FN Thomson Reuters Web of Science™ VR 1.0 PT J AU DeCarli, C Kawas, C Morrison, JH Reuter-Lorenz, PA Sperling, RA Wright, CB AF DeCarli, Charles Kawas, Claudia Morrison, John H. Reuter-Lorenz, Patricia A. Sperling, Reisa A. Wright, Clinton B. TI Session II: Mechanisms of Age-Related Cognitive Change and Targets for Intervention: Neural Circuits, Networks, and Plasticity SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE cognitive changes; aging; Neural networks ID WHITE-MATTER LESIONS; POSITRON-EMISSION-TOMOGRAPHY; PREFRONTAL CORTEX FUNCTION; OLDER-ADULTS; AMYLOID DEPOSITION; ALZHEIMERS-DISEASE; AGING BRAIN; MEMORY; ACTIVATION; MONKEY AB Age-related changes in neural circuits, neural networks, and their plasticity are central to our understanding of age changes in cognition and brain structure and function. This paper summarizes selected findings on these topics presented at the Cognitive Aging Summit II. Specific areas discussed were synaptic vulnerability and plasticity, including the role of different types of synaptic spines, and hormonal effects in the dorsolateral prefrontal cortex of nonhuman primates, the impact of both compensatory processes and dedifferentiation on demand-dependent differences in prefrontal activation in relation to age and performance, the role of vascular disease, indexed by white matter signal abnormalities, on prefrontal activation during a functional magnetic resonance imaging-based cognitive control paradigm, and the influence of amyloid-beta neuropathology on memory performance in older adults and the networks of brain activity underlying variability in performance. A greater understanding of age-related changes in brain plasticity and neural networks in healthy aging and in the presence of underlying vascular disease or amyloid pathology will be essential to identify new targets for intervention. Moreover, this understanding will assist in promoting the utilization of existing interventions, such as lifestyle and therapeutic modifiers of vascular disease. C1 [Wright, Clinton B.] Univ Miami, Evelyn F McKnight Brain Inst, Dept Neurol, Leonard M Miller Sch Med, Miami, FL 33136 USA. [DeCarli, Charles] Univ Calif Davis, Dept Neurol, Davis, CA 95616 USA. [DeCarli, Charles] Univ Calif Davis, Ctr Neurosci, Davis, CA 95616 USA. [Kawas, Claudia] Univ Calif Irvine, Dept Neurol, Irvine, CA 92717 USA. [Kawas, Claudia] Univ Calif Irvine, Dept Neurobiol & Behav, Irvine, CA USA. [Morrison, John H.] Mt Sinai Sch Med, Dept Neurosci, New York, NY USA. [Sperling, Reisa A.] Harvard Univ, Brigham & Womens Hosp, Dept Neurol, Massachusetts Gen Hosp,Med Sch, Boston, MA 02115 USA. RP Wright, CB (reprint author), Univ Miami, Evelyn F McKnight Brain Inst, Dept Neurol, Leonard M Miller Sch Med, Clini Res Bldg,CRB 1349,1120 NW 14th St, Miami, FL 33136 USA. EM CWright@med.miami.edu FU NIA NIH HHS [P30 AG010129, R01 AG021028] NR 46 TC 15 Z9 15 U1 0 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JUL PY 2012 VL 67 IS 7 BP 747 EP 753 DI 10.1093/gerona/gls111 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 970PD UT WOS:000306143700007 PM 22570135 ER PT J AU Craft, S Foster, TC Landfield, PW Maier, SF Resnick, SM Yaffe, K AF Craft, Suzanne Foster, Thomas C. Landfield, Philip W. Maier, Steven F. Resnick, Susan M. Yaffe, Kristine TI Session III: Mechanisms of Age-Related Cognitive Change and Targets for Intervention: Inflammatory, Oxidative, and Metabolic Processes SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Aging; Cognition; Inflammation; Oxidative stress; Metabolism ID ALZHEIMER-DISEASE; IMPAIRMENT; DECLINE; MEMORY; RISK; HIPPOCAMPUS; PREVALENCE; DEMENTIA; LATINOS; PROTEIN AB There is increasing evidence from basic science and human epidemiological studies that inflammation, oxidative stress, and metabolic abnormalities are associated with age-related cognitive decline and impairment. This article summarizes selected research on these topics presented at the Cognitive Aging Summit II. Speakers in this session presented evidence highlighting the roles of these processes and pathways on age-related cognitive decline, pointing to possible targets for intervention in nondemented older adults. Specific areas discussed included age differences in the production of cytokines following injury or infection, mechanisms underlying oxidative stress-induced changes in memory consolidation, insulin effects on brain signaling and memory, and the association between metabolic syndrome and cognitive decline in older adults. These presentations emphasize advances in our understanding of mechanisms and modifiers of age-related cognitive decline and provide insights into potential targets to promote cognitive health in older adults. C1 [Resnick, Susan M.] NIA, Lab Behav Neurosci, BRC, Baltimore, MD 21224 USA. [Craft, Suzanne] Univ Washington, Dept Psychiat & Behav Sci, Geriatr Res Educ & Clin Ctr, Seattle, WA 98195 USA. [Foster, Thomas C.] Univ Florida, Dept Neurosci, Evelyn F & William L McKnight Brain Inst, Gainesville, FL 32610 USA. [Landfield, Philip W.] Univ Kentucky, Dept Mol & Biomed Pharmacol, Coll Med, Lexington, KY 40506 USA. [Maier, Steven F.] Univ Colorado, Dept Psychol, Boulder, CO 80309 USA. [Maier, Steven F.] Univ Colorado, Dept Neurosci, Boulder, CO 80309 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. RP Resnick, SM (reprint author), NIA, Lab Behav Neurosci, BRC, Room 4B335,251 Bayview Blvd, Baltimore, MD 21224 USA. EM susan.resnick@nih.gov FU Intramural NIH HHS [ZIA AG000191-15]; NCATS NIH HHS [UL1 TR000064]; NIA NIH HHS [R01 AG014979, R01 AG034605, R37 AG036800] NR 26 TC 29 Z9 30 U1 1 U2 9 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JUL PY 2012 VL 67 IS 7 BP 754 EP 759 DI 10.1093/gerona/gls112 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 970PD UT WOS:000306143700008 PM 22570133 ER PT J AU Brown, JR Hanna, M Tesar, B Pochet, N Vartanov, A Fernandes, SM Werner, L Ash, M Roden, CA MacConaill, L Hainz, U Longtine, J Wang, YE Correll, M Van de Peer, Y Regev, A Wu, C Neuberg, D Freedman, AS AF Brown, J. R. Hanna, M. Tesar, B. Pochet, N. Vartanov, A. Fernandes, S. M. Werner, L. Ash, M. Roden, C. A. MacConaill, L. Hainz, U. Longtine, J. Wang, Y. E. Correll, M. Van de Peer, Y. Regev, A. Wu, C. Neuberg, D. Freedman, A. S. TI Germline copy number variation associated with Mendelian inheritance of CLL in two families SO LEUKEMIA LA English DT Letter ID CHRONIC LYMPHOCYTIC-LEUKEMIA; B-CLL; 13Q14; LOCUS C1 [Brown, J. R.; Tesar, B.; Vartanov, A.; Fernandes, S. M.; Ash, M.; Hainz, U.; Wu, C.; Freedman, A. S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Brown, J. R.; Wu, C.; Freedman, A. S.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Hanna, M.; Roden, C. A.; MacConaill, L.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Hanna, M.; Pochet, N.; Regev, A.] Broad Inst Harvard & MIT, Cambridge, MA USA. [Pochet, N.; Van de Peer, Y.] Univ Ghent, Dept Plant Biotechnol & Bioinformat, VIB, Dept Plant Syst Biol, B-9000 Ghent, Belgium. [Werner, L.; Neuberg, D.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Longtine, J.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Wang, Y. E.; Correll, M.] Dana Farber Canc Inst, Ctr Canc Computat Biol, Boston, MA 02115 USA. [Regev, A.] MIT, Howard Hughes Med Inst, Dept Biol, Cambridge, MA USA. RP Brown, JR (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM jennifer_brown@dfci.harvard.edu RI Van de Peer, Yves/D-4388-2009 OI Van de Peer, Yves/0000-0003-4327-3730 FU NCI NIH HHS [5 PO1CA092625, K23 CA115682] NR 15 TC 6 Z9 6 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD JUL PY 2012 VL 26 IS 7 BP 1710 EP 1713 DI 10.1038/leu.2012.33 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA 972UY UT WOS:000306307600040 PM 22382893 ER PT J AU Craft, S AF Craft, Suzanne TI Insulin resistance and AD-extending the translational path SO NATURE REVIEWS NEUROLOGY LA English DT Editorial Material ID TRANSGENIC MOUSE MODEL; ALZHEIMERS-DISEASE; AMYLOIDOSIS; OLIGOMERS; BRAIN AB Two recent studies have carefully characterized amyloid-related brain insulin resistance in animal models of, and patients with, Alzheimer disease (AD). The researchers show that exendin-4, a glucagon-like peptide 1 receptor agonist, ameliorates pathology and symptoms in a mouse model of AD, suggesting a novel therapeutic approach to this disease. C1 Vet Affairs Puget Sound, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. RP Craft, S (reprint author), Vet Affairs Puget Sound, Geriatr Res Educ & Clin Ctr, S-182,1660 S Columbian Way, Seattle, WA 98108 USA. EM scraft@u.washington.edu NR 9 TC 45 Z9 47 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4758 J9 NAT REV NEUROL JI Nat. Rev. Neurol. PD JUL PY 2012 VL 8 IS 7 BP 360 EP 362 DI 10.1038/nrneurol.2012.112 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 970BU UT WOS:000306103900002 PM 22710630 ER PT J AU Delgado-Escueta, AV AF Delgado-Escueta, Antonio V. TI Lafora progressive myoclonus epilepsy Glycogen storage disease vs neurodegenerative disease SO NEUROLOGY LA English DT Editorial Material ID MALIN; MICE C1 [Delgado-Escueta, Antonio V.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Delgado-Escueta, Antonio V.] VA Greater Los Angeles Healthcare Syst, VA Epilepsy Ctr Excellence, Los Angeles, CA USA. RP Delgado-Escueta, AV (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. EM escueta@ucla.edu OI Delgado-Escueta, Antonio V./0000-0002-1581-6999 FU NINDS NIH HHS [R01 NS042376] NR 10 TC 3 Z9 3 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUL PY 2012 VL 79 IS 1 BP 21 EP 22 DI 10.1212/WNL.0b013e31825dcea6 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 971BE UT WOS:000306176000008 PM 22622859 ER PT J AU Weaver, FM Follett, KA Stern, M Luo, P Harris, CL Hur, K Marks, WJ Rothlind, J Sagher, O Moy, C Pahwa, R Burchiel, K Hogarth, P Lai, EC Duda, JE Holloway, K Samii, A Horn, S Bronstein, JM Stoner, G Starr, PA Simpson, R Baltuch, G De Salles, A Huang, GD Reda, DJ AF Weaver, Frances M. Follett, Kenneth A. Stern, Matthew Luo, Ping Harris, Crystal L. Hur, Kwan Marks, William J., Jr. Rothlind, Johannes Sagher, Oren Moy, Claudia Pahwa, Rajesh Burchiel, Kim Hogarth, Penelope Lai, Eugene C. Duda, John E. Holloway, Kathryn Samii, Ali Horn, Stacy Bronstein, Jeff M. Stoner, Gatana Starr, Philip A. Simpson, Richard Baltuch, Gordon De Salles, Antonio Huang, Grant D. Reda, Domenic J. CA CSP 468 Study Grp TI Randomized trial of deep brain stimulation for Parkinson disease Thirty-six-month outcomes SO NEUROLOGY LA English DT Article ID QUALITY-OF-LIFE; 5-YEAR FOLLOW-UP; PALLIDAL STIMULATION; GLOBUS-PALLIDUS; SUBTHALAMIC NUCLEUS; MOTOR FLUCTUATIONS; MEDICAL THERAPY; MULTICENTER; VALIDATION; EFFICACY AB Objectives: Our objective was to compare long-term outcomes of deep brain stimulation (DBS) of the globus pallidus interna (GPi) and subthalamic nucleus (STN) for patients with Parkinson disease (PD) in a multicenter randomized controlled trial. Methods: Patients randomly assigned to GPi (n = 89) or STN DBS (n = 70) were followed for 36 months. The primary outcome was motor function on stimulation/off medication using the Unified Parkinson's Disease Rating Scale motor subscale. Secondary outcomes included quality of life and neurocognitive function. Results: Motor function improved between baseline and 36 months for GPi (41.1 to 27.1; 95% confidence interval [CI] -16.4 to -10.8; p < 0.001) and STN (42.5 to 29.7; 95% CI -15.8 to -9.4; p < 0.001); improvements were similar between targets and stable over time (p = 0.59). Health-related quality of life improved at 6 months on all subscales (all p values significant), but improvement diminished over time. Mattis Dementia Rating Scale scores declined faster for STN than GPi patients (p = 0.01); other neurocognitive measures showed gradual decline overall. Conclusions: The beneficial effect of DBS on motor function was stable and comparable by target over 36 months. Slight declines in quality of life following initial gains and gradual decline in neurocognitive function likely reflect underlying disease progression and highlight the importance of nonmotor symptoms in determining quality of life. Classification of Evidence: This study provides Class III evidence that improvement of motor symptoms of PD by DBS remains stable over 3 years and does not differ by surgical target. Neurology (R) 2012; 79:55-65 C1 [Weaver, Frances M.] Hines VA Hosp, Ctr Management Complex Chron Care, Hines, IL USA. [Weaver, Frances M.] Loyola Univ Stritch Sch Med, Maywood, IL USA. [Follett, Kenneth A.] Iowa City VA Med Ctr, Iowa City, IA USA. [Follett, Kenneth A.] Univ Nebraska Med Ctr, Omaha, NE USA. [Stern, Matthew; Horn, Stacy; Baltuch, Gordon] Univ Penn Hlth Syst, Philadelphia, PA USA. [Luo, Ping; Hur, Kwan; Reda, Domenic J.] Hines VA Hosp, Cooperat Studies Coordinating Ctr, Hines, IL USA. [Harris, Crystal L.] VA Cooperat Studies Program, Albuquerque, NM USA. [Marks, William J., Jr.; Rothlind, Johannes; Starr, Philip A.] San Francisco VA Med Ctr, San Francisco, CA USA. [Marks, William J., Jr.; Rothlind, Johannes; Starr, Philip A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Sagher, Oren] Univ Michigan Med Ctr, Ann Arbor, MI USA. [Moy, Claudia] NINDS, Rockville, MD USA. [Pahwa, Rajesh] Univ Kansas Med Ctr, Kansas City, KS USA. [Burchiel, Kim] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Burchiel, Kim; Hogarth, Penelope] Portland VA Med Ctr, Portland, OR USA. [Lai, Eugene C.; Simpson, Richard] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Lai, Eugene C.; Simpson, Richard] Methodist Neurol Inst, Houston, TX USA. [Stern, Matthew; Duda, John E.; Baltuch, Gordon] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Holloway, Kathryn] Richmond VA Med Ctr, Richmond, VA USA. [Samii, Ali] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Bronstein, Jeff M.; De Salles, Antonio] W Los Angeles VA Med Ctr, Los Angeles, CA USA. [Bronstein, Jeff M.; De Salles, Antonio] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Stoner, Gatana] Univ Iowa Hlth Care, Iowa City, IA USA. [Huang, Grant D.] US Dept Vet Affairs, Cooperat Studies Program, Cent Off, Washington, DC USA. RP Weaver, FM (reprint author), Hines VA Hosp, Ctr Management Complex Chron Care, Hines, IL USA. EM Frances.Weaver@va.gov FU Medtronic Neurological, Inc.; Cooperative Studies Program, Department of Veterans Affairs Office of Research and Development; NINDS; Teva; Ipsen; Medtronic; Adamas Pharma; Schering-Plough; GSK; GE Healthcare; EMD Serono; Boehringer Ingelheim; St Jude Medical; Impax Pharma; Novartis; Biogen; Xenoport; Solvay; Eisai; NIH/NINDS; NPF; Allon; Acadia; Valeant; Kyowa; Johnson Johnson; Schering; Santhera FX Medtronic Neurological, Inc. provided financial support. The Cooperative Studies Program, Department of Veterans Affairs Office of Research and Development, provided financial support and contributed to the study design. NINDS provided financial support and contributed to the design of the study.; F. Weaver reports no disclosures relevant to the manuscript. K. Follett reports serving as a consultant for Medtronic Neurological (safety monitoring panel). M. Stern reports receiving consulting fees from Teva, Ipsen, Medtronic, Adamas Pharma, Schering-Plough, payment for speakers bureaus from Teva, Novartis, and the Movement Disorder Society, payment for development of educational presentations from Teva and Medtronic. P. Luo, C. Harris, and K. Hur report no disclosures relevant to the manuscript. W. Marks reports receiving consulting fees from Medtronic and lecture fees from Medtronic. J. Rothlind, O. Sagher, and C. Moy report no disclosures relevant to the manuscript. R. Pahwa reports receiving consulting fees from Teva, GSK, GE Healthcare, EMD Serono, Boehringer Ingelheim, Medtronic, St Jude Medical, Impax Pharma, Novartis, Adamas Pharma, and Biogen, providing expert testimony, grants/grants pending from Teva, Novartis, Xenoport, Impax Pharma, Boehringer Ingelheim, Solvay, EMD Serono, Eisai, NIH/NINDS, NPF, Allon, Acadia, GSK, Valeant, Kyowa, Johnson & Johnson, Santhera, and Schering, payment for lectures from Teva, GSK, and Medtronic, royalties from Oxford Press and Informa Healthcare, payment for development of educational presentations from Medscape, Co-Editor in Chief International Journal of Neuroscience, and DSMB member (Ceregene). K. Burchiel reports grants/grants pending from Medtronic, and owning stock/stock options in Medtronic. P. Hogarth, E. Lai, and J. Duda report no disclosures relevant to the manuscript. K. Holloway reports receiving consulting fees and grant/grants pending from Medtronic. A. Samii reports receiving payment for lectures from Teva, Ipsen, and Boehringer Ingelheim. S. Horn, J. Bronstein, and G. Stoner report no disclosures relevant to the manuscript. P. Starr reports receiving consulting fees from Medtronic. R. Simpson reports participating on advisory board and receiving consulting fees from Medtronic, and providing expert testimony. G. Baltuch, A. DeSalles, G. Huang, and D. Reda report no disclosures relevant to the manuscript. Go to Neurology.org for full disclosures. NR 30 TC 114 Z9 118 U1 4 U2 24 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUL PY 2012 VL 79 IS 1 BP 55 EP 65 DI 10.1212/WNL.0b013e31825dcdc1 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA 971BE UT WOS:000306176000014 PM 22722632 ER PT J AU Vucic, S Stein, TD Hedley-Whyte, ET Reddel, SR Tisch, S Kotschet, K Cros, D Kiernan, MC AF Vucic, Steve Stein, Thor D. Hedley-Whyte, E. Tessa Reddel, Stephen R. Tisch, Stephen Kotschet, Katya Cros, Didier Kiernan, Matthew C. TI FOSMN syndrome Novel insight into disease pathophysiology SO NEUROLOGY LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; TRANSCRANIAL MAGNETIC STIMULATION; THRESHOLD TRACKING TECHNIQUES; CORTICAL HYPEREXCITABILITY; SJOGRENS-SYNDROME; TANGIER-DISEASE; ONSET; EXCITABILITY; NEUROPATHY; MUTATIONS AB Objective: To better define the pathophysiologic mechanisms underlying the development of the novel facial-onset sensory and motor neuronopathy (FOSMN) syndrome and, in particular, to determine whether neurodegenerative processes, mediated by excitotoxicity, or autoimmune mechanisms contribute to the development of FOSMN syndrome. Methods: Clinical, laboratory, neurophysiologic, and pathologic assessments were undertaken for 5 patients with FOSMN syndrome (3 male and 2 female), the largest cohort of FOSMN syndrome reported to date. In addition to conventional neurophysiologic studies, novel threshold tracking transcranial magnetic stimulation (TMS) techniques were undertaken to assess for the presence of cortical excitability. Results: Clinically, all patients exhibited the typical FOSMN syndrome phenotype, heralded by facial-onset sensory deficits with subsequent development of motor deficits evolving in a rostral-caudal direction. Pathologic studies, including an autopsy, disclosed widespread degeneration of sensory and motor neurons with no evidence of inflammation, amyloid deposition, or intraneuronal inclusions, such as TDP-43, Bunina bodies, or ubiquitin inclusions. Conventional neurophysiologic studies revealed abnormalities of blink reflexes, along with features of motor and sensory neuronopathy. Threshold tracking TMS disclosed normal cortical excitability in patients with FOSMN syndrome, with preserved short-interval intracortical inhibition, resting motor threshold, motor evoked potential amplitude, and cortical silent period duration. Patients with FOSMN syndrome failed to respond to immunomodulatory approaches. Conclusions: Findings from the present study suggest that FOSMN syndrome is a primary neurodegenerative disorder of sensory and motor neurons, with distinct pathophysiologic mechanisms. Neurology (R) 2012; 79:73-79 C1 [Vucic, Steve] Univ Sydney, Sydney Med Sch Westmead, Sydney, NSW 2006, Australia. [Vucic, Steve; Kiernan, Matthew C.] Neurosci Res Australia, Sydney, NSW, Australia. [Stein, Thor D.; Hedley-Whyte, E. Tessa] Harvard Univ, Sch Med, Dept Pathol, CS Kubik Lab Neuropathol,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Cros, Didier] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Reddel, Stephen R.] Concord Repatriat Gen Hosp, Dept Neurol & Mol Med, Concord, Australia. [Tisch, Stephen] Univ New S Wales, St Vincents Hosp, Dept Neurol, Sydney, NSW, Australia. [Kotschet, Katya] St Vincents Hosp, Melbourne, Vic, Australia. [Kiernan, Matthew C.] Prince Wales Clin Sch, Sydney, NSW, Australia. [Kiernan, Matthew C.] Univ New S Wales, Sydney, NSW, Australia. RP Vucic, S (reprint author), Univ Sydney, Sydney Med Sch Westmead, Sydney, NSW 2006, Australia. EM s.vucic@neura.edu.au RI Kiernan, Matthew/E-4460-2011; OI Reddel, Stephen/0000-0002-0169-3350; Stein, Thor/0000-0001-6954-4477 FU Bayer Schering FX S. Vucic is a member of the scientific boards for Merck Serono Australia, Novartis, and Bayer Schering and serves as a medical consultant for Merck Serotures from sanofi-aventis. T. Stein reports no disclosures relevant to the manuscript. E. T. Hedley-Whyte reports no disclosures relevant to the manuscript. S. Reddel reports receiving grants and honoraria for lectures by Bayer Schering. S. Tisch, K. Kotschet, and D. Cros report no disclosures relevant to the manuscript. M. Kiernan reports that he is the Editor-in-Chief of the Journal of Neurology, Neurosurgery and Psychiatry (BMJ Group). Go to Neurology.org for full disclosures. NR 31 TC 14 Z9 15 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUL PY 2012 VL 79 IS 1 BP 73 EP 79 DI 10.1212/WNL.0b013e31825dce13 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 971BE UT WOS:000306176000016 PM 22722633 ER PT J AU Cheng, EM Keyhani, S Ofner, S Williams, LS Hebert, PL Ordin, DL Bravata, DM AF Cheng, Eric M. Keyhani, Salomeh Ofner, Susan Williams, Linda S. Hebert, Paul L. Ordin, Diana L. Bravata, Dawn M. TI Lower use of carotid artery imaging at minority-serving hospitals SO NEUROLOGY LA English DT Article ID ASSOCIATION/AMERICAN STROKE ASSOCIATION; HEALTH-CARE PROFESSIONALS; ETHNIC DISPARITIES; ISCHEMIC-STROKE; ENDARTERECTOMY; AMERICAN; RACE; QUALITY; MODELS; SYSTEM AB Objective: We determined whether site of care explains a previously identified racial disparity in carotid artery imaging. Methods: In this retrospective cohort study, data were obtained from a chart review of veterans hospitalized with ischemic stroke at 127 Veterans Administration hospitals in 2007. Extensive exclusion criteria were applied to obtain a sample who should have received carotid artery imaging. Minority-serving hospitals were defined as the top 10% of hospitals ranked by the proportion of stroke patients who were black. Population level multivariate logistic regression models with adjustment for correlation of patients in hospitals were used to calculate predictive probabilities of carotid artery imaging by race and minority-service hospital status. Bootstrapping was used to obtain 95% confidence intervals (CIs). Results: The sample consisted of 1,534 white patients and 628 black patients. Nearly 40% of all black patients were admitted to 1 of 13 minority-serving hospitals. No racial disparity in receipt of carotid artery imaging was detected within nonminority serving hospitals. However, the predicted probability of receiving carotid artery imaging for white patients at nonminority-serving hospitals (89.7%, 95% CI [87.3%, 92.1%]) was significantly higher than both white patients (78.0% [68.3%, 87.8%] and black patients (70.5% [59.3%, 81.6%]) at minority-serving hospitals. Conclusions: Underuse of carotid artery imaging occurred most often among patients hospitalized at minority-serving hospitals. Further work is required to explore why site of care is a mechanism for racial disparities in this clinically important diagnostic test. Neurology (R) 2012;79:138-144 C1 [Cheng, Eric M.] VA Greater Los Angeles Healthcare Syst, Dept Neurol, Los Angeles, CA USA. [Cheng, Eric M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Keyhani, Salomeh] UCSF, Div Gen Internal Med, Dept Med, San Francisco, CA USA. [Keyhani, Salomeh] San Francisco VA Med Ctr, Res Enhancement Award Program, San Francisco, CA USA. [Ofner, Susan] Indiana Univ Sch Med, Div Biostat, Indianapolis, IN USA. [Williams, Linda S.] Indiana Univ Sch Med, Dept Neurol, Indianapolis, IN USA. [Bravata, Dawn M.] Indiana Univ Sch Med, Dept Internal Med, Indianapolis, IN USA. [Williams, Linda S.; Ordin, Diana L.; Bravata, Dawn M.] Richard L Roudebush VA Med Ctr, HSR & D Ctr Implementing Evidence Based Practice, Indianapolis, IN USA. [Williams, Linda S.] Richard L Roudebush VA Med Ctr, Dept Neurol, Indianapolis, IN USA. [Hebert, Paul L.] Puget Sound Med Ctr, Ctr Excellence, VA HSR & D NW Ctr Outcomes Res Older Adults, Seattle, WA USA. [Ordin, Diana L.] Dept Vet Affairs, Off Informat & Analyt, Washington, DC USA. RP Cheng, EM (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Neurol, Los Angeles, CA USA. EM eric.cheng@va.gov FU Veterans Administration [RRP 09-184, RRP 09-185]; VHA HSR&D Center of Excellence on Implementing Evidence-Based Practice (CIEBP); Richard L. Roudebush VA Medical Center, Indianapolis; VHA HSR&D Stroke Quality Enhancement Research Initiative (QUERI) Program, Indianapolis, IN; Career Development Award from NIH/NINDS [K23NS058571]; Project EXPORT (NCMHD) [P20MD000182]; UCLA Outcomes Research Center; American Heart Association Pharmaceutical Roundtable and David and Stevie Spina; Career Development Award from the Veterans Administration FX Supported by Veterans Administration RRP 09-184 (PI: Dr. Bravata) and RRP 09-185 (PI: Dr. Keyhani) and by the VHA HSR&D Center of Excellence on Implementing Evidence-Based Practice (CIEBP), Richard L. Roudebush VA Medical Center, Indianapolis, and the VHA HSR&D Stroke Quality Enhancement Research Initiative (QUERI) Program, Indianapolis, IN. Dr. Cheng is supported by a Career Development Award from NIH/NINDS (K23NS058571), by Project EXPORT (NCMHD grants P20MD000182), and by the UCLA Outcomes Research Center, funded through the American Heart Association Pharmaceutical Roundtable and David and Stevie Spina. Dr. Keyhani is supported by a Career Development Award from the Veterans Administration. 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 34 TC 11 Z9 11 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUL PY 2012 VL 79 IS 2 BP 138 EP 144 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 971XV UT WOS:000306241000011 PM 22700815 ER PT J AU Plow, EB Obretenova, SN Fregni, F Pascual-Leone, A Merabet, LB AF Plow, Ela B. Obretenova, Souzana N. Fregni, Felipe Pascual-Leone, Alvaro Merabet, Lotfi B. TI Comparison of Visual Field Training for Hemianopia With Active Versus Sham Transcranial Direct Cortical Stimulation SO NEUROREHABILITATION AND NEURAL REPAIR LA English DT Article DE transcranial direct current stimulation (tDCS); brain stimulation; hemianopia; visual field; rehabilitation; Vision Restoration Therapy (VRT) ID VISION RESTORATION THERAPY; MAGNETIC STIMULATION; FUNCTIONAL RECOVERY; BRAIN-STIMULATION; EYE-MOVEMENTS; DOUBLE-BLIND; REHABILITATION; STROKE; PLASTICITY; DEFECTS AB Background. Vision Restoration Therapy (VRT) aims to improve visual field function by systematically training regions of residual vision associated with the activity of suboptimal firing neurons within the occipital cortex. Transcranial direct current stimulation (tDCS) has been shown to modulate cortical excitability. Objective. Assess the possible efficacy of tDCS combined with VRT. Methods. The authors conducted a randomized, double-blind, demonstration-of-concept pilot study where participants were assigned to either VRT and tDCS or VRT and sham. The anode was placed over the occipital pole to target both affected and unaffected lobes. One hour training sessions were carried out 3 times per week for 3 months in a laboratory. Outcome measures included objective and subjective changes in visual field, recording of visual fixation performance, and vision-related activities of daily living (ADLs) and quality of life (QOL). Results. Although 12 participants were enrolled, only 8 could be analyzed. The VRT and tDCS group demonstrated significantly greater expansion in visual field and improvement on ADLs compared with the VRT and sham group. Contrary to expectations, subjective perception of visual field change was greater in the VRT and sham group. QOL did not change for either group. The observed changes in visual field were unrelated to compensatory eye movements, as shown with fixation monitoring. Conclusions. The combination of occipital cortical tDCS with visual field rehabilitation appears to enhance visual functional outcomes compared with visual rehabilitation alone. TDCS may enhance inherent mechanisms of plasticity associated with training. C1 [Merabet, Lotfi B.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Plow, Ela B.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Pascual-Leone, Alvaro] Univ Autonoma Barcelona, Badalona, Spain. RP Merabet, LB (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM lotfi_merabet@meei.harvard.edu FU Novavision VRT Inc; National Institutes of Health [K23-EY016131] FX This work was supported by an investigator-initiated pilot grant from Novavision VRT Inc and by the National Institutes of Health (K23-EY016131 to LBM). NR 55 TC 32 Z9 33 U1 0 U2 9 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1545-9683 J9 NEUROREHAB NEURAL RE JI Neurorehabil. Neural Repair PD JUL-AUG PY 2012 VL 26 IS 6 BP 616 EP 626 DI 10.1177/1545968311431963 PG 11 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 969VV UT WOS:000306088400007 PM 22291042 ER PT J AU Regan, S Reyen, M Richards, AE Lockhart, AC Liebman, AK Rigotti, NA AF Regan, Susan Reyen, Michele Richards, Ann E. Lockhart, Abigail C. Liebman, Aliza K. Rigotti, Nancy A. TI Nicotine Replacement Therapy Use at Home After Use During a Hospitalization SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID SMOKING-CESSATION; AIDS; SMOKERS AB Introduction: We assessed whether providing inpatient smokers with nicotine replacement therapy (NRT) to relieve withdrawal symptoms while hospitalized was associated with self-initiated NRT use soon after hospital discharge. Methods: We conducted an observational study of 1,895 cigarette smokers admitted to a large hospital over 24 months (July 2007 through June 2009) and seen by a tobacco counselor during hospitalization. Participants were surveyed at 2 weeks after discharge to assess postdischarge NRT use. We calculated adjusted rate ratios (ARRs) for the effect of NRT use in the hospital on the rate of NRT use after discharge, adjusting for gender, age, hospital service, intention to quit, baseline smoking level, length of stay, and counseling duration. Results: 62 percent (1,166/1,895) of enrolled participants received NRT during hospitalization. The survey response rate was 72%. 42 percent (544/1,293) of survey respondents reported initiating postdischarge NRT use within 2 weeks of discharge. NRT use after discharge was more likely to be reported by those who used it in hospital whether they had ever used it prior to hospitalization (ARR: 5.64, 95% CI: 3.95-8.05) or had never used it before (ARR: 4.68, 95% CI: 3.25-6.73). Conclusions: Smokers who received NRT during a hospitalization were more likely to use it after discharge compared with those who did not use NRT in hospital. By encouraging use of this effective cessation aid, supplementing counseling with NRT for hospitalized smokers may promote smoking cessation efforts after discharge. C1 [Regan, Susan; Reyen, Michele; Richards, Ann E.; Lockhart, Abigail C.; Liebman, Aliza K.; Rigotti, Nancy A.] Massachusetts Gen Hosp, Div Gen Med, Tobacco Res & Treatment Ctr, Dept Med, Boston, MA 02114 USA. [Regan, Susan; Rigotti, Nancy A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Regan, S (reprint author), Massachusetts Gen Hosp, Div Gen Med, Tobacco Res & Treatment Ctr, Dept Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM sregan@partners.org FU National Heart, Lung, and Blood Institute [K24-HL04440]; Partners Health Care System; Pfizer; Sanofi-Aventis; Nabi Biopharmaceuticals; Free Clear, Inc. FX This work was supported by grant #K24-HL04440 from the National Heart, Lung, and Blood Institute and by Partners Health Care System.; NAR has received research grant funding from Pfizer, Sanofi-Aventis, and Nabi Biopharmaceuticals for the study of investigational and/or marketed smoking cessation products. She has received fees for consultation about smoking cessation from Pfizer (prior to July 2008) and Free & Clear, Inc. (prior to February 2009). NR 18 TC 7 Z9 7 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD JUL PY 2012 VL 14 IS 7 BP 885 EP 889 DI 10.1093/ntr/ntr244 PG 5 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 971CD UT WOS:000306179500016 PM 22121242 ER PT J AU Carroll, DL Dykes, PC Hurley, AC AF Carroll, Diane L. Dykes, Patricia C. Hurley, Ann C. TI An Electronic Fall Prevention Toolkit Effect on Documentation Quality SO NURSING RESEARCH LA English DT Article DE documentation; fall prevention; health information technology ID ACUTE-CARE HOSPITALS; INJURIES; PATIENT AB Background: Nursing documentation is the record of care that is planned and given to patients, yet it is often missing or incomplete. A study of translating results from nurses' assessments of fall risk into tailored interventions using health information technology was used to examine nursing documentation of risk assessment, plans to manage those risks, and interventions to prevent falls. Objective: The aim of this study was to evaluate the effectiveness of an electronic fall prevention toolkit for promoting documentation of fall risk status and planned and completed fall prevention interventions. Methods: Nursing documentation related to fall risk and prevention was reviewed in 30% of randomly selected medical records for patients on the eight study units (four intervention units; 5,267 patients) and four usual care units (5,116 patients) during three separate study visits. Results: Patients on the intervention units were more likely to have fall risk documented (89% vs. 64%, p < .0001). There were significantly more comprehensive plans of care for the patients on the interventions documented, although no differences were found related to documentation of completed interventions compared with usual care unit patient records. Discussion: The documentation of fall risk status and planned interventions tailored to patient-specific areas of risk was significantly better on the intervention units that used the fall prevention toolkit as compared with usual care units. Improved documentation quality did not extend to the documentation of completed interventions. C1 [Carroll, Diane L.] Massachusetts Gen Hosp, Inst Patient Care, Yvonne L Munn Ctr Nursing Res, Boston, MA 02114 USA. [Dykes, Patricia C.; Hurley, Ann C.] Brigham & Womens Hosp, Ctr Nursing Excellence, Boston, MA 02115 USA. RP Carroll, DL (reprint author), Massachusetts Gen Hosp, Inst Patient Care, Yvonne L Munn Ctr Nursing Res, Boston, MA 02114 USA. EM dcarroll3@partners.org FU Robert Wood Johnson Foundation, Interdisciplinary Nursing Quality Research Institute FX Funding for this work was given by the Robert Wood Johnson Foundation, Interdisciplinary Nursing Quality Research Institute. The authors have no conflicts of interest to disclose. NR 16 TC 5 Z9 5 U1 1 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-6562 J9 NURS RES JI Nurs. Res. PD JUL-AUG PY 2012 VL 61 IS 4 BP 309 EP 313 DI 10.1097/NNR.0b013e31825569de PG 5 WC Nursing SC Nursing GA 973KM UT WOS:000306359000009 PM 22592389 ER PT J AU Dickstein, BD Schorr, Y Stein, N Krantz, LH Solomon, Z Litz, BT AF Dickstein, Benjamin D. Schorr, Yonit Stein, Nathan Krantz, Lillian H. Solomon, Zahava Litz, Brett T. TI Coping and Mental Health Outcomes Among Israelis Living With the Chronic Threat of Terrorism SO PSYCHOLOGICAL TRAUMA-THEORY RESEARCH PRACTICE AND POLICY LA English DT Article DE coping; terrorism; Israel; PTSD ID POSTTRAUMATIC-STRESS-DISORDER; ONGOING TERRORISM; BRIEF COPE; EXPOSURE; DISTRESS; STRATEGIES; SYMPTOMS; TRAUMA; JEWS; METAANALYSIS AB Relatively little is known about how people cope with the chronic threat of terrorism or how coping behaviors relate to mental health outcomes within this context. Through the use of exploratory factor analysis, we identified seven latent coping factors among Israeli citizens living near the Gaza border, a region that has been regularly subjected to rocket and mortar attacks. Moderation analysis revealed that three coping factors (substance use coping, denial/disengagement, and social support seeking) exacerbated the relationship between terror-related exposure and psychological functioning, and that one factor (acceptance/positive reframing) protected against psychological distress. These findings help elucidate the types of coping strategies employed by individuals living with the chronic threat of terror and their impact on mental health. In addition, they underscore the need for researchers and clinicians to consider coping behaviors differently when they occur in an environment of chronic terrorist threat. C1 [Dickstein, Benjamin D.; Schorr, Yonit; Stein, Nathan; Krantz, Lillian H.; Litz, Brett T.] VA Boston Healthcare Syst, Boston, MA USA. [Schorr, Yonit; Stein, Nathan; Litz, Brett T.] Boston Univ, Sch Med, Boston, MA 02215 USA. [Solomon, Zahava] Tel Aviv Univ, Bob Shapell Sch Social Work, Tel Aviv, Israel. RP Dickstein, BD (reprint author), Vet Affairs Med Ctr, Boston Dept, VA Boston Healthcare Syst 116 B4, Boston, MA 02130 USA. EM Benjamin.Dickstein@va.gov NR 36 TC 8 Z9 8 U1 0 U2 5 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1942-9681 EI 1942-969X J9 PSYCHOL TRAUMA-US JI Psychol. Trauma PD JUL PY 2012 VL 4 IS 4 BP 392 EP 399 DI 10.1037/a0024927 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 972UD UT WOS:000306305100006 ER PT J AU DuBois, CM Beach, SR Kashdan, TB Nyer, MB Park, ER Celano, CM Huffman, JC AF DuBois, Christina M. Beach, Scott R. Kashdan, Todd B. Nyer, Maren B. Park, Elyse R. Celano, Christopher M. Huffman, Jeff C. TI Positive Psychological Attributes and Cardiac Outcomes: Associations, Mechanisms, and Interventions SO PSYCHOSOMATICS LA English DT Review ID CORONARY-HEART-DISEASE; QUALITY-OF-LIFE; MYOCARDIAL-INFARCTION PATIENTS; BYPASS GRAFT-SURGERY; ARTERY-DISEASE; DISPOSITIONAL OPTIMISM; DEPRESSIVE SYMPTOMS; RANDOMIZED-TRIAL; STRESS REDUCTION; BREAST-CANCER AB Background: Intervention research at the intersection of psychiatry and cardiology has primarily focused on the relationship between negative psychological syndromes (e.g., depression) and cardiac outcomes, with less emphasis on positive psychological attributes, such as optimism, gratitude, and well-being, as they relate to cardiac disease. Methods: Literature is reviewed in three specific areas regarding positive attributes and cardiac disease: (1) associations between positive attributes and cardiac outcomes, (2) potential mechanisms both behavioral and physiologic-by which positive psychological states may impact cardiovascular health, and (3) interventions aimed at cultivating positive psychological attributes in healthy and medically ill persons. Results: There is significant evidence that positive psychological attributes especially optimism may be independently associated with superior cardiac outcomes. Positive attributes appear to be associated with increased participation in cardiac health behaviors (e.g., healthy eating, physical activity) linked to beneficial outcomes; data linking positive psychological states and biomarkers of cardiac health (e.g., inflammatory markers) is mixed but suggests a potential association. Positive psychological interventions have consistently been associated with improved well-being and reduced depressive symptoms, though there have been few such studies in the medically ill. Conclusions: These findings regarding the relationship between positive psychological attributes and cardiac health are promising and suggest that positive psychology interventions may be worth study in this population. However, questions remain about the strength and specificity of these relationships, the most salient positive psychological attributes, and the impact of positive psychological interventions on health outcomes in cardiac patients. (Psychosomatics 2012; 53:303-318) C1 [DuBois, Christina M.; Beach, Scott R.; Nyer, Maren B.; Park, Elyse R.; Celano, Christopher M.; Huffman, Jeff C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Beach, Scott R.; Nyer, Maren B.; Park, Elyse R.; Celano, Christopher M.; Huffman, Jeff C.] Harvard Univ, Sch Med, Boston, MA USA. [Kashdan, Todd B.] George Mason Univ, Dept Psychol, Fairfax, VA 22030 USA. [Park, Elyse R.] Benson Henry Inst Mind Body Med, Boston, MA USA. RP Huffman, JC (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 55 Fruit St,Blake 11, Boston, MA 02114 USA. EM jhuffman@partners.org FU United States Disease Control and Prevention (CDC) [R01-DP00336]; Center for Consciousness and Transformation at George Mason University FX This work was supported in part by grant R01-DP00336 from the United States Disease Control and Prevention (CDC) to Herbert Benson. Todd Kashdan was funded by the Center for Consciousness and Transformation at George Mason University. NR 152 TC 35 Z9 36 U1 7 U2 35 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD JUL-AUG PY 2012 VL 53 IS 4 BP 303 EP 318 PG 16 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 970XD UT WOS:000306164700001 PM 22748749 ER PT J AU Sahani, DV Bonaffini, PA Catalano, OA Guimaraes, AR Blake, MA AF Sahani, Dushyant V. Bonaffini, Pietro A. Catalano, Onofrio A. Guimaraes, Alexander R. Blake, Michael A. TI State-of-the-Art PET/CT of the Pancreas: Current Role and Emerging Indications SO RADIOGRAPHICS LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; PHASE HELICAL CT; PAPILLARY-MUCINOUS NEOPLASM; ROW COMPUTED-TOMOGRAPHY; F-18 FDG PET/CT; AUTOIMMUNE PANCREATITIS; MULTIDETECTOR CT; FOLLOW-UP; ENDOSCOPIC ULTRASONOGRAPHY; PREOPERATIVE EVALUATION AB Fused positron emission tomography (PET)/computed tomography (CT) is a recently developed technology that couples the functional information of PET with the anatomic details of CT. Integrated PET/CT scanners produce both PET and contrast material-enhanced CT images of the entire body in one setting. Typically, the amount of fluorine 18 (F-18) fluorodeoxyglucose (FDG) uptake in normal pancreatic parenchyma is insignificant compared with that of the liver. However, both malignant (eg, adenocarcinoma) and benign (eg, acute pancreatitis) pancreatic conditions may demonstrate intense FDG uptake. PET/CT provides an opportunity to depict pancreatic tumors and distant metastases, perform preoperative staging, and monitor response to treatment, and it has proved useful in distinguishing postoperative fibrosis from recurrence. In selected cases, PET/CT findings may be used to help diagnose autoimmune pancreatitis mimicking a mass by depicting systemic involvement. PET/CT may also be used to direct biopsy to sites more likely to yield representative tumor tissue. Novel radiolabeled molecules, such as sigma-receptor ligands and F-18-3'-fluoro-3'-deoxy-l-thymidine (FLT), may play an even greater role in distinguishing tumor recurrence from postoperative fibrosis or inflammation. (C)RSNA, 2012 . radiographics.rsna.org C1 [Sahani, Dushyant V.; Guimaraes, Alexander R.; Blake, Michael A.] Harvard Univ, Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent Radiol, Sch Med,Dept Radiol, Boston, MA 02114 USA. [Bonaffini, Pietro A.] Univ Milano Bicocca, Sch Med, Dept Diagnost Radiol, Monza, Italy. [Catalano, Onofrio A.] SDN Ist Ric Diagnost Nucl, Naples, Italy. RP Sahani, DV (reprint author), Harvard Univ, Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent Radiol, Sch Med,Dept Radiol, 55 Fruit St,White 270, Boston, MA 02114 USA. EM dsahani@partners.org RI Bonaffini, Pietro/M-8067-2016 OI Bonaffini, Pietro/0000-0001-5335-9429 FU Springer FX D.V.S.: Related financial activities: none. Other financial activities: consultant for Bracco Diagnostic. M.A.B.: Related financial activities: none. Other financial activities: royalties from Springer. NR 103 TC 20 Z9 20 U1 1 U2 9 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 JUL-AUG PY 2012 VL 32 IS 4 BP 1133 EP + DI 10.1148/rg.324115143 PG 27 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 972OE UT WOS:000306285600017 PM 22786999 ER PT J AU Yeh, BM Yee, J AF Yeh, Benjamin M. Yee, Judy TI State-of-the-Art PET/CT of the Pancreas: Current Role and Emerging Indications Invited Commentary SO RADIOGRAPHICS LA English DT Editorial Material ID CT C1 [Yeh, Benjamin M.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Yee, Judy] San Francisco VA Med Ctr, Dept Radiol, San Francisco, CA USA. RP Yeh, BM (reprint author), Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. NR 7 TC 0 Z9 0 U1 0 U2 1 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 JUL-AUG PY 2012 VL 32 IS 4 BP 1158 EP 1160 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 972OE UT WOS:000306285600018 ER PT J AU Sahani, DV Guimaraes, AR Blake, MA Bonaffini, PA Catalano, OA AF Sahani, Dushyant V. Guimaraes, Alexander R. Blake, Michael A. Bonaffini, Pietro A. Catalano, Onofrio A. TI State-of-the-Art PET/CT of the Pancreas: Current Role and Emerging Indications Response SO RADIOGRAPHICS LA English DT Editorial Material ID ENDOSCOPIC ULTRASONOGRAPHY; AUTOIMMUNE PANCREATITIS; CANCER; TOMOGRAPHY C1 [Sahani, Dushyant V.; Guimaraes, Alexander R.; Blake, Michael A.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp,Div Abdominal Imaging & In, Boston, MA 02115 USA. [Bonaffini, Pietro A.] Univ Milano Bicocca, Sch Med, Dept Diagnost Radiol, Monza, Italy. [Catalano, Onofrio A.] SDN Ist Ric Diagnost Nucl, Naples, Italy. RP Sahani, DV (reprint author), Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp,Div Abdominal Imaging & In, Boston, MA 02115 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD JUL-AUG PY 2012 VL 32 IS 4 BP 1160 EP 1160 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 972OE UT WOS:000306285600019 ER PT J AU van Kimmenade, RRJ Januzzi, JL AF van Kimmenade, Roland R. J. Januzzi, James L. TI Red Cell Distribution Width Measurement: What Role Does It Have in Heart Failure? SO REVISTA ESPANOLA DE CARDIOLOGIA LA English DT Editorial Material ID NATRIURETIC PEPTIDE; PROGNOSTIC MARKER; ERYTHROPOIETIN; ANEMIA; RISK C1 [Januzzi, James L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [van Kimmenade, Roland R. J.] Univ Med Ctr Utrecht, Dept Cardiol, Utrecht, 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 NR 13 TC 3 Z9 3 U1 0 U2 1 PU EDICIONES DOYMA S A PI BARCELONA PA TRAV DE GRACIA 17-21, 08021 BARCELONA, SPAIN SN 0300-8932 J9 REV ESP CARDIOL JI Rev. Esp. Cardiol. PD JUL PY 2012 VL 65 IS 7 BP 593 EP 594 DI 10.1016/j.rec.2012.02.017 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 972LU UT WOS:000306279400001 PM 22608018 ER PT J AU Hideshima, T Anderson, KC AF Hideshima, Teru Anderson, Kenneth C. TI Biologic Impact of Proteasome Inhibition in Multiple Myeloma Cells-From the Aspects of Preclinical Studies SO SEMINARS IN HEMATOLOGY LA English DT Article ID NF-KAPPA-B; THERAPEUTIC IMPLICATIONS; IN-VITRO; BORTEZOMIB; APOPTOSIS; DEGRADATION; PS-341; ACTIVATION; MECHANISMS; RESISTANCE AB The ubiquitin-proteasome pathway (UPP) is a major protein degradation system that maintains homeostasis of intracellular proteins, involved in DNA repair, cell cycle regulation, cell proliferation, and drug resistance. Since numerous proteins are processed by proteasomes, their inhibition triggers dramatic disruption of protein homeostasis. Consequently, accumulation of polyubiquitinated proteins triggers different types of cellular stress responses, followed by growth arrest and cytotoxicity. Importantly, multiple myeloma (MM) cells are considered to have lower threshold against these stresses than other cell types, which makes these cells sensitive to proteasome inhibitors. Semin Hematol 49:223-227. (C) 2012 Elsevier Inc. All rights reserved. C1 [Hideshima, Teru] Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Hideshima, T (reprint author), Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM teru_hideshima@dfci.harvard.edu FU NCI NIH HHS [P01 CA078378, P50 CA100707, R01 CA050947] NR 32 TC 9 Z9 10 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 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD JUL PY 2012 VL 49 IS 3 BP 223 EP 227 DI 10.1053/j.seminhematol.2012.04.006 PG 5 WC Hematology SC Hematology GA 970TX UT WOS:000306156300005 PM 22726545 ER PT J AU Bauman, WA Biering-Sorensen, F Krassioukov, A AF Bauman, W. A. Biering-Sorensen, F. Krassioukov, A. TI International spinal cord injury endocrine and metabolic basic data set (version 1.2) SO SPINAL CORD LA English DT Letter C1 [Bauman, W. A.] James J Peters Vet Affairs Med Ctr, Vet Affairs Rehabil Res & Dev Ctr Excellence Med, Bronx, NY USA. [Biering-Sorensen, F.] Univ Copenhagen, Rigshosp, Clin Spinal Cord Injuries, Ctr Neurosci, DK-2100 Copenhagen, Denmark. [Biering-Sorensen, F.] Univ Copenhagen, Fac Hlth Sci, Copenhagen, Denmark. [Krassioukov, A.] Univ British Columbia, Dept Med, ICORD, Vancouver, BC, Canada. [Krassioukov, A.] Vancouver Coastal Hlth, Vancouver, BC, Canada. RP Bauman, WA (reprint author), James J Peters Vet Affairs Med Ctr, Vet Affairs Rehabil Res & Dev Ctr Excellence Med, Bronx, NY USA. EM william.bauman@va.gov NR 1 TC 4 Z9 4 U1 0 U2 2 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 JUL PY 2012 VL 50 IS 7 BP 567 EP 567 DI 10.1038/sc.2012.37 PG 1 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 972NB UT WOS:000306282700021 PM 22508533 ER PT J AU Rankin, JK Jakobiec, FA Zakka, FR Foster, CS AF Rankin, Jessica K. Jakobiec, Frederick A. Zakka, Fouad R. Foster, C. Stephen TI An Improved Approach to Diagnosing and Treating Conjunctival Mucoepidermoid Carcinoma SO SURVEY OF OPHTHALMOLOGY LA English DT Review DE mucoepidermoid carcinoma; squamous cell carcinoma; conjunctiva; salivary glands; intraocular invasion; goblet cells; mucus; Alcian blue; mucicarmine; immunohistochemistry; CK7 ID SQUAMOUS-CELL CARCINOMA; OF-THE-LITERATURE; INTRAOCULAR INVASION; FEATURES; PATIENT; EXPRESSION; NEOPLASIA; TUMORS; GLAND AB The current case of conjunctival mucoepidermoid carcinoma offers features that expand the biologic spectrum afforded by this tumor. More focused strategies should be developed for its earlier histopathologic diagnosis and improved management (historical recurrence rate of 85%). A 63-year-old woman with a history, of rheumatoid arthritis and idiopathic sclerosing cholangitis developed scleral thinning, anterior chamber cells and flare, and uveal prolapse. Biopsies of the epibulbar lesion were initially misinterpreted as a squamous cell carcinoma but on review harbored CK7-positive cells and contained rare goblet cells brought. out with Alcian blue and mucicarmine staining. Intraocular extension exhibited micro-and macrocysts with minimal goblet cells. Focal CK7 immunopositivity in any epibulbar squamous dysplasia or in invasive carcinoma should lead to suspicion of a mucoepidermoid carcinoma. Behaviorally aggressive or rapidly recurrent epithelial squamous tumors with "inflammatory" features or unusual clinical characteristics should be initially stained at multiple levels for the detection of parsimonious mucus secretion. Surgical options include wide excision and partial sclerectomy with cryotherapy for superficial invasion and/or interferon therapy. Results with radiotherapy and cryotherapy for deep scleral invasion have been unpredictable or unacceptable compared with surgery. (Surv Ophthalmol 57:337-346, 2012. (c) 2012 Elsevier Inc. All rights reserved.) C1 [Rankin, Jessica K.; Jakobiec, Frederick A.; Zakka, Fouad R.; Foster, C. Stephen] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. [Rankin, Jessica K.; Jakobiec, Frederick A.; Zakka, Fouad R.] Massachusetts Eye & Ear Infirm, Cogan Eye Pathol Lab, Boston, MA 02114 USA. [Foster, C. Stephen] Massachusetts Eye Res & Surg Inst, Cambridge, MA USA. RP Jakobiec, FA (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Suite 32,243 Charles St, Boston, MA 02114 USA. EM Fred_Jakobiec@MEEI.Harvard.edu NR 45 TC 4 Z9 5 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6257 EI 1879-3304 J9 SURV OPHTHALMOL JI Surv. Ophthalmol. PD JUL-AUG PY 2012 VL 57 IS 4 BP 337 EP 346 DI 10.1016/j.survophthal.2011.12.002 PG 10 WC Ophthalmology SC Ophthalmology GA 971HL UT WOS:000306194600003 PM 22541742 ER PT J AU Yu, BL Lei, C Baron, DM Steinbicker, AU Bloch, KD Zapol, WM AF Yu, Binglan Lei, Chong Baron, David M. Steinbicker, Andrea U. Bloch, Kenneth D. Zapol, Warren M. TI Diabetes augments and inhaled nitric oxide prevents the adverse hemodynamic effects of transfusing syngeneic stored blood in mice SO TRANSFUSION LA English DT Article ID RED-CELL STORAGE; CARDIAC-SURGERY; UNIVERSAL LEUKOREDUCTION; INDEPENDENT PREDICTOR; PROLONGED STORAGE; PLASMA HEMOGLOBIN; CRITICALLY-ILL; SEVERE INJURY; BANKED BLOOD; MOUSE MODEL AB BACKGROUND: Stored red blood cells (RBCs) undergo progressive deleterious functional, biochemical, and structural changes. The mechanisms responsible for the adverse effects of transfusing stored RBCs remain incompletely elucidated. STUDY DESIGN AND METHODS: Awake wild-type (WT) mice, WT mice fed a high-fat diet (HFD-fed WT) for 4 to 6 weeks, and diabetic (db/db) mice were transfused with syngeneic leukoreduced RBCs or supernatant with or without oxidation (10% of total blood volume) after storage for not more than 24 hours (FRBCs) or 2 weeks (SRBCs). Inhaled nitric oxide (NO) at 80 parts per million was administered to a group of mice transfused with SRBCs. Blood and tissue samples were collected 2 hours after transfusion to measure iron and cytokine levels. RESULTS: SRBCs had altered RBC morphology and a reduced P50. Transfusion of SRBCs into WT or HFD-fed WT mice did not produce systemic hemodynamic changes. In contrast, transfusion of SRBCs or supernatant from SRBCs into db/db mice induced systemic hypertension that was prevented by concurrent inhalation of NO. Infusion of washed SRBCs or oxidized SRBC supernatant into db/db mice did not induce hypertension. Two hours after SRBC transfusion, plasma hemoglobin (Hb), interleukin-6, and serum iron levels were increased. CONCLUSION: Transfusion of syngeneic SRBCs or the supernatant from SRBCs produces systemic hypertension and vasoconstriction in db/db mice. It is likely that RBC storage, by causing in vitro hemolysis and posttransfusion hemoglobinemia, produces sustained NO scavenging and vasoconstriction in mice with endothelial dysfunction. Vasoconstriction is prevented by oxidizing the supernatant of SRBCs or breathing NO during SRBC transfusion. C1 [Yu, Binglan; Lei, Chong; Baron, David M.; Steinbicker, Andrea U.; Bloch, Kenneth D.; Zapol, Warren M.] Harvard Univ, Massachusetts Gen Hosp, Anesthesia Ctr Crit Care Res, Dept Anesthesia Crit Care & Pain Med,Sch Med, Boston, MA 02114 USA. RP Zapol, WM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Anesthesia Ctr Crit Care Res, Dept Anesthesia Crit Care & Pain Med,Sch Med, 55 Fruit St,Thier 503, Boston, MA 02114 USA. EM wzapol@partners.org FU Eleanor and Miles Shore 50th Anniversary Fellowship [217249]; National Natural Science Foundation of China [81000232]; NHLBI [R01 DK082971]; Ikaria, Inc. FX This work was supported by Eleanor and Miles Shore 50th Anniversary Fellowship (217249) to BY at Harvard Medical School and by grants from the National Natural Science Foundation of China to CL (81000232) and from the NHLBI (R01 DK082971) to KDB.; WMZ receives royalties from patents on inhaled nitric oxide licensed by Massachusetts General Hospital to Linde Corp., Munich, Germany, and Ikaria, Inc., Clinton, NJ. KDB has received grants from Ikaria, Inc., to study inhaled nitric oxide. WMZ and BY have applied for patents on inhaled nitric oxide and blood transfusion. The remaining authors report no conflicts of interest. NR 49 TC 29 Z9 29 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUL PY 2012 VL 52 IS 7 BP 1410 EP 1422 DI 10.1111/j.1537-2995.2011.03473.x PG 13 WC Hematology SC Hematology GA 972PO UT WOS:000306289500006 PM 22233290 ER PT J AU MacArthur, DG Lek, M AF MacArthur, Daniel G. Lek, Monkol TI The uncertain road towards genomic medicine SO TRENDS IN GENETICS LA English DT Editorial Material AB Cheap, high-throughput approaches to generating biological data are transforming biology into a data-driven science and promise to similarly transform medicine. However, the road to genomic medicine is paved with challenges and uncertainty. C1 [MacArthur, Daniel G.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [MacArthur, Daniel G.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Lek, Monkol] Childrens Hosp Westmead, Inst Neurosci & Muscle Res, Westmead, NSW 2145, Australia. RP MacArthur, DG (reprint author), Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. EM macarthur@atgu.mgh.harvard.edu NR 5 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD JUL PY 2012 VL 28 IS 7 BP 303 EP 305 DI 10.1016/j.tig.2012.05.001 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 972BU UT WOS:000306252300001 PM 22658726 ER PT J AU Leape, LL Shore, MF Dienstag, JL Mayer, RJ Edgman-Levitan, S Meyer, GS Healy, GB AF Leape, Lucian L. Shore, Miles F. Dienstag, Jules L. Mayer, Robert J. Edgman-Levitan, Susan Meyer, Gregg S. Healy, Gerald B. TI Perspective: A Culture of Respect, Part 1: The Nature and Causes of Disrespectful Behavior by Physicians SO ACADEMIC MEDICINE LA English DT Article ID SHARED DECISION-MAKING; MEDICAL-STUDENTS; PATIENT SAFETY; BURNOUT; INTERNS; RISK; CARE; MORTALITY; RESIDENTS; NURSES AB A substantial barrier to progress in patient safety is a dysfunctional culture rooted in widespread disrespect. The authors identify a broad range of disrespectful conduct, suggesting six categories for classifying disrespectful behavior in the health care setting: disruptive behavior; humiliating, demeaning treatment of nurses, residents, and students; passive-aggressive behavior; passive disrespect; dismissive treatment of patients; and systemic disrespect. At one end of the spectrum, a single disruptive physician can poison the atmosphere of an entire unit. More common are everyday humiliations of nurses and physicians in training, as well as passive resistance to collaboration and change. Even more common are lesser degrees of disrespectful conduct toward patients that are taken for granted and not recognized by health workers as disrespectful. Disrespect is a threat to patient safety because it inhibits collegiality and cooperation essential to teamwork, cuts off communication, undermines morale, and inhibits compliance with and implementation of new practices. Nurses and students are particularly at risk, but disrespectful treatment is also devastating for patients. Disrespect underlies the tensions and dissatisfactions that diminish joy and fulfillment in work for all health care workers and contributes to turnover of highly qualified staff. Disrespectful behavior is rooted, in part, in characteristics of the individual, such as insecurity or aggressiveness, but it is also learned, tolerated, and reinforced in the hierarchical hospital culture. A major contributor to disrespectful behavior is the stressful health care environment, particularly the presence of "production pressure," such as the requirement to see a high volume of patients. C1 [Leape, Lucian L.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Shore, Miles F.] Harvard Univ, Sch Med, Promot & Review Board, Boston, MA 02115 USA. [Mayer, Robert J.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Edgman-Levitan, Susan] Massachusetts Gen Hosp, Stoeckle Ctr Primary Care Innovat, Boston, MA 02114 USA. [Healy, Gerald B.] Inst Healthcare Improvement, Cambridge, MA USA. RP Leape, LL (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, 677 Huntington Ave, Boston, MA 02115 USA. EM leape@hsph.harvard.edu NR 59 TC 75 Z9 76 U1 5 U2 43 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-2446 EI 1938-808X J9 ACAD MED JI Acad. Med. PD JUL PY 2012 VL 87 IS 7 BP 845 EP 852 DI 10.1097/ACM.0b013e318258338d PG 8 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 967HL UT WOS:000305897400010 PM 22622217 ER PT J AU Leape, LL Shore, MF Dienstag, JL Mayer, RJ Edgman-Levitan, S Meyer, GS Healy, GB AF Leape, Lucian L. Shore, Miles F. Dienstag, Jules L. Mayer, Robert J. Edgman-Levitan, Susan Meyer, Gregg S. Healy, Gerald B. TI Perspective: A Culture of Respect, Part 2: Creating a Culture of Respect SO ACADEMIC MEDICINE LA English DT Article ID HIGH-RELIABILITY ORGANIZATIONS; APPRECIATIVE INQUIRY; PROFESSIONALISM; LESSONS; SYSTEMS AB Creating a culture of respect is the essential first step in a health care organization's journey to becoming a safe, high-reliability organization that provides a supportive and nurturing environment and a workplace that enables staff to engage wholeheartedly in their work. A culture of respect requires that the institution develop effective methods for responding to episodes of disrespectful behavior while also initiating the cultural changes needed to prevent such episodes from occurring. Both responding to and preventing disrespect are major challenges for the organization's leader, who must create the preconditions for change, lead in establishing and enforcing policies, enable frontline worker engagement, and facilitate the creation of a safe learning environment. When disrespectful behavior occurs, it must be addressed consistently and transparently. Central to an effective response is a code of conduct that establishes unequivocally the expectation that everyone is entitled to be treated with courtesy, honesty, respect, and dignity. The code must be enforced through a clear and explicit process and applied consistently regardless of rank or station. Creating a culture of respect requires action on many fronts: modeling respectful conduct; educating students, physicians, and nonphysicians on appropriate behavior; conducting performance evaluations to identify those in need of help; providing counseling and training when needed; and supporting frontline changes that increase the sense of fairness, transparency, collaboration, and individual responsibility. C1 [Leape, Lucian L.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Shore, Miles F.] Harvard Univ, Sch Med, Promot & Review Board, Boston, MA 02115 USA. [Mayer, Robert J.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Edgman-Levitan, Susan] Massachusetts Gen Hosp, Stoeckle Ctr Primary Care Innovat, Boston, MA 02114 USA. [Healy, Gerald B.] Inst Healthcare Improvement, Cambridge, MA USA. RP Leape, LL (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, 677 Huntington Ave, Boston, MA 02115 USA. EM leape@hsph.harvard.edu NR 26 TC 60 Z9 60 U1 3 U2 25 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD JUL PY 2012 VL 87 IS 7 BP 853 EP 858 DI 10.1097/ACM.0b013e3182583536 PG 6 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 967HL UT WOS:000305897400011 PM 22622219 ER PT J AU Shea, JA Weissman, A McKinney, S Silber, JH Volpp, KG AF Shea, Judy A. Weissman, Arlene McKinney, Sean Silber, Jeffrey H. Volpp, Kevin G. TI Internal Medicine Trainees' Views of Training Adequacy and Duty Hours Restrictions in 2009 SO ACADEMIC MEDICINE LA English DT Article ID WORK-HOURS; RESIDENTS PERCEPTIONS; ACCREDITATION-COUNCIL; SURGICAL RESIDENTS; HOURS REGULATIONS; SLEEP; MORTALITY; REFORM; IMPACT; REQUIREMENTS AB Purpose To gauge internal medicine (IM) trainees' perceptions regarding aspects of their inpatient rotations, including supervision, educational opportunities, the perceived effect of duty hours regulations on quality of patient care, the causes of medical errors, and sleep. Method The authors analyzed the results of questionnaires administered to trainees following the October 2009 in-training examinations (ITE). Results Of the 21,768 IM trainees in postgraduate years 1 through 3 who took the IM-ITE, 18,272 (83.9%) responded. The majority of these trainees (87.7%) reported that supervision was adequate, and nearly half (46.3%) reported insufficient or minimal time to participate in learning activities. Two-thirds or more thought that specific work regulations such as limited shift length and more time off after nights and extended shifts would at least "occasionally," if not "usually" or "always," improve patient care. IM trainees at least "occasionally" attributed errors to workload (68.8% of respondents), fatigue (66.9%), inexperience or lack of knowledge (61.0%), incomplete handoffs (60.2%), and insufficient ancillary staff (53.5%). IM trainees' sleep hours were limited during extended and overnight shifts. Conclusions IM trainees agree that limited educational opportunities are the weakest part of the average inpatient rotation. Few have complaints about the adequacy of supervision. These trainees' optimism regarding the positive influence of potential work hours restrictions on patient care and their views of likely causes of medical errors suggest the need for innovative patient care schedules and education curricula. C1 [Shea, Judy A.; Silber, Jeffrey H.; Volpp, Kevin G.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Weissman, Arlene] Amer Coll Physicians, Res Ctr, Philadelphia, PA USA. [McKinney, Sean] Amer Coll Physicians, Self Assessment Programs, Philadelphia, PA USA. [Silber, Jeffrey H.; Volpp, Kevin G.] Univ Penn, Wharton Sch Business, Philadelphia, PA 19104 USA. [Volpp, Kevin G.] Univ Penn, Philadelphia Vet Affairs Med Ctr, CHERP, Philadelphia, PA 19104 USA. RP Shea, JA (reprint author), Univ Penn, Perelman Sch Med, 1223 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM sheaja@mail.med.upenn.edu FU NHLBI [1R01HL094593] FX The work was supported by NHLBI grant #1R01HL094593: Work Hour Regulation for Physician Trainees: Educational and Clinical Outcomes (Volpp). NR 30 TC 6 Z9 6 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-2446 EI 1938-808X J9 ACAD MED JI Acad. Med. PD JUL PY 2012 VL 87 IS 7 BP 889 EP 894 DI 10.1097/ACM.0b013e3182582583 PG 6 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 967HL UT WOS:000305897400017 PM 22622211 ER PT J AU Shea, JA Willett, LL Borman, KR Itani, KMF McDonald, FS Call, SA Chaudhry, S Adams, M Chacko, KM Volpp, KG Arora, VM AF Shea, Judy A. Willett, Lisa L. Borman, Karen R. Itani, Kamal M. F. McDonald, Furman S. Call, Stephanie A. Chaudhry, Saima Adams, Michael Chacko, Karen M. Volpp, Kevin G. Arora, Vineet M. TI Anticipated Consequences of the 2011 Duty Hours Standards: Views of Internal Medicine and Surgery Program Directors SO ACADEMIC MEDICINE LA English DT Article ID RESIDENCY PROGRAM; ACCREDITATION COUNCIL; SURGICAL RESIDENTS; NATIONAL-SURVEY; HOURS REFORM; IMPACT; ACGME; REGULATIONS; EDUCATION; MORTALITY AB Purpose To assess internal medicine (IM) and surgery program directors' views of the likely effects of the 2011 Accreditation Council for Graduate Medical Education duty hours regulations. Method In fall 2010, investigators surveyed IM and surgery program directors, assessing their views of the likely impact of the 2011 duty hours standards on learning environment, workload, education opportunities, program administration, and patient outcomes. Results Of 381 IM program directors, 287 (75.3%) responded; of 225 surgery program directors, 118 (52.4%) responded. Significantly more surgeons than internists indicated that the new regulations would likely negatively impact learning climate, including faculty morale and residents' relationships (P < .001). Most leaders in both specialties (80.8% IM, 80.2% surgery) felt that the regulations would likely increase faculty workload (P = .73). Both IM (82.2%) and surgery (96.6%) leaders most often rated, of all education opportunities, first-year resident clinical experience to be adversely affected (P < .001). Respondents from both specialties indicated that they will hire more nonphysician/midlevel providers (59.5% IM, 89.0% surgery, P < .001) and use more nonteaching services (66.8% IM, 70.1% surgery, P = .81). Respondents expect patient safety (45.1% IM, 76.9% surgery, P < .001) and continuity of care (83.6% IM across all training levels, 97.5% surgery regarding first-year residents) to decrease. Conclusions IM and surgery program directors agree that the 2011 duty hours regulations will likely negatively affect the quality of the learning environment, workload, education opportunities, program administration, and patient outcomes. Careful evaluation of actual impact is important. C1 [Shea, Judy A.; Volpp, Kevin G.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Willett, Lisa L.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Borman, Karen R.] Abington Mem Hosp, Philadelphia, PA USA. [Borman, Karen R.] Temple Univ, Sch Med, Philadelphia, PA 19122 USA. [Itani, Kamal M. F.] Vet Affairs Boston Hlth Care Syst, Surg Serv, Boston, MA USA. [Itani, Kamal M. F.] Boston Univ, Boston, MA 02215 USA. [McDonald, Furman S.] Mayo Clin Internal Med Residency, Rochester, MN USA. [Call, Stephanie A.] Virginia Commonwealth Univ, Richmond, VA USA. [Chaudhry, Saima] Hofstra N Shore LIJ Sch Med, Residency Program Internal Med, Hempstead, NY USA. [Adams, Michael] MedStar Georgetown Univ Hosp, Washington, DC USA. [Chacko, Karen M.] Univ Colorado, Primary Care Internal Med Residency Training Prog, Denver, CO 80202 USA. [Volpp, Kevin G.] Univ Penn, CHERP, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Volpp, Kevin G.] Univ Penn, Wharton Sch Business, Philadelphia, PA 19104 USA. [Arora, Vineet M.] Univ Chicago, Dept Med, Chicago, IL 60637 USA. RP Shea, JA (reprint author), Univ Penn, Perelman Sch Med, 1223 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM sheaja@mail.med.upenn.edu OI Arora, Vineet/0000-0002-4745-7599 FU National Heart, Lung, and Blood Institute [1R01HL094593] FX The work was supported by National Heart, Lung, and Blood Institute grant no. 1R01HL094593: Work Hour Regulation for Physician Trainees: Educational and Clinical Outcomes (Volpp). NR 32 TC 21 Z9 21 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-2446 EI 1938-808X J9 ACAD MED JI Acad. Med. PD JUL PY 2012 VL 87 IS 7 BP 895 EP 903 DI 10.1097/ACM.0b013e3182584118 PG 9 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 967HL UT WOS:000305897400018 PM 22622221 ER PT J AU Hauer, KE Carney, PA Chang, A Satterfield, J AF Hauer, Karen E. Carney, Patricia A. Chang, Anna Satterfield, Jason TI Behavior Change Counseling Curricula for Medical Trainees: A Systematic Review SO ACADEMIC MEDICINE LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; PATIENT-CENTERED APPROACH; FAMILY-PRACTICE RESIDENTS; SEXUAL HISTORY INQUIRY; PRIMARY-CARE PRACTICE; SMOKING-CESSATION; STANDARDIZED PATIENTS; HEALTH-CARE; UNITED-STATES; EDUCATION RESEARCH AB Purpose Unhealthy behaviors contribute to half of U. S. deaths. However, physicians lack sufficient skill in counseling patients to change behaviors. Characterizing effective published curricular interventions for behavior change counseling for medical trainees would inform educators toward improved training. Method The authors conducted a systematic literature search of studies published between 1965 and 2011 evaluating curricula on behavior change counseling for medical trainees. Included studies described behavior change counseling, teaching interventions for medical trainees, and assessment of interventions. The authors extracted eligible articles, rated outcomes for learners and patients using Kirkpatrick's hierarchy, and determined study quality. Results Of 2,788 identified citations, 109 met inclusion criteria. Most studies were performed in the United States (98), 93 at a single institution, and 81 in primary care settings. Curricular topics for counseling included smoking (67 studies), nutrition (30), alcohol/drug use (26), and exercise (22). Although most studies did not include theoretical frameworks, 39 used the Transtheoretical Model of Change. Sixty-two studies involved eight or fewer hours of curricular time, and 51 spanned four or fewer weeks. The studies with highest-level outcomes and quality employed multiple curricular techniques and included practice of counseling techniques in either simulated or actual clinical settings. Conclusions Existing literature suggests that trainees learn behavior change counseling through active, realistic practice and implementation of reminder and feedback systems within actual clinical practice settings. Multiinstitutional medical education research on methods of teaching behavior change counseling that influence patients' health outcomes are needed to ensure trainees' clinical competence and improve patient care. C1 [Hauer, Karen E.; Satterfield, Jason] Univ Calif San Francisco, Dept Med, Sch Med, San Francisco, CA 94143 USA. [Carney, Patricia A.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Chang, Anna] Dept Med, Div Geriatr, San Francisco, CA USA. [Chang, Anna] San Francisco VA Med Ctr, San Francisco, CA USA. RP Hauer, KE (reprint author), Univ Calif San Francisco, Dept Med, Sch Med, 505 Parnassus Ave,M1078,Box 0120, San Francisco, CA 94143 USA. EM karen.hauer@ucsf.edu FU NIH/NCCAM [K07 AT003131]; NIH.NCI [CA121457]; University of California, San Francisco Department of Medicine; Haile T. Debas Academy of Medical Educators FX This study was funded in part by NIH/NCCAM (K07 AT003131-Drs. Satterfield, Hauer), the Gold-Headed Cane Endowed Education Chair in Internal Medicine (University of California, San Francisco Department of Medicine and the Haile T. Debas Academy of Medical Educators) (Dr. Hauer), and NIH.NCI CA121457 (Dr. Carney). NR 86 TC 20 Z9 20 U1 3 U2 18 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD JUL PY 2012 VL 87 IS 7 BP 956 EP 968 DI 10.1097/ACM.0b013e31825837be PG 13 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 967HL UT WOS:000305897400026 PM 22622220 ER PT J AU White, JM Mimiaga, MJ Krakower, DS Mayer, KH AF White, Jaclyn M. Mimiaga, Matthew J. Krakower, Douglas S. Mayer, Kenneth H. TI Evolution of Massachusetts Physician Attitudes, Knowledge, and Experience Regarding the Use of Antiretrovirals for HIV Prevention SO AIDS PATIENT CARE AND STDS LA English DT Article ID PREEXPOSURE PROPHYLAXIS; SEXUAL RISK; DRUG-RESISTANCE; MIXED METHODS; PRIMARY-CARE; MEN; IMPLEMENTATION; TRANSMISSION; INFECTION; BEHAVIOR AB The Center for the AIDS Programme of Research in South Africa (CAPRISA) 004 and Pre-exposure Prophylaxis Initiative (iPrEx) studies demonstrated that topical or oral chemoprophylaxis could decrease HIV transmission. Yet to have an appreciable public health impact, physicians will need to be educated about these new HIV prevention modalities. Massachusetts physicians were recruited via e-mail to complete an online survey of their knowledge and use of HIV prevention interventions. Data were collected before (July-December, 2010) (n = 178) and after (December, 2010-April, 2011) (n = 115) the release of iPrEx data. Over the two time intervals, knowledge of oral PrEP significantly increased (79% to 92%, p < 0.01), whereas knowledge about topical microbicides was already high (89% pre-iPrEx). Post-iPrEx, specialists were more knowledgeable about oral PrEP (p < 0.01) and topical microbicides (p < 0.001) than generalists. The majority of the respondents would prefer to prescribe topical microbicides (75%) than oral PrEP (25%; p < 0.001), primarily because they perceived fewer side effects (95%). Respondents indicated that PrEP should be available if it were a highly effective, daily pill; however, ongoing concerns included: potential drug resistance (93%), decreased funds for other forms of HIV prevention (88%), medication side effects (83%), and limited data regarding PrEP's clinical efficacy (75%). Participants indicated that formal CDC guidelines would have the greatest impact on their willingness to prescribe PrEP (96%). Among Massachusetts physicians sampled, chemoprophylaxis knowledge was high, but current experience was limited. Although topical gel was preferred, responses suggest a willingness to adapt practices pending additional efficacy data and further guidance from normative bodies. Educational programs aimed at incorporating antiretroviral chemoprophylaxis into physicians' HIV prevention practices are warranted. C1 [White, Jaclyn M.; Mimiaga, Matthew J.; Mayer, Kenneth H.] Fenway Hlth, Fenway Inst, Boston, MA 02215 USA. [Mimiaga, Matthew J.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02215 USA. [Mimiaga, Matthew J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. [Krakower, Douglas S.; Mayer, Kenneth H.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA. RP Mayer, KH (reprint author), Fenway Hlth, Fenway Inst, 1340 Boylston St, Boston, MA 02215 USA. EM Mayer@fenwayhealth.org FU Gilead Sciences; Harvard T32 post-doctoral HIV Clinical Research Fellowship [NIAID AI 007433] FX The current study was funded by an unrestricted grant from Gilead Sciences (www.gilead.com). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Dr. Krakower was supported by the Harvard T32 post-doctoral HIV Clinical Research Fellowship (Grant NIAID AI 007433). NR 36 TC 38 Z9 38 U1 0 U2 9 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 JUL PY 2012 VL 26 IS 7 BP 395 EP 405 DI 10.1089/apc.2012.0030 PG 11 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 970AW UT WOS:000306101500004 PM 22694239 ER PT J AU McBane, S Thomas, T Karr, S Kelley, KW AF McBane, Sarah Thomas, Tyan Karr, Samantha Kelley, Kristi W. TI Serving as a student preceptor: Focus on emerging challenges SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Editorial Material ID EDUCATION C1 [McBane, Sarah] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA. [Thomas, Tyan] Univ Sci Philadelphia, Philadelphia Coll Pharm, Philadelphia, PA USA. [Thomas, Tyan] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Karr, Samantha] Midwestern Univ, Coll Pharm Glendale, Glendale, AZ USA. [Kelley, Kristi W.] Auburn Univ, Harrison Sch Pharm, Auburn, AL 36849 USA. [Kelley, Kristi W.] Baptist Hlth Syst Inc, Continu Clin, Trinity Med Ctr, Birmingham, AL USA. RP McBane, S (reprint author), Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, 9500 Gilman Dr,MC 0719, La Jolla, CA 92093 USA. EM smcbane@ucsd.edu NR 9 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD JUL 1 PY 2012 VL 69 IS 13 BP 1110 EP 1111 DI 10.2146/ajhp110291 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 969EB UT WOS:000306037400013 PM 22722589 ER PT J AU Okanobo, A Chauhan, SK Dastjerdi, MH Kodati, S Dana, R AF Okanobo, Andre Chauhan, Sunil K. Dastjerdi, Mohammad H. Kodati, Shilpa Dana, Reza TI Efficacy of Topical Blockade of Interleukin-1 in Experimental Dry Eye Disease SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID GROWTH-FACTOR C; RECEPTOR ANTAGONIST; CORNEAL EPITHELIUM; DESICCATING STRESS; LANGERHANS CELLS; DENDRITIC CELLS; T-CELLS; LYMPHANGIOGENESIS; MACROPHAGES; INFLAMMATION AB PURPOSE: To evaluate the therapeutic efficacy of topical interleukin-1 receptor antagonist (IL-1Ra) in the treatment of dry eye disease. DESIGN: Laboratory investigation. METHODS: Dry eye disease was induced in C57BL/6 female mice through exposure to a desiccating environment within a controlled environment chamber. Topical formulations containing 5% IL-1Ra, 1% methylprednisolone, 0.05% cyclosporin A, and a vehicle control containing carboxymethylcellulose sodium were applied after the induction of dry eye. Corneal fluorescein staining was performed by a masked observer in the different treatment groups. Immunohistochemical studies were undertaken to enumerate corneal CD11b+ cells, as well as to evaluate corneal lymphangiogenesis. Real-time polymerase reaction was used to quantify the expression of interleukin-1 beta in the cornea. RESULTS: A significant decrease in corneal fluorescein staining was observed after topical treatment with 5% IL-1Ra (P < .01), 1% methylprednisolone (P < .01), and 0.05% cyclosporin A (P < .03). Additionally, a significant decrease in the numbers of central corneal CD11b+ cells (P < .05), corneal lymphatic growth (P < .05), and corneal interleukin-1 beta expression (P < .003), compared with vehicle treated, were demonstrated only after treatment with 5% IL-1Ra and 1% methylprednisolone, and were absent after cyclosporin A treatment. CONCLUSIONS: Topical treatment with IL-1Ra is effective in ameliorating the clinical signs of the dry eye disease, as well as in reducing underlying inflammation. These effects are comparable with those resulting from treatment with topical methylprednisolone. Topical IL-1Ra may hold promise as a novel therapeutic strategy in the treatment of dry eye. (Am J Ophthalmol 2012; 154:63-71. (C) 2012 by Elsevier Inc. All rights reserved.) C1 [Okanobo, Andre; Chauhan, Sunil K.; Dastjerdi, Mohammad H.; Kodati, Shilpa; Dana, Reza] Harvard Univ, Schepens Eye Res Inst, Sch Med, Boston, MA 02114 USA. [Okanobo, Andre; Chauhan, Sunil K.; Dastjerdi, Mohammad H.; Kodati, Shilpa; Dana, Reza] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. RP Dana, R (reprint author), Harvard Univ, Schepens Eye Res Inst, Sch Med, 20 Staniford St, Boston, MA 02114 USA. EM reza.dana@schepens.harvard.edu FU National Institutes of Health, Bethesda, Maryland [NIH/EY20889] FX ALL AUTHORS HAVE COMPLETED AND SUBMITTED THE ICMJE FORM FOR DISCLOSURE OF POTENTIAL CONFLICTS OF Interest and the following were reported. The Schepens Eye Research Institute has filed for intellectual property rights for the use of IL-1 blockade in the treatment of ocular diseases. Drs Chauhan, Dastjerdi, and Dana are coinventors of a patent application licensed by their institution to Eleven Biotherapeutics, Inc, Cambridge, Massachusetts. Dr Dana holds an equity position at Eleven Biotherapeutics, Inc. Publication of this article was supported by Grant NIH/EY20889 from the National Institutes of Health, Bethesda, Maryland. Involved in Design of study (S.K.C., R.D.); Conduct of study (A.O., M.H.D.); Collection (A.O., M.H.D.), management (S.K.C., R.D.), and analysis and interpretation (A.O., S.K.C., S.K.) of data; Preparation of manuscript (S.K.C., A.O., S.K.); and Review or approval of manuscript (S.K.C., S.K., R.D.). The research protocol was approved by the Schepens Eye Research Institute Animal Care and Use Committee, and it conformed to the standards in the Association for Research in Vision and Ophthalmology Statement for the Use of Animals in Ophthalmic and Vision Research. The authors thank Dr Qiang Zhang and Nambi Nallasamy, Schepens Eye Research Institute, Boston, Massachusetts, for assisting in immunohistochemical and morphometric experiments. NR 47 TC 27 Z9 27 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD JUL PY 2012 VL 154 IS 1 BP 63 EP 71 DI 10.1016/j.ajo.2012.01.034 PG 9 WC Ophthalmology SC Ophthalmology GA 966XX UT WOS:000305871800010 PM 22541929 ER PT J AU Stacy, RC Jakobiec, FA Herwig, MC Schoenfield, L Singh, A Grossniklaus, HE AF Stacy, Rebecca C. Jakobiec, Frederick A. Herwig, Martina C. Schoenfield, Lynn Singh, Arun Grossniklaus, Hans E. TI Diffuse Large B-Cell Lymphoma of the Orbit: Clinicopathologic, Immunohistochemical, and Prognostic Features of 20 Cases SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID OCULAR ADNEXAL LYMPHOMA; GERMINAL CENTER PHENOTYPE; NON-HODGKINS-LYMPHOMA; LYMPHOPROLIFERATIVE DISEASE; INTRAOCULAR LYMPHOMA; SYSTEMIC INVOLVEMENT; MOLECULAR SUBTYPES; MALIGNANT-LYMPHOMA; CLASSIFICATION; EXPRESSION AB PURPOSE: To evaluate a series of orbital diffuse large B-cell lymphomas (DLBCL) for prognostic features and therapeutic outcomes. DESIGN: Retrospective multicenter case study of clinical and immunohistochemical features of 20 patients. METHODS: Clinical, histopathologic, and immunohistochemical features were correlated with outcomes. Immunohistochemistry for biomarkers including Bcl-6, CD5, CD10, CD20, FOXP1, GCET1, and MUM1 was performed to differentiate between 2 major genetic sub-types of DLBCL: activated B-cell-like (ABC) and germinal center B-cell-like (GCB). RESULTS: Sixteen patients presented with unilateral and 4 with bilateral tumors. Three had bony erosion of the orbit on imaging studies. Of 14 patients with detailed follow-ups, 3 had a prior or concurrent lymphomatous disease; 8 had stage I disease (limited to the orbit) at presentation; and 3 were newly diagnosed with systemic (stage IV) DLBCL. Localized disease was treated with combined systemic chemotherapy, including rituximab and radiation with no deaths to date; there was 1 death related to systemic DLBCL. Clinical staging was the best predictive method and no immunohistochemical feature or subcategory (ABC vs GCB) correlated with outcome. CONCLUSIONS: Primary orbital DLBCL has a more favorable prognosis than systemic DLBCL and may arise from a preexistent hematolymphomatous neoplasm (4 out of 20 cases). In our series, orbital DLBCL had a 57% likelihood of being restricted to the ocular adnexa. Clinical staging was more helpful in predicting outcome than any single immunohistopathologic feature or combination of biomarkers. Orbital radiation of 30 gray in conjunction with systemic chemotherapy with rituximab can achieve disease-specific survival approaching 100% in purely localized cases. (Am J Ophthalmol 2012; 154:87-98. (C) 2012 by Elsevier Inc. All rights reserved.) C1 [Stacy, Rebecca C.; Jakobiec, Frederick A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, David G Cogan Ophthalm Pathol Lab, Boston, MA USA. [Herwig, Martina C.; Grossniklaus, Hans E.] Emory Univ, Sch Med, Dept Ophthalmol, Atlanta, GA 30322 USA. [Schoenfield, Lynn; Singh, Arun] Cleveland Clin Fdn, Dept Anat Pathol, Cleveland, OH 44195 USA. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, DG Cogan Pathol Lab, Suite 321,243 Charles St, Boston, MA 02114 USA. EM Fred_Jakobiec@meei.harvard.edu RI Schoenfield, Lynn/J-6183-2013 NR 57 TC 12 Z9 13 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD JUL PY 2012 VL 154 IS 1 BP 87 EP 98 DI 10.1016/j.ajo.2012.01.021 PG 12 WC Ophthalmology SC Ophthalmology GA 966XX UT WOS:000305871800013 PM 22503694 ER PT J AU Hisatomi, T Nakao, S Murakami, Y Noda, K Nakazawa, T Notomi, S Connolly, E She, HC Almulki, L Ito, Y Vavvas, DG Ishibashi, T Miller, JW AF Hisatomi, Toshio Nakao, Shintaro Murakami, Yusuke Noda, Kousuke Nakazawa, Toru Notomi, Shoji Connolly, Edward She, Haicheng Almulki, Lama Ito, Yasuhiro Vavvas, Demetrios G. Ishibashi, Tatsuro Miller, Joan W. TI The Regulatory Roles of Apoptosis-Inducing Factor in the Formation and Regression Processes of Ocular Neovascularization SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID EXPERIMENTAL CHOROIDAL NEOVASCULARIZATION; ENDOTHELIAL GROWTH-FACTOR; PIGMENT EPITHELIAL-CELLS; PHOTODYNAMIC THERAPY; RETINAL-DETACHMENT; PHOTORECEPTOR APOPTOSIS; RAT MODEL; MITOCHONDRIAL APOPTOSIS; ISCHEMIC RETINOPATHY; VASCULAR DEVELOPMENT AB The role of apoptosis in the formation and regression of neovascularization is largely hypothesized, although the detailed mechanism remains unclear. Inflammatory cells and endothelial cells both participate and interact during neovascularization. During the early stage, these cells may migrate into an angiogenic site and form a pro-angiogenic microenvironment. Some angiogenic vessels appear to regress, whereas some vessels mature and remain. The control mechanisms of these processes, however, remain unknown. Previously, we reported that the prevention of :mitochondrial apoptosis contributed to cellular survival via the prevention of the release of proapoptotic factors, such as apoptosis-inducing factor (AIF) and cytochrome c. In this study, we investigated the regulatory role of cellular apoptosis in angiogenesis using two models of ocular neovascularization: laser injury choroidal neovascularization and VEGF-induced corneal neovascularization in AIF-deficient mice. Averting apoptosis in AIF-deficient mice decreased apoptosis of leukocytes and endothelial cells compared to wild-type mice and resulted in the persistence of these cells at angiogenic sites in vitro and in vivo. Consequently, AIF deficiency expanded neovascularization and diminished vessel regression in these two models. We also observed that peritoneal macrophages from AIF-deficient mice showed anti-apoptotic survival compared to wild-type mice under conditions of starvation. Our data suggest that ALF-related apoptosis plays an important role in neovascularization and that mitochondria-regulated apoptosis could offer a new target for the treatment of pathological angiogenesis. (Am J Pathol 2012, 181:53-61; http://dx.doi.org/10.1016/j.ajpath.2012.03.022) C1 [Hisatomi, Toshio; Nakao, Shintaro; Murakami, Yusuke; Noda, Kousuke; Nakazawa, Toru; Connolly, Edward; She, Haicheng; Almulki, Lama; Ito, Yasuhiro; Vavvas, Demetrios G.; Miller, Joan W.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Angiogenesis Lab,Dept Ophthalmol, Boston, MA 02114 USA. [Ishibashi, Tatsuro] Kyushu Univ, Grad Sch Med Sci, Dept Ophthalmol, Higashi Ku, Fukuoka 8128582, Japan. [Hisatomi, Toshio] Kyushu Med Ctr, Clin Res Inst, Fukuoka, Japan. RP Miller, JW (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Angiogenesis Lab,Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM ishi@eye.med.kyushu-u.ac.jp; Joan_Miller@meei.harvard.edu OI Hisatomi, Toshio/0000-0003-2552-9595; Vavvas, Demetrios/0000-0002-8622-6478 FU Massachusetts Lions Research Fund; Research to Prevent Blindness; Alcon Research Award; Japan Eye Bank Association; Bausch & Lomb Vitreoretinal Fellowship; National Eye Institute [EY014104] FX We thank Mari Imamura and Fumiyo Morikawa (Kyushu University) and Kennard Thomas, Sreedevi Mallemadugula, Norman Michaud, and Miin Roh (Massachusetts Eye and Ear Infirmary) for their technical assistance. We also thank the Massachusetts Lions Research Fund for generous funds provided for laboratory equipment used in this project and Research to Prevent Blindness for unrestricted funds awarded to the Department of Ophthalmology at Harvard Medical School.; Supported by an Alcon Research Award (J.W.M.), Japan Eye Bank Association (T.H.), a Bausch & Lomb Vitreoretinal Fellowship (T.N.), and National Eye Institute Grant EY014104 (Massachusetts Eye and Ear Infirmary Core Grant). NR 54 TC 9 Z9 10 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUL PY 2012 VL 181 IS 1 BP 53 EP 61 DI 10.1016/j.ajpath.2012.03.022 PG 9 WC Pathology SC Pathology GA 966PY UT WOS:000305851100007 PM 22613025 ER PT J AU Ablon, JS Levy, RA AF Ablon, J. Stuart Levy, Raymond A. TI Manual of Panic Focused Psychodynamic Psychotherapy: eXtended Range SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Book Review ID TRIALS C1 [Ablon, J. Stuart] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Ablon, J. Stuart; Levy, Raymond A.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Levy, Raymond A.] Massachusetts Gen Hosp, Psychotherapy Res Program, Boston, MA 02114 USA. RP Ablon, JS (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. NR 6 TC 0 Z9 0 U1 1 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 JUL PY 2012 VL 169 IS 7 BP 763 EP 764 DI 10.1176/appi.ajp.2012.12020222 PG 2 WC Psychiatry SC Psychiatry GA 966QV UT WOS:000305853400020 ER PT J AU Delmonico, F Danovitch, G Capron, A Levin, A Chapman, J AF Delmonico, F. Danovitch, G. Capron, A. Levin, A. Chapman, J. CA Council Declaration Istanbul Custo TI "Proposed Standards for Incentives for Organs Donation" Are Neither International nor Acceptable SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Letter ID SYSTEM C1 [Delmonico, F.] Harvard Univ, Massachusetts Gen Hosp, Med Sch Renal Transplantat, Boston, MA 02114 USA. [Danovitch, G.] Univ Calif Los Angeles, Kidney & Pancreas Transplant Program, Los Angeles, CA USA. [Levin, A.] St Pauls Hosp, Med Vancouver, BC, Canada. [Chapman, J.] Westmead Hosp, Sydney, NSW, Australia. RP Delmonico, F (reprint author), Harvard Univ, Massachusetts Gen Hosp, Med Sch Renal Transplantat, White Bldg 505, Boston, MA 02114 USA. NR 6 TC 4 Z9 4 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUL PY 2012 VL 12 IS 7 BP 1954 EP 1955 DI 10.1111/j.1600-6143.2012.04119.x PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 965TE UT WOS:000305789400037 PM 22741755 ER PT J AU Wolf, EJ Miller, MW Reardon, AF Ryabchenko, KA Castillo, D Freund, R AF Wolf, Erika J. Miller, Mark W. Reardon, Annemarie F. Ryabchenko, Karen A. Castillo, Diane Freund, Rachel TI A Latent Class Analysis of Dissociation and Posttraumatic Stress Disorder Evidence for a Dissociative Subtype SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID EXPERIENCES; TRAUMA; PTSD; PREDICTORS; EXPOSURE; MIXTURE; SYMPTOMATOLOGY; VETERANS; NUMBER; SAMPLE AB Context: The nature of the relationship of dissociation to posttraumatic stress disorder (PTSD) is controversial and of considerable clinical and nosologic importance. Objectives: To examine evidence for a dissociative subtype of PTSD and to examine its association with different types of trauma. Design: A latent profile analysis of cross-sectional data from structured clinical interviews indexing DSM-IV symptoms of current PTSD and dissociation. Settings: The VA Boston Healthcare System and the New Mexico VA Health Care System. Participants: A total of 492 veterans and their intimate partners, all of whom had a history of trauma. Participants reported exposure to a variety of traumatic events, including combat, childhood physical and sexual abuse, partner abuse, motor vehicle accidents, and natural disasters, with most participants reporting exposure to multiple types of traumatic events. Forty-two percent of the sample met the criteria for a current diagnosis of PTSD. Main Outcome Measures: Item-level scores on the Clinician-Administered PTSD Scale. Results: A latent profile analysis suggested a 3-class solution: a low PTSD severity subgroup, a high PTSD severity subgroup characterized by elevations across the 17 core symptoms of the disorder, and a small but distinctly dissociative subgroup that composed 12% of individuals with a current diagnosis of PTSD. The latter group was characterized by severe PTSD symptoms combined with marked elevations on items assessing flashbacks, derealization, and depersonalization. Individuals in this subgroup also endorsed greater exposure to childhood and adult sexual trauma compared with the other 2 groups, suggesting a possible etiologic link with the experience of repeated sexual trauma. Conclusions: These results support the subtype hypothesis of the association between PTSD and dissociation and suggest that dissociation is a highly salient facet of posttraumatic psychopathology in a subset of individuals with the disorder. C1 [Wolf, Erika J.; Miller, Mark W.; Reardon, Annemarie F.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Wolf, Erika J.; Miller, Mark W.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Ryabchenko, Karen A.] VA Boston Healthcare Syst, Albuquerque, NM USA. [Castillo, Diane; Freund, Rachel] New Mexico VA Hlth Care Syst, Albuquerque, NM USA. RP Miller, MW (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD 116B 2, Boston, MA 02130 USA. EM mark.miller5@va.gov OI Wolf, Erika/0000-0003-2666-2435 FU National Institute of Mental Health [RO1 MH079806]; VA Merit Review grant; VA Career Development Award FX Funding for this study was provided by National Institute of Mental Health award RO1 MH079806 and a VA Merit Review grant (Dr Miller) and by a VA Career Development Award (Dr Wolf). NR 43 TC 79 Z9 80 U1 3 U2 23 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 JUL PY 2012 VL 69 IS 7 BP 698 EP 705 PG 8 WC Psychiatry SC Psychiatry GA 967KV UT WOS:000305907600009 PM 22752235 ER PT J AU Cunningham, MT Olson, JD Chandler, WL Van Cott, EM Eby, CS Teruya, J Hollensead, SC Adcock, DM Allison, PM Kottke-Marchant, KK Smith, MD AF Cunningham, Mark T. Olson, John D. Chandler, Wayne L. Van Cott, Elizabeth M. Eby, Charles S. Teruya, Jun Hollensead, Sandra C. Adcock, Dorothy M. Allison, Paul M. Kottke-Marchant, Kandice K. Smith, Marc D. TI External Quality Assurance of Fibrinogen Assays Using Normal Plasma Results of the 2008 College of American Pathologists Proficiency Testing Program in Coagulation SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID FRESH-FROZEN PLASMA; COMMON CALIBRATOR; DYSFIBRINOGENEMIA; CRYOPRECIPITATE; COAGULOPATHY; GUIDELINES; DIAGNOSIS; CLAUSS; RISK AB Context.-Proper diagnosis and therapy of fibrinogen deficiency requires high-quality fibrinogen assays. Objective.-To assess the interlaboratory bias, precision, and grading of fibrinogen assays used by laboratories participating in the United States College of American Pathologists proficiency testing program in coagulation. Design.-Two identical vials of normal plasma were sent to more than 3500 laboratories. Participants measured fibrinogen levels using local methods. Results.-Fifty different fibrinogen methods were evaluated. All-method bias was 8.3% (range of method-specific biases, 0.0%-27.0%) and all-method coefficient of variation was 7.7%(range of method-specific coefficients of variation, 0.7%-25.8%). After controlling for reagent/instrument type, mean fibrinogen levels were 11.6% higher for prothrombin time-based reagents compared to Clauss (P<.001), and coefficient of variation was 46% lower for mechanical endpoint instruments compared to photo-optical. Most testing events (97.4%) could be reliably graded as pass or fail using a target range of +/- 20% from the method mean (total pass rate, 98.8%). Total fail rate was 3.0-fold lower for mechanical instruments compared to photo-optical (0.5% versus 1.5%, P=.001). Nonetheless many photo-optical methods had very high precision and very low fail rates. Conclusions.-Fibrinogen assays showed highly variable methodology and performance characteristics. Bias, precision, and grading were affected by the type of reagent or instrument used. (Arch Pathol Lab Med. 2012; 136: 789-795; doi: 10.5858/arpa.2011-0322-OA) C1 [Cunningham, Mark T.] Univ Kansas, Med Ctr, Dept Pathol, Kansas City, KS 66160 USA. [Olson, John D.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Chandler, Wayne L.] Methodist Hosp, Phys Org, Dept Pathol & Lab Med, Houston, TX 77030 USA. [Van Cott, Elizabeth M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Eby, Charles S.] Washington Univ, Sch Med, Dept Pathol, St Louis, MO 63110 USA. [Teruya, Jun] Texas Childrens Hosp, Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. [Hollensead, Sandra C.] Univ Louisville Hosp, Dept Pathol, Louisville, KY USA. [Adcock, Dorothy M.] Esoterix Inc, Englewood, CO USA. [Allison, Paul M.] St Lukes Episcopal Hosp, Dept Pathol, Houston, TX 77030 USA. [Kottke-Marchant, Kandice K.] Cleveland Clin, Dept Pathol & Lab Med, Cleveland, OH 44106 USA. [Smith, Marc D.] William Beaumont Hosp, Dept Clin Pathol, Royal Oak, MI 48072 USA. RP Cunningham, MT (reprint author), Univ Kansas, Med Ctr, Dept Pathol, Mail Stop 4049,3901 Rainbow Blvd, Kansas City, KS 66160 USA. EM mcunningham@kumc.edu NR 20 TC 5 Z9 5 U1 0 U2 4 PU COLL AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD JUL PY 2012 VL 136 IS 7 BP 789 EP 795 DI 10.5858/arpa.2011-0322-OA PG 7 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 969MC UT WOS:000306058600010 PM 22742551 ER PT J AU Barisoni, L Jennette, JC Colvin, R Sitaraman, S Bragat, A Castelli, J Walker, D Boudes, P AF Barisoni, Laura Jennette, J. Charles Colvin, Robert Sitaraman, Sheela Bragat, Alexander Castelli, Jeff Walker, Dan Boudes, Pol TI Novel Quantitative Method to Evaluate Globotriaosylceramide Inclusions in Renal Peritubular Capillaries by Virtual Microscopy in Patients With Fabry Disease SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID ENZYME REPLACEMENT THERAPY; TELEPATHOLOGY AB Context.-Assessing the amount of globotriaosylceramide inclusions in renal peritubular capillaries by a semiquantitative approach is a standard and useful measure of therapeutic efficacy in Fabry disease, achievable by light microscopy analysis. Objective.-To describe a novel virtual microscopy quantitative method to measure globotriaosylceramide inclusions (Barisoni Lipid Inclusion Scoring System [BLISS]) in renal biopsies from patients with Fabry disease. Design.-Plastic embedded 1-mm-thick sections from kidney biopsies from 17 patients enrolled in a Fabry disease clinical trial were evaluated using a standard semiquantitative methodology and BLISS to compare sensitivity. We also tested intrareader and interreader variability of BLISS and compared results from conventional light microscopy analysis with a virtual microscopy-based methodology. Peritubular capillaries were first annotated on digital images of whole slides by 1 pathologist and then scored for globotriaosylceramide inclusions by 2 additional pathologists. Results.-We demonstrated that (1) quantitative analysis by BLISS results in detection of small amount of globotriaosylceramide inclusions even when by semiquantitative analysis the score is 0, (2) application of BLISS combined with conventional light microscopy results in low intrareader and interreader variability, and (3) BLISS combined with virtual microscopy results in significant reduction of intrareader and interreader variability compared with BLISS-light microscopy. Conclusions.