U1 1 U2 1 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 JAN PY 2012 VL 112 IS 1 BP 48 EP 53 DI 10.1152/japplphysiol.00820.2011 PG 6 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 866SR UT WOS:000298403700007 PM 21998262 ER PT J AU Wongviriyawong, C Harris, RS Zheng, H Kone, M Winkler, T Venegas, JG AF Wongviriyawong, C. Harris, R. S. Zheng, H. Kone, M. Winkler, T. Venegas, J. G. TI Functional effect of longitudinal heterogeneity in constricted airways before and after lung expansion SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE airway resistance; asthma; airway hyperresponsiveness ID ASTHMA; VENTILATION; HYPERRESPONSIVENESS; MODEL; BRONCHOCONSTRICTION; SEGMENTATION; METHACHOLINE; VARIABILITY; RESISTANCE; MECHANICS AB Wongviriyawong C, Harris RS, Zheng H, Kone M, Winkler T, Venegas JG. Functional effect of longitudinal heterogeneity in constricted airways before and after lung expansion. J Appl Physiol 112: 237-245, 2012. First published September 22, 2011; doi: 10.1152/japplphysiol.01400.2010.-Heterogeneity in narrowing among individual airways is an important contributor to airway hyperresponsiveness. This paper investigates the contribution of longitudinal heterogeneity (the variability along the airway in cross-sectional area and shape) to airway resistance (R(aw)). We analyzed chest high-resolution computed tomography scans of 8 asthmatic (AS) and 9 nonasthmatic (NA) subjects before and after methacholine (MCh) challenge, and after lung expansion to total lung capacity. In each subject, R(aw) was calculated for 35 defined central airways with >2 mm diameter. Ignoring the area variability and noncircular shape results in an underestimation of R(aw) (%U(total)) that was substantial in some airways (similar to 50%) but generally small (median <6%). The average contribution of the underestimation of Raw caused by longitudinal heterogeneity in the area (%U(area)) to % Utotal was 36%, while the rest was due to the noncircularity of the shape (%U(shape)). After MCh challenge, %U(area) increased in AS and NA (P < 0.05). A lung volume increase to TLC reduced % U(total) and % U(area) in both AS and NA (P < 0.0001, except for %U(total) in AS with P < 0.01). Only in NA, %U(shape) had a significant reduction after increasing lung volume to TLC (P < 0.005). %U(area) was highly correlated, but not identical to the mean-normalized longitudinal heterogeneity in the cross-sectional area [CV(2)(A)] and %U(shape) to the average eccentricity of the elliptical shape. This study demonstrates that R(aw) calculated assuming a cylindrical shape and derived from an average area along its length may, in some airways, substantially underestimate R(aw). The observed changes in underestimations of R(aw) with the increase in lung volume to total lung capacity may be consistent with, and contribute in part to, the differences in effects of deep inhalations in airway function between AS and NA subjects. C1 [Wongviriyawong, C.; Winkler, T.; Venegas, J. G.] Harvard Univ, Sch Med, Dept Anesthesia Crit Care & Pain Med, Massachusetts Gen Hosp, Boston, MA USA. [Wongviriyawong, C.] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Harris, R. S.] Harvard Univ, Sch Med, Dept Med, Pulm & Crit Care Unit, Boston, MA USA. [Zheng, H.; Kone, M.] Harvard Univ, Sch Med, Ctr Biostat, Massachusetts Gen Hosp, Boston, MA USA. RP Venegas, JG (reprint author), 55 Fruit St,Thier 429, Boston, MA 02114 USA. EM jvenegas@habanero.mgh.harvard.edu RI Winkler, Tilo/B-5337-2009 OI Winkler, Tilo/0000-0002-7276-5550 FU National Heart, Lung, and Blood Institute [HL68011] FX This research was funded by National Heart, Lung, and Blood Institute Grant HL68011. NR 31 TC 3 Z9 3 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 JAN PY 2012 VL 112 IS 1 BP 237 EP 245 DI 10.1152/japplphysiol.01400.2010 PG 9 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 866SR UT WOS:000298403700028 PM 21940845 ER PT J AU Micheli, BR Wannomae, KK Lozynsky, AJ Christensen, SD Muratoglu, OK AF Micheli, Brad R. Wannomae, Keith K. Lozynsky, Andrew J. Christensen, Steven D. Muratoglu, Orhun K. TI Knee Simulator Wear of Vitamin E Stabilized Irradiated Ultrahigh Molecular Weight Polyethylene SO JOURNAL OF ARTHROPLASTY LA English DT Article DE polyethylene; wear; fatigue; oxidation; vitamin E; knee arthroplasty ID CROSS-LINKED POLYETHYLENE; MECHANICAL-PROPERTIES; ORTHOPEDIC UHMWPE; ALPHA-TOCOPHEROL; FREE-RADICALS; OXIDATION; RADIATION; IMPLANTS; RESISTANCE; LINKING AB Wear and damage of ultrahigh molecular weight polyethylene (UHMWPE) tibial inserts used in total knee arthroplasty are accelerated by oxidation. Radiation crosslinking reduces wear but produces residual free radicals adversely affecting stability. One alternative to stabilize radiation-crosslinked UHMWPE is to infuse the material with vitamin E (vit E). We investigated the properties of 100-kGy e-beam-irradiated UHMWPE that was subsequently doped with vitamin E in comparison with conventional UHMWPE. Both polymers were sterilized with gamma irradiation in vacuum packaging. Vitamin E-doped UHMWPE showed lower wear before and after aging (2.4 +/- 0.5 and 2.5 +/- 0.8 mg/million cycle, respectively, vs 26.9 +/- 3.5 and 40.8 +/- 3.0 mg/million cycle for conventional UHMWPE). Conventional UHMWPE showed oxidation after accelerated aging, and its mechanical properties were adversely affected, whereas vit E-doped UHMWPE showed no oxidation or changes in its mechanical properties. Vitamin E stabilization of radiation-crosslinked UHMWPE resulted in low wear and high oxidation resistance; it is an alternative load-bearing material for total knee applications. C1 [Micheli, Brad R.; Wannomae, Keith K.; Lozynsky, Andrew J.; Christensen, Steven D.; Muratoglu, Orhun K.] Massachusetts Gen Hosp, Harris Orthopaed Lab, Boston, MA 02114 USA. [Muratoglu, Orhun K.] Harvard Univ, Sch Med, Boston, MA USA. RP Muratoglu, OK (reprint author), Massachusetts Gen Hosp, Harris Orthopaed Lab, 55 Fruit St,GRJ-1206, Boston, MA 02114 USA. FU Biomet, Inc. FX This study was funded by a research grant from Biomet, Inc. NR 22 TC 11 Z9 12 U1 0 U2 11 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD JAN PY 2012 VL 27 IS 1 BP 95 EP 104 DI 10.1016/j.arth.2011.03.006 PG 10 WC Orthopedics SC Orthopedics GA 873HP UT WOS:000298872000016 PM 21550762 ER PT J AU Kwon, YM AF Kwon, Young-Min TI Untitled Reply SO JOURNAL OF ARTHROPLASTY LA English DT Letter C1 Harvard Univ, Sch Med, Dept Orthoped Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Kwon, YM (reprint author), Harvard Univ, Sch Med, Dept Orthoped Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD JAN PY 2012 VL 27 IS 1 BP 160 EP 161 DI 10.1016/j.arth.2011.09.003 PG 2 WC Orthopedics SC Orthopedics GA 873HP UT WOS:000298872000028 ER PT J AU Hovik, H Yu, WH Olsen, I Chen, T AF Hovik, Hedda Yu, Wen-Han Olsen, Ingar Chen, Tsute TI Comprehensive Transcriptome Analysis of the Periodontopathogenic Bacterium Porphyromonas gingivalis W83 SO JOURNAL OF BACTERIOLOGY LA English DT Article ID GENOMIC TILING MICROARRAYS; SMALL NONCODING RNAS; GENE-EXPRESSION; ESCHERICHIA-COLI; DIFFERENTIAL EXPRESSION; INSERTION-SEQUENCE; OXIDATIVE STRESS; EPITHELIAL-CELLS; REGULATORY RNAS; OUTER-MEMBRANE AB High-density tiling microarray and RNA sequencing technologies were used to analyze the transcriptome of the periodontopathogenic bacterium Porphyromonas gingivalis. The compiled P. gingivalis transcriptome profiles were based on total RNA samples isolated from three different laboratory culturing conditions, and the strand-specific transcription profiles generated covered the entire genome, including both protein coding and noncoding regions. The transcription profiles revealed various operon structures, 5'- and 3'-end untranslated regions (UTRs), differential expression patterns, and many novel, not-yet-annotated transcripts within intergenic and antisense regions. Further transcriptome analysis identified the majority of the genes as being expressed within operons and most 5' and 3' ends to be protruding UTRs, of which several 3' UTRs were extended to overlap genes carried on the opposite/antisense strand. Extensive antisense RNAs were detected opposite most insertion sequence (IS) elements. Pairwise comparative analyses were also performed among transcriptome profiles of the three culture conditions, and differentially expressed genes and metabolic pathways were identified. With the growing realization that noncoding RNAs play important biological functions, the discovery of novel RNAs and the comprehensive transcriptome profiles compiled in this study may provide a foundation to further understand the gene regulation and virulence mechanisms in P. gingivalis. The transcriptome profiles can be viewed at and downloaded from the Microbial Transcriptome Database website, http://bioinformatics.forsyth.org/mtd. C1 [Yu, Wen-Han; Chen, Tsute] Forsyth Inst, Dept Mol Genet, Cambridge, MA USA. [Hovik, Hedda; Olsen, Ingar] Univ Oslo, Fac Dent, Dept Oral Biol, Oslo, Norway. RP Chen, T (reprint author), Forsyth Inst, Dept Mol Genet, Cambridge, MA USA. EM tchen@forsyth.org FU National Institute for Dental and Craniofacial Research [R21 DE018803]; Faculty of Dentistry, University of Oslo, Oslo, Norway FX This project was funded by grant R21 DE018803 from the National Institute for Dental and Craniofacial Research. H. Hovik was supported by a Ph.D. stipend and mobility grant from the Faculty of Dentistry, University of Oslo, Oslo, Norway. NR 92 TC 16 Z9 16 U1 0 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD JAN PY 2012 VL 194 IS 1 BP 100 EP 114 DI 10.1128/JB.06385-11 PG 15 WC Microbiology SC Microbiology GA 866AA UT WOS:000298350800012 PM 22037400 ER PT J AU Trivedi, RB Piette, J Fihn, SD Edelman, D AF Trivedi, Ranak B. Piette, John Fihn, Stephan D. Edelman, David TI Examining the Interrelatedness of Patient and Spousal Stress in Heart Failure Conceptual Model and Pilot Data SO JOURNAL OF CARDIOVASCULAR NURSING LA English DT Article DE caregivers; heart failure; patient compliance; social support; spouse ID SELF-CARE; PSYCHOSOCIAL INTERVENTIONS; PROGNOSTIC IMPORTANCE; HOSPITAL READMISSION; MARITAL QUALITY; CHRONIC ILLNESS; SOCIAL SUPPORT; RISK-FACTOR; DEPRESSION; FAMILY AB Background and Research Objective: Recent research has highlighted the positive influence that spouses can have on patient outcomes. It is not clear whether patients and spouses influence each other's well-being reciprocally or whether spousal well-being affects the success of patients' disease management. Our goals were 2-fold: (a) to propose a conceptual framework to examine the reciprocity between patient and spouses' well-being, especially as it relates to disease management, and (b) to begin to assess the validity of this model using pilot data. Subjects and Methods: Twenty-three veterans with heart failure (HF) and their spouses were recruited into a pilot cross-sectional observational study. Participants completed psychosocial surveys to assess depressive symptoms, caregiver burden, relationship satisfaction, and disease management. Descriptive analyses and bivariate correlations between these measures were calculated. Results: Using standard cutoffs, analyses suggested clinically significant depressive symptoms in patients (Center for Epidemiological Studies-Depression score >16; mean, 21.8 [SD, 13]) and a high level of caregiver burden among spouses (Zarit Burden Interview score >15; mean, 22.4 [SD, 15.4]). Both patients and spouses reported high relationship satisfaction levels (Dyadic Adjustment Scale score >100; mean, 112.6 [SD, 26.5] and 115.9 [SD, 14.4], respectively). On average, patients reported poor disease management (Self-care of Heart Failure Index subscale <70 across all subscales: confidence = 53.3 [SD, 28.2]; maintenance = 59.7 [SD, 17.3]; management = 54.0 [SD, 19.4]). Patient depressive symptoms were positively correlated with spouse depressive symptoms (r = 0.53) and caregiver burden (r = 0.64; all P's < .05). Spouses' depressive symptoms were additionally correlated with lower levels of perceived social support among patients (r = -0.47), poor patient relationship satisfaction (r = -0.51), and worse patient confidence in HF management (r = -0.48). Greater caregiver burden was associated with more patient disease complaints (r = 0.49), poorer patients' relationship satisfaction (r = -0.72), and poorer patients' perceived social support (r = -0.73). Conclusions: These results provide preliminary support to the proposed conceptual model. Further research is necessary to determine which spousal factors appear to be most relevant to disease management. Disease management interventions may benefit from engaging spouses in a way that enhances their role without adding to their burden. C1 [Trivedi, Ranak B.] VA Puget Sound Hlth Care Syst, NW HSR&D Ctr Excellence, Seattle, WA USA. [Fihn, Stephan D.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Piette, John] Ann Arbor HSR&D Ctr Excellence, Ann Arbor, MI USA. [Fihn, Stephan D.] Vet Affairs Puget Sound, NW HSR&D Ctr Excellence, Seattle, WA USA. [Edelman, David] Duke Univ, Med Ctr, Durham, NC USA. RP Trivedi, RB (reprint author), 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM ranak.trivedi@va.gov OI Edelman, David/0000-0001-7112-6151 FU VA Puget Sound Health Care System; Durham VA Medical Center FX This work was supported in part by the resources provided by the VA Puget Sound Health Care System and the NR 46 TC 9 Z9 9 U1 5 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0889-4655 J9 J CARDIOVASC NURS JI J. Cardiovasc. Nurs. PD JAN-FEB PY 2012 VL 27 IS 1 BP 24 EP 32 DI 10.1097/JCN.0b013e3182129ce7 PG 9 WC Cardiac & Cardiovascular Systems; Nursing SC Cardiovascular System & Cardiology; Nursing GA 866JO UT WOS:000298376900004 PM 21743348 ER PT J AU Liu, R Kalva, SP AF Liu, Raymond Kalva, Sanjeeva P. TI Multidetector CT for GI Bleeding First-line Diagnostic Study? SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Editorial Material ID ENTEROGRAPHY; ANGIOGRAPHY; HEMORRHAGE C1 [Liu, Raymond; Kalva, Sanjeeva P.] Massachusetts Gen Hosp, Dept Imaging, Div Vasc Imaging & Intervent, Boston, MA 02114 USA. RP Kalva, SP (reprint author), Massachusetts Gen Hosp, Dept Imaging, Div Vasc Imaging & Intervent, Boston, MA 02114 USA. EM skalva@partners.org NR 11 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-0790 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD JAN PY 2012 VL 46 IS 1 BP 6 EP 7 DI 10.1097/MCG.0b013e31823a4b2f PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 863FA UT WOS:000298147000006 PM 22157219 ER PT J AU Davila, JA Duan, ZG McGlynn, KA El-Serag, HB AF Davila, Jessica A. Duan, Zhigang McGlynn, Katherine A. El-Serag, Hashem B. TI Utilization and Outcomes of Palliative Therapy for Hepatocellular Carcinoma A Population-based Study in the United States SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Article DE hepatocellular carcinoma; palliative treatment; chemotherapy ID RANDOMIZED CONTROLLED TRIAL; CHEMOEMBOLIZATION; DOXORUBICIN AB Goals: To evaluate the utilization and determinants of receiving palliative treatment for hepatocellular carcinoma (HCC), and its effect on survival. Background: Palliative treatment for HCC, including transarterial chemoembolization (TACE) and systemic chemotherapy, is available for patients who do not receive potentially curative therapy. The utilization and outcomes of these therapies in clinical practice are unknown. Study: We conducted a population-based cohort study using the Surveillance, Epidemiology, and End-Results Registry data linked to Medicare claims of HCC patients aged above 65 years diagnosed during 2000 to 2005 who did not receive liver transplant, resection, or ablation. The proportions of patients who received TACE or systemic chemotherapy were calculated by tumor stage, liver disease status, and non-HCC comorbidity. Determinants of receiving palliative therapy were examined in logistic regression models and propensity scores were calculated. Cox proportional hazards models were used to evaluate mortality risk. Results: We identified 3163 HCC patients (median age, 75 y; 67% men) who did not receive potentially curative treatment. Approximately 12.5% of patients received TACE and 11.0% received chemotherapy. In patients with early or intermediate stage HCC, no liver decompensation, and little or no comorbidity, only 22.8% received TACE and 13.8% received chemotherapy. Median survival was significantly higher among patients who received TACE (14.0 mo) compared with who received chemotherapy (5.0 mo) or no therapy (2.0 mo). A significant reduction in overall mortality was observed for TACE (54%) and chemotherapy (33%). Conclusions: Utilization of palliative treatment for HCC is low, which could not be explained by clinical features. However, misclassification could have occurred due to the data source. Receipt of TACE or systemic chemotherapy was associated with a reduction in mortality. C1 [Davila, Jessica A.; Duan, Zhigang] Houston Vet Affairs Med Ctr, Sect Hlth Serv Res, Houston, TX USA. [El-Serag, Hashem B.] Houston Vet Affairs Med Ctr, Gastroenterol Sect, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. RP Davila, JA (reprint author), Michael E DeBakey VA Med Ctr, 2002 Holcombe Blvd,152, Houston, TX 77030 USA. EM jdavila@bcm.tmc.edu FU Onyx Pharmaceuticals; Houston VA HSR&D Center of Excellence [HFP90-020] FX Supported in part by Onyx Pharmaceuticals and the Houston VA HSR&D Center of Excellence (HFP90-020). NR 19 TC 29 Z9 30 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-0790 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD JAN PY 2012 VL 46 IS 1 BP 71 EP 77 DI 10.1097/MCG.0b013e318224d669 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 863FA UT WOS:000298147000016 PM 22157221 ER PT J AU Cushman, WC Davis, BR Pressel, SL Cutler, JA Einhorn, PT Ford, CE Oparil, S Probstfield, JL Whelton, PK Wright, JT Alderman, MH Basile, JN Black, HR Grimm, RH Hamilton, BP Haywood, LJ Ong, ST Piller, LB Simpson, LM Stanford, C Weiss, RJ AF Cushman, William C. Davis, Barry R. Pressel, Sara L. Cutler, Jeffrey A. Einhorn, Paula T. Ford, Charles E. Oparil, Suzanne Probstfield, Jeffrey L. Whelton, Paul K. Wright, Jackson T., Jr. Alderman, Michael H. Basile, Jan N. Black, Henry R. Grimm, Richard H., Jr. Hamilton, Bruce P. Haywood, L. Julian Ong, Stephen T. Piller, Linda B. Simpson, Lara M. Stanford, Carol Weiss, Robert J. CA ALLHAT Collaborative Res Grp TI Mortality and Morbidity During and After the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial SO JOURNAL OF CLINICAL HYPERTENSION LA English DT Article ID CONVERTING-ENZYME-INHIBITOR; BLOOD-PRESSURE; CARDIOVASCULAR EVENTS; FOLLOW-UP; ALLHAT; OUTCOMES; THERAPY; RISK; PARTICIPANTS; HYPERTENSION AB A randomized, double-blind, active-controlled, multicenter trial assigned 32,804 participants aged 55 years and older with hypertension and =1 other coronary heart disease risk factors to receive chlorthalidone (n=15,002), amlodipine (n=8898), or lisinopril (n=8904) for 4 to 8 years, when double-blinded therapy was discontinued. Passive surveillance continued for a total follow-up of 8 to 13 years using national administrative databases to ascertain deaths and hospitalizations. During the post-trial period, fatal outcomes and nonfatal outcomes were available for 98% and 65% of participants, respectively, due to lack of access to administrative databases for the remainder. This paper assesses whether mortality and morbidity differences persisted or new differences developed during the extended follow-up. Primary outcome was cardiovascular mortality and secondary outcomes were mortality, stroke, coronary heart disease, heart failure, cardiovascular disease, and end-stage renal disease. For the post-trial period, data are not available on medications or blood pressure levels. No significant differences (P<.05) appeared in cardiovascular mortality for amlodipine (hazard ratio [HR], 1.00; 95% confidence interval [CI], 0.931.06) or lisinopril (HR, 0.97; CI, 0.901.03), each compared with chlorthalidone. The only significant differences in secondary outcomes were for heart failure, which was higher with amlodipine (HR, 1.12; CI, 1.021.22), and stroke mortality, which was higher with lisinopril (HR, 1.20; CI, 1.011.41), each compared with chlorthalidone. Similar to the previously reported in-trial result, there was a significant treatment-by-race interaction for cardiovascular disease for lisinopril vs chlorthalidone. Black participants had higher risk than non-black participants taking lisinopril compared with chlorthalidone. After accounting for multiple comparisons, none of these results were significant. These findings suggest that neither calcium channel blockers nor angiotensin-converting enzyme inhibitors are superior to diuretics for the long-term prevention of major cardiovascular complications of hypertension. J Clin Hypertens (Greenwich). 2012; 14: 20-31. (C) 2011 Wiley Periodicals, Inc. C1 [Pressel, Sara L.] Univ Texas Hlth Sci Ctr Houston, Univ Texas Houston, ALLHAT Clin Trials Ctr, Sch Publ Hlth, Houston, TX 77030 USA. [Cushman, William C.] Memphis Vet Affairs Med Ctr, Memphis, TN USA. [Cutler, Jeffrey A.; Einhorn, Paula T.] Natl Heart Lung & Blood Inst, Bethesda, MD USA. [Oparil, Suzanne] Univ Alabama Birmingham, Sch Med, Birmingham, AL USA. [Probstfield, Jeffrey L.] Univ Washington, Med Ctr, Seattle, WA 98195 USA. [Whelton, Paul K.] Loyola Univ, Med Ctr, Maywood, IL 60153 USA. [Wright, Jackson T., Jr.] Case Western Reserve Univ, Med Ctr, Cleveland, OH 44106 USA. [Alderman, Michael H.] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Basile, Jan N.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Black, Henry R.] NYU, Langone Med Ctr, New York, NY USA. [Grimm, Richard H., Jr.] Berman Ctr Outcomes & Clin Res, Minneapolis, MN USA. [Hamilton, Bruce P.] Baltimore Vet Adm, Med Ctr, Baltimore, MD USA. [Haywood, L. Julian] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Ong, Stephen T.] Healthcare Greater Washington, Oxon Hill, MD USA. [Stanford, Carol] Univ Missouri, Kansas City Sch Med, Kansas City, MO 64110 USA. [Weiss, Robert J.] Androscoggin Cardiol Associates, Auburn, AL USA. RP Pressel, SL (reprint author), Univ Texas Hlth Sci Ctr Houston, Univ Texas Houston, ALLHAT Clin Trials Ctr, Sch Publ Hlth, RAS W908,,1200 Herman Pressler Dr, Houston, TX 77030 USA. EM sara.l.pressel@uth.tmc.edu FU National Heart, Lung, and Blood Institute (NHLBI) [NO1-HC-35130]; Pfizer; AstraZeneca; Bristol-Myers Squibb; Pfizer Inc.; Merck; GlaxoSmithKline; Forest; Novartis; Takeda FX This study was supported by contract NO1-HC-35130 with the National Heart, Lung, and Blood Institute (NHLBI). ALLHAT investigators received contributions of study medications supplied by Pfizer (amlodipine besylate and doxazosin mesylate), AstraZeneca (atenolol and lisinopril), and Bristol-Myers Squibb (pravastatin), and financial support provided by Pfizer Inc. The authors report no conflicts of interest with regard to this paper. Michael H. Alderman has consulted for AstraZeneca, Merck, and Sankyo; has received honoraria from Bristol-Myers Squibb and Merck; has had grants/contracts with Sankyo; and has held a financial interest in Merck. Jan N. Basile has consulted for Abbott Laboratories, Boehringer Ingelheim, Daiichi Sankyo, Forest Laboratories, Forest Pharmaceuticals, Merck, Novartis, Reddy Pharmaceuticals, Sankyo, and SmithKline Beecham/Glaxo Wellcome; and has received honoraria from Abbott Laboratories, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Forest Laboratories, Merck, Novartis, and Pfizer; Henry R. Black has consulted for Abbott Laboratories, AstraZeneca, Aventis, Bayer Corporation, Biovail, Boehringer Ingelheim, Bristol-Meyers Squibb, CVRx, Daiichi Sankyo, Forest Pharmaceuticals, Gilead, GlaxoSmithKline, Horizons Pharmaceuticals, Inter-cure, Merck, Novartis, Pfizer, Sankyo, Sanofi Aventis, Sanofi-Synthelabo, Servier, and Takeda; has received honoraria from Biovail, Boehringer Ingelheim, Bristol-Myers Squibb, CV Therapeutics, Forest Laboratories, Merck, Novartis, Pfizer, Sanofi-Synthelabo, and Servier; and has had grants/contracts with Pfizer. William C. Cushman has consulted for Abbott Laboratories, Bristol-Myers Squibb, Calpis, Daiichi Sankyo, Forest Pharmaceuticals, Gilead Colorado, Johnson and Johnson, King, Myogen, Novartis, Pfizer, Pharmacopeia, Reddy Pharmaceuticals, Roche, Sankyo, Sanofi Aventis, Sanofi-Synthelabo, Sciele, Takeda, and Theravance; has received honoraria from Abbott Laboratories, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Forest Pharmaceuticals, King, and Novartis and has had grants/contracts with Abbott Laboratories, Biovail, King, and Novartis. Barry R. Davis has consulted for BioMarin, Forest Pharmaceuticals, GlaxoSmithKline, Merck, Proctor and Gamble, and Takeda; and has held a financial interest in Amgen. Charles E. Ford has consulted for BioMarin. Richard H. Grimm, Jr has consulted for Calpis, Merck, Merck/SP, Novartis, Pfizer, and Takeda; has received honoraria from AstraZeneca, Merck, Novartis, and Takeda; and has had grants/contracts with Merck, Novartis, and Pfizer. Bruce P. Hamilton has had grants/contracts with GlaxoSmithKline. L. Julian Haywood has held a financial interest in Pfizer. Stephen T. Ong has received honoraria from Novartis; and has had grants/contracts with Abbott Laboratories, Arena, Daiichi Sankyo, Ferring, Forest Pharmaceutical, Gilead Colorado, GlaxoSmithKline, Mylan Bertek, Novartis, Pharmacopeia, Roche, Sankyo, and Sanofi Aventis. Suzanne Oparil has consulted for Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, Encysive Pharm, Forest Pharmaceuticals, GlaxoSmithKline, Merck, NicOx, Novartis, Pfizer, Salt Institute, Sankyo, Sanofi Aventis, Schering Plough, and SmithKline Beecham/Glaxo Wellcome; has received honoraria from Boehringer Ingelheim, Bristol-Myers Squibb, and Encysive Pharm; has had grants/contracts with Daiichi Sankyo, Eisai Medical Research, Encysive Pharm, Gilead, Novartis, Pfizer, Sankyo, and Takeda; and has held a financial interest in Encysive Pharm. Jeffrey L.; Prob-stfield has consulted for Boehringer Ingelheim, King, and King Pharmceuticals/Monarch; has received honoraria from Boehringer Ingelheim; and has had grants/contracts with Boehringer Ingelheim, King, King Pharmaceuticals/Monarch, KOS, and Sanofi Aventis. Carol Stanford has held a financial interest in Pfizer. Robert J. Weiss has had grants/contracts with Forest, Novartis, and Takeda. Jackson T. Wright, Jr has consulted for Abbott Laboratories, AstraZeneca, Bayer Corporation, Biovail, CV Therapeutics, CVRx, Daiichi Sankyo, Forest Pharmaceuticals, GlaxoSmithKline, Merck, NitroMed, Novartis, Pfizer, Reliant Pharm, Sankyo, Sanofi Aventis, Sanofi-Synthelabo, and SmithKline Beecham/Glaxo Wellcome; and has had grants/contracts with GlaxoSmithKline and Novartis. Jeffrey A. Cutler, Paula T. Einhorn, Linda B. Piller, Sara L. Pressel, Lara M. Simpson, and Paul K. Whelton have no financial conflicts of interest to report. The NHLBI sponsored the study and was involved in all aspects other than direct operations of the study centers. This included collection, analysis, and interpretation of the data plus the decision to submit the manuscript for publication. Pfizer Inc, AstraZeneca, and Bristol-Myers Squibb had no role in the design and conduct of the study, the collection, analysis, and interpretation of the data or the preparation or approval of the manuscript. Editorial assistance was provided by Ellen Breckenridge, an employee of the ALLHAT Collaborative Research Group. The position was paid for by grant funds provided by the NHLBI for the ALLHAT project. NR 27 TC 20 Z9 23 U1 2 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1524-6175 EI 1751-7176 J9 J CLIN HYPERTENS JI J. Clin. Hypertens. PD JAN PY 2012 VL 14 IS 1 BP 20 EP 31 DI 10.1111/j.1751-7176.2011.00568.x PG 12 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 871IV UT WOS:000298732400006 PM 22235820 ER PT J AU Panigrahy, D Edin, ML Lee, CR Huang, S Bielenberg, DR Butterfield, CE Barnes, CM Mammoto, A Mammoto, T Luria, A Benny, O Chaponis, DM Dudley, AC Greene, ER Vergilio, JA Pietramaggiori, G Scherer-Pietramaggiori, SS Short, SM Seth, M Lih, FB Tomer, KB Yang, J Schwendener, RA Hammock, BD Falck, JR Manthati, VL Ingber, DE Kaipainen, A D'Amore, PA Kieran, MW Zeldin, DC AF Panigrahy, Dipak Edin, Matthew L. Lee, Craig R. Huang, Sui Bielenberg, Diane R. Butterfield, Catherine E. Barnes, Carmen M. Mammoto, Akiko Mammoto, Tadanori Luria, Ayala Benny, Ofra Chaponis, Deviney M. Dudley, Andrew C. Greene, Emily R. Vergilio, Jo-Anne Pietramaggiori, Giorgio Scherer-Pietramaggiori, Sandra S. Short, Sarah M. Seth, Meetu Lih, Fred B. Tomer, Kenneth B. Yang, Jun Schwendener, Reto A. Hammock, Bruce D. Falck, John R. Manthati, Vijaya L. Ingber, Donald E. Kaipainen, Arja D'Amore, Patricia A. Kieran, Mark W. Zeldin, Darryl C. TI Epoxyeicosanoids stimulate multiorgan metastasis and tumor dormancy escape in mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID SOLUBLE EPOXIDE HYDROLASE; ISCHEMIA-REPERFUSION INJURY; IN-VIVO; ENDOTHELIAL EXPRESSION; THERAPEUTIC TARGET; CORONARY-ARTERIES; ANGIOGENIC SWITCH; BLOOD-PRESSURE; CANCER-CELLS; NUDE-MICE AB Epoxyeicosatrienoic acids (EETs) are small molecules produced by cytochrome P450 epoxygenases. They are lipid mediators that act as autocrine or paracrine factors to regulate inflammation and vascular tone. As a result, drugs that raise EET levels are in clinical trials for the treatment of hypertension and many other diseases. However, despite their pleiotropic effects on cells, little is known about the role of these epoxyeicosanoids in cancer. Here, using genetic and pharmacological manipulation of endogenous EET levels, we demonstrate that EETs are critical for primary tumor growth and metastasis in a variety of mouse models of cancer. Remarkably, we found that EETs stimulated extensive multiorgan metastasis and escape from tumor dormancy in several tumor models. This systemic metastasis was not caused by excessive primary tumor growth but depended on endothelium-derived EETs at the site of metastasis. Administration of synthetic EETs recapitulated these results, while EET antagonists suppressed tumor growth and metastasis, demonstrating in vivo that pharmacological modulation of EETs can affect cancer growth. Furthermore, inhibitors of soluble epoxide hydrolase (sEH), the enzyme that metabolizes EETs, elevated endogenous EET levels and promoted primary tumor growth and metastasis. Thus, our data indicate a central role for EETs in tumorigenesis, offering a mechanistic link between lipid signaling and cancer and emphasizing the critical importance of considering possible effects of EET-modulating drugs on cancer. C1 [Panigrahy, Dipak; Bielenberg, Diane R.; Butterfield, Catherine E.; Barnes, Carmen M.; Mammoto, Akiko; Mammoto, Tadanori; Benny, Ofra; Chaponis, Deviney M.; Dudley, Andrew C.; Greene, Emily R.; Short, Sarah M.; Seth, Meetu; Ingber, Donald E.; Kieran, Mark W.] Childrens Hosp Boston, Vasc Biol Program, Boston, MA USA. [Panigrahy, Dipak; Chaponis, Deviney M.; Greene, Emily R.; Kieran, Mark W.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. [Edin, Matthew L.; Lee, Craig R.; Lih, Fred B.; Tomer, Kenneth B.; Zeldin, Darryl C.] NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. [Lee, Craig R.] Univ N Carolina, Eshelman Sch Pharm, Div Pharmacotherapy & Expt Therapeut, Chapel Hill, NC USA. [Huang, Sui] Univ Calgary, Inst Biocomplex & Informat, Calgary, AB, Canada. [Huang, Sui] Inst Syst Biol, Seattle, WA USA. [Luria, Ayala; Yang, Jun; Hammock, Bruce D.] UCD, Dept Entomol, Davis, CA USA. [Luria, Ayala; Yang, Jun; Hammock, Bruce D.] UCD, Ctr Canc, Davis, CA USA. [Vergilio, Jo-Anne] Harvard Univ, Sch Med, Dept Pathol, Childrens Hosp Boston, Boston, MA 02115 USA. [Pietramaggiori, Giorgio; Scherer-Pietramaggiori, Sandra S.] Univ Lausanne, Div Plast Surg, Lausanne, Switzerland. [Schwendener, Reto A.] Univ Zurich, Inst Mol Canc Res, Zurich, Switzerland. [Falck, John R.; Manthati, Vijaya L.] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA. [Ingber, Donald E.] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA. [Kaipainen, Arja] Univ Calgary, Dept Biochem & Mol Biol, Calgary, AB, Canada. [D'Amore, Patricia A.] Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02115 USA. RP Panigrahy, D (reprint author), 300 Longwood Ave, Boston, MA 02115 USA. EM dipak.panigrahy@childrens.harvard.edu; sui.huang@systemsbiology.org; mark_kieran@dfci.harvard.edu; zeldin@niehs.nih.gov RI Yang, Jun/B-2262-2010; Tomer, Kenneth/E-8018-2013; OI Yang, Jun/0000-0002-4630-3838; Kieran, Mark/0000-0003-2184-7692; Falck, John/0000-0002-9219-7845; Edin, Matthew/0000-0002-7042-500X; Lee, Craig/0000-0003-3595-5301 FU National Cancer Institute [R01CA148633-01A1]; Stop and Shop Pediatric Brain Tumor Fund; C.J. Buckley Pediatric Brain Tumor Fund; Division of Intramural Research of the NIH, National Institute of Environmental Health Sciences [Z01 ES025034, Z01 ES050167]; NIH [R01 GM088199, CA045548]; Robert A. Welch Foundation; NIEHS [NIH P42 ES004699, NIH R01 ES002710, NIH R01 ES013933] FX We thank and gratefully acknowledge Kristin Johnson for photography and preparation of the figures; J. Alyce Bradbury, Joan P. Graves, Laura M. DeGraff, Ricky Sanchez, Lyndsay Leach, and Tony Walshe for excellent technical assistance; and Sung Hee Hwang for sEH inhibitors and eicosanoid profiling assays. We thank Isaiah J. Fidler for PC3M-LN4 cells. This work was supported by National Cancer Institute grant R01CA148633-01A1 (to D. Panigrahy); the Stop and Shop Pediatric Brain Tumor Fund and the C.J. Buckley Pediatric Brain Tumor Fund (to M.W. Kieran); Division of Intramural Research of the NIH, National Institute of Environmental Health Sciences grants Z01 ES025034 and Z01 ES050167 (to D.C. Zeldin and K.B. Tomer); NIH grant R01 GM088199 (to C.R. Lee); the Robert A. Welch Foundation (to J.R Falck); NIEHS Superfund Basic Research Program grants NIH P42 ES004699, NIH R01 ES002710, and NIH R01 ES013933 (to B.D. Hammock); and NIH grant CA045548 (to D.E. Ingber). B.D. Hammock is a George and Judy Marcus Senior Fellow of the American Asthma Foundation. NR 62 TC 88 Z9 90 U1 2 U2 21 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JAN PY 2012 VL 122 IS 1 BP 178 EP 191 DI 10.1172/JCI58128 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 871WW UT WOS:000298769400023 PM 22182838 ER PT J AU Yoshioka, J Chutkow, WA Lee, S Kim, JB Yan, J Tian, R Lindsey, ML Feener, EP Seidman, CE Seidman, JG Lee, RT AF Yoshioka, Jun Chutkow, William A. Lee, Samuel Kim, Jae Bum Yan, Jie Tian, Rong Lindsey, Merry L. Feener, Edward P. Seidman, Christine E. Seidman, Jonathan G. Lee, Richard T. TI Deletion of thioredoxin-interacting protein in mice impairs mitochondrial function but protects the myocardium from ischemia-reperfusion injury SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID CARBOHYDRATE RESPONSE ELEMENT; OXIDATIVE STRESS; PERMEABILITY TRANSITION; CARDIAC MITOCHONDRIA; PRESSURE-OVERLOAD; NITRIC-OXIDE; HELA-CELLS; EXPRESSION; GLUCOSE; DYSFUNCTION AB Classic therapeutics for ischemic heart disease are less effective in individuals with the metabolic syndrome. As the prevalence of the metabolic syndrome is increasing, better understanding of cardiac metabolism is needed to identify potential new targets for therapeutic intervention. Thioredoxin-interacting protein (Txnip) is a regulator of metabolism and an inhibitor of the antioxidant thioredoxins, but little is known about its roles in the myocardium. We examined hearts from Txnip-KO mice by polony multiplex analysis of gene expression and an independent proteomic approach; both methods indicated suppression of genes and proteins participating in mitochondrial metabolism. Consistently, Txnip-KO mitochondria were functionally and structurally altered, showing reduced oxygen consumption and ultrastructural derangements. Given the central role that mitochondria play during hypoxia, we hypothesized that Txnip deletion would enhance ischemia-reperfusion damage. Surprisingly, Txnip-KO hearts had greater recovery of cardiac function after an ischemia-reperfusion insult. Similarly, cardiomyocyte-specific Txnip deletion reduced infarct size after reversible coronary ligation. Coordinated with reduced mitochondrial function, deletion of Txnip enhanced anaerobic glycolysis. Whereas mitochondrial ATP synthesis was minimally decreased by Txnip deletion, cellular ATP content and lactate formation were higher in Txnip-KO hearts after ischemia-reperfusion injury. Pharmacologic inhibition of glycolytic metabolism completely abolished the protection afforded the heart by Txnip deficiency under hypoxic conditions. Thus, although Txnip deletion suppresses mitochondrial function, protection from myocardial ischemia is enhanced as a result of a coordinated shift to enhanced anaerobic metabolism, which provides an energy source outside of mitochondria. C1 [Yoshioka, Jun; Chutkow, William A.; Lee, Samuel; Kim, Jae Bum; Yan, Jie; Tian, Rong; Seidman, Christine E.; Lee, Richard T.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Lindsey, Merry L.] Univ Texas Hlth Sci Ctr UTHSCSA, Dept Med, Div Cardiol, San Antonio, TX USA. [Feener, Edward P.] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Seidman, Christine E.; Seidman, Jonathan G.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Lee, Richard T.] Harvard Stem Cell Inst, Cambridge, MA USA. RP Lee, RT (reprint author), 65 Landsdowne St,Room 279, Cambridge, MA 02139 USA. EM rlee@partners.org RI Lindsey, Merry/B-2650-2012; OI Tian, Rong/0000-0002-3676-3830 FU American Heart Association [0835484N]; Deutsche Forschungsgemeinschaft [LE 2728/1-1]; NIH [HL088977, NHLBI268201000036C-0-0-1, HL048743, HL103582] FX We thank Hayden Huang (Columbia University) and Kenichi Imahashi (National Institute of Environmental Health Sciences) for their technical advice. We also thank Joseph Gannon and Qiuxia Dai for their technical assistance. This work was supported by American Heart Association Scientist Development Grant 0835484N (to J. Yoshioka); Deutsche Forschungsgemeinschaft LE 2728/1-1 (to S. Lee); and NIH grants HL088977 (to W.A. Chutkow), NHLBI268201000036C-0-0-1 for the UTHSCSA Cardiovascular Proteomics Center (to M.L. Lindsey), and HL048743 and HL103582 (to R.T. Lee). NR 56 TC 55 Z9 56 U1 2 U2 13 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JAN PY 2012 VL 122 IS 1 BP 267 EP 279 DI 10.1172/JCI44927 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 871WW UT WOS:000298769400030 PM 22201682 ER PT J AU Kearney, DJ McDermott, K Malte, C Martinez, M Simpson, TL AF Kearney, David J. McDermott, Kelly Malte, Carol Martinez, Michelle Simpson, Tracy L. TI Association of participation in a mindfulness program with measures of PTSD, depression and quality of life in a veteran sample SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article DE mindfulness; posttraumatic stress disorder; acceptance; depression; meditation ID POSTTRAUMATIC-STRESS-DISORDER; PROSTATE-CANCER OUTPATIENTS; NATIONAL COMORBIDITY SURVEY; BEHAVIORAL ACTIVATION; REDUCTION PROGRAM; COGNITIVE THERAPY; SEXUAL TRAUMA; SCALE BADS; SYMPTOMS; MEDITATION AB Objectives: To assess outcomes of veterans who participated in mindfulness-based stress reduction (MBSR). Design: Posttraumatic stress disorder (PTSD) symptoms, depression, functional status, behavioral activation, experiential avoidance, and mindfulness were assessed at baseline, and 2 and 6 months after enrollment. Results: At 6 months, there were significant improvements in PTSD symptoms (standardized effect size, d = -0.64, p< 0.001); depression (d = -0.70, p<0.001); behavioral activation (d = 0.62, p<0.001); mental component summary score of the Short Form-8 (d = 0.72, p<0.001); acceptance (d = 0.67, p<0.001); and mindfulness (d = 0.78, p<0.001), and 47.7% of veterans had clinically significant improvements in PTSD symptoms. Conclusions: MBSR shows promise as an intervention for PTSD and warrants further study in randomized controlled trials. (c) 2011 Wiley Periodicals, Inc. J Clin Psychol 68:116, 2012. C1 [Kearney, David J.; McDermott, Kelly; Malte, Carol; Martinez, Michelle; Simpson, Tracy L.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Kearney, DJ (reprint author), Seattle VAMC 111GI,1660 S Columbian Way, Seattle, WA 98108 USA. EM david.kearney@va.gov RI Schueter, nicos/A-3625-2014 NR 59 TC 72 Z9 72 U1 8 U2 55 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9762 J9 J CLIN PSYCHOL JI J. Clin. Psychol. PD JAN PY 2012 VL 68 IS 1 BP 101 EP 116 DI 10.1002/jclp.20853 PG 16 WC Psychology, Clinical SC Psychology GA 865HE UT WOS:000298301000009 PM 22125187 ER PT J AU Mayotte-Blum, J Slavin-Mulford, J Lehmann, M Pesale, F Becker-Matero, N Hilsenroth, M AF Mayotte-Blum, Jason Slavin-Mulford, Jenelle Lehmann, Meaghan Pesale, Frank Becker-Matero, Nikaya Hilsenroth, Mark TI Therapeutic Immediacy Across Long-Term Psychodynamic Psychotherapy: An Evidence-Based Case Study SO JOURNAL OF COUNSELING PSYCHOLOGY LA English DT Article DE therapeutic immediacy; psychodynamic psychotherapy; case study; self-disclosure; transference ID CONSENSUAL QUALITATIVE RESEARCH; TRANSFERENCE INTERPRETATIONS; INTERPERSONAL PROBLEMS; PERSONALITY-DISORDERS; DYNAMIC PSYCHOTHERAPY; THERAPIST IMMEDIACY; SOCIAL-ADJUSTMENT; SELF-REPORT; ALLIANCE; PATIENT AB C. E. Hill (2004) recently developed the concept of therapist immediacy to capture discussion by the therapist about the therapeutic relationship that occurs in the here-and-now of a therapy session. This concept has been expanded to include discussion about the therapeutic relationship by both the client and therapist, captured by the term therapeutic immediacy (K. Kuutmann & M. Hilsenroth, 2011). Although prior research has examined the use of therapeutic immediacy across short-term treatment, the present study is the first to examine the use of immediacy across a long-term (4 years) psychotherapy. Also, this is the first study to assess the interrater reliability of therapeutic immediacy, which was found to achieve good to excellent levels across raters. The most frequently used categories of client and therapist immediacy are presented. Finally, the authors provide an in-depth qualitative examination of 5 therapeutic immediacy segments across the treatment judged by the raters to have high levels of depth/intensity (4.5 or higher out of 5) to examine the role of therapeutic immediacy in exploring meaningful treatment issues. Clinical utility, potential limitations, and future research on therapeutic immediacy are discussed. C1 [Mayotte-Blum, Jason; Lehmann, Meaghan; Pesale, Frank; Becker-Matero, Nikaya; Hilsenroth, Mark] Adelphi Univ, Derner Inst Adv Psychol Studies, Garden City, NY 11530 USA. [Slavin-Mulford, Jenelle] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Slavin-Mulford, Jenelle] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Mayotte-Blum, J (reprint author), Adelphi Univ, Derner Inst Adv Psychol Studies, Hy Weinberg Bldg,158 Cambridge Ave, Garden City, NY 11530 USA. EM jasonblum@nyc.rr.com NR 39 TC 12 Z9 12 U1 1 U2 15 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-0167 J9 J COUNS PSYCHOL JI J. Couns. Psychol. PD JAN PY 2012 VL 59 IS 1 BP 27 EP 40 DI 10.1037/a0026087 PG 14 WC Psychology, Educational; Psychology, Applied SC Psychology GA 875SB UT WOS:000299053900004 PM 22059428 ER PT J AU Li, Y Rimbara, E Thirumurthi, S Trespalacios, A Reddy, R Sabounchi, S Attumi, TA Graham, DY AF Li, Yuan Rimbara, Emiko Thirumurthi, Selvi Trespalacios, Alba Reddy, Rita Sabounchi, Saman Attumi, Taraq Assed Graham, David Yates TI Detection of clarithromycin resistance in Helicobacter pylori following noncryogenic storage of rapid urease tests for 30 days SO JOURNAL OF DIGESTIVE DISEASES LA English DT Article DE clarithromycin resistance; Helicobacter pylori; noncryogenic storage; polymerase chain reaction; rapid urease test; susceptibility test ID POLYMERASE-CHAIN-REACTION; 23S RIBOSOMAL-RNA; ANTIBIOTIC-RESISTANCE; BIOPSY SPECIMENS; GASTRIC TISSUE; INFECTION; SUSCEPTIBILITY; POLYMORPHISM; PREVALENCE; MUTATIONS AB OBJECTIVE: Traditional Helicobacter pylori (H. pylori) eradication therapy has been undermined by increasing antimicrobial, especially clarithromycin, resistance. Susceptibility testing in some areas is difficult to achieve or unavailable. We aimed to determine whether gastric biopsy specimens stored at room temperature for rapid urease test (RUT) were suitable for clarithromycin susceptibility testing of H. pylori. METHODS: After 30 days of storage at room temperature, DNA was extracted from gastric biopsies present in RUTs (Hpfast). H. pylori status and clarithromycin susceptibility were evaluated using H. pylori- specific polymerase chain reaction (PCR) for ureA, vacA, and allele- specific primer- PCR of the 23S rRNA genes. The PCR results were compared with histology, RUT, and culture results. H. pylori positive was defined as RUT and either culture or histology positive; H. pylori negative as RUT, culture and histology negative. RESULTS: Samples from 31 patients were evaluated; 11 were H. pylori positive including 9 by culture; seven of which had allele- specific primer- PCR results from the RUT specimen for the detection of mutations of the 23S rRNA gene. When both tests were available, culture and PCR results were concordant in 7 cases. In 15 of the 20 histology, RUT and culture negative patients, three PCR were negative. In one patient, all of the three tests were positive; and in three only the 23S rRNA was positive and in one only ureA was positive. CONCLUSION: Gastric biopsy specimens stored in the gel of RUT for 30 days can be used for molecular testing to confirm the diagnosis of H. pylori infection and test for clarithromycin susceptibility. C1 [Li, Yuan; Rimbara, Emiko; Thirumurthi, Selvi; Trespalacios, Alba; Reddy, Rita; Sabounchi, Saman; Attumi, Taraq Assed; Graham, David Yates] Baylor Coll Med, Ben Taub Gen Hosp, Dept Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Graham, DY (reprint author), Baylor Coll Med, Dept Med, Michael E DeBakey Vet Affairs, Affairs Med Ctr, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM dgraham@bcm.edu RI Rimbara, Emiko/F-4113-2017 OI Rimbara, Emiko/0000-0001-8847-1840 FU Office of Research and Development Medical Research Service, Department of Veterans Affairs, Public Health Service [DK56338]; Texas Medical Center Digestive Diseases Center [DK067366, CA116845] FX Dr GRAHAM is supported in part by the Office of Research and Development Medical Research Service, Department of Veterans Affairs, Public Health Service grant DK56338 which funds the Texas Medical Center Digestive Diseases Center, DK067366 and CA116845. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the Veterans Affairs or National Institutes of Health. Dr GRAHAM is an unpaid consultant for Novartis in relation to vaccine development for the treatment or prevention of H. pylori infection. Dr GRAHAM is also a paid consultant for Otsuka Pharmaceuticals regarding diagnostic testing and has received royalties on the Baylor College of Medicine patent covering materials related to the 13C-urea breath test. The other authors have nothing to declare. NR 21 TC 8 Z9 9 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1751-2972 J9 J DIGEST DIS JI J. Dig. Dis. PD JAN PY 2012 VL 13 IS 1 BP 54 EP 59 DI 10.1111/j.1751-2980.2011.00549.x PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 867UK UT WOS:000298480100009 PM 22188917 ER PT J AU Smith, KW Proctor, SP Ozonoff, AL McClean, MD AF Smith, Kristen W. Proctor, Susan P. Ozonoff, A. L. McClean, Michael D. TI Urinary biomarkers of occupational jet fuel exposure among air force personnel SO JOURNAL OF EXPOSURE SCIENCE AND ENVIRONMENTAL EPIDEMIOLOGY LA English DT Article DE jet fuel; JP8; urinary biomarkers; 1-naphthol; 2-naphthol; naphthalene ID DERMAL EXPOSURE; WORKERS; JP-8; NAPHTHALENE; PENETRATION; 1-NAPHTHOL; COMPONENTS; ABSORPTION; INHALATION; NAPHTHOLS AB There is a potential for widespread occupational exposure to jet fuel among military and civilian personnel. Urinary metabolites of naphthalene have been suggested for use as short-term biomarkers of exposure to jet fuel (jet propulsion fuel 8 (JP8)). In this study, urinary biomarkers of JP8 were evaluated among US Air Force personnel. Personnel (n = 24) were divided a priori into high, moderate, and low exposure groups. Pre- and post-shift urine samples were collected from each worker over three workdays and analyzed for metabolites of naphthalene (1- and 2-naphthol). Questionnaires and breathingzone naphthalene samples were collected from each worker during the same workdays. Linear mixed-effects models were used to evaluate the exposure data. Post-shift levels of 1- and 2-naphthol varied significantly by a priori exposure group (levels in high group>moderate group>low group), and breathing-zone naphthalene was a significant predictor of post-shift levels of 1-and 2-naphthol, indicating that for every unit increase in breathing-zone naphthalene, there was an increase in naphthol levels. These results indicate that post-shift levels of urinary 1-and 2-naphthol reflect JP8 exposure during the work-shift and may be useful surrogates of JP8 exposure. Among the high exposed workers, significant job-related predictors of post-shift levels of 1-and 2-naphthol included entering the fuel tank, repairing leaks, direct skin contact with JP8, and not wearing gloves during the work-shift. The job-related predictors of 1-and 2-naphthol emphasize the importance of reducing inhalation and dermal exposure through the use of personal protective equipment while working in an environment with JP8. Journal of Exposure Science and Environmental Epidemiology (2012) 22, 35-45; doi: 10.1038/jes.2011.38; published online 2 November 2011 C1 [Smith, Kristen W.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Smith, Kristen W.; Proctor, Susan P.; McClean, Michael D.] Boston Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA. [Smith, Kristen W.; Proctor, Susan P.] USA, Mil Performance Div, Environm Med Res Inst, Natick, MA 01760 USA. [Proctor, Susan P.] VA Boston Healthcare Syst, Boston, MA USA. [Ozonoff, A. L.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. RP Smith, KW (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, 665 Huntington Ave,Bldg 1,Room 1402, Boston, MA 02115 USA. EM ksmith@hsph.harvard.edu RI McClean, Michael/J-2934-2015; OI McClean, Michael/0000-0002-3902-8823; Ozonoff, Al/0000-0003-4233-5899 FU US Air Force personnel; US Army Medical Research and Materiel Command [W81XWH-06-10105]; Henry M. Jackson Foundation of the Advancement of Military Medicine FX We sincerely thank the US Air Force personnel for their cooperation and generous participation in this research project. This work was supported by the US Army Medical Research and Materiel Command award (W81XWH-06-10105) to the Henry M. Jackson Foundation of the Advancement of Military Medicine (PI: SP Proctor). The opinions or assertions contained herein are the private views of the author(s) and are not to be construed as official or as reflecting the views of the Army or the Department of Defense. NR 28 TC 5 Z9 5 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1559-0631 J9 J EXPO SCI ENV EPID JI J. Expo. Sci. Environ. Epidemiol. PD JAN-FEB PY 2012 VL 22 IS 1 BP 35 EP 45 DI 10.1038/jes.2011.38 PG 11 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 864NZ UT WOS:000298248200004 PM 22044926 ER PT J AU Drazner, MH Brown, RN Kaiser, PA Cabuay, B Lewis, NP Semigran, MJ Torre-Amione, G Naftel, DC Kirklin, JK AF Drazner, Mark H. Brown, Robert N. Kaiser, Patricia A. Cabuay, Barry Lewis, Neil. P. Semigran, Marc J. Torre-Amione, Guillermo Naftel, David C. Kirklin, James K. TI Relationship of right- and left-sided filling pressures in patients with advanced heart failure: A 14-year multi-institutional analysis SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article DE hemodynamics; physical examination; heart failure; outcomes; survival; cardiac transplantation AB BACKGROUND: Jugular venous pressure (JVP) is assessed to estimate volume status in patients with heart failure because right atrial pressure (RAP) reflects pulmonary capillary wedge pressure (PCWP). In a large cohort of heart failure patients spanning 14 years, we sought to further characterize the relationship between RAP and PCWP, including identifying temporal trends, to optimize estimates of PCWP by JVP. We also sought to determine whether the RAP to PCWP relationship impacts post-transplant mortality. METHODS: Hemodynamic data were obtained from 4,079 patients before cardiac transplantation. Elevated RAP was defined as >= 10 mm Hg and elevated PCWP >= 22 mm Hg. Hemodynamics were "concordant" when both RAP and PCWP were elevated or when both were not elevated. The frequency of concordant hemodynamics was assessed over 3 eras (1993 to 1997, 1998 to 2002, 2003 to 2007). Baseline characteristics were compared among quartiles of the ratio (RAP+1)/PCWP. The association of (RAP+1)/PCWP with 2-year mortality after cardiac transplantation was assessed using multivariate models. RESULTS: The frequency of concordant hemodynamics over time was stable (74%, 72%, 73%; p = 0.4). Increasing (RAP+ 1)/PCWP was associated with the following variables: female gender; cardiomyopathy etiology besides ischemic or non-ischemic; prior sternotomies; and lower creatinine clearance (p < 0.01 for all). Elevated (RAP+1)/PCWP was associated with post-transplant mortality (relative risk 1.2, 95% confidence interval 1.02 to 1.37, p = 0.02). CCONCLUSIONS: RAP and PCWP remain concordant in most heart failure patients, supporting the ongoing use of JVP to estimate PCWP. Easily identifiable patient characteristics were associated with an increased RAP/PCWP ratio, and their presence should alert clinicians that PCWP may be overestimated by JVP assessment. A higher RAP/PCWP ratio was an adverse risk factor for post cardiac transplant survival. J Heart Lung Transplant 2012;31:67-72 (C) 2012 International Society for Heart and Lung Transplantation. All rights reserved. C1 [Drazner, Mark H.; Kaiser, Patricia A.] Univ Texas SW Med Ctr Dallas, Div Cardiol, Dept Internal Med, Dallas, TX 75390 USA. [Brown, Robert N.; Naftel, David C.; Kirklin, James K.] Univ Alabama, Dept Surg, Birmingham, AL 35294 USA. [Cabuay, Barry] Univ Iowa, Dept Cardiovasc Med, Iowa City, IA USA. [Lewis, Neil. P.] Virginia Commonwealth Univ, Dept Cardiol, Richmond, VA USA. [Lewis, Neil. P.] McGuire VA Med Ctr, Richmond, VA USA. [Semigran, Marc J.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Torre-Amione, Guillermo] Methodist Hosp, Methodist DeBakey Heart Ctr, Houston, TX 77030 USA. RP Drazner, MH (reprint author), Univ Texas SW Med Ctr Dallas, Div Cardiol, Dept Internal Med, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM mark.drazner@utsouthwestern.edu FU James M. Wooten Chair in Cardiology FX The authors have no conflicts of interest to disclose. M.H.D. was supported by the James M. Wooten Chair in Cardiology. NR 6 TC 17 Z9 17 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD JAN PY 2012 VL 31 IS 1 BP 67 EP 72 DI 10.1016/j.healun.2011.09.003 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 867GF UT WOS:000298442200009 PM 22071240 ER PT J AU Jilg, N Chung, RT AF Jilg, Nikolaus Chung, Raymond T. TI Adding to the toolbox: Receptor tyrosine kinases as potential targets in the treatment of hepatitis C SO JOURNAL OF HEPATOLOGY LA English DT Article DE HCV; HCV entry; Entry factors; EGFR; Host factors; Receptor tyrosine kinases ID FUNCTIONAL GENOMIC SCREEN; VIRUS-REPLICATION; INFECTION 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 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. (C) 2011 European Association for the study of the Liver. Published by Elsevier B.V. All rights reserved. C1 [Jilg, Nikolaus; Chung, Raymond T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St, Boston, MA 02114 USA. EM rtchung@partners.org NR 12 TC 2 Z9 2 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD JAN PY 2012 VL 56 IS 1 BP 282 EP 284 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 867WC UT WOS:000298484500044 PM 21784050 ER PT J AU Burks, DJ Robbins, R AF Burks, Derek J. Robbins, Rockey TI Psychologists' Authenticity: Implications for Work in Professional and Therapeutic Settings SO JOURNAL OF HUMANISTIC PSYCHOLOGY LA English DT Article DE authenticity; genuineness; humanistic psychotherapy; therapeutic relationship ID QUALITATIVE RESEARCH; CONCEPTUALIZATION AB Psychologists engage in a multitude of social roles of varying degrees of emotionality, subjectivity, and objectivity because of the nature of their profession as well as their unique backgrounds that have drawn them to that profession. This study sought to understand how psychologists recognize and experience the concept of authenticity in the context of their professional lives. A purposeful sample of 17 clinical psychologists from metropolitan areas in the Southwest and the Pacific Northwest were interviewed. Using a phenomenological, qualitative research design, 262 significant statements were extracted and grouped together, resulting in 11 emergent themes specifically relating to a therapeutic, health care context. Rigor and thoroughness were achieved via multiple validation procedures. Psychologists defined authenticity as the matching of one's inner thoughts, beliefs, and feelings with one's outer presentation and behaviors. They believed that authenticity involves sensory and emotional qualities rather than purely cognitive or verbal qualities. Concepts of self-disclosure and mindful awareness were discussed as related to authenticity. It is of note that both humanistic and nonhumanistically inclined psychologists equally valued authenticity in the professional and therapeutic setting. Participants also discussed how authenticity and inauthenticity are experienced and modified in the therapeutic relationship, as well as the negative effects of inauthenticity in professional contexts. C1 [Robbins, Rockey] Univ Oklahoma, Coll Educ, Norman, OK 73019 USA. RP Burks, DJ (reprint author), Portland VA Med Ctr, P3MIRECC,POB 1034, Portland, OR 97207 USA. EM derek.burks@va.gov NR 41 TC 2 Z9 4 U1 1 U2 10 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-1678 J9 J HUMANIST PSYCHOL JI J. Humanist. Psychol. PD JAN PY 2012 VL 52 IS 1 BP 75 EP 104 DI 10.1177/0022167810381472 PG 30 WC Psychology, Multidisciplinary SC Psychology GA 868YR UT WOS:000298563000005 ER PT J AU Ling, MT Tu, WW Han, Y Mao, HW Chong, WP Guan, J Liu, M Lam, KT Law, HKW Peiris, JSM Takahashi, K Lau, YL AF Ling, Man To Tu, Wenwei Han, Yan Mao, Huawei Chong, Wai Po Guan, Jing Liu, Ming Lam, Kwok Tai Law, Helen K. W. Peiris, J. S. Malik Takahashi, K. Lau, Yu Lung TI Mannose-Binding Lectin Contributes to Deleterious Inflammatory Response in Pandemic H1N1 and Avian H9N2 Infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID INFLUENZA-A-VIRUS; PATTERN-RECOGNITION MOLECULE; CYTOKINE RESPONSES; PROTEIN FUNCTIONS; GENE-EXPRESSION; HOST-DEFENSE; MICE; INTERLEUKIN-1; PATHOGENESIS; MACROPHAGES AB Background. Mannose-binding lectin (MBL) is a pattern-recognition molecule, which functions as a first line of host defense. Pandemic H1N1 (pdmH1N1) influenza A virus caused massive infection in 2009 and currently circulates worldwide. Avian influenza A H9N2 (H9N2/G1) virus has infected humans and has the potential to be the next pandemic virus. Antiviral function and immunomodulatory role of MBL in pdmH1N1 and H9N2/G1 virus infection have not been investigated. Methods. In this study, MBL wild-type (WT) and MBL knockout (KO) murine models were used to examine the role of MBL in pdmH1N1 and H9N2/G1 virus infection. Results. Our study demonstrated that in vitro, MBL binds to pdmH1N1 and H9N2/G1 viruses, likely via the carbohydrate recognition domain of MBL. Wild-type mice developed more severe disease, as evidenced by a greater weight loss than MBL KO mice during influenza virus infection. Furthermore, MBL WT mice had enhanced production of proinflammatory cytokines and chemokines compared with MBL KO mice, suggesting that MBL could upregulate inflammatory responses that may potentially worsen pdmH1N1 and H9N2/G1 virus infections. Conclusions. Our study provided the first in vivo evidence that MBL may be a risk factor during pdmH1N1 and H9N2/G1 infection by upregulating proinflammatory response. C1 [Ling, Man To; Tu, Wenwei; Han, Yan; Mao, Huawei; Chong, Wai Po; Guan, Jing; Lam, Kwok Tai; Law, Helen K. W.; Lau, Yu Lung] Univ Hong Kong, Dept Paediat & Adolescent Med, Li Ka Shing Fac Med, Hong Kong, Hong Kong, Peoples R China. [Peiris, J. S. Malik] Univ Hong Kong, Dept Microbiol, Li Ka Shing Fac Med, Hong Kong, Hong Kong, Peoples R China. [Liu, Ming] Guangzhou Med Coll, Guangzhou Inst Resp Dis, Guangzhou, Guangdong, Peoples R China. [Takahashi, K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat, Boston, MA USA. RP Lau, YL (reprint author), Univ Hong Kong, Dept Paediat & Adolescent Med, Queen Mary Hosp, Li Ka Shing Fac Med, Hong Kong, Hong Kong, Peoples R China. EM lauylung@hkucc.hku.hk RI Mao, Huawei/C-9255-2012; Lau, Yu Lung/C-4322-2009 FU National Institutes of Health [U01AI074503]; University Grants Committee of the Hong Kong Special Administrative Region, China [AoE/M-12/06]; Hong Kong SAR government [Lab-11]; Chung Ko Lee and Cheung Yuen Kan Education and Research Fund in Paediatric Immunology FX This work was supported in part by the National Institutes of Health (U01AI074503); the Area of Excellence program on influenza supported by the University Grants Committee of the Hong Kong Special Administrative Region, China (AoE/M-12/06); the Research Fund for the Control of Infectious Diseases, Hong Kong SAR government (Lab-11); and the Chung Ko Lee and Cheung Yuen Kan Education and Research Fund in Paediatric Immunology. NR 50 TC 22 Z9 23 U1 1 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JAN 1 PY 2012 VL 205 IS 1 BP 44 EP 53 DI 10.1093/infdis/jir691 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 866MW UT WOS:000298386200009 PM 22080095 ER PT J AU Grobman, LE Wu, DY Dong, DZ Wu, PC AF Grobman, L. E. Wu, D. Y. Dong, D. Z. Wu, P. C. TI THE ROLE OF COXSACKIE-ADENOVIRUS RECEPTOR AS A SENESCENCE BIOMARKER DURING RECTAL CANCER TREATMENT SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting CY JAN 25-28, 2012 CL Carmel, CA C1 [Grobman, L. E.; Wu, D. Y.; Wu, P. C.] Univ Washington, Seattle, WA 98195 USA. [Wu, D. Y.; Dong, D. Z.; Wu, P. C.] VA Puget Sound, Seattle, WA USA. 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 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2012 VL 60 IS 1 BP 148 EP 148 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 869XV UT WOS:000298634401081 ER PT J AU MIller, M Knaub, L Reusch, JE AF MIller, M. Knaub, L. Reusch, J. E. TI ATTENUATION OF ACUTE EXERCISE-INDUCED MITOCHONDRIAL BIOGENESIS AND OXIDANT DEFENSE IN A MODEL OF INSULIN RESISTANT DIABETES SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting CY JAN 25-28, 2012 CL Carmel, CA C1 [MIller, M.; Knaub, L.; Reusch, J. E.] Univ Colorado, Sch Med, Aurora, CO USA. [Reusch, J. E.] Denver VA Med Ctr, Denver, CO USA. 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 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2012 VL 60 IS 1 BP 176 EP 176 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 869XV UT WOS:000298634401178 ER PT J AU Hartvigson, PE Erikson, MA Banks, WA AF Hartvigson, P. E. Erikson, M. A. Banks, W. A. TI SYSTEMIC INFLAMMATION INHIBITS LOW-DENSITY LIPOPROTEIN RECEPTOR-RELATED PROTEIN-1 MEDIATED CLEARANCE OF AMYLOID-beta FROM BLOOD: IMPLICATIONS FOR ALZHEIMER'S DISEASE SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting CY JAN 25-28, 2012 CL Carmel, CA C1 [Hartvigson, P. E.; Erikson, M. A.; Banks, W. A.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Hartvigson, P. E.; Banks, W. A.] Univ Washington, Sch Med, Seattle, WA USA. [Erikson, M. A.] St Louis Univ, St Louis, MO 63103 USA. 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 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2012 VL 60 IS 1 BP 240 EP 240 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 869XV UT WOS:000298634401409 ER PT J AU Obioha, O Bassett, J Saigal, C Bennett, C AF Obioha, O. Bassett, J. Saigal, C. Bennett, C. TI DISSEMINATION OF TOBACCO CONTROL GUIDELINES TO A SPECIALTY CARE SETTING: A UROLOGIC PERSPECTIVE SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting CY JAN 25-28, 2012 CL Carmel, CA C1 [Obioha, O.; Bassett, J.; Saigal, C.; Bennett, C.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Bassett, J.; Saigal, C.; Bennett, C.] W Los Angeles VA Hosp, Los Angeles, CA USA. 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 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2012 VL 60 IS 1 BP 244 EP 245 PG 2 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 869XV UT WOS:000298634401424 ER PT J AU Bains, S Egede, LE AF Bains, S. Egede, L. E. TI ASSOCIATIONS BETWEEN HEALTH LITERACY AND PREVENTATIVE CARE BEHAVIOR: ANALYSIS OF A NATIONAL SAMPLE SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting CY JAN 25-28, 2012 CL Carmel, CA C1 [Bains, S.; Egede, L. E.] Med Univ S Carolina, Charleston, SC 29425 USA. [Egede, L. E.] Ralph H Johnson VAMC, Charleston, SC USA. 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 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2012 VL 60 IS 1 BP 353 EP 353 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 869XV UT WOS:000298634402152 ER PT J AU Vasquez, K Wagner, BT AF Vasquez, K. Wagner, B. T. TI NEPHROGENIC SYSTEMIC FIBROSIS: THE CONTRIBUTION OF BONE MARROW-DERIVED FIBROCYTES TO SKIN LESIONS AND ASSOCIATION WITH L-CATHEPSIN SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting CY JAN 25-28, 2012 CL Carmel, CA C1 [Vasquez, K.; Wagner, B. T.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Vasquez, K.; Wagner, B. T.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. 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 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2012 VL 60 IS 1 BP 425 EP 425 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 869XV UT WOS:000298634402416 ER PT J AU Billue, K Safford, M Salanitro, A Houston, T Curry, W Kim, Y Allison, J Estrada, C AF Billue, K. Safford, M. Salanitro, A. Houston, T. Curry, W. Kim, Y. Allison, J. Estrada, C. TI DIABETES MEDICATION INTENSIFICATION IN RURAL PRIMARY CARE PRACTICES: A CLUSTER-RANDOMIZED EFFECTIVENESS TRIAL SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting CY JAN 25-28, 2012 CL Carmel, CA C1 [Billue, K.; Safford, M.; Salanitro, A.; Curry, W.; Kim, Y.; Estrada, C.] Univ Alabama, Birmingham, AL USA. [Estrada, C.] Birmingham VAMC, Birmingham, AL USA. [Houston, T.; Allison, J.] Univ Massachusetts, Sch Med, Worcester, MA USA. RI Houston, Thomas/F-2469-2013 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 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2012 VL 60 IS 1 BP 460 EP 461 PG 2 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 869XV UT WOS:000298634402541 ER PT J AU Bains, S Egede, LE AF Bains, S. Egede, L. E. TI DEMOGRAPHIC, GEOGRAPHIC AND LANGUAGE PREDICTORS OF HEALTH LITERACY: ANALYSIS OF THE 2003 NATIONAL ASSESSMENT OF ADULT LITERACY SURVEY SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting CY JAN 25-28, 2012 CL Carmel, CA C1 [Bains, S.; Egede, L. E.] Med Univ S Carolina, Charleston, SC 29425 USA. [Egede, L. E.] Ralph H Johnson VAMC, Charleston, SC USA. 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 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2012 VL 60 IS 1 BP 463 EP 463 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 869XV UT WOS:000298634402551 ER PT J AU Newsom, J Taylor, B AF Newsom, J. Taylor, B. TI CAN MEDICAL TEAM MEMBERS PREDICT 30-DAY READMISSION RISK ON ADMISSION? SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting CY JAN 25-28, 2012 CL Carmel, CA C1 [Newsom, J.; Taylor, B.] Univ Alabama, Birmingham, AL USA. [Newsom, J.; Taylor, B.] Birmingham VA Med Ctr, Birmingham, AL USA. 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 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2012 VL 60 IS 1 BP 463 EP 464 PG 2 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 869XV UT WOS:000298634402552 ER PT J AU Newsom, J Kraemer, R Estrada, C Morris, J Willett, L AF Newsom, J. Kraemer, R. Estrada, C. Morris, J. Willett, L. TI EXTERNAL VALIDATION OF A CLINICAL VIGNETTE SCORING TOOL SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting CY JAN 25-28, 2012 CL Carmel, CA C1 [Newsom, J.; Kraemer, R.; Estrada, C.; Morris, J.; Willett, L.] Univ Alabama, Birmingham, AL USA. [Newsom, J.; Estrada, C.] Birmingham VA Med Ctr, Birmingham, AL USA. 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 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2012 VL 60 IS 1 BP 464 EP 464 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 869XV UT WOS:000298634402553 ER PT J AU Kertesz, S Steward, J Johnson, N Pollio, D Holt, C Austin, E Gordon, A Stringfellow, E Granstaff, U AF Kertesz, S. Steward, J. Johnson, N. Pollio, D. Holt, C. Austin, E. Gordon, A. Stringfellow, E. Granstaff, U. TI COMPARISON OF CUSTOMIZED VERSUS MAINSTREAM PRIMARY CARE FOR HOMELESS INDIVIDUALS: THE PRIMARY CARE QUALITY-HOMELESS SURVEY SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting CY JAN 25-28, 2012 CL Carmel, CA C1 [Kertesz, S.; Johnson, N.; Austin, E.; Granstaff, U.] Birmingham VAMC, Birmingham, AL USA. [Kertesz, S.; Steward, J.] Univ Alabama, Birmingham, AL USA. [Pollio, D.] Univ Alabama, Tuscaloosa, AL USA. [Holt, C.] Univ Maryland, Baltimore, MD 21201 USA. [Gordon, A.] Pittsburgh VAMC, Pittsburgh, PA USA. [Stringfellow, E.] Boston HCH, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2012 VL 60 IS 1 BP 465 EP 465 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 869XV UT WOS:000298634402556 ER PT J AU Potter, RM Harikumar, KG Wu, SV Miller, LJ AF Potter, Ross M. Harikumar, Kaleeckal G. Wu, S. Vincent Miller, Laurence J. TI Differential sensitivity of types 1 and 2 cholecystokinin receptors to membrane cholesterol SO JOURNAL OF LIPID RESEARCH LA English DT Article DE receptor binding; biological activity; chimeric receptors; G protein-coupled receptors; perfringolysin ID PROTEIN-COUPLED RECEPTOR; PERFRINGOLYSIN-O; BETA(2)-ADRENERGIC RECEPTOR; CANNABINOID RECEPTORS; INTRACELLULAR LOOP; HUMAN GALLBLADDERS; PLASMA-MEMBRANE; LIGAND-BINDING; CCK RECEPTOR; II-RECEPTOR AB Recent studies indicate that membrane cholesterol can associate with G protein-coupled receptors (GPCRs) and affect their function. Previously, we reported that manipulation of membrane cholesterol affects ligand binding and signal transduction of the type 1 cholecystokinin receptor (CCK1R), a Class A GPCR. We now demonstrate that the closely related type 2 cholecystokinin receptor (CCK2R) does not share this cholesterol sensitivity. The sequences of both receptors reveal almost identical cholesterol interaction motifs in analogous locations in transmembrane segments two, three, four, and five. The disparity in cholesterol sensitivity between these receptors, despite their close structural relationship, provides a unique opportunity to define the possible structural basis of cholesterol sensitivity of CCK1R. To evaluate the relative contributions of different regions of CCK1R to cholesterol sensitivity, we performed ligand binding studies and biological activity assays of wildtype and CCK2R/CCK1R chimeric receptor-bearing Chinese hamster ovary cells after manipulation of membrane cholesterol. We also extended these studies to site-directed mutations within the cholesterol interaction motifs. The results contribute to a better understanding of the structural requirements for cholesterol sensitivity in CCK1R and provides insight into the function of other cholesterol-sensitive Class A GPCRs.-Potter, R.M., K.G. Harikumar, S.V. Wu, and L.J. Miller. Differential sensitivity of types 1 and 2 cholecystokinin receptors to membrane cholesterol. J. Lipid Res. 2012. 53: 137-148. C1 [Potter, Ross M.; Harikumar, Kaleeckal G.; Miller, Laurence J.] Mayo Clin, Dept Mol Pharmacol & Expt Therapeut, Scottsdale, AZ 85259 USA. [Wu, S. Vincent] Vet Adm Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA 90073 USA. RP Miller, LJ (reprint author), Mayo Clin, Dept Mol Pharmacol & Expt Therapeut, Scottsdale, AZ 85259 USA. EM miller@mayo.edu FU National Institutes of Health [DK-32878]; Mayo Clinic FX This work was supported by Grant DK-32878 from the National Institutes of Health and by the Mayo Clinic-Kinney Career Development Award. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health or other granting agencies. NR 62 TC 17 Z9 17 U1 0 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD JAN PY 2012 VL 53 IS 1 BP 137 EP 148 DI 10.1194/jlr.M020065 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 866TI UT WOS:000298405900014 PM 22021636 ER PT J AU Richman, AR Coronado, GD Arnold, LD Fernandez, ME Glenn, BA Allen, JD Wilson, KM Brewer, NT AF Richman, Alice R. Coronado, Gloria D. Arnold, Lauren D. Fernandez, Maria E. Glenn, Beth A. Allen, Jennifer D. Wilson, Katherine M. Brewer, Noel T. TI Cognitive Testing of Human Papillomavirus Vaccine Survey Items for Parents of Adolescent Girls SO JOURNAL OF LOWER GENITAL TRACT DISEASE LA English DT Article DE cognitive interviewing; survey design; cervical cancer; human papillomavirus; HPV vaccine ID EPIDEMIOLOGIC RESEARCH; HEALTH-SERVICES; ACCEPTABILITY; INSTRUMENT AB Objective. Many studies have been conducted to understand what factors are associated with human papillomavirus (HPV) vaccine acceptability and completion of the 3-dose vaccination series, but few have examined whether people understand the survey items used to assess these relationships. Through a multisite collaborative effort, we developed and cognitively tested survey items that represent constructs known to affect vaccine acceptability and completion. Materials and Methods. Investigators from 7 research centers in the United States used cognitive interviewing techniques and in-person and telephone interviews to test 21 items. Four rounds of testing, revising, and retesting were conducted among racially and ethnically diverse parents (n = 62) of girls between the ages of 9 and 17 years. Results. The final survey contained 20 items on attitudes and beliefs relevant to HPV vaccine. Some parents misinterpreted statements about hypothetical vaccine harms as statements of fact. Others were unwilling to answer items about perceived disease likelihood and perceived vaccine effectiveness, because they said the items seemed to have a "right" answer that they did not know. On the basis of these and other findings from cognitive testing, we revised the wording of 14 questions to improve clarity and comprehension. We also revised instructions, response options, and item order. Conclusions. Cognitive testing of HPV vaccine survey items revealed important differences between intended and ascribed item meaning by participants. Use of the tested survey questions presented here may increase measurement validity and researchers' ability to compare findings across studies and populations. Additional testing using quantitative methods can help to further validate these items. C1 [Richman, Alice R.] Univ N Carolina, Dept Hlth Behav & Hlth Educ, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27516 USA. [Coronado, Gloria D.] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. [Arnold, Lauren D.] Washington Univ, Sch Med, Dept Surg, Siteman Canc Ctr, St Louis, MO 63110 USA. [Fernandez, Maria E.] Univ Texas Houston, Hlth Sci Ctr, Houston, TX USA. [Glenn, Beth A.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA. [Glenn, Beth A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. [Allen, Jennifer D.] Harvard Univ, Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA USA. [Wilson, Katherine M.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Brewer, Noel T.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. RP Richman, AR (reprint author), Univ N Carolina, Dept Hlth Behav & Hlth Educ, Gillings Sch Global Publ Hlth, 325 Rosenau Hall,CB 7440, Chapel Hill, NC 27516 USA. EM richmana@ecu.edu; ntb1@unc.edu RI Allen, Jennifer/M-2113-2015 FU Centers for Disease Control and Prevention; National Cancer Institute for the Cancer Prevention and Control Research Network at the University of California at Los Angeles School of Public Health [1-U48-DP000056]; Harvard School of Public Health/Boston School of Public Health [1-U48-DP000064]; University of North Carolina at Chapel Hill, Gillings School of Global Public Health [5-U48-DP000059]; University of Texas School of Public Health [1-U48-DP000057]; University of Washington School of Public Health and Community Medicine/Fred Hutchinson Cancer Research Center [1-U48-DP000050]; Washington University School of Medicine, Department of Surgery, Siteman Cancer Center [5-U48-DP000060]; American Cancer Society [MSRG-06-259-01-CPPB] FX Research for this publication was supported by the Centers for Disease Control and Prevention and the National Cancer Institute cooperative agreements for the Cancer Prevention and Control Research Network at the University of California at Los Angeles School of Public Health (1-U48-DP000056); Harvard School of Public Health/Boston School of Public Health (1-U48-DP000064); University of North Carolina at Chapel Hill, Gillings School of Global Public Health (5-U48-DP000059); University of Texas School of Public Health (1-U48-DP000057); University of Washington School of Public Health and Community Medicine/Fred Hutchinson Cancer Research Center (1-U48-DP000050); and Washington University School of Medicine, Department of Surgery, Siteman Cancer Center (5-U48-DP000060). In addition, the research at the University of North Carolina was supported by grants from the American Cancer Society (MSRG-06-259-01-CPPB). The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. NR 22 TC 3 Z9 3 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1089-2591 J9 J LOW GENIT TRACT DI JI J. Low. Genit. Tract. Dis. PD JAN PY 2012 VL 16 IS 1 BP 16 EP 23 DI 10.1097/LGT.0b013e3182293a49 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 870KP UT WOS:000298668500005 PM 21964205 ER PT J AU Eatesam, M Noworolski, SM Tien, PC Nystrom, M Dodge, JL Merriman, RB Qayyum, A AF Eatesam, Mamak Noworolski, Susan M. Tien, Phyllis C. Nystrom, Michelle Dodge, Jennifer L. Merriman, Raphael B. Qayyum, Aliya TI Liver diffusivity in healthy volunteers and patients with chronic liver disease: Comparison of breathhold and free-breathing techniques SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE diffusion-weighted imaging (DWI); breathhold (BH); free-breathing (FB); nonalcoholic fatty liver disease (NAFLD); hepatitis C (HCV) ID WOMENS INTERAGENCY HIV; WEIGHTED MRI; FIBROSIS; COEFFICIENT; EXPERIENCE; DIAGNOSIS; CIRRHOSIS; REPRODUCIBILITY; PARAMETERS; HEPATITIS AB Purpose: To compare liver ADC obtained with breathhold and free-breathing diffusion weighted imaging (DWI) in healthy volunteers and patients with liver disease. Materials and Methods: Twenty-eight subjects, 12 healthy volunteers and 16 patients (9 NAFLD, 7 chronic active HCV), underwent breathhold (BH) and free-breathing (FB) DWI MRI at 1.5 Tesla. Pearson's correlation coefficient was used to determine correlation while paired t-tests assessed differences between BH and FB ADC. Estimated bias was calculated using the Bland-Altman method. Results: Liver ADC (x10(-3) mm(2)/s) was lower on BH for all groups (mean difference 0.36 +/- 0.20; P < 0.01). ADC was higher in healthy volunteers (BH 1.80 +/- 0.18; FB 2.24 +/- 0.20) compared with NAFLD patients (BH 1.43 +/- 0.27; FB 1.78 +/- 0.28) (P < 0.001) and HCV patients (BH 1.63 +/- 0.191; FB 1.88 +/- 0.12). Overall correlation between BH and FB ADC was (r = 0.75), greatest in NAFLD (r = 0.90) compared with the correlation in HCV (r = 0.24) and healthy subjects (r = 0.34). Bland-Altman plots did not show agreement in mean absolute difference and estimated bias between subjects. Conclusion: Correlation between BH and FB liver ADC is moderate indicating that BH and FB should not be used interchangeably. Additionally, the lower ADC values in BH versus FB should be accounted for when comparing different liver DWI studies. C1 [Eatesam, Mamak; Noworolski, Susan M.; Nystrom, Michelle; Qayyum, Aliya] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Noworolski, Susan M.] Univ Calif San Francisco & Berkeley, Grad Grp Bioengn, Berkeley, CA USA. [Tien, Phyllis C.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Tien, Phyllis C.] San Francisco VA Med Ctr, Med Serv, San Francisco, CA USA. [Dodge, Jennifer L.] Univ Calif San Francisco, Dept Internal Med, Fresno Med Educ Program, San Francisco, CA 94143 USA. [Merriman, Raphael B.] Calif Pacific Med Ctr, Dept Med, San Francisco, CA USA. RP Qayyum, A (reprint author), Univ Calif San Francisco, Dept Radiol & Biomed Imaging, Box 0628,M-372,505 Parnassus Ave, San Francisco, CA 94143 USA. EM aliya.qayyum@radiology.ucsf.edu FU NIH [K23 AI-66943, UO1 AI-34989, MO1-RR-00083, R01 DK061738-SI, R01 DK074718-01]; National Institute of Allergy and Infectious Diseases [UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, UO1-AI-42590]; National Institute of Child Health and Human Development [UO1-HD-32632]; National Cancer Institute; National Institute on Drug Abuse; National Institute on Deafness and Other Communication Disorders; National Center for Research Resources (UCSF-CTSI) [UL1 RR024131]; UCSF FX Contract grant sponsor: NIH; Contract grant number: K23 AI-66943, UO1 AI-34989, MO1-RR-00083, R01 DK061738-SI, R01 DK074718-01; Contract grant sponsor: National Institute of Allergy and Infectious Diseases; Contract grant number: UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, UO1-AI-42590; Contract grant sponsor: National Institute of Child Health and Human Development; Contract grant number: UO1-HD-32632; Contract grant sponsor: National Cancer Institute; Contract grant sponsor: National Institute on Drug Abuse; Contract grant sponsor: National Institute on Deafness and Other Communication Disorders; Contract grant sponsor: National Center for Research Resources (UCSF-CTSI); Contract grant number: UL1 RR024131; Contract grant sponsor: UCSF Hellman Family Award. NR 30 TC 3 Z9 4 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD JAN PY 2012 VL 35 IS 1 BP 103 EP 109 DI 10.1002/jmri.22748 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 862LT UT WOS:000298093200011 PM 22034200 ER PT J AU Biederman, J Fried, R Petty, CR Henin, A Wozniak, J Corkum, L Claudat, K Faraone, SV AF Biederman, Joseph Fried, Ronna Petty, Carter R. Henin, Aude Wozniak, Janet Corkum, Lyndsey Claudat, Kim Faraone, Stephen V. TI Examining the Association Between Stimulant Treatment and Cognitive Outcomes Across the Life Cycle of Adults With Attention-Deficit/Hyperactivity Disorder A Controlled Cross-Sectional Study SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE ADHD; adults; stimulants; adult ADHD and cognition; ADHD over lifespan ID DEFICIT-HYPERACTIVITY DISORDER; EXECUTIVE FUNCTION; NEUROPSYCHOLOGICAL FUNCTION; BIPOLAR DISORDER; CHILDREN; PERFORMANCE; ADHD; ADOLESCENTS; MEDICATION; VIGILANCE AB Few studies have evaluated the effects of stimulants on cognition in adults with attention-deficit/hyperactivity disorder (ADHD). We evaluated the impact of stimulant treatment on neurocognition in a cross-sectional sample of adults with ADHD. Comparisons were made between adults with ADHD who received (n = 105) and who had never received pharmacotherapy (n = 116) and 146 controls. The subjects were assessed cross-sectionally using a structured diagnostic interview and a neurocognitive battery. We modeled cognitive measures as a function of age and group status using linear regression. Treated ADHD subjects had statistically significantly better scores on measures of IQ than did untreated ones. The treated group also had better (not statistically significant) scores on neuropsychological measures. The direction of the effects of stimulant on neurocognition suggests that either good cognitive functioning may be a determinant of seeking treatment or that stimulant treatment may improve cognition in adults with ADHD. However, this does not indicate a clear causal relationship. C1 [Biederman, Joseph] Massachusetts Gen Hosp, Pediat Psychopharmacol Program, Clin & Res Programs Pediat Psychiat & Adult ADHD, Boston, MA 02114 USA. [Biederman, Joseph; Fried, Ronna; Henin, Aude; Wozniak, Janet] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Program, Clin & Res Programs Pediat Psychiat & Adult ADHD, 55 Fruit St,YAW 6A-6900, Boston, MA 02114 USA. EM jbiederman@partners.org OI Faraone, Stephen/0000-0002-9217-3982 FU Neal-Kimmerly MGH; MGH Pediatric Psychopharmacology Philanthropy Fund; National Institutes of Health [R01MH57934]; Elminda; Janssen; McNeil; Next Wave Pharmaceuticals; Shire; Fundacion Areces (Spain); Medice Pharmaceuticals (Germany); Spanish Child Psychiatry Association; Abbott; Alza; AstraZeneca; Bristol Myers Squibb; Celltech; Cephalon; Eli Lilly and Co.; Esai; Forest; Glaxo; Gliatech; Merck; NARSAD; NIDA; New River; NICHD; NIMH; Novartis; Noven; Neurosearch; Organon; Otsuka; Pfizer; Pharmacia; Prechter Foundation; Stanley Foundation; UCB Pharma, Inc.; Wyeth; Johnson and Johnson; Independent Medical Education; Lilly; McNeil Pediatrics; Forest Laboratories Inc.; Sanofi Aventis; Bristol-Myers Squibb; National Institutes of Health (NIH) FX This study was supported, in part, by the Neal-Kimmerly MGH Fund for the Study of Cognition, the MGH Pediatric Psychopharmacology Philanthropy Fund and by grants to S. Faraone from the National Institutes of Health (R01MH57934).; Dr. Joseph Biederman is currently receiving research support from the following sources: Elminda, Janssen, McNeil, Next Wave Pharmaceuticals, and Shire. In 2011, Dr. Joseph Biederman gave a single unpaid talk for Juste Pharmaceutical Spain and received honoraria from the MGH Psychiatry Academy for a tuition-funded CME course. He also received an honorarium from Cambridge University Press for a chapter publication. Dr. Biederman received royalties from a copyrighted rating scale used for ADHD diagnoses. These royalties are paid to the Department of Psychiatry at MGH. During the past year, Dr. Biederman, through the MGH Department of Psychiatry, has received royalty payments from Eli Lilly, Shire, and AstraZeneca. In 2010, Dr. Joseph Biederman received a speaker's fee from a single talk given at Fundacion Dr. Manuel Camelo A. C. in Monterrey, Mexico. Dr. Biederman provided single consultations for Shionogi Pharma Inc. and Cipher Pharmaceuticals Inc.; the honoraria for these consultations were paid to the Department of Psychiatry at the MGH. Dr. Biederman received honoraria from the MGH Psychiatry Academy for a tuition-funded CME course. In 2009, Dr. Joseph Biederman received a speaker's fee from the following sources: Fundacion Areces (Spain), Medice Pharmaceuticals (Germany), and the Spanish Child Psychiatry Association. In previous years, Dr. Joseph Biederman received research support, consultation fees, or speaker's fees for/from the following additional sources: Abbott, Alza, AstraZeneca, Bristol Myers Squibb, Celltech, Cephalon, Eli Lilly and Co., Esai, Forest, Glaxo, Gliatech, Janssen, McNeil, Merck, NARSAD, NIDA, New River, NICHD, NIMH, Novartis, Noven, Neurosearch, Organon, Otsuka, Pfizer, Pharmacia, The Prechter Foundation, Shire, The Stanley Foundation, UCB Pharma, Inc., and Wyeth.; Dr. Janet Wozniak, MD, is the author of "Is Your Child Bipolar,'' published in May 2008 by Bantam Books. She is a speaker for Primedia/MGH Psychiatry Academy. She received research support from the following: McNeil, Shire, Janssen, Johnson and Johnson. Her spouse, John Winkelman, MD, PhD, is a member of the speaker's bureau for the following: Sanofi-Aventis, Sepracor. He is a consultant/advisory board member for Covance, GlaxoSmithKline, Impax Laboratories, Luitpold Pharmaceuticals, Neurogen, Pfizer, UCB, Zeo Inc. He received research support from GlaxoSmithKline and Sepracor.; In the past 12 months, Dr. Henin has been a consultant for Concordant Rater Systems and Pfizer. She receives royalties from Oxford University Press. She has also received honoraria from the MGH Psychiatry Academy. The education programs conducted by the MGH Psychiatry Academy were, in part, supported though Independent Medical Education grants from pharmaceutical companies, including AstraZeneca, Lilly, McNeil Pediatrics, Shire, Forest Laboratories Inc., Sanofi Aventis, Janssen, Bristol-Myers Squibb, and Pfizer.; In the past year, Dr. Faraone received consulting fees and was on advisory boards for Shire Development and received research support from Shire and the National Institutes of Health (NIH). In previous years, he received consulting fees or was on advisory boards or participated in continuing medical education programs sponsored by Shire, McNeil, Janssen, Novartis, Pfizer, and Eli Lilly. In previous years, he received research support from Eli Lilly, Shire, Pfizer and the NIH. Dr. Faraone receives royalties from a book published by Guilford Press named Straight Talk About Your Child's Mental Health. NR 37 TC 1 Z9 1 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD JAN PY 2012 VL 200 IS 1 BP 69 EP 75 DI 10.1097/NMD.0b013e31823e55ef PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 869YP UT WOS:000298636600009 PM 22210365 ER PT J AU Rei, ALDP Bui, E Bousquet, B Simon, NM Rieu, J Schmitt, L Billard, J Rodgers, R Birmes, P AF Rei, Agnes Ladois-Do Pilar Bui, Eric Bousquet, Benjamin Simon, Naomi M. Rieu, Julie Schmitt, Laurent Billard, Julien Rodgers, Rachel Birmes, Philippe TI Peritraumatic Reactions and Posttraumatic Stress Disorder Symptoms After Psychiatric Admission SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE Posttraumatic stress disorder; admission; hospitalization; peritraumatic distress; peritraumatic dissociation ID PTSD CHECKLIST; SECLUSION; RESTRAINT; TRAUMA AB The present study aimed to explore exposure to stressful events during a psychiatric admission and the predictive power of peritraumatic distress and dissociation in the development of posttraumatic stress disorder (PTSD) symptoms after exposure to such events. Psychiatric inpatients (N = 239) were asked to report exposure to stressful events during their admission within 48 hours of being admitted. Individuals reporting at least one stressful event during admission (n = 70, 29%) were assessed for peritraumatic dissociation and distress in relation to this event and, 5 weeks later, were reassessed for PTSD symptoms. Eight participants (12.3%) scored above the cutoff for probable PTSD. Multiple regression analyses revealed that peritraumatic distress was a significant predictor of 5-week PTSD symptoms. Our findings suggest that individuals experiencing increased peritraumatic distress in relation to a stressful event experienced during a psychiatric admission might be at risk of PTSD symptoms and might benefit from increased attention. C1 [Rei, Agnes Ladois-Do Pilar; Bui, Eric; Schmitt, Laurent; Rodgers, Rachel; Birmes, Philippe] Univ Toulouse, UPS, Lab Stress Traumat LST EA 4560, F-31059 Toulouse 9, France. [Bui, Eric; Simon, Naomi M.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Bousquet, Benjamin; Rieu, Julie; Billard, Julien] Hop Casselardit Psychiat, Toulouse, France. [Rodgers, Rachel] Univ Toulouse 2, Ctr Etud & Rech Psychopathol, Toulouse, France. RP Bui, E (reprint author), Univ Toulouse, UPS, Lab Stress Traumat LST EA 4560, CHU Toulouse,Hop Casselardit, 170 Av Casselardit,TSA 40031, F-31059 Toulouse 9, France. EM bui.e@chu-toulouse.fr RI Bui, Eric/J-8347-2015 OI Bui, Eric/0000-0002-1413-6473 NR 15 TC 2 Z9 2 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD JAN PY 2012 VL 200 IS 1 BP 88 EP 90 DI 10.1097/NMD.0b013e31823fafb9 PG 3 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 869YP UT WOS:000298636600012 ER PT J AU Buhlmann, U Marques, LM Wilhelm, S AF Buhlmann, Ulrike Marques, Luana M. Wilhelm, Sabine TI Traumatic Experiences in Individuals With Body Dysmorphic Disorder SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE Body dysmorphic disorder; traumatic experience; sexual abuse; physical abuse; emotional abuse; body image ID OBSESSIVE-COMPULSIVE SCALE; IMAGE DISTORTION; SEXUAL ABUSE; RELIABILITY AB Individuals with body dysmorphic disorder (BDD) are excessively concerned about perceived defects in their appearance (e.g., blemishes on their skin). BDD is a severe mental disorder often associated with increased suicidality as well as significant social and occupational interference (e.g., J Clin Psychiatry 2005; 66: 717Y725). Recently, investigators have begun to explore variables that might function as risk factors in the development of BDD, such as traumatic experiences (e. g., Child Abuse Negl 2006; 30: 1105-1115). As such, one of the goals of the current study was to examine the role of early-life sexual, physical, or emotional abuse in BDD. Specifically, the Traumatic Stress Institute Life Event Questionnaire (Treat Abuse Today 1992; 2: 9-11) was used to examine whether individuals with BDD (n = 18) self-reported having experienced more traumatic events than mentally healthy controls (n = 19). The BDD group reported more retrospective experiences of sexual and physical abuse in childhood or adolescence than did healthy controls. Surprisingly, there was no significant group difference in reports of emotional abuse in early life. This study provides preliminary evidence of the importance of examining abuse as a potential risk factor in the development of BDD. C1 [Wilhelm, Sabine] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp,Body Dysmorph Disorder Cli, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Wilhelm, S (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp,Body Dysmorph Disorder Cli, 185 Cambridge St, Boston, MA 02114 USA. EM wilhelm@psych.mgh.harvard.edu FU German Research Society (DFG) [BU 1814/7-1, BU 1814/7-2]; NIMH; Obsessive-Compulsive Foundation; Tourette Syndrome Association FX Dr. Buhlmann has received research support from the German Research Society (DFG; Grant #s BU 1814/7-1 and BU 1814/7-2).; Dr. Wilhelm has received research support from NIMH, the Obsessive-Compulsive Foundation, and the Tourette Syndrome Association. Forest Laboratories provided her with medication and placebo for an NIMH-funded study. She is a presenter for the Massachusetts General Hospital Psychiatry Academy in educational programs supported through independent medical education grants from pharmaceutical companies; and has received royalties from Elsevier Publications, Guilford Publications, and New Harbinger Publications from Oxford University Press. She has also received speaking honorarium from various academic institutions. NR 25 TC 4 Z9 4 U1 0 U2 20 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD JAN PY 2012 VL 200 IS 1 BP 95 EP 98 DI 10.1097/NMD.0b013e31823f6775 PG 4 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 869YP UT WOS:000298636600014 PM 22210370 ER PT J AU Meyers, PM Blackham, KA Abruzzo, TA Gandhi, CD Higashida, RT Hirsch, JA Moran, CJ Narayanan, S Prestigiacomo, CJ Tarr, R AF Meyers, P. M. Blackham, K. A. Abruzzo, T. A. Gandhi, C. D. Higashida, R. T. Hirsch, J. A. Moran, C. J. Narayanan, S. Prestigiacomo, C. J. Tarr, R. CA Soc NeuroInterventional Surg TI Society of NeuroInterventional Surgery Standards of Practice: general considerations SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Article ID CLINICAL-PRACTICE GUIDELINES; REPORTING STANDARDS; AMERICAN-COLLEGE; ANGIOPLASTY; STROKE AB This is the first in a set of documents intended to standardize techniques, procedures, and practices in the field of endovascular surgical neuroradiology. Standards are meant to define core practices for peer review, comparison, and improvement. Standards and guidelines also form the basic dialogue, reporting, and recommendations for ongoing practices and future development. C1 [Meyers, P. M.] Columbia Univ, Dept Radiol & Neurol Surg, Coll Phys & Surg, New York, NY 10032 USA. [Blackham, K. A.] Univ Hosp, Case Med Ctr, Cleveland, OH USA. [Abruzzo, T. A.; Tarr, R.] Univ Cincinnati, Med Ctr, Cincinnati, OH 45267 USA. [Gandhi, C. D.] UMDNJ New Jersey Med Sch, Newark, NJ USA. [Higashida, R. T.] Univ Calif San Francisco, Med Ctr, San Francisco, CA USA. [Hirsch, J. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Moran, C. J.] Edward Mallinckrodt Inst Radiol, St Louis, MO 63110 USA. [Narayanan, S.] Wayne State Univ, Dept Neurosurg & Neurol, Detroit Med Ctr, Detroit, MI USA. [Prestigiacomo, C. J.] Univ Med & Dent New Jersey, Newark, NJ 07103 USA. RP Meyers, PM (reprint author), Columbia Univ, Dept Radiol & Neurol Surg, Coll Phys & Surg, 710 W 168th St,Rm 428, New York, NY 10032 USA. EM pmm2002@columbia.edu NR 12 TC 8 Z9 8 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD JAN PY 2012 VL 4 IS 1 BP 11 EP 15 DI 10.1136/neurintsurg-2011-010180 PG 5 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 866XF UT WOS:000298418800005 PM 22166819 ER PT J AU Oh, DC Hirsch, JA Yoo, AJ AF Oh, Daniel C. Hirsch, Joshua A. Yoo, Albert J. TI Novel use of Onyx for treatment of intracranial vertebral artery dissection SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Article ID ENDOVASCULAR MANAGEMENT; SUBARACHNOID HEMORRHAGE; ANEURYSMS AB This report describes a patient who presented with subarachnoid hemorrhage and extensive right posterior inferior cerebellar artery territory infarct secondary to a dissecting aneurysm of the right intracranial vertebral artery. Urgent endovascular treatment was undertaken with plans for trapping of the diseased segment with coils. However, significant intralesional stenosis limited distal microcatheter access. Therefore, using proximal flow arrest and adjunctive coiling, the liquid embolic agent Onyx was injected within the pseudoaneurysm and was able to traverse the stenosis, resulting in proximal and distal parent vessel closure. There were no embolic complications. During the 3 month hospital stay, there was no rebleeding. The patient was discharged to skilled nursing facility and was lost to follow-up. C1 [Oh, Daniel C.; Hirsch, Joshua A.; Yoo, Albert J.] Massachusetts Gen Hosp, Dept Intervent Neuroradiol Endovasc Neurosurg, Boston, MA 02114 USA. RP Yoo, AJ (reprint author), Massachusetts Gen Hosp, Dept Intervent Neuroradiol Endovasc Neurosurg, Gray 241,55 Fruit St, Boston, MA 02114 USA. EM ajyoo@partners.org NR 7 TC 3 Z9 4 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD JAN PY 2012 VL 4 IS 1 BP 31 EP 33 DI 10.1136/jnis.2011.004952 PG 3 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 866XF UT WOS:000298418800010 PM 21990480 ER PT J AU Bruguera, C Tremble, T Hirsch, JA AF Bruguera, Carolyn Tremble, Thomas Hirsch, Joshua A. TI Coming soon to a state near you? SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Editorial Material C1 [Bruguera, Carolyn] Micrus Corp, San Jose, CA USA. [Tremble, Thomas] Adv Med Technol Assoc AdvaMed, State Govt Relat & Reg Affairs, Washington, DC USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Neuroendovasc Program, Boston, MA 02114 USA. RP Bruguera, C (reprint author), 2810 Belmont Canyon Rd, Belmont, CA 94002 USA. EM carolyn.bruguera@gmail.com NR 12 TC 1 Z9 1 U1 2 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD JAN PY 2012 VL 4 IS 1 BP 75 EP 78 DI 10.1136/neurintsurg-2011-010120 PG 4 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 866XF UT WOS:000298418800019 PM 22006867 ER PT J AU Walcott, BP Nahed, BV Kahle, KT Duhaime, AC Sharma, N Eskandar, EN AF Walcott, Brian P. Nahed, Brian V. Kahle, Kristopher T. Duhaime, Ann-Christine Sharma, Nutan Eskandar, Emad N. TI Deep brain stimulation for medically refractory life-threatening status dystonicus in children Report of 3 cases SO JOURNAL OF NEUROSURGERY-PEDIATRICS LA English DT Article DE deep brain stimulation; globus pallidus; movement disorder; rhabdomyolysis; status dystonicus; functional neurosurgery ID HALLERVORDEN-SPATZ-DISEASE; GENERALIZED DYSTONIA; PALLIDOTOMY; MANAGEMENT; EXPERIENCE AB Generalized dystonic syndromes may escalate into persistent episodes of generalized dystonia known as status dystonicus that can be life-threatening due to dystonia-induced rhabdomyolysis and/or respiratory compromise. Treatment of these conditions usually entails parenteral infusion of antispasmodic agents and sedatives and occasionally necessitates a medically induced coma for symptom control. The authors report a series of 3 children who presented with medically intractable, life-threatening status dystonicus and were successfully treated with bilateral pallidal deep brain stimulation. Bilateral globus pallidus internus stimulation appears to be effective in the urgent treatment of medically refractory and life-threatening movement disorders. (http://thejns.org/doi/abs/10.3171/2011.10.PEDS11360) C1 [Walcott, Brian P.; Nahed, Brian V.; Kahle, Kristopher T.; Duhaime, Ann-Christine; Eskandar, Emad N.