-BLISS is a simpler and more sensitive scoring system compared to the semiquantitative approach. The virtual microscopy-based methodology increases accuracy and reproducibility; moreover, it provides a permanent record of retrievable data with full transparency in clinical trials. (Arch Pathol Lab Med. 2012; 136: 816-824; doi: 10.5858/ arpa. 2011-0350-OA) C1 [Barisoni, Laura] NYU, Dept Pathol & Med, Langone Med Ctr, New York, NY 10016 USA. [Jennette, J. Charles] Univ N Carolina, Dept Pathol, Med Ctr, Chapel Hill, NC USA. [Colvin, Robert] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Sitaraman, Sheela; Bragat, Alexander; Castelli, Jeff; Boudes, Pol] Amicus Therapeut Inc, Cranbury, NJ USA. [Walker, Dan] Aperio, Vista, CA USA. RP Barisoni, L (reprint author), NYU, Dept Pathol & Med, Langone Med Ctr, 560 1st Ave, New York, NY 10016 USA. EM barisl01@med.nyu.edu OI Bragat, Alexander/0000-0002-0993-9896 NR 18 TC 10 Z9 10 U1 0 U2 2 PU COLL AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD JUL PY 2012 VL 136 IS 7 BP 816 EP 824 DI 10.5858/arpa.2011-0350-OA PG 9 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 969MC UT WOS:000306058600014 PM 22742555 ER PT J AU Gomez-Puerta, JA Quintana, LF Stone, JH Ramos-Casals, M Bosch, X AF Gomez-Puerta, Jose A. Quintana, Luis F. Stone, John H. Ramos-Casals, Manuel Bosch, Xavier TI B-cell depleting agents for ANCA vasculitides: A new therapeutic approach SO AUTOIMMUNITY REVIEWS LA English DT Review DE ANCA; Vasculitis; Pathogenesis; Histopathological; Treatment; Rituximab ID OF-THE-LITERATURE; WEGENERS-GRANULOMATOSIS; DELAYED-HYPERSENSITIVITY; AUTOIMMUNE-DISEASES; RENAL VASCULITIS; RITUXIMAB; GLOMERULONEPHRITIS; COMPLEMENTARY; ANTIBODIES; MICE AB Vasculitides associated with anti-neutrophil cytoplasmic antibody (ANCA) serum positivity affecting small and medium-sized vessels are defined as ANCA-associated vasculitis (AAV). Glomerulonephritis in AAV is characterized by focal necrosis, crescent formation, and few or no immunoglobulin deposits. In vitro and animal evidence suggests that ANCA play a pathogenic role in AAV. Specific gene expression signatures are reported to predict long-term prognosis in AAV, suggesting the possibility of individualizing therapy and identifying new therapeutic targets. Although immunosuppressants and glucocorticoids are the cornerstone of AAV therapy, results from two recent randomized controlled trials have shown the non-inferiority of rituximab, compared with cyclophosphamide, for the induction of remission in patients with severe AAV. In fact in April 2011, the US Food and Drug Administration (FDA) approved rituximab, combined with glucocorticoids, as a front-line therapy for adult patients with granulomatosis with polyangiitis (GPA; Wegener's granulomatosis) or microscopic polyangiitis. This new indication for rituximab provided the first ever FDA-approved therapy for these two diseases and the first alternative to cyclophosphamide for the treatment of severe disease in almost 40 years. However, issues regarding the use of maintenance therapy after rituximab, the concurrent use of cyclophosphamide and the toxicity of rituximab remain unanswered and should be clarified in ongoing and future randomized controlled trials. (C) 2011 Elsevier B.V. All rights reserved. C1 [Bosch, Xavier] Univ Barcelona, Hosp Clin, Dept Internal Med, IDIBAPS, E-08036 Barcelona, Spain. [Gomez-Puerta, Jose A.] Univ Barcelona, Hosp Clin, Dept Rheumatol, IDIBAPS, E-08036 Barcelona, Spain. [Quintana, Luis F.] Univ Barcelona, Hosp Clin, Dept Nephrol, IDIBAPS, E-08036 Barcelona, Spain. [Stone, John H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Rheumatol Unit,Dept Med, Boston, MA USA. [Ramos-Casals, Manuel] Univ Barcelona, Hosp Clin, Dept Syst Autoimmune Dis, IDIBAPS, E-08036 Barcelona, Spain. RP Bosch, X (reprint author), Univ Barcelona, Hosp Clin, Dept Internal Med, IDIBAPS, Villarroel 170, E-08036 Barcelona, Spain. EM xavbosch@clinic.ub.es RI Gomez-Puerta, Jose /H-3550-2015; OI Ramos-Casals, Manuel/0000-0001-5709-6734 NR 58 TC 20 Z9 20 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-9972 J9 AUTOIMMUN REV JI Autoimmun. Rev. PD JUL PY 2012 VL 11 IS 9 BP 646 EP 652 DI 10.1016/j.autrev.2011.11.007 PG 7 WC Immunology SC Immunology GA 967TU UT WOS:000305931500007 PM 22146313 ER PT J AU Singh, RP Waldron, RT Hahn, BH AF Singh, Ram P. Waldron, Richard T. Hahn, Bevra H. TI Genes, tolerance and systemic autoimmunity SO AUTOIMMUNITY REVIEWS LA English DT Review DE Autoimmunity; Systemic lupus erythematosus; Genes; Tolerance; CD8(+)Ti ID REGULATORY T-CELLS; VERSUS-HOST-DISEASE; GENERATED EX-VIVO; COMPLEMENTARITY-DETERMINING REGION-1; INTERFERON-INDUCIBLE GENE; LUPUS-LIKE DISEASE; MURINE LUPUS; MEDIATED SUPPRESSION; SUSCEPTIBILITY GENE; PROGRAMMED DEATH-1 AB The characterization of functional CD8(+) inhibitory or regulatory T cells and their gene regulation remains a critical challenge in the field of tolerance and autoimmunity. Investigating the genes induced in regulatory cells and the regulatory networks and pathways that underlie mechanisms of immune resistance and prevent apoptosis in the CD8(+) T cell compartment are crucial to understanding tolerance mechanisms in systemic autoimmunity. Little is currently known about the genetic control that governs the ability of CD8(+) Ti or regulatory cells to suppress anti-DNA Ab production in B cells. Silencing genes with siRNA or shRNA and overexpression of genes with lentiviral cDNA transduction are established approaches to identifying and understanding the function of candidate genes in tolerance and immunity. Elucidation of interactions between genes and proteins, and their synergistic effects in establishing cell-cell cross talk, including receptor modulation/antagonism, are essential for delineating the roles of these cells. In this review, we will examine recent reports which describe the modulation of cells from lupus prone mice or lupus patients to confer anti-inflammatory and protective gene expression and novel associated phenotypes. We will highlight recent findings on the role of selected genes induced by peptide tolerance in CD8(+) Ti. (C) 2011 Elsevier B.V. All rights reserved. C1 [Singh, Ram P.] Univ Calif Los Angeles, David Geffen Sch Med, Div Rheumatol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Pancreat Res Grp, VA Greater Los Angeles Healthcare Syst,Dept Med,D, Los Angeles, CA 90095 USA. RP Singh, RP (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Rheumatol, Los Angeles, CA 90095 USA. EM rpsingh@mednet.ucla.edu FU NIH [AR54034, AI083894, AI65645]; UCLA Clinical Translational Seed Grant (CTSG); American Autoimmune Related Disease Association grant (AARDA); TEVA Pharmaceuticals; UCLA Senate Core Grant FX RPS is supported by NIH grants AR54034, AI083894, AI65645, UCLA Clinical Translational Seed Grant (CTSG) and the American Autoimmune Related Disease Association grant (AARDA). BHH is supported by an award from TEVA Pharmaceuticals. BHH and RPS are also supported by UCLA Senate Core Grant. NR 114 TC 15 Z9 15 U1 3 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-9972 J9 AUTOIMMUN REV JI Autoimmun. Rev. PD JUL PY 2012 VL 11 IS 9 BP 664 EP 669 DI 10.1016/j.autrev.2011.11.017 PG 6 WC Immunology SC Immunology GA 967TU UT WOS:000305931500010 PM 22155015 ER PT J AU Derti, A Roth, FP AF Derti, Adnan Roth, Frederick P. TI Response to "MHC-dependent mate choice in humans: Why genomic patterns from the HapMap European American data set support the hypothesis" (DOI: 10.1002/bies.201100150) SO BIOESSAYS LA English DT Editorial Material DE HapMap; major histocompatibility locus; mate selection; MHC C1 [Roth, Frederick P.] Univ Toronto, Donnelly Ctr, Toronto, ON, Canada. [Roth, Frederick P.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. [Roth, Frederick P.] Mt Sinai Hosp, Lunenfeld Inst, Toronto, ON M5G 1X5, Canada. [Derti, Adnan] Novartis Inst BioMed Res, Cambridge, MA USA. [Roth, Frederick P.] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. RP Roth, FP (reprint author), Univ Toronto, Donnelly Ctr, Toronto, ON, Canada. EM fritz.roth@utoronto.ca RI Roth, Frederick/H-6308-2011 FU NHGRI NIH HHS [P50 HG004233] NR 3 TC 4 Z9 4 U1 1 U2 19 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0265-9247 J9 BIOESSAYS JI Bioessays PD JUL PY 2012 VL 34 IS 7 BP 576 EP 577 DI 10.1002/bies.201200023 PG 2 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 958KG UT WOS:000305234800014 PM 22467222 ER PT J AU Zaitlen, N Pasaniuc, B Patterson, N Pollack, S Voight, B Groop, L Altshuler, D Henderson, BE Kolonel, LN Le Marchand, L Waters, K Haiman, CA Stranger, BE Dermitzakis, ET Kraft, P Price, AL AF Zaitlen, Noah Pasaniuc, Bogdan Patterson, Nick Pollack, Samuela Voight, Benjamin Groop, Leif Altshuler, David Henderson, Brian E. Kolonel, Laurence N. Le Marchand, Loic Waters, Kevin Haiman, Christopher A. Stranger, Barbara E. Dermitzakis, Emmanouil T. Kraft, Peter Price, Alkes L. TI Analysis of case-control association studies with known risk variants SO BIOINFORMATICS LA English DT Article ID GENOME-WIDE ASSOCIATION; DIABETES SUSCEPTIBILITY; HUMAN-DISEASES; LOCI; TRAITS AB Motivation: The question of how to best use information from known associated variants when conducting disease association studies has yet to be answered. Some studies compute a marginal P-value for each Several Nucleotide Polymorphisms independently, ignoring previously discovered variants. Other studies include known variants as covariates in logistic regression, but a weakness of this standard conditioning strategy is that it does not account for disease prevalence and non-random ascertainment, which can induce a correlation structure between candidate variants and known associated variants even if the variants lie on different chromosomes. Here, we propose a new conditioning approach, which is based in part on the classical technique of liability threshold modeling. Roughly, this method estimates model parameters for each known variant while accounting for the published disease prevalence from the epidemiological literature. Results: We show via simulation and application to empirical datasets that our approach outperforms both the no conditioning strategy and the standard conditioning strategy, with a properly controlled false-positive rate. Furthermore, in multiple data sets involving diseases of low prevalence, standard conditioning produces a severe drop in test statistics whereas our approach generally performs as well or better than no conditioning. Our approach may substantially improve disease gene discovery for diseases with many known risk variants. C1 [Zaitlen, Noah; Pasaniuc, Bogdan; Pollack, Samuela; Kraft, Peter; Price, Alkes L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Zaitlen, Noah; Pasaniuc, Bogdan; Kraft, Peter; Price, Alkes L.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Zaitlen, Noah; Pasaniuc, Bogdan; Patterson, Nick; Voight, Benjamin; Altshuler, David; Stranger, Barbara E.; Kraft, Peter; Price, Alkes L.] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Zaitlen, Noah; Pasaniuc, Bogdan; Kraft, Peter; Price, Alkes L.] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. [Voight, Benjamin; Altshuler, David] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res,Dept Mol Biol, Boston, MA 02115 USA. [Voight, Benjamin; Altshuler, David] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02115 USA. [Voight, Benjamin; Altshuler, David; Stranger, Barbara E.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Voight, Benjamin; Altshuler, David; Stranger, Barbara E.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Groop, Leif] Lund Univ, Scania Univ Hosp, Dept Clin Sci, Diabet & Endocrinol Res Unit, SE-205 Malm, Sweden. [Henderson, Brian E.; Waters, Kevin; Haiman, Christopher A.] Univ So Calif, Norris Comprehens Canc Ctr, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90089 USA. [Kolonel, Laurence N.; Le Marchand, Loic] Univ Hawaii, Program Epidemiol, Canc Res Ctr, Honolulu, HI 96813 USA. [Stranger, Barbara E.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Dermitzakis, Emmanouil T.] Univ Geneva, Sch Med, Dept Genet Med & Dev, CH-1211 Geneva, Switzerland. RP Zaitlen, N (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. EM nzaitlen@hsph.harvard.edu; aprice@hsph.harvard.edu RI Dermitzakis, Emmanouil/B-7687-2013; Altshuler, David/A-4476-2009; OI Altshuler, David/0000-0002-7250-4107; Stranger, Barbara/0000-0001-9021-7331 FU NIH [5T32ES007142-27, CA63464, CA54281, 1U01HG004802]; NHGRI [R01 HG006399]; US National Institutes of Health; National Cancer Institute [U01-CA98233-07, U01-CA98710-06, U01-CA98216-06, U01-CA98758-07]; NIH/National Cancer Institute, Division of Cancer Epidemiology and Genetics; Multiethnic Cohort (MEC) [R37-CA54281] FX Funding: NIH fellowship [5T32ES007142-27 N.Z.]; NHGRI [R01 HG006399 and N.Z., B. P., N.P., A. L. P.]; US National Institutes of Health; National Cancer Institute [cooperative agreements U01-CA98233-07 to David J. Hunter, U01-CA98710-06 to Susan Gapstur, U01-CA98216-06 to Elio Riboli and Rudolf Kaaks, and U01-CA98758-07 to Brian E. Henderson, and Intramural Research Program of NIH/National Cancer Institute, Division of Cancer Epidemiology and Genetics]. The T2D study in the MEC was supported by NIH CA63464, CA54281, 1U01HG004802 and Multiethnic Cohort (MEC) [R37-CA54281 to Laurence N. Kolonel]. NR 39 TC 16 Z9 17 U1 1 U2 13 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD JUL 1 PY 2012 VL 28 IS 13 BP 1729 EP 1737 DI 10.1093/bioinformatics/bts259 PG 9 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 966GJ UT WOS:000305825600009 PM 22556366 ER PT J AU Lee, PH O'Dushlaine, C Thomas, B Purcell, SM AF Lee, Phil H. O'Dushlaine, Colm Thomas, Brett Purcell, Shaun M. TI INRICH: interval-based enrichment analysis for genome-wide association studies SO BIOINFORMATICS LA English DT Article ID DISEASES; DRUGS; TOOL AB Here we present INRICH (INterval enRICHment analysis), a pathway-based genome-wide association analysis tool that tests for enriched association signals of predefined gene-sets across independent genomic intervals. INRICH has wide applicability, fast running time and, most importantly, robustness to potential genomic biases and confounding factors. Such factors, including varying gene size and single-nucleotide polymorphism density, linkage disequilibrium within and between genes and overlapping genes with similar annotations, are often not accounted for by existing gene-set enrichment methods. By using a genomic permutation procedure, we generate experiment-wide empirical significance values, corrected for the total number of sets tested, implicitly taking overlap of sets into account. By simulation we confirm a properly controlled type I error rate and reasonable power of INRICH under diverse parameter settings. As a proof of principle, we describe the application of INRICH on the NHGRI GWAS catalog. C1 [Lee, Phil H.; Thomas, Brett; Purcell, Shaun M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Lee, Phil H.; Purcell, Shaun M.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Lee, Phil H.; O'Dushlaine, Colm; Purcell, Shaun M.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA. [Purcell, Shaun M.] Mt Sinai Sch Med, Ctr Stat Genet, New York, NY 10029 USA. RP Purcell, SM (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Analyt & Translat Genet Unit, Boston, MA 02114 USA. EM shaun@atgu.mgh.harvard.edu FU NIMH/NIH [U01MH0855513] FX Funding: We gratefully acknowledge support from NIMH/NIH grant U01MH0855513. NR 10 TC 89 Z9 89 U1 1 U2 13 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD JUL 1 PY 2012 VL 28 IS 13 BP 1797 EP 1799 DI 10.1093/bioinformatics/bts191 PG 3 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 966GJ UT WOS:000305825600020 PM 22513993 ER PT J AU Nguyen, PL Chen, MH Hoffman, KE Chen, RC Hu, JC Bennett, CL Kattan, MW Sartor, O Stein, K D'Amico, AV AF Nguyen, Paul L. Chen, Ming-Hui Hoffman, Karen E. Chen, Ronald C. Hu, Jim C. Bennett, Charles L. Kattan, Michael W. Sartor, Oliver Stein, Karen D'Amico, Anthony V. TI Cardiovascular comorbidity and treatment regret in men with recurrent prostate cancer SO BJU INTERNATIONAL LA English DT Article DE prostate cancer; comorbidity; regret ID QUALITY-OF-LIFE; RADICAL PROSTATECTOMY; ANDROGEN SUPPRESSION; RADIATION; REGISTRY AB OBJECTIVE To determine whether cardiovascular comorbidity is associated with increased treatment regret among men with recurrent prostate cancer. METHODS The study cohort comprised 795 men in the Comprehensive, Observational, Multicenter, Prostate Adenocarcinoma (COMPARE) registry who experienced biochemical recurrence at a median (interquartile range) of 5.5 (2.8-9.1) years after prostatectomy (n = 410), external beam radiation therapy (n = 237), brachytherapy (n = 124) or primary androgen deprivation therapy (n = 24). Multivariable logistic regression analysis was used to determine whether cardiovascular comorbidity was associated with treatment regret. Cardiovascular comorbidity, which included myocardial infarction, congestive heart failure, angina, diabetes, stroke or circulation problems, was defined using a validated two-question screening process after adjusting for sociodemographic and treatment factors and post-treatment bladder and bowel toxicity. RESULTS Of 795 men, 14.8% reported regret. Men with cardiovascular comorbidity were more likely to experience post-therapy bowel toxicity (P = 0.022). In the adjusted multivariable model, the factors associated with increased treatment regret were: cardiovascular comorbidity (adjusted odds ratio [AOR] = 1.52 [95% CI: 1.00-2.31], P = 0.048); younger age (AOR: 0.97 [95% CI 0.94-0.99] per year increase in age, P = 0.019); and bowel toxicity after treatment (AOR 1.58 [95% CI 1.03-2.43], P = 0.038). CONCLUSIONS Among men with recurrent prostate cancer, those with cardiovascular comorbidity were >50% more likely to experience treatment regret than men without cardiovascular comorbidity. These data provide a rationale for men with cardiovascular comorbidity to give additional consideration to active surveillance for their newly diagnosed prostate cancer. C1 [Nguyen, Paul L.; D'Amico, Anthony V.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Chen, Ming-Hui] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. [Hoffman, Karen E.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. [Chen, Ronald C.] Univ N Carolina, Lineberger Canc Ctr, Dept Radiat Oncol, Chapel Hill, NC USA. [Hu, Jim C.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Hu, Jim C.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Urol Surg, Boston, MA 02115 USA. [Bennett, Charles L.] Hollings Canc Ctr, Charleston, SC USA. [Bennett, Charles L.] S Carolina Coll Pharm, Charleston, SC USA. [Kattan, Michael W.] Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH 44106 USA. [Sartor, Oliver] Tulane Univ, Dept Med, New Orleans, LA 70118 USA. [Sartor, Oliver] Tulane Univ, Dept Urol, New Orleans, LA 70118 USA. [Stein, Karen] Eisai Pharmaceut, Woodcliff Lake, NJ USA. RP Nguyen, PL (reprint author), Dana Farber Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. EM pnguyen@LROC.harvard.edu FU Sanofi-Aventis; family foundation FX This research was supported in part by a grant from Sanofi-Aventis, David and Cynthia Chapin, and an anonymous grant from a family foundation. NR 17 TC 9 Z9 9 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 J9 BJU INT JI BJU Int. PD JUL PY 2012 VL 110 IS 2 BP 201 EP 205 DI 10.1111/j.1464-410X.2011.10709.x PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 971RW UT WOS:000306222500011 PM 22085233 ER PT J AU Koffie, RM Hashimoto, T Tai, HC Kay, KR Serrano-Pozo, A Joyner, D Hou, S Kopeikina, KJ Frosch, MP Lee, VM Holtzman, DM Hyman, BT Spires-Jones, TL AF Koffie, Robert M. Hashimoto, Tadafumi Tai, Hwan-Ching Kay, Kevin R. Serrano-Pozo, Alberto Joyner, Daniel Hou, Steven Kopeikina, Katherine J. Frosch, Matthew P. Lee, Virginia M. Holtzman, David M. Hyman, Bradley T. Spires-Jones, Tara L. TI Apolipoprotein E4 effects in Alzheimer's disease are mediated by synaptotoxic oligomeric amyloid-beta SO BRAIN LA English DT Article DE Alzheimer's disease; apolipoprotein E; synapse; array tomography; oligomeric amyloid-beta ID LONG-TERM POTENTIATION; APP TRANSGENIC MICE; A-BETA; PRECURSOR PROTEIN; SYNAPSE LOSS; LIGAND RECOGNITION; NATURAL OLIGOMERS; EPSILON-4 ALLELE; RECEPTOR FAMILY; NERVOUS-SYSTEM AB The apolipoprotein E epsilon 4 gene is the most important genetic risk factor for sporadic Alzheimer's disease, but the link between this gene and neurodegeneration remains unclear. Using array tomography, we analysed > 50 000 synapses in brains of 11 patients with Alzheimer's disease and five non-demented control subjects and found that synapse loss around senile plaques in Alzheimer's disease correlates with the burden of oligomeric amyloid-beta in the neuropil and that this synaptotoxic oligomerized peptide is present at a subset of synapses. Further analysis reveals apolipoprotein E epsilon 4 patients with Alzheimer's disease have significantly higher oligomeric amyloid-beta burden and exacerbated synapse loss around plaques compared with apolipoprotein E epsilon 3 patients. Apolipoprotein E4 protein colocalizes with oligomeric amyloid-beta and enhances synaptic localization of oligomeric amyloid-beta by > 5-fold. Biochemical characterization shows that the amyloid-beta enriched at synapses by apolipoprotein E4 includes sodium dodecyl sulphate-stable dimers and trimers. In mouse primary neuronal culture, lipidated apolipoprotein E4 enhances oligomeric amyloid-beta association with synapses via a mechanism involving apolipoprotein E receptors. Together, these data suggest that apolipoprotein E4 is a co-factor that enhances the toxicity of oligomeric amyloid-beta both by increasing its levels and directing it to synapses, providing a link between apolipoprotein E epsilon 4 genotype and synapse loss, a major correlate of cognitive decline in Alzheimer's disease. C1 [Koffie, Robert M.; Hashimoto, Tadafumi; Tai, Hwan-Ching; Kay, Kevin R.; Serrano-Pozo, Alberto; Joyner, Daniel; Hou, Steven; Kopeikina, Katherine J.; Frosch, Matthew P.; Hyman, Bradley T.; Spires-Jones, Tara L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Koffie, Robert M.] Harvard Biophys Program, Boston, MA 02115 USA. [Kopeikina, Katherine J.] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. [Lee, Virginia M.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Holtzman, David M.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. RP Spires-Jones, TL (reprint author), Massachusetts Gen Inst Neurodegenerat Dis, 114 16th St, Charlestown, MA 02129 USA. EM tspires@partners.org RI Hashimoto, Tadafumi/A-7723-2013; SERRANO-POZO, ALBERTO/F-5119-2013 FU NIH [K99 (AG033670-01A1), P50 AG005134, AG12406, AG08487, T32 GM07753]; Alzheimer's disease Drug Discovery Foundation/Association for Frontotemporal Dementias; Harvard Biophysics Training Program; Paul and Daisy Soros Foundation; Ellison/American Federation for Aging Research Postdoctoral Fellowship [2009A059868]; American Health Assistance Foundation Alzheimer's Disease Fellowship; Harvard Medical Scientist Training Program FX NIH K99 (AG033670-01A1), Alzheimer's disease Drug Discovery Foundation/Association for Frontotemporal Dementias, NIH grants P50 AG005134, AG12406, AG08487, Harvard Biophysics and Medical Scientist Training Programs, NIH T32 GM07753, Paul and Daisy Soros Foundation, Ellison/American Federation for Aging Research Postdoctoral Fellowship (2009A059868). American Health Assistance Foundation Alzheimer's Disease Fellowship. NR 56 TC 73 Z9 73 U1 1 U2 18 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD JUL PY 2012 VL 135 BP 2155 EP 2168 DI 10.1093/brain/aws127 PN 7 PG 14 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 966GQ UT WOS:000305826300015 PM 22637583 ER PT J AU Zalesky, A Solowij, N Yucel, M Lubman, DI Takagi, M Harding, IH Lorenzetti, V Wang, RP Searle, K Pantelis, C Seal, M AF Zalesky, Andrew Solowij, Nadia Yuecel, Murat Lubman, Dan I. Takagi, Michael Harding, Ian H. Lorenzetti, Valentina Wang, Ruopeng Searle, Karissa Pantelis, Christos Seal, Marc TI Effect of long-term cannabis use on axonal fibre connectivity SO BRAIN LA English DT Article DE cannabis; axonal connectivity; white matter; diffusion-weighted imaging; diffusion-tensor imaging ID WHITE-MATTER DEVELOPMENT; BRAIN NETWORKS; 1ST-EPISODE SCHIZOPHRENIA; CORPUS-CALLOSUM; HIPPOCAMPAL VOLUME; MARIJUANA SMOKERS; YOUNG-ADULTS; ABNORMALITIES; ADOLESCENTS; RECEPTORS AB Cannabis use typically begins during adolescence and early adulthood, a period when cannabinoid receptors are still abundant in white matter pathways across the brain. However, few studies to date have explored the impact of regular cannabis use on white matter structure, with no previous studies examining its impact on axonal connectivity. The aim of this study was to examine axonal fibre pathways across the brain for evidence of microstructural alterations associated with long-term cannabis use and to test whether age of regular cannabis use is associated with severity of any microstructural change. To this end, diffusion-weighted magnetic resonance imaging and brain connectivity mapping techniques were performed in 59 cannabis users with longstanding histories of heavy use and 33 matched controls. Axonal connectivity was found to be impaired in the right fimbria of the hippocampus (fornix), splenium of the corpus callosum and commissural fibres. Radial and axial diffusivity in these pathways were associated with the age at which regular cannabis use commenced. Our findings indicate long-term cannabis use is hazardous to the white matter of the developing brain. Delaying the age at which regular use begins may minimize the severity of microstructural impairment. C1 [Solowij, Nadia] Univ Wollongong, Sch Psychol, Wollongong, NSW 2522, Australia. [Zalesky, Andrew; Yuecel, Murat; Takagi, Michael; Harding, Ian H.; Lorenzetti, Valentina; Searle, Karissa; Pantelis, Christos] Univ Melbourne, Melbourne Neuropsychiat Ctr, Melbourne, Vic 3053, Australia. [Zalesky, Andrew; Yuecel, Murat; Takagi, Michael; Harding, Ian H.; Lorenzetti, Valentina; Searle, Karissa; Pantelis, Christos] Melbourne Hlth, Melbourne, Vic 3053, Australia. [Lubman, Dan I.] Eastern Hlth, Turning Point Alcohol & Drug Ctr, Melbourne, Vic 3065, Australia. [Lubman, Dan I.] Monash Univ, Melbourne, Vic 3065, Australia. [Wang, Ruopeng] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. [Seal, Marc] Royal Childrens Hosp Melbourne, Murdoch Childrens Res Inst, Parkville, Vic 3052, Australia. RP Solowij, N (reprint author), Univ Wollongong, Sch Psychol, Northfields Ave, Wollongong, NSW 2522, Australia. EM nadia@uow.edu.au RI Pantelis, Christos/H-7722-2014; OI Pantelis, Christos/0000-0002-9565-0238; ZALESKY, ANDREW/0000-0003-2298-9908; Solowij, Nadia/0000-0002-5222-5637; Yucel, Murat/0000-0002-4705-452X; Lubman, Dan/0000-0002-6747-1937; Harding, Ian/0000-0002-6843-9592 FU National Health and Medical Research Council of Australia [459111, 509345, 628386]; Australian Research Council [DP0986320, FT110100752]; Melbourne Neuroscience Institute FX This work was supported by the National Health and Medical Research Council of Australia [Project Grant 459111, Clinical Career Development Award 509345 to M.Y., Senior Principal Research Fellowship 628386 to C. P.]; the Australian Research Council [DP0986320 to A.Z. and Future Fellowship FT110100752 to N.S.]; and the Melbourne Neuroscience Institute [MNI Fellowship to A.Z.]. NR 74 TC 97 Z9 98 U1 2 U2 47 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD JUL PY 2012 VL 135 BP 2245 EP 2255 DI 10.1093/brain/aws136 PN 7 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 966GQ UT WOS:000305826300022 PM 22669080 ER PT J AU Bhatt, DL Bakris, GL AF Bhatt, Deepak L. Bakris, George L. TI The promise of renal denervation SO CLEVELAND CLINIC JOURNAL OF MEDICINE LA English DT Editorial Material ID HIGH BLOOD-PRESSURE; RESISTANT HYPERTENSION; SYMPATHETIC DENERVATION; COMMITTEE; TRIAL C1 [Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA 02132 USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, Integrated Intervent Cardiovasc Program, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. [Bakris, George L.] Univ Chicago Med, ASH Comprehens Hypertens Ctr, Chicago, IL 60637 USA. [Bhatt, Deepak L.] TIMI Study Grp, Boston, MA USA. [Bakris, George L.] Univ Chicago, Chicago, IL 60637 USA. RP Bhatt, DL (reprint author), VA Boston Healthcare Syst, 1400 VFW Pkwy, Boston, MA 02132 USA. EM dlbhattmd@post.harvard.edu NR 12 TC 9 Z9 9 U1 0 U2 3 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 JUL PY 2012 VL 79 IS 7 BP 498 EP 500 DI 10.3949/ccjm.79a.12051 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 967PU UT WOS:000305921100009 PM 22751634 ER PT J AU Kohli, P Desai, NR Giugliano, RP Kim, JB Somaratne, R Huang, F Knusel, B McDonald, S Abrahamsen, T Wasserman, SM Scott, R Sabatine, MS AF Kohli, Payal Desai, Nihar R. Giugliano, Robert P. Kim, Jae B. Somaratne, Ransi Huang, Fannie Knusel, Beat McDonald, Shannon Abrahamsen, Timothy Wasserman, Scott M. Scott, Robert Sabatine, Marc S. TI Design and Rationale of the LAPLACE-TIMI 57 Trial: A Phase II, Double-Blind, Placebo-Controlled Study of the Efficacy and Tolerability of a Monoclonal Antibody Inhibitor of PCSK9 in Subjects With Hypercholesterolemia on Background Statin Therapy SO CLINICAL CARDIOLOGY LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; 14 RANDOMIZED-TRIALS; LDL-CHOLESTEROL; HEART-DISEASE; LOWERING THERAPY; SAFETY; METAANALYSIS; ROSUVASTATIN; PARTICIPANTS; MUTATIONS AB Lowering low-density lipoprotein cholesterol (LDL-C) is a cornerstone for the prevention of atherosclerotic heart disease, improving clinical outcomes and reducing vascular mortality in patients with hypercholesterolemia. The clinical benefits of LDL-C reduction appear to extend even to patients starting with LDL-C as low as 6080 mg/dL prior to initiating therapy. Statins are the first-line agents for treating hypercholesterolemia and are effective in reducing LDL-C, but many patients are unable to achieve their optimal lipid targets despite intensive statin therapy. Therefore, there has been a strong impetus for the development of novel pharmacologic agents designed to lower LDL-C further in patients already on statin therapy. Genetic mutations resulting in altered cholesterol homeostasis provide valuable information regarding novel approaches for treating hypercholesterolemia. To that end, mutations in proprotein convertase subtilisin/kexin type 9 (PCSK9) were linked to altered levels of LDL-C, illustrating this protein's role in lipid metabolism. PCSK9 promotes degradation of the LDL receptor, preventing its transport back to the cell surface and thereby increasing circulating LDL-C. Conversely, inhibition of PCSK9 can profoundly decrease circulating LDL-C, and thus is an attractive new target for LDL-Clowering therapy. AMG 145 is a fully human monoclonal immunoglobulin G2 antibody that binds specifically to human PCSK9 and inhibits its interaction with the low-density lipoprotein receptor. In this manuscript, we describe the rationale and design of LDL-C Assessment with PCSK9 Monoclonal Antibody Inhibition Combined With Statin TherapyThrombolysis In Myocardial Infarction 57 (LAPLACE-TIMI 57; NCT01380730), a 12-week, randomized, double-blind, dose-ranging, placebo-controlled study designed to assess the safety and efficacy of AMG 145 when added to statin therapy in patients with hypercholesterolemia. Clin. Cardiol. 2012. doi: 10.1002/clc.22014 This trial was supported by Amgen. Payal Kohli, Nihar R. Desai, Robert P. Giugliano, Timothy Abrahamsen, Shannon McDonald and Marc S. Sabatine are members of the TIMI Study Group, which received research grant support from Amgen for the conduct of this trial. Payal Kohli has received honorarium for consultation from Daiichi-Sankyo. Robert P. Giugliano has received honoraria for lectures and consultation from Amgen, Merck, Regeneron, and Sanofi-Aventis, and research-grant support from Merck for work related to lipid-lowering therapies. Marc S. Sabatine has received research-grant support from AstraZeneca, Bristol-Myers Squibb/Sanofi-Aventis Joint Venture, Merck, and Pfizer and honoraria for lectures and consultation from Amgen, Bristol-Myers Squibb/Sanofi-Aventis Joint Venture, GlaxoSmithKline, Merck, and Pfizer. Jae B. Kim, Ransi Somaratne, Fannie Huang, Beat Knusel, Scott M. Wasserman, and Robert Scott are employees and stockholders of Amgen, Inc. Payal Kohli, MD, and Nihar R. Desai, MD, MPH, contributed equally to this work. The authors have no other funding, financial relationships, or conflicts of interest to disclose. C1 [Kohli, Payal; Desai, Nihar R.; Giugliano, Robert P.; McDonald, Shannon; Abrahamsen, Timothy; Sabatine, Marc S.] Brigham & Womens Hosp, Cardiovasc Div, TIMI Study Grp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. [Kim, Jae B.; Somaratne, Ransi; Huang, Fannie; Knusel, Beat; Wasserman, Scott M.; Scott, Robert] Amgen Inc, Thousand Oaks, CA 91320 USA. RP Giugliano, RP (reprint author), Brigham & Womens Hosp, Cardiovasc Div, TIMI Study Grp, Dept Med, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM rgiugliano@partners.org OI Scott, Robert/0000-0001-8266-1061 FU Amgen; Merck; AstraZeneca; Bristol-Myers Squibb/Sanofi-Aventis Joint Venture; Pfizer FX This trial was supported by Amgen. Payal Kohli, Nihar R. Desai, Robert P. Giugliano, Timothy Abrahamsen, Shannon McDonald and Marc S. Sabatine are members of the TIMI Study Group, which received research grant support from Amgen for the conduct of this trial. Payal Kohli has received honorarium for consultation from Daiichi-Sankyo. Robert P. Giugliano has received honoraria for lectures and consultation from Amgen, Merck, Regeneron, and Sanofi-Aventis, and research-grant support from Merck for work related to lipid-lowering therapies. Marc S. Sabatine has received research-grant support from AstraZeneca, Bristol-Myers Squibb/Sanofi-Aventis Joint Venture, Merck, and Pfizer and honoraria for lectures and consultation from Amgen, Bristol-Myers Squibb/Sanofi-Aventis Joint Venture, GlaxoSmithKline, Merck, and Pfizer. Jae B. Kim, Ransi Somaratne, Fannie Huang, Beat Knusel, Scott M. Wasserman, and Robert Scott are employees and stockholders of Amgen, Inc. NR 32 TC 33 Z9 35 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0160-9289 EI 1932-8737 J9 CLIN CARDIOL JI Clin. Cardiol. PD JUL PY 2012 VL 35 IS 7 BP 385 EP 391 DI 10.1002/clc.22014 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 967EZ UT WOS:000305890500002 PM 22714699 ER PT J AU Huang, PH Kim, CX Lerman, A Cannon, CP Dai, D Laskey, W Peacock, WF Hernandez, AF Peterson, ED Smith, EE Fonarow, GC Schwamm, LH Bhatt, DL AF Huang, Pei-Hsiu Kim, Charles X. Lerman, Amir Cannon, Christopher P. Dai, David Laskey, Warren Peacock, W. Frank Hernandez, Adrian F. Peterson, Eric D. Smith, Eric E. Fonarow, Gregg C. Schwamm, Lee H. Bhatt, Deepak L. TI Trends in Smoking Cessation Counseling: Experience From American Heart Association-Get With The Guidelines SO CLINICAL CARDIOLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; TRANSIENT ISCHEMIC ATTACK; ACUTE-STROKE-REGISTRY; ALL-CAUSE MORTALITY; QUALITY-OF-CARE; SECONDARY PREVENTION; HEMORRHAGIC STROKE; VASCULAR-DISEASE; RISK; OUTCOMES AB Background: Successful smoking cessation in stroke and coronary artery disease (CAD) patients is important, as smoking contributes to significant morbidity and mortality. The American Heart Association developed Get With The Guidelines (GWTG) to improve compliance with national guideline recommendations for cardiovascular care. Using data from GWTG, we examined trends associated with the smoking-cessation counseling (SCC) performance measure. Hypothesis: Implementation of a systematic quality improvement program will increase compliance with the SCC performance measure. Methods: We evaluated compliance with SCC in current or recent smokers identified from 224 671 CAD admissions between 2002 and 2008 in the GWTG-CAD database, and from 405 681 stroke admissions between 2002 and 2007 in the GWTG-Stroke database. Additionally, we examined adherence to other performance and quality measures related to CAD and stroke care. Results: Overall, 55 904 GWTG-CAD and 58 865 GWTG-Stroke admissions were used for the analysis. Rates of SCC improved in each successive year during the study, from 67.6% to 97.4% (P < 0.001) in GWTG-CAD and from 40.1% to 90.7% (P < 0.001) in GWTG-Stroke. Compliance with SCC was up to 34.7% lower (P < 0.0001) in GWTG-Stroke compared with GWTG-CAD, but this difference decreased to 6.7% (P < 0.0001) by the end of the study period. Compliance with many other performance and quality measures was significantly lower among patients not receiving SCC. Conclusions: Get With The Guidelines has improved compliance with the SCC performance measure among patients with CAD and stroke. Although the initial disparity in rates of SCC between CAD and stroke patients gradually improved, the difference remained significant. All authors had access to the data and participated in the preparation of this manuscript. GWTG-CAD is a program of the American Heart Association (Dallas, TX) and is supported in part by an unrestricted educational grant from Merck/Schering-Plough Pharmaceutical (White House Station, NJ) and Pfizer (New York, NY). The analysis of registry data was performed at Duke Clinical Research Institute (Durham, NC), which receives funding from the American Heart Association. The sponsors were not involved in the design, analysis, preparation, review, or approval of this manuscript. Pei-Hsiu Huang, Charles X. Kim, Amir Lerman, David Dai, Warren Laskey, W. Frank Peacock, Eric D. Peterson, Eric E. Smith, Gregg C. Fonarow, and Lee H. Schwamm have no relevant disclosures. Christopher P. Cannon reports receiving research grants and support from Accumetrics, AstraZeneca, GlaxoSmithKline, Merck, Essentialis, and Takeda; involvement in the advisory board for Bristol-Myers Squibb/Sanofi, Novartis, and Alnylam; honoraria for development of independent educational symposia from Pfizer and AstraZeneca; and is a clinical advisor having equity in Automedics Medical Systems. Adrian F. Hernandez reports receiving research grants from Johnson & Johnson and Amylin, and honoraria from AstraZeneca, Corthera, and Sanofi-Aventis. Deepak L. Bhatt reports the following associations and memberships: advisory board, Medscape Cardiology; board of directors, Boston VA Research Institute, Society of Chest Pain Centers; chair, American Heart Association Get With The Guidelines Science Subcommittee; honoraria, American College of Cardiology (editor, Clinical Trials, Cardiosource), Duke Clinical Research Institute (clinical trial steering committees), Slack Publications (chief medical editor, Cardiology Today Intervention), and WebMD (CME steering committees); research grants, Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi Aventis, and The Medicines Company; and unfunded research, PLx Pharma and Takeda. The authors have no other funding, financial relationships, or conflicts of interest to disclose. C1 [Cannon, Christopher P.] Brigham & Womens Hosp, Div Cardiovasc Med, TIMI Study Grp, Boston, MA 02115 USA. [Huang, Pei-Hsiu; Cannon, Christopher P.; Schwamm, Lee H.; Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. [Kim, Charles X.] Univ Minnesota, Div Cardiovasc, Rochester, MN USA. [Lerman, Amir] Mayo Clin, Div Cardiovasc Dis, Rochester, MN USA. [Dai, David] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Hernandez, Adrian F.; Peterson, Eric D.] Duke Univ, Med Ctr, Div Cardiol, Durham, NC 27710 USA. [Laskey, Warren] Univ New Mexico, Sch Med, Div Cardiol, Albuquerque, NM 87131 USA. [Peacock, W. Frank] Baylor Coll Med, Dept Emergency Med, Houston, TX 77030 USA. [Smith, Eric E.] Univ Calgary, Hotchkiss Brain Inst, Dept Clin Neurosci, Calgary, AB, Canada. [Fonarow, Gregg C.] Univ Calif Los Angeles, Div Cardiol, Los Angeles, CA USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, Div Cardiovasc, VA Boston Healthcare Syst, Boston, MA 02115 USA. RP Bhatt, DL (reprint author), 1400 VFW Pkwy, Boston, MA 02132 USA. EM dlbhattmd@post.harvard.edu RI Hernandez, Adrian F./A-7818-2016; OI Schwamm, Lee/0000-0003-0592-9145; Hernandez, Adrian F./0000-0003-3387-9616; Smith, Eric/0000-0003-3956-1668 FU Accumetrics; AstraZeneca; GlaxoSmithKline; Merck; Essentialis; Takeda; Johnson Johnson; Amylin FX Pei-Hsiu Huang, Charles X. Kim, Amir Lerman, David Dai, Warren Laskey, W. Frank Peacock, Eric D. Peterson, Eric E. Smith, Gregg C. Fonarow, and Lee H. Schwamm have no relevant disclosures. Christopher P. Cannon reports receiving research grants and support from Accumetrics, AstraZeneca, GlaxoSmithKline, Merck, Essentialis, and Takeda; involvement in the advisory board for Bristol-Myers Squibb/Sanofi, Novartis, and Alnylam; honoraria for development of independent educational symposia from Pfizer and AstraZeneca; and is a clinical advisor having equity in Automedics Medical Systems. Adrian F. Hernandez reports receiving research grants from Johnson & Johnson and Amylin, and honoraria from AstraZeneca, Corthera, and Sanofi-Aventis. Deepak L. Bhatt reports the following associations and memberships: advisory board, Medscape Cardiology; board of directors, Boston VA Research Institute, Society of Chest Pain Centers; chair, American Heart Association Get With The Guidelines Science Subcommittee; honoraria, American College of Cardiology (editor, Clinical Trials, Cardiosource), Duke Clinical Research Institute (clinical trial steering committees), Slack Publications (chief medical editor, Cardiology Today Intervention), and WebMD (CME steering committees); research grants, Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi Aventis, and The Medicines Company; and unfunded research, PLx Pharma and Takeda. NR 41 TC 3 Z9 3 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0160-9289 EI 1932-8737 J9 CLIN CARDIOL JI Clin. Cardiol. PD JUL PY 2012 VL 35 IS 7 BP 396 EP 403 DI 10.1002/clc.22023 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 967EZ UT WOS:000305890500003 PM 22753250 ER PT J AU Joshi, PH Chaudhari, S Blaha, MJ Jones, SR Martin, SS Post, WS Cannon, CP Fonarow, GC Wong, ND Amsterdam, E Hirshfeld, JW Blumenthal, RS AF Joshi, Parag H. Chaudhari, Sameer Blaha, Michael J. Jones, Steven R. Martin, Seth S. Post, Wendy S. Cannon, Christopher P. Fonarow, Gregg C. Wong, Nathan D. Amsterdam, Ezra Hirshfeld, John W. Blumenthal, Roger S. TI A Point-by-Point Response to Recent Arguments Against the Use of Statins in Primary Prevention This Statement Endorsed by the American Society for Preventive Cardiology SO CLINICAL CARDIOLOGY LA English DT Editorial Material ID CORONARY-HEART-DISEASE; RANDOMIZED CONTROLLED-TRIALS; C-REACTIVE PROTEIN; CARDIOVASCULAR-DISEASE; FAMILIAL HYPERCHOLESTEROLEMIA; 11-YEAR MORTALITY; LDL CHOLESTEROL; CLINICAL-TRIALS; FOLLOW-UP; ALL-CAUSE AB Recently, a debate over the merits of statin therapy in primary prevention was published in the Wall Street Journal. The statin opponent claimed that statins should only be used in secondary prevention and never in any primary-prevention patients at risk for cardiovascular events. In this evidence-based rebuttal to those claims, we review the evidence supporting the efficacy of statin therapy in primary prevention. Cardiovascular risk is a continuum in which those at an elevated risk of events stand to benefit from early initiation of therapy. Statins should not be reserved until after a patient suffers the catastrophic consequences of atherosclerosis. Contrary to the assertions of the statin opponent, this principle has been demonstrated through reductions in heart attacks, strokes, and mortality in numerous randomized controlled primary-prevention statin trials. Furthermore, data show that once a patient tolerates the initial treatment period, the few side effects that subsequently emerge are largely reversible. Accordingly, every major guidelines committee endorses statin use in secondary prevention and selectively in primary prevention for those with risk factors. The foundation for prevention remains increased physical activity, better dietary habits, and smoking cessation. However, prevention of heart attacks, strokes, and death from cardiovascular disease does not have to be all or noneall statin or all lifestyle. In selected at-risk individuals, the combination of pharmacotherapy and lifestyle changes is more effective than either alone. Future investigation in prevention should focus on improving our ability to identify these at-risk individuals. Drs Amsterdam, Blumenthal, and Wong serve on the board of directors and/or are officers of the American Society for Preventive Cardiology. Dr Wong has received research support from Merck and Bristol Myers-Squibb and advisory board consultant fees from Merck in the past 12 months. Dr Cannon is a senior investigator in the TIMI Study Group; has received research support from Accumetrics, AstraZeneca, GlaxoSmithKline, Merck, Essentialis, and Takeda; has donated advisory board consultant fees to charity from Bristol-Myers Squibb/Sanofi, Novartis, and Alnylam; has received honoraria for development of independent educational symposia from Pfizer and AstraZeneca; and has equity in Automedics Medical Systems. Dr Jones has received research support and advisory board consultant fees from Atherotech Diagnostics Lab and has served as a consultant for Amylin Pharmaceuticals. The authors have no other funding, financial relationships, or conflicts of interest to disclose. C1 [Joshi, Parag H.; Chaudhari, Sameer; Blaha, Michael J.; Jones, Steven R.; Martin, Seth S.; Post, Wendy S.; Blumenthal, Roger S.] Johns Hopkins Sch Med, Johns Hopkins Ciccarone Ctr Prevent Heart Dis, Baltimore, MD 21287 USA. [Cannon, Christopher P.] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Div Cardiol, Los Angeles, CA USA. [Wong, Nathan D.] Univ Calif Irvine, Div Cardiol, Heart Dis Prevent Program, Irvine, CA USA. [Amsterdam, Ezra] Univ Calif Davis, Div Cardiovasc Med, Davis, CA 95616 USA. [Hirshfeld, John W.] Univ Penn, Sch Med, Div Cardiovasc, Philadelphia, PA 19104 USA. RP Blumenthal, RS (reprint author), Johns Hopkins Sch Med, Ciccarone Ctr Prevent Heart Dis, 600 N Wolfe St,Blalock 524C, Baltimore, MD 21287 USA. EM rblument@jhmi.edu NR 40 TC 9 Z9 9 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0160-9289 J9 CLIN CARDIOL JI Clin. Cardiol. PD JUL PY 2012 VL 35 IS 7 BP 404 EP 409 DI 10.1002/clc.22016 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 967EZ UT WOS:000305890500004 PM 22674150 ER PT J AU Rahilly-Tierney, C Vokonas, P Gaziano, JM Spiro, A AF Rahilly-Tierney, Catherine Vokonas, Pantel Gaziano, J. Michael Spiro, Avron, III TI Lifestyle Change and High-Density Lipoprotein Change: The US Department of Veterans Affairs Normative Aging Study SO CLINICAL CARDIOLOGY LA English DT Article ID CORONARY-HEART-DISEASE; MIDDLE-AGED MEN; MYOCARDIAL-INFARCTION; HDL-CHOLESTEROL; RISK; GEMFIBROZIL; PREVENTION; FRAMINGHAM; MORTALITY; FAMILY AB Background: We sought to determine whether lifestyle modifications are associated with high-density lipoprotein cholesterol (HDL-C) change in a cohort with long-term follow-up. Hypothesis: Changes in alcohol consumption, smoking, or body mass index (BMI) are associated with within-individual changes in HDL-C. Methods: We selected 1420 men with =2 HDL-C measurements from the US Department of Veterans Affairs Normative Aging Study (NAS). Changes in HDL-C (in milligrams/deciliter) over a 3-year period were calculated for each pair of exams. For each interval of HDL-C change, lifestyle exposures were categorized: participants maintained a stable BMI >25 kg/m2 (reference) or =25 kg/m2 since the previous exam, or increased or decreased BMI; participants were actively smoking at both exams (reference), nonsmokers at both exams, quit, or initiated smoking between exams; and participants maintained alcohol intake of <2 (reference) or =2 drinks daily since the previous exam, or increased or decreased alcohol intake. Longitudinal analysis was used to examine the relationship between the lifestyle change categories and 3-year change in HDL-C for each interval, adjusting for comorbidities, lipids, and cholesterol medication. Results: Participants were followed for approximately 14.3 years. Increases in HDL-C were associated with maintaining alcohol intake of =2 drinks daily (mean HDL-C increase, 0.86; P = 0.02), increasing alcohol intake from <2 to =2 drinks daily (mean, 2.53; P = 0.0003), and with maintaining a BMI of =25 kg/m2 (mean, 0.71; P = 0.04). Conclusions: Increases in alcohol consumption, maintaining moderate alcohol intake, and maintaining BMI =25 kg/m2 were associated with significant 3-year increases in HDL-C. Clin. Cardiol. 2012 DOI: 10.1002/clc.21978 The VA NAS is sponsored by the Cooperative Studies Program/ERIC, US Department of Veterans Affairs. This research was also supported by a VA Merit Review and a VA Research Career Scientist award to Avron Spiro. The authors have no other funding, financial relationships, or conflicts of interest to disclose. C1 [Rahilly-Tierney, Catherine; Vokonas, Pantel; Gaziano, J. Michael; Spiro, Avron, III] Boston VA Healthcare Syst, Massachusetts Vet Epidemiol & Res Informat Ctr MA, Boston, MA USA. [Rahilly-Tierney, Catherine; Gaziano, J. Michael] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. [Rahilly-Tierney, Catherine; Gaziano, J. Michael] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Vokonas, Pantel] Boston Univ, Dept Med, Boston, MA 02215 USA. [Spiro, Avron, III] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Spiro, Avron, III] Boston Univ, Dept Psychiat, Boston, MA 02215 USA. RP Rahilly-Tierney, C (reprint author), 13th Floor,150 S Huntington Ave, Jamaica Plain, MA 02130 USA. EM crahilly-tierney@partners.org OI Spiro III, Avron/0000-0003-4080-8621 FU Cooperative Studies Program/ERIC, US Department of Veterans Affairs; VA Merit Review; VA Research Career Scientist award FX The VA NAS is sponsored by the Cooperative Studies Program/ERIC, US Department of Veterans Affairs. This research was also supported by a VA Merit Review and a VA Research Career Scientist award to Avron Spiro. The authors have no other funding, financial relationships, or conflicts of interest to disclose. NR 20 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0160-9289 J9 CLIN CARDIOL JI Clin. Cardiol. PD JUL PY 2012 VL 35 IS 7 BP 437 EP 442 DI 10.1002/clc.21978 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 967EZ UT WOS:000305890500009 PM 22407520 ER PT J AU El-Serag, HB AF El-Serag, Hashem B. TI The New Board of Editors for Clinical Gastroenterology and Hepatology: Our Vision and Plans SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Editorial Material C1 Baylor Coll Med, Houston VA Med Ctr, Houston, TX 77030 USA. RP El-Serag, HB (reprint author), Baylor Coll Med, Houston VA Med Ctr, Houston, TX 77030 USA. EM hasheme@bcm.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD JUL PY 2012 VL 10 IS 7 BP 690 EP 691 DI 10.1016/j.cgh.2012.05.001 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 969QA UT WOS:000306069300003 PM 22721437 ER PT J AU Omer, ZB Ananthakrishnan, AN Nattinger, KJ Cole, EB Lin, JJ Kong, CY Hur, C AF Omer, Zehra B. Ananthakrishnan, Ashwin N. Nattinger, Kevin J. Cole, Elisabeth B. Lin, Jesse J. Kong, Chung Yin Hur, Chin TI Aspirin Protects Against Barrett's Esophagus in a Multivariate Logistic Regression Analysis SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE Esophagus; GERD; Cancer Risk; NSAID ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; NONEROSIVE REFLUX DISEASE; CYCLOOXYGENASE-2 EXPRESSION; RISK-FACTORS; ADENOCARCINOMA SEQUENCE; EROSIVE ESOPHAGITIS; US ADULTS; CANCER; SURVEILLANCE; INFLAMMATION AB BACKGROUND & AIMS: Better criteria are needed to identify patients who should be screened for Barrett's esophagus (BE) to reduce overtesting and improve the cost effectiveness. There is evidence that chemopreventive agents such as nonsteroidal anti-inflammatory drugs, particularly aspirin, reduce the risk of esophageal adenocarcinoma (EAC), but little is known about their effects on BE. We analyzed characteristics of patients with BE for factors that might be used in screening and management. METHODS: In this case-controlled study, we identified 434 patients with BE diagnosed at the first endoscopy (incident cases) at a single institution (1997-2010). BE cases were matched with controls on the basis of indication for endoscopy, year of endoscopy, and endoscopist. Risk factors analyzed included age, sex, body mass index, medical and social history, and medications. We performed a multivariate logistic regression analysis to identify clinical risk factors for BE. RESULTS: In a multivariate regression model, men had a greater risk for developing BE (odds ratio, 3.2; 95% confidence interval, 2.3-4.4), whereas current aspirin users had a lower risk than nonusers (odds ratio, 0.56; 95% confidence interval, 0.39-0.80). A subset analysis, limited to patients who had endoscopies for symptoms of gastroesophageal reflux disease, yielded similar findings. No interactions were found between aspirin use and smoking or use of acid-suppressive medications. CONCLUSIONS: In a case-controlled study of 434 patients with BE, current aspirin use appeared to reduce the risk of BE; previous studies associated aspirin use with a reduced risk of EAC. Although efforts were made to minimize biases in our analysis, the possibility of residual confounding remains. C1 [Kong, Chung Yin; Hur, Chin] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Omer, Zehra B.; Ananthakrishnan, Ashwin N.; Nattinger, Kevin J.; Cole, Elisabeth B.; Lin, Jesse J.; Hur, Chin] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Ananthakrishnan, Ashwin N.; Kong, Chung Yin; Hur, Chin] Harvard Univ, Sch Med, Boston, MA USA. RP Hur, C (reprint author), Massachusetts Gen Hosp, Inst Technol Assessment, 101 Merrimac St,10th Floor, Boston, MA 02114 USA. EM chur@partners.org OI Hur, Chin/0000-0002-2819-7576 FU NIH/NCI [R01-CA140574, U01-CA152926, K25-CA133141] FX Funding Supported by NIH/NCI grants R01-CA140574 and U01-CA152926 (C.H.) and K25-CA133141 (C.Y.K). NR 32 TC 28 Z9 28 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD JUL PY 2012 VL 10 IS 7 BP 722 EP 727 DI 10.1016/j.cgh.2012.02.031 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 969QA UT WOS:000306069300008 PM 22426086 ER PT J AU Fleischhacker, WW DeLisi, LE AF Fleischhacker, W. Wolfgang DeLisi, Lynn E. TI Should a 'psychosis risk syndrome' be a separate diagnosis in DSM-5? SO CURRENT OPINION IN PSYCHIATRY LA English DT Editorial Material C1 [Fleischhacker, W. Wolfgang] VA Boston Healthcare Syst, Brockton, MA USA. RP Fleischhacker, WW (reprint author), VA Boston Healthcare Syst, Brockton, MA USA. EM wolfgang.fleischhacker@i-med.ac.at NR 8 TC 3 Z9 3 U1 0 U2 1 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 JUL PY 2012 VL 25 IS 4 BP 327 EP 328 DI 10.1097/YCO.0b013e3283535921 PG 2 WC Psychiatry SC Psychiatry GA 967PB UT WOS:000305919200012 PM 22634520 ER PT J AU Barteneva, N Duckett, L Fasler-Kan, E Vorobjev, I AF Barteneva, Natasha Duckett, Larry Fasler-Kan, Elizaveta Vorobjev, Ivan TI Microparticles-in the search of biomarkers for infectious diseases and cancer SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Meeting Abstract CT 2nd Bi-Annual International Practical Cytometry Workshop CY AUG 26-30, 2011 CL Moscow, RUSSIA C1 [Barteneva, Natasha] Childrens Hosp, IDI, Boston, MA 02115 USA. [Barteneva, Natasha] Harvard Univ, Boston, MA 02115 USA. [Duckett, Larry] BD Biosci, San Jose, CA USA. Univ Appl Sci, Basel, Switzerland. Moscow MV Lomonosov State Univ, Moscow, Russia. Minist Publ Hlth Russia, Hematol Res Ctr, Moscow, Russia. [Barteneva, Natasha] Childrens Hosp, PCIMM, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD JUL PY 2012 VL 82B IS 4 BP O2 EP O2 PG 1 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 962PH UT WOS:000305556900005 ER PT J AU Barteneva, N AF Barteneva, Natasha TI Design of multicolor panels in flow cytometry SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Meeting Abstract CT 2nd Bi-Annual International Practical Cytometry Workshop CY AUG 26-30, 2011 CL Moscow, RUSSIA C1 [Barteneva, Natasha] Childrens Hosp, IDI, Boston, MA 02115 USA. [Barteneva, Natasha] Harvard Univ, Boston, MA 02115 USA. [Barteneva, Natasha] Childrens Hosp, PCIMM, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD JUL PY 2012 VL 82B IS 4 BP O2 EP O2 PG 1 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 962PH UT WOS:000305556900004 ER PT J AU Lieberman, J AF Lieberman, Judy TI How Cytotoxic Cells Kill SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Meeting Abstract CT 2nd Bi-Annual International Practical Cytometry Workshop CY AUG 26-30, 2011 CL Moscow, RUSSIA C1 [Lieberman, Judy] Childrens Hosp, IDI, Boston, MA 02115 USA. [Lieberman, Judy] Harvard Univ, Boston, MA 02115 USA. [Lieberman, Judy] Childrens Hosp, PCIMM, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD JUL PY 2012 VL 82B IS 4 BP O1 EP O1 PG 1 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 962PH UT WOS:000305556900002 ER PT J AU Potashnikova, D Gladkikh, A Gretsov, E Barteneva, N Vorobjev, I AF Potashnikova, D. Gladkikh, A. Gretsov, E. Barteneva, N. Vorobjev, I TI Expression of BCR-associated signaling components in sorted B-cell cells SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Meeting Abstract CT 2nd Bi-Annual International Practical Cytometry Workshop CY AUG 26-30, 2011 CL Moscow, RUSSIA C1 [Potashnikova, D.; Gladkikh, A.; Gretsov, E.; Vorobjev, I] Natl Res Ctr Hematol, Moscow, Russia. [Potashnikova, D.; Barteneva, N.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA USA. [Vorobjev, I] Moscow MV Lomonosov State Univ, Moscow, Russia. RI Gladkikh, Alina/C-3589-2015 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD JUL PY 2012 VL 82B IS 4 BP O13 EP O14 PG 2 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 962PH UT WOS:000305556900029 ER PT J AU Preffer, FI AF Preffer, Frederic I. TI Modern approaches to diagnostics of leukemia and lymphoma SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Meeting Abstract CT 2nd Bi-Annual International Practical Cytometry Workshop CY AUG 26-30, 2011 CL Moscow, RUSSIA C1 [Preffer, Frederic I.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD JUL PY 2012 VL 82B IS 4 BP O6 EP O7 PG 2 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 962PH UT WOS:000305556900015 ER PT J AU Simon, NM AF Simon, Naomi Michele TI IS COMPLICATED GRIEF A POST-LOSS STRESS DISORDER? SO DEPRESSION AND ANXIETY LA English DT Article ID POSTTRAUMATIC-STRESS; DIAGNOSTIC-CRITERIA; INDIVIDUALS; COMORBIDITY; PREVALENCE; TRAUMA C1 [Simon, Naomi Michele] Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Boston, MA 02114 USA. [Simon, Naomi Michele] Massachusetts Gen Hosp, Complicated Grief Program, Boston, MA 02114 USA. [Simon, Naomi Michele] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Simon, Naomi Michele] Massachusetts Gen Hosp, Home Base Program, Boston, MA 02114 USA. [Simon, Naomi Michele] Amer Psychiat Assoc, Washington, DC 20005 USA. RP Simon, NM (reprint author), Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, 1 Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM nsimon@partners.org NR 20 TC 13 Z9 13 U1 2 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PD JUL PY 2012 VL 29 IS 7 BP 541 EP 544 DI 10.1002/da.21979 PG 4 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 967VP UT WOS:000305936200001 PM 22761109 ER PT J AU Zisook, S Corruble, E Duan, NH Iglewicz, A Karam, EG Lanouette, N Lebowitz, B Pies, R Reynolds, C Seay, K Shear, MK Simon, N Young, IT AF Zisook, Sidney Corruble, Emmanuelle Duan, Naihua Iglewicz, Alana Karam, Elie G. Lanouette, Nicole Lebowitz, Barry Pies, Ronald Reynolds, Charles Seay, Kathryn Shear, M. Katherine Simon, Naomi Young, Ilanit Tal TI THE BEREAVEMENT EXCLUSION AND DSM-5 (vol 29, pg 425, 2012) SO DEPRESSION AND ANXIETY LA English DT Correction C1 [Zisook, Sidney; Iglewicz, Alana; Lanouette, Nicole; Lebowitz, Barry; Young, Ilanit Tal] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Zisook, Sidney; Iglewicz, Alana; Lanouette, Nicole; Young, Ilanit Tal] Vet Affairs San Diego Healthcare Syst, La Jolla, CA USA. [Corruble, Emmanuelle] Bicetre Univ Hosp, Assistance Publ Hop Paris, Dept Psychiat, INSERM U669, Le Kremlin Bicetre, France. [Duan, Naihua; Lebowitz, Barry] Columbia Univ, Dept Biostat, New York, NY USA. [Duan, Naihua] New York State Psychiat Inst & Hosp, Div Biostat & Data Coordinat, New York, NY 10032 USA. [Karam, Elie G.] Balamand Univ, St George Hosp Univ Med Ctr, Dept Psychiat & Clin Psychol, Beirut, Lebanon. [Karam, Elie G.] MIND, Fac Med, Beirut, Lebanon. [Duan, Naihua; Lebowitz, Barry] Columbia Univ, Dept Psychiat, New York, NY USA. [Pies, Ronald] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. [Pies, Ronald] Tufts Univ, Sch Med, Dept Psychiat, Boston, MA 02111 USA. [Reynolds, Charles] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Reynolds, Charles] Univ Pittsburgh, Western Psychiat Inst & Clin, Dept Community & Behav Hlth Sci, Grad Sch Publ Hlth, Pittsburgh, PA 15213 USA. [Seay, Kathryn] Educ & Res Fdn, San Diego State Joint Doctoral Program Clin Psych, La Jolla, CA USA. [Seay, Kathryn] Univ Calif, La Jolla, CA 92093 USA. [Karam, Elie G.] IDRAAC, Beirut, Lebanon. [Zisook, Sidney] Vet Med & Res Fdn, La Jolla, CA USA. [Shear, M. Katherine] Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. [Shear, M. Katherine] Columbia Univ, Sch Social Work, Complicated Grief Treatment Res Program, New York, NY USA. [Simon, Naomi] Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Boston, MA 02114 USA. [Simon, Naomi] Massachusetts Gen Hosp, Complicated Grief Program, Boston, MA 02114 USA. RP Zisook, S (reprint author), Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PD JUL PY 2012 VL 29 IS 7 BP 665 EP 665 DI 10.1002/da.21972 PG 1 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 967VP UT WOS:000305936200014 ER PT J AU Wu, WL Ibrahimi, OA Eisen, DB AF Wu, Wesley Ibrahimi, Omar A. Eisen, Daniel B. TI Cheek Advancement Flap with Retained Standing Cone for Reconstruction of a Defect Involving the Upper Lip, Nasal Sill, Alar Insertion, and Medial Cheek SO DERMATOLOGIC SURGERY LA English DT Editorial Material ID ISLAND PEDICLE FLAP; BUROWS WEDGE FLAP; PERIALAR; GRAFTS C1 [Eisen, Daniel B.] Univ Calif Davis, Dept Dermatol, Med Ctr, Sacramento, CA 95816 USA. [Wu, Wesley] Brown Univ, Dept Dermatol, Warren Alpert Med Sch, Providence, RI 02912 USA. [Ibrahimi, Omar A.] Univ Connecticut, Ctr Hlth, Div Dermatol, Farmington, CT 06032 USA. [Ibrahimi, Omar A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. RP Eisen, DB (reprint author), Univ Calif Davis, Dept Dermatol, Med Ctr, 3301 C St,1400, Sacramento, CA 95816 USA. EM deisen123@gmail.com OI Eisen, Daniel/0000-0001-6741-3182 NR 33 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1076-0512 EI 1524-4725 J9 DERMATOL SURG JI Dermatol. Surg. PD JUL PY 2012 VL 38 IS 7 BP 1077 EP 1082 DI 10.1111/j.1524-4725.2012.02377.x PN 1 PG 6 WC Dermatology; Surgery SC Dermatology; Surgery GA 967XC UT WOS:000305940400020 PM 22404296 ER PT J AU Ezra, N Hamid, O Behroozan, D AF Ezra, Navid Hamid, Omid Behroozan, Daniel TI Eruptive Squamous Cell Carcinomas Associated with BRAF-Inhibitor Therapy in a Patient with Metastatic Melanoma SO DERMATOLOGIC SURGERY LA English DT Editorial Material ID RAF INHIBITORS; RAS/RAF/MEK/ERK PATHWAY; ACTINIC KERATOSES; GENE MUTATION; MAPK PATHWAY; HUMAN SKIN; CANCER; SORAFENIB; KERATOACANTHOMAS; PROGRESSION C1 [Behroozan, Daniel] Dermatol Inst So Calif, Santa Monica, CA 90405 USA. [Ezra, Navid; Behroozan, Daniel] Univ Calif Los Angeles, David Geffen Sch Med, Div Dermatol, Dept Med, Los Angeles, CA 90095 USA. [Hamid, Omid] Angeles Clin & Res Inst, Los Angeles, CA USA. [Behroozan, Daniel] W Los Angeles Vet Adm Med Ctr, Dept Dermatol, Los Angeles, CA USA. RP Behroozan, D (reprint author), Dermatol Inst So Calif, 2221 Lincoln Blvd,Suite 100, Santa Monica, CA 90405 USA. EM db@dermsurgery.net NR 39 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1076-0512 EI 1524-4725 J9 DERMATOL SURG JI Dermatol. Surg. PD JUL PY 2012 VL 38 IS 7 BP 1086 EP 1090 DI 10.1111/j.1524-4725.2012.02396.x PN 1 PG 5 WC Dermatology; Surgery SC Dermatology; Surgery GA 967XC UT WOS:000305940400022 PM 22563699 ER PT J AU Barton, FB Rickels, MR Alejandro, R Hering, BJ Wease, S Naziruddin, B Oberholzer, J Odorico, JS Garfinkel, MR Levy, M Pattou, F Berney, T Secchi, A Messinger, S Senior, PA Maffi, P Posselt, A Stock, PG Kaufman, DB Luo, XR Kandeel, F Cagliero, E Turgeon, NA Witkowski, P Naji, A O'Connell, PJ Greenbaum, C Kudva, YC Brayman, KL Aull, MJ Larsen, C Kay, TWH Fernandez, LA Vantyghem, MC Bellin, M Shapiro, AMJ AF Barton, Franca B. Rickels, Michael R. Alejandro, Rodolfo Hering, Bernhard J. Wease, Stephen Naziruddin, Bashoo Oberholzer, Jose Odorico, Jon S. Garfinkel, Marc R. Levy, Marlon Pattou, Francois Berney, Thierry Secchi, Antonio Messinger, Shari Senior, Peter A. Maffi, Paola Posselt, Andrew Stock, Peter G. Kaufman, Dixon B. Luo, Xunrong Kandeel, Fouad Cagliero, Enrico Turgeon, Nicole A. Witkowski, Piotr Naji, Ali O'Connell, Philip J. Greenbaum, Carla Kudva, Yogish C. Brayman, Kenneth L. Aull, Meredith J. Larsen, Christian Kay, Tom W. H. Fernandez, Luis A. Vantyghem, Marie-Christine Bellin, Melena Shapiro, A. M. James TI Improvement in Outcomes of Clinical Islet Transplantation: 1999-2010 SO DIABETES CARE LA English DT Article ID CELL SECRETORY CAPACITY; DIABETES-MELLITUS; EDMONTON PROTOCOL; RECIPIENTS; PANCREAS; DONOR AB OBJECTIVE-To describe trends of primary efficacy and safety outcomes of islet transplantation in type 1 diabetes recipients with severe hypoglycemia from the Collaborative Islet Transplant Registry (CITR) from 1999 to 2010. RESEARCH DESIGN AND METHODS-A total of 677 islet transplant-alone or islet-after-kidney recipients with type 1 diabetes in the CITR were analyzed for five primary efficacy outcomes and overall safety to identify any differences by early (1999-2002), mid (2003-2006), or recent (2007-2010) transplant era based on annual follow-up to 5 years. RESULTS-Insulin independence at 3 years after transplant improved from 27% in the early era (1999-2002, n = 214) to 37% in the mid (2003-2006, n = 255) and to 44% in the most recent era (2007-2010, n = 208; P = 0.006 for years-by-era; P = 0.01 for era alone). C-peptide >= 0.3 ng/mL, indicative of islet graft function, was retained longer in the most recent era (P < 0.001). Reduction of HbA(1c) and resolution of severe hypoglycemia exhibited enduring long-term effects. Fasting blood glucose stabilization also showed improvements in the most recent era. There were also modest reductions in the occurrence of adverse events. The islet reinfusion rate was lower: 48% by 1 year in 2007-2010 vs. 60-65% in 1999-2006 (P < 0.01). Recipients that ever achieved insulin-independence experienced longer duration of islet graft function (P < 0.001). CONCLUSIONS-The CITR shows improvement in primary efficacy and safety outcomes of islet transplantation in recipients who received transplants in 2007-2010 compared with those in 1999-2006, with fewer islet infusions and adverse events per recipient. C1 [Barton, Franca B.; Wease, Stephen] EMMES Corp, Rockville, MD USA. [Rickels, Michael R.; Naji, Ali] Univ Penn, Dept Surg, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA. [Alejandro, Rodolfo; Messinger, Shari] Univ Miami, Dept Med, Div Endocrinol Diabet & Metab, Miami, FL USA. [Hering, Bernhard J.; Bellin, Melena] Univ Minnesota, Dept Surg, Minneapolis, MN 55455 USA. [Hering, Bernhard J.; Bellin, Melena] Univ Minnesota, Schultze Diabet Inst, Minneapolis, MN USA. [Naziruddin, Bashoo] Baylor Univ, Med Ctr, Inst Biomed Sci, Islet Proc Lab, Dallas, TX USA. [Oberholzer, Jose] Univ Illinois, Dept Surg, Div Transplant Surg, Chicago, IL 60680 USA. [Odorico, Jon S.; Kaufman, Dixon B.; Fernandez, Luis A.] Univ Wisconsin, Dept Surg, Div Transplantat, Madison, WI USA. [Garfinkel, Marc R.] So Illinois Univ, Div Gen Surg, Dept Surg, Springfield, IL USA. [Levy, Marlon] Univ Texas Dallas, Dept Transplant Serv, SW Med Sch, Dallas, TX 75230 USA. [Pattou, Francois; Vantyghem, Marie-Christine] Univ Lille, Dept Gen & Endocrine Surg, Lille, France. [Berney, Thierry] Univ Hosp Geneva, Dept Surg, Div Transplantat & Visceral Surg, Geneva, Switzerland. [Secchi, Antonio; Maffi, Paola] San Raffaele Univ, Dept Internal Med, Milan, Italy. [Senior, Peter A.; Shapiro, A. M. James] Univ Alberta, Dept Med, Div Endocrinol, Edmonton, AB, Canada. [Posselt, Andrew; Stock, Peter G.] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. [Luo, Xunrong] Northwestern Univ, Dept Med, Chicago, IL 60611 USA. [Kandeel, Fouad] City Hope Natl Med Ctr, Div Endocrinol Diabet & Metab, Duarte, CA USA. [Cagliero, Enrico] Massachusetts Gen Hosp, MGH Diabet Ctr, Boston, MA 02114 USA. [Turgeon, Nicole A.; Larsen, Christian] Emory Univ, Dept Surg, Div Transplantat, Atlanta, GA 30322 USA. [Witkowski, Piotr] Univ Chicago, Dept Surg, Chicago, IL 60637 USA. [O'Connell, Philip J.] Westmead Hosp, Ctr Transplant & Renal Res, Westmead, NSW 2145, Australia. [Greenbaum, Carla] Benaroya Res Inst, Diabet Program, Seattle, WA USA. [Kudva, Yogish C.] Mayo Clin, Dept Endocrinol, Rochester, MN USA. [Brayman, Kenneth L.] Univ Virginia, Dept Transplantat Surg, Charlottesville, VA USA. [Aull, Meredith J.] Weill Cornell Med Coll, Div Transplantat Surg, New York, NY USA. [Kay, Tom W. H.] St Vincents Inst Med Res, Dept Med, Fitzroy, Vic 3065, Australia. RP Barton, FB (reprint author), EMMES Corp, Rockville, MD USA. EM fbarton@emmes.com RI Senior, Peter/E-3031-2013 OI Senior, Peter/0000-0003-1033-8673 FU NIDDK; National Institutes of Health; JDRF International FX The CITR is funded by the NIDDK, National Institutes of Health, and by a supplemental grant from the JDRF International. Additional data were made available through cooperative agreements with the U.S. United Network for Organ Sharing, Alexandria, Virginia, the Administrative and Bioinformatics Coordinating Center of the City of Hope, Duarte, California (1999-2009), and the NIDDK-sponsoral CIT (www.citisletstudy.org), coordinated by the University of Iowa Clinical Trials and Data Management Center (2008 present). NR 23 TC 248 Z9 253 U1 2 U2 29 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 JUL PY 2012 VL 35 IS 7 BP 1436 EP 1445 DI 10.2337/dc12-0063 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 962MJ UT WOS:000305548900008 PM 22723582 ER PT J AU Beverly, EA Ganda, OP Ritholz, MD Lee, Y Brooks, KM Lewis-Schroeder, NF Hirose, M Weinger, K AF Beverly, Elizabeth A. Ganda, Om P. Ritholz, Marilyn D. Lee, Yishan Brooks, Kelly M. Lewis-Schroeder, Nina F. Hirose, Masakazu Weinger, Katie TI Look Who's (Not) Talking Diabetic patients' willingness to discuss self-care with physicians SO DIABETES CARE LA English DT Article ID QUALITY-OF-LIFE; GLYCEMIC CONTROL; PROVIDER COMMUNICATION; DEPRESSIVE SYMPTOMS; HEALTH-CARE; ADULTS; COMPLICATIONS; MANAGEMENT; METAANALYSIS; PREVALENCE AB OBJECTIVE-Nearly one-half of diabetic patients have glycated hemoglobin A(1c) (HbA(1c)) levels above recommended targets. Effective physician patient communication improves glycemia and diabetes self-care; however, communication gaps may exist that prevent patients from discussing self-care problems with treatment providers. RESEARCH DESIGN AND METHODS-We assessed diabetic patients' (n = 316, 85% white, 51% female, 71% type 2 diabetes, 59 +/- 11 years old, 16 +/- 3 years education, 19 +/- 13 years diabetes duration, and HbA(1c) = 7.9 +/- 1.4%) HbA(1c), frequency of self-care, diabetes-related distress, depressive and anxiety symptoms, coping styles, diabetes quality of life, and self-care communication in the treatment relationship. Multivariate logistic regression models examined the main and interaction effects of health and psychosocial factors associated with patients' reluctance to discuss self-care. RESULTS-Patients reported positive relationships with their doctors and valued honest communication; however, 30% of patients were reluctant to discuss self-care. Reluctant patients reported less frequent self-care (P = 0.05), lower diabetes quality of life (P = 0.002), and more diabetes-related distress (P = 0.001), depressive symptoms (P < 0.001), and anxiety symptoms (P = 0.001). Patients who reported elevated depressive symptoms, although not necessarily major depression, were more likely to be reluctant to discuss self-care (odds ratio [OR] 1.66 for 10-point change in t score; P < 0.001), whereas patients who were older (OR 0.78 for 10-year change; P = 0.05) and those who used more self-controlled coping styles (OR 0.78 for 10-point change; P = 0.007) were less likely to be reluctant. CONCLUSIONS-Awareness of elevated depressive symptoms is important in clinical practice given that these patients may be more reluctant to discuss self-care. Interventions and evidence-based approaches are needed to improve both depressive symptoms and physician-patient communication about self-care. C1 [Beverly, Elizabeth A.; Ganda, Om P.; Ritholz, Marilyn D.; Lee, Yishan; Brooks, Kelly M.; Lewis-Schroeder, Nina F.; Hirose, Masakazu; Weinger, Katie] Joslin Diabet Ctr, Boston, MA 02215 USA. [Beverly, Elizabeth A.; Ganda, Om P.; Ritholz, Marilyn D.; Lewis-Schroeder, Nina F.; Hirose, Masakazu; Weinger, Katie] Harvard Univ, Sch Med, Boston, MA USA. [Ritholz, Marilyn D.] Childrens Hosp, Boston, MA 02115 USA. RP Weinger, K (reprint author), Joslin Diabet Ctr, Boston, MA 02215 USA. EM katie.weinger@joslin.harvard.edu FU Kathleen P. Welsh Fund; National Institutes of Health (NIH) Grant [R01-DK-60115]; American Diabetes Association Grant [7-08-CR-62]; Diabetes and Endocrinology Research Core NIH [P30-DK-36836]; NIH Training Grant [T32-DK-007260]; Merck; Abbott; GlaxoSmithKline; Bristol-Myers Squibb; AstraZeneca; Daiichi Sankyo FX This work was supported by the Kathleen P. Welsh Fund, National Institutes of Health (NIH) Grant R01-DK-60115, American Diabetes Association Grant 7-08-CR-62, the Diabetes and Endocrinology Research Core NIH P30-DK-36836, and NIH Training Grant T32-DK-007260.; O.P.G. has provided consulting services to Abbott; received payment for lectures from Merck, Abbott, GlaxoSmithKline, Bristol-Myers Squibb, AstraZeneca, and Daiichi Sankyo; and has stock options with BMS. No other potential conflicts of interest relevant to this article were reported. NR 41 TC 26 Z9 27 U1 5 U2 12 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 JUL PY 2012 VL 35 IS 7 BP 1466 EP 1472 DI 10.2337/dc11-2422 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 962MJ UT WOS:000305548900012 PM 22619085 ER PT J AU Sosenko, JM Skyler, JS Mahon, J Krischer, JP Beam, CA Boulware, DC Greenbaum, CJ Rafkin, LE Cowie, C Cuthbertson, D Palmer, JP AF Sosenko, Jay M. Skyler, Jay S. Mahon, Jeffrey Krischer, Jeffrey P. Beam, Craig A. Boulware, David C. Greenbaum, Carla J. Rafkin, Lisa E. Cowie, Catherine Cuthbertson, David Palmer, Jerry P. CA Type 1 Diabet TrialNet & Diabet Pr TI The Application of the Diabetes Prevention Trial-Type 1 Risk Score for Identifying a Preclinical State of Type 1 Diabetes SO DIABETES CARE LA English DT Article ID BETA-CELL FUNCTION; GLUCOSE-TOLERANCE; INSULIN; ONSET; TRIAL-TYPE-1; MELLITUS; PARTICIPANTS; PROGRESSION; ANTIBODIES AB OBJECTIVE-We assessed the utility of the Diabetes Prevention Trial Type 1 Risk Score (DPTRS) for identifying individuals who are highly likely to progress to type 1 diabetes (T ID) within 2 years. RESEARCH DESIGN AND METHODS-The DPTRS was previously developed from Diabetes Prevention Trial Type 1 (DPT-1) data and was subsequently validated in the TrialNet Natural History Study (TNNHS). DPTRS components included C-peptide and glucose indexes from oral glucose tolerance testing, along with age and BM1. The cumulative incidence of T ID was determined after DPTRS thresholds were first exceeded and after the first occurrences of glucose abnormalities. RESULTS-The 2-year risks after the 9.00 DPTRS threshold was exceeded were 0.88 and 0.77 in DPT-1 (n = 90) and the TNNHS (n = 69), respectively. In DPT-1, the 2-year risks were much lower after dysglycemia first occurred (0.37; n = 306) and after a 2-h glucose value between 190 and 199 mg/dL was first reached (0.64; n = 59). Among those who developed T1D in DPT-1, the 9.00 threshold was exceeded 0.81 +/- 0.53 years prior to the conventional diagnosis. Post-challenge C-peptide levels were substantially higher (P = 0.001 for 30 min; P < 0.001 for other time points) when the 9.00 threshold was first exceeded compared with the levels at diagnosis. CONCLUSIONS-A DPTRS threshold of 9.00 identifies individuals who are very highly likely to progress to the conventional diagnosis of T ID within 2 years and, thus, are essentially in a preclinical diabetic state. The 9.00 threshold is exceeded well before diagnosis, when stimulated C-peptide levels are substantially higher. Diabetes Care 35:1552-1555,2012 C1 [Sosenko, Jay M.; Skyler, Jay S.; Rafkin, Lisa E.] Univ Miami, Div Endocrinol, Miami, FL 33136 USA. [Mahon, Jeffrey] Univ Western Ontario, Dept Epidemiol & Biostat, London, ON, Canada. [Krischer, Jeffrey P.; Beam, Craig A.; Boulware, David C.] Univ S Florida, Div Informat & Biostat, Tampa, FL USA. [Greenbaum, Carla J.] Benaroya Res Inst Virginia Mason, Seattle, WA USA. [Cowie, Catherine] NIDDK, NIH, Bethesda, MD USA. [Cuthbertson, David] Univ S Florida, Pediat Epidemiol Ctr, Tampa, FL USA. [Palmer, Jerry P.] Univ Washington, VA Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. RP Sosenko, JM (reprint author), Univ Miami, Div Endocrinol, Miami, FL 33136 USA. EM jsosenko@med.miami.edu RI Skyler, Jay/F-4211-2016 FU National Institutes of Health through the National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Allergy and Infectious Diseases; Eunice Kennedy Shriver National Institute for Child Health and Human Development; National Center for Research Resources; Juvenile Diabetes Research Foundation International; American Diabetes Association FX This work was funded by the National Institutes of Health through the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute for Child Health and Human Development, and the National Center for Research Resources; by the Juvenile Diabetes Research Foundation International; and by the American Diabetes Association. NR 20 TC 17 Z9 17 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 JUL PY 2012 VL 35 IS 7 BP 1552 EP 1555 DI 10.2337/dc12-0011 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 962MJ UT WOS:000305548900026 PM 22547092 ER PT J AU Wexler, DJ Porneala, B Chang, YC Huang, ES Huffman, JC Grant, RW AF Wexler, Deborah J. Porneala, Bianca Chang, Yuchiao Huang, Elbert S. Huffman, Jeff C. Grant, Richard W. TI Diabetes Differentially Affects Depression and Self-Rated Health by Age in the U.S SO DIABETES CARE LA English DT Article ID NATIONAL SOCIAL-LIFE; AGING PROJECT; MELLITUS; MORTALITY; ADULTS; RISK AB OBJECTIVE-To determine whether the relationship between age and physical and mental health varies by diabetes status in older U.S. adults. RESEARCH DESIGN AND METHODS-Using data from the National Social Life, Health, and Aging Project, a national sample of 3,005 adults aged 57-85 years, we tested the significance of the interaction between age and diabetes in association with health states. RESULTS-Respondents with diabetes in the youngest age cohort had more medical conditions than those without diabetes, a difference that narrowed with age (P for interaction <0.01). The youngest cohort with diabetes had a higher rate of depression compared to those without diabetes (14 vs. 8%). Depression declined with age and did not differ by diabetes status in the oldest respondents (P = 0.01 for age-diabetes interaction). CONCLUSIONS-Diabetes differentially affects self-rated overall health and depression by age, with convergence in the oldest age-group with and without diabetes. Diabetes Care 35:1575-1577,2012 C1 [Wexler, Deborah J.] Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. [Wexler, Deborah J.; Huffman, Jeff C.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Porneala, Bianca; Chang, Yuchiao] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Huang, Elbert S.] Univ Chicago, Div Gen Med, Chicago, IL 60637 USA. [Huffman, Jeff C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Grant, Richard W.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. RP Wexler, DJ (reprint author), Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. EM dwexler@partners.org OI Grant, Richard/0000-0002-6164-8025 FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [R03 DK090196-01A1]; NIDDK Career Development Award [K23 DK 080228-05]; National Institute on Aging at the National Institutes of Health [R01 AG030481]; NIDDK Diabetes and Research Training Center at the University of Chicago [P60 DK20595]; Chicago Center for Diabetes Translation Research at the University of Chicago [P30 DK092949] FX This research study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (R03 DK090196-01A1), and D.J.W. is supported by an NIDDK Career Development Award (K23 DK 080228-05). E.S.H. receives support from the National Institute on Aging at the National Institutes of Health (R01 AG030481). E.S.H. also receives support from the NIDDK Diabetes and Research Training Center (P60 DK20595) and the Chicago Center for Diabetes Translation Research (P30 DK092949), both at the University of Chicago. NR 15 TC 10 Z9 11 U1 1 U2 5 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 JUL PY 2012 VL 35 IS 7 BP 1575 EP 1577 DI 10.2337/dc11-2266 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 962MJ UT WOS:000305548900030 PM 22611066 ER PT J AU Tapias, LF Morse, CR AF Tapias, L. F. Morse, C. R. TI A preliminary experience with minimally invasive Ivor Lewis esophagectomy SO DISEASES OF THE ESOPHAGUS LA English DT Article DE esophageal neoplasm; esophagectomy; laparoscopy; minimally invasive surgical procedure; video-assisted thoracic surgery ID PERIOPERATIVE OUTCOMES; LAPAROSCOPIC ESOPHAGECTOMY; CANCER AB With several small series examining minimally invasive Ivor Lewis esophagectomies, we look to contribute to a growing experience. In reporting our initial results, safety, initial oncologic completeness, and preliminary outcomes with a minimally invasive Ivor Lewis esophagectomy were demonstrated. From 2007 to 2010, 40 minimally invasive Ivor Lewis esophagectomies were carried out. The approach was a laparoscopic mobilization of the stomach and a thoracoscopic esophageal mobilization and creation of a high intrathoracic anastomosis. Indications included esophageal cancer in 39 patients and esophageal gastrointestinal stromal tumor in one patient. Median age was 62 (range 3977) with 31 (78%) male patients. Non-emergent conversion was required in two (5%) patients. Twenty-five (63%) patients underwent neoadjuvant therapy. Mean operative time was 364 minutes (range 285455), and mean blood loss was 205 cc (range 100400). All patients underwent an R0 resection including the removal of all Barrett's esophagus, and mean number of nodes harvested was 21 (range 1141). Median intensive care unit stay was 1 day (range 13), and hospital stay was 7 days (range 619). There were no anastomotic leaks and no 30-day mortality. Postoperative complications included eight (21%) patients with atrial fibrillation and two (5%) chylothorax, one requiring ligation. At a mean follow-up of 16.5 months (range 139 months), five (13%) patients have had a distant recurrence; there have been no local recurrences. Minimally invasive Ivor Lewis esophagectomy, although technically challenging, can be carried out with reasonable operative times, a short length of stay, and minimal complication. Final oncologic validity is pending longer follow-up and a larger series. C1 [Tapias, L. F.; Morse, C. R.] Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. RP Morse, CR (reprint author), 55 Fruit St,Blake 1570, Boston, MA 02114 USA. EM crmorse@partners.org NR 20 TC 11 Z9 12 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1120-8694 J9 DIS ESOPHAGUS JI Dis. Esophagus PD JUL PY 2012 VL 25 IS 5 BP 449 EP 455 DI 10.1111/j.1442-2050.2011.01269.x PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 967WW UT WOS:000305939800013 PM 21967644 ER PT J AU Maxwell, MM Zaldivar-Jolissaint, JF Mai, A Outeiro, TF Kazanstev, AG AF Maxwell, Michele M. Zaldivar-Jolissaint, Julien Francisco Mai, Antonello Outeiro, Tiago F. Kazanstev, Aleksey G. TI Highlights of the Keystone Symposium: sirtuins in metabolism, aging and disease SO EMBO MOLECULAR MEDICINE LA English DT Editorial Material AB From February 1216, 2012, leading members of the sirtuin scientific community assembled in Tahoe, CA to attend the Keystone Symposium Sirtuins in Aging, Metabolism, and Disease. It was a vibrant and lively meeting, and in the spirit of Keystone Symposia, both established sirtuin researchers and those new to the field enjoyed a unique opportunity to interact and exchange ideas. C1 [Maxwell, Michele M.; Kazanstev, Aleksey G.] Massachusetts Gen Hosp, MassGeneral Inst Neuodegenerat Dis, Charlestown, MA 02129 USA. [Maxwell, Michele M.; Kazanstev, Aleksey G.] Harvard Univ, Sch Med, Charlestown, MA USA. [Zaldivar-Jolissaint, Julien Francisco] Ecole Polytech Fed Lausanne, Lab Integrat Syst Physiol, Lausanne, Switzerland. [Mai, Antonello] Univ Roma La Sapienza, Dept Drug Chem & Technol, Rome, Italy. [Outeiro, Tiago F.] Univ Med Goettingen, Dept Neurodegenerat & Restorat Res, Gottingen, Germany. RP Kazanstev, AG (reprint author), Massachusetts Gen Hosp, MassGeneral Inst Neuodegenerat Dis, Charlestown, MA 02129 USA. EM akazantsev@partners.org OI Mai, Antonello/0000-0001-9176-2382 NR 0 TC 4 Z9 4 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1757-4676 EI 1757-4684 J9 EMBO MOL MED JI EMBO Mol. Med. PD JUL PY 2012 VL 4 IS 7 BP 557 EP 560 DI 10.1002/emmm.201201452 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 967YH UT WOS:000305943600005 PM 22610822 ER PT J AU Scaglioni, PP Rabellino, A Yung, TM Bernardi, R Choi, S Konstantinidou, G Nardella, C Cheng, K Pandolfi, PP AF Scaglioni, Pier Paolo Rabellino, Andrea Yung, Thomas M. Bernardi, Rosa Choi, Sooyeon Konstantinidou, Georgia Nardella, Caterina Cheng, Ke Pandolfi, Pier Paolo TI Translation-dependent mechanisms lead to PML upregulation and mediate oncogenic K-RAS-induced cellular senescence SO EMBO MOLECULAR MEDICINE LA English DT Article DE mTOR; oncogene-induced cellular senescence; oncogenic K-RAS; PML; protein translation ID PREMATURE SENESCENCE; TUMOR-SUPPRESSOR; TUBEROUS SCLEROSIS; P53 TRANSLATION; INDUCTION; PROTEIN; CANCER; CELLS; TUMORIGENESIS; PATHWAYS AB Expression of oncogenic K-RAS in primary cells elicits oncogene-induced cellular senescence (OIS), a form of growth arrest that potently opposes tumourigenesis. This effect has been largely attributed to transcriptional mechanisms that depend on the p53 tumour suppressor protein. The PML tumour suppressor was initially identified as a component of the PML-RARa oncoprotein of acute promyelocytic leukaemia (APL). PML, a critical OIS mediator, is upregulated by oncogenic K-RAS in vivo and in vitro. We demonstrate here that oncogenic K-RAS induces PML protein upregulation by activating the RAS/MEK1/mTOR/eIF4E pathway even in the absence of p53. Under these circumstances, PML mRNA is selectively associated to polysomes. Importantly, we find that the PML 5' untranslated mRNA region plays a key role in mediating PML protein upregulation and that its presence is essential for an efficient OIS response. These findings demonstrate that upregulation of PML translation plays a central role in oncogenic K-RAS-induced OIS. Thus, selective translation initiation plays a critical role in tumour suppression with important therapeutic implications for the treatment of solid tumours and APL. C1 [Scaglioni, Pier Paolo; Yung, Thomas M.; Bernardi, Rosa; Nardella, Caterina; Cheng, Ke; Pandolfi, Pier Paolo] Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst, Canc Biol & Genet Program, New York, NY 10021 USA. [Scaglioni, Pier Paolo; Rabellino, Andrea; Choi, Sooyeon; Konstantinidou, Georgia] Univ Texas SW Med Ctr Dallas, Div Hematol & Oncol, Dept Med, Dallas, TX 75390 USA. [Bernardi, Rosa; Nardella, Caterina; Cheng, Ke; Pandolfi, Pier Paolo] Harvard Univ, Beth Israel Deaconess Med Ctr, Med Sch,Canc Genet Program,Div Genet, Beth Israel Deaconess Canc Ctr,Dept Med & Pathol, Boston, MA 02215 USA. RP Scaglioni, PP (reprint author), Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst, Canc Biol & Genet Program, 1275 York Ave, New York, NY 10021 USA. EM pier.scaglioni@utsouthwestern.edu; ppandolf@bidmc.harvard.edu RI bernardi, rosa/B-1650-2013; Rabellino, Andrea/E-8756-2016; Konstantinidou, Georgia/O-9192-2016; OI Konstantinidou, Georgia/0000-0001-9513-0286; Scaglioni, Pier Paolo/0000-0002-6036-5138 FU NIH [CA 112325, RO1 CA 137195A1, R01 CA-71692, K01 CA118259]; American Cancer Society [02-196]; Concern Foundation; Gibson Foundation; Leukaemia Texas Inc.; American-Italian Cancer Foundation; Cancer prevention and Research Institute of Texas [RP101496] FX We are grateful to Drs. Harold E. Varmus, William Pao and Katerina Politi for providing the CC10-rtTA/tet-op-K-Ras transgenic mice and reagents. PPS was supported by NIH K08 grant CA 112325, NIH RO1 CA 137195A1, American Cancer Society Institutional Research Grant # 02-196, the Concern Foundation, the Gibson Foundation, Leukaemia Texas Inc. The American-Italian Cancer Foundation supported Andrea Rabellino. GK was supported by a Cancer prevention and Research Institute of Texas training grant RP101496. PPP was supported by NIH grant R01 CA-71692 and RB by K01 CA118259. NR 35 TC 13 Z9 14 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1757-4676 J9 EMBO MOL MED JI EMBO Mol. Med. PD JUL PY 2012 VL 4 IS 7 BP 594 EP 602 DI 10.1002/emmm.201200233 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 967YH UT WOS:000305943600009 PM 22359342 ER PT J AU Guix, FX Wahle, T Vennekens, K Snellinx, A Chavez-Gutierrez, L Ill-Raga, G Ramos-Fernandez, E Guardia-Laguarta, C Lleo, A Arimon, M Berezovska, O Munoz, FJ Dotti, CG De Strooper, B AF Guix, Francesc X. Wahle, Tina Vennekens, Kristel Snellinx, An Chavez-Gutierrez, Lucia Ill-Raga, Gerard Ramos-Fernandez, Eva Guardia-Laguarta, Cristina Lleo, Alberto Arimon, Muriel Berezovska, Oksana Munoz, Francisco J. Dotti, Carlos G. De Strooper, Bart TI Modification of gamma-secretase by nitrosative stress links neuronal ageing to sporadic Alzheimer's disease SO EMBO MOLECULAR MEDICINE LA English DT Article DE ageing; Alzheimer's disease; gamma-secretase; peroxynitrite; presenilin-1 ID AMYLOID PRECURSOR PROTEIN; OXIDATIVE STRESS; A-BETA; HIPPOCAMPAL-NEURONS; URIC-ACID; PRESENILIN MUTATIONS; MULTIPLE-SCLEROSIS; TALKING POINT; MOUSE MODEL; CELL-DEATH AB Inherited familial Alzheimer's disease (AD) is characterized by small increases in the ratio of A beta 42 versus A beta 40 peptide which is thought to drive the amyloid plaque formation in the brain of these patients. Little is known however whether ageing, the major risk factor for sporadic AD, affects amyloid beta-peptide (A beta) generation as well. Here we demonstrate that the secretion of A beta is enhanced in an in vitro model of neuronal ageing, correlating with an increase in gamma-secretase complex formation. Moreover we found that peroxynitrite (ONOO-), produced by the reaction of superoxide anion with nitric oxide, promoted the nitrotyrosination of presenilin 1 (PS1), the catalytic subunit of gamma-secretase. This was associated with an increased association of the two PS1 fragments, PS1-CTF and PS1-NTF, which constitute the active catalytic centre. Furthermore, we found that peroxynitrite shifted the production of A beta towards A beta 42 and increased the A beta 42/A beta 40 ratio. Our work identifies nitrosative stress as a potential mechanistic link between ageing and AD. C1 [Guix, Francesc X.; Wahle, Tina; Vennekens, Kristel; Snellinx, An; Chavez-Gutierrez, Lucia; Dotti, Carlos G.; De Strooper, Bart] VIB Ctr Biol Dis VIB, Louvain, Belgium. [Guix, Francesc X.; Wahle, Tina; Vennekens, Kristel; Snellinx, An; Chavez-Gutierrez, Lucia; Dotti, Carlos G.; De Strooper, Bart] KULeuven, Ctr Human Genet, Louvain, Gasthuisberg O&, Belgium. [Guix, Francesc X.; Wahle, Tina; Vennekens, Kristel; Snellinx, An; Chavez-Gutierrez, Lucia; Dotti, Carlos G.; De Strooper, Bart] KULeuven, Leuven Inst Neurodegenerat Dis LIND, Louvain, Gasthuisberg O&, Belgium. [Ill-Raga, Gerard; Ramos-Fernandez, Eva; Munoz, Francisco J.] Univ Pompeu Fabra, Dept Expt & Hlth Sci, Lab Mol Physiol & Channelopathies, Barcelona, Spain. [Guardia-Laguarta, Cristina; Lleo, Alberto] Hosp Santa Creu & Sant Pau, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Alzheimer Lab, Dept Neurol, Barcelona, Spain. [Arimon, Muriel; Berezovska, Oksana] Massachusetts Gen Hosp, MassGeneral Inst Neurodegenerat Dis, Alzheimer Res Unit, Charlestown, MA USA. [Dotti, Carlos G.] Ctr Biol Mol Severo Ochoa CSIC UAM, Madrid, Spain. RP Dotti, CG (reprint author), VIB Ctr Biol Dis VIB, Louvain, Belgium. EM cdotti@cbm.uam.es; Bart.DeStrooper@cme.vib-kuleuven.be RI De Strooper, Bart/F-6507-2012; Munoz, F/E-6751-2014; Arimon, Muriel/I-4054-2015; Dotti, Carlos /I-5533-2015; Chavez-Gutierrez, Lucia/E-2657-2017; OI De Strooper, Bart/0000-0001-5455-5819; Munoz, F/0000-0002-1343-3599; Arimon, Muriel/0000-0002-0894-3324; Dotti, Carlos /0000-0003-4052-1719; Guardia-Laguarta, Cristina/0000-0003-0811-9068 FU Fund for Scientific Research, Flanders; K.U. Leuven; VIB, Methusalem (K.U. Leuven and the Flemisch government); Foundation for Alzheimer Research (SAO/FRMA); European Research council; NIH [AG15379]; Spanish Ministry of Science and Innovation SAF [2010-14906, Consolider 2010-00045]; Spanish Ministery of Health (Fondo de Investigacion Sanitaria) [PI10/00587, Red HERACLES RD06/0009]; European FEDER Fundings; Fundacio La Marato de TV3 (Catalonia; Spain) [100310]; Marie Curie Actions program; Beatriu de Pinos grant of the Generalitat de Catalunya, Spain; EMBO; DFG FX This work was made possible by grants from the Fund for Scientific Research, Flanders; the K.U. Leuven; the VIB, Methusalem (K.U. Leuven and the Flemisch government), the Foundation for Alzheimer Research (SAO/FRMA), the European Research council (BDS), NIH AG15379 (OB), Spanish Ministry of Science and Innovation SAF 2010-14906, Consolider 2010-00045 (CGD), Spanish Ministery of Health (Fondo de Investigacion Sanitaria-PI10/00587 and Red HERACLES RD06/0009); The European FEDER Fundings; and Fundacio La Marato de TV3 (Catalonia; Spain; no. 100310). We would like to acknowledge the Banc de Teixits Neurologics de l' Hospital Clinic de Barcelona and the Unidad de Neuropatologia y Banco de Cerebros of Fundacion Hospital Alcorcon for providing the brain samples. BDS is the Arthur Bax and Anna Vanluffelen chair for AD. FG obtained a IEF fellowship of the Marie Curie Actions program in FP7 and a Beatriu de Pinos grant of the Generalitat de Catalunya, Spain. TW was supported by EMBO and DFG long-term fellowships. We thank Miguel A. Valverde for his contribution at the discussion. NR 56 TC 24 Z9 24 U1 0 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1757-4676 J9 EMBO MOL MED JI EMBO Mol. Med. PD JUL PY 2012 VL 4 IS 7 BP 660 EP 673 DI 10.1002/emmm.201200243 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 967YH UT WOS:000305943600014 PM 22488900 ER PT J AU Ehrlich, S Williams, PL Missmer, SA Flaws, JA Berry, KF Calafat, AM Ye, XY Petrozza, JC Wright, D Hauser, R AF Ehrlich, Shelley Williams, Paige L. Missmer, Stacey A. Flaws, Jodi A. Berry, Katharine F. Calafat, Antonia M. Ye, Xiaoyun Petrozza, John C. Wright, Diane Hauser, Russ TI Urinary Bisphenol A Concentrations and Implantation Failure among Women Undergoing in Vitro Fertilization SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE bisphenol A; embryo implantation; fertility; human; reproduction; women ID INTRAUTERINE IMPLANTATION; PREIMPLANTATION EXPOSURE; UTERINE RECEPTIVITY; EARLY-PREGNANCY; ESTROGEN; VARIABILITY; RECEPTOR; MOUSE; 17-BETA-ESTRADIOL; PREDICTORS AB BACKGROUND: Bisphenol A (BPA) is a synthetic chemical widely used in the production of polycarbonate plastic and epoxy resins found in numerous consumer products. In experimental animals, BPA increases embryo implantation failure and reduces litter size. OBJECTIVE: We evaluated the association of urinary BPA concentrations with implantation failure among women undergoing in vitro fertilization (IVF). METHODS: We used online solid phase extraction-high performance liquid chromatography-isotope dilution tandem mass spectrometry to measure urinary BPA concentrations in 137 women in a prospective cohort study among women undergoing IVF at the Massachusetts General Hospital Fertility Center in Boston, Massachusetts. We used logistic regression to evaluate the association of cycle-specific urinary BPA concentrations with implantation failure, accounting for correlation among multiple IVF cycles in the same woman using generalized estimating equations. Implantation failure was defined as a negative serum beta-human chorionic gonadotropin test (beta-hCG < 6 IU/L) 17 days after egg retrieval. RESULTS: Among 137 women undergoing 180 IVF cycles, urinary BPA concentrations had a geometric mean (SD) of 1.53 (2.22) mu g/L. Overall, 42% (n = 75) of the IVF cycles resulted in implantation failure. In adjusted models, there was an increased odds of implantation failure with higher quartiles of urinary BPA concentrations {odds ratio (OR) 1.02 [95% confidence interval (CI): 0.35, 2.95}, 1.60 (95% CI: 0.70, 3.78), and 2.11 (95% CI: 0.84, 5.31) for quartiles 2, 3, and 4, respectively, compared with the lowest quartile (p-trend = 0.06). CONCLUSION: There was a positive linear dose response association between BPA urinary concentrations and implantation failure. C1 [Ehrlich, Shelley; Hauser, Russ] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Williams, Paige L.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Missmer, Stacey A.; Berry, Katharine F.] Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. [Missmer, Stacey A.; Berry, Katharine F.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Missmer, Stacey A.; Hauser, Russ] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Flaws, Jodi A.] Univ Illinois, Urbana, IL USA. [Calafat, Antonia M.; Ye, Xiaoyun] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA. [Petrozza, John C.; Wright, Diane; Hauser, Russ] Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Boston, MA 02114 USA. RP Hauser, R (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, 665 Huntington Ave,Bldg 1,14th Floor, Boston, MA 02115 USA. EM rhauser@hsph.harvard.edu RI Ehrlich , Shelley/L-6991-2015 FU National Institute of Environmental Health Sciences [ES009718, ES000002]; National Institute for Occupational Safety and Health [OH008578] FX This work was supported by grants ES009718 and ES000002 from the National Institute of Environmental Health Sciences and OH008578 from the National Institute for Occupational Safety and Health. NR 46 TC 60 Z9 63 U1 1 U2 22 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUL PY 2012 VL 120 IS 7 BP 978 EP 983 DI 10.1289/ehp.1104307 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 969DG UT WOS:000306035300022 PM 22484414 ER PT J AU Machado-Salas, J Avila-Costa, MR Guevara, P Guevara, J Duron, RM Bai, DS Tanaka, M Yamakawa, K Delgado-Escueta, AV AF Machado-Salas, Jesus Rosa Avila-Costa, Maria Guevara, Patricia Guevara, Jorge Duron, Reyna M. Bai, Dongsheng Tanaka, Miyabi Yamakawa, Kazuhiro Delgado-Escueta, Antonio V. TI Ontogeny of Lafora bodies and neurocytoskeleton changes in Laforin-deficient mice SO EXPERIMENTAL NEUROLOGY LA English DT Article DE Lafora body disease; Laforin protein; Mouse; Cytoskeleton ID PROGRESSIVE MYOCLONUS EPILEPSY; GLYCOGEN-SYNTHASE KINASE-3; POLYGLUCOSAN BODIES; BIELSCHOWSKY BODIES; INCLUSION-BODIES; NERVOUS-SYSTEM; TAU-PROTEIN; EPM2A GENE; AGED DOGS; DISEASE AB Lafora disease (LD) is an autosomal recessive, always fatal progressive myoclonus epilepsy with rapid cognitive and neurologic deterioration. One of the pathological hallmarks of LD is the presence of cytoplasmic PAS + polyglucosan inclusions called Lafora bodies (LBs). Current clinical and neuropathological views consider LBs to be the cause of neurological derangement of patients. A systematic study of the ontogeny and structural features of the LBs has not been done in the past. Therefore, we undertook a detailed microscopic analysis of the neuropile of a Laforin-deficient (epm2a-/-) mouse model. Wild type and epm2a-/- mice were sacrificed at different ages and their encephalon processed for light microscopy. Luxol-fast-blue, PAS, Bielschowski techniques, as well as immunocytochemistry (TUNEL, Caspase-3, Apaf-1, Cytochrome-C and Neurofilament L antibodies) were used. Young null mice (11 days old) showed necrotic neuronal death in the absence of LBs. Both cell death and LBs showed a progressive increment in size and number with age. Type I LBs emerged at two weeks of age and were distributed in somata and neurites. Type 11 LBs appeared around the second month of age and always showed a complex architecture and restricted to neuronal somata. Their number was considerably less than type I LBs. Bielschowski method showed neurofibrillary degeneration and senile-like plaques. These changes were more prominent in the hippocampus and ventral pons. Neurofibrillary tangles were already present in 11 days-old experimental animals, whereas senile-like plaques appeared around the third to fourth month of life. The encephalon of null mice was not uniformly affected: Diencephalic structures were spared, whereas cerebral cortex, basal ganglia, pons, hippocampus and cerebellum were notoriously affected. This uneven distribution was present even within the same structure, i.e., hippocampal sectors. Of special relevance, was the observation of the presence of immunoreactivity to neurofilament L on the external rim of type II LBs. Perhaps, type II LB is not the end point of a metabolic abnormality. Instead, we suggest that type II LB is a highly specialized structural and functional entity that emerges as a neuronal response to major carbohydrate metabolism impairment. Early necrotic cell death, neurocytoskeleton derangement, different structural and probably functional profiles for both forms of LBs, a potential relationship between the external rim of the LB type II and the cytoskeleton and an uneven distribution of these abnormalities indicate that LD is both a complex neurodegenerative disease and a glycogen metabolism disorder. Our findings are critical for future studies on disease mechanisms and therapies for LD. Interestingly, the neurodegenerative changes observed in this LD model can also be useful for understanding the process of dementia. (C) 2012 Elsevier Inc. All rights reserved. C1 [Machado-Salas, Jesus; Duron, Reyna M.; Bai, Dongsheng; Tanaka, Miyabi; Delgado-Escueta, Antonio V.] VA Greater Los Angeles Healthcare Syst, W Los Angeles Med Ctr, Epilepsy Ctr Excellence Neurol & Res Serv, Epilepsy Genet Genom Labs, Los Angeles, CA USA. [Rosa Avila-Costa, Maria] Univ Nacl Autonoma Mexico, UNAM, Neurosci Dept FES Iztacala, Mexico City, DF, Mexico. [Guevara, Patricia] Natl Inst Neurol & Neurosurg Manuel Velasco Suare, Mexico City, DF, Mexico. [Guevara, Jorge] Univ Nacl Autonoma Mexico, UNAM, Fac Med, Dept Biochem, Mexico City, DF, Mexico. [Yamakawa, Kazuhiro] RIKEN Brain Sci Inst, Saitama, Japan. [Machado-Salas, Jesus; Duron, Reyna M.; Bai, Dongsheng; Tanaka, Miyabi; Delgado-Escueta, Antonio V.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Machado-Salas, J (reprint author), VA Greater Los Angeles Healthcare Syst, Epilepsy Genet Genom Labs, Los Angeles, CA 90073 USA. EM msmdphd@hotmail.com RI Yamakawa, Kazuhiro/N-5050-2015; OI Duron, Reyna M./0000-0002-9425-2289; Delgado-Escueta, Antonio V./0000-0002-1581-6999 FU National Institutes of Health [1RO1NS055057]; Chelsea's Hope Foundation for Lafora Disease; Programa de Apoyo a Proyectos de Investigacion e Innovacion Tecnologica-DGAPA UNAM [IN214609, 1220111, PAPCA 2010-2011] FX This work was supported by the grants from: National Institutes of Health [1RO1NS055057], Chelsea's Hope Foundation for Lafora Disease, Programa de Apoyo a Proyectos de Investigacion e Innovacion Tecnologica-DGAPA UNAM [IN214609, 1220111 and PAPCA 2010-2011]. NR 51 TC 1 Z9 1 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 EI 1090-2430 J9 EXP NEUROL JI Exp. Neurol. PD JUL PY 2012 VL 236 IS 1 BP 131 EP 140 DI 10.1016/j.expneurol.2012.04.008 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 959IM UT WOS:000305306100015 PM 22542948 ER PT J AU Mima, A Kitada, M Geraldes, P Li, Q Matsumoto, M Mizutani, K Qi, W Li, CZ Leitges, M Rask-Madsen, C King, GL AF Mima, Akira Kitada, Munehiro Geraldes, Pedro Li, Qian Matsumoto, Motonobu Mizutani, Koji Qi, Weier Li, Chenzhong Leitges, Michael Rask-Madsen, Christian King, George L. TI Glomerular VEGF resistance induced by PKC beta/SHP-1 activation and contribution to diabetic nephropathy SO FASEB JOURNAL LA English DT Article DE podocyte apoptosis; hyperglycemia; VEGFR-2 ID KINASE-C-DELTA; ENDOTHELIAL GROWTH-FACTOR; PROTEIN-KINASE; INSULIN-RESISTANCE; CELL APOPTOSIS; MAPK PATHWAY; PKC-DELTA; EXPRESSION; GLUCOSE; BETA AB This study characterizes the effect of glucose-induced activation of protein kinase C delta (PKC delta) and Src homology-2 domain-containing phosphatase-1 (SHP-1) expression on vascular endothelial growth factor (VEGF) actions in glomerular podocytes in cultures and in glomeruli of diabetic rodents. Elevation of glucose levels induced PKC delta and p38 mitogen-activated protein kinase (p38 MAPK) to increase SHP-1 expression, increased podocyte apoptosis, and inhibited VEGF activation in podocytes and glomerular endothelial cells. The adverse effects of high glucose levels can be negated by molecular inhibitors of PKC delta, p38MAPK, and SHP-1 and only partially reduced by antioxidants and nuclear factor-kappa B (NF-kappa B) inhibitor. Increased PKC delta activation and SHP-1 expression correlated with loss of VEGF signaling and podocyte numbers in the glomeruli of diabetic rats and mice. In contrast, diabetic PKC delta -knockout (Prkcd(-/-)) mice did not exhibit activation of p38 MAPK and SHP-1 or inhibition of VEGF signaling in renal glomeruli. Functionally, diabetic Prkcd(-/-) mice had decreased expressions of TGF beta, VEGF, and extracellular matrix and less albuminuria than diabetic Prkcd(+/+) mice. Hyperglycemia and diabetes can cause glomerular podocyte apoptosis and endothelial dysfunction partly due to increased PKC beta/p38 MAPK activation and the expression of SHP-1 to cause VEGF resistance, independent of NF-kappa B activation.-Mima, A., Kitada, M., Geraldes, P., Li, Q., Matsumoto, M., Mizutani, K., Qi, W., Li, C., Leitges, M., Rask-Madsen, C., King, G. L. Glomerular VEGF resistance induced by PKC delta/SHP-1 activation and contribution to diabetic nephropathy. FASEB J. 26, 2963-2974 (2012). www.fasebj.org C1 [King, George L.] Harvard Univ, Joslin Diabet Ctr, Div Res, Sch Med,Dianne Nunnally Hoppes Lab Diabet Complic, Boston, MA 02215 USA. [Geraldes, Pedro] Univ Sherbrooke, Dept Med, Sherbrooke, PQ J1K 2R1, Canada. [Leitges, Michael] Univ Oslo, Biotechnol Ctr Oslo, Oslo, Norway. RP King, GL (reprint author), Harvard Univ, Joslin Diabet Ctr, Div Res, Sch Med,Dianne Nunnally Hoppes Lab Diabet Complic, 1 Joslin Pl, Boston, MA 02215 USA. EM george.king@joslin.harvard.edu FU U.S. National Institutes of Health/National Eye Institute [EY016150]; Manpei Suzuki Diabetes Foundation; Kanzawa Medical Research Foundation; Novartis Foundation, Japan; Diabetes and Endocrinology Research Center [P30DK036836] FX The authors thank Dr. Hillary Keenan for the discussions on the statistical analysis and Ms. Patti Muehter for excellent assistance with manuscript preparation. This work is supported by grants to G. L. K. from the U.S. National Institutes of Health/National Eye Institute (EY016150). A. M. is the recipient of a Research Fellowship (Manpei Suzuki Diabetes Foundation, Kanzawa Medical Research Foundation, Novartis Foundation, Japan). This project has been supported by Diabetes and Endocrinology Research Center grant P30DK036836. NR 39 TC 19 Z9 22 U1 1 U2 9 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 JUL PY 2012 VL 26 IS 7 BP 2963 EP 2974 DI 10.1096/fj.11-202994 PG 12 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 967MP UT WOS:000305912500024 PM 22499584 ER PT J AU Chavarro, JE Ehrlich, S Colaci, DS Wright, DL Toth, TL Petrozza, JC Hauser, R AF Chavarro, Jorge E. Ehrlich, Shelley Colaci, Daniela S. Wright, Diane L. Toth, Thomas L. Petrozza, John C. Hauser, Russ TI Body mass index and short-term weight change in relation to treatment outcomes in women undergoing assisted reproduction SO FERTILITY AND STERILITY LA English DT Article DE Body weight; weight loss; obesity; infertility; assisted reproduction ID IN-VITRO FERTILIZATION; POLYCYSTIC-OVARY-SYNDROME; OVULATORY DISORDER INFERTILITY; OBESE WOMEN; FERTILITY TREATMENT; ADVERSELY AFFECT; EMBRYO-TRANSFER; IVF; PREGNANCY; IMPACT AB Objective: To assess the relation between body mass index (BMI) and short-term weight change with assisted reproductive technology (ART) outcomes. Design: Prospective cohort study. Setting: Fertility center. Patient(s): A total of 170 women undergoing 233 ART cycles. Intervention(s): Baseline BMI and short-term weight change were related to ART outcomes. Regression models accounting for repeated observations were used to adjust data for potential confounders. Main Outcome Measure(s): Peak E2 levels, oocyte yield, MII yield, fertilization rate, embryo quality, postive [beta]-hCH, clinical pregnancy and live birth rates. Result(s): Overweight and obesity were associated with lower live birth rates. The adjusted live birth rate (95% confidence interval) was 42% (28%-58%) among women with a BMI between 20 and 22.4 kg/m(2) and 23% (14%-36%) among overweight or obese women. Short-term weight loss was associated with a higher proportion of metaphase II (MII) oocytes retrieved. The adjusted proportion of MII eggs was 91% (87%-94%) for women who lost 3 kg or more and 86% (81%-89%) for women whose weight remained stable. This association was stronger among women who were overweight or obese at baseline. Short-term weight loss was unrelated to positive beta-hCG, clinical pregnancy, or live birth rates. Conclusion(s): Overweight and obesity were related to lower live birth rates in women undergoing ART. Short-term weight loss was related to higher MII yield, particularly among overweight and obese women, but unrelated to clinical outcomes. (Fertil Steril (R) 2012. (C) 2012 by American Society for Reproductive Medicine.) C1 [Chavarro, Jorge E.; Colaci, Daniela S.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Chavarro, Jorge E.; Hauser, Russ] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Chavarro, Jorge E.; Wright, Diane L.; Toth, Thomas L.; Petrozza, John C.; Hauser, Russ] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Chavarro, Jorge E.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Ehrlich, Shelley; Hauser, Russ] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Wright, Diane L.; Toth, Thomas L.; Petrozza, John C.; Hauser, Russ] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Chavarro, JE (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. EM jchavarr@hsph.harvard.edu RI Ehrlich , Shelley/L-6991-2015 FU National Institute of Environmental Health Sciences [ES009718, ES000002]; National Institute of Diabetes and Digestive and Kidney Diseases [DK46200] FX This work was supported by grants ES009718 and ES000002 from the National Institute of Environmental Health Sciences and DK46200 from the National Institute of Diabetes and Digestive and Kidney Diseases. NR 40 TC 27 Z9 27 U1 0 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 JUL PY 2012 VL 98 IS 1 DI 10.1016/j.fertnstert.2012.04.012 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 968AU UT WOS:000305950200026 PM 22607889 ER PT J AU Woods, DC Tilly, JL AF Woods, Dori C. Tilly, Jonathan L. TI The next (re) generation of ovarian biology and fertility in women: is current science tomorrow's practice? SO FERTILITY AND STERILITY LA English DT Article DE Infertility; IVF; stem cells; germline stem cells; oocyte; ovary; aging ID EMBRYONIC STEM-CELLS; PRIMORDIAL GERM-CELLS; IN-VITRO; OOPLASMIC TRANSPLANTATION; POSTNATAL OOGENESIS; DROSOPHILA OVARY; MAMMALIAN OVARY; HUMAN OOCYTES; MOUSE OVARY; DIFFERENTIATION AB Stem cell-based strategies for ovarian regeneration and oocyte production have been proposed as future clinical therapies for treating infertility in women. However, utilization of embryonic stem cells or induced pluripotent stem cells to produce oocytes has had limited success in vitro. A recent report of the isolation and characterization of endogenous oocyte-producing or oogonial stem cells (OSCs) from ovaries of reproductive age women describes the first stable and pure human female germ cell culture model in which a subset of cells appear to initiate and complete meiosis. In addition, purified human OSCs introduced into adult human ovarian cortical tissue generate oocytes that arrest at the diplotene stage of meiosis and successfully recruit granulosa cells to form new primordial follicles. This overview examines the current landscape of in vitro and in vivo gametogenesis from stem cells, with emphasis on generation of human oocytes. Future research objectives for this area of work, as well as potential clinical applications involving the use of human OSCs, are discussed. (Fertil Steril (R) 2012; square:square-square. (C) 2012 by American Society for Reproductive Medicine.) C1 [Woods, Dori C.; Tilly, Jonathan L.] Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Vincent Dept Obstet & Gynecol, Boston, MA 02114 USA. [Woods, Dori C.; Tilly, Jonathan L.] Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. RP Woods, DC (reprint author), Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Vincent Dept Obstet & Gynecol, THR 901,55 Fruit St, Boston, MA 02114 USA. EM dwoods2@partners.org; jtilly@partners.org FU National Institute on Aging [NIH R37-AG012279]; Ruth L. Kirschstein National Research Service Award [NIH F32-AG034809]; Henry and Vivian Rosenberg Philanthropic Fund; Sea Breeze Foundation; Vincent Memorial Hospital Research Funds FX Supported by Method to Extend Research in Time (MERIT) Award from the National Institute on Aging (NIH R37-AG012279 to J.L.T.), a Ruth L. Kirschstein National Research Service Award (NIH F32-AG034809 to D. C. W.), the Henry and Vivian Rosenberg Philanthropic Fund, the Sea Breeze Foundation, and Vincent Memorial Hospital Research Funds. NR 70 TC 28 Z9 30 U1 2 U2 30 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 JUL PY 2012 VL 98 IS 1 DI 10.1016/j.fertnstert.2012.05.005 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 968AU UT WOS:000305950200009 PM 22682028 ER PT J AU Kubarych, TS Prom-Wormley, EC Franz, CE Panizzon, MS Dale, AM Fischl, B Eyler, LT Fennema-Notestine, C Grant, MD Hauger, RL Hellhammer, DH Jak, AJ Jernigan, TL Lupien, SJ Lyons, MJ Mendoza, SP Neale, MC Seidman, LJ Tsuang, MT Kremen, WS AF Kubarych, T. S. Prom-Wormley, E. C. Franz, C. E. Panizzon, M. S. Dale, A. M. Fischl, B. Eyler, L. T. Fennema-Notestine, C. Grant, M. D. Hauger, R. L. Hellhammer, D. H. Jak, A. J. Jernigan, T. L. Lupien, S. J. Lyons, M. J. Mendoza, S. P. Neale, M. C. Seidman, L. J. Tsuang, M. T. Kremen, W. S. TI A multivariate twin study of hippocampal volume, self-esteem and well-being in middle-aged men SO GENES BRAIN AND BEHAVIOR LA English DT Article DE Aging; heritability; hippocampus; self-esteem; twins; well-being ID SURFACE-BASED ANALYSIS; CORTISOL-LEVELS; SEGMENTATION; YOUNG; RECONSTRUCTION; ADULTHOOD; RESPONSES; HAPPINESS; VALIDITY; ATROPHY AB Self-esteem and well-being are important for successful aging, and some evidence suggests that self-esteem and well-being are associated with hippocampal volume, cognition and stress responsivity. Whereas most of this evidence is based on studies on older adults, we investigated self-esteem, well-being and hippocampal volume in 474 male middle-aged twins. Self-esteem was significantly positively correlated with hippocampal volume (0.09, P = 0.03 for left hippocampus, 0.10, P = 0.04 for right). Correlations for well-being were not significant (Ps > 0.05). There were strong phenotypic correlations between self-esteem and well-being (0.72, P < 0.001) and between left and right hippocampal volume (0.72, P < 0.001). In multivariate genetic analyses, a two-factor additive genetic and unique environmental (AE) model with well-being and self-esteem on one factor and left and right hippocampal volumes on the other factor fits the data better than Cholesky, independent pathway or common pathway models. The correlation between the two genetic factors was 0.12 (P = 0.03); the correlation between the environmental factors was 0.09 (P > 0.05). Our results indicate that largely different genetic and environmental factors underlie self-esteem and well-being on one hand and hippocampal volume on the other. C1 [Kubarych, T. S.; Prom-Wormley, E. C.; Eyler, L. T.; Neale, M. C.] Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA 23219 USA. [Prom-Wormley, E. C.; Neale, M. C.] Virginia Commonwealth Univ, Dept Human Genet, Richmond, VA 23219 USA. [Franz, C. E.; Panizzon, M. S.; Fennema-Notestine, C.; Hauger, R. L.; Jak, A. J.; Jernigan, T. L.; Tsuang, M. T.; Kremen, W. S.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Dale, A. M.] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. [Franz, C. E.; Tsuang, M. T.; Kremen, W. S.] Univ Calif San Diego, Ctr Behav Genom, San Diego, CA 92103 USA. [Dale, A. M.; Fennema-Notestine, C.] Univ Calif San Diego, Dept Radiol, San Diego, CA 92103 USA. [Fischl, B.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Fischl, B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Panizzon, M. S.; Eyler, L. T.; Jak, A. J.; Tsuang, M. T.; Kremen, W. S.] VA San Diego Hlth Care Syst, Ctr Excellence Stress & Mental Hlth, San Diego, CA USA. [Grant, M. D.; Lyons, M. J.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Hellhammer, D. H.] Univ Trier, Ctr Psychobiol & Psychosomat Res, Trier, Germany. [Lupien, S. J.] McGill Univ, Dept Psychiat, Montreal, PQ, Canada. [Lupien, S. J.] McGill Univ, Dept Neurol & Neurosurg, Montreal, PQ, Canada. [Mendoza, S. P.] Univ Calif Davis, Dept Psychol, Davis, CA 95616 USA. [Seidman, L. J.] Harvard Univ, Dept Psychiat, Cambridge, MA 02138 USA. RP Kubarych, TS (reprint author), Virginia Commonwealth Univ, Dept Psychiat, Box 980126, Richmond, VA 23219 USA. EM tkubarych@vcu.edu RI Hellhammer, Dirk/F-1888-2013; OI Prom-Wormley, Elizabeth/0000-0001-9230-9723; Lyons, Michael/0000-0001-6516-9219; Fennema-Notestine, Christine/0000-0002-6527-6361 FU NIH/NIA [R01 AG018386, R01 AG018384, R01 AG022381, R01 AG022982]; US Department of Veterans Affairs FX The VETSA is supported by grants from NIH/NIA (R01 AG018386, R01 AG018384, R01 AG022381, and R01 AG022982). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIA or the NIH. The Cooperative Studies Program of 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; the Internal Revenue Service; National Opinion Research Center; National Research Council, National Academy of Sciences; the Institute for Survey Research, Temple University. This material was, in part, the result of work supported with resources of the Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System. 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. We also appreciate the time and energy of many staff and students on the VETSA projects. NR 44 TC 5 Z9 6 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1601-1848 J9 GENES BRAIN BEHAV JI Genes Brain Behav. PD JUL PY 2012 VL 11 IS 5 BP 539 EP 544 DI 10.1111/j.1601-183X.2012.00789.x PG 6 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 967KF UT WOS:000305905700005 PM 22471516 ER PT J AU Matulonis, UA Pereira, L Liu, J Lee, H Lee, J Whalen, C Campos, S Atkinson, T Hill, M Berlin, S AF Matulonis, Ursula A. Pereira, Lauren Liu, Joyce Lee, Hang Lee, Julie Whalen, Christin Campos, Susana Atkinson, Tina Hill, Margaret Berlin, Suzanne TI Sequential bevacizumab and oral cyclophosphamide for recurrent ovarian cancer SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Ovarian cancer; Anti-angiogenic agents; Bevacizumab; Metronomic therapy ID HEAVILY PRETREATED PATIENTS; EPITHELIAL OVARIAN; PHASE-II; CLINICAL-TRIAL; THERAPY; CHEMOTHERAPY; PAZOPANIB; TOPOTECAN; ANGIOGENESIS; PACLITAXEL AB Objective. Test the safety and efficacy of sequentially blocking angiogenesis by adding oral cyclophosphamide to bevacizumab following cancer progression on bevacizumab in patients with recurrent ovarian cancer. Methods. Eligibility included <= 2 lines of treatment for recurrence and measurable cancer by RECIST 1.0. Patients received bevacizumab (15 mg/kg every 3 weeks IV) and upon RECIST progression, oral cyclophosphamide (50 mg orally daily) was added. Objectives included safety, toxicities, 3- and 6-month PFS rates, response rate, PFS, and OS. Results. 20 patients were enrolled. Overall response rate was 10%, and 65% of patients had confirmed stable disease (SD). Thirteen of 20 patients received oral cyclophosphamide added to bevacizumab upon bevacizumab progression. Of these 13 patients, 1 patient subsequently achieved a PR (this patient had SD as best response during bevacizumab) and 3 patients had a confirmed SD. For all patients, median PFS was 8.41 months, 6 month PFS rate was 65%, duration of response (DOR) was 7.3 months, and median OS was 22.72 months. Median DOR for patients receiving both bevacizumab and cyclophosphamide was 8.4 months. Most toxicities were grades 1 and 2 and manageable. Grades 3 and grade 4 toxicities included 1 myocardial infarction, 1 gastrointestinal perforation (GIP), and 12/20 patients (60%) developed grade 3 HTN. Conclusions. Addition of oral cyclophosphamide to bevacizumab at the time of cancer progression on bevacizumab appears to have continued anti-cancer effects in a subgroup of patients and appears to be safe. Randomized trials testing combination versus sequential anti-angiogenic therapy for recurrent ovarian cancer are warranted. (c) 2012 Elsevier Inc. All rights reserved. C1 [Matulonis, Ursula A.; Pereira, Lauren; Liu, Joyce; Lee, Julie; Whalen, Christin; Campos, Susana; Atkinson, Tina; Hill, Margaret; Berlin, Suzanne] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Lee, Hang] Massachusetts Gen Hosp, MGH Biostat Ctr, Boston, MA 02478 USA. RP Matulonis, UA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. NR 34 TC 9 Z9 10 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 JUL PY 2012 VL 126 IS 1 BP 41 EP 46 DI 10.1016/j.ygyno.2012.04.003 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 967AL UT WOS:000305878400009 PM 22487536 ER PT J AU Schytz, HW Hansen, JM Phillip, D Selb, J Boas, DA Ashina, M AF Schytz, Henrik W. Hansen, Jakob M. Phillip, Dorte Selb, Juliette Boas, David A. Ashina, Messoud TI Nitric Oxide Modulation of Low-Frequency Oscillations in Cortical Vessels in FHM - a NIRS Study SO HEADACHE LA English DT Article DE familial hemiplegic migraine; nitric oxide; low-frequency oscillation; cortical vessel; near-infrared spectroscopy ID FAMILIAL HEMIPLEGIC MIGRAINE; CEREBRAL-BLOOD-FLOW; SPREADING DEPRESSION; GLYCERYL TRINITRATE; MOUSE MODEL; HYPERSENSITIVITY; NITROGLYCERIN; HEMODYNAMICS; SUFFERERS; ESTROGEN AB Background. The pathophysiological alterations in patients with familial hemiplegic migraine (FHM) are not yet fully known. The headache characteristics in patients with FHM mutations have been examined in a series of glyceryl trinitrate (GTN) provocation studies in FHM patients, but the cortical vascular response to GTN in FHM patients has never been investigated before. Objective. To investigate changes in spontaneous low-frequency oscillations (LFO) of cortical vessels in response to the nitric oxide donor GTN by near-infrared spectroscopy in FHM patients. Methods. Twenty-three FHM patients without known mutations and 9 healthy controls received a continuous intravenous infusion of GTN 0.5 mu g/kg/minute over 20 minutes. Using near-infrared spectroscopy, we recorded oxygenated hemoglobin (oxyHb) LFO amplitude bilateral at the frontal cortex at baseline and 15 minutes and 40 minutes after start of the GTN infusion. Results. GTN changed oxyHb LFO amplitude in FHM patients (P = .002), but not in healthy controls (P = .121). Only in FHM patients with coexisting common migraine types did GTN infusion induced changes in LFO amplitudes (P < .001), where post-hoc analysis revealed an increase in LFO amplitude 15 minutes (P = .003) and 40 (P = .013) minutes after start of infusion compared with baseline. Interestingly, GTN infusion induced no changes in LFO amplitude in patients with a pure FHM phenotype (P = .695). Conclusion. FHM patients with a mixed phenotype (coexisting common type of migraine) showed an increase in oxyHb LFO amplitude during GTN infusion, whereas FHM patients with pure phenotype showed no changes. These data suggest possible differences in frontal cortical nitric oxide vascular sensitivity between FHM patients with a mixed phenotype and patients with pure FHM. C1 [Schytz, Henrik W.; Hansen, Jakob M.; Phillip, Dorte; Ashina, Messoud] Univ Copenhagen, Danish Headache Ctr, Glostrup Hosp, Fac Hlth Sci, DK-2600 Copenhagen, Denmark. [Schytz, Henrik W.; Hansen, Jakob M.; Phillip, Dorte; Ashina, Messoud] Univ Copenhagen, Dept Neurol, Glostrup Hosp, Fac Hlth Sci, DK-2600 Copenhagen, Denmark. [Selb, Juliette; Boas, David A.] Harvard Univ, Photon Migrat Imaging Lab, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp,Med Sch, Charlestown, MA USA. RP Ashina, M (reprint author), Univ Copenhagen, Danish Headache Ctr, Glostrup Hosp, Fac Hlth Sci, Nordre Ringvej 57, DK-2600 Copenhagen, Denmark. EM ashina@dadlnet.dk OI Hansen, Jakob Moller/0000-0002-9417-2481; Schytz, Henrik Winther/0000-0002-6262-2986 FU Lundbeck Foundation Center for Neurovascular Signaling FX Supported through the Lundbeck Foundation Center for Neurovascular Signaling. NR 35 TC 3 Z9 3 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0017-8748 J9 HEADACHE JI Headache PD JUL-AUG PY 2012 VL 52 IS 7 BP 1146 EP 1154 DI 10.1111/j.1526-4610.2012.02098.x PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 967ZJ UT WOS:000305946400009 PM 22352839 ER PT J AU Cassidy, B Long, CJ Rae, C Solo, V AF Cassidy, Ben Long, Christopher J. Rae, Caroline Solo, Victor TI Identifying fMRI Model Violations With Lagrange Multiplier Tests SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE Functional magnetic resonance imaging (fMRI); hemodynamic response function; model criticism ID FUNCTIONAL MRI; SIGNAL; RESPONSES AB The standard modeling framework in functional magnetic resonance imaging (fMRI) is predicated on assumptions of linearity, time invariance and stationarity. These assumptions are rarely checked because doing so requires specialized software, although failure to do so can lead to bias and mistaken inference. Identifying model violations is an essential but largely neglected step in standard fMRI data analysis. Using Lagrange multiplier testing methods we have developed simple and efficient procedures for detecting model violations such as nonlinearity, nonstationarity and validity of the common double gamma specification for hemodynamic response. These procedures are computationally cheap and can easily be added to a conventional analysis. The test statistic is calculated at each voxel and displayed as a spatial anomaly map which shows regions where a model is violated. The methodology is illustrated with a large number of real data examples. C1 [Cassidy, Ben; Solo, Victor] Univ New S Wales, Sch Elect Engn, Sydney, NSW 2052, Australia. [Cassidy, Ben; Rae, Caroline; Solo, Victor] Neurosci Res Australia, Sydney, NSW 2031, Australia. [Solo, Victor] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. [Solo, Victor] Harvard Univ, Sch Med, Boston, MA 02129 USA. [Long, Christopher J.] MIT Ctr Neuroecon, Cambridge, MA 02139 USA. RP Cassidy, B (reprint author), Univ New S Wales, Sch Elect Engn, Sydney, NSW 2052, Australia. EM b.cassidy@unsw.edu.au; cjlong1@mit.edu; c.rae@neura.edu.au; v.solo@unsw.edu.au RI Rae, Caroline/B-7537-2008 OI Rae, Caroline/0000-0003-0673-8084 FU NIH [NCRR 2P41RR014075-11]; NHMRC [400955] FX This work was supported in part by NIH P41 under Grant NCRR 2P41RR014075-11 and by NHMRC under Grant 400955. Asterisk indicates corresponding author. NR 41 TC 3 Z9 3 U1 1 U2 3 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD JUL PY 2012 VL 31 IS 7 BP 1481 EP 1492 DI 10.1109/TMI.2012.2195327 PG 12 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 967HW UT WOS:000305898500014 PM 22542665 ER PT J AU De Costa, AMA Justis, DN Schuyler, CA Young, MRI AF De Costa, Anna-Maria A. Justis, Danielle N. Schuyler, Corinne A. Young, M. Rita I. TI Administration of a vaccine composed of dendritic cells pulsed with premalignant oral lesion lysate to mice bearing carcinogen-induced premalignant oral lesions stimulates a protective immune response SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Article DE HNSCC; Premalignant; Immunotherapy; Dendritic cell vaccination ID NECK-CANCER; TH17 CELLS; T-CELLS; HEAD; SUPPRESSION; GENERATION; REACTIVITY; CYTOKINES AB The use of dendritic cell (DC) vaccines as treatment for malignancy is complicated by immune evasion tactics often employed by carcinomas such as head and neck squamous cell carcinoma (HNSCC). The present study aims to determine if an immune response can be elicited by administering a DC vaccine during the premalignant stages of HNSCC, prior to development of immune escape. Mice treated with the carcinogen 4-nitroquinoline 1-oxide (4NQO) in drinking water develop premalignant oral lesions that progress to HNSCC. As previous studies demonstrated that premalignant lesions and HNSCC overexpress common tumor antigens, bone marrow-derived DCs were pulsed with premalignant lesion lysate (DCpm) and administered to 4NQO-treated mice exhibiting premalignant lesions. Lesion progression was tracked through endoscopy. which revealed that DCpm vaccination and control vaccination with dendritic cells pulsed with normal tongue epithelium lysate (DCnt) significantly decreased lesion burden at 8 weeks. Analysis of lymph node cells revealed that while DCnt vaccination resulted in a rapid increase in total lymphocyte count, levels of activated conventional CD4(+) T cells and Th1, Tc1, Th17, Tc17, and Th2 cells, DCpm vaccination results in a delayed, yet substantial, increase in these immune effector mechanisms. This suggests that dendritic cell vaccination may have a beneficial effect on clinical outcome regardless of type of antigenic stimulation. Also, pulsing DCs with premalignant lysate rather than normal tongue epithelium lysate affects the dendritic cells in a way that delays the immune effector response upon vaccination of premalignant lesion-bearing mice. Published by Elsevier B.V. C1 [De Costa, Anna-Maria A.; Schuyler, Corinne A.; Young, M. Rita I.] Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC 29401 USA. [De Costa, Anna-Maria A.; Justis, Danielle N.; Young, M. Rita I.] Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29401 USA. [De Costa, Anna-Maria A.; Justis, Danielle N.; Young, M. Rita I.] Med Univ S Carolina, Dept Med, Charleston, SC 29401 USA. RP Young, MRI (reprint author), Ralph H Johnson VA Med Ctr, Res Serv 151, Charleston, SC 29401 USA. EM rita.young@va.gov FU Biomedical Laboratory and Clinical Sciences Programs of the Department of Veterans Affairs; National Institute of Health (MRIY) [101-CX000100, R01-CA128837, R01-DE018268] FX This work has been supported by awards from the Biomedical Laboratory and Clinical Sciences Programs of the Department of Veterans Affairs and by grants from the National Institute of Health (MRIY, 101-CX000100, R01-CA128837 and R01-DE018268). NR 26 TC 4 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-5769 J9 INT IMMUNOPHARMACOL JI Int. Immunopharmacol. PD JUL PY 2012 VL 13 IS 3 BP 322 EP 330 DI 10.1016/j.intimp.2012.05.004 PG 9 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA 969EC UT WOS:000306037500014 PM 22609090 ER PT J AU Dizon, DS Damstrup, L Finkler, NJ Lassen, U Celano, P Glasspool, R Crowley, E Lichenstein, HS Knoblach, P Penson, RT AF Dizon, Don S. Damstrup, Lars Finkler, Neil J. Lassen, Ulrik Celano, Paul Glasspool, Ros Crowley, Elizabeth Lichenstein, Henri S. Knoblach, Poul Penson, Richard T. TI Phase II Activity of Belinostat (PXD-101), Carboplatin, and Paclitaxel in Women With Previously Treated Ovarian Cancer SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Article DE Ovarian cancer; Chemotherapy; Carboplatin; Histone deacetylase inhibitor; Recurrent disease ID PEGYLATED-LIPOSOMAL-DOXORUBICIN; HISTONE DEACETYLASE INHIBITOR; PLATINUM-RESISTANT OVARIAN; GYNECOLOGIC-ONCOLOGY-GROUP; RECURRENT OVARIAN; SOLID TUMORS; PERITONEAL CANCER; FREE-INTERVAL; GEMCITABINE; RETREATMENT AB Background: Preclinical data show that belinostat (Bel) is synergistic with carboplatin and paclitaxel in ovarian cancer. To further evaluate the clinical activity of belinostat, carboplatin, and paclitaxel (BelCaP), a phase 1b/2 study was performed, with an exploratory phase 2 expansion planned specifically for women with recurrent epithelial ovarian cancer (EOC). Methods: Thirty-five women were treated on the phase 2 expansion cohort. BelCap was given as follows: belinostat, 1000 mg/m(2) daily for 5 days with carboplatin, AUC 5; and paclitaxel, 175 mg/m(2) given on day 3 of a 21-day cycle. The primary end point was overall response rate (ORR), using a Simon 2 stage design. Results: The median age was 60 years (range, 39-80 years), and patients had received a median of 3 prior regimens (range, 1-4). Fifty-four percent had received more than two prior platinum-based combinations, sixteen patients (46%) had primary platinum-resistant disease, whereas 19 patients (54%) recurred within 6 months of their most recent platinum treatment. The median number of cycles of BelCaP administered was 6 (range, 1-23). Three patients had a complete response, and 12 had a partial response, for an ORR of 43% (95% confidence interval, 26%-61%). When stratified by primary platinum status, the ORR was 44% among resistant patients and 63% among sensitive patients. The most common drug-related adverse events related to BelCaP were nausea (83%), fatigue (74%), vomiting (63%), alopecia (57%), and diarrhea (37%). With a median follow-up of 4 months (range, 0-23.3 months), 6-month progression-free survival is 48% (95% confidence interval, 31%-66%). Median overall survival was not reached during study follow-up. Conclusions: Belinostat, carboplatin, and paclitaxel combined was reasonably well tolerated and demonstrated clinical benefit in heavily-pretreated patients with EOC. The addition of belinostat to this platinum-based regimen represents a novel approach to EOC therapy and warrants further exploration. C1 [Dizon, Don S.] Brown Univ, Alpert Med Sch, Women & Infants Hosp, Program Womens Oncol, Providence, RI 02905 USA. [Damstrup, Lars; Knoblach, Poul] TopoTarget AS, Copenhagen, Denmark. [Finkler, Neil J.] Florida Hosp Canc Inst, Orlando, FL USA. [Lassen, Ulrik] Univ Hosp, Copenhagen, Denmark. [Celano, Paul] Greater Baltimore Med Ctr, Baltimore, MD USA. [Glasspool, Ros] Beatson W Scotland Canc Ctr, Glasgow, Lanark, Scotland. [Crowley, Elizabeth; Lichenstein, Henri S.] CuraGen Corp, Branford, CT USA. [Penson, Richard T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Dizon, DS (reprint author), Brown Univ, Alpert Med Sch, Women & Infants Hosp, Program Womens Oncol, 101 Dudley St, Providence, RI 02905 USA. EM ddizon@wihri.org OI Glasspool, Rosalind/0000-0002-5000-1680; Lassen, Ulrik/0000-0002-3865-4574 FU Topotarget; Curagen Corporation; Glasspool; Dizon FX The study was fully supported by Topotarget and Curagen Corporation.; Institutional funds received for clinical trial support: Glasspool, Dizon. Research funding from Topotarget: Penson Employee of Topotarget (makers of belinostat): Damstrup, Knoblauch, Lichenstein (previously employed), NR 27 TC 20 Z9 20 U1 0 U2 3 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 JUL PY 2012 VL 22 IS 6 BP 979 EP 986 DI 10.1097/IGC.0b013e31825736fd PG 8 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 967LH UT WOS:000305908800012 PM 22694911 ER PT J AU Papakostas, GI AF Papakostas, George I. TI Surrogate markers of treatment outcome in major depressive disorder SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Review DE Marker; mediator; moderator; predictor; surrogate ID SEROTONIN TRANSPORTER GENE; STAR-ASTERISK-D; FLUVOXAMINE ANTIDEPRESSANT ACTIVITY; MAGNETIC-RESONANCE SPECTROSCOPY; TREATMENT-RESISTANT DEPRESSION; WHITE-MATTER HYPERINTENSITIES; GENERALIZED ANXIETY DISORDER; FUNCTIONAL BRAIN ASYMMETRY; AUDITORY-EVOKED-POTENTIALS; RANDOMIZED CLINICAL-TRIALS AB Major depressive disorder (MDD) is a common medical illness affecting millions worldwide. Despite their widespread use since the 1950s and 1960s, the 'downstream' mechanism by which antidepressants ultimately exert their therapeutic effects remains elusive. In addition, except for a few exceptions such as episode severity and the presence of comorbid Axis-I or Axis-Ill disorders, biological or clinical characteristics which can accurately quantify the risk of poor treatment outcome are lacking, as are factors which could help patients and clinicians select treatment options that would result in superior outcome. The identification of such markers, termed 'surrogate' markers, could help shed further insights into what constitutes illness and recovery, help identify molecular targets for the development of future antidepressants, and lead the way to the design and refinement of a personalized medicine treatment model for MDD. In the following text, several major areas ('leads') where evidence exists regarding the presence of surrogate markers of efficacy outcome in MDD will be briefly reviewed. Leads include evidence from the role of demographic and clinical factors as surrogate markers, to the role of various biological markers including genotype, brain functional imaging, electroencephalography, dichotic listening, and molecular biology and immunology. The purpose of this work is to focus selectively on areas where there have been findings, as opposed to conducting an exhaustive literature review of studies which have failed to yield any significant breakthrough in our knowledge. C1 [Papakostas, George I.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. [Papakostas, George I.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Papakostas, GI (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, 1 Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM gpapakostas@partners.org RI Papakostas, George/I-6905-2013 OI Papakostas, George/0000-0002-2465-5103 FU Bristol Myers Squibb Company; Forest Pharmaceuticals; National Institute of Mental Health; PAMLAB LLC; Pfizer Inc.; Ridge Diagnostics FX Dr Papakostas has received research support from Bristol Myers Squibb Company, Forest Pharmaceuticals, the National Institute of Mental Health, PAMLAB LLC, Pfizer Inc., and Ridge Diagnostics (formerly known as Precision Human Biolaboratories). NR 154 TC 8 Z9 8 U1 1 U2 8 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JUL PY 2012 VL 15 IS 6 BP 841 EP 854 DI 10.1017/S1461145711001246 PG 14 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 969DJ UT WOS:000306035600010 PM 21813045 ER PT J AU Hansen, GM Lawler, ME Williams, WB Troulis, MJ Kaban, LB AF Hansen, G. M. Lawler, M. E. Williams, W. B. Troulis, M. J. Kaban, L. B. TI BMP4 localization and PCNA expression during distraction osteogenesis of the porcine mandible SO INTERNATIONAL JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article DE mandibular distraction osteogenesis; immunohistochemistry; PCNA; BMP4 ID BONE MORPHOGENETIC PROTEIN-2; INFERIOR ALVEOLAR NERVE; CELL NUCLEAR ANTIGEN; MESSENGER-RNA; GROWTH-FACTOR; RAT; PIG; PROLIFERATION; MODEL; MINIPIGS AB This study characterized sequential molecular and cellular events in the porcine mandibular distraction osteogenesis (DO) wound. Nineteen Yucatan minipigs were divided into three treatment groups: Group A, unilateral mandibular distraction with 0 day latency, 1 mm/day rate for 12 days, 24 days fixation (n = 16); Group B, acute lengthening 12 mm (n = 2); Group C, sham control (n = 1). Group A was further divided by death date: mid-DO (n = 5), end-DO (n = 4), mid-fixation (n = 5) and end-fixation (n = 2). Groups B and C were killed on postoperative day 36, corresponding to end-fixation. Specimens were stained for proliferating cell nuclear antigen (PCNA) and bone morphogenetic protein-4 (BMP4). Cellular proliferation (PCNA) was assessed quantitatively and BMP4 staining was assessed on a semi-quantitative scale. Progenitor cell proliferation was greatest during mid-DO and decreased from end-DO through end-fixation. Proliferation in the acute lengthening group was elevated relative to sham control and comparable to end-DO. BMP4 staining intensity (localized to the periosteal cambium layer) was greatest during mid- and end-DO, decreased at mid-fixation and was undetectable at end-fixation. Progenitor cell proliferation and BMP4 expression are greatest during mid-DO and decrease progressively thereafter. At the time of death of the acute lengthening group, only increased cell proliferation was demonstrated. C1 [Hansen, G. M.; Lawler, M. E.; Williams, W. B.; Troulis, M. J.; Kaban, L. B.] Harvard Univ, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Sch Dent Med, Boston, MA 02114 USA. RP Kaban, LB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Sch Dent Med, 55 Fruit St,WRN 1201, Boston, MA 02114 USA. EM lkaban@partners.org FU AO-ASIF Foundation (Berne, Switzerland); Hanson Foundation (Boston, MA); CMF (West Chester, PA); Massachusetts General Hospital Oral and Maxillofacial Surgery Education and Research Fund (Boston, MA); Harvard Medical School Office of Enrichment FX This project was funded in part by the AO-ASIF Foundation (Berne, Switzerland), the Hanson Foundation (Boston, MA), Synthes CMF (West Chester, PA), the Massachusetts General Hospital Oral and Maxillofacial Surgery Education and Research Fund (Boston, MA) and the Harvard Medical School Office of Enrichment. NR 40 TC 4 Z9 5 U1 1 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0901-5027 J9 INT J ORAL MAX SURG JI Int. J. Oral Maxillofac. Surg. PD JUL PY 2012 VL 41 IS 7 BP 867 EP 873 DI 10.1016/j.ijom.2011.12.032 PG 7 WC Dentistry, Oral Surgery & Medicine; Surgery SC Dentistry, Oral Surgery & Medicine; Surgery GA 967AR UT WOS:000305879000015 PM 22285012 ER PT J AU High, KP Brennan-Ing, M Clifford, DB Cohen, MH Currier, J Deeks, SG Deren, S Effros, RB Gebo, K Goronzy, JJ Justice, AC Landay, A Levin, J Miotti, PG Munk, RJ Nass, H Rinaldo, CR Shlipak, MG Tracy, R Valcour, V Vance, DE Walston, JD Volberding, P AF High, Kevin P. Brennan-Ing, Mark Clifford, David B. Cohen, Mardge H. Currier, Judith Deeks, Steven G. Deren, Sherry Effros, Rita B. Gebo, Kelly Goronzy, Joerg J. Justice, Amy C. Landay, Alan Levin, Jules Miotti, Paolo G. Munk, Robert J. Nass, Heidi Rinaldo, Charles R., Jr. Shlipak, Michael G. Tracy, Russell Valcour, Victor Vance, David E. Walston, Jeremy D. Volberding, Paul CA OAR Working Grp HIV Aging TI HIV and Aging: State of Knowledge and Areas of Critical Need for Research. A Report to the NIH Office of AIDS Research by the HIV and Aging Working Group SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE aging; HIV/AIDS; co-morbidity; research priorities ID HUMAN-IMMUNODEFICIENCY-VIRUS; CHRONIC KIDNEY-DISEASE; OLDER-ADULTS; CARDIOVASCULAR-DISEASE; INFECTED PATIENTS; IMMUNE-SYSTEM; COHORT; BIOMARKERS; RISK; INFLAMMATION AB HIV risk behaviors, susceptibility to HIV acquisition, progression of disease after infection, and response to antiretroviral therapy all vary by age. In those living with HIV, current effective treatment has increased the median life expectancy to >70 years of age. Biologic, medical, individual, social, and societal issues change as one ages with HIV infection, but there has been only a small amount of research in this field. Therefore, the Office of AIDS Research of the National Institutes of Health commissioned a working group to develop an outline of the current state of knowledge and areas of critical need for research in HIV and Aging; the working groups' findings and recommendations are summarized in this report. Key overarching themes identified by the group included the following: multimorbidity, polypharmacy, and the need to emphasize maintenance of function; the complexity of assessing HIV versus treatment effects versus aging versus concurrent disease; the inter-related mechanisms of immune senescence, inflammation, and hypercoagulability; the utility of multivariable indices for predicting outcomes; a need to emphasize human studies to account for complexity; and a required focus on issues of community support, caregivers, and systems infrastructure. Critical resources are needed to enact this research agenda and include expanded review panel expertise in aging, functional measures, and multimorbidity, and facilitated use and continued funding to allow long-term follow-up of cohorts aging with HIV. C1 [High, Kevin P.] Wake Forest Univ, Baptist Med Ctr, Infect Dis Sect, Dept Internal Med,Wake Forest Sch Med, Winston Salem, NC 27157 USA. [Brennan-Ing, Mark] ACRIA Ctr HIV & Aging, New York, NY USA. [Clifford, David B.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [Cohen, Mardge H.] Rush Univ, Dept Internal Med, WIHS, Chicago, IL 60612 USA. [Currier, Judith; Effros, Rita B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Currier, Judith; Effros, Rita B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Deren, Sherry] NYU, Coll Nursing, New York, NY USA. [Gebo, Kelly] Johns Hopkins Univ, Sch Med, Dept Med, Div Infect Dis, Baltimore, MD 21205 USA. [Goronzy, Joerg J.] Stanford Univ, Sch Med, Dept Immunol & Rheumatol, Stanford, CA 94305 USA. [Justice, Amy C.] Yale Univ, Dept Med, Vet Affairs Connecticut Healthcare Syst, West Haven, CT USA. [Landay, Alan] Rush Univ, Med Ctr, Dept Immunol & Microbiol, Chicago, IL 60612 USA. [Levin, Jules] Natl AIDS Treatment Advocacy Project, Off AIDS Res, New York, NY USA. [Miotti, Paolo G.] NIH, Off AIDS Res, DHHS, Rockville, MD USA. [Munk, Robert J.] AIDS InfoNet, Arroyo Seco, NM USA. [Rinaldo, Charles R., Jr.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Infect Dis & Microbiol, Pittsburgh, PA USA. [Shlipak, Michael G.] Univ Calif San Francisco, Dept Med, Vet Affairs Med Ctr, San Francisco, CA USA. [Tracy, Russell] Univ Vermont, Coll Med, Dept Pathol & Biochem, Colchester, VT USA. [Valcour, Victor] Univ Calif San Francisco, Dept Neurol, Div Geriatr Med, Memory & Aging Ctr, San Francisco, CA USA. [Vance, David E.] Univ Alabama Birmingham, Sch Nursing, Birmingham, AL USA. [Volberding, Paul] Univ Calif San Francisco, Dept Med, San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. [Walston, Jeremy D.] Johns Hopkins Univ, Sch Med, Div Geriatr Med & Gerontol, Baltimore, MD USA. RP High, KP (reprint author), Wake Forest Univ, Baptist Med Ctr, Infect Dis Sect, Dept Internal Med,Wake Forest Sch Med, 100 Med Ctr Blvd, Winston Salem, NC 27157 USA. EM khigh@wakehealth.edu FU Office of AIDS Research, National Institutes of Health FX Supported by the Office of AIDS Research, National Institutes of Health. NR 88 TC 157 Z9 159 U1 5 U2 23 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 JUL 1 PY 2012 VL 60 SU 1 BP S1 EP S18 PG 18 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 968ZH UT WOS:000306024400001 PM 22688010 ER PT J AU Terpolilli, NA Moskowitz, MA Plesnila, N AF Terpolilli, Nicole A. Moskowitz, Michael A. Plesnila, Nikolaus TI Nitric oxide: considerations for the treatment of ischemic stroke SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Review DE acute stroke; experimental; focal ischemia; neuroprotection; nitric oxide ID CEREBRAL-BLOOD-FLOW; HIGH-DENSITY-LIPOPROTEIN; COA REDUCTASE INHIBITOR; SPONTANEOUSLY HYPERTENSIVE-RATS; ENDOTHELIAL GROWTH-FACTOR; PROTEIN-KINASE AKT; SOLUBLE GUANYLATE-CYCLASE; HDL CHOLESTEROL LEVELS; ARTERY OCCLUSION; L-ARGININE AB Some 40 years ago it was recognized by Furchgott and colleagues that the endothelium releases a vasodilator, endothelium-derived relaxing factor (EDRF). Later on, several groups identified EDRF to be a gas, nitric oxide (NO). Since then, NO was identified as one of the most versatile and unique molecules in animal and human biology. Nitric oxide mediates a plethora of physiological functions, for example, maintenance of vascular tone and inflammation. Apart from these physiological functions, NO is also involved in the pathophysiology of various disorders, specifically those in which regulation of blood flow and inflammation has a key role. The aim of the current review is to summarize the role of NO in cerebral ischemia, the most common cause of stroke. Journal of Cerebral Blood Flow & Metabolism (2012) 32, 1332-1346; doi: 10.1038/jcbfm.2012.12; published online 15 February 2012 C1 [Plesnila, Nikolaus] Univ Munich, Sch Med, Inst Stroke & Dementia Res, Munich, Germany. [Terpolilli, Nicole A.] Univ Munich, Sch Med, Dept Neurosurg, Munich, Germany. [Moskowitz, Michael A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Neurosci, Boston, MA USA. RP Plesnila, N (reprint author), Univ Munich, Sch Med, Inst Stroke & Dementia Res, Munich, Germany. EM nikolaus.plesnila@med.uni-muenchen.de NR 210 TC 36 Z9 42 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUL PY 2012 VL 32 IS 7 BP 1332 EP 1346 DI 10.1038/jcbfm.2012.12 PG 15 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 968IH UT WOS:000305970800017 PM 22333622 ER PT J AU Santoriello, C Zon, LI AF Santoriello, Cristina Zon, Leonard I. TI Hooked! Modeling human disease in zebrafish SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID DIAMOND-BLACKFAN ANEMIA; ZINC-FINGER NUCLEASES; RIBOSOMAL-PROTEIN S19; T-CELL LEUKEMIA; TRANSGENIC ZEBRAFISH; MUSCULAR-DYSTROPHY; HEART REGENERATION; MELANOMA-CELLS; POSITIONAL CLONING; GENE INACTIVATION AB Zebrafish have been widely used as a model system for studying developmental processes, but in the last decade, they have also emerged as a valuable system for modeling human disease. The development and function of zebrafish organs are strikingly similar to those of humans, and the ease of creating mutant or transgenic fish has facilitated the generation of disease models. Here, we highlight the use of zebrafish for defining disease pathways and for discovering new therapies. C1 [Zon, Leonard I.] Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. [Zon, Leonard I.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Zon, Leonard I.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Zon, Leonard I.] Harvard Univ, Sch Med, Boston, MA USA. [Santoriello, Cristina; Zon, Leonard I.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. RP Zon, LI (reprint author), Childrens Hosp, Stem Cell Program, Karp Family Res Bldg,300 Longwood Ave, Boston, MA 02115 USA. EM zon@enders.tch.harvard.edu FU NCI NIH HHS [R01 CA103846] NR 106 TC 108 Z9 112 U1 4 U2 45 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 JUL PY 2012 VL 122 IS 7 BP 2337 EP 2343 DI 10.1172/JCI60434 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 969GV UT WOS:000306044600003 PM 22751109 ER PT J AU Bellucci, R Nguyen, HN Martin, A Heinrichs, S Schinzel, AC Hahn, WC Ritz, J AF Bellucci, Roberto Hong-Nam Nguyen Martin, Allison Heinrichs, Stefan Schinzel, Anna C. Hahn, William C. Ritz, Jerome TI Tyrosine kinase pathways modulate tumor susceptibility to natural killer cells SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID LENTIVIRAL RNAI LIBRARY; FACTOR-I RECEPTOR; DENDRITIC CELLS; NK; ACTIVATION; PROTEIN; INHIBITOR; LEUKEMIA; GROWTH; SORAFENIB AB Natural killer (NK) cells are primary effectors of innate immunity directed against transformed tumor cells. In response, tumor cells have developed mechanisms to evade NK cell-mediated lysis through molecular mechanisms that are not well understood. In the present study, we used a lentiviral shRNA library targeting more than 1,000 human genes to identify 83 genes that promote target cell resistance to human NK cell-mediated killing. Many of the genes identified in this genetic screen belong to common signaling pathways; however, none of them have previously been known to modulate susceptibility of human tumor cells to immunologic destruction. Gene silencing of two members of the JAK family (JAK1 and JAK2) increased the susceptibility of a variety of tumor cell types to NK-mediated lysis and induced increased secretion of IFN-gamma by NK cells. Treatment of tumor cells with JAK inhibitors also increased susceptibility to NK cell activity. These findings may have important clinical implications and suggest that small molecule inhibitors of tyrosine kinases being developed as therapeutic antitumor agents may also have significant immunologic effects in vivo. C1 [Bellucci, Roberto; Hong-Nam Nguyen; Martin, Allison; Schinzel, Anna C.; Hahn, William C.; Ritz, Jerome] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Bellucci, Roberto; Hahn, William C.; Ritz, Jerome] Brigham & Womans Hosp, Dept Med, Boston, MA USA. [Bellucci, Roberto; Heinrichs, Stefan; Hahn, William C.; Ritz, Jerome] Harvard Univ, Sch Med, Boston, MA USA. [Ritz, Jerome] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02215 USA. [Schinzel, Anna C.; Hahn, William C.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02215 USA. [Heinrichs, Stefan] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. RP Ritz, J (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave,M530, Boston, MA 02215 USA. EM Roberto_Bellucci@dfci.harvard.edu; Jerome_Ritz@dfci.harvard.edu OI Ritz, Jerome/0000-0001-5526-4669 FU NIH [P01 CA078378, R21 AI088521]; International Myeloma Foundation (IMF); Multiple Myeloma Research Foundation (MMRF); Claudia Adams Barr Research Program FX This work was supported by NIH grants P01 CA078378 (to J. Ritz) and R21 AI088521 (to R. Bellucci), the International Myeloma Foundation (IMF), Multiple Myeloma Research Foundation (MMRF), and Claudia Adams Barr Research Program (to R. Bellucci). We thank Amanda Carmignani for helpful suggestions and discussion on the statistical analysis. NR 46 TC 21 Z9 21 U1 0 U2 5 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 JUL PY 2012 VL 122 IS 7 BP 2369 EP 2383 DI 10.1172/JCI58457 PG 15 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 969GV UT WOS:000306044600011 PM 22684105 ER PT J AU Sankaran, VG Ghazvinian, R Do, R Thiru, P Vergilio, JA Beggs, AH Sieff, CA Orkin, SH Nathan, DG Lander, ES Gazda, HT AF Sankaran, Vijay G. Ghazvinian, Roxanne Do, Ron Thiru, Prathapan Vergilio, Jo-Anne Beggs, Alan H. Sieff, Colin A. Orkin, Stuart H. Nathan, David G. Lander, Eric S. Gazda, Hanna T. TI Exome sequencing identifies GATA1 mutations resulting in Diamond-Blackfan anemia SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID INHERITED MUTATION; GENE DELETIONS; DOWN-SYNDROME; PROTEIN; ERYTHROPOIESIS; EXPRESSION; LEUKEMIA AB Diamond-Blackfan anemia (DBA) is a hypoplastic anemia characterized by impaired production of red blood cells, with approximately half of all cases attributed to ribosomal protein gene mutations. We performed exome sequencing on two siblings who had no known pathogenic mutations for DBA and identified a mutation in the gene encoding the hematopoietic transcription factor GATA1. This mutation, which occurred at a splice site of the GATA1 gene, impaired production of the full-length form of the protein. We further identified an additional patient carrying a distinct mutation at the same splice site of the GATA1 gene. These findings provide insight into the pathogenesis of DBA, showing that the reduction in erythropoiesis associated with the disease can arise from causes other than defects in ribosomal protein genes. These results also illustrate the multifactorial role of GATA1 in human hematopoiesis. C1 [Ghazvinian, Roxanne; Beggs, Alan H.; Gazda, Hanna T.] Childrens Hosp, Div Genet, Manton Ctr Orphan Dis Res, Boston, MA 02115 USA. [Ghazvinian, Roxanne; Beggs, Alan H.; Gazda, Hanna T.] Childrens Hosp, Program Genom, Manton Ctr Orphan Dis Res, Boston, MA 02115 USA. [Lander, Eric S.] Broad Inst, Cambridge Ctr 7, Cambridge, MA 02142 USA. [Sankaran, Vijay G.; Thiru, Prathapan] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Sankaran, Vijay G.] Childrens Hosp, Dept Med, Boston, MA 02115 USA. [Sankaran, Vijay G.; Beggs, Alan H.; Sieff, Colin A.; Orkin, Stuart H.; Nathan, David G.; Gazda, Hanna T.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Vergilio, Jo-Anne] Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. [Sieff, Colin A.; Orkin, Stuart H.; Nathan, David G.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Sieff, Colin A.; Orkin, Stuart H.; Nathan, David G.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Lander, Eric S.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. [Lander, Eric S.] MIT, Dept Biol, Cambridge, MA USA. RP Gazda, HT (reprint author), Childrens Hosp, Div Genet, Manton Ctr Orphan Dis Res, 300 Longwood Ave, Boston, MA 02115 USA. EM lander@broadinstitute.org; hanna.gazda@childrens.harvard.edu OI Beggs, Alan/0000-0001-8818-0568 FU NIH grant [R01 HL107558, T32 HL007574-30, U54 HG003067-09]; Manton Center for Orphan Disease Research; Diamond-Blackfan Anemia Foundation FX We are grateful to the families involved in this work for their courage and commitment to research and to the clinicians caring for these patients. We thank M. Ilzarbe, N. Gupta, J. Murphy, and S. Flynn for their assistance in study organization; M. DePristo, C. Hartl, and K. Shakir for assistance with genetic analysis; H. Lodish, L. Ludwig, O. Zuk, M. Garber, and M. Schnall-Levin for valuable comments and assistance; and T. DiCesare for assistance with illustrations. This work was supported by NIH grant T32 HL007574-30 (to V.G. Sankaran); NIH grant R01 HL107558 and grants from the Manton Center for Orphan Disease Research and the Diamond-Blackfan Anemia Foundation (to H.T. Gazda); and NIH grant U54 HG003067-09 (to E.S. Lander). NR 22 TC 101 Z9 108 U1 2 U2 7 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 2012 VL 122 IS 7 BP 2439 EP 2443 DI 10.1172/JCI63597 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 969GV UT WOS:000306044600017 PM 22706301 ER PT J AU Maioli, M Zeymer, U van 't Hof, AWJ Gibson, CM Dudek, D Bellandi, F Noc, M Secco, GG Zorman, S Gabriel, HM Emre, A Cutlip, D Rakowski, T Gyongyosi, M Huber, K De Luca, G AF Maioli, Mauro Zeymer, Uwe van 't Hof, Arnoud W. J. Gibson, C. Michael Dudek, Dariusz Bellandi, Francesco Noc, Marko Secco, Gioel Gabrio Zorman, Simona Gabriel, H. Mesquita Emre, Ayse Cutlip, Donald Rakowski, Tomasz Gyongyosi, Maryann Huber, Kurt De Luca, Giuseppe CA EGYPT Cooperation TI Impact of Preprocedural TIMI Flow on Myocardial Perfusion, Distal Embolization and Mortality in Patients with ST-Segment Elevation Myocardial Infarction Treated by Primary Angioplasty and Glycoprotein IIb/IIIa Inhibitors SO JOURNAL OF INVASIVE CARDIOLOGY LA English DT Article DE primary angioplasty; perfusion; preprocedural recanalization; mortality ID MECHANICAL REPERFUSION; RANDOMIZED-TRIALS; NO-REFLOW; INTERVENTION; DETERMINANT; DURATION; REGISTRY; THERAPY; BENEFIT; BLUSH AB Background. Despite optimal epicardial recanalization, primary angioplasty for ST-elevation myocardial infarction (STEMI) is still associated with suboptimal reperfusion in a relatively large proportion of patients. The aim of the current study was to evaluate the impact of preprocedural TIMI flow on myocardial perfusion, distal embolization, and survival among STEMI patients undergoing primary angioplasty with glycoprotein (GP) IIb/IIIa inhibitors. Methods. Our population is represented by a total of 1637 patients undergoing primary angioplasty for STEMI treated with GP IIb/IIIa inhibitors. Myocardial perfusion was evaluated by myocardial blush grade and ST-segment resolution. Followup data were collected between 30 days and 1 year after primary angioplasty. Results. Poor preprocedural TIMI flow (TIMI 0-1) was observed in 1039 patients (63.5%), and was associated with higher Killip class at presentation (P=.006), longer time-to-treatment (P=.03), less often with early administration of GP IIb/IIIa inhibitors (P<.001), impaired post-procedural epicardial (P=.001) and myocardial perfusion (determined by myocardial blush grade, P<.001 and/or ST-segment resolution (P<.001), and distal embolization (P=.041). At 206 +/- 158 days follow-up, poor preprocedural recanalization was associated with a significantly higher mortality (adjusted odds ratio, 0.58; 95% CI, 0.34-0.96; P=.034). Conclusion. This study shows that among patients with STEMI undergoing primary angioplasty with GP IIb/IIIa inhibitors, poor preprocedural TIMI flow is associated with higher incidence of distal embolization and impaired epicardial and myocardial perfusion, and significantly higher mortality. C1 [Maioli, Mauro; Bellandi, Francesco] Prato Hosp, Div Cardiol, Prato, Italy. [Zeymer, Uwe] Herzzentrum Ludwigshafen, Div Cardiol, Ludwigshafen, Germany. [van 't Hof, Arnoud W. J.] Hosp Weezenlanden, Div Cardiol, Zwolle, Netherlands. [Gibson, C. Michael] Beth Israel Deaconess Med Ctr, Div Cardiovasc, TIMI Study Grp, Boston, MA 02215 USA. [Dudek, Dariusz; Rakowski, Tomasz] Jagiellonian Univ, Dept Cardiol, Inst Cardiol, Krakow, Poland. [Noc, Marko; Zorman, Simona] Univ Med Ctr, Ctr Intens Internal Med, Ljubljana, Slovenia. [De Luca, Giuseppe] Univ Piemonte Orientale, Div Cardiol, Dept Clin & Expt Med, Novara, Italy. [Gabriel, H. Mesquita] Hosp Santa Maria, Div Cardiol, Lisbon, Portugal. [Emre, Ayse] Siyami Ersek Thorac & Cardiovasc Surg Ctr, Instabul, Turkey. [Cutlip, Donald] Beth Israel Deaconess Med Ctr, Intervent Cardiol Sect, Boston, MA 02215 USA. [Gyongyosi, Maryann] Med Univ Vienna, Dept Cardiol, Vienna, Austria. [Huber, Kurt] Wilhelminenspital Stadt Wien, Dept Med Cardiol & Emergency Med, Vienna, Austria. [De Luca, Giuseppe] Eastern Piedmont Univ, Div Cardiol, Maggiore della Carita Hosp, Novara, Italy. RP De Luca, G (reprint author), Univ Piemonte Orientale, Div Cardiol, Dept Clin & Expt Med, Novara, Italy. EM giuseppe.deluca@maggioreosp.novara.it NR 19 TC 3 Z9 5 U1 0 U2 1 PU H M P COMMUNICATIONS PI MALVERN PA 83 GENERAL WARREN BLVD, STE 100, MALVERN, PA 19355 USA SN 1042-3931 J9 J INVASIVE CARDIOL JI J. Invasive Cardiol. PD JUL PY 2012 VL 24 IS 7 BP 324 EP 327 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 967HR UT WOS:000305898000011 PM 22781470 ER PT J AU Friedman, AD Burns, JA Lutch, MJ Zeitels, SM AF Friedman, A. D. Burns, J. A. Lutch, M. J. Zeitels, S. M. TI Submucosal neoplasms of the laryngeal introitus SO JOURNAL OF LARYNGOLOGY AND OTOLOGY LA English DT Article DE Larynx; Laryngeal Neoplasms; Laryngeal Cancer, Sarcoma, Synovial; Chondrosarcoma; Granular Cell Tumor ID SYNOVIAL SARCOMA; LASER TREATMENT; TUMOR; HEAD; NECK AB Background: The differential diagnosis of endolaryngeal mesenchymal neoplasms includes a wide spectrum of benign and malignant pathologies, which have been rarely photo-documented and assessed as a group. Methods: Non-epithelial neoplasms of the endolarynx seen at our centre from 2002 to 2011 (n = 38; 36 treated at our institution) were retrospectively reviewed, with attention to clinical presentation, radiographic imaging, operative management, histology, and pre- and post-operative endoscopy. Submucosal squamous cell carcinomas, mucosal cysts, amyloid and Teflon granulomas were excluded. Results: Twenty-three of a total of 36 patients underwent definitive endoscopic surgical treatment. Supraglottic pathologies included lymphoma, lipoma, neuroendocrine carcinoma, lymphangioma, oncocytoma, haemangioma, synovial cell sarcoma and benign spindle cell neoplasm. Transglottic pathologies included synovial cell sarcoma and granular cell tumour. Glottic pathologies included granular cell tumour, osteoma, rhabdomyoma, rhabdomycosarcoma and myofibroblastic sarcoma. Subglottic pathologies included chondrosarcoma, neurofibroma, adenoid cystic carcinoma and vascular malformation. Conclusion: The site of origin, degree of malignant behaviour and sensitivity to adjuvant treatment determined the course of surgical management, i.e. endolaryngeal versus transcervical, and limited removal versus wider resection. C1 [Friedman, A. D.; Burns, J. A.; Zeitels, S. M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. [Lutch, M. J.] So Calif Permanente Med Grp, Dept Otolaryngol, San Diego, CA 92120 USA. RP Friedman, AD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Ctr Laryngeal Surg & Voice Rehabil, 1 Bowdoin Sq,11th Floor, Boston, MA 02114 USA. EM afriedman3@partners.org FU Eugene B Casey Foundation; Institute of Laryngology and Voice Restoration FX This work was supported in part by the Eugene B Casey Foundation and the Institute of Laryngology and Voice Restoration. NR 18 TC 5 Z9 5 U1 1 U2 5 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 0022-2151 J9 J LARYNGOL OTOL JI J. Laryngol. Otol. PD JUL PY 2012 VL 126 IS 7 BP 706 EP 713 DI 10.1017/S0022215112000928 PG 8 WC Otorhinolaryngology SC Otorhinolaryngology GA 969ZK UT WOS:000306097700010 PM 22624973 ER PT J AU Saslow, D Solomon, D Lawson, HW Killackey, M Kulasingam, SL Cain, JM Garcia, FAR Moriarty, AT Waxman, AG Wilbur, DC Wentzensen, N Downs, LS Spitzer, M Moscicki, AB Franco, EL Stoler, MH Schiffman, M Castle, PE Myers, ER AF Saslow, Debbie Solomon, Diane Lawson, Herschel W. Killackey, Maureen Kulasingam, Shalini L. Cain, Joanna M. Garcia, Francisco A. R. Moriarty, Ann T. Waxman, Alan G. Wilbur, David C. Wentzensen, Nicolas Downs, Levi S., Jr. Spitzer, Mark Moscicki, Anna-Barbara Franco, Eduardo L. Stoler, Mark H. Schiffman, Mark Castle, Philip E. Myers, Evan R. TI American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology Screening Guidelines for the Prevention and Early Detection of Cervical Cancer SO JOURNAL OF LOWER GENITAL TRACT DISEASE LA English DT Article DE adult HPV; cervical intraepithelial neoplasia/epidemiology/prevention; female cervical cancer ID HUMAN-PAPILLOMAVIRUS DNA; RANDOMIZED CONTROLLED-TRIAL; ATYPICAL SQUAMOUS-CELLS; INTRAEPITHELIAL NEOPLASIA GRADE-2; INTERNATIONAL INCIDENCE RATES; ADENOCARCINOMA IN-SITU; LIQUID-BASED CYTOLOGY; LONG-TERM RISK; COST-EFFECTIVENESS; UNITED-STATES AB An update to the American Cancer Society (ACS) guideline regarding screening for the early detection of cervical precancerous lesions and cancer is presented. The guidelines are based on a systematic evidence review, contributions from six working groups, and a recent symposium co-sponsored by the ACS, American Society for Colposcopy and Cervical Pathology (ASCCP), and American Society for Clinical Pathology (ASCP), which was attended by 25 organizations. The new screening recommendations address age-appropriate screening strategies, including the use of cytology and high-risk human papillomavirus (HPV) testing, follow-up (e.g., management of screen positives and screening interval for screen negatives) of women after screening, age at which to exit screening, future considerations regarding HPV testing alone as a primary screening approach, and screening strategies for women vaccinated against HPV16/18 infections. C1 [Saslow, Debbie] Amer Canc Soc, Canc Control Sci Dept, Atlanta, GA 30303 USA. [Solomon, Diane] NCI, Canc Prevent Div, NIH, Rockville, MD USA. [Lawson, Herschel W.] Emory Univ, Sch Med, Dept Gynecol & Obstet, Atlanta, GA USA. [Killackey, Maureen] Mem Sloan Kettering Canc Ctr, Dept Surg, Gynecol Serv, Mem Sloan Kettering Canc Ctr Reg Network, New York, NY 10021 USA. [Kulasingam, Shalini L.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Cain, Joanna M.] Univ Massachusetts, Sch Med, Dept Obstet & Gynecol, Worcester, MA USA. [Garcia, Francisco A. R.] Univ Arizona, Mel & Enid Zuckerman Coll Publ Hlth, Ctr Excellence Womens Hlth, Tucson, AZ USA. [Moriarty, Ann T.] AmeriPath Indiana, Dept Esoter Testing, Indianapolis, IN USA. [Moriarty, Ann T.] Univ New Mexico, Sch Med, Dept Obstet & Gynecol, Albuquerque, NM 87131 USA. [Wilbur, David C.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Wentzensen, Nicolas] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. [Downs, Levi S., Jr.] Univ Minnesota, Sch Med, Div Gynecol Oncol, Dept Obstet Gynecol & Womens Hlth,Mason Canc Ctr, Minneapolis, MN 55455 USA. [Spitzer, Mark] Cornell Univ, Weill Med Coll, New York, NY 10021 USA. [Moscicki, Anna-Barbara] Univ Calif San Francisco, Dept Pediat, San Francisco, CA USA. [Franco, Eduardo L.] McGill Univ, Dept Oncol, Montreal, PQ, Canada. [Franco, Eduardo L.] McGill Univ, Dept Epidemiol, Montreal, PQ, Canada. [Stoler, Mark H.] Univ Virginia Hlth Syst, Dept Pathol, Charlottesville, VA USA. [Schiffman, Mark] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Castle, Philip E.] Amer Chem Soc, Clin Pathol Inst, Washington, DC 20036 USA. [Myers, Evan R.] Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA. RP Saslow, D (reprint author), Amer Canc Soc, Canc Control Sci Dept, 250 Williams St NW,Suite 600, Atlanta, GA 30303 USA. EM debbie.saslow@cancer.org OI Franco, Eduardo/0000-0002-4409-8084 FU Merck Sharp Dohme; Merck, Inc.; Roche Pharmaceutical/Roche Molecular; Hologic; Third Wave; MTM; Qiagen; Becton Dickinson; Medispectra/Luma; Roche; Gen-Probe; Abbott; Gen-Probe, Inc.; GSK, Inc.; Precision Therapeutics; National Surgical Adjuvant Breast and Bowel Project; Merck Research Laboratories; Ventana Medical Systems; IKONOBGYN; Hatt, Co.; Merck, Inc; National Institute of Allergy and Infectious Diseases; Gen Probe FX Philip E. Castle, PhD, MPH, receives payment for service on the Data Monitoring and Safety Board for Merck Sharp & Dohme. Carmel Cohen, MD, serves as a speaker for Merck, Inc. and receives honoraria. The spouse of Mitchell Edelson, MD, is employed and receives salary from Merck, Inc. Francisco Garcia, MD, MPH, is employed by the University of Arizona, which holds contracts for the performance of research with Roche Pharmaceutical/Roche Molecular, Hologic, Third Wave, MTM, Qiagen, Becton Dickinson, and Medispectra/Luma. Dr Garcia also serves on the speakers' list for Qiagen and receives honoraria. Jack Cuzick, MD, serves on advisory boards and as an ad hoc consultant for Qiagen, Roche, Gen-Probe, Becton Dickinson, and Abbott, with research fund provided to his institution from Qiagen, Roche, Gen-Probe, Becton Dickinson, and Abbott. Patti Gravitt, MD, provides service on the scientific advisory board from Qiagen and for which she received honoraria. Evan R. Myers, MD, MPH, received research support for investigations for Gen-Probe, Inc. and from GSK, Inc. He served as a speaker for and received honoraria from Gen-Probe, Inc. and has served as a consultant for Merck, Inc., for which he received an honorarium. Mark Schiffman, MD, MPH, holds a research agreement to serve as a medical monitor in the National Cancer Institute vaccine trial through GlaxoSmithKline; Dr Schiffman also receives research support from Qiagen for CareHPV research in Nigeria. Carolyn Runowicz, MD, serves on the board of directors for the American Society for Clinical Oncology and provides service on the scientific advisory board from Bayer for which she receives honoraria. Dr Runowicz has provided scientific review for and received payment from Precision Therapeutics, as well as served on the advisory board for Ovarian Cancer Research Fund (no payments received). Dr Runowicz is a paid reviewer for Champions Oncology, and she has received research funding from National Surgical Adjuvant Breast and Bowel Project. Diane Solomon, MD, serves as a medical monitor for the National Cancer Institute's HPV Vaccine Trial in Costa Rica: the trial receives vaccine from GlaxoSmithKline. Mark H. Stoler, MD, received fees for serving as a consultant to Merck Research Laboratories, Roche, Ventana Medical Systems, Becton Dickinson, Hologic, MTM, and Gen-Probe. Richard S. Guido, MD, received research funds for services as the primary investigator on a multicenter study (contracted research and serves local PI) for IKONOBGYN. Dr Guido also received research funds to be a primary investigator on a multicenter study (local PI) for Hatt, Co. Dina R. Mody, MD, conducted lectures/workshops for both CAP and the American Society for Clinical Pathology and from which she received honoraria. Dr Mody received reimbursement for her travel expenses for conducting an ASC lecture/workshop. Jeffrey Waldman, MD, attended a consultants meeting for Graceway Pharmaceuticals and received an honorarium. The employer of George Birdsong, MD, receives funding for contracted research performed by Dr Birdsong for Becton Dickinson Diagnostics. Cosette Wheeler, PhD, is an employee of University of New Mexico, which is contracted by GlaxoSmithKline for its vaccine trials and for which Dr Wheeler serves as a principal investigator. Dr Wheeler also serves as a principal investigator employee of the University of New Mexico, which receives equipment/reagents from Roche Molecular Systems for human papillomavirus genotyping. J.; Thomas Cox, MD, serves on the scientific advisory boards for Gen-Probe, Graceway, and Bradley Pharmaceuticals and receives honoraria for these services. Dr Cox also serves on the Data and Safety Monitoring Board and receives a fee from Merck, Inc; he was reimbursed for travel expenses for meetings of the Roche Data and Steering Committee. Dr Cox serves on the speakers' bureau for Bradley Pharmaceuticals and has served to both speak and moderate at a symposium for Becton Dickinson Diagnostics; honoraria were received for these activities. David Wilbur, MD, serves on the scientific advisory board for Corista, LLC. Teresa M. Darragh, MD, received Thin Prep supplies for research from Ho logic. She serves on an advisory board from OncoHealth and has received stock options as payment. Dr Darragh also serves on an advisory board for Arbor Vita Corporation and receives honoraria. Edward J. Mayeaux, Jr., MD, serves on the speakers' advisory board for both Merck, Inc. and PharmaDerm, and he receives honoraria from both companies for his service. Mark Spitzer, MD, serves as a speaker for both Merck, Inc. and Qiagen and receives honoraria. He received an honorarium and royalties from Elsevier for book editorship; Dr Spitzer also received royalties as an author for the Colposcopy Image Library CD-ROM produced by SABK, Inc. Kevin A. Ault, MD, received clinical research grants from National Institute of Allergy and Infectious Diseases, Gen Probe, Merck, Inc., and Roche and served as a site principal investigator for the research. All grants were provided to his employer, Emory University. Eduardo Franco, MD, received honorarium as a study steering committee member for GlaxoSmithKline; Dr Franco serves on the advisory boards of Merck, Inc., Roche, and GenProbe and from which he receives honoraria. Michael A. Gold, MD, received honorarium for serving as a speaker and consultant for Hologic. Warner K. Huh, MD, serves as a consultant to Roche, Qiagen, Merck, Inc., and Inovio and receives honoraria from all four companies. Anna-Barbara Moscicki, MD, received honorarium for serving as a consultant to an advisory board for Merck, Inc. Mark E. Einstein, MD, has advised or participated in educational speaking activities but does not receive an honorarium from any companies. His employer, Montefiore Medical Center, has received payment for his time spent on activities for Merck, Inc., GlaxoSmithKline, Roche, Bristol-Myers Squibb, Hologic, Advaxis, Aura Biosciences, Inovio, Photocure, Neodiagnostix, and PDS Biotechnologies. Montefiore Medical Center has received grant funding for research related to the costs of those Merck, GlaxoSmithKline, Roche, Advaxis, and Hologic clinical trials for which Dr Einstein served as the principal investigator of Montefiore Medical Center's. Ann T. Moriarty, MD, received honorarium as a speaker for the American Society of Cytopathology; Dr Moriarty also receives a salary as compensation for her employment with AmeriPath. NR 156 TC 92 Z9 97 U1 3 U2 15 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 JUL PY 2012 VL 16 IS 3 BP 175 EP 204 PG 30 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 966OC UT WOS:000305846300004 PM 22418039 ER PT J AU Darragh, TM Colgan, TJ Cox, JT Heller, DS Henry, MR Luff, RD McCalmont, T Nayar, R Palefsky, JM Stoler, MH Wilkinson, EJ Zaino, RJ Wilbur, DC AF Darragh, Teresa M. Colgan, Terence J. Cox, J. Thomas Heller, Debra S. Henry, Michael R. Luff, Ronald D. McCalmont, Timothy Nayar, Ritu Palefsky, Joel M. Stoler, Mark H. Wilkinson, Edward J. Zaino, Richard J. Wilbur, David C. CA LAST Project Work Grp TI The Lower Anogenital Squamous Terminology Standardization Project for HPV-Associated Lesions: Background and Consensus Recommendations From the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology SO JOURNAL OF LOWER GENITAL TRACT DISEASE LA English DT Article DE squamous intraepithelial lesion; human papillomavirus; superficially invasive carcinoma; p16; terminology ID VULVAR INTRAEPITHELIAL NEOPLASIA; HUMAN-PAPILLOMAVIRUS INFECTION; RISK HUMAN-PAPILLOMAVIRUS; STAGE-IA CARCINOMA; SUPERFICIALLY INVASIVE-CARCINOMA; IMPROVES INTEROBSERVER AGREEMENT; DIAGNOSTIC SURGICAL PATHOLOGY; BETHESDA SYSTEM TERMINOLOGY; ADENOCARCINOMA IN-SITU; CELL CARCINOMA AB The terminology for human papillomavirus (HPV)-associated squamous lesions of the lower anogenital tract has a long history marked by disparate diagnostic terms derived from multiple specialties. It often does not reflect current knowledge of HPV biology and pathogenesis. A consensus process was convened to recommend terminology unified across lower anogenital sites. The goal was to create a histopathologic nomenclature system that reflects current knowledge of HPV biology, optimally uses available biomarkers, and facilitates clear communication across different medical specialties. The Lower Anogenital Squamous Terminology (LAST) Project was cosponsored by the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology and included 5 working groups; 3 work groups performed comprehensive literature reviews and developed draft recommendations. Another work group provided the historical background and the fifth will continue to foster implementation of the LAST recommendations. After an open comment period, the draft recommendations were presented at a consensus conference attended by LAST work group members, advisors, and representatives from 35 stakeholder organizations including professional societies and government agencies. Recommendations were finalized and voted on at the consensus meeting. The final, approved recommendations standardize biologically relevant histopathologic terminology for HPV-associated squamous intraepithelial lesions and superficially invasive squamous carcinomas across all lower anogenital tract sites and detail the appropriate use of specific biomarkers to clarify histologic interpretations and enhance diagnostic accuracy. A plan for disseminating and monitoring recommendation implementation in the practicing community was also developed. The implemented recommendations will facilitate communication between pathologists and their clinical colleagues and improve accuracy of histologic diagnosis with the ultimate goal of providing optimal patient care. C1 [Darragh, Teresa M.] Univ Calif San Francisco, Mt Zion Med Ctr, Dept Pathol, San Francisco, CA 94115 USA. [Colgan, Terence J.] Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. [Heller, Debra S.] UMDNJ, New Jersey Med Sch, Newark, NJ USA. [Henry, Michael R.] Mayo Clin, Rochester, MN USA. [Luff, Ronald D.] Quest Diagnost, Teterboro, NJ USA. [Luff, Ronald D.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Nayar, Ritu] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Stoler, Mark H.] Univ Virginia Hlth Syst, Charlottesville, VA USA. [Wilkinson, Edward J.] Univ Florida, Coll Med, Gainesville, FL USA. [Zaino, Richard J.] Penn State Univ, Milton S Hershey Med Ctr, Hershey, PA 17033 USA. [Wilbur, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Cox, J. Thomas] Univ Calif Santa Barbara, Santa Barbara Student Hlth Serv, Santa Barbara, CA 93106 USA. RP Darragh, TM (reprint author), Univ Calif San Francisco, Mt Zion Med Ctr, Dept Pathol, 1600 Divisadero St,Room B618, San Francisco, CA 94115 USA. EM teresa.darragh@ucsf.edu RI Colgan, Terence/J-2339-2016 FU American Society for Colposcopy and Cervical Pathology (ASCCP); College of American Pathologists (CAP); National Institutes of Health (NIH)/National Cancer Institute (NCI); NIH/National Institute of Allergy and infectious Disease; GlaxoSmithKline; BD TriPath; Hologic; Pennsylvania State University; University of Washington; Oregon Dermatological Society; CAP; Cornell University; University of Iowa; US State Department; US Agency for International Development; MTM Laboratories; BD Diagnostics, Veregen; OncoHealth; Indian Health Service; ASCCP; Gynecologic Oncology Group; ACOG; Michigan Hematology Oncology Association; NIH/NCI; ACOG District IV; Minority Health Research Committee; Toledo Hospital; Society of Obstetricians and Gynecologists of Canada (SOGC); Florida OBGYN Society; Kentucky ACOG Section; Indiana ACOG Section; ACOG District V; Miami Grand Rounds; Missouri OBGYN Associates; Ohio Dermatologic Association; Flint Hospital; University of Wisconsin; University of Connecticut; Turkish Society; NIH; Washington University in St Louis; Meridian Conferences; SOGC; Merck Frosst; Merck and Co.; Gilead Biosciences; American Social Health Association; University of Ottawa; Thai Red Cross; University of Minnesota; University of Illinois; University of British Columbia; Louisiana State University; American Association for Cancer Research; Gynecologic Oncology Society of Canada; University of Alberta; European Society for Sexual Medicine; Aura Biosciences; Australian Society for Colposcopy and Cervical Pathology; Merck Research Laboratories; Meriter Foundation; University of Chicago; Chicago Dermatology Society; Harvard Medical School; Oakstone Medical Publishing; National Library of Medicine; New Mexico Department of Health/Center for Health Training; Center for Health Training (Austin, TX); SouthEast Alaska Regional Health Corporation; Arctic Slope Native Association; Yukon Kuskokwim Health Corporation; Breast Cancer Detection of Alaska; Sutter Medical Center of Santa Rosa Medical; AIDS Healthcare Foundation of Los Angeles; American Society of Colon and Rectal Surgeons; Merck and Company; NIH/AMC Working Group; Canadian Institute of Health Research; Institute of Science & Technology Partnerships, Canada; Canadian Health Research Institute; ASCP; ASC; Hartford Hospital; PA Association of Pathologists, Gynecologic Oncology Group; Scientific Symposium International (travel reimbursement included); Medical University of South Carolina; California Society of Pathologists; Burrough's Wellcome Fund; NIH/National Institute of General Medical Sciences; Roche; Innovio; Photocure; BDD; NIH for SEER, ovarian, and HPV research; Indiana University; McGill University; United States Academy of Pathology; Canadian Academy of Pathology; University of New Mexico School of Medicine; BD; Merck, Inc; Gen-Probe; Agency for Healthcare Research and Quality (AHRQ) FX The American Society for Colposcopy and Cervical Pathology (ASCCP) and College of American Pathologists (CAP) provided the funding for this project; no industry funds were used in the development of the consensus statements and recommendations.; Steering Committee: Dr Darragh serves on the advisory boards of OncoHealth and Arbor Vita Corporation; she owns stock in OncoHealth and receives grants from the National Institutes of Health (NIH)/National Cancer Institute (NCI) and NIH/National Institute of Allergy and infectious Disease. In addition, she receives fees for lecturing for the American College of Obstetricians and Gynecologists (ACOG), ASCCP, Society of Gynecologic Oncologists (SGO), Planned Parenthood, and the American Society for Clinical Pathology (ASCP). Dr Henry receives royalties from the CAP. Dr Luff is an employee of Quest Diagnostics and holds stock ownership in the corporation. Quest Diagnostics receives grants from GlaxoSmithKline, BD TriPath, and Hologic to support clinical trials. Dr Luff received coverage for his travel to an Endo Pharmaceuticals investigators' meeting. He serves on the Foundation Board of the American Society of Cytopathology (ASC). Dr McCalmont receives lecture fees from the Pennsylvania State University, University of Washington, and the Oregon Dermatological Society. He serves as an expert witness for Filice, Brown and receives consultancy fees from various law firms. Dr Wilbur serves as an expert witness for MCIC Vermont, Ohio State University, Pro-mutual, Memorial Sloan-Kettering Cancer Center, CMIC, Lavin, O'Neill, CRICO, Claims Management, and the Mayo Clinic. He serves as a consultant for Becker Consulting. He receives lecture fees from CAP, Cornell University, and the University of Iowa and receives royalties from both CAP and Elsevier. He serves on an advisory board for Corista LLC and VisionGate. He receives grants from the US State Department and the US Agency for International Development. Dr Wilkinson serves as a consultant for Hologic and Guided Therapeutics and serves on the advisory boards of Merck, Inc, and the ASCCP. He receives royalties from Lippincott, Williams, and Wilkins and grants from MTM Laboratories. Dr Wilkinson owns stock in Johnson & Johnson and Procter & Gamble.; Work Group 1: Dr Cox serves on the advisory boards for Gen-Probe, Graceway, and Roche; he also serves on the Merck HPV Vaccine Data and Safety Monitoring Board. Dr Cox receives lecture fees from BD Diagnostics, Veregen, GlaxoSmithKline, and OncoHealth. Dennis O'Connor serves as a consultant to the National Children's Tissue Bank. He receives lecture fees from the Indian Health Service and the ASCCP and grants from the Gynecologic Oncology Group. R. Kevin Reynolds receives lecture fees from ACOG, ASCCP, and the Michigan Hematology Oncology Association. James Scurry (advisor) owns stocks in Sonic Health Care, Impedimed, Nib Holdings Limited, and Biota Holdings. M. Angelica Selim received a grant from NIH/NCI. For Dr Wilkinson, see Steering Committee listing.; Work Group 2: David Chelmow serves on the eMedicine Editorial Board and Medscape Reference Editorial Board. He has served as an expert witness for various obstetrical cases. He receives lecture fees from ACOG District IV. Leona Council is a part-time employee of LabCorp and receives grants from the Minority Health Research Committee. Hope Haefner has received lecture fees from ACOG, ASCCP, Toledo Hospital, Society of Obstetricians and Gynecologists of Canada (SOGC), Florida OBGYN Society, Kentucky ACOG Section, Indiana ACOG Section, ACOG District V, Miami Grand Rounds, Missouri OBGYN Associates, Ohio Dermatologic Association, Flint Hospital, University of Wisconsin, University of Connecticut, and the Turkish Society. She serves as an expert witness for Kitch Attorneys & Counselors. For Dr Henry, see Steering Committee listing. Lydia Howell serves on an advisory board for the American Council on Education and as an expert witness for Ubaldi and McPherson, LLC. She has received grants from NIH and lecture fees from Washington University in St Louis. Kieron Leslie serves both as a consultant and as an advisory board member for Novartis. Dr Leslie receives lecture fees from Meridian Conferences. Alice Lytwyn provides expert review and consulting for the Program for Appropriate Technology in Health. She receives lecture fees from the SOGC and Merck Frosst. Dr Lytwyn also receives grants from Merck Frosst. For Dr McCalmont, see Steering Committee listing. Joel Palefsky serves on the advisory boards of Merck and Co, Pharmajet, Inc, Aura Biosciences, Inc, and the Arbor Vita Corporation. He serves as a consultant and receives grants and travel expenses from Merck and Co. Dr Palefsky receives lecture fees from the Gilead Biosciences, American Social Health Association, University of Ottawa, Thai Red Cross, University of Minnesota, University of Illinois, University of British Columbia, Louisiana State University, American Association for Cancer Research, ASCCP, Gynecologic Oncology Society of Canada, University of Alberta, and the European Society for Sexual Medicine. He serves as an expert witness for the Schoenberg Law Firm. He receives grants from Aura Biosciences and NIH for research and royalties from UpToDate. Jennifer Roberts (advisor) receives lecture fees from the Australian Society for Colposcopy and Cervical Pathology. Brigitte Ronnett receives grants from NIH/NCI and Merck Research Laboratories. She serves as a consultant to Merck Research Laboratories and receives lecture fees from MTM Laboratories. She also receives royalties from Springer Verlag. Christopher Shea serves on the Editorial Board of the Journal of American Academy of Dermatology. He receives lecture fees from Meriter Foundation. Dr Shea serves as an expert witness for Healthcare Litigation Support, LLC, Wicker, Smith, O'Hara, McCoy & Ford, PA, Gary Osborne & Associates, Eichorn and Eichorn, and Benito H. Diaz, Esq. He receives grants from the University of Chicago, Chicago Dermatology Society, and NIH. Paul Staats receives lecture fees from Harvard Medical School. Alan Waxman serves on advisory boards for ACOG, ASCCP, the American Cancer Society Cervical Cancer Screening Work Group.; He receives a partial salary grant from NIH and lecture fees from ACOG, ASCCP, Oakstone Medical Publishing, the National Library of Medicine, the New Mexico Department of Health/Center for Health Training, Center for Health Training (Austin, TX), SouthEast Alaska Regional Health Corporation, Arctic Slope Native Association, Yukon Kuskokwim Health Corporation, and Breast Cancer Detection of Alaska. Dr Waxman also receives a retirement pension from the United States Public Health Service.; Work Group 3: J. Michael Berry receives lecture fees from Sutter Medical Center of Santa Rosa Medical, AIDS Healthcare Foundation of Los Angeles, American Society of Colon and Rectal Surgeons, and ASCCP. He serves as a consultant for the Cancer Research Center of Hawaii. Dr Berry is employed by the University of California San Francisco, which holds contracts and receives grants for the performance of research from Merck and Company and the NIH/AMC Working Group. He serves on an advisory board for Arbor Vita Corporation. Terence Colgan is a consultant for LifeLabs and Ontario Medical Associates. He receives lecture fees from the ASCCP and grants from the Canadian Institute of Health Research, Institute of Science & Technology Partnerships, Canada, and the Canadian Health Research Institute. He has patents pending or received relative to protein markers of endometrial cancer and endometrial biomarkers. He receives honoraria for serving as the Associate Editor of Cancer Cytopathology. For Dr Darragh, see Steering Committee listing. Levi Downs receives grants from GlaxoSmithKline. Olga Ioffe receives lecture fees from the ASCP. Nancy Joste serves on the Board of Directors for both Grounds for Health (NGO) and Planned Parenthood of New Mexico. She receives grants from the NIH/NCI. Oscar Lin receives grants from NIH and lecture fees from the ASC. Richard Zaino holds a consultancy with the United States Food & Drug Administration and serves as the co-chair of the NCI Uterine Task Force. He receives lecture fees from Hartford Hospital, PA Association of Pathologists, Gynecologic Oncology Group, CAP, Scientific Symposium International (travel reimbursement included), ASCP, and the Medical University of South Carolina.; Work Group 4: Christina Kong serves as an expert witness for PG&E, Rissman, Barrett, Hurt, Donahue, & McLain, PA, Garrett Hemann Robertson, PC, Martin & Jones, LLC, Cabaniss, Johnston, Gardner, Dumas, and O'Neal, LLP, and Andrada & Associates. She receives lecture fees from the California Society of Pathologists and grants from Burrough's Wellcome Fund and NIH. She received travel reimbursement from the Philippine Society of Pathologists. Bradley Quade serves as an expert witness for William E. Artz, PC, Bonezzi, Switzer, Murphy, Polito & Hupp, Co, LPA, Risk Management Foundation, Margolis Edelstein, Professional Casualty Association, Mary Hitchcock Memorial Hospital, University Hospitals Health System, Kline & Specter, Berman and Simmons, Martin, Magnuson, McCarthy & Kenney, Trobh, Heisler & Piampiano, and Foster & Eldridge. He serves on an advisory board for the Columbia Hospital Research Foundation and he receives a grant from NIH/National Institute of General Medical Sciences. Mark Stoler serves as a consultant to Merck Research Labs, Roche, Gen-Probe, Qiagen, BD, Ventana Medical Systems, MTM Laboratories, and Abraxis. For Dr Wilbur, see Steering Committee listing.; Work Group 5: Alicia Carter (advisor) is employed by Laboratory Corporation of America Holdings. Philip E. Castle serves as a consultant for Merck, Inc, and Roche. Maire Duggan receives grants (materials only, no funding) from Hologic for the PALS Trial. Francisco Garcia is employed by the University of Arizona, which holds contracts for the performance of research with Roche, Innovio, Photocure, Hologic, and BDD. Marc Goodman (advisor) is a consultant for Vanderbilt University, University of Iowa, the North American Association of Central Cancer Registries, and Moffitt Cancer Center. He serves on the Board of Scientific Counselors of NCI and receives grants from NIH for SEER, ovarian, and HPV research. For Dr Luff, see Steering Committee listing. Ann Moriarty is employed by AmeriPath and serves on the Cancer Support Community Physicians Advisory Board. She receives lecture fees from the ASC and serves as an expert witness for Eichorn and Eichorn, LLP. Ritu Nayar serves on the Cytopathology Test Development Committee for the American Board of Pathology and as an Associate Editor for Cancer (Cytopathology). She receives lecture fees from Indiana University, McGill University, and the United States & Canadian Academy of Pathology and receives grants from MTM Laboratories. Margaret Neal (advisor) serves on an advisory board for PathPAC. George Niedt serves as a consultant to Bronx Lebanon Hospital and Jacobi Hospital. Vijaya Reddy (advisor) receives royalties from both Cambridge Publishers and Elsevier. Mona Saraiya (advisor) serves on the American Cancer Society Steering Committee for Gynecologic Cancer. Susan Spires (advisor) receives lecture fees from CAP and ASC. Steve Silverberg (advisor) receives royalties from Elsevier, Wolters Kluwer, and the American Registry of Pathology. He receives lecture fees from the ASCP.; Herschel Lawson (conference moderator) receives lecture fees from the University of New Mexico School of Medicine and the ASCCP. Thomas Wright (technical reviewer) serves as a consultant for GlaxoSmithKline, Roche Molecular Diagnostics, Merck, Inc, i3 Innovus, MTM Laboratories, Gen-Probe, and BID. He also serves on advisory boards for BD, Merck, Inc, and Roche. He receives lecture fees from BD, Merck, Inc, and Roche. Evan Myers (LAST methodologist) serves as a consultant for Gen-Probe, Merck, Inc, and GlaxoSmithKline. He serves on an advisory board for Merck, Inc and receives fees for lecturing for Gen-Probe. Dr Myers receives grants from Gen-Probe, GlaxoSmithKline, and the Agency for Healthcare Research and Quality (AHRQ). NR 181 TC 118 Z9 124 U1 1 U2 2 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 JUL PY 2012 VL 16 IS 3 BP 205 EP 242 PG 38 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 966OC UT WOS:000305846300005 PM 22820980 ER PT J AU Zaidat, OO Lazzaro, MA Gupta, R Yavagal, DR Rasmussen, PA Hirsch, JA Castonguay, AC Tarr, RW AF Zaidat, Osama O. Lazzaro, Marc A. Gupta, Rishi Yavagal, Dileep R. Rasmussen, Peter A. Hirsch, Joshua A. Castonguay, Alicia C. Tarr, Robert W. TI Interventional Management of Stroke III Trial: establishing the foundation SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Editorial Material ID ACUTE ISCHEMIC-STROKE; INTRAVENOUS THROMBOLYSIS; RECANALIZATION; INFUSION; THERAPY C1 [Zaidat, Osama O.] Med Coll Wisconsin, Froedtert Hosp, Dept Neurol, Neurointervent Div, Milwaukee, WI 53226 USA. [Zaidat, Osama O.] Med Coll Wisconsin, Dept Neurosurg, Milwaukee, WI 53226 USA. [Zaidat, Osama O.] Med Coll Wisconsin, Dept Radiol, Milwaukee, WI 53226 USA. [Gupta, Rishi] Emory Univ, Sch Med, Dept Neurol Neurosurg & Radiol, Atlanta, GA USA. [Yavagal, Dileep R.] Univ Miami, Dept Neurol & Neurosurg, Miami, FL USA. [Rasmussen, Peter A.] Cleveland Clin, Dept Neurosurg, Cleveland, OH 44106 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept Radiol, NeuroEndovasc Program, Boston, MA 02114 USA. RP Zaidat, OO (reprint author), Med Coll Wisconsin, Froedtert Hosp, Dept Neurol, Neurointervent Div, Milwaukee, WI 53226 USA. EM szaidat@mcw.edu NR 19 TC 9 Z9 9 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 JUL PY 2012 VL 4 IS 4 BP 235 EP 237 DI 10.1136/neurintsurg-2012-010409 PG 3 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 968ZV UT WOS:000306026400001 PM 22613883 ER PT J AU Gonzalez, RG AF Gonzalez, R. Gilberto TI Low signal, high noise and large uncertainty make CT perfusion unsuitable for acute ischemic stroke patient selection for endovascular therapy SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Editorial Material ID DIFFUSION; VOLUME; MRI C1 [Gonzalez, R. Gilberto] Massachusetts Gen Hosp, Dept Neuroradiol, Boston, MA 02114 USA. [Gonzalez, R. Gilberto] Harvard Univ, Sch Med, Boston, MA USA. RP Gonzalez, RG (reprint author), Massachusetts Gen Hosp, Dept Neuroradiol, Boston, MA 02114 USA. EM rggonzalez@partners.org NR 10 TC 15 Z9 15 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 JUL PY 2012 VL 4 IS 4 BP 242 EP 245 DI 10.1136/neurintsurg-2012-010404 PG 4 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 968ZV UT WOS:000306026400004 PM 22679196 ER PT J AU Duffis, EJ Gandhi, CD Prestigiacomo, CJ Abruzzo, T Albuquerque, F Bulsara, KR Derdeyn, CP Fraser, JF Hirsch, JA Hussain, MS Do, HM Jayaraman, MV Meyers, PM Narayanan, S AF Duffis, E. Jesus Gandhi, Chirag D. Prestigiacomo, Charles Joseph Abruzzo, Todd Albuquerque, Felipe Bulsara, Ketan R. Derdeyn, Colin P. Fraser, Justin F. Hirsch, Joshua A. Hussain, Muhammad Shazam Do, Huy M. Jayaraman, Mahesh V. Meyers, Philip M. Narayanan, Sandra CA Soc Neurointerventional Surg TI Head, neck, and brain tumor embolization guidelines SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Article ID SKULL-BASE TUMORS; PREOPERATIVE EMBOLIZATION; GLOMUS TUMORS; INTRACRANIAL MENINGIOMAS; THERAPEUTIC EMBOLIZATION; PARTICLE EMBOLIZATION; MANAGEMENT; PARAGANGLIOMAS; EXPERIENCE; COMPLICATIONS AB Background Management of vascular tumors of the head, neck, and brain is often complex and requires a multidisciplinary approach. Pen-operative embolization of vascular tumors may help to reduce intra-operative bleeding and operative times and have thus become an integral part of the management of these tumors. Advances in catheter and non-catheter based techniques in conjunction with the growing field of neurointerventional surgery is likely to expand the number of Peri-operative embolizations performed. The goal of this article is to provide consensus reporting standards and guidelines for embolization treatment of vascular head, neck, and brain tumors. Summary This article was produced by a writing group comprised of members of the Society of Neurointerventional Surgery. A computerized literature search using the National Library of Medicine database (Pubmed) was conducted for relevant articles published between 1 January 1990 and 31 December 2010. The article summarizes the effectiveness and safety of peri-operative vascular tumor embolization. In addition, this document provides consensus definitions and reporting standards as well as guidelines not intended to represent the standard of care, but rather to provide uniformity in subsequent trials and studies involving embolization of vascular head and neck as well as brain tumors. Conclusions Pen-operative embolization of vascular head, neck, and brain tumors is an effective and safe adjuvant to surgical resection. Major complications reported in the literature are rare when these procedures are performed by operators with appropriate training and knowledge of the relevant vascular and surgical anatomy. These standards may help to standardize reporting and publication in future studies. C1 [Duffis, E. Jesus; Gandhi, Chirag D.; Prestigiacomo, Charles Joseph] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Neurosurg, Newark, NJ 07103 USA. [Gandhi, Chirag D.; Prestigiacomo, Charles Joseph] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Radiol, Newark, NJ 07103 USA. [Prestigiacomo, Charles Joseph] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Neurol & Neurosci, Newark, NJ 07103 USA. [Abruzzo, Todd] Univ Cincinnati, Mayfield Clin, Cincinnati, OH USA. [Abruzzo, Todd] Cincinnati Childrens Hosp, Cincinnati, OH USA. [Albuquerque, Felipe] Barrow Neurosurg Associates LTD, Phoenix, AZ USA. [Bulsara, Ketan R.] Yale Dept Neurosurg, New Haven, CT USA. [Derdeyn, Colin P.] Mallinckrodt Inst Radiol, St Louis, MO USA. [Derdeyn, Colin P.] Washington Univ, Sch Med, Barnes Jewish Hosp, St Louis, MO USA. [Fraser, Justin F.] Univ Kentucky, Dept Neurol Surg, Lexington, KY USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hussain, Muhammad Shazam] Cleveland Clin, Neurol Inst, Cerebrovasc Ctr, Cleveland, OH 44106 USA. [Do, Huy M.] Stanford Univ, Med Ctr, Dept Radiol, Stanford, CA 94305 USA. [Jayaraman, Mahesh V.] Brown Univ, Rhode Isl Hosp, Warren Alpert Sch Med, Providence, RI 02903 USA. [Meyers, Philip M.] Columbia Univ, Coll Phys & Surg, New York, NY 10027 USA. [Narayanan, Sandra] Wayne State Univ, Sch Med, Dept Neurosurg, Detroit, MI USA. [Narayanan, Sandra] Wayne State Univ, Sch Med, Dept Neurol, Detroit, MI 48201 USA. [Meyers, Philip M.] Neurol Inst New York, Neuroendovasc Serv New York Presbyterian Columbia, New York, NY USA. RP Gandhi, CD (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Neurosurg, 90 Bergen St,Suite 8100, Newark, NJ 07103 USA. EM gandhich@umdnj.edu OI Fraser, Justin/0000-0002-5980-3989; Derdeyn, Colin/0000-0002-5932-2683 NR 52 TC 12 Z9 13 U1 0 U2 3 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 JUL PY 2012 VL 4 IS 4 BP 251 EP 255 DI 10.1136/neurintsurg-2012-010350 PG 5 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 968ZV UT WOS:000306026400006 PM 22539531 ER PT J AU Mehra, M Henninger, N Hirsch, JA Chueh, J Wakhloo, AK Gounis, MJ AF Mehra, Manik Henninger, Nils Hirsch, Joshua A. Chueh, Juyu Wakhloo, Ajay K. Gounis, Matthew J. TI Preclinical acute ischemic stroke modeling SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Review ID TISSUE PLASMINOGEN-ACTIVATOR; THROMBOEMBOLIC STROKE; CEREBRAL-ISCHEMIA; CANINE MODEL; INTRAARTERIAL; INFARCTION; OCCLUSION; BRAIN; NEUROPROTECTION; THROMBOLYSIS AB Preclinical ischemic stroke is at the crossroads in search of reliable and robust simulation models as past experiences with their translation from the laboratory to the standard of clinical care have often been disappointing. The efficacy of neuroprotective agents is still elusive, and the use of thrombolytics alone is limited to the narrow time window of presentation from the onset of the deficit. Hence, the focus has shifted to interventional revascularization to salvage the parenchyma at the risk of infarction. As the burden of disease morbidity and mortality is so enormous, neurointerventionalists have adopted a more aggressive approach to mechanical revascularization with the limited approved tools available-the Penumbra and the MERCI retrieval system, and the recently incorporated stent retrievers. In fact, the interventional space is among the fastest growing fields in stroke research today. Assessing treatment efficacy in these scenarios is infinitely complex as the heterogeneity of the cerebrovasculature, physical and mechanical nature of the occlusive embolus and the time of presentation are all confounders in assessing treatment outcomes. As no single thromboembolic model is apt to address all of these questions, an integrated methodology with a combination of both in vitro and in vivo assessment needs to be adopted. This involves clinically relevant thromboembolic analogs in device evaluation in vascular replicas, thromboembolic stroke induction in large animal gyrencephalic ischemic stroke models for thrombolytic, imaging and neuroprotection research and a native cerebrovascular target for evaluation of the safety and efficacy of mechanical thrombectomy devices. C1 [Mehra, Manik; Chueh, Juyu; Wakhloo, Ajay K.; Gounis, Matthew J.] Univ Massachusetts, Dept Radiol, Worcester, MA 01605 USA. [Henninger, Nils] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Neurol, Boston, MA 02215 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Gounis, MJ (reprint author), Univ Massachusetts, Dept Radiol, 55 Lake Ave N,SA-107R, Worcester, MA 01605 USA. EM matthew.gounis@umassmed.edu OI Henninger, Nils/0000-0002-3883-5623 NR 38 TC 13 Z9 13 U1 1 U2 5 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 JUL PY 2012 VL 4 IS 4 BP 307 EP 313 DI 10.1136/neurintsurg-2011-010101 PG 7 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 968ZV UT WOS:000306026400017 PM 21990535 ER PT J AU Hirsch, JA Chandra, RV Leslie-Mazwi, TM AF Hirsch, Joshua A. Chandra, Ronil Vikesh Leslie-Mazwi, Thabele M. TI Pipeline, aneurysms and the FDA SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Letter C1 [Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept NeuroIntervent Radiol, Boston, MA 02114 USA. [Chandra, Ronil Vikesh; Leslie-Mazwi, Thabele M.] Massachusetts Gen Hosp, Dept Intervent Neuroradiol, Boston, MA 02114 USA. [Chandra, Ronil Vikesh; Leslie-Mazwi, Thabele M.] Massachusetts Gen Hosp, Dept Endovasular Neurosurg, Boston, MA 02114 USA. RP Hirsch, JA (reprint author), Massachusetts Gen Hosp, Dept NeuroIntervent Radiol, 55 Fruit St,Gray 241B, Boston, MA 02114 USA. EM hirsch@snisonline.org NR 1 TC 0 Z9 1 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 JUL PY 2012 VL 4 IS 4 BP 314 EP 314 DI 10.1136/neurintsurg-2012-010326 PG 1 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 968ZV UT WOS:000306026400019 PM 22442403 ER PT J AU Merport, A Recklitis, CJ AF Merport, Anna Recklitis, Christopher J. TI Does the Brief Symptom Inventory-18 Case Rule Apply in Adult Survivors of Childhood Cancer?: Comparison With the Symptom Checklist-90 SO JOURNAL OF PEDIATRIC PSYCHOLOGY LA English DT Article DE BSI-18; cancer; long-term survivors; oncology; psychological distress; screening ID BECK DEPRESSION INVENTORY; QUALITY-OF-LIFE; PSYCHOLOGICAL DISTRESS; PRIMARY-CARE; HEALTH QUESTIONNAIRE; SCREENING MEASURE; PEDIATRIC CANCER; SCALE; ADOLESCENT; DISORDERS AB Objective Screening for psychological distress is an important tool for improving survivors' access to psychosocial care. The Brief Symptom Inventory-18 (BSI-18) has been widely used to identify psychological distress in cancer survivors, but few studies have reported on its validity. This study evaluated validity of the BSI-18 by comparing it to the Symptom Checklist-90 (SCL-90). Methods Concordance of cases identified by the BSI-18 and SCL-90 was examined in a sample of 193 adult survivors of childhood cancer. Results Receiver operating characteristics analysis showed strong diagnostic utility of the BSI-18 (area under curve = 0.922). However, the standard BSI-18 case-rule demonstrated low sensitivity (45.2%) against the SCL-90. An alternative case-rule showed better results; sensitivity (87.10%), specificity (83.33%). Conclusions The BSI-18 is a useful measure for evaluating distress in adult survivors of childhood cancers; however, the standard BSI-18 case-rule has not been validated for this population, and an alternative case rule should be considered. C1 [Recklitis, Christopher J.] Dana Farber Canc Inst, Perini Family Survivors Ctr, Boston, MA 02215 USA. [Recklitis, Christopher J.