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Sharma, Nutan] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Sharma, Nutan] Harvard Univ, Sch Med, Boston, MA USA. RP Walcott, BP (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 55 Fruit St,White Bldg Room 502, Boston, MA 02114 USA. EM walcott.brian@mgh.harvard.edu FU NINDS NIH HHS [P50 NS037409] NR 24 TC 12 Z9 12 U1 0 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 1933-0707 J9 J NEUROSURG-PEDIATR JI J. Neurosurg.-Pediatr. PD JAN PY 2012 VL 9 IS 1 BP 99 EP 102 DI 10.3171/2011.10.PEDS11360 PG 4 WC Clinical Neurology; Pediatrics; Surgery SC Neurosciences & Neurology; Pediatrics; Surgery GA 869WW UT WOS:000298630700018 PM 22208329 ER PT J AU Erickson, JI AF Erickson, Jeanette Ives TI 200 Years of Nursing-A Chief Nurse's Reflections on Practice, Theory, Policy, Education, and Research SO JOURNAL OF NURSING ADMINISTRATION LA English DT Editorial Material ID CLINICAL EXCELLENCE C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Erickson, JI (reprint author), Massachusetts Gen Hosp, Bulfinch 230B,55 Fruit St, Boston, MA 02114 USA. EM jiveserickson@partners.org NR 17 TC 1 Z9 1 U1 1 U2 4 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 JAN PY 2012 VL 42 IS 1 BP 9 EP 11 DI 10.1097/NNA.0b013e31823c1710 PG 3 WC Nursing SC Nursing GA 863HL UT WOS:000298153300004 PM 22157375 ER PT J AU Adams, JM AF Adams, Jeffrey M. TI Exploring Influential Nurse Executive Leadership An Interview With Marla Weston SO JOURNAL OF NURSING ADMINISTRATION LA English DT Editorial Material C1 [Adams, Jeffrey M.] Massachusetts Gen Hosp, Yvonne L Munn Ctr Nursing Res, Boston, MA 02114 USA. [Adams, Jeffrey M.] Massachusetts Gen Hosp, Ctr Innovat Care Delivery, 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 1 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-0443 J9 J NURS ADMIN JI J. Nurs. Adm. PD JAN PY 2012 VL 42 IS 1 BP 12 EP 14 DI 10.1097/NNA.0b013e31823c17e0 PG 3 WC Nursing SC Nursing GA 863HL UT WOS:000298153300005 PM 22157376 ER PT J AU Yip, S Butterfield, YS Morozova, O Chittaranjan, S Blough, MD An, JH Birol, I Chesnelong, C Chiu, R Chuah, E Corbett, R Docking, R Firme, M Hirst, M Jackman, S Karsan, A Li, HY Louis, DN Maslova, A Moore, R Moradian, A Mungall, KL Perizzolo, M Qian, J Roldan, G Smith, EE Tamura-Wells, J Thiessen, N Varhol, R Weiss, S Wu, W Young, S Zhao, YJ Mungall, AJ Jones, SJM Morin, GB Chan, JA Cairncross, JG Marra, MA AF Yip, Stephen Butterfield, Yaron S. Morozova, Olena Chittaranjan, Suganthi Blough, Michael D. An, Jianghong Birol, Inanc Chesnelong, Charles Chiu, Readman Chuah, Eric Corbett, Richard Docking, Rod Firme, Marlo Hirst, Martin Jackman, Shaun Karsan, Aly Li, Haiyan Louis, David N. Maslova, Alexandra Moore, Richard Moradian, Annie Mungall, Karen L. Perizzolo, Marco Qian, Jenny Roldan, Gloria Smith, Eric E. Tamura-Wells, Jessica Thiessen, Nina Varhol, Richard Weiss, Samuel Wu, Wei Young, Sean Zhao, Yongjun Mungall, Andrew J. Jones, Steven J. M. Morin, Gregg B. Chan, Jennifer A. Cairncross, J. Gregory Marra, Marco A. TI Concurrent CIC mutations, IDH mutations, and 1p/19q loss distinguish oligodendrogliomas from other cancers SO JOURNAL OF PATHOLOGY LA English DT Article DE glioma; oligodendroglioma; next-generation sequencing; Capicua; IDH1 ID ANAPLASTIC OLIGODENDROGLIOMAS; SIGNALING PATHWAY; MSH6 MUTATIONS; BRAIN-TUMORS; CELL; GLIOMAS; CAPICUA; SURVIVAL; ALIGNMENT; ATAXIN-1 AB Oligodendroglioma is characterized by unique clinical, pathological, and genetic features. Recurrent losses of chromosomes 1p and 19q are strongly associated with this brain cancer but knowledge of the identity and function of the genes affected by these alterations is limited. We performed exome sequencing on a discovery set of 16 oligodendrogliomas with 1p/19q co-deletion to identify new molecular features at base-pair resolution. As anticipated, there was a high rate of IDH mutations: all cases had mutations in either IDH1 (14/16) or IDH2 (2/16). In addition, we discovered somatic mutations and insertions/deletions in the CIC gene on chromosome 19q13.2 in 13/16 tumours. These discovery set mutations were validated by deep sequencing of 13 additional tumours, which revealed seven others with CIC mutations, thus bringing the overall mutation rate in oligodendrogliomas in this study to 20/29 (69%). In contrast, deep sequencing of astrocytomas and oligoastrocytomas without 1p/19q loss revealed that CIC alterations were otherwise rare (1/60; 2%). Of the 21 non-synonymous somatic mutations in 20 CIC-mutant oligodendrogliomas, nine were in exon 5 within an annotated DNA-interacting domain and three were in exon 20 within an annotated protein-interacting domain. The remaining nine were found in other exons and frequently included truncations. CIC mutations were highly associated with oligodendroglioma histology, 1p/19q co-deletion, and IDH1/2 mutation (p < 0.001). Although we observed no differences in the clinical outcomes of CIC mutant versus wild-type tumours, in a background of 1p/19q co-deletion, hemizygous CIC mutations are likely important. We hypothesize that the mutant CIC on the single retained 19q allele is linked to the pathogenesis of oligodendrogliomas with IDH mutation. Our detailed study of genetic aberrations in oligodendroglioma suggests a functional interaction between CIC mutation, IDH1/2 mutation, and 1p/19q co-deletion. Copyright (C) 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. C1 [Yip, Stephen; Karsan, Aly; Young, Sean] BC Canc Agcy, Dept Pathol & Lab Med, Vancouver, BC, Canada. [Butterfield, Yaron S.; Morozova, Olena; Chittaranjan, Suganthi; An, Jianghong; Birol, Inanc; Chiu, Readman; Chuah, Eric; Corbett, Richard; Docking, Rod; Firme, Marlo; Hirst, Martin; Jackman, Shaun; Karsan, Aly; Li, Haiyan; Maslova, Alexandra; Moore, Richard; Moradian, Annie; Mungall, Karen L.; Qian, Jenny; Tamura-Wells, Jessica; Thiessen, Nina; Varhol, Richard; Zhao, Yongjun; Mungall, Andrew J.; Jones, Steven J. M.; Morin, Gregg B.; Marra, Marco A.] BC Canc Agcy, Michael Smith Genome Sci Ctr, Vancouver, BC, Canada. [Blough, Michael D.; Chesnelong, Charles; Chan, Jennifer A.] Univ Calgary, So Alberta Canc Res Inst, Calgary, AB, Canada. [Louis, David N.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Louis, David N.] Harvard Univ, Sch Med, Boston, MA USA. [Perizzolo, Marco; Chan, Jennifer A.] Univ Calgary, Dept Pathol & Lab Med, Calgary, AB, Canada. [Roldan, Gloria] Univ Calgary, Dept Med, Calgary, AB, Canada. [Smith, Eric E.] Univ Calgary, Dept Clin Neurosci, Hotchkiss Brain Inst, Calgary, AB, Canada. [Weiss, Samuel] Univ Calgary, Dept Cell Biol & Anat, Hotchkiss Brain Inst, Calgary, AB, Canada. [Wu, Wei] Univ Calgary, Dept Biol Sci, Inst Biocomplex & Bioinformat, Calgary, AB T2N 1N4, Canada. [Marra, Marco A.] Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada. RP Cairncross, JG (reprint author), Foothills Prov Gen Hosp, Dept Clin Neurosci, 1403-29th St NW, Calgary, AB T2N 2T9, Canada. EM jgcairnx@ucalgary.ca; mmarra@bcgsc.ca RI Morin, Gregg/E-9123-2012; Blough, Michael/O-1186-2013; Tang, Macy/B-9798-2014; Karsan, Aly/K-2067-2015; Hirst, Martin/B-7684-2016; Smith, Eric/C-5443-2012; Jones, Steven/C-3621-2009; Birol, Inanc/G-5440-2011; Marra, Marco/B-5987-2008; OI Morin, Gregg/0000-0001-8949-4374; Smith, Eric/0000-0003-3956-1668; Birol, Inanc/0000-0003-0950-7839; Docking, Rod/0000-0003-3248-4081 FU BC Cancer Foundation; Western Economic Diversification; Genome Canada; Genome British Columbia FX We would like to acknowledge Dr John Kelly for cell lines, Dr Peter Forsyth and the Calgary Brain Tumour Bank for tissues, Colleen Anderson and Susan Hui for technical assistance, Alberta Innovates Health Solutions (JAC, EES), the Brain Tumour Foundation of Canada (JGC), the Alberta Cancer Foundation (JGC), and the Clark Smith Family. We also acknowledge Dr Robert Jenkins for performing mFISH on the brain tumour-initiating cell lines BT054 and BT088 and sharing the data. MAM acknowledges the support of the BC Cancer Foundation, Western Economic Diversification, Genome Canada, and Genome British Columbia. MAM is also grateful to Dr Brian Thiessen, BCCA, for early conversations that helped shape the project. SY acknowledges the generous support of BrainCare BC and the BCCA Hershey and Yvette Porte Neuro-Oncology Endowment Fund. We would also like to acknowledge Maria Mendez-Lago, Diane Trinh, Kane Tse, and Thomas Zeng at the BCGSC for invaluable scientific advice and technical support. NR 52 TC 120 Z9 125 U1 0 U2 27 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3417 J9 J PATHOL JI J. Pathol. PD JAN PY 2012 VL 226 IS 1 BP 7 EP 16 DI 10.1002/path.2995 PG 10 WC Oncology; Pathology SC Oncology; Pathology GA 864RJ UT WOS:000298257300002 PM 22072542 ER PT J AU Tran, P Skolnick, P Czobor, P Huang, NY Bradshaw, M McKinney, A Fava, M AF Tran, Pierre Skolnick, Phil Czobor, Pal Huang, N. Y. Bradshaw, Mark McKinney, Anthony Fava, Maurizio TI Efficacy and tolerability of the novel triple reuptake inhibitor amitifadine in the treatment of patients with major depressive disorder: A randomized, double-blind, placebo-controlled trial SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Amitifadine; Anhedonia; Major depressive disorder; Sexual function; Triple reuptake inhibitor; Weight ID BROAD-SPECTRUM ANTIDEPRESSANTS; SEXUAL DYSFUNCTION; TRICYCLIC ANTIDEPRESSANTS; PHARMACOLOGICAL-TREATMENT; PSYCHIATRIC-DISORDERS; CLINICAL-TRIALS; NEXT-GENERATION; SEROTONIN; METAANALYSIS; DOPAMINE AB Amitifadine (EB-1010, formerly DOV 21,947) is a serotonin-preferring triple reuptake inhibitor with a relative potency to inhibit serotonin, norepinephrine, and dopamine uptake of similar to 1:2:8, respectively. This 6-week, multicenter, randomized, double-blind, parallel, placebo-controlled study evaluated the efficacy and tolerability of amitifadine in 63 patients with major depressive disorder. Eligible patients (17-item Hamilton Depression Rating Scale [HAMD-17] >= 22 at baseline) were randomized to amitifadine 25 mg twice daily (BID) for 2 weeks, then 50 mg BID for 4 weeks or placebo. Mean baseline scores in the modified intent-to-treat population (n = 56) were 31.4 for the Montgomery-Asberg Depression Rating Scale (MADRS), 29.6 for the HAMD-17, and 25.4 for the Derogatis Interview for Sexual Functioning - Self Report (DISF-SR). At the end of the 6-week double-blind treatment, estimated least squares mean change from baseline (mixed-model repeated measures [MMRM]) in MADRS total score was statistically significantly superior for amitifadine compared to placebo (18.2 vs. 22.0; p = 0.028), with an overall statistical effect size of -0.601 (Cohen's d). Amitifadine also was statistically significantly superior to placebo (p = 0.03) for the Clinical Global Impression of Change Improvement. An anhedonia factor score grouping of MADRS Items 1 (apparent sadness), 2 (reported sadness), 6 (concentration difficulties), 7 (lassitude), and 8 (inability to feel) demonstrated a statistically significant difference in favor of amitifadine compared to placebo (p = 0.049). No differences were observed between treatments in DISF-SR scores. Amitifadine was well-tolerated. Two patients on each treatment discontinued the study early due to adverse events: however, no serious adverse events were reported. This initial clinical trial in patients with severe major depression demonstrated significant antidepressant activity with amitifadine, including attenuating symptoms of anhedonia, and a tolerability profile that was comparable to placebo. The efficacy and tolerability of amitifadine for major depressive disorder are being investigated in additional clinical trials. (C )2011 Elsevier Ltd. All rights reserved. C1 [Tran, Pierre; McKinney, Anthony] Euthym Biosci Inc, Cambridge, MA 02141 USA. [Skolnick, Phil; Czobor, Pal; Huang, N. Y.] DOV Pharmaceut, Somerset, NJ USA. [Bradshaw, Mark] Global Consulting Partners, Princeton, NJ USA. [Fava, Maurizio] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Tran, P (reprint author), Euthym Biosci Inc, 43 Thorndike St,Suite S1-3, Cambridge, MA 02141 USA. EM ptran@euthymics.com FU Euthymics Bioscience, Cambridge, MA FX The authors acknowledge the editorial assistance of Richard S. Perry, PharmD in the preparation of this manuscript, which was supported by Euthymics Bioscience, Cambridge, MA. NR 65 TC 42 Z9 44 U1 4 U2 15 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 JAN PY 2012 VL 46 IS 1 BP 64 EP 71 DI 10.1016/j.jpsychires.2011.09.003 PG 8 WC Psychiatry SC Psychiatry GA 868MR UT WOS:000298527900009 PM 21925682 ER PT J AU Lydecker, JA Pisetsky, EM Mitchell, KS Thornton, LM Kendler, KS Reichborn-Kjennerud, T Lichtenstein, P Bulik, CM Mazzeo, SE AF Lydecker, Janet A. Pisetsky, Emily M. Mitchell, Karen S. Thornton, Laura M. Kendler, Kenneth S. Reichborn-Kjennerud, Ted Lichtenstein, Paul Bulik, Cynthia M. Mazzeo, Suzanne E. TI Association between co-twin sex and eating disorders in opposite sex twin pairs: Evaluations in North American, Norwegian, and Swedish samples SO JOURNAL OF PSYCHOSOMATIC RESEARCH LA English DT Article DE Eating disorders; Estrogen; Opposite sex twin pairs; Prenatal hormone exposure; Testosterone; Twin study ID SAME-SEX; OVARIAN HORMONES; BULIMIA-NERVOSA; FEMALE RATS; BEHAVIOR; TESTOSTERONE; EXPOSURE; ANOREXIA; REGISTRY; WOMEN AB Objective: These three studies examined the hypothesis that prenatal exposure to sex hormones influences twins' risk for eating disorders based on co-twin sex, such that individuals with a female co-twin would be more likely than individuals with a male co-twin to meet diagnostic criteria for an eating disorder. Methods: Male and female twins from the United States (N=2607), Norway (N=2796) and Sweden (N=16,458) with known co-twin sex and zygosity were assessed for eating disorders. Results: In the U.S. and Swedish samples, sex was significantly associated with eating disorder diagnoses, and although co-twin sex was not associated with eating disorders overall, it was associated with broadly defined bulimia nervosa in the Swedish sample. The effects for bulimia were not sustained when monozygotic twins were excluded, suggesting that the effects of prenatal sex hormones play a minor role in influencing eating disorders. Sex and co-twin sex were not associated with eating disorders in the Norwegian sample. Conclusion: The prenatal sex hormone hypothesis, which proposes that prenatal hormone exposure is associated with later eating disorder symptomatology, was not supported in these three population-based twin samples. (C) 2011 Elsevier Inc. All rights reserved. C1 [Lydecker, Janet A.; Mitchell, Karen S.; Mazzeo, Suzanne E.] Virginia Commonwealth Univ, Dept Psychol, Richmond, VA 23284 USA. [Pisetsky, Emily M.] Univ N Carolina, Dept Psychol, Chapel Hill, NC USA. [Mitchell, Karen S.; Kendler, Kenneth S.; Mazzeo, Suzanne E.] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA USA. [Mitchell, Karen S.] VA Boston Healthcare Syst, Womens Hlth Sci Div, Natl Ctr PTSD, Boston, MA USA. [Mitchell, Karen S.] Boston Univ, Dept Psychiat, Boston, MA 02215 USA. [Thornton, Laura M.; Bulik, Cynthia M.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. [Kendler, Kenneth S.] Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA USA. [Reichborn-Kjennerud, Ted] Norwegian Inst Publ Hlth, Div Mental Hlth, Oslo, Norway. [Reichborn-Kjennerud, Ted] Univ Oslo, Inst Psychiat, N-0316 Oslo, Norway. [Reichborn-Kjennerud, Ted] Columbia Univ, Dept Epidemiol, New York, NY USA. [Lichtenstein, Paul] Karolinska Inst, Dept Med Epidemiol & Biostat, S-10401 Stockholm, Sweden. [Bulik, Cynthia M.] Univ N Carolina, Dept Nutr, Chapel Hill, NC USA. [Mazzeo, Suzanne E.] Virginia Commonwealth Univ, Dept Pediat, Richmond, VA USA. RP Mazzeo, SE (reprint author), 806 W Franklin St,POB 842018, Richmond, VA 23220 USA. EM semazzeo@vcu.edu RI Lydecker, Janet/B-3349-2016; OI Lydecker, Janet/0000-0001-6425-514X; lichtenstein, paul/0000-0003-3037-5287 FU NIMH NIH HHS [K01 MH068520-05] NR 36 TC 12 Z9 12 U1 0 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3999 EI 1879-1360 J9 J PSYCHOSOM RES JI J. Psychosomat. Res. PD JAN PY 2012 VL 72 IS 1 BP 73 EP 77 DI 10.1016/j.jpsychores.2011.05.014 PG 5 WC Psychiatry SC Psychiatry GA 874DU UT WOS:000298936400014 PM 22200526 ER PT J AU Sorrentino, R AF Sorrentino, Renee TI Degarelix: An Antagonist to GnRHu-Theoretical and Treatment Considerations in Paraphilia SO JOURNAL OF SEXUAL MEDICINE LA English DT Letter ID HORMONE-II; BEHAVIOR C1 Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Sorrentino, R (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 10 TC 2 Z9 2 U1 2 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1743-6095 J9 J SEX MED JI J. Sex. Med. PD JAN PY 2012 VL 9 IS 1 BP 327 EP 329 DI 10.1111/j.1743-6109.2011.02540.x PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 872HE UT WOS:000298799100042 PM 22082230 ER PT J AU Saoiabi, S El Asri, S Laghzizil, A Masse, S Ackerman, JL AF Saoiabi, Sanaa El Asri, Sanae Laghzizil, Abdelaziz Masse, Sylvie Ackerman, Jerome L. TI Synthesis and characterization of nanoapatites organofunctionalized with aminotriphosphonate agents SO JOURNAL OF SOLID STATE CHEMISTRY LA English DT Article DE Apatite; Functionalized surface; Mesoporous materials; Surface properties ID CALCIUM HYDROXYAPATITE; SURFACE MODIFICATION; AQUEOUS-SOLUTION; PHOSPHATE; BONE; REMOVAL; SPECTROSCOPY; KINETICS; COATINGS; APATITES AB Organofunctionalized apatite nanoparticles were prepared using a one step process involving dissolution/precipitation of natural phosphate rock and covalent grafting of nitrilotris(methylene)triphosphonate (NTP). The synthesized materials were characterized by Brunauer-Emmett-Teller (BET) surface measurement, thermogravimetry, inductively coupled plasma emission spectroscopy (ICP-ES), elemental analysis, multinuclear solid state cross-polarization/magic angle spinning (CP/MAS) and single-pulse NMR spectroscopy, transmission electron microscopy (TEM) and energy dispersive X-ray analysis (EDXA). After grafting BET measurements yielded particle specific surface areas ranging from 88 to 193 m(2) g(-1) depending on the grafted phosphonate. The results show that the surfaces of the nanoapatite particles can be covered with functional groups bound through a variable number of R-P-O-Ca bonds to render them organoapatites. Published by Elsevier Inc. C1 [Saoiabi, Sanaa; El Asri, Sanae; Laghzizil, Abdelaziz] Univ Mohamed V Agdal, Fac Sci, Lab Chim Phys Gen, Rabat, Morocco. [Saoiabi, Sanaa; Masse, Sylvie] Univ Paris 06, UMR 7574, F-75005 Paris, France. [Saoiabi, Sanaa; Ackerman, Jerome L.] Massachusetts Gen Hosp, Dept Radiol, Biomat Lab, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Saoiabi, Sanaa; Ackerman, Jerome L.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Laghzizil, A (reprint author), Univ Mohamed V Agdal, Fac Sci, Lab Chim Phys Gen, BP 1014, Rabat, Morocco. EM laghzizi@fsr.ac.ma; jerry@nmr.mgh.harvard.edu RI Ackerman, Jerome/E-2646-2015 OI Ackerman, Jerome/0000-0001-5176-7496 FU Office Cherifien des Phosphates (OCP); Center d'Etudes et de Recherches des Phosphates Mineraux (CERPHOS); National Institutes of Health [P41RR14075]; Fulbright Foundation FX The authors would like to thank the Office Cherifien des Phosphates (OCP) and the Center d'Etudes et de Recherches des Phosphates Mineraux (CERPHOS) for their support, UATRS-CNRST-Rabat for chemical analyses, the Martinos Center for Biomedical Imaging at Massachusetts General Hospital and National Institutes of Health grant P41RR14075. S. Saoiabi wishes to acknowledge the Moroccan-American Commission for Educational and Cultural Exchange (MACECE) and the Fulbright Foundation for fellowship support. NR 38 TC 6 Z9 6 U1 0 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4596 J9 J SOLID STATE CHEM JI J. Solid State Chem. PD JAN PY 2012 VL 185 BP 95 EP 100 DI 10.1016/j.jssc.2011.10.031 PG 6 WC Chemistry, Inorganic & Nuclear; Chemistry, Physical SC Chemistry GA 874EA UT WOS:000298937000015 PM 22287800 ER PT J AU Baer, JS Carpenter, KM Beadnell, B Stoner, SA Ingalsbe, MH Hartzler, B Rosengren, DB Drager, Z AF Baer, John S. Carpenter, Kelly M. Beadnell, Blair Stoner, Susan A. Ingalsbe, Michelle Hansten Hartzler, Bryan Rosengren, David B. Drager, Zach TI Computer Assessment of Simulated Patient Interviews (CASPI): Psychometric Properties of a Web-Based System for the Assessment of Motivational Interviewing Skills SO JOURNAL OF STUDIES ON ALCOHOL AND DRUGS LA English DT Article ID VIDEO ASSESSMENT; CLINICIAN; COMPETENCE; VALIDITY; RELIABILITY; VALIDATION; ADDICTION; BEHAVIOR; SCALE; VASE AB Objective: Benefits of empirically supported interventions hinge on clinician skill, particularly for motivational interviewing (MI). Existing MI skill assessments are limited with respect to validity (e.g., self-report) and practicality (e.g., coding session tapes). To address these limitations, we developed and evaluated two versions of a web-based assessment of MI skills, the Computer Assessment of Simulated Patient Interviews (CASPI). Method: Ninety-six counselors from the community and 24 members of the Motivational Interviewing Network of Trainers (MINT) completed the CASPI (N = 120), in which they verbally responded via microphones to video clips comprising three 9-item vignettes. Three coders used an emergent coding scheme, which was compared with alternative MI skills measures. Results: CASPI demonstrated excellent internal consistency when averaging across two or three vignettes (alpha's = .86.89). Intraclass correlations were above 40 for most items. Confirmatory factor analyses supported a correlated three-factor model: MI-consistent, resistance-engendering, and global change talk orientation rating. Means and factor loadings were invariant across forms (i.e., the two alternative versions of CASPI), and factor loadings were invariant across subgroup (i.e., community counselor or MINT member). Test retest reliability was good for MI-consistent and resistance-engendering scores (r = .74 and .80, respectively) but low for change talk orientation (r = .29) unless coder was taken into account (r = .69). CASPI showed excellent construct and criterion-related validity. Conclusions: CASPI represents a promising method of assessing MI skills. Future studies are needed to establish its performance in real-world contexts. (J. Stud. Alcohol Drugs, 73, 154-164, 2012) C1 [Baer, John S.] Univ Washington, Dept Psychol, Seattle, WA 98195 USA. [Baer, John S.; Ingalsbe, Michelle Hansten; Hartzler, Bryan; Rosengren, David B.] Univ Washington, Inst Alcohol & Drug Abuse, Seattle, WA 98195 USA. [Carpenter, Kelly M.; Stoner, Susan A.; Drager, Zach] Talaria Inc, Seattle, WA USA. [Beadnell, Blair] Univ Washington, Sch Social Work, Seattle, WA 98195 USA. [Beadnell, Blair; Rosengren, David B.] Prevent Res Inst, Lexington, KY USA. RP Baer, JS (reprint author), VA Puget Sound HCS, S-116-ATC,1660 S Columbian Way, Seattle, WA 98108 USA. EM jsbaer@uw.edu FU National Institute on Drug Abuse [R42 DA020284] FX This research was supported by a Small Business Technology Transfer grant from the National Institute on Drug Abuse (R42 DA020284). NR 24 TC 4 Z9 4 U1 0 U2 2 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA SN 1937-1888 J9 J STUD ALCOHOL DRUGS JI J. Stud. Alcohol Drugs PD JAN PY 2012 VL 73 IS 1 BP 154 EP 164 PG 11 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA 873QP UT WOS:000298898400020 PM 22152673 ER PT J AU Klein, AA Slaymaker, VJ Dugosh, KL Mckay, JR AF Klein, Audrey A. Slaymaker, Valerie J. Dugosh, Karen L. Mckay, James R. TI Computerized continuing care support for alcohol and drug dependence: A preliminary analysis of usage and outcomes SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article DE Alcohol dependence; Drug dependence; Continuing care; Computer based; Residential treatment ID RANDOMIZED CONTROLLED-TRIAL; COGNITIVE-BEHAVIORAL THERAPY; ASSISTED INTERVENTION; PROBLEM DRINKERS; CLINICAL-TRIAL; DIABETES CARE; FOLLOW-UP; RELIABILITY; PROGRAM; INSTRUMENT AB The central aim of this administrative data analysis was to examine usage of a Web-based disease management program designed to provide continuing recovery support to patients discharged from residential drug and alcohol treatment. Tailored clinical content was delivered in a multimedia format over the course of 18 months posttreatment. The program also included access to a recovery coach across the 18 months. Consistent with other disease management programs, program usage decreased over time. A small subsample of patients accessed a large number of program modules in the year following treatment; these patients had significantly higher abstinence rates and consumed less alcohol than patients accessing few or no modules. Regression analyses revealed a significant relationship between the number of modules accessed and substance use outcomes in the year following treatment when controlling for motivation, self-efficacy, and pretreatment substance use. Limiting the analyses to only the more compliant patients did not reduce the magnitude of these effects. These preliminary results suggest that computerized support programs may be beneficial to patients recently treated for drug and alcohol issues. Methods to increase program engagement need additional study. (C) 2012 Elsevier Inc. All rights reserved. C1 [Klein, Audrey A.; Slaymaker, Valerie J.] Hazelden Fdn, Butler Ctr Res, Ctr City, MN 55012 USA. [Dugosh, Karen L.] Treatment Res Inst, Philadelphia, PA USA. [Mckay, James R.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Mckay, James R.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Klein, AA (reprint author), Hazelden Fdn, Butler Ctr Res, POB 11,BC-4, Ctr City, MN 55012 USA. EM aklein@hazelden.org NR 27 TC 14 Z9 15 U1 0 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD JAN PY 2012 VL 42 IS 1 BP 25 EP 34 DI 10.1016/j.jsat.2011.07.002 PG 10 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 860OF UT WOS:000297956900004 PM 21862275 ER PT J AU Brewster, LP Palmatier, J Manley, CJ Hall, DE Brems, JJ AF Brewster, Luke P. Palmatier, Jason Manley, C. J. Hall, Daniel E. Brems, J. J. TI Limitations on Surrogate Decision-Making for Emergent Liver Transplantation SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE surrogate consent; ethics; fulminant hepatic failure; liver transplantation ID RISK-RELATED STANDARDS; INFORMED-CONSENT; OF-LIFE; COMPETENCE; ACCURACY; PERSPECTIVE; DEBATE; ETHICS; CARE AB Background. Surrogate consent is an accepted form of promoting patient autonomy when patients cannot consent, but it can lead to surrogate duress and may be unreliable. Since consent for liver transplantation in patients with fulminant hepatic failure (FHF) is typically performed by surrogates and these patients typically regain decisional capacity, we chose this population to query patients' opinion on the surrogate consent process. Materials and Methods. We developed a questionnaire that queried transplanted patients' experience and opinion on surrogate consent, suitability of surrogates, and return of decisional capacity. This survey was then sent to consecutive survivors of liver transplantation for FHF at our institution. Results. Eleven of 14 patients eligible to participate completed the questionnaire. The mean follow-up for all survivors was 41 mo, with a range of survival since transplant of 5 mo to 10 y. Although 10/11 respondents agreed with their surrogates to consent to liver transplantation, all 11 patients thought that surrogates should not be able to decline liver transplantation for this condition. In distinction, 3/11 patients believed patients could decline liver transplantation. Conclusions. This is the first study to demonstrate that liver transplant patients do not think surrogate decision-makers should be permitted to contravene physician recommendations regarding transplant. In clinical settings when patients cannot speak for themselves, it may be appropriate for surrogates and clinicians to act together according to the patients' best interest rather than attempt to determine what the patient would want. This approach might reduce surrogate distress, better represent patient preferences, and improve the decision-making process for affected patients. (C) 2012 Elsevier Inc. All rights reserved. C1 [Brewster, Luke P.] Emory Univ Hosp, Dept Surg, Atlanta, GA 30322 USA. [Palmatier, Jason; Manley, C. J.] Loyola Univ, Stritch Sch Med, Maywood, IL 60153 USA. [Hall, Daniel E.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Hall, Daniel E.] Univ Pittsburgh, Dept Surg, Med Ctr, Pittsburgh, PA USA. [Brems, J. J.] Sherman Hosp, Dept Surg, Elgin, IL USA. RP Brewster, LP (reprint author), Emory Univ Hosp, Dept Surg, 676 N Parkwood Rd, Decatur, GA 30030 USA. EM lukebrewst@aol.com RI Hall, Daniel/H-4843-2013; OI Hall, Daniel/0000-0001-6382-0522 NR 31 TC 1 Z9 1 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD JAN PY 2012 VL 172 IS 1 BP 48 EP 52 DI 10.1016/j.jss.2011.04.042 PG 5 WC Surgery SC Surgery GA 864DK UT WOS:000298217000007 PM 21696773 ER PT J AU Mukherjee, R Snipes, JM Saunders, SM Zavadzkas, JA Spinale, FG AF Mukherjee, Rupak Snipes, Jonathan M. Saunders, Stuart M. Zavadzkas, Juozas A. Spinale, Francis G. TI Discordant Activation of Gene Promoters for Matrix Metalloproteinases and Tissue Inhibitors of the Metalloproteinases Following Myocardial Infarction SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE matrix metalloproteinase; tissue inhibitor of metalloproteinase; myocardial infarction; remodeling ID LEFT-VENTRICULAR ENLARGEMENT; EXTRACELLULAR-MATRIX; HEART-FAILURE; TRANSCRIPTIONAL REGULATION; TARGETED DELETION; TRANSGENIC MICE; CARDIAC RUPTURE; EXPRESSION; RAT; INDUCTION AB Background. Left ventricular (LV) remodeling following myocardial infarction (MI) is associated with increased levels of specific matrix metalloproteinases (MMPs) and relative reduction of endogenous tissue inhibitors of the MMPs (TIMPs). However, transcriptional mechanisms for the disparate post-MI MMP/TIMP expression remain unknown. Using murine constructs designed to report gene promoter activation, this study tested the hypothesis that distinctly different temporal profiles of MMP-2, MMP-9, and TIMP-1 transcription occurs post-MI. Methods/Results. Transcriptional activity (beta-galactosidase (beta-gal) reporter constructs) of MMP-2 (n = 49), MMP-9 (n = 62), or TIMP-1 (n = 40) was assayed at 1 h (acute), and 1-28 d after MI (coronary ligation) in transgenic reporter mice. At 7 d post-MI, the area of promoter activation normalized to LV area was increased from acute values for MMP-2 (63.4 +/- 5.8 versus 1.1% +/- 1.0%, P < 0.05) and MMP-9 (53.1 +/- 6.1 versus 1.3% +/- 0.9%, P < 0.05). While TIMP-1 promoter activation at 7 d post-MI increased from acute values (3.6 +/- 1.3 versus 0.3% +/- 0.5%, P < 0.05), this increase was smaller than that for MMP-2 or MMP-9 (both P < 0.05). MMP-2 promoter activation peaked in the MI region at 7 d post-MI and MMP-9 promoter activation was highest in the border region at 7 and 14 d post-MI. TIMP-1 promoter activation peaked within the MI region at 7 d post-MI and within the remote region at 14 d post-MI. Conclusions. These findings provided direct in vivo evidence that discordant changes in temporal and spatial patterns of MMP/TIMP transcription occurs with MI. Restoration of TIMP-1 promoter activation may represent a molecular therapeutic target to attenuate/prevent adverse post-MI LV remodeling. (C) 2012 Elsevier Inc. All rights reserved. C1 [Mukherjee, Rupak; Snipes, Jonathan M.; Saunders, Stuart M.; Zavadzkas, Juozas A.; Spinale, Francis G.] Med Univ S Carolina, Div Cardiothorac Surg, Charleston, SC 29425 USA. [Spinale, Francis G.] Ralph H Johnson Vet Adm Med Ctr, Charleston, SC USA. RP Mukherjee, R (reprint author), Med Univ S Carolina, Div Cardiothorac Surg, Strom Thurmond Res Bldg,770 MUSC Complex,Suite 62, Charleston, SC 29425 USA. EM mukherr@musc.edu FU National Institutes of Health [HL-66029, HL-45024, HL-97012, PO1-HL48788] FX This study was supported by National Institutes of Health grants HL-66029 (RM), HL-45024, HL-97012, and PO1-HL48788 (FGS). NR 36 TC 2 Z9 4 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD JAN PY 2012 VL 172 IS 1 BP 59 EP 67 DI 10.1016/j.jss.2010.06.015 PG 9 WC Surgery SC Surgery GA 864DK UT WOS:000298217000009 PM 20863528 ER PT J AU Wilens, TE Bukstein, O Brams, M Cutler, AJ Childress, A Rugino, T Lyne, A Grannis, K Youcha, S AF Wilens, Timothy E. Bukstein, Oscar Brams, Matthew Cutler, Andrew J. Childress, Ann Rugino, Thomas Lyne, Andrew Grannis, Kara Youcha, Sharon TI A Controlled Trial of Extended-Release Guanfacine and Psychostimulants for Attention-Deficit/Hyperactivity Disorder SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE Attention-deficit/hyperactivity disorder; alpha(2)-adrenoceptor agonist ID DEFICIT HYPERACTIVITY DISORDER; COMORBIDITY SURVEY REPLICATION; PLACEBO-CONTROLLED EVALUATION; RANDOMIZED CONTROLLED-TRIAL; DOUBLE-BLIND; LISDEXAMFETAMINE DIMESYLATE; LIFETIME PREVALENCE; CHILDREN; ADOLESCENTS; ADHD AB Objective: To examine efficacy, tolerability, and safety of guanfacine extended release (GXR; <= 4 mg/d) adjunctive to a long-acting psychostimulant for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents 6 to 17 years of age with suboptimal, but partial, response to psychostimulant alone. Method: In this multicenter, 9-week, double-blind, placebo-controlled, dose-optimization study, subjects (N = 461) continued their stable dose of psychostimulant given in the morning and were randomized to receive GXR in the morning (GXR AM), GXR in the evening (GXR PM), or placebo. Efficacy measures included ADHD Rating Scale IV (ADHD-RS-IV) and Clinical Global Impressions of Severity of Illness (CGI-S) and Improvement (CGI-I) scales. Safety measures included adverse events (AEs), vital signs, electrocardiograms, and laboratory evaluations. Results: At endpoint, GXR treatment groups showed significantly greater improvement from baseline ADHD-RS-IV total scores compared with placebo plus psychostimulant (GXR AM, p = .002; GXR PM, p < .001). Significant benefits of GXR treatment versus placebo plus psychostimulant were observed on the CGI-S (GXR AM, p = .013; GXR PM, p < .001) and CGI-I (GXR AM, p = .024; GXR PM, p = .003). At endpoint, small mean decreases in pulse, systolic, and diastolic blood pressure were observed in GXR treatment groups versus placebo plus psychostimulant. No new safety signals emerged following administration of GXR with psychostimulants versus psychostimulants alone. Most AEs were mild to moderate in severity. Conclusions: Morning or evening GXR administered adjunctively to a psychostimulant showed significantly greater improvement over placebo plus psychostimulant in ADHD symptoms and generated no new safety signals. J. Am. Acad. Child Adolesc. Psychiatry, 2012; 51(1):74-85. Clinical trial registration information Efficacy and Safety of SPD503 in Combination With Psychostimulants; http://www.clinicaltriaLs.gov; NCT00734578. C1 [Wilens, Timothy E.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Wilens, Timothy E.] Harvard Univ, Sch Med, Boston, MA USA. [Bukstein, Oscar] Univ Texas Houston, Houston, TX USA. [Brams, Matthew] Bayou City Res, Houston, TX USA. [Cutler, Andrew J.] Florida Clin Res Ctr LLC, Bradenton, FL USA. [Childress, Ann] Ctr Psychiat & Behav Med, Las Vegas, NV USA. [Rugino, Thomas] Childrens Specialized Hosp, Toms River, NJ USA. [Lyne, Andrew] Shire Pharmaceut Dev Ltd, Basingstoke, Hants, England. [Grannis, Kara; Youcha, Sharon] Shire Dev Inc, Wayne, PA USA. RP Wilens, TE (reprint author), Massachusetts Gen Hosp, Dept Psychiat, YAW 6900,55 Fruit St, Boston, MA 02114 USA. EM twilens@partners.org FU Shire Development Inc., Wayne, PA; Shire Development Inc.; Abbott; Eli Lilly and Co.; McNeil; Merck; National Institutes of Health (NIH); National Institute on Drug Abuse (NIDA); Shire; AstraZeneca; Addremax; Bristol-Myers Squibb; Cephalon; GlaxoSmithKline; Janssen; Johnson and Johnson; Novartis; Ortho McNeil; Otsuka; Pfizer; Sepracor; Shionogi; Sunovion; AstraZeneca Pharmaceuticals; Jazz Pharmaceuticals; McNeil Pharmaceuticals; Memory Pharmaceuticals; Sanofi; Solvay; Supernus; Targacept; NextWave; Janssen Scientific Affairs; Rhodes; Somerset; Forest Research Institute; Lexicor FX This study was supported by Shire Development Inc., Wayne, PA.; Clinical research was funded by the sponsor, Shire Development Inc. The primary manuscript was written by Dr. Wilens after discussion about the manuscript's content with the independent authors. Under the direction of the authors, Jennifer Steeber, PhD, an employee of SCI Scientific Communications and Information SCI), provided additional writing assistance for this publication. Editorial assistance in formatting, proofreading, copy editing, and fact checking was also provided by SCI. Jonathan Rubin, M.D., M.B.A., Ryan Dammerman, M.D., Ph.D., Carla White, B.Sc., C.Stat., Edward Johnson, Michael Kahn, and Gina D'Angelo, Pharm.D., M.B.A., from Shire Development Inc., also reviewed and edited the manuscript for scientific accuracy. Shire Development Inc. provided funding to OCHSC for support in writing and editing this manuscript. Although the sponsor was involved in the design, collection, analysis, interpretation, and fact checking of information, the content of this manuscript, the ultimate interpretation, and the decision to submit it for publication in Journal of the American Academy of Child and Adolescent Psychiatry were mode by the authors independently.; Dr. Wilens receives or has received grant support from Abbott, Eli Lilly and Co., McNeil, Merck, the National Institutes of Health (NIH), National Institute on Drug Abuse (NIDA), and Shire. He has served as a speaker for Eli Lilly and Co., McNeil, Novartis, and Shire. He has served as a consultant for Abbott, AstraZeneca, Eli Lilly and Co., Euthymics, McNeil, Merck, NextWave, NIH, NIDA, Novortis, and Shire. Dr. Wilens receives royalties from Guilford Press. Dr. Bukstein receives or has received research support from McNeil and Shire. He has acted as a consultant, and/or served on a speakers' bureau for Cephalon, McNeil, Novartis, and Shire. He receives royalties from Routledge Press. Dr. Brams has served on the speakers' bureau and as a consultant for AstraZeneca, Eli Lilly and Co., Cephalon, McNeil, Novartis, Pfizer, Shire, Shionogi, Sunovion. He has received research support from AstraZeneca, Addremax, Bristol-Myers Squibb, Cephalon, GlaxoSmithKline, Janssen, Johnson and Johnson, Merck, Novartis, Ortho McNeil, Otsuka, Pfizer, Sepracor, Shionogi, Shire, and Sunovion. Dr. Cutler has received research grants from Abbott, Addrenex, AstraZeneca Pharmaceuticals, Bristol-Myers Squibb, Cephalon, Eli Lilly and Co., GlaxoSmithKline, Janssen, Jazz Pharmaceuticals, Johnson and Johnson, McNeil Pharmaceuticals, Memory Pharmaceuticals, Merck, Novartis, Ortho-McNeil, Otsuka, Pfizer, Sanofi, Sepracor, Shionogi, Shire, Solvay, Supernus, and Targacept. He has served as a consultant for Abbott, Addrenex, AstraZeneca, Bristol-Myers Squibb, Cephalon, Eli Lilly and Co., GlaxoSmithKline, Janssen, Johnson and Johnson, Neuroscience Education Institute, Novartis, Ortho-McNeil, Otsuka, Pfizer, Sepracor, Shionogi, Shire, Supernus, and Targacept. He has served on the speakers' bureau for Abbott, AstraZeneca, Bristol-Myers Squibb, Eli Lilly and Co., GlaxoSmithKline, Janssen, Neuroscience Education Institute, Novartis, Ortho-McNeil, Pfizer, Sepracor, Shionogi, and Shire. He has received continuing medical education credits from an advisory board for Neuroscience Education Institute. Dr. Childress has served as a consultant for NextWave, Novartis, and Shire. She has served on the speakers' bureau for Bristol-Myers Squibb, GlaxoSmithKline, Shire, and Novartis. She receives research support from Abbott, Bristol-Myers Squibb, Eli Lilly and Co., Johnson and Johnson, NextWave, Novartis, Ortho-McNeill, Otsuka, Janssen Scientific Affairs, Rhodes, Sepracor, Shire, and Somerset. Dr. Rugino has served as a consultant for Lexicor, Bristol-Myers Squibb, and Shire. He has served on the speakers' bureau for Shire. Children's Specialized Hospital received research support from Bristol-Myers Squibb, Eli Lilly and Co., Forest Research Institute, Lexicor, Novartis, and Shire. Ms. Grannis holds stock and/or stock options in Shire. Mr. Lyne holds stock and/or stock options in Shire. Dr. Youcha holds stock and/or stock options in Shire. NR 41 TC 39 Z9 39 U1 3 U2 7 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 JAN PY 2012 VL 51 IS 1 BP 74 EP 85 DI 10.1016/j.jaac.2011.10.012 PG 12 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 868NP UT WOS:000298530300009 PM 22176941 ER PT J AU Kardos, M Kimball, AB AF Kardos, Marisa Kimball, Alexa Boer TI Time for a change? Updated guidelines using interferon gamma release assays for detection of latent tuberculosis infection in the office setting SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Editorial Material DE anti-tumor necrosis factor; interferon gamma release assay; latent tuberculosis; psoriasis; screening ID ANTITUMOR NECROSIS FACTOR; FACTOR ANTAGONISTS; SKIN-TEST; PSORIASIS; THERAPY; PERFORMANCE; AGENTS; RISK AB Treatment with tumor necrosis factor-alfa inhibitors and other systemic medications increases the risk of reactivating a latent tuberculosis (TB) infection. Therefore, screening for latent TB infection is important in dermatology patients eligible for treatment with these medications. Although the tuberculin skin test (TST) has its limitations, it has been the standard choice for diagnosis of latent TB infection. Since the development of interferon gamma release assays (IGRAs), the role of the TST has been re-evaluated and IGRAs have increasingly been incorporated into national guidelines. Although there are situations when either test may be performed, in individuals who have received a BCG vaccination and in those who are unlikely to return for a TST reading, IGRAs may be particularly helpful in distinguishing patients at risk for TB. This article discusses the advantages and disadvantages of both the TST and the IGRA and presents a summary of the Centers for Disease Control and Prevention 2010 guidelines for using IGRAs. (J Am Acacl Dermatol 2012;66:148-52.) C1 [Kardos, Marisa; Kimball, Alexa Boer] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. RP Kimball, AB (reprint author), 50 Staniford St,Suite 240, Boston, MA 02114 USA. EM harvardskinstudies@partners.org NR 22 TC 8 Z9 8 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD JAN PY 2012 VL 66 IS 1 BP 148 EP 152 DI 10.1016/j.jaad.2011.09.007 PG 5 WC Dermatology SC Dermatology GA 871BH UT WOS:000298712100021 PM 22177633 ER PT J AU Lang, RM Badano, LP Tsang, W Adams, DH Agricola, E Buck, T Faletra, FF Franke, A Hung, J de Isla, LP Kamp, O Kasprzak, JD Lancellotti, P Marwick, TH McCulloch, ML Monaghan, MJ Nihoyannopoulos, P Pandian, NG Pellikka, PA Pepi, M Roberson, DA Shernan, SK Shirali, GS Sugeng, L Ten Cate, FJ Vannan, MA Zamorano, JL Zoghbi, WA AF Lang, Roberto M. Badano, Luigi P. Tsang, Wendy Adams, David H. Agricola, Eustachio Buck, Thomas Faletra, Francesco F. Franke, Andreas Hung, Judy Perez de Isla, Leopoldo Kamp, Otto Kasprzak, Jaroslaw D. Lancellotti, Patrizio Marwick, Thomas H. McCulloch, Marti L. Monaghan, Mark J. Nihoyannopoulos, Petros Pandian, Natesa G. Pellikka, Patricia A. Pepi, Mauro Roberson, David A. Shernan, Stanton K. Shirali, Girish S. Sugeng, Lissa Ten Cate, Folkert J. Vannan, Mani A. Luis Zamorano, Jose Zoghbi, William A. TI EAE/ASE Recommendations for Image Acquisition and Display Using Three-Dimensional Echocardiography SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article DE Echocardiography; Two-dimensional; Three-dimensional; Transthoracic; Transesophageal ID DOBUTAMINE-STRESS-ECHOCARDIOGRAPHY; LEFT-VENTRICULAR VOLUMES; CARDIAC MAGNETIC-RESONANCE; VENA CONTRACTA AREA; CORONARY-ARTERY-DISEASE; LEFT ATRIAL APPENDAGE; AORTIC-VALVE AREA; 3D TRANSESOPHAGEAL ECHOCARDIOGRAPHY; FUNCTIONAL TRICUSPID REGURGITATION; COLOR DOPPLER-ECHOCARDIOGRAPHY C1 [Lang, Roberto M.; Tsang, Wendy] Univ Chicago, Chicago, IL 60637 USA. [Badano, Luigi P.] Univ Padua, Padua, Italy. [Adams, David H.] Mt Sinai Med Ctr, New York, NY 10029 USA. [Agricola, Eustachio] Hosp San Raffaele, I-20132 Milan, Italy. [Buck, Thomas] Univ Duisburg Essen, Essen, Germany. [Faletra, Francesco F.] Fdn Cardioctr Ticino, Lugano, Switzerland. [Franke, Andreas] Klinikum Reg Hannover Siloah, Hannover, Germany. [Hung, Judy] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Perez de Isla, Leopoldo; Luis Zamorano, Jose] Univ Clin San Carlos, Madrid, Spain. [Kamp, Otto] Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands. [Kasprzak, Jaroslaw D.] Med Univ Lodz, Lodz, Poland. [Lancellotti, Patrizio] Univ Liege, Liege, Belgium. [Marwick, Thomas H.] Cleveland Clin, Cleveland, OH 44106 USA. [McCulloch, Marti L.; Zoghbi, William A.] Methodist Hosp, Methodist DeBakey Heart & Vasc Ctr, Houston, TX 77030 USA. [Monaghan, Mark J.] Kings Coll Hosp London, London, England. [Nihoyannopoulos, Petros] Univ London Imperial Coll Sci Technol & Med, London, England. [Pandian, Natesa G.] Tufts Univ, Med Ctr, Boston, MA 02111 USA. [Pellikka, Patricia A.] Mayo Clin, Rochester, MN USA. [Pepi, Mauro] IRCCS, Ctr Cardiol Monzino, Milan, Italy. [Roberson, David A.] Heart Inst Children, Oak Lawn, IL USA. [Shernan, Stanton K.] Harvard Univ, Sch Med, Boston, MA USA. [Shirali, Girish S.] Med Univ S Carolina, Charleston, SC 29425 USA. [Sugeng, Lissa] Yale Univ, New Haven, CT USA. [Ten Cate, Folkert J.] Erasmus MC, Rotterdam, Netherlands. [Vannan, Mani A.] ASE Writing Grp, Morrisville, NC USA. RP Lang, RM (reprint author), Amer Soc Echocardiog, 2100 Gateway Ctr Blvd,Suite 310, Morrisville, NC 27560 USA. RI Marwick, Thomas/C-7261-2013; Kasprzak, Jaroslaw/S-4496-2016; OI Marwick, Thomas/0000-0001-9065-0899; Badano, Luigi/0000-0002-0379-3283 NR 153 TC 192 Z9 202 U1 2 U2 21 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD JAN PY 2012 VL 25 IS 1 BP 3 EP 46 DI 10.1016/j.echo.2011.11.010 PG 44 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 864YN UT WOS:000298276500003 PM 22183020 ER PT J AU Stavitsky, K Neargarder, S Bogdanova, Y McNamara, P Cronin-Golomb, A AF Stavitsky, Karina Neargarder, Sandy Bogdanova, Yelena McNamara, Patrick Cronin-Golomb, Alice TI The Impact of Sleep Quality on Cognitive Functioning in Parkinson's Disease SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Article DE Parkinson's disease; Sleep; Cognition; Executive function; Actigraphy; Memory ID REM-SLEEP; BEHAVIOR DISORDER; CHRONIC INSOMNIA; MEMORY CONSOLIDATION; SUBJECTIVE MEASURES; DAYTIME SLEEPINESS; PREFRONTAL CORTEX; WORKING-MEMORY; OLDER-ADULTS; PERFORMANCE AB In healthy individuals and those with insomnia, poor sleep quality is associated with decrements in performance on tests of cognition, especially executive function. Sleep disturbances and cognitive deficits are both prevalent in Parkinson's disease (PD). Sleep problems occur in over 75% of patients, with sleep fragmentation and decreased sleep efficiency being the most common sleep complaints, but their relation to cognition is unknown. We examined the association between sleep quality and cognition in PD. In 35 non-demented individuals with PD and 18 normal control adults (NC), sleep was measured using 24-hr wrist actigraphy over 7 days. Cognitive domains tested included attention and executive function, memory and psychomotor function. In both groups, poor sleep was associated with worse performance on tests of attention/executive function but not memory or psychomotor function. In the PD group, attention/executive function was predicted by sleep efficiency, whereas memory and psychomotor function were not predicted by sleep quality. Psychomotor and memory function were predicted by motor symptom severity. This study is the first to demonstrate that sleep quality in PD is significantly correlated with cognition and that it differentially impacts attention and executive function, thereby furthering our understanding of the link between sleep and cognition. (JINS, 2012, 18, 108-117) C1 [Stavitsky, Karina; Neargarder, Sandy; Bogdanova, Yelena; Cronin-Golomb, Alice] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Neargarder, Sandy] Bridgewater State Univ, Dept Psychol, Bridgewater, MA USA. [Bogdanova, Yelena] VA Boston Healthcare Syst, Boston, MA USA. [Bogdanova, Yelena] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [McNamara, Patrick] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [McNamara, Patrick] VA Boston Healthcare Syst, Dept Neurol, Boston, MA USA. RP Cronin-Golomb, A (reprint author), Boston Univ, Dept Psychol, 648 Beacon St,2nd Floor, Boston, MA 02215 USA. EM alicecg@bu.edu FU National Institute of Neurological Disorders and Stroke [1F31NS061555, R01 NS050446]; Clara Mayo Foundation from the Department of Psychology, Boston University FX This study was supported by a Ruth L. Kirschstein National Research Service Award from the National Institute of Neurological Disorders and Stroke (1F31NS061555) and a Clara Mayo Foundation fellowship from the Department of Psychology, Boston University (K. S.), and by NINDS grant R01 NS050446 (A. C. G.). We report no conflicts of interest. Marie Saint-Hilaire, MD, FRCPC, Cathi Thomas, RN, MS, and Denyse Turpin, RN, MPH of the Department of Neurology, Boston Medical Center, provided valuable support of our participant recruitment efforts. Chase Ansok, Erica Appleman, Sophie Blease, Eric Griffith, Patricia Johnson, Barrett Phillips, and Jessica Saurman assisted with testing participants and scoring data. We acknowledge with gratitude the efforts of these colleagues and especially the efforts of all of the individuals who participated in this study. NR 75 TC 12 Z9 14 U1 3 U2 13 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 JAN PY 2012 VL 18 IS 1 BP 108 EP 117 DI 10.1017/S1355617711001482 PG 10 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 874LL UT WOS:000298958800011 PM 22152279 ER PT J AU Kanai, R Rabkin, SD Yip, S Sgubin, D Zaupa, CM Hirose, Y Louis, DN Wakimoto, H Martuza, RL AF Kanai, Ryuichi Rabkin, Samuel D. Yip, Stephen Sgubin, Donatella Zaupa, Cecile M. Hirose, Yuichi Louis, David N. Wakimoto, Hiroaki Martuza, Robert L. TI Oncolytic Virus-Mediated Manipulation of DNA Damage Responses: Synergy With Chemotherapy in Killing Glioblastoma Stem Cells SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID HERPES-SIMPLEX-VIRUS; DOUBLE-STRAND BREAKS; ATAXIA-TELANGIECTASIA; MALIGNANT GLIOMA; GENE-EXPRESSION; REPAIR PROTEINS; BRAIN-TUMOR; TEMOZOLOMIDE; CANCER; REPLICATION AB Although both the alkylating agent temozolomide (TMZ) and oncolytic viruses hold promise for treating glioblastoma, which remains uniformly lethal, the effectiveness of combining the two treatments and the mechanism of their interaction on cancer stem cells are unknown. We investigated the efficacy of combining TMZ and the oncolytic herpes simplex virus (oHSV) G47 delta in killing glioblastoma stem cells (GSCs), using Chou-Talalay combination index analysis, immunocytochemistry and fluorescence microscopy, and neutral comet assay. The role of treatment-induced DNA double-strand breaks, activation of DNA damage responses, and virus replication in the cytotoxic interaction between G47 delta and TMZ was examined with a panel of pharmacological inhibitors and short-hairpin RNA (shRNA)-mediated knockdown of DNA repair pathways. Comparisons of cell survival and virus replication were performed using a two-sided t test (unpaired). The survival of athymic mice (n = 6-8 mice per group) bearing GSC-derived glioblastoma tumors treated with the combination of G47 delta and TMZ was analyzed by the Kaplan-Meier method and evaluated with a two-sided log-rank test. The combination of G47 delta and TMZ acted synergistically in killing GSCs but not neurons, with associated robust induction of DNA damage. Pharmacological and shRNA-mediated knockdown studies suggested that activated ataxia telangiectasia mutated (ATM) is a crucial mediator of synergy. Activated ATM relocalized to HSV DNA replication compartments where it likely enhanced oHSV replication and could not participate in repairing TMZ-induced DNA damage. Sensitivity to TMZ and synergy with G47 delta decreased with O(6)-methylguanine-DNA-methyltransferase (MGMT) expression and MSH6 knockdown. Combined G47 delta and TMZ treatment extended survival of mice bearing GSC-derived intracranial tumors, achieving long-term remission in four of eight mice (median survival = 228 days; G47 delta alone vs G47 delta + TMZ, hazard ratio of survival = 7.1, 95% confidence interval = 1.9 to 26.1, P = .003) at TMZ doses attainable in patients. The combination of G47 delta and TMZ acts synergistically in killing GSCs through oHSV-mediated manipulation of DNA damage responses. This strategy is highly efficacious in representative preclinical models and warrants clinical translation. C1 [Kanai, Ryuichi; Rabkin, Samuel D.; Sgubin, Donatella; Zaupa, Cecile M.; Wakimoto, Hiroaki] Massachusetts Gen Hosp, Dept Neurosurg, Brain Tumor Res Ctr, Boston, MA 02114 USA. [Kanai, Ryuichi; Rabkin, Samuel D.; Yip, Stephen; Sgubin, Donatella; Zaupa, Cecile M.; Louis, David N.; Wakimoto, Hiroaki; Martuza, Robert L.] Harvard Univ, Sch Med, Boston, MA USA. [Yip, Stephen; Louis, David N.