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Recklitis, CJ (reprint author), Dana Farber Canc Inst, Perini Family Survivors Ctr, 450 Brookline Ave, Boston, MA 02215 USA. EM christopher_recklitis@dfci.harvard.edu NR 70 TC 8 Z9 8 U1 0 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0146-8693 J9 J PEDIATR PSYCHOL JI J. Pediatr. Psychol. PD JUL PY 2012 VL 37 IS 6 BP 650 EP 659 DI 10.1093/jpepsy/jss050 PG 10 WC Psychology, Developmental SC Psychology GA 966HD UT WOS:000305827600007 PM 22451261 ER PT J AU Harte, CB Meston, CM AF Harte, Christopher B. Meston, Cindy M. TI Recreational Use of Erectile Dysfunction Medications and Its Adverse Effects on Erectile Function in Young Healthy Men: The Mediating Role of Confidence in Erectile Ability SO JOURNAL OF SEXUAL MEDICINE LA English DT Article DE Erectile Dysfunction; Psychogenic Sexual Dysfunction; Erectile Function in Young Men; Erectile Dysfunction Medication; Recreational Use; Sildenafil; Confidence in Erectile Ability ID INTERNATIONAL INDEX; UNITED-STATES; PSYCHOLOGICAL-RESEARCH; SILDENAFIL USE; HIV-INFECTION; RISK-FACTORS; PREVALENCE; MODELS; ONLINE; MALES AB Introduction. Oral erectile dysfunction medications (EDMs) have become an increasingly popular drug of abuse among young men without a medical indication. In addition to being associated with increased sexual risk behaviors, recreational EDM use may adversely impact psychological aspects of sexual function, primarily by affecting one's confidence in pharmacologically unaided erectile ability. To date, these associations have not been investigated empirically. Aim. This study examined the mediating role of confidence in erectile ability on the concurrent relationship between recreational EDM use and erectile function among young healthy men. A secondary aim was to examine erectile function characteristics among recreational users, prescribed users, and nonusers to control for the possibility that recreational users were using EDMs to treat ED. Methods. The sample comprised 1,207 sexually active men (mean age = 21.9 years; standard deviation = 4.48) who were recruited from undergraduate institutions within the United States. Main Outcome Measures. Participants completed an online survey assessing frequency of EDM use, as well as levels of sexual function (erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall sexual satisfaction) and levels of confidence in ability to gain and maintain erection, as per the International Index of Erectile Function. Results. Recreational users (N = 72) reported similar erectile function levels compared with nonusers (N = 1,111), and both groups differed from prescribed users (N = 24). Recreational users also reported lower erectile confidence and lower overall satisfaction compared with nonusers. Results were consistent with mediation, in that more frequent EDM use was inversely associated with erectile confidence, which in turn showed negative relations with erectile function. Conclusions. Confidence in erectile abilities mediates the inverse relationship between recreational EDM use and erectile function. Results underscore the possibility that recreational EDM use among healthy young men may lead to psychogenic ED. Additional longitudinal research is necessary to establish a causal link between these variables. Harte CB and Meston CM. Recreational use of erectile dysfunction medications and its adverse effects on erectile function in young healthy men: The mediating role of confidence in erectile ability. J Sex Med 2012;9:18691876. C1 [Meston, Cindy M.] Univ Texas Austin, Dept Psychol, Austin, TX 78712 USA. [Harte, Christopher B.] VA Boston Healthcare Syst, Boston, MA USA. RP Harte, CB (reprint author), Univ Texas Austin, Dept Psychol, 1 Univ Stn,A8000, Austin, TX 78712 USA. EM c.b.harte@gmail.com OI Harte, Christopher/0000-0002-8097-7369 FU National Institute of Child Health and Human Development (NICHD) [1 RO1 HD051676-01 A1] FX Portions of this work were supported by Grant Number 1 RO1 HD051676-01 A1 to Cindy Meston from the National Institute of Child Health and Human Development (NICHD). The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NICHD. The authors thank Alison Marks for help with online data management and data acquisition, as well as Angela Nickerson, PhD, for her guidance with statistical approaches to mediation. NR 30 TC 8 Z9 8 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1743-6095 J9 J SEX MED JI J. Sex. Med. PD JUL PY 2012 VL 9 IS 7 BP 1852 EP 1859 DI 10.1111/j.1743-6109.2012.02755.x PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 968JS UT WOS:000305976700013 PM 22568639 ER PT J AU Dille, MF Wilmington, D McMillan, GP Helt, W Fausti, SA Konrad-Martin, D AF Dille, Marilyn F. Wilmington, Debra McMillan, Garnett P. Helt, Wendy Fausti, Stephen A. Konrad-Martin, Dawn TI Development and Validation of a Cisplatin Dose-Ototoxicity Model SO JOURNAL OF THE AMERICAN ACADEMY OF AUDIOLOGY LA English DT Article DE Cisplatin; ototoxicity; ototoxicity monitoring; Veterans ID PRODUCT OTOACOUSTIC EMISSIONS; TESTICULAR CANCER; HEARING-LOSS; RISK-FACTORS; CHEMOTHERAPY; SENSITIVITY; TOXICITY; CHILDREN; TINNITUS; PROTOCOL AB Background: Cisplatin is effective in the treatment of several cancers but is a known ototoxin resulting in shifts to hearing sensitivity in up to 50-60% of patients. Cisplatin-induced hearing shifts tend to occur first within an octave of a patient's high frequency hearing limit, termed the sensitive range for ototoxicity (SRO), and progress to lower frequencies. While it is currently not possible to know which patients will experience ototoxicity without testing their hearing directly, monitoring the SRO provides an early indication of damage. A tool to help forecast susceptibility to ototoxic-induced changes in the SRO in advance of each chemotherapy treatment visit may prove useful for ototoxicity monitoring efforts, patient counseling, and therapeutic planning. Purpose: This project was designed to (1) establish pretreatment risk curves that quantify the probability that a new patient will suffer hearing loss within the SRO during treatment with cisplatin and (2) evaluate the accuracy of these predictions in an independent sample of Veterans receiving cisplatin for the treatment of cancer. Study Sample: Two study samples were used. The Developmental sample contained 23 subjects while the Validation sample consisted of 12 subjects. Data Collection and Analysis: Risk curve predictions for SRO threshold shifts following cisplatin exposure were developed using a Developmental sample comprised of data from a total of 155 treatment visits obtained in 45 ears of 23 Veterans. Pure-tone thresholds were obtained within each subject's SRO at each treatment visit and compared with baseline measures. The risk of incurring an SRO shift was statistically modeled as a function of factors related to chemotherapy treatment (cisplatin dose, radiation treatment, doublet medication) and patient status (age, pre-exposure hearing, cancer location and stage). The model was reduced so that only statistically significant variables were included. Receiver-operating characteristic (ROC) curve analyses were then used to determine the accuracy of the risk curve predictions in an independent Validation sample of observations from over 62 treatment visits obtained in 24 ears of 12 Veterans. Results: Only cumulative cisplatin dose and pre-exposure hearing were found to be significantly related to the risk for hearing shift. The dose-ototoxicity risk curve predictions developed from the Developmental sample yielded area under the ROC curve accuracy estimates of 0.85 when applied to an independent Validation sample. Conclusions: Cumulative cisplatin dose in combination with pre-exposure hearing provides an indication of whether hearing will shift in the SRO in advance of cisplatin administration. The validated dose-ototoxicity risk curves described herein can be used before and during treatment to anticipate hearing loss. While having such a tool would not replace serial hearing testing, it would be of great benefit to an ototoxicity monitoring program. It would promote relevant pretreatment counseling. Furthermore, for those found to be at risk of SRO shifts within the speech frequencies, the oncology treatment plan could incorporate anticipated dosing adjustments-that could stave off the impact that ototoxicity might bring. C1 [Dille, Marilyn F.; Wilmington, Debra; McMillan, Garnett P.; Helt, Wendy; Fausti, Stephen A.; Konrad-Martin, Dawn] Oregon Hlth & Sci Univ, Vet Affairs Med Ctr, VA RR&D Natl Ctr Rehabil Auditory Res, Portland, OR 97201 USA. [Dille, Marilyn F.; Wilmington, Debra; Fausti, Stephen A.; Konrad-Martin, Dawn] Oregon Hlth & Sci Univ, Dept Otolaryngol Head & Neck Surg, Portland, OR 97201 USA. [McMillan, Garnett P.] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. RP Dille, MF (reprint author), Portland VA Med Ctr, VA RR&D Natl Ctr Rehabil Auditory Res NCRAR, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM Marilyn.Dille@va.gov FU Department of Veterans Affairs RRD Service [C4183R, C7113N]; VA RR&D National Center for Rehabilitative Auditory Research, Portland, OR; Office of Rehabilitation Research and Development (RR&D) Service, Department of Veterans Affairs [C4183R, C4447K] FX Work supported by the Department of Veterans Affairs RR&D Service (grants C4183R and C7113N) and the VA RR&D National Center for Rehabilitative Auditory Research, Portland, OR.; This work was supported by the Office of Rehabilitation Research and Development (RR&D) Service, Department of Veterans Affairs (Grants C4183R and C4447K) and the VA RR&D National Center for Rehabilitative Auditory Research, Portland, OR. NR 44 TC 8 Z9 8 U1 1 U2 5 PU AMER ACAD AUDIOLOGY PI RESTON PA 11730 PLAZA DR, STE 300, RESTON, VA 20190 USA SN 1050-0545 J9 J AM ACAD AUDIOL JI J. Am. Acad. Audiol. PD JUL-AUG PY 2012 VL 23 IS 7 BP 510 EP 521 DI 10.3766/jaaa.23.7.3 PG 12 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA 969HI UT WOS:000306045900003 PM 22992258 ER PT J AU Bergeron, SG Desy, NM Bernstein, M Harvey, EJ AF Bergeron, Stephane G. Desy, Nicholas M. Bernstein, Mithell Harvey, Edward J. TI Management of Posttraumatic Radioulnar Synostosis SO JOURNAL OF THE AMERICAN ACADEMY OF ORTHOPAEDIC SURGEONS LA English DT Review ID HETEROTOPIC OSSIFICATION; FOREARM FRACTURES; PLATE FIXATION; ADIPOFASCIAL FLAP; CROSS-UNION; EXCISION; INTERPOSITION; MOTION; ROTATION; ULNA AB Posttraumatic radioulnar synostosis is a rare complication following fracture of the forearm and elbow. Risk factors for synostosis are related to the initial injury and surgical management of the fracture. Typically, patients present with complete loss of active and passive forearm pronation and supination. Evidence of bridging heterotopic bone between the radius and ulna can be seen on plain radiographs. Although nonsurgical management is sufficient in some cases, surgical excision is typically required. The timing of surgical intervention remains controversial. However, early resection between 6 and 12 months after the initial injury can be performed safely in patients with radiographic evidence of bony maturation. Surgical management consists of complete resection of the synostosis with optional interposition of biologic or synthetic materials to restore forearm rotation. A low recurrence rate can be achieved following primary radioulnar synostosis excision without the need for routine adjuvant prophylaxis. C1 [Bergeron, Stephane G.] Harvard Univ, Sch Med, Dept Orthoped Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Desy, Nicholas M.; Bernstein, Mithell; Harvey, Edward J.] McGill Univ, Montreal Gen Hosp, Div Orthopaed Surg, Ctr Hlth, Montreal, PQ H3G 1A4, Canada. RP Bergeron, SG (reprint author), Harvard Univ, Sch Med, Dept Orthoped Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. OI harvey, edward/0000-0003-3934-8920 NR 38 TC 3 Z9 3 U1 0 U2 2 PU AMER ACAD ORTHOPAEDIC SURGEONS PI ROSEMENT PA 6300 N RIVER ROAD, ROSEMENT, IL 60018-4262 USA SN 1067-151X J9 J AM ACAD ORTHOP SUR JI J. Am. Acad. Orthop. Surg. PD JUL PY 2012 VL 20 IS 7 BP 450 EP 458 DI 10.5435/JAAOS-20-07-450 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 968ZR UT WOS:000306026000006 PM 22751164 ER PT J AU Fleurant, M Kell, R Jenter, C Volk, LA Zhang, F Bates, DW Simon, SR AF Fleurant, Marshall Kell, Rachel Jenter, Chelsea Volk, Lynn A. Zhang, Fang Bates, David W. Simon, Steven R. TI Factors associated with difficult electronic health record implementation in office practice SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID STATEWIDE SURVEY; MASSACHUSETTS; PHYSICIANS; ADOPTION; CARE; EXPERIENCE AB Little is known about physicians' perception of the ease or difficulty of implementing electronic health records (EHR). This study identified factors related to the perceived difficulty of implementing EHR. 163 physicians completed surveys before and after the implementation of EHR in an externally funded pilot program in three Massachusetts communities. Ordinal hierarchical logistic regression was used to identify baseline factors that correlated with physicians' report of difficulty with EHR implementation. Compared with physicians with ownership stake in their practices, physician employees were less likely to describe EHR implementation as difficult (adjusted OR 0.5, 95% Cl 0.3 to 1.0). Physicians who perceived their staff to be innovative were also less likely to view EHR implementation as difficult (adjusted OR 0.4, 95% Cl 0.2 to 0.8). Physicians who own their practice may need more external support for EHR implementation than those who do not. Innovative clinical support staff may ease the EHR implementation process and contribute to its success. C1 [Fleurant, Marshall] Boston Univ, Sch Med, Gen Internal Med Sect, Boston Med Ctr, Boston, MA 02118 USA. [Kell, Rachel] Massachusetts eHlth Collaborat, Waltham, MA USA. [Jenter, Chelsea; Bates, David W.; Simon, Steven R.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. [Volk, Lynn A.; Bates, David W.] Partners HlthCare Syst Inc, Wellesley, MA USA. [Zhang, Fang] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Zhang, Fang] Dept Populat Med, Boston, MA USA. [Bates, David W.; Simon, Steven R.] Harvard Univ, Sch Med, Boston, MA USA. [Bates, David W.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Simon, Steven R.] VA Boston Healthcare Syst, Gen Internal Med Sect, Boston, MA USA. RP Fleurant, M (reprint author), Boston Univ, Sch Med, Gen Internal Med Sect, Boston Med Ctr, 801 Massachusetts Ave,2nd Floor, Boston, MA 02118 USA. EM marshall.fleurant@bmc.org FU Agency for Healthcare Research and Quality [1UC1HS015397]; Massachusetts e-Health Collaborative; Ruth L. Kirschstein National Research Service [T32 HP12706] FX This study was funded in part by the Agency for Healthcare Research and Quality cooperative agreement no 1UC1HS015397 and the Massachusetts e-Health Collaborative. MF was supported by a Ruth L. Kirschstein National Research Service Award grant no T32 HP12706. NR 16 TC 7 Z9 7 U1 6 U2 19 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD JUL PY 2012 VL 19 IS 4 BP 541 EP 544 DI 10.1136/amiajnl-2011-000689 PG 4 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics SC Computer Science; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics GA 968ZG UT WOS:000306024100010 PM 22249965 ER PT J AU Ronquillo, JG Li, C Lester, WT AF Ronquillo, Jeremiah Geronimo Li, Cheng Lester, William T. TI Genetic testing behavior and reporting patterns in electronic medical records for physicians trained in a primary care specialty or subspecialty SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID FACTOR-V-LEIDEN; GENOMIC MEDICINE; INTERFACE DESIGN; HEALTH RECORDS; RECOMMENDATIONS; ATTITUDES AB Objective To characterize important patterns of genetic testing behavior and reporting in modern electronic medical records (EMRs) at the institutional level. Materials and methods Retrospective observational study using EMR data of all 10 715 patients who received genetic testing by physicians trained in a primary care specialty or subspecialty at an academic medical center between January 1, 2008 and December 31, 2010. Results Patients had a meant +/- SD age of 38.3 +/- 15.8 years (median 36.1, IQR 30.0-43.8). The proportion of female subjects in the study population was larger than in the general patient population (77.2% vs 55.0%, p<0.001) and they were younger than the male subjects in the study (36.5 +/- 13.2 vs 44.6 +/- 21.2 years, p<0.001). Approximately 1.1% of all patients received genetic testing. There were 942 physicians who ordered a total of 15 320 genetic tests. By volume, commonly tested genes involved mutations for cystic fibrosis (36.7%), prothrombin (13.7%), Tay Sachs disease (6.7%), hereditary hemochromatosis (4.4%), and chronic myelogenous leukemia (4.1%). EMRs stored reports as free text with categorical descriptions of mutations and an average length of 269.4 +/- 153.2 words (median 242, IGR 146-401). Conclusions In this study, genetic tests were often ordered by a diverse group of physicians for women of childbearing age being evaluated for diseases that may affect potential offspring. EMRs currently serve primarily as a storage warehouse for textual reports that could potentially be transformed into meaningful structured data for next-generation clinical decision support. Further studies are needed to address the design, development, and implementation of EMRs capable of managing the critical genetic health information challenges of the future. C1 [Ronquillo, Jeremiah Geronimo; Lester, William T.] Massachusetts Gen Hosp, Comp Sci Lab, Boston, MA 02114 USA. [Ronquillo, Jeremiah Geronimo; Lester, William T.] Harvard Univ, Sch Med, Boston, MA USA. [Li, Cheng] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Ronquillo, JG (reprint author), Massachusetts Gen Hosp, Comp Sci Lab, 50 Staniford St,7th Floor, Boston, MA 02114 USA. EM jronquillo@partners.org OI Lester, William/0000-0003-4086-9280 FU National Library of Medicine [T15LM007092] FX This research was supported in part by training grant T15LM007092 from the National Library of Medicine. NR 39 TC 4 Z9 4 U1 1 U2 7 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD JUL PY 2012 VL 19 IS 4 BP 570 EP 574 DI 10.1136/amiajnl-2011-000621 PG 5 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics SC Computer Science; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics GA 968ZG UT WOS:000306024100015 PM 22511017 ER PT J AU Feldman, MJ Hoffer, EP Barnett, GO Kim, RJ Famiglietti, KT Chueh, H AF Feldman, Mitchell J. Hoffer, Edward P. Barnett, G. Octo Kim, Richard J. Famiglietti, Kathleen T. Chueh, Henry TI Presence of key findings in the medical record prior to a documented high-risk diagnosis SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID CLOSED MALPRACTICE CLAIMS; PHYSICAL-EXAMINATION; COMPUTER REMINDERS; AMBULATORY-CARE; SYSTEM; CANCER; CONSULTATION; INSURERS; ACCURACY; HISTORY AB Background Failure or delay in diagnosis is a common preventable source of error. The authors sought to determine the frequency with which high-information clinical findings (HIFs) suggestive of a high-risk diagnosis (HAD) appear in the medical record before HAD documentation. Methods A knowledge base from a diagnostic decision support system was used to identify HIFs for selected HADs: lumbar disc disease, myocardial infarction, appendicitis, and colon, breast, lung, ovarian and bladder carcinomas. Two physicians reviewed at least 20 patient records retrieved from a research patient data registry for each of these eight HRDs and for age- and gender-compatible controls. Records were searched for HIFs in visit notes that were created before the HAD was established in the electronic record and in general medical visit notes for controls. Results 25% of records reviewed (61/243) contained HIFs in notes before the HAD was established. The mean duration between HIFs first occurring in the record and time of diagnosis ranged from 19 days for breast cancer to 2 years for bladder cancer. In three of the eight HRDs, HIFs were much less likely in control patients without the HAD. Conclusions In many records of patients with an HAD, HIFs were present before the HRD was established. Reasons for delay include non-compliance with recommended follow-up, unusual presentation of a disease, and system errors (eg, lack of laboratory follow-up). The presence of HIFs in clinical records suggests a potential role for the integration of diagnostic decision support into the clinical workflow to provide reminder alerts to improve the diagnostic focus. C1 [Feldman, Mitchell J.; Hoffer, Edward P.; Barnett, G. Octo; Kim, Richard J.; Famiglietti, Kathleen T.; Chueh, Henry] Massachusetts Gen Hosp, Comp Sci Lab, Boston, MA 02420 USA. [Feldman, Mitchell J.; Hoffer, Edward P.; Barnett, G. Octo; Chueh, Henry] Harvard Univ, Sch Med, Boston, MA USA. RP Feldman, MJ (reprint author), Massachusetts Gen Hosp, Comp Sci Lab, MGH 50 Staniford St,7th Floor, Boston, MA 02420 USA. EM mfeldman@partners.org FU Partners-Siemens Research Council; Harvard Catalyst; Harvard Clinical and Translational Science Center (NIH) [UL1 RR 025758]; Harvard University FX Funding for this study was provided by a grant from the Partners-Siemens Research Council. The Partners-Siemens Research Council did not participate in the design of the study, in the collection, analysis or interpretation of the data, in the writing of the report or in the decision to submit the article for publication. The researchers were independent from the Partners-Siemens Research Council. This work was conducted with support from Harvard Catalyst. The Harvard Clinical and Translational Science Center (NIH Award #UL1 RR 025758 and financial contributions from Harvard University and its affiliated academic health care centers). The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic health care centers, the National Center for Research Resources, or the National Institutes of Health. NR 32 TC 2 Z9 2 U1 5 U2 14 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD JUL PY 2012 VL 19 IS 4 BP 591 EP 596 DI 10.1136/amiajnl-2011-000375 PG 6 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics SC Computer Science; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics GA 968ZG UT WOS:000306024100018 PM 22431555 ER PT J AU Mandl, KD Mandel, JC Murphy, SN Bernstam, EV Ramoni, RL Kreda, DA McCoy, JM Adida, B Kohane, IS AF Mandl, Kenneth D. Mandel, Joshua C. Murphy, Shawn N. Bernstam, Elmer Victor Ramoni, Rachel L. Kreda, David A. McCoy, J. Michael Adida, Ben Kohane, Isaac S. TI The SMART Platform: early experience enabling substitutable applications for electronic health records SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID INFORMATION ECONOMY AB Objective The Substitutable Medical Applications, Reusable Technologies (SMART) Platforms project seeks to develop a health information technology platform with substitutable applications (apps) constructed around core services. The authors believe this is a promising approach to driving down healthcare costs, supporting standards evolution, accommodating differences in care workflow, fostering competition in the market, and accelerating innovation. Materials and methods The Office of the National Coordinator for Health Information Technology, through the Strategic Health IT Advanced Research Projects (SHARP) Program, funds the project. The SMART team has focused on enabling the property of substitutability through an app programming interface leveraging web standards, presenting predictable data payloads, and abstracting away many details of enterprise health information technology systems. Containers health information technology systems, such as electronic health records (EHR), personally controlled health records, and health information exchanges that use the SMART app programming interface or a portion of it marshal data sources and present data simply, reliably, and consistently to apps. Results The SMART team has completed the first phase of the project (a) defining an app programming interface, (b) developing containers, and (c) producing a set of charter apps that showcase the system capabilities. A focal point of this phase was the SMART Apps Challenge, publicized by the White House, using http://www.challenge.gov website, and generating 15 app submissions with diverse functionality. Conclusion Key strategic decisions must be made about the most effective market for further disseminating SMART: existing market-leading EHR vendors, new entrants into the EHR market, or other stakeholders such as health information exchanges. C1 [Mandl, Kenneth D.; Mandel, Joshua C.; Ramoni, Rachel L.; Kohane, Isaac S.] Harvard MIT Hlth Sci & Technol, Childrens Hosp Informat Program, Boston, MA USA. [Mandl, Kenneth D.; Ramoni, Rachel L.; Kohane, Isaac S.] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA USA. [Mandel, Joshua C.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Murphy, Shawn N.] Partners HlthCare Syst, Informat Syst, Charlestown, MA USA. [Murphy, Shawn N.] Massachusetts Gen Hosp, Comp Sci Lab, Boston, MA 02114 USA. [Bernstam, Elmer Victor] Univ Texas Hlth Sci Ctr, Dept Internal Med, Sch Biomed Informat, Houston, TX USA. [Kreda, David A.] Harvard Univ, Sch Med, Ctr Biomed Informat, SMART Platforms Project, Boston, MA USA. [McCoy, J. Michael] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Adida, Ben] Mozilla, Mountain View, CA USA. RP Mandl, KD (reprint author), Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA. EM kenneth_mandl@harvard.edu RI Kohane, Isaac Kohane/K-3716-2012 OI Kohane, Isaac Kohane/0000-0003-2192-5160 FU Office of the National Coordinator of Health Information Technology [90TR000101] FX This work was funded by the Strategic Health IT Advanced Research Projects Award 90TR000101 from the Office of the National Coordinator of Health Information Technology. NR 26 TC 48 Z9 48 U1 0 U2 30 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD JUL PY 2012 VL 19 IS 4 BP 597 EP 603 DI 10.1136/amiajnl-2011-000622 PG 7 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics SC Computer Science; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics GA 968ZG UT WOS:000306024100019 PM 22427539 ER PT J AU Love, JS Wright, A Simon, SR Jenter, CA Soran, CS Volk, LA Bates, DW Poon, EG AF Love, Jennifer S. Wright, Adam Simon, Steven R. Jenter, Chelsea A. Soran, Christine S. Volk, Lynn A. Bates, David W. Poon, Eric G. TI Are physicians' perceptions of healthcare quality and practice satisfaction affected by errors associated with electronic health record use? SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID PROVIDER ORDER ENTRY; UNINTENDED CONSEQUENCES; INFORMATION-TECHNOLOGY; AMBULATORY-CARE; MEDICATION ERRORS; STATEWIDE-SURVEY; SYSTEMS; ADOPTION; IMPACT AB Background Electronic health record (EHR) adoption is a national priority in the USA, and well-designed EHRs have the potential to improve quality and safety. However, physicians are reluctant to implement EHRs due to financial constraints, usability concerns, and apprehension about unintended consequences, including the introduction of medical errors related to EHR use. The goal of this study was to characterize and describe physicians' attitudes towards three consequences of EHR implementation: (1) the potential for EHRs to introduce new errors; (2) improvements in healthcare quality; and (3) changes in overall physician satisfaction. Methods Using data from a 2007 statewide survey of Massachusetts physicians, we conducted multivariate regression analysis to examine relationships between practice characteristics, perceptions of EHR-related errors, perceptions of healthcare quality, and overall physician satisfaction. Results 30% of physicians agreed that EHRs create new opportunities for error, but only 2% believed their EHR has created more errors than it prevented. With respect to perceptions of quality, there was no significant association between perceptions of EHR-associated errors and perceptions of EHR-associated changes in healthcare quality. Finally, physicians who believed that EHRs created new opportunities for error were less likely be satisfied with their practice situation (adjusted OR 0.49, p=0.001). Conclusions Almost one third of physicians perceived that EHRs create new opportunities for error. This perception was associated with lower levels of physician satisfaction. C1 [Love, Jennifer S.; Soran, Christine S.; Volk, Lynn A.] Partners HealthCare, Clin & Qual Anal Informat Syst, Boston, MA USA. [Wright, Adam; Simon, Steven R.; Jenter, Chelsea A.; Bates, David W.; Poon, Eric G.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Simon, Steven R.] VA Boston Healthcare Syst, Boston, MA USA. RP Love, JS (reprint author), Univ Penn, Perelman Sch Med, 3450 Hamilton Walk,Suite 100, Philadelphia, PA 19107 USA. EM jslove@post.harvard.edu FU Agency for Healthcare Research and Quality [1UC1HS015397-01]; Massachusetts eHealth Collaborative FX This study was funded in part by the Agency for Healthcare Research and Quality cooperative agreement #1UC1HS015397-01 and the Massachusetts eHealth Collaborative. NR 23 TC 10 Z9 10 U1 8 U2 17 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD JUL PY 2012 VL 19 IS 4 BP 610 EP 614 DI 10.1136/amiajnl-2011-000544 PG 5 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics SC Computer Science; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics GA 968ZG UT WOS:000306024100021 PM 22199017 ER PT J AU Abramson, EL Bates, DW Jenter, C Volk, LA Barron, Y Quaresimo, J Seger, AC Burdick, E Simon, S Kaushal, R AF Abramson, Erika L. Bates, David W. Jenter, Chelsea Volk, Lynn A. Barron, Yolanda Quaresimo, Jill Seger, Andrew C. Burdick, Elisabeth Simon, Steven Kaushal, Rainu TI Ambulatory prescribing errors among community-based providers in two states SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID ADVERSE DRUG EVENTS; TIME-SERIES EVALUATION; MEDICATION ERRORS; ORDER ENTRY; IMPACT; CARE AB Objective Little is known about the frequency and types of prescribing errors in the ambulatory setting among community-based, primary care providers. Therefore, the rates and types of prescribing errors were assessed among community-based, primary care providers in two states. Material and Methods A non-randomized cross-sectional study was conducted of 48 providers in New York and 30 providers in Massachusetts, all of whom used paper prescriptions, from September 2005 to November 2006. Using standardized methodology, prescriptions and medical records were reviewed to identify errors. Results 9385 prescriptions were analyzed from 5955 patients. The overall prescribing error rate, excluding illegibility errors, was 36.7 per 100 prescriptions (95% CI 30.7 to 44.0) and did not vary significantly between providers from each state (p=0.39). One or more non-illegibility errors were found in 28% of prescriptions. Rates of illegibility errors were very high (175.0 per 100 prescriptions, 95% CI 169.1 to 181.3). Inappropriate abbreviation and direction errors also occurred frequently (13.4 and 4.2 errors per 100 prescriptions, respectively). Reviewers determined that the vast majority of errors could have been eliminated through the use of e-prescribing with clinical decision support. Discussion Prescribing errors appear to occur at very high rates among community-based primary care providers, especially when compared with studies of academic-affiliated providers that have found nearly threefold lower error rates. Illegibility errors are particularly problematical. Conclusions Further characterizing prescribing errors of community-based providers may inform strategies to improve ambulatory medication safety, especially e-prescribing. C1 [Abramson, Erika L.; Kaushal, Rainu] Cornell Univ, Weill Med Coll, Dept Pediat, New York, NY 10065 USA. [Abramson, Erika L.; Barron, Yolanda; Kaushal, Rainu] Cornell Univ, Weill Med Coll, Dept Publ Hlth, New York, NY 10065 USA. [Abramson, Erika L.; Kaushal, Rainu] New York Presbyterian Hosp, New York, NY USA. [Bates, David W.; Jenter, Chelsea; Seger, Andrew C.; Burdick, Elisabeth; Simon, Steven] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. [Bates, David W.; Simon, Steven] Harvard Univ, Sch Med, Boston, MA USA. [Bates, David W.; Volk, Lynn A.] Partners Healthcare Syst, Informat Syst, Boston, MA USA. [Quaresimo, Jill] Tacon IPA, Fishkill, New York, NY USA. [Simon, Steven] VA Boston Healthcare Syst, Boston, MA USA. [Kaushal, Rainu] Cornell Univ, Weill Med Coll, Dept Med, New York, NY 10065 USA. RP Abramson, EL (reprint author), Cornell Univ, Weill Med Coll, Dept Pediat, 525 E 68th St,Room M-610, New York, NY 10065 USA. EM err9009@med.cornell.edu FU Agency for Healthcare Research and Quality [1UC1HS015397]; Massachusetts eHealth Collaborative; Hudson Valley study by the Taconic Independent Practice Association FX This study was funded by grant number 1UC1HS015397 from the Agency for Healthcare Research and Quality. The Massachusetts study was also co-funded by the Massachusetts eHealth Collaborative and the Hudson Valley study by the Taconic Independent Practice Association. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Agency for Healthcare Research and Quality or that of the Massachusetts e-Health Collaborative or the Taconic Independent Practice Association. NR 24 TC 9 Z9 9 U1 1 U2 8 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD JUL PY 2012 VL 19 IS 4 BP 644 EP 648 DI 10.1136/amiajnl-2011-000345 PG 5 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics SC Computer Science; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics GA 968ZG UT WOS:000306024100026 PM 22140209 ER PT J AU Rodriguez-Ortiz, ME Lopez, I Munoz-Castaneda, JR Martinez-Moreno, JM Ramirez, AP Pineda, C Canalejo, A Jaeger, P Aguilera-Tejero, E Rodriguez, M Felsenfeld, A Almaden, Y AF Rodriguez-Ortiz, Maria E. Lopez, Ignacio Munoz-Castaneda, Juan R. Martinez-Moreno, Julio M. Peralta Ramirez, Alan Pineda, Carmen Canalejo, Antonio Jaeger, Philippe Aguilera-Tejero, Escolastico Rodriguez, Mariano Felsenfeld, Arnold Almaden, Yolanda TI Calcium Deficiency Reduces Circulating Levels of FGF23 SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CHRONIC KIDNEY-DISEASE; VITAMIN-D METABOLISM; GROWTH-FACTOR 23; SECONDARY HYPERPARATHYROIDISM; TRANSPLANT RECIPIENTS; PARATHYROID-HORMONE; RECEPTOR 1; EXPRESSION; PHOSPHATE; KLOTHO AB Fibroblast growth factor (FGF) 23 inhibits calcitriol production, which could exacerbate calcium deficiency or hypocalcemia unless calcium itself modulates FGF23 in this setting. In Wistar rats with normal renal function fed a diet low in both calcium and vitamin D, the resulting hypocalcemia was associated with low FGF23 despite high parathyroid hormone (PTH) and high calcitriol levels. FGF23 correlated positively with calcium and negatively with PTH. Addition of high dietary phosphorus to this diet increased FGF23 except in rats with hypocalcemia despite high PTH levels. In parathyroidectomized rats, an increase in dietary calcium for 10 days increased serum calcium, with an associated increase in FGF23, decrease in calcitriol, and no change in phosphorus. Also in parathyroidectomized rats, FGF23 increased significantly 6 hours after administration of calcium gluconate. Taken together, these results suggest that hypocalcemia reduces the circulating concentrations of FGF23. This decrease in FGF23 could be a response to avoid a subsequent reduction in calcitriol, which could exacerbate hypocalcemia. C1 [Rodriguez, Mariano] Hosp Univ Reina Sofia, Unidad Invest, Serv Nefrol, IMIBIC, Cordoba 14004, Spain. [Rodriguez-Ortiz, Maria E.; Munoz-Castaneda, Juan R.; Martinez-Moreno, Julio M.; Almaden, Yolanda] Hosp Univ Reina Sofia, IMIBIC, Res Unit, Cordoba 14004, Spain. [Lopez, Ignacio; Pineda, Carmen; Aguilera-Tejero, Escolastico] Univ Cordoba, Dept Med & Cirugia Anim, Cordoba, Spain. [Canalejo, Antonio] Univ Huelva, Dept Biol Ambiental & Salud Publ, Huelva, Spain. [Jaeger, Philippe] UCL, Ctr Nephrol, London, England. [Felsenfeld, Arnold] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Felsenfeld, Arnold] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Rodriguez, M (reprint author), Hosp Univ Reina Sofia, Unidad Invest, Serv Nefrol, IMIBIC, Avda Menendez Pidal S-N, Cordoba 14004, Spain. EM juanm.rodriguez.sspa@juntadeandalucia.es RI Canalejo, Antonio/L-8407-2014; OI Canalejo, Antonio/0000-0003-2098-8960; Pineda Martos, Carmen Maria/0000-0002-3664-8699 FU Instituto Carlos III [FIS 07/0287, FIS 07/0315, 010/1311]; Consejeria de Salud [JA 0127/2008]; UE Grant from Framework Programme 7 Syskid (FP7) [241544]; Consejeria de Innovacion, Ciencia y Empresa of Junta de Andalucia [CTS-5205, CTS-170]; Fundacion Progreso y Salud, Consejeria de Salud (Junta de Andalucia); Amgen; Fresenius; Abbott; Shire FX This study was supported by Instituto Carlos III (FIS 07/0287, FIS 07/0315, 010/1311), Consejeria de Salud (JA 0127/2008), a UE Grant from Framework Programme 7 Syskid (FP7-241544), and Consejeria de Innovacion, Ciencia y Empresa (CTS-5205 and CTS-170) of Junta de Andalucia. Y.A. is a senior researcher supported by the Fundacion Progreso y Salud, Consejeria de Salud (Junta de Andalucia).; M.R. has received research grants from Amgen and Fresenius and lecture fees from the following companies: Amgen, Abbott, Shire, and Fresenius. NR 25 TC 78 Z9 80 U1 1 U2 31 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JUL PY 2012 VL 23 IS 7 BP 1190 EP 1197 DI 10.1681/ASN.2011101006 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 968ZZ UT WOS:000306026800012 PM 22581996 ER PT J AU Herlitz, LC Bomback, AS Markowitz, GS Stokes, MB Smith, RN Colvin, RB Appel, GB D'Agati, VD AF Herlitz, Leal C. Bomback, Andrew S. Markowitz, Glen S. Stokes, M. Barry Smith, R. Neal Colvin, Robert B. Appel, Gerald B. D'Agati, Vivette D. TI Pathology after Eculizumab in Dense Deposit Disease and C3 GN SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; COMPLEMENT INHIBITOR ECULIZUMAB; HEMOLYTIC-UREMIC SYNDROME; ALTERNATIVE PATHWAY; GLOMERULONEPHRITIS; INFECTIONS AB Eculizumab might benefit C3 glomerulopathies mediated by dysregulation of the alternative complement pathway. Here, we report renal biopsy findings before and after eculizumab therapy in three patients with dense deposit disease and two with C:3 GN. All pretreatment biopsies had glomerular and tubular basement membrane deposits that stained exclusively for C3 without significant Ig. After 1 year of therapy, there was reduction in active glomerular proliferation and neutrophil infiltration in three of five patients, consistent with effective C5 blockade, which prevents production of chemotactin C5a. One individual with mild mesangial disease had no significant change in activity or chronicity. One patient exhibited persistent activity and worsening chronicity despite therapy. Immunofluorescence showed no significant reduction in C3 or C5b-9, and electron microscopy revealed persistent deposits in all cases, suggesting a long t(1/2) of C5b-9 in extracellular matrix. Normal renal biopsies stained positive for C5b-9 in glomeruli, tubular basement membranes, and vessel walls, albeit at lower intensity than in C3 glomerulopathy. This indication of physiologic levels of C5b-9 activation in normal kidney potentially explains the localization of deposits in patients with dysregulation of the alternative complement pathway. All post-treatment biopsies showed de novo monoclonal staining for IgG-kappa in the same distribution as C3 and C5b-9, mimicking monoclonal Ig deposition disease (MIDD). Staining of the gamma heavy chain was restricted to the IgG2 and IgG4 subclasses, suggesting the binding of monoclonal eculizumab to C5 in renal tissues. The long-term effects of this apparent drug-tissue Interaction are unknown. C1 [Herlitz, Leal C.; Markowitz, Glen S.; Stokes, M. Barry; D'Agati, Vivette D.] Columbia Univ, Med Ctr, Dept Pathol & Cell Biol, Div Renal Pathol, New York, NY 10032 USA. [Herlitz, Leal C.; Bomback, Andrew S.; Markowitz, Glen S.; Stokes, M. Barry; Appel, Gerald B.; D'Agati, Vivette D.] New York Presbyterian Hosp, New York, NY 10032 USA. [Bomback, Andrew S.; Appel, Gerald B.] Columbia Univ, Med Ctr, Dept Med, Div Nephrol, New York, NY 10032 USA. [Smith, R. Neal; Colvin, Robert B.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Herlitz, LC (reprint author), Columbia Univ, Med Ctr, Dept Pathol & Cell Biol, Div Renal Pathol, 630 W 168th St,VC14-238, New York, NY 10032 USA. EM LB684@columbia.edu OI Herlitz, Leal/0000-0003-2665-8559; Stokes, Michael/0000-0003-0958-7672 FU Alexion Pharmaceuticals, manufacturer of Soliris (eculizumab) FX The clinical study was supported by Alexion Pharmaceuticals, manufacturer of Soliris (eculizumab); however, the pathology specimens were processed independently, without any financial support from Alexion. NR 17 TC 67 Z9 72 U1 1 U2 2 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JUL PY 2012 VL 23 IS 7 BP 1229 EP 1237 DI 10.1681/ASN.2011121186 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 968ZZ UT WOS:000306026800016 PM 22677550 ER PT J AU Campigotto, F Neuberg, D Zwicker, JI AF Campigotto, F. Neuberg, D. Zwicker, J. I. TI Biased estimation of thrombosis rates in cancer studies using the method of Kaplan and Meier SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Letter ID RECURRENT VENOUS THROMBOEMBOLISM; MOLECULAR-WEIGHT HEPARIN; VIENNA CANCER; PREVENTION; WARFARIN; RISK AB To cite this article: Campigotto F, Neuberg D, Zwicker JI. Biased estimation of thrombosis rates in cancer studies using the method of Kaplan and Meier. J Thromb Haemost 2012; 10: 144951. C1 [Zwicker, J. I.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Hemostasis & Thrombosis, Boston, MA 02215 USA. [Campigotto, F.; Neuberg, D.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Zwicker, JI (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Hemostasis & Thrombosis, 330 Brookline Ave, Boston, MA 02215 USA. EM jzwicker@bidmc.harvard.edu OI Zwicker, Jeffrey/0000-0001-5810-6893 FU NHLBI NIH HHS [K23 HL084052]; PHS HHS [NHLBI K23 HL084052] NR 13 TC 10 Z9 10 U1 0 U2 0 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 JUL PY 2012 VL 10 IS 7 BP 1449 EP 1451 DI 10.1111/j.1538-7836.2012.04766.x PG 3 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 968KI UT WOS:000305979300032 PM 22554355 ER PT J AU Gorlin, A Warren, L AF Gorlin, Andrew Warren, Lisa TI Ultrasound-Guided Interscalene Blocks SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Editorial Material ID REGIONAL ANESTHESIA; SHOULDER SURGERY; GUIDANCE C1 [Gorlin, Andrew] Brigham & Womens Hosp, Dept Anesthesiol, Boston, MA 02115 USA. [Warren, Lisa] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Gorlin, A (reprint author), Brigham & Womens Hosp, Pain Management Ctr, 850 Boylston St, Chestnut Hill, MA 02467 USA. EM andy.gorlin@gmail.com NR 12 TC 1 Z9 1 U1 0 U2 1 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD JUL PY 2012 VL 31 IS 7 BP 979 EP 983 PG 5 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 969HU UT WOS:000306047100001 PM 22733845 ER PT J AU Kulkarni, NM Sahani, DV Desai, GS Kalva, SP AF Kulkarni, Naveen M. Sahani, Dushyant V. Desai, Gaurav S. Kalva, Sanjeeva P. TI Indirect Computed Tomography Venography of the Lower Extremities Using Single-Source Dual-Energy Computed Tomography: Advantage of Low-Kiloelectron Volt Monochromatic Images SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID CT PULMONARY ANGIOGRAPHY; MULTIDETECTOR-ROW CT; DEEP VENOUS THROMBOSIS; ABDOMINAL AORTIC-ANEURYSM; THROMBOEMBOLIC DISEASE; CLINICAL-APPLICATIONS; ENDOVASCULAR REPAIR; VEIN THROMBOSIS; HELICAL CT; EMBOLISM AB Purpose: To study the performance of dual-energy indirect computed tomography (CT) venography from single-source dual-energy CT in the assessment of lower extremity deep venous thrombosis (DVT). Materials and Methods: En a retrospective study, 110 patients suspected to have pulmonary embolism (PE) underwent dual-energy CT venography on a single-source dual-energy CT scanner as a part of CT pulmonary angiography protocol at 3 minutes after injection of contrast material. Two radiologists evaluated 50-kiloelectron volt (keV) and 70-keV monochromatic images reconstructed from a dual-energy CT scan for image quality, image noise, venous contrast, and confidence level in interpretation for DVT using a scale of 1-5. In addition, a combined 50-keV and 70-keV data set was assessed for confidence level in image interpretation. Attenuation, contrast-to-noise ratio (CNR), and objective noise were measured in bilateral common femoral and popliteal veins. Data were analyzed using Student t test and Wilcoxon rank sum test. Radiation dose was measured for dual-energy CT venography protocol. Results: A diagnosis of DVT was made in 8 of 110 patients (7.27%). The subjective image quality was comparable between 50-keV and 70-keV images (4.3 vs 4.5; P > .05). The subjective venous contrast pacification (4.7 vs 3.5; P = .0036) and confidence (4.8 vs 3.9; P = .0028) in image interpretation were superior at 50 keV. Confidence level for interpretation on combined 50-keV and 70-keV series (score 4.7) was similar to that for 50-keV series (score 4.8). Compared with 70-keV data, 50-keV data yielded 90% increase in intravascular CT attenuation (207.4 Hounsfield units [HU] +/- 39.0 vs 106.8 HU +/- 7.6; P < .0001) and higher CNR (10.7 +/- 4.07 vs 7.2 +/- 4.1; P = .0001) of the deep veins. However, objective noise at 50 keV was higher (14.8 HU vs 6.5 HU; P = .0031). Because of inadequate contrast pacification, 6% of CT venography studies were deemed suboptimal for rendering a diagnostic interpretation on 70-keV images, but these images were considered acceptable at 50 keV. The mean effective radiation dose for the dual-energy CT venography examination was 4.2 mSv. Conclusions: Optimal image quality with substantially higher venous attenuation is provided by 50-keV monochromatic images from dual-energy CT venography acquisition compared with 70-keV images. The 50-keV monochromatic images increase the confidence in the image interpretation of DVT and decrease the number of indeterminate studies. C1 [Kalva, Sanjeeva P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Vasc Imaging & Intervent, Boston, MA 02114 USA. [Kulkarni, Naveen M.; Sahani, Dushyant V.; Desai, Gaurav S.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Imaging,Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Kalva, SP (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Vasc Imaging & Intervent, 55 Fruit St, Boston, MA 02114 USA. EM skalva@partners.org FU GE Healthcare FX D.V.S. has received grant support from GE Healthcare. None of the other authors have identified a conflict of interest. NR 40 TC 15 Z9 15 U1 0 U2 0 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 JUL PY 2012 VL 23 IS 7 BP 879 EP 886 DI 10.1016/j.jvir.2012.04.012 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 967TI UT WOS:000305930300004 PM 22633619 ER PT J AU Tsai, S Conrad, MF Patel, VI Kwolek, CJ LaMuraglia, GM Brewster, DC Cambria, RP AF Tsai, Shirling Conrad, Mark F. Patel, Virendra I. Kwolek, Christopher J. LaMuraglia, Glenn M. Brewster, David C. Cambria, Richard P. TI Long-term durability of open repair of juxtarenal abdominal aortic aneurysms SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID OPEN SURGICAL REPAIR; RENAL-FAILURE; FOLLOW-UP; SURGERY; EXPERIENCE; OUTCOMES; DISEASE; TRIAL; ERA AB Objective: As branched/fenestrated endografts expand endovascular options for juxtarenal abdominal aortic aneurysms (JAAAs), long-term durability will be compared to that of open JAAA repair, which has not been documented in large contemporary series. The goal of this study was to assess the late clinical and anatomic outcomes after open JAAA repair. Methods: From July 2001 to December 2007, 199 patients underwent open elective JAAA repair, as defined by a need for suprarenal clamping. End points included perioperative and late survival, long-term follow-up of renal function, and freedom from graft-related complications. Factors predictive of survival were determined by multivariate analysis. Results: The mean patient age was 74 years, 71% were men, and 20% had baseline renal insufficiency (Cr >1.5). Thirty-seven renal artery bypasses, for anatomic necessity or ostial stenosis, were performed in 36 patients. Overall 30-day mortality was 2.5%. Four patients (2.0%) required early dialysis; one patient recovered by discharge. Two additional patients progressed to dialysis over long-term follow-up. There was one graft infection involving one limb of a bifurcated graft. Surveillance imaging was obtained in 101 patients (72% of survivors) at a mean follow-up of 41 +/- 28 months. Renal artery occlusion occurred in four patients (3% of imaged renal arteries; one native/three grafts). Two patients (2.0%) had aneurysmal degeneration of the aorta either proximal or distal to the repaired segment, but there were no anastomotic pseudoaneurysms. Remote aneurysms were found in 29 patients (29% of imaged patients), 14 of whom had descending thoracic aneurysm or TAAA. Four patients underwent subsequent thoracic endovascular aneurysm repair (TEVAR). Actuarial survival was 74 +/- 3.3% at 5 years. Negative predictors of survival included increasing age at the time of operation (relative risk [RR], 1.05; P = .01), steroid use (RR, 2.20; P = .001), and elevated preoperative creatinine (RR, 1.73; P = .02). Conclusions: Open JAAA repair yields excellent long-term anatomic durability and preserves renal function. Perioperative renal insufficiency occurs in 8.5% of patients, but few of them progress to dialysis. Graft-related complications are rare (2% at 40 months); however, axial imaging revealed descending thoracic aneurysms in 14% of imaged patients, making continued surveillance for remote aneurysms prudent. These data provide a benchmark against which fenestrated/branched endovascular aneurysm repair (EVAR) outcomes can be compared. (J Vasc Surg 2012;) C1 [Tsai, Shirling; Conrad, Mark F.; Patel, Virendra I.; Kwolek, Christopher J.; LaMuraglia, Glenn M.; Brewster, David C.; Cambria, Richard P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. RP Conrad, MF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc & Endovasc Surg, 15 Parkman St,Wang ACC 440, Boston, MA 02114 USA. EM mfc16@partners.org NR 33 TC 23 Z9 23 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUL PY 2012 VL 56 IS 1 BP 2 EP 7 DI 10.1016/j.jvs.2011.12.085 PG 6 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 968GJ UT WOS:000305965000003 PM 22534029 ER PT J AU Reilly, LM Rapp, JH Grenon, SM Hiramoto, JS Sobel, J Chuter, TAM AF Reilly, Linda M. Rapp, Joseph H. Grenon, S. Marlene Hiramoto, Jade S. Sobel, Julia Chuter, Timothy A. M. TI Efficacy and durability of endovascular thoracoabdominal aortic aneurysm repair using the caudally directed cuff technique SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID STENT-GRAFTS; HYBRID PROCEDURES; SURGICAL REPAIR; UNITED-STATES; EXPERIENCE; MORTALITY; ENDOGRAFTS; MORBIDITY; OUTCOMES; IV AB Purpose: This study determined early and intermediate results of multibranched endovascular thoracoabdominal (TAAA) and pararenal aortic aneurysm (PRAA) repair using a uniform operative technique. Methods: Eighty-one patients (mean age, 73 +/- 8 years, 19 [23.5%] women) underwent endovascular TAAA repair in a prospective trial using self-expanding covered stents connecting axially oriented, caudally directed cuffs to target aortic branches. Mean aneurysm diameter was 67 +/- 10 mm. Thirty-nine TAAA (48.1%) were Crawford type II, III, or V; 42 (51.9%) were type IV or pararenal. Thirty-three procedures (40.7%) were staged. The insertion approach was femoral for aortic components and brachial for branch components. Follow-up assessments were performed at 1, 6, and 12 months, and yearly thereafter. Results: All devices (n = 81) and branches (n = 306) were successfully inserted and deployed, with no conversions to open repair. Overall mortality was 6.2% (n = 5), including three perioperative (3.7%) and two late treatment-related deaths (2.5%). Permanent paraplegia occurred in three patients (3.7%), and transient paraplegia/paraparesis occurred in 16 (19.8%). Four patients (4.9%) required dialysis postoperatively, three permanently and one transiently. Women accounted for 67% of the paraplegia, 75% of the perioperative dialysis, and 60% of the perioperative or treatment-related deaths. During a mean follow-up of 21.2 months, no aneurysms ruptured, but four (4.9%) enlarged: two were successfully treated, one was unsuccessfully treated, and one was not treated. No late onset spinal cord ischemia symptoms developed. Of the five patients starting dialysis during follow-up, two resulted from renal branch occlusion. Sixteen branches occluded (nine renal, two celiac) or developed stenoses (four renal, one superior mesenteric artery), requiring stenting. Primary patency was 94.8%, and primary-assisted patency was 95.1%. Thirty-two patients (39.5%) underwent 42 reinterventions. Of 25 early reinterventions (<= 45 days), 10 were to treat access or insertion complications, and 5 were for endoleak. Of 17 late reinterventions, eight were for endoleak and five were for branch stenosis/occlusion. New endoleaks developed in two patients during follow-up. Overall, 73 of 81 patients (90.1%) were treated without procedure-related death, dialysis, paralysis, aneurysm rupture, or conversion to open repair. Conclusions: Total endovascular TAAA/PRAA repair using caudally directed cuffs is safe, effective, and durable in the intermediate term. The most common form of late failure, renal artery occlusion, rarely had a clinically significant consequence (dialysis). The trend toward worse outcome in women needs further study. (J Vasc Surg 2012;) C1 [Reilly, Linda M.; Hiramoto, Jade S.; Sobel, Julia; Chuter, Timothy A. M.] Univ Calif San Francisco, Div Vasc & Endovasc Surg, San Francisco, CA 94143 USA. [Rapp, Joseph H.; Grenon, S. Marlene] San Francisco VA Med Ctr, Vasc Surg Sect, San Francisco, CA USA. RP Reilly, LM (reprint author), Univ Calif San Francisco, Div Vasc Surg, Rm A-581,400 Parnassus Ave, San Francisco, CA 94143 USA. EM linda.reilly@ucsfmedctr.org FU Cook Medical, Inc FX Dr Chuter receives royalties from licensed patents, travel expenses and research funding from Cook Medical, Inc, the manufacturer of the multibranched thoracoabdominal stent graft. NR 44 TC 40 Z9 40 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUL PY 2012 VL 56 IS 1 BP 53 EP 64 DI 10.1016/j.jvs.2012.01.006 PG 13 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 968GJ UT WOS:000305965000010 PM 22560233 ER PT J AU Cambria, RP AF Cambria, Richard P. TI Centers for Medicare and Medicaid Services conducts a medical evidence development and coverage advisory committee meeting on carotid atherosclerosis: Executive summary SO JOURNAL OF VASCULAR SURGERY LA English DT Article C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Soc Vasc Surg,Div Vasc & Endovasc Surg, Boston, MA 02114 USA. RP Cambria, RP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Soc Vasc Surg,Div Vasc & Endovasc Surg, 15 Parkman St,WAC 458, Boston, MA 02114 USA. EM rcambria@partners.org NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUL PY 2012 VL 56 IS 1 BP 199 EP 200 DI 10.1016/j.jvs.2012.04.050 PG 2 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 968GJ UT WOS:000305965000027 PM 22749267 ER PT J AU Cambria, RP AF Cambria, Richard P. TI Centers for Medicare and Medicaid Services conducts a medical evidence development and coverage advisory committee meeting on carotid atherosclerosis SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; HEALTH-CARE PROFESSIONALS; HIGH-RISK PATIENTS; ARTERY STENOSIS; NATURAL-HISTORY; PATIENT CHARACTERISTICS; ASYMPTOMATIC PATIENTS; SURGICAL-MANAGEMENT; STROKE-ASSOCIATION; TASK-FORCE AB Publication of the eagerly anticipated Carotid Revascularization Endarterectomy Versus Stenting Trial in May 2010 was anticipated to engender much activity in the realm of interventions for carotid stenosis. Specifically, a variety of professional societies, including the Society for Vascular Surgery (SVS), published updated practice guidelines in the calendar year 2011, timed to include data from large-scale well-conducted clinical trials comparing carotid endarterectomy with carotid artery stenting (CAS). In anticipation of a renewed application to the Centers for Medicare and Medicaid Services (CMS) to reconsider the national coverage determination for CAS, the SVS Board of Directors voted in June 2011 against any change in the national coverage determination for CAS. CMS convened a Medicare evidence development and coverage advisory committee (MEDCAC) meeting to consider fundamental aspects of the treatment of carotid atherosclerosis on January 25, 2012, to allow an unbiased and current deliberation of the state-of-the-art technology and science referable to the management of carotid atherosclerosis. The MEDCAC differs substantially from a reconsideration of coverage determination and, in this case, was built around seven research questions. The MEDCAC consists of a panel of experts who, after reviewing the literature and submitted comments by interested stakeholders, and after hearing testimony from invited speakers and at-large presentations, held a panel vote on the research questions. Given that management of carotid atherosclerosis is a core element of vascular surgical practice, the SVS had a major presence at the MEDCAC in the form of a comprehensive written document individually considering the research questions and a variety of presentations addressing various aspects in carotid disease management. The purpose of this report is to detail the SVS's position on the MEDCAC research questions referable to the management of carotid atherosclerosis and to otherwise detail the proceedings of the MEDCAC. (J Vasc Surg 2012;56:e1-16.) C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, President Soc Vasc Surg,Div Vasc & Endovasc Surg, Boston, MA 02114 USA. RP Cambria, RP (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, President Soc Vasc Surg,Div Vasc & Endovasc Surg, 15 Parkman St,WAC 458, Boston, MA 02114 USA. EM rcambria@partners.org NR 79 TC 3 Z9 3 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUL PY 2012 VL 56 IS 1 BP E1 EP E16 DI 10.1016/j.jvs.2012.04.051 PG 16 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 968GJ UT WOS:000305965000001 PM 22749277 ER PT J AU Reardon, DA AF Reardon, David A. TI Treatment of elderly patients with glioblastoma SO LANCET ONCOLOGY LA English DT Editorial Material ID TEMOZOLOMIDE; RADIOTHERAPY; CONCOMITANT; RADIATION; ADJUVANT; TRIAL C1 Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. RP Reardon, DA (reprint author), Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. EM david_reardon@dfci.harvard.edu NR 10 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 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD JUL PY 2012 VL 13 IS 7 BP 656 EP 657 DI 10.1016/S1470-2045(12)70186-9 PG 3 WC Oncology SC Oncology GA 968CX UT WOS:000305955700034 PM 22578792 ER PT J AU Pettengell, R Coiffier, B Narayanan, G de Mendoza, FH Digumarti, R Gomez, H Zinzani, PL Schiller, G Rizzieri, D Boland, G Cernohous, P Wang, LX Kuepfer, C Gorbatchevsky, I Singer, JW AF Pettengell, Ruth Coiffier, Bertrand Narayanan, Geetha Hurtado de Mendoza, Fernando Digumarti, Raghunadharao Gomez, Henry Zinzani, Pier Luigi Schiller, Gary Rizzieri, David Boland, Giles Cernohous, Paul Wang, Lixia Kuepfer, Christine Gorbatchevsky, Igor Singer, Jack W. TI Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin lymphoma: a phase 3, multicentre, open-label, randomised trial SO LANCET ONCOLOGY LA English DT Article ID CARDIOTOXICITY; DOXORUBICIN; REGIMENS; BBR-2778 AB Background Pixantrone dimaleate (pixantrone)-a novel aza-anthracenedione-was synthesised to reduce anthracycline-related cardiotoxicity without compromising antitumour efficacy. We aimed to assess the efficacy and safety of pixantrone versus an investigator's choice of a single-agent therapy in heavily pretreated patients with relapsed or refractory aggressive non-Hodgkin lymphoma. Methods In this phase 3, multicentre, open-label, randomised trial at 66 hospitals in Europe, India, Russia, South America, the UK, and the USA, patients with histologically confirmed aggressive non-Hodgkin lymphoma who had relapsed after two or more previous chemotherapy regimens were randomly assigned (1:1) by an interactive voice response system to treatment with pixantrone dimaleate (85 mg/m(2) intravenously on days 1, 8, and 15 of a 28-day cycle, for up to six cycles) or to a comparator (vinorelbine, oxaliplatin, ifosfamide, etoposide, mitoxantrone, or gemcitabine) given at prespecified standard doses and schedules. Patients were stratified by region, International Prognostic Index score, and previous stem-cell transplantation. Patients and investigators were not masked to treatment assignment; however, an independent assessment panel was masked. The primary endpoint was the proportion of patients with a complete or unconfirmed complete response in the intention-to-treat (ITT) population at the end of treatment. Primary analyses of efficacy were based on the independent assessment panel's data review. The study is registered at ClinicalTrials.gov, number NCT00088530. Findings The ITT population comprised 70 patients randomly assigned to the pixantrone group and 70 to the comparator. Five patients (two in the pixantrone group and three in the comparator group) dropped out before receiving their study drug. 14 patients (20.0% [95% CI 11.4-31.3]) who received pixantrone achieved a complete or unconfirmed complete response at end of treatment compared with four patients (5.7% [1.6-14.0]) in the comparator group (p=0.021). The most common grade 3 or 4 adverse events in patients given pixantrone were uncomplicated, non-cumulative neutropenia (28 [41.2%] of 68 patients vs 13 [19.4%] of 67 patients in the comparator group), leucopenia (16 [23.5%] vs five [7.5%]), and thrombocytopenia (eight [11.8%] vs seven [10.4%]). Interpretation Pixantrone, given as a single-agent salvage therapy in heavily pretreated patients with relapsed or refractory aggressive non-Hodgkin lymphoma, is efficacious and tolerable. It could be a treatment option for patients whose aggressive non-Hodgkin lymphoma has failed to respond to at least two previous chemotherapy regimens. C1 [Pettengell, Ruth] Univ London, St Georges Hosp, Dept Haematol, London SW17 ORE, England. [Coiffier, Bertrand] Ctr Hosp Lyon Sud, F-69310 Pierre Benite, France. [Coiffier, Bertrand] Univ Lyon 1, F-69365 Lyon, France. [Narayanan, Geetha] Reg Canc Ctr, Thiruvananthapuram, Kerala, India. [Hurtado de Mendoza, Fernando] Edgardo Rebagliati Martins Hosp, Lima, Peru. [Digumarti, Raghunadharao] Nizams Inst Med Sci, Hyderabad, Andhra Pradesh, India. [Gomez, Henry] Oncosalud, Oncoctr, Lima, Peru. [Zinzani, Pier Luigi] Univ Bologna, Inst Haematol L&A Seragnoli, I-40126 Bologna, Italy. [Schiller, Gary] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Rizzieri, David] Duke Univ, Durham, NC USA. [Boland, Giles] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Boland, Giles] Harvard Univ, Sch Med, Boston, MA USA. [Cernohous, Paul; Wang, Lixia; Kuepfer, Christine; Gorbatchevsky, Igor; Singer, Jack W.] Cell Therapeut Inc, Seattle, WA USA. [Singer, Jack W.] Univ Washington, Seattle, WA 98195 USA. RP Pettengell, R (reprint author), Univ London, St Georges Hosp, Dept Haematol, London SW17 ORE, England. EM rpetteng@sgul.ac.uk RI Zinzani, Pier Luigi/J-9182-2016; OI Zinzani, Pier Luigi/0000-0002-2112-2651; Singer, Jack/0000-0003-4001-4549; Gomez, Henry/0000-0003-2660-1843; Narayanan, Geetha/0000-0002-0345-6623 FU Cell Therapeutics, Inc. FX Funding Cell Therapeutics, Inc. NR 21 TC 34 Z9 34 U1 2 U2 9 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 JUL PY 2012 VL 13 IS 7 BP 696 EP 706 DI 10.1016/S1470-2045(12)70212-7 PG 11 WC Oncology SC Oncology GA 968CX UT WOS:000305955700048 PM 22652183 ER PT J AU Margolin, K Hodi, FS AF Margolin, Kim Hodi, F. Stephen TI Ipilimumab in patients with melanoma and brain metastases Reply SO LANCET ONCOLOGY LA English DT Letter C1 [Margolin, Kim] Univ Washington, Seattle, WA 98109 USA. [Hodi, F. Stephen] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Margolin, K (reprint author), Univ Washington, Seattle, WA 98109 USA. EM kmargoli@seattlecca.org NR 2 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD JUL PY 2012 VL 13 IS 7 BP E277 EP E278 PG 2 WC Oncology SC Oncology GA 968CX UT WOS:000305955700002 ER PT J AU Basseres, DS D'Alo, F Yeap, BY Lowenberg, EC Gonzalez, DA Yasuda, H Dayaram, T Kocher, ON Godleski, JJ Richards, WG Meyerson, M Kobayashi, S Tenen, DG Halmos, B Costa, DB AF Basseres, Daniela S. D'Alo, Francesco Yeap, Beow Y. Loewenberg, Ester C. Gonzalez, David A. Yasuda, Hiroyuki Dayaram, Tajhal Kocher, Olivier N. Godleski, John J. Richards, William G. Meyerson, Matthew Kobayashi, Susumu Tenen, Daniel G. Halmos, Balazs Costa, Daniel B. TI Frequent downregulation of the transcription factor Foxa2 in lung cancer through epigenetic silencing SO LUNG CANCER LA English DT Article DE Lung cancer; Non-small-cell lung cancer; Foxa2; Methylation; Transcription factors; Epigenetic; Downregulation; Adenocarcinoma; Mutation; Prognosis ID HEPATOCYTE NUCLEAR FACTOR-3; C/EBP-ALPHA; GENE AMPLIFICATION; PROTEIN EXPRESSION; TUMOR-SUPPRESSOR; ADENOCARCINOMA; SOX2; MORPHOGENESIS; TRANSITION; ONCOGENE AB Purpose: We sought to determine the mechanisms of downregulation of the airway transcription factor Foxa2 in lung cancer and the expression status of Foxa2 in non-small-cell lung cancer (NSCLC). Methods: A series of 25 lung cancer cell lines were evaluated for Foxa2 protein expression, FOXA2 mRNA levels, FOXA2 mutations, FOXA2 copy number changes and for evidence of FOXA2 promoter hypermethylation. In addition, 32 NSCLCs were sequenced for FOXA2 mutations and 173 primary NSCLC tumors evaluated for Foxa2 expression using an immunohistochemical assay. Results: Out of the 25 cell lines, 13 (52%) had undetectable FOXA2 mRNA. The expression of FOXA2 mRNA and Foxa2 protein were congruent in 19/22 cells (p = 0.001). FOXA2 mutations were not identified in primary NSCLCs and were infrequent in cell lines. Focal or broad chromosomal deletions involving FOXA2 were not present. The promoter region of FOXA2 had evidence of hypermethylation, with an inverse correlation between FOXA2 mRNA expression and presence of CpG dinucleotide methylation (p < 0.0001). In primary NSCLC tumor specimens, there was a high frequency of either absence (42/173, 24.2%) or no/low expression (96/173,55.4%) of Foxa2. In 130 patients with stage I NSCLC there was a trend towards decreased survival in tumors with no/low expression of Foxa2 (HR of 1.6, 95%CI 0.9-3.1; p = 0.122). Conclusions: Loss of expression of Foxa2 is frequent in lung cancer cell lines and NSCLCs. The main mechanism of downregulation of Foxa2 is epigenetic silencing through promoter hypermethylation. Further elucidation of the involvement of Foxa2 and other airway transcription factors in the pathogenesis of lung cancer may identify novel therapeutic targets. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Costa, Daniel B.] Harvard Univ, Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Sch Med, Boston, MA 02215 USA. [Yeap, Beow Y.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02215 USA. [Godleski, John J.; Richards, William G.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02215 USA. [Meyerson, Matthew] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. [Halmos, Balazs] Columbia Univ Coll Phys & Surg, New York Presbyterian Hosp, New York, NY 10032 USA. [Basseres, Daniela S.] Univ Sao Paulo, Sao Paulo, Brazil. RP Costa, DB (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Sch Med, 330 Brookline Av, Boston, MA 02215 USA. EM dbcosta@bidmc.harvard.edu RI Meyerson, Matthew/E-7123-2012; Basseres, Daniela/C-6623-2013; OI Basseres, Daniela/0000-0001-7745-3567; Costa, Daniel/0000-0002-0689-395X; Tenen, Daniel/0000-0002-6423-3888 FU Pfizer; Roche; AstraZeneca; American Society of Clinical Oncology Conquer Cancer Foundation; American Association for Cancer Research; Clinical Investigator Training Program at Beth Israel Deaconess Medical Center; American Cancer Society [RSG 11-186]; FAMRI Young Clinical Scientist award; National Institutes of Health [CA090578] FX DBC has received consulting fees from Pfizer, Roche and AstraZeneca within the last 3 years. These conflicts did not interfere with the conduct of this study.; This work was funded in part through fellowships from the American Society of Clinical Oncology Conquer Cancer Foundation, American Association for Cancer Research, and Clinical Investigator Training Program at Beth Israel Deaconess Medical Center (DBC), an American Cancer Society grant RSG 11-186 (DBC), a FAMRI Young Clinical Scientist award (DSB), and a National Institutes of Health grant CA090578 (DBC, DGT, BH, SK, BY, JJG, MM, WGR). The funding agencies provided financial research support and were not involved in the writing of this manuscript. NR 28 TC 13 Z9 15 U1 0 U2 9 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 EI 1872-8332 J9 LUNG CANCER JI Lung Cancer PD JUL PY 2012 VL 77 IS 1 BP 31 EP 37 DI 10.1016/j.lungcan.2012.01.011 PG 7 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 966MO UT WOS:000305842200006 PM 22341411 ER PT J AU van de Donk, NWCJ Dhimolea, E AF van de Donk, Niels W. C. J. Dhimolea, Eugen TI Brentuximab vedotin SO MABS LA English DT Article DE brentuximab vedotin; CD30; Hodgkin lymphoma; anaplastic large cell lymphoma; immunotherapy; monoclonal antibody ID LARGE-CELL LYMPHOMA; ANTIBODY-DRUG CONJUGATE; PHASE-II TRIAL; FACTOR-KAPPA-B; HODGKIN LYMPHOMA; T-CELL; SOLUBLE CD30; LYMPHOPROLIFERATIVE DISORDERS; HEMATOLOGIC MALIGNANCIES; NEGATIVE SELECTION AB Brentuximab vedotin (SGN-35; Adcetris (R)) is an anti-CD30 antibody conjugated via a protease-cleavable linker to the potent anti-microtubule agent monomethyl auristatin E (MMAE). Following binding to CD30, brentuximab vedotin is rapidly internalized and transported to lysosomes where MMAE is released and binds to tubulin, leading to cell cycle arrest and apoptosis. Several trials have shown durable antitumor activity with a manageable safety profile in patients with relapsed/refractory Hodgkin lymphoma, systemic anaplastic large cell lymphoma or primary cutaneous CD30-positive lymphoproliferative disorders. Peripheral sensory neuropathy is a significant adverse event associated with brentuximab vedotin administration. Neuropathy symptoms are cumulative and dose-related. Multiple ongoing trials are currently evaluating brentuximab vedotin alone or in combination with other agents in relapsed/refractory patients, as well as patients with newly diagnosed disease. C1 [van de Donk, Niels W. C. J.; Dhimolea, Eugen] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [van de Donk, Niels W. C. J.] Univ Med Ctr Utrecht, Dept Hematol, Utrecht, Netherlands. RP van de Donk, NWCJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM n.w.c.j.vandedonk@umcutrecht.nl FU Celgene FX N.W.vdD received research funding and contracted research from Celgene. E.D. did not receive funding. NR 58 TC 21 Z9 21 U1 2 U2 11 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1942-0862 EI 1942-0870 J9 MABS-AUSTIN JI mAbs PD JUL-AUG PY 2012 VL 4 IS 4 BP 458 EP 465 DI 10.4161/mabs.20230 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 968FD UT WOS:000305961800003 PM 22684302 ER PT J AU Szeto, FL Reardon, CA Yoon, D Wang, YL Wong, KE Chen, YZ Kong, J Liu, SQ Thadhani, R Getz, GS Li, YC AF Szeto, Frances L. Reardon, Catherine A. Yoon, Dosuk Wang, Youli Wong, Kari E. Chen, Yunzi Kong, Juan Liu, Shu Q. Thadhani, Ravi Getz, Godfrey S. Li, Yan Chun TI Vitamin D Receptor Signaling Inhibits Atherosclerosis in Mice SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID ANGIOTENSIN-CONVERTING ENZYME; NUTRITION EXAMINATION SURVEY; SMOOTH-MUSCLE-CELLS; 3RD NATIONAL-HEALTH; E-DEFICIENT MICE; VASCULAR ADHESION MOLECULES; COLONY-STIMULATING FACTOR; KAPPA-B ACTIVATION; APOLIPOPROTEIN-E; 1,25-DIHYDROXYVITAMIN D-3 AB Although vitamin D has been implicated in cardiovascular protection, few studies have addressed the role of vitamin D receptor (VDR) in atherosclerosis. Here we investigate the effect of inactivation of the VDR signaling on atherogenesis and the antiatherosclerotic mechanism of vitamin D. Low density lipoprotein receptor (LDLR)(-/-)/VDR-/- mice exhibited site-specific accelerated atherogenesis, accompanied by increases in adhesion molecules and proinflammatory cytokines in the aorta and cholesterol influx in macrophages. Macrophages showed marked renin up-regulation in the absence of VDR, and inhibition of renin by aliskiren reduced atherosclerosis in LDLR-/-/VDR-/- mice, suggesting that the renin-angiotensin system (RAS) promotes atherosclerosis in the absence of VDR. LDLR-/- mice receiving LDLR-/-/VDR-/- BMT developed larger lesions than LDLR-/- BMT controls. Moreover, LDLR-/- mice receiving Rag-1(-/-)/VDR-/- BMT, which were unable to generate functional T and B lymphocytes, still had more severe atherosclerosis than Rag-1(-/-) BMT controls, suggesting a critical role of macrophage VDR signaling in atherosclerotic suppression. Aliskiren treatment eliminated the difference in lesions between Rag-1(-/-)/VDR-/- BMT and Rag-1(-/-) BMT recipients, indicating that local RAS activation in macrophages contributes to the enhanced atherogenesis seen in Rag-1(-/-)/VDR-/- BMT mice. Taken together, these observations provide evidence that macrophage VDR signaling, in part by suppressing the local RAS, inhibits atherosclerosis in mice. (Molecular Endocrinology 26: 1091-1101, 2012) C1 [Yoon, Dosuk; Wang, Youli; Chen, Yunzi; Kong, Juan; Li, Yan Chun] Univ Chicago, Dept Med, Div Biol Sci, Chicago, IL 60637 USA. [Szeto, Frances L.; Reardon, Catherine A.; Wong, Kari E.; Getz, Godfrey S.; Li, Yan Chun] Univ Chicago, Comm Mol Metab & Nutr, Chicago, IL 60637 USA. [Reardon, Catherine A.; Getz, Godfrey S.] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. [Kong, Juan; Li, Yan Chun] China Med Univ, Lab Metab Dis Res & Drug Dev, Shenyang 110001, Peoples R China. [Liu, Shu Q.] Northwestern Univ, Dept Biomed Engn, Evanston, IL 60208 USA. [Thadhani, Ravi] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. RP Li, YC (reprint author), Univ Chicago, Dept Med, Div Biol Sci, 900 E 57th St,KCBD,Mailbox 9-9110, Chicago, IL 60637 USA. EM cyan@medicine.bsd.uchicago.edu RI Liu, Shu/B-7626-2009 FU National Institutes of Health [HL085793]; Center for D-Receptor Activation Research; Molecular and Cellular Biology Training Grant [T32 GM007183-35]; Abbott Laboratories FX This work was supported in part by National Institutes of Health grant HL085793, a research grant from the Center for D-Receptor Activation Research, and Molecular and Cellular Biology Training Grant (T32 GM007183-35).; R.T. received a research grant support from Abbott Laboratories. All other authors declare no conflict of interest. NR 62 TC 33 Z9 37 U1 2 U2 15 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD JUL PY 2012 VL 26 IS 7 BP 1091 EP 1101 DI 10.1210/me.2011-1329 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 968FK UT WOS:000305962500003 PM 22638071 ER PT J AU Cash, JN Angerman, EB Keutmann, HT Thompson, TB AF Cash, Jennifer N. Angerman, Elizabeth B. Keutmann, Henry T. Thompson, Thomas B. TI Characterization of Follistatin-Type Domains and Their Contribution to Myostatin and Activin A Antagonism SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID STRUCTURE ANALYSIS REVEALS; BETA SUPERFAMILY MEMBER; SKELETAL-MUSCLE MASS; TGF-BETA; CRYSTAL-STRUCTURE; RECEPTOR-BINDING; STRUCTURAL BASIS; MICE DEFICIENT; COMPLEX; PROTEIN AB Follistatin (FST)-type proteins are important antagonists of some members of the large TGF-beta family of cytokines. These include myostatin, an important negative regulator of muscle growth, and the closely related activin A, which is involved in many physiological functions, including maintenance of a normal reproductive axis. FST-type proteins, including FST and FST-like 3 (FSTL3), differentially inhibit various TGF-beta family ligands by binding each ligand with two FST-type molecules. In this study, we sought to examine features that are important for ligand antagonism by FST-type proteins. Previous work has shown that a modified construct consisting of the FST N-terminal domain (ND) followed by two repeating follistatin domains (FSD), herein called FST ND-FSD1-FSD1, exhibits strong specificity for myostatin over activin A. Using cell-based assays, we show that FST ND-FSD1-FSD1 is unique in its specificity for myostatin as compared with similar constructs containing domains from FSTL3 and that the ND is critical to its activity. Furthermore, we demonstrate that FSD3 of FST provides affinity to ligand inhibition and confers resistance to perturbations in the ND and FSD2, likely through the interaction of FSD3 of one FST molecule with the ND of the other FST molecule. Additionally, our data suggest that this contact provides cooperativity to ligand antagonism. Cross-linking studies show that this interaction also potentiates formation of 1: 2 ligand-FST complexes, whereas lack of FSD3 allows formation of 1: 1 complexes. Altogether, these studies support that domain differences generate FST-type molecules that are each uniquely suited ligand antagonists. (Molecular Endocrinology 26: 1167-1178, 2012) C1 [Cash, Jennifer N.; Angerman, Elizabeth B.; Thompson, Thomas B.] Univ Cincinnati, Dept Mol Genet Biochem & Microbiol, Cincinnati, OH 45267 USA. [Keutmann, Henry T.] Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. RP Thompson, TB (reprint author), Univ Cincinnati, Dept Mol Genet Biochem & Microbiol, Med Sci Bldg,231 Albert Sabin Way, Cincinnati, OH 45267 USA. EM thompstb@ucmail.uc.edu FU National Institutes of Health [GM R01 (GM084186)]; Muscular Dystrophy Association [93887]; American Heart Association FX This work was supported by research grants from the National Institutes of Health GM R01 (GM084186) and Muscular Dystrophy Association (93887) to T. B. T. J.N.C. was supported by an American Heart Association predoctoral fellowship. NR 48 TC 6 Z9 6 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD JUL PY 2012 VL 26 IS 7 BP 1167 EP 1178 DI 10.1210/me.2012-1061 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 968FK UT WOS:000305962500009 PM 22593183 ER PT J AU Zhu, S Pan, W Song, XY Liu, Y Shao, XR Tang, YJ Liang, D He, DY Wang, HL Liu, WJ Shi, YF Harley, JB Shen, N Qian, YC AF Zhu, Shu Pan, Wen Song, Xinyang Liu, Yan Shao, Xinrui Tang, Yuanjia Liang, Dong He, Dongyi Wang, Honglin Liu, Wenjun Shi, Yufang Harley, John B. Shen, Nan Qian, Youcun TI The microRNA miR-23b suppresses IL-17-associated autoimmune inflammation by targeting TAB2, TAB3 and IKK-alpha SO NATURE MEDICINE LA English DT Article ID CD4(+) T-CELLS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; KAPPA-B-ZETA; RHEUMATOID-ARTHRITIS; MULTIPLE-SCLEROSIS; IMMUNE-RESPONSES; MESSENGER-RNA; EXPRESSION; RECEPTOR; DISEASE AB Inflammatory cytokines such as interleukin-17 (IL-17) promote inflammatory autoimmune diseases. Although several microRNAs (miRNAs) have been shown to regulate autoimmune pathogenesis by affecting lymphocyte development and function, the role of miRNAs in resident cells present in inflammatory lesions remains unclear. Here we show that miR-23b is downregulated in inflammatory lesions of humans with lupus or rheumatoid arthritis, as well as in the mouse models of lupus, rheumatoid arthritis or multiple sclerosis. IL-17 downregulates miR-23b expression in human fibroblast-like synoviocytes, mouse primary kidney cells and astrocytes and is essential for the downregulation of miR-23b during autoimmune pathogenesis. In turn, miR-23b suppresses IL-17-, tumor necrosis factor alpha (TNF-alpha)- or IL-1 beta-induced NF-kappa B activation and inflammatory cytokine expression by targeting TGF-beta-activated kinase 1/MAP3K7 binding protein 2 (TAB2), TAB3 and inhibitor of nuclear factor kappa-B kinase subunit alpha (IKK-alpha) and, consequently, represses autoimmune inflammation. Thus, IL-17 contributes to autoimmune pathogenesis by suppressing miR-23b expression in radio-resident cells and promoting proinflammatory cytokine expression. C1 [Zhu, Shu; Pan, Wen; Song, Xinyang; Liu, Yan; Shao, Xinrui; Shi, Yufang; Shen, Nan; Qian, Youcun] Chinese Acad Sci, Shanghai Inst Biol Sci, Key Lab Stem Cell Biol, Inst Hlth Sci, Shanghai 200031, Peoples R China. [Tang, Yuanjia; Shen, Nan] Shanghai Jiao Tong Univ, Sch Med, Shanghai Renji Hosp, Shanghai Inst Rheumatol, Shanghai 200030, Peoples R China. [Liang, Dong; Harley, John B.; Shen, Nan] Cincinnati Childrens Hosp Med Ctr, Div Rheumatol, Cincinnati, OH USA. [Liang, Dong; Harley, John B.; Shen, Nan] Cincinnati Childrens Hosp Med Ctr, CAGE, Cincinnati, OH USA. [Wang, Honglin] Shanghai Jiao Tong Univ, Sch Med, Inst Med Sci, Shanghai Inst Immunol, Shanghai 200030, Peoples R China. [He, Dongyi] Guanghua Rheumatol Hosp, Shanghai, Peoples R China. [Liu, Wenjun] Univ Manitoba, Dept Biochem & Med Genet, Winnipeg, MB, Canada. [Harley, John B.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA. RP Qian, YC (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Key Lab Stem Cell Biol, Inst Hlth Sci, Shanghai 200031, Peoples R China. EM nanshensibs@gmail.com; ycqian@sibs.ac.cn RI Pan, Wen/I-9965-2016 FU National Natural Science Foundation of China and 973 program [30930084, 2010CB529705, 91029708, 30871298]; Chinese Academy of Sciences [KSCX2-YW-R-146]; Science and Technology Commission of Shanghai Municipality [10JC1416600]; National Natural Science Foundation of China [30971632, 81025016]; Chinese Ministry of Health [201202008]; Program of the Shanghai Commission of Science and Technology [10JC1409300] FX We thank R. Flavell (Yale University) for providing Pi 17a-deficient mice. This work is supported by grants from National Natural Science Foundation of China and 973 program (30930084, 2010CB529705, 91029708 and 30871298), Chinese Academy of Sciences (KSCX2-YW-R-146) and the Science and Technology Commission of Shanghai Municipality (10JC1416600) to Y.Q.; as well as National Natural Science Foundation of China (30971632 and 81025016), Chinese Ministry of Health (201202008) and the Program of the Shanghai Commission of Science and Technology (10JC1409300) to N. S. NR 58 TC 147 Z9 162 U1 1 U2 37 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 JUL PY 2012 VL 18 IS 7 BP 1077 EP + DI 10.1038/nm.2815 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 970IM UT WOS:000306121600037 PM 22660635 ER PT J AU Kentsis, A Reed, C Rice, KL Sanda, T Rodig, SJ Tholouli, E Christie, A Valk, PJM Delwel, R Ngo, V Kutok, JL Dahlberg, SE Moreau, LA Byers, RJ Christensen, JG Woude, GV Licht, JD Kung, AL Staudt, LM Look, AT AF Kentsis, Alex Reed, Casie Rice, Kim L. Sanda, Takaomi Rodig, Scott J. Tholouli, Eleni Christie, Amanda Valk, Peter J. M. Delwel, Ruud Vu Ngo Kutok, Jeffery L. Dahlberg, Suzanne E. Moreau, Lisa A. Byers, Richard J. Christensen, James G. Woude, George Vande Licht, Jonathan D. Kung, Andrew L. Staudt, Louis M. Look, A. Thomas TI Autocrine activation of the MET receptor tyrosine kinase in acute myeloid leukemia SO NATURE MEDICINE LA English DT Article ID CANCER-CELLS; INHIBITOR; SCREEN; AML; CLASSIFICATION; PATHWAYS; TARGETS; FLT3 AB Although the treatment of acute myeloid leukemia (AML) has improved substantially in the past three decades, more than half of all patients develop disease that is refractory to intensive chemotherapy(1,2). Functional genomics approaches offer a means to discover specific molecules mediating the aberrant growth and survival of cancer cells(3-8). Thus, using a loss-of-function RNA interference genomic screen, we identified the aberrant expression of hepatocyte growth factor (HGF) as a crucial element in AML pathogenesis. We found HGF expression leading to autocrine activation of its receptor tyrosine kinase, MET, in nearly half of the AML cell lines and clinical samples we studied. Genetic depletion of HGF or MET potently inhibited the growth and survival of HGF-expressing AML cells. However, leukemic cells treated with the specific MET kinase inhibitor crizotinib developed resistance resulting from compensatory upregulation of HGF expression, leading to the restoration of MET signaling. In cases of AML where MET is coactivated with other tyrosine kinases, such as fibroblast growth factor receptor 1 (FGFR1)(9), concomitant inhibition of FGFR1 and MET blocked this compensatory HGF upregulation, resulting in sustained logarithmic cell killing both in vitro and in xenograft models in vivo. Our results show a widespread dependence of AML cells on autocrine activation of MET, as well as the key role of compensatory upregulation of HGF expression in maintaining leukemogenic signaling by this receptor. We anticipate that these findings will lead to the design of additional strategies to block adaptive cellular responses that drive compensatory ligand expression as an essential component of the targeted inhibition of oncogenic receptors in human cancers. C1 [Kentsis, Alex; Reed, Casie; Sanda, Takaomi; Christie, Amanda; Moreau, Lisa A.; Kung, Andrew L.; Look, A. Thomas] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Kentsis, Alex; Reed, Casie; Sanda, Takaomi; Christie, Amanda; Moreau, Lisa A.; Kung, Andrew L.; Look, A. Thomas] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Hematol & Oncol, Boston, MA USA. [Rice, Kim L.; Licht, Jonathan D.] Northwestern Univ, Feinberg Sch Med, Div Hematol & Oncol, Chicago, IL 60611 USA. [Rodig, Scott J.; Kutok, Jeffery L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Tholouli, Eleni; Byers, Richard J.] Cent Manchester Univ Hosp Natl Hlth Serv Fdn Trus, Manchester Royal Infirm, Dept Haematol, Manchester, Lancs, England. [Tholouli, Eleni; Byers, Richard J.] Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England. [Christie, Amanda; Kung, Andrew L.] Dana Farber Canc Inst, Lurie Family Imaging Ctr, Boston, MA 02115 USA. [Valk, Peter J. M.; Delwel, Ruud] Erasmus MC, Dept Hematol, Rotterdam, Netherlands. [Vu Ngo] City Hope Natl Med Ctr, Div Hematopoiet Stem Cell & Leukemia Res, Duarte, CA 91010 USA. [Dahlberg, Suzanne E.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Byers, Richard J.] Univ Manchester, Fac Med & Human Sci, Sch Canc & Enabling Sci, Manchester, Lancs, England. [Christensen, James G.] Pfizer Global Res & Dev, Dept Res Pharmacol, La Jolla, CA USA. [Woude, George Vande] Van Andel Res Inst, Dept Mol Oncol, Grand Rapids, MI USA. [Staudt, Louis M.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Look, AT (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM thomas_look@dfci.harvard.edu OI Kentsis, Alex/0000-0002-8063-9191; Byers, Richard/0000-0003-0796-0365; Kung, Andrew/0000-0002-9091-488X FU US National Institutes of Health grant [K08CA160660]; William Lawrence and Blanche Hughes Foundation; Samuel Waxman Cancer Research Foundation; V Foundation; Intramural Research Program of the National Cancer Institute, Center for Cancer Research FX We thank A. Gutierrez, M. Mansour and E. Gjini for critical discussions and J. Gilbert for editorial advice. This research was supported by the US National Institutes of Health grant K08CA160660 (A.K.), the William Lawrence and Blanche Hughes Foundation (T.S.), the Samuel Waxman Cancer Research Foundation (J.D.L.), the V Foundation (A.T.L.) and the Intramural Research Program of the National Cancer Institute, Center for Cancer Research (L.M.S.). NR 25 TC 64 Z9 65 U1 2 U2 17 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 JUL PY 2012 VL 18 IS 7 BP 1118 EP + DI 10.1038/nm.2819 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 970IM UT WOS:000306121600042 PM 22683780 ER PT J AU Wahlby, C Kamentsky, L Liu, ZHH Riklin-Raviv, T Conery, AL O'Rourke, EJ Sokolnicki, KL Visvikis, O Ljosa, V Irazoqui, JE Golland, P Ruvkun, G Ausubel, FM Carpenter, AE AF Wahlby, Carolina Kamentsky, Lee Liu, Zihan H. Riklin-Raviv, Tammy Conery, Annie L. O'Rourke, Eyleen J. Sokolnicki, Katherine L. Visvikis, Orane Ljosa, Vebjorn Irazoqui, Javier E. Golland, Polina Ruvkun, Gary Ausubel, Frederick M. Carpenter, Anne E. TI An image analysis toolbox for high-throughput C. elegans assays SO NATURE METHODS LA English DT Article ID CAENORHABDITIS-ELEGANS; AUTOMATED-ANALYSIS; RESOLUTION; INSIGHTS; NEMATODE; SCREENS; MODEL AB We present a toolbox for high-throughput screening of image-based Caenorhabditis elegans phenotypes. The image analysis algorithms measure morphological phenotypes in individual worms and are effective for a variety of assays and imaging systems. This WormToolbox is available through the open-source CellProfiler project and enables objective scoring of whole-worm high-throughput image-based assays of C. elegans for the study of diverse biological pathways that are relevant to human disease. C1 [Wahlby, Carolina; Kamentsky, Lee; Liu, Zihan H.; Sokolnicki, Katherine L.; Ljosa, Vebjorn; Carpenter, Anne E.] Broad Inst Massachusetts Inst Technol & Harvard, Cambridge, MA USA. [Wahlby, Carolina] Uppsala Univ, Ctr Image Anal, Sci Life Lab, Uppsala, Sweden. [Riklin-Raviv, Tammy; Golland, Polina] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Conery, Annie L.; O'Rourke, Eyleen J.; Ruvkun, Gary; Ausubel, Frederick M.] Massachusetts Gen Hosp, Dept Mol Biol, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Visvikis, Orane; Irazoqui, Javier E.] Massachusetts Gen Hosp, Dept Pediat, Dev Immunol Program, Boston, MA 02114 USA. RP Wahlby, C (reprint author), Broad Inst Massachusetts Inst Technol & Harvard, Cambridge, MA USA. EM carolina@broadinstitute.org RI Irazoqui, Javier/A-8028-2013; Riklin Raviv, Tammy/A-3462-2013; VISVIKIS, ORANE/N-1818-2016; OI VISVIKIS, ORANE/0000-0001-7719-5836; Irazoqui, Javier/0000-0001-6553-1329 FU US National Institutes of Health [R01 GM095672, R01 GM089652, R01 AI072508, P01 AI083214, R01 AI085581, K99DK087928, U54 EB005149]; Broad Institute SPARC (Scientific Planning and Allocation of Resources Committee) program FX Funding for this work was provided by the US National Institutes of Health to C. W. (R01 GM095672), A. E. C. (R01 GM089652), F. M. A. (R01 AI072508, P01 AI083214 and R01 AI085581), E.J.O. (K99DK087928) and P. G. (U54 EB005149). The Broad Institute SPARC (Scientific Planning and Allocation of Resources Committee) program also funded this work. The authors thank S. C. Pak and G. A. Silverman (University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA) for the images of assay 1, J. Larkins-Ford and P. Lim for technical assistance and members of the Imaging Platform and the international C. elegans community for scientific guidance and helpful comments. NR 23 TC 43 Z9 43 U1 3 U2 28 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 EI 1548-7105 J9 NAT METHODS JI Nat. Methods PD JUL PY 2012 VL 9 IS 7 BP 714 EP U273 DI 10.1038/NMETH.1984 PG 6 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 967XT UT WOS:000305942200026 PM 22522656 ER PT J AU Slotine, JJ Liu, YY AF Slotine, Jean-Jacques Liu, Yang-Yu TI COMPLEX NETWORKS The missing link SO NATURE PHYSICS LA English DT News Item C1 [Slotine, Jean-Jacques] MIT, Nonlinear Syst Lab, Cambridge, MA 02139 USA. [Slotine, Jean-Jacques] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Slotine, Jean-Jacques] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Liu, Yang-Yu] Northeastern Univ, Ctr Complex Network Res, Boston, MA 02115 USA. [Liu, Yang-Yu] Northeastern Univ, Dept Phys, Boston, MA 02115 USA. [Liu, Yang-Yu] Northeastern Univ, Dept Comp Sci, Boston, MA 02115 USA. [Liu, Yang-Yu] Northeastern Univ, Dept Biol, Boston, MA 02115 USA. [Liu, Yang-Yu] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. RP Slotine, JJ (reprint author), MIT, Nonlinear Syst Lab, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM jjs@mit.edu; ya.liu@neu.edu RI Liu, Yang-Yu/G-8885-2011 OI Liu, Yang-Yu/0000-0003-2728-4907 NR 9 TC 5 Z9 5 U1 0 U2 18 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 JUL PY 2012 VL 8 IS 7 BP 512 EP 513 DI 10.1038/nphys2342 PG 3 WC Physics, Multidisciplinary SC Physics GA 968IE UT WOS:000305970400005 ER PT J AU Ramirez, CL Certo, MT Mussolino, C Goodwin, MJ Cradick, TJ McCaffrey, AP Cathomen, T Scharenberg, AM Joung, JK AF Ramirez, Cherie L. Certo, Michael T. Mussolino, Claudio Goodwin, Mathew J. Cradick, Thomas J. McCaffrey, Anton P. Cathomen, Toni Scharenberg, Andrew M. Joung, J. Keith TI Engineered zinc finger nickases induce homology-directed repair with reduced mutagenic effects SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DOUBLE-STRAND BREAKS; HUMAN STEM-CELLS; GENE CONVERSION; DNA CLEAVAGE; NUCLEASES; RECOMBINATION; ENDONUCLEASE; SPECIFICITY; TOXICITY; BINDING AB Engineered zinc finger nucleases (ZFNs) induce DNA double-strand breaks at specific recognition sequences and can promote efficient introduction of desired insertions, deletions or substitutions at or near the cut site via homology-directed repair (HDR) with a double- and/or single-stranded donor DNA template. However, mutagenic events caused by error-prone non-homologous end-joining (NHEJ)-mediated repair are introduced with equal or higher frequency at the nuclease cleavage site. Furthermore, unintended mutations can also result from NHEJ-mediated repair of off-target nuclease cleavage sites. Here, we describe a simple and general method for converting engineered ZFNs into zinc finger nickases (ZFNickases) by inactivating the catalytic activity of one monomer in a ZFN dimer. ZFNickases show robust strand-specific nicking activity in vitro. In addition, we demonstrate that ZFNickases can stimulate HDR at their nicking site in human cells, albeit at a lower frequency than by the ZFNs from which they were derived. Finally, we find that ZFNickases appear to induce greatly reduced levels of mutagenic NHEJ at their target nicking site. ZFNickases thus provide a promising means for inducing HDR-mediated gene modifications while reducing unwanted mutagenesis caused by error-prone NHEJ. C1 [Ramirez, Cherie L.; Goodwin, Mathew J.; Joung, J. Keith] Massachusetts Gen Hosp, Mol Pathol Unit, Ctr Canc Res, Charlestown, MA 02129 USA. [Ramirez, Cherie L.; Goodwin, Mathew J.; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Charlestown, MA 02129 USA. [Ramirez, Cherie L.; Joung, J. Keith] Harvard Univ, Sch Med, Biol & Biomed Sci Program, Boston, MA 02115 USA. [Certo, Michael T.] Univ Washington, Program Mol & Cellular Biol, Seattle, WA 98195 USA. [Certo, Michael T.; Scharenberg, Andrew M.] Seattle Childrens Res Inst, Ctr Immun & Immunotherapies, Seattle, WA 98105 USA. [Mussolino, Claudio; Cathomen, Toni] Hannover Med Sch, Inst Expt Hematol, D-30625 Hannover, Germany. [Cradick, Thomas J.; McCaffrey, Anton P.] Univ Iowa, Dept Internal Med, Sch Med, Iowa City, IA 52245 USA. [Scharenberg, Andrew M.] Univ Washington, Dept Pediat, Seattle, WA 98195 USA. [Joung, J. Keith] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Joung, JK (reprint author), Massachusetts Gen Hosp, Mol Pathol Unit, Ctr Canc Res, Charlestown, MA 02129 USA. EM jjoung@partners.org OI Cradick, Thomas/0000-0002-8489-8318; Cathomen, Toni/0000-0002-7757-4630 FU National Institutes of Health (NIH) [DP1 OD006862]; NIH [DP1 OD006862, R01 GM088040, P50 HG005550, RL1 CA133832, UL1 DE019582, R01 AI068885, T32 GM07270]; Jim and Ann Orr Massachusetts General Hospital; European Commission [PERSIST-222878]; National Science Foundation; Ford Foundation FX The National Institutes of Health (NIH) Director's Pioneer Award DP1 OD006862 (to J.K.J.); NIH R01 GM088040 (to J.K.J.), P50 HG005550 (to J.K.J.), RL1 CA133832 (to A. M. S.), UL1 DE019582 (to A. M. S.), R01 AI068885 (to A. P. M.), and T32 GM07270 (to M. T. C.); the Jim and Ann Orr Massachusetts General Hospital Research Scholar award (to J.K.J.); the European Commission (PERSIST-222878 to T. C.); National Science Foundation Graduate Research Fellowship (to C. L. R.); Ford Foundation Predoctoral Fellowship (to C. L. R.). Funding for open access charge: NIH Director's Pioneer Award (DP1 OD006862 to J.K.J). NR 43 TC 91 Z9 92 U1 2 U2 20 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 JUL PY 2012 VL 40 IS 12 BP 5560 EP 5568 DI 10.1093/nar/gks179 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 966HR UT WOS:000305829000039 PM 22373919 ER PT J AU Chen, YI Cypess, AM Sass, CA Brownell, AL Jokivarsi, KT Kahn, CR Kwong, KK AF Chen, Y. Iris Cypess, Aaron M. Sass, Christina A. Brownell, Anna-Liisa Jokivarsi, Kimmo T. Kahn, C. Ronald Kwong, Kenneth K. TI Anatomical and Functional Assessment of Brown Adipose Tissue by Magnetic Resonance Imaging SO OBESITY LA English DT Article ID NONSHIVERING THERMOGENESIS; IN-VIVO; FAT; SUSCEPTIBILITY; HIBERNOMA; CONTRAST; MICE; RARE; UCP1; IDENTIFICATION AB Brown adipose tissue (BAT) is the primary tissue responsible for nonshivering thermogenesis in mammals. The amount of BAT and its level of activation help regulate the utilization of excessive calories for thermogenesis as opposed to storage in white adipose tissue (WAT) which would lead to weight gain. Over the past several years, BAT activity in vivo has been primarily assessed by positron emission tomography-computed tomography (PET-CT) scan using 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG) to measure glucose utilization associated with BAT mitochondrial respiration. In this study, we demonstrate the feasibility of mapping and estimating BAT volume and metabolic function in vivo in rats at a 9.4T magnetic resonance imaging (MRI) scanner using sequences available from clinical MR scanners. Based on the morphological characteristics of BAT, we measured the volume distribution of BAT with MRI sequences that have strong fat-water contrast. We also investigated BAT volume by utilizing spin-echo MRI sequences. The in vivo MRI-estimated BAT volumes were correlated with direct measurement of BAT mass from dissected samples. Using MRI, we also were able to map hemodynamic responses to changes in BAT metabolism induced pharmacologically by beta 3-adrenergic receptor agonist, CL-316,243 and compare this to BAT activity in response to CL-316,243 assessed by PET 18F-FDG. In conclusion, we demonstrate the feasibility of measuring BAT volume and function in vivo using routine MRI sequences. The MRI measurement of BAT volume is consistent with quantitative measurement of the tissue ex vivo. C1 [Chen, Y. Iris; Brownell, Anna-Liisa; Jokivarsi, Kimmo T.; Kwong, Kenneth K.] Massachusetts Gen Hosp, A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA USA. [Chen, Y. Iris; Cypess, Aaron M.; Brownell, Anna-Liisa; Kahn, C. Ronald; Kwong, Kenneth K.] Harvard Univ, Sch Med, Boston, MA USA. [Cypess, Aaron M.; Sass, Christina A.; Kahn, C. Ronald] Joslin Diabet Ctr, Boston, MA 02215 USA. RP Chen, YI (reprint author), Massachusetts Gen Hosp, A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA USA. EM iris@nmr.mgh.harvard.edu FU NIH NIDDK [5-RC1-DK087317-02, K23 DK081604] FX MR contrast agent was synthesized by Anna Moore's laboratory at the Martino's Center for Biomedical Imaging. This study was supported by a NIH NIDDK grant 5-RC1-DK087317-02 and K23 DK081604. NR 33 TC 45 Z9 46 U1 1 U2 18 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD JUL PY 2012 VL 20 IS 7 BP 1519 EP 1526 DI 10.1038/oby.2012.22 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 966LW UT WOS:000305840200027 PM 22343821 ER PT J AU Strasser, B Arvandi, M Siebert, U AF Strasser, B. Arvandi, M. Siebert, U. TI Resistance training, visceral obesity and inflammatory response: a review of the evidence SO OBESITY REVIEWS LA English DT Review DE Dose-response; inflammation; resistance training; visceral fat ID C-REACTIVE PROTEIN; NECROSIS-FACTOR-ALPHA; AMERICAN-HEART-ASSOCIATION; METABOLIC RISK-FACTORS; SUBCUTANEOUS ADIPOSE-TISSUE; TYPE-2 DIABETES-MELLITUS; CARDIOVASCULAR-DISEASE; PHYSICAL-ACTIVITY; BODY-COMPOSITION; SKELETAL-MUSCLE AB Intra-abdominal obesity is an important risk factor for low-grade inflammation, which is associated with increased risk for diabetes mellitus and cardiovascular disease. For the most part, recommendations to treat or prevent overweight and obesity via physical activity have focused on aerobic endurance training as it is clear that aerobic training is associated with much greater energy expenditure during the exercise session than resistance training. However, due to the metabolic consequences of reduced muscle mass, it is understood that normal ageing and/or decreased physical activity may lead to a higher prevalence of metabolic disorders. Whether resistance training alters visceral fat and the levels of several pro-inflammatory cytokines produced in adipose tissue has not been addressed in earlier reviews. Because evidence suggests that resistance training may promote a negative energy balance and may change body fat distribution, it is possible that an increase in muscle mass after resistance training may be a key mediator leading to a better metabolic control. Considering the benefits of resistance training on visceral fat and inflammatory response, an important question is: how much resistance training is needed to confer such benefits? Therefore, the purpose of this review was to address the importance of resistance training on abdominal obesity, visceral fat and inflammatory response. C1 [Strasser, B.] Univ Hlth Sci Med Informat & Technol, Inst Nutr Sci & Physiol, Hall I T, Austria. [Arvandi, M.; Siebert, U.] Univ Hlth Sci Med Informat & Technol, Dept Publ Hlth & Hlth Technol Assessment, Hall I T, Austria. [Siebert, U.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Siebert, U.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Program,Inst Technol Assessment, Boston, MA USA. [Siebert, U.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Ctr Hlth Decis Sci, Boston, MA 02115 USA. RP Strasser, B (reprint author), UMIT Univ Hlth Sci Med Informat & Technol, Inst Nutr Sci & Physiol, Eduard Wallnoefer Zentrum 1, A-6060 Hall In Tirol, Austria. EM barbara.strasser@umit.at NR 101 TC 20 Z9 22 U1 1 U2 31 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1467-7881 J9 OBES REV JI Obes. Rev. PD JUL PY 2012 VL 13 IS 7 BP 578 EP 591 DI 10.1111/j.1467-789X.2012.00988.x PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 967DG UT WOS:000305885900002 PM 22385646 ER PT J AU Pellegrini, CN AF Pellegrini, Cara N. TI Can AV Node Ablation Help Save AV Conduction? SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Editorial Material ID SLOW PATHWAY ABLATION; REENTRANT TACHYCARDIA; RADIOFREQUENCY ABLATION; ATRIOVENTRICULAR-BLOCK; JUNCTIONAL TACHYCARDIA; KOCHS TRIANGLE; PREDICTS; ECTOPY; RISK C1 [Pellegrini, Cara N.] VA Med Ctr, Cardiol Sect, San Francisco, CA USA. [Pellegrini, Cara N.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. RP Pellegrini, CN (reprint author), San Francisco VA Med Ctr, 4150 Clement St,Cardiol 111C, San Francisco, CA 94121 USA. EM pellegrinic@medicine.ucsf.edu NR 12 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0147-8389 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD JUL PY 2012 VL 35 IS 7 BP 785 EP 786 DI 10.1111/j.1540-8159.2012.03390.x PG 2 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA 967HM UT WOS:000305897500015 PM 22519423 ER PT J AU Volpe, D Harrison, S Damian, F Rachh, P Kahlon, PS Morrissey, L Mack, J Akenroye, A Stack, AM AF Volpe, Diana Harrison, Stephanie Damian, Fran Rachh, Pratik Kahlon, Prerna S. Morrissey, Lisa Mack, Jennifer Akenroye, Ayobami Stack, Anne M. TI Improving Timeliness of Antibiotic Delivery for Patients With Fever and Suspected Neutropenia in a Pediatric Emergency Department SO PEDIATRICS LA English DT Article DE febrile neutropenia; pediatric emergency; quality improvement ID CANCER AB OBJECTIVE: There is a high risk for morbidity and mortality in immunocompromised patients with fever if antibiotics are not received in a timely manner. We designed a quality improvement effort geared at reducing the time to antibiotic delivery for this high risk population. METHODS: The setting was the emergency department in an academic pediatric tertiary care hospital that sees similar to 60 000 patients annually. We assembled a multidisciplinary team who set a target of 60 minutes from time of presentation to antibiotic delivery for patients with known neutropenia and 90 minutes for patients with possible neutropenia. Quality improvement methods were used to effect change and evaluate when the targets were not met. Improved communication between providers and patients and timely feedback were implemented. RESULTS: Mean time to antibiotic delivery in febrile oncology patients with known neutropenic status dropped from 99 minutes in the pre-implementation period to 49 minutes in the postimplementation period, whereas it dropped from 90 minutes to 81 minutes in possibly neutropenic patients. The percentage of patients who met the targets for time to antibiotics rose from 50% to 88.5%. CONCLUSIONS: A multidisciplinary team approach and standardization of the process of care were effective in reducing the time from arrival to antibiotic delivery for febrile neutropenic patients in the pediatric emergency department. Pediatrics 2012; 130: e201-e210 C1 [Akenroye, Ayobami; Stack, Anne M.] Childrens Hosp Boston, Div Emergency Med, Boston, MA 02115 USA. [Mack, Jennifer] Childrens Hosp Boston, Div Hematol Oncol, Boston, MA 02115 USA. [Volpe, Diana; Damian, Fran; Morrissey, Lisa] Childrens Hosp Boston, Dept Nursing, Boston, MA 02115 USA. [Rachh, Pratik; Kahlon, Prerna S.; Mack, Jennifer] Childrens Hosp Boston, Dept Med, Boston, MA 02115 USA. [Harrison, Stephanie] Childrens Hosp Colorado, Dept Nursing, Aurora, CO USA. [Mack, Jennifer] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Stack, AM (reprint author), Childrens Hosp Boston, Div Emergency Med, 300 Longwood Ave, Boston, MA 02115 USA. EM anne.stack@childrens.harvard.edu OI akenroye, ayobami/0000-0002-1909-1470 NR 10 TC 12 Z9 12 U1 5 U2 6 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 JUL PY 2012 VL 130 IS 1 BP E201 EP E210 DI 10.1542/peds.2012-0153 PG 10 WC Pediatrics SC Pediatrics GA 967KH UT WOS:000305905900028 PM 22711718 ER PT J AU Beidas, RS Edmunds, JM Marcus, SC Kendall, PC AF Beidas, Rinad S. Edmunds, Julie M. Marcus, Steven C. Kendall, Philip C. TI Training and Consultation to Promote Implementation of an Empirically Supported Treatment: A Randomized Trial SO PSYCHIATRIC SERVICES LA English DT Article ID COGNITIVE-BEHAVIORAL THERAPY; PSYCHOTHERAPY-RESEARCH; DISSEMINATION; CLINICIAN; MODEL AB Objective: The study evaluated the efficacy of three training modalities and the impact of ongoing consultation after training. Cognitive-behavioral therapy (CBT) for anxiety among youths, an empirically supported treatment, was used as the exemplar. Participants were randomly assigned to one of three one-day workshops to examine the efficacy of training modality: routine training (training as usual), computer training (computerized version of training as usual), and augmented training (training that emphasized active learning). After training, all participants received three months of ongoing consultation that included case consultation, didactics, and problem solving. Methods: Participants were 115 community therapists (mean age of 35.9 years; 90% were women). Outcome measures included the Adherence and Skill Checklist, used to rate a performance-based role-play; a knowledge test; and the Training Satisfaction Bating Scale. Results: All three training modalities resulted in limited gains in therapist adherence, skill, and knowledge. There was no significant effect of modality on adherence, skill, or knowledge from pretraining to posttraining. Participants were more satisfied with augmented and routine training than with Computer training. Most important, number of consultation hours after training significantly predicted higher therapist adherence and skill at the three-month follow-up. Conclusions: The findings suggest that training alone did not result in therapist behavior change. The inclusion of ongoing consultation was critical to influencing therapist adherence and skill. Implications for implementation science and mental health services research are discussed. (Psychiatric Services 63:660-665, 2012; doi: 10.1176/appi.ps.201100401) C1 [Beidas, Rinad S.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Edmunds, Julie M.; Kendall, Philip C.] Temple Univ, Dept Psychol, Philadelphia, PA 19122 USA. [Marcus, Steven C.] Univ Penn, Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA. [Marcus, Steven C.] Univ Penn, Sch Social Policy & Practice, Philadelphia, PA 19104 USA. RP Beidas, RS (reprint author), Univ Penn, Dept Psychiat, 3535 Market St,Room 3015, Philadelphia, PA 19104 USA. EM rbeidas@upenn.edu FU National Institute of Mental Health [F31-MH083333]; Shipley Research Prize; Ortho-McNeil Janssen; Forest Research Institute FX This study was funded by grant F31-MH083333 from the National Institute of Mental Health and by the Shipley Research Prize awarded to Dr. Beidas. The authors thank Robert Fauber, Ph.D., Philip Hineline, Ph.D., and David Mandell, Sc.D., for comments on drafts of this article. The authors thank the following individuals for their help as consultants: Kathleen Carroll, Ph.D., Wench Cross, Ph.D., and Kimberly Hoagwood, Ph.D. The authors thank the following research assistants: Stacey Austin, Kayla Brehm, Mamatha Chary, Margaret Downey, Philip Fizur, Kyle Peer, and Anna Slavachevskaya.; Dr. Marcus has received grant support from Ortho-McNeil Janssen and Forest Research Institute and has served as a consultant to Astra-Zeneca. Dr. Kendall reports receiving royalties from sales of materials related to the treatment of anxiety among youths. The other authors report no competing interests. NR 28 TC 70 Z9 70 U1 0 U2 16 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD JUL PY 2012 VL 63 IS 7 BP 660 EP 665 DI 10.1176/appi.ps.201100401 PG 6 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 967TY UT WOS:000305931900008 PM 22549401 ER PT J AU Harris, AHS Oliva, E Bowe, T Humphreys, KN Kivlahan, DR Trafton, JA AF Harris, Alex H. S. Oliva, Elizabeth Bowe, Thomas Humphreys, Keith N. Kivlahan, Daniel R. Trafton, Jodie A. TI Pharmacotherapy of Alcohol Use Disorders by the Veterans Health Administration: Patterns of Receipt and Persistence SO PSYCHIATRIC SERVICES LA English DT Article ID MEDICATION COMPLIANCE; NALTREXONE; DEFINITIONS; TRENDS; CARE AB Objective: This study assessed changes since 2007 at Veterans Health Administration (VHA) facilities (N=129) in use of the medications approved by the U.S. Food and Drug Administration for treatment of alcohol use disorders. Methods: VHA data from fiscal years (FYs) 2008 and 2009 were used to identify patients with a diagnosis of an alcohol use disorder who received oral or extended-release naltrexone, disulfiram, or acamprosate as well as the proportion of days covered (PDC) in the 180 days after initiation and the time to first ten-day gap in possession (persistence) for each medication. Multilevel, mixed-effects logistic regression models examined the association between patient and facility characteristics and use of medications. Results: Nationally, 3.4% of VHA patients with an alcohol use disorder received medications in FY 2009 (11,165 of 331,635 patients), up from 3.0% in FY 2007. Use of medications by patients at the facilities ranged from 0% to 12%. In fully adjusted analyses, facilities offering evening and weekend services had higher rates of medication receipt, but other facility characteristics, such as having prescribers on the addiction program's staff or using medication to treat opioid or tobacco dependence, were unrelated to medication receipt. The mean PDC of acamprosate was significantly lower than mean PDCs of the other medications (p<.05), and persistence in use of naltrexone was significantly greater than use of acamprosate and significantly less than use of disulfiram (p<.05). Conclusions: Use of these medications is increasing but remains variable across the VHA system. Interventions are needed to optimize initiation of and persistence in use of these medications. (Psychiatric Services 63: 679-685, 2012; doi: 10.1176/appi.ps.201000553) C1 [Harris, Alex H. S.; Oliva, Elizabeth; Bowe, Thomas; Humphreys, Keith N.; Kivlahan, Daniel R.; Trafton, Jodie A.] US Dept Vet Affairs VA Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, Menlo Pk, CA 94025 USA. [Harris, Alex H. S.; Oliva, Elizabeth; Bowe, Thomas; Humphreys, Keith N.; Kivlahan, Daniel R.; Trafton, Jodie A.] Stanford Univ, Sch Med, Menlo Pk, CA 94025 USA. [Kivlahan, Daniel R.] Univ Washington, Sch Med, Seattle, WA USA. [Kivlahan, Daniel R.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Harris, AHS (reprint author), US Dept Vet Affairs VA Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, 795 Willow Rd,152-MPD, Menlo Pk, CA 94025 USA. EM alexander.harris2@va.gov NR 19 TC 25 Z9 25 U1 0 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD JUL PY 2012 VL 63 IS 7 BP 679 EP 685 DI 10.1176/appi.ps.201000553 PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 967TY UT WOS:000305931900011 PM 22549276 ER PT J AU Maciejewski, PK Phelps, AC Kacel, EL Balboni, TA Balboni, M Wright, AA Pirl, W Prigerson, HG AF Maciejewski, Paul K. Phelps, Andrea C. Kacel, Elizabeth L. Balboni, Tracy A. Balboni, Michael Wright, Alexi A. Pirl, William Prigerson, Holly G. TI Religious coping and behavioral disengagement: opposing influences on advance care planning and receipt of intensive care near death SO PSYCHO-ONCOLOGY LA English DT Article DE coping; cancer; oncology; advance care planning; end-of-life care ID QUALITY-OF-LIFE; BREAST-CANCER DIAGNOSIS; GYNECOLOGIC CANCER; PSYCHOLOGICAL ADJUSTMENT; TREATMENT PREFERENCES; ELDERLY-PATIENTS; END; WOMEN; STRATEGIES; RESUSCITATION AB Objective: This study examines the relationships between methods of coping with advanced cancer, completion of advance care directives, and receipt of intensive, life-prolonging care near death. Methods: The analysis is based on a sample of 345 patients interviewed between January 1, 2003, and August 31, 2007, and followed until death as part of the Coping with Cancer Study, an NCI/NIMH-funded, multi-site, prospective, longitudinal, cohort study of patients with advanced cancer. The Brief COPE was used to assess active coping, use of emotional-support, and behavioral disengagement. The Brief RCOPE was used to assess positive and negative religious coping. The main outcome was intensive, life-prolonging care near death, defined as receipt of ventilation or resuscitation in the last week of life. Results: Positive religious coping was associated with lower rates of having a living will (AOR = 0.39, p = 0.003) and predicted higher rates of intensive, life-prolonging care near death (AOR, 5.43; p<0.001), adjusting for other coping methods and potential socio-demographic and health status confounds. Behavioral disengagement was associated with higher rates of DNR order completion (AOR, 2.78; p = 0.003) and predicted lower rates of intensive life-prolonging care near death (AOR, 0.20; p = 0.036). Not having a living will partially mediate the influence of positive religious coping on receipt of intensive, life-prolonging care near death. Conclusion: Positive religious coping and behavioral disengagement are important determinants of completion of advance care directives and receipt of intensive, life-prolonging care near death. Copyright (c) 2011 John Wiley & Sons, Ltd. C1 [Maciejewski, Paul K.; Phelps, Andrea C.; Kacel, Elizabeth L.; Balboni, Tracy A.; Balboni, Michael; Wright, Alexi A.; Prigerson, Holly G.] Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, Boston, MA 02115 USA. [Maciejewski, Paul K.; Prigerson, Holly G.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Phelps, Andrea C.; Wright, Alexi A.; Prigerson, Holly G.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Balboni, Tracy A.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Balboni, Michael] Boston Univ, Dept Theol, Boston, MA 02215 USA. [Pirl, William] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Pirl, William] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Prigerson, Holly G.] Harvard Univ, Sch Med, Ctr Palliat Care, Boston, MA USA. RP Prigerson, HG (reprint author), Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, 268 Smith Bldg,44 Binney St, Boston, MA 02115 USA. EM holly_prigerson@dfci.harvard.edu FU National Institute of Mental Health [MH63892]; National Cancer Institute [CA 106370]; Fetzer Foundation; Center for Psycho-Oncology and Palliative Care Research, Dana-Farber Cancer Institute FX Funding/support: This research was supported in part by the following grants to Dr. Prigerson: MH63892 from the National Institute of Mental Health and CA 106370 from the National Cancer Institute; a Fetzer Foundation grant to study religiousness at the end of life; the Center for Psycho-Oncology and Palliative Care Research, Dana-Farber Cancer Institute. NR 43 TC 12 Z9 13 U1 2 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD JUL PY 2012 VL 21 IS 7 BP 714 EP 723 DI 10.1002/pon.1967 PG 10 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 967EN UT WOS:000305889300005 PM 21449037 ER PT J AU Mohr, JP Caplan, LR Kistler, JP AF Mohr, J. P. Caplan, Louis R. Kistler, J. Philip TI C. Miller Fisher An Appreciation In Memoriam SO STROKE LA English DT Biographical-Item C1 [Mohr, J. P.] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. [Caplan, Louis R.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Kistler, J. Philip] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Mohr, JP (reprint author), Columbia Univ Coll Phys & Surg, 710 W 168th St, New York, NY 10032 USA. EM jpm10@columbia.edu NR 1 TC 1 Z9 1 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 JUL PY 2012 VL 43 IS 7 BP 1739 EP 1740 DI 10.1161/STROKEAHA.112.661512 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 967BV UT WOS:000305882000011 ER PT J AU Fang, MC Go, AS Chang, YC Borowsky, LH Pomernacki, NK Udaltsova, N Singer, DE AF Fang, Margaret C. Go, Alan S. Chang, Yuchiao Borowsky, Leila H. Pomernacki, Niela K. Udaltsova, Natalia Singer, Daniel E. TI Thirty-Day Mortality After Ischemic Stroke and Intracranial Hemorrhage in Patients With Atrial Fibrillation On and Off Anticoagulants SO STROKE LA English DT Article DE acute stroke; anticoagulants; atrial fibrillation; intracranial hemorrhage; warfarin ID INTRACEREBRAL HEMORRHAGE; WARFARIN; INTENSITY; THERAPY AB Background and Purpose-Prescribing warfarin for atrial fibrillation depends in large part on the expected reduction in ischemic stroke risk versus the expected increased risk of intracranial hemorrhage (ICH). However, the anticoagulation decision also depends on the relative severity of such events. We assessed the impact of anticoagulation on 30-day mortality from ischemic stroke versus ICH in a large community-based cohort of patients with atrial fibrillation. Methods-We followed 13 559 patients with atrial fibrillation enrolled in an integrated healthcare delivery system for a median 6 years. Incident ischemic strokes and ICHs were identified from computerized databases and validated through medical record review. The association of warfarin and international normalized ratio at presentation with 30-day mortality was modeled using multivariable logistic regression adjusting for clinical factors. Results-We identified 1025 incident ischemic strokes and 299 ICHs during follow-up. Compared with no antithrombotic therapy, warfarin was associated with reduced Rankin score and lower 30-day mortality from ischemic stroke (adjusted OR, 0.64; 95% CI, 0.45-0.91) but a higher mortality from ICH (OR, 1.62; 95% CI, 0.88-2.98). Therapeutic international normalized ratios (2-3) were associated with an especially low ischemic stroke mortality (OR, 0.38; 95% CI, 0.20-0.70), whereas international normalized ratios >3 increased the odds of dying of ICH by 2.66-fold (95% CI, 1.21-5.86). Conclusions-Warfarin reduces 30-day mortality from ischemic stroke but increases ICH-related mortality. Both effects on event severity as well as on event rates need to be incorporated into rational decision-making about anticoagulants for atrial fibrillation. (Stroke. 2012;43:1795-1799.) C1 [Fang, Margaret C.] Univ Calif San Francisco, Div Hosp Med, Dept Med, San Francisco, CA 94143 USA. [Go, Alan S.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Go, Alan S.; Pomernacki, Niela K.; Udaltsova, Natalia] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Chang, Yuchiao; Borowsky, Leila H.; Singer, Daniel E.] Massachusetts Gen Hosp, Clin Epidemiol Unit, Boston, MA 02114 USA. RP Fang, MC (reprint author), Univ Calif San Francisco, Div Hosp Med, Dept Med, 505 Parnassus Ave,Box 0131, San Francisco, CA 94143 USA. EM mfang@medicine.ucsf.edu FU National Institute on Aging [R01 AG15478, K23 AG028978]; National Heart, Lung and Blood Institute [U19 HL91179, RC2HL101589]; Eliot B. and Edith C. Shoolman fund of the Massachusetts General Hospital (Boston, MA); Daiichi Sankyo, Inc.; Johnson Johnson, Inc. FX This study was supported by the National Institute on Aging (R01 AG15478 and K23 AG028978), the National Heart, Lung and Blood Institute (U19 HL91179 and RC2HL101589), and the Eliot B. and Edith C. Shoolman fund of the Massachusetts General Hospital (Boston, MA). The funding sources had no role in study design, data collection, data analysis, data interpretation, or preparation of this article.; Dr Singer has consulted for Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Inc, Johnson & Johnson, Inc, Merck and Co, Bayer Healthcare, Pfizer, and Sanofi Aventis, Inc and has received research support from Daiichi Sankyo, Inc. Dr Go has received research support from Johnson & Johnson, Inc. NR 11 TC 35 Z9 35 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JUL PY 2012 VL 43 IS 7 BP 1795 EP 1799 DI 10.1161/STROKEAHA.111.630731 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 967BV UT WOS:000305882000022 PM 22539546 ER PT J AU Allen, NB Kaltenbach, L Goldstein, LB Olson, DM Smith, EE Peterson, ED Schwamm, L Lichtman, JH AF Allen, Norrina B. Kaltenbach, Lisa Goldstein, Larry B. Olson, DaiWai M. Smith, Eric E. Peterson, Eric D. Schwamm, Lee Lichtman, Judith H. TI Regional Variation in Recommended Treatments for Ischemic Stroke and TIA Get With the Guidelines-Stroke 2003-2010 SO STROKE LA English DT Article DE cerebrovascular disease; epidemiology; health care; medical Rx; stroke care; tPA; treatment ID QUALITY-OF-CARE; MEDICARE BENEFICIARIES; PERSISTENCE; ADHERENCE; PROGRAM; USA AB Background and Purpose-Secondary stroke prevention treatments vary in different regions of the US. We determined the degree to which guideline-recommended stroke treatments vary by region for patients treated at hospitals participating in a voluntary national quality improvement program, Get With The Guidelines-Stroke. Methods-Receipt of 8 guideline-recommended treatments (intravenous tissue-type plasminogen activator, antihypertensives, antithrombotics, anticoagulants for atrial fibrillation, deep vein thrombosis prophylaxis, lipid-lowering medications at discharge, smoking cessation counseling, weight loss education) and defect-free care were compared in 4 US regions among eligible patients with ischemic stroke and transient ischemic attack; there was adjustment for patient demographics, medical history, and hospital characteristics. Results-Among 991 995 admissions (South, 37%; Northeast, 27.6%; Midwest, 19.3%; West, 15.9%). Receipt varied regionally for tissue-type plasminogen activator (58.2%-67.8%), lipid-lowering medications (72.5%-75.7%), antihypertensives (80.1%-83.6%), antithrombotics (95.6%-96.8%), deep vein thrombosis prophylaxis (88.0%-91.4%), weight loss education (49.3%-54.7%), and defect-free care (72.1%-76.5%). In adjusted analyses, patients in the South had lower odds of use of intravenous tissue-type plasminogen activator (OR [95% CI]; 0.82 [0.69-0.97]), antihypertensives (0.82 [0.67-0.99]), and defect-free care (0.83 [0.75-0.92]); but, they were more likely to receive lipid-lowering medications (1.28 [1.05-1.54]) compared with those in the Northeast. Patients in the Midwest had lower odds of intravenous tissue-type plasminogen activator administration (0.82 [0.68-0.99]) and defect-free care (0.81 [0.72-0.92]). Those in the West had lower odds of antihypertensives (0.81 [0.67-0.99]), but had greater odds of receiving lipid-lowering medications (1.26 [1.03-1.53]). Conclusions-Despite relatively high rates of adherence to stroke-related therapies in Get With The Guidelines-Stroke hospitals, regional variations exist, with over one quarter of patients receiving suboptimal care. Systematic improvements may lead to better patient outcomes. (Stroke. 2012;43:1858-1864.) C1 [Allen, Norrina B.] Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Kaltenbach, Lisa; Olson, DaiWai M.; Peterson, Eric D.] Duke Univ, Duke Clin Res Inst, Durham, NC USA. [Goldstein, Larry B.] Duke Univ, Dept Med, Duke Stroke Ctr, Durham, NC USA. Durham VA Med Ctr, Durham, NC USA. [Smith, Eric E.] Univ Calgary, Hotchkiss Brain Inst, Calgary, AB, Canada. [Schwamm, Lee] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Lichtman, Judith H.] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, Div Chron Dis Epidemiol, New Haven, CT 06510 USA. RP Allen, NB (reprint author), Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, 680 N Lake Shore Dr,Suite 1400, Chicago, IL 60611 USA. EM norrina-allen@northwestern.edu RI Smith, Eric/C-5443-2012; OI Smith, Eric/0000-0003-3956-1668; Schwamm, Lee/0000-0003-0592-9145 FU Ortho-McNeil; Boeringher-Ingelheim; Bristol-Myers Squib/Sanofi Pharmaceutical; AHA Pharmaceutical Roundtable; NHLBI [T32 HL 069771-07]; Merck FX The Get With The Guidelines (R)-Stroke (GWTG-Stroke) program is provided by the American Heart Association (AHA)/American Stroke Association. The GWTG-Stroke program is currently supported in part by a charitable contribution from Ortho-McNeil. GWTG-Stroke has been funded in the past through support from Boeringher-Ingelheim and Merck; Bristol-Myers Squib/Sanofi Pharmaceutical Partnership; and the AHA Pharmaceutical Roundtable. The AHA Pharmaceutical Roundtable did not participate in the design of conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. N.B.A. was supported by an NHLBI T32 grant (T32 HL 069771-07 (Daviglus, principal investigator)). NR 23 TC 18 Z9 18 U1 0 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 JUL PY 2012 VL 43 IS 7 BP 1858 EP 1864 DI 10.1161/STROKEAHA.112.652305 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 967BV UT WOS:000305882000032 PM 22588262 ER PT J AU Tong, D Reeves, MJ Hernandez, AF Zhao, X Olson, DM Fonarow, GC Schwamm, LH Smith, EE AF Tong, David Reeves, Mathew J. Hernandez, Adrian F. Zhao, Xin Olson, DaiWai M. Fonarow, Gregg C. Schwamm, Lee H. Smith, Eric E. TI Times From Symptom Onset to Hospital Arrival in the Get With The Guidelines-Stroke Program 2002 to 2009 Temporal Trends and Implications SO STROKE LA English DT Article DE ischemic stroke; epidemiology; thrombolysis ID TRANSIENT ISCHEMIC ATTACK; PLASMINOGEN-ACTIVATOR; WARNING SIGNS; RISK-FACTORS; REGISTRY; RECOMMENDATIONS; THROMBOLYSIS; EXPERIENCE; KNOWLEDGE; CENTERS AB Background and Purpose-Time from symptom onset to hospital arrival is the most important factor in determining eligibility for intravenous tissue-type plasminogen activator. We used data from a large contemporary nationwide study to determine temporal trends in the proportions of patients arriving within time windows for potential acute ischemic stroke therapies. Methods-Trends in symptom onset to hospital arrival time ("onset-to-door time") for patients with acute ischemic stroke in the Get With The Guidelines-Stroke (GWTG-Stroke) program were analyzed between 2003 and 2009. Factors associated with early onset-to-door time (<= 2 hours) were also examined. Results-Between April 2003 and March 2009, 1287 hospitals submitted data on 413 147 patients with acute ischemic stroke of whom 194 352 (47.0%) had a specific onset time documented. Among all 413 147 patients, onset-to-door time was documented as <= 2 hours in 20.6%, <= 3 hours in 25.1%, <= 3.5 hours in 26.8%, and <= 8 hours in 35.8%. Early arrival within 2 hours was significantly associated with emergency medical services transport (P<0.0001). There was no substantial change in onset-to-door time over the 6-year study period. Expansion of the tissue-type plasminogen activator treatment window from 3 to 4.5 hours (allowing 60 minutes for provision of tissue-type plasminogen activator) increases the pool of potentially eligible patients by 6.3% (30.1% relative increase). Conclusions-More than one fourth of patients with ischemic stroke arrive within the time window for tissue-type plasminogen activator therapy; however, this percentage has remained unchanged over recent years. Further efforts are needed to increase the portion of patients with acute ischemic stroke presenting within the time window for acute interventions. (Stroke. 2012;43:1912-1917.) C1 [Tong, David] Michigan State Univ, Comprehens Stroke Care Ctr, CPMC, E Lansing, MI 48824 USA. [Tong, David] Michigan State Univ, CPMC Ctr Stroke Res, E Lansing, MI 48824 USA. [Reeves, Mathew J.] Michigan State Univ, CPMC Dept Neurosci, E Lansing, MI 48824 USA. [Reeves, Mathew J.] Michigan State Univ, Dept Epidemiol, E Lansing, MI 48824 USA. [Hernandez, Adrian F.; Zhao, Xin; Olson, DaiWai M.] Duke Clin Res Inst, Durham, NC USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Ronald Reagan UCLA Med Ctr, Los Angeles, CA USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Smith, Eric E.] Univ Calgary, Dept Clin Neurosci, Foothills Med Ctr, Hotchkiss Brain Inst, Calgary, AB T2N 2T9, Canada. RP Smith, EE (reprint author), Univ Calgary, Dept Clin Neurosci, Foothills Med Ctr, Hotchkiss Brain Inst, Room C1212,1403 29 St NW, Calgary, AB T2N 2T9, Canada. EM eesmith@ucalgary.ca 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 Bristol-Myers Squib/Sanofi Pharmaceutical Partnership; American Heart Association Pharmaceutical Roundtable; Boehringer-Ingelheim and Merck FX The Get With The Guidelines (R)-Stroke (GWTG-Stroke) program is provided by the American Heart Association/American Stroke Association. The GWTG-Stroke program is currently supported in part by a charitable contribution from Bristol-Myers Squib/Sanofi Pharmaceutical Partnership and the American Heart Association Pharmaceutical Roundtable. GWTG-Stroke has been funded in the past through support from Boehringer-Ingelheim and Merck. NR 23 TC 42 Z9 42 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JUL PY 2012 VL 43 IS 7 BP 1912 EP 1917 DI 10.1161/STROKEAHA.111.644963 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 967BV UT WOS:000305882000040 PM 22539544 ER PT J AU Furie, KL AF Furie, Karen L. TI High-Dose Statins Should Only Be Used in Atherosclerotic Strokes SO STROKE LA English DT Editorial Material ID TRANSIENT ISCHEMIC ATTACK; CHOLESTEROL; PREVENTION C1 Massachusetts Gen Hosp, Dept Neurol, J Philip Kistler MGH Stroke Res Ctr, Stroke Serv, Boston, MA 02114 USA. RP Furie, KL (reprint author), Massachusetts Gen Hosp, Dept Neurol, J Philip Kistler MGH Stroke Res Ctr, Stroke Serv, 175 Cambridge St,Suite 300, Boston, MA 02114 USA. EM kfurie@partners.org NR 8 TC 5 Z9 6 U1 1 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 JUL PY 2012 VL 43 IS 7 BP 1994 EP 1995 DI 10.1161/STROKEAHA.111.633339 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 967BV UT WOS:000305882000058 PM 22581818 ER PT J AU Bradley, KA Rubinsky, AD Sun, HL Blough, DK Tonnesen, H Hughes, G Beste, LA Bishop, MJ Hawn, MT Maynard, C Harris, ASH Hawkins, EJ Bryson, CL Houston, TK Henderson, WG Kivlahan, DR AF Bradley, Katharine A. Rubinsky, Anna D. Sun, Haili Blough, David K. Tonnesen, Hanne Hughes, Grant Beste, Lauren A. Bishop, Michael J. Hawn, Mary T. Maynard, Charles Harris, Alex S. H. Hawkins, Eric J. Bryson, Chris L. Houston, Thomas K. Henderson, William G. Kivlahan, Daniel R. TI Prevalence of alcohol misuse among men and women undergoing major noncardiac surgery in the Veterans Affairs health care system SO SURGERY LA English DT Article ID DISORDERS IDENTIFICATION TEST; PROSTATE-CANCER; SCREENING SCORES; AUDIT-C; RISK; CONSUMPTION; QUALITY; COMPLICATIONS; ASSOCIATION; MORBIDITY AB Background. Patients who screen positive for alcohol misuse on the Alcohol Use Disorder Identification Test Consumption Questionnaire (AUDIT-C >= 5 points) have significantly increased postoperative complications. Severe alcohol misuse (AUDIT-C >= 9 points) is associated with increased postoperative health care use; however, little is known about the prevalence of alcohol misuse in demographic and clinical subgroups of surgical patients. Methods. The prevalence of alcohol misuse was evaluated among 10,284 patients (9,771 men and 513 women) who underwent major noncardiac surgery in Veterans Affairs (VA) hospitals during the fiscal years 2004 to 2006 and completed the AUDIT-C. Sex-stratified analyses evaluated prevalence rates of alcohol misuse (AUDIT-C >= 5) and severe misuse (AUDIT-C >= 9) across demographic and clinical subgroups. Results. Overall, 1,607(16%) men and 24 (5%) women screened positive for alcohol misuse (AUDIT-C >= 5) in the year before operation, with 4% and 2% screening positive for severe misuse (AUDIT-C >= 9), respectively. Alcohol misuse was more common among men who were <60 years of age, divorced or separated, current smokers, or American Stoke Association class 1 or 2, and those with cirrhosis/hepatitis or substance use disorders. Among patients with alcohol misuse, 36% of men and 58% of women were American Society Of Anesthesiologists class I or 2, and most did not have diagnoses that were commonly associated with alcohol misuse. Conclusion. Alcohol misuse is relatively common in male surgical patients. Moreover, surgical patients undergoing operation who screen positive for alcohol misuse are often relatively healthy, without health problems that might alert providers to their alcohol misuse in the absence of screening. (Surgery 2012;152:69-81.) C1 [Bradley, Katharine A.] Univ Washington, Grp Hlth Res Inst, Seattle, WA 98101 USA. [Bradley, Katharine A.; Hawkins, Eric J.; Kivlahan, Daniel R.] Univ Washington, Dept Vet Affairs Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA 98101 USA. [Bradley, Katharine A.] Univ Washington, Dept Med, Seattle, WA 98101 USA. [Bradley, Katharine A.; Rubinsky, Anna D.; Beste, Lauren A.; Maynard, Charles] Univ Washington, Dept Hlth Serv, Seattle, WA 98101 USA. [Blough, David K.] Univ Washington, Dept Pharm, Seattle, WA 98101 USA. [Tonnesen, Hanne] Bispebjerg Hosp, World Hlth Org Collaborating Ctr Evidence Based H, Copenhagen, Denmark. [Hughes, Grant; Henderson, William G.] Dept Vet Affairs Eastern Colorado Healthcare Syst, Denver, CO USA. [Bryson, Chris L.] Univ Washington, Dept Vet Affairs Puget Sound Hlth Care Syst, Gen Med Serv, Seattle, WA 98101 USA. [Hawn, Mary T.] Univ Alabama Birmingham, Dept Surg, Birmingham, AL 35294 USA. [Hawn, Mary T.] Birmingham Vet Affairs Med Ctr, Ctr Surg Med Acute Care Res & Transit C SMART, Birmingham, AL USA. [Harris, Alex S. H.] Dept Vet Affairs Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, Menlo Pk, CA USA. [Houston, Thomas K.] Bedford Vet Affairs Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Houston, Thomas K.] Univ Massachusetts, Sch Med, Div Hlth Informat & Implementat Sci, Dept Quantitat Hlth Sci, Worcester, MA USA. [Henderson, William G.] Univ Colorado, Hlth Outcomes Program, Aurora, CO USA. RP Bradley, KA (reprint author), Univ Washington, Grp Hlth Res Inst, 1730 Minor Ave,Suite 1600, Seattle, WA 98101 USA. EM bradley.k@ghc.org RI Houston, Thomas/F-2469-2013; Maynard, Charles/N-3906-2015 OI Maynard, Charles/0000-0002-1644-7814 FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development and Health Services Research and Development (HSRD) [IAC 06-021]; US Department of Veterans Affairs, Office of Research and Development FX Supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development and Health Services Research and Development (HSR & D; project IAC 06-021). Dr Bradley was an investigator at the Veterans Affairs Northwest HSR&D Center of Excellence and at the Center of Excellence in Substance Abuse Treatment and Education, VA Puget Sound Health Care System, Seattle, WA, while this work was conducted.; This material is based upon work supported by the US Department of Veterans Affairs, Office of Research and Development. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States Government. NR 38 TC 9 Z9 9 U1 2 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD JUL PY 2012 VL 152 IS 1 BP 69 EP 81 DI 10.1016/j.surg.2012.02.007 PG 13 WC Surgery SC Surgery GA 966QZ UT WOS:000305853800011 PM 22503319 ER PT J AU Yin, XM Latif, R Bahn, R Davies, TF AF Yin, Xiaoming Latif, Rauf Bahn, Rebecca Davies, Terry F. TI Genetic Profiling in Graves' Disease: Further Evidence for Lack of a Distinct Genetic Contribution to Graves' Ophthalmopathy SO THYROID LA English DT Article ID AUTOIMMUNE THYROID-DISEASE; INTERLEUKIN-23 RECEPTOR GENE; T-LYMPHOCYTE ANTIGEN-4; THYROTROPIN RECEPTOR; RHEUMATOID-ARTHRITIS; FUNCTIONAL VARIANTS; SUSCEPTIBILITY GENE; TSH-RECEPTOR; ASSOCIATION; CTLA-4 AB Background: Graves' disease (GD), including Graves' ophthalmopathy or orbitopathy (GO), is an autoimmune disease with an environmental and genetic component to its etiology. The genetic contribution to the GO clinical phenotype remains unclear. Previous data from our laboratory and others have suggested that GO has no specific genetic component distinct from GD itself, while other reports have occasionally appeared suggesting that polymorphisms in genes such as CTLA4 and IL23R specifically increase the risk for GO. One of the criticisms of all these reports has been the clinical definition of the GO phenotype as distinct from hyperthyroid GD devoid of clinically significant eye involvement. The objective of this study was to take advantage of a phenotypically pure group of GD patients with GO and examine a series of genes associated with GD to determine if any were more definitively associated with GO rather than Graves' thyroid disease itself. Methods: To further examine whether specific susceptibility genes are associated with GO, we have performed further genetic association studies using highly characterized GO patients, many of whom had undergone orbital decompression surgery for their exophthalmos. We genotyped HLA, CTLA4, IL23R, and TSHR genes in a group of 256 Caucasian patients with severe GO (n = 199) and less severe GO (n = 57), and 90 patients with GD but no clinically apparent GO. Results: We found that the allele and genotype frequencies were not statistically different between GO and non-GO patients for any of the genes and gene combinations assessed. Conclusions: These results provide further evidence that patients with GO do not have a distinct genetic susceptibility to their eye disease and again suggest that environmental and/or epigenetic influences are at play. C1 [Yin, Xiaoming; Latif, Rauf; Davies, Terry F.] James J Peters VA Med Ctr, Mt Sinai Sch Med, Thyroid Res Unit, New York, NY 10468 USA. [Bahn, Rebecca] Mayo Clin, Sch Med, Div Endocrinol, Rochester, MN USA. RP Yin, XM (reprint author), James J Peters VA Med Ctr, Mt Sinai Sch Med, Thyroid Res Unit, Room 2F-26,130 W Kingsbridge Rd, New York, NY 10468 USA. EM xiaoming.yin@mssm.edu OI latif, rauf/0000-0002-4226-3728 FU NIH-NIDDK the David Owen Segal Endowment [DK052464, DK69713]; James J. Peters VAMC; VA Merit Award program FX This work was supported in part by DK052464 and DK69713 from NIH-NIDDK the David Owen Segal Endowment, the James J. Peters VAMC, and the VA Merit Award program. We thank our colleague Dr. Yaron Tomer for his help and advice. NR 58 TC 15 Z9 17 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 J9 THYROID JI Thyroid PD JUL PY 2012 VL 22 IS 7 BP 730 EP 736 DI 10.1089/thy.2012.0007 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 968JE UT WOS:000305974400011 PM 22663548 ER PT J AU Gershman, B Sheth, S Dretler, SP Herrick, B Lang, K Pais, VM Eisner, BH AF Gershman, Boris Sheth, Sonali Dretler, Stephen P. Herrick, Benjamin Lang, Katherine Pais, Vernon M., Jr. Eisner, Brian H. TI Relationship Between Glomerular Filtration Rate and 24-Hour Urine Composition in Patients With Nephrolithiasis SO UROLOGY LA English DT Article ID CHRONIC KIDNEY-DISEASE; UNITED-STATES; PREVALENCE; STONES; HEALTH; RISK AB OBJECTIVE To examine the relationship between GFR and 24-hour urine composition in patients with nephrolithiasis to understand how renal function may affect stone risk. Alterations in glomerular filtration rate (GFR) are associated with a number of physiological changes. METHODS A retrospective, institutional review board-approved review of patients from 2 metabolic stone clinics was performed. One-way analysis of variance and multivariate linear regression models were used to evaluate the relationship between GFR quintile and 24-hour urine composition. RESULTS A total of 403 patients (241 male, 162 female) with a mean age of 52.6 +/- 14.2 years were included in the study. On univariate analysis, decreasing GFR by quintile was associated with significant reductions in urine calcium, citrate, supersaturation of calcium oxalate, and supersaturation of calcium phosphate (P < .05 for each). In multivariate linear regression models, decreasing GFR by quintile was associated with significant decreases in urine calcium (beta = -11.2, 95% CI = -18.3 to 4.01), urine citrate (beta = -32.4, 95% CI = -54.1 to 10.8), oxalate (beta = -1.83, 95% CI = -2.85 to 0.81), supersaturation of calcium oxalate (beta = -0.58, 95% CI = 0.84 to 0.33) and supersaturation of calcium phosphate (beta = -0.09, 95% CI = 0.17 to 0.02), as well as an increase in urine magnesium (beta = 3.40, 95% CI = 0.7 to 6.1). CONCLUSION Reduction in GFR is associated with decreased urine calcium, oxalate, and citrate, and increased urine magnesium. These findings have implications for treatment of patients with stone disease and impaired renal function. UROLOGY 80: 38-42, 2012. (c) 2012 Elsevier Inc. C1 [Eisner, Brian H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. Dartmouth Hitchcock Med Ctr, Dept Urol, Lebanon, NH 03766 USA. RP Eisner, BH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Urol, GRB 1102,55 Fruit St, Boston, MA 02114 USA. EM beisner@partners.org NR 13 TC 4 Z9 4 U1 0 U2 28 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 JUL PY 2012 VL 80 IS 1 BP 38 EP 42 DI 10.1016/j.urology.2011.12.019 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 968DP UT WOS:000305957500015 PM 22608801 ER PT J AU Eisner, BH Sheth, S Dretler, SP Herrick, B Pais, VM AF Eisner, Brian H. Sheth, Sonali Dretler, Stephen P. Herrick, Benjamin Pais, Vernon M., Jr. TI Effect of Socioeconomic Status on 24-Hour Urine Composition in Patients With Nephrolithiasis SO UROLOGY LA English DT Article ID ADJUSTED MORTALITY PREDICTORS; STAGE RENAL-DISEASE; IDIOPATHIC HYPERCALCIURIA; INCOME MEASURES; HEALTH; DISPARITIES; RISK; EDUCATION; HYPERTENSION; STONES AB OBJECTIVE To examine the relationship between the poverty and education levels and 24-hour urine composition in patients with nephrolithiasis because little is known about the relationship between socioeconomic status and kidney stone risk. METHODS A retrospective review was performed of patients evaluated at 2 metabolic stone clinics. The poverty level (ie, percentage of those living below the poverty level) and education level (ie, percentage of those with a high school education or greater) for each postal code were determined from the U. S. Census Bureau data. Multivariate linear regression analysis was used to examine the relationship between the poverty and education levels and 24-hour urine composition. RESULTS A total of 435 patients were included in the present study. Of the 435 patients, 173 were women and 262 were men (40% women), the mean age was 52.5 +/- 14.4 years, and the mean body mass index was 28.6 +/- 6.5 kg/m(2). The mean percentage of those below the poverty level was 8.2% +/- 6.2%, and the mean percentage of those with a high school education or greater was 87.4% +/- 7.4%. On multivariate linear regression analysis, an increasing local poverty level was associated with significant increases in urine calcium (beta = 1.51, 95% confidence interval [CI] 0.16-2.86). A decreasing local level of education (ie, decreasing percentage of those with a high school diploma or greater) was associated with significant increases in urine calcium (beta = 1.26, 95% CI 0.10-2.42), supersaturation of calcium oxalate (beta = 0.04, 95% CI 0.006-0.09), and supersaturation of calcium phosphate (beta = 0.013, 95% CI 0.0002-0.03). No other associations were found between the poverty and education levels and any urine constituents or supersaturations. CONCLUSION In the present study of patients with stone formation, increasing poverty was associated with increased urine calcium, and increasing education appeared to be protective by decreasing urine calcium and the supersaturation of calcium oxalate and calcium phosphate. Additional studies are important to elucidate the mechanisms underlying these findings. UROLOGY 80: 43-47, 2012. (c) 2012 Elsevier Inc. C1 [Eisner, Brian H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02114 USA. Dartmouth Hitchcock Med Ctr, Dept Urol, Lebanon, NH 03766 USA. RP Eisner, BH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, GRB 1102,55 Fruit St, Boston, MA 02114 USA. EM beisner@partners.org NR 29 TC 6 Z9 6 U1 0 U2 27 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 JUL PY 2012 VL 80 IS 1 BP 43 EP 47 DI 10.1016/j.urology.2011.12.017 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 968DP UT WOS:000305957500016 PM 22608802 ER PT J AU Demidova-Rice, TN Hamblin, MR Herman, IM AF Demidova-Rice, Tatiana N. Hamblin, Michael R. Herman, Ira M. TI Acute and Impaired Wound Healing: Pathophysiology and Current Methods for Drug Delivery, Part 1: Normal and Chronic Wounds: Biology, Causes, and Approaches to Care SO ADVANCES IN SKIN & WOUND CARE LA English DT Article DE acute wound healing; drug delivery and wounds; wound care strategies ID ENDOTHELIAL GROWTH-FACTOR; PROGENITOR-CELL MOBILIZATION; DIABETIC FOOT; IN-VITRO; BED PREPARATION; VENOUS ULCERS; LEG ULCERS; KERATINOCYTE DIFFERENTIATION; EXTRACELLULAR MATRICES; CONTACT-DERMATITIS AB This is the first installment of 2 articles that discuss the biology and pathophysiology of wound healing, review the role that growth factors play in this process, and describe current ways of growth factor delivery into the wound bed. Part 1 discusses the latest advances in clinicians' understanding of the control points that regulate wound healing. Importantly, biological similarities and differences between acute and chronic wounds are considered, including the signaling pathways that initiate cellular and tissue responses after injury, which may be impeded during chronic wound healing. C1 [Herman, Ira M.] Tufts Univ, Sackler Sch Grad Biomed Sci, Program Cellular & Mol Physiol, Boston, MA 02111 USA. [Herman, Ira M.] Ctr Innovat Wound Healing Res, Boston, MA USA. [Herman, Ira M.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Demidova-Rice, Tatiana N.] Massachusetts Gen Hosp, EL Steele Lab Tumor Biol, Boston, MA 02114 USA. [Hamblin, Michael R.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Herman, IM (reprint author), Tufts Univ, Sackler Sch Grad Biomed Sci, Program Cellular & Mol Physiol, Boston, MA 02111 USA. EM ira.herman@tufts.edu OI Hamblin, Michael/0000-0001-6431-4605 FU National Institutes of Health; Wound Care Partners, LLC FX Tatiana N. Demidova-Rice, PhD, is a post-doctoral fellow at E.L. Steele Laboratory of Tumor Biology, Massachusetts General Hospital, Boston, Massachusetts. Michael R. Hamblin, PhD, is Associate Professor, Department of Dermatology and Principal Investigator, Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts. Ira M. Herman, PhD, is Professor and Director, Program in Cellular and Molecular Physiology, Sackler School of Graduate Biomedical Sciences and The Center for Innovations in Wound Healing Research, and Tufts University School of Medicine, Boston, Massachusetts. Drs Demidova-Rice and Hamblin have disclosed they have no financial relationships related to this article. Dr Herman has disclosed that he is/was a recipient of grant/research funding from the National Institutes of Health and Wound Care Partners, LLC; is/was a consultant/advisor to Healthpoint Biotherapeutics, Inc, and Nell One, Inc; was a consultant/advisor to Healthpro Bioventures and Amach Partners; and is a stock shareholder in Wound Care Partners, LLC. Correspondence may be sent to Dr Herman at ira.herman@tufts.edu. Submitted January 27, 2011; accepted in revised version June 8, 2011. NR 96 TC 44 Z9 46 U1 5 U2 23 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1527-7941 J9 ADV SKIN WOUND CARE JI Adv. Skin Wound Care PD JUL PY 2012 VL 25 IS 7 BP 304 EP 314 DI 10.1097/01.ASW.0000416006.55218.d0 PG 11 WC Dermatology; Nursing; Surgery SC Dermatology; Nursing; Surgery GA 963RG UT WOS:000305640700004 PM 22713781 ER PT J AU Nechuta, SJ Caan, BJ Chen, WY Lu, W Chen, Z Kwan, ML Flatt, SW Zheng, Y Zheng, W Pierce, JP Shu, XO AF Nechuta, Sarah J. Caan, Bette J. Chen, Wendy Y. Lu, Wei Chen, Zhi Kwan, Marilyn L. Flatt, Shirley W. Zheng, Ying Zheng, Wei Pierce, John P. Shu, Xiao Ou TI Soy food intake after diagnosis of breast cancer and survival: an in-depth analysis of combined evidence from cohort studies of US and Chinese women SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID FREQUENCY QUESTIONNAIRE; RANDOMIZED-TRIAL; POOLING PROJECT; UNITED-STATES; LIVING WHEL; HEALTH; RISK; DIET; ISOFLAVONES; RECURRENCE AB Background: Soy isoflavones have antiestrogenic and anticancer properties but also possess estrogen-like properties, which has raised concern about soy food consumption among breast cancer survivors. Objective: We prospectively evaluated the association between postdiagnosis soy food consumption and breast cancer outcomes among US and Chinese women by using data from the After Breast Cancer Pooling Project. Design: The analysis included 9514 breast cancer survivors with a diagnosis of invasive breast cancer between 1991 and 2006 from 2 US cohorts and 1 Chinese cohort. Soy isoflavone intake (mg/d) was measured with validated food-frequency questionnaires. HRs and 95% CIs were estimated by using delayed-entry Cox regression models, adjusted for sociodemographic, clinical, and lifestyle factors. Results: After a mean follow-up of 7.4 y, we identified 1171 total deaths (881 from breast cancer) and 1348 recurrences. Despite large differences in soy isoflavone intake by country, isoflavone consumption was inversely associated with recurrence among both US and Chinese women, regardless of whether data were analyzed separately by country or combined. No heterogeneity was observed. In the pooled analysis, consumption of >= 10 mg isoflavones/d was associated with a nonsignificant reduced risk of all-cause (HR: 0.87; 95% Cl: 0.70, 1.10) and breast cancer specific (HR: 0.83; 95% Cl: 0.64, 1.07) mortality and a statistically significant reduced risk of recurrence (HR: 0.75; 95% Cl: 0.61, 0.92). Conclusion: In this large study of combined data on US and Chinese women, postdiagnosis soy food consumption of >= 10 mg isoflavones/d was associated with a nonsignificant reduced risk of breast cancer specific mortality and a statistically significant reduced risk of recurrence. One of the studies included in the After Breast Cancer Pooling Project, the Women's Healthy Eating & Living Study, was registered at clinicaltrials.gov as NCT00003787. Am J Clin Nutr 2012;96:123-32. C1 [Shu, Xiao Ou] Vanderbilt Univ, Med Ctr, Vanderbilt Epidemiol Ctr, Div Epidemiol,Dept Med,Sch Med,IMPH, Nashville, TN 37203 USA. [Caan, Bette J.; Kwan, Marilyn L.] Kaiser Permanente, Div Res, Oakland, CA USA. [Chen, Wendy Y.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Chen, Wendy Y.] Harvard Univ, Sch Med, Boston, MA USA. [Chen, Wendy Y.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Lu, Wei; Zheng, Ying] Shanghai Municipal Ctr Dis Control & Prevent, Shanghai, Peoples R China. [Flatt, Shirley W.; Pierce, John P.] Univ Calif San Diego, Canc Prevent & Control Program, Moores UCSD Canc Ctr, San Diego, CA 92103 USA. RP Shu, XO (reprint author), Vanderbilt Univ, Med Ctr, Vanderbilt Epidemiol Ctr, Div Epidemiol,Dept Med,Sch Med,IMPH, 2525 W End Ave,Suite 600, Nashville, TN 37203 USA. EM xiao-ou.shu@vanderbilt.edu FU National Cancer Institute, NIH [3R01 CA118229-03S1]; Shanghai Breast Cancer Survival Study (Department of Defense) [DAMD 17-02-1-0607]; National Cancer Institute [R01 CA118229]; Women's Healthy Eating & Living Study (Susan G. Komen Foundation) [KG100988]; LACE (National Cancer Institute) [R01 CA129059] FX Supported by the National Cancer Institute, NIH (grant 3R01 CA118229-03S1). The parent grants for each individual cohort included in the After Breast Cancer Pooling Project are as follows: Shanghai Breast Cancer Survival Study (Department of Defense, DAMD 17-02-1-0607; National Cancer Institute, R01 CA118229), Women's Healthy Eating & Living Study (Susan G. Komen Foundation, KG100988), and LACE (National Cancer Institute, R01 CA129059). NR 41 TC 43 Z9 44 U1 1 U2 22 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 JUL PY 2012 VL 96 IS 1 BP 123 EP 132 DI 10.3945/ajcn.112.035972 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 964CA UT WOS:000305670100017 PM 22648714 ER PT J AU Fischer, MJ Xie, DW Jordan, N Kop, WJ Krousel-Wood, M Tamura, MK Kusek, JW Ford, V Rosen, LK Strauss, L Teal, VL Yaffe, K Powe, NR Lash, JP AF Fischer, Michael J. Xie, Dawei Jordan, Neil Kop, Willem J. Krousel-Wood, Marie Tamura, Manjula Kurella Kusek, John W. Ford, Virginia Rosen, Leigh K. Strauss, Louise Teal, Valerie L. Yaffe, Kristine Powe, Neil R. Lash, James P. CA CRIC Study Grp Investigators TI Factors Associated With Depressive Symptoms and Use of Antidepressant Medications Among Participants in the Chronic Renal Insufficiency Cohort (CRIC) and Hispanic-CRIC Studies SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Depression; chronic kidney disease; disparities; antidepressants ID CHRONIC KIDNEY-DISEASE; QUALITY-OF-LIFE; NATIONAL COMORBIDITY SURVEY; BASE-LINE CHARACTERISTICS; HEMODIALYSIS-PATIENTS; DIALYSIS PATIENTS; PRIMARY-CARE; AFRICAN-AMERICANS; MAJOR DEPRESSION; COMMUNITY SAMPLE AB Background: Depressive symptoms are correlated with poor health outcomes in adults with chronic kidney disease (CKD). The prevalence, severity, and treatment of depressive symptoms and potential risk factors, including level of kidney function, in diverse populations with CKD have not been well studied. Study Design: Cross-sectional analysis. Settings & Participants: Participants at enrollment into the Chronic Renal Insufficiency Cohort (CRIC) and Hispanic-CRIC (H-CRIC) Studies. CRIC enrolled Hispanics and non-Hispanics at 7 centers in 2003-2007, and H-CRIC enrolled Hispanics at the University of Illinois in 2005-2008. Measurement: Depressive symptoms measured by Beck Depression Inventory (BDI). Predictors: Demographic and clinical factors. Outcomes: Elevated depressive symptoms (BDI score >= 11) and antidepressant medication use. Results: Of 3,853 participants, 27.4% had evidence of elevated depressive symptoms and 18.2% were using antidepressant medications; 31.0% of persons with elevated depressive symptoms were using antidepressants. The prevalence of elevated depressive symptoms varied by level of kidney function: 23.6% for participants with estimated glomerular filtration rate (eGFR) >= 60 mL/min/1.73 m(2) and 33.8% of those with eGFR <30 mL/min/1.73 m(2). Lower eGFR (OR per 10-mL/min/1.73 m(2) decrease, 1.10; 95% CI, 1.04-1.17), and non-Hispanic black race (OR, 1.42; 95% CI, 1.16-1.74) were each associated with increased odds of elevated depressive symptoms after controlling for other factors. In regression analyses incorporating BDI score, whereas female sex was associated with greater odds of antidepressant use, Hispanic ethnicity, non-Hispanic black race, and higher urine albumin levels were associated with decreased odds of antidepressant use (P < 0.05 for each). Limitations: Absence of clinical diagnosis of depression and use of nonpharmacologic treatments. Conclusions: Although elevated depressive symptoms were common in individuals with CKD, use of antidepressant medications is low. Individuals of racial and ethnic minority background and with more advanced CKD had a greater burden of elevated depressive symptoms and lower use of antidepressant medications. Am J Kidney Dis. 60(1): 27-38. 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 [Fischer, Michael J.; Lash, James P.] Univ Illinois, Med Ctr, Chicago, IL USA. [Fischer, Michael J.; Lash, James P.] Jesse Brown VA Med Ctr, Chicago, IL USA. [Xie, Dawei; Ford, Virginia; Rosen, Leigh K.; Teal, Valerie L.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Jordan, Neil] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Kop, Willem J.] Univ Maryland, Baltimore, MD 21201 USA. [Kop, Willem J.] Tilburg Univ, NL-5000 LE Tilburg, Netherlands. [Krousel-Wood, Marie] Tulane Univ, New Orleans, LA 70118 USA. [Krousel-Wood, Marie] Ochsner Clin Fdn, Ctr Hlth Res, New Orleans, LA USA. [Tamura, Manjula Kurella] Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. [Kusek, John W.] NIDDK, NIH, Bethesda, MD USA. [Strauss, Louise] Univ Hosp Cleveland, Case Med Ctr, Cleveland, OH 44106 USA. [Yaffe, Kristine; Powe, Neil R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. [Powe, Neil R.] San Francisco Gen Hosp, San Francisco, CA 94110 USA. [Fischer, Michael J.; Jordan, Neil] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Ctr Management Complex Chron Care, Hines, IL 60141 USA. RP Fischer, MJ (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Ctr Management Complex Chron Care, 5000 S 5th Ave 151H, Hines, IL 60141 USA. EM fischerm@uic.edu RI Krousel-Wood, Marie Antoinette/D-4718-2011; Kurella Tamura, Manjula/C-8284-2014 OI Kurella Tamura, Manjula/0000-0001-5227-2479 FU National Institute of Diabetes and Digestive and Kidney Diseases [5U01DK060990, 5U01DK060984, 5U01DK06102, 5U01DK061021, 5U01DK061028, 5U01DK60980, 5U01DK060963, 5U01DK060902, R01 DK072231]; Clinical Translational Science Awards (CTSA); National Institutes of Health (NIH) Johns Hopkins University [UL1 RR-025005]; National Institutes of Health (NIH) University of Maryland GRCR [M01 RR-16500]; National Institutes of Health (NIH) Case Western Reserve University Clinical and Translational Science Collaborative (University Hospitals of Cleveland, Cleveland Clinic Foundation, and MetroHealth) [UL1 RR-024989]; National Institutes of Health (NIH) University of Michigan GCRC [M01 RR-000042, CTSA UL1 RR-024986]; National Institutes of Health (NIH) University of Illinois at Chicago Clinical Research Center [M01 RR-013987-06]; National Institutes of Health (NIH) Tulane/LSU/Charity Hospital General Clinical Research Center [RR-05096]; National Institutes of Health (NIH) Kaiser NIH/National Center for Research Resources UCSF-CTSI [UL1 RR-024131, 5K24DK002651] FX In addition to funding under a cooperative agreement from the National Institute of Diabetes and Digestive and Kidney Diseases (5U01DK060990, 5U01DK060984, 5U01DK06102, 5U01DK061021, 5U01DK061028, 5U01DK60980, 5U01DK060963, and 5U01DK060902) and R01 DK072231 (H-CRIC), this work was supported in part by the following institutional Clinical Translational Science Awards (CTSA) and other National Institutes of Health (NIH) grants: Johns Hopkins University UL1 RR-025005, University of Maryland GRCR M01 RR-16500, Case Western Reserve University Clinical and Translational Science Collaborative (University Hospitals of Cleveland, Cleveland Clinic Foundation, and MetroHealth) UL1 RR-024989, University of Michigan GCRC M01 RR-000042, CTSA UL1 RR-024986, University of Illinois at Chicago Clinical Research Center, M01 RR-013987-06, Tulane/LSU/Charity Hospital General Clinical Research Center RR-05096, and Kaiser NIH/National Center for Research Resources UCSF-CTSI UL1 RR-024131, 5K24DK002651. Additional support provided by the National Center for Minority Health and Health Disparities, NIH, and Department of Veterans Affairs Health Services Research and Development Service (Career Development Award to Dr Fischer). NR 49 TC 9 Z9 10 U1 1 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 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD JUL PY 2012 VL 60 IS 1 BP 27 EP 38 DI 10.1053/j.ajkd.2011.12.033 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 960RJ UT WOS:000305406200007 PM 22497791 ER PT J AU Nigwekar, SU Bhan, I Thadhani, R AF Nigwekar, Sagar U. Bhan, Ishir Thadhani, Ravi TI Ergocalciferol and Cholecalciferol in CKD SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Cholecalciferol; chronic kidney disease; end-stage renal disease; ergocalciferol; vitamin D ID CHRONIC KIDNEY-DISEASE; VITAMIN-D DEFICIENCY; NUTRITION EXAMINATION SURVEY; CHRONIC-RENAL-FAILURE; 3RD NATIONAL-HEALTH; AMBULATORY PERITONEAL-DIALYSIS; 25-HYDROXYVITAMIN D LEVELS; SERUM PARATHYROID-HORMONE; D-BINDING PROTEIN; HEMODIALYSIS-PATIENTS AB The development of chronic kidney disease (CKD) is accompanied by a progressive decrease in the ability to produce 1,25-dihydroxyvitamin D. Pharmacological replacement with active vitamin D therefore has been a cornerstone of secondary hyperparathyroidism therapy in the end-stage renal disease population treated by long-term dialysis. Recent evidence suggests that extrarenal conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D may have significant biological roles beyond those traditionally ascribed to vitamin D. Furthermore, low 25-hydroxyvitamin D levels are common in patients with all stages of CKD. This article focuses on the role of nutritional vitamin D replacement in CKD and aims to review vitamin D biology and summarize the existing literature regarding nutritional vitamin D replacement in these populations. Based on the current state of the evidence, we provide suggestions for clinical practice and address areas of uncertainty that need further research. Am J Kidney Dis. 60(1):139-156. (C) 2012 by the National Kidney Foundation, Inc. C1 [Nigwekar, Sagar U.; Bhan, Ishir; Thadhani, Ravi] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [Nigwekar, Sagar U.] Harvard Univ, Sch Med, Clin Sci Program, Boston, MA USA. RP Thadhani, R (reprint author), Massachusetts Gen Hosp, Div Nephrol, Bulfinch 127,55 Fruit St, Boston, MA 02114 USA. EM rthadhani@partners.org FU Abbott Laboratories FX Disclosure: Dr Thadhani has received a research grant from Abbott Laboratories. Drs Nigwekar and Bhan declare that they have no relevant financial interests. NR 174 TC 43 Z9 45 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 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD JUL PY 2012 VL 60 IS 1 BP 139 EP 156 DI 10.1053/j.ajkd.2011.12.035 PG 18 WC Urology & Nephrology SC Urology & Nephrology GA 960RJ UT WOS:000305406200020 PM 22560832 ER PT J AU Siegel, AJ AF Siegel, Arthur J. TI Pheidippides Redux: Reducing Risk for Acute Cardiac Events During Marathon Running SO AMERICAN JOURNAL OF MEDICINE LA English DT Review DE Aspirin prophylaxis; Cardiac arrest; Marathon running ID AMERICAN-HEART-ASSOCIATION; CORONARY-ARTERY-DISEASE; C-REACTIVE PROTEIN; EXERCISE-ASSOCIATED HYPONATREMIA; OF-CARDIOLOGY FOUNDATION; CARDIOVASCULAR-DISEASE; PHYSICAL-ACTIVITY; SUDDEN-DEATH; MYOCARDIAL-INFARCTION; SCIENTIFIC STATEMENT AB Prolonged strenuous exercise such as marathon running transiently increases the absolute and relative risk for sudden cardiac death. A 17-fold increase in the latter over resting baseline in previously sedentary middle-aged men is reduced due to cardioprotection from training in experienced marathon runners. Exertional rhabdomyolysis as a common occurrence during the race is accompanied by neutrophilia and elevated biomarkers of inflammation, including interleukin-6 and C-reactive protein. A hemostatic imbalance with prothrombotic effects includes in vivo platelet activation during the race. Suggesting a pathogenic role for these findings, plaque rupture due to atherothrombosis triggers acute exertional cardiac events, including sudden death, in low-risk runners as in high-risk patients such as those with diabetes mellitus. Strategies including prophylactic aspirin are considered to decrease the risk for acute cardiac events. (C) 2012 Elsevier Inc. All rights reserved. . The American Journal of Medicine (2012) 125, 630-635 C1 [Siegel, Arthur J.] McLean Hosp, Dept Med, Belmont, MA 02478 USA. [Siegel, Arthur J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Siegel, Arthur J.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Siegel, AJ (reprint author), McLean Hosp, Dept Med, 115 Mill St, Belmont, MA 02478 USA. EM asiegel@partners.org NR 71 TC 16 Z9 17 U1 3 U2 14 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 JUL PY 2012 VL 125 IS 7 BP 630 EP 635 DI 10.1016/j.amjmed.2011.11.008 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 965FN UT WOS:000305752700013 PM 22608535 ER PT J AU Wilson, PWF D'Agostino, R Bhatt, DL Eagle, K Pencina, MJ Smith, SC Alberts, MJ Dallongeville, J Goto, S Hirsch, AT Liau, CS Ohman, EM Rother, J Reid, C Mas, JL Steg, G AF Wilson, Peter W. F. D'Agostino, Ralph, Sr. Bhatt, Deepak L. Eagle, Kim Pencina, Michael J. Smith, Sidney C. Alberts, Mark J. Dallongeville, Jean Goto, Shinya Hirsch, Alan T. Liau, Chiau-Suong Ohman, E. Magnus Roether, Joachim Reid, Christopher Mas, Jean-Louis Steg, Gabriel CA REACH Registry TI An International Model to Predict Recurrent Cardiovascular Disease SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Acute coronary syndromes; Cardiovascular disease; Cerebrovascular disease/stroke; Coronary disease; Mortality; Peripheral vascular disease; Risk factors ID SURVIVAL ANALYSIS; CORONARY EVENTS; RISK SCORE; ATHEROTHROMBOSIS; OUTPATIENTS; DISCRIMINATION; POPULATION; VALIDATION; MANAGEMENT; COHORT AB BACKGROUND: Prediction models for cardiovascular events and cardiovascular death in patients with established cardiovascular disease are not generally available. METHODS: Participants from the prospective REduction of Atherothrombosis for Continued Health (REACH) Registry provided a global outpatient population with known cardiovascular disease at entry. Cardiovascular prediction models were estimated from the 2-year follow-up data of 49,689 participants from around the world. RESULTS: A developmental prediction model was estimated from 33,419 randomly selected participants (2394 cardiovascular events with 1029 cardiovascular deaths) from the pool of 49,689. The number of vascular beds with clinical disease, diabetes, smoking, low body mass index, history of atrial fibrillation, cardiac failure, and history of cardiovascular event(s) <1 year before baseline examination increased risk of a subsequent cardiovascular event. Statin (hazard ratio 0.75; 95% confidence interval, 0.69-0.82) and acetylsalicylic acid therapy (hazard ratio 0.90; 95% confidence interval, 0.83-0.99) also were significantly associated with reduced risk of cardiovascular events. The prediction model was validated in the remaining 16,270 REACH subjects (1172 cardiovascular events, 494 cardiovascular deaths). Risk of cardiovascular death was similarly estimated with the same set of risk factors. Simple algorithms were developed for prediction of overall cardiovascular events and for cardiovascular death. CONCLUSIONS: This study establishes and validates a risk model to predict secondary cardiovascular events and cardiovascular death in outpatients with established atherothrombotic disease. Traditional risk factors, burden of disease, lack of treatment, and geographic location all are related to an increased risk of subsequent cardiovascular morbidity and cardiovascular mortality. (C) 2012 Elsevier Inc. All rights reserved. . The American Journal of Medicine (2012) 125, 695-703 C1 [Wilson, Peter W. F.] Emory Univ, Sch Med, Atlanta VAMC, Atlanta, GA 30322 USA. [Wilson, Peter W. F.] Emory Univ, Sch Med, Div Cardiol, Atlanta, GA 30322 USA. [Pencina, Michael J.] Boston Univ, Stat & Consulting Unit, Dept Biostat, Boston, MA 02215 USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. [Eagle, Kim] Univ Michigan, Ctr Cardiovasc, Ann Arbor, MI 48109 USA. [Smith, Sidney C.] Univ N Carolina, Chapel Hill, NC USA. [Alberts, Mark J.] Northwestern Univ, Sch Med, Chicago, IL USA. [Dallongeville, Jean] Inst Pasteur, Lille, France. [Goto, Shinya] Tokai Univ, Sch Med, Dept Med, Hiratsuka, Kanagawa 25912, Japan. [Hirsch, Alan T.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Hirsch, Alan T.] Minneapolis Heart Inst Fdn, Minneapolis, MN USA. [Liau, Chiau-Suong] Natl Taiwan Univ Hosp, Dept Internal Med, Taipei 100, Taiwan. [Liau, Chiau-Suong] Sch Med, Taipei, Taiwan. [Ohman, E. Magnus] Duke Univ, Div Cardiol, Durham, NC USA. [Roether, Joachim] Klinikum Minden, Dept Neurol, Minden, Germany. [Reid, Christopher] Monash Univ, Clayton, Vic 3800, Australia. [Mas, Jean-Louis] Hop St Anne, Ctr Raymond Garcin, Serv Neurol, F-75674 Paris, France. [Steg, Gabriel] INSERM, U 698, Paris, France. [Steg, Gabriel] Univ Paris VII Denis Diderot, Hop Bichat Claude Bernard, Paris, France. RP Wilson, PWF (reprint author), Emory Univ, Sch Med, Atlanta VAMC, 1462 Clifton Rd,Suite 500, Atlanta, GA 30322 USA. EM peter.wf.wilson@emory.edu FU sanofi-aventis; Bristol-Myers Squibb; Waksman Foundation (Tokyo, Japan); Pfizer; Amarin; AstraZeneca; Eisai; Ethicon; Medtronic; Medicines Company; National Heart, Lung, and Blood Institute; R.W. Johnson Foundation; GlaxoSmithKline; Fournier; Bayer; Merck; AGA Medical; Boehringer Ingelheim; Novo Nordisk; Photo Thera; Schering Plough; MSD; MSD-SP; Astellas; Daiichi-Sankyo; Kowa; Novartis; Otsuka; Schering-Plough; Takeda; Ono; Eli Lilly; Abiomed; Data-scope; Inovise; Liposcience; Response Biomedical; Savacor; CV Therapeutics; Servier; Nycomed FX The REACH Registry is sponsored by sanofi-aventis, Bristol-Myers Squibb, and the Waksman Foundation (Tokyo, Japan). The sponsors provide logistical support. All the publication activity is controlled by the REACH Registry Global Publication Committee (Ph. Gabriel Steg, Deepak L. Bhatt, Mark Alberts, Ralph D'Agostino, Kim Eagle, Shinya Goto, Alan T. Hirsch, Chiau-Suong Liau, Jean-Louis Mas, E. Magnus Ohman, Joachim Rother, Sidney C. Smith, and Peter W. F. Wilson). All manuscripts in the REACH Registry are prepared by independent authors who are not governed by the funding sponsors and are reviewed by an academic publication committee before submission. The funding sponsors have the opportunity to review manuscript submissions but do not have authority to change any aspect of a manuscript.; Dr Wilson has received research grants from sanofi-aventis within the last 3 years. Prof. D'Agostino has received consultancy fees from sanofi-aventis and grant support from Pfizer. Dr Bhatt discloses the following relationships: advisory board: Medscape Cardiology; board of directors: Boston VA Research Institute, Society of Chest Pain Centers; chair: American Heart Association Get With The Guidelines Science Subcommittee; honoraria: American College of Cardiology (Editor, Clinical Trials, Cardiosource), Duke Clinical Research Institute (clinical trial steering committees), Slack Publications (Chief Medical Editor, Cardiology Today Intervention), WebMD (CME steering committees); research grants: Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, sanofi-aventis, The Medicines Company; unfunded research: FlowCo, PLx Pharma, Takeda. Dr Eagle has received consulting fees or served on paid advisory boards from the National Heart, Lung, and Blood Institute and the R.W. Johnson Foundation, and received grant support from sanofi-aventis. Dr Pencina has received consultancy fees from sanofi-aventis for work on this project. Dr Smith has received honoraria for consulting or Data and Safety Monitoring Board fees from sanofi-aventis, GlaxoSmithKline, Fournier, and AstraZeneca, and lecture fees for speaking at Continuing Medical Education symposia supported by unrestricted educational grants from Bayer, Pfizer, Merck, and sanofi-aventis. Dr Alberts discloses the following relationships: consultant/advisory board-AGA Medical, AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Diadexus, Eli Lilly & Co, Genentech, KOS, Medicines Company, Merck, Novo Nordisk, PDL Biopharma Inc, Pfizer, Photo Thera, and sanofi-aventis; research grants-AGA Medical, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Novo Nordisk, Photo Thera, sanofi-aventis, and Schering Plough; speaker's bureau-AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Diadexus, Genentech, Medicines Company, Novo Nordisk, PDL Biopharma Inc, and sanofi-aventis; honoraria-AGA Medical, AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Diadexus, Eli Lilly & Co, Genentech, KOS, Medicines Company, Merck, Novo Nordisk, PDL Biopharma Inc, Pfizer, sanofi-aventis, TAP Pharmaceuticals-Data and Safety Monitoring Board, and Schering Plough; review panel-TAP Pharmaceuticals-Data and Safety Monitoring Board, and Schering Plough. Dr Dallongeville has received consulting fees from Bristol-Myers Squibb, MSD, and sanofi-aventis; and lecture fees from MSD-SP and sanofi-aventis; and grant support from Pfizer. Prof. Goto has received honoraria and consulting fees from Astellas, AstraZeneca, Bayer, Bristol-Myers Squibb, Daiichi-Sankyo, Eisai, GlaxoSmithKline, Kowa, Novartis, Otsuka, sanofi-aventis, Schering-Plough, and Takeda. Prof. Goto also received research grants from Eisai, Ono, sanofi-aventis, AstraZeneca, Kowa, and Pfizer within the past 3 years. Dr Hirsch has received research grants from Bristol-Myers Squibb, sanofi-aventis, AstraZeneca, and the National Heart, Lung, and Blood Institute; and consulting fees from Pfizer, Bristol-Myers Squibb, and sanofi-aventis. Prof.; Ohman has received grant support from Bristol-Myers Squibb, The Medicines Company, Eli Lilly, sanofi-aventis, and Schering-Plough; consultancy fees from Abiomed, Data-scope, Inovise, Liposcience, Response Biomedical, Savacor, and The Medicines Company; payment for speaker's bureau from CV Therapeutics and Schering-Plough within the past 3 years; and is a shareholder of Inovise, Medtronic, and Savacor. Prof. Rother has received payment for speakers' bureau and consultancy fees from sanofi-aventis, Boehringer Ingelheim, MSD, and Bristol-Myers Squibb. Dr Mas has received consulting fees from sanofi-aventis, Servier, and Bristol-Myers Squibb; and lecture fees from sanofi-aventis, Bristol-Myers Squibb, and Boehringer Ingelheim. Prof. Steg has received honoraria for advisory board attendance and consulting fees from AstraZeneca, Boehringer Ingelheim, Bayer, Medtronic, GlaxoSmithKline, Merck, Nycomed, sanofi-aventis, Servier, Astellas, and The Medicines Company; and payment for speakers' bureau from Boehringer Ingelheim, Bristol Myers-Squibb, GlaxoSmithKline, Medtronic, Nycomed, sanofi-aventis, and Servier. None of the other authors reported disclosures. NR 22 TC 30 Z9 32 U1 7 U2 11 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 JUL PY 2012 VL 125 IS 7 BP 695 EP + DI 10.1016/j.amjmed.2012.01.014 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 965FN UT WOS:000305752700023 PM 22727237 ER PT J AU Qureshi, AI Palesch, YY Martin, R Novitzke, J Flores, SC Ehtisham, A Goldstein, JN Kirmani, JF Hussein, HM Suri, MFK Tariq, N AF Qureshi, Adnan I. Palesch, Yuko Y. Martin, Renee Novitzke, Jill Flores, Salvador Cruz Ehtisham, Asad Goldstein, Joshua N. Kirmani, Jawad F. Hussein, Haitham M. Suri, M. Fareed K. Tariq, Nauman CA Antihypertensive Treatment Acute C TI Systolic Blood Pressure Reduction and Risk of Acute Renal Injury in Patients with Intracerebral Hemorrhage SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Acute hypertensive response; Acute renal injury; Calcium channel blocker; Intracerebral hemorrhage; Systolic blood pressure ID ANEURYSMAL SUBARACHNOID HEMORRHAGE; ACUTE CEREBRAL-HEMORRHAGE; ACUTE KIDNEY INJURY; INTRAVENOUS NICARDIPINE; COOPERATIVE ANEURYSM; ACUTE HYPERTENSION; SERUM CREATININE; ACUTE STROKE; NEPHROPATHY; ASSOCIATION AB BACKGROUND: Aggressive systolic blood pressure reduction may precipitate acute renal injury because of underlying hypertensive nephropathy in patients with intracerebral hemorrhage. The study's objective was to determine the rate and determinants of acute renal injury during acute hospitalization among subjects with intracerebral hemorrhage using a post hoc analysis of a multicenter prospective study. METHODS: Subjects with intracerebral hemorrhage and elevated systolic blood pressure of 170 mm Hg or greater who presented within 6 hours of symptom onset and underwent treatment of acute hypertensive response and fluid management as per study and local protocols, respectively. Acute renal injury was defined post hoc using the criteria used in Acute Kidney Injury Network classifications within 72 hours of admission. Descriptive statistics and standard statistical tests were used to characterize and evaluate the effect of systolic blood pressure reduction parameters (relative to initial systolic blood pressure) and average maximum hourly dose of nicardipine on the occurrence of acute renal injury. RESULTS: A total of 60 subjects were recruited (57% were men; mean age of 62.0 +/- 15.1 years). Five subjects (9%) had stage I acute renal injury according to the Acute Kidney Injury Network criteria. None of the subjects had stage II or III acute renal injury. The serum creatinine course for the first 3 days suggested that the peak elevation of creatinine was seen at 18, 30, 57, 58, and 71 hours after baseline measurements in these 5 subjects, all of which except for the first one were beyond the protocol-specified treatment period. The incidences of neurologic deterioration and symptomatic hematoma expansion were significantly greater in the subjects with stage I renal impairment. The systolic blood pressure reduction parameters (in particular, the area under the curve depicting the 24-hour systolic blood pressure summary statistic) and the higher average maximum hourly nicardipine dose were strongly associated with stage I renal impairment. CONCLUSIONS: Although acute renal injury is infrequent and mild among subjects with intracerebral hemorrhage undergoing systolic blood pressure reduction, a trend in association between systolic blood pressure reduction and renal impairment was observed in this small study. Therefore, it is important to carefully monitor the renal function when administering treatment to reduce systolic blood pressure in patients with intracerebral hemorrhage. (C) 2012 Elsevier Inc. All rights reserved. circle The American Journal of Medicine (2012) 125, 718.e1-718.e6 C1 [Qureshi, Adnan I.] Univ Minnesota, Dept Neurol, Zeenat Qureshi Stroke Res Ctr, Minneapolis, MN 55455 USA. [Palesch, Yuko Y.; Martin, Renee] Med Univ S Carolina, Div Biostat & Epidemiol, Charleston, SC USA. [Flores, Salvador Cruz] St Louis Univ, Hlth Sci Ctr, St Louis, MO 63103 USA. [Ehtisham, Asad] Univ Kansas, Sch Med, ViaChristi Reg Med Ctr, Neurosci Crit Care Unit, Wichita, KS 67214 USA. [Goldstein, Joshua N.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Kirmani, Jawad F.] John F Kennedy Med Ctr, Inst Neurosci, Edison, NJ USA. RP Qureshi, AI (reprint author), Univ Minnesota, Dept Neurol, Zeenat Qureshi Stroke Res Ctr, 420 Delaware St SE,MMC 295, Minneapolis, MN 55455 USA. EM aiqureshi@hotmail.com RI Goldstein, Joshua/H-8953-2016 FU National Institutes of Health [RO-1-NS44976-01A2, U01 NS054630, U01 NS059041, R01 NS057127, R01 NS062778]; American Heart Association [0840053N]; Minnesota Medical Foundation, Minneapolis; Boehringer-Ingelheim FX National Institutes of Health RO-1-NS44976-01A2 (medication provided by ESP Pharma).; Dr Qureshi has received funding from American Heart Association Established Investigator Award 0840053N, and Minnesota Medical Foundation, Minneapolis. Dr Palesch is funded by the National Institutes of Health U01 NS054630, U01 NS059041, R01 NS057127, and R01 NS062778, and by Boehringer-Ingelheim. NR 27 TC 1 Z9 1 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 EI 1555-7162 J9 AM J MED JI Am. J. Med. PD JUL PY 2012 VL 125 IS 7 AR 718.e1 DI 10.1016/j.amjmed.2011.09.031 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 965FN UT WOS:000305752700028 PM 22560810 ER PT J AU Dominici, LS Lester, S Liao, GS Guo, LF Specht, M Smith, BL Golshan, M AF Dominici, Laura S. Lester, Susan Liao, Guo-Shiou Guo, Life Specht, Michelle Smith, Barbara L. Golshan, Mehra TI Current surgical approach to Paget's disease SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Breast neoplasm; Breast-conserving surgery ID LYMPH-NODE BIOPSY; CARCINOMA IN-SITU; BREAST MRI; NIPPLE; EXPERIENCE; LESIONS; CANCER AB BACKGROUND: Paget's disease constitutes between 1% and 3% of all breast malignancies, which makes defining standard surgical therapy difficult. We sought to identify preoperative factors that would select patients for successful breast conservation. METHODS: Fifty-one patients with Paget's disease underwent surgical therapy between October 1998 and January 2010. Clinical presentation of Paget's disease, preoperative imaging, pathologic tumor characteristics, as well as surgical, radiation, and adjuvant therapies were reviewed. RESULTS: Thirty-seven percent underwent breast conservation whereas 63% underwent mastectomy. Twelve patients presented with a palpable mass, and all were treated with mastectomy. Twenty-two patients underwent a mammogram, identifying extensive abnormality requiring mastectomy. Magnetic resonance imaging added to surgical planning in 52% of patients who participated in the study. None of our patients had a local/regional recurrence at 29 months of follow-up evaluation. CONCLUSIONS: Paget's disease of the breast can be treated with breast conservation in a properly selected subset of patients. Successful breast conservation was achieved in patients without a palpable finding, a benign mammogram, and a normal magnetic resonance imaging scan. (C) 2012 Elsevier Inc. All rights reserved. C1 [Dominici, Laura S.; Golshan, Mehra] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Surg Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA. [Lester, Susan] Brigham & Womens Hosp, Dept Pathol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Liao, Guo-Shiou] Natl Def Med Ctr, Triserv Gen Hosp, Dept Surg, Taipei, Taiwan. [Guo, Life] Brigham & Womens Hosp, Dept Plast Surg, Boston, MA 02115 USA. [Specht, Michelle; Smith, Barbara L.] Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02114 USA. RP Golshan, M (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Surg Oncol,Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. EM mgolshan@partners.org NR 31 TC 6 Z9 7 U1 0 U2 4 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD JUL PY 2012 VL 204 IS 1 BP 18 EP 22 DI 10.1016/j.amjsurg.2011.07.010 PG 5 WC Surgery SC Surgery GA 963VY UT WOS:000305654300004 PM 22036205 ER PT J AU Pierce, DW Pejo, E Raines, DE Forman, SA AF Pierce, David W. Pejo, Ervin Raines, Douglas E. Forman, Stuart A. TI Carboetomidate Inhibits Alpha4/Beta2 Neuronal Nicotinic Acetylcholine Receptors at Concentrations Affecting Animals SO ANESTHESIA AND ANALGESIA LA English DT Article ID D-ASPARTATE RECEPTORS; INHALED ANESTHETICS; ETOMIDATE; SUPPRESS; MEDIATE AB BACKGROUND: Carboetomidate is an etomidate derivative that produces hypnosis without inhibiting adrenal corticosteroid synthesis. Similar to etomidate, carboetomidate modulates gamma-aminobutyric acid type A receptors, but its effects on other ion channel targets of general anesthetics are unknown. METHODS: We compared etomidate and carboetomidate effects on human N-methyl-D-aspartate receptors or neuronal nicotinic acetylcholine receptors (nnAChRs) expressed in Xenopus oocytes, using 2-microelectrode voltage clamp electrophysiology. RESULTS: Etomidate did not affect either type of receptor at clinically relevant concentrations, whereas carboetomidate concentrations near 50% effective concentration for anesthesia significantly inhibited nnAChRs. CONCLUSIONS: Compared with etomidate, carboetomidate's higher hydrophobicity is associated with greater inhibition of nnAChRs. (Anesth Analg 2012;115:70-2) C1 [Pierce, David W.; Pejo, Ervin; Raines, Douglas E.; Forman, Stuart A.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Forman, SA (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Jackson 444,55 Fruit St, Boston, MA 02114 USA. EM saforman@partners.org FU NIH [R01GM089745, R01GM087316]; Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA FX Supported by NIH grants (R01GM089745 to SAF and R01GM087316 to DER) and a summer research internship grant from the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA to DWP. NR 12 TC 2 Z9 4 U1 1 U2 4 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 JUL PY 2012 VL 115 IS 1 BP 70 EP 72 DI 10.1213/ANE.0b013e318254273e PG 3 WC Anesthesiology SC Anesthesiology GA 963DR UT WOS:000305600800015 PM 22543065 ER PT J AU Ehrenfeld, JM Cassedy, EA Forbes, VE Mercaldo, ND Sandberg, WS AF Ehrenfeld, Jesse M. Cassedy, Eva A. Forbes, Victoria E. Mercaldo, Nathaniel D. Sandberg, Warren S. TI Modified Rapid Sequence Induction and Intubation: A Survey of United States Current Practice SO ANESTHESIA AND ANALGESIA LA English DT Article ID CRICOID PRESSURE AB BACKGROUND: Rapid sequence induction and intubation (RSII) is a technique commonly used to resist regurgitation of gastric contents and protect the airway. A modification of this technique is implemented in certain clinical circumstances. However, there is currently no standard definition for a modified RSII. Therefore, we surveyed clinicians at academic centers across the United States to establish a working definition of a modified RSII as well as the clinical scenarios in which it is being used. METHODS: A survey was created that queried the use and definition of modified RSII, and validated with test respondents. We then mailed the survey to all 131 anesthesia residency training programs across the United States. Logistic regression models were created to estimate the percentage of affirmative responses among respondents that performed modified RSII procedures and answered survey items in a consistent manner. Similar quantities were calculated by physician status (resident and attending). RESULTS: Four hundred ninety surveys were received from 58 institutions (44% institution response rate); 93% of respondents reported using a modified RSII, and of those 85% consistently completed the survey instrument. A majority of respondents (71%, Cl: 63%-77%) reported administering oxygen before anesthesia induction, applying cricoid pressure, and attempting to ventilate the lungs via a facemask before securing the airway. Respondents noted that they would use a modified RSII procedure if the patient were either moderately or morbidly obese (each similar to 59%, 53%-64%), had a history but no current symptoms of gastroesophageal reflux disease (52%, 46%-57%), had a hiatal hernia (42%, 36%-48%) or were a trauma patient who had been NPO for at least 8 h (39%, 33%-45%). Similar RSII results were obtained when repeating the analysis on the subset that did not enforce the consistency requirements. CONCLUSIONS: Based on our survey we have established three defining features of a modified RSII: (1) oxygen administration before induction; (2) the use of cricoid pressure; and (3) all attempt to ventilate the patient's lungs before securing the airway. Although this definition seems intuitively obvious, no previous work has tested whether it is commonly accepted. (Anesth Analg 2012;115:95-101) C1 [Ehrenfeld, Jesse M.; Sandberg, Warren S.] Vanderbilt Univ, Dept Anesthesiol, Nashville, TN 37232 USA. [Ehrenfeld, Jesse M.; Sandberg, Warren S.] Vanderbilt Univ, Dept Biomed Informat, Nashville, TN 37232 USA. [Cassedy, Eva A.; Forbes, Victoria E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mercaldo, Nathaniel D.] Vanderbilt Univ, Med Ctr, Dept Biostat, Nashville, TN 37232 USA. RP Ehrenfeld, JM (reprint author), Vanderbilt Univ, Dept Anesthesiol, 1301 Med Ctr Dr,TVC 4648, Nashville, TN 37232 USA. EM jesse.ehrenfeld@vanderbilt.edu OI Ehrenfeld, Jesse/0000-0003-3427-0140 FU Foundation for Anesthesia Education and Research from National Institute of Health [5T32GM007592]; Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital; Department of Anesthesiology, Vanderbilt University School of Medicine FX Financial support for the preparation of this manuscript was provided from a Research Fellowship grant from the Foundation for Anesthesia Education and Research, 5T32GM007592 from the National Institute of Health, as well as by department funds of the Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, and the Department of Anesthesiology, Vanderbilt University School of Medicine. NR 12 TC 17 Z9 18 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD JUL PY 2012 VL 115 IS 1 BP 95 EP 101 DI 10.1213/ANE.0b013e1822dac35 PG 7 WC Anesthesiology SC Anesthesiology GA 963DR UT WOS:000305600800019 PM 22025487 ER PT J AU Zhang, B Sherman, J Xie, ZC AF Zhang, Bin Sherman, Janet Xie, Zhongcong TI Postoperative Cognitive Deficit Might Relate to Intraoperative Hypotension In Response SO ANESTHESIA AND ANALGESIA LA English DT Letter C1 [Zhang, Bin] Beijing Friendship Hosp, Dept Anesthesia, Beijing, Peoples R China. [Zhang, Bin] Capital Med Univ, Beijing, Peoples R China. [Sherman, Janet] Massachusetts Gen Hosp, Psychol Assessment Ctr, Boston, MA 02114 USA. [Sherman, Janet] Harvard Univ, Sch Med, Boston, MA USA. [Xie, Zhongcong] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Charlestown, MA USA. [Xie, Zhongcong] Harvard Univ, Sch Med, Charlestown, MA USA. RP Zhang, B (reprint author), Beijing Friendship Hosp, Dept Anesthesia, Beijing, Peoples R China. EM zxie@partners.org NR 4 TC 0 Z9 0 U1 1 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 JUL PY 2012 VL 115 IS 1 BP 208 EP 208 DI 10.1213/ANE.0b013e3182572906 PG 1 WC Anesthesiology SC Anesthesiology GA 963DR UT WOS:000305600800037 ER PT J AU Berra, L Coppadoro, A Yu, BL Lei, C Spagnolli, E Steinbicker, AU Bloch, KD Lin, T Sammy, FY Warren, S Fernandez, BO Feelisch, M Dzik, WH Stowell, CP Zapol, WM AF Berra, Lorenzo Coppadoro, Andrea Yu, Binglan Lei, Chong Spagnolli, Ester Steinbicker, Andrea U. Bloch, Kenneth D. Lin, Tian Sammy, Fatima Y. Warren, Shaw Fernandez, Bernadette O. Feelisch, Martin Dzik, Walter H. Stowell, Christopher P. Zapol, Warren M. TI Transfusion of Stored Autologous Blood Does Not Alter Reactive Hyperemia Index in Healthy Volunteers SO ANESTHESIOLOGY LA English DT Article ID NITRIC-OXIDE BIOAVAILABILITY; RED-CELL STORAGE; ENDOTHELIAL DYSFUNCTION; VASCULAR FUNCTION; CARDIAC-SURGERY; FREE HEMOGLOBIN; BANKED BLOOD; IN-VIVO; MECHANISM; HEMOLYSIS AB Background: Transfusion of human blood stored for more than 2 weeks is associated with increased mortality and morbidity. During storage, packed erythrocytes progressively release hemoglobin, which avidly binds nitric oxide. We hypothesized that the nitric oxide mediated hyperemic response after ischemia would be reduced after transfusion of packed erythrocytes stored for 40 days. Methods and Results: We conducted a crossover randomized interventional study, enrolling 10 healthy adults. Nine volunteers completed the study. Each volunteer received one unit of 40-day and one of 3-day stored autologous leukoreduced packed erythrocytes, on different study days according to a randomization scheme. Blood withdrawal and reactive hyperemia index measurements were performed before and 10 min, 1 h, 2 h, and 4 h after transfusion. The reactive hyperemia index during the first 4 h after transfusion of 40-day compared with 3-day stored packed erythrocytes was unchanged. Plasma hemoglobin and bilirubin concentrations were higher after transfusion of 40-day than after 3-day stored packed erythrocytes (P = 0.02, [95% CI difference 10-114 mg/l] and 0.001, [95% CI difference 0.6-1.5 mg/dl], respectively). Plasma concentrations of potassium, lactate dehydrogenase, haptoglobin, and cytokines, as well as blood pressure, did not differ between the two transfusions and remained within the normal range. Plasma nitrite concentrations increased after transfusion of 40-day stored packed erythrocytes, but not after transfusion of 3-day stored packed erythrocytes (P = 0.01, [95% CI difference 0.446-0.66 mu M]). Conclusions: Transfusion of autologous packed erythrocytes stored for 40 days is associated with increased hemolysis, an unchanged reactive hyperemia index, and increased concentrations of plasma nitrite. C1 [Berra, Lorenzo; Coppadoro, Andrea; Yu, Binglan; Lei, Chong; Spagnolli, Ester; Steinbicker, Andrea U.; Bloch, Kenneth D.; Zapol, Warren M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Lin, Tian; Sammy, Fatima Y.; Warren, Shaw] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. [Fernandez, Bernadette O.; Feelisch, Martin] Univ Warwick, Sch Med, Dept Med & Biol, Coventry CV4 7AL, W Midlands, England. [Dzik, Walter H.; Stowell, Christopher P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Blood Transfus Serv,Dept Pathol, Boston, MA 02114 USA. RP Zapol, WM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Thier Bldg 503,55 Fruit St, Boston, MA 02114 USA. EM wzapol@partners.org RI Feelisch, Martin/C-3042-2008; OI Feelisch, Martin/0000-0003-2320-1158; Fernandez, Bernadette/0000-0001-6337-0381 FU Medical Research Council [G0701115]; NIDDK NIH HHS [R01 DK082971] NR 35 TC 20 Z9 21 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD JUL PY 2012 VL 117 IS 1 BP 56 EP 63 DI 10.1097/ALN.0b013e31825575e6 PG 8 WC Anesthesiology SC Anesthesiology GA 964DB UT WOS:000305672800010 PM 22531338 ER PT J AU Choi, JC Bakaeen, FG Cornwell, LD Dao, TK Coselli, JS LeMaire, SA Chu, D AF Choi, Justin C. Bakaeen, Faisal G. Cornwell, Lorraine D. Dao, Tam K. Coselli, Joseph S. LeMaire, Scott A. Chu, Danny TI Morbid Obesity Is Associated With Increased Resource Utilization in Coronary Artery Bypass Grafting SO ANNALS OF THORACIC SURGERY LA English DT Article ID BODY-MASS INDEX; AMERICAN-HEART-ASSOCIATION; QUALITY-OF-LIFE; CARDIOVASCULAR-DISEASE; CARDIAC-SURGERY; UNITED-STATES; PHYSICAL-ACTIVITY; OPERATING-ROOM; WEIGHT-LOSS; RISK-FACTOR AB Background. Studies have shown good outcomes for morbidly obese patients who undergo cardiac surgery. However, little is known about how much additional resource utilization treating these challenging patients requires. We hypothesized that morbidly obese patients (body mass index >= 40 kg/m(2)) undergoing coronary artery bypass grafting needed longer operating room times and had longer hospital and intensive care unit stays than non-morbidly obese patients. Methods. We reviewed data from all morbidly obese patients (n = 56, body mass index = 42.7 +/- 2.6 kg/m(2)) who underwent coronary artery bypass grafting at our institution between 1999 and 2009. These patients' outcomes were compared with those of non-morbidly obese patients (n = 168, body mass index = 30.0 +/- 2.8 kg/m(2)) who were propensity-matched 3: 1 with the morbidly obese patients. Results. Of the 14 preoperative characteristics examined, only 1, creatinine level, differed significantly between the two groups (p = 0.02). Intraoperative and postoperative complication rates and the mortality rate were similar between groups (p > 0.09). However, morbidly obese patients had longer operating times (449 +/- 70 versus 420 +/- 59 minutes; p = 0.002), intensive care unit stays (5.2 versus 3.3 days; p < 0.005), and postoperative hospital stays (14.2 versus 9.5 days; p < 0.005) than the non-morbidly obese patients. Conclusions. Although good outcomes can be achieved for morbidly obese patients who undergo coronary artery bypass grafting, these patients require considerably more resource utilization in the operating room and intensive care unit, and they spend more time in the hospital after surgery. At a cardiac surgical operating room cost of approximately $50 per minute and $4,500 per intensive care unit day, the financial implications for morbidly obese patients who need coronary artery bypass grafting are not insignificant. C1 [Chu, Danny] Baylor Coll Med, Texas Heart Inst, Michael E DeBakey Vet Affairs Med Ctr, Dept Surg,Div Cardiothorac Surg, Houston, TX 77030 USA. Baylor Coll Med, Michael E DeBakey Dept Surg, Div Cardiothorac Surg, Houston, TX 77030 USA. St Lukes Episcopal Hosp, Texas Heart Inst, Div Cardiovasc Surg, Houston, TX USA. Univ Houston, Dept Educ Psychol, Houston, TX USA. RP Chu, D (reprint author), Baylor Coll Med, Texas Heart Inst, Michael E DeBakey Vet Affairs Med Ctr, Dept Surg,Div Cardiothorac Surg, 2002 Holcombe Blvd,OCL 112, Houston, TX 77030 USA. EM dchu@bcm.edu NR 39 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JUL PY 2012 VL 94 IS 1 BP 23 EP 28 DI 10.1016/j.athoracsur.2012.03.036 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 965XS UT WOS:000305801600014 PM 22607785 ER PT J AU Salhab, KF Said, SM Sundt, TM AF Salhab, Khaled F. Said, Sameh M. Sundt, Thoralf M., III TI Pseudocoarctation of the Aorta Secondary to Aortic Intimal Sarcoma SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material ID OF-THE-LITERATURE; ANGIOSARCOMA AB We describe a case of a 66-year-old woman who presented with upper extremity hypertension and a pseudocoarctation-like picture secondary to an aortic arch intimal sarcoma. (Ann Thorac Surg 2012;94:279-81) (C) 2012 by The Society of Thoracic Surgeons C1 [Salhab, Khaled F.] Mayo Clin, Div Cardiovasc Surg, Rochester, MN 55905 USA. Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. RP Salhab, KF (reprint author), Mayo Clin, Div Cardiovasc Surg, 200 1st St SW, Rochester, MN 55905 USA. EM salhab.khaled@mayo.edu NR 7 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 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JUL PY 2012 VL 94 IS 1 BP 279 EP 281 DI 10.1016/j.athoracsur.2011.08.088 PG 3 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 965XS UT WOS:000305801600056 PM 22734995 ER PT J AU Dai, TH Garcia, B Murray, CK Vrahas, MS Hamblin, MR AF Dai, Tianhong Garcia, Barbara Murray, Clinton K. Vrahas, Mark S. Hamblin, Michael R. TI UVC Light Prophylaxis for Cutaneous Wound Infections in Mice SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID SOFT-TISSUE INFECTIONS; TARGETED PHOTODYNAMIC THERAPY; NO ESKAPE; IN-VIVO; SKIN; INACTIVATION; MILITARY; BACTERIA; AFGHANISTAN; PATHOGENS AB UVC light has long been known to be highly germicidal but has not been much developed as a therapy for infections. This study investigated the potential of UVC light for the prophylaxis of infections developing in highly contaminated superficial cutaneous wounds. In vitro studies demonstrated that the pathogenic bacteria Pseudomonas aeruginosa and Staphylococcus aureus were inactivated at UVC light exposures much lower than those needed for a similar effect on mammalian keratinocytes. Mouse models of partial-thickness skin abrasions infected with bioluminescent P. aeruginosa and S. aureus were developed. Approximately 10(7) bacterial cells were inoculated onto wounds measuring 1.2 by 1.2 cm on the dorsal surfaces of mice. UVC light was delivered at 30 min after bacterial inoculation. It was found that for both bacterial infections, UVC light at a single radiant exposure of 2.59 J/cm(2) reduced the bacterial burden in the infected mouse wounds by approximately 10-fold in comparison to those in untreated mouse wounds (P < 0.00001). Furthermore, UVC light increased the survival rate of mice infected with P. aeruginosa by 58.3% (P = 0.0023) and increased the wound healing rate in mice infected with S. aureus by 31.2% (P < 0.00001). DNA lesions were observed in the UVC light-treated mouse wounds; however, the lesions were extensively repaired by 48 h after UVC light exposure. These results suggested that UVC light may be used for the prophylaxis of cutaneous wound infections. C1 [Dai, Tianhong; Garcia, Barbara; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Dai, Tianhong; Garcia, Barbara; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Murray, Clinton K.] Brooke Army Med Ctr, Infect Dis Serv, Ft Sam Houston, TX 78234 USA. [Vrahas, Mark S.