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Yip, Stephen] BC Canc Agcy, Dept Pathol & Lab Med, Vancouver, BC, Canada. [Hirose, Yuichi] Fujita Hlth Univ, Dept Neurosurg, Toyoake, Aichi, Japan. RP Martuza, RL (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, Brain Tumor Res Ctr, White Bldg,Rm 502,55 Fruit St, Boston, MA 02114 USA. EM rmartuza@partners.org RI rabkin, samuel/C-2443-2012 OI rabkin, samuel/0000-0003-2344-2795 FU National Institutes of Health [NS-032677, CA57683]; Department of Defense [W81XWH-07-1-0359]; Royal College of Physicians and Surgeons of Canada; BrainCare BC FX This work was supported by the National Institutes of Health (NS-032677 to R. L. M. and CA57683 to D.N.L.), and the Department of Defense (W81XWH-07-1-0359 to S. D. R.). S.Y. was supported by a Clinician Investigator Fellowship from the Royal College of Physicians and Surgeons of Canada and BrainCare BC. NR 58 TC 35 Z9 36 U1 0 U2 17 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 JAN PY 2012 VL 104 IS 1 BP 42 EP 55 DI 10.1093/jnci/djr509 PG 14 WC Oncology SC Oncology GA 873OH UT WOS:000298892200009 PM 22173583 ER PT J AU Burstein, HJ AF Burstein, Harold J. TI JNCCN Reaches 10 SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Editorial Material C1 [Burstein, Harold J.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Burstein, Harold J.] Dana Farber Canc Inst, Boston, MA USA. [Burstein, Harold J.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Burstein, HJ (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 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 JAN PY 2012 VL 10 IS 1 BP 3 EP 3 PG 1 WC Oncology SC Oncology GA 875CL UT WOS:000299007500002 PM 22223863 ER PT J AU Ettinger, DS Akerley, W Borghaei, H Chang, A Cheney, RT Chirieac, LR D'Amico, TA Demmy, TL Ganti, AKP Govindan, R Grannis, FW Horn, L Jahan, TM Jahanzeb, M Kessinger, A Komaki, R Kong, FM Kris, MG Krug, LM Lennes, IT Loo, BW Martins, R O'Malley, J Osarogiagbon, RU Otterson, GA Patel, JD Pinder-Schenck, M Pisters, KM Reckamp, K Riely, GJ Rohren, E Swanson, SJ Wood, DE Yang, SC AF Ettinger, David S. Akerley, Wallace Borghaei, Hossein Chang, Andrew Cheney, Richard T. Chirieac, Lucian R. D'Amico, Thomas A. Demmy, Todd L. Ganti, Apar Kishor P. Govindan, Ramaswamy Grannis, Frederic W., Jr. Horn, Leora Jahan, Thierry M. Jahanzeb, Mohammad Kessinger, Anne Komaki, Ritsuko Kong, Feng-Ming (Spring) Kris, Mark G. Krug, Lee M. Lennes, Inga T. Loo, Billy W., Jr. Martins, Renato O'Malley, Janis Osarogiagbon, Raymond U. Otterson, Gregory A. Patel, Jyoti D. Pinder-Schenck, Mary Pisters, Katherine M. Reckamp, Karen Riely, Gregory J. Rohren, Eric Swanson, Scott J. Wood, Douglas E. Yang, Stephen C. CA NCCN Clinical Practice Guidelines TI Malignant Pleural Mesothelioma SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review DE NCCN Clinical Practice Guidelines; NCCN Guidelines; malignant pleural mesothelioma; asbestos; chemotherapy; surgery; radiation therapy; pleural effusion ID INTENSITY-MODULATED RADIOTHERAPY; POSITRON-EMISSION-TOMOGRAPHY; PEMETREXED PLUS CISPLATIN; MULTICENTER PHASE-II; MEGAKARYOCYTE POTENTIATING FACTOR; DOSE HEMITHORACIC RADIATION; RANDOMIZED CONTROLLED-TRIAL; EXPANDED ACCESS PROGRAM; EXTRAPLEURAL PNEUMONECTOMY; TRIMODALITY THERAPY C1 [Ettinger, David S.; Yang, Stephen C.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Akerley, Wallace] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Borghaei, Hossein] Fox Chase Canc Ctr, Philadelphia, PA USA. [Chang, Andrew; Kong, Feng-Ming (Spring)] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Cheney, Richard T.; Demmy, Todd L.] Roswell Pk Canc Inst, Buffalo, NY USA. [Chirieac, Lucian R.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Govindan, Ramaswamy] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Govindan, Ramaswamy] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Grannis, Frederic W., Jr.; Reckamp, Karen] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Horn, Leora] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Jahanzeb, Mohammad; Osarogiagbon, Raymond U.] Univ Tennessee, St Jude Childrens Hosp, Inst Canc, Knoxville, TN 37996 USA. [Kessinger, Anne] Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE USA. [Komaki, Ritsuko; Pisters, Katherine M.; Rohren, Eric] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Kris, Mark G.; Krug, Lee M.; Riely, Gregory J.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Lennes, Inga T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Loo, Billy W., Jr.] Stanford Canc Inst, Stanford, CA USA. [Martins, Renato; Wood, Douglas E.] Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [O'Malley, Janis] Univ Alabama, Ctr Comprehens Canc, Birmingham, AL USA. [Otterson, Gregory A.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Patel, Jyoti D.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Pinder-Schenck, Mary] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Swanson, Scott J.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. RP Ettinger, DS (reprint author), Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. RI Ganti, Apar Kishor/D-5498-2015; OI Ganti, Apar Kishor/0000-0003-3724-2671; Chang, Andrew/0000-0001-9506-0425; Reckamp, Karen/0000-0002-9213-0325 NR 116 TC 19 Z9 19 U1 2 U2 6 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD JAN PY 2012 VL 10 IS 1 BP 26 EP 41 PG 16 WC Oncology SC Oncology GA 875CL UT WOS:000299007500006 PM 22223867 ER PT J AU O'Brien, S Abboud, CN Akhtari, M Altman, J Berman, E DeAngelo, DJ Devine, S Fathi, AT Gotlib, J Jagasia, M Moore, JO Pinilla-Ibarz, J Radich, JP Reddy, VVB Shah, NP Shami, PJ Smith, BD Snyder, DS Wetzler, M Yunus, F AF O'Brien, Susan Abboud, Camille N. Akhtari, Mojtaba Altman, Jessica Berman, Ellin DeAngelo, Daniel J. Devine, Steven Fathi, Amir T. Gotlib, Jason Jagasia, Madan Moore, Joseph O. Pinilla-Ibarz, Javier Radich, Jerald P. Reddy, Vishnu V. B. Shah, Neil P. Shami, Paul J. Smith, B. Douglas Snyder, David S. Wetzler, Meir Yunus, Furhan CA NCCN Clinical Practice TI Chronic Myelogenous Leukemia SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review DE NCCN Clinical Practice Guidelines; NCCN Guidelines; chronic myelogenous leukemia; BCR-ABL; tyrosine kinase inhibitor; stem cell transplant; imatinib; dasatinib; nilotinib ID CHRONIC MYELOID-LEUKEMIA; STEM-CELL TRANSPLANTATION; TYROSINE KINASE INHIBITORS; IMATINIB MESYLATE THERAPY; BONE-MARROW-TRANSPLANTATION; POLYMERASE-CHAIN-REACTION; COMPLETE CYTOGENETIC RESPONSE; IN-SITU HYBRIDIZATION; EARLY CHRONIC-PHASE; HIGH-DOSE IMATINIB C1 [O'Brien, Susan] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Abboud, Camille N.] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Abboud, Camille N.] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Akhtari, Mojtaba] Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE USA. [Altman, Jessica] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Berman, Ellin] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Devine, Steven] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Fathi, Amir T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Gotlib, Jason] Stanford Comprehens Canc Ctr, Stanford, CA USA. [Jagasia, Madan] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Pinilla-Ibarz, Javier] Univ S Florida, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33620 USA. [Radich, Jerald P.] Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [Reddy, Vishnu V. B.] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL USA. [Shah, Neil P.] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Shami, Paul J.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Smith, B. Douglas] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Snyder, David S.] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Wetzler, Meir] Roswell Pk Canc Inst, Buffalo, NY USA. [Yunus, Furhan] Univ Tennessee, Inst Canc, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. RP O'Brien, S (reprint author), Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. OI Reddy, Vishnu/0000-0001-5474-3289 FU NCI NIH HHS [P30 CA016672] NR 263 TC 9 Z9 11 U1 1 U2 5 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 JAN PY 2012 VL 10 IS 1 BP 64 EP 110 PG 47 WC Oncology SC Oncology GA 875CL UT WOS:000299007500009 PM 22223870 ER PT J AU Wright, CD AF Wright, Cameron D. TI Historical perspectives of The American Association for Thoracic Surgery: Edward D. Churchill (1895-1972) SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Biographical-Item C1 Massachusetts Gen Hosp, Dept Thorac Surg, Boston, MA 02114 USA. RP Wright, CD (reprint author), Massachusetts Gen Hosp, Dept Thorac Surg, Blake 1570,55 Fruit St, Boston, MA 02114 USA. EM wright.cameron@mgh.harvard.edu NR 1 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD JAN PY 2012 VL 143 IS 1 BP 1 EP 3 DI 10.1016/j.jtcvs.2011.06.032 PG 3 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 863GW UT WOS:000298151800005 PM 21820679 ER PT J AU Yarbrough, WM Mukherjee, R Stroud, RE Rivers, WT Oelsen, JM Dixon, JA Eckhouse, SR Ikonomidis, JS Zile, MR Spinale, FG AF Yarbrough, William M. Mukherjee, Rupak Stroud, Robert E. Rivers, William T. Oelsen, J. Marshall Dixon, Jennifer A. Eckhouse, Shaina R. Ikonomidis, John S. Zile, Michael R. Spinale, Francis G. TI Progressive induction of left ventricular pressure overload in a large animal model elicits myocardial remodeling and a unique matrix signature SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article; Proceedings Paper CT 91st Annual Meeting of the American-Association-for-Thoracic-Surgery CY MAY 07-11, 2011 CL Philadelphia, PA SP Amer Assoc Thorac Surg ID AORTIC-VALVE-REPLACEMENT; HEART-FAILURE; TISSUE INHIBITOR; GENE-EXPRESSION; DIASTOLIC DYSFUNCTION; CARDIAC FIBROBLASTS; DEPENDENT CHANGES; FIBROSIS; HYPERTROPHY; DISEASE AB Objective: Patients with severe left ventricular pressure overload secondary to aortic stenosis can present with signs and symptoms of heart failure despite normal left ventricular ejection fraction. This process occurs, at least in part, as a result of left ventricular pressure overload-induced extracellular matrix remodeling that promulgates increased left ventricular stiffness and impaired diastolic function. However, the determinants that drive extracellular matrix remodeling in this form of left ventricular pressure overload remain to be fully defined. Methods: Left ventricular pressure overload was induced in mature pigs (n = 15) by progressive ascending aortic cuff inflation (once per week for 4 weeks), whereby left ventricular mass, left ventricular ejection fraction, and regional myocardial stiffness (rK(m)) were compared with referent controls (n = 12). Determinants of extracellular matrix remodeling were assessed by measuring levels of mRNA expression for fibrillar collagens, matrix metalloproteinases, and tissue inhibitors of matrix metalloproteinase 1 and 4. Results: With left ventricular pressure overload, left ventricular mass and rK(m) increased by 2- and 3-fold, respectively, compared with control, with no change in left ventricular ejection fraction. Left ventricular myocardial collagen increased approximately 2-fold, which was accompanied by reduced solubility (ie, increased cross-linking) with left ventricular pressure overload, but mRNA expression for fibrillar collagen and matrix metalloproteinases remained relatively unchanged. In contrast, a robust increase in mRNA expression for tissue inhibitors of matrix metalloproteinase-1 and 4 occurred with left ventricular pressure overload. Conclusions: In a progressive model of left ventricular pressure overload, which recapitulates the phenotype of aortic stenosis, increased extracellular matrix accumulation and subsequently increased myocardial stiffness were not due to increased fibrillar collagen expression but rather to determinants of post-translational control that included increased collagen stability (thereby resistant to matrix metalloproteinase degradation) and increased endogenous matrix metalloproteinase inhibition. Targeting these extracellular matrix post-translational events with left ventricular pressure overload may hold both diagnostic and therapeutic relevance. (J Thorac Cardiovasc Surg 2012;143:215-23) C1 [Spinale, Francis G.] Univ S Carolina, Sch Med, CBA, Cardiovasc Translat Res Ctr, Columbia, SC 29208 USA. [Yarbrough, William M.] Sisters Char Providence Hosp, Columbia, SC USA. [Zile, Michael R.] Med Univ S Carolina, Charleston, SC 29425 USA. [Mukherjee, Rupak; Stroud, Robert E.; Rivers, William T.; Oelsen, J. Marshall; Dixon, Jennifer A.; Eckhouse, Shaina R.; Ikonomidis, John S.; Spinale, Francis G.] Div Cardiothorac Surg & Adult Cardiol, Charleston, SC USA. [Zile, Michael R.; Spinale, Francis G.] Ralph H Johnson Vet Adm Med Ctr, Charleston, SC USA. RP Spinale, FG (reprint author), Univ S Carolina, Sch Med, CBA, Cardiovasc Translat Res Ctr, 6439 Garners Ferry Rd, Columbia, SC 29208 USA. EM cvctrc@uscmed.sc.edu FU NHLBI NIH HHS [R01 HL095608, T32 HL007260, HL059165, R01 HL059165-08, R01 HL095608-03, R01 HL057952, HL057952, HL095608, R01 HL111090, R01 HL059165, R01 HL057952-12, HL 57952] NR 32 TC 20 Z9 21 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD JAN PY 2012 VL 143 IS 1 BP 215 EP 223 DI 10.1016/j.jtcvs.2011.09.032 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 863GW UT WOS:000298151800031 PM 22056365 ER PT J AU Ranasinghe, S Flanders, M Cutler, S Soghoian, DZ Ghebremichael, M Davis, I Lindqvist, M Pereyra, F Walker, BD Heckerman, D Streeck, H AF Ranasinghe, Srinika Flanders, Michael Cutler, Sam Soghoian, Damien Z. Ghebremichael, Musie Davis, Isaiah Lindqvist, Madelene Pereyra, Florencia Walker, Bruce D. Heckerman, David Streeck, Hendrik TI HIV-Specific CD4 T Cell Responses to Different Viral Proteins Have Discordant Associations with Viral Load and Clinical Outcome SO JOURNAL OF VIROLOGY LA English DT Article ID COMPREHENSIVE ANALYSIS; INFECTION; EPITOPES; GAG; INDIVIDUALS; HELP AB A successful prophylactic vaccine is characterized by long-lived immunity, which is critically dependent on CD4 T cell-mediated helper signals. Indeed, most licensed vaccines induce antigen-specific CD4 T cell responses, in addition to high-affinity antibodies. However, despite the important role of CD4 T cells in vaccine design and natural infection, few studies have characterized HIV-specific CD4 T cells due to their preferential susceptibility to HIV infection. To establish at the population level the impact of HIV-specific CD4 T cells on viral control and define the specificity of HIV-specific CD4 T cell peptide targeting, we conducted a comprehensive analysis of these responses to the entire HIV proteome in 93 subjects at different stages of HIV infection. We show that HIV-specific CD4 T cell responses were detectable in 92% of individuals and that the breadth of these responses showed a significant inverse correlation with the viral load (P = 0.009, R = -0.31). In particular, CD4 T cell responses targeting Gag were robustly associated with lower levels of viremia (P = 0.0002, R = -0.45). Importantly, differences in the immunodominance profile of HIV-specific CD4 T cell responses distinguished HIV controllers from progressors. Furthermore, Gag/Env ratios were a potent marker of viral control, with a high frequency and magnitude of Gag responses and low proportion of Env responses associated with effective immune control. At the epitope level, targeting of three distinct Gag peptides was linked to spontaneous HIV control (P = 0.60 to 0.85). Inclusion of these immunogenic proteins and peptides in future HIV vaccines may act as a critical cornerstone for enhancing protective T cell responses. C1 [Ranasinghe, Srinika; Flanders, Michael; Cutler, Sam; Soghoian, Damien Z.; Ghebremichael, Musie; Davis, Isaiah; Lindqvist, Madelene; Pereyra, Florencia; Walker, Bruce D.; Streeck, Hendrik] Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, Boston, MA 02114 USA. [Ranasinghe, Srinika; Flanders, Michael; Cutler, Sam; Soghoian, Damien Z.; Ghebremichael, Musie; Davis, Isaiah; Lindqvist, Madelene; Pereyra, Florencia; Walker, Bruce D.; Streeck, Hendrik] Harvard Univ, Sch Med, Boston, MA USA. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Heckerman, David] Microsoft Res, Redmond, WA USA. RP Streeck, H (reprint author), Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, Boston, MA 02114 USA. EM hstreeck@partners.org FU National Institutes of Health [1R01AI091450-01, 1R01AI094602-01]; Bill and Melinda Gates Foundation FX This study was funded by the National Institutes of Health (1R01AI091450-01 and 1R01AI094602-01) and the Bill and Melinda Gates Foundation. NR 28 TC 47 Z9 47 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2012 VL 86 IS 1 BP 277 EP 283 DI 10.1128/JVI.05577-11 PG 7 WC Virology SC Virology GA 865YV UT WOS:000298347700026 PM 22031937 ER PT J AU Dehghan, S Liu, EB Seto, J Torres, SF Hudson, NR Kajon, AE Metzgar, D Dyer, DW Chodosh, J Jones, MS Seto, D AF Dehghan, Shoaleh Liu, Elizabeth B. Seto, Jason Torres, Sarah F. Hudson, Nolan R. Kajon, Adriana E. Metzgar, David Dyer, David W. Chodosh, James Jones, Morris S. Seto, Donald TI Five Genome Sequences of Subspecies B1 Human Adenoviruses Associated with Acute Respiratory Disease SO JOURNAL OF VIROLOGY LA English DT Article ID COMPUTATIONAL ANALYSIS; RECOMBINATION; INFECTION; GENE AB Five genomes of human subspecies B1 adenoviruses isolated from cases of acute respiratory disease have been sequenced and archived for reference. These include representatives of two prevalent genomic variants of HAdV-7, i.e., HAdV-7h and HAdV7d2. The other three are HAdV-3/16, HAdV-16 strain E26, and HAdV-3+7 strain Takeuchi. All are recombinant genomes. Genomics and bioinformatics provide detailed views into the genetic makeup of these pathogens and insight into their molecular evolution. Retrospective characterization of particularly problematic older pathogens such as HAdV-7h (1987) and intriguing isolates such as HAdV-3+7 strain Takeuchi (1958) may provide clues to their phenotypes and serology and may suggest protocols for prevention and treatment. C1 [Dehghan, Shoaleh; Liu, Elizabeth B.; Seto, Jason; Seto, Donald] George Mason Univ, Sch Syst Biol, Manassas, VA 20110 USA. [Torres, Sarah F.; Hudson, Nolan R.] David Grant USAF Med Ctr, Clin Invest Facil, Travis AFB, CA 94535 USA. [Kajon, Adriana E.] Lovelace Resp Res Inst, Albuquerque, NM 87108 USA. [Metzgar, David] USN, Dept Resp Dis Res, Hlth Res Ctr, San Diego, CA 92106 USA. [Dyer, David W.] Univ Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Oklahoma City, OK 73104 USA. [Chodosh, James] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Howe Lab, Boston, MA 02114 USA. [Jones, Morris S.] Calif Dept Publ Hlth, Viral & Rickettsial Dis Lab, Richmond, CA 94804 USA. RP Seto, D (reprint author), George Mason Univ, Sch Syst Biol, Manassas, VA 20110 USA. EM dseto@gmu.edu RI Valle, Ruben/A-7512-2013 FU U.S. Public Health Service NIH [EY013124, P30EY014104]; Research to Prevent Blindness, Inc. FX This work was supported in part by U.S. Public Health Service NIH grants EY013124 (D. S., M.S.J., D. W. D., and J.C.) and P30EY014104 (J.C.). J.C. is also funded by an unrestricted grant to the Department of Ophthalmology, Harvard Medical School, from Research to Prevent Blindness, Inc. NR 13 TC 8 Z9 10 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2012 VL 86 IS 1 BP 635 EP 636 DI 10.1128/JVI.06593-11 PG 2 WC Virology SC Virology GA 865YV UT WOS:000298347700066 PM 22158846 ER PT J AU He, JC Chuang, PY Ma'ayan, A Iyengar, R AF He, John Cijiang Chuang, Peter Y. Ma'ayan, Avi Iyengar, Ravi TI Systems biology of kidney diseases SO KIDNEY INTERNATIONAL LA English DT Review DE cell signaling; gene transcription; kidney disease; microarray analysis; protein interaction ID HUMAN DIABETIC-NEPHROPATHY; FOCAL SEGMENTAL GLOMERULOSCLEROSIS; GENOME-WIDE ASSOCIATION; BLOOD-PRESSURE REGULATION; VEGF-A EXPRESSION; GENE-EXPRESSION; PROTEOMIC ANALYSIS; AFRICAN-AMERICANS; HUMAN URINE; 3-DIMENSIONAL RECONSTRUCTION AB Kidney diseases manifest in progressive loss of renal function, which ultimately leads to complete kidney failure. The mechanisms underlying the origins and progression of kidney diseases are not fully understood. Multiple factors involved in the pathogenesis of kidney diseases have made the traditional candidate gene approach of limited value toward full understanding of the molecular mechanisms of these diseases. A systems biology approach that integrates computational modeling with large-scale data gathering of the molecular changes could be useful in identifying the multiple interacting genes and their products that drive kidney diseases. Advances in biotechnology now make it possible to gather large data sets to characterize the role of the genome, epigenome, transcriptome, proteome, and metabolome in kidney diseases. When combined with computational analyses, these experimental approaches will provide a comprehensive understanding of the underlying biological processes. Multiscale analysis that connects the molecular interactions and cell biology of different kidney cells to renal physiology and pathology can be utilized to identify modules of biological and clinical importance that are perturbed in disease processes. This integration of experimental approaches and computational modeling is expected to generate new knowledge that can help to identify marker sets to guide the diagnosis, monitor disease progression, and identify new therapeutic targets. Kidney International (2012) 81, 22-39; doi:10.1038/ki.2011.314; published online 31 August 2011 C1 [He, John Cijiang] Mt Sinai Sch Med, Dept Med, Div Nephrol, New York, NY 10029 USA. [He, John Cijiang; Ma'ayan, Avi; Iyengar, Ravi] Mt Sinai Sch Med, Dept Pharmacol & Syst Therapeut, New York, NY 10029 USA. [He, John Cijiang] James J Peters VAMC, Dept Med, New York, NY USA. [Ma'ayan, Avi; Iyengar, Ravi] Mt Sinai Sch Med, Syst Biol Ctr New York, New York, NY 10029 USA. RP He, JC (reprint author), Mt Sinai Sch Med, Dept Med, Div Nephrol, 1 Gustave L Levy Pl, New York, NY 10029 USA. EM cijiang.he@mssm.edu FU NIH [1R01DK078897, 1R01DK088541, 1RC4DK090860, RC2LM010994-01, 5R01DK087650, 5K08DK082760]; Systems Biology Center [5P50GM071558] FX JCH is supported by NIH 1R01DK078897 and VA Merit Award; JCH and AM are supported by NIH 1R01DK088541 and 1RC4DK090860; AM is supported by NIH RC2LM010994-01. RI and AM are supported by the Systems Biology Center grant 5P50GM071558; RI and JCH are supported by NIH 5R01DK087650. PYC is supported by NIH 5K08DK082760. NR 127 TC 39 Z9 39 U1 0 U2 21 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JAN PY 2012 VL 81 IS 1 BP 22 EP 39 DI 10.1038/ki.2011.314 PG 18 WC Urology & Nephrology SC Urology & Nephrology GA 869XP UT WOS:000298633600006 PM 21881558 ER PT J AU Berman, DM Bosenberg, MW Orwant, RL Thurberg, BL Draetta, GF Fletcher, CDM Loda, M AF Berman, David M. Bosenberg, Marcus W. Orwant, Robin L. Thurberg, Beth L. Draetta, Gulio F. Fletcher, Christopher D. M. Loda, Massimo TI Investigative pathology: leading the post-genomic revolution SO LABORATORY INVESTIGATION LA English DT Article DE career development; collaborative research; genomics; industry; pathobiology; pharmaceuticals ID BREAST-CANCER; MUTATIONS; CARCINOMAS; RECURRENCE; PATTERNS; REVEALS; PATIENT; IMPACT; TUMORS; ASSAY AB The completion of the Human Genome Project and the development of genome-based technologies over the past decade have set the stage for a new era of personalized medicine. By all rights, molecularly trained investigative pathologists should be leading this revolution. Singularly well suited for this work, molecular pathologists have the rare ability to wed genomic tools with unique diagnostic skills and tissue-based pathology techniques for integrated diagnosis of human disease. However, the number of pathologists with expertise in genome-based research has remained relatively low due to outdated training methods and a reluctance among some traditional pathologists to embrace new technologies. Moreover, because budding pathologists may not appreciate the vast selection of jobs available to them, they often end up choosing jobs that focus almost entirely on routine diagnosis rather than new frontiers in molecular pathology. This review calls for changes aimed at rectifying these troubling trends to ensure that pathology continues to guide patient care in a post-genomic era. Laboratory Investigation (2012) 92, 4-8; doi: 10.1038/labinvest.2011.147; published online 10 October 2011 C1 [Berman, David M.] Johns Hopkins Univ, Sch Med, Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21231 USA. [Berman, David M.] Johns Hopkins Med Inst, Dept Oncol, Baltimore, MD 21205 USA. [Berman, David M.] Johns Hopkins Med Inst, Dept Urol, Baltimore, MD 21205 USA. [Bosenberg, Marcus W.] Yale Univ, Sch Med, Dept Dermatol, New Haven, CT 06510 USA. [Draetta, Gulio F.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA. [Thurberg, Beth L.] Genzyme Corp, Dept Pathol, Framingham, MA 01701 USA. [Fletcher, Christopher D. M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Loda, Massimo] Harvard Univ, Brigham & Womens Hosp, Sch Med,Dept Pathol, Ctr Mol Oncol Pathol,Dana Farber Canc Inst, Boston, MA 02115 USA. [Loda, Massimo] Harvard Univ, Brigham & Womens Hosp, Sch Med,Dept Med Oncol, Ctr Mol Oncol Pathol,Dana Farber Canc Inst, Boston, MA 02115 USA. [Loda, Massimo] Broad Inst Harvard & MIT, Cambridge, MA USA. [Loda, Massimo] Kings Coll London, Div Canc Studies, London WC2R 2LS, England. RP Berman, DM (reprint author), Johns Hopkins Univ, Sch Med, Johns Hopkins Med Inst, Dept Pathol, 1550 Orleans St,CRB2 Room 545, Baltimore, MD 21231 USA. EM dberman@jhmi.edu FU National Institutes of Health [RO1DK072000, R01CA131945]; Prostate Cancer Foundation FX We thank the journal's reviewers for insightful and significant contributions to the manuscript. We also gratefully acknowledge the USCAP Education Committee, including Dr J Goldblum and Dr D Huntsman, for hosting a course on investigative pathology careers, which formed the basis of this review. Finally, we thank our financial supporters: the National Institutes of Health (RO1DK072000 and R01CA131945) and the Prostate Cancer Foundation. NR 23 TC 14 Z9 14 U1 0 U2 1 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 JAN PY 2012 VL 92 IS 1 BP 4 EP 8 DI 10.1038/labinvest.2011.147 PG 5 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 871MZ UT WOS:000298743600001 PM 21986811 ER PT J AU Barchue, SM AF Barchue, Sylvia M. TI Should Children Visit Patients in an Intensive Care Unit (ICU)? SO MCN-THE AMERICAN JOURNAL OF MATERNAL-CHILD NURSING LA English DT Editorial Material C1 James J Peters VA Med Ctr, Patient Care Ctr, Med Surg Units, ICU,ED & Pulm Care, Bronx, NY USA. RP Barchue, SM (reprint author), James J Peters VA Med Ctr, Patient Care Ctr, Med Surg Units, ICU,ED & Pulm Care, Bronx, NY USA. NR 3 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0361-929X J9 MCN-AM J MATERN-CHIL JI MCN-Am. J. Matern.-Child Nurs. PD JAN-FEB PY 2012 VL 37 IS 1 BP 8 EP 8 PG 1 WC Nursing SC Nursing GA 864OR UT WOS:000298250000002 ER PT J AU Morgan, A AF Morgan, Aneita TI Coordinated by Kathleen Leask Capitulo, DNSc, RN, FAAN SO MCN-THE AMERICAN JOURNAL OF MATERNAL-CHILD NURSING LA English DT Editorial Material C1 James J Peters VA Med Ctr, Clin Care Team, Intens Care Unit, Bronx, NY USA. RP Morgan, A (reprint author), James J Peters VA Med Ctr, Clin Care Team, Intens Care Unit, Bronx, NY USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0361-929X J9 MCN-AM J MATERN-CHIL JI MCN-Am. J. Matern.-Child Nurs. PD JAN-FEB PY 2012 VL 37 IS 1 BP 9 EP 9 PG 1 WC Nursing SC Nursing GA 864OR UT WOS:000298250000003 ER PT J AU Epstein, AJ Ketcham, JD Rathore, SS Groeneveld, PW AF Epstein, Andrew J. Ketcham, Jonathan D. Rathore, Saif S. Groeneveld, Peter W. TI Variations in the Use of an Innovative Technology by Payer The Case of Drug-Eluting Stents SO MEDICAL CARE LA English DT Article DE variations in care; technology; access ID ACUTE CORONARY SYNDROMES; HEALTH-CARE COSTS; INSURANCE TYPE; OUTCOMES; CLOPIDOGREL; PREDICTORS; REGISTRY; THERAPY; ARTERY AB Background: Despite receiving identical reimbursement for treating heart disease patients with bare metal stents (BMS) or drug-eluting coronary stents (DES), cardiologists' use of the new technology (DES) may have varied by patient payer type as DES diffused. Payer-related factors that differ between hospitals and/or differential treatment inside hospitals might explain any overall differences by payer type. Objectives: To assess the association between payer and DES use and to examine between-hospital and within-hospital variation in DES use over time. Methods: We conducted a retrospective analysis of 4.1 million hospitalizations involving DES or BMS from 2003 to 2008 Nationwide Inpatient Sample. We estimated hybrid-fixed effects logit models and calculated the adjusted within-quarter, cross-payer differences in DES use. Results: Coronary stent patients with Medicaid or without insurance were significantly less likely to receive DES than were patients with private insurance throughout the study period. The differences fluctuated over time as the popularity of DES relative to BMS increased and decreased. The within-hospital gaps paralleled the overall differences, and were largest in Q3 2003 (Medicaid: 11.9, uninsured: 10.9% points) and Q4 2008 (Medicaid: 12.8, uninsured: 20.7% points), and smallest in Q4 2004 (Medicaid: 1.4, uninsured: 1.1% points). The between-hospital adjusted differences in DES use by payer were small and rarely significant. Conclusions: We found substantial differences in DES use by payer within hospitals, suggesting physicians selected the new technology for patients in a manner associated with patients' payer type. C1 [Epstein, Andrew J.; Groeneveld, Peter W.] Univ Penn, Sch Med, Dept Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. [Epstein, Andrew J.] Philadelphia Vet Affairs Med Ctr, Dept Vet Affairs, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Epstein, Andrew J.; Groeneveld, Peter W.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Ketcham, Jonathan D.] Arizona State Univ, WP Carey Sch Business, Dept Mkt, Tempe, AZ USA. [Rathore, Saif S.] Yale Univ, Sch Med, MD PhD Program, New Haven, CT USA. RP Epstein, AJ (reprint author), Univ Penn, Sch Med, Dept Med, Div Gen Internal Med, 423 Guardian Dr,11th Floor, Philadelphia, PA 19104 USA. EM eandrew@mail.med.upenn.edu FU National Heart, Lung, and Blood Institute [1R01HL086919]; Agency for Healthcare Research and Quality [1R01HS018403] FX This research was supported by the National Heart, Lung, and Blood Institute (1R01HL086919) and by the Agency for Healthcare Research and Quality (1R01HS018403). The content of this study does not reflect the views of the VA or the United States government. NR 38 TC 8 Z9 8 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD JAN PY 2012 VL 50 IS 1 BP 1 EP 9 DI 10.1097/MLR.0b013e31822d5de9 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 863IY UT WOS:000298157200001 PM 22167062 ER PT J AU Epstein, AJ Polsky, D Yang, FF Yang, L Groeneveld, PW AF Epstein, Andrew J. Polsky, Daniel Yang, Feifei Yang, Lin Groeneveld, Peter W. TI Geographic Variation in Implantable Cardioverter-Defibrillator Use and Heart Failure Survival SO MEDICAL CARE LA English DT Article DE cardiovascular disease; congestive heart failure; health care technology; mortality; utilization ID CARDIAC RESYNCHRONIZATION THERAPY; PROPHYLACTIC IMPLANTATION; PRIMARY PREVENTION; PROPENSITY SCORE; COMORBIDITY; DYSFUNCTION; COMMUNITY AB Background: Implantable cardioverter-defibrillators and cardiac resynchronization therapy-defibrillators (ICD/CRT-Ds) are evidence-based preventative treatments for many patients with heart failure (HF), yet large numbers of eligible patients remain untreated. It is uncertain if localities with more frequent ICD/CRT-D use have had better rates of HF survival. Objectives: To determine if US Hospital Referral Regions (HRRs) with larger increases in the rate of ICD/CRT-D utilization during 2002 to 2007 also had commensurate increases in HF survival. Research Design: Retrospective cohort. Participants: Medicare beneficiaries age 66 to 80 nonelectively hospitalized for HF from 2002 to 2007. Measures: Each HRR's annual ICD/CRT-D rate was estimated from the cohort's Medicare procedure claims. Survival duration was determined from Medicare mortality records. HRR-year-level panel regression models were estimated to assess whether an HRR's ICD/CRT-D rate predicted HF survival, adjusting for baseline differences in survival across HRRs and secular trends. Results: A total of 883,002 HF patients were propensity-score matched within HRR across 2002 to 2007. Across HRRs, growth in ICD/CRT-D use among such patients varied from 1 to 12 percentage points. Regression models indicated that a 1 percentage point increase in an HRR's ICD/CRT-D utilization among hospitalized HF patients was associated with an increase in 1-year survival of 0.12% [95% confidence interval (CI), 0.03%-0.21%, P = 0.009] and with a 0.26% increase in HF survival at 2 years (95% CI, 0.14%-0.37%, P < 0.001). Conclusions: Localities with greater increases in ICD/CRT-D utilization from 2002 to 2007 also had greater improvements in HF survival. Areas with persistently low ICD/CRT-D use may be good targets for programs designed to increase the evidence-based use of defibrillators. C1 [Epstein, Andrew J.; Groeneveld, Peter W.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Dept Vet Affairs, Philadelphia, PA USA. [Epstein, Andrew J.; Polsky, Daniel; Yang, Feifei; Yang, Lin; Groeneveld, Peter W.] Univ Penn, Sch Med, Dept Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. [Epstein, Andrew J.; Polsky, Daniel; Groeneveld, Peter W.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. RP Groeneveld, PW (reprint author), 1229 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM petergro@mail.med.upenn.edu FU National Heart, Lung, and Blood Institute [1R01HL086919]; Agency for Healthcare Research and Quality [1R01HS018403]; Department of Veterans Affairs' Health Services Research and Development Service, Washington, DC; Pennsylvania Department of Health FX Supported by the National Heart, Lung, and Blood Institute (1R01HL086919) and by the Agency for Healthcare Research and Quality (1R01HS018403). Dr Groeneveld was additionally supported by a Career Development Transition Award from the Department of Veterans Affairs' Health Services Research and Development Service, Washington, DC. This project was also funded, in part, under a grant from the Pennsylvania Department of Health, which specifically disclaims responsibility for any analyses, interpretations, or conclusions. NR 27 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD JAN PY 2012 VL 50 IS 1 BP 10 EP 17 DI 10.1097/MLR.0b013e3182293510 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 863IY UT WOS:000298157200002 PM 22167063 ER PT J AU Keyhani, S Arling, G Williams, LS Ross, JS Ordin, DL Myers, J Tyndall, G Vogel, B Bravata, DM AF Keyhani, Salomeh Arling, Greg Williams, Linda S. Ross, Joseph S. Ordin, Diana L. Myers, Jennifer Tyndall, Gary Vogel, Bruce Bravata, Dawn M. TI The Use and Misuse of Thrombolytic Therapy Within the Veterans Health Administration SO MEDICAL CARE LA English DT Article DE stroke; thrombolytic therapy; health services research ID ACUTE ISCHEMIC-STROKE; TISSUE-PLASMINOGEN ACTIVATOR; QUALITY-OF-CARE; ASSOCIATION; IMPROVEMENT; GUIDELINES; CENTERS; SYSTEM; ATTACK AB Background: Within the Veterans Health Administration (VHA), approximately 6000 veterans are hospitalized with acute ischemic stroke annually. We examined the use and misuse of thrombolytic therapy with tissue plasminogen activator (tPA) in a national sample of veterans who were admitted to a VHA Medical Center (VAMC) with acute ischemic stroke. Methods: Medical record reviews were conducted on 5000 acute stroke patients who were admitted to a VAMC in 2007. Patients were defined as eligible to receive tPA if they arrived at the hospital within 3 hours of stroke symptom onset and had no contra-indications to tPA. We compared eligible patients who received tPA to those who did not and examined the distribution of eligible patients across the 129 VAMCs included in this study. Results: Among the 3931 ischemic stroke patients, 174 (4.4%) were eligible for tPA. Among the 135 patients who arrived within 2 hours of symptom onset which allowed adequate time for testing and evaluation, 19 (14.1%) received tPA. An additional 11 patients received tPA but did not meet eligibility criteria. Eligible patients receiving tPA were similar to eligible patients not receiving tPA in terms of clinical conditions and time to brain imaging. Among the 30 patients that received tPA, 5 (16.6%) received the wrong dose. Among the 85 VAMCs that received Z1 eligible patient, on average 2.3 patients were eligible for tPA annually. Conclusions: Relatively few eligible veterans receive thrombolysis across the VHA system. Strategies to improve thrombolysis delivery will have to account for the low annual volume of eligible stroke patients cared for at individual VAMCs. C1 [Keyhani, Salomeh] Univ Calif San Francisco, Dept Vet Affairs VHA, Hlth Serv Res & Dev Serv HSR&D, REAP, San Francisco, CA 94143 USA. [Keyhani, Salomeh] Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94143 USA. [Keyhani, Salomeh; Williams, Linda S.; Ordin, Diana L.; Myers, Jennifer; Vogel, Bruce; Bravata, Dawn M.] VHA HSR&D Stroke Qual Enhancement Res Initiat QUE, Indianapolis, IN USA. [Arling, Greg] Indiana Univ Sch Med, Indiana Univ Ctr Aging Res, Indianapolis, IN USA. [Arling, Greg; Williams, Linda S.; Bravata, Dawn M.] Regenstrief Inst Hlth Care, Indianapolis, IN USA. [Williams, Linda S.; Myers, Jennifer; Bravata, Dawn M.] Richard L Roudebush VA Med Ctr, VHA HSR&D Ctr Excellence Implementing Evidence Ba, Indianapolis, IN USA. [Williams, Linda S.] Indiana Univ Sch Med, Dept Neurol, Indianapolis, IN USA. [Ross, Joseph S.] Yale Univ, Sch Med, Washington, DC USA. [Ordin, Diana L.] VHA Off Qual & Performance OQP, Washington, DC USA. [Tyndall, Gary] Syracuse VA Med Ctr, Emergency Dept, Syracuse, NY USA. [Vogel, Bruce] N Florida S Georgia Vet Hlth Syst, VHA Rehabil Outcomes Res Ctr RORC, Gainesville, FL USA. [Bravata, Dawn M.] Indiana Univ Sch Med, Dept Internal Med, Indianapolis, IN USA. RP Keyhani, S (reprint author), San Francisco VA Med Ctr, 4150 Clement,111A1, San Francisco, CA 94121 USA. EM salomeh.keyhani@va.gov OI Tyndall, Gary/0000-0001-9984-4809 FU Department of Veterans Affairs; Veterans Health Administration (VHA); Office of Quality and Performance and Health Services Research and Development Service Quality Enhancement Research Initiative [RRP 09-184]; VA HSRD FX The project reported here was supported by the Department of Veterans Affairs, Veterans Health Administration (VHA), Office of Quality and Performance and Health Services Research and Development Service Quality Enhancement Research Initiative (RRP 09-184). Dr. Keyhani is also supported by a VA HSR&D Career Development Award. NR 25 TC 9 Z9 9 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD JAN PY 2012 VL 50 IS 1 BP 66 EP 73 DI 10.1097/MLR.0b013e3182294092 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 863IY UT WOS:000298157200009 PM 22182924 ER PT J AU Rosen, AK Itani, KMF Cevasco, M Kaafarani, HMA Hanchate, A Shin, M Shwartz, M Loveland, S Chen, Q Borzecki, A AF Rosen, Amy K. Itani, Kamal M. F. Cevasco, Marisa Kaafarani, Haytham M. A. Hanchate, Amresh Shin, Marlena Shwartz, Michael Loveland, Susan Chen, Qi Borzecki, Ann TI Validating the Patient Safety Indicators in the Veterans Health Administration Do They Accurately Identify True Safety Events? SO MEDICAL CARE LA English DT Article DE patient safety; ICD-9-CM coding; criterion validation; adverse events; administrative data ID POSITIVE PREDICTIVE-VALUE; POSTOPERATIVE HEMORRHAGE; ADVERSE EVENTS; CARE RESEARCH; VALIDITY; HOSPITALS; HEMATOMA; TRAUMA; AGENCY; RATES AB Background: The Agency for Healthcare Research and Quality (AHRQ) Patient Safety Indicators (PSIs) use administrative data to detect potentially preventable in-hospital adverse events. However, few studies have determined how accurately the PSIs identify true safety events. Objectives: We examined the criterion validity, specifically the positive predictive value (PPV), of 12 selected PSIs using clinical data abstracted from the Veterans Health Administration (VA) electronic medical record as the gold standard. Methods: We identified PSI-flagged cases from 28 representative hospitals by applying the AHRQ PSI software (v.3.1a) to VA fiscal year 2003 to 2007 administrative data. Trained nurse-abstractors used standardized abstraction tools to review a random sample of flagged medical records (112 records per PSI) for the presence of true adverse events. Interrater reliability was assessed. We evaluated PPVs and associated 95% confidence intervals of each PSI and examined false positive (FP) cases to determine why they were incorrectly flagged and gain insight into how each PSI might be improved. Results: PPVs ranged from 28% (95% CI, 15%-43%) for Postoperative Hip Fracture to 87% (95% CI, 79%-92%) for Postoperative Wound Dehiscence. Common reasons for FPs included conditions that were present on admission (POA), coding errors, and lack of coding specificity. PSIs with the lowest PPVs had the highest proportion of FPs owing to POA. Conclusions: Overall, PPVs were moderate for most of the PSIs. Implementing POA codes and using more specific ICD-9-CM codes would improve their validity. Our results suggest that additional coding improvements are needed before the PSIs evaluated herein are used for hospital reporting or pay for performance. C1 [Rosen, Amy K.; Hanchate, Amresh; Shin, Marlena; Shwartz, Michael; Loveland, Susan; Chen, Qi] VA Boston Healthcare Syst, COLMR, Boston, MA 02130 USA. [Rosen, Amy K.; Chen, Qi; Borzecki, Ann] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Rosen, Amy K.; Itani, Kamal M. F.; Hanchate, Amresh; Borzecki, Ann] Boston Univ, Sch Med, Boston, MA 02118 USA. [Itani, Kamal M. F.; Cevasco, Marisa] VA Boston Healthcare Syst, Dept Surg, Boston, MA 02130 USA. [Itani, Kamal M. F.] Harvard Univ, Sch Med, Boston, MA USA. [Cevasco, Marisa] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Kaafarani, Haytham M. A.] Tufts Med Ctr, Dept Surg, Boston, MA USA. [Kaafarani, Haytham M. A.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Shwartz, Michael] Boston Univ, Sch Management, Dept Operat & Technol Management, Boston, MA 02215 USA. [Borzecki, Ann] Bedford VAMC, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. RP Rosen, AK (reprint author), VA Boston Healthcare Syst, COLMR, 150 S Huntington Ave,152 M, Boston, MA 02130 USA. EM akrosen@bu.edu OI Hanchate, Amresh/0000-0002-7038-4463 FU VA [HSRD SDR-07-002] FX Supported by VA grant HSR&D SDR-07-002. NR 50 TC 35 Z9 35 U1 2 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD JAN PY 2012 VL 50 IS 1 BP 74 EP 85 DI 10.1097/MLR.0b013e3182293edf PG 12 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 863IY UT WOS:000298157200010 PM 21993057 ER PT J AU Lin, WC Chien, HL Willis, G O'Connell, E Rennie, KS Bottella, HM Ferris, TG AF Lin, Wen-Chieh Chien, Hung-Lun Willis, Georgianna O'Connell, Elizabeth Rennie, Kate Staunton Bottella, Heather M. Ferris, Timothy G. TI The Effect of a Telephone-based Health Coaching Disease Management Program on Medicaid Members With Chronic Conditions SO MEDICAL CARE LA English DT Article DE disease management; chronic condition; Medicaid; difference-in-differences ID CARE UTILIZATION; HEART-FAILURE; BENEFICIARIES; DISORDERS; QUALITY; IMPACT; EXPENDITURES; DEPRESSION; ASTHMA; COSTS AB Background: Despite the growing popularity of disease management programs for chronic conditions, evidence regarding the effect of these programs has been mixed. In addition, few peer-reviewed studies have examined the effect of these programs on publicly insured populations. Objectives: To examine the effect of a telephone-based health coaching disease management program on healthcare utilization and expenditures in Medicaid members with chronic conditions. Research Design: Using a difference-in-differences analysis, we examined changes in hospitalizations, emergency department (ED) visits, ambulatory care visits, and Medicaid expenditures among program members for 1 year before and 2 years after their enrollment compared with a matched comparison group. Subjects: Medicaid members aged 18 to 64 with a diagnosis of qualifying chronic conditions and 2 acute health service events of hospitalizations and/or ED visits within a 12-month period. Results: Changes in acute hospitalizations, ambulatory care visits, and Medicaid expenditures before and after program enrollment were similar between the 2 study groups. However, during the second year after enrollment, program members had a significantly smaller decrease in ED visits than the comparisons (8% in program members and 23% in comparisons, P value = 0.03). Conclusions: Compared with a matched comparison group, the telephone-based health coaching disease management program did not demonstrate significant effects on healthcare utilization and expenditures in Medicaid members with chronic conditions. C1 [Lin, Wen-Chieh; Chien, Hung-Lun; Willis, Georgianna; O'Connell, Elizabeth] Univ Massachusetts, Sch Med, Ctr Hlth Policy & Res, Shrewsbury, MA 01545 USA. [Lin, Wen-Chieh] Univ Massachusetts, Sch Med, Dept Family Med & Community Hlth, Worcester, MA USA. [Rennie, Kate Staunton] Massachusetts Execut Off Hlth & Human Serv, MassHlth Off Acute & Ambulatory Care, Boston, MA USA. [Bottella, Heather M.] Humana, Louisville, KY USA. [Ferris, Timothy G.] Mass Gen Hosp, Mongan Inst Hlth Policy, Boston, MA USA. RP Lin, WC (reprint author), Univ Massachusetts, Sch Med, Ctr Hlth Policy & Res, 333 South St, Shrewsbury, MA 01545 USA. EM wen.lin@umassmed.edu NR 26 TC 15 Z9 16 U1 5 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD JAN PY 2012 VL 50 IS 1 BP 91 EP 98 DI 10.1097/MLR.0b013e31822dcedf PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 863IY UT WOS:000298157200012 PM 21993059 ER PT J AU Teal, CR Gill, AC Green, AR Crandall, S AF Teal, Cayla R. Gill, Anne C. Green, Alexander R. Crandall, Sonia TI Helping medical learners recognise and manage unconscious bias toward certain patient groups SO MEDICAL EDUCATION LA English DT Article ID IMPLICIT ASSOCIATION TEST; DIAGNOSTIC ERROR; CULTURAL COMPETENCE; PROVIDERS CONTRIBUTE; COGNITIVE-PSYCHOLOGY; AVERSIVE RACISM; CARE; HEALTH; DISPARITIES; STUDENTS AB CONTEXT For the last 30 years, developments in cognitive sciences have demonstrated that human behaviour, beliefs and attitudes are shaped by automatic and unconscious cognitive processes. Only recently has much attention been paid to how unconscious biases based on certain patient characteristics may: (i) result in behaviour that is preferential toward or against specific patients; (ii) influence treatment decisions, and (iii) adversely influence the patient-doctor relationship. Partly in response to accreditation requirements, medical educators are now exploring how they might help students and residents to develop awareness of their own potential biases and strategies to mitigate them. METHODS In this paper, we briefly review key cognition concepts and describe the limited published literature about educational strategies for addressing unconscious bias. DISCUSSION We propose a developmental model to illustrate how individuals might move from absolute denial of unconscious bias to the integration of strategies to mitigate its influence on their interactions with patients and offer recommendations to educators and education researchers. C1 [Teal, Cayla R.; Gill, Anne C.] Baylor Coll Med, Off Undergrad Med Educ, Houston, TX 77030 USA. [Teal, Cayla R.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Gill, Anne C.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Gill, Anne C.] Baylor Coll Med, Dept Med Eth, Houston, TX 77030 USA. [Green, Alexander R.] Massachusetts Gen Hosp, Dispar Solut Ctr, Boston, MA 02114 USA. [Green, Alexander R.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Crandall, Sonia] Wake Forest Sch Med, Dept Family & Community Med, Winston Salem, NC USA. [Crandall, Sonia] Wake Forest Sch Med, Dept Phys Assistant Studies, Winston Salem, NC USA. RP Teal, CR (reprint author), Baylor Coll Med, Off Undergrad Med Educ, 1 Baylor Plaza,MS BCM300, Houston, TX 77030 USA. EM cteal@bcm.edu NR 59 TC 30 Z9 30 U1 3 U2 29 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0308-0110 J9 MED EDUC JI Med. Educ. PD JAN PY 2012 VL 46 IS 1 BP 80 EP 88 DI 10.1111/j.1365-2923.2011.04101.x PG 9 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 862KV UT WOS:000298090500014 PM 22150199 ER PT J AU Ngwa, W Makrigiorgos, GM Berbeco, RI AF Ngwa, Wilfred Makrigiorgos, G. Mike Berbeco, Ross I. TI Gold nanoparticle-aided brachytherapy with vascular dose painting: Estimation of dose enhancement to the tumor endothelial cell nucleus SO MEDICAL PHYSICS LA English DT Article DE brachytherapy; gold nanoparticles; vascular disrupting agents; dose enhancement ID RADIATION RESPONSE; DISRUPTING AGENTS; SOLID TUMORS; IN-VIVO; THERAPY; SIZE; SURFACE; CANCER; ENERGY; RADIOTHERAPY AB Purpose: Theoretical microdosimetry at the subcellular level is employed in this study to estimate the dose enhancement to tumor endothelial cell nuclei, caused by radiation-induced photo/Auger electrons originating from gold nanoparticles (AuNPs) targeting the tumor endothelium, during brachytherapy. Methods: A tumor vascular endothelial cell (EC) is modeled as a slab of 2 mu m (thickness) x 10 mu m (length) x 10 mu m (width). The EC contains a nucleus of 5 mu m diameter and thickness of 0.5-1 mu m, corresponding to nucleus size 5%-10% of cellular volume, respectively. Analytic calculations based on the electron energy loss formula of Cole were carried out to estimate the dose enhancement to the nucleus caused by photo/Auger electrons from AuNPs attached to the exterior surface of the EC. The nucleus dose enhancement factor (nDEF), representing the ratio of the dose to the nucleus with and without the presence of gold nanoparticles was calculated for different AuNP local concentrations. The investigated concentration range considers the potential for significantly higher local concentration near the EC due to preferential accumulation of AuNP in the tumor vasculature. Four brachytherapy sources: I-125, Pd-103, Yb-169, and 50 kVp x-rays were investigated. Results: For nucleus size of 10% of the cellular volume and AuNP concentrations ranging from 7 to 140 mg/g, brachytherapy sources Pd-103, I-125, 50 kVp, and Yb-169 yielded nDEF values of 5.6-73, 4.8-58.3, 4.7-56.6, and 3.2-25.8, respectively. Meanwhile, for nucleus size 5% of the cellular volume in the same concentration range, Pd-103, I-125, 50 kVp, and Yb-169 yielded nDEF values of 6.9-79.2, 5.1-63.2, 5.0-61.5, and 3.3-28.3, respectively. Conclusions: The results predict that a substantial dose boost to the nucleus of endothelial cells can be achieved by applying tumor vasculature-targeted AuNPs in combination with brachytherapy. Such vascular dose boosts could induce tumor vascular shutdown, prompting extensive tumor cell death. (C) 2012 American Association of Physicists in Medicine. [DOI: 10.1118/1.3671905] C1 [Ngwa, Wilfred] Brigham & Womens Hosp, Dana Farber Canc Inst, Div Med Phys & Biophys, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Ngwa, W (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Div Med Phys & Biophys, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. EM wngwa@lroc.harvard.edu NR 55 TC 24 Z9 25 U1 3 U2 14 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 JAN PY 2012 VL 39 IS 1 BP 392 EP 398 DI 10.1118/1.3671905 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 872LX UT WOS:000298812200041 PM 22225308 ER PT J AU Khosroshahi, A Carruthers, MN Deshpande, V Unizony, S Bloch, DB Stone, JH AF Khosroshahi, Arezou Carruthers, Mollie N. Deshpande, Vikram Unizony, Sebastian Bloch, Donald B. Stone, John H. TI Rituximab for the Treatment of IgG4-Related Disease Lessons From 10 Consecutive Patients SO MEDICINE LA English DT Article ID AUTOIMMUNE PANCREATITIS; SYSTEMIC-DISEASE; SCLEROSING DISEASE; CLINICOPATHOLOGICAL-ENTITY; RHEUMATOID-ARTHRITIS; THERAPY; FEATURES; AZATHIOPRINE; SAFETY AB Patients with IgG4-related disease (IgG4-RD) typically have elevated serum concentrations of IgG4 and share histopathologic features that are similar across affected organ(s). IgG4-RD patients frequently require prolonged treatment with glucocorticoids and are often unable to taper these medications. Traditional disease-modifying antirheumatic drugs (DMARDs) are generally ineffective. We assessed the clinical and serologic responses to B lymphocyte depletion therapy in 10 consecutive patients with steroid-and DMARD-refractory IgG4-RD. Ten patients with IgG4-RD were treated with rituximab (RTX) (2 infusions of 1000 mg, 15 days apart). Clinical improvement was assessed by monitoring the patient's ability to taper prednisone to discontinuation and to stop DMARDs; by serial measurements of total IgG and IgG subclasses; and by follow-up radiologic assessments guided by the patient's particular pattern of organ involvement. We also developed and retrospectively applied the IgG4-RD Disease Activity Index and Flare Tool. Organ involvement included the pancreas, biliary tree, aorta, salivary glands (submandibular and parotid), lacrimal glands, lymph nodes, thyroid gland, and retroperitoneum. Nine of 10 patients demonstrated striking clinical improvement within 1 month of starting RTX. One patient with advanced thyroid fibrosis associated with Riedel thyroiditis and a history of disease in multiple other organ systems did not have improvement in the thyroid gland, but the disease did not progress to involve new organs. All 10 patients were able to discontinue prednisone and DMARDs following RTX therapy. Significant decreases in IgG concentrations were observed for the IgG4 subclass only. Four patients were re-treated with RTX after 6 months because of either symptom recurrence and increasing IgG4 concentration at the time of peripheral B cell reconstitution (n = 2) or because of physician discretion (n = 2). Repeated courses of RTX maintained their effectiveness and resulted in further decreases in IgG4 concentrations. In patients who had an increased IgG4 concentration at the time of presentation, the level of serum IgG4 appeared to be a reliable measure of disease activity. IgG4-RD is an idiopathic, multiorgan inflammatory disease in which diverse organ manifestations are linked by characteristic histopathologic and immunohistochemical features. Treatment with RTX led to prompt clinical and serologic improvement in refractory IgG4-RD in all patients with active inflammation. Serial treatments with RTX may lead to progressive declines in serum IgG4 concentrations and better disease control. Serum IgG4 concentrations may remain low, and clinical disease activity may remain quiescent even after B cell reconstitution in a significant proportion of patients. C1 [Khosroshahi, Arezou; Carruthers, Mollie N.; Unizony, Sebastian; Bloch, Donald B.; Stone, John H.] Massachusetts Gen Hosp, Rheumatol Unit, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. [Deshpande, Vikram] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Stone, JH (reprint author), Massachusetts Gen Hosp, Rheumatol Unit, Div Rheumatol Allergy & Immunol, 55 Fruit St, Boston, MA 02114 USA. EM jhstone@partners.org FU Genentech FX Dr. Deshpande has served as a consultant for Chugai Pharmaceutical. Dr. Stone has served as a consultant and his institution has a grant pending with Genentech. The other authors declare no funding or conflicts of interest. NR 35 TC 178 Z9 195 U1 1 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7974 J9 MEDICINE JI Medicine (Baltimore) PD JAN PY 2012 VL 91 IS 1 BP 57 EP 66 DI 10.1097/MD.0b013e3182431ef6 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 873CD UT WOS:000298857600007 PM 22210556 ER PT J AU Tracy, EE Speakman, E AF Tracy, Erin E. Speakman, Elizabeth TI Intimate partner violence: not just a concern of the reproductive ages SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Editorial Material ID WOMEN; FAMILY; ABUSE C1 [Tracy, Erin E.; Speakman, Elizabeth] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Tracy, EE (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 18 TC 3 Z9 3 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD JAN PY 2012 VL 19 IS 1 BP 3 EP 5 DI 10.1097/gme.0b013e318239c985 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 870IJ UT WOS:000298662300002 PM 22198633 ER PT J AU Sugita, M Sugita, H Kim, M Mao, J Yasuda, Y Habiro, M Shinozaki, S Yasuhara, S Shimizu, N Martyn, JAJ Kaneki, M AF Sugita, Michiko Sugita, Hiroki Kim, Minhye Mao, Ji Yasuda, Yoshikazu Habiro, Mayu Shinozaki, Shohei Yasuhara, Shingo Shimizu, Nobuyuki Martyn, J. A. Jeevendra Kaneki, Masao TI Inducible nitric oxide synthase deficiency ameliorates skeletal muscle insulin resistance but does not alter unexpected lower blood glucose levels after burn injury in C57BL/6 mice SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID CRITICAL ILLNESS POLYNEUROPATHY; RECEPTOR SUBSTRATE-1; TARGETED DISRUPTION; ADIPOSE-TISSUE; PROTEIN-KINASE; LIVER; INFLAMMATION; OBESITY; HYPERGLYCEMIA; CARBOHYDRATE AB Burn injury is associated with inflammatory responses and metabolic alterations including insulin resistance. Impaired insulin receptor substrate-1 (IRS-1)-mediated insulin signal transduction is a major component of insulin resistance in skeletal muscle following bum injury. To further investigate molecular mechanisms that underlie bum injury-induced insulin resistance, we study a role of inducible nitric oxide synthase (iNOS), a major mediator of inflammation, on burn-induced muscle insulin resistance in iNOS-deficient mice. Full-thickness third-degree bum injury comprising 12% of total body surface area was produced in wild-type and iNOS-deficient C57BL/6 mice. Insulin-stimulated activation (phosphorylation) of IR, IRS-1, and Akt was assessed by immunoblotting and immunoprecipitation. Insulin-stimulated glucose uptake by skeletal muscle was evaluated ex vivo. Burn injury caused induction of iNOS in skeletal muscle of wild-type mice. The increase of iNOS expression paralleled the increase of insulin resistance, as evidenced by decreased tyrosine phosphorylation of IR and IRS-1, IRS-1 expression, insulin-stimulated activation of phosphatidylinositol 3-kinase and Akt/PKB, and insulin-stimulated glucose uptake in mouse skeletal muscle. The absence of iNOS in genetically engineered mice significantly lessened burn injury-induced insulin resistance in skeletal muscle. In wild-type mice, insulin tolerance test revealed whole-body insulin resistance in burned mice compared with sham-burned controls. This effect was reversed by iNOS deficiency. Unexpectedly, however, blood glucose levels were depressed in both wild-type and iNOS-deficient mice after burn injury. Gene disruption of iNOS ameliorated the effect of burn on IRS-1-mediated insulin signaling in skeletal muscle of mice. These findings indicate that iNOS plays a significant role in burn injury-induced skeletal muscle insulin resistance. (C) 2012 Elsevier Inc. All rights reserved. C1 [Sugita, Michiko; Sugita, Hiroki; Kim, Minhye; Mao, Ji; Yasuda, Yoshikazu; Habiro, Mayu; Shinozaki, Shohei; Yasuhara, Shingo; Shimizu, Nobuyuki; Martyn, J. A. Jeevendra; Kaneki, Masao] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Sugita, Michiko; Sugita, Hiroki; Mao, Ji; Yasuda, Yoshikazu; Shinozaki, Shohei; Yasuhara, Shingo; Shimizu, Nobuyuki; Martyn, J. A. Jeevendra; Kaneki, Masao] Shriners Hosp Children, Boston, MA 02114 USA. RP Kaneki, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Charlestown, MA 02129 USA. EM mkaneki@helix.mgh.harvard.edu FU National Institutes of Health [R01-DK-058127, R01-GM-31569, R01-GM-055082, R01-GM-61411, GM-21700]; Shriners Hospitals for Children [8540, 71000, 8530, 8510, 8830] FX This work was supported by grants from the National Institutes of Health (R01-DK-058127 to M Kaneki; R01-GM-31569, R01-GM-055082, R01-GM-61411, and GM-21700 [Project IV] to JAJ Martyn) and by the Shriners Hospitals for Children grants 8540 and 71000 (to M Kaneki), 8530 and 8510 (to JAJ Martyn), and 8830 (to S Yasuhara). NR 41 TC 12 Z9 12 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD JAN PY 2012 VL 61 IS 1 BP 127 EP 136 DI 10.1016/j.metabol.2011.06.001 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 864DH UT WOS:000298216700019 PM 21816442 ER PT J AU Afrin, LB AF Afrin, Lawrence B. TI Mast Cell Activation Syndrome Masquerading as Agranulocytosis SO MILITARY MEDICINE LA English DT Article ID SYSTEMIC MASTOCYTOSIS; DISEASE; KIT AB Acquired agranulocytosis is a Tare, life-threatening disorder. The few known causes/associations usually are readily identifiable (e.g., drug reaction. Felty syndrome, megaloblastosis, large granular lymphocytic leukemia, etc.). We report a novel association with mast cell disease. A 61-year-old morbidly obese man developed rheumatoid arthritis unresponsive to several medications. Agranulocytosis developed shortly alter sulfasalazine was started but did not improve when the drug was soon stopped. Other symptoms across many systems developed including hives and presyncope. Marrow aspiration and biopsy showed only neutropenia. Serum tryptase was mildly elevated; urinary prostaglandin D, was markedly elevated. Other causes were not found. Mast cell activation syndrome (MCAS) was diagnosed. Oral antihistamines, montelukast, and cromolyn were unhelpful; aspirin was initially felt contraindicated. Imatinib immediately increased neutrophils from 0% to 25% but did not help symptoms; subsequent addition of aspirin increased neutrophils further and abated symptoms. Different presentations of different MCAS patients reflect elaboration of different mediators likely consequent to different Kit mutations. Mast cells (MCs) help regulate adipocytes, and adipocytes can inhibit granulopoiesis; thus, a Kit-mutated MC clone may have directly and/or indirectly driven agranulocytosis. MCAS should be considered in otherwise idiopathic agranulocytosis presenting with comorbidities best explained by MC mediator release. C1 [Afrin, Lawrence B.] Ralph H Johnson Vet Affairs Med Ctr, Hematol Oncol Sect, Med Serv, Charleston, SC 29401 USA. [Afrin, Lawrence B.] Med Univ S Carolina, Div Hematol Oncol, Charleston, SC 29425 USA. RP Afrin, LB (reprint author), Ralph H Johnson Vet Affairs Med Ctr, Hematol Oncol Sect, Med Serv, 103 Bee St, Charleston, SC 29401 USA. NR 16 TC 6 Z9 6 U1 0 U2 1 PU ASSOC MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 J9 MIL MED JI Milit. Med. PD JAN PY 2012 VL 177 IS 1 BP 113 EP 117 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 874RP UT WOS:000298976100025 PM 22338992 ER PT J AU Wan, M Easton, RM Gleason, CE Monks, BR Ueki, K Kahn, CR Birnbaum, MJ AF Wan, Min Easton, Rachael M. Gleason, Catherine E. Monks, Bobby R. Ueki, Kohjiro Kahn, C. Ronald Birnbaum, Morris J. TI Loss of Akt1 in Mice Increases Energy Expenditure and Protects against Diet-Induced Obesity SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID BROWN ADIPOSE-TISSUE; SKELETAL-MUSCLE; GLUCOSE-HOMEOSTASIS; INSULIN-RESISTANCE; UNCOUPLING PROTEIN-3; KINASE-B; METABOLIC SYNDROME; HEPATIC STEATOSIS; EXERCISE; LACKING AB Akt is encoded by a gene family for which each isoform serves distinct but overlapping functions. Based on the phenotypes of the germ line gene disruptions, Akt1 has been associated with control of growth, whereas Akt2 has been linked to metabolic regulation. Here we show that Akt1 serves an unexpected role in the regulation of energy metabolism, as mice deficient for Akt1 exhibit protection from diet-induced obesity and its associated insulin resistance. Although skeletal muscle contributes most of the resting and exercising energy expenditure, muscle-specific deletion of Akt1 does not recapitulate the phenotype, indicating that the role of Akt1 in skeletal muscle is cell nonautonomous. These data indicate a previously unknown function of Akt1 in energy metabolism and provide a novel target for treatment of obesity. C1 [Wan, Min; Easton, Rachael M.; Gleason, Catherine E.; Monks, Bobby R.; Birnbaum, Morris J.] Univ Penn, Inst Diabet Obes & Metab, Philadelphia, PA 19104 USA. [Ueki, Kohjiro] Univ Tokyo, Grad Sch Med, Tokyo, Japan. [Kahn, C. Ronald] Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. RP Birnbaum, MJ (reprint author), Univ Penn, Inst Diabet Obes & Metab, Philadelphia, PA 19104 USA. EM birnbaum@mail.med.upenn.edu OI Birnbaum, Morris/0000-0001-9972-8680 FU NIH [RO1 DK56886, PO1 DK49210]; Diabetes and Endocrinology Research Center, University of Pennsylvania [NIH DK-19525] FX This work was supported by NIH grants RO1 DK56886 and PO1 DK49210 to M.J.B. The Mouse Phenotyping, Physiology and Metabolism Core and the Radioimmunoassay and Biomarker Core were supported by the Diabetes and Endocrinology Research Center, University of Pennsylvania (NIH DK-19525). NR 42 TC 17 Z9 17 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2012 VL 32 IS 1 BP 96 EP 106 DI 10.1128/MCB.05806-11 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 866FN UT WOS:000298366000009 PM 22037765 ER PT J AU Huang, SC Ou, AC Park, J Yu, F Yu, B Lee, A Yang, G Zhou, A Benz, EJ AF Huang, Shu-Ching Ou, Alexander C. Park, Jennie Yu, Faye Yu, Brian Lee, Angela Yang, Guang Zhou, Anyu Benz, Edward J., Jr. TI RBFOX2 Promotes Protein 4.1R Exon 16 Selection via U1 snRNP Recruitment SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PRE-MESSENGER-RNA; 5' SPLICE SITE; ERYTHROID-DIFFERENTIATION; MEMBRANE STABILITY; COMPLEX-FORMATION; SR PROTEINS; FOX-1; INTRON; BINDING; GENE AB The erythroid differentiation-specific splicing switch of protein 4.1R exon 16, which encodes a spectrin/actin-binding peptide critical for erythrocyte membrane stability, is modulated by the differentiation-induced splicing factor RBFOX2. We have now characterized the mechanism by which RBFOX2 regulates exon 16 splicing through the downstream intronic element UGCAUG. Exon 16 possesses a weak 5' splice site (GAG/GTTTGT), which when strengthened to a consensus sequence (GAG/GTAAGT) leads to near-total exon 16 inclusion. Impaired RBFOX2 binding reduces exon 16 inclusion in the context of the native weak 5' splice site, but not the engineered strong 5' splice site, implying that RBFOX2 achieves its effect by promoting utilization of the weak 5' splice site. We further demonstrate that RBFOX2 increases U1 snRNP recruitment to the weak 5' splice site through direct interaction between its C-terminal domain (CTD) and the zinc finger region of U1C and that the CTD is required for the effect of RBFOX2 on exon 16 splicing. Our data suggest a novel mechanism for exon 165' splice site activation in which the binding of RBFOX2 to downstream intronic splicing enhancers stabilizes the pre-mRNA-U1 snRNP complex through interactions with U1 C. C1 [Huang, Shu-Ching; Ou, Alexander C.; Park, Jennie; Yu, Faye; Yu, Brian; Lee, Angela; Yang, Guang; Zhou, Anyu; Benz, Edward J., Jr.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Huang, Shu-Ching; Yang, Guang; Zhou, Anyu; Benz, Edward J., Jr.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Benz, Edward J., Jr.] Harvard Univ, Sch Med, Dana Farber Harvard Canc Inst, Boston, MA USA. RP Huang, SC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM shu-ching_huang@dfci.harvard.edu FU NIH [HL24385]; Claudia Barr Award FX This work was supported by NIH grant HL24385 (to E.J.B.) and the Claudia Barr Award (to S.C.H.). NR 52 TC 10 Z9 10 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2012 VL 32 IS 2 BP 513 EP 526 DI 10.1128/MCB.06423-11 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 875HD UT WOS:000299020100023 PM 22083953 ER PT J AU Avila-Elchiver, M Nagrath, D Yarmush, ML AF Avila-Elchiver, Marco Nagrath, Deepak Yarmush, Martin L. TI Optimality and thermodynamics determine the evolution of transcriptional regulatory networks SO MOLECULAR BIOSYSTEMS LA English DT Article ID ESCHERICHIA-COLI; IN-SILICO; CULTURED-HEPATOCYTES; SIGNAL-TRANSDUCTION; ADAPTIVE EVOLUTION; COMPLEX NETWORKS; MOTIFS; OPTIMIZATION; EQUILIBRIUM; FRAMEWORK AB Transcriptional motifs are small regulatory interaction patterns that regulate biological functions in highly-interacting cellular networks. Recently, attempts have been made to explain the significance of transcriptional motifs through dynamic function. However, fundamental questions remain unanswered. Why are certain transcriptional motifs with similar dynamic function abundant while others occur rarely? What are the criteria for topological generalization of these motifs into complex networks? Here, we present a novel paradigm that combines non-equilibrium thermodynamics with multiobjective-optimality for network analysis. We found that energetic cost, defined herein as specific dissipation energy, is minimal at the optimal environmental conditions and it correlates inversely with the abundance of the network motifs obtained experimentally for E. coli and S. cerevisiae. This yields evidence that dissipative energetics is the underlying criteria used during evolution for motif selection and that biological systems during transcription tend towards evolutionary selection of subgraphs which produces minimum specific heat dissipation under optimal conditions, thereby explaining the abundance/rare occurrence of some motifs. We show that although certain motifs had similar dynamical functionality, they had significantly different energetic cost, thus explaining the abundance/rare occurrence of these motifs. The presented insights may establish global thermodynamic analysis as a backbone in designing and understanding complex networks systems, such as metabolic and protein interaction networks. C1 [Avila-Elchiver, Marco; Yarmush, Martin L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Avila-Elchiver, Marco; Yarmush, Martin L.] Harvard Univ, Sch Med, Shriners Hosp Children, Boston, MA 02114 USA. [Nagrath, Deepak] Rice Univ, Chem & Biomol Engn Dept, Houston, TX 77005 USA. RP Yarmush, ML (reprint author), Massachusetts Gen Hosp, 51 Blossom St, Boston, MA 02114 USA. EM ireis@sbi.org; dn7@rice.edu OI Nagrath, Deepak/0000-0002-8999-2282 FU NIBIB NIH HHS [P41 EB002503] NR 52 TC 2 Z9 2 U1 0 U2 8 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1742-206X EI 1742-2051 J9 MOL BIOSYST JI Mol. Biosyst. PY 2012 VL 8 IS 2 BP 511 EP 530 DI 10.1039/c1mb05177f PG 20 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 874YP UT WOS:000298994900011 PM 22076617 ER PT J AU Wray, NR Pergadia, ML Blackwood, DHR Penninx, BWJH Gordon, SD Nyholt, DR Ripke, S MacIntyre, DJ McGhee, KA Maclean, AW Smit, JH Hottenga, JJ Willemsen, G Middeldorp, CM de Geus, EJC Lewis, CM McGuffin, P Hickie, IB van den Oord, EJCG Liu, JZ Macgregor, S McEvoy, BP Byrne, EM Medland, SE Statham, DJ Henders, AK Heath, AC Montgomery, GW Martin, NG Boomsma, DI Madden, PAF Sullivan, PF AF Wray, N. R. Pergadia, M. L. Blackwood, D. H. R. Penninx, B. W. J. H. Gordon, S. D. Nyholt, D. R. Ripke, S. MacIntyre, D. J. McGhee, K. A. Maclean, A. W. Smit, J. H. Hottenga, J. J. Willemsen, G. Middeldorp, C. M. de Geus, E. J. C. Lewis, C. M. McGuffin, P. Hickie, I. B. van den Oord, E. J. C. G. Liu, J. Z. Macgregor, S. McEvoy, B. P. Byrne, E. M. Medland, S. E. Statham, D. J. Henders, A. K. Heath, A. C. Montgomery, G. W. Martin, N. G. Boomsma, D. I. Madden, P. A. F. Sullivan, P. F. TI Genome-wide association study of major depressive disorder: new results, meta-analysis, and lessons learned SO MOLECULAR PSYCHIATRY LA English DT Article DE major depressive disorder; depression; genome-wide association study; CACNA1C; ADCY3; GAL ID NATIONAL COMORBIDITY SURVEY; SEROTONIN TRANSPORTER GENE; MOOD DISORDERS; PSYCHIATRIC-DISORDERS; BIPOLAR DISORDER; TWIN SAMPLE; GALANIN; POPULATION; HERITABILITY; STABILITY AB Major depressive disorder (MDD) is a common complex disorder with a partly genetic etiology. We conducted a genome-wide association study of the MDD2000+ sample (2431 cases, 3673 screened controls and >1M imputed single-nucleotide polymorphisms (SNPs)). No SNPs achieved genome-wide significance either in the MDD2000+ study, or in meta-analysis with two other studies totaling 5763 cases and 6901 controls. These results imply that common variants of intermediate or large effect do not have main effects in the genetic architecture of MDD. Suggestive but notable results were (a) gene-based tests suggesting roles for adenylate cyclase 3 (ADCY3, 2p23.3) and galanin (GAL, 11q13.3); published functional evidence relates both of these to MDD and serotonergic signaling; (b) support for the bipolar disorder risk variant SNP rs1006737 in CACNA1C (P = 0.020, odds ratio = 1.10); and (c) lack of support for rs2251219, a SNP identified in a meta-analysis of affective disorder studies (P = 0.51). We estimate that sample sizes 1.8- to 2.4-fold greater are needed for association studies of MDD compared with those for schizophrenia to detect variants that explain the same proportion of total variance in liability. Larger study cohorts characterized for genetic and environmental risk factors accumulated prospectively are likely to be needed to dissect more fully the etiology of MDD. Molecular Psychiatry (2012) 17, 36-48; doi:10.1038/mp.2010.109; published online 2 November 2010 C1 [Pergadia, M. L.; Heath, A. C.; Madden, P. A. F.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [Blackwood, D. H. R.; MacIntyre, D. J.; McGhee, K. A.; Maclean, A. W.] Univ Edinburgh, Royal Edinburgh Hosp, Div Psychiat, Edinburgh, Midlothian, Scotland. [Penninx, B. W. J. H.; Smit, J. H.; Hottenga, J. J.; Willemsen, G.; Middeldorp, C. M.; de Geus, E. J. C.; Boomsma, D. I.] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands. [Penninx, B. W. J. H.; Smit, J. H.; Hottenga, J. J.; Willemsen, G.; Middeldorp, C. M.; de Geus, E. J. C.; Boomsma, D. I.] Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands. [Ripke, S.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Ripke, S.] Broad Inst Harvard & MIT, Cambridge, MA USA. [Lewis, C. M.; McGuffin, P.] Kings Coll London, MRC SGDP Ctr, Inst Psychiat, Dept Med & Mol Genet, London WC2R 2LS, England. [Hickie, I. B.] Univ Sydney, Brain & Mind Res Inst, Clin Res Unit, Sydney, NSW 2006, Australia. [van den Oord, E. J. C. G.] Virginia Commonwealth Univ, Ctr Biomarker Res & Personalized Med, Richmond, VA USA. [Sullivan, P. F.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Wray, N. R.; Gordon, S. D.; Nyholt, D. R.; Liu, J. Z.; Macgregor, S.; McEvoy, B. P.; Byrne, E. M.; Medland, S. E.; Statham, D. J.; Henders, A. K.; Montgomery, G. W.; Martin, N. G.] Queensland Inst Med Res, Psychiat Genet Lab, Brisbane, Qld 4029, Australia. [Wray, N. R.; Gordon, S. D.; Nyholt, D. R.; Liu, J. Z.; Macgregor, S.; McEvoy, B. P.; Byrne, E. M.; Medland, S. E.; Statham, D. J.; Henders, A. K.; Montgomery, G. W.; Martin, N. G.] Queensland Inst Med Res, Genet Epidemiol Lab, Brisbane, Qld 4029, Australia. [Wray, N. R.; Gordon, S. D.; Nyholt, D. R.; Liu, J. Z.; Macgregor, S.; McEvoy, B. P.; Byrne, E. M.; Medland, S. E.; Statham, D. J.; Henders, A. K.; Montgomery, G. W.; Martin, N. G.] Queensland Inst Med Res, Mol Epidemiol Lab, Brisbane, Qld 4029, Australia. [Wray, N. R.; Gordon, S. D.; Nyholt, D. R.; Liu, J. Z.; Macgregor, S.; McEvoy, B. P.; Byrne, E. M.; Medland, S. E.; Statham, D. J.; Henders, A. K.; Montgomery, G. W.; Martin, N. G.] Queensland Inst Med Res, Queensland Stat Genet Lab, Brisbane, Qld 4029, Australia. RP Wray, NR (reprint author), Queensland Inst Med Res, Psychiat Genet Lab, Herston Rd, Brisbane, Qld 4029, Australia. EM naomi.wray@qimr.edu.au; pfsulliv@med.unc.edu RI Lewis, Cathryn/A-5225-2010; Medland, Sarah/C-7630-2013; Macgregor, Stuart/C-6442-2009; Nyholt, Dale/C-8384-2013; McGuffin, Peter/A-1565-2012; Wray, Naomi/C-8639-2015; de Geus, Eco/M-9318-2015; Montgomery, Grant/B-7148-2008; OI Middeldorp, Christel/0000-0002-6218-0428; Martin, Nicholas/0000-0003-4069-8020; Lewis, Cathryn/0000-0002-8249-8476; Medland, Sarah/0000-0003-1382-380X; Macgregor, Stuart/0000-0001-6731-8142; McGuffin, Peter/0000-0002-9888-2907; Wray, Naomi/0000-0001-7421-3357; de Geus, Eco/0000-0001-6022-2666; Montgomery, Grant/0000-0002-4140-8139; MacIntyre, Donald J/0000-0001-6963-1335 FU Australian National Health and Medical Research Council [241944, 339462, 389927, 389875, 389891, 389892, 389938, 442915, 442981, 496675, 496739, 552485, 552498, 613608]; FP-5 GenomEUtwin Project [QLG2-CT-2002-01254]; US National Institutes of Health [AA07535, AA10248, AA13320, AA13321, AA13326, AA14041, MH66206, DA12854, DA019951]; Netherlands Scientific Organization (NWO) [480-05-003]; National Health and Medical Research Council; Australian Research Council; Netherlands Scientific Organization [904-61-090, 904-61-193, 480-04-004, 400-05-717]; Neuroscience Campus Amsterdam and the EMGO+ institute; European Union [EU/WLRT-2001-01254]; ZonMW (Geestkracht program) [10-000-1002]; National Institute of Mental Health Schizophrenia (NIMH) [RO1 MH059160, MH080403]; NESDA; NTR; Wellcome Trust, London; Chief Scientist Office of the Scottish Government; [NWO-SPI 56-464-1419] FX We thank the twins and their families registered at the Australian Twin Registry for their participation in the many studies that have contributed to this research. We thank Dixie Statham (sample collection); Leanne Wallace, Anthony Caracella and staff of the Molecular Epidemiology Laboratory (DNA processing); David Smyth, Harry Beeby, and Daniel Park (IT support). Funding was provided by the Australian National Health and Medical Research Council (241944, 339462, 389927, 389875, 389891, 389892, 389938, 442915, 442981, 496675, 496739, 552485, 552498, 613608), the FP-5 GenomEUtwin Project (QLG2-CT-2002-01254), and the US National Institutes of Health (NIH grants AA07535, AA10248, AA13320, AA13321, AA13326, AA14041, MH66206, DA12854, DA019951). A portion of the genotyping on which this study was based (Illumina 370K scans on 4300 individuals) was carried out at the Center for Inherited Disease Research, Baltimore through an access award to our late colleague Dr Richard Todd (Psychiatry, Washington University School of Medicine, St Louis). Statistical analyses were partly conducted at the Genetic Cluster Computer (http://www.geneticcluster.org), which is financially supported by the Netherlands Scientific Organization (NWO 480-05-003). SEM, SM and GWM are supported by the National Health and Medical Research Council Fellowship Scheme. NRW and DRN are supported by the Australian Research Council Future Fellowship Scheme.; Funding support was provided by the Netherlands Scientific Organization (904-61-090, 904-61-193, 480-04-004, 400-05-717, Centre for Medical Systems Biology (NWO Genomics), the Neuroscience Campus Amsterdam and the EMGO+ institute; the European Union (EU/WLRT-2001-01254), ZonMW (Geestkracht program, 10-000-1002), NIMH (RO1 MH059160) and matching funds from participating institutes in NESDA and NTR. The NTR controls were genotyped in the Genomics platform (certified service provider (CSPro(R)) for Illumina) at the LIFE and BRAIN Center Bonn (funded by NWO-SPI 56-464-1419).; We would like to record our appreciation for much practical support from our late colleague Walter J Muir, Professor of Developmental Psychiatry at the University of Edinburgh and especially for his many stimulating ideas for genetic studies in depression. We thank Margaret Van Beck for sample collection and Lee Murphy, Wellcome Trust Clinical Research Facility, Western General Hospital, Crewe Road South, Edinburgh, for sample management. The collection of the Edinburgh cohort was supported by grants from The Wellcome Trust, London and the Chief Scientist Office of the Scottish Government.; Additional funding was provided by National Institute of Mental Health Schizophrenia (NIMH) grant MH080403 to EJGCvdO and PFS. Control subjects from the NIMH Genetics Initiative, data and biomaterials are being collected by the 'Molecular Genetics of Schizophrenia II' collaboration. The investigators and coinvestigators are: ENH/Northwestern University, Evanston, IL, MH059571, Pablo V Gejman, MD (Collaboration Coordinator; PI), Alan R Sanders, MD; Emory University School of Medicine, Atlanta, GA, MH59587, Farooq Amin, MD (PI); Louisiana State University Health Sciences Center; New Orleans, Louisiana, MH067257, Nancy Buccola APRN, BC, MSN (PI); University of California-Irvine, Irvine, CA, MH60870, William Byerley, MD (PI); Washington University, St Louis, MO, U01, MH060879, C Robert Cloninger, MD (PI); University of Iowa, Iowa, IA, MH59566, Raymond Crowe, MD (PI), Donald Black, MD; University of Colorado, Denver, CO, MH059565, Robert Freedman, MD (PI); University of Pennsylvania, Philadelphia, PA, MH061675, Douglas Levinson, MD (PI); University of Queensland, Queensland, Australia, MH059588, Bryan Mowry, MD (PI); Mt. Sinai School of Medicine, New York, NY, MH59586, Jeremy Silverman, PhD (PI). NR 59 TC 156 Z9 160 U1 7 U2 40 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD JAN PY 2012 VL 17 IS 1 BP 36 EP 48 DI 10.1038/mp.2010.109 PG 13 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 875EU UT WOS:000299014000009 PM 21042317 ER PT J AU Zhang, W Fulci, G Buhrman, JS Stemmer-Rachamimov, AO Chen, JW Wojtkiewicz, GR Weissleder, R Rabkin, SD Martuza, RL AF Zhang, Wei Fulci, Giulia Buhrman, Jason S. Stemmer-Rachamimov, Anat O. Chen, John W. Wojtkiewicz, Gregory R. Weissleder, Ralph Rabkin, Samuel D. Martuza, Robert L. TI Bevacizumab With Angiostatin-armed oHSV Increases Antiangiogenesis and Decreases Bevacizumab-induced Invasion in U87 Glioma SO MOLECULAR THERAPY LA English DT Article ID HERPES-SIMPLEX-VIRUS; VESICULAR STOMATITIS-VIRUS; INNATE IMMUNE-RESPONSES; ANTITUMOR EFFICACY; ONCOLYTIC VIRUSES; VIRAL REPLICATION; COMBINATION THERAPY; MALIGNANT GLIOMAS; CANCER-CELLS; FUSION GENE AB Bevacizumab (BEV) is an antiangiogenic drug approved for glioblastoma (GBM) treatment. However, it does not increase survival and is associated with glioma invasion. Angiostatin is an antiangiogenic polypeptide that also inhibits migration of cancer cells, but is difficult to deliver. Oncolytic viruses (OV) can potentially spread throughout the tumor, reach isolated infiltrating cells, kill them and deliver anticancer agents to uninfected cells. We have tested a combination treatment of BEV plus an OV expressing angiostatin (G47 Delta-mAngio) in mice-bearing human GBM. Using a vascular intracranial human glioma model (U87) in athymic mice, we performed histopathological,analysis of tumors treated with G47 Delta-mAngio or BEV alone or in combination, followed tumor response by magnetic resonance imaging (MRI), and assessed animal survival. Our results indicate that injection of G47 Delta-mAngio during BEV treatment allows increased virus distribution, tumor lysis, and angiostatin-mediated inhibition of vascular endothelial growth factor (VEGF) expression and of BEV-induced invasion markers (matrix metalloproteinases-2 (MMP2), MMP9, and collagen). This leads to increased survival and antiangiogenesis and decreased invasive phenotypes. We show for the first time the possibility of improving the antiangiogenic effect of BEV while decreasing the tumor invasive-like phenotype induced by this drug, and demonstrate the therapeutic advantage of combining systemic and local antiangiogenic treatments with viral oncolytic therapy. C1 [Zhang, Wei; Fulci, Giulia; Buhrman, Jason S.; Rabkin, Samuel D.; Martuza, Robert L.] Massachusetts Gen Hosp, Brain Tumor Res Ctr, Dept Neurosurg, Boston, MA 02114 USA. [Zhang, Wei] Fourth Mil Med Univ, Xijing Hosp, Dept Neurosurg, Xian 710032, Peoples R China. [Stemmer-Rachamimov, Anat O.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Chen, John W.; Wojtkiewicz, Gregory R.; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol & Mol Imaging Res, Boston, MA 02114 USA. RP Martuza, RL (reprint author), Massachusetts Gen Hosp, Brain Tumor Res Ctr, Dept Neurosurg, 55 Fruit St, Boston, MA 02114 USA. EM rmartuza@partners.org RI rabkin, samuel/C-2443-2012 OI rabkin, samuel/0000-0003-2344-2795 FU China Scholarship Council (CSC); National Institute for Neurological Disorders [R01-NS032677, P30-NS045776, U24CA092782, R01-NS070835, R01-NS072167]; National Heart, Lung and Blood Institute at the National Institutes of Health, USA [K08-HL081170] FX We thank Prof Xiang Zhang (Department of Neurosurgery, Xijing Hospital, P.R. China) and Prof Takashi Tamiya (Department of Neurological Surgery, Kagawa University Faculty of Medicine, Japan) for their great spiritual inspiration and editorial assistance. We thank Christopher J. Owen for his help in computer assistance. We thank the support from Postgraduate Scholarship Program of China Scholarship Council (CSC). This work was supported in part by grants from the National Institute for Neurological Disorders (R01-NS032677 to R.L.M., P30-NS045776 to S.D.R. for the real-time PCR core, U24CA092782 to R.W. for imaging core, R01-NS070835 and R01-NS072167 to J.W.C.) and the National Heart, Lung and Blood Institute (K08-HL081170 to J.W.C.) at the National Institutes of Health, USA. The authors declared no conflict of interest. NR 49 TC 23 Z9 24 U1 1 U2 16 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 JAN PY 2012 VL 20 IS 1 BP 37 EP 45 DI 10.1038/mt.2011.187 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 875HV UT WOS:000299021900009 PM 21915104 ER PT J AU Parekkadan, B Fletcher, AL Li, M Tjota, MY Bellemare-Pelletier, A Milwid, JM Lee, JW Yarmush, ML Turley, SJ AF Parekkadan, Biju Fletcher, Anne L. Li, Matthew Tjota, Melissa Y. Bellemare-Pelletier, Angelique Milwid, Jack M. Lee, Je-Wook Yarmush, Martin L. Turley, Shannon J. TI Aire Controls Mesenchymal Stem Cell-mediated Suppression in Chronic Colitis SO MOLECULAR THERAPY LA English DT Article ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; COLLAGEN-INDUCED ARTHRITIS; PROLIFERATION IN-VITRO; NATURAL-KILLER-CELLS; VERSUS-HOST-DISEASE; BONE-MARROW; STROMAL CELLS; T-CELLS; MYOCARDIAL-INFARCTION; DENDRITIC CELLS AB Mesenchymal stem cells (MSCs) are emerging as a promising immunotherapeutic, based largely on their overt suppression of T lymphocytes under inflammatory and autoimmune conditions. While paracrine crosstalk between MSCs and T cells has been well-studied, an intrinsic transcriptional switch that programs MSCs for immunomodulation has remained undefined. Here we show that bone marrow-derived MSCs require the transcriptional regulator Aire to suppress T cell-mediated pathogenesis in a mouse model of chronic colitis. Surprisingly, Aire did not control MSC suppression of T cell proliferation in vitro. Instead, Aire reduced T cell mitochondrial reductase by negatively regulating a proinflammatory cytokine, early T cell activation factor (Eta)-1. Neutralization of Eta-1 enabled Aire(-/-) MSCs to ameliorate colitis, reducing the number of infiltrating effector T cells in the colon, and normalizing T cell reductase levels. We propose that Aire represents an early molecular switch imposing a suppressive MSC phenotype via regulation of Eta-1. Monitoring Aire expression in MSCs may thus be a critical parameter for clinical use. C1 [Parekkadan, Biju; Li, Matthew; Milwid, Jack M.; Yarmush, Martin L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med & Surg Serv,Dept Surg, Boston, MA USA. [Parekkadan, Biju; Li, Matthew; Milwid, Jack M.; Yarmush, Martin L.] Shriners Hosp Children, Boston, MA USA. [Fletcher, Anne L.; Tjota, Melissa Y.; Bellemare-Pelletier, Angelique; Lee, Je-Wook; Turley, Shannon J.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Fletcher, Anne L.; Tjota, Melissa Y.; Bellemare-Pelletier, Angelique; Lee, Je-Wook; Turley, Shannon J.] Harvard Univ, Sch Med, Dept Microbiol & Immunol, Boston, MA USA. RP Turley, SJ (reprint author), 44 Binney St, Boston, MA 02115 USA. EM biju_parekkadan@hms.harvard.edu; shannon_turley@dfci.harvard.edu OI Tjota, Melissa/0000-0002-5869-3175 FU National Institutes of Health [DK074500, AI045757, DK059766-06, DK087770]; NHMRC Australia [546259]; Broad Foundation [BMRP498382]; Shriners Hospitals for Children FX We thank the Dana Farber Microarray and Biostatistics Core Facility for hybridizing cDNA chips and performing computational analysis. We thank Myriam Armant for kindly providing amniotic fluid-derived MSCs. We thank Veronika Lukacs-Kornek for thoughtful opinions on the manuscript. This work was supported by the National Institutes of Health (DK074500, AI045757, DK059766-06, and DK087770), NHMRC Australia: (546259), the Broad Medical Research Program of The Broad Foundation (BMRP498382) and Shriners Hospitals for Children. NR 50 TC 8 Z9 9 U1 0 U2 3 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 JAN PY 2012 VL 20 IS 1 BP 178 EP 186 DI 10.1038/mt.2011.192 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 875HV UT WOS:000299021900024 PM 21952165 ER PT J AU Sips, M Sciaranghella, G Diefenbach, T Dugast, AS Berger, CT Liu, Q Kwon, D Ghebremichael, M Estes, JD Carrington, M Martin, JN Deeks, SG Hunt, PW Alter, G AF Sips, M. Sciaranghella, G. Diefenbach, T. Dugast, A-S Berger, C. T. Liu, Q. Kwon, D. Ghebremichael, M. Estes, J. D. Carrington, M. Martin, J. N. Deeks, S. G. Hunt, P. W. Alter, G. TI Altered distribution of mucosal NK cells during HIV infection SO MUCOSAL IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; INTRA-EPITHELIAL LYMPHOCYTES; CD4(+) T-CELLS; GASTROINTESTINAL-TRACT; INTRAEPITHELIAL LYMPHOCYTES; FUNCTIONAL-CHARACTERISTICS; LYMPHADENOPATHY SYNDROME; INTESTINAL EPITHELIUM; COLLAGEN DEPOSITION; CYTOLYTIC FUNCTION AB The human gut mucosa is a major site of human immunodeficiency virus (HIV) infection and infection-associated pathogenesis. Increasing evidence shows that natural killer (NK) cells have an important role in control of HIV infection, but the mechanism(s) by which they mediate antiviral activity in the gut is unclear. Here, we show that two distinct subsets of NK cells exist in the gut, one localized to intraepithelial spaces (intraepithelial lymphocytes, IELs) and the other to the lamina propria (LP). The frequency of both subsets of NK cells was reduced in chronic infection, whereas IEL NK cells remained stable in spontaneous controllers with protective killer immunoglobulin-like receptor/human leukocyte antigen genotypes. Both IEL and LP NK cells were significantly expanded in immunological non-responsive patients, who incompletely recovered CD4 + T cells on highly active antiretroviral therapy (HAART). These data suggest that both IEL and LP NK cells may expand in the gut in an effort to compensate for compromised CD4 + T-cell recovery, but that only IEL NK cells may be involved in providing durable control of HIV in the gut. C1 [Sips, M.; Sciaranghella, G.; Diefenbach, T.; Dugast, A-S; Berger, C. T.; Liu, Q.; Kwon, D.; Ghebremichael, M.; Carrington, M.; Alter, G.] Harvard Univ & Massachusetts Inst Technol, Ragon Inst Massachusetts Gen Hosp, Boston, MA USA. [Estes, J. D.] Frederick Inc, NCI, AIDS & Canc Virus Program, Frederick, MD USA. [Carrington, M.] SAIC Frederick Inc, NCI Frederick, Canc & Inflammat Program, Expt Immunol Lab, Frederick, MD USA. [Martin, J. N.; Deeks, S. G.; Hunt, P. W.] Univ Calif San Francisco, Dept Med, Posit Hlth Program, San Francisco, CA USA. RP Alter, G (reprint author), Harvard Univ & Massachusetts Inst Technol, Ragon Inst Massachusetts Gen Hosp, Boston, MA USA. EM galter@partners.org RI Dugast, AnneSophie/L-9541-2015 FU NCI NIH HHS [HHSN261200800001E]; NIAID NIH HHS [K08 AI084546, P30 AI027763, R01 AI080289] NR 51 TC 24 Z9 24 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1933-0219 J9 MUCOSAL IMMUNOL JI Mucosal Immunol. PD JAN PY 2012 VL 5 IS 1 BP 30 EP 40 DI 10.1038/mi.2011.40 PG 11 WC Immunology SC Immunology GA 866UP UT WOS:000298411100005 PM 21993602 ER PT J AU Andres, PL Skerry, LM Munsat, TL Thornell, BJ Szymonifka, J Schoenfeld, DA Cudkowicz, ME AF Andres, Patricia L. Skerry, Linda M. Munsat, Theodore L. Thornell, Brenda J. Szymonifka, Jackie Schoenfeld, David A. Cudkowicz, Merit E. TI Validation of a new strength measurement device for amyotrophic lateral sclerosis clinical trials SO MUSCLE & NERVE LA English DT Article DE ALS; neuromuscular; outcomes measures; reliability; strength testing ID VOLUNTARY ISOMETRIC CONTRACTION; NATURAL-HISTORY; ALSFRS-R; SURVIVAL AB Introduction: Strength measures with reduced variability and higher sensitivity could improve efficiency in clinical trials of amyotrophic lateral sclerosis (ALS). The Accurate Test of Limb Isometric Strength (ATLIS) was developed to precisely and conveniently measure force in 12 muscle groups. In this study we evaluate the reliability and validity of the ATLIS testing protocol. Methods: Twenty healthy adults and 10 patients with ALS were tested twice by the same or by different evaluators to determine test-retest and interrater reliability. Twenty healthy adults were examined using ATLIS and a wellvalidated strength testing protocol (TQNE) to assess criterionbased validity. Results: Mean absolute variation between tests was 8.6%, and intraclass correlation coefficients for each muscle group were high (range 0.82-0.99). The Pearson correlation coefficient of mean ATLIS and TQNE scores was 0.90. A subject survey demonstrated high user acceptance of ATLIS. Conclusions: ATLIS is convenient for patients and evaluators, produces precise strength measurements, and is easily moved between examining rooms. C1 [Andres, Patricia L.; Skerry, Linda M.; Thornell, Brenda J.; Cudkowicz, Merit E.] Massachusetts Gen Hosp, Neurol Clin Trials Unit, Charlestown, MA 02129 USA. [Munsat, Theodore L.] Tufts Med Ctr, Dept Neurol, Boston, MA USA. [Szymonifka, Jackie; Schoenfeld, David A.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Andres, PL (reprint author), Massachusetts Gen Hosp, Neurol Clin Trials Unit, 149 13th St,Room 2274, Charlestown, MA 02129 USA. EM pandres1@partners.org FU ALS Association; Muscular Dystrophy Association; ALS Therapy Alliance FX The authors gratefully acknowledge the support of the ALS Association, the Muscular Dystrophy Association, and the ALS Therapy Alliance. NR 36 TC 10 Z9 10 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0148-639X J9 MUSCLE NERVE JI Muscle Nerve PD JAN PY 2012 VL 45 IS 1 BP 81 EP 85 DI 10.1002/mus.22253 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 867TI UT WOS:000298477000016 PM 22190312 ER PT J AU Creton, S Aardema, MJ Carmichael, PL Harvey, JS Martin, FL Newbold, RF O'Donovan, MR Pant, K Poth, A Sakai, A Sasaki, K Scott, AD Schechtman, LM Shen, RR Tanaka, N Yasaei, H AF Creton, Stuart Aardema, Marilyn J. Carmichael, Paul L. Harvey, James S. Martin, Francis L. Newbold, Robert F. O'Donovan, Michael R. Pant, Kamala Poth, Albrecht Sakai, Ayako Sasaki, Kiyoshi Scott, Andrew D. Schechtman, Leonard M. Shen, Rhine R. Tanaka, Noriho Yasaei, Hemad TI Cell transformation assays for prediction of carcinogenic potential: state of the science and future research needs SO MUTAGENESIS LA English DT Article ID DISCRIMINATE RODENT CARCINOGENS; VITRO GENOTOXICITY TESTS; HAMSTER EMBRYO CELLS; MORPHOLOGICAL TRANSFORMATION; EXPERIMENTAL-MODELS; RELATIVE PREDICTIVITY; ALTERNATIVE MODELS; RESEARCH-PROGRAM; HUMAN CANCER; TUMOR-CELLS AB Cell transformation assays (CTAs) have long been proposed as in vitro methods for the identification of potential chemical carcinogens. Despite showing good correlation with rodent bioassay data, concerns over the subjective nature of using morphological criteria for identifying transformed cells and a lack of understanding of the mechanistic basis of the assays has limited their acceptance for regulatory purposes. However, recent drivers to find alternative carcinogenicity assessment methodologies, such as the Seventh Amendment to the EU Cosmetics Directive, have fuelled renewed interest in CTAs. Research is currently ongoing to improve the objectivity of the assays, reveal the underlying molecular changes leading to transformation and explore the use of novel cell types. The UK NC3Rs held an international workshop in November 2010 to review the current state of the art in this field and provide directions for future research. This paper outlines the key points highlighted at this meeting. C1 [Creton, Stuart] Natl Ctr Replacement Refinement & Reduct Anim Res, London NW1 2BE, England. [Aardema, Marilyn J.] Marilyn Aardema Consulting LLC, Fairfield, OH 45014 USA. [Carmichael, Paul L.; Scott, Andrew D.] Unilever Safety & Environm Assurance Ctr, Sharnbrook MK44 1LQ, Beds, England. [Harvey, James S.] GlaxoSmithKline Plc, Genet Toxicol, Ware SG12 0DP, Herts, England. [Martin, Francis L.] Univ Lancaster, Ctr Biophoton, Lancaster Environm Ctr, Lancaster LA1 4YQ, England. [Newbold, Robert F.; Yasaei, Hemad] Brunel Univ, Brunel Inst Canc Genet & Pharmacogen, Uxbridge UB8 3PH, Middx, England. [O'Donovan, Michael R.] AstraZeneca R&D, Macclesfield SK10 4TG, Cheshire, England. [Pant, Kamala] Bioreliance Corp, Rockville, MD 20850 USA. [Poth, Albrecht] Harlan Cytotest Cell Res GmbH, D-64380 Rossdorf, Germany. [Sakai, Ayako; Sasaki, Kiyoshi; Tanaka, Noriho] Food & Drug Safety Ctr, Hatano Res Inst, Div Alternat Res, Kanagawa 2578523, Japan. [Schechtman, Leonard M.] Innovat Toxicol Consulting LLC, Lake Worth, FL 33467 USA. [Shen, Rhine R.