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu OI Hamblin, Michael/0000-0001-6431-4605 FU Airlift Research Foundation Extremity Trauma research grant [109421]; COTA/Smith Nephew grant [2012-16]; NIH [RO1AI050875] FX This study was supported in part by an Airlift Research Foundation Extremity Trauma research grant (109421 to T.D.), by a COTA/Smith & Nephew grant (2012-16 to T.D.), and by the NIH (grant RO1AI050875 to M.R.H.). We have no conflict of interest. NR 39 TC 11 Z9 11 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUL PY 2012 VL 56 IS 7 BP 3841 EP 3848 DI 10.1128/AAC.00161-12 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 964DD UT WOS:000305673000050 PM 22564833 ER PT J AU Napadow, V Kim, J Clauw, DJ Harris, RE AF Napadow, Vitaly Kim, Jieun Clauw, Daniel J. Harris, Richard E. TI Decreased intrinsic brain connectivity is associated with reduced clinical pain in fibromyalgia SO ARTHRITIS AND RHEUMATISM LA English DT Article ID ACUPUNCTURE; GLUTAMATE; NETWORKS; DEFAULT; DISEASE AB Objective A major impediment to the development of novel treatment strategies for fibromyalgia (FM) is the lack of an objective marker that reflects spontaneously reported clinical pain in patients with FM. Studies of resting-state intrinsic brain connectivity in FM have demonstrated increased insular connectivity to the default mode network (DMN), a network whose activity is increased during nontask states. Moreover, increased insular connectivity to the DMN was associated with increased spontaneous pain levels. However, as these analyses were cross-sectional in nature, they provided no insight into dynamic changes in connectivity or their relationship to variations in self-reported clinical pain. The purpose of this study was to evaluate longitudinal changes in the intrinsic brain connectivity of FM patients treated with nonpharmacologic interventions known to modulate pain levels in this patient population, and to test the hypothesis that the reduction of DMNinsula connectivity following therapy would correlate with diminished pain. Methods Seventeen FM patients underwent resting-state functional magnetic resonance imaging at baseline and following 4 weeks of a nonpharmacologic intervention to diminish pain. Intrinsic DMN connectivity was evaluated using probabilistic independent components analysis. Longitudinal changes in intrinsic DMN connectivity were evaluated by paired analysis, and correlations between longitudinal changes in clinical pain and changes in intrinsic DMN connectivity were investigated by multiple linear regression analysis. Changes in clinical pain were assessed with the short form of the McGill Pain Questionnaire (SF-MPQ). Results Clinical pain as assessed using the sensory scale of the SF-MPQ was reduced following therapy (P = 0.02). Intrinsic DMN connectivity to the insula was reduced, and this reduction correlated with reductions in pain (corrected P < 0.05). Conclusion Our findings suggest that intrinsic brain connectivity can be used as a candidate objective marker that reflects changes in spontaneous chronic pain within individual FM patients. We propose that intrinsic connectivity measures could potentially be used in either research or clinical settings as a complementary, more objective outcome measure for use in FM. C1 [Napadow, Vitaly; Kim, Jieun] Massachusetts Gen Hosp, Charlestown, MA USA. [Napadow, Vitaly] Logan Coll Chiropract, Chesterfield, MO USA. [Clauw, Daniel J.; Harris, Richard E.] Univ Michigan, Ann Arbor, MI 48109 USA. RP Napadow, V (reprint author), Martinos Ctr Biomed Imaging, 149 13th St 2301, Charlestown, MA 02129 USA. EM vitaly@nmr.mgh.harvard.edu FU National Center for Complementary and Alternative Medicine, NIH [R01-AT-004714, P01-AT-002048, P01-AT-006663, R01-AT-005280, K01-AT-01111]; Department of the Army [DAMD W81XWH-07-2-0050]; Dana Foundation; Cypress Biosciences; Eli Lilly; Forest Laboratories; Jazz Pharmaceuticals; Merck; UCB; Pierre Fabre Pharmaceuticals; Pfizer FX Supported by grants from the National Center for Complementary and Alternative Medicine, NIH (grants R01-AT-004714, P01-AT-002048, P01-AT-006663, R01-AT-005280, and K01-AT-01111). Dr. Harris' work was also supported by the Department of the Army (grant DAMD W81XWH-07-2-0050) and a Dana Foundation award in brain and immunoimaging.; Dr. Clauw has received consulting fees, speaking fees, and/or honoraria from Cypress Biosciences, Eli Lilly, Forest Laboratories, Jazz Pharmaceuticals, Merck, UCB, Pierre Fabre Pharmaceuticals, and Pfizer (more than $10,000 each) and has received grant funding from Merck and Forest Laboratories. Dr. Harris has received consulting fees from Pfizer (less than $10,000) and has received grant funding from Pfizer. NR 16 TC 79 Z9 81 U1 1 U2 14 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 JUL PY 2012 VL 64 IS 7 BP 2398 EP 2403 DI 10.1002/art.34412 PG 6 WC Rheumatology SC Rheumatology GA 965CD UT WOS:000305742800036 PM 22294427 ER PT J AU Schumacher, HR AF Schumacher, H. Ralph, Jr. TI The need to compare rilonacept against active treatment for prevention of gout flares: comment on the article by Schumacher et al Reply SO ARTHRITIS AND RHEUMATISM LA English DT Letter ID ARTHRITIS C1 [Schumacher, H. Ralph, Jr.] Univ Penn, Philadelphia, PA 19104 USA. [Schumacher, H. Ralph, Jr.] Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Schumacher, HR (reprint author), Univ Penn, Philadelphia, PA 19104 USA. NR 2 TC 0 Z9 0 U1 1 U2 3 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 JUL PY 2012 VL 64 IS 7 BP 2416 EP 2416 DI 10.1002/art.34475 PG 1 WC Rheumatology SC Rheumatology GA 965CD UT WOS:000305742800041 ER PT J AU Kimball, AB Papp, KA Wasfi, Y Chan, D Bissonnette, R Sofen, H Yeilding, N Li, S Szapary, PO Gordon, KB AF Kimball, A. B. Papp, K. A. Wasfi, Y. Chan, D. Bissonnette, R. Sofen, H. Yeilding, N. Li, S. Szapary, P. O. Gordon, K. B. CA Phoenix Investigators TI Long-term efficacy and safety of ustekinumab in patients with moderate to severe psoriasis through 5 years of follow-up: results from the PHOENIX 1 long-term extension SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the British-Association-of-Dermatologists CY JUL 03-05, 2012 CL Birmingham, ENGLAND SP British Assoc Dermatol C1 [Kimball, A. B.] Harvard Univ, Sch Med, Boston, MA USA. [Kimball, A. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Papp, K. A.] Prob Med Res, Waterloo, ON, Canada. [Wasfi, Y.; Chan, D.; Yeilding, N.; Li, S.; Szapary, P. O.] Janssen Res & Dev LLC, Spring House, PA USA. [Bissonnette, R.] Innovaderm Res Inc, Montreal, PQ, Canada. [Sofen, H.] Dermatol Res Associates, Los Angeles, CA USA. [Gordon, K. B.] N Shore Univ Hlth Syst, Chicago, IL USA. [Gordon, K. B.] Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-0963 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD JUL PY 2012 VL 167 SU 1 SI SI BP 63 EP 64 PG 2 WC Dermatology SC Dermatology GA 967WU UT WOS:000305939600132 ER PT J AU Liel, MS Greenberg, DL Recht, M Vanek, C Klein, RF Taylor, JA AF Liel, Meghan S. Greenberg, Daniel L. Recht, Michael Vanek, Chaim Klein, Robert F. Taylor, Jason A. TI Decreased bone density and bone strength in a mouse model of severe factor VIII deficiency SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Letter DE haemophilia; factor VIII; bone density; osteoporosis ID HEMOPHILIA; OSTEOPOROSIS; RISK C1 [Liel, Meghan S.; Greenberg, Daniel L.; Recht, Michael; Taylor, Jason A.] Oregon Hlth & Sci Univ, Hemophilia Ctr, Portland, OR 97201 USA. [Liel, Meghan S.; Klein, Robert F.; Taylor, Jason A.] Portland VA Med Ctr, Med Serv, Portland, OR USA. [Vanek, Chaim; Klein, Robert F.] Oregon Hlth & Sci Univ, Bone & Mineral Res Unit, Portland, OR 97201 USA. RP Liel, MS (reprint author), Oregon Hlth & Sci Univ, Hemophilia Ctr, Portland, OR 97201 USA. EM taylojas@ohsu.edu NR 10 TC 10 Z9 10 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUL PY 2012 VL 158 IS 1 BP 140 EP 143 DI 10.1111/j.1365-2141.2012.09101.x PG 4 WC Hematology SC Hematology GA 956ZC UT WOS:000305127100015 PM 22469061 ER PT J AU Burke, MN Hermiller, J Jaff, MR AF Burke, M. Nicholas Hermiller, James Jaff, Michael R. TI StarClose (R) vascular closure system (VCS) is safe and effective in patients who ambulate early following successful femoral artery access closureuresults from the RISE clinical trial SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE catheterization; femoral access; vessel closure; vascular complications; ambulation time ID CARDIAC-CATHETERIZATION; CORONARY ANGIOPLASTY; COMPLICATIONS; REGISTRY; DEVICES AB Objective: The RISE study was a prospective, multicenter, single-arm study evaluating the safety and efficacy of the StarClose (R) Vascular Closure System (VCS) in the femoral artery in subjects who were ambulated early following percutaneous diagnostic coronary or peripheral catheterization procedures. Background: Previous studies have demonstrated that several vascular closure devices are able to safely decrease the amount of bedrest needed following angiography. To date, no device has been shown to be safe for immediate ambulation. Methods: Between April 2006 and November 2006, 315 patients undergoing a catheterization via the femoral artery were enrolled (intent-to-treat population, ITT). Of these, 171 subjects were not excluded by angiographic or clinical criteria and had a StarClose device placed to attain hemostasis. If hemostasis was immediately achieved, patients were ambulated within 20 min for 20 feet without assistance (per-protocol population, PP). Patients were followed for 30 days after the index procedure. The primary endpoint of the study was time to ambulation (TTA). Results: Immediate hemostasis was achieved in 156 patients (91.2%). The mean TTA in the PP was 8.29 min, median 5.92. There were no deaths or major vascular complications, and the rate of minor vascular complications was 1.9% (3/156). Conclusion: The StarClose (R) VCS device is both safe and effective allowing immediate ambulation of patients who have undergone catheterization via the femoral artery. (c) 2011 Wiley Periodicals, Inc. C1 [Burke, M. Nicholas] Abbott NW Hosp, Minneapolis Heart Inst Fdn, Minneapolis, MN 55407 USA. [Hermiller, James] St Vincents Hosp, Indianapolis, IN USA. [Jaff, Michael R.] Massachusetts Gen Hosp, Dept Med, Div Cardiovasc Med, Boston, MA 02114 USA. [Jaff, Michael R.] Massachusetts Gen Hosp, Vasc Ultrasound Core Lab, Boston, MA 02114 USA. RP Burke, MN (reprint author), Minneapolis Heart Inst, 920 E 28th St,Suite 300, Minneapolis, MN 55407 USA. EM nburke@mplsheart.com FU Abbott Vascular FX Grant sponsor: Abbott Vascular NR 17 TC 8 Z9 8 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD JUL 1 PY 2012 VL 80 IS 1 BP 45 EP 52 DI 10.1002/ccd.23176 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 964KC UT WOS:000305692100007 PM 22162141 ER PT J AU Lu, WD Wayne, PM Davis, RB Buring, JE Li, HL Goguen, LA Rosenthal, DS Tishler, RB Posner, MR Haddad, RI AF Lu, Weidong Wayne, Peter M. Davis, Roger B. Buring, Julie E. Li, Hailun Goguen, Laura A. Rosenthal, David S. Tishler, Roy B. Posner, Marshall R. Haddad, Robert I. TI Acupuncture for dysphagia after chemoradiation in head and neck cancer: Rationale and design of a randomized, sham-controlled trial SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE Acupuncture; Chemoradiation therapy; Head and neck cancer; Dysphagia; MDADI; Randomized sham-controlled trial ID QUALITY-OF-LIFE; SALIVARY FLOW-RATES; INTENSITY-MODULATED RADIOTHERAPY; PERFORMANCE STATUS SCALE; LOCALLY ADVANCED HEAD; OROPHARYNGEAL CANCER; CONVENTIONAL RADIOTHERAPY; POSTSTROKE PATIENTS; RADIATION-THERAPY; CLINICAL-TRIALS AB Introduction: Dysphagia is a common side effect following chemoradiation therapy (CRT) in head and neck cancer (HNC) patients. Current dysphagia management includes swallowing therapy and dilation procedures, but these treatments have limitations. While acupuncture has been reported to positively impact swallowing function and quality of life (QOL) in patients with dysphagia, current evidence is inconclusive. Material and methods: In an ongoing trial, 42 squamous cell carcinoma HNC patients, who are receiving platinum-based CRT with curative intent, are being recruited from a comprehensive cancer center. They are randomized to 12 sessions of either active acupuncture or to sham acupuncture during and following CRT over a 24-week period. Blinded research staff assesses outcomes at baseline, 20 weeks post-CRT (end of acupuncture), and 12 months after baseline (6-month follow-up). The primary outcome is change in M.D. Anderson Dysphagia Inventory score from baseline to 12 months. Secondary outcomes include QOL measures pertaining to HNC patients. In addition, a subset of study patients are tested for salivary flow rates and cytokines, including plasma transforming growth factor-beta 1 and interleukin 6 (n = 10 per arm), to preliminarily explore the biological mechanisms of acupuncture for dysphagia. Discussion: This paper addresses unique challenges related to study design in nonpharmacological, sham-controlled acupuncture trials including development of evidence-based credible verum and sham treatment protocols, blinding, and assuring fidelity of treatment. Results of this study will inform the feasibility of conducting a large scale trial and will provide preliminary evidence regarding the value of acupuncture for dysphagia in HNC patients. (C) 2012 Elsevier Inc. All rights reserved. C1 [Lu, Weidong; Rosenthal, David S.] Dana Farber Canc Inst, Leonard P Zakim Ctr Integrat Therapies, Boston, MA 02215 USA. [Wayne, Peter M.; Buring, Julie E.] Brigham & Womens Hosp, Osher Ctr Integrat Med, Boston, MA 02115 USA. [Wayne, Peter M.; Buring, Julie E.] Harvard Univ, Sch Med, Boston, MA USA. [Davis, Roger B.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Li, Hailun] Dana Farber Harvard Canc Ctr, Boston, MA USA. [Goguen, Laura A.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Tishler, Roy B.; Posner, Marshall R.; Haddad, Robert I.] Dana Farber Canc Inst, Head & Neck Oncol Program, Boston, MA 02215 USA. RP Lu, WD (reprint author), Dana Farber Canc Inst, Leonard P Zakim Ctr Integrat Therapies, 450 Brookline Ave, Boston, MA 02215 USA. EM weidong_lu@dfci.harvard.edu; peter_wayne@hms.harvard.edu; rdavis@bidmc.harvard.edu; jburing@rics.bwh.harvard.edu; hailunli@jimmy.harvard.edu; lgoguen@partners.org; drose@uhs.harvard.edu; rtishler@lroc.harvard.edu; marshall.posner@mssm.edu; Robert_Haddad@dfci.harvard.edu RI Lu, Weidong/C-3844-2008 OI Lu, Weidong/0000-0003-2838-6307 FU National Center for Complementary and Alternative Medicine (NCCAM) [1K01 AT004415] FX This study is supported by grant 1K01 AT004415 from the National Center for Complementary and Alternative Medicine (NCCAM). NR 72 TC 7 Z9 7 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD JUL PY 2012 VL 33 IS 4 BP 700 EP 711 DI 10.1016/j.cct.2012.02.017 PG 12 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 964QL UT WOS:000305711700020 PM 22406102 ER PT J AU Frank, AJ Sheu, CC Zhao, Y Chen, F Su, L Gong, MN Bajwa, E Thompson, BT Christiani, DC AF Frank, Angela J. Sheu, Chau-Chyun Zhao, Yang Chen, Feng Su, Li Gong, Michelle N. Bajwa, Ednan Thompson, B. Taylor Christiani, David C. TI BCL2 genetic variants are associated with acute kidney injury in septic shock SO CRITICAL CARE MEDICINE LA English DT Article DE acute kidney injury; apoptosis; BCL2; genetic susceptibility; sepsis; SERPINA4 ID ACUTE-RENAL-FAILURE; CRITICALLY-ILL PATIENTS; INTENSIVE-CARE UNITS; PROTEIN-C INHIBITOR; CLINICAL CHARACTERISTICS; MULTICENTER EVALUATION; ADVERSE OUTCOMES; OXIDATIVE STRESS; SEVERE SEPSIS; KALLISTATIN AB Objective: Acute kidney injury frequently complicates septic shock and independently predicts mortality in this population. Clinical factors alone do not entirely account for differences in risk of acute kidney injury between patients. Genetic variants are likely to explain this differential susceptibility. To identify genetic variants linked to acute kidney injury susceptibility, we conducted a high-density genotyping association study in a large population of patients with septic shock. Design: Retrospective study. Setting: Tertiary academic medical center. Patients: One thousand two hundred and sixty-four patients with septic shock were analyzed to elucidate clinical risk factors associated with the development of acute kidney injury. Among them, 887 Caucasian patients were randomly split into discovery and validation cohorts and genotyped using the Illumina Human-CVD Bead Chip (Illumina, San Diego, CA). Interventions: None. Measurements and Main Results: Six hundred and twenty-seven of the 1,264 patients with septic shock and 441 of the 887 patients with genotyping data developed acute kidney injury within the first 72 hrs of intensive care unit admission. Five single nucleotide polymorphisms were associated with acute kidney injury in both the discovery and validation cohorts. Two of these were in the BCL2 gene and both were associated with a decreased risk of acute kidney injury (rs8094315: odds ratio 0.61, p = .0002; rs12457893: odds ratio 0.67, p = .0002, both for combined data). Bcl-2 is involved in the apoptosis pathway, which has previously been implicated in acute kidney injury. Another single nucleotide polymorphism was in the SERPINA4 gene, whose protein product, kallistatin, has been linked to apoptosis in the kidney. Conclusions: Large-scale genotyping reveals two single nucleotide polymorphisms in the BCL2 gene and a single nucleotide polymorphism in the SERPINA4 gene associated with a decreased risk of developing acute kidney injury, supporting the putative role of apoptosis in the pathogenesis of acute kidney injury. (Crit Care Med 2012; 40:2116-2123) C1 [Frank, Angela J.; Sheu, Chau-Chyun; Zhao, Yang; Chen, Feng; Su, Li; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Frank, Angela J.; Bajwa, Ednan; Thompson, B. Taylor; Christiani, David C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pulm & Crit Care Unit,Dept Med, Boston, MA 02115 USA. [Sheu, Chau-Chyun] Kaohsiung Med Univ, Kaohsiung Med Univ Hosp, Div Pulm & Crit Care Med, Kaohsiung, Taiwan. [Gong, Michelle N.] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Med, Div Crit Care Med, Bronx, NY 10467 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Bldg 1,14th Floor,665 Huntington Ave, Boston, MA 02115 USA. EM dchris@hsph.harvard.edu FU NIH [R01HL60710, ES00002, T32HL07874] FX Supported, in part, by NIH grants R01HL60710, ES00002, and T32HL07874. NR 58 TC 16 Z9 18 U1 0 U2 2 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 JUL PY 2012 VL 40 IS 7 BP 2116 EP 2123 DI 10.1097/CCM.0b013e3182514bca PG 8 WC Critical Care Medicine SC General & Internal Medicine GA 965KX UT WOS:000305767800015 PM 22710204 ER PT J AU Singal, G Currier, P AF Singal, Gaurav Currier, Paul TI How can we best use electronic data to find and treat the critically ill? SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE electronic alerts; natural language processing; sepsis; septic shock; systemic inflammatory response C1 [Singal, Gaurav; Currier, Paul] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Singal, G (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 9 TC 2 Z9 2 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JUL PY 2012 VL 40 IS 7 BP 2242 EP 2243 DI 10.1097/CCM.0b013e318256b99b PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 965KX UT WOS:000305767800040 PM 22710217 ER PT J AU Kacmarek, RM Villar, J AF Kacmarek, Robert M. Villar, Jesus TI The chest wall: The all too commonly forgotten cause of pulmonary dysfunction SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE acute respiratory distress syndrome; chest wall elastance; plateau pressure; transpulmonary pressure ID RESPIRATORY-DISTRESS-SYNDROME; TRANSPULMONARY PRESSURE; INTRAABDOMINAL HYPERTENSION; MECHANICAL VENTILATION; ESOPHAGEAL; PLATEAU C1 [Kacmarek, Robert M.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. [Kacmarek, Robert M.] Harvard Univ, Dept Anesthesia, Boston, MA 02115 USA. [Villar, Jesus] Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain. [Villar, Jesus] Hosp Univ Dr Negrin, Multidisciplinary Organ Dysfunct Evaluat Res Netw, Res Unit, Las Palmas Gran Canaria, Spain. RP Kacmarek, RM (reprint author), Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. NR 11 TC 0 Z9 0 U1 2 U2 2 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 JUL PY 2012 VL 40 IS 7 BP 2258 EP 2259 DI 10.1097/CCM.0b013e318256b974 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 965KX UT WOS:000305767800050 PM 22710227 ER PT J AU Jati, A Tatli, S Morgan, JA Glickman, JN Demetri, GD Van den Abbele, A Silverman, SG AF Jati, Anupma Tatli, Servet Morgan, Jeffrey A. Glickman, Jonathan N. Demetri, George D. Van den Abbele, Annick Silverman, Stuart G. TI Imaging features of bone metastases in patients with gastrointestinal stromal tumors SO DIAGNOSTIC AND INTERVENTIONAL RADIOLOGY LA English DT Article DE gastrointestinal stromal tumors; metastases; bone; positron-emission tomography and computed tomography ID PROGNOSIS AB PURPOSE To determine the prevalence and imaging features, of bone: metastases in patients with gastrointestinal stromal tumors (GISTs). MATERIALS AND METHODS The medical records of 190 'patients with pathologically proven GISTs were reviewed, and patients with bone metastases were identified. Computed tomography (CT) scans of the chest, abdomen, and pelvis were examined for features of bone metastases, and findings were correlated with the results of positron-emission tomography (PET) and histopathology. RESULTS Of 190 GIST patients, six (3.2%) had bone metastases: four patients had multiple bone metastases, and two patients had a solitary metastasis. The maximum diameter of the metastases ranged from 2 to 40 mm, and they most commonly involved the vertebrae, ribs, pelvic bone's, and femurs: All lesions were well-marginated and lytic. A soft tissue component was identified in three patients. The bone metastases showed intense fluorine-18 fluorodeoxyglucose..:(FOG) uptake. After treatment with imatinib mesylate in three patients, the bone metastases developed peripheral sclerosis on CT and became, less FOG-avid on PET. All six primary tumors were morphologically high-grade with high mitotic rates and necrosis. CONCLUSION Bone metastases from GISTs are uncommon; when detected with CT, they are characterized by single of multiple lytic lesions with or without soft tissue involvement. A sclerotic rim may appear around the metastatic lesions in response to treatment. Similar to the disease in other sites bone metastases show intense FDG uptake, which decreases following :treatment. C1 [Tatli, Servet; Silverman, Stuart G.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Glickman, Jonathan N.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Jati, Anupma; Van den Abbele, Annick] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. [Morgan, Jeffrey A.; Demetri, George D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Oncol, Boston, MA 02115 USA. RP Tatli, S (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. EM statli@partners.org NR 15 TC 10 Z9 10 U1 0 U2 3 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 JUL-AUG PY 2012 VL 18 IS 4 BP 391 EP 396 DI 10.4261/1305-3825.DIR.5179-11.1 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 964VR UT WOS:000305725300008 PM 22407696 ER PT J AU Kaunitz, JD AF Kaunitz, Jonathan D. TI Digestive Diseases and Sciences: Sadness, Satisfaction, and Sanguinity SO DIGESTIVE DISEASES AND SCIENCES LA English DT Editorial Material C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Greater Los Angeles VA Hlth Care Syst, Los Angeles, CA 90095 USA. RP Kaunitz, JD (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Greater Los Angeles VA Hlth Care Syst, Los Angeles, CA 90095 USA. EM Jonathan.Kaunitz@va.gov NR 4 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD JUL PY 2012 VL 57 IS 7 BP 1742 EP 1744 DI 10.1007/s10620-012-2287-0 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 965DH UT WOS:000305746100002 ER PT J AU Iezzoni, LI Long-Bellil, LM AF Iezzoni, Lisa I. Long-Bellil, Linda M. TI Training physicians about caring for persons with disabilities: "Nothing about us without us!" SO DISABILITY AND HEALTH JOURNAL LA English DT Article DE Disability; Physicians; Medical education; World Report on Disability ID HEALTH; CARE AB According to the World Report on Disability, physicians worldwide generally lack training about caring for persons with disabilities, thus frequently compromising their health care experiences and health outcomes. Many U. S. physicians are similarly untrained about critical aspects of providing care to persons with disabilities, perhaps contributing to disparities in their care. Recognizing these inadequacies, U. S. medical educators are beginning to develop core competencies for trainees relating to the care of patients with disabilities, including understanding patients' perceptions of their quality of life and skills in providing patient-centered care. Having today's physicians, even when genuinely well-intentioned, retain control over designing disability-related training programs for future doctors may miss critical issues in caring empathically and effectively for persons with disabilities. Involving persons with disabilities in identifying training needs and implementing curricula for future physicians may offer important opportunities for ensuring their competency to provide patient-entered care to persons with disabilities. (C) 2012 Elsevier Inc. All rights reserved. C1 [Iezzoni, Lisa I.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Long-Bellil, Linda M.] Univ Massachusetts, Sch Med, Ctr Hlth Policy & Res, Disabil Hlth & Employment Policy Unit, Shrewsbury, MA USA. RP Iezzoni, LI (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mongan Inst Hlth Policy, 50 Staniford St,Room 901B, Boston, MA 02114 USA. EM liezzoni@partners.org NR 22 TC 7 Z9 7 U1 5 U2 18 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-6574 J9 DISABIL HEALTH J JI Disabil. Health J. PD JUL PY 2012 VL 5 IS 3 BP 136 EP 139 DI 10.1016/j.dhjo.2012.03.003 PG 4 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health; Rehabilitation SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Rehabilitation GA 965FD UT WOS:000305751500004 PM 22726853 ER PT J AU Koncarevic, A Kajimura, S Cornwall-Brady, M Andreucci, A Pullen, A Sako, D Kumar, R Grinberg, AV Liharska, K Ucran, JA Howard, E Spiegelman, BM Seehra, J Lachey, J AF Koncarevic, Alan Kajimura, Shingo Cornwall-Brady, Milton Andreucci, Amy Pullen, Abigail Sako, Dianne Kumar, Ravindra Grinberg, Asya V. Liharska, Katia Ucran, Jeffrey A. Howard, Elizabeth Spiegelman, Bruce M. Seehra, Jasbir Lachey, Jennifer TI A Novel Therapeutic Approach to Treating Obesity through Modulation of TGF beta Signaling SO ENDOCRINOLOGY LA English DT Article ID BROWN ADIPOSE-TISSUE; DIET-INDUCED OBESITY; MODEST WEIGHT-LOSS; RECEPTOR-TYPE IIB; ACTIVIN RECEPTOR; HIGH-FAT; INSULIN SENSITIVITY; METABOLIC DISEASE; BODY-COMPOSITION; SKELETAL-MUSCLE AB Obesity results from disproportionately high energy intake relative to energy expenditure. Many therapeutic strategies have focused on the intake side of the equation, including pharmaceutical targeting of appetite and digestion. An alternative approach is to increase energy expenditure through physical activity or adaptive thermogenesis. A pharmacological way to increase muscle mass and hence exercise capacity is through inhibition of the activin receptor type IIB (ActRIIB). Muscle mass and strength is regulated, at least in part, by growth factors that signal via ActRIIB. Administration of a soluble ActRIIB protein comprised of a form of the extracellular domain of ActRIIB fused to a human Fc (ActRIIB-Fc) results in a substantial muscle mass increase in normal mice. However, ActRIIB is also present on and mediates the action of growth factors in adipose tissue, although the function of this system is poorly understood. In the current study, we report the effect of ActRIIB-Fc to suppress diet-induced obesity and linked metabolic dysfunctions in mice fed a high-fat diet. ActRIIB-Fc induced a brown fat-like thermogenic gene program in epididymal white fat, as shown by robustly increased expression of the thermogenic genes uncoupling protein 1 and peroxisomal proliferator-activated receptor-gamma coactivator 1 alpha. Finally, we identified multiple ligands capable of reducing thermogenesis that represent likely target ligands for the ActRIIB-Fc effects on the white fat depots. These data demonstrate that novel therapeutic ActRIIB-Fc improves obesity and obesity-linked metabolic disease by both increasing skeletal muscle mass and by inducing a gene program of thermogenesis in the white adipose tissues. (Endocrinology 153: 3133-3146, 2012) C1 [Koncarevic, Alan; Cornwall-Brady, Milton; Pullen, Abigail; Seehra, Jasbir; Lachey, Jennifer] Acceleron Pharma Inc, Preclin Pharmacol, Cambridge, MA 02139 USA. [Andreucci, Amy; Sako, Dianne; Kumar, Ravindra; Grinberg, Asya V.; Liharska, Katia; Ucran, Jeffrey A.; Howard, Elizabeth] Acceleron Pharma Inc, Bioanalyt Dev & Cell Biol, Cambridge, MA 02139 USA. [Kajimura, Shingo] Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA. [Kajimura, Shingo] Univ Calif San Francisco, Dept Cell & Tissue Biol, San Francisco, CA 94143 USA. [Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Lachey, J (reprint author), 128 Sidney St, Cambridge, MA 02139 USA. EM jlachey@acceleronpharma.com FU Acceleron Pharma FX We thank Dr. Monique Davies, Dr. Kathryn Underwood, Dr. Kathleen Tomkinson, June Liu, Rashel Burton, Theresa Baker, Ben Umiker, Travis Monnell, Joseph Barberio, and Matthew Spaits for all of their efforts in construct design, protein purification, and pharmacology support. We also express our thanks to the Mouse Phenotyping Core (Baylor College of Medicine, Houston, TX) for their help in coordinating and running the comprehensive laboratory animal monitoring system studies. All studies were funded by Acceleron Pharma. NR 48 TC 43 Z9 44 U1 0 U2 10 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JUL PY 2012 VL 153 IS 7 BP 3133 EP 3146 DI 10.1210/en.2012-1016 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 965QH UT WOS:000305781800021 PM 22549226 ER PT J AU Phipps, AI Newcomb, PA Garcia-Albeniz, X Hutter, CM White, E Fuchs, CS Hazra, A Ogino, S Nan, H Ma, J Campbell, PT Figueiredo, JC Peters, U Chan, AT AF Phipps, Amanda I. Newcomb, Polly A. Garcia-Albeniz, Xabier Hutter, Carolyn M. White, Emily Fuchs, Charles S. Hazra, Aditi Ogino, Shuji Nan, Hongmei Ma, Jing Campbell, Peter T. Figueiredo, Jane C. Peters, Ulrike Chan, Andrew T. TI Association Between Colorectal Cancer Susceptibility Loci and Survival Time After Diagnosis With Colorectal Cancer SO GASTROENTEROLOGY LA English DT Article DE Colon Cancer; Genetic; GWAS; Prognosis ID GENOME-WIDE ASSOCIATION; NURSES HEALTH; COLON-CANCER; RISK; METAANALYSIS; VARIANTS; DISEASE; ASPIRIN; DESIGN; WOMEN AB Genome-wide Association Studies Have Identified 16 Germline Single-nucleotide Polymorphisms (snps) That Are Associated With Colorectal Cancer (crc) Incidence. We Examined The Relationship Between These Snps And Survival Of 2611 Individuals With Crc, Enrolled In 5 Cohort Studies. We Used Cox Regression Analysis To Associate Snps With Overall And Crc-specific Survival Times. The Minor Allele In Rs4939827 (smad7) was associated with reduced overall survival (hazard ratio, 1.16; 95% confidence interval, 1.06-1.27; P = .002) and disease-specific survival (hazard ratio, 1.17; 95% confidence interval, 1.05-1.30; P = .005). Other SNPs were not associated significantly with survival. Common germline variations might be prognostic factors for patients with CRC. A variant in SMAD7 could affect progression of CRC. C1 [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02144 USA. [Phipps, Amanda I.; Newcomb, Polly A.; Hutter, Carolyn M.; White, Emily; Peters, Ulrike] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Canc Prevent Program, Seattle, WA 98104 USA. [Garcia-Albeniz, Xabier] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Fuchs, Charles S.; Hazra, Aditi; Nan, Hongmei; Ma, Jing; Chan, Andrew T.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Ogino, Shuji] Brigham & Womens Hosp, Ctr Mol Pathol Oncol, Boston, MA 02115 USA. [Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Campbell, Peter T.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Figueiredo, Jane C.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. RP Chan, AT (reprint author), Massachusetts Gen Hosp, Div Gastroenterol, 55 Fruit St, Boston, MA 02144 USA. EM achan@partners.org FU National Cancer Institute, National Institutes of Health, US Department of Health and Human Services [U01 CA137088, R25 CA094880, R01 CA059045]; National Institutes of Health [P01 CA 055075, R01 137178, P50 CA 127003, P01 CA 087969, CA 42182]; National Institutes of Health from the National Cancer Institute [K05 CA154337]; Office of Dietary Supplements; National Heart, Lung, and Blood Institute, National Institutes of Health, US 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 This work was supported by the National Cancer Institute, National Institutes of Health, US Department of Health and Human Services (U01 CA137088 to U. P.), and was supported in part by a training grant from the National Cancer Institute, National Institutes of Health, US Department of Health and Human Services (R25 CA094880 to E. W., A. I. P., and C. M. H.). Andrew Chan is a Damon Runyon Clinical Investigator. Additional funding support for included individual studies was as follows: the Health Professionals' Follow-up Study was supported by the National Institutes of Health (P01 CA 055075 to C. S. F., R01 137178 to A. T. C., and P50 CA 127003 to C. S. F.); the Nurses' Health Study was supported by the National Institutes of Health (R01 137178 to A. T. C., P50 CA 127003 to C. S. F., and P01 CA 087969 to C. S. F.); the Physicians' Health Study was supported by the National Institutes of Health (CA 42182); the VItamins And Lifestyle Study was supported in part by the National Institutes of Health (K05 CA154337 to E. W.) from the National Cancer Institute and Office of Dietary Supplements; and the Women's Health Initiative program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, US 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. Funding for the genome-wide scan of the Women's Health Initiative was provided by the National Cancer Institute, Institutes of Health, US Department of Health and Human Services (R01 CA059045 to U.P.) NR 32 TC 17 Z9 17 U1 0 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUL PY 2012 VL 143 IS 1 BP 51 EP U555 DI 10.1053/j.gastro.2012.04.052 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 965QE UT WOS:000305781500027 PM 22580541 ER PT J AU Sandborn, WJ Colombel, JF Sands, BE Rutgeerts, P Targan, SR Panaccione, R Bressler, B Geboes, K Schreiber, S Aranda, R Gujrathi, S Luo, A Peng, Y Salter-Cid, L Hanauer, SB AF Sandborn, William J. Colombel, Jean-Frederic Sands, Bruce E. Rutgeerts, Paul Targan, Stephan R. Panaccione, Remo Bressler, Brian Geboes, Karl Schreiber, Stefan Aranda, Richard Gujrathi, Sheila Luo, Allison Peng, Yun Salter-Cid, Luisa Hanauer, Stephen B. TI Abatacept for Crohn's Disease and Ulcerative Colitis SO GASTROENTEROLOGY LA English DT Article DE Clinical Trial; Inflammatory Bowel Disease; IBD; T-Cell Signaling Inhibitor ID INFLAMMATORY-BOWEL-DISEASE; PLACEBO-CONTROLLED TRIAL; EFFICACY END-POINTS; DOUBLE-BLIND; RHEUMATOID-ARTHRITIS; T-CELLS; REGULATORY CELLS; ACTIVITY INDEXES; MEDICAL THERAPY; CLINICAL-TRIALS AB BACKGROUND & AIMS: The efficacy of abatacept, a selective costimulation modulator, in Crohn's disease (CD) and ulcerative colitis (UC) is unknown. METHODS: Four placebo-controlled trials evaluated the efficacy and safety of abatacept as induction (IP) and maintenance (MP) therapy in adults with active, moderate-to-severe CD (CD-IP; CD-MP) and UC (UC-IP1; UC-MP). In CD-IP and UC-IP1, 451 patients with CD and 490 patients with UC were randomized to abatacept 30, 10, or 3 mg/kg (according to body weight) or placebo, and dosed at weeks 0, 2, 4, and 8. In MP, 90 patients with CD and 131 patients with UC who responded to abatacept at week 12 in the induction trials were randomized to abatacept 10 mg/kg or placebo every 4 weeks through week 52. RESULTS: In CD-IP, 17.2%, 10.2%, and 15.5% of patients receiving abatacept 30, 10, and 3 mg/kg achieved a clinical response at weeks 8 and 12, vs 14.4% receiving placebo (P = .611, P = .311, and P = .812, respectively). In UC-IP1, 21.4%, 19.0%, and 20.3% of patients receiving abatacept 30, 10, and 3 mg/kg achieved a clinical response at week 12, vs 29.5% receiving placebo (P = .124, P = .043, and P = .158, respectively). In CD-MP, 23.8% vs 11.1% of abatacept vs placebo patients were in remission at week 52. In UC-MP, 12.5% vs 14.1% of patients receiving abatacept vs placebo were in remission at week 52. Safety generally was comparable between groups. CONCLUSIONS: The studies showed that abatacept is not efficacious for the treatment of moderate-to-severe CD or UC. C1 [Sandborn, William J.] Univ Calif San Diego, Div Gastroenterol, La Jolla, CA 92093 USA. [Sandborn, William J.] Mayo Clin, Rochester, MN USA. [Colombel, Jean-Frederic] Ctr Hosp Reg & Univ Lille, Hop Huriez, F-59037 Lille, France. [Sands, Bruce E.] Mt Sinai Sch Med, New York, NY USA. [Sands, Bruce E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sands, Bruce E.] Harvard Univ, Sch Med, Boston, MA USA. [Rutgeerts, Paul] Univ Hosp Gasthuisberg, B-3000 Louvain, Belgium. [Targan, Stephan R.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Panaccione, Remo] Univ Calgary, Calgary, AB, Canada. [Bressler, Brian] Gastrointestinal Res Inst, Vancouver, BC, Canada. [Geboes, Karl] Katholieke Univ Leuven, Dept Pathol, Louvain, Belgium. [Schreiber, Stefan] Univ Kiel, Kiel, Germany. [Aranda, Richard; Gujrathi, Sheila; Luo, Allison; Peng, Yun; Salter-Cid, Luisa] Bristol Myers Squibb Co, Princeton, NJ USA. [Hanauer, Stephen B.] Univ Chicago, Chicago, IL 60637 USA. RP Sandborn, WJ (reprint author), Univ Calif San Diego, Div Gastroenterol, 9500 Gilman Dr, La Jolla, CA 92093 USA. EM wsandborn@ucsd.edu RI Schreiber, Stefan/B-6748-2008 OI Schreiber, Stefan/0000-0003-2254-7771 FU Abbott; ActoGeniX NV; AGI Therapeutics Inc; Alba Therapeutics Corp; Albireo; Alfa Wasserman; Amgen; AM-Pharma BV; Anaphore; Astellas; Athersys Inc; Atlantic Healthcare Ltd; Aptalis; BioBalance Corp; Boehringer-Ingelheim; Bristol-Myers Squibb; Celgene; Celek Pharmaceuticals; Cellerix SL; Cerimon Pharmaceuticals; ChemoCentryx; CoMentis; Cosmo Technologies; Coronado Biosciences; Cytokine Pharmasciences; Eagle Pharmaceuticals; EnGene Inc; Eli Lilly; Enteromedics; Exagen Diagnostics Inc; Ferring Pharmaceuticals; Flexio Therapeutics Inc; Funxional Therapeutics Ltd; Genzyme Corp; Gilead Sciences; Given Imaging; GSK; Human Genome Sciences; Ironwood Pharmaceuticals; KaloBios Pharmaceuticals; Lexicon Pharmaceuticals; Lycera Corp; Meda Pharmaceuticals; Merck Research Laboratories; Merck Serono; Millenium Pharmaceuticals; Nisshin Kyorin Pharmaceuticals; Novo Nordisk; NPS Pharmaceuticals; Optimer Pharmaceuticals; Orexigen Therapeutics Inc; PDL Biopharma; Pfizer; Procter and Gamble; Prometheus Laboratories; ProtAb Ltd; Purgenesis Technologies Inc; Relypsa Inc; Roche; Salient Pharmaceuticals; Salix Pharmaceuticals; Santarus; Schering Plough; Shire Pharmaceuticals; Sigmoid Pharma Ltd; Sirtris Pharmaceuticals; SLA Pharma UK Ltd; Targacept; Teva Pharmaceuticals; Therakos; Tilliotts Pharma AG; TxCell SA; UCB Pharma; Viamet Pharmaceuticals; Vascular Biogenics Ltd; Warner Chilcott UK Ltd; Wyeth; Genentech; Janssen; Milennium Pharmaceuticals; Novartis; ActoGenix; Albireo Pharma; AstraZeneca; Bayer; Biogen Idec; Centocor; Danone; Elan Pharma; Giuliani; Merck; Hutchinson Medi Pharma; Takeda; Neovacs; Ocerra Therapeutics Inc; Otsuka American Pharmaceuticals; Ribovacs Biotech; Sanofi-Aventis; Schering-Plough; Shire Pharma; Synta Pharma; Teva Pharma; Ferring; Shire; Advanced Biotherapeutics; Avaxia Biologics; Ironwood Pharma; Merrimack Pharma; Otsuka America Pharmaceuticals; Resolvyx Pharma; Vertx Pharma; Viamet Pharma; Cerimon Pharma; Millennium Pharma; Otsuka America Pharma; Axis Healthcare Communications; IMEDEX; Potomac Center for Medical Education; Strategic Consultants International; UCB; Genentech-Roche; Millennium-Takeda; Robarts; Johnson Johnson; Genexion; MSD; Bristol-Myers Squibb (Princeton, NJ) FX The authors disclose the following: William Sandborn has received consulting fees from Abbott, ActoGeniX NV, AGI Therapeutics Inc, Alba Therapeutics Corp, Albireo, Alfa Wasserman, Amgen, AM-Pharma BV, Anaphore, Astellas, Athersys Inc, Atlantic Healthcare Ltd, Aptalis, BioBalance Corp, Boehringer-Ingelheim, Bristol-Myers Squibb, Celgene, Celek Pharmaceuticals, Cellerix SL, Cerimon Pharmaceuticals, ChemoCentryx, CoMentis, Cosmo Technologies, Coronado Biosciences, Cytokine Pharmasciences, Eagle Pharmaceuticals, EnGene Inc, Eli Lilly, Enteromedics, Exagen Diagnostics Inc, Ferring Pharmaceuticals, Flexio Therapeutics Inc, Funxional Therapeutics Ltd, Genzyme Corp, Gilead Sciences, Given Imaging, GSK, Human Genome Sciences, Ironwood Pharmaceuticals, KaloBios Pharmaceuticals, Lexicon Pharmaceuticals, Lycera Corp, Meda Pharmaceuticals, Merck Research Laboratories, Merck Serono, Millenium Pharmaceuticals, Nisshin Kyorin Pharmaceuticals, Novo Nordisk, NPS Pharmaceuticals, Optimer Pharmaceuticals, Orexigen Therapeutics Inc, PDL Biopharma, Pfizer, Procter and Gamble, Prometheus Laboratories, ProtAb Ltd, Purgenesis Technologies Inc, Relypsa Inc, Roche, Salient Pharmaceuticals, Salix Pharmaceuticals, Santarus, Schering Plough, Shire Pharmaceuticals, Sigmoid Pharma Ltd, Sirtris Pharmaceuticals, SLA Pharma UK Ltd, Targacept, Teva Pharmaceuticals, Therakos, Tilliotts Pharma AG, TxCell SA, UCB Pharma, Viamet Pharmaceuticals, Vascular Biogenics Ltd, Warner Chilcott UK Ltd, and Wyeth; research grants from Abbott, Bristol-Myers Squibb, Genentech, GSK, Janssen, Milennium Pharmaceuticals, Novartis, Pfizer, Procter and Gamble, Shire Pharmaceuticals, and UCB Pharma; payments for lectures/speakers bureau from Abbott, Bristol-Myers Squibb, and Janssen; and holds stock/stock options in Enteromedics; Jean-Frederic Colombel has taken part in advisory boards for Abbott, Centocor, Schering-Plough, ActoGenix, Albireo Pharma, AstraZeneca, Bayer, Biogen Idec, Bristol-Myers Squibb, Cellerix SL, Chemocentryx, Cosmo Technologies, Danone, Elan Pharma, Genentech, Guiliani, GSK, Merck, Given Imaging, Hutchinson Medi Pharma, Sanofi-Aventis, Takeda, Neovacs, Ocerra Therapeutics Inc, Otsuka American Pharmaceuticals, PDL Biopharma, Pfizer, Prometheus Laboratories, Ribovacs Biotech, Shire Pharma, Synta Pharma, Teva Pharma, Therakos, UCB Pharma, and Wyeth; received consulting fees from Abbott, ActoGenix, Albireo Pharma, AstraZeneca, Bayer, Biogen Idec, Bristol-Myers Squibb, Cellerix SL, Centocor, Chemocentryx, Cosmo Technologies, Danone, Elan Pharma, Genentech, Giuliani, GSK, Merck, Given Imaging, Hutchinson Medi Pharma, Takeda, Neovacs, Ocerra Therapeutics Inc, Otsuka American Pharmaceuticals, PDL Biopharma, Pfizer, Prometheus Laboratories, Ribovacs Biotech, Sanofi-Aventis, Schering-Plough, Shire Pharma, Synta Pharma, and Teva Pharma; research grants from Abbott, Ferring, and Schering-Plough; payments for lectures/speakers bureau from Abbott, Centocor, Given Imaging, Merck, Schering-Plough, Shire, and UCB Pharma; payments for preparation of educational material from Abbott, Centocor, and Schering-Plough; holds stock/stock options in Intestinal Biotech Development; and has received reimbursement for travel expenses from Abbott, Bayer, Biogen Idec, Centocor, Chemocentryx, Cosmo Technologies, Danone, Elan Pharma, Ferring, Genentech, Given Imaging, Takeda, Pfizer, Teva Pharma, Bristol-Myers Squibb, UCB Pharma, Prometheus Laboratories, Sanofi-Aventis, and Schering-Plough; Bruce Sands has taken part in advisory boards for Axcan Pharma; received consulting fees from Abbott, Advanced Biot; herapeutics, Amgen, Avaxia Biologics, Biogen Idec, Centocor, Elan Pharma, GSK, Ironwood Pharma, Merrimack Pharma, Novartis, Otsuka America Pharmaceuticals, Pfizer, Procter and Gamble, Prometheus Laboratories, Resolvyx Pharma, Takeda, UCB Pharma, Vertx Pharma, and Viamet Pharma; received research grants from Abbott, Celgene, Centocor, Cerimon Pharma, Elan Pharma, Millennium Pharma, Novartis, Otsuka America Pharma, Pfizer, and Prometheus Laboratories; payments for lectures/speakers bureau from Axis Healthcare Communications, IMEDEX, Potomac Center for Medical Education, Strategic Consultants International; holds stock/stock options in Avaxia Biologics and Marina Biotech; Paul Rutgeert's institute has received research grants from Abbott, Centocor, Merck, and UCB; received consulting fees from Abbott, Bristol-Myers Squib, Centocor, Chemocentryx, Genentech-Roche, Merck, Millennium-Takeda, and Robarts; has received reimbursement for travel expenses from Abbott, Johnson & Johnson, and Merck; has received fees for review activities from Genentech-Roche, Genexion, and Robarts; Remo Panaccione has taken part in advisory boards and received consulting fees/honorarium from Bristol-Myers Squibb; Brian Bressler's institute has received research expenses for clinical trial work related to this study; Stefan Schreiber has received consulting fees from Abbot, MSD, Schering-Plough, and UCB Pharma; Richard Aranda and Sheila Gujrathi (at the time of the study) were employees of, and held stock options in, Bristol-Myers Squibb; Allison Luo is an employee of, and holds stock options in, Bristol-Myers Squibb; Yun Peng and Luisa Salter-Cid are employees of Bristol-Myers Squibb; Stephen Hanauer has received consulting fees/honorarium from Bristol-Myers Squibb relating to this study; his institute has received clinical trial support in the form of a grant from Bristol-Myers Squibb. The remaining authors disclose no conflicts.; This study and the editorial assistance provided by Medicus International were funded by Bristol-Myers Squibb (Princeton, NJ). NR 28 TC 55 Z9 57 U1 0 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUL PY 2012 VL 143 IS 1 BP 62 EP U575 DI 10.1053/j.gastro.2012.04.010 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 965QE UT WOS:000305781500029 PM 22504093 ER PT J AU Kanwal, F Kramer, JR Buchanan, P Asch, SM Assioun, Y Bacon, BR Li, J El-Serag, HB AF Kanwal, Fasiha Kramer, Jennifer R. Buchanan, Paula Asch, Steven M. Assioun, Youssef Bacon, Bruce R. Li, Juan El-Serag, Hashem B. TI The Quality of Care Provided to Patients With Cirrhosis and Ascites in the Department of Veterans Affairs SO GASTROENTEROLOGY LA English DT Article DE SBP; Best Practices; Quality Measurement; Predictors ID SPONTANEOUS BACTERIAL PERITONITIS; CHRONIC HEPATITIS-C; LIVER-DISEASE; UNITED-STATES; MANAGEMENT; PROPHYLAXIS; MORTALITY; SURVIVAL; COHORT; PREDICT AB BACKGROUND & AIMS: Ascites are the most common complication of cirrhosis. Evidence-based guidelines define the criteria and standards of care for patients with cirrhosis and ascites. However, little is known about the extent to which patients with ascites meet these standards. METHODS: We evaluated the quality of ascites care, measured by 8 explicit Delphi panel-derived quality indicators, in 774 patients with cirrhosis and ascites, seen at 3 Veterans Affairs Medical Centers between 2000 and 2007. We also conducted a structured implicit review of patients' medical charts to determine whether patient refusal, outside care, or other justifiable exceptions to care processes account for nonadherence to the quality indicators. RESULTS: Quality scores (maximum 100%) varied among individual indicators, ranging from 30% for secondary prophylaxis of spontaneous bacterial peritonitis, to 90% for assays for cell number and type in the paracentesis fluid. In general, care targeted at treatment was more likely to meet standards than preventive care. Only 33.2% (95% confidence interval [CI]: 29.9% - 32.9%) of patients received all recommended care. Patients with no comorbidity (Deyo index 0 vs >3; odds ratio = 2.21; 95% CI: 1.43 - 3.43), who saw a gastroenterologist (odds ratio = 1.33; 95% CI, 1.01 - 1.74), or were seen in a facility with academic affiliation (odds ratio = 1.73; 95% CI: 1.29 - 2.35) received higher-quality care. Justifiable exceptions to indicated care, documented in charts, were common for patients with paracentesis after diagnosis with ascites, patients that received antibiotics for gastrointestinal bleeding, and patients that required diuretics. However, most patients did not have an explanation documented for nonadherence to recommended care. CONCLUSIONS: Health care quality, measured by whether patients received recommended services, was suboptimal for patients with cirrhosis-related ascites. Care that included gastroenterologists was associated with high quality. However, for some of the quality indicators, too many denominator exceptions existed to allow for accurate automated measurement. C1 [Kanwal, Fasiha] Michael E DeBakey VA Med Ctr, Dept Gastroenterol & Hepatol, Houston, TX 77030 USA. [Kanwal, Fasiha; Kramer, Jennifer R.; El-Serag, Hashem B.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Buchanan, Paula] St Louis Univ, Sch Publ Hlth, St Louis, MO 63103 USA. [Asch, Steven M.] Greater Los Angeles VA Healthcare Syst, Dept Med, Los Angeles, CA USA. [Asch, Steven M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Assioun, Youssef; Bacon, Bruce R.; Li, Juan] St Louis Univ, Sch Med, Div Gastroenterol & Hepatol, St Louis, MO USA. RP Kanwal, F (reprint author), Michael E DeBakey VA Med Ctr, Dept Gastroenterol & Hepatol, 2002 Holcombe Blvd,152, Houston, TX 77030 USA. EM fasiha.kanwal@va.gov FU American Society of Gastrointestinal Endoscopy Quality of Care Award; American College of Gastroenterology Clinical Research Award; Veteran's Affairs Health Services Research and Development (HSR&D) Investigator Initiated Research Award [IIR-07-111]; Houston VA HSR&D Center of Excellence [HFP90-020] FX This material is based upon work supported by the 2008 American Society of Gastrointestinal Endoscopy Quality of Care Award and by the 2009 American College of Gastroenterology Clinical Research Award. Dr Kanwal is supported by Veteran's Affairs Health Services Research and Development (HSR&D) Investigator Initiated Research Award IIR-07-111. This material is also supported in part by the Houston VA HSR&D Center of Excellence (HFP90-020). NR 26 TC 38 Z9 38 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUL PY 2012 VL 143 IS 1 BP 70 EP 77 DI 10.1053/j.gastro.2012.03.038 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 965QE UT WOS:000305781500030 PM 22465432 ER PT J AU Kamat, A Lyons, JL Misra, V Uno, H Morgello, S Singer, EJ Gabuzda, D AF Kamat, Anupa Lyons, Jennifer L. Misra, Vikas Uno, Hajime Morgello, Susan Singer, Elyse J. Gabuzda, Dana TI Monocyte Activation Markers in Cerebrospinal Fluid Associated With Impaired Neurocognitive Testing in Advanced HIV Infection SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV; HIV-associated neurocognitive disorders; immune activation; cerebrospinal fluid; biomarkers ID HUMAN-IMMUNODEFICIENCY-VIRUS; CENTRAL-NERVOUS-SYSTEM; ACTIVE ANTIRETROVIRAL THERAPY; HEPATITIS-C INFECTION; IMMUNE ACTIVATION; TYPE-1 INFECTION; AIDS DEMENTIA; CHEMOKINE CONCENTRATIONS; CHEMOTACTIC PROTEIN-1; INTERFERON-GAMMA AB Background: Activated monocytes/macrophages play a role in severe forms of HIV-associated neurocognitive disorders (HAND), but little is known about the mechanisms driving milder forms that are prevalent despite combination antiretroviral therapy (cART). To examine relationships of monocyte activation markers to HAND of varying severity, we compared plasma and cerebrospinal fluid (CSF) biomarker levels with neurocognitive test scores in HIV+ subjects. Methods: Plasma and CSF soluble CD14 (sCD14), CCL2, and interleukin (IL) 6 were measured by enzyme-linked immunosorbent assay in 67 HIV+ subjects with nadir CD4 <300, and CSF inflammatory biomarkers were measured by multiplex assay in 14 subjects on suppressive cART. Results: Eighty-two percent were on cART, with 31% having undetectable plasma viral load (VL). CSF sCD14 was increased in subjects with impaired neurocognitive testing (P = 0.02), correlated inversely with global T scores in subjects with detectable but not undetectable plasma VL (P = 0.02), and yielded higher area under the receiver operating characteristic curve values for predicting impaired T scores (0.659) than plasma or CSF VL and current or nadir CD4 counts in single-marker and multivariate models. CSF sCD14, IL-6, IL-8, CCL2, CCL3, CXCL10, and interferon (IFN) gamma were increased in subjects on suppressive cART regardless of cognitive status and predicted patient class in unsupervised analyses, with IL-8, CCL2, and IFN gamma explaining most of the variance. Conclusions: CSF sCD14 is associated with impaired neurocognitive testing in patients with HIV on nonsuppressive cART, suggesting potential utility as a biomarker to monitor HAND progression. CSF sCD14, IL-6, IL-8, CCL2, CCL3, CXCL10, and IFN gamma remain elevated in patients on suppressive cART regardless of cognitive status, implying ongoing intrathecal inflammation even in the absence of clinical manifestations. C1 [Kamat, Anupa; Lyons, Jennifer L.; Misra, Vikas; Uno, Hajime; Gabuzda, Dana] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Morgello, Susan] Mt Sinai Med Ctr, New York, NY 10029 USA. [Singer, Elyse J.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Gabuzda, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 450 Brookline Ave,CLS 1010, Boston, MA 02115 USA. EM dana_gabuzda@dfci.harvard.edu FU National Institutes of Health [DA26322, DA28994, MH083588, U01MH083501, R24MH59724, U01MH083506, R24MH59745, U01MH083507, R24 NS45491, 5U01MH083500, NS38841, U01MH083545, N01MH32002]; Mount Sinai Institute for NeuroAIDS Disparities [R25MH080663]; Harvard Center for AIDS Research; Dana-Farber Cancer Institute/Harvard Center for Cancer Research; Harvard Center for AIDS Research Biostatistics Core; [N01MH22005] FX Supported by National Institutes of Health Grant DA26322, DA28994, and MH083588 to D. Gabuzda and a Mount Sinai Institute for NeuroAIDS Disparities Scholar Grant (funded through R25MH080663) to J. L. Lyons National NeuroAIDS Tissue Consortium sites were supported by National Institutes of Health Grants U01MH083501, R24MH59724, U01MH083506, R24MH59745, U01MH083507, R24 NS45491, 5U01MH083500, NS38841, U01MH083545, and N01MH32002. CNS HIV Antiretroviral Therapy Effects Research was supported by N01MH22005. Core facilities were supported by the Harvard Center for AIDS Research and Dana-Farber Cancer Institute/Harvard Center for Cancer Research grants.; The authors thank NNTC and CHARTER sites for providing plasma samples and clinical data for patients with AIDS. The authors also acknowledge support from the Harvard Center for AIDS Research Biostatistics Core and the Mount Sinai Institute for NeuroAIDS Disparities. NR 54 TC 63 Z9 63 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 JUL 1 PY 2012 VL 60 IS 3 BP 234 EP 243 DI 10.1097/QAI.0b013e318256f3bc PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 965YT UT WOS:000305804400013 PM 22569268 ER PT J AU Nichols, JM Maiellaro, I Abi-Jaoude, J Curci, S Hofer, AM AF Nichols, Jonathan M. Maiellaro, Isabella Abi-Jaoude, Joanne Curci, Silvana Hofer, Aldebaran M. TI Store-operated cAMP Signaling in the Regulation of Colonic Secretory Function SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-General-Physiologists CY SEP 05-09, 2012 CL Woods Hole, MA SP Soc Gen Physiologists C1 [Nichols, Jonathan M.; Maiellaro, Isabella; Abi-Jaoude, Joanne; Curci, Silvana; Hofer, Aldebaran M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, VA Boston Healthcare Syst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD JUL PY 2012 VL 140 IS 1 MA 19 BP 8A EP 8A PG 1 WC Physiology SC Physiology GA 965ZJ UT WOS:000305806000027 ER PT J AU Filetti, LC Imudia, AN Al-Safi, Z Hobson, DT Awonuga, AO Bahado-Singh, RO AF Filetti, Lusia C. Imudia, Anthony N. Al-Safi, Zain Hobson, Deslyn T. Awonuga, Awoniyi O. Bahado-Singh, Ray O. TI New onset delayed postpartum preeclampsia: different disorders? SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE Eclampsia; late; postpartum preeclampsia; persistent; recurrent ID ECLAMPSIA AB Objective: Delayed postpartum preeclampsia is a poorly studied disorder. We compared new onset delayed postpartum preeclampsia (NOPP) to recurrent/persistent, delayed onset postpartum preeclampsia (RPP) to see whether these were different disorders. Methods: Delayed onset preeclampsia was defined as readmission >2 days to <= 6 weeks postpartum for preeclampsia. The NOPP group had no antecedent diagnosis of hypertensive disorders in the current pregnancy, and was compared to the RPP defined as a prior hypertensive disorder in the current pregnancy in terms of maternal demographics, obstetric and medical history, intrapartum and early postpartum course and clinical signs and symptoms and outcomes on postpartum readmission. Results: There were a total of 56 (36.8%) patients in the RPP and 96 (63.2%) patients in the NOPP groups. NOPP cases delivered significantly later 39.0 +/- 2 weeks vs. 37 +/- 3.0 weeks p < 0.001, and had significantly lower blood pressure during the antepartum, early postpartum and readmission periods. In addition the NOPP group had significantly higher average number of symptoms 2 vs. 1.5 p = 0.013 on postpartum readmission. There were no statistically significant differences in the rates of major complications. Conclusions: In this comprehensive study of delayed postpartum preeclampsia, there were few significant differences in the clinical course and no differences in complications in the NOPP subgroup compared to cases with preeclampsia recurring in the late postpartum period. C1 [Filetti, Lusia C.; Imudia, Anthony N.; Al-Safi, Zain; Hobson, Deslyn T.; Awonuga, Awoniyi O.; Bahado-Singh, Ray O.] Wayne State Univ, Sch Med, Detroit Med Ctr, Dept Obstet & Gynecol, Detroit, MI 48201 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Dept Obstet & Gynecol, Boston, MA USA. RP Bahado-Singh, RO (reprint author), Wayne State Univ, Harper Hosp, 3980 John R,Box 160, Detroit, MI 48201 USA. EM rbahados@med.wayne.edu NR 10 TC 3 Z9 3 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PD JUL PY 2012 VL 25 IS 7 BP 957 EP 960 DI 10.3109/14767058.2011.601365 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 964NZ UT WOS:000305704000017 PM 21740315 ER PT J AU Goldberg, JM Scully, RE Sallan, SE Lipshultz, SE AF Goldberg, John M. Scully, Rebecca E. Sallan, Stephen E. Lipshultz, Steven E. TI Cardiac Failure 30 Years After Treatment Containing Anthracycline for Childhood Acute Lymphoblastic Leukemia SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE heart failure; cancer survivorship; late-effects ID DOXORUBICIN-INDUCED CARDIOMYOPATHY; PEDIATRIC HEART-TRANSPLANTATION; VITAMIN-D DEFICIENCY; LONG-TERM SURVIVORS; CANCER SURVIVORS; ADULT SURVIVORS; BODY-COMPOSITION; BARIATRIC SURGERY; THERAPY; RISK AB In 1977, a 5-year-old girl diagnosed with acute lymphoblastic leukemia was treated on Dana-Farber Cancer Institute Childhood Acute Lymphoblastic Leukemia Protocol 77-01, receiving a cumulative doxorubicin dose of 465 mg/m(2), cranial radiation, and other drugs. After being in continuous complete remission for 34 months, she developed heart failure and was treated with digoxin and furosemide. At 16 years of age, she was diagnosed and treated for dilated cardiomyopathy. Over the years, she continued to have bouts of heart failure, which became less responsive to treatment. At 36 years of age, she received a heart transplant. Six months later, she stopped taking her medications and suffered a sudden cardiac death. C1 [Goldberg, John M.; Scully, Rebecca E.; Lipshultz, Steven E.] Univ Miami, Leonard M Miller Sch Med, Dept Pediat, Miami, FL 33101 USA. [Goldberg, John M.; Lipshultz, Steven E.] Univ Miami, Holtz Childrens Hosp, Jackson Mem Med Ctr, Miami, FL 33101 USA. [Goldberg, John M.; Lipshultz, Steven E.] Sylvester Comprehens Canc Ctr, Miami, FL USA. [Scully, Rebecca E.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Hanover, NH 03756 USA. [Sallan, Stephen E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Lipshultz, SE (reprint author), Univ Miami, Leonard M Miller Sch Med, Dept Pediat D820, POB 016820, Miami, FL 33101 USA. EM slipshultz@med.miami.edu OI Scully, Rebecca/0000-0002-6887-9600 FU Bankhead Coley New Investigator Research Award; National Institutes of Health [HL072705, HL078522, HL053392, CA127642, CA068484, HD052104, AI50274, HD052102, HL087708, HL079233, HL004537, HL087000, HL007188, HL094100, HL095127, HD80002]; Children's Cardiomyopathy Foundation; University of Miami Women's Cancer Association; Lance Armstrong Foundation; Michael Garil Fund; American Society of Hematology Trainee Research Award FX Supported in part by a Bankhead Coley New Investigator Research Award, the National Institutes of Health (HL072705, HL078522, HL053392, CA127642, CA068484, HD052104, AI50274, CA068484, HD052102, HL087708, HL079233, HL004537, HL087000, HL007188, HL094100, HL095127, and HD80002), the Children's Cardiomyopathy Foundation, the University of Miami Women's Cancer Association, and the Lance Armstrong Foundation, the Michael Garil Fund, and the American Society of Hematology Trainee Research Award. NR 43 TC 5 Z9 5 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD JUL PY 2012 VL 34 IS 5 BP 395 EP 397 DI 10.1097/MPH.0b013e3182532078 PG 3 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 964IQ UT WOS:000305687800030 PM 22584777 ER PT J AU Gordon, PL Doyle, JW Johansen, KL AF Gordon, Patricia L. Doyle, Julie W. Johansen, Kirsten L. TI Association of 1,25-Dihydroxyvitamin D Levels With Physical Performance and Thigh Muscle Cross-sectional Area in Chronic Kidney Disease Stage 3 and 4 SO JOURNAL OF RENAL NUTRITION LA English DT Article ID CHRONIC-RENAL-FAILURE; QUALITY-OF-LIFE; VITAMIN-D INSUFFICIENCY; SKELETAL-MUSCLE; HEMODIALYSIS-PATIENTS; RESISTANCE EXERCISE; 25-HYDROXYVITAMIN D; BODY-COMPOSITION; CONTROLLED-TRIAL; 6-MINUTE WALK AB Background: Declines in 1,25-dihydroxyvitamin D (1,25(OH)(2)D) levels and physical functioning follow the course of chronic kidney disease (CKD). Although the molecular actions of vitamin D in skeletal muscle are well known, and muscle weakness and atrophy are observed in vitamin D-deficient states, there is little information regarding vitamin D and muscle function and size in CKD. Objective: To examine associations of vitamin D with physical performance (PF) and muscle size. Design: Cross-sectional. Setting: CKD clinic. Subjects: Twenty-six patients (61 +/- 13 years, 92% men) with CKD stage 3 or 4. Main Outcome Measures: Gait speed, 6-minute walk, sit-to-stand time, 1-legged balance, and thigh muscle cross-sectional area (MCSA), measured by magnetic resonance imaging (MRI). Results: Overall, 73% were 25-hydroxyvitamin D(25(OH)D) deficient (n = 10) or insufficient (n = 9) (Kidney Disease Outcomes Quality Initiative guidelines). 25(OH)D level was associated with normal gait speed only (r = 0.41, P = .04). Normal and fast gait speed, the distance walked in 6 minutes, and sit-to-stand time were best explained by 1,25(OH)(2)D and body mass index (P < .05 for all) and 1-legged stand by 1,25(OH)(2)D (r = 0.40, P < .05) only. There were no associations of age, estimated glomerular filtration rate (eGFR), intact parathyroid hormone (iPTH), or albumin with any PF measures. MCSA was associated with eGFR (r = 0.54, P < .01) only. Variance in MCSA was best explained by a model containing 1,25(OH)(2)D, plasma Ca2+, and daily physical activity (by accelerometry) (P < .05 for all). Once these variables were in the model, there was no contribution of eGFR. Conclusion: These results suggest that 1,25(OH)(2)D is a determinant of PF and muscle size in patients with stage 3 and 4 CKD. (C) 2012 by the National Kidney Foundation, Inc. All rights reserved. C1 [Gordon, Patricia L.] Univ Calif San Francisco, Div Nephrol, Dept Med, San Francisco, CA 94121 USA. [Gordon, Patricia L.; Doyle, Julie W.; Johansen, Kirsten L.] San Francisco VA Med Ctr, Nephrol Sect, San Francisco, CA USA. RP Gordon, PL (reprint author), Univ Calif San Francisco, Div Nephrol, Dept Med, Box 111J,4150 Clement St, San Francisco, CA 94121 USA. EM patricia.gordon@ucsf.edu FU Abbott Laboratories FX This study was funded through investigator-initiated funding by Abbott Laboratories. P.L.G. and K.L.J. have received financial support for this study from Abbott Laboratories. NR 59 TC 4 Z9 5 U1 1 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1051-2276 J9 J RENAL NUTR JI J. Renal Nutr. PD JUL PY 2012 VL 22 IS 4 BP 423 EP 433 DI 10.1053/j.jrn.2011.10.006 PG 11 WC Nutrition & Dietetics; Urology & Nephrology SC Nutrition & Dietetics; Urology & Nephrology GA 965DY UT WOS:000305748100008 PM 22227183 ER PT J AU Subramanian, A Timberlake, M Mittakanti, H Lara, M Brandt, ML AF Subramanian, Anuradha Timberlake, Matthew Mittakanti, Harsha Lara, Michael Brandt, Mary L. TI Novel Educational Approach for Medical Students: Improved Retention Rates Using Interactive Medical Software Compared with Traditional Lecture-Based Format SO JOURNAL OF SURGICAL EDUCATION LA English DT Article DE web-based; surgical education; interactive tool AB BACKGROUND: Mannequin and computer-based simulators are useful for the practice of patient management, physical procedures, and competency. However, they are ineffective in teaching clinical medicine. StepStone Interactive Medical Software (SS) is a web-based medical learning modality that provides the user with a highly focused set of evaluative and interventional tasks to treat memorable virtual patients in a visual case-based format. OBJECTIVE: To determine whether the SS learning modality is superior to traditional lecture format in medical student learning and retention. METHODS: After Institutional Review Board (IRB) approval was obtained and the consents were signed, 30 third-year medical students were assigned randomly to 2 groups of 15 students each: The control group received two 30-minute PowerPoint lectures (Microsoft Corporation, Redmond, Washington) about torsades de pointes (TdP) and pulseless electrical activity (PEA), and the SS group was given 1 hour to review 2 SS cases teaching TdP and PEA. A preintervention test was given to assess their baseline knowledge. An immediate postintervention test was given to both groups. Twenty-two days later, a long-term retention test was administered. The results were analyzed using a Student t test for continuous variables. RESULTS: The mean scores for the preintervention test in the control and SS groups were 44.9 +/- 3% and 44.1 +/- 2%, respectively (p = 0.41). The mean scores for the postintervention test in the control and SS groups were 61.7 +/- 2% and 86.7 +/- 2%, respectively (p < 0.001). Improvement from baseline knowledge was calculated, and the mean improvement was 16.8 +/- 3% in the control group and 42.5 +/- 2% in the SS group (p < 0.001). The long-term retention test revealed the mean scores of 55.8 +/- 3% in the control group and 70.1 +/- 3% in the SS group (p < 0.001). Long-term improvement from baseline knowledge was calculated and the control group improved by 10.9 +/- 4%, whereas the SS group improved by 26 +/- 3% (p = 0.002). CONCLUSIONS: The SS learning modality demonstrated a significant improvement in student learning retention compared to traditional didactic lecture format. SS is an effective web-based medical education tool. (J Surg 69:449-452. (C) 2012 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.) C1 [Subramanian, Anuradha] Baylor Coll Med, VA Med Ctr, Michael E DeBakey Dept Surg, Houston, TX 77030 USA. RP Subramanian, A (reprint author), Baylor Coll Med, VA Med Ctr, Michael E DeBakey Dept Surg, 2002 Holcombe Blvd,OCL 112, Houston, TX 77030 USA. EM asubrama@bcm.edu NR 6 TC 14 Z9 14 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1931-7204 J9 J SURG EDUC JI J. Surg. Educ. PD JUL-AUG PY 2012 VL 69 IS 4 BP 449 EP 452 DI 10.1016/j.jsurg.2012.05.013 PG 4 WC Education, Scientific Disciplines; Surgery SC Education & Educational Research; Surgery GA 960CS UT WOS:000305366200003 PM 22677580 ER PT J AU Blanpain, C Daley, GQ Hochedlinger, K Passegue, E Rossant, J Yamanaka, S AF Blanpain, Cedric Daley, George Q. Hochedlinger, Konrad Passegue, Emmanuelle Rossant, Janet Yamanaka, Shinya TI Stem cells assessed SO NATURE REVIEWS MOLECULAR CELL BIOLOGY LA English DT Article ID 3-DIMENSIONAL CULTURE AB The increasing momentum of stem cell research continues, with the better characterization of induced pluripotent stem (iPS) cells, the conversion of differentiated cells into different cell types and the use of pluripotent stem cells to generate whole tissues, among other advances. Here, six experts in the field of stem cell research compare different stem cell models and highlight the importance of pursuing complementary experimental approaches for a better understanding of pluripotency and differentiation and an informed approach to medical applications. C1 [Blanpain, Cedric] Univ Libre Brussels, Walloon Excellence Life Sci & Biotechnol WELBIO, Interdisciplinary Res Inst IRIBHM, B-1070 Brussels, Belgium. [Daley, George Q.] Childrens Hosp, Boston, MA 02115 USA. [Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hochedlinger, Konrad] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. [Hochedlinger, Konrad] Harvard Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Hochedlinger, Konrad] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Hochedlinger, Konrad] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Passegue, Emmanuelle] Univ Calif San Francisco, Dept Med, Div Hematol & Oncol, San Francisco, CA 94143 USA. [Passegue, Emmanuelle] Univ Calif San Francisco, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA. [Rossant, Janet] Univ Toronto, Hosp Sick Children, Dept Mol Genet, Toronto, ON M5G 1X8, Canada. [Rossant, Janet] Univ Toronto, Hosp Sick Children, Dept Obstet & Gynecol, Toronto, ON M5G 1X8, Canada. [Yamanaka, Shinya] Gladstone Inst Cardiovasc Dis, San Francisco, CA 94158 USA. [Yamanaka, Shinya] Kyoto Univ, Ctr iPS Cell Res & Applicat, Sakyo Ku, Kyoto 6068507, Japan. RP Blanpain, C (reprint author), Univ Libre Brussels, Walloon Excellence Life Sci & Biotechnol WELBIO, Interdisciplinary Res Inst IRIBHM, 808 Route Lennik,BatC,C6-130, B-1070 Brussels, Belgium. EM Cedric.Blanpain@ulb.ac.be; daley.lab@childrens.harvard.edu; khochedlinger@helix.mgh.harvard.edu; passeguee@stemcell.ucsf.edu; janet.rossant@sickkids.ca; yamanaka@cira.kyoto-u.ac.jp NR 6 TC 18 Z9 18 U1 3 U2 30 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0072 EI 1471-0080 J9 NAT REV MOL CELL BIO JI Nat. Rev. Mol. Cell Biol. PD JUL PY 2012 VL 13 IS 7 BP 471 EP 476 DI 10.1038/nrm3371 PG 6 WC Cell Biology SC Cell Biology GA 966AT UT WOS:000305809700014 PM 22678486 ER PT J AU Wen, PY Lee, EQ Reardon, DA Ligon, KL Yung, WKA AF Wen, Patrick Y. Lee, Eudocia Q. Reardon, David A. Ligon, Keith L. Yung, W. K. Alfred TI Current clinical development of PI3K pathway inhibitors in glioblastoma SO NEURO-ONCOLOGY LA English DT Review DE AKT; glioblastoma; GBM; mTOR; PI3K ID ADVANCED SOLID TUMORS; PHASE-II TRIAL; PHOSPHATIDYLINOSITOL 3-KINASE/MAMMALIAN TARGET; DUAL PI3K/MTOR INHIBITOR; RENAL-CELL CARCINOMA; FACTOR RECEPTOR GENE; ANTITUMOR-ACTIVITY; IN-VIVO; RECURRENT GLIOBLASTOMA; RAPAMYCIN INHIBITOR AB Glioblastoma (GBM) is the most common and lethal primary malignant tumor of the central nervous system, and effective therapeutic options are lacking. The phosphatidylinositol 3-kinase (PI3K) pathway is frequently dysregulated in many human cancers, including GBM. Agents inhibiting PI3K and its effectors have demonstrated preliminary activity in various tumor types and have the potential to change the clinical treatment landscape of patients with solid tumors. In this review, we describe the activation of the PI3K pathway in GBM, explore why inhibition of this pathway may be a compelling therapeutic target for this disease, and provide an update of the data on PI3K inhibitors in clinical trials and from earlier investigation. C1 [Wen, Patrick Y.; Lee, Eudocia Q.; Reardon, David A.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA USA. [Wen, Patrick Y.; Lee, Eudocia Q.] Brigham & Womens Hosp, Dept Neurol, Div Neurooncol, Boston, MA 02115 USA. [Ligon, Keith L.] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02215 USA. [Ligon, Keith L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Ligon, Keith L.] Childrens Hosp Boston, Boston, MA USA. [Wen, Patrick Y.; Lee, Eudocia Q.; Reardon, David A.; Ligon, Keith L.] Harvard Univ, Sch Med, Boston, MA USA. [Yung, W. K. Alfred] Univ Texas MD Anderson Canc Ctr, Div Neurooncol, Houston, TX 77030 USA. RP Wen, PY (reprint author), Dana Farber Canc Inst, Ctr Neurooncol, SW430D,450 Brookline Ave, Boston, MA 02215 USA. EM pwen@partners.org RI Waha, Andreas/J-2950-2014 FU Novartis Pharmaceuticals; Amgen; Astra Zeneca; Boehringer; Esai; Novartis; Genentech/Roche; Genzyme; Medimmune; Merck; Vascular Biogenics; Exelixis; Sanofi-Aventis; Plexxikon FX This work was supported by Novartis Pharmaceuticals.; P.Y.W. has received research support from Amgen, Astra Zeneca, Boehringer, Esai, Novartis, Genentech/Roche, Genzyme, Medimmune, Merck, Vascular Biogenics, Exelixis, and Sanofi-Aventis; has served on advisory boards for Merck, Novartis, and EMD Serono; and has received fees for lectures from Merck. E.Q.L. has served on advisory boards for Novartis and Genentech/Roche. D.A.R. has carried out consultant work for Novartis and Genentech/Roche. K.L.L. receives research funding from Plexxikon and Novartis. W.K.A.Y. receives research funding from Novartis and has performed consultant work for Eden. NR 101 TC 54 Z9 59 U1 1 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUL PY 2012 VL 14 IS 7 BP 819 EP 829 DI 10.1093/neuonc/nos117 PG 11 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 963OE UT WOS:000305630300001 PM 22619466 ER PT J AU Mansbach, JM Piedra, PA Laham, FR McAdam, AJ Clark, S Sullivan, AF Camargo, CA AF Mansbach, Jonathan M. Piedra, Pedro A. Laham, Federico R. McAdam, Alexander J. Clark, Sunday Sullivan, Ashley F. Camargo, Carlos A., Jr. TI NASOPHARYNGEAL LACTATE DEHYDROGENASE CONCENTRATIONS PREDICT BRONCHIOLITIS SEVERITY IN A PROSPECTIVE MULTICENTER EMERGENCY DEPARTMENT STUDY SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE severity of illness; biomarker; respiratory syncytial virus; human rhinovirus ID RESPIRATORY SYNCYTIAL VIRUS; RESPONSES; CHILDREN AB We reexamined the finding of an inverse relationship between values of nasopharyngeal lactate dehydrogenase, a marker of the innate immune response, and bronchiolitis severity. In a prospective, multicenter study of 258 children, we found in a multivariable model that higher nasopharyngeal lactate dehydrogenase values in young children with bronchiolitis were independently associated with a decreased risk of hospitalization. C1 [Mansbach, Jonathan M.] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Med, Boston, MA 02115 USA. [Piedra, Pedro A.] Baylor Coll Med, Dept Mol Virol & Microbiol & Pediat, Houston, TX 77030 USA. [Laham, Federico R.] Arnold Palmer Hosp Children, Orlando, FL USA. [McAdam, Alexander J.] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Lab Med, Boston, MA 02115 USA. [Clark, Sunday] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Sullivan, Ashley F.; Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Mansbach, JM (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Med, Main Clin Bldg 9 S,9157, Boston, MA 02115 USA. EM jonathan.mansbach@childrens.harvard.edu FU MedImmune (Gaithersburg, MD); Thrasher Research Fund (Salt Lake City, UT); National Institutes of Health (Bethesda, MD) [K23 AI-77801, U01 AI-67693] FX This study was supported by investigator-initiated research grant from MedImmune (Gaithersburg, MD), the Thrasher Research Fund (Salt Lake City, UT) and grants K23 AI-77801 and U01 AI-67693 from the National Institutes of Health (Bethesda, MD). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy And Infectious Diseases or the National Institutes of Health. The authors have no other funding or conflicts of interest to disclose. NR 10 TC 4 Z9 4 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD JUL PY 2012 VL 31 IS 7 BP 767 EP 769 DI 10.1097/INF.0b013e3182565eae PG 4 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 964PJ UT WOS:000305708300024 PM 22517336 ER PT J AU Anghel, SI Correa-Rochal, R Budinska, E Boliganl, KF Abraham, S Colombetti, S Fontao, L Mariotti, A Rimoldi, D Ghanem, GE Fisher, DE Levy, F Delorenzi, M Piguet, V AF Anghel, Silvia I. Correa-Rochal, Rafael Budinska, Eva Boliganl, Kayluz F. Abraham, Shahnaz Colombetti, Sara Fontao, Lionel Mariotti, Agnese Rimoldi, Donata Ghanem, Ghanem E. Fisher, David E. Levy, Frederic Delorenzi, Mauro Piguet, Vincent TI Breast cancer suppressor candidate-1 (BCSC-1) is a melanoma tumor suppressor that down regulates MITF SO PIGMENT CELL & MELANOMA RESEARCH LA English DT Article DE human; melanoma; potential biomarker; BCSC-1; tumor suppressor; MITF; proliferation ID GENE-EXPRESSION PROFILES; PROGRESSION; HETEROZYGOSITY; IDENTIFICATION; TRANSITION; SIGNATURES; TARGETS; CELLS AB Understanding the molecular aberrations involved in the development and progression of metastatic melanoma (MM) is essential for a better diagnosis and targeted therapy. We identified breast cancer suppressor candidate-1 (BCSC-1) as a novel tumor suppressor in melanoma. BCSC-1 expression is decreased in human MM, and its ectopic expression in MMderived cell lines blocks tumor formation in vivo and melanoma cell proliferation in vitro while increasing cell migration. We demonstrate that BCSC-1 binds to Sox10, which down regulates MITF, and results in a switch of melanoma cells from a proliferative to a migratory phenotype. In conclusion, we have identified BCSC-1 as a tumor suppressor in melanoma and as a novel regulator of the MITF pathway. C1 [Anghel, Silvia I.; Correa-Rochal, Rafael; Boliganl, Kayluz F.; Abraham, Shahnaz; Fontao, Lionel; Piguet, Vincent] Univ Hosp, Dept Dermatol & Venereol, Geneva, Switzerland. [Anghel, Silvia I.; Correa-Rochal, Rafael; Boliganl, Kayluz F.; Abraham, Shahnaz; Fontao, Lionel; Piguet, Vincent] Univ Hosp, Dept Microbiol, Geneva, Switzerland. [Anghel, Silvia I.; Correa-Rochal, Rafael; Boliganl, Kayluz F.; Abraham, Shahnaz; Fontao, Lionel; Piguet, Vincent] Univ Hosp, Dept Mol Med, Geneva, Switzerland. [Anghel, Silvia I.; Correa-Rochal, Rafael; Boliganl, Kayluz F.; Abraham, Shahnaz; Fontao, Lionel; Piguet, Vincent] Med Sch Geneva, Geneva, Switzerland. [Correa-Rochal, Rafael] Univ Gregorio Maranon, Lab Mol Immunobiol, Gen Hosp, Madrid, Spain. [Budinska, Eva; Delorenzi, Mauro] Univ Lausanne, Swiss Inst Bioinformat, Lausanne, Switzerland. [Budinska, Eva] Masaryk Univ, Inst Biostat & Anal, Brno, Czech Republic. [Boliganl, Kayluz F.] Natl Inst Oncol & Radiobiol, Dept Basic Res, Havana, Cuba. [Colombetti, Sara; Rimoldi, Donata; Levy, Frederic] Univ Lausanne, Ludwig Inst Canc Res, CH-1066 Epalinges, Switzerland. [Mariotti, Agnese] Univ Lausanne, Div Expt Oncol, Fac Biol & Med, CH-1066 Epalinges, Switzerland. [Ghanem, Ghanem E.] Univ Libre Brussels, Lab Oncol & Chirurg Expt, Inst J Bordet, Brussels, Belgium. [Fisher, David E.] Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Levy, Frederic] Debiopharm SA, Lausanne, Switzerland. [Delorenzi, Mauro] CHU Vaudois, Dept Format & Rech, CH-1011 Lausanne, Switzerland. [Delorenzi, Mauro] ISREC SV EPFL, Natl Ctr Competence Res Mol Oncol, Lausanne, Switzerland. [Piguet, Vincent] Cardiff Univ, Dept Dermatol & Wound Healing, Cardiff Inst Infect & Immun, Cardiff, S Glam, Wales. [Piguet, Vincent] Univ Wales Hosp, Cardiff CF4 4XW, S Glam, Wales. RP Piguet, V (reprint author), Univ Hosp, Dept Dermatol & Venereol, Geneva, Switzerland. EM piguetv@cardiff.ac.uk RI Correa-Rocha, Rafael/C-8213-2011; Budinska, Eva/F-2698-2011 OI Correa-Rocha, Rafael/0000-0003-3456-9986; Budinska, Eva/0000-0002-9004-9187 FU Swiss National Science Foundation via an NCCR Oncology program; MEDIC foundation; Leenaards Foundation; CARIGEST SA FX We thank F Leuba, F Jaunin, M Docquier, and C Delucinge Vivier for excellent technical help. We thank M Herlyn for cell lines. We thank Professor D Trono for lentiviral expression vectors. We thank T Sengstag and F Schutz for gene set analysis and P Wirapati for the nclust R package. We thank C Ruegg and B Wehrle-Haller for helpful discussions. We thank Dr P. Bowden for helpful discussions and critical comments on the manuscript. This work was supported by the Swiss National Science Foundation via an NCCR Oncology program awarded to VP. This work was also supported by grants from the MEDIC foundation and Leenaards Foundation to VP. We also thank the anonymous donator who supported our project via CARIGEST SA. The funders had no role in the study design, data collection and analysis, decisions to publish, or preparation of the manuscript. NR 19 TC 5 Z9 7 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1755-1471 J9 PIGM CELL MELANOMA R JI Pigment Cell Melanoma Res. PD JUL PY 2012 VL 25 IS 4 BP 482 EP 487 DI 10.1111/j.1755-148X.2012.01018.x PG 6 WC Oncology; Cell Biology; Dermatology SC Oncology; Cell Biology; Dermatology GA 962AK UT WOS:000305511200012 PM 22594792 ER PT J AU Zhang, XY Liang, J Chen, DC Xiu, MH Yang, FD Kosten, TA Kosten, TR AF Zhang, Xiang Yang Liang, Jun Chen, Da Chun Xiu, Mei Hong Yang, Fu De Kosten, Therese A. Kosten, Thomas R. TI Low BDNF is associated with cognitive impairment in chronic patients with schizophrenia SO PSYCHOPHARMACOLOGY LA English DT Article DE Schizophrenia; Cognition; Brain-derived neurotrophic factor; Serum ID NEUROTROPHIC FACTOR LEVELS; LONG-TERM TREATMENT; LOW SERUM-LEVELS; BIPOLAR DISORDER; 1ST-EPISODE SCHIZOPHRENIA; NEUROPSYCHOLOGICAL STATUS; ATYPICAL ANTIPSYCHOTICS; VAL66MET POLYMORPHISM; TARDIVE-DYSKINESIA; REPEATABLE BATTERY AB Several lines of evidence suggest that brain-derived neurotrophic factor (BDNF) plays a critical role in activity-dependent neuroplasticity underlying learning and memory in the hippocampus. Schizophrenia has a range of cognitive deficits that may evolve from decreased BDNF, and this study examines this association of BDNF with cognitive deficits in schizophrenia. We recruited 251 chronic schizophrenic patients and 206 healthy control subjects and examined the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and serum BDNF in both groups. Schizophrenic symptoms were assessed using the Positive and Negative Syndrome Scale. BDNF levels were significantly lower in patients than controls (p < 0.001). Cognitive scores on the RBANS and nearly all of its five subscales (all p < 0.001) except for the visuospatial/constructional index (p > 0.05) were significantly lower in schizophrenic patients than normal controls. For the patients, BDNF was positively associated with immediate memory in schizophrenia. Our findings suggest that BDNF may be involved in the pathophysiology of schizophrenia, and its associated cognitive impairment, especially immediate memory. C1 [Zhang, Xiang Yang; Kosten, Thomas R.] VA Med Ctr, Houston, TX 77030 USA. [Chen, Da Chun; Xiu, Mei Hong; Yang, Fu De] Beijing HuiLongGuan Hosp, Beijing 100096, Peoples R China. [Liang, Jun] Peking Univ, Inst Mental Hlth, Beijing 100083, Peoples R China. [Zhang, Xiang Yang; Kosten, Therese A.; Kosten, Thomas R.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. RP Zhang, XY (reprint author), VA Med Ctr, Res Bldg 109,Room 130,2002 Holcombe Blvd, Houston, TX 77030 USA. EM xyzhang@bcm.edu; kosten@bcm.edu FU Stanley Medical Research Institute [03T-459, 05T-726]; Department of Veterans Affairs, VISN 16, Mental Illness Research, Education and Clinical Center (MIRECC), United States National Institute of Health [K05-DA0454, P50-DA18827, U01-MH79639] FX This study was funded by the Stanley Medical Research Institute (03T-459 and 05T-726), and the Department of Veterans Affairs, VISN 16, Mental Illness Research, Education and Clinical Center (MIRECC), United States National Institute of Health K05-DA0454, P50-DA18827, and U01-MH79639. NR 55 TC 44 Z9 47 U1 0 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JUL PY 2012 VL 222 IS 2 BP 277 EP 284 DI 10.1007/s00213-012-2643-y PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 964GI UT WOS:000305681600009 PM 22274000 ER PT J AU Moschak, TM Stang, KA Phillips, TJ Mitchell, SH AF Moschak, Travis M. Stang, Katherine A. Phillips, Tamara J. Mitchell, Suzanne H. TI Behavioral inhibition in mice bred for high vs. low levels of methamphetamine consumption or sensitization SO PSYCHOPHARMACOLOGY LA English DT Article DE Inhibition; Go/no-go; Behavioral sensitization; Self-administration; Selected lines; Methamphetamine; Impulsivity ID REACTION-TIME-TASK; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; GO/NO-GO TASK; D-AMPHETAMINE; STOP-SIGNAL; RATS; PERFORMANCE; IMPULSIVITY; LESIONS; METHYLPHENIDATE AB Research indicates that genetics influence methamphetamine self-administration as well as sensitization to the psychomotor-stimulating effects of methamphetamine (MA). Other studies have suggested that heightened levels of impulsivity, including low levels of behavioral inhibition, are associated with the use of drugs, including MA. The current study examined whether lines of mice selected for traits associated with a heightened risk of developing MA dependence would also exhibit low levels of drug-na < ve inhibition and whether administration of MA would result in different levels of inhibition in animals selected to consume or respond more to MA. A go/no-go task was used to assess inhibition in male and female mice selected for low or high levels of MA consumption or selected for high or low levels of locomotor sensitization to repeated injections of MA. Mice selected for MA sensitization differed in false alarms, precue response rates (measures of behavioral inhibition), and also hits (measure of operant responding). Mice selected for MA consumption did not differ in measures of behavioral inhibition, though hits differed. When MA was administered prior to the task, false alarms, precue response rates, and hits decreased for mice from all selected lines. Female high drinking mice were particularly resistant to MA's effects on hits, but not precue response rate or false alarms. These data suggest a shared, but complex, genetic association between inhibition processes, general levels of operant responding, and MA sensitization or consumption. C1 [Moschak, Travis M.; Stang, Katherine A.; Phillips, Tamara J.; Mitchell, Suzanne H.] Oregon Hlth & Sci Univ, Dept Behav Neurosci L470, Portland, OR 97239 USA. [Mitchell, Suzanne H.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97239 USA. [Phillips, Tamara J.; Mitchell, Suzanne H.] Oregon Hlth & Sci Univ, Methamphetamine Abuse Res Ctr, Portland, OR 97239 USA. [Phillips, Tamara J.] Portland VA Med Ctr, Portland, OR USA. RP Mitchell, SH (reprint author), Oregon Hlth & Sci Univ, Dept Behav Neurosci L470, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM mitchesu@ohsu.edu OI Mitchell, Suzanne/0000-0002-0225-7200 FU Methamphetamine Abuse Research Center [P50 DA018165]; Department of Veterans Affairs; Portland Alcohol Research Center [P60 AA10760]; NIAAA [AA007468] FX SHM and TJP designed the study, TMM and KAS collected the data with help from Noah Gubner and Ryan McLaughlin, data analysis was performed by TMM, KAS and SHM, all authors were involved in data interpretation and manuscript preparation. This research was supported by the Methamphetamine Abuse Research Center (P50 DA018165), the Department of Veterans Affairs, and the Portland Alcohol Research Center (P60 AA10760). TMM was supported by NIAAA T32 training grant AA007468. All research was conducted in compliance with laws in USA. NR 49 TC 7 Z9 7 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JUL PY 2012 VL 222 IS 2 BP 353 EP 365 DI 10.1007/s00213-012-2650-z PG 13 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 964GI UT WOS:000305681600017 PM 22311384 ER PT J AU Yilmaz-Rastoder, E Gold, MS Hough, KA Gebhart, GF Williams, BA AF Yilmaz-Rastoder, Eser Gold, Michael S. Hough, Karen A. Gebhart, G. F. Williams, Brian A. TI Effect of Adjuvant Drugs on the Action of Local Anesthetics in Isolated Rat Sciatic Nerves SO REGIONAL ANESTHESIA AND PAIN MEDICINE LA English DT Article ID PERIPHERAL BENZODIAZEPINE-RECEPTORS; PERINEURAL INFUSION; CLONIDINE; ROPIVACAINE; ANALGESIA; BLOCK; DEXAMETHASONE; NEUROTOXICITY; BUPIVACAINE; CONDUCTION AB Background and Objectives: There is increasing clinical use of adjuvant drugs to prolong the duration of local anesthetic-induced block of peripheral nerves. However, the mechanistic understanding regarding drug interactions between these compounds in the periphery is quite limited. Accordingly, we undertook this study to determine whether selected adjuvant drugs are efficacious in blocking action potential propagation in peripheral nerves at concentrations used clinically and whether these drugs influence peripheral nerve block produced by local anesthetics. Methods: Isolated rat sciatic nerves were used to assess (1) the efficacy of buprenorphine, clonidine, dexamethasone, or midazolam, alone and in combination, on action potential propagation; and (2) their influence on the blocking actions of local anesthetics ropivacaine and lidocaine. Compound action potentials (CAPs) from A- and C-fibers were studied before and after drug application. Results: At estimated clinical concentrations, neither buprenorphine nor dexamethasone affected either A- or C-waves of the CAP. Clonidine produced a small but significant attenuation of the C-wave amplitude. Midazolam attenuated both A- and C-wave amplitudes, but with greater potency on the C-wave. The combination of clonidine, buprenorphine, and dexamethasone had no influence on the potency or duration of local anesthetic- or midazolam-induced block of A- and C-waves of the CAP. Conclusions: These results suggest that the reported clinical efficacy of clonidine, buprenorphine, and dexamethasone influences the actions of local anesthetics via indirect mechanisms. Further identification of these indirect mechanisms may enable the development of novel approaches to achieve longer-duration, modality-specific peripheral nerve block. C1 [Yilmaz-Rastoder, Eser; Gold, Michael S.; Hough, Karen A.; Gebhart, G. F.; Williams, Brian A.] Univ Pittsburgh, Sch Med, Dept Anesthesiol, Ctr Pain Res, Pittsburgh, PA 15261 USA. [Williams, Brian A.] VA Pittsburgh Hlth Syst, Pittsburgh, PA USA. RP Williams, BA (reprint author), Univ Pittsburgh, Sch Med, Dept Anesthesiol, Ctr Pain Res, W-1403 BST WR, Pittsburgh, PA 15261 USA. EM williamsba@anes.upmc.edu OI Gold, Michael/0000-0002-2083-6206 FU Department of Defense grant [OR090012] FX This research is supported by a Department of Defense grant (OR090012) to Drs. Williams, Gold, and Gebhart. The article review by Department of Defense grant coprincipal investigator Chester C. Buckenmaier, III, MD (Walter Reed Army Medical Center), is also acknowledged. NR 20 TC 18 Z9 18 U1 1 U2 4 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 JUL-AUG PY 2012 VL 37 IS 4 BP 403 EP 409 DI 10.1097/AAP.0b013e3182485965 PG 7 WC Anesthesiology SC Anesthesiology GA 965QI UT WOS:000305781900008 PM 22430023 ER PT J AU Ulbricht, C AF Ulbricht, Catherine TI Polypharmacy SO SCIENTIST LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ulbricht, C (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SCIENTIST INC PI PHILADELPHIA PA 400 MARKET ST, STE 1250, PHILADELPHIA, PA 19106 USA SN 0890-3670 J9 SCIENTIST JI Scientist PD JUL PY 2012 VL 26 IS 7 BP 23 EP 23 PG 1 WC Information Science & Library Science; Multidisciplinary Sciences SC Information Science & Library Science; Science & Technology - Other Topics GA 964SY UT WOS:000305718200006 ER PT J AU Khan, SM Hamnvik, OPR Brinkoetter, M Mantzoros, CS AF Khan, Sami M. Hamnvik, Ole-Petter R. Brinkoetter, Mary Mantzoros, Christos S. TI Leptin as a Modulator of Neuroendocrine Function in Humans SO YONSEI MEDICAL JOURNAL LA English DT Review DE Leptin; leptin deficiency; amenorrhea ID PROTHYROTROPIN-RELEASING HORMONE; RECOMBINANT HUMAN LEPTIN; HYPOTHALAMIC AMENORRHEA; HUMAN PHYSIOLOGY; ANOREXIA-NERVOSA; MESSENGER-RNA; HEALTHY-MEN; CLINICAL-IMPLICATIONS; PITUITARY-FUNCTION; DIABETES-MELLITUS AB Leptin, a peptide hormone secreted by adipocytes in proportion of the amount of energy stored in fat, plays a central role in regulating human energy homeostasis. In addition, leptin plays a significant permissive role in the physiological regulation of several neuroendocrine axes, including the hypothalamic-pituitary-gonadal, -thyroid, -growth hormone, and -adrenal axes. Decreased levels of leptin, also known as hypoleptinemia, signal to the brain a state of energy deprivation. Hypoleptinemia can be a congenital or acquired condition, and is associated with alterations of the aforementioned axes aimed at promoting survival. More specifically, gonadotropin levels decrease and become less pulsatile under conditions of energy deprivation, and these changes can be at least partially reversed through leptin administration in physiological replacement doses. Similarly, leptin deficiency is associated with thyroid axis abnormalities including abnormal levels of thyrotropinreleasing hormone, and leptin administration may at least partially attenuate this effect. Leptin deficiency results in decreased insulin-like growth factor 1 levels which can be partially ameliorated through leptin administration, and leptin appears to have a much more pronounced effect on the growth of rodents than that of humans. Similarly, adrenal axis function is regulated more tightly by low leptin in rodents than in humans. In addition to congenital leptin deficiency, conditions that may be associated with decreased leptin levels include hypothalamic amenorrhea, anorexia nervosa, and congenital or acquired lipodystrophy syndromes. Accumulating evidence from proof of concept studies suggests that leptin administration, in replacement doses, may ameliorate neuroendocrine abnormalities in individuals who suffer from these conditions. C1 [Khan, Sami M.; Hamnvik, Ole-Petter R.; Brinkoetter, Mary; Mantzoros, Christos S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. [Brinkoetter, Mary; Mantzoros, Christos S.] Boston VA Healthcare Syst, Endocrinol Sect, Boston, MA USA. [Hamnvik, Ole-Petter R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Endocrinol Diabet & Hypertens, Boston, MA 02215 USA. RP Mantzoros, CS (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab, 330 Brookline Ave, Boston, MA 02215 USA. EM cmantzor@bidmc.harvard.edu RI Hamnvik, Ole-Petter/D-1719-2011 NR 101 TC 20 Z9 22 U1 1 U2 6 PU YONSEI UNIV COLL MEDICINE PI SEOUL PA IN-HONG CHOI, M D, PH D, 50-1 YONSEI-RO, SEODAEMUN-GU, SEOUL 120-752, SOUTH KOREA SN 0513-5796 EI 1976-2437 J9 YONSEI MED J JI Yonsei Med. J. PD JUL 1 PY 2012 VL 53 IS 4 BP 671 EP 679 DI 10.3349/ymj.2012.53.4.671 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 958RQ UT WOS:000305258500001 PM 22665330 ER PT J AU Morikawa, T Shima, K Kuchiba, A Yamauchi, M Tanaka, N Imamura, Y Liao, XY Qian, ZR Brahmandam, M Longtine, JA Lindeman, NI Fuchs, CS Ogino, S AF Morikawa, Teppei Shima, Kaori Kuchiba, Aya Yamauchi, Mai Tanaka, Noriko Imamura, Yu Liao, Xiaoyun Qian, Zhi Rong Brahmandam, Mohan Longtine, Janina A. Lindeman, Neal I. Fuchs, Charles S. Ogino, Shuji TI No Evidence for Interference of H&E Staining in DNA Testing Usefulness of DNA Extraction From H&E-Stained Archival Tissue Sections SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE Histochemical staining; Polymerase chain reaction; Molecular diagnostics; Mutation detection; Microdissection; Solid tumor ID ISLAND METHYLATOR PHENOTYPE; POLYMERASE-CHAIN-REACTION; GASTROINTESTINAL STROMAL TUMORS; POPULATION-BASED SAMPLE; MELTING CURVE ANALYSIS; COLORECTAL-CANCER; COLON-CANCER; MICROSATELLITE INSTABILITY; MUTATION DETECTION; KRAS MUTATIONS AB Although histochemical staining has been believed to inhibit the DNA amplification reaction, no previous study has systematically evaluated the influence of histochemical staining on downstream molecular assays. To evaluate an influence of H&E staining on DNA testing, we isolated DNA from 10 unstained, 10 hematoxylin-stained, 10 eosin-stained, and 10 H&E-stained tissue sections (ie, 4 groups), from each of 5 colon cancers. Among the 4 groups, we did not observe any significant or appreciable difference in DNA fragmentation by agarose gel electrophoresis, in DNA amplification by real-time polymerase chain reaction (PCR), in microsatellite PCR fragment analyses, or in a PCR-pyrosequencing assay. As a proof-of-principle study, we successfully performed microsatellite instability analysis and sequencing of KRAS and BRAF on more than 1,300 colorectal cancers using DNA extracted from H&E-stained tissue sections. Our data provide no evidence for an interfering effect of H&E staining on DNA testing, suggesting that DNA from H&E-stained sections can be effectively used for routine DNA testing. C1 [Morikawa, Teppei] Harvard Univ, Sch Med, Ctr Mol Oncol Pathol, Dana Farber Canc Inst, Boston, MA 02215 USA. [Morikawa, Teppei; Shima, Kaori; Kuchiba, Aya; Yamauchi, Mai; Tanaka, Noriko; Imamura, Yu; Liao, Xiaoyun; Qian, Zhi Rong; Brahmandam, Mohan; Fuchs, Charles S.; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. [Ogino, Shuji] Harvard Univ, Ctr Mol Oncol Pathol, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Pathol,Sch Med, Boston, MA 02215 USA. [Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Morikawa, T (reprint author), Harvard Univ, Sch Med, Ctr Mol Oncol Pathol, Dana Farber Canc Inst, 450 Brookline Ave,Room JF-208E, Boston, MA 02215 USA. OI Qian, Zhi rong/0000-0003-1633-4120 FU US National Institute of Health (NIH) [P01 CA87969, P01 CA55075, P50 CA127003, R01 CA118553, R01 CA124908, R01 CA151993] FX Supported by US National Institute of Health (NIH) grants P01 CA87969 (SE. Hankinson), P01 CA55075 (WC. Willett), P50 CA127003 (Dr Fuchs), R01 CA118553 (Dr Fuchs), R01 CA124908 (Dr Fuchs), and R01 CA151993 (Dr Ogino). NR 54 TC 12 Z9 12 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 JUL PY 2012 VL 138 IS 1 BP 122 EP 129 DI 10.1309/AJCP28LAOOKSZSVW PG 8 WC Pathology SC Pathology GA 961DV UT WOS:000305445000018 PM 22706867 ER PT J AU Burke, LE Styn, MA Sereika, SM Conroy, MB Ye, L Glanz, K Sevick, MA Ewing, LJ AF Burke, Lora E. Styn, Mindi A. Sereika, Susan M. Conroy, Molly B. Ye, Lei Glanz, Karen Sevick, Mary Ann Ewing, Linda J. TI Using mHealth Technology to Enhance Self-Monitoring for Weight Loss A Randomized Trial SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID LIFE-STYLE MODIFICATION; LOSS MAINTENANCE; TREATMENT PREFERENCE; PHYSICAL-ACTIVITY; CLINICAL-TRIAL; MOBILE PHONE; OBESE ADULTS; PROGRAM; INTERVENTIONS; MANAGEMENT AB Background: Self-monitoring for weight loss has traditionally been performed with paper diaries. Technologic advances could reduce the burden of self-monitoring and provide feedback to enhance adherence. Purpose: To determine if self-monitoring diet using a PDA only or the PDA with daily tailored feedback ( PDA + feedback [FB]), was superior to using a paper diary on weight loss and maintenance. Design: The Self-Monitoring and Recording Using Technology (SMART) Trial was a 24-month randomized clinical trial; participants were randomly assigned to one of three self-monitoring groups. Setting/participants: From 2006 to 2008, a total of 210 overweight/obese adults (84.8% female, 78.1% white) were recruited from the community. Data were analyzed in 2011. Intervention: Participants received standard behavioral treatment for weight loss that included dietary and physical activity goals, encouraged the use of self-monitoring, and was delivered in group sessions. Main outcome measures: Percentage weight change at 24 months, adherence to self-monitoring over time. Results: Study retention was 85.6%. The mean percentage weight loss at 24 months was not different among groups (paper diary: -1.94%, 95% CI = -3.88, 0.01; PDA: -1.38%, 95% CI = -3.38, 0.62; PDA + FB: -2.32%, 95% CI = -4.29, -0.35); only the PDA + FB group (p = 0.02) demonstrated a significant loss. For adherence to self-monitoring, there was a time-by-treatment group interaction between the combined PDA groups and the paper diary group (p = 0.03) but no difference between PDA and PDA + FB groups (p = 0.49). Across all groups, weight loss was greater for those who were adherent >= 60% versus <30% of the time (p < 0.001). Conclusions: PDA + FB use resulted in a small weight loss at 24 months; PDAuse resulted in greater adherence to dietary self-monitoring over time. However, for sustained weight loss, adherence to self-monitoring is more important than the method used to self-monitor. A daily feedback message delivered remotely enhanced adherence and improved weight loss, which suggests that technology can play a role in improving weight loss. Trial registration: This study is registered at clinicaltrials. gov NCT00277771. (Am J Prev Med 2012;43(1):20-26) (C) 2012 American Journal of Preventive Medicine C1 [Burke, Lora E.; Styn, Mindi A.; Sereika, Susan M.; Ye, Lei] Univ Pittsburgh, Sch Nursing, Dept Hlth & Community Syst, Pittsburgh, PA 15261 USA. [Burke, Lora E.; Styn, Mindi A.; Sereika, Susan M.; Conroy, Molly B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Sereika, Susan M.; Ye, Lei] Univ Pittsburgh, Dept Biostat, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA. [Conroy, Molly B.; Sevick, Mary Ann] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15261 USA. [Ewing, Linda J.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15261 USA. [Sevick, Mary Ann] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Glanz, Karen] Univ Penn, Sch Med & Nursing, Philadelphia, PA 19104 USA. RP Burke, LE (reprint author), Univ Pittsburgh, Sch Nursing, Dept Hlth & Community Syst, 3500 Victoria St,415 Victoria Bldg, Pittsburgh, PA 15261 USA. EM lbu100@pitt.edu RI Emchi, Karma/Q-1952-2016 FU NIH [NIH/NIDDK R01-DK071817, R01-DK071817-04S1, R01-DK071817-05S1, NIH/NINR K24-NR010742]; Data Management Core of the Center for Research in Chronic Disorders at the University of Pittsburgh School of Nursing [NIH-NINR P30-NR03924]; General Clinical Research Center [NIH-NCRR-GCRC 5M01-RR000056]; Clinical Translational Research Center (NIH/NCRR/CTSA) at University of Pittsburgh [UL1 RR024153] FX This work was supported by NIH grants NIH/NIDDK R01-DK071817, R01-DK071817-04S1, R01-DK071817-05S1, and NIH/NINR K24-NR010742. The conduct of the study also was supported by the Data Management Core of the Center for Research in Chronic Disorders at the University of Pittsburgh School of Nursing (NIH-NINR P30-NR03924), the General Clinical Research Center (NIH-NCRR-GCRC 5M01-RR000056) and the Clinical Translational Research Center (NIH/NCRR/CTSA Grant UL1 RR024153) at the University of Pittsburgh. NR 32 TC 75 Z9 75 U1 7 U2 40 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD JUL PY 2012 VL 43 IS 1 BP 20 EP 26 DI 10.1016/j.amepre.2012.03.016 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 959VJ UT WOS:000305344000003 PM 22704741 ER PT J AU Thorndike, AN Sonnenberg, L Healey, E Myint-U, K Kvedar, JC Regan, S AF Thorndike, Anne N. Sonnenberg, Lillian Healey, Erica Myint-U, Khinlei Kvedar, Joseph C. Regan, Susan TI Prevention of Weight Gain Following a Worksite Nutrition and Exercise Program A Randomized Controlled Trial SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID PHYSICAL-ACTIVITY INTERVENTIONS; INTERNET; OBESITY; MAINTENANCE; HEALTH; OVERWEIGHT; TRENDS AB Background: Many employers are now providing wellness programs to help employees make changes in diet and exercise behaviors. Improving health outcomes and reducing costs will depend on whether employees sustain lifestyle changes and maintain a healthy weight over time. Purpose: To determine if a 9-month maintenance intervention immediately following a 10-week worksite exercise and nutrition program would prevent regain of the weight lost during the program. Design: RCT. Setting/participants: In 2008, a total of 330 employees from 24 teams completed a 10-week exercise and nutrition program at a large hospital worksite and were randomized by team to maintenance or control (usual care) for 9 months. Intervention: Internet support with a website for goal-setting and self-monitoring of weight and exercise plus minimal personal support. Main outcome measures: Weight loss, percentage weight loss, time spent in physical activity, and frequency of consumption of fruits/vegetables, fatty foods, and sugary foods at 1 year compared to baseline. One-year follow-up was completed in 2010, and data were analyzed in 2011. Results: At 1 year, 238 subjects (72%) completed follow-up assessments. Mean baseline BMI was 27.6 and did not differ between intervention and control. Compared to baseline, both groups lost weight during the 10-week program and maintained 65% of weight loss at 1 year (p < 0.001). There was no difference in weight loss between groups at the end of the 10-week program (4.8 lbs vs 4.3 lbs, p = 0.53 for group X time interaction) or end of maintenance at 1 year (3.4 lbs vs 2.5 lbs, p = 0.40 for group X time interaction). All subjects had improvements in physical activity and nutrition (increased fruits/vegetables and decreased fat and sugar intake) at 1 year but did not differ by group. Conclusions: An intensive 10-week team-based worksite exercise and nutrition program resulted in moderate weight loss and improvements in diet and exercise behaviors at 1 year, but an Internet-based maintenance program immediately following the 10-week program did not improve these outcomes. Trial registration: This study is registered at clinicaltrials. gov NCT00707577. (Am J Prev Med 2012;43(1):27-33) (C) 2012 American Journal of Preventive Medicine C1 [Thorndike, Anne N.; Regan, Susan] Massachusetts Gen Hosp, Gen Med Unit, Boston, MA 02114 USA. [Sonnenberg, Lillian] Massachusetts Gen Hosp, Nutr Serv, Boston, MA 02114 USA. [Thorndike, Anne N.; Sonnenberg, Lillian; Kvedar, Joseph C.; Regan, Susan] Harvard Univ, Sch Med, Boston, MA USA. [Healey, Erica] Massachusetts Sch Profess Psychol, Boston, MA USA. [Myint-U, Khinlei; Kvedar, Joseph C.] Partners HealthCare, Ctr Connected Hlth, Boston, MA USA. [Sonnenberg, Lillian] Massachusetts Gen Hosp, Food Serv, Boston, MA 02114 USA. RP Thorndike, AN (reprint author), Massachusetts Gen Hosp, Gen Med Unit, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM athorndike@partners.org FU NIH/National Heart Lung and Blood Institute [K23 HL93221]; Partners Healthcare FX This project was supported by the NIH/National Heart Lung and Blood Institute grant K23 HL93221 and by Partners Healthcare. NR 27 TC 14 Z9 14 U1 4 U2 32 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD JUL PY 2012 VL 43 IS 1 BP 27 EP 33 DI 10.1016/j.amepre.2012.02.029 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 959VJ UT WOS:000305344000004 PM 22704742 ER PT J AU Lubitz, CC Chen, H AF Lubitz, Carrie C. Chen, Herbert TI Sestamibi-Negative Patients: To Operate or Image? SO ANNALS OF SURGICAL ONCOLOGY LA English DT Editorial Material ID ASYMPTOMATIC PRIMARY HYPERPARATHYROIDISM; 3RD INTERNATIONAL WORKSHOP; PARATHYROID SURGERY C1 [Chen, Herbert] UW Sch Med & Publ Hlth, Dept Surg, Madison, WI USA. [Lubitz, Carrie C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Surg Unit,Dept Surg, Boston, MA USA. RP Chen, H (reprint author), UW Sch Med & Publ Hlth, Dept Surg, Madison, WI USA. EM chen@surgery.wisc.edu NR 13 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD JUL PY 2012 VL 19 IS 7 BP 2086 EP 2087 DI 10.1245/s10434-012-2369-4 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA 962PS UT WOS:000305558000004 PM 22526912 ER PT J AU Wang, D Zhang, Q Blanke, CD Demetri, GD Heinrich, MC Watson, JC Hoffman, JP Okuno, S Kane, JM von Mehren, M Eisenberg, BL AF Wang, Dian Zhang, Qiang Blanke, Charles D. Demetri, George D. Heinrich, Michael C. Watson, James C. Hoffman, John P. Okuno, Scott Kane, John M. von Mehren, Margaret Eisenberg, Burton L. TI Phase II Trial of Neoadjuvant/adjuvant Imatinib Mesylate for Advanced Primary and Metastatic/recurrent Operable Gastrointestinal Stromal Tumors: Long-term Follow-up Results of Radiation Therapy Oncology Group 0132 (vol 19, pg 1074, 2012) SO ANNALS OF SURGICAL ONCOLOGY LA English DT Correction C1 [Wang, Dian] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Zhang, Qiang] Ctr Stat, Radiat Therapy Oncol Grp, Philadelphia, PA USA. [Blanke, Charles D.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Blanke, Charles D.] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. [Demetri, George D.] Harvard Univ, Sch Med, Boston, MA USA. [Demetri, George D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Heinrich, Michael C.] Portland VA Med Ctr, Portland, OR USA. [Heinrich, Michael C.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Watson, James C.; Hoffman, John P.; von Mehren, Margaret] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Okuno, Scott] Mayo Clin, Rochester, MN USA. [Kane, John M.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Eisenberg, Burton L.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. RP Wang, D (reprint author), Med Coll Wisconsin, Milwaukee, WI 53226 USA. EM dwang@mcw.edu NR 1 TC 0 Z9 0 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD JUL PY 2012 VL 19 IS 7 BP 2420 EP 2420 DI 10.1245/s10434-012-2228-3 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA 962PS UT WOS:000305558000046 ER PT J AU Glotzbecker, B Duncan, C Alyea, E Campbell, B Soiffer, R AF Glotzbecker, Brett Duncan, Christine Alyea, Edwin, III Campbell, Bonnie Soiffer, Robert TI Important Drug Interactions in Hematopoietic Stem Cell Transplantation: What Every Physician Should Know SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Review DE Drug metabolism; Chemotherapy; Calcineurin inhibitor; Cytochrome P-450 enzyme system ID BONE-MARROW TRANSPLANT; RENAL-ALLOGRAFT RECIPIENTS; INVASIVE FUNGAL-INFECTIONS; HIGH-DOSE BUSULFAN; ITRACONAZOLE ORAL SOLUTION; HUMAN LIVER-MICROSOMES; PHARMACOKINETIC INTERACTION; CLINICAL PHARMACOKINETICS; MYCOPHENOLATE-MOFETIL; HEALTHY-VOLUNTEERS AB Morbidity is increased in patients undergoing hematopoietic stem cell transplantation when drug drug interactions lead to unexpected outcomes. These interactions occur as a result of exposure to complicated medical regimens with drugs with narrow therapeutic windows and high toxicity profiles. In this report, we review the available evidence and possible mechanisms of the most clinically relevant drug interactions, including those involving inhibitors and inducers of the P450 isoenzyme system. We identify key interactions that should be familiar to any physician caring for patients after hematopoietic stem cell transplantation. We discuss drug metabolism in children and in the elderly and examine how age-related differences in metabolism make complicate drug regimens in these populations. A better understanding of these interactions and the responsible mechanisms will promote efficient delivery of the safest medical regimens to patients undergoing hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 18: 989-1006 (2012) (C) 2012 American Society for Blood and Marrow Transplantation C1 [Glotzbecker, Brett; Duncan, Christine; Alyea, Edwin, III; Campbell, Bonnie; Soiffer, Robert] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Duncan, Christine] Childrens Hosp, Dept Pediat Oncol, Boston, MA 02115 USA. RP Glotzbecker, B (reprint author), 450 Brookline Ave, Boston, MA 02115 USA. EM brett_glotzbecker@dfci.harvard.edu NR 158 TC 16 Z9 16 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JUL PY 2012 VL 18 IS 7 BP 989 EP 1006 DI 10.1016/j.bbmt.2011.11.029 PG 18 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 964BE UT WOS:000305667900004 PM 22155504 ER PT J AU Tolar, J Deeg, HJ Arai, S Horwitz, M Antin, JH McCarty, JM Adams, RH Ewell, M Leifer, ES Gersten, ID Carter, SL Horowitz, MM Nakamura, R Pulsipher, MA DiFronzo, NL Confer, DL Eapen, M Anderlini, P AF Tolar, Jakub Deeg, H. Joachim Arai, Sally Horwitz, Mitchell Antin, Joseph H. McCarty, John M. Adams, Roberta H. Ewell, Marian Leifer, Eric S. Gersten, Iris D. Carter, Shelly L. Horowitz, Mary M. Nakamura, Ryotaro Pulsipher, Michael A. DiFronzo, Nancy L. Confer, Dennis L. Eapen, Mary Anderlini, Paolo TI Fludarabine-Based Conditioning for Marrow Transplantation from Unrelated Donors in Severe Aplastic Anemia: Early Results of a Cyclophosphamide Dose Deescalation Study Show Life-Threatening Adverse Events at Predefined Cyclophosphamide Dose Levels SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Bone marrow transplantation; Stem cell transplantation; Matched unrelated donor; Antithymocyte globulin ID TOTAL-BODY IRRADIATION; STEM-CELL TRANSPLANTATION; SAA WORKING PARTY; ANTITHYMOCYTE GLOBULIN; BONE-MARROW; REGIMEN; BLOOD AB Excessive adverse events were encountered in a Phase I/II study of cyclophosphamide (CY) dose deescalation in a fludarabine-based conditioning regimen for bone marrow transplantation from unrelated donors in patients with severe aplastic anemia. All patients received fixed doses of antithymocyte globulin, fludarabine, and low-dose total body irradiation. The starting CY dose was 150 mg/kg, with deescalation to 100 mg/kg, 50 mg/kg, or 0 mg/kg. CY dose level 0 mg/kg was closed due to graft failure in 3 of 3 patients. CY dose level 150 mg/kg was closed due to excessive organ toxicity (n = 6) or viral pneumonia (n = 1), resulting in the death of 7 of 14 patients. CY dose levels 50 and 100 mg/kg remain open. Thus, CY at doses of 150 mg/kg in combination with total body irradiation (2 Gy), fludarabine (120 mg/m(2)), and antithymocyte globulin was associated with excessive organ toxicity. Biol Blood Marrow Transplant 18: 1007-1011 (2012) (C) 2012 American Society for Blood and Marrow Transplantation C1 [Tolar, Jakub] Univ Minnesota, Sch Med, Dept Pediat, Div Blood & Marrow Transplantat, Minneapolis, MN 55455 USA. [Deeg, H. Joachim] Univ Washington, Div Oncol, Seattle, WA 98195 USA. [Deeg, H. Joachim] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA USA. [Arai, Sally] Stanford Univ, Med Ctr, Div Blood & Marrow Transplantat, Stanford, CA 94305 USA. [Horwitz, Mitchell] Duke Univ, Sch Med, Div Cellular Therapy, Adult Stem Cell Transplant Program, Durham, NC USA. [Antin, Joseph H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [McCarty, John M.] Virginia Commonwealth Univ, Dept Hematol Oncol, Massey Canc Ctr, Richmond, VA USA. [McCarty, John M.] Virginia Commonwealth Univ, Bone Marrow Transplantat Program, Massey Canc Ctr, Richmond, VA USA. [Adams, Roberta H.] Phoenix Childrens Hosp, Dept Hematol Oncol, Phoenix, AZ USA. [Ewell, Marian; Gersten, Iris D.; Carter, Shelly L.] EMMES Corp, Rockville, MD USA. [Leifer, Eric S.] NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA. [Horowitz, Mary M.; Eapen, Mary] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Nakamura, Ryotaro] City Hope Natl Med Ctr, Dept Hematol Hematopoiet Cell Transplantat, Duarte, CA USA. [Pulsipher, Michael A.] Univ Utah, Dept Pediat, Huntsman Canc Inst, Div Hematol & Hematol Malignancies, Salt Lake City, UT USA. [DiFronzo, Nancy L.] NHLBI, Div Blood Dis & Resources, NIH, Bethesda, MD 20892 USA. [Confer, Dennis L.] Natl Marrow Donor Program, Minneapolis, MN USA. [Anderlini, Paolo] Univ Texas MD Anderson Canc Ctr, Div Canc Med, Dept Stem Cell Transplantat, Houston, TX 77030 USA. RP Tolar, J (reprint author), Univ Minnesota, Sch Med, Dept Pediat, Div Blood & Marrow Transplantat, 420 Delaware St SE,MMC 366, Minneapolis, MN 55455 USA. EM tolar003@umn.edu OI Tolar, Jakub/0000-0002-0957-4380 FU National Heart, Lung, and Blood Institute [EQ1 U10HL069294]; National Cancer Institute FX We thank Juan Wu and Yanli Wang for help with manuscript preparation, Erica Sanchez for secretarial assistance, and the clinical investigators who entered and managed the patients in this study. The BMT CTN is supported in part by Grant EQ1 U10HL069294 from the National Heart, Lung, and Blood Institute and the National Cancer Institute. NR 14 TC 22 Z9 22 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JUL PY 2012 VL 18 IS 7 BP 1007 EP 1011 DI 10.1016/j.bbmt.2012.04.014 PG 5 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 964BE UT WOS:000305667900005 PM 22546497 ER PT J AU Hale, GA Shrestha, S Le-Rademacher, J Burns, LJ Gibson, J Inwards, DJ Freytes, CO Bolwell, BJ Hsu, JW Slavin, S Isola, L Rizzieri, DA Gale, RP Laport, GG Montoto, S Lazarus, HM Hari, PN AF Hale, Gregory A. Shrestha, Smriti Le-Rademacher, Jennifer Burns, Linda J. Gibson, John Inwards, David J. Freytes, Cesar O. Bolwell, Brian J. Hsu, Jack W. Slavin, Shimon Isola, Luis Rizzieri, David A. Gale, Robert Peter Laport, Ginna G. Montoto, Silvia Lazarus, Hillard M. Hari, Parameswaran N. TI Alternate Donor Hematopoietic Cell Transplantation (HCT) in Non-Hodgkin Lymphoma Using Lower Intensity Conditioning: A Report from the CIBMTR SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Non-Hodgkin lymphoma; HCT ID ALLOGENEIC TRANSPLANTATION; MARROW-TRANSPLANTATION; RETROSPECTIVE ANALYSIS; HOST DISEASE; FOLLOW-UP; GRAFT; SURVIVAL; REGIMEN; LEUKEMIA; OUTCOMES AB We analyzed the outcomes of 248 (61% male) adult recipients of HLA-matched unrelated and HLA-mismatched related donor hematopoietic cell transplantation (HCT) for non-Hodgkin lymphoma (NHL) after reduced or lower intensity conditioning (RIC), reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) from 1997 to 2004. Median age was 52 (range: 18-72 years); 31% had a Karnofsky performance score <90. Follicular NHL (43%) was the major histology. Incidence of grades II-IV acute graft-versus-host disease (aGVHD) was 43% at 100 days; and chronic GVHD (cGVHD) was 44% at 3 years. Treatment-related mortality (TRM) at 100 days was 24%. Three-year overall survival (OS) and progression-free survival (PFS) were 41% and 32%, respectively. In multivariate analysis, use of antithymocyte globulin (ATG) and HLA mismatch were associated with increased TRM. High-grade histology, ATG use, and chemotherapy resistance were associated with lower PFS. Older age, shorter interval from diagnosis to HCT, non total body irridiation (TBI) conditioning regimens, ex vivo T cell depletion, and HLA-mismatched unrelated donors were associated with mortality. GVHD did not influence relapse or PFS. Older age, aggressive histology, and chemotherapy resistance correlated with poorer survival. For selected patients with NHL, lack of an available sibling donor should not be a barrier to allogeneic HCT. Biol Blood Marrow Transplant 18: 1036-1043 (2012) (C) 2012 American Society for Blood and Marrow Transplantation C1 [Shrestha, Smriti; Le-Rademacher, Jennifer; Hari, Parameswaran N.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplantat Res, Milwaukee, WI 53226 USA. [Hale, Gregory A.] Univ S Florida, All Childrens Hosp, St Petersburg, FL 33701 USA. [Burns, Linda J.] Univ Minnesota, Med Ctr, Minneapolis, MN 55455 USA. [Gibson, John] Royal Prince Alfred Hosp, Inst Haematol, Camperdown, NSW 2050, Australia. [Inwards, David J.] Mayo Clin, Rochester, MN USA. [Freytes, Cesar O.] Univ Texas Hlth Sci Ctr San Antonio, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Bolwell, Brian J.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Hsu, Jack W.] Univ Florida, Shands Hosp, Gainesville, FL USA. [Slavin, Shimon] Int Ctr Cell Therapy & Canc Immunotherapy, Tel Aviv, Israel. [Isola, Luis] Mt Sinai Hosp, New York, NY 10029 USA. [Rizzieri, David A.] Duke Univ, Med Ctr, Durham, NC USA. [Gale, Robert Peter] Celgene Corp, Summit, NJ USA. [Laport, Ginna G.] Stanford Hosp & Clin, Stanford, CA USA. [Montoto, Silvia] Queen Mary Univ London, Sch Med, London, England. [Lazarus, Hillard M.] Univ Hosp, Case Med Ctr, Cleveland, OH USA. RP Hari, PN (reprint author), Med Coll Wisconsin, Ctr Int Blood & Marrow Transplantat Res, 9200 W Wisconsin Ave,Suite C5500, Milwaukee, WI 53226 USA. EM phari@mcw.edu OI Hari, Parameswaran/0000-0002-8800-297X FU National Cancer Institute (NCI) [U24-CA76518, 5U01HL069294]; National Heart, Lung and Blood Institute (NHLBI) [U24-CA76518, 5U01HL069294]; National Institute of Allergy and Infectious Diseases (NIAID) [U24-CA76518]; Health Resources and Services Administration (HRSA/DHHS) [HHSH234200637015C]; Office of Naval Research [N00014-06-1-0704, N00014-08-1-0058]; Allos, Inc.; Amgen, Inc.; Angioblast FX The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA76518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI), and the National Institute of Allergy and Infectious Diseases (NIAID); a Grant/Cooperative Agreement 5U01HL069294 from NHLBI and NCI; a contract HHSH234200637015C with Health Resources and Services Administration (HRSA/DHHS); 2 grants, N00014-06-1-0704 and N00014-08-1-0058, from the Office of Naval Research; and grants from Allos, Inc.; Amgen, Inc.; Angioblast; anonymous donation to the Medical College of Wisconsin; Ariad; Be the Match Foundation; Blue Cross and Blue Shield Association; Buchanan Family Foundation; CaridianBCT; Celgene Corporation; CellGenix, GmbH; Children's Leukemia Research Association; Fresenius-Biotech North America, Inc.; Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; Genzyme Corporation; GlaxoSmithKline; Kiadis Pharma; The Leukemia & Lymphoma Society; The Medical College of Wisconsin; Millennium Pharmaceuticals, Inc.; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Optum Healthcare Solutions, Inc.; Otsuka America Pharmaceutical, Inc.; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; Swedish Orphan Biovitrum; THERAKOS, Inc.; and Wellpoint, Inc. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, or any other agency of the U.S. Government. NR 23 TC 9 Z9 9 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JUL PY 2012 VL 18 IS 7 BP 1036 EP 1043 DI 10.1016/j.bbmt.2011.11.026 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 964BE UT WOS:000305667900008 PM 22155506 ER PT J AU Carroll, JS Williams, M Gallivan, TM AF Carroll, John S. Williams, Michele Gallivan, Theresa M. TI The ins and outs of change of shift handoffs between nurses: a communication challenge SO BMJ QUALITY & SAFETY LA English DT Article ID BEHAVIOR; FAILURES; SAFETY AB Background: Communication breakdowns have been identified as a source of problems in complex work settings such as hospital-based healthcare. Methods: The authors conducted a multi-method study of change of shift handoffs between nurses, including interviews, survey, audio taping and direct observation of handoffs, posthandoff questionnaires, and archival coding of clinical records. Results: The authors found considerable variability across units, nurses and, surprisingly, roles. Incoming and outgoing nurses had different expectations for a good handoff: incoming nurses wanted a conversation with questions and eye contact, whereas outgoing nurses wanted to tell their story without interruptions. More experienced nurses abbreviated their reports when incoming nurses knew the patient, but the incoming nurses responded with a large number of questions, creating a contest for control. Nurses' ratings did not correspond to expert ratings of information adequacy, suggesting that nurses consider other functions of handoffs beyond information processing, such as social interaction and learning. Discussion: These results suggest that variability across roles as information provider versus receiver and experience level (as well as across individual and organisational contexts) are reasons why improvement efforts directed at standardising and improving handoffs have been challenging in nursing and in other healthcare professions as well. C1 [Carroll, John S.] MIT, Alfred P Sloan Sch Management, Cambridge, MA 02142 USA. [Williams, Michele] Cornell Univ, Sch Ind & Labor Relat, Ithaca, NY 14853 USA. [Gallivan, Theresa M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Carroll, JS (reprint author), MIT, Alfred P Sloan Sch Management, 100 Main St,E62-318, Cambridge, MA 02142 USA. EM jcarroll@mit.edu FU CRICO/RMF (part of Partners hospitals) FX The work was supported by a seed grant for exploratory research from CRICO/RMF (part of Partners hospitals), but they had no role in the design and conduct of the studies. NR 28 TC 14 Z9 14 U1 1 U2 21 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-5415 J9 BMJ QUAL SAF JI BMJ Qual. Saf. PD JUL PY 2012 VL 21 IS 7 BP 586 EP 593 DI 10.1136/bmjqs-2011-000614 PG 8 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 961PG UT WOS:000305477700006 PM 22328456 ER PT J AU Merkow, RP Bilimoria, KY McCarter, MD Chow, WB Gordon, HS Stewart, AK Ko, CY Bentrem, DJ AF Merkow, Ryan P. Bilimoria, Karl Y. McCarter, Martin D. Chow, Warren B. Gordon, Howard S. Stewart, Andrew K. Ko, Clifford Y. Bentrem, David J. TI Effect of histologic subtype on treatment and outcomes for esophageal cancer in the United States SO CANCER LA English DT Article DE esophageal cancer; tumor histology; surgery; survival; hospital type; adenocarcinoma; squamous cell carcinoma; treatment utilization; outcomes ID PROPENSITY SCORE; SURGERY; CARCINOMA; CHEMORADIATION; ADENOCARCINOMA; PATTERNS; THERAPY; CARE AB BACKGROUND: Esophageal adenocarcinoma (AC) and squamous cell carcinoma (SCC) have distinct clinico-pathologic characteristics; however, it is unclear whether treatment patterns differ by histologic subtype. The objective of this study was to examine differences in treatment use and outcomes by histologic subtype for esophageal cancer in the United States. METHODS: From the National Cancer Data Base, patients with esophageal cancer were identified. Regression models were formulated to assess the influence of histologic subtype on treatment use and overall survival. RESULTS: From 1998 to 2007, 80,961 patients were identified with esophageal cancer in the United States. A higher percentage of patients with nonmetastatic AC underwent surgical resection compared with patients with nonmetastatic SCC (AC, 65.7%; SCC, 36.0%; P<.001), who were more often treated with chemoradiotherapy alone (AC, 25.7%; SCC, 54.1%; P<.001). High-volume academic centers used surgery more frequently for both AC and SCC than did other centers, yet even at high-volume academic centers, surgery was used much less often to treat SCC than AC (AC, 79.3%; SCC, 53.7%; P<.001). The likelihood of operative treatment for nonmetastatic disease was significantly lower in patients with SCC compared with patients with AC (P<.001). Overall survival was lower for patients with stage II/III disease of either histologic subtype treated with chemoradiotherapy alone compared with surgery plus chemoradiotherapy (P<.001). CONCLUSION: A large proportion of patients with esophageal cancer are being treated nonoperatively, and treatment use varies according to tumor histology, particularly by center type. Cancer 2011. (c) 2011 American Cancer Society. C1 [Merkow, Ryan P.; Bilimoria, Karl Y.; Bentrem, David J.] Northwestern Univ, Dept Surg, Feinberg Sch Med, Chicago, IL 60611 USA. [Bentrem, David J.] Jesse Brown VA Med Ctr, Dept Surg, Chicago, IL USA. [Merkow, Ryan P.; McCarter, Martin D.] Univ Colorado, Dept Surg, Sch Med, Aurora, CO USA. [Bilimoria, Karl Y.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. [Gordon, Howard S.] Univ Illinois, Coll Med, VA Ctr Management Complex Chron Care, Jesse Brown VA Med Ctr,Dept Med, Chicago, IL USA. [Stewart, Andrew K.] Amer Coll Surg, Canc Programs, Chicago, IL USA. [Chow, Warren B.; Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. [Chow, Warren B.; Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Bentrem, DJ (reprint author), 676 N St Clair St,Suite 650, Chicago, IL 60611 USA. EM dbentrem@nmff.org RI Gordon, Howard/E-4420-2010 OI Gordon, Howard/0000-0002-6712-5954 FU Health Services Research Division, Department of Veterans Affairs FX D.J.B. is supported by a Career Development Award from the Health Services Research Division, Department of Veterans Affairs. NR 32 TC 12 Z9 12 U1 0 U2 2 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 JUL 1 PY 2012 VL 118 IS 13 BP 3268 EP 3276 DI 10.1002/cncr.26608 PG 9 WC Oncology SC Oncology GA 960LM UT WOS:000305389500011 PM 22006369 ER PT J AU Landrum, MB Keating, NL Lamont, EB Bozeman, SR McNeil, BJ AF Landrum, Mary Beth Keating, Nancy L. Lamont, Elizabeth B. Bozeman, Samuel R. McNeil, Barbara J. TI Reasons for underuse of recommended therapies for colorectal and lung cancer in the Veterans Health Administration SO CANCER LA English DT Article DE quality of care; health care delivery; disparities; veterans health administration; underuse ID III COLON-CANCER; MEDICARE CHEMOTHERAPY CLAIMS; ADJUVANT-CHEMOTHERAPY; RACIAL-DIFFERENCES; SURGERY; COMORBIDITY; VALIDITY; QUALITY; RECEIPT; CARE AB BACKGROUND: Many studies have documented low rates of effective cancer therapies, particularly in older or minority populations. However, little is known about why effective therapies are underused in these populations. METHODS: The authors examined medical records of 584 patients with cancer diagnosed or treated in Department of Veterans Affairs facilities to assess reasons for lack of 1) surgery for stage I/II nonsmall cell lung cancer, 2) surgery for stage I/II/III rectal cancer, 3) adjuvant radiation therapy for stage II/III rectal cancer, and 4) adjuvant chemotherapy for stage III colon cancer. They also assessed differences in reasons for underuse by patient age and race. RESULTS: Across the 4 guideline-recommended treatments, 92% to 99% of eligible patients were referred to the appropriate cancer specialist; however, therapy was recommended in only 74% to 92% of eligible cases. Poor health was cited in the medical record as the reason for lack of therapy in 15% to 61% of underuse cases; patient refusal explained 26% to 58% of underuse cases. African American patients were more likely to refuse surgery. Older patients were more likely to refuse treatments. CONCLUSIONS: Recommendation against therapy was a primary factor in underuse of effective therapies in older and sicker patients. Patients' refusal of therapy contributed to age and racial disparities in care. Improved data on the effectiveness of cancer therapies in community populations and interventions aimed at improved communication of known risks and benefits of therapy to cancer patients could be effective tools to reduce underuse and lingering disparities in care. Cancer 2011. (c) 2011 American Cancer Society. C1 [Landrum, Mary Beth; Keating, Nancy L.; Lamont, Elizabeth B.; McNeil, Barbara J.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Keating, Nancy L.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Lamont, Elizabeth B.] Massachusetts Gen Hosp, Div Adult Oncol, Boston, MA 02114 USA. [Bozeman, Samuel R.] Abt Associates Inc, Cambridge, MA USA. [McNeil, Barbara J.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Landrum, MB (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. EM landrum@hcp.med.harvard.edu FU Department of Veterans Affairs through the Office of Policy and Planning FX This work was supported by the Department of Veterans Affairs through the Office of Policy and Planning. A team consisting of individuals from the Department of Veterans Affairs Office of Policy and Planning and Veterans Health Administration clinicians reviewed the research findings and provided feedback to the investigative team. NR 30 TC 30 Z9 30 U1 2 U2 7 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 JUL 1 PY 2012 VL 118 IS 13 BP 3345 EP 3355 DI 10.1002/cncr.26628 PG 11 WC Oncology SC Oncology GA 960LM UT WOS:000305389500020 PM 22072536 ER PT J AU Bradbury, AR Patrick-Miller, L Egleston, BL Olopade, OI Daly, MB Moore, CW Sands, CB Schmidheiser, H Kondamudi, PK Feigon, M Ibe, CN Daugherty, CK AF Bradbury, Angela R. Patrick-Miller, Linda Egleston, Brian L. Olopade, Olufunmilayo I. Daly, Mary B. Moore, Cynthia W. Sands, Colleen B. Schmidheiser, Helen Kondamudi, Preethi K. Feigon, Maia Ibe, Comfort N. Daugherty, Christopher K. TI When parents disclose BRCA1/2 test results: Their communication and perceptions of offspring response SO CANCER LA English DT Article DE communication; genetic testing; children; hereditary breast cancer; psychosocial adaptation; BRCA1; 2 ID HEREDITARY BREAST-CANCER; POLICY STATEMENT UPDATE; ONSET GENETIC-DISEASES; PERSONALIZED MEDICINE; AMERICAN-SOCIETY; YOUNG-CHILDREN; HEALTH-CARE; ADOLESCENT; RISK; SUSCEPTIBILITY AB BACKGROUND: BRCA1/2 testing is not recommended for children, as risk reduction measures and screening are not generally recommended before 25 years old (YO). Little is known about the prevalence and predictors of parent communication to offspring and how offspring respond to this communication. METHODS: Semi-structured interviews were conducted with parents who had BRCA1/2 testing and at least 1 child <25 YO. Logistic regressions were utilized to evaluate associations with communication. Framework analysis was utilized to analyze open-ended responses. RESULTS: A total of 253 parents completed interviews (61% response rate), reporting on 505 offspring. Twenty-nine percent of parents were BRCA1/2 mutation carriers. Three hundred thirty-four (66%) offspring learned of their parent's test result. Older offspring age (P = .01), offspring gender (female, P = .05), parents' negative test result (P = .03), and parents' education (high school only, P = .02) were associated with communication to offspring. The most frequently reported initial offspring responses were neutral (41%) or relief (28%). Thirteen percent of offspring were reported to experience concern or distress (11%) in response to parental communication of their test results. Distress was more frequently perceived among offspring learning of their parent's BRCA1/2 positive or variant of uncertain significance result. CONCLUSIONS: Many parents communicate their BRCA1/2 test results to young offspring. Parents' perceptions of offspring responses appear to vary by offspring age and parent test result. A better understanding of how young offspring respond to information about hereditary risk for adult cancer could provide opportunities to optimize adaptive psychosocial responses to risk information and performance of health behaviors, in adolescence and throughout an at-risk life span. Cancer 2012. (c) 2012 American Cancer Society. C1 [Bradbury, Angela R.; Daly, Mary B.; Sands, Colleen B.; Schmidheiser, Helen; Kondamudi, Preethi K.] Fox Chase Canc Ctr, Dept Clin Genet, Philadelphia, PA 19111 USA. [Patrick-Miller, Linda] Univ Chicago, MacLean Ctr Clin Med Eth, Chicago, IL 60637 USA. [Egleston, Brian L.] Fox Chase Canc Ctr, Biostat Facil, Philadelphia, PA 19111 USA. [Olopade, Olufunmilayo I.; Feigon, Maia; Ibe, Comfort N.; Daugherty, Christopher K.] Univ Chicago, Dept Med, Hematol Oncol Sect, Chicago, IL 60637 USA. [Moore, Cynthia W.] Massachusetts Gen Hosp, Dept Child & Adolescent Psychiat, Boston, MA 02114 USA. RP Bradbury, AR (reprint author), Fox Chase Canc Ctr, Dept Clin Genet, 333 Cottman Ave, Philadelphia, PA 19111 USA. EM Angela.Bradbury@fccc.edu FU American Cancer Society, Mentored Research Scholar Award (MRSG) [07-014-01-CPPB]; NIH [P30 CA006927] FX This study was supported by the American Cancer Society, Mentored Research Scholar Award (MRSG 07-014-01-CPPB). Support was also provided by NIH Grant P30 CA006927. NR 54 TC 19 Z9 19 U1 1 U2 4 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 JUL 1 PY 2012 VL 118 IS 13 BP 3417 EP 3425 DI 10.1002/cncr.26471 PG 9 WC Oncology SC Oncology GA 960LM UT WOS:000305389500027 PM 22231763 ER PT J AU Ahdout, J Kotlerman, J Elashoff, D Kim, J Chiu, MW AF Ahdout, J. Kotlerman, J. Elashoff, D. Kim, J. Chiu, M. W. TI Modifiable lifestyle factors associated with metabolic syndrome in patients with psoriasis SO CLINICAL AND EXPERIMENTAL DERMATOLOGY LA English DT Article ID DISEASE; PREVALENCE; RISK; EPIDEMIOLOGY; SMOKING; OBESITY; STRESS; DIET AB Background. Psoriasis is a chronic inflammatory skin disease, which is associated with obesity and with cardiovascular morbidity and mortality. Aim. To evaluate modifiable lifestyle factors including stress level, physical activity and nutrition, which may be associated with metabolic syndrome in patients with psoriasis. Methods. In total, 65 patients with psoriasis and 52 control subjects from our university dermatology clinic were enrolled in this casecontrol pilot study. The study questionnaire included the Perceived Stress Scale (PSS), the Godin Leisure-Time Exercise Questionnaire (GLTEQ) and the Rapid Eating Assessment for patients (REAP). For subjects with psoriasis, the Psoriasis Area and Severity Index (PASI) was measured. Results. Subjects with psoriasis (mean BMI 27.72) displayed a trend towards a higher BMI compared with controls (mean BMI 25.67). Subjects with psoriasis were not found to have an increased prevalence of self-reported metabolic syndrome-associated diseases including diabetes, heart disease, high cholesterol, hypertension or stroke compared with controls (P = 0.25, P = 0.46, P = 0.96, P = 0.26, and P = 0.16, respectively). There was no significant difference in exercise or stress between patients with psoriasis and controls (P = 0.06 and P = 0.26, respectively). However, compared with controls, subjects with psoriasis (mean REAP score = 2.23) did report poorer overall nutrition as assessed by the REAP score (mean = 2.38, P < 0.01). Among subjects with psoriasis, the factors of stress, smoking and systemic therapy were associated with increased PASI (r = 0.13, r = 3.47 and r = 3.19, respectively). Conclusions. Our study suggests that poor dietary and exercise habits may be factors contributing to obesity and metabolic syndrome in patients with psoriasis. Further studies with larger numbers are needed to confirm these results. C1 [Ahdout, J.] Univ Calif Irvine, Dept Dermatol, Irvine, CA 92697 USA. [Kotlerman, J.; Elashoff, D.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med Stat Core, Los Angeles, CA 90095 USA. [Kim, J.; Chiu, M. W.] Univ Calif Los Angeles, David Geffen Sch Med, Div Dermatol, Dept Med, Los Angeles, CA 90095 USA. [Kim, J.; Chiu, M. W.] Greater Los Angeles Vet Affairs Healthcare Syst, Dermatol Serv, Los Angeles, CA USA. RP Ahdout, J (reprint author), Univ Calif Irvine, Dept Dermatol, C340 Med Sci 1, Irvine, CA 92697 USA. EM jahdout@gmail.com FU UCLA Department of Medicine, Division of Dermatology; Dermatologic Research Foundation of California FX This study was supported in part by the UCLA Department of Medicine, Division of Dermatology and the Dermatologic Research Foundation of California. The sponsors had no role in the design and conduct of the study, the collection, analysis and interpretation of the data, or in the preparation, review or approval of the manuscript. NR 25 TC 9 Z9 9 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0307-6938 J9 CLIN EXP DERMATOL JI Clin. Exp. Dermatol. PD JUL PY 2012 VL 37 IS 5 BP 477 EP 483 DI 10.1111/j.1365-2230.2012.04360.x PG 7 WC Dermatology SC Dermatology GA 961ZX UT WOS:000305509800003 PM 22712856 ER PT J AU Hajrasouliha, AR Sadrai, Z Chauhan, SK Dana, R AF Hajrasouliha, Amir R. Sadrai, Zahra Chauhan, Sunil K. Dana, Reza TI b-FGF Induces Corneal Blood and Lymphatic Vessel Growth in a Spatially Distinct Pattern SO CORNEA LA English DT Article DE corneal angiogenesis; fibroblast growth factor; vascular endothelial growth factor ID LYMPHANGIOGENESIS; ANGIOGENESIS; METASTASIS; DISEASE; MICE; NEOVASCULARIZATION; BLOCKADE; DEFECTS AB Purpose: To study the spatial variances in ligand expression and angiogenic effect in response to the inflammatory response induced by basic fibroblast growth factor (b-FGF). Methods: b-FGF micropellets (80 ng) were implanted in the temporal side of the cornea of Balb/c mice. On days 1, 3, and 7, blood (heme-) and lymphangiogenesis were observed by immunofluorescence staining of corneal flat mounts with LYVE-1 and CD31 to identify lymphatic and blood vessels, respectively. A second group of corneas were harvested for quantitative real-time polymerase chain reaction. Each cornea was divided into 2 different areas: (1) pre-pellet area and (2) opposite-pellet area. Expression of vascular endothelial growth factor (VEGF) ligands was evaluated using real-time polymerase chain reaction in each respective zone. Results: Blood vessels grew into the cornea from the pre-pellet area, whereas corneal lymphatic vessels grew from the opposite-pellet area toward the center of the cornea. VEGF-A was upregulated in the pre-pellet, whereas VEGF-D expression was mostly observed in the opposite-pellet area. VEGF-C level increased simultaneously in both areas. Conclusions: A single inducing factor, that is, b-FGF, may simultaneously provoke hemangiogenesis and lymphangiogenesis in different locations of the cornea through differential expression of VEGF ligands. This distinctive spatial pattern should be considered while evaluating the corneal predilection for inflammation beyond that which is directly visible by slit lamp examination. C1 [Hajrasouliha, Amir R.; Sadrai, Zahra; Chauhan, Sunil K.; Dana, Reza] Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. [Dana, Reza] Harvard Univ, Sch Med, Dept Ophthalmol, 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 [EY-12963]; Research to Prevent Blindness Lew R. Wasserman Award FX Supported by the National Institutes of Health (EY-12963), and a Research to Prevent Blindness Lew R. Wasserman Award. NR 30 TC 9 Z9 10 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 J9 CORNEA JI Cornea PD JUL PY 2012 VL 31 IS 7 BP 804 EP 809 DI 10.1097/ICO.0b013e31823f8b5a PG 6 WC Ophthalmology SC Ophthalmology GA 963LI UT WOS:000305621800017 PM 22467003 ER PT J AU Jain, V Mhatre, K Shome, D Pineda, R AF Jain, Vandana Mhatre, Kanupriya Shome, Debraj Pineda, Roberto TI Fungal Keratitis With the Type 1 Boston Keratoprosthesis: Early Indian Experience SO CORNEA LA English DT Article DE keratoprosthesis; fungal keratitis; failed graft AB Purpose: To report 2 cases of fungal keratitis and endophthalmitis in patients with the type 1 Boston keratoprosthesis (KPro) in India. Method: Two patients underwent type 1 Boston KPro with uneventful intraoperative and early postoperative courses. The patients presented with keratitis and endophthalmitis within a few months after surgery. Both patients had soft bandage contact lenses in place and were on maintenance low-dose topical steroids and antibiotic eyedrops. Culture was positive for fungus in both the cases. Results: Despite aggressive antifungal medical therapy and surgical management, one patient's eye was eviscerated and the other lost the potential for any useful vision. Conclusions: Fungal infection after KPro surgery can be devastating, negating the extraordinary visual recovery these patients achieve immediately after surgery. Chronic use of topical corticosteroids and broad-spectrum antibiotic and bandage contact lens, although indispensable, may enhance the risk of fungal infection especially in the endemic areas like India. The decision for KPro in such tropical climatic conditions should therefore be taken with absolute caution and frequent patient follow-up. A prophylactic antifungal regime may be mandatory when this procedure is undertaken in fungal endemic areas to improve outcomes. C1 [Jain, Vandana; Mhatre, Kanupriya] Aditya Jyot Eye Hosp Pvt Ltd, Dept Cornea & External Dis, Bombay 400031, Maharashtra, India. [Jain, Vandana; Pineda, Roberto] Massachusetts Eye & Ear Infirm, Dept Cornea, Boston, MA 02114 USA. [Shome, Debraj] Tata Mem Hosp, Dept Oculoplasty & Ocular Oncol, Mumbai 400012, Maharashtra, India. RP Jain, V (reprint author), Aditya Jyot Eye Hosp Pvt Ltd, Dept Cornea & External Dis, Plot 153,Rd 9, Bombay 400031, Maharashtra, India. EM docvandanajain@rediffmail.com NR 6 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 J9 CORNEA JI Cornea PD JUL PY 2012 VL 31 IS 7 BP 841 EP 843 DI 10.1097/ICO.0b013e3182068614 PG 3 WC Ophthalmology SC Ophthalmology GA 963LI UT WOS:000305621800024 PM 22531432 ER PT J AU Tothova, Z Wagner, AJ AF Tothova, Zuzana Wagner, Andrew J. TI Anaplastic lymphoma kinase-directed therapy in inflammatory myofibroblastic tumors SO CURRENT OPINION IN ONCOLOGY LA English DT Review DE anaplastic lymphoma kinase; crizotinib; inflammatory myofibroblastic tumors ID CELL LUNG-CANCER; ALK KINASE; ACTIVATING MUTATIONS; FUSION; GENE; NEUROBLASTOMA; RESISTANCE; CRIZOTINIB; IDENTIFICATION; REARRANGEMENT AB Purpose of review Inflammatory myofibroblastic tumors (IMTs) are indolent mesenchymal neoplasms associated with a small risk of aggressive behavior and metastasis. Surgery is the mainstay of treatment and until recently there have been limited effective treatment options for unresectable disease. This review describes the identification of anaplastic lymphoma kinase (ALK) fusion genes in approximately 50% of IMTs and the role of ALK inhibition in the treatment of this disease. Recent findings A recent phase I dose-escalation trial of the selective MET/ALK inhibitor crizotinib showed a long-term partial response in a patient with IMT carrying an ALK translocation but not in a patient with ALK-negative disease. Emergence of resistance to crizotinib occurs approximately 5-8 months after initiation of therapy and has been shown to be driven by different mechanisms. Multiple second-generation ALK inhibitors are currently being investigated in the preclinical and clinical trial setting. Summary ALK-directed therapy has emerged as a highly effective treatment option for a subset of patients with IMT and pulmonary adenocarcinoma. A number of additional malignancies, including rhabdomyosarcoma, neuroblastoma, anaplastic large cell lymphoma, renal cell carcinoma, and inflammatory breast cancer, have been shown to activate ALK expression by means of ALK fusion proteins, ALK mutations, or increased ALK copy number. Development of more selective ALK inhibitors, which can overcome emergent crizotinib resistance mutations, as well as development of combination treatments with drugs targeting compensatory pathways, will be key to achieving therapeutic success in targeting this potent and prevalent oncogenic driver. C1 [Wagner, Andrew J.] Harvard Univ, Sch Med, Dana Farber Canc Inst,Ctr Sarcoma & Bone Oncol, Ludwig Ctr Canc Res Dana Farber Harvard,Dept Med, Boston, MA 02115 USA. RP Wagner, AJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst,Ctr Sarcoma & Bone Oncol, Ludwig Ctr Canc Res Dana Farber Harvard,Dept Med, 450 Brookline Ave, Boston, MA 02115 USA. EM Andrew_Wagner@dfci.harvard.edu FU Virginia and D.K. Ludwig Fund for Cancer Research FX This work was supported in part by the Virginia and D.K. Ludwig Fund for Cancer Research supporting the Dana-Farber/Harvard Ludwig Center. A.J.W. has served as a consultant and receives clinical trial support from Novartis and Pfizer. There are no conflicts of interest for Z.T. NR 34 TC 26 Z9 27 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8746 J9 CURR OPIN ONCOL JI Curr. Opin. Oncol. PD JUL PY 2012 VL 24 IS 4 BP 409 EP 413 DI 10.1097/CCO.0b013e328354c155 PG 5 WC Oncology SC Oncology GA 959SD UT WOS:000305332200010 PM 22664824 ER PT J AU Loeken, MR AF Loeken, Mary R. TI A New Role for Pancreatic Insulin in the Male Reproductive Axis SO DIABETES LA English DT Editorial Material ID EXPRESSION; TESTES; MOUSE C1 [Loeken, Mary R.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Cell & Regenerat Biol, Boston, MA 02115 USA. [Loeken, Mary R.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Loeken, MR (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Cell & Regenerat Biol, Boston, MA 02115 USA. EM mary.loeken@joslin.harvard.edu OI Loeken, Mary/0000-0002-8056-9816 FU NIDDK NIH HHS [R01 DK052865, R01 DK058300, R01 DK52865, R01 DK58300] NR 12 TC 2 Z9 2 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUL PY 2012 VL 61 IS 7 BP 1667 EP 1668 DI 10.2337/db12-0539 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 962KL UT WOS:000305543900006 PM 22723275 ER PT J AU Macotela, Y Emanuelli, B Mori, MA Gesta, S Schulz, TJ Tseng, YH Kahn, CR AF Macotela, Yazmin Emanuelli, Brice Mori, Marcelo A. Gesta, Stephane Schulz, Tim J. Tseng, Yu-Hua Kahn, C. Ronald TI Intrinsic Differences in Adipocyte Precursor Cells From Different White Fat Depots SO DIABETES LA English DT Article ID VISCERAL ADIPOSE-TISSUE; INSULIN SENSITIVITY; GENE-EXPRESSION; IN-VIVO; ADIPOGENESIS; IDENTIFICATION; METABOLISM; OBESITY; SEX; HETEROGENEITY AB Obesity and body fat distribution are important risk factors for the development of type 2 diabetes and metabolic syndrome. Evidence has accumulated that this risk is related to intrinsic differences in behavior of adipocytes in different fat depots. In the current study, we demonstrate that adipocyte precursor cells (APCs) isolated from visceral and subcutaneous white adipose depots of mice have distinct patterns of gene expression, differentiation potential, and response to environmental and genetic influences. APCs derived from subcutaneous fat differentiate well in the presence of classical induction cocktail, whereas those from visceral fat differentiate poorly but can be induced to differentiate by addition of bone morphogenetic protein (BMP)-2 or BMP-4. This difference correlates with major differences in gene expression signature between subcutaneous and visceral APCs. The number of APCs is higher in obesity-prone C57BL/6 mice than obesity-resistant 129 mice, and the number in both depots is increased by up to 270% by exposure of mice to high-fat diet. Thus, APCs from visceral and subcutaneous depots are dynamic populations, which have intrinsic differences hi gene expression, differentiation properties, and responses to environmental/genetic factors. Regulation of these populations may provide a new target for the treatment and prevention of obesity and its metabolic complications. Diabetes 61:1691-1699, 2012 C1 [Macotela, Yazmin; Emanuelli, Brice; Mori, Marcelo A.; Gesta, Stephane; Schulz, Tim J.; Tseng, Yu-Hua; Kahn, C. Ronald] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Kahn, CR (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. EM c.ronald.kahn@joslin.harvard.edu RI Schulz, Tim/F-4842-2013; Emanuelli, Brice/M-2097-2016; OI Schulz, Tim/0000-0002-8413-3972; Emanuelli, Brice/0000-0001-5795-5666 FU National Institutes of Health [R01-DK-082659]; Mary K. Iacocca Professorship; Joslin Diabetes and Endocrinology Research Center Core Laboratories [DK-036836]; Pew Latin American Fellows Program in the Biological Sciences; Mentor-Based American Diabetes Association Grant Award; Mexican Council of Science (CONACyT) Postdoctoral Fellowship; Loveman Foundation FX This work was supported by National Institutes of Health Grant R01-DK-082659 and the Mary K. Iacocca Professorship. The study was also facilitated by support from the Joslin Diabetes and Endocrinology Research Center Core Laboratories (DK-036836). Y.M. was supported by the Pew Latin American Fellows Program in the Biological Sciences, the Mentor-Based American Diabetes Association Grant Award, and the Mexican Council of Science (CONACyT) Postdoctoral Fellowship. C.R.K. was supported by a grant from the Loveman Foundation. NR 36 TC 83 Z9 85 U1 1 U2 13 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUL PY 2012 VL 61 IS 7 BP 1691 EP 1699 DI 10.2337/db11-1753 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 962KL UT WOS:000305543900009 PM 22596050 ER PT J AU Katz, ML Volkening, LK Anderson, BJ Laffel, LM AF Katz, M. L. Volkening, L. K. Anderson, B. J. Laffel, L. M. TI Contemporary rates of severe hypoglycaemia in youth with Type 1 diabetes: variability by insulin regimen SO DIABETIC MEDICINE LA English DT Article DE hypoglycaemia; insulin therapy; paediatrics; Type 1 diabetes ID GLYCEMIC CONTROL; INTENSIVE TREATMENT; CHILDREN; ADOLESCENTS; COUNTRIES; INFUSION; MELLITUS; FEAR; COMPLICATIONS; METAANALYSIS AB Diabet. Med. 29, 926932 (2012) Abstract Aims To determine incidence rates of severe hypoglycaemia and compare incidence rates by insulin regimen in a diverse sample of youth with Type 1 diabetes from two sites. Methods In this observational study, 255 youth (51% female) aged 915 years receiving varied insulin regimens provided data prospectively for a median of 1.2 years. Reported episodes of severe hypoglycaemia, defined as episodes requiring help from another person for oral treatment or episodes resulting in seizure/coma, and current insulin regimens were collected systematically. Incidence rates were calculated and compared according to insulin regimen in bivariate and multivariate analyses. Results At first encounter, participants had a median age of 12.2 years (range 9.015.0), median diabetes duration of 4.4 years (range 1.013.0) and mean HbA1c of 67 +/- 12 mmol/mol (8.3 +/- 1.1%). The incidence rate was 37.6/100 patient-years for all severe hypoglycaemia and 9.6/100 patient-years for seizure/coma. The incidence rate for severe hypoglycaemia was 31.8/100 patient-years on continuous subcutaneous insulin infusion (pump therapy), 34.4/100 patient-years on basalbolus injections and 46.1/100 patient-years on NPH (NPH vs. pump therapy: P = 0.04). The incidence rate for seizure/coma was 4.5/100 patient-years on pump therapy, 11.1/100 patient-years on basalbolus injections and 14.4/100 patients-years on NPH (NPH vs. pump therapy: P = 0.004). In the multivariate analysis, the rate of seizure/coma was significantly higher for those on NPH vs. pump therapy (rate ratio 2.9, P = 0.03). Conclusions Rates of severe hypoglycaemia in youth with Type 1 diabetes remain high. Pump therapy was associated with lower rates of all severe hypoglycaemia and seizure/coma in comparison with NPH. C1 [Katz, M. L.; Volkening, L. K.; Laffel, L. M.] Joslin Diabet Ctr, Genet & Epidemiol Sect, Boston, MA 02215 USA. [Anderson, B. J.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. RP Laffel, LM (reprint author), Joslin Diabet Ctr, Genet & Epidemiol Sect, 1 Joslin Pl, Boston, MA 02215 USA. EM lori.laffel@joslin.harvard.edu FU Joslin Diabetes Center, Boston [N01-HD-4-3364]; Texas Children's Hospital, Houston [N01-HD-4-3362] FX We want to thank the families who participated in this project and the study staff at the Joslin Diabetes Center in Boston, Massachusetts, and the Texas Children's Hospital in Houston, Texas. This research was supported by contracts N01-HD-4-3364 (Joslin Diabetes Center, Boston) and N01-HD-4-3362 (Texas Children's Hospital, Houston). Portions of this manuscript were presented at the 70th Scientific Sessions of the American Diabetes Association (2010). NR 30 TC 21 Z9 22 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0742-3071 J9 DIABETIC MED JI Diabetic Med. PD JUL PY 2012 VL 29 IS 7 BP 926 EP 932 DI 10.1111/j.1464-5491.2012.03646.x PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 961IQ UT WOS:000305458500035 PM 22417321 ER PT J AU Riegel, B Ratcliffe, SJ Weintraub, WS Sayers, SL Goldberg, LR Potashnik, S Weaver, TE Pressler, SJ AF Riegel, Barbara Ratcliffe, Sarah J. Weintraub, William S. Sayers, Steven L. Goldberg, Lee R. Potashnik, Sheryl Weaver, Terri E. Pressler, Susan J. TI Double jeopardy: the influence of excessive daytime sleepiness and impaired cognition on health-related quality of life in adults with heart failure SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Article DE Heart failure; Quality of life; Sleep; Cognition ID SYMPTOM BURDEN; APNEA; VALIDATION; QUESTIONNAIRE; DEPRESSION; INSOMNIA; PROGRAM; SYSTEM; IMPACT; CARE AB To determine how excessive daytime sleepiness (EDS) and impaired cognition contribute to health-related quality of life (HRQL) in heart failure (HF). Adults with chronic HF were enrolled into a prospective cohort study. Data were obtained from 280 subjects enrolled from three sites in the northeastern USA; 242 completed the 6-month study. At baseline, cohorts with and without EDS were identified using the Epworth Sleepiness Scale. Each EDS group was further subdivided into those with and without impaired cognition using a battery of five neuropsychological tests. Two disease-specific measures, the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the Functional Outcomes of Sleep Questionnaire (FOSQ), were used to measure HRQL. General linear modelling of square-transformed variables was used to test the hypothesis that cohort membership was a significant predictor of HRQL. At 6 months the remaining sample was 62.5 [standard deviation (SD) 12] years old, mostly male (63), white (65), and functionally compromised [72 New York Heart Association (NYHA) class III/IV]. The cohort with both EDS and impaired cognition had the lowest KCCQ overall summary score (60.5 22.5) compared with the cohort without EDS or impaired cognition (74.6 17.4, P 0.001). A similar effect was seen on the FOSQ (16.0 2.8 vs. 18.5 2.2, P 0.001). Impaired cognition alone did not explain poor HRQL, but the addition of EDS poses a significant risk for poor HRQL. Interventions designed to influence EDS may improve HRQL in this population. C1 [Riegel, Barbara; Potashnik, Sheryl] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. [Ratcliffe, Sarah J.; Sayers, Steven L.; Goldberg, Lee R.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Weintraub, William S.] Christiana Care Hlth Syst, Newark, DE USA. [Sayers, Steven L.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Weaver, Terri E.] Univ Illinois, Coll Nursing, Chicago, IL USA. [Pressler, Susan J.] Univ Michigan, Sch Nursing, Ann Arbor, MI 48109 USA. RP Riegel, B (reprint author), Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. EM briegel@nursing.upenn.edu OI Goldberg, Lee/0000-0002-7906-9638; Ratcliffe, Sarah/0000-0002-6644-8284 FU National Heart, Lung, and Blood Institute at the National Institutes of Health [RO1 HL084394-01A1]; Philadelphia Veterans Affairs Medical Center; VISN 4 Mental Illness Research, Education, and Clinical Center (MIREC) FX The National Heart, Lung, and Blood Institute (RO1 HL084394-01A1) at the National Institutes of Health; the Philadelphia Veterans Affairs Medical Center; VISN 4 Mental Illness Research, Education, and Clinical Center (MIREC). NR 42 TC 6 Z9 6 U1 2 U2 7 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 JUL PY 2012 VL 14 IS 7 BP 730 EP 736 DI 10.1093/eurjhf/hfs054 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 963OT UT WOS:000305632300007 PM 22510422 ER PT J AU Zhou, C Tsai, TH Lee, HC Kirtane, T Figueiredo, M Tao, YKK Ahsen, OO Adler, DC Schmitt, JM Huang, Q Fujimoto, JG Mashimo, H AF Zhou, Chao Tsai, Tsung-Han Lee, Hsiang-Chieh Kirtane, Tejas Figueiredo, Marisa Tao, Yuankai K. Ahsen, Osman O. Adler, Desmond C. Schmitt, Joseph M. Huang, Qin Fujimoto, James G. Mashimo, Hiroshi TI Characterization of buried glands before and after radiofrequency ablation by using 3-dimensional optical coherence tomography (with videos) SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID HIGH-GRADE DYSPLASIA; BARRETTS-ESOPHAGUS; NEOSQUAMOUS EPITHELIUM; ENDOSCOPIC ABLATION; FOLLOW-UP; MULTICENTER; ENDOMICROSCOPY; TECHNOLOGY; MICROSCOPY; METAPLASIA AB Background: Radiofrequency ablation (RFA) is an endoscopic technique used to eradicate Barrett's esophagus (BE). However, such ablation can commonly lead to neosquamous epithelium overlying residual BE glands not visible by conventional endoscopy and may evade detection on random biopsy samples. Objective: To demonstrate the capability of endoscopic 3-dimensional optical coherence tomography (3D-OCT) for the identification and characterization of buried glands before and after RFA therapy. Design: Cross-sectional study. Setting: Single teaching hospital. Patients: Twenty-six male and 1 female white patients with BE undergoing RFA treatment. Interventions: 3D-OCT was performed at the gastroesophageal junction in 18 patients before attaining complete eradication of intestinal metaplasia (pre-CE-IM group) and in 16 patients after CE-IM (post-CE-IM group). Main Outcome Measurements: Prevalence, size, and location of buried glands relative to the squamocolumnar junction. Results: 3D-OCT provided an approximately 30 to 60 times larger field of view compared with jumbo and standard biopsy and sufficient imaging depth for detecting buried glands. Based on 3D-OCT results, buried glands were found in 72% of patients (13/18) in the pre-CE-IM group and 63% of patients (10/16) in the post-CE-IM group. The number (mean [standard deviation]) of buried glands per patient in the post-CE-IM group (7.1 [9.3]) was significantly lower compared with the pre-CE-IM group (34.4 [44.6]; P = .02). The buried gland size (P = .69) and distribution (P = .54) were not significantly different before and after CE-IM. Limitations: A single-center, cross-sectional study comparing patients at different time points in treatment. Lack of 1-to-1 coregistered histology for all OCT data sets obtained in vivo. Conclusion: Buried glands were frequently detected with 3D-OCT near the gastroesophageal junction before and after radiofrequency ablation. (Gastrointest Endosc 2012;76:32-40.) C1 [Mashimo, Hiroshi] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Gastroenterol Sect, Boston, MA 02130 USA. [Zhou, Chao; Tsai, Tsung-Han; Lee, Hsiang-Chieh; Tao, Yuankai K.; Ahsen, Osman O.; Fujimoto, James G.] MIT, Dept Elect Engn & Comp Sci, Elect Res Lab, Cambridge, MA 02139 USA. [Adler, Desmond C.; Schmitt, Joseph M.] St Jude Med Inc, LightLab Imaging, Westford, MA USA. RP Mashimo, H (reprint author), Harvard Univ, Sch Med, VA Boston Healthcare Syst, Gastroenterol Sect, Boston, MA 02130 USA. EM hmashimo@hms.harvard.edu RI Tao, Yuankai/F-7417-2012; Zhou, Chao/A-1327-2007; Ahsen, Osman/K-4524-2015; OI Ahsen, Osman/0000-0003-4811-3429; Tsai, Tsung-Han/0000-0002-2306-2269 FU NCI NIH HHS [R44CA101067-06, R01 CA075289, R44 CA101067, R01-CA75289-15]; NHLBI NIH HHS [R01 HL095717, R01-HL095717-03]; NIBIB NIH HHS [K99-EB010071-01A1, K99 EB010071]; NINDS NIH HHS [R01-NS057476-05, R01 NS057476] NR 39 TC 43 Z9 43 U1 3 U2 11 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD JUL PY 2012 VL 76 IS 1 BP 32 EP 40 DI 10.1016/j.gie.2012.02.003 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 963JK UT WOS:000305616400006 PM 22482920 ER PT J AU Thompson, JS Lebwohl, B Syngal, S Kastrinos, F AF Thompson, Jennifer S. Lebwohl, Benjamin Syngal, Sapna Kastrinos, Fay TI Knowledge of quality performance measures associated with endoscopy among gastroenterology trainees and the impact of a web-based intervention SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID SOCIETY-TASK-FORCE; AMERICAN-CANCER-SOCIETY; COLORECTAL-CANCER; ADENOMA DETECTION; COLONOSCOPY; SURVEILLANCE; INDICATORS; GUIDELINE; RADIOLOGY; POLYPS AB Background: Knowledge of quality measures in endoscopy among trainees is unknown. Objective: To assess knowledge of endoscopy-related quality indicators among U.S. trainees and determine whether it improves with a Web-based intervention. Design: Randomized, controlled study. Setting: Multicenter. Participants: This study involved trainees identified from the American Society for Gastrointestinal Endoscopy membership database. Intervention: Participants were invited to complete an 18-question online test. Respondents were randomized to receive a Web-based tutorial (intervention) or not. The test was readministered 6 weeks after randomization to determine the intervention's impact. Main Outcome Measurements: Baseline knowledge of endoscopy-related quality indicators and impact of the tutorial. Results: A total of 347 of 1220 trainees (28%) completed the test; the mean percentage of correct responses was 55%. For screening colonoscopy, 44% knew the adenoma detection rate benchmark, 42% identified the cecal intubation rate goal, and 74% knew the recommended minimum withdrawal time. A total of 208 of 347 trainees (59%) completed the second test; baseline scores were similar for the tutorial (n = 106) and no tutorial (n = 102) groups (56.4% vs 56.9%, respectively). Scores improved after intervention for the tutorial group (65%, P = .003) but remained unchanged in the no tutorial group. On multivariate analysis, each additional year in training (odds ratio [OR] 2.3; 95% confidence interval [CI], 1.5-3.4), training at an academic institution (OR 2.6; 95% CI, 1.1-6.3), and receiving the tutorial (OR 3.2; 95% CI, 1.7-5.9) were associated with scores in the upper tertile. Limitations: Low response rate. Conclusion: Knowledge of endoscopy-related quality performance measures is low among trainees but can improve with a Web-based tutorial. Gastroenterology training programs may need to incorporate a formal didactic curriculum to supplement practice-based learning of quality standards in endoscopy. (Gastrointest Endosc 2012;76:100-6.) C1 [Lebwohl, Benjamin; Kastrinos, Fay] Columbia Univ, Med Ctr, Div Liver & Digest Dis, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA. [Syngal, Sapna] Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. [Syngal, Sapna] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. RP Kastrinos, F (reprint author), Columbia Univ, Med Ctr, Div Liver & Digest Dis, Herbert Irving Comprehens Canc Ctr, 630 W 168th St, New York, NY 10032 USA. FU American Society for Gastrointestinal Endoscopy Olympus Career Development Award [NCI K24 113433] FX Funding was provided by a 2008 American Society for Gastrointestinal Endoscopy Olympus Career Development Award (F. Kastrinos), NCI K24 113433 (S. Syngal). No other financial relationships relevant to this publication were disclosed. NR 29 TC 3 Z9 3 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD JUL PY 2012 VL 76 IS 1 BP 100 EP + DI 10.1016/j.gie.2012.01.019 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 963JK UT WOS:000305616400015 PM 22421498 ER PT J AU Grace, R Morrison, J Konter, J Saxena, K Kalish, L Neufeld, E AF Grace, R. Morrison, J. Konter, J. Saxena, K. Kalish, L. Neufeld, E. TI Clinical Utility of Joint Assessment by the Hemophilia Joint Health Score (HJHS) at an Academic Pediatric Hemophilia Center SO HAEMOPHILIA LA English DT Meeting Abstract C1 [Grace, R.; Morrison, J.; Saxena, K.; Neufeld, E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Childrens Hosp Boston, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp Boston, Clin Res Program, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1351-8216 J9 HAEMOPHILIA JI Haemophilia PD JUL PY 2012 VL 18 SU 3 SI SI BP 120 EP 120 PG 1 WC Hematology SC Hematology GA 961IJ UT WOS:000305457801111 ER PT J AU Morrison, J Grace, R Konter, J Kalish, L Neufeld, E AF Morrison, J. Grace, R. Konter, J. Kalish, L. Neufeld, E. TI Sensitivity and Specificity of Joint Health Measures: Comparative Study of Referrals Generated by Joint Abnormalities Detected by the US-CDC "Universal Data Collection" Range Of Motion Assessment (UDC) versus the Hemophilia Joint Health Score (HJHS) at Annual Hemophilia Visits SO HAEMOPHILIA LA English DT Meeting Abstract C1 [Morrison, J.; Grace, R.; Neufeld, E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Childrens Hosp Boston, Boston, MA 02115 USA. [Kalish, L.] Harvard Univ, Sch Med, Clin Res Program, Childrens Hosp Boston, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1351-8216 J9 HAEMOPHILIA JI Haemophilia PD JUL PY 2012 VL 18 SU 3 SI SI BP 120 EP 120 PG 1 WC Hematology SC Hematology GA 961IJ UT WOS:000305457801112 ER PT J AU Wang, JJ Goldsmith, TA Holman, AS Cianchetti, M Chan, AW AF Wang, Jing Jing Goldsmith, Tessa A. Holman, Allison S. Cianchetti, Marco Chan, Annie W. TI Pharyngoesophageal stricture after treatment for head and neck cancer SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Article DE head and neck cancer; intensity-modulated radiation therapy; chemotherapy; pharyngoesophageal stricture; swallowing function ID INTENSITY-MODULATED RADIOTHERAPY; SQUAMOUS-CELL CARCINOMA; LOCALLY ADVANCED HEAD; ACCELERATED RADIATION-THERAPY; LONG-TERM DYSPHAGIA; ESOPHAGEAL STRICTURE; CONCURRENT CHEMORADIATION; DEFINITIVE RADIOTHERAPY; ORGAN PRESERVATION; PROXIMAL ESOPHAGUS AB Background The purpose of this study was to report the risk of pharyngoesophageal stricture after treatment for head and neck cancer. Methods Human studies on radiation therapy with or without chemotherapy for head and neck cancer published in peer-reviewed journals with assessment of pharyngoesophageal stricture with barium swallow or endoscopy were included. Results A total of 4727 patients from 26 studies treated between 1989 and 2008 were eligible for analysis. The reported overall risk of stricture was 7.2%. The risks of pharyngoesophageal stricture in both conventional and intensity-modulated radiation therapy (IMRT) studies were 5.7% and 16.7%, respectively (p < .001). Use of concurrent (p < .001) and taxane (p = .01) chemotherapy was associated with the IMRT technique. Prospective studies reported a 3.3-fold increased risk of stricture compared with that of retrospective studies (odds ratio: 3.3; 95% confidence interval: 2.34.8; p < .001). Conclusions Pharyngoesophageal stricture after IMRT and chemotherapy treatment for head and neck cancer is not uncommon. Videofluoroscopic swallow study should be performed prospectively to evaluate swallowing function. (c) 2011 Wiley Periodicals, Inc. Head Neck, 2012 C1 [Wang, Jing Jing; Cianchetti, Marco; Chan, Annie W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. [Goldsmith, Tessa A.; Holman, Allison S.] Massachusetts Gen Hosp, Dept Speech Language & Swallowing Disorders, Boston, MA 02114 USA. RP Chan, AW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. EM awchan@partners.org NR 34 TC 12 Z9 12 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1043-3074 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD JUL PY 2012 VL 34 IS 7 BP 967 EP 973 DI 10.1002/hed.21842 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 962BC UT WOS:000305513100009 PM 21953721 ER PT J AU Marjamaa, A Oikarinen, L Porthan, K Ripatti, S Peloso, G Noseworthy, PA Viitasalo, M Nieminen, MS Toivonen, L Kontula, K Peltonen, L Havulinna, AS Jula, A O'Donnell, CJ Newton-Cheh, C Perola, M Salomaa, V AF Marjamaa, Annukka Oikarinen, Lasse Porthan, Kimmo Ripatti, Samuli Peloso, Gina Noseworthy, Peter A. Viitasalo, Matti Nieminen, Markku S. Toivonen, Lauri Kontula, Kimmo Peltonen, Leena Havulinna, Aki S. Jula, Antti O'Donnell, Christopher J. Newton-Cheh, Christopher Perola, Markus Salomaa, Veikko TI A common variant near the KCNJ2 gene is associated with T-peak to T-end interval SO HEART RHYTHM LA English DT Article DE Electrocardiogram; Repolarization; T wave; Gene; Polymorphism ID SUDDEN CARDIAC DEATH; LEFT-VENTRICULAR HYPERTROPHY; LONG-QT-SYNDROME; POSTMYOCARDIAL INFARCTION PATIENTS; WAVE MORPHOLOGY; HYPERTENSIVE PATIENTS; FINNISH POPULATION; TEND INTERVAL; DISPERSION; REPOLARIZATION AB BACKGROUND T-peak to T-end (TPE) interval on the electrocardiogram is a measure of myocardial dispersion of repolarization and is associated with an increased risk of ventricular arrhythmias. The genetic factors affecting the TPE interval are largely unknown. OBJECTIVE To identify common genetic variants that affect the duration of the TPE interval in the general population. METHODS We performed a genome-wide association study on 1870 individuals of Finnish origin participating in the Health 2000 Study. The TPE interval was measured from T-peak to T-wave end in leads II, V-2, and V-5 on resting electrocardiograms, and the mean of these TPE intervals was adjusted for age, sex, and Cornell voltage-duration product. We sought replication for a genome-wide significant result in the 3745 subjects from the Framingham Heart Study. RESULTS We identified a locus on 17q24 that was associated with the TPE interval. The minor allele of the common variant rs7219669 was associated with a 1.8-ms shortening of the TPE interval (P = 1.1 x 10(-10)). The association was replicated in the Framingham Heart Study (-1.5 ms; P = 1.3 x 10(-4)). The overall effect estimate of rs7219669 in the 2 studies was -1.7 ms (P = 5.7 x 10(-14)). The common variant rs7219669 maps downstream of the KCNJ2 gene, in which rare mutations cause congenital long and short QT syndromes. CONCLUSION The common variant rs7219669 is associated with the TPE interval and is thus a candidate to modify repolarization-related arrhythmia susceptibility in individuals carrying the major allele of this polymorphism. C1 [Marjamaa, Annukka; Kontula, Kimmo] Univ Helsinki, Res Program Mol Med, Helsinki, Finland. [Oikarinen, Lasse; Porthan, Kimmo; Viitasalo, Matti; Nieminen, Markku S.; Toivonen, Lauri] Univ Helsinki, Cent Hosp, Dept Med, Div Cardiol, Helsinki, Finland. [Ripatti, Samuli; Peltonen, Leena; Perola, Markus] Univ Helsinki, FIMM, Helsinki, Finland. [Peloso, Gina; Noseworthy, Peter A.; Newton-Cheh, Christopher] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA USA. [Peloso, Gina; Noseworthy, Peter A.; Newton-Cheh, Christopher] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA. [Perola, Markus] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia. [Kontula, Kimmo] Univ Helsinki, Dept Med, Helsinki, Finland. [Perola, Markus] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Publ Hlth Genom Unit, Helsinki, Finland. [O'Donnell, Christopher J.; Newton-Cheh, Christopher] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [O'Donnell, Christopher J.; Newton-Cheh, Christopher] Harvard Univ, Sch Med, Boston, MA USA. [Peloso, Gina; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, NIH, Bethesda, MD 20892 USA. RP Marjamaa, A (reprint author), Univ Helsinki, Biomedicum Helsinki, Res Program Mol Med, B327b,POB 700, Huch 00029, Finland. EM Annukka.Marjamaa@helsinki.fi RI Ripatti, Samuli/H-9446-2014; OI Ripatti, Samuli/0000-0002-0504-1202; Perola, Markus/0000-0003-4842-1667 FU Finnish Foundation for Cardiovascular Research; Orion-Farmos Research Foundation; Finnish Academy SALVE program "Pubgensense" [129322]; Academy of Finland [129494, 139635]; Sigrid Juselius Foundation; National Heart, Lung, and Blood Institute of the National Institutes of Health; Boston University School of Medicine [N01-HC-25195]; Affymetrix, Inc [N02-HL-6-4278]; Doris Duke Charitable Foundation; Burroughs Wellcome Fund FX Leena Peltonen is deceased. Dr Porthan, Dr Oikarinen, and Dr Viitasalo were financially supported by the Finnish Foundation for Cardiovascular Research. Dr Porthan was also supported by the Orion-Farmos Research Foundation. Dr Perola was supported by the Finnish Academy SALVE program "Pubgensense" 129322 and the Finnish Foundation for Cardiovascular Research. Dr Salomaa was supported by the Academy of Finland (grant numbers 129494 and 139635). Dr Kontula was supported by grants from the Sigrid Juselius Foundation and Finnish Foundation for Cardiovascular Research. The Framingham Heart Study work was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health and Boston University School of Medicine (contract number N01-HC-25195), its contract with Affymetrix, Inc, for genotyping services (contract number N02-HL-6-4278), and the Doris Duke Charitable Foundation (to Dr Newton-Cheh) and Burroughs Wellcome Fund (to Dr Newton-Cheh), based on analyses by Framingham Heart Study investigators participating in the SNP Health Association Resource (SHARe) project. Address for reprints and correspondence: Dr Annukka Marjamaa, MD, PhD, Research Program in Molecular Medicine, University of Helsinki, Biomedicum Helsinki, B327b, PO Box 700, 00029 Huch, Finland. E-mail address: Annukka.Marjamaa@helsinki.fi. NR 30 TC 4 Z9 4 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD JUL PY 2012 VL 9 IS 7 BP 1099 EP 1103 DI 10.1016/j.hrthm.2012.02.019 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 963JP UT WOS:000305616900015 PM 22342860 ER PT J AU Chirinos, JA Segers, P Gillebert, TC Gupta, AK De Buyzere, ML De Bacquer, D St John-Sutton, M Rietzschel, ER AF Chirinos, Julio A. Segers, Patrick Gillebert, Thierry C. Gupta, Amit K. De Buyzere, Marc L. De Bacquer, Dirk St John-Sutton, Martin Rietzschel, Ernst R. CA Asklepios Investigators TI Arterial Properties as Determinants of Time-Varying Myocardial Stress in Humans SO HYPERTENSION LA English DT Article DE myocardial stress; arterial load; afterload; wave reflections; sex differences ID LEFT-VENTRICULAR HYPERTROPHY; SYSTOLIC PRESSURE; WAVE REFLECTION; HEART-FAILURE; IMPEDANCE; VOLUME AB Myocardial and arterial load are time-varying phenomena. Despite their importance in myocardial function, the arterial properties that determine time-resolved myocardial wall stress are unknown. We aimed to assess arterial properties as determinants of time-resolved myocardial stress among 1214 men and women enrolled in the Asklepios Study. Time-resolved central pressure, flow, and left ventricular geometry were measured with carotid tonometry, Doppler, and speckle-tracking echocardiography, respectively, for computation of arterial load and ejection-phase time-varying myocardial wall stress. For any given end-diastolic left ventricular geometry and cardiac output, peak myocardial stress correlated directly with systemic vascular resistance (standardized beta=1.12; P<0.0001) and aortic characteristic impedance (standardized beta=0.17; P<0.0001). The ejection-phase stress-time integral correlated with systemic vascular resistance (standardized beta=1.06; P<0.0001), lower total arterial compliance (standardized beta=-0.13; P=0.0008), and earlier return of wave reflections (standardized beta=-0.10; P<0.0001) but not with reflection magnitude, whereas end-systolic wall stress correlated with systemic vascular resistance (standardized beta=1.06; P<0.0001) and reflection magnitude (standardized beta=0.12; P<0.0001). After adjustment for age, all of the measured arterial properties, end-diastolic left ventricular geometry, and cardiac output, women demonstrated greater peak (534 versus 507 kdyne/cm(2); P<0.0001), end-systolic (335 versus 320 kdyne/cm(2); P<0.0001), and ejection-phase stress-time integral (157 versus 142 kdyne . s . cm(-2); P<0.0001). In conclusion, different arterial properties have selective effects on time-resolved ejection-phase myocardial wall stress, which are not apparent from single-time point measurements. Women demonstrate less efficient myocardial-arterial coupling, with higher wall stress development for any given left ventricular geometry, arterial properties, and flow output. These observations may relate to the differential susceptibility of women to heart failure. (Hypertension. 2012;60:64-70.). Online Data Supplement C1 [Chirinos, Julio A.; St John-Sutton, Martin] Univ Penn, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Segers, Patrick] Ghent Univ Hosp, Inst Biomed Technol, Ghent, Belgium. [Gillebert, Thierry C.; De Buyzere, Marc L.; Rietzschel, Ernst R.] Ghent Univ Hosp, Dept Cardiovasc Dis, Ghent, Belgium. [De Bacquer, Dirk; Rietzschel, Ernst R.] Ghent Univ Hosp, Dept Publ Hlth, Ghent, Belgium. [Gupta, Amit K.] Baylor Coll Med, Houston, TX 77030 USA. RP Chirinos, JA (reprint author), Room 8B111,5800 Woodland Ave, Philadelphia, PA 19143 USA. EM julio.chirinos@uphs.upenn.edu OI Gillebert, Thierry/0000-0002-3832-919X FU Fonds voor Wetenschappelijk Onderzoek Vlaanderen [G.0.838.10]; American Heart Association [0885031N]; National Institutes of Health FX This study was supported by Fonds voor Wetenschappelijk Onderzoek Vlaanderen grant G.0.838.10 and American Heart Association research award 0885031N.; J.A.C. has received significant (more than $10 000) grants from the National Institutes of Health and the American Heart Association for research studies related to arterial hemodynamics and has received minor support (equipment loans) from Atcor Medical, Cardiodynamics, and APC Cardiovascular. NR 16 TC 30 Z9 30 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD JUL PY 2012 VL 60 IS 1 BP 64 EP 70 DI 10.1161/HYPERTENSIONAHA.112.190710 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 962VF UT WOS:000305574200022 PM 22665121 ER PT J AU Kim, Y Mylonakis, E AF Kim, Younghoon Mylonakis, Eleftherios TI Caenorhabditis elegans Immune Conditioning with the Probiotic Bacterium Lactobacillus acidophilus Strain NCFM Enhances Gram-Positive Immune Responses SO INFECTION AND IMMUNITY LA English DT Article ID ANTIMICROBIAL PEPTIDE EXPRESSION; LACTIC-ACID BACTERIA; INNATE IMMUNITY; LIFE-SPAN; SALMONELLA-TYPHIMURIUM; SIGNALING PATHWAY; C. ELEGANS; HOST; PROTEIN; INFECTION AB Although the immune response of Caenorhabditis elegans to microbial infections is well established, very little is known about the effects of health-promoting probiotic bacteria on evolutionarily conserved C. elegans host responses. We found that the probiotic Gram-positive bacterium Lactobacillus acidophilus NCFM is not harmful to C. elegans and that L. acidophilus NCFM is unable to colonize the C. elegans intestine. Conditioning with L. acidophilus NCFM significantly decreased the burden of a subsequent Enterococcus faecalis infection in the nematode intestine and prolonged the survival of nematodes exposed to pathogenic strains of E. faecalis and Staphylococcus aureus, including multidrug-resistant (MDR) isolates. Preexposure of nematodes to Bacillus subtilis did not provide any beneficial effects. Importantly, L. acidophilus NCFM activates key immune signaling pathways involved in C. elegans defenses against Gram-positive bacteria, including the p38 mitogen-activated protein kinase pathway (via TIR-1 and PMK-1) and the beta-catenin signaling pathway (via BAR-1). Interestingly, conditioning with L. acidophilus NCFM had a minimal effect on Gram-negative infection with Pseudomonas aeruginosa or Salmonella enterica serovar Typhimurium and had no or a negative effect on defense genes associated with Gram-negative pathogens or general stress. In conclusion, we describe a new system for the study of probiotic immune agents and our findings demonstrate that probiotic conditioning with L. acidophilus NCFM modulates specific C. elegans immunity traits. C1 [Mylonakis, Eleftherios] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA. [Kim, Younghoon] Chonbuk Natl Univ, Dept Anim Sci, Jeonju, South Korea. RP Mylonakis, E (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA. EM ykeys2584@jbnu.ac.kr; emylonakis@partners.org FU Chonbuk National University; NIH [P01 AI083214] FX This work was supported by grants from Chonbuk National University (2012) to Y.K. and the NIH (P01 AI083214) to E.M. NR 48 TC 39 Z9 43 U1 5 U2 21 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUL PY 2012 VL 80 IS 7 BP 2500 EP 2508 DI 10.1128/IAI.06350-11 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 963DD UT WOS:000305599400026 PM 22585961 ER PT J AU Theivanthiran, B Batra, S Balamayooran, G Cai, SS Kobayashi, K Flavell, RA Jeyaseelan, S AF Theivanthiran, Balamayooran Batra, Sanjay Balamayooran, Gayathriy Cai, Shanshan Kobayashi, Koichi Flavell, Richard A. Jeyaseelan, Samithamby TI NOD2 Signaling Contributes to Host Defense in the Lungs against Escherichia coli Infection (Retracted article. See vol. 83, pg. 2199, 2015) SO INFECTION AND IMMUNITY LA English DT Article; Retracted Publication ID CONTAINING ADAPTER PROTEIN; HUMAN ENDOTHELIAL-CELLS; NF-KAPPA-B; NEUTROPHIL RECRUITMENT; STAPHYLOCOCCUS-AUREUS; INNATE IMMUNITY; LEGIONELLA-PNEUMOPHILA; KLEBSIELLA-PNEUMONIAE; DIAMINOPIMELIC ACID; CROHNS-DISEASE AB Bacterial pneumonia remains a significant cause of mortality in the United States. The innate immune response is the first line of defense against invading bacteria. Neutrophil recruitment to the lungs is the first step in a multistep sequence leading to bacterial clearance. Ligand interaction with pattern-recognizing receptors (PRRs) leads to chemokine production, which drives neutrophils to the site of infection. Although we demonstrated that RIP2 is important for host defense in the lungs against Escherichia coli, the individual roles of NODI and NOD2(-/-) in pulmonary defense have not been addressed. Here, we explored the role of NOD2 in neutrophil-mediated host defense against an extracellular pathogen, E. coli. We found enhanced bacterial burden and reduced neutrophil and cytokine/chemokine levels in the lungs of NOD2(-/-) mice following E. coli infection. Furthermore, we observed reduced activation of NF-kappa B and mitogen-activated protein kinases (MAPKs) in the lungs of NOD2(-/-) mice upon E. coli challenge. Moreover, NOD2(-/-) neutrophils show impaired intracellular bacterial killing. Using NOD2/RIP2(-/-) mice, we observed bacterial burden and neutrophil accumulation in the lungs similar to those seen with NOD2(-/-) mice. In addition, bone marrow-derived macrophages obtained from NOD2/RIP2(-/-) mice demonstrate a reduction in activation of NF-kappa B and MAPKs similar to that seen with NOD2(-/-) mice in response to E. coli. These findings unveil a previously unrecognized role of the NOD2-RIP2 axis for host defense against extracellular Gram-negative bacteria. This pathway may represent a novel target for the treatment of lung infection/inflammation. C1 [Theivanthiran, Balamayooran; Batra, Sanjay; Balamayooran, Gayathriy; Cai, Shanshan; Jeyaseelan, Samithamby] Harvard Univ, Sch Med, Dept Pathobiol Sci, Lab Lung Biol, Boston, MA 02114 USA. [Theivanthiran, Balamayooran; Batra, Sanjay; Balamayooran, Gayathriy; Cai, Shanshan; Jeyaseelan, Samithamby] Harvard Univ, Sch Med, Ctr Expt Infect Dis Res, Boston, MA USA. [Kobayashi, Koichi] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Flavell, Richard A.] Yale Univ, Sch Med, Howard Hughes Med Inst, Dept Immunobiol, New Haven, CT 06510 USA. [Jeyaseelan, Samithamby] LSU Hlth Sci Ctr, Dept Med, Sect Pulm & Crit Care Med, New Orleans, LA USA. RP Jeyaseelan, S (reprint author), Harvard Univ, Sch Med, Dept Pathobiol Sci, Lab Lung Biol, Boston, MA 02114 USA. EM jey@lsu.edu FU Flight Attendant Medical Research Institute [YCSA-062466]; NIH [R01 HL-091958, R01 HL-091958S1] FX This work was supported by a Scientist Award from the Flight Attendant Medical Research Institute (YCSA-062466) and grants from the NIH (R01 HL-091958 and R01 HL-091958S1 via ARRA) to S.J. NR 64 TC 17 Z9 18 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 EI 1098-5522 J9 INFECT IMMUN JI Infect. Immun. PD JUL PY 2012 VL 80 IS 7 BP 2558 EP 2569 DI 10.1128/IAI.06230-11 PG 12 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 963DD UT WOS:000305599400032 PM 22547547 ER PT J AU Holodniy, M Oda, G Schirmer, PL Lucero, CA Khudyakov, YE Xia, GL Lin, YL Valdiserri, R Duncan, WE Davey, VJ Cross, GM AF Holodniy, Mark Oda, Gina Schirmer, Patricia L. Lucero, Cynthia A. Khudyakov, Yury E. Xia, Guoliang Lin, Yulin Valdiserri, Ronald Duncan, William E. Davey, Victoria J. Cross, Gerald M. TI Results from a Large-Scale Epidemiologic Look-Back Investigation of Improperly Reprocessed Endoscopy Equipment SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID HEPATITIS-C VIRUS; GASTROINTESTINAL ENDOSCOPY; UNITED-STATES; DISEASE TRANSMISSION; FLEXIBLE ENDOSCOPY; INFECTION-CONTROL; BRITISH-SOCIETY; WORKING PARTY; DISINFECTION; RISK AB OBJECTIVE. To determine whether improper high-level disinfection practices during endoscopy procedures resulted in bloodborne viral infection transmission. DESIGN. Retrospective cohort study. SETTING. Four Veterans Affairs medical centers (VAMCs). PATIENTS. Veterans who underwent colonoscopy and laryngoscopy (ear, nose, and throat [ENT]) procedures from 2003 to 2009. METHODS. Patients were identified through electronic health record searches and serotested for human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis B virus (HBV). Newly discovered case patients were linked to a potential source with known identical infection, whose procedure occurred no more than 1 day prior to the case patient's procedure. Viral genetic testing was performed for case/proximate pairs to determine relatedness. RESULTS. Of 10,737 veterans who underwent endoscopy at 4 VAMCs, 9,879 patients agreed to viral testing. Of these, 90 patients were newly diagnosed with 1 or more viral bloodborne pathogens (BBPs). There were no case/proximate pairings found for patients with either HIV or HBV; 24 HCV case/proximate pairings were found, of which 7 case patients and 8 proximate patients had sufficient viral load for further genetic testing. Only 2 of these cases, both of whom underwent laryngoscopy, and their 4 proximates agreed to further testing. None of the 4 remaining proximate patients who underwent colonoscopy agreed to further testing. Mean genetic distance between the 2 case patients and 4 proximate patients ranged from 13.5% to 19.1%. CONCLUSIONS. Our investigation revealed that exposure to improperly reprocessed ENT endoscopes did not result in viral transmission in those patients who had viral genetic analysis performed. Any potential transmission of BBPs from colonoscopy remains unknown. Infect Control Hosp Epidemiol 2012;33(7):649-656 C1 [Holodniy, Mark; Oda, Gina; Schirmer, Patricia L.; Lucero, Cynthia A.; Davey, Victoria J.] US Dept Vet Affairs, Off Publ Hlth, Washington, DC USA. [Holodniy, Mark] Stanford Univ, Dept Med, Div Infect Dis & Geog Med, Stanford, CA 94305 USA. [Khudyakov, Yury E.; Xia, Guoliang; Lin, Yulin] Ctr Dis Control & Prevent, Div Viral Hepatitis, Atlanta, GA USA. [Valdiserri, Ronald] US Dept HHS, Off HIV AIDS Policy, Washington, DC 20201 USA. [Duncan, William E.] US Dept Vet Affairs, Off Qual & Safety, Washington, DC USA. [Cross, Gerald M.] US Dept Vet Affairs, Off Patient Care Serv, Washington, DC USA. RP Holodniy, M (reprint author), Off Publ Hlth Surveillance & Res, 3801 Miranda Ave 132, Palo Alto, CA 94304 USA. EM mark.holodniy@va.gov FU Department of Veterans Affairs FX Financial support. This study was funded by intramural funds from the Department of Veterans Affairs. NR 39 TC 14 Z9 14 U1 0 U2 1 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 JUL PY 2012 VL 33 IS 7 BP 649 EP 656 DI 10.1086/666345 PG 8 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 955DW UT WOS:000304998300001 PM 22669224 ER PT J AU Wijffels, MME Orbay, JL Indriago, I Ring, D AF Wijffels, Mathieu M. E. Orbay, Jorge L. Indriago, Igor Ring, David TI The extended flexor carpi radialis approach for partially healed malaligned fractures of the distal radius SO INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED LA English DT Article DE Distal radius; Extended FCR; Malunion; Volar plating ID VOLAR PLATE FIXATION; CLASSIFICATION; PART; END AB Purpose: The aim of the study is to evaluate the safety and utility of the extended flexor carpi radialis (FCR) exposure and volar locking plate fixation for partially healed malaligned fractures of distal radius. Materials and methods: Thirty-five patients with a partially healed malaligned fracture of the distal radius had realignment of the fracture using an extended FCR approach (release of the insertion of the brachioradialis and dorsal periosteum) and volar locked plate and screw fixation. Results: Retrospective review an average of 20 months after the index operation patients identified an average wrist extension of 68 degrees, flexion of 64 degrees, pronation of 84 degrees and supination of 85 degrees. Radial inclination, volar tilt and ulnar variance significantly improved compared to preoperative radiographs. All fractures healed, and there were no infections, implant loosening or breakage or tendon ruptures. Conclusions: This study demonstrated that the extended FCR approach is safe and effective as a treatment method for nascent malunions of the distal radius. (c) 2012 Elsevier Ltd. All rights reserved. C1 [Wijffels, Mathieu M. E.; Ring, David] Massachusetts Gen Hosp, Orthopead Hand & Upper Extrem Serv, Boston, MA 02114 USA. [Orbay, Jorge L.; Indriago, Igor] Hand Inst, Miami, FL 33176 USA. [Ring, David] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Orthopead Hand & Upper Extrem Serv, Yawkey Ctr Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 10 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0020-1383 J9 INJURY JI Injury-Int. J. Care Inj. PD JUL PY 2012 VL 43 IS 7 BP 1204 EP 1208 DI 10.1016/j.injury.2012.04.002 PG 5 WC Critical Care Medicine; Emergency Medicine; Orthopedics; Surgery SC General & Internal Medicine; Emergency Medicine; Orthopedics; Surgery GA 960WA UT WOS:000305422000040 PM 22542167 ER PT J AU Hodges, KM Greene, LR Fauth, J Mangione, L AF Hodges, Karin M. Greene, Les R. Fauth, James Mangione, Lorraine TI Processes and Outcomes in Prevention-Focused Time-Limited Groups for Girls SO INTERNATIONAL JOURNAL OF GROUP PSYCHOTHERAPY LA English DT Article ID PSYCHOTHERAPY; ADOLESCENTS; CHILDREN AB Processes and outcomes in 8-week prevention-focused, school-based groups for preadolescent girls were assessed in a naturalistic study. Specifically, whether such groups would facilitate their social-emotional development and whether affiliative processes in the groups were related to outcome were explored. In addition to expecting the groups to be effective, it was hypothesized that affiliative processes would be directly related to outcome and, more particularly, that increased positive affiliative feelings from the group toward the individual would be more predictive of positive treatment outcome than increased positive feelings from the individual toward the group. While findings did not support these hypotheses linking process to outcome, ancillary analyses revealed that different patterns of affiliation over time (i.e., U-shape pattern versus inverted U-shape pattern) distinguished the high-versus low-outcome participants, respectively. C1 [Hodges, Karin M.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Greene, Les R.] W Haven VA, Hamden, CT USA. [Fauth, James; Mangione, Lorraine] Antioch Univ New England, Keene, NH USA. RP Hodges, KM (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Wang Bldg,8th Floor,55 Fruit St, Boston, MA 02114 USA. EM khodges1@partners.org NR 24 TC 0 Z9 0 U1 0 U2 1 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0020-7284 J9 INT J GROUP PSYCHOTH JI Int. J. Group Psychother. PD JUL PY 2012 VL 62 IS 3 BP 459 EP 469 PG 11 WC Psychology, Clinical SC Psychology GA 962JV UT WOS:000305542300012 PM 22676790 ER PT J AU Caligtan, CA Carroll, DL Hurley, AC Gersh-Zaremski, R Dykes, PC AF Caligtan, Christine A. Carroll, Diane L. Hurley, Ann C. Gersh-Zaremski, Ronna Dykes, Patricia C. TI Bedside information technology to support patient-centered care SO INTERNATIONAL JOURNAL OF MEDICAL INFORMATICS LA English DT Article DE Bedside information technology; Information communication technology; Communication break-down; Information needs; Patient-provider communication; Patient-centered care ID HEALTH-CARE; SATISFACTION; RECORD; PILOT; NEEDS; PREFERENCES; HOSPITALS; OUTCOMES; QUALITY; IMPACT AB Purpose: Patients and health care providers often lack real time access to information at the bedside required to provide safe patient-centered care. Both groups identified pertinent information needed at the patient's bedside. The purpose of our research was to identify the essential data elements that will be used to define requirements for a useful bedside communication tool in the acute care hospital setting. Methods: Descriptive research methods were used to identify bedside information requirements through group and individual interviews. Data from patients and health care providers were analyzed to identify common themes, compiled into a survey, and validated by both groups. Results: Thirty-seven information requirements were identified and classified under five themes: (1) plan of care, (2) patient education, (3) communication of safety alerts, (4) diet, and (5) medications. A survey completed by 30 patients and 30 health care providers confirmed 36 specific bedside information requirements (mean >= 5 on an 11-point scale). Patients and health providers each identified 24 specific information requirements that were similar in importance. When compared with nurses, significant differences were noted in the degree to which patients identified knowing the "daily routine schedule," e.g. when their doctor typically sees patients as a key requirement for the electronic bedside communication tool, t = 3.52, p = .001. Conclusion: Patients and health care providers identified information requirements at the bedside to promote self-care management of healthcare needs and an understanding of the hospital environment. Accurate, easily accessed information at the bedside is needed for providing safe patient-centered care. (C) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Caligtan, Christine A.] Partners HealthCare Syst, Boston, MA USA. [Carroll, Diane L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hurley, Ann C.; Gersh-Zaremski, Ronna; Dykes, Patricia C.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Caligtan, CA (reprint author), Partners HealthCare Syst, Clin Informat Res & Dev, 93 Worcester St, Wellesley, MA 02481 USA. EM ccaligtan@gmail.com FU Siemens; Partners-Siemens Research Council; Center for Connected Health; Partners Healthcare System FX Partners-Siemens Research Council, Center for Connected Health, and Partners Healthcare System.; This article is an outgrowth of work from the Nursing Informatics Research Group funded by a Siemens award to Partners HealthCare Information Systems. NR 33 TC 21 Z9 22 U1 5 U2 14 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1386-5056 J9 INT J MED INFORM JI Int. J. Med. Inform. PD JUL PY 2012 VL 81 IS 7 BP 442 EP 451 DI 10.1016/j.ijmedinf.2011.12.005 PG 10 WC Computer Science, Information Systems; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA 958AK UT WOS:000305208100002 PM 22285034 ER PT J AU Xing, CH Arai, K Lo, EH Hommel, M AF Xing, Changhong Arai, Ken Lo, Eng H. Hommel, Marc TI Pathophysiologic cascades in ischemic stroke SO INTERNATIONAL JOURNAL OF STROKE LA English DT Review DE microglia; neurovascular unit; penumbra; reperfusion; white matter ID FOCAL CEREBRAL-ISCHEMIA; CENTRAL-NERVOUS-SYSTEM; TUMOR-NECROSIS-FACTOR; WHITE-MATTER INJURY; OLIGODENDROCYTE PRECURSOR CELLS; CORTICAL SPREADING DEPRESSION; BRAIN-INJURY; MICROGLIAL CELLS; RAT-BRAIN; IN-VIVO AB Many advances have been achieved in terms of understanding the molecular and cellular mechanisms of ischemic stroke. But thus far, clinically effective neuroprotectants remain elusive. In this minireview, we summarize the basics of ischemic cascades after stroke, covering neuronal death mechanisms, white matter pathophysiology, and inflammation with an emphasis on microglia. Translating promising mechanistic knowledge into clinically meaningful stroke drugs is very challenging. An integrative approach that encompasses the multimodal and multicell signaling phenomenon of stroke will be required to move forward. C1 [Xing, Changhong; Arai, Ken; Lo, Eng H.] Massachusetts Gen Hosp, Dept Radiol & Neurol, Boston, MA 02114 USA. [Xing, Changhong; Arai, Ken; Lo, Eng H.] Harvard Univ, Sch Med, Boston, MA USA. [Hommel, Marc] CHU Grenoble, INSERM, CIC 003, Ctr Invest Clin MH, F-38043 Grenoble, France. RP Hommel, M (reprint author), CHU UJ Fourier, INSERM, CIC 003, BP 217X, F-38043 Grenoble, France. EM mhommel@ujf-grenoble.fr FU American Heart Association; National Institutes of Health FX The authors thank all their colleagues for many helpful discussions over the years and apologize to colleagues whose important work could not all be properly cited in this mini-review due to space limits. Note: ideas herein have been extensively drawn from our previous review papers - Lo et al., 2003 Nat Rev Neurosci; Lo, 2008 Nat Med, Arai et al., 2009 FEBS J; Arai and Lo, 2009 Biol Pharm Bull; Arai and Lo, 2009 Exp Transl Stroke Med, Arai et al., 2011 J Child Neurol; Hayakawa et al., in press Acta Neurochir Suppl. Supported in part by grants from the American Heart Association and the National Institutes of Health. NR 115 TC 44 Z9 45 U1 0 U2 18 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1747-4930 J9 INT J STROKE JI Int. J. Stroke PD JUL PY 2012 VL 7 IS 5 BP 378 EP 385 DI 10.1111/j.1747-4949.2012.00839.x PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 961GK UT WOS:000305452000004 PM 22712739 ER PT J AU Yue, B Varadarajan, KM Rubash, HE Li, GA AF Yue, Bing Varadarajan, Kartik M. Rubash, Harry E. Li, Guoan TI In vivo function of posterior cruciate ligament before and after posterior cruciate ligament-retaining total knee arthroplasty SO INTERNATIONAL ORTHOPAEDICS LA English DT Article ID OSTEOARTHRITIC KNEES; MUSCLE LOADS; FLEXION; KINEMATICS; STABILITY; ANTERIOR; BUNDLES; FORCES; SAVE; PCL AB The object of this study was to investigate the in vivo function of the posterior cruciate ligament (PCL) in patients before and after a PCL-retaining total knee arthroplasty (TKA). Eleven patients with advanced osteoarthritis (OA) of the knee were recruited. Magnetic resonance scans of each OA knee were obtained, and 3D computer models, including the femoral and tibial insertion areas of the anterolateral and posteromedial bundles of the PCL, were created. Before and after PCL-retaining TKA, dual fluoroscopic images of each knee were acquired during weight-bearing knee flexion. The images and computer models were used to reproduce the in vivo motion of the knee. The function of the PCL bundles was described in terms of elongation, elevation and deviation. Twenty-two healthy controls were also included as normal references. PCL bundles of the OA knees were overstretched during late knee flexion and orientated more medially throughout flexion compared with normal knees. After PCL-retaining TKA, PCL bundles were further overstretched during late flexion and changed from medially directed in normal and OA knees to almost sagittally directed, which may compromise function in controlling knee rotation. The current PCL-retaining TKA systems and surgical techniques may not adequately re-establish normal biomechanics of PCL bundles after PCL-retaining TKA. C1 [Yue, Bing; Varadarajan, Kartik M.; Rubash, Harry E.; Li, Guoan] Massachusetts Gen Hosp, Dept Orthopaed Surg, Bioengn Lab, Boston, MA 02114 USA. [Yue, Bing; Varadarajan, Kartik M.; Rubash, Harry E.; Li, Guoan] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Yue, Bing] Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 9, Shanghai Key Lab Orthopaed Implant,Dept Orthopaed, Shanghai 200011, Peoples R China. RP Li, GA (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Bioengn Lab, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM gli1@partners.org FU AEF grant from the Department of Orthopaedics, Massachusetts General Hospital; Science and Technology Commission of Shanghai [11QA1404100]; Shanghai Municipal Health Bureau [XYQ2011024]; National Natural Science Foundation of China [30901517] FX This study was partially supported by an AEF grant from the Department of Orthopaedics, Massachusetts General Hospital. This study was also supported by the Fund of Science and Technology Commission of Shanghai (11QA1404100), Shanghai Municipal Health Bureau (XYQ2011024), and National Natural Science Foundation of China (30901517). NR 24 TC 16 Z9 17 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0341-2695 J9 INT ORTHOP JI Int. Orthop. PD JUL PY 2012 VL 36 IS 7 BP 1387 EP 1392 DI 10.1007/s00264-011-1481-6 PG 6 WC Orthopedics SC Orthopedics GA 963EG UT WOS:000305602300009 PM 22270863 ER PT J AU Vaduganathan, M Gheorghiade, M Pang, PS Konstam, MA Zannad, F Swedberg, K Grinfeld, L Burnett, JC Krasa, HB Zimmer, C Blair, J Ouyang, J Maggioni, AP AF Vaduganathan, Muthiah Gheorghiade, Mihai Pang, Peter S. Konstam, Marvin A. Zannad, Faiez Swedberg, Karl Grinfeld, Liliana Burnett, John C., Jr. Krasa, Holly B. Zimmer, Christopher Blair, John Ouyang, John Maggioni, Aldo P. CA EVEREST Investigators TI Efficacy of oral tolvaptan in acute heart failure patients with hypotension and renal impairment SO JOURNAL OF CARDIOVASCULAR MEDICINE LA English DT Article DE acute heart failure; hemodynamics; hypotension; renal failure ID BLOOD UREA NITROGEN; VASOPRESSIN ANTAGONIST; HOSPITALIZED-PATIENTS; RISK STRATIFICATION; DOUBLE-BLIND; OUTCOMES; IMPACT; MORTALITY; TRIAL; ADMISSION AB Aims Although congestion is the main reason for admission in patients with worsening acute heart failure syndromes, patients presenting with low SBP and renal impairment often do not respond adequately to and may not tolerate traditional diuretic therapy. We sought to determine the short-term hemodynamic effects of tolvaptan in this high-risk population. Methods In a subset analysis of the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan trial, 759 patients (18% of total) had elevated blood urea nitrogen (BUN) (>20 mg/dl) and low SBP (<105 mmHg) at admission. Of these, 386 were randomized to tolvaptan and 373 to placebo. Results Demographics and baseline characteristics were similar in both groups. Greater reductions from baseline in body weight were observed for tolvaptan (1.63 +/- 2.00 vs. 0.76 +/- 1.75 kg, P < 0.0001 at day 1 and 3.23 +/- 3.36 vs. 2.10 +/- 3.47 kg, P<0.0001 at day 7 or discharge). Greater increases in serum sodium concentration were also observed in the tolvaptan group as early as day 1 (4.41 +/- 3.67 vs. 1.32 +/- 3.93 mEq/l, P < 0.0001) and persisted through day 7 or discharge (4.79 +/- 4.89 vs. 1.25 +/- 5.00 mEq/l, P<0.0001). Similarly, improvements in patient-reported dyspnea and investigator-assessed orthopnea were significantly greater in the tolvaptan group as early as day 1 of treatment. These changes were not associated with significant differences in heart rate, SBP, DBP or serum creatinine between patients in the two treatment groups during hospitalization. In-hospital mortality rates (total and cause-specific) were comparable to patients who had presented with SBP more than 105 mmHg and BUN less than 20 mg/dl. Conclusion In this subgroup analysis of patients with hypotension and renal impairment, tolvaptan improved symptoms, reduced body weight and increased serum sodium as early as inpatient day 1 without adversely affecting blood pressure or renal function. J Cardiovasc Med 2012, 13:415-422 C1 [Gheorghiade, Mihai] Northwestern Univ, Div Cardiol, Feinberg Sch Med, Ctr Cardiovasc Innovat, Chicago, IL 60611 USA. [Vaduganathan, Muthiah] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Pang, Peter S.] Northwestern Univ, Dept Emergency Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Konstam, Marvin A.] Tufts Med Ctr, Div Cardiol, Boston, MA USA. [Konstam, Marvin A.