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Creton, S (reprint author), Natl Ctr Replacement Refinement & Reduct Anim Res, Gibbs Bldg,215 Euston Rd, London NW1 2BE, England. EM stuart.creton@nc3rs.org.uk RI Yasaei, Hemad/A-6351-2014; OI L Martin, Francis/0000-0001-8562-4944 FU UK NC3Rs; UK Environmental Mutagen Society FX The CTA workshop was funded by the UK NC3Rs with additional sponsorship for the meeting provided by the UK Environmental Mutagen Society.; The authors are grateful to the UK Environmental Mutagen Society for financial sponsorship of the workshop. NR 61 TC 29 Z9 30 U1 0 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0267-8357 EI 1464-3804 J9 MUTAGENESIS JI Mutagenesis PD JAN PY 2012 VL 27 IS 1 BP 93 EP 101 DI 10.1093/mutage/ger053 PG 9 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 866MP UT WOS:000298385400010 PM 21852270 ER PT J AU Ghosh, K Kanapathipillai, M Korin, N McCarthy, JR Ingber, DE AF Ghosh, Kaustabh Kanapathipillai, Mathumai Korin, Netanel McCarthy, Jason R. Ingber, Donald E. TI Polymeric Nanomaterials for Islet Targeting and Immunotherapeutic Delivery SO NANO LETTERS LA English DT Article DE Diabetes; pancreatic islet; nanoparticle; drug delivery; vascular endothelium; inflammation; tissue targeting ID DIABETES PREVENTION TRIAL-TYPE-1; RECENT-ONSET; DRUG-DELIVERY; TYPE-1; THERAPY; CELLS; IMMUNOSUPPRESSION; NANOTECHNOLOGY; NANOPARTICLES; INFLAMMATION AB Here we report a proof-of-concept for development of pancreatic islet-targeting nanoparticles for immunomodulatory therapy of autoimmune type 1 diabetes. Modified with a unique islet-homing peptide, these polymeric nanomaterials exhibit 3-fold greater binding to islet endothelial cells and a 200-fold greater anti-inflammatory effect through targeted islet endothelial cell delivery of an immunosuppressant drug. Our findings also underscore the need to carefully tailor drug loading and nanoparticle dosage to achieve maximal vascular targeting and immunosuppression. C1 [Ghosh, Kaustabh; Ingber, Donald E.] Childrens Hosp, Dept Pathol, Vasc Biol Program, Boston, MA 02115 USA. [Ghosh, Kaustabh; Ingber, Donald E.] Childrens Hosp, Dept Surg, Vasc Biol Program, Boston, MA 02115 USA. [Ghosh, Kaustabh; McCarthy, Jason R.; Ingber, Donald E.] Harvard Univ, Sch Med, Boston, MA USA. [Ghosh, Kaustabh; Kanapathipillai, Mathumai; Korin, Netanel; Ingber, Donald E.] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA. [McCarthy, Jason R.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Ingber, Donald E.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. RP Ingber, DE (reprint author), Childrens Hosp, Dept Pathol, Vasc Biol Program, Boston, MA 02115 USA. EM don.ingber@wyss.harvard.edu FU NIH [1RL9EB008539-01, RL1 DE019023-01]; Wyss Institute for Biologically Inspired Engineering at Harvard University FX This work was supported by NIH U54 sysCODE Postdoctoral Training grant (1RL9EB008539-01 to KG.), NIH U54 sysCODE grant (RL1 DE019023-01 to D.E.I), and the Wyss Institute for Biologically Inspired Engineering at Harvard University. NR 27 TC 14 Z9 14 U1 2 U2 23 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1530-6984 J9 NANO LETT JI Nano Lett. PD JAN PY 2012 VL 12 IS 1 BP 203 EP 208 DI 10.1021/nl203334c PG 6 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA 874GJ UT WOS:000298943100036 PM 22196766 ER PT J AU Trowbridge, JJ Orkin, SH AF Trowbridge, Jennifer J. Orkin, Stuart H. TI Dnmt3a silences hematopoietic stem cell self-renewal SO NATURE GENETICS LA English DT Editorial Material ID NOVO DNA METHYLTRANSFERASE; METHYLATION; MUTATIONS C1 [Trowbridge, Jennifer J.] Childrens Hosp Boston, Dept Pediat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp Boston, Div Hematol Oncol, Boston, MA USA. RP Trowbridge, JJ (reprint author), Childrens Hosp Boston, Dept Pediat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. EM trowbridge@bloodgroup.tch.harvard.edu; stuart_orkin@dfci.harvard.edu NR 12 TC 12 Z9 12 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JAN PY 2012 VL 44 IS 1 BP 13 EP 14 DI 10.1038/ng.1043 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 870JA UT WOS:000298664000006 PM 22200773 ER PT J AU Zhang, JW Jackson, AF Naito, T Dose, M Seavitt, J Liu, FF Heller, EJ Kashiwagi, M Yoshida, T Gounari, F Petrie, HT Georgopoulos, K AF Zhang, Jiangwen Jackson, Audrey F. Naito, Taku Dose, Marei Seavitt, John Liu, Feifei Heller, Elizabeth J. Kashiwagi, Mariko Yoshida, Toshimi Gounari, Fotini Petrie, Howard T. Georgopoulos, Katia TI Harnessing of the nucleosome-remodeling-deacetylase complex controls lymphocyte development and prevents leukemogenesis SO NATURE IMMUNOLOGY LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; DNA-BINDING PROTEINS; GENE-EXPRESSION; POLYCOMB GROUP; CELL-FATE; CHROMATIN; IKAROS; TRANSCRIPTION; NETWORK; COHESIN AB Cell fate depends on the interplay between chromatin regulators and transcription factors. Here we show that activity of the Mi-2 beta nucleosome-remodeling and histone-deacetylase (NuRD) complex was controlled by the Ikaros family of lymphoid lineage-determining proteins. Ikaros, an integral component of the NuRD complex in lymphocytes, tethered this complex to active genes encoding molecules involved in lymphoid differentiation. Loss of Ikaros DNA-binding activity caused a local increase in chromatin remodeling and histone deacetylation and suppression of lymphoid cell-specific gene expression. Without Ikaros, the NuRD complex also redistributed to transcriptionally poised genes that were not targets of Ikaros (encoding molecules involved in proliferation and metabolism), which induced their reactivation. Thus, release of NuRD from Ikaros regulation blocks lymphocyte maturation and mediates progression to a leukemic state by engaging functionally opposing epigenetic and genetic networks. C1 [Jackson, Audrey F.; Naito, Taku; Seavitt, John; Liu, Feifei; Heller, Elizabeth J.; Kashiwagi, Mariko; Yoshida, Toshimi; Georgopoulos, Katia] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cuteneous Biol Res Ctr, Charlestown, MA USA. [Zhang, Jiangwen] Harvard Univ, Fac Arts & Sci Res Comp, Cambridge, MA 02138 USA. [Petrie, Howard T.] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Petrie, Howard T.] Scripps Res Inst, Dept Canc Biol, Jupiter, FL USA. RP Georgopoulos, K (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cuteneous Biol Res Ctr, Charlestown, MA USA. EM katia.georgopoulos@cbrc2.mgh.harvard.edu RI Zhang, Jiangwen/A-7654-2013; OI Dose, Marei/0000-0001-5394-9779 FU US National Institutes of Health [2T32AI007529, 5R01AI042254, R01CA158006] FX We thank P. Gomez for analysis of the expression of Mi-2 beta protein in thymocytes; the Kingston laboratory (Massachusetts General Hospital) for the hSWI-SNF complex and help with setting up the mononucleosome and 5S array assays; I. Joshi for help with cell sorting; B. Czyzewski for mouse husbandry; and B. Morgan for discussions of the project and critical review of the manuscript. Protein microsequencing was done at the Microchemistry and Proteomics Facility of Harvard University, Cambridge, and at the Taplin Mass Spectrometry Facility of Harvard Medical School, Boston, and high-throughput DNA sequencing and RNA profiling were done at the Bauer Center for Genomic Research of Harvard University, Cambridge. Supported by the US National Institutes of Health (2T32AI007529 to A.F.J.; and 5R01AI042254 and R01CA158006 to K.G.). NR 47 TC 83 Z9 83 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD JAN PY 2012 VL 13 IS 1 BP 86 EP U132 DI 10.1038/ni.2150 PG 10 WC Immunology SC Immunology GA 866VB UT WOS:000298412800015 PM 22080921 ER PT J AU Tschop, MH Speakman, JR Arch, JRS Auwerx, J Bruning, JC Chan, L Eckel, RH Farese, RV Galgani, JE Hambly, C Herman, MA Horvath, TL Kahn, BB Kozma, SC Maratos-Flier, E Muller, TD Munzberg, H Pfluger, PT Plum, L Reitman, ML Rahmouni, K Shulman, GI Thomas, G Kahn, CR Ravussin, E AF Tschoep, Matthias H. Speakman, John R. Arch, Jonathan R. S. Auwerx, Johan Bruening, Jens C. Chan, Lawrence Eckel, Robert H. Farese, Robert V., Jr. Galgani, Jose E. Hambly, Catherine Herman, Mark A. Horvath, Tamas L. Kahn, Barbara B. Kozma, Sara C. Maratos-Flier, Eleftheria Mueller, Timo D. Muenzberg, Heike Pfluger, Paul T. Plum, Leona Reitman, Marc L. Rahmouni, Kamal Shulman, Gerald I. Thomas, George Kahn, C. Ronald Ravussin, Eric TI A guide to analysis of mouse energy metabolism SO NATURE METHODS LA English DT Article ID CHRONIC SOCIAL STRESS; DIET-INDUCED OBESITY; FAT-FREE MASS; BODY-COMPOSITION; LABORATORY MICE; FOOD-INTAKE; EXPENDITURE; TISSUE; AGE; BEHAVIOR AB We present a consolidated view of the complexity and challenges of designing studies for measurement of energy metabolism in mouse models, including a practical guide to the assessment of energy expenditure, energy intake and body composition and statistical analysis thereof. We hope this guide will facilitate comparisons across studies and minimize spurious interpretations of data. We recommend that division of energy expenditure data by either body weight or lean body weight and that presentation of group effects as histograms should be replaced by plotting individual data and analyzing both group and body-composition effects using analysis of covariance (ANCOVA). The epidemic of obesity has generated a large C1 [Muenzberg, Heike; Ravussin, Eric] Pennington Biomed Res Ctr, Baton Rouge, LA USA. [Tschoep, Matthias H.; Mueller, Timo D.; Pfluger, Paul T.] Tech Univ Munich, Dept Med, Helmholz Ctr Munich, Inst Diabet & Obes, Munich, Germany. [Speakman, John R.; Hambly, Catherine] Univ Aberdeen, Inst Biol & Environm Sci, Aberdeen, Scotland. [Speakman, John R.] Chinese Acad Sci, Inst Genet & Dev Biol, Beijing, Peoples R China. [Arch, Jonathan R. S.] Univ Buckingham, Clore Lab, Buckingham, England. [Auwerx, Johan] Ecole Polytech Fed Lausanne, Lausanne, Switzerland. [Bruening, Jens C.] Max Planck Inst Neurol Res, D-50931 Cologne, Germany. [Chan, Lawrence] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Chan, Lawrence] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. [Eckel, Robert H.] Univ Colorado Denver Sch Med, Div Endocrinol Diabet & Metab, Dept Med, Aurora, CO USA. [Farese, Robert V., Jr.] Univ Calif San Francisco, Gladstone Inst Cardiovasc Dis, San Francisco, CA 94143 USA. [Galgani, Jose E.] Univ Chile, Fac Med, Dept Nutr, Santiago 7, Chile. [Herman, Mark A.; Kahn, Barbara B.; Maratos-Flier, Eleftheria] Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. [Horvath, Tamas L.] Yale Univ, Sch Med, Comparat Med Sect, Program Integrat Cell Signaling & Neurobiol Met, New Haven, CT 06510 USA. [Kozma, Sara C.; Thomas, George] Univ Cincinnati, Coll Med, Dept Canc & Cell Biol, Metab Dis Inst, Cincinnati, OH USA. [Plum, Leona] Columbia Univ, Naomi Berrie Diabet Ctr, New York, NY USA. [Plum, Leona] Columbia Univ, Dept Med, New York, NY USA. [Reitman, Marc L.] NIDDKD, Diabet Endocrinol & Obes Branch, US Natl Inst Hlth, Bethesda, MD 20892 USA. [Rahmouni, Kamal] Univ Iowa Carver Coll Med, Ctr Funct Genom Hypertens, Dept Internal Med, Iowa City, IA USA. [Shulman, Gerald I.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. [Kahn, C. Ronald] Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. RP Ravussin, E (reprint author), Pennington Biomed Res Ctr, Baton Rouge, LA USA. EM c.ronald.kahn@joslin.harvard.edu; e.ravussin@pbrc.edu RI Herman, Mark/H-3232-2012; Reitman, Marc/B-4448-2013; John, Speakman/A-9494-2008; Tschoep, Matthias/I-5443-2014; Thomas, George/K-9235-2014; OI Reitman, Marc/0000-0002-0426-9475; John, Speakman/0000-0002-2457-1823; Thomas, George/0000-0003-3518-8149; Tschoep, Matthias/0000-0002-4744-371X FU Biotechnology and Biological Sciences Research Council [BB/G009953/1]; NHLBI NIH HHS [R01 HL051586]; NIDDK NIH HHS [R01 DK056084, R01 DK040936, R01 DK082659, R37 DK031036, R37 DK043051, U24 DK059635] NR 56 TC 216 Z9 216 U1 3 U2 49 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 J9 NAT METHODS JI Nat. Methods PD JAN PY 2012 VL 9 IS 1 BP 57 EP 63 DI 10.1038/NMETH.1806 PG 7 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 870KB UT WOS:000298667000028 PM 22205519 ER PT J AU Barabasi, AL AF Barabasi, Albert-Laszlo TI The network takeover SO NATURE PHYSICS LA English DT Editorial Material ID COMPLEX NETWORKS AB Reductionism, as a paradigm, is expired, and complexity, as a field, is tired. Data-based mathematical models of complex systems are offering a fresh perspective, rapidly developing into a new discipline: network science. C1 [Barabasi, Albert-Laszlo] Northeastern Univ, Ctr Complex Network Res, Boston, MA 02115 USA. [Barabasi, Albert-Laszlo] Northeastern Univ, Dept Phys Comp Sci & Biol, Boston, MA 02115 USA. [Barabasi, Albert-Laszlo] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. [Barabasi, Albert-Laszlo] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. RP Barabasi, AL (reprint author), Northeastern Univ, Ctr Complex Network Res, Boston, MA 02115 USA. EM alb@neu.edu NR 11 TC 91 Z9 93 U1 8 U2 61 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1745-2473 J9 NAT PHYS JI Nat. Phys. PD JAN PY 2012 VL 8 IS 1 BP 14 EP 16 PG 3 WC Physics, Multidisciplinary SC Physics GA 866YV UT WOS:000298423000009 ER PT J AU Olson, EM Lin, NU Krop, IE Winer, EP AF Olson, Erin M. Lin, Nancy U. Krop, Ian E. Winer, Eric P. TI Use of discard pleural fluid in molecular research SO NATURE REVIEWS CLINICAL ONCOLOGY LA English DT Letter ID LUNG-CANCER; GEFITINIB C1 [Lin, Nancy U.; Krop, Ian E.; Winer, Eric P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. [Olson, Erin M.] Ohio State Univ, Coll Med, Richard J Solove Res Inst, Columbus, OH 43210 USA. [Olson, Erin M.] Ohio State Univ, Coll Med, Arthur G James Canc Hosp, Columbus, OH 43210 USA. RP Winer, EP (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM ewiner@partners.org NR 8 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4774 J9 NAT REV CLIN ONCOL JI Nat. Rev. Clin. Oncol. PD JAN PY 2012 VL 9 IS 1 DI 10.1038/nrclinonc.2011.114-c2 PG 1 WC Oncology SC Oncology GA 866TQ UT WOS:000298407300013 ER PT J AU Jensen, DM AF Jensen, Dennis M. TI ULCER Prediction and prevention of peptic ulcer rebleeding SO NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY LA English DT Editorial Material ID UPPER-GASTROINTESTINAL HEMORRHAGE C1 VA Greater Los Angeles Healthcare Syst, CURE DDRC, Los Angeles, CA 90073 USA. RP Jensen, DM (reprint author), VA Greater Los Angeles Healthcare Syst, CURE DDRC, Room 318,Bldg 115,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM djensen@mednet.ucla.edu NR 9 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5045 J9 NAT REV GASTRO HEPAT JI Nat. Rev. Gastroenterol. Hepatol. PD JAN PY 2012 VL 9 IS 1 BP 7 EP 8 DI 10.1038/nrgastro.2011.243 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 866FY UT WOS:000298367100001 PM 22143269 ER PT J AU Mercier, FE Ragu, C Scadden, DT AF Mercier, Francois E. Ragu, Christine Scadden, David T. TI The bone marrow at the crossroads of blood and immunity SO NATURE REVIEWS IMMUNOLOGY LA English DT Review ID HEMATOPOIETIC STEM-CELLS; HYPOXIA-INDUCIBLE FACTOR; SYMPATHETIC-NERVOUS-SYSTEM; RENEWAL IN-VIVO; ENDOTHELIAL-CELLS; PROGENITOR CELLS; SELF-RENEWAL; B-CELLS; STROMAL CELLS; MESENCHYMAL STEM AB Progenitor cells that are the basis for all blood cell production share the bone marrow with more mature elements of the adaptive immune system. Specialized niches within the bone marrow guide and, at times, constrain the development of haematopoietic stem and progenitor cells (HSPCs) and lineage-restricted immune progenitor cells. Specific niche components are organized into distinct domains to create a diversified landscape in which specialized cell differentiation or population expansion programmes proceed. Local cues that reflect the tissue and organismal state affect cellular interactions to alter the production of a range of cell types. Here, we review the organization of regulatory elements in the bone marrow and discuss how these elements provide a dynamic means for the host to modulate stem cell and adaptive immune cell responses to physiological challenges. C1 [Mercier, Francois E.; Ragu, Christine; Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Mercier, Francois E.; Ragu, Christine; Scadden, David T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Mercier, Francois E.; Ragu, Christine; Scadden, David T.] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Mercier, Francois E.; Ragu, Christine; Scadden, David T.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. RP Scadden, DT (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. EM dscadden@mgh.harvard.edu OI Ragu, Christine/0000-0002-1150-1105 FU Canadian Institutes of Health Research; Massachusetts General Hospital; Ellison Medical Foundation; National Heart, Lung and Blood Institute [U01HL10042, R01HL44851] FX The authors would like to thank D. B. Sykes, L. Silberstein and I. Droujinine for their comments on the manuscript. Thanks also go to J.-P. Levesque and S. Mendez-Ferrer for generously contributing to FIG. 3. F. E. M. is a recipient of a Clinician Scientist Training Award from the Canadian Institutes of Health Research. C. R. was funded by Massachusetts General Hospital institutional funds. This work was supported by the Ellison Medical Foundation and the National Heart, Lung and Blood Institute (grants U01HL10042 and R01HL44851). NR 125 TC 109 Z9 113 U1 1 U2 37 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 EI 1474-1741 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD JAN PY 2012 VL 12 IS 1 BP 49 EP 60 DI 10.1038/nri3132 PG 12 WC Immunology SC Immunology GA 866GM UT WOS:000298368500013 PM 22193770 ER PT J AU Dranoff, G AF Dranoff, Glenn TI Experimental mouse tumour models: what can be learnt about human cancer immunology? SO NATURE REVIEWS IMMUNOLOGY LA English DT Article ID REGULATORY T-CELLS; METHYLCHOLANTHRENE-INDUCED SARCOMAS; RESISTANT PROSTATE-CANCER; COMBINATION IMMUNOTHERAPY; ESTABLISHED TUMORS; ADOPTIVE IMMUNOTHERAPY; IMMUNE-RESPONSE; CTLA-4 BLOCKADE; ANIMAL-MODELS; SIPULEUCEL-T AB The recent demonstration that cancer immunotherapy extends patient survival has reinvigorated interest in elucidating the role of immunity in tumour pathogenesis. Experimental mouse tumour models have provided key mechanistic insights into host antitumour immune responses, and these have guided the development of novel treatment strategies. To accelerate the translation of these findings into clinical benefits, investigators need to gain a better understanding of the strengths and limitations of mouse model systems as tools for deciphering human antitumour immune responses. C1 [Dranoff, Glenn] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Dranoff, Glenn] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02215 USA. [Dranoff, Glenn] Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. [Dranoff, Glenn] Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Dranoff, G (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. EM glenn_dranoff@dfci.harvard.edu FU US National Cancer Institute; Leukemia and Lymphoma Society; Melanoma Research Alliance; Alliance for Cancer Gene Therapy; Research Foundation for the Treatment of Ovarian Cancer FX Glenn Dranoff is supported by grants from the US National Cancer Institute, the Leukemia and Lymphoma Society, the Melanoma Research Alliance, the Alliance for Cancer Gene Therapy and the Research Foundation for the Treatment of Ovarian Cancer. NR 61 TC 27 Z9 28 U1 3 U2 20 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD JAN PY 2012 VL 12 IS 1 BP 61 EP 66 DI 10.1038/nri3129 PG 6 WC Immunology SC Immunology GA 866GM UT WOS:000298368500014 ER PT J AU Barkhof, F Simon, JH Fazekas, F Rovaris, M Kappos, L de Stefano, N Polman, CH Petkau, J Radue, EW Sormani, MP Li, DK O'Connor, P Montalban, X Miller, DH Filippi, M AF Barkhof, Frederik Simon, Jack H. Fazekas, Franz Rovaris, Marco Kappos, Ludwig de Stefano, Nicola Polman, Chris H. Petkau, John Radue, Ernst W. Sormani, Maria P. Li, David K. O'Connor, Paul Montalban, Xavier Miller, David H. Filippi, Massimo TI MRI monitoring of immunomodulation in relapse-onset multiple sclerosis trials SO NATURE REVIEWS NEUROLOGY LA English DT Review ID PLACEBO-CONTROLLED TRIAL; GADOLINIUM-ENHANCED MRI; SURROGATE END-POINTS; CONTROLLED PHASE IIB; DOUBLE-BLIND; CLINICAL-TRIALS; SPINAL-CORD; ORAL FINGOLIMOD; INTRAMUSCULAR INTERFERON; CONTROLLED MULTICENTER AB Over the past 15 years, MRI lesion activity has become the accepted surrogate primary outcome measure in proof-of-concept placebo-controlled clinical trials of new immunomodulating therapies in relapse-onset multiple sclerosis (MS). In parallel, the number of patients that are available for the placebo arm of trials has declined, and more-aggressive drugs are being developed. A critical review is warranted to ensure efficient MRI-and patient-resource utilization. Recently, an international panel reviewed the methodology for efficient use of MRI-monitored trials in relapse-onset MS. In this article, we provide up-to-date recommendations for scan acquisition, image analysis, outcome-measure definition and standards of reporting. Factors to consider for optimizing trial design, such as outcome measure selection and the unique requirements of phase II and phase III trials, including active-comparator studies, are outlined. Finally, we address safety considerations in the use of MRI in MS trials, and the safety-related responsibilities of the various parties involved in conducting such trials. C1 [Barkhof, Frederik; Polman, Chris H.] Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands. [Simon, Jack H.] Portland VA Med Ctr, Portland, OR USA. [Fazekas, Franz] Med Univ Graz, Graz, Austria. [Rovaris, Marco] Sci Inst Fdn Don Gnocchi, Milan, Italy. [Kappos, Ludwig; Radue, Ernst W.] Univ Basel Hosp, Basel, Switzerland. [de Stefano, Nicola] Univ Siena, I-53100 Siena, Italy. [Petkau, John; Li, David K.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Sormani, Maria P.] Univ Genoa, I-16126 Genoa, Italy. [O'Connor, Paul] St Michaels Hosp, Toronto, ON M5B 1W8, Canada. [Montalban, Xavier] Hosp Valle De Hebron, Barcelona, Spain. [Miller, David H.] UCL, London WC1E 6BT, England. [Filippi, Massimo] Inst Sci, Milan, Italy. [Filippi, Massimo] Univ Hosp San Raffaele, Milan, Italy. RP Barkhof, F (reprint author), Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands. EM f.barkhof@vumc.nl FU MAGNIMS; US National Multiple Sclerosis Society; Multiple Sclerosis Society of Canada; Bayer-Schering Pharma FX This work is based on a workshop of the Magnetic Resonance Imaging Network in Multiple Sclerosis (MAGNIMS) working group, co-sponsored by MAGNIMS, the US National Multiple Sclerosis Society and the Multiple Sclerosis Society of Canada, and supported by an unrestricted educational grant by Bayer-Schering Pharma. We thank A. Thompson and J. Palace for their helpful input. NR 80 TC 22 Z9 22 U1 1 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4758 EI 1759-4766 J9 NAT REV NEUROL JI Nat. Rev. Neurol. PD JAN PY 2012 VL 8 IS 1 BP 13 EP 21 DI 10.1038/nrneurol.2011.190 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 866VT UT WOS:000298415000006 PM 22143362 ER PT J AU Spires-Jones, T Knafo, S AF Spires-Jones, Tara Knafo, Shira TI Spines, Plasticity, and Cognition in Alzheimer's Model Mice SO NEURAL PLASTICITY LA English DT Review ID AMYLOID PRECURSOR PROTEIN; TRANSGENIC MOUSE MODEL; LONG-TERM POTENTIATION; CONTEXTUAL FEAR EXTINCTION; TANGLE-BEARING NEURONS; A-BETA OLIGOMERS; SYNAPTIC PLASTICITY; IN-VIVO; DENDRITIC SPINES; MEMORY DEFICITS AB The pathological hallmarks of Alzheimer's disease (AD)-widespread synaptic and neuronal loss and the pathological accumulation of amyloid-beta peptide (A beta) in senile plaques, as well as hyperphosphorylated tau in neurofibrillary tangles-have been known for many decades, but the links between AD pathology and dementia and effective therapeutic strategies remain elusive. Transgenic mice have been developed based on rare familial forms of AD and frontotemporal dementia, allowing investigators to test in detail the structural, functional, and behavioral consequences of AD-associated pathology. Here, we review work on transgenic AD models that investigate the degeneration of dendritic spine structure, synaptic function, and cognition. Together, these data support a model of AD pathogenesis in which soluble A beta initiates synaptic dysfunction and loss, as well as pathological changes in tau, which contribute to both synaptic and neuronal loss. These changes in synapse structure and function as well as frank synapse and neuronal loss contribute to the neural system dysfunction which causes cognitive deficits. Understanding the underpinnings of dementia in AD will be essential to develop and evaluate therapeutic approaches for this widespread and devastating disease. C1 [Spires-Jones, Tara] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Knafo, Shira] Univ Autonoma Madrid, E-28049 Madrid, Spain. [Knafo, Shira] CSIC, Ctr Biol Mol Severo Ochoa, E-28049 Madrid, Spain. RP Spires-Jones, T (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, 114 16th St, Charlestown, MA 02129 USA. EM tspires@partners.org; sknafo@cbm.uam.es OI Knafo, Shira/0000-0002-4478-7584; Spires-Jones, Tara/0000-0003-2530-0598 NR 145 TC 35 Z9 35 U1 2 U2 12 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 0792-8483 J9 NEURAL PLAST JI Neural. Plast. PY 2012 AR 319836 DI 10.1155/2012/319836 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 871NP UT WOS:000298745200001 ER PT J AU Kremen, WS Panizzon, MS Neale, MC Fennema-Notestine, C Prom-Wormley, E Eyler, LT Stevens, A Franz, CE Lyons, MJ Grant, MD Jak, AJ Jernigan, TL Xian, H Fischl, B Thermenos, HW Seidman, LJ Tsuang, MT Dale, AM AF Kremen, William S. Panizzon, Matthew S. Neale, Michael C. Fennema-Notestine, Christine Prom-Wormley, Elizabeth Eyler, Lisa T. Stevens, Allison Franz, Carol E. Lyons, Michael J. Grant, Michael D. Jak, Amy J. Jernigan, Terry L. Xian, Hong Fischl, Bruce Thermenos, Heidi W. Seidman, Larry J. Tsuang, Ming T. Dale, Anders M. TI Heritability of brain ventricle volume: Converging evidence from inconsistent results SO NEUROBIOLOGY OF AGING LA English DT Article DE Aging; Alzheimer's Disease; Endophenotype; Genetics; Lateral ventricles; Mild cognitive impairment; Structural MRI; Twins ID DISEASE PROGRESSION; ALZHEIMERS-DISEASE; GENETIC INFLUENCES; TWIN; POWER; SAMPLE AB Twin studies generally show great consistency for the heritability of brain structures. Ironically, the lateral ventricles-perhaps the most reliably measured brain regions of interest-are the most inconsistent when it comes to estimating genetic influences on their volume. Heritability estimates in twin studies have ranged from zero to almost 0.80. Here we aggregate heritability estimates from extant twin studies, and we review and reinterpret some of the findings. Based on our revised estimates, we conclude that lateral ventricular volume is indeed heritable. The weighted average heritability of the revised estimates was 0.54. Although accumulated environmental insults might seem most logical as the predominant cause of age-related ventricular expansion, the data strongly suggest that genetic influences on lateral ventricular volume are increasing with age. Genetic influences accounted for 32-35% of the variance in lateral ventricular volume in childhood, but about 75% of the variance in late middle and older age. These conclusions have implications for the basic understanding of the genetic and environmental underpinnings of normative and pathological brain aging. (C) 2012 Elsevier Inc. All rights reserved. C1 [Kremen, William S.; Panizzon, Matthew S.; Fennema-Notestine, Christine; Eyler, Lisa T.; Franz, Carol E.; Jak, Amy J.; Jernigan, Terry L.; Tsuang, Ming T.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Kremen, William S.; Tsuang, Ming T.] Univ Calif San Diego, Ctr Behav Genom, La Jolla, CA 92093 USA. [Kremen, William S.; Eyler, Lisa T.; Jak, Amy J.; Tsuang, Ming T.] VA Hlth Care Syst, San Diego, CA 92093 USA. [Neale, Michael C.; Prom-Wormley, Elizabeth] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Sch Med, Richmond, VA 23219 USA. [Fennema-Notestine, Christine; Dale, Anders M.] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA. [Stevens, Allison; Fischl, Bruce; Thermenos, Heidi W.; Seidman, Larry J.] Massachusetts Gen Hosp, AA Martinos Ctr, Dept Radiol, Boston, MA 02129 USA. [Lyons, Michael J.; Grant, Michael D.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Xian, Hong] Washington Univ, VA Med Ctr, Sch Med, St Louis, MO 63108 USA. [Xian, Hong] Washington Univ, Dept Internal Med, Sch Med, St Louis, MO 63108 USA. [Thermenos, Heidi W.; Seidman, Larry J.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Dale, Anders M.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. RP Kremen, WS (reprint author), Univ Calif San Diego, Dept Psychiat, 9500 Gilman Dr,MC 0738, La Jolla, CA 92093 USA. EM wkremen@ucsd.edu OI Lyons, Michael/0000-0001-6516-9219; Prom-Wormley, Elizabeth/0000-0001-9230-9723; Fennema-Notestine, Christine/0000-0002-6527-6361 FU National Institute on Aging [AG022381, AG018384, AG018386, AG022982]; National Center for Research Resources [P41-RR14075, BIRN002]; National Institute for Biomedical Imaging and Bioengineering [R01EB006758]; National Institute for Neurological Disorders and Stroke [R01 NS052585-01]; Mental Illness and Neuroscience Discovery (MIND) Institute; National Alliance for Medical Image Computing (nemic); National Institutes of Health through the NIH Roadmap for Medical Research [U54 EB005149]; Autism and Dyslexia Project; Ellison Medical Foundation; US Department of Veterans Affairs FX This work was supported by National Institute on Aging (AG022381, AG018384, AG018386, AG022982); National Center for Research Resources (P41-RR14075; NCRR Birn Morphometric Project BIRN002); National Institute for Biomedical Imaging and Bioengineering (R01EB006758); National Institute for Neurological Disorders and Stroke (R01 NS052585-01); Mental Illness and Neuroscience Discovery (MIND) Institute, part of the National Alliance for Medical Image Computing (nemic), funded by the National Institutes of Health through the NIH Roadmap for Medical Research Grants U54 EB005149. Additional support was provided by the Autism and Dyslexia Project funded by the Ellison Medical Foundation. The US Department of Veterans Affairs has provided financial support for the development and maintenance of the Vietnam Era Twin (VET) Registry. Numerous organizations have provided invaluable assistance in the conduct of this study, including: Department of Defense; National Personnel Records Center, National Archives and Records Administration; Internal Revenue Service; National Opinion Research Center; National Research Council, National Academy of Sciences; the Institute for Survey Research, Temple University. Most importantly, the authors gratefully acknowledge the continued cooperation and participation of the members of the VET Registry and their families. Without their contribution this research would not have been possible. NR 32 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JAN PY 2012 VL 33 IS 1 BP 1 EP 8 DI 10.1016/j.neurobiolaging.2010.02.007 PG 8 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 860FR UT WOS:000297934700001 PM 20363053 ER PT J AU Voineskos, AN Rajji, TK Lobaugh, NJ Miranda, D Shenton, ME Kennedy, JL Pollock, BG Mulsant, BH AF Voineskos, Aristotle N. Rajji, Tarek K. Lobaugh, Nancy J. Miranda, Dielle Shenton, Martha E. Kennedy, James L. Pollock, Bruce G. Mulsant, Benoit H. TI Age-related decline in white matter tract integrity and cognitive performance: A DTI tractography and structural equation modeling study SO NEUROBIOLOGY OF AGING LA English DT Article DE Aging; Anisotropy; Cognition; Diffusion tensor imaging; White matter ID MAGNETIC-RESONANCE DIFFUSION; TENSOR IMAGING TRACTOGRAPHY; HUMAN BRAIN; CORPUS-CALLOSUM; FIBER TRACKING; IN-VIVO; NEUROPSYCHOLOGICAL STATUS; UNCINATE FASCICULUS; REPEATABLE BATTERY; EXECUTIVE FUNCTION AB Age-related decline in microstructural integrity of certain white matter tracts may explain cognitive decline associated with normal aging. Whole brain tractography and a clustering segmentation in 48 healthy individuals across the adult lifespan were used to examine: interhemispheric (corpus callosum), intrahemispheric association (cingulum, uncinate, arcuate, inferior longitudinal, inferior occipitofrontal), and projection (corticospinal) fibers. Principal components analysis reduced cognitive tests into 6 meaningful factors: (1) memory and executive function; (2) visuomotor dexterity; (3) motor speed; (4) attention and working memory; (5) set-shifting/ flexibility; and (6) visuospatial construction. Using theory-based structural equation modeling, relationships among age, white matter tract integrity, and cognitive performance were investigated. Parsimonious model fit demonstrated relationships where decline in white matter integrity may explain age-related decline in cognitive performance: inferior longitudinal fasciculus (ILF) with visuomotor dexterity; the inferior occipitofrontal fasciculus with visuospatial construction; and posterior fibers (i. e., splenium) of the corpus callosum with memory and executive function. Our findings suggest that decline in the microstructural integrity of white matter fibers can account for cognitive decline in normal aging. (C) 2012 Elsevier Inc. All rights reserved. C1 [Voineskos, Aristotle N.; Rajji, Tarek K.; Miranda, Dielle; Pollock, Bruce G.; Mulsant, Benoit H.] Univ Toronto, Geriatr Mental Hlth Program, Ctr Addict & Mental Hlth, Dept Psychiat, Toronto, ON M6J 1H4, Canada. [Voineskos, Aristotle N.; Kennedy, James L.] Univ Toronto, Dept Neurosci, Ctr Addict & Mental Hlth, Dept Psychiat, Toronto, ON M6J 1H4, Canada. [Lobaugh, Nancy J.] Univ Toronto, Sunnybrook Hlth Sci Ctr, Dept Med, Toronto, ON M6J 1H4, Canada. [Shenton, Martha E.] Harvard Univ, Brigham & Womens Hosp, Psychiat Neuroimaging Lab, Dept Psychiat,Med Sch, Boston, MA 02115 USA. [Shenton, Martha E.] Harvard Univ, VA Boston Healthcare Syst, Brockton Div, Sch Med, Brockton, MA 02401 USA. [Pollock, Bruce G.] Univ Toronto, Rotman Res Inst, Baycrest Hosp, Dept Psychiat, Toronto, ON M6J 1H4, Canada. RP Mulsant, BH (reprint author), Univ Toronto, Geriatr Mental Hlth Program, Ctr Addict & Mental Hlth, Dept Psychiat, Toronto, ON M6J 1H4, Canada. EM benoit_mulsant@camh.net RI Voineskos, Aristotle/J-5014-2013; OI Kennedy, Kristen/0000-0001-5373-9026 FU Canadian Institutes of Health Research; APA/APIRE AstraZeneca; National Institutes of Health (NIH) [MH074794, MH 50, 740, 1P50, MH08272]; NIG/HS Nih [GM072977-01]; VA merit; VA Schizophrenia Center; Sandra A. Rotman Research Institute; Centre for Addiction and Mental Health FX This work was supported by the Canadian Institutes of Health Research Clinician scientist Award (ANV); APA/APIRE AstraZeneca Young Minds in Psychiatry Award (ANV); Canadian Institutes of Health Research Fellowship (TKR); National Institutes of Health (NIH) [R01, grant no. MH074794] (MES), [R01, grant number MH 50,740] (MES), NIH [1P50, grant no. MH08272] (MES), NIG/HS Nih [U54 grant no. GM072977-01] (MES), VA merit (MES), VA Schizophrenia Center Grant (MES), the Sandra A. Rotman Research Institute (BGP), and the Centre for Addiction and Mental Health. NR 88 TC 94 Z9 96 U1 1 U2 27 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 EI 1558-1497 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JAN PY 2012 VL 33 IS 1 BP 21 EP 34 DI 10.1016/j.neurobiolaging.2010.02.009 PG 14 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 860FR UT WOS:000297934700003 PM 20363050 ER PT J AU Aasly, JO Shi, M Sossi, V Stewart, T Johansen, KK Wszolek, ZK Uitti, RJ Hasegawa, K Yokoyama, T Zabetian, CP Kim, HM Leverenz, JB Ginghina, C Armaly, J Edwards, KL Snapinn, KW Stoessl, AJ Zhang, J AF Aasly, J. O. Shi, M. Sossi, V. Stewart, T. Johansen, K. K. Wszolek, Z. K. Uitti, R. J. Hasegawa, K. Yokoyama, T. Zabetian, C. P. Kim, H. M. Leverenz, J. B. Ginghina, C. Armaly, J. Edwards, K. L. Snapinn, K. W. Stoessl, A. J. Zhang, J. TI Cerebrospinal fluid amyloid beta and tau in LRRK2 mutation carriers SO NEUROLOGY LA English DT Article ID PARKINSONS-DISEASE; ALPHA-SYNUCLEIN; COGNITIVE DECLINE; ALZHEIMERS; PET AB Objective: The goal of the current investigation was to examine a cohort of symptomatic and asymptomatic LRRK2 mutation carriers, in order to address whether the reported alterations in amyloid beta (A beta) and tau species in the CSF of patients with sporadic Parkinson disease (PD) are a part of PD pathogenesis, the aging process, or a comorbid disease in patients with PD, and to explore the possibility of A beta and tau as markers of early or presymptomatic PD. Methods: CSF A beta 42, total tau, and phosphorylated tau were measured with Luminex assays in 26 LRRK2 mutation carriers, who were either asymptomatic (n = 18) or had a phenotype resembling sporadic PD (n = 8). All patients also underwent PET scans with (18)F-6-fluoro-L-dopa (FD), (11)C-(+/-)-alpha-dihydrotetrabenazine (DTBZ), and (11)C-d-threo-methylphenidate (MP) to measure dopaminergic function in the striatum. The levels of CSF markers were then compared to each PET measurement. Results: Reduced CSF A beta 42 and tau levels correlated with lower striatal dopaminergic function as determined by all 3 PET tracers, with a significant association between A beta 42 and FD uptake. When cases were restricted to carriers of the G2019S mutation, the most common LRRK2 variant in our cohort, significant correlations were also observed for tau. Conclusions: The disposition of A beta and tau is likely important in both LRRK2-related and sporadic PD, even during early phases of the disease. A better understanding of their production, aggregation, and degradation, including changes in their CSF levels, may provide insights into the pathogenesis of PD and the potential utility of these proteins as biomarkers. Neurology (R) 2012;78:55-61 C1 [Shi, M.; Stewart, T.; Ginghina, C.; Armaly, J.; Zhang, J.] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. [Aasly, J. O.; Johansen, K. K.] Norwegian Univ Sci & Technol, Dept Neurosci, N-7034 Trondheim, Norway. [Aasly, J. O.; Johansen, K. K.] St Olavs Univ Hosp, Dept Neurol, Trondheim, Norway. [Zabetian, C. P.; Kim, H. M.; Leverenz, J. B.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA. [Leverenz, J. B.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Sossi, V.] Univ British Columbia, Dept Phys & Astron, Vancouver Hosp & Hlth Sci Ctr, Vancouver, BC V5Z 1M9, Canada. [Wszolek, Z. K.; Uitti, R. J.] Mayo Clin Florida, Dept Neurol, Jacksonville, FL USA. [Hasegawa, K.; Yokoyama, T.] Sagamihara Natl Hosp, Natl Hosp Org, Dept Neurol, Sagamihara, Kanagawa, Japan. [Zabetian, C. P.] Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. [Zabetian, C. P.; Kim, H. M.; Leverenz, J. B.] Vet Affairs Puget Sound Hlth Care Syst, Parkinsons Dis Res Educ & Clin Ctr, Seattle, WA USA. [Leverenz, J. B.] Vet Affairs Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. [Edwards, K. L.; Snapinn, K. W.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Stoessl, A. J.] Univ British Columbia, Pacific Parkinsons Res Ctr, Vancouver, BC V5Z 1M9, Canada. [Stoessl, A. J.] Vancouver Coastal Hlth, Vancouver, BC, Canada. RP Zhang, J (reprint author), Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. EM zhangj@uw.edu RI Shi, Min/G-6165-2012 OI Shi, Min/0000-0002-6901-2558 FU NIH [AG025327, AG033398, P30ES007033-6364, ES004696-5897, ES012703, ES016873, NS057567, NS060252, P50NS062684, NS065070, P50NS072187]; Department of Veterans Affairs [1I01BX000531]; Canadian Institutes of Health Research; Michael Smith Foundation for Health Research; Pacific Alzheimer Research Foundation; Canada Research Chairs program; Mayo Clinic Florida Research Committee; Research Committee of CNS Degenerative Diseases; Ministry of Health, Labour and Welfare of Japan; Lundbeck Inc.; Allergan, Inc.; NIH/NINDS; Pacific Alzheimer Research Foundation (Canada); CIHR; NIH; NIH (NINDS/NIA); US Department of Veterans Affairs; Parkinson's Disease Foundation; American Parkinson Disease Association; NIH/NIND; Michael J. Fox Foundation; Washington Chapter American Parkinson's Disease Association/Northwest Collaborative Care; Centers for Disease Control FX Supported by NIH (AG025327, AG033398, P30ES007033-6364, ES004696-5897, ES012703, ES016873, NS057567, NS060252 to J.Z., P50NS062684 to C.P.Z., J.B.L., and J.Z., NS065070 to C.P.Z., NS057567 and P50NS072187 to Z.K.W. and R.J.U.), Department of Veterans Affairs (to J.B.L. and H. M. K., and 1I01BX000531 to C.P.Z.), Canadian Institutes of Health Research (to A.J.S.), Michael Smith Foundation for Health Research (to A.J.S.), Pacific Alzheimer Research Foundation (to A.J.S.), Canada Research Chairs program (to A.J.S.), TRIUMF (to A.J.S.), Mayo Clinic Florida Research Committee CR program (to Z.K.W. and R.J.U.), the gift from Carl Edward Bolch, Jr. and Susan Bass Bolch (to Z.K.W. and R.J.U.), and Grants-in-Aid from the Research Committee of CNS Degenerative Diseases, the Ministry of Health, Labour and Welfare of Japan (to K.H. and T.Y.).; Dr. Aasly serves on the editorial boards of Parkinsonism and Related Disorders, Parkinson's Disease, and the Journal of the Norwegian Medical Association; and his institution receives annual royalties from Lundbeck Inc. from the licensing of the technology related to PARK8/LRRK2. Dr. Shi reports no disclosures. Dr. Sossi has received research support from Pacific Alzheimer Research Foundation. Dr. Stewart and Dr. Johansen report no disclosures. Dr. Wszolek serves as Co-Editor-in-Chief of Parkinsonism and Related Disorders, Regional Editor of the European Journal of Neurology, and on the editorial boards of Neurologia i Neurochirurgia Polska, Advances in Rehabilitation, the Medical Journal of the Rzeszow University, and Clinical and Experimental Medical Letters; holds and has contractual rights for receipt of future royalty payments from patents re: A novel polynucleotide involved in heritable Parkinson's disease; receives royalties from publishing Parkinsonism and Related Disorders (Elsevier, 2007, 2008, 2009) and the European Journal of Neurology (Wiley-Blackwell, 2007, 2008, 2009); and receives research support from Allergan, Inc., the NIH/NINDS, Mayo Clinic Florida Research Committee CR program, the Pacific Alzheimer Research Foundation (Canada), the CIHR, the Mayo Clinic Florida Research Committee CR program, and a gift from Carl Edward Bolch, Jr., and Susan Bass Bolch. Dr. Uitti serves as an Associate Editor of Neurology (R); has received research support from Advanced Neuromodulations Systems and from the NIH; and his institution receives annual royalties from Lundbeck Inc. from the licensing of the technology related to PARK8/LRRK2. Dr. Hasegawa and Dr. Yokoyama report no disclosures. Dr. Zabetian has received research support from NIH (NINDS/NIA), the US Department of Veterans Affairs, the Parkinson's Disease Foundation, and the American Parkinson Disease Association. Dr. Kim reports no disclosures. Dr. Leverenz has served as a consultant for Bayer Schering Pharma, Novartis, and Teva Pharmaceutical Industries Ltd.; has received speaker honoraria from Novartis; and receives research support from the NIH/NIND, the Michael J. Fox Foundation, the Washington Chapter American Parkinson's Disease Association/Northwest Collaborative Care, and the US Department of Veterans Affairs. Dr. Ginghina and J. Armaly report no disclosures. Dr. Edwards has received research support from the NIH and the Centers for Disease Control. K. W. Snapinn has received research support from the NIH, the US Department of Veterans Affairs, and the Centers for Disease Control. Dr. Stoessl serves on a scientific advisory board for Biovail Corporation/Medgenesis; has received funding for travel and speaker honoraria from Novartis, Teva Pharmaceutical Industries Ltd., Allergan, Inc., and Abbott; serves on the editorial boards of Annals of Neurology, Lancet Neurology, and Parkinsonism & Related Disorders; and receives research support from CIHR, the Michael Smith Foundation for Health Research, the Michael J. Fox Foundation, and the Pacific Alzheimer Research Foundation. Dr. Zhang serves on the editorial boards of Neurological Disease, Neurochemical Research, the Journal of Alzheimer's Disease, and Proteomics; and has received research support from the NIH. NR 20 TC 22 Z9 22 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JAN PY 2012 VL 78 IS 1 BP 55 EP 61 DI 10.1212/WNL.0b013e31823ed101 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 869YG UT WOS:000298635700011 PM 22170881 ER PT J AU Deason, RG Hussey, EP Ally, BA Budson, AE AF Deason, Rebecca G. Hussey, Erin P. Ally, Brandon A. Budson, Andrew E. TI Changes in Response Bias With Different Study-Test Delays: Evidence From Young Adults, Older Adults, and Patients With Alzheimer's Disease SO NEUROPSYCHOLOGY LA English DT Article DE recognition memory; Alzheimer's disease; response bias; familiarity; recollection ID MILD COGNITIVE IMPAIRMENT; RECOGNITION MEMORY; FALSE RECOGNITION; EPISODIC MEMORY; PARIETAL LOBE; FRONTAL-LOBE; ASSOCIATIVE RECOGNITION; CRITERION SHIFT; RECOLLECTION; LESIONS AB Objective: Along with impaired discrimination, patients with Alzheimer's disease ( AD) often show an abnormally liberal response bias ( greater tendency to respond "old"). Previously we matched discrimination by varying study-test list length and found that participants' usual bias is maintained, such that patients with AD were more liberal than healthy controls. However, this pattern could be a result of the way in which discrimination was matched. In this experiment, we examined whether matching discrimination with the use of a delay would lead to a liberal response bias in healthy younger and older adults as it might lead to the use of more similar memorial processing to the patients with AD. Method: Younger adults, older adults, and patients with AD were run in 2 study-test sessions, with study and recognition test separated by either a 1-min or 1-day delay. Results: With the 1-min delay, both younger adults and healthy older adults showed a conservative response bias, while patients with AD showed a liberal response bias. When discrimination was matched between patients with AD and controls by the use of a delay, response bias was also matched, with all participants showing a more liberal response bias. Conclusions: The current study suggests that how discrimination is matched between patients with AD and controls matters greatly. Potentially, this liberal bias is a result of healthy younger and older adults relying primarily on familiarity at the longer delay, thus using more similar memorial processes to patients with AD who are dependent on familiarity at any delay. C1 [Deason, Rebecca G.; Budson, Andrew E.] VA Boston Healthcare Syst, Ctr Translat Cognit Neurosci, Boston, MA 02130 USA. [Deason, Rebecca G.; Budson, Andrew E.] Boston Univ, Sch Med, Alzheimers Dis Ctr, Boston, MA 02215 USA. [Hussey, Erin P.; Ally, Brandon A.] Vanderbilt Univ, Dept Neurol, Nashville, TN USA. [Ally, Brandon A.] Vanderbilt Univ, Dept Psychiat & Psychol, Nashville, TN USA. RP Deason, RG (reprint author), VA Boston Healthcare Syst, Ctr Translat Cognit Neurosci, 150 S Huntington Ave,Mailstop 151-C, Boston, MA 02130 USA. EM rdeason@bu.edu OI Ally, Brandon/0000-0002-6034-7968 FU National Institute on Aging [R01 AG025815, K23 AG031925, P30 AG13846]; Department of Veterans Affairs, Veterans Health Administration FX This research was supported by National Institute on Aging, grants R01 AG025815 (AEB), K23 AG031925 (BAA), P30 AG13846 (AEB); and a Department of Veterans Affairs, Veterans Health Administration, VISN 1 Early Career Development Award to RGD. This material is also the result of work supported with resources and the use of facilities at the Bedford VA Hospital in Bedford, MA and the VA Boston Healthcare System, Boston, MA. NR 55 TC 6 Z9 6 U1 2 U2 9 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0894-4105 J9 NEUROPSYCHOLOGY JI Neuropsychology PD JAN PY 2012 VL 26 IS 1 BP 119 EP 126 DI 10.1037/a0026330 PG 8 WC Psychology, Clinical; Neurosciences; Psychology SC Psychology; Neurosciences & Neurology GA 867XI UT WOS:000298487700011 PM 22409339 ER PT J AU Almandoz, JED Jagadeesan, BD Moran, CJ Cross, DT Zipfel, GJ Lee, JM Romero, JM Derdeyn, CP AF Almandoz, Josser E. Delgado Jagadeesan, Bharathi D. Moran, Christopher J. Cross, DeWitte T., III Zipfel, Gregory J. Lee, Jin-Moo Romero, Javier M. Derdeyn, Colin P. TI Independent Validation of the Secondary Intracerebral Hemorrhage Score With Catheter Angiography and Findings of Emergent Hematoma Evacuation SO NEUROSURGERY LA English DT Article DE Aneurysm; Arteriovenous malformation; Catheter angiography; Dural venous sinus thrombosis; Intracerebral hemorrhage ID CENTRAL-NERVOUS-SYSTEM; SPOT SIGN SCORE; ARTERIOVENOUS-MALFORMATIONS; HIGHEST RISK; IDENTIFIES PATIENTS; BENIGN ANGIOPATHY; NATURAL-HISTORY; CT ANGIOGRAPHY; FOLLOW-UP; EXPANSION AB BACKGROUND: The secondary intracerebral hemorrhage (SICH) score, derived from a cohort of patients with intracerebral hemorrhage examined with computed tomographic (CT) angiography, predicts a patient's risk of harboring a vascular etiology. OBJECTIVE: To validate the SICH score in an independent patient population. METHODS: We retrospectively reviewed all adults with nontraumatic ICH who presented to our institution during a 5.4-year period and were evaluated with catheter angiography or underwent emergent hematoma evacuation, and applied the SICH score to this cohort. Receiver operating characteristic analysis was performed to determine the area under the curve (AUC) and maximum operating point (MOP). Patients with subarachnoid hemorrhage in the basal cisterns were excluded. RESULTS: The study included 341 patients, with a mean age of 57.2 years (range, 18-88). Of these, 179 patients were male (52.5%) and 162 were female (47.5%). Two hundred ninety-two patients were evaluated with catheter angiography (85.6%), and 49 underwent emergent hematoma evacuation (14.4%). The SICH score successfully predicted an increasing risk of underlying vascular etiologies in the independent patient cohort, which was similar to the cohort examined with CT angiography. The MOP was reached at a SICH score >2, with the highest incidence of vascular etiologies in patients with SICH scores of 3 (18.8%), 4 (39%), and 5 (79.2%). There was no significant difference in the AUC between the 2 cohorts (0.82-0.87). CONCLUSION: The SICH score successfully predicted the risk of a patient with ICH of harboring a vascular etiology in an independent patient population. This scoring system could be used to select patients with ICH for neurovascular evaluation to exclude an underlying vascular abnormality. C1 [Almandoz, Josser E. Delgado; Jagadeesan, Bharathi D.; Moran, Christopher J.; Cross, DeWitte T., III; Derdeyn, Colin P.] Washington Univ, Mallinckrodt Inst Radiol, Div Neuroradiol, St Louis, MO 63110 USA. [Almandoz, Josser E. Delgado; Romero, Javier M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Neuroradiol,Dept Radiol, Boston, MA USA. [Moran, Christopher J.; Cross, DeWitte T., III; Zipfel, Gregory J.; Derdeyn, Colin P.] Washington Univ, Dept Neurol Surg, St Louis, MO 63110 USA. [Zipfel, Gregory J.; Lee, Jin-Moo; Derdeyn, Colin P.] Washington Univ, Dept Neurol, St Louis, MO 63110 USA. RP Almandoz, JED (reprint author), Washington Univ, Mallinckrodt Inst Radiol, Div Neuroradiol, Campus Box 8131,510 S Kingshighway Blvd, St Louis, MO 63110 USA. EM josser.delgado@gmail.com OI Derdeyn, Colin/0000-0002-5932-2683 FU National Institute of Neurological Disorders and Stroke [P5055977] FX National Institute of Neurological Disorders and Stroke grant # P5055977 was used, in part, for the preparation of this manuscript. The authors have no personal financial or institutional interest in any of the drugs, materials, or devices described in this article. NR 17 TC 7 Z9 7 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD JAN PY 2012 VL 70 IS 1 BP 131 EP 140 DI 10.1227/NEU.0b013e31822fbf43 PG 10 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 863EP UT WOS:000298145900032 ER PT J AU Ropper, AE Cahill, KS Hanna, JW McCarthy, EF Gokaslan, ZL Chi, JH AF Ropper, Alexander E. Cahill, Kevin S. Hanna, John W. McCarthy, Edward F. Gokaslan, Ziya L. Chi, John H. TI Primary Vertebral Tumors: A Review of Epidemiologic, Histological and Imaging Findings, Part II: Locally Aggressive and Malignant Tumors SO NEUROSURGERY LA English DT Review DE Bone tumors; Chondrosarcoma; Chordoma; Multiple myeloma; Osteosarcoma; Primary vertebral tumor; Spinal malignancies ID GIANT-CELL TUMOR; EWINGS-SARCOMA; MULTIPLE-MYELOMA; MOBILE SPINE; SOLITARY PLASMACYTOMA; SACRAL CHORDOMA; BONE-TUMORS; SKULL BASE; OSTEOSARCOMA; EXPERIENCE AB This second part of a comprehensive review of primary vertebral tumors focuses on locally aggressive and malignant tumors. As discussed in the earlier part of the review, both benign and malignant types of these tumors affect the adult and the pediatric population, and an understanding of their subtleties may increase their effective resection. In this review, we discuss the epidemiologic, histological, and imaging features of the most common locally aggressive primary vertebral tumors (chordoma and giant-cell tumor) and malignant tumors (chondrosarcoma, Ewing sarcoma, multiple myeloma or plasmacytoma, and osteosarcoma). The figures used for illustration are from operative patients of the senior authors (Z.L.G. and J.H.C.). Taken together, parts 1 and 2 of this article provide a thorough and illustrative review of primary vertebral tumors. C1 [Ropper, Alexander E.; Cahill, Kevin S.; Chi, John H.] Harvard Univ, Dana Farber Canc Inst, Sch Med, Brigham & Womens Hosp,Dept Neurosurg, Boston, MA 02115 USA. [Hanna, John W.] Harvard Univ, Dana Farber Canc Inst, Sch Med, Brigham & Womens Hosp,Dept Pathol, Boston, MA 02115 USA. [McCarthy, Edward F.] Johns Hopkins Univ, Sch Med, Dept Pathol, Johns Hopkins Hosp, Baltimore, MD 21205 USA. [Gokaslan, Ziya L.] Johns Hopkins Univ, Sch Med, Dept Neurosurg, Johns Hopkins Hosp, Baltimore, MD 21205 USA. RP Chi, JH (reprint author), Harvard Univ, Dana Farber Canc Inst, Sch Med, Brigham & Womens Hosp,Dept Neurosurg, 15 Francis St, Boston, MA 02115 USA. EM jchi@partners.org NR 55 TC 13 Z9 13 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD JAN PY 2012 VL 70 IS 1 BP 211 EP 219 DI 10.1227/NEU.0b013e31822d5f17 PG 9 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 863EP UT WOS:000298145900051 PM 21768918 ER PT J AU Vogelbaum, MA Jost, S Aghi, MK Heimberger, AB Sampson, JH Wen, PY Macdonald, DR Van den Bent, MJ Chang, SM AF Vogelbaum, Michael A. Jost, Sarah Aghi, Manish K. Heimberger, Amy B. Sampson, John H. Wen, Patrick Y. Macdonald, David R. Van den Bent, Martin J. Chang, Susan M. TI Application of Novel Response/Progression Measures for Surgically Delivered Therapies for Gliomas: Response Assessment in Neuro-Oncology (RANO) Working Group SO NEUROSURGERY LA English DT Article DE Brain surgery; Clinical trials; End points; Macdonald criteria; Response evaluation ID HIGH-GRADE GLIOMAS; RECURRENT MALIGNANT GLIOMA; MAGNETIC-RESONANCE-SPECTROSCOPY; PROGRESSION-FREE SURVIVAL; TUMOR VOLUME DELINEATION; ADULT BRAIN-TUMORS; GLIOBLASTOMA-MULTIFORME; RADIATION NECROSIS; CONTRAST ENHANCEMENT; PROGNOSTIC-FACTORS AB BACKGROUND: The Response Assessment in Neuro-Oncology (RANO) Working Group is an international, multidisciplinary effort to develop new standardized response criteria for clinical trials in brain tumors. The RANO group identified knowledge gaps relating to the definitions of tumor response and progression after the use of surgical or surgically based treatments. OBJECTIVE: To outline a proposal for new response and progression criteria for the assessment of the effects of surgery and surgically delivered therapies for patients with gliomas. METHODS: The Surgery Working Group of RANO identified surgically related end-point evaluation problems that were not addressed in the original Macdonald criteria, performed an extensive literature review, and used a consensus-building process to develop recommendations for how to address these issues in the setting of clinical trials. RESULTS: Recommendations were formulated for surgically related issues, including imaging changes associated with surgical resection or surgically mediated adjuvant local therapies, the determination of progression in the setting where all enhancing tumor has been removed, and how new enhancement should be interpreted in the setting where local therapies that are known to produce nonspecific enhancement have been used. Additionally, the terminology used to describe the completeness of surgical resections has been recognized to be inconsistently applied to enhancing vs nonenhancing tumors, and a new set of descriptors is proposed. CONCLUSION: The RANO process is intended to produce end-point criteria for clinical trials that take into account the effects of prior and ongoing therapies. The RANO criteria will continue to evolve as new therapies and technologies are introduced into clinical trial and/or practice. C1 [Vogelbaum, Michael A.] Cleveland Clin, Dept Neurosurg, Neurol Inst, Brain Tumor & Neurooncol Ctr, Cleveland, OH 44195 USA. [Jost, Sarah] Swedish Neurosci Inst, Dept Neurosurg, Ivy Ctr Adv Brain Tumor Treatment, Seattle, WA USA. [Aghi, Manish K.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA USA. [Heimberger, Amy B.] Univ Texas MD Anderson Canc Ctr, Dept Neurosurg, Houston, TX 77030 USA. [Sampson, John H.] Duke Univ, Med Ctr, Preston Robert Tisch Brain Tumor Ctr, Durham, NC USA. [Wen, Patrick Y.] Brigham & Womens Hosp, Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA 02115 USA. [Wen, Patrick Y.] Brigham & Womens Hosp, Div Neurol, Boston, MA 02115 USA. [Macdonald, David R.] Univ Western Ontario, Dept Oncol, London Reg Canc Program, London, ON, Canada. [Van den Bent, Martin J.] Erasmus Univ Hosp Rotterdam, Daniel den Hoed Canc Ctr, Neurooncol Unit, Rotterdam, Netherlands. [Chang, Susan M.] Univ Calif San Francisco, Dept Neurol Surg, Div Neurooncol, San Francisco, CA USA. RP Vogelbaum, MA (reprint author), Cleveland Clin, Dept Neurosurg, Neurol Inst, Brain Tumor & Neurooncol Ctr, 9500 Euclid Ave ND40, Cleveland, OH 44195 USA. EM vogelbm@ccf.org NR 78 TC 83 Z9 83 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD JAN PY 2012 VL 70 IS 1 BP 234 EP 243 DI 10.1227/NEU.0b013e318223f5a7 PG 10 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 863EP UT WOS:000298145900055 PM 21593697 ER PT J AU Ferreira, M Nahed, BV Babu, MA Walcott, BP Ellenbogen, RG Sekhar, LN AF Ferreira, Manuel Nahed, Brian V. Babu, Maya A. Walcott, Brian P. Ellenbogen, Richard G. Sekhar, Laligam N. TI Trapped Fourth Ventricle Phenomenon Following Aneurysm Rupture of the Posterior Circulation: Case Reports SO NEUROSURGERY LA English DT Article DE Aneurysm; Cerebrospinal fluid; Clipping; Fourth ventricle; Microsurgery; Shunt ID ISOLATED 4TH VENTRICLE; ENDOSCOPIC TREATMENT; STENT PLACEMENT; HYDROCEPHALUS; SHUNT; HEMORRHAGE; STENOSIS; CHILDREN AB BACKGROUND AND IMPORTANCE: Cerebral ventricular noncommunication has been described in the setting of infection and acutely in the setting of intracranial hemorrhage. We describe the first adult case series of individuals who developed delayed isolated fourth ventricles after rupture of intracranial posterior circulation aneurysms and define treatment modality. CLINICAL PRESENTATION: A retrospective review was performed of all patients with aneurysms treated at a single institution from 2005 to 2009. Both microsurgical obliteration and endovascular cases were queried. Of 1044 aneurysms treated in this period, 3 patients were identified who required fourth ventricular shunting, for the treatment of the isolated ventricle. All 3 patients underwent microsurgical clip obliteration of their aneurysms and had subsequent frontal approach ventriculoperitoneal cerebrospinal fluid diversion. These patients had no evidence of infection of the cerebrospinal fluid as measured by serial cultures. Subsequently, all 3 patients presented in a delayed fashion with symptoms attributable to a dilated fourth ventricle and syringomyelia or syringobulbia. Either exploration or percutaneous tapping confirmed the function of the supratentorial shunt. These patients then underwent fourth ventriculoperitoneal cerebrospinal fluid diversion by the use of a low-pressure shunt system. The symptoms attributable to the isolated fourth ventricle resolved rapidly in all 3 patients after shunting. This clinical improvement correlated with the fourth ventricular size. CONCLUSION: Isolated fourth ventricle, in an adult, is a rare phenomenon associated with intracranial posterior circulation aneurysm rupture treated with microsurgical clip obliteration. Fourth ventriculoperitoneal cerebrospinal fluid diversion is effective at resolving the symptoms attributed to the trapped ventricle and associated syrinx. C1 [Ferreira, Manuel] Univ Washington, Harborview Med Ctr, Dept Neurosurg, UW Med,Med Sch, Seattle, WA 98104 USA. [Nahed, Brian V.; Walcott, Brian P.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Nahed, Brian V.; Walcott, Brian P.] Harvard Univ, Sch Med, Boston, MA USA. [Babu, Maya A.] Mayo Clin, Coll Med, Dept Neurosurg, Rochester, MN USA. RP Ferreira, M (reprint author), Univ Washington, Harborview Med Ctr, Dept Neurosurg, UW Med,Med Sch, Box 359924,325 9Th Ave, Seattle, WA 98104 USA. EM manuelf3@u.washington.edu NR 28 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD JAN PY 2012 VL 70 IS 1 BP E253 EP E258 DI 10.1227/NEU.0b013e31822abf95 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 863EP UT WOS:000298145900059 PM 21795864 ER PT J AU Barr, JC Ogilvy, CS AF Barr, John C. Ogilvy, Christopher S. TI Selection of Treatment Modalities or Observation of Arteriovenous Malformations SO NEUROSURGERY CLINICS OF NORTH AMERICA LA English DT Article DE Arteriovenous malformations; Surgical excision; Endovascular embolization; Radiosurgery ID GAMMA-KNIFE RADIOSURGERY; SEIZURE CONTROL; INTRACRANIAL HEMORRHAGE; MULTIMODALITY TREATMENT; ARTERIAL ANEURYSMS; GRADING SYSTEM; BRAIN; SURGERY; EMBOLIZATION; RISK AB This article provides management guidelines for arteriovenous malformations (AVMs). Management options include observation, surgical excision, endovascular embolization, and radiosurgery. Each of these can be used individually or combined for multimodal therapy based on the characteristics of the lesion. The article stratifies each lesion based on the AVM and patient characteristics to either observation or a single or multimodal treatment arm. The treatment of an AVM must be carefully weighed in each patient because of the risk of neurologic injury in functional areas of the brain and weighed against the natural history of hemorrhage. C1 [Barr, John C.; Ogilvy, Christopher S.] Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. RP Ogilvy, CS (reprint author), Massachusetts Gen Hosp, Neurosurg Serv, WAC-745,55 Fruit St, Boston, MA 02114 USA. EM cogilvy@partners.org NR 61 TC 17 Z9 18 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 1042-3680 J9 NEUROSURG CLIN N AM JI Neurosurg. Clin. N. Am. PD JAN PY 2012 VL 23 IS 1 BP 63 EP + DI 10.1016/j.nec.2011.09.010 PG 14 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 865LI UT WOS:000298312000008 PM 22107859 ER PT J AU Nagel, JM Brinkoetter, M Magkos, F Liu, X Chamberland, JP Shah, S Zhou, JR Blackburn, G Mantzoros, CS AF Nagel, Jutta M. Brinkoetter, Mary Magkos, Faidon Liu, Xiaowen Chamberland, John P. Shah, Sunali Zhou, Jinrong Blackburn, George Mantzoros, Christos S. TI Dietary walnuts inhibit colorectal cancer growth in mice by suppressing angiogenesis SO NUTRITION LA English DT Article DE Nuts; Linseed; Colon cancer; Xenograft; VEGF ID ALPHA-LINOLENIC ACID; CARDIOVASCULAR RISK-FACTORS; COLON-TUMOR DEVELOPMENT; DOUBLE-BLIND; IN-VIVO; FLAXSEED; METASTASIS; CELLS; WOMEN; XENOGRAFTS AB Objective: Animal studies have demonstrated that dietary supplementation with flaxseed oil inhibits colorectal cancer growth. Recent data indicate that walnuts have strong antiproliferative properties against colon cancer cells in vitro but no previous study has assessed the effects of walnuts in vivo or performed a joint evaluation of flaxseed oil and walnuts. The aim of the present study was to examine the effect of dietary walnuts on colorectal cancer in vivo and to comparatively evaluate their efficacy in relation to flaxseed oil. Methods: HT-29 human colon cancer cells were injected in 6-wk-old female nude mice. After a 1-wk acclimation period, mice (n = 48) were randomized to diets containing similar to 19% of total energy from walnuts, flaxseed oil, or corn oil (control) and were subsequently studied for 25 d. Results: Tumor growth rate was significantly slower in walnut-fed and flaxseed-fed mice compared with corn oil-fed animals (P < 0.05) by 27% and 43%, respectively. Accordingly, final tumor weight was reduced by 33% and 44%, respectively (P < 0.05 versus control); the differences between walnut and flaxseed diets did not reach significance. We found no differences among groups in metabolic and hormonal profile, serum antioxidant capacity, or inflammation (P > 0.05). However, walnuts and flaxseed oil significantly reduced serum expression levels of angiogenesis factors, including vascular endothelial growth factor (by 30% and 80%, respectively), and approximately doubled total necrotic areas despite smaller tumor sizes (P < 0.05 versus control). Dietary walnuts significantly decreased angiogenesis (CD34 staining; P = 0.017 versus control), whereas this effect did not reach significance in the flaxseed oil group (P = 0.454 versus control). Conclusion: We conclude that walnuts in the diet inhibit colorectal cancer growth by suppressing angiogenesis. Further studies are needed to confirm our findings in humans and explore underlying mechanisms. Published by Elsevier Inc. C1 [Nagel, Jutta M.; Brinkoetter, Mary; Magkos, Faidon; Liu, Xiaowen; Chamberland, John P.; Shah, Sunali; Mantzoros, Christos S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Sch Med, Boston, MA 02215 USA. [Zhou, Jinrong; Blackburn, George] Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Surg, Sch Med, Boston, MA 02215 USA. [Mantzoros, Christos S.] Boston VA Healthcare Syst, Boston, MA USA. RP Mantzoros, CS (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Sch Med, Boston, MA 02215 USA. EM cmantzor@bidmc.harvard.edu OI Chamberland, John/0000-0002-7862-1371 FU National Institutes of Health [DK081913]; American Institute for Cancer Research; California Walnut Commission FX This work was supported by the National Institutes of Health (DK081913) and the American Institute for Cancer Research and the California Walnut Commission; sponsors had no input on interpretation or reporting of the findings. NR 43 TC 15 Z9 16 U1 1 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0899-9007 EI 1873-1244 J9 NUTRITION JI Nutrition PD JAN PY 2012 VL 28 IS 1 BP 67 EP 75 DI 10.1016/j.nut.2011.03.004 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 873RF UT WOS:000298900000012 PM 21795022 ER PT J AU Flanagan, J Winters, LN Habin, K Cashavelly, B AF Flanagan, Jane Winters, Loren N. Habin, Karleen Cashavelly, Barbara TI Women's Experiences With Antiestrogen Therapy to Treat Breast Cancer SO ONCOLOGY NURSING FORUM LA English DT Article ID QUALITY-OF-LIFE; POSTMENOPAUSAL WOMEN; AFRICAN-AMERICAN; TAMOXIFEN THERAPY; CONTROLLED-TRIAL; ADJUVANT BREAST; SURVIVORS; INTERVENTIONS; LETROZOLE; SYMPTOMS AB Purpose/Objectives: To understand the experiences of women undergoing antiestrogen therapy (AET) to treat breast cancer. Research Approach: Content analysis of tape-recorded focus group interviews. Setting: Breast oncology center of a large medical center in the northeastern United States. Participants: Purposive sample of 21 women undergoing AFT to treat breast cancer. Methodologic Approach: A nonexperimental qualitative, descriptive design using open-ended interviews and content analysis to isolate themes. Main Research Variables: Women's experiences with AET. Findings: Five themes were isolated and were focused on the overall experience of having breast cancer: symptoms related to AET, shared decision making, being strong for others, discovering new priorities, and recognizing vulnerability. Conclusions: Oral therapies are an increasingly popular treatment option for various types of cancer, particularly in women with estrogen-sensitive breast cancer. Although this type of treatment has been efficacious in terms of disease-free and overall survival, women undergoing AET face many challenges related to treatment. Healthcare providers need to understand women's perceptions of AFT and its effects as a first step in the process of developing interventions to improve care. Interpretation: More research is needed to distinguish whether the presence of preexisting chronic illness, differences in type of AET, age, and ethnicity impact the overall experience of women on AET. Individual interviews may be necessary to fully explore the experience. Oncology nurses should implement surveillance care to explore the effects of AET on women with breast cancer. C1 [Flanagan, Jane] Boston Coll, Connell Sch Nursing, Chestnut Hill, MA 02167 USA. [Winters, Loren N.; Habin, Karleen] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Flanagan, J (reprint author), Boston Coll, Connell Sch Nursing, Chestnut Hill, MA 02167 USA. EM flanagjg@bc.edu FU Boston College; Yvonne L. Munn Research Grant FX Jane Flanagan, PhD, ANP-BC, is an assistant professor of nursing in the Connell School of Nursing at Boston College in Massachusetts; and Loren N. Winters, MSN, ANP-BC, RCN, OCN (R), is a nurse practitioner and Karleen Habin, RN, is a research nurse, both in the Cancer Center, and Barbara Cashavelly, RN, MSN, AOCN (R), is the nurse director, all at Massachusetts General Hospital in Boston. This study was funded, in part, by a Boston College Research Expense Grant and an Yvonne L. Munn Research Grant. Flanagan can be reached at flanagjg@bc.edu, with copy to editor at ONFEditor@ons.org. (Submitted January 2011. Accepted for publication March 11, 2011.) NR 36 TC 3 Z9 3 U1 0 U2 7 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X EI 1538-0688 J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD JAN PY 2012 VL 39 IS 1 BP 70 EP 77 DI 10.1188/12.ONF.70-77 PG 8 WC Oncology; Nursing SC Oncology; Nursing GA 873RW UT WOS:000298901700009 PM 22201657 ER PT J AU Kang, JH Loomis, S Wiggs, JL Stein, JD Pasquale, LR AF Kang, Jae Hee Loomis, Stephanie Wiggs, Janey L. Stein, Joshua D. Pasquale, Louis R. TI Demographic and Geographic Features of Exfoliation Glaucoma in 2 United States-Based Prospective Cohorts SO OPHTHALMOLOGY LA English DT Article ID OPEN-ANGLE GLAUCOMA; RETINAL VEIN OCCLUSION; PSEUDOEXFOLIATION SYNDROME; NORTHERN SWEDEN; REYKJAVIK EYE; FOLLOW-UP; PREVALENCE; POPULATION; VARIANTS; EPIDEMIOLOGY AB Purpose: To examine prospectively the association between demographic and geographic factors in relation to exfoliation glaucoma (EG) or exfoliation glaucoma suspect (EGS). Design: Prospective cohort study. Participants: Seventy-eight thousand nine hundred fifty-five women in the Nurses' Health Study and 41 191 men in the Health Professionals Follow-up Study. Methods: Female and male health professionals were followed prospectively from 1980 through 2008 and from 1986 through 2008, respectively. Eligible participants were 40 years of age or older, did not have EG or EGS at baseline, and reported undergoing eye examinations during follow-up. Information regarding demographic features, lifetime geographic residence, and potential confounders was collected. During follow-up, 348 EG or EGS cases were confirmed with medical record review. The relative risk of EG or EGS in each cohort was estimated separately and the results were pooled with meta-analysis. Main Outcome Measures: Multivariate rate ratios (MVRRs) of EG or EGS and their 95% confidence intervals (CIs). Results: Exfoliation glaucoma or EGS was strongly age related with subjects 75 years of age or older at 46.22-fold (95% CI, 22.77-93.80) increased risk compared with those between 40 and 55 years of age. Although men were 68% less likely to develop EG or EGS than women (MVRR, 0.32; 95% CI, 0.23-0.46), no predisposition to EG or EGS by ancestry, particularly Scandinavian ancestry, emerged. Compared with a lifetime of living in the northern tier of the continental United States, lifetime residence in the middle geographic tier (MVRR, 0.53; 95% CI, 0.40-0.71) and in the southern geographic tier (MVRR, 0.25; 95% CI, 0.09-0.71) was associated with markedly reduced risks of EG or EGS. Conclusions: In this mainly white cohort from the United States, increasing age and female gender were significant risk factors for EG or EGS; however, Scandinavian heritage was not. Living in the middle or southern regions of the United States relative to living in the northern region was associated with a reduced risk of EG or EGS. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2012; 119: 27-35 (C) 2012 by the American Academy of Ophthalmology. C1 [Loomis, Stephanie; Wiggs, Janey L.; Pasquale, Louis R.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. [Kang, Jae Hee; Pasquale, Louis R.] Harvard Univ, Dept Med, Sch Med, Channing Lab, Boston, MA 02114 USA. [Kang, Jae Hee; Pasquale, Louis R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Stein, Joshua D.] Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48109 USA. RP Pasquale, LR (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM Louis_Pasquale@meei.harvard.edu FU Research to Prevent Blindness, Inc., New York, New York; National Institutes of Health, Bethesda, Maryland [CA87969, CA55075, EY09611, HL35464, EY019511, EY015473]; Arthur Ashley Williams Foundation, Holliston, Massachusetts; Harvard Glaucoma Center of Excellence, Boston, Massachusetts FX A Physician Scientist Award from Research to Prevent Blindness, Inc., New York, New York, supports Dr. Pasquale. The National Institutes of Health, Bethesda, Maryland (grant nos.: CA87969, CA55075, EY09611, HL35464, EY019511, EY015473 [LRP]); the Arthur Ashley Williams Foundation, Holliston, Massachusetts; and the Harvard Glaucoma Center of Excellence (JLW and LRP), Boston, Massachusetts. NR 50 TC 27 Z9 28 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD JAN PY 2012 VL 119 IS 1 BP 27 EP 35 DI 10.1016/j.ophtha.2011.06.018 PG 9 WC Ophthalmology SC Ophthalmology GA 869ZS UT WOS:000298639500006 PM 21982415 ER PT J AU Jea, SY Francis, BA Vakili, G Filippopoulos, T Rhee, DJ AF Jea, Seung Youn Francis, Brian A. Vakili, Ghazal Filippopoulos, Theodoros Rhee, Douglas J. TI Ab Interno Trabeculectomy Versus Trabeculectomy for Open-Angle Glaucoma SO OPHTHALMOLOGY LA English DT Article ID FLUOROURACIL FILTERING SURGERY; FOLLOW-UP; MITOMYCIN-C; COMPLICATIONS; 5-FLUOROURACIL; TRIAL; TUBE AB Purpose: To compare the effect of ab interno trabeculectomy with trabeculectomy. Design: Retrospective, cohort study. Participants: A total of 115 patients who underwent ab interno trabeculectomy (study group) compared with 102 patients who underwent trabeculectomy with intraoperative mitomycin as an initial surgical procedure (trabeculectomy group). Inclusion criteria were open-angle glaucoma, age >= 40 years, and uncontrolled on maximally tolerated medical therapy. Exclusion criterion was concurrent surgery. Methods: Clinical variables were collected from patient medical records. Main Outcome Measures: Intraocular pressure (IOP) and Cox proportional hazard ratio (HR) and Kaplan-Meier survival analyses with failure defined as IOP >21 mmHg or less than 20% reduction below baseline on 2 consecutive follow-up visits after 1 month; IOP <= 5 mmHg on 2 consecutive follow-up visits after 1 month; additional glaucoma surgery; or loss of light perception vision. Secondary outcome measures include number of glaucoma medications and occurrence of complications. Results: Mean follow-up was 27.3 and 25.5 months for the study and trabeculectomy groups, respectively. Intraocular pressure decreased from 28.1 +/- 8.6 mmHg at baseline to 15.9 +/- 4.5 mmHg (43.5% reduction) at month 24 in the study group, and from 26.3 +/- 10.9 mmHg at baseline to 10.2 +/- 4.1 mmHg (61.3% reduction) at month 24 in the trabeculectomy group. The success rates at 2 years were 22.4% and 76.1% in the study and trabeculectomy groups, respectively (P < 0.001). Younger age (P = 0.037; adjusted HR, 0.98 per year; 95% confidence interval [CI], 0.97-0.99) and lower baseline IOP (P = 0.016; adjusted HR, 0.96 per 1 mmHg; 95% CI, 0.92-0.99) were significant risk factors for failure in the multivariate analysis of the study group. With the exception of hyphema, the occurrence of postoperative complications was more frequent in the trabeculectomy group (P < 0.001). More additional glaucoma procedures were performed after ab interno trabeculectomy (43.5%) than after trabeculectomy (10.8%, P < 0.001). Conclusions: Ab interno trabeculectomy has a lower success rate than trabeculectomy. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2012; 119: 36-42 (C) 2012 by the American Academy of Ophthalmology. C1 [Jea, Seung Youn; Filippopoulos, Theodoros; Rhee, Douglas J.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. [Francis, Brian A.; Vakili, Ghazal] Univ So Calif, Keck Sch Med, Doheny Eye Inst, Los Angeles, CA 90033 USA. RP Rhee, DJ (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02114 USA. EM dougrhee@aol.com NR 20 TC 30 Z9 30 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD JAN PY 2012 VL 119 IS 1 BP 36 EP 42 DI 10.1016/j.ophtha.2011.06.046 PG 7 WC Ophthalmology SC Ophthalmology GA 869ZS UT WOS:000298639500007 PM 21982416 ER PT J AU Yoon, N Kwon, JW Seo, SW Ahn, G Choi, YL AF Yoon, Nara Kwon, Jong Won Seo, Sung Wook Ahn, Geunghwan Choi, Yoon-La TI Sclerosing epithelioid fibrosarcoma: Cytogenetic analysis of FUS rearrangement SO PATHOLOGY INTERNATIONAL LA English DT Article DE beta-catenin; FUS; sclerosing epithelioid fibrosarcoma ID GRADE FIBROMYXOID SARCOMA; DESMOID TUMORS; BETA-CATENIN; GENE AB Sclerosing epithelioid fibrosarcoma (SEF) is a rare but distinct variant of fibrosarcoma. A 43-year-old man presented with a lesion in his back that had been present for three years but had recently increased in size. Magnetic resonance imaging (MRI) revealed a 6-cm sized ovoid mass showing low intensities on T1 and T2 weighted images. Histologically, the tumor was of moderate cellularity, and the cells were relatively uniform in size and shape. The cells were epithelioid, round, oval and polygonal with clear and slightly eosinophilic cytoplasm, forming nests, cords, or sheet-like patterns with a dense collagenous and hyalinized matrix. The tumor was positive for vimentin, but negative for smooth muscle actin, desmin, HMB45, and CD34. Although the tumor showed nuclear overexpression of beta-catenin protein, the CTNNB1 exon3 mutation was not detected. Fluorescent in situ hybridization for FUS using dual color break-apart probes showed rearrangement of the FUS. In accordance with previous studies, our case showed positive findings of FUS rearrangement, reinforcing the notion of a close relationship between low grade fibromyxoid sarcoma and SEF. C1 [Choi, Yoon-La] Sungkyunkwan Univ, Dept Pathol, Samsung Med Ctr, Sch Med,Coll Med, Seoul 135710, South Korea. [Kwon, Jong Won] Sungkyunkwan Univ, Dept Radiol, Samsung Med Ctr, Coll Med, Seoul 135710, South Korea. [Seo, Sung Wook] Sungkyunkwan Univ, Dept Orthoped Surg, Samsung Med Ctr, Coll Med, Seoul 135710, South Korea. [Ahn, Geunghwan] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Dept Pathol, San Francisco, CA 94143 USA. RP Choi, YL (reprint author), Sungkyunkwan Univ, Dept Pathol, Samsung Med Ctr, Sch Med,Coll Med, 50 Ilwondong, Seoul 135710, South Korea. EM ylachoi@skku.edu NR 15 TC 6 Z9 6 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1320-5463 J9 PATHOL INT JI Pathol. Int. PD JAN PY 2012 VL 62 IS 1 BP 65 EP 68 DI 10.1111/j.1440-1827.2011.02752.x PG 4 WC Pathology SC Pathology GA 867US UT WOS:000298480900010 PM 22192807 ER PT J AU Rosen, LJ Ben Noach, M Winickoff, JP Hovell, MF AF Rosen, Laura J. Ben Noach, Michal Winickoff, Jonathan P. Hovell, Mel F. TI Parental Smoking Cessation to Protect Young Children: A Systematic Review and Meta-analysis SO PEDIATRICS LA English DT Review DE parenting; second hand smoke; smoking cessation; systematic reviews; tobacco use/smoking ID ENVIRONMENTAL TOBACCO-SMOKE; RANDOMIZED CONTROLLED-TRIAL; RELAPSE PREVENTION INTERVENTION; LOW-INCOME CHILDREN; PASSIVE SMOKING; ASTHMATIC-CHILDREN; MATERNAL SMOKING; RESPIRATORY ILLNESS; ETS EXPOSURE; LATINO CHILDREN AB BACKGROUND: Young children can be protected from much of the harm from tobacco smoke exposure if their parents quit smoking. Some researchers encourage parents to quit for their children's benefit, but the evidence for effectiveness of such approaches is mixed. OBJECTIVE: To perform a systematic review and meta-analysis to quantify the effects of interventions that encourage parental cessation. METHODS: We searched PubMed, the Cochrane Library, Web of Science, and PsycINFO. Controlled trials published before April 2011 that targeted smoking parents of infants or young children, encouraged parents to quit smoking for their children's benefit, and measured parental quit rates were included. Study quality was assessed. Relative risks and risk differences were calculated by using the DerSimonian and Laird random-effects model. RESULTS: Eighteen trials were included. Interventions took place in hospitals, pediatric clinical settings, well-baby clinics, and family homes. Quit rates averaged 23.1% in the intervention group and 18.4% in the control group. The interventions successfully increased the parental quit rate. Subgroups with significant intervention benefits were children aged 4 to 17 years, interventions whose primary goal was cessation, interventions that offered medications, and interventions with high follow-up rates (>80%). CONCLUSIONS: Interventions to achieve cessation among parents, for the sake of the children, provide a worthwhile addition to the arsenal of cessation approaches, and can help protect vulnerable children from harm due to tobacco smoke exposure. However, most parents do not quit, and additional strategies to protect children are needed. Pediatrics 2012; 129: 141-152 C1 [Rosen, Laura J.; Ben Noach, Michal] Tel Aviv Univ, Sch Publ Hlth, Sackler Fac Med, Dept Hlth Promot, IL-69978 Ramat Aviv, Israel. [Winickoff, Jonathan P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat, Boston, MA USA. [Hovell, Mel F.] San Diego State Univ, Sch Publ Hlth, Ctr Behav Epidemiol & Community Hlth, San Diego, CA 92182 USA. RP Rosen, LJ (reprint author), Tel Aviv Univ, Sch Publ Hlth, Fac Med, Dept Hlth Promot, POB 39040, IL-69978 Ramat Aviv, Israel. EM rosenl@post.tau.ac.il FU Flight Attendants' Medical Research Institute (FAMRI) [072086_YCSA] FX This work was funded by the Flight Attendants' Medical Research Institute (FAMRI) FAMRI Award 072086_YCSA. NR 89 TC 82 Z9 84 U1 5 U2 28 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JAN PY 2012 VL 129 IS 1 BP 141 EP 152 DI 10.1542/peds.2010-3209 PG 12 WC Pediatrics SC Pediatrics GA 870BT UT WOS:000298644800052 PM 22201152 ER PT J AU Bienvenu, OJ Samuels, JF Wuyek, LA Liang, KY Wang, Y Grados, MA Cullen, BA Riddle, MA Greenberg, BD Rasmussen, SA Fyer, AJ Pinto, A Rauch, SL Pauls, DL McCracken, JT Piacentini, J Murphy, DL Knowles, JA Nestadt, G AF Bienvenu, O. J. Samuels, J. F. Wuyek, L. A. Liang, K-Y. Wang, Y. Grados, M. A. Cullen, B. A. Riddle, M. A. Greenberg, B. D. Rasmussen, S. A. Fyer, A. J. Pinto, A. Rauch, S. L. Pauls, D. L. McCracken, J. T. Piacentini, J. Murphy, D. L. Knowles, J. A. Nestadt, G. TI Is obsessive-compulsive disorder an anxiety disorder, and what, if any, are spectrum conditions? A family study perspective SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Anxiety disorders; genetic epidemiology; obsessive-compulsive disorder; obsessive-compulsive personality disorder; obsessive-compulsive spectrum ID HOPKINS OCD FAMILY; DSM-V; PERSONALITY-DISORDERS; MAJOR DEPRESSION; PANIC DISORDER; COMORBIDITY; RELATIVES; HYPOCHONDRIASIS; PROBANDS; LA AB Background. Experts have proposed removing obsessive-compulsive disorder (OCD) from the anxiety disorders section and grouping it with putatively related conditions in DSM-5. The current study uses co-morbidity and familiality data to inform these issues. Method. Case family data from the OCD Collaborative Genetics Study (382 OCD-affected probands and 974 of their first-degree relatives) were compared with control family data from the Johns Hopkins OCD Family Study (73 non-OCD-affected probands and 233 of their first-degree relatives). Results. Anxiety disorders (especially agoraphobia and generalized anxiety disorder), cluster C personality disorders (especially obsessive-compulsive and avoidant), tic disorders, somatoform disorders (hypochondriasis and body dysmorphic disorder), grooming disorders (especially trichotillomania and pathological skin picking) and mood disorders (especially unipolar depressive disorders) were more common in case than control probands; however, the prevalences of eating disorders (anorexia and bulimia nervosa), other impulse-control disorders (pathological gambling, pyromania, kleptomania) and substance dependence (alcohol or drug) did not differ between the groups. The same general pattern was evident in relatives of case versus control probands. Results in relatives did not differ markedly when adjusted for demographic variables and proband diagnosis of the same disorder, though the strength of associations was lower when adjusted for OCD in relatives. Nevertheless, several anxiety, depressive and putative OCD-related conditions remained significantly more common in case than control relatives when adjusting for all of these variables simultaneously. Conclusions. On the basis of co-morbidity and familiality, OCD appears related both to anxiety disorders and to some conditions currently classified in other sections of DSM-IV. C1 [Bienvenu, O. J.; Samuels, J. F.; Wuyek, L. A.; Wang, Y.; Grados, M. A.; Cullen, B. A.; Riddle, M. A.; Nestadt, G.] Johns Hopkins Univ, Dept Psychiat & Behav Sci, Sch Med, Baltimore, MD 21287 USA. [Liang, K-Y.] Johns Hopkins Univ, Dept Biostat, Bloomberg Sch Publ Hlth, Baltimore, MD 21287 USA. [Greenberg, B. D.; Rasmussen, S. A.] Brown Med Sch, Dept Psychiat & Human Behav, Providence, RI USA. [Fyer, A. J.; Pinto, A.] Columbia Univ, Coll Phys & Surg, New York, NY USA. [Fyer, A. J.; Pinto, A.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Rauch, S. L.; Pauls, D. L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rauch, S. L.; Pauls, D. L.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [McCracken, J. T.; Piacentini, J.] Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Murphy, D. L.] NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. [Knowles, J. A.] Univ So Calif, Keck Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90033 USA. RP Bienvenu, OJ (reprint author), Johns Hopkins Univ, Dept Psychiat & Behav Sci, Sch Med, Meyer 115,600 N Wolfe St, Baltimore, MD 21287 USA. EM jbienven@jhmi.edu RI Pinto, Anthony/D-2718-2017; OI Pinto, Anthony/0000-0002-6078-7242; Samuels, Jack/0000-0002-6715-7905 FU American Psychiatric Association; National Institutes of Health [MH50125, RR00052, NS42609, MH64543, MH80221, MH66284] FX This study was commissioned and funded by the American Psychiatric Association to support the work of the DSM-5 Anxiety, Obsessive-Compulsive Spectrum, Post-Traumatic, and Dissociative Disorders Work Group. National Institutes of Health grants MH50125, RR00052, NS42609, MH64543, MH80221 and MH66284 also supported this work. NR 43 TC 62 Z9 63 U1 6 U2 37 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD JAN PY 2012 VL 42 IS 1 BP 1 EP 13 DI 10.1017/S0033291711000742 PG 13 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 874MG UT WOS:000298961600001 PM 21733222 ER PT J AU Perlis, RH Iosifescu, DV Castro, VM Murphy, SN Gainer, VS Minnier, J Cai, T Goryachev, S Zeng, Q Gallagher, PJ Fava, M Weilburg, JB Churchill, SE Kohane, IS Smoller, JW AF Perlis, R. H. Iosifescu, D. V. Castro, V. M. Murphy, S. N. Gainer, V. S. Minnier, J. Cai, T. Goryachev, S. Zeng, Q. Gallagher, P. J. Fava, M. Weilburg, J. B. Churchill, S. E. Kohane, I. S. Smoller, J. W. TI Using electronic medical records to enable large-scale studies in psychiatry: treatment resistant depression as a model SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Antidepressant; classification; machine learning; natural language processing; remission; treatment resistant depression ID REPORT QIDS-SR; AUTOMATED IDENTIFICATION; PSYCHOMETRIC EVALUATION; QUICK INVENTORY; DISORDER; REMISSION; SYMPTOMATOLOGY; AUGMENTATION; TECHNOLOGY; VALIDATION AB Background. Electronic medical records (EMR) provide a unique opportunity for efficient, large-scale clinical investigation in psychiatry. However, such studies will require development of tools to define treatment outcome. Method. Natural language processing (NLP) was applied to classify notes from 127 504 patients with a billing diagnosis of major depressive disorder, drawn from out-patient psychiatry practices affiliated with multiple, large New England hospitals. Classifications were compared with results using billing data (ICD-9 codes) alone and to a clinical gold standard based on chart review by a panel of senior clinicians. These cross-sectional classifications were then used to define longitudinal treatment outcomes, which were compared with a clinician-rated gold standard. Results. Models incorporating NLP were superior to those relying on billing data alone for classifying current mood state (area under receiver operating characteristic curve of 0.85-0.88 v. 0.54-0.55). When these cross-sectional visits were integrated to define longitudinal outcomes and incorporate treatment data, 15% of the cohort remitted with a single antidepressant treatment, while 13% were identified as failing to remit despite at least two antidepressant trials. Non-remitting patients were more likely to be non-Caucasian (p < 0.001). Conclusions. The application of bioinformatics tools such as NLP should enable accurate and efficient determination of longitudinal outcomes, enabling existing EMR data to be applied to clinical research, including biomarker investigations. Continued development will be required to better address moderators of outcome such as adherence and co-morbidity. C1 [Perlis, R. H.; Iosifescu, D. V.; Fava, M.; Weilburg, J. B.] Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, Boston, MA 02114 USA. [Perlis, R. H.; Gallagher, P. J.; Smoller, J. W.] Massachusetts Gen Hosp, Dept Psychiat, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Iosifescu, D. V.] Mt Sinai Hosp, Dept Psychiat, Mood & Anxiety Disorders Program, New York, NY 10029 USA. [Castro, V. M.; Gainer, V. S.; Goryachev, S.] Partners HealthCare Syst, Partners Res Comp, Boston, MA USA. [Murphy, S. N.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Minnier, J.; Cai, T.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Zeng, Q.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Churchill, S. E.] Partners HealthCare Syst, Informat Syst, Boston, MA USA. [Kohane, I. S.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Perlis, RH (reprint author), Simches Res Bldg,185 Cambridge St,6th Floor, Boston, MA 02114 USA. EM rperlis@partners.org RI Kohane, Isaac Kohane/K-3716-2012; OI Kohane, Isaac Kohane/0000-0003-2192-5160; Minnier, Jessica/0000-0002-3527-2757 FU National Library of Medicine [U54LM008748]; National Institute of Mental Health [R01MH086026, R01MH085542]; Proteus Biomedical; Concordant Rater Systems; Genomind; RID Ventures; Aspect Medical Systems; Forest Laboratories; Janssen Pharmaceuticals; NARSAD; NIH; Abbott Laboratories; Alkermes, Inc.; AstraZeneca; Bio-Research; BrainCells Inc.; Bristol-Myers Squibb; Cephalon, Inc.; Clinical Trials Solutions, LLC; Covidien; Eli Lilly and Company; EnVivo Pharmaceuticals, Inc.; Forest Pharmaceuticals, Inc.; Ganeden Biotech, Inc.; GlaxoSmithKline; Johnson & Johnson Pharmaceutical Research Development; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; Novartis AG; Organon Pharmaceuticals; PamLab, LLC; Pfizer Inc.; Pharmavite(R) LLC; Roche; RTC Logic, LLC; Sanofi-Aventis US LLC; Shire; Solvay Pharmaceuticals, Inc.; Synthelabo; Wyeth-Ayerst Laboratories FX The project described was supported by Award # U54LM008748 from the National Library of Medicine (to ISK) and R01MH086026 and R01MH085542 from the National Institute of Mental Health (to R. H. P. and J.W.S., respectively). The content is solely the responsibility of the authors and does not necessarily represent the official view of the National Library of Medicine or the National Institutes of Health.; Roy Perlis has received consulting fees from Proteus Biomedical, Concordant Rater Systems, Genomind, and RID Ventures.; Dan Iosifescu has received grant support from Aspect Medical Systems, Forest Laboratories, Janssen Pharmaceuticals, NARSAD, and NIH. He has received speaker honoraria from Eli & Co., Pfizer, Inc., Forest Laboratories, and Reed Medical Education.; Research Support: Abbott Laboratories; Alkermes, Inc.; Aspect Medical Systems; AstraZeneca; Bio-Research; BrainCells Inc.; Bristol-Myers Squibb; Cephalon, Inc.; Clinical Trials Solutions, LLC; Covidien; Eli Lilly and Company; EnVivo Pharmaceuticals, Inc.; Forest Pharmaceuticals, Inc.; Ganeden Biotech, Inc.; GlaxoSmithKline; Johnson & Johnson Pharmaceutical Research & Development; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; Novartis AG; Organon Pharmaceuticals; PamLab, LLC.; Pfizer Inc.; Pharmavite (R) LLC; Roche; RTC Logic, LLC; Sanofi-Aventis US LLC; Shire; Solvay Pharmaceuticals, Inc.; Synthelabo; Wyeth-Ayerst Laboratories. NR 34 TC 46 Z9 47 U1 1 U2 15 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD JAN PY 2012 VL 42 IS 1 BP 41 EP 50 DI 10.1017/S0033291711000997 PG 10 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 874MG UT WOS:000298961600004 PM 21682950 ER PT J AU Jahshan, C Cadenhead, KS Rissling, AJ Kirihara, K Braff, DL Light, GA AF Jahshan, C. Cadenhead, K. S. Rissling, A. J. Kirihara, K. Braff, D. L. Light, G. A. TI Automatic sensory information processing abnormalities across the illness course of schizophrenia SO PSYCHOLOGICAL MEDICINE LA English DT Article DE MMN; prodromal; P300; RON; schizophrenia ID MISMATCH NEGATIVITY GENERATION; EVENT-RELATED POTENTIALS; NEUROCOGNITIVE DEFICITS; 1ST-EPISODE SCHIZOPHRENIA; 1ST EPISODE; PRODROMAL SCHIZOPHRENIA; INVOLUNTARY ATTENTION; AUDITORY DISTRACTION; SELECTIVE-ATTENTION; SPECTRUM DISORDERS AB Background. Deficits in automatic sensory discrimination, as indexed by a reduction in the mismatch negativity (MMN) and P3a event-related potential amplitudes, are well documented in chronic schizophrenia. However, MMN and P3a have not been sufficiently studied early in the course of psychotic illness. The present study aimed to investigate MMN, P3a and reorienting negativity (RON) across the course of schizophrenia. Method. MMN, P3a, and RON were assessed in 118 subjects across four groups: (1) individuals at risk for psychosis (n=26); (2) recent-onset patients (n=31); (3) chronic patients (n=33); and (4) normal controls (n=28) using a duration-deviant auditory oddball paradigm. Results. Frontocentral deficits in MMN and P3a were present in all patient groups. The at-risk group's MMN and P3a amplitudes were intermediate to those of the control and recent-onset groups. The recent-onset and chronic patients, but not the at-risk subjects, showed significant RON amplitude reductions, relative to the control group. Associations between MMN, P3a, RON and psychosocial functioning were present in the chronic patients. In the at-risk subjects, P3a and RON deficits were significantly associated with higher levels of negative symptoms. Conclusions. Abnormalities in the automatic processes of sensory discrimination, orienting and reorienting of attention are evident in the early phases of schizophrenia and raise the possibility of progressive worsening across stages of the illness. The finding that MMN and P3a, but not RON, were reduced before psychosis onset supports the continued examination of these components as potential early biomarkers of schizophrenia. C1 [Cadenhead, K. S.; Rissling, A. J.; Kirihara, K.; Braff, D. L.; Light, G. A.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Jahshan, C.] Vet Affairs Greater Los Angeles Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Los Angeles, CA USA. RP Light, GA (reprint author), Univ Calif San Diego, Dept Psychiat, 9500 Gilman Dr, La Jolla, CA 92093 USA. EM glight@ucsd.edu FU Department of Veteran Affairs (VISN 22 Mental Illness Research, Education, and Clinical Center); National Institute of Mental Health [MH079777, MH042228, MH065571] FX This work was supported by grants from the Department of Veteran Affairs (VISN 22 Mental Illness Research, Education, and Clinical Center) and National Institute of Mental Health (MH079777; MH042228, and MH065571). The authors wish to thank Jason Nunag, Steven Reding, Kathleen Shafer, Marlena Pela, Joyce Sprock, and Richard Sharp for their assistance. NR 86 TC 52 Z9 52 U1 0 U2 4 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 EI 1469-8978 J9 PSYCHOL MED JI Psychol. Med. PD JAN PY 2012 VL 42 IS 1 BP 85 EP 97 DI 10.1017/S0033291711001061 PG 13 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 874MG UT WOS:000298961600008 PM 21740622 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: effects on smoking behavior and reward sensitivity SO PSYCHOPHARMACOLOGY LA English DT Article DE Nicotine; Schizophrenia; Varenicline; Reward; Anhedonia; Affective flattening; Smoking cessation ID NICOTINE DEPENDENCE; NEGATIVE SYMPTOMS; DOPAMINE-D-2 RECEPTOR; CIGARETTE-SMOKING; TRANSDERMAL NICOTINE; VENTRAL STRIATUM; HUMANS; HYPOTHESIS; NONSMOKERS; SYSTEMS AB Smoking rates are up to five times higher in people with schizophrenia than in the general population, placing these individuals at high risk for smoking-related health problems. Varenicline, an alpha 4 beta 2 nicotinic acetylcholine receptor partial agonist, is a promising aid for smoking cessation in this population. To maximize treatment efficacy while minimizing risks, it is critical to identify reliable predictors of positive response to varenicline in smokers with schizophrenia. Negative symptoms of schizophrenia are related to dysfunctions in the brain reward system, are associated with nicotine dependence, and may be improved by nicotine or nicotinic receptor agonists, suggesting that smoking cessation may be especially difficult for patients with substantial negative symptoms. The purpose of the study was to evaluate negative symptoms as predictors of response to varenicline. Patients with schizophrenia (N = 53) completed a 12-week smoking cessation trial combining varenicline with cognitive behavioral therapy. Negative symptoms were assessed via the Scale for the Assessment of Negative Symptoms (Andreasen 1983). Outcomes included smoking abstinence as assessed by self-report and expired carbon monoxide. Change in performance on a probabilistic reward task was used as an index of change in reward sensitivity during treatment. At week 12, 32 participants met criteria for 14-day point-prevalence abstinence. Patients with lower baseline symptoms of affective flattening (more typical affect) were more likely to achieve smoking abstinence and demonstrated larger increases in reward sensitivity during treatment. These data suggest that affective flattening symptoms in smokers with schizophrenia may predict response to varenicline. C1 [Dutra, Sunny J.] Yale Univ, Dept Psychol, New Haven, CT 06520 USA. [Stoeckel, Luke E.; Carlini, Sara V.; Evins, A. Eden] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Pizzagalli, Diego A.] McLean Hosp, Dept Psychiat, Belmont, MA 02478 USA. RP Evins, AE (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 60 Staniford St, Boston, MA 02114 USA. EM a_eden_evins@hms.harvard.edu FU NIDA [R01 DA021245]; Harvard Medical School; NIMH [R01MH68376, R21MH078979]; GSK; Janssen; Pfizer; Boehringer-Ingelheim; ANT Inc.; AstraZeneca FX The study was funded by NIDA R01 DA021245 (Evins). This grant supported Dr. Evins' effort on the project. During the study, Dr. Stoeckel was partially supported by the Harvard Medical School Zinberg Fellowship in Clinical Addiction Research and a NIDA Loan Repayment Program Grant, and Dr. Pizzagalli was partially supported by NIMH grants R01MH68376 and R21MH078979.; The authors declare no competing financial interests. Dr. Evins has received research support from GSK, Janssen and Pfizer, and honoraria or consulting fees from Boehringer-Ingelheim and Pfizer. Dr. Pizzagalli has received research support and consulting fees from ANT Inc. and honoraria and consulting fee from AstraZeneca. NR 69 TC 18 Z9 18 U1 1 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JAN PY 2012 VL 219 IS 1 BP 25 EP 34 DI 10.1007/s00213-011-2373-6 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 870BX UT WOS:000298645200003 PM 21695488 ER PT J AU Brink, JA Goske, MJ Patti, JA AF Brink, James A. Goske, Marilyn J. Patti, John A. TI Informed Decision Making Trumps Informed Consent for Medical Imaging with Ionizing Radiation SO RADIOLOGY LA English DT Editorial Material ID CANCER-RISKS; EXPOSURE; PATIENT; RATHER; CT C1 [Brink, James A.] Yale Univ, Dept Diagnost Radiol, Sch Med, New Haven, CT 06520 USA. [Goske, Marilyn J.] Cincinnati Childrens Hosp, Med Ctr, Dept Radiol, Cincinnati, OH USA. [Patti, John A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Brink, JA (reprint author), Yale Univ, Dept Diagnost Radiol, Sch Med, 789 Howard Ave,Room TE2-230, New Haven, CT 06520 USA. EM james.brink@yale.edu NR 23 TC 32 Z9 32 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JAN PY 2012 VL 262 IS 1 BP 11 EP 14 DI 10.1148/radiol.11111421 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 869PY UT WOS:000298611500004 PM 22190652 ER PT J AU Su, HS Nahrendorf, M Panizzi, P Breckwoldt, MO Rodriguez, E Iwamoto, Y Aikawa, E Weissleder, R Chen, JW AF Su, Henry S. Nahrendorf, Matthias Panizzi, Peter Breckwoldt, Michael O. Rodriguez, Elisenda Iwamoto, Yoshiko Aikawa, Elena Weissleder, Ralph Chen, John W. TI Vasculitis: Molecular Imaging by Targeting the Inflammatory Enzyme Myeloperoxidase SO RADIOLOGY LA English DT Article ID ANCA-ASSOCIATED VASCULITIDES; LARGE VESSEL VASCULITIS; GIANT-CELL ARTERITIS; KAWASAKI-DISEASE; CARDIOVASCULAR-DISEASE; EULAR RECOMMENDATIONS; SYSTEMIC VASCULITIS; ANIMAL-MODEL; 3T MRI; MICE AB Purpose: To determine if a molecular imaging approach targeting the highly oxidative enzyme myeloperoxidase (MPO) can help noninvasively identify and confirm sites of vascular wall inflammation in a murine model of vasculitis. Materials and Methods: Animal experiments were approved by the institutional animal care committee. Twenty-six mice were studied, including eight MPO-deficient and six sham-operated mice as controls. Vasculitis was induced with intraperitoneal injection of Candida albicans water-soluble fraction (CAWS). Aortic root magnetic resonance imaging was performed after intravenous injection of the activatable MPO sensor (bis-5-hydroxytryptamide-diethylenetriaminepentatacetate gadolinium) (n = 23), referred to as MPO-Gd, or gadopentetate dimeglumine (n = 10). Seven mice were randomly assigned to receive either MPO-Gd or gadopentetate dimeglumine first. Aortic root specimens were collected for biochemical and histopathologic analyses to validate imaging findings. Statistical significance was calculated for contrast-to-noise ratios (CNRs) by using the paired t test. Results: In the aortic root, the mean MPO-Gd CNRs after agent injection (CNR = 28.1) were more than 2.5-fold higher than those of sham-operated mice imaged with MPO-Gd and vasculitis mice imaged with gadopentetate dimeglumine (CNR = 10.6) (P > .05). MPO-Gd MR imaging helped identify areas of vasculitis that were not seen at unenhanced and contrast material-enhanced imaging with gadopentetate dimeglumine. Histopathologic and biochemical analyses for MPO and myeloid cells confirmed imaging findings. In MPO-deficient mice, injection of CAWS did not result in a vasculitis phenotype, implying a key role of the imaging target in disease cause. Conclusion: Molecular imaging targeting MPO can be a useful biomarker to noninvasively detect and confirm inflammation in vasculitis by using a murine model of Kawasaki disease. (C) RSNA, 2011 C1 [Su, Henry S.; Nahrendorf, Matthias; Panizzi, Peter; Breckwoldt, Michael O.; Rodriguez, Elisenda; Iwamoto, Yoshiko; Aikawa, Elena; Weissleder, Ralph; Chen, John W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res,Ctr Syst Biol, Boston, MA 02114 USA. [Su, Henry S.; Chen, John W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Neuroradiol,Dept Radiol, Boston, MA 02114 USA. RP Chen, JW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res,Ctr Syst Biol, Boston, MA 02114 USA. EM jwchen@mgh.harvard.edu OI Panizzi, Peter/0000-0003-0141-8807 FU European Commission; National Institutes of Health [K08 HL081170, R01 NS070835, R01 NS072167, R01 HL078641]; Pfizer; Elsevier for a book FX From the Center for Molecular Imaging Research, Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Mass (H.S.S., M.N., P.R.P., M.O.B., E.R., Y.I., E.A., R.W., J.W.C.); and Division of Neuroradiology, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit St, Gray 2, Boston, MA 02114 (H.S.S., J.W.C.). From the 2008 RSNA Annual Meeting. Received January 5, 2011; revision requested March 23; revision received June 21; accepted July 21; final version accepted August 15. E.R. supported by a Marie Curie Fellowship from the European Commission. Address correspondence to J.W.C. (e-mail: jwchen@mgh.harvard.edu).; This research was supported by the National Institutes of Health (grants K08 HL081170, R01 NS070835, R01 NS072167, and R01 HL078641).; Disclosures of Potential Conflicts of Interest: H.S.S. No potential conflicts of interest to disclose. M.N. No potential conflicts of interest to disclose. P.R.P. No potential conflicts of interest to disclose. M.O.B. No potential conflicts of interest to disclose. E.R. No potential conflicts of interest to disclose. Y.I. No potential conflicts of interest to disclose. E.A. No potential conflicts of interest to disclose. R.W. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: author receives money for board membership to T2 BioSystems (author is founder) and has stock in T2 BioSystems; author is consultant for Lumicell; author is employee of Massachusetts General Hospital; institution has many grants pending; author has many patents. Other relationships: none to disclose. J.W.C. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: author is employee of Massachusetts General Hospital; institution has grants pending from Pfizer; author receives royalties from Elsevier for a book. Other relationships: none to disclose. NR 41 TC 9 Z9 11 U1 0 U2 9 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JAN PY 2012 VL 262 IS 1 BP 181 EP 190 DI 10.1148/radiol.11110040 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 869PY UT WOS:000298611500022 PM 22084204 ER PT J AU Nanji, KC Cooper, JB AF Nanji, Karen C. Cooper, Jeffrey B. TI It Is Time to Use Checklists for Anesthesia Emergencies Simulation Is the Vehicle for Testing and Learning SO REGIONAL ANESTHESIA AND PAIN MEDICINE LA English DT Editorial Material ID PERFORMANCE C1 [Nanji, Karen C.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Nanji, Karen C.; Cooper, Jeffrey B.] Harvard Univ, Sch Med, Boston, MA USA. RP Nanji, KC (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM knanji@partners.org NR 12 TC 9 Z9 9 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-7339 J9 REGION ANESTH PAIN M JI Region. Anesth. Pain Med. PD JAN-FEB PY 2012 VL 37 IS 1 BP 1 EP 2 DI 10.1097/AAP.0b013e31823e75b2 PG 2 WC Anesthesiology SC Anesthesiology GA 866FS UT WOS:000298366500001 PM 22189573 ER PT J AU Lambrechts, G Van Leeuwen, K Boonen, H Maes, B Noens, I AF Lambrechts, Greet Van Leeuwen, Karla Boonen, Hannah Maes, Bea Noens, Ilse TI Parenting behaviour among parents of children with autism spectrum disorder (vol 5, pg 1143, 2011) SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Correction C1 [Lambrechts, Greet; Van Leeuwen, Karla; Boonen, Hannah; Maes, Bea; Noens, Ilse] Katholieke Univ Leuven, Parenting & Special Educ Res Grp, B-3000 Louvain, Belgium. [Lambrechts, Greet; Boonen, Hannah; Noens, Ilse] Katholieke Univ Leuven, Leuven Autism Res Consortium LAuRes, B-3000 Louvain, Belgium. [Noens, Ilse] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. RP Lambrechts, G (reprint author), Katholieke Univ Leuven, Parenting & Special Educ Res Grp, Vesaliusstr 2,POB 3765, B-3000 Louvain, Belgium. EM Greet.Lambrechts@ped.kuleuven.be; Karla.Vanleeuwen@ped.kuleuven.be; Hannah.Boonen@ped.kuleuven.be; Bea.Maes@ped.kuleuven.be; Ilse.Noens@ped.kuleuven.be NR 1 TC 0 Z9 0 U1 1 U2 14 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1750-9467 J9 RES AUTISM SPECT DIS JI Res. Autism Spectr. Disord. PD JAN-MAR PY 2012 VL 6 IS 1 BP 311 EP 312 DI 10.1016/j.rasd.2011.06.001 PG 2 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA 858TU UT WOS:000297826400036 ER PT J AU Barch, DM Moore, H Nee, DE Manoach, DS Luck, SJ AF Barch, Deanna M. Moore, Holly Nee, Derek E. Manoach, Dara S. Luck, Steven J. TI CNTRICS Imaging Biomarkers Selection: Working Memory SO SCHIZOPHRENIA BULLETIN LA English DT Article DE schizophrenia; treatment; working memory; prefrontal cortex; capacity ID PREDICTS INDIVIDUAL-DIFFERENCES; DORSOLATERAL PREFRONTAL CORTEX; INTERFERENCE-CONTROL PROCESSES; POSTERIOR PARIETAL CORTEX; SHORT-TERM-MEMORY; PROACTIVE-INTERFERENCE; COGNITIVE NEUROSCIENCE; SCHIZOPHRENIC SUBJECTS; NEURAL MECHANISMS; CAPACITY LIMIT AB The sixth meeting of the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) consortium was focused on selecting promising imaging biomarker measures for each of the cognitive constructs selected in the first CNTRICS meeting. In the domain of working memory (WM), the 2 constructs of interest were "goal maintenance" and "interference control." CNTRICS received 7 task nominations for goal maintenance and 3 task nominations for interference control. For goal maintenance, the breakout group for WM recommended the AX Continuous Performance Test/Dot Pattern Expectancy (DPX) and the Switching Stroop task for translation and further development for use in clinical trial contexts in schizophrenia research. Notably, these same 2 paradigms were recommended for "rule generation and selection" in executive control, a highly related construct. For interference control, the breakout group recommended the Suppress Task and the Sternberg Item Recognition Paradigm for translation for use in clinical trials. This manuscript describes the ways in which each of these tasks met the criteria used by the breakout group to recommend tasks for further development. In addition, the group revisited the construct of WM capacity. Since the initial CNTRICS meeting, a growing body of work has emerged on the neurobiological substrates of WM capacity, making measure of this construct ready for translation. The group suggested a promising imaging biomarker measure for capacity, a version of the change detection task that measures delay activity over posterior parietal and occipital cortex. C1 [Barch, Deanna M.] Washington Univ, Dept Psychol, St Louis, MO 63130 USA. [Barch, Deanna M.] Washington Univ, Dept Psychiat, St Louis, MO 63130 USA. [Barch, Deanna M.] Washington Univ, Dept Radiol, St Louis, MO 63130 USA. [Moore, Holly] Columbia Univ, Dept Psychiat, New York, NY USA. [Moore, Holly] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Nee, Derek E.] Indiana Univ, Dept Psychol & Brain Sci, Bloomington, IN USA. [Nee, Derek E.] Univ Michigan, Dept Psychol, Ann Arbor, MI USA. [Manoach, Dara S.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Manoach, Dara S.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Luck, Steven J.] Univ Calif Davis, Dept Psychol, Ctr Mind & Brain, Davis, CA 95616 USA. RP Barch, DM (reprint author), Washington Univ, Dept Psychol, St Louis, MO 63130 USA. EM dbarch@artsci.wustl.edu RI Barch, Deanna/G-8638-2013; OI Nee, Derek/0000-0001-7858-6871 FU National Institutes of Mental Health [5R 13MH078710]; National Institute of Health (NIH); McDonnell Center for Higher Brain Function; National Alliance for Research on Schizophrenia and Depression (NARSAD); New York State Office of Mental Health; Sidney R. Baer Jr Foundation; national science foundation (NSF) FX National Institutes of Mental Health (5R 13MH078710).; We would also like to thank Deb Tussing and Carol Cox, whose efforts have been invaluable in the CNTRICS process. In addition, we would like to thank the other members of the Working Memory breakout group, including. Financial Disclosures: D.M.B. receives funding from the National Institute of Health (NIH), the McDonnell Center for Higher Brain Function, and National Alliance for Research on Schizophrenia and Depression (NARSAD). H.M. receives funding from the NIH, the New York State Office of Mental Health, and the Sidney R. Baer Jr Foundation. D.E.N. receives funding from national science foundation (NSF) and NIH. D.S.M. receives funding from National Institutes of Mental Health and NARSAD. S.J.L. receives funding from NSF and NIH. NR 50 TC 24 Z9 24 U1 5 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD JAN PY 2012 VL 38 IS 1 BP 43 EP 52 DI 10.1093/schbul/sbr160 PG 10 WC Psychiatry SC Psychiatry GA 875DZ UT WOS:000299011900008 PM 22080498 ER PT J AU Butler, PD Chen, Y Ford, JM Geyer, MA Silverstein, SM Green, MF AF Butler, Pamela D. Chen, Yue Ford, Judith M. Geyer, Mark A. Silverstein, Steven M. Green, Michael F. TI Perceptual Measurement in Schizophrenia: Promising Electrophysiology and Neuroimaging Paradigms From CNTRICS SO SCHIZOPHRENIA BULLETIN LA English DT Article DE perception; CNTRICS; sensory processes; gain control; integration ID PREPULSE INHIBITION; COROLLARY DISCHARGE; MISMATCH NEGATIVITY; AUDITORY HALLUCINATIONS; EVOKED-POTENTIALS; MOTION PERCEPTION; ACOUSTIC STARTLE; GATING DEFICITS; VISUAL-CORTEX; HUMANS AB The sixth meeting of the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) focused on selecting promising imaging paradigms for each of the cognitive constructs selected in the first CNTRICS meeting. In the domain of perception, the 2 constructs of interest were "gain control" and "visual integration." CNTRICS received 6 task nominations for imaging paradigms for gain control and 3 task nominations for integration. The breakout group for perception evaluated the degree to which each of these tasks met prespecified criteria. For gain control, the breakout group believed that one task (mismatch negativity) was already mature and was being incorporated into multisite clinical trials. The breakout group recommended that I visual task (steady-state visual evoked potentials to magnocellular- vs parvocellular-biased stimuli) and 2 auditory measures (an event-related potential (ERP) measure of corollary discharge and a functional magnetic resonance imaging (fMRI) version of prepulse inhibition of startle) be adapted for use in clinical trials in schizophrenia research. For visual integration, the breakout group recommended that fMRI and ERP versions of a contour integration test and an fMRI version of a coherent motion test be adapted for use in clinical trials. This manuscript describes the ways in which each of these tasks met the criteria used in the breakout group to evaluate and recommend tasks for further development. C1 [Butler, Pamela D.] Schizophrenia Res Ctr, Nathan Kline Inst Psychiat Res, Orangeburg, NY USA. [Butler, Pamela D.] NYU, Sch Med, Dept Psychiat, New York, NY USA. [Chen, Yue] Harvard Univ, McLean Hosp, Sch Med, Dept Psychiat, Belmont, MA USA. [Ford, Judith M.] Univ Calif San Francisco, VA Med Ctr, Dept Psychiat, San Francisco, CA 94143 USA. [Geyer, Mark A.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Silverstein, Steven M.] Univ Behav HealthCare, Univ Med & Dent New Jersey, Div Schizophrenia Res, Piscataway, NJ USA. [Silverstein, Steven M.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Psychiat, Piscataway, NJ 08854 USA. [Green, Michael F.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA USA. [Green, Michael F.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Butler, PD (reprint author), 140 Old Orangeburg Rd, Orangeburg, NY 10962 USA. EM butler@nki.rfmh.org FU National Institutes of Health [MH84848, MH61824, MH58262, MH067967, MH052885, MH084828, MH043292]; Veteran's Administration VISN 22 Mental Illness Research, Education, and Clinical Center; VA Merit FX National Institutes of Health (MH84848 to P.D.B., MH61824 to Y.C., MH58262 and MH067967 to J.M.F., MH052885 to M.A.G., MH084828 to S.M.S., MH043292 to M.F.G.); Veteran's Administration VISN 22 Mental Illness Research, Education, and Clinical Center to M.F.G. and M.A.G.; VA Merit to J.M.F. NR 50 TC 37 Z9 38 U1 2 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD JAN PY 2012 VL 38 IS 1 BP 81 EP 91 DI 10.1093/schbul/sbr106 PG 11 WC Psychiatry SC Psychiatry GA 875DZ UT WOS:000299011900012 PM 21890745 ER PT J AU Zietman, A Ibbott, G AF Zietman, Anthony Ibbott, Geoffrey TI A Clinical Approach to Technology Assessment: How Do We and How Should We Choose the Right Treatment? SO SEMINARS IN RADIATION ONCOLOGY LA English DT Article ID PROSTATE-CANCER; DECISIONS; PATIENT AB The evidence required to support the use of new technology in medicine differs from that required for new drugs. On one extreme, very little may be required for small devices, but on the other strong evidence is required to support the use of truly novel, potentially dangerous, and high-cost machines. The randomized controlled trial is built into the evaluation of drugs and suits them well. It is not so well suited to the evaluation of major devices in which installation costs and return on investment are important. We discuss where the randomized controlled trial may still play a role and what alternatives may exist when this is not possible. We also discuss the role that independent bodies may have in determining whether or not a new device is not only safe but also adds to the medical landscape in a way that justifies its cost. Semin Radiat Oncol 22:11-17 (C) 2012 Elsevier Inc. All rights reserved. C1 [Zietman, Anthony] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Ibbott, Geoffrey] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Zietman, A (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Fruit St, Boston, MA 02114 USA. EM azietman@partners.org NR 16 TC 9 Z9 9 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1053-4296 J9 SEMIN RADIAT ONCOL JI Semin. Radiat. Oncol. PD JAN PY 2012 VL 22 IS 1 BP 11 EP 17 DI 10.1016/j.semradonc.2011.09.008 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 867GI UT WOS:000298442500003 PM 22177874 ER PT J AU Boriani, S Bandiera, S Casadei, R Boriani, L Donthineni, R Gasbarrini, A Pignotti, E Biagini, R Schwab, JH AF Boriani, Stefano Bandiera, Stefano Casadei, Roberto Boriani, Luca Donthineni, Rakesh Gasbarrini, Alessandro Pignotti, Elettra Biagini, Roberto Schwab, Joseph H. TI Giant Cell Tumor of the Mobile Spine A Review of 49 Cases SO SPINE LA English DT Review DE giant cell tumor of bone; mobile spine; local recurrence ID BONE-TUMORS; RADIATION-THERAPY; SOFT-TISSUE; CRYOSURGERY; SARCOMA; RADIOTHERAPY; MANAGEMENT; RESECTION AB Study Design. This is a retrospective review of 49 cases of giant cell tumor (GCT) of the mobile spine treated surgically. Objective. Our goal was to determine which factors influenced local recurrence. Summary of Background Data. GCT is a benign, locally aggressive tumor that rarely occurs in the spine. The management of local recurrence can be challenging. Methods. We performed a retrospective analysis of GCTs of the mobile spine managed between 1970 and 2005. Median follow-up was 145 months with a minimum of 2 years or until death. We used the Kaplan-Meier method to test whether Enneking stage, surgery type, and surgical margin had statistically significant impact on local recurrence. The log rank test was used for comparison, and a P value of less than 0.05 was deemed significant. Results. Of the 49 patients, 11 (22%) local recurrences occurred. The latest recurrence occurred at 60 months. Age less than 25 years was associated with a worse relapse-free survival (P = 0.03). En bloc resection was associated with better local control with Enneking stage III tumors (P = 0.01); however, intralesional resection provided adequate control of Enneking stage II tumors. There were 6 (12%) cases of metastasis, and 2 patients died from the progression of their disease. One patient died from the complications of the surgery. Conclusion. En bloc resection should be considered for Enneking stage III GCTs of the mobile spine. The choice of en bloc resection must be balanced with the inherent risks of the procedure. Intralesional resection of Enneking stage II tumors provides adequate local control. Patients should be followed for at least 5 years because local relapse can occur late. C1 [Schwab, Joseph H.] Massachusetts Gen Hosp, Sect Orthoped Oncol, Dept Orthoped Surg, Boston, MA 02114 USA. [Boriani, Stefano; Bandiera, Stefano; Gasbarrini, Alessandro] Rizzoli Inst, Dept Spine Oncol, Bologna, Italy. [Casadei, Roberto; Boriani, Luca] Rizzoli Inst, Dept Surg Oncol, Bologna, Italy. [Donthineni, Rakesh] Alta Bates Med Ctr, Berkeley, CA USA. [Pignotti, Elettra] Rizzoli Inst, Stat Anal TF, Bologna, Italy. [Biagini, Roberto] IFO, Dept Orthoped Oncol, Rome, Italy. RP Schwab, JH (reprint author), Massachusetts Gen Hosp, Sect Orthoped Oncol, Dept Orthoped Surg, 55 Fruit St, Boston, MA 02114 USA. EM jhschwab@partners.org OI Biagini, Roberto/0000-0002-6819-2841 NR 40 TC 26 Z9 29 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD JAN 1 PY 2012 VL 37 IS 1 BP E37 EP E45 DI 10.1097/BRS.0b013e3182233ccd PG 9 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 866UN UT WOS:000298410500007 PM 22179322 ER PT J AU Reeves, MJ Fonarow, GC Smith, EE Pan, WQ Olson, D Hernandez, AF Peterson, ED Schwamm, LH AF Reeves, Mathew J. Fonarow, Gregg C. Smith, Eric E. Pan, Wenqin Olson, DaiWai Hernandez, Adrian F. Peterson, Eric D. Schwamm, Lee H. TI Representativeness of the Get With The Guidelines-Stroke Registry Comparison of Patient and Hospital Characteristics Among Medicare Beneficiaries Hospitalized With Ischemic Stroke SO STROKE LA English DT Article DE ischemic stroke; Medicare; registries; representativeness ID EXPERIENCE; OUTCOMES; ATTACK; CARE AB Background and Purpose-Get With The Guidelines (GWTG)-Stroke is a large quality improvement-based registry of acute stroke; however, its generalizability is unclear. We used fee-for-service Medicare claims to ascertain the representativeness of ischemic stroke admissions in GWTG-Stroke. Methods-All 228 815 ischemic stroke admissions aged >= 65 years enrolled in GWTG-Stroke between April 2003 and December 2007 were linked to 926 756 unique fee-for-service Medicare patients with ischemic stroke (primary International Classification of Diseases, 9th Revision discharge code 434 or 436) from the same period. Patient characteristics and in-hospital outcomes were compared between the linked GWTG-Stroke Medicare cohort and the remaining unlinked Medicare cohort. Characteristics of GWTG-Stroke hospitals were compared with non-GWTG-Stroke hospitals. Results-A total of 144 344 of the 228,815 GWTG-Stroke admissions (63.1%) were successfully linked to the 926 756 Medicare ischemic stroke beneficiaries, leaving 782 412 unlinked Medicare patients. Differences in patient characteristics, including age, race, gender, and comorbidities, between the linked and unlinked Medicare cohorts were minimal. Length of stay and rate of discharge home were almost identical between the linked and unlinked groups; however, in-hospital mortality was slightly lower in the linked Medicare cohort (6.3%) compared with the unlinked cohort (7.0%). There were large differences in hospital characteristics between GWTG-Stroke and non-GWTG-Stroke hospitals; GWTG-Stroke hospitals tended to be larger, urban, teaching centers. Conclusions-Despite substantial differences between GWTG-Stroke and non-GWTG-Stroke hospitals, Medicare beneficiaries with acute ischemic stroke entered in the GWTG-Stroke program were similar to other Medicare beneficiaries. These data suggest that the Medicare-aged GWTG-Stroke ischemic stroke admissions are generally representative of the national fee-for-service Medicare ischemic stroke population. (Stroke. 2012;43:44-49.) C1 [Reeves, Mathew J.] Michigan State Univ, Dept Epidemiol, E Lansing, MI 48824 USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Div Cardiol, Los Angeles, CA USA. [Smith, Eric E.] Univ Calgary, Dept Clin Neurosci, Calgary, AB, Canada. [Pan, Wenqin; Olson, DaiWai; Hernandez, Adrian F.; Peterson, Eric D.] Duke Clin Res Inst, Durham, NC USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Reeves, MJ (reprint author), Michigan State Univ, Dept Epidemiol, B601 W Fee Hall, E Lansing, MI 48824 USA. EM reevesm@msu.edu RI Smith, Eric/C-5443-2012; Hernandez, Adrian F./A-7818-2016 OI Smith, Eric/0000-0003-3956-1668; Schwamm, Lee/0000-0003-0592-9145; Hernandez, Adrian F./0000-0003-3387-9616 FU Michigan Stroke Registry; National Institutes of Health (NIH); Agency for Healthcare Research and Quality; Canadian Stroke Network; Heart and Stroke Foundation of Canada; Canadian Institute for Health Research; Bristol-Myers Squibb; Sanofi-Aventis; Merck; Ortho McNeil Pharmaceuticals FX M.J.R. receives salary support from the Michigan Stroke Registry and serves on several American Heart Association Get With The Guidelines (AHA GWTG) Committees. G. C. F. serves as a member of the AHA GWTG Steering Committee; receives research support from the National Institutes of Health (NIH; significant) and the Agency for Healthcare Research and Quality (significant); and serves as a consultant to Novartis (significant). E. E. S. serves as a member of the GWTG Subcommittee and receives research support from the NIH and the Canadian Stroke Network and salary support from the Heart and Stroke Foundation of Canada and the Canadian Institute for Health Research. W. P. is a member of the Duke Clinical Research Institute (DCRI), which serves as the AHA GWTG data coordinating center. D. O. is a member of the DCRI, which serves as the AHA GWTG data coordinating center. A. F. H. is a member of the DCRI, which serves as the AHA GWTG data coordinating center. A. F. H. is a recipient of an AHA Pharmaceutical Roundtable grant. E. D. P. has received research grants from Bristol-Myers Squibb, Sanofi-Aventis, Merck, and Ortho McNeil Pharmaceuticals. E. D. P. serves as Principal Investigator of the Data Analytic Center for AHA GWTG. L. H. S. serves as chair of the AHA GWTG Steering Committee and serves as a consultant to the Massachusetts Department of Public Health. NR 13 TC 42 Z9 42 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2012 VL 43 IS 1 BP 44 EP 49 DI 10.1161/STROKEAHA.111.626978 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 866LY UT WOS:000298383600027 PM 21980197 ER PT J AU Parker, C Schwamm, LH Fonarow, GC Smith, EE Reeves, MJ AF Parker, Carol Schwamm, Lee H. Fonarow, Gregg C. Smith, Eric E. Reeves, Mathew J. TI Stroke Quality Metrics Systematic Reviews of the Relationships to Patient-Centered Outcomes and Impact of Public Reporting SO STROKE LA English DT Article DE acute stroke; outcomes; public reporting; quality metrics ID ACUTE MYOCARDIAL-INFARCTION; TRANSIENT ISCHEMIC ATTACK; OF-CARE; PERFORMANCE-MEASURES; GUIDELINES-STROKE; HOSPITAL OUTCOMES; MORTALITY-RATES; ASSOCIATION; REHABILITATION; IMPROVEMENTS AB Background and Purpose-Stroke quality metrics play an increasingly important role in quality improvement and policies related to provider reimbursement, accreditation, and public reporting. We conducted 2 systematic reviews examining the relationships between compliance with stroke quality metrics and patient-centered outcomes, and public reporting of stroke metrics and quality improvement, quality of care, or outcomes. Methods-MEDLINE and EMBASE databases were searched to identify studies that evaluated the relationship between stroke quality metric compliance and patient-centered outcomes in acute hospital settings and public reporting of stroke quality metrics and quality improvement activities, quality of care, or patient outcomes. We specifically excluded studies that evaluated the effect of stroke units or hospital certification. Results-Fourteen studies met eligibility criteria for the review of stroke quality metric compliance and patient-centered outcomes; 9 found mostly positive associations, whereas 5 found no or very limited associations. Only 2 eligible studies were found that directly addressed the public reporting of stroke quality metrics. Conclusions-Some studies have found positive associations between stroke metric compliance and improved patient-centered outcomes. However, high-quality studies are lacking and several methodological difficulties make the interpretation of the reported associations challenging. Information on the impact of public reporting of stroke quality metric data is extremely limited. Legitimate questions remain as to whether public reporting of stroke metrics is accurate, effective, or has the potential for unintended consequences. The generation of high-quality data examining quality metrics and stroke outcomes as well as the impact of public reporting should be given priority. (Stroke. 2012;43:155-162.) C1 [Parker, Carol; Reeves, Mathew J.] Michigan State Univ, Dept Epidemiol, E Lansing, MI 48824 USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Div Cardiol, Los Angeles, CA USA. [Smith, Eric E.] Dept Clin Neurosci, Calgary, AB, Canada. RP Reeves, MJ (reprint author), Michigan State Univ, Dept Epidemiol, B601 W Fee Hall, E Lansing, MI 48824 USA. EM reevesm@msu.edu OI Schwamm, Lee/0000-0003-0592-9145; Smith, Eric/0000-0003-3956-1668 FU National Institutes of Health; Agency of Healthcare Research and Quality; Canadian Institutes for Health Research; Canadian Stroke Network; Heart and Stroke Foundation of Canada; Michigan Paul Coverdell Stroke Registry FX L. H. S. serves as chair of the American Heart Association (AHA) Get With The Guidelines (GWTG) Steering Committee, is a consultant to the Massachusetts Department of Public Health, and provided expert medical opinions in malpractice lawsuits regarding stroke treatment and prevention. G. C. F. is a member of the AHA GWTG Steering Committee, is a consultant to Novartis, and receives research support from the National Institutes of Health and the Agency of Healthcare Research and Quality. E. E. S. serves as chair of the AHA GWTG-Stroke Science Subcommittee and reports research funding from the National Institutes of Health, Canadian Institutes for Health Research, Canadian Stroke Network, and Heart and Stroke Foundation of Canada. M.J.R. serves as a member of the AHA GWTG Quality Improvement and Stroke Science Subcommittees and receives salary support from the Michigan Paul Coverdell Stroke Registry. NR 50 TC 21 Z9 21 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2012 VL 43 IS 1 BP 155 EP 162 DI 10.1161/STROKEAHA.111.635011 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 866LY UT WOS:000298383600046 PM 21980213 ER PT J AU Yung, LM Wei, Y Qin, T Wang, YM Smith, CD Waeber, C AF Yung, Lai Ming Wei, Ying Qin, Tao Wang, Yumei Smith, Charles D. Waeber, Christian TI Sphingosine Kinase 2 Mediates Cerebral Preconditioning and Protects the Mouse Brain Against Ischemic Injury SO STROKE LA English DT Article DE cell death; cerebral ischemia; hypoxia; isoflurane; neurons; preconditioning; sphingosine kinase 2 ID HIPPOCAMPAL SLICE CULTURES; NITRIC-OXIDE SYNTHASE; FOCAL ISCHEMIA; UP-REGULATION; RAT-BRAIN; ISOFLURANE; HYPOXIA; TOLERANCE; FTY720; STROKE AB Background and Purpose-Cerebral preconditioning provides insights into endogenous mechanisms that protect the brain from ischemic injury. Hypoxia and the anesthetic isoflurane are powerful preconditioning agents. Recent data show that sphingosine 1-phosphate receptor stimulation improves outcome in rodent models of stroke. Endogenous sphingosine 1-phosphate levels are controlled by the expression and activity of sphingosine kinases (SPK). We hypothesize that SPK upregulation mediates preconditioning induced by isoflurane and hypoxia and reduces ischemic injury. Methods-Male wild-type C57BL/J, SPK1(-/-) and SPK2(-/-) mice were exposed to isoflurane or hypoxia preconditioning before transient middle cerebral artery occlusion. Infarct volume and neurological outcome were measured 24 hours later. SPK inhibitors (SKI-II and ABC294640) were used to test the involvement of SPK2. Expressions of SPK1, SPK2, and hypoxia-inducible factor 1 alpha were determined. Primary cultures of mouse cortical neurons were exposed to isoflurane before glutamate-or hydrogen peroxide-induced cell death. Results-Isoflurane preconditioning and hypoxia preconditioning significantly reduced infarct volume and improved neurological outcome in wild-type and SPK1 (/) mice but not in SPK2 (/) mice. Pretreatment with SKI-II or ABC294640 abolished the isoflurane preconditioning-induced tolerance. Western blot showed a rapid and sustained increase in SPK2 level, whereas SPK1 level was similar between preconditioned mice and controls. Hypoxia-inducible factor 1 alpha was upregulated in wild-type isoflurane-preconditioned mice but not in SPK2(-/-). Isoflurane preconditioning protected primary neurons against cell death, which was abolished in ABC294640-treated cells. Conclusions-Applying genetic and pharmacological approaches, we demonstrate that neuronal SPK2 isoform plays an important role in cerebral preconditioning. (Stroke. 2012;43:199-204.) C1 [Yung, Lai Ming; Wei, Ying; Qin, Tao; Wang, Yumei; Waeber, Christian] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab,Dept Radiol, Charlestown, MA USA. [Smith, Charles D.] Apogee Biotechnol Corp, Hummelstown, PA USA. RP Waeber, C (reprint author), MGH, Bldg 149,Room 6403, Charlestown, MA 02129 USA. EM waeber@helix.mgh.harvard.edu RI Waeber, Christian/A-8333-2009 OI Waeber, Christian/0000-0001-6078-0027 FU National Institutes of Health [NS049263, NS055104]; Interdepartmental Neuroscience Center [P30NS045776] FX This work was supported by National Institutes of Health grants (NS049263 and NS055104) to C.W. and grant P30NS045776 (Interdepartmental Neuroscience Center). NR 48 TC 26 Z9 26 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2012 VL 43 IS 1 BP 199 EP U377 DI 10.1161/STROKEAHA.111.626911 PG 17 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 866LY UT WOS:000298383600052 PM 21980199 ER PT J AU Schlunk, F Van Cott, EM Hayakawa, K Pfeilschifter, W Lo, EH Foerch, C AF Schlunk, Frieder Van Cott, Elizabeth M. Hayakawa, Kazuhide Pfeilschifter, Waltraud Lo, Eng H. Foerch, Christian TI Recombinant Activated Coagulation Factor VII and Prothrombin Complex Concentrates Are Equally Effective in Reducing Hematoma Volume in Experimental Warfarin-Associated Intracerebral Hemorrhage SO STROKE LA English DT Article DE animal models; anticoagulation; ICH; intracerebral hemorrhage; warfarin ID ANTICOAGULATION; REVERSAL; MODEL AB Background and Purpose-Based on an experimental model of warfarin-associated intracerebral hemorrhage, we investigated whether the rapid reversal of anticoagulation using prothrombin complex concentrates (PCC) or recombinant activated coagulation factor VII (rFVIIa) reduces hematoma volume. Methods-Mice were orally pretreated with warfarin (2 mg/kg). Intracerebral hemorrhage was induced by collagenase injection into the right striatum. Forty-five minutes later, PCC (100 IE/kg), rFVIIa (1 mg/kg), or an equal volume of saline was administered intravenously. Hematoma volume after 24 hours was quantified using a photometric hemoglobin assay. Results-International normalized ratio was 4.3 +/- 0.4 in saline-treated mice, 0.9 +/- 0.1 in rFVIIa mice, and 1.4 +/- 0.2 in PCC mice. Intracerebral hemorrhage volume was 29.0 +/- 19.7 mu L in the saline group (n=7), 8.6 +/- 4.3 mu L in the rFVIIa group (n=6), and 6.1 +/- 1.8 mu L in the PCC group (n=7; analysis of variance between-group differences P=0.004; post hoc rFVIIa versus saline P=0.021; PCC versus saline P=0.007). No significant difference was found between PCC- and rFVIIa-treated animals. Conclusions-Our results suggest that PCC and rFVIIa are equally effective in restoring coagulation and preventing excessive hematoma growth in acute warfarin-associated intracerebral hemorrhage. (Stroke. 2012;43:246-249.) C1 [Schlunk, Frieder; Pfeilschifter, Waltraud; Foerch, Christian] Goethe Univ Frankfurt, Dept Neurol, D-60528 Frankfurt, Germany. [Schlunk, Frieder; Hayakawa, Kazuhide; Lo, Eng H.; Foerch, Christian] Massachusetts Gen Hosp, Neuroprotect Res Lab, Charlestown, MA USA. [Van Cott, Elizabeth M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Foerch, C (reprint author), Goethe Univ Frankfurt, Dept Neurol, Schleusenweg 2-16, D-60528 Frankfurt, Germany. EM foerch@em.uni-frankfurt.de RI Pfeilschifter, Waltraud/K-6134-2012 OI Pfeilschifter, Waltraud/0000-0001-6935-8842 FU NINDS NIH HHS [R37 NS037074, P01 NS055104, R01 NS076694, RC2 NS069335] NR 13 TC 17 Z9 19 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2012 VL 43 IS 1 BP 246 EP 249 DI 10.1161/STROKEAHA.111.629360 PG 4 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 866LY UT WOS:000298383600061 PM 21998055 ER PT J AU Wallace, ZS Khosroshahi, A Jakobiec, FA Deshpande, V Hatton, MP Ritter, J Ferry, JA Stone, JH AF Wallace, Zachary S. Khosroshahi, Arezou Jakobiec, Frederick A. Deshpande, Vikram Hatton, Mark P. Ritter, Jill Ferry, Judith A. Stone, John H. TI IgG4-Related Systemic Disease as a Cause of "Idiopathic" Orbital Inflammation, Including Orbital Myositis, and Trigeminal Nerve Involvement SO SURVEY OF OPHTHALMOLOGY LA English DT Review DE dacryoadenitis; Idiopathic Inflammation; IgG4-related systemic disease; myositis; orbital pseudotumor; rituximab ID PATHOLOGICAL FEATURES; SCLEROSING DISEASE; RITUXIMAB THERAPY; DIAGNOSIS; TUMOR AB IgG4-related systemic disease (IgG4-RD) is an inflammatory condition of unknown etiology that has been identified as the cause of tumefactive lesions in a number of tissues and organs. The role of the IgG4 remains to be clarified fully, but the histopathologic diagnosis hinges upon the finding of IgG4-bearing plasma cells in addition to characteristic morphologic features, with or without elevated scum IgG4. We present a 56-year-old man with orbital pseudotumor in whom, after 30 years of intractable disease, biopsy showed IgG4-RD involving the lacrimal gland, extraocular muscles, intraconal fat, and trigeminal nerve. Six months after initiating treatment with rituximab, his disease remained dormant, with improvement in his proptosis and normalization of serum IgG4 levels. We review the differential of idiopathic orbital inflammatory disease, including IgG4-RD, and emphasize the need for biopsy for accurate diagnosis and to guide appropriate treatment. (Surv Ophthalmol 57:26-33, 2012. (C) 2012 Elsevier Inc. All rights reserved.) C1 [Wallace, Zachary S.; Khosroshahi, Arezou; Stone, John H.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Jakobiec, Frederick A.; Deshpande, Vikram; Ferry, Judith A.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Hatton, Mark P.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. [Khosroshahi, Arezou; Stone, John H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Khosroshahi, Arezou; Stone, John H.] Massachusetts Eye & Ear Infirm, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. [Jakobiec, Frederick A.] Massachusetts Eye & Ear Infirm, Cogan Eye Pathol Lab, Boston, MA 02114 USA. RP Stone, JH (reprint author), Massachusetts Gen Hosp, Rheumatol Unit, Yawkey 2,55 Fruit St, Boston, MA 02114 USA. EM jhstone@partners.org NR 25 TC 68 Z9 75 U1 0 U2 4 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 JAN-FEB PY 2012 VL 57 IS 1 BP 26 EP 33 DI 10.1016/j.survophthal.2011.07.004 PG 8 WC Ophthalmology SC Ophthalmology GA 862WG UT WOS:000298124200002 PM 22018678 ER PT J AU Rossi, A Baumgart, F van Hoek, AN Verkman, AS AF Rossi, Andrea Baumgart, Florian van Hoek, Alfred N. Verkman, A. S. TI Post-Golgi Supramolecular Assembly of Aquaporin-4 in Orthogonal Arrays SO TRAFFIC LA English DT Article DE AQP4; Golgi; NMO; OAP ID INSENSITIVE WATER CHANNEL; NEUROMYELITIS-OPTICA; ENDOPLASMIC-RETICULUM; CELL-ADHESION; KNOCKOUT MICE; M23 ISOFORMS; PROTEIN; BRAIN; LOCALIZATION; MEMBRANES AB The supramolecular assembly of aquaporin-4 (AQP4) in orthogonal arrays of particles (OAPs) involves N-terminus interactions of the M23-AQP4 isoform. We found AQP4 OAPs in cell plasma membranes but not in endoplasmic reticulum (ER) or Golgi, as shown by: (i) native gel electrophoresis of brain and AQP4-transfected cells, (ii) photobleaching recovery of green fluorescent protein-AQP4 chimeras in live cells and (iii) freeze-fracture electron microscopy (FFEM). We found that AQP4 OAP formation in plasma membranes, but not in the Golgi, was not related to AQP4 density, pH, membrane lipid composition, C-terminal PDZ domain interactions or a-syntrophin expression. Remarkably, however, fusion of AQP4-containing Golgi vesicles with (AQP4-free) plasma membrane vesicles produced OAPs, suggesting the involvement of plasma membrane factor(s) in AQP4 OAP formation. In investigating additional possible determinants of OAP assembly we discovered membrane curvature-dependent OAP assembly, in which OAPs were disrupted by extrusion of plasma membrane vesicles to similar to 110 nm diameter, but not to similar to 220 nm diameter. We conclude that AQP4 supramolecular assembly in OAPs is a post-Golgi phenomenon involving plasma membrane-specific factor(s). Post-Golgi and membrane curvature-dependent OAP assembly may be important for vesicle transport of AQP4 in the secretory pathway and AQP4-facilitated astrocyte migration, and suggests a novel therapeutic approach for neuromyelitis optica. C1 [Rossi, Andrea; Baumgart, Florian; Verkman, A. S.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Rossi, Andrea; Baumgart, Florian; Verkman, A. S.] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA. [van Hoek, Alfred N.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [van Hoek, Alfred N.] Massachusetts Gen Hosp, Program Membrane Biol, Boston, MA 02114 USA. [van Hoek, Alfred N.] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [van Hoek, Alfred N.] Harvard Univ, Sch Med, Boston, MA USA. RP Verkman, AS (reprint author), Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. EM Alan.Verkman@ucsf.edu OI Baumgart, Florian/0000-0003-1352-8632 FU National Institutes of Health [EY13574, EB00415, DK35124, HL73856, DK86125, DK72517]; Guthy-Jackson Charitable Foundation FX This work was supported by grants EY13574, EB00415, DK35124, HL73856, DK86125 and DK72517 from the National Institutes of Health and grants from the Guthy-Jackson Charitable Foundation. We thank Cambier Stephanie (UCSF) for providing human astrocyte cultures. NR 47 TC 15 Z9 15 U1 1 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1398-9219 J9 TRAFFIC JI Traffic PD JAN PY 2012 VL 13 IS 1 BP 43 EP 53 DI 10.1111/j.1600-0854.2011.01299.x PG 11 WC Cell Biology SC Cell Biology GA 865RR UT WOS:000298328500006 PM 21981006 ER PT J AU Fagenholz, PJ Murray, AF Noble, VE Baggish, AL Harris, NS AF Fagenholz, Peter J. Murray, Alice F. Noble, Vicki E. Baggish, Aaron L. Harris, N. Stuart TI ULTRASOUND FOR HIGH ALTITUDE RESEARCH SO ULTRASOUND IN MEDICINE AND BIOLOGY LA English DT Review DE Ultrasonography; Altitude sickness; Mountaineering; Biomedical research ID OPTIC-NERVE SHEATH; ACUTE MOUNTAIN-SICKNESS; PULMONARY-ARTERY PRESSURE; EXTRAVASCULAR LUNG WATER; INCREASED INTRACRANIAL-PRESSURE; CEREBROSPINAL-FLUID PRESSURE; PATENT FORAMEN OVALE; INFERIOR VENA-CAVA; DOPPLER-ECHOCARDIOGRAPHY; SONOGRAPHIC MEASUREMENT AB This review describes ultrasound techniques of potential use to high altitude researchers and discusses technical issues related to using ultrasound for high altitude research. Ultrasound allows portable, noninvasive evaluation of many physiologic parameters of interest to high altitude researchers. We discuss techniques that have been extensively used and emerging techniques that can be used to assess parameters of particular interest to high altitude researchers. We do not provide a definitive description of all ultrasound scanning methods but references to instructive sources are included. Potential drawbacks of ultrasound use, such as the need for sometimes extensive training and the potential for interobserver variation, are discussed and strategies for mitigating these are suggested. This review is meant to encourage other high altitude researchers to consider using ultrasound, either as a primary investigative modality or as an adjunct for monitoring parameters of interest in studies of physiology, altitude illness, or therapeutics. (E-mail: pfagenholz@partners.org) (C) 2012 World Federation for Ultrasound in Medicine & Biology. C1 [Fagenholz, Peter J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Trauma Emergency Surg & Surg Crit C, Boston, MA 02114 USA. [Noble, Vicki E.; Harris, N. Stuart] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02114 USA. [Baggish, Aaron L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. [Murray, Alice F.] Royal Infirm Edinburgh NHS Trust, Dept Emergency Med, Edinburgh, Midlothian, Scotland. RP Fagenholz, PJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Trauma Emergency Surg & Surg Crit C, CPZ 810,55 Fruit St, Boston, MA 02114 USA. EM pfagenholz@partners.org NR 70 TC 7 Z9 9 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-5629 J9 ULTRASOUND MED BIOL JI Ultrasound Med. Biol. PD JAN PY 2012 VL 38 IS 1 BP 1 EP 12 DI 10.1016/j.ultrasmedbio.2011.10.004 PG 12 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 863AO UT WOS:000298135400001 PM 22104522 ER PT J AU Gershman, B Eisner, BH AF Gershman, Boris Eisner, Brian H. TI Increased Risk of Urinary Tract Calculi Among Patients With Diabetes Mellitus-A Population-based Cohort Study EDITORIAL COMMENT SO UROLOGY LA English DT Editorial Material ID STONE DISEASE C1 [Gershman, Boris; Eisner, Brian H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02115 USA. RP Gershman, B (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02115 USA. NR 9 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 0090-4295 J9 UROLOGY JI Urology PD JAN PY 2012 VL 79 IS 1 BP 92 EP 93 DI 10.1016/j.urology.2011.08.068 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 870LO UT WOS:000298671000022 PM 22202545 ER PT J AU Stefanik, JJ Roemer, FW Zumwalt, AC Zhu, YY Gross, KD Lynch, JA Frey-Law, LA Lewis, CE Guermazi, A Powers, CM Felson, DT AF Stefanik, Joshua J. Roemer, Frank W. Zumwalt, Ann C. Zhu, Yanyan Gross, K. Douglas Lynch, John A. Frey-Law, Laura A. Lewis, Cora E. Guermazi, Ali Powers, Christopher M. Felson, David T. TI Association between measures of trochlear morphology and structural features of patellofemoral joint osteoarthritis on MRI: The MOST study SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE osteoarthritis; patellofemoral; trochlea ID KNEE OSTEOARTHRITIS; PATELLAR ALIGNMENT; WEIGHT-BEARING; PAIN; KINEMATICS; ALTA AB The sulcus angle has been widely used in the literature as a measure of trochlear morphology. Recently, lateral trochlear inclination and trochlear angle have been reported as alternatives. The purpose of this study was to determine the association between measures of trochlear morphology and patellofemoral joint (PFJ) cartilage damage and bone marrow lesions (BMLs). Nine hundred seven knees were selected from the Multicenter Osteoarthritis Study, a cohort study of persons aged 5079 years with or at risk for knee OA. Trochlear morphology was measured using lateral trochlear inclination, trochlear angle, and sulcus angle on axial MRI images; cartilage damage and BMLs were graded on MRI. We determined the association between quartiles of each trochlear morphology variable with the presence or absence of cartilage damage and BMLs in the PFJ using logistic regression. The strongest associations were seen with lateral trochlear inclination and lateral PFJ cartilage damage and BMLs, with knees in the lowest quartile (flattened lateral trochlea) having more than two times the odds of lateral cartilage damage and BMLs compared to those in the highest quartile (p?