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Zannad, Faiez] Nancy Univ, Dept Cardiol, Nancy, France. [Swedberg, Karl] Univ Gothenburg, Sahlgrenska Acad, Dept Emergency & Cardiovasc Med, Gothenburg, Sweden. [Grinfeld, Liliana] Hosp Italiano Buenos Aires, Serv Hemodinamia, Dept Diagnost & Tratamiento, Buenos Aires, DF, Argentina. [Burnett, John C., Jr.] Mayo Clin, Div Cardiovasc Dis, Rochester, MN USA. [Krasa, Holly B.; Zimmer, Christopher] Otsuka Maryland Res Inst, Dept Clin Dev, Rockville, MD USA. [Ouyang, John] Otsuka Maryland Res Inst, Dept Biometr, Rockville, MD USA. [Maggioni, Aldo P.] Assoc Nazl Med Cardiologi Osped Res Ctr, Florence, Italy. RP Gheorghiade, M (reprint author), Northwestern Univ, Div Cardiol, Feinberg Sch Med, Ctr Cardiovasc Innovat, 251 E Huron St, Chicago, IL 60611 USA. OI Maggioni, Aldo Pietro/0000-0003-2764-6779 FU Otsuka Pharmaceuticals FX The EVEREST trials were sponsored by Otsuka Pharmaceuticals. NR 34 TC 13 Z9 16 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1558-2027 J9 J CARDIOVASC MED JI J. Cardiovasc. Med. PD JUL PY 2012 VL 13 IS 7 BP 415 EP 422 DI 10.2459/JCM.0b013e328355a740 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 962KN UT WOS:000305544100001 PM 22673023 ER PT J AU Meeker, JD Calafat, AM Hauser, R AF Meeker, John D. Calafat, Antonia M. Hauser, Russ TI Urinary phthalate metabolites and their biotransformation products: predictors and temporal variability among men and women SO JOURNAL OF EXPOSURE SCIENCE AND ENVIRONMENTAL EPIDEMIOLOGY LA English DT Article DE biomarker; environment; metabolism ID DI(2-ETHYLHEXYL) PHTHALATE; QUANTITATIVE DETECTION; DIETHYL PHTHALATE; MASS-SPECTROMETRY; PREGNANT-WOMEN; HUMAN EXPOSURE; HORMONE LEVELS; HUMANS; HEALTH; REPRODUCIBILITY AB Most epidemiology studies investigating the potential adverse health effects in relation to phthalates measure the urinary concentration of the free plus glucuronidated species of phthalate metabolites (i.e., total concentration) to estimate exposure. However, the free species may represent the biologically relevant dose. In this study, we collected 943 urine samples from 112 men and 157 women and assessed the between-and within-person variability and predictors of (1) the free and total urinary concentrations of phthalate metabolites, and (2) the percentage of free phthalate metabolites (a potential phenotypic indicator of individual susceptibility). We also explored the proportion of urinary di-(2-ethylhexyl) phthalate (DEHP) metabolites contributed to by the bioactive mono-2-ethylhexyl phthalate (MEHP), considered a possible indicator of susceptibility to phthalate exposure. The percentage of phthalate metabolites present in the free form was less stable over time than the total metabolite concentration, and, therefore, it is not likely a useful indicator of metabolic susceptibility. Thus, the added costs and effort involved in the measurement of free in addition to total metabolite concentrations in large-scale studies may not be justified. Conversely, the proportion of DEHP metabolites contributed to by MEHP was more stable within individuals over time and may be a promising indicator of susceptibility if time of day of sample collection is carefully considered. C1 [Meeker, John D.] Univ Michigan, Dept Environm Hlth Sci, Sch Publ Hlth, Ann Arbor, MI 48109 USA. [Calafat, Antonia M.] Ctr Dis & Control & Prevent, Atlanta, GA USA. [Hauser, Russ] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Hauser, Russ] Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Androl Lab, Boston, MA 02114 USA. [Hauser, Russ] Massachusetts Gen Hosp, Vitro Fertilizat Unit, Boston, MA 02114 USA. RP Meeker, JD (reprint author), Univ Michigan, Dept Environm Hlth Sci, Sch Publ Hlth, 6635 SPH Tower,109 S Observ St, Ann Arbor, MI 48109 USA. EM meekerj@umich.edu OI Meeker, John/0000-0001-8357-5085 FU National Institute of Environmental Health Sciences (NIEHS) [P30ES000002, R01ES009718, R01ES018872, P20ES018171, P42ES017198, P30ES017885]; US Environmental Protection Agency (USEPA) [RD83480001] FX This work was supported by grants P30ES000002, R01ES009718, R01ES018872, P20ES018171, P42ES017198, and P30ES017885 from the National Institute of Environmental Health Sciences (NIEHS), and RD83480001 from the US Environmental Protection Agency (USEPA). We acknowledge Manori Silva, Ella Samandar, and Jim Preau for measuring the urinary concentrations of phthalate metabolites. NR 35 TC 30 Z9 30 U1 3 U2 30 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 JUL-AUG PY 2012 VL 22 IS 4 BP 376 EP 385 DI 10.1038/jes.2012.7 PG 10 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 964KR UT WOS:000305694000010 PM 22354176 ER PT J AU Kelley, AS Ettner, SL Morrison, RS Du, QL Sarkisian, CA AF Kelley, Amy S. Ettner, Susan L. Morrison, R. Sean Du, Qingling Sarkisian, Catherine A. TI Disability and Decline in Physical Function Associated with Hospital Use at End of Life SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE disability; end-of-life decisions; functional decline; Medicare; Medigap ID OLDER PERSONS PREFERENCES; LAST 6 MONTHS; TREATMENT INTENSITY; CARE; ILLNESS; OUTCOMES; ADULTS; DEATH; DETERMINANTS; MORTALITY AB Hospital use near the end of life is often undesirable to patients, represents considerable Medicare cost, and varies widely across regions. To concurrently examine regional and patient factors, including disability and functional decline, associated with end-of-life hospital use. We sampled decedents aged 65 and older (n = 2,493) from the Health and Retirement Study (2000-2006), and linked data from individual Medicare claims and the Dartmouth Atlas of Health Care. Two-part regression models estimated the relationship between total hospital days in the last 6 months and patient characteristics including physical function, while adjusting for regional resources and hospital care intensity (HCI). Median hospital days was 7 (range = 0-183). 53% of respondents had functional decline. Compared with decedents without functional decline, those with severe disability or decline had more regression-adjusted hospital days (range 3.47-9.05, depending on category). Dementia was associated with fewer days (-3.02); while chronic kidney disease (2.37), diabetes (2.40), stroke or transient ischemic attack (2.11), and congestive heart failure (1.74) were associated with more days. African Americans and Hispanics had more days (5.91 and 4.61, respectively). Those with family nearby had 1.62 fewer days and hospice enrollees had 1.88 fewer days. Additional hospital days were associated with urban residence (1.74) and residence in a region with more specialists (1.97) and higher HCI (2.27). Functional decline is significantly associated with end-of-life hospital use among older adults. To improve care and reduce costs, health care programs and policies should address specific needs of patients with functional decline and disability. C1 [Kelley, Amy S.; Morrison, R. Sean; Du, Qingling] Mt Sinai Sch Med, Brookdale Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Ettner, Susan L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA. [Morrison, R. Sean] James J Peters VA Med Ctr, Bronx, NY USA. [Sarkisian, Catherine A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Geriatr, Los Angeles, CA 90095 USA. [Sarkisian, Catherine A.] VA Greater Los Angeles Healthcare Syst, Ctr Geriatr Res Educ & Clin, Los Angeles, CA USA. RP Kelley, AS (reprint author), Mt Sinai Sch Med, Brookdale Dept Geriatr & Palliat Med, 1 Gustave L Levy Pl,Box 1070, New York, NY 10029 USA. EM amy.kelley@mssm.edu FU National Institute on Aging [K24 AG022345]; National Palliative Care Research Center; VA Greater Los Angeles Healthcare System Geriatric Research Education Clinical Center FX Dr. Kelley is a Brookdale Leadership in Aging Fellow. Dr. Morrison is the recipient of a Mid-Career Investigator Award in Patient-Oriented Research (K24 AG022345) from the National Institute on Aging and supported by the National Palliative Care Research Center. Dr. Sarkisian is supported by the VA Greater Los Angeles Healthcare System Geriatric Research Education Clinical Center. No sponsors or funders had any role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript. NR 41 TC 11 Z9 11 U1 2 U2 15 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 IS 7 BP 794 EP 800 DI 10.1007/s11606-012-2013-9 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 962ET UT WOS:000305524400011 PM 22382455 ER PT J AU Kertesz, SG Khodneva, Y Richman, J Tucker, JA Safford, MM Jones, B Schumacher, J Pletcher, MJ AF Kertesz, Stefan G. Khodneva, Yulia Richman, Joshua Tucker, Jalie A. Safford, Monika M. Jones, Bobby Schumacher, Joseph Pletcher, Mark J. TI Trajectories of Drug Use and Mortality Outcomes Among Adults Followed Over 18 Years SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE opioids; stimulants; cocaine; trajectory; epidemiology; longitudinal data ID ARTERY RISK DEVELOPMENT; YOUNG-ADULTS; SCREENING-TEST; CARDIA; ALCOHOL; HEALTH; RECRUITMENT; MARIJUANA; SMOKING; DISEASE AB For adults in general population community settings, data regarding long-term course and outcomes of illicit drug use are sparse, limiting the formulation of evidence-based recommendations for drug use screening of adults in primary care. To describe trajectories of three illicit drugs (cocaine, opioids, amphetamines) among adults in community settings, and to assess their relation to all-cause mortality. Longitudinal cohort, 1987/88 - 2005/06. Community-based recruitment from four cities (Birmingham, Chicago, Oakland, Minneapolis). Healthy adults, balanced for race (black and white) and gender were assessed for drug use from 1987/88-2005/06, and for mortality through 12/31/2008 (n = 4301) Use of cocaine, amphetamines, and opioids (last 30 days) was queried in the following years: 1987/88, 1990/91, 1992/93, 1995/96, 2000/01, 2005/06. Survey-based assessment of demographics and psychosocial characteristics. Mortality over 18 years. Trajectory analysis identified four groups: Nonusers (n = 3691, 85.8%), Early Occasional Users (n = 340, 7.9%), Persistent Occasional Users (n = 160, 3.7%), and Early Frequent/Later Occasional Users (n = 110, 2.6%). Trajectories conformed to expected patterns regarding demographics, other substance use, family background and education. Adjusting for demographics, baseline health status, health behaviors (alcohol, tobacco), and psychosocial characteristics, Early Frequent/Later Occasional Users had greater all-cause mortality (Hazard Ratio, HR = 4.94, 95% CI = 1.58-15.51, p = 0.006). Study is restricted to three common drugs, and trajectory analyses represent statistical approximations rather than identifiable "types". Causal inferences are tentative. Four trajectories describe illicit drug use from young adulthood to middle age. Two trajectories, representing over one third of adult users, continued use into middle age. These persons were more likely to continue harmful risk behaviors such as smoking, and more likely to die. C1 [Kertesz, Stefan G.; Safford, Monika M.; Schumacher, Joseph] Univ Alabama Birmingham, Div Prevent Med, Sch Med, Birmingham, AL 35294 USA. [Jones, Bobby] Carnegie Mellon Univ, Dept Stat, Pittsburgh, PA 15213 USA. [Pletcher, Mark J.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Richman, Joshua] Univ Alabama Birmingham, Sch Med, Dept Surg, Birmingham, AL 35294 USA. [Kertesz, Stefan G.; Khodneva, Yulia; Tucker, Jalie A.] Univ Alabama Birmingham, Dept Hlth Behav, Sch Publ Hlth, Birmingham, AL 35294 USA. [Kertesz, Stefan G.] Birmingham VA Med Ctr, Ctr Surg Med & Acute Care Res, Birmingham, AL USA. RP Kertesz, SG (reprint author), Univ Alabama Birmingham, Div Prevent Med, Sch Med, 1530 3rd Ave S,MT608, Birmingham, AL 35294 USA. EM skertesz@uab.edu FU [NIDA: R01-DA-025067]; [NHLBI: N01-HC-95095]; [NO1-HC-48047] FX Support: NIDA: R01-DA-025067; NHLBI: N01-HC-95095 AND NO1-HC-48047 NR 41 TC 15 Z9 15 U1 1 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 IS 7 BP 808 EP 816 DI 10.1007/s11606-011-1975-3 PG 9 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 962ET UT WOS:000305524400013 PM 22274889 ER PT J AU Madaras-Kelly, KJ Remington, RE Sloan, KL Fan, VS AF Madaras-Kelly, Karl J. Remington, Richard E. Sloan, Kevin L. Fan, Vincent S. TI Guideline-Based Antibiotics and Mortality in Healthcare-Associated Pneumonia SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE pneumonia; anti bacterial agents; guideline; methicillin resistant Staphylococcus aureus; Pseudomonas aeruginosa; healthcare-associated infection ID HOSPITAL-ACQUIRED PNEUMONIA; RESISTANT BACTERIA; THERAPY; OUTCOMES; INFECTION; ADMISSION; ACCURACY; UNIT AB Guidelines recommend administration of antibiotics with activity against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa for treatment of healthcare-associated pneumonia (HCAP). It is unclear if this therapy improves outcomes for patients with HCAP. To determine if administration of guideline-similar therapy (GST) was associated with a reduction in 30-day mortality for HCAP. Multi-center retrospective study. Thirteen hundred and eleven admissions for HCAP in six Veterans Affairs Medical Centers. Each admission was classified as receiving GST, anti-MRSA or anti-pseudomonal components of GST, or other non-HCAP therapy initiated within 48 hours of hospitalization. Association between 30-day mortality and GST was estimated with a logistic regression model that included GST, propensity to receive GST, probability of recovering an organism from culture resistant to antibiotics traditionally used to treat community-acquired pneumonia (CAP-resistance), and a GST by CAP-resistance probability interaction. Odds ratios and 95% confidence intervals [OR (95% CI)] of 30-day mortality for patients treated with GST and predicted probability of recovering a CAP-resistant organism, and ratio of odds ratios [ROR (95% CI)] for treatment by CAP-resistance probability interaction. Receipt of GST was associated with increased odds of 30-day mortality [OR = 2.11 (1.11, 4.04), P = 0.02)] as was the predicted probability of recovering a CAP-resistant organism [OR = 1.67 (1.26, 2.20), P < 0.001 for a 25% increase in probability]. An interaction between predicted probability of recovering a CAP-resistant organism and receipt of GST demonstrated lower mortality with GST at high probability of CAP resistance [ROR = 0.71(a parts per thousand currency sign1.00) for a 25% increase in probability, P = 0.05]. For HCAP patients with high probability of CAP-resistant organisms, GST was associated with lower mortality. Consideration of the magnitude of patient-specific risk for CAP-resistant organisms should be considered when selecting HCAP therapy. C1 [Madaras-Kelly, Karl J.] Vet Affairs Med Ctr, Clin Pharm Serv 119A, Boise, ID 83702 USA. [Remington, Richard E.] Vet Affairs Med Ctr, Res Serv, Boise, ID 83702 USA. [Fan, Vincent S.] Vet Affairs Puget Sound Hlth Care Syst, Med Serv, Seattle, WA USA. [Madaras-Kelly, Karl J.; Remington, Richard E.] Idaho State Univ, Dept Pharm Practice & Adm Sci, Coll Pharm, Meridian, ID USA. [Fan, Vincent S.] Univ Washington, Sch Med, Dept Pulm & Crit Care Med, Seattle, WA USA. RP Madaras-Kelly, KJ (reprint author), Vet Affairs Med Ctr, Clin Pharm Serv 119A, 500 W Ft St, Boise, ID 83702 USA. EM KMK@pharmacy.isu.edu FU National Institute of Allergy and Infectious Diseases [RO3AI074894-01A2]; Boise and Puget Sound Health Care System Veterans Affairs Medical Centers FX This study was supported through a grant from the National Institute of Allergy and Infectious Diseases (RO3AI074894-01A2). This work was supported in part with resources of the Boise and Puget Sound Health Care System Veterans Affairs Medical Centers. NR 26 TC 15 Z9 15 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 IS 7 BP 845 EP 852 DI 10.1007/s11606-012-2011-y PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 962ET UT WOS:000305524400018 PM 22396110 ER PT J AU Kim, JS Bashir, MM Werth, VP AF Kim, Jessica S. Bashir, Muhammad M. Werth, Victoria P. TI Gottron's Papules Exhibit Dermal Accumulation of CD44 Variant 7 (CD44v7) and Its Binding Partner Osteopontin: A Unique Molecular Signature SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; B-CELL ACTIVATION; AUTOIMMUNE-DISEASE; MONONUCLEAR-CELLS; INTERFERON-GAMMA; IMMUNE-RESPONSE; DENDRITIC CELLS; EXPRESSION; DERMATOMYOSITIS; SKIN AB The accumulated mucin in non-Gottron's dermatomyositis (DM) lesions is primarily chondroitin-4-sulfate (C4S), which is immunomodulatory in vitro. Gottron's papules are a particularly resistant manifestation of DM that often persist after other lesions have resolved with therapy. We examined non-Gottron's DM lesions and Gottron's papule skin biopsies for C4S, CD44 variant 7 (CD44v7), a chondroitin sulfate-binding isoform causally implicated in autoimmunity, and osteopontin (OPN), a CD44v7 ligand implicated in chronic inflammation. Gottron's papule dermis contained more C4S and CD44v7 than non-Gottron's lesions. Normal skin showed less CD44v7 over joints relative to Gottron's lesions. All DM dermis had increased OPN compared with healthy skin. Mechanically stretching cultured fibroblasts for 6 hours induced CD44v7 mRNA and protein, whereas IFN-gamma treatment induced OPN mRNA and protein. OPN alone did not induce CD44v7, but stretching dermal fibroblasts in the presence of OPN increased human acute monocytic leukemia cell line (THP-1) monocyte binding, which is blunted by anti-CD44v7 blocking antibody. C4S, CD44v7, and OPN are three molecules uniquely present in Gottron's papules that contribute to inflammation individually and in association with one another. We propose that stretch-induced CD44v7 over joints, in concert with dysregulated OPN levels in the skin of DM patients, increases local inflammatory cell recruitment and contributes to the pathogenesis and resistance of Gottron's papules. Journal of Investigative Dermatology (2012) 132, 1825-1832; doi:10.1038/jid.2012.54; published online 29 March 2012 C1 [Kim, Jessica S.; Bashir, Muhammad M.; Werth, Victoria P.] Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. [Kim, Jessica S.] NYU, Sch Med, New York, NY USA. [Kim, Jessica S.; Bashir, Muhammad M.; Werth, Victoria P.] Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Werth, VP (reprint author), Univ Penn, Dept Dermatol, 2 Maloney Bldg,36th & Spruce St, Philadelphia, PA 19104 USA. EM werth@mail.med.upenn.edu FU Lupus Foundation of America; Department of Veterans Affairs (Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development); National Institutes of Health [NIH K24-AR 02207] FX This material is based on the work supported by the Lupus Foundation of America and in part by a Merit Review Grant from the Department of Veterans Affairs (Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development) and by the National Institutes of Health (NIH K24-AR 02207) to VPW. The authors state no conflict of interest. NR 49 TC 6 Z9 7 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2012 VL 132 IS 7 BP 1825 EP 1832 DI 10.1038/jid.2012.54 PG 8 WC Dermatology SC Dermatology GA 961TR UT WOS:000305492900014 PM 22456539 ER PT J AU Valente, AJ Clark, RA Siddesha, JM Siebenlist, U Chandrasekar, B AF Valente, Anthony J. Clark, Robert A. Siddesha, Jalahalli M. Siebenlist, Ulrich Chandrasekar, Bysani TI CIKS (Act1 or TRAF3IP2) mediates Angiotensin-II-induced Interleukin-18 expression, and Nox2-dependent cardiomyocyte hypertrophy SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE RAAS; NADPH oxidase; Act1; TRAF3IP2; Fibrosis; Cardiac hypertrophy ID NF-KAPPA-B; INDUCED CARDIAC-HYPERTROPHY; NOX2-CONTAINING NADPH OXIDASE; HEART-FAILURE; SIGNALING PATHWAYS; GENE-EXPRESSION; PROTEIN-KINASE; IN-VIVO; ACTIVATION; REQUIREMENT AB Chronic elevation of angiotensin (Ang)-II can lead to myocardial inflammation, hypertrophy and cardiac failure. The adaptor molecule CIKS (connection to IKK and SAPK/JNK) activates the I kappa B kinase/nuclear factor (NF)-kappa B and JNK/activator protein (AP)-1 pathways in autoimmune and inflammatory diseases. Since Ang-II is a potent activator of NF-kappa B and AP-1, we investigated whether CIKS is critical in Ang-II-mediated cardiac hypertrophy. Here we report that Ang-II induced CIKS mRNA and protein expression, CIKS binding to IKK and JNK perhaps functioning as a scaffold protein, CIKS-dependent IKK/NF-kappa B and JNK/AP-1 activation, p65 and c-Jun phosphorylation and nuclear translocation, NF-kappa B- and AP-1-dependent IL-18 and MMP-9 induction, and hypertrophy of adult cardiomyocytes isolated from WT, but not CIKS-null mice. These results were recapitulated in WT-cardiomyocytes following CIKS knockdown. Infusion of Ang-II for 7 days induced cardiac hypertrophy, increased collagen content, and upregulated CIKS mRNA and protein expression in WT mice, whereas cardiac hypertrophy and collagen deposition were markedly attenuated in the CIKS-null mice, despite a similar increase in systolic blood pressure and DPI-inhibitable superoxide generation in both types of animals. Further, Ang-II-induced IKK/p65 and JNK/c-Jun phosphorylation, NF-kappa B and AP-1 activation, and IL-18 and MMP-9 expression were also markedly attenuated in CIKS-null mice. These results demonstrate that CIKS is critical in Ang-II-induced cardiomyocyte hypertrophy and fibrosis, and that CIKS is an important intermediate in Ang-II-induced redox signaling. CIKS is a potential therapeutic target in cardiac hypertrophy, fibrosis, and congestive heart failure. (c) 2012 Elsevier Ltd. All rights reserved. C1 [Siddesha, Jalahalli M.; Chandrasekar, Bysani] Tulane Univ, Sch Med, Inst Heart & Vasc, New Orleans, LA 70112 USA. [Valente, Anthony J.; Clark, Robert A.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Valente, Anthony J.; Clark, Robert A.] S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Siebenlist, Ulrich] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Chandrasekar, Bysani] SE Louisiana Vet Hlth Care Syst, Res Serv, New Orleans, LA 70161 USA. RP Chandrasekar, B (reprint author), Tulane Univ, Sch Med, Inst Heart & Vasc, 1430 Tulane Ave,SL-48, New Orleans, LA 70112 USA. EM bchandra@tulane.edu FU Veterans Affairs Office of Research and Development Biomedical Laboratory Research and Development Service Award [1IO1BX000246]; NIH/NHLBI [HL-86787] FX This work was supported by Veterans Affairs Office of Research and Development Biomedical Laboratory Research and Development Service Award 1IO1BX000246 and the NIH/NHLBI Grant HL-86787 (to BC). The contents of this report do not represent the views of the Department of Veterans Affairs or the United States Government. NR 45 TC 25 Z9 25 U1 0 U2 5 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD JUL PY 2012 VL 53 IS 1 BP 113 EP 124 DI 10.1016/j.yjmcc.2012.04.009 PG 12 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 963AI UT WOS:000305592100014 PM 22575763 ER PT J AU Wills, LP Trager, RE Beeson, GC Lindsey, CC Peterson, YK Beeson, CC Schnellmann, RG AF Wills, Lauren P. Trager, Richard E. Beeson, Gyda C. Lindsey, Christopher C. Peterson, Yuri K. Beeson, Craig C. Schnellmann, Rick G. TI The beta(2)-Adrenoceptor Agonist Formoterol Stimulates Mitochondrial Biogenesis SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID PGC-1-ALPHA MESSENGER-RNA; PROXIMAL TUBULE CELLS; HUMAN SKELETAL-MUSCLE; REUPTAKE INHIBITORS; PROMOTES RECOVERY; GENE-EXPRESSION; RECEPTOR; METABOLISM; EXERCISE; CULTURE AB Mitochondrial dysfunction is a common mediator of disease and organ injury. Although recent studies show that inducing mitochondrial biogenesis (MB) stimulates cell repair and regeneration, only a limited number of chemicals are known to induce MB. To examine the impact of the beta-adrenoceptor (beta-AR) signaling pathway on MB, primary renal proximal tubule cells (RPTC) and adult feline cardiomyocytes were exposed for 24 h to multiple beta-AR agonists: isoproterenol (nonselective beta-AR agonist), (+/-)-(R*,R*)-[4-[2-[[2-(3-chlorophenyl)-2-hydroxyethyl] amino]propyl]phenoxy] acetic acid sodium hydrate (BRL 37344) (selective beta(3)-AR agonist), and formoterol (selective beta(2)-AR agonist). The Seahorse Biosciences (North Billerica, MA) extracellular flux analyzer was used to quantify carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP)-uncoupled oxygen consumption rate (OCR), a marker of maximal electron transport chain activity. Isoproterenol and BRL 37244 did not alter mitochondrial respiration at any of the concentrations examined. Formoterol exposure resulted in increases in both FCCP-uncoupled OCR and mitochondrial DNA (mtDNA) copy number. The effect of formoterol on OCR in RPTC was inhibited by the beta-AR antagonist propranolol and the beta(2)-AR inverse agonist 3-(isopropylamino)-1-[(7-methyl-4-indanyl)oxy]butan-2-ol hydrochloride (ICI-118,551). Mice exposed to formoterol for 24 or 72 h exhibited increases in kidney and heart mtDNA copy number, peroxisome proliferator-activated receptor gamma coactivator 1 alpha, and multiple genes involved in the mitochondrial electron transport chain (F0 subunit 6 of transmembrane F-type ATP synthase, NADH dehydrogenase subunit 1, NADH dehydrogenase subunit 6, and NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 8). Cheminformatic modeling, virtual chemical library screening, and experimental validation identified nisoxetine from the Sigma Library of Pharmacologically Active Compounds and two compounds from the ChemBridge DIVERSet that increased mitochondrial respiratory capacity. These data provide compelling evidence for the use and development of beta(2)-AR ligands for therapeutic MB. C1 [Wills, Lauren P.; Trager, Richard E.; Beeson, Gyda C.; Lindsey, Christopher C.; Peterson, Yuri K.; Beeson, Craig C.; Schnellmann, Rick G.] Med Univ S Carolina, Dept Pharmaceut & Biomed Sci, Ctr Cell Death Injury & Regenerat, Charleston, SC 29425 USA. [Schnellmann, Rick G.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Schnellmann, RG (reprint author), Med Univ S Carolina, Dept Pharmaceut & Biomed Sci, Ctr Cell Death Injury & Regenerat, 280 Calhoun St,MSC140, Charleston, SC 29425 USA. EM schnell@musc.edu FU National Institutes of Health National Cancer Institute [T32 CA119945-04]; National Institutes of Health National Institute of Environmental Health Sciences [F32 ES020103-01, ES012878]; National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [DK062028, DK071997]; National Institutes of Health National Institute of General Medical Sciences [GM084147]; Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs; National Institutes of Health National Center for Research Resources [C06 RR-015455] FX L.P.W. is funded by the National Institutes of Health National Cancer Institute [Grant T32 CA119945-04] and the National Institutes of Health National Institute of Environmental Health Sciences [Grant F32 ES020103-01]. R.G.S. is funded by the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [Grants DK062028, DK071997], the National Institutes of Health National Institute of Environmental Health Sciences [Grant ES012878], the National Institutes of Health National Institute of General Medical Sciences [Grant GM084147], and the Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs. Animal facilities were funded by the National Institutes of Health National Center for Research Resources [Grant C06 RR-015455]. NR 42 TC 27 Z9 27 U1 0 U2 8 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JUL PY 2012 VL 342 IS 1 BP 106 EP 118 DI 10.1124/jpet.112.191528 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 960NO UT WOS:000305395400012 PM 22490378 ER PT J AU Maas, MB Lev, MH Ay, H Singhal, AB Greer, DM Smith, WS Harris, GJ Halpern, EF Koroshetz, WJ Furie, KL AF Maas, Matthew B. Lev, Michael H. Ay, Hakan Singhal, Aneesh B. Greer, David M. Smith, Wade S. Harris, Gordon J. Halpern, Elkan F. Koroshetz, Walter J. Furie, Karen L. TI The Prognosis for Aphasia in Stroke SO JOURNAL OF STROKE & CEREBROVASCULAR DISEASES LA English DT Article DE Aphasia; prognosis; stroke; recovery ID ACUTE ISCHEMIC-STROKE; CAUSATIVE CLASSIFICATION; THROMBOLYSIS; RECOVERY; SYSTEM AB Background: Aphasia is a disabling chronic stroke symptom, but the prognosis for patients presenting with aphasia in the hyperacute window has not been well characterized. The purpose of this study is to assess the prognosis for recovery of language function in subjects presenting with aphasia caused by ischemic stroke within 12 hours of symptom onset. Methods: Subjects presenting with aphasia were identified from a prospective cohort study of 669 subjects presenting emergently with acute stroke. Subjects were characterized by demographics, serial clinical examinations, unenhanced computed tomography, and computed tomographic angiography. Aphasia severity was assessed by National Institutes of Health Stroke Scale (NIHSS) examinations performed at baseline, discharge, and 6 months. Demographic, clinical, and imaging factors were assessed for prognostic impact. Results: Aphasia was present in 30% of subjects (n = 204). Of the 166 aphasic patients alive at discharge (median 5 days), aphasia improved in 57% and resolved in 38%. In the 102 aphasic subjects evaluated at 6 months, aphasia improved in 86% and completely resolved in 74% of subjects. Among aphasic subjects with "mild" stroke (initial NIHSS <5), aphasia resolved in 90% of subjects by 6 months. Factors significantly associated with better outcome included clinically and radiographically smaller strokes and lower prestroke disability. Conclusions: The prognosis for full recovery of aphasia present in the hyperacute window is good. Radiographic and clinical markers indicating lesser extent of ischemia correlated to greater recovery. Given the excellent prognosis for language recovery in mild stroke, the net benefit of thrombolysis in such cases is uncertain. C1 [Maas, Matthew B.; Singhal, Aneesh B.; Greer, David M.; Furie, Karen L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. [Lev, Michael H.; Ay, Hakan; Harris, Gordon J.; Halpern, Elkan F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Smith, Wade S.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Koroshetz, Walter J.] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. RP Maas, MB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, 175 Cambridge St,Ste 300, Boston, MA 02114 USA. EM mmaas@partners.org FU Agency for Healthcare Research and Quality [R01 HS11392]; National Institutes of Health [P50NS051343]; Deane Institute for Integrative research in Stroke and Atrial Fibrillation; Lakeside Foundation FX Supported by an Agency for Healthcare Research and Quality grant (R01 HS11392). Dr Maas is supported by a National Institutes of Health grant (P50NS051343). We gratefully acknowledge the support of the Deane Institute for Integrative research in Stroke and Atrial Fibrillation and the Lakeside Foundation. NR 16 TC 22 Z9 25 U1 0 U2 15 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1052-3057 J9 J STROKE CEREBROVASC JI J. Stroke Cerebrovasc. Dis. PD JUL PY 2012 VL 21 IS 5 BP 350 EP 357 DI 10.1016/j.jstrokecerebrovasdis.2010.09.009 PG 8 WC Neurosciences; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 963JM UT WOS:000305616600002 PM 21185744 ER PT J AU Chutinet, A Suwanwela, NC Snabboon, T Chaisinanunkul, N Furie, KL Phanthumchinda, K AF Chutinet, Aurauma Suwanwela, Nijasri C. Snabboon, Thiti Chaisinanunkul, Napasri Furie, Karen L. Phanthumchinda, Kammant TI Association between Genetic Polymorphisms and Sites of Cervicocerebral Artery Atherosclerosis SO JOURNAL OF STROKE & CEREBROVASCULAR DISEASES LA English DT Article DE Apolipoprotein E; angiotensin-converting enzyme; methylenetetrahydrofolate reductase; intracranial stenosis; extracranial carotid stenosis ID APOLIPOPROTEIN-E POLYMORPHISM; INTIMA-MEDIA THICKNESS; ISCHEMIC-STROKE; METHYLENETETRAHYDROFOLATE REDUCTASE; CAROTID ATHEROSCLEROSIS; RISK-FACTORS; E GENOTYPE; CHINESE PATIENTS; DISEASE; POPULATION AB Ischemic stroke is a multifactorial disease with strong genetic elements. The purpose of this case-control study was to find relationships between apolipoprotein E (APOE), angiotensin-converting enzyme (ACE), and methylenetetrahydrofolate reductase (MTHFR) genotypes and atherosclerosis of the extracranial internal carotid and intracranial arteries in the Thai population. Patients aged >45 years with significant intracranial stenosis (IC group) or extracranial carotid artery stenosis (EC group) diagnosed by duplex ultrasound and/or computed tomography angiography (CTA) or magnetic resonance angiography (MRA) were studied. The control group comprised volunteers with no history of stroke and no evidence of significant cervicocerebral artery stenosis by ultrasound. Genomic DNA was extracted and genotyped for APOE isoforms, ACE insertion/deletion (I/D) polymorphism, and MTHFR C677T polymorphisms. There were 141 cases (83 in the IC group and 58 in the EC group) and 167 controls. The APOE epsilon 3/epsilon 4 genotype and APOE epsilon 4 allele were significantly associated with extracranial carotid artery stenosis (odds ratio, 2.55; 95% confidence interval, 1.07-6.05 and odds ratio, 2.85; 95% confidence interval, 1.35-5.99, respectively). These associations were not observed in patients with intracranial atherosclerosis. There was no significant association between ACE and MTHFR polymorphisms and stenosis at any site. In a multivariate model, sex, diabetes mellitus, hypertension, ischemic heart disease, and APOE epsilon 4 allele remained predictive of extracranial atherosclerosis. In our Thai population, the epsilon 4 allele in the APOE gene contributes to the genetic susceptibility of extracranial internal carotid atherosclerosis. The low prevalence of extracranial carotid stenosis in this population might result from low frequencies of the APOE epsilon 4 allele. C1 [Chutinet, Aurauma; Suwanwela, Nijasri C.; Chaisinanunkul, Napasri; Phanthumchinda, Kammant] Chulalongkorn Univ, Fac Med, Dept Med, Div Neurol, Bangkok 10330, Thailand. [Snabboon, Thiti] Chulalongkorn Univ, Fac Med, Dept Med, Div Endocrinol, Bangkok 10330, Thailand. [Furie, Karen L.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Chutinet, A (reprint author), Chulalongkorn Univ, Fac Med, Dept Med, Div Neurol, Rama 4 Rd, Bangkok 10330, Thailand. EM aurauma@yahoo.com FU Neurological Society of Thailand FX Supported by the Neurological Society of Thailand. NR 39 TC 10 Z9 12 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1052-3057 J9 J STROKE CEREBROVASC JI J. Stroke Cerebrovasc. Dis. PD JUL PY 2012 VL 21 IS 5 BP 379 EP 385 DI 10.1016/j.jstrokecerebrovasdis.2010.10.002 PG 7 WC Neurosciences; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 963JM UT WOS:000305616600007 PM 21296594 ER PT J AU Stevens, LM Cooper, JB Raemer, DB Schneider, RC Frankel, AS Berry, WR Agnihotri, AK AF Stevens, Louis-Mathieu Cooper, Jeffrey B. Raemer, Daniel B. Schneider, Robert C. Frankel, Allan S. Berry, William R. Agnihotri, Arvind K. TI Educational program in crisis management for cardiac surgery teams including high realism simulation SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID OPERATING-ROOM; RESOURCE-MANAGEMENT; PERFORMANCE; TEAMWORK; SAFETY; DESIGN; CARE AB Introduction: Cardiac surgery demands effective teamwork for safe, high-quality care. The objective of this pilot study was to develop a comprehensive program to sharpen performance of experienced cardiac surgical teams in acute crisis management. Methods: We developed and implemented an educational program for cardiac surgery based on high realism acute crisis simulation scenarios and interactive whole-unit workshop. The impact of these interventions was assessed with postintervention questionnaires, preintervention and 6-month postintervention surveys, and structured interviews. Results: The realism of the acute crisis simulation scenarios gradually improved; most participants rated both the simulation and whole-unit workshop as very good or excellent. Repeat simulation training was recommended every 6 to 12 months by 82% of the participants. Participants of the interactive workshop identified 2 areas of highest priority: encouraging speaking up about critical information and interprofessional information sharing. They also stressed the importance of briefings, early communication of surgical plan, knowing members of the team, and continued simulation for practice. The pre/post survey response rates were 70% (55/79) and 66% (52/79), respectively. The concept of working as a team improved between surveys (P = .028), with a trend for improvement in gaining common understanding of the plan before a procedure (P = .075) and appropriate resolution of disagreements (P = .092). Interviewees reported that the training had a positive effect on their personal behaviors and patient care, including speaking up more readily and communicating more clearly. Conclusions: Comprehensive team training using simulation and a whole-unit interactive workshop can be successfully deployed for experienced cardiac surgery teams with demonstrable benefits in participant's perception of team performance. (J Thorac Cardiovasc Surg 2012;144:17-24) C1 [Stevens, Louis-Mathieu] Ctr Hosp Univ Montreal, Div Cardiac Surg, Montreal, PQ H2W 1T8, Canada. [Stevens, Louis-Mathieu; Agnihotri, Arvind K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiac Surg, Boston, MA USA. [Cooper, Jeffrey B.; Raemer, Daniel B.; Schneider, Robert C.; Berry, William R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. [Frankel, Allan S.] Pascal Metr, Washington, DC USA. [Cooper, Jeffrey B.; Raemer, Daniel B.] Ctr Med Simulat, Cambridge, MA USA. RP Stevens, LM (reprint author), Ctr Hosp Univ Montreal, Div Cardiac Surg, 3840 St Urbain St,Off 2-420, Montreal, PQ H2W 1T8, Canada. EM lm.stevens@videotron.ca RI Stevens, Louis-Mathieu/E-6453-2016 OI Stevens, Louis-Mathieu/0000-0003-3372-3419 FU CRICO/Risk Management Foundation of the Harvard Medical Institutions; Canadian Institutes of Health Research's Clinical Research Initiative; Rossetti Fund (Massachusetts General Hospital, Boston, Massachusetts) FX This study was supported by an unrestricted grant from CRICO/Risk Management Foundation of the Harvard Medical Institutions. Salary support (to L. M. S.) was provided by a fellowship award from the Canadian Institutes of Health Research's Clinical Research Initiative and the Rossetti Fund (Massachusetts General Hospital, Boston, Massachusetts). NR 25 TC 27 Z9 27 U1 2 U2 13 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 EI 1097-685X J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD JUL PY 2012 VL 144 IS 1 BP 17 EP 24 DI 10.1016/j.jtcvs.2012.03.006 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 960TB UT WOS:000305412200010 PM 22502966 ER PT J AU Jacobson, FL Austin, JHM Field, JK Jett, JR Keshavjee, S MacMahon, H Mulshine, JL Munden, RF Salgia, R Strauss, GM Sugarbaker, DJ Swanson, SJ Travis, WD Jaklitsch, MT AF Jacobson, Francine L. Austin, John H. M. Field, John K. Jett, James R. Keshavjee, Shaf MacMahon, Heber Mulshine, James L. Munden, Reginald F. Salgia, Ravi Strauss, Gary M. Sugarbaker, David J. Swanson, Scott J. Travis, William D. Jaklitsch, Michael T. TI Development of The American Association for Thoracic Surgery guidelines for low-dose computed tomography scans to screen for lung cancer in North America: Recommendations of The American Association for Thoracic Surgery Task Force for Lung Cancer Screening and Surveillance SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID MORTALITY; TRIAL AB Objective: The study objective was to establish The American Association for Thoracic Surgery (AATS) lung cancer screening guidelines for clinical practice. Methods: The AATS established the Lung Cancer Screening and Surveillance Task Force with multidisciplinary representation including 4 thoracic surgeons, 4 thoracic radiologists, 4 medical oncologists, 1 pulmonologist, 1 pathologist, and 1 epidemiologist. Members have engaged in interdisciplinary collaborations regarding lung cancer screening and clinical care of patients with, and at risk for, lung cancer. The task force reviewed the literature, including screening trials in the United States and Europe, and discussed local best clinical practices in the United States and Canada on 4 conference calls. A reference library supported the discussions and increased individual study across disciplines. The task force met to review the literature, state of clinical practice, and recommend consensus-based guidelines. Results: Nine of 14 task force members were present at the meeting, and 3 participated by telephone. Two absent task force members were polled afterward. Six unanimous recommendations and supporting work-up algorithms were presented to the Council of the AATS at the 2012 annual meeting in San Francisco, California. Conclusions: Annual lung cancer screening and surveillance with low-dose computed tomography is recommended for smokers and former smokers with a 30 pack-year history of smoking and long-term lung cancer survivors aged 55 to 79 years. Screening may begin at age 50 years with a 20 pack-year history of smoking and additional comorbidity that produces a cumulative risk of developing lung cancer of 5% or greater over the following 5 years. Screening should be undertaken with a subspecialty qualified interdisciplinary team. Patient risk calculator application and intersociety engagement will provide data needed to refine future lung cancer screening guidelines. (J Thorac Cardiovasc Surg 2012;144:25-32) C1 [Jacobson, Francine L.] Harvard Univ, Brigham & Womens Hosp, Dept Radiol, Sch Med, Boston, MA 02115 USA. [Austin, John H. M.] Columbia Presbyterian Med Ctr, New York, NY USA. [Field, John K.] Univ Liverpool, Liverpool L69 3BX, Merseyside, England. [Jett, James R.] Natl Jewish Hosp, Denver, CO USA. [Keshavjee, Shaf] Toronto Gen Hosp, Toronto, ON, Canada. [MacMahon, Heber; Salgia, Ravi] Univ Chicago, Chicago, IL 60637 USA. [Mulshine, James L.] Rush Univ, Rush Med Coll, Chicago, IL 60612 USA. [Munden, Reginald F.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Strauss, Gary M.] Tufts Med Ctr, Boston, MA USA. [Swanson, Scott J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Travis, William D.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Jacobson, FL (reprint author), Harvard Univ, Brigham & Womens Hosp, Dept Radiol, Sch Med, 75 Francis St, Boston, MA 02115 USA. EM fjacobson@partners.org FU Toshiba; Oncimmune; Metabolomx; Astellas Canada; Axela/Exceed; Eli Lilly FX John H. M. Austin, Reginald F. Munden, Gary M. Strauss, David J. Sugarbaker, William D. Travis, and Michael T. Jaklitsch have no commercial interests to disclose. Francine L. Jacobson reports grant funding from Toshiba. John K. Field reports advisory board member work for Epigenomics and Roche Diagnostics. James R. Jett reports grant research support from Oncimmune and Metabolomx. Shaf Keshavjee reports grant research support from Astellas Canada and Axela/Exceed, clinical trial support from Vitrolife, and being awarded a Wyeth Pharmaceuticals/CIHR Rx&D Clinical Research Chair in Transplantation. Heber MacMahon reports advisory board member and consultant work for Riverain Medical, consultant work for Biomet, and royalties from UC Tech (University of Chicago). James L. Mulshine reports a family member who is an employee of Accretive Health. Ravi Salgia reports advisory board member work for Cephalon and Methylgene, and research funding from Eli Lilly. Scott J. Swanson reports consulting fees for Ethicon and Covidien. NR 15 TC 46 Z9 47 U1 1 U2 8 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 JUL PY 2012 VL 144 IS 1 BP 25 EP 32 DI 10.1016/j.jtcvs.2012.05.059 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 960TB UT WOS:000305412200011 PM 22710038 ER PT J AU Jaklitsch, MT Jacobson, FL Austin, JHM Field, JK Jett, JR Keshavjee, S MacMahon, H Mulshine, JL Munden, RF Salgia, R Strauss, GM Swanson, SJ Travis, WD Sugarbaker, DJ AF Jaklitsch, Michael T. Jacobson, Francine L. Austin, John H. M. Field, John K. Jett, James R. Keshavjee, Shaf MacMahon, Heber Mulshine, James L. Munden, Reginald F. Salgia, Ravi Strauss, Gary M. Swanson, Scott J. Travis, William D. Sugarbaker, David J. TI The American Association for Thoracic Surgery guidelines for lung cancer screening using low-dose computed tomography scans for lung cancer survivors and other high-risk groups SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article AB Objective: Lung cancer is the leading cause of cancer death in North America. Low-dose computed tomography screening can reduce lung cancer-specific mortality by 20%. Method: The American Association for Thoracic Surgery created a multispecialty task force to create screening guidelines for groups at high risk of developing lung cancer and survivors of previous lung cancer. Results: The American Association for Thoracic Surgery guidelines call for annual lung cancer screening with low-dose computed tomography screening for North Americans from age 55 to 79 years with a 30 pack-year history of smoking. Long-term lung cancer survivors should have annual low-dose computed tomography to detect second primary lung cancer until the age of 79 years. Annual low-dose computed tomography lung cancer screening should be offered starting at age 50 years with a 20 pack-year history if there is an additional cumulative risk of developing lung cancer of 5% or greater over the following 5 years. Lung cancer screening requires participation by a subspecialty-qualified team. The American Association for Thoracic Surgery will continue engagement with other specialty societies to refine future screening guidelines. Conclusions: The American Association for Thoracic Surgery provides specific guidelines for lung cancer screening in North America. (J Thorac Cardiovasc Surg 2012;144:33-8) C1 [Jaklitsch, Michael T.] Harvard Univ, Brigham & Womens Hosp, Dept Thorac Surg, Sch Med, Boston, MA 02115 USA. [Austin, John H. M.] Columbia Presbyterian Med Ctr, New York, NY USA. [Field, John K.] Univ Liverpool, Liverpool L69 3BX, Merseyside, England. [Keshavjee, Shaf] Toronto Gen Hosp, Toronto, ON, Canada. [Jett, James R.] Natl Jewish Hosp, Denver, CO USA. [MacMahon, Heber; Salgia, Ravi] Univ Chicago, Chicago, IL 60637 USA. [Mulshine, James L.] Rush Univ, Rush Med Coll, Chicago, IL 60612 USA. [Munden, Reginald F.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Strauss, Gary M.] Tufts Med Ctr, Boston, MA USA. [Swanson, Scott J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Travis, William D.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Jaklitsch, MT (reprint author), Harvard Univ, Brigham & Womens Hosp, Dept Thorac Surg, Sch Med, 75 Francis St,CA-257, Boston, MA 02115 USA. EM mjaklitsch@partners.org OI Munden, Reginald/0000-0003-3836-5067; Field, John/0000-0003-3951-6365 FU Toshiba; Oncimmune; Metabolomx; Astellas Canada; Axela/Exceed; Eli Lilly FX Michael T. Jaklitsch, John H. M. Austin, Reginald F. Munden, Gary M. Strauss, William D. Travis, and David J. Sugarbaker have no commercial interests to disclose. Francine L. Jacobson reports grant funding from Toshiba. John K. Field reports advisory board member work for Epigenomics and Roche Diagnostics. James R. Jett reports grant research support from Oncimmune and Metabolomx. Shaf Keshavjee reports grant research support from Astellas Canada and Axela/Exceed, clinical trial support from Vitrolife, and being awarded a Wyeth Pharmaceuticals/CIHR Rx&D Clinical Research Chair in Transplantation. Heber MacMahon reports advisory board member and consultant work for Riverain Medical, consultant work for Biomet, and royalties from UC Tech (University of Chicago). James L. Mulshine reports a family member who is an employee of Accretive Health. Ravi Salgia reports advisory board member work for Cephalon and Methylgene, and research funding from Eli Lilly. Scott J. Swanson reports consulting fees for Ethicon and Covidien. NR 15 TC 199 Z9 204 U1 1 U2 16 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 JUL PY 2012 VL 144 IS 1 BP 33 EP 38 DI 10.1016/j.jtcvs.2012.05.060 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 960TB UT WOS:000305412200012 PM 22710039 ER PT J AU O'Donoghue, ML Bhatt, DL Flather, MD Goto, S Angiolillo, DJ Goodman, SG Zeymer, U Aylward, PE Montalescot, G Ziecina, R Kobayashi, H Ren, F Wiviott, SD AF O'Donoghue, Michelle L. Bhatt, Deepak L. Flather, Marcus D. Goto, Shinya Angiolillo, Dominick J. Goodman, Shaun G. Zeymer, Uwe Aylward, Philip E. Montalescot, Gilles Ziecina, Rafal Kobayashi, Hiroyuki Ren, Fang Wiviott, Stephen D. TI Atopaxar and its effects on markers of platelet activation and inflammation: results from the LANCELOT CAD program SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Article DE Biomarkers; PAR-1 receptor antagonist; Atopaxar; Coronary artery disease ID CORONARY-ARTERY-DISEASE; IN-VITRO; TRIAL; CLOPIDOGREL; BIOMARKERS; ANTAGONIST; LESSONS; E5555 AB Atopaxar is a reversible protease activated receptor (PAR)-1 thrombin receptor antagonist that interferes with platelet signaling. The effects of PAR-1 antagonists on biomarkers remain unknown. The primary objective was to assess the effects of atopaxar on biomarkers of inflammation and platelet activation. The LANCELOT-CAD trial randomized 720 subjects to atopaxar (50, 100, or 200 mg daily) or matching placebo for 24 weeks. Biomarkers were assessed at serial time points. A linear mixed model to account for repeated measures was used to evaluate the change in biomarker concentration from randomization across time to week 24. Least square means were determined from the linear mixed models. The concentration of sCD40L decreased on average over time by -553 (95 % CI -677, -429) ng/L in the combined atopaxar group versus -30.3 (-249 to 189) ng/L fall in the placebo arm (P < 0.001) and a dose-dependent trend was seen across treatment groups (P < 0.001 for trend). In contrast, Lp-PLA(2) mass rose on average over time by 12.6 (95 % CI 10.0, 15.3) ng/ml in the combined atopaxar group as compared with 2.6 (95 % CI -2.1, 7.3) ng/ml in the placebo arm (P < 0.001). Similarly, the concentration of IL-18 rose by 17.5 (95 % CI 12.4, 22.6) pg/ml in the atopaxar group versus a -1.2 (95 % CI -10.2, 7.8) pg/ml fall in the placebo group (P < 0.001). The effects of atopaxar on Lp-PLA(2) and IL-18 appeared to be dose-dependent (P < 0.001 for trend) and were observed in J-LANCELOT. Atopaxar did not have a significant effect on other inflammatory markers. In conclusion, atopaxar appeared to decrease sCD40L, but did not demonstrate an anti-inflammatory effect in patients with stable CAD. Although atopaxar increased the concentration of Lp-PLA(2) and IL-18, the clinical relevance of these findings remains unknown and warrants further investigation and validation. C1 [O'Donoghue, Michelle L.; Ren, Fang; Wiviott, Stephen D.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [O'Donoghue, Michelle L.; Bhatt, Deepak L.; Ren, Fang; Wiviott, Stephen D.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Flather, Marcus D.] Royal Brompton Hosp, Clin Trials & Evaluat Unit, London SW3 6LY, England. [Goto, Shinya] Tokai Univ, Sch Med, Dept Med Cardiol, Hiratsuka, Kanagawa 25912, Japan. [Angiolillo, Dominick J.] Univ Florida, Coll Med, Jacksonville, FL USA. [Goodman, Shaun G.] Univ Toronto, St Michaels Hosp, Div Cardiol, Toronto, ON M5B 1W8, Canada. [Zeymer, Uwe] Herzzentrum Ludwigshafen, Ludwigshafen, Germany. [Aylward, Philip E.] Flinders Cardiovasc Ctr, Dept Cardiovasc Med, Adelaide, SA, Australia. [Montalescot, Gilles] Pitie Salpetriere Univ Hosp, Inst Cardiol, Paris, France. [Ziecina, Rafal] Eisai Ltd, Frontier Prod Creat Unit, European Knowledge Ctr, Hatfield, Herts, England. [Kobayashi, Hiroyuki] Tokai Univ, Sch Med, Dept Clin Pharmacol, Hiratsuka, Kanagawa 25912, Japan. RP O'Donoghue, ML (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM modonoghue@partners.org FU Eisai Incorporated; Eisai; GlaxoSmithKline; Astra Zeneca; sanofi aventis; Otsuka; Merck; Bristol-Myers Squibb; Eli Lilly; Daiichi Sankyo; Medicines Company; Portola; Novartis; Medicure; Accumetrics; Arena Pharmaceuticals; Abbott Vascular; Boston Scientific; Schering-Plough; Evolva; Johnson and Johnson; sanofi-aventis; Bristol Myers Squibb; Boehringer Ingelheim; Pfizer; Abott Vascular; BMS; Centocor; INSERM; ITC Edison; Medtronic; Stago; Bayer; Menarini; Cordis; GSK; Schering Plough; ARENA; Medco FX The LANCELOT program and biomarker analyses were funded by Eisai Incorporated.; Dr. O'Donoghue has received research grants from Eisai, GlaxoSmithKline and Astra Zeneca. Dr. Bhatt discloses the following relationships - Advisory Board: Medscape Cardiology; Board of Directors: Boston VA Research Institute, Society of Chest Pain Centers; Chair: American Heart Association Get With The Guidelines Science Subcommittee; Honoraria: American College of Cardiology (Editor, Clinical Trials, Cardiosource), Duke Clinical Research Institute (clinical trial steering committees), Slack Publications (Chief Medical Editor, Cardiology Today Intervention), WebMD (CME steering committees); Research Grants: Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi Aventis, The Medicines Company; Unfunded Research: PLx Pharma, Takeda. Dr Flather has received honoraria for his participation at meetings related to the development of atopaxar and also receives research grants and honoraria for speaker meetings and advisory boards from sanofi aventis, Bristol Myers Squibb, Eli Lilly, Daiichi Sankyo, Novartis and GlaxoSmithKline. Dr. Goto has received research grants from sanofi aventis, Eisai, Otsuka; honoraria from sanofi aventis, Eisai, Otsuka; consulting fees from Merck and Eisai. Dr. Angiolillo reports honoraria for lectures from Bristol Myers Squibb, sanofi aventis, Eli Lilly, Daiichi Sankyo, Abbott Vascular, and Astra Zeneca; consulting fees from Bristol-Myers Squibb, sanofi aventis, Eli Lilly, Daiichi Sankyo, The Medicines Company, Portola, Novartis, Medicure, Accumetrics, Arena Pharmaceuticals, Merck, Abbott Vascular, and Astra Zeneca; and research grants from GlaxoSmithKline, Otsuka, Boston Scientific, Eli Lilly, Daiichi Sankyo, The Medicines Company, Portola, Accumetrics, Schering-Plough, Astra Zeneca, Eisai, Evolva, and Johnson and Johnson. Dr. Goodman has received research grant support and/or speaking/consulting/ advisory board honoraria from Eisai, sanofi-aventis, Bristol Myers Squibb, Eli Lilly, Daiichi Sankyo, Astra Zeneca, and Merck. Dr Zeymer has received honoraria for his participation at meetings related to the development of atopaxar; research grants and honoraria for speaker meetings and advisory boards from sanofi aventis, Bristol Myers Squibb, Eli Lilly, Daiichi Sankyo and Astra Zeneca; consulting fees for Eli Lilly, Astra Zeneca and sanofi aventis. Dr. Aylward has received grants from Eisai, Merck and Astra Zeneca; speaking fees and/or honoraria from Astra Zeneca, sanofi Aventis, Boehringer Ingelheim, Merck; consulting fees for Astra Zeneca, Pfizer and Boehringer Ingelheim. Dr. Montalescot has received grants, consulting fees and/or lecture fees from Abott Vascular, BMS, Boston Scientific, Centocor, Eli Lilly, INSERM, ITC Edison, Medtronic, Pfizer, sanofi Aventis, Stago, Astra Zeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Eisai, Eli Lilly, Menarini, Novartis, Portola, The Medicines Company, Accumetrics, Cordis, GSK, Menarini, Merck. Dr. Ziecina is an employee of Eisai. Fang Ren has no disclosures. Dr Wiviott has received grants from Eli Lilly, Daiichi Sankyo, Schering Plough; consulting fees from Bristol Myers Squibb, sanofi aventis, Astra Zeneca, ARENA, Medco. NR 12 TC 10 Z9 10 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5305 J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD JUL PY 2012 VL 34 IS 1 BP 36 EP 43 DI 10.1007/s11239-012-0750-6 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 962EN UT WOS:000305523300006 PM 22653705 ER PT J AU Angiolillo, DJ Schneider, DJ Bhatt, DL French, WJ Price, MJ Saucedo, JF Shaburishvili, T Huber, K Prats, J Liu, TP Harrington, RA Becker, RC AF Angiolillo, Dominick J. Schneider, David J. Bhatt, Deepak L. French, William J. Price, Matthew J. Saucedo, Jorge F. Shaburishvili, Tamaz Huber, Kurt Prats, Jayne Liu, Tiepu Harrington, Robert A. Becker, Richard C. TI Pharmacodynamic effects of cangrelor and clopidogrel: the platelet function substudy from the cangrelor versus standard therapy to achieve optimal management of platelet inhibition (CHAMPION) trials SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Article DE Platelet function; PCI; Clopidogrel; Cangrelor ID PERCUTANEOUS CORONARY INTERVENTION; OF-CARE ASSAY; MYOCARDIAL-INFARCTION; ANTIPLATELET THERAPY; STENT IMPLANTATION; ISCHEMIC EVENTS; REACTIVITY; AGGREGATION; PRASUGREL; PCI AB Cangrelor is an intravenous antagonist of the P2Y(12) receptor characterized by rapid, potent, predictable, and reversible platelet inhibition. However, cangrelor was not superior to clopidogrel in reducing the incidence of ischemic events in the cangrelor versus standard therapy to achieve optimal management of platelet inhibition (CHAMPION) trials. A prospectively designed platelet function substudy was performed in a selected cohort of patients to provide insight into the pharmacodynamic effects of cangrelor, particularly in regard to whether cangrelor therapy may interfere with the inhibitory effects of clopidogrel. This pre-defined substudy was conducted in a subset of patients from the CHAMPION-PCI trial (n = 230) comparing cangrelor with 600 mg of clopidogrel administered before percutaneous coronary intervention (PCI) and from the CHAMPION-PLATFORM trial (n = 4) comparing cangrelor at the time of PCI and 600 mg clopidogrel given after the PCI. Pharmacodynamic measures included P2Y12 reaction units (PRU) assessed by VerifyNow P2Y12 testing (primary endpoint marker), platelet aggregation by light transmittance aggregometry following 5 and 20 mu mol/L adenosine diphosphate stimuli, and markers of platelet activation determined by flow cytometry. The primary endpoint was the percentage of patients who achieved < 20 % change in PRU between baseline and > 10 h after PCI. The main trial was stopped early limiting enrollment in the platelet substudy. A total of 167 patients had valid pharmacodynamic assessments for the primary endpoint. The percent of individuals achieving < 20 % change in PRU between baseline and > 10 h after PCI was higher with cangrelor + clopidogrel (32/84, 38.1 %) compared with placebo + clopidogrel (21/83, 25.3 %), but this was not statistically significant (difference:12.79 %, 95 % CI: -1.18 %, 26.77 %;p = 0.076). All pharmacodynamic markers as well as the prevalence of patients with high on-treatment platelet reactivity were significantly lower in patients treated with cangrelor. A rapid platelet inhibitory effect was achieved during cangrelor infusion and a rapid offset of action after treatment discontinuation. This CHAMPION platelet function substudy represents the largest pharmacodynamic experience with cangrelor, demonstrating its potent P2Y(12) receptor inhibitory effects, and rapid onset/offset of action. Although there was no significant pharmacodynamic interaction when transitioning to clopidogrel therapy, further studies are warranted given that enrollment in this study was limited due to premature interruption of the main trial. C1 [Angiolillo, Dominick J.] Univ Florida, Coll Medicine Jacksonville, Jacksonville, FL 32209 USA. [Schneider, David J.] Univ Vermont, Burlington, VT USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. [French, William J.] Harbor UCLA Med Ctr, Torrance, CA 90509 USA. [Price, Matthew J.] Scripps Clin, Div Cardiovasc Dis, La Jolla, CA 92037 USA. [Saucedo, Jorge F.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Shaburishvili, Tamaz] Diagnost Serv Clin, Tbilisi, GA USA. [Huber, Kurt] Wilhelminen Hosp, Dept Med Cardiol & Emergency Med 3, Vienna, Austria. [Prats, Jayne; Liu, Tiepu] Medicines Co, Parsippany, NJ USA. [Harrington, Robert A.; Becker, Richard C.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. RP Angiolillo, DJ (reprint author), Univ Florida, Coll Medicine Jacksonville, 655 W 8th St, Jacksonville, FL 32209 USA. EM dominick.angiolillo@jax.ufl.edu FU Medicines Company; Bristol Myers Squibb; Sanofi-Aventis; Eli Lilly Co; Daiichi Sankyo, Inc.; Portola; Novartis; Medicure; Accumetrics; Arena Pharmaceuticals; Astra Zeneca; Merck; GlaxoSmithKline; Otsuka; Schering-Plough; Astra-Zeneca; Johnson Johnson; Bayer Pharmaceuticals; Bristol-Myers Squibb; Eisai; Sanofi Aventis; AstraZeneca; Daiichi-Sankyo/Eli Lily Co; Bristol-Myers Squibb/sanofi aventis; New England Research Institute; Eli Lilly; Daiichi Sankyo; Bristol-Myers-Squibb; BMS; Bayer; Regado Biosciences FX Funding: This work was supported by The Medicines Company.; Dominick J. Angiolillo reports receiving: honoraria for lectures from Bristol Myers Squibb; Sanofi-Aventis; Eli Lilly Co; Daiichi Sankyo, Inc; Astra Zeneca; Abbott Vascular; consulting fees from Bristol Myers Squibb; Sanofi-Aventis; Eli Lilly Co; Daiichi Sankyo, Inc.; The Medicines Company; Portola; Novartis; Medicure; Accumetrics; Arena Pharmaceuticals; Astra Zeneca; Merck; research grants from Bristol Myers Squibb; Sanofi-Aventis; GlaxoSmithKline; Otsuka; Eli Lilly Co; Daiichi Sankyo, Inc., The Medicines Company; Portola; Accumetrics; Schering-Plough; Astra-Zeneca; Eisai. David J. Schneider reports receiving honoraria and research grants from Bristol Myers Squibb; Sanofi-Aventis; The Medicines Company; Johnson & Johnson; Bayer Pharmaceuticals. Deepak L. Bhatt reports receiving: research grants (all significant) from Astra Zeneca, Bristol-Myers Squibb, Eisai, Sanofi Aventis, The Medicines Company. William J. French reports receiving: honoraria for lectures from Sanofi-Aventis and Eli Lilly Co; consulting fees from The Medicines Company and Portola; and research grants from Eli Lilly Co; Daiichi Sankyo, Inc., The Medicines Company, Portola and Schering-Plough. Matthew J. Price reports receiving received consulting fees and honoraria from The Medicines Company, AstraZeneca, Daiichi-Sankyo/Eli Lily & Co, Accumetrics, Bristol-Myers Squibb/sanofi aventis, and Medicure; honoraria for lectures from the Medicines Company and Daiichi-Sankyo/Eli Lily & Co.; and research grants from Accumetrics and Bristol-Myers Squibb/sanofi aventis. Jorge Saucedo reports receiving: honoraria for lectures from Eli Lilly Co; Daiichi Sankyo, Inc; and Merck; consulting fees; Eli Lilly Co; Daiichi Sankyo, Inc.; Medicure; Merck; research grants from Eli Lilly Co; Daiichi Sankyo, Inc., The Medicines Company; Accumetrics; Schering-Plough. Tamaz Shaburishvili reports receiving: consulting fees from New England Research Institute, The Medicines Company. Kurt Huber reports receiving: honoraria for lectures from Astra-ZenecaM; Bayer Austira; Boehringer-Ingelheim; Eli Lilly Co; Daiichi Sankyo, Inc; Sanofi-Aventis; The Medicines Company. Jayne Prats is an employee of The Medicines Company. Tiepu Liu is an employee of The Medicines Company. Robert A. Harrington reports receiving: research funding to the DCRI from The Medicines Company, Eli Lilly, Daiichi Sankyo, Sanofi-Aventis, Bristol-Myers-Squibb, Portola, Novartis, Merck, and AstraZeneca. Consulting fees from AstraZeneca, Sanofi-aventis, BMS, Novartis, and Merck. Full disclosure of all relationships with industry are available at http://www.dcri.duke.edu/research/coi.jsp. Richard C. Becker reports receiving: research grants from The Medicines Company, AstraZeneca, Johnson and Johnson, Bayer, and Regado Biosciences. Scientific advisory boards and honoraria from Daiich-Sankyo, Regado Biosciences, Boehringer Ingelheim, Merck, and Bristol-Myers-Squibb. NR 29 TC 56 Z9 57 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5305 J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD JUL PY 2012 VL 34 IS 1 BP 44 EP 55 DI 10.1007/s11239-012-0737-3 PG 12 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 962EN UT WOS:000305523300007 PM 22569899 ER PT J AU Bouley, R AF Bouley, Richard TI Corin: a key protein of an adaptive renal mechanism to respond to salt variation? SO KIDNEY INTERNATIONAL LA English DT Editorial Material ID CHANNEL; SYSTEM AB The protease corin generates atrial natriuretic peptide and affects blood pressure and salt-water homeostasis. Under dietary salt challenge, corin knockout mice show blood pressure exacerbation and significant weight gain due to water and salt retention. This phenotype involves the epithelial sodium channel but is independent of the renin-angiotensin-aldosterone system. This suggests that corin has an important role in a new adaptive mechanism of the response to variations of salt in the diet. Kidney International (2012) 32, 7-8. doi:10.1038/ki.2012.123 C1 Massachusetts Gen Hosp, Program Membrane Biol, Boston, MA 02114 USA. RP Bouley, R (reprint author), Massachusetts Gen Hosp, Program Membrane Biol, 185 Cambridge St,CPZN 8150, Boston, MA 02114 USA. EM bouley@receptor.mgh.harvard.edu NR 11 TC 3 Z9 3 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JUL PY 2012 VL 82 IS 1 BP 7 EP 8 DI 10.1038/ki.2012.123 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 959XK UT WOS:000305351300002 PM 22699378 ER PT J AU Bhan, I Powe, CE Berg, AH Ankers, E Wenger, JB Karumanchi, SA Thadhani, RI AF Bhan, Ishir Powe, Camille E. Berg, Anders H. Ankers, Elizabeth Wenger, Julia B. Karumanchi, S. Ananth Thadhani, Ravi I. TI Bioavailable vitamin D is more tightly linked to mineral metabolism than total vitamin D in incident hemodialysis patients SO KIDNEY INTERNATIONAL LA English DT Article DE chronic kidney disease; dialysis; free hormone hypothesis; vitamin D; vitamin D deficiency; vitamin D-binding protein ID D-BINDING PROTEIN; CHRONIC KIDNEY-DISEASE; NUTRITION EXAMINATION SURVEY; STAGE RENAL-DISEASE; D DEFICIENCY; PARATHYROID-HORMONE; DIALYSIS PATIENTS; NATIONAL-HEALTH; 25-HYDROXYVITAMIN-D; SERUM AB Prior studies showed conflicting results regarding the association between 25-hydroxyvitamin D (25(OH) D) levels and mineral metabolism in end-stage renal disease. In order to determine whether the bioavailable vitamin D (that fraction not bound to vitamin D-binding protein) associates more strongly with measures of mineral metabolism than total levels, we identified 94 patients with previously measured 25(OH) D and 1,25-dihydroxyvitamin D (1,25(OH)(2)D) from a cohort of incident hemodialysis patients. Vitamin D-binding protein was measured from stored serum samples. Bioavailable 25(OH) D and 1,25(OH)(2)D were determined using previously validated formulae. Associations with demographic factors and measures of mineral metabolism were examined. When compared with whites, black patients had lower levels of total, but not bioavailable, 25(OH) D. Bioavailable, but not total, 25(OH) D and 1,25(OH)(2)D were each significantly correlated with serum calcium. In univariate and multivariate regression analysis, only bioavailable 25(OH) D was significantly associated with parathyroid hormone levels. Hence, bioavailable vitamin D levels are better correlated with measures of mineral metabolism than total levels in patients on hemodialysis. Kidney International (2012) 82, 84-89; doi: 10.1038/ki.2012.19; published online 7 March 2012 C1 [Bhan, Ishir; Powe, Camille E.; Ankers, Elizabeth; Wenger, Julia B.; Thadhani, Ravi I.] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. [Bhan, Ishir; Powe, Camille E.; Ankers, Elizabeth; Wenger, Julia B.; Thadhani, Ravi I.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Berg, Anders H.] Beth Israel Deaconess Med Ctr, Div Clin Pathol, Dept Clin Chem, Boston, MA 02215 USA. [Karumanchi, S. Ananth] Harvard Univ, Sch Med, Howard Hughes Med Inst,Div Nephrol, Beth Israel Deaconess Med Ctr,Dept Med, Boston, MA 02114 USA. RP Bhan, I (reprint author), Massachusetts Gen Hosp, Dept Med, Div Nephrol, Bullfinch 127,Suite 750, Boston, MA 02114 USA. EM ibhan@partners.org FU NIH Young Investigator Grant (Bethesda, MD) [K23 1K23DK081677] FX We thank Kathryn Lucchesi, PhD, RPh, for helpful comments and suggestions about the manuscript. IB is supported by NIH Young Investigator Grant K23 1K23DK081677 (Bethesda, MD). NR 34 TC 79 Z9 79 U1 0 U2 6 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 JUL PY 2012 VL 82 IS 1 BP 84 EP 89 DI 10.1038/ki.2012.19 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 959XK UT WOS:000305351300011 PM 22398410 ER PT J AU Yu, FG Zhao, XN Li, CW Li, YY Yan, Y Shi, L Gordon, BR Wang, DY AF Yu, Fenggang Zhao, Xuening Li, Chunwei Li, Yingying Yan, Yan Shi, Li Gordon, Bruce R. Wang, De-Yun TI Airway Stem Cells: Review of Potential Impact on Understanding of Upper Airway Diseases SO LARYNGOSCOPE LA English DT Review DE Airway mucosa; nasal epithelial remodelling; epithelial stem; progenitor cells; in vitro cell culture; P63 positive cells ID EPITHELIAL PROGENITOR CELLS; RAT FOLLOWING EXPOSURE; BASAL-CELLS; CLARA CELL; ALVEOLAR EPITHELIUM; LUNG DEVELOPMENT; MOUSE TRACHEA; TYPE-2 CELLS; REPAIR; RENEWAL AB Epithelial remodeling is a part of our natural defense mechanisms, and includes migration, proliferation, and differentiation of epithelial cells, as well as the interactions between epithelial and stromal cells. It is not yet possible to distinguish between cause and effect during epithelium remodeling, and are there no clear roles for the many factors involved in respiratory infectious and inflammatory diseases due to a lack of critical information about epithelial cell responses. Most reported data are from lower airway studies or animal models. Therefore, research based on human nasal epithelial stem/progenitor cells can illuminate the pathophysiology of nasal airway disease from a different, more specific perspective. In this review, we discuss epithelial stem/progenitor cell research throughout the airway, with special attention to phenotypes and characterization of these cells from the nasal airway. Recently, we have isolated and cultured P63-positive human epithelial stem/progenitor cells from turbinate biopsies of healthy volunteers and from inflamed mucosa of patients with chronic rhinosinusitis with and without nasal polyposis. These cells propagate in serum-free, growth factor-supplemented, Dulbecco's modified Eagle's medium/F12 media, on either human fibroblast or 3T3 feeder layers. Self-renewal, proliferation, and differentiation potential at an air-liquid interface are being investigated to understand the molecular pathways underlying nasal inflammation. This in vitro culture system for nasal epithelial regeneration will allow molecular studies of human nasal epithelial cell interactions, differentiation, and repair, as well as responses to both environmental agents and to potential anti-inflammatory treatments. C1 [Yu, Fenggang; Zhao, Xuening; Li, Chunwei; Li, Yingying; Yan, Yan; Wang, De-Yun] Natl Univ Singapore, Dept Otolaryngol, Yong Loo Lin Sch Med, Singapore 119260, Singapore. [Zhao, Xuening; Shi, Li] Shandong Univ, Qilu Hosp, Dept Otolaryngol, Jinan 250012, Shandong, Peoples R China. [Gordon, Bruce R.] Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA. [Gordon, Bruce R.] Cape Cod Hosp, Div Otolaryngol, Hyannis, MA USA. RP Wang, DY (reprint author), Natl Univ Singapore, Dept Otolaryngol, Yong Loo Lin Sch Med, 10 Lower Kent Ridge Rd, Singapore 119260, Singapore. EM shili126@sina.com; entwdy@nus.edu.sg FU National Medical Research Council (NMRC) of Singapore [IRG10may086]; Singapore Immunology Network (SIgN) of Singapore [SIgN 10-028]; National Nature Science Foundation of China [81170897] FX This study was supported by grants from the National Medical Research Council (NMRC, IRG10may086) of Singapore, from the Singapore Immunology Network (SIgN, SIgN 10-028) of Singapore, and from the National Nature Science Foundation of China (grant awarded number 81170897). The authors have no other funding, financial relationships, or conflicts of interest to disclose. NR 54 TC 8 Z9 8 U1 1 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X EI 1531-4995 J9 LARYNGOSCOPE JI Laryngoscope PD JUL PY 2012 VL 122 IS 7 BP 1463 EP 1469 DI 10.1002/lary.23320 PG 7 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 962WE UT WOS:000305577400008 PM 22555982 ER PT J AU Lin, HW Reilly, BK AF Lin, Harrison W. Reilly, Brian K. TI Pseudoaneurysm of the superior thyroid artery following revision tracheostomy SO LARYNGOSCOPE LA English DT Article DE Pseudoaneurysm; post-tracheostomy bleeding; embolization; superior thyroid artery ID FISTULA AB This case report describes the presentation and management of a rare complication of pseudoaneurysm of the superior thyroid artery following tracheostomy. The majority of post-tracheostomy bleeding is managed either with packing or surgical re-exploration. However, angiography can pinpoint an arterial source of bleeding and allow the surgeon to address it via either a traditional open surgical approach or with minimally invasive endovascular embolization. C1 [Reilly, Brian K.] Childrens Natl Med Ctr, Dept Otolaryngol, Washington, DC 20010 USA. [Lin, Harrison W.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Reilly, BK (reprint author), Childrens Natl Med Ctr, Dept Otolaryngol, 111 Michigan Ave NW, Washington, DC 20010 USA. EM breilly@cnmc.org NR 6 TC 4 Z9 4 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD JUL PY 2012 VL 122 IS 7 BP 1641 EP 1643 DI 10.1002/lary.23291 PG 3 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 962WE UT WOS:000305577400039 PM 22532258 ER PT J AU Ellingson, LD Colbert, LH Cook, DB AF Ellingson, Laura D. Colbert, Lisa H. Cook, Dane B. TI Physical Activity Is Related to Pain Sensitivity in Healthy Women SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE ACCELEROMETER; VIGOROUS; PAIN RATINGS; PHYSICAL ACTIVITY RECOMMENDATIONS ID UNITED-STATES; SEDENTARY BEHAVIOR; EXERCISE; ACCELEROMETER; FIBROMYALGIA; NEUROANATOMY; CALIBRATION; RESPONSES; SAMPLE; ADULTS AB ELLINGSON, L. D., L. H. COLBERT, and D. B. COOK. Physical Activity Is Related to Pain Sensitivity in Healthy Women. Med. Sci. Sports Exerc., Vol. 44, No. 7, pp. 1401-1406, 2012. There are many benefits associated with meeting current physical activity recommendations. At present, it is unknown whether a reduced sensitivity to pain is included among these benefits. Purpose: The study's purpose was to assess the relationship between pain sensitivity and physical activity and sedentary behaviors in a sample of healthy women. Methods: Self-reported and accelerometer measures of physical activity and sedentary behavior were collected and compared with pain intensity and unpleasantness ratings to noxious thermal stimuli in a sample of 21 healthy women (age = 30.0 +/- 5.8 yr). On the basis of accelerometer data, participants were classified into two groups: meets recommendations (n = 12) and insufficiently active (n = 9). Independent-samples t-tests were conducted to compare pain ratings and physical activity behaviors between groups, and correlation coefficients (Spearman rho) were calculated between average minutes per day spent in moderate, vigorous, and sedentary behaviors, and average intensity and unpleasantness ratings. Results: Participants meeting physical activity recommendations had significantly lower unpleasantness ratings than their insufficiently active peers. Correlational analyses demonstrated a significant relationship between minutes spent in vigorous physical activity and both pain intensity and pain unpleasantness ratings. Relationships were not significant for moderate activity or sedentary behavior. Conclusions: These results provide preliminary evidence that meeting current physical activity recommendations may be beneficial for pain in women. Moreover, participation in vigorous activity seems to account for the decreased pain sensitivity. In our sample, sedentary behavior did not seem to have a deleterious effect on pain. Results from this study have many potential applications including aiding our understanding of why exercise functions as a treatment for those with chronic pain conditions and providing a rationale for including physical activity assessment in pain research. C1 [Cook, Dane B.] Univ Wisconsin Madison, Sch Educ, Dept Kinesiol, Unit Gymnasium Natatorium 2, Madison, WI 53706 USA. [Cook, Dane B.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Cook, DB (reprint author), Univ Wisconsin Madison, Sch Educ, Dept Kinesiol, Unit Gymnasium Natatorium 2, 2000 Observ Dr, Madison, WI 53706 USA. EM dcook@education.wisc.edu NR 32 TC 27 Z9 27 U1 3 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD JUL PY 2012 VL 44 IS 7 BP 1401 EP 1406 DI 10.1249/MSS.0b013e318248f648 PG 6 WC Sport Sciences SC Sport Sciences GA 961NX UT WOS:000305473200027 PM 22217571 ER PT J AU Foo, JP Hamnvik, OPR Mantzoros, CS AF Foo, Joo-Pin Hamnvik, Ole-Petter R. Mantzoros, Christos S. TI Optimizing bone health in anorexia nervosa and hypothalamic amenorrhea: new trials and tribulations SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Editorial Material ID GROWTH-FACTOR-I; EMERGING CLINICAL-APPLICATIONS; FACTOR-BINDING PROTEIN-3; NORMAL-WEIGHT WOMEN; SEX STEROID-LEVELS; OF-THE-LITERATURE; MINERAL DENSITY; ADOLESCENT GIRLS; HUMAN LEPTIN; YOUNG-WOMEN C1 [Foo, Joo-Pin; Hamnvik, Ole-Petter R.; Mantzoros, Christos S.] Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. [Hamnvik, Ole-Petter R.; Mantzoros, Christos S.] Boston VA Healthcare Syst, Endocrinol Sect, Boston, MA 02130 USA. [Hamnvik, Ole-Petter R.; Mantzoros, Christos S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. RP Foo, JP (reprint author), Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. EM cmantzor@bidmc.harvard.edu RI Hamnvik, Ole-Petter/D-1719-2011 FU NHLBI NIH HHS [T32 HL007609] NR 101 TC 5 Z9 5 U1 0 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 EI 1532-8600 J9 METABOLISM JI Metab.-Clin. Exp. PD JUL PY 2012 VL 61 IS 7 BP 899 EP 905 DI 10.1016/j.metabol.2012.01.003 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 960EV UT WOS:000305371700001 PM 22300837 ER PT J AU Skiadas, CC Duan, SH Correll, M Rubio, R Karaca, N Ginsburg, ES Quackenbush, J Racowsky, C AF Skiadas, Christine C. Duan, Shenghua Correll, Mick Rubio, Renee Karaca, Nilay Ginsburg, Elizabeth S. Quackenbush, John Racowsky, Catherine TI Ovarian reserve status in young women is associated with altered gene expression in membrana granulosa cells SO MOLECULAR HUMAN REPRODUCTION LA English DT Article DE granulosa cells; oocyte quality; diminished ovarian reserve; IVF; microarray analysis ID ANTI-MULLERIAN HORMONE; ACUTE REGULATORY PROTEIN; IN-VITRO FERTILIZATION; LUTEINIZING-HORMONE; PREMATURE LUTEINIZATION; PROGESTERONE PRODUCTION; FOLLICLE DEVELOPMENT; MICROARRAY ANALYSIS; EMBRYO-TRANSFER; GROWTH-FACTORS AB Diminished ovarian reserve (DOR) is a challenging diagnosis of infertility, as there are currently no tests to predict who may become affected with this condition, or at what age. We designed the present study to compare the gene expression profile of membrana granulosa cells from young women affected with DOR with those from egg donors of similar age and to determine if distinct genetic patterns could be identified to provide insight into the etiology of DOR. Young women with DOR were identified based on FSH level in conjunction with poor follicular development during an IVF cycle (n 13). Egg donors with normal ovarian reserve (NOR) comprised the control group (n 13). Granulosa cells were collected following retrieval, RNA was extracted and microarray analysis was conducted to evaluate genetic differences between the groups. Confirmatory studies were undertaken with quantitative RTPCR (qRTPCR). Multiple significant differences in gene expression were observed between the DOR patients and egg donors. Two genes linked with ovarian function, anti-Mullerian hormone (AMH) and luteinizing hormone receptor (LHCGR), were further analyzed with qRTPCR in all patients. The average expression of AMH was significantly higher in egg donors (adjusted P-value 0.01), and the average expression of LHCGR was significantly higher in DOR patients (adjusted P-value 0.005). Expression levels for four additional genes, progesterone receptor membrane component 2 (PGRMC2), prostaglandin E receptor 3 (subtype EP3) (PTGER3), steroidogenic acute regulatory protein (StAR), and StAR-related lipid transfer domain containing 4 (StarD4), were validated in a group consisting of five NOR and five DOR patients. We conclude that gene expression analysis has substantial potential to determine which young women may be affected with DOR. More importantly, our analysis suggests that DOR patients fall into two distinct subgroups based on gene expression profiles, indicating that different mechanisms may be involved during development of this pathology. C1 [Skiadas, Christine C.; Karaca, Nilay; Ginsburg, Elizabeth S.; Racowsky, Catherine] Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. [Quackenbush, John] Harvard Univ, Sch Med, Dept Biostat, Boston, MA 02115 USA. [Duan, Shenghua; Correll, Mick; Rubio, Renee; Quackenbush, John] Dana Farber Canc Ctr, Ctr Canc Computat Biol, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Racowsky, C (reprint author), Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, 75 Francis St,ASB 1 3,Rm 082, Boston, MA 02115 USA. EM cracowsky@partners.org FU Endocrine Fellows' Foundation Grant; Dana-Farber High-Tech Fund; NIH [R01-LM008795] FX This work was supported by The Endocrine Fellows' Foundation Grant; the Dana-Farber High-Tech Fund; and a grant from the NIH (R01-LM008795). NR 51 TC 17 Z9 18 U1 2 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1360-9947 J9 MOL HUM REPROD JI Mol. Hum. Reprod. PD JUL PY 2012 VL 18 IS 7 BP 362 EP 371 DI 10.1093/molehr/gas008 PG 10 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA 963NY UT WOS:000305629500004 PM 22355044 ER PT J AU Kajiya, M Ichimonji, I Min, C Zhu, TB Jin, JO Yu, Q Almazrooa, SA Cha, SH Kawai, T AF Kajiya, Mikihito Ichimonji, Isao Min, Christine Zhu, Tongbo Jin, Jun-O Yu, Qing Almazrooa, Soulafa A. Cha, Seunghee Kawai, Toshihisa TI Muscarinic Type 3 Receptor Induces Cytoprotective Signaling in Salivary Gland Cells through Epidermal Growth Factor Receptor Transactivation SO MOLECULAR PHARMACOLOGY LA English DT Article ID PROTEIN-COUPLED RECEPTORS; NECROSIS-FACTOR-ALPHA; KINASE-C-DELTA; SJOGRENS-SYNDROME; EPITHELIAL-CELLS; INTERFERON-GAMMA; DISTINCT PATHWAYS; ACINAR-CELLS; EGF RECEPTOR; CANCER CELLS AB Muscarinic type 3 receptor (M3R) plays a pivotal role in the induction of glandular fluid secretions. Although M3R is often the target of autoantibodies in Sjogren's syndrome (SjS), chemical agonists for M3R are clinically used to stimulate saliva secretion in patients with SjS. Aside from its activity in promoting glandular fluid secretion, however, it is unclear whether activation of M3R is related to other biological events in SjS. This study aimed to investigate the cytoprotective effect of chemical agonist-mediated M3R activation on apoptosis induced in human salivary gland (HSG) cells. Carbachol (CCh), a muscarinic receptor-specific agonist, abrogated tumor necrosis factor alpha/interferon gamma-induced apoptosis through pathways involving caspase 3/7, but its cytoprotective effect was decreased by a M3R antagonist, a mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (ERK) inhibitor, a phosphatidylinositol 3-kinase/Akt inhibitor, or an epidermal growth factor receptor (EGFR) inhibitor. Ligation of M3R with CCh transactivated EGFR and phosphorylated ERK and Akt, the downstream targets of EGFR. Inhibition of intracellular calcium release or protein kinase C delta, both of which are involved in the cell signaling of M3R-mediated fluid secretion, did not affect CCh-induced ERK or Akt phosphorylation. CCh stimulated Src phosphorylation and binding to EGFR. A Src inhibitor attenuated the CCh/M3R-induced cytoprotective effect and EGFR transactivation cascades. Overall, these results indicated that CCh/M3R induced transactivation of EGFR through Src activation leading to ERK and Akt phosphorylation, which in turn suppressed caspase 3/7-mediated apoptotic signals in HSG cells. This study, for the first time, proposes that CCh-mediated M3R activation can promote not only fluid secretion but also survival of salivary gland cells in the inflammatory context of SjS. C1 [Kajiya, Mikihito; Ichimonji, Isao; Min, Christine; Zhu, Tongbo; Jin, Jun-O; Yu, Qing; Kawai, Toshihisa] Forsyth Inst, Dept Immunol, Cambridge, MA 02142 USA. [Kajiya, Mikihito; Zhu, Tongbo; Almazrooa, Soulafa A.; Kawai, Toshihisa] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Almazrooa, Soulafa A.] King Abdulaziz Univ, Oral Med Div, Fac Dent, Jeddah 21413, Saudi Arabia. [Cha, Seunghee] Univ Florida, Coll Dent, Dept Oral & Maxillofacial Diagnost Sci, Gainesville, FL USA. RP Kawai, T (reprint author), Forsyth Inst, Dept Immunol, 245 1st St, Cambridge, MA 02142 USA. EM tkawai@forsyth.org FU National Institutes of Health National Institute of Dental and Craniofacial Research [DE019644] FX This study was supported by the National Institutes of Health National Institute of Dental and Craniofacial Research [Grant DE019644]. NR 54 TC 10 Z9 10 U1 1 U2 3 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD JUL PY 2012 VL 82 IS 1 BP 115 EP 124 DI 10.1124/mol.111.077354 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 961MZ UT WOS:000305470000013 PM 22511543 ER PT J AU Gavathiotis, E Reyna, DE Bellairs, JA Leshchiner, ES Walensky, LD AF Gavathiotis, Evripidis Reyna, Denis E. Bellairs, Joseph A. Leshchiner, Elizaveta S. Walensky, Loren D. TI Direct and selective small-molecule activation of proapoptotic BAX SO NATURE CHEMICAL BIOLOGY LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; BCL-2 FAMILY; CYTOCHROME-C; CELL-DEATH; BH3 HELIX; MEMBRANE PERMEABILIZATION; MITOCHONDRIAL APOPTOSIS; PHASE-I; INHIBITOR; PROTEINS AB BCL-2 family proteins are key regulators of the apoptotic pathway. Antiapoptotic members sequester the BCL-2 homology 3 (BH3) death domains of proapoptotic members such as BAX to maintain cell survival. The antiapoptotic BH3-binding groove has been successfully targeted to reactivate apoptosis in cancer. We recently identified a geographically distinct BH3-binding groove that mediates direct BAX activation, suggesting a new strategy for inducing apoptosis by flipping BAX's 'on switch'. Here we applied computational screening to identify a BAX activator molecule that directly and selectively activates BAX. We demonstrate by NMR and biochemical analyses that the molecule engages the BAX trigger site and promotes the functional oligomerization of BAX. The molecule does not interact with the BH3-binding pocket of antiapoptotic proteins or proapoptotic BAK and induces cell death in a BAX-dependent fashion. To our knowledge, we report the first gain-of-function molecular modulator of a BCL-2 family protein and demonstrate a new paradigm for pharmacologic induction of apoptosis. C1 [Gavathiotis, Evripidis; Reyna, Denis E.; Bellairs, Joseph A.; Leshchiner, Elizaveta S.; Walensky, Loren D.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Gavathiotis, Evripidis; Reyna, Denis E.; Bellairs, Joseph A.; Leshchiner, Elizaveta S.; Walensky, Loren D.] Dana Farber Canc Inst, Program Canc Chem Biol, Boston, MA 02115 USA. [Gavathiotis, Evripidis; Reyna, Denis E.; Bellairs, Joseph A.; Leshchiner, Elizaveta S.; Walensky, Loren D.] Childrens Hosp Boston, Div Hematol & Oncol, Boston, MA USA. [Gavathiotis, Evripidis; Reyna, Denis E.; Bellairs, Joseph A.; Leshchiner, Elizaveta S.; Walensky, Loren D.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Gavathiotis, Evripidis; Reyna, Denis E.] Albert Einstein Coll Med, Dept Biochem, Bronx, NY 10467 USA. [Gavathiotis, Evripidis; Reyna, Denis E.] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA. [Gavathiotis, Evripidis; Reyna, Denis E.] Albert Einstein Coll Med, Wilf Family Cardiovasc Res Inst, Bronx, NY 10467 USA. [Gavathiotis, Evripidis; Reyna, Denis E.] Albert Einstein Coll Med, Albert Einstein Canc Ctr, Bronx, NY 10467 USA. RP Gavathiotis, E (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. EM evripidis.gavathiotis@einstein.yu.edu; loren_walensky@dfci.harvard.edu RI Leshchiner, Elizaveta/F-3312-2010 FU William Lawrence and Blanche Hughes Foundation; US National Institutes of Health (NIH) [4R00HL095929]; NIH [5R01CA050239]; Stand Up to Cancer Innovative Research Grant FX We thank E. Smith for editorial and graphics assistance, M. Davis for help with establishing the competitive BAX binding assay, G. Bird for BIM SAHB production and characterization and CreaGen Biosciences for BAM7 resynthesis and characterization. This research program was supported by a grant from the William Lawrence and Blanche Hughes Foundation to L. D. W. Additional funding was provided by US National Institutes of Health (NIH) grant 4R00HL095929 to E. G. and NIH grant 5R01CA050239 and a Stand Up to Cancer Innovative Research Grant to L.D.W. NR 45 TC 57 Z9 58 U1 3 U2 22 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1552-4450 J9 NAT CHEM BIOL JI Nat. Chem. Biol. PD JUL PY 2012 VL 8 IS 7 BP 639 EP 645 DI 10.1038/NCHEMBIO.995 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 961NJ UT WOS:000305471400011 PM 22634637 ER PT J AU Zhao, J Wei, JX Mialki, RK Mallampalli, DF Chen, BB Coon, T Zou, CB Mallampalli, RK Zhao, YT AF Zhao, Jing Wei, Jianxin Mialki, Rachel K. Mallampalli, Daniel F. Chen, Bill B. Coon, Tiffany Zou, Chunbin Mallampalli, Rama K. Zhao, Yutong TI F-box protein FBXL19-mediated ubiquitination and degradation of the receptor for IL-33 limits pulmonary inflammation SO NATURE IMMUNOLOGY LA English DT Article ID EPIDERMAL-GROWTH-FACTOR; AIRWAY INFLAMMATION; INDUCED ARTHRITIS; CELLS; INTERLEUKIN-33; EXPRESSION; ACTIVATION; CORTACTIN; GENE; INHIBITION AB The ST2L receptor for interleukin 33 (IL-33) mediates pulmonary inflammation and immune system-related disorders, such as asthma and rheumatoid arthritis. At present, very little is known about the molecular regulation of ST2L expression. Here we found that FBXL19, an 'orphan' member of the Skp1-Cullin-F-box family of E3 ubiquitin ligases, selectively bound to ST2L to mediate its polyubiquitination and elimination in the proteasome. Degradation of ST2L involved phosphorylation of ST2L at Ser442 catalyzed by the kinase GSK3 beta. Overexpression of FBXL19 abrogated the proapoptotic and inflammatory effects of IL-33 and lessened the severity of lung injury in mouse models of pneumonia. Our results suggest that modulation of the IL-33-ST2L axis by ubiquitin ligases might serve as a unique strategy for lessening pulmonary inflammation. C1 [Zhao, Jing; Wei, Jianxin; Mialki, Rachel K.; Mallampalli, Daniel F.; Chen, Bill B.; Coon, Tiffany; Zou, Chunbin; Mallampalli, Rama K.; Zhao, Yutong] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15260 USA. [Zhao, Jing; Wei, Jianxin; Mialki, Rachel K.; Mallampalli, Daniel F.; Chen, Bill B.; Coon, Tiffany; Zou, Chunbin; Mallampalli, Rama K.; Zhao, Yutong] Univ Pittsburgh, Sch Med, Acute Lung Injury Ctr Excellence, Pittsburgh, PA USA. [Mallampalli, Rama K.] Univ Pittsburgh, Sch Med, Dept Cell Biol & Physiol, Pittsburgh, PA USA. [Mallampalli, Rama K.] Vet Affairs Pittsburgh Healthcare Syst, Med Specialty Serv Line, Pittsburgh, PA USA. RP Zhao, YT (reprint author), Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15260 USA. EM zhaoy3@upmc.edu RI Wei, Jianxin/P-5431-2016 FU US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development; US Department of Veterans Affairs; US National Institutes of Health [R01 HL01916, R01 HL096376, R01 HL097376, R01 HL098174]; American Heart Association [12SDG9050005] FX We thank L. Wallace for technical assistance. This study is based on work supported in part by the US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development. Supported by the US Department of Veterans Affairs (Merit Review Award), the US National Institutes of Health (R01 HL01916 to Y.Z. and R01 HL096376, R01 HL097376 and R01 HL098174 to R. K. M.) and the American Heart Association (12SDG9050005 to J.Z.). The contents presented do not represent the views of the Department of Veterans Affairs or the United States Government. NR 44 TC 44 Z9 49 U1 1 U2 15 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD JUL PY 2012 VL 13 IS 7 BP 651 EP + DI 10.1038/ni.2341 PG 9 WC Immunology SC Immunology GA 961QZ UT WOS:000305483800010 PM 22660580 ER PT J AU Chen, HB Ndhlovu, ZM Liu, DF Porter, LC Fang, JW Darko, S Brockman, MA Miura, T Brumme, ZL Schneidewind, A Piechocka-Trocha, A Cesa, KT Sela, J Cung, TD Toth, I Pereyra, F Yu, XG Douek, DC Kaufmann, DE Allen, TM Walker, BD AF Chen, Huabiao Ndhlovu, Zaza M. Liu, Dongfang Porter, Lindsay C. Fang, Justin W. Darko, Sam Brockman, Mark A. Miura, Toshiyuki Brumme, Zabrina L. Schneidewind, Arne Piechocka-Trocha, Alicja Cesa, Kevin T. Sela, Jennifer Cung, Thai D. Toth, Ildiko Pereyra, Florencia Yu, Xu G. Douek, Daniel C. Kaufmann, Daniel E. Allen, Todd M. Walker, Bruce D. TI TCR clonotypes modulate the protective effect of HLA class I molecules in HIV-1 infection SO NATURE IMMUNOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CD8(+) T-CELLS; VIRAL LOAD; ELITE CONTROLLERS; REPLICATION CAPACITY; DISEASE PROGRESSION; LYMPHOCYTE ESCAPE; IMMUNE CONTROL; RESPONSES; EPITOPE AB The human leukocyte antigens HLA-B*27 and HLA-B*57 are associated with protection against progression of disease that results from infection with human immunodeficiency virus type 1 (HIV-1), yet most people with alleles encoding HLA-B*27 and HLA-B*57 are unable to control HIV-1. Here we found that HLA-B*27-restricted CD8(+) T cells in people able to control infection with HIV-1 (controllers) and those who progress to disease after infection with HIV-1 (progressors) differed in their ability to inhibit viral replication through targeting of the immunodominant epitope of group-associated antigen (Gag) of HIV-1. This was associated with distinct T cell antigen receptor (TCR) clonotypes, characterized by superior control of HIV-1 replication in vitro, greater cross-reactivity to epitope variants and enhanced loading and delivery of perforin. We also observed clonotype-specific differences in antiviral efficacy for an immunodominant HLA-B*57-restricted response in controllers and progressors. Thus, the efficacy of such so-called 'protective alleles' is modulated by specific TCR clonotypes selected during natural infection, which provides a functional explanation for divergent HIV-1 outcomes. C1 [Chen, Huabiao; Ndhlovu, Zaza M.; Liu, Dongfang; Porter, Lindsay C.; Fang, Justin W.; Brockman, Mark A.; Miura, Toshiyuki; Brumme, Zabrina L.; Schneidewind, Arne; Piechocka-Trocha, Alicja; Cesa, Kevin T.; Sela, Jennifer; Cung, Thai D.; Toth, Ildiko; Pereyra, Florencia; Yu, Xu G.; Kaufmann, Daniel E.; Allen, Todd M.; Walker, Bruce D.] Massachusetts Gen Hosp, MIT, Ragon Inst, Boston, MA 02114 USA. [Chen, Huabiao; Ndhlovu, Zaza M.; Liu, Dongfang; Porter, Lindsay C.; Fang, Justin W.; Brockman, Mark A.; Miura, Toshiyuki; Brumme, Zabrina L.; Schneidewind, Arne; Piechocka-Trocha, Alicja; Cesa, Kevin T.; Sela, Jennifer; Cung, Thai D.; Toth, Ildiko; Pereyra, Florencia; Yu, Xu G.; Kaufmann, Daniel E.; Allen, Todd M.; Walker, Bruce D.] Harvard Univ, Boston, MA 02115 USA. [Chen, Huabiao; Ndhlovu, Zaza M.; Piechocka-Trocha, Alicja; Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Darko, Sam; Douek, Daniel C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Brockman, Mark A.; Brumme, Zabrina L.] Simon Fraser Univ, Fac Hlth Sci, Burnaby, BC V5A 1S6, Canada. [Miura, Toshiyuki] Univ Tokyo, Inst Med Sci, Tokyo, Japan. [Schneidewind, Arne] Univ Hosp Regensburg, Dept Internal Med, Regensburg, Germany. RP Walker, BD (reprint author), Massachusetts Gen Hosp, MIT, Ragon Inst, Boston, MA 02114 USA. EM bwalker@partners.org RI Allen, Todd/F-5473-2011; OI Brockman, Mark/0000-0001-6432-1426 FU Harvard University Center for AIDS Research [5 P30 AI060354-04]; Bill and Melinda Gates Foundation; Doris Duke Charitable Foundation; US National Institutes of Health [AI030914, AI074415]; Howard Hughes Medical Institute; Mark and Lisa Schwartz Foundation; Office of AIDS Research of the US National Institutes of Health; Canadian Institutes for Health Research; Canada Research Chair in Viral Pathogenesis and Immunity; US National Institutes of Health FX We thank J. Wong (Massachusetts General Hospital) for monoclonal antibody 12F6 to CD3 and monoclonal antibody CD3: 8 bispecific for CD3 and CD8; and all study participants for their contributions. Supported by the Harvard University Center for AIDS Research (5 P30 AI060354-04), the Bill and Melinda Gates Foundation (B. D. W. and D. C. D.), the Doris Duke Charitable Foundation (B. D. W.), the US National Institutes of Health (AI030914 to B. D. W. and AI074415 to T. M. A.), the Howard Hughes Medical Institute (B. D. W.), the Mark and Lisa Schwartz Foundation (B. D. W.), the Intramural Research Program and the Office of AIDS Research of the US National Institutes of Health (D. C. D. and S. D.), the Canadian Institutes for Health Research (New Investigator Award to Z.L.B.) and the Canada Research Chair in Viral Pathogenesis and Immunity (M.A.B.). NR 50 TC 108 Z9 109 U1 0 U2 18 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 JUL PY 2012 VL 13 IS 7 BP 691 EP + DI 10.1038/ni.2342 PG 12 WC Immunology SC Immunology GA 961QZ UT WOS:000305483800015 PM 22683743 ER PT J AU Lee, A Wilding, G Kuo, B AF Lee, A. Wilding, G. Kuo, B. TI Variable abnormal physiological motility in the proximal upper gastrointestinal tract in gastroparesis SO NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Article DE gastric emptying scintigraphy; gastroparesis; wireless motility capsule ID POSTPRANDIAL ANTROPYLORODUODENAL MOTILITY; GASTRIC-EMPTYING SCINTIGRAPHY; ACID BREATH TEST; DIABETES-MELLITUS; HEIDELBERG CAPSULE; HUMANS; SOLIDS; PROFILES; HEALTHY; LIQUIDS AB Background Traditional testing for gastroparesis with gastric emptying scintigraphy (GES) likely misses a subset of patients because of the heterogeneous nature of the disease. The primary aim of this study is to determine the prevalence of simultaneously measured transit and pressure abnormalities in patients with gastroparesis. The secondary aim is to assess diagnostic gain realized by measuring antroduodenal pressure and gastric transit with wireless motility capsule (WMC) compared to gastric transit measured by GES. Identification of abnormalities beyond gastric transit delay in gastroparesis may yield novel targets for pharmacological therapies. Methods Forty-three subjects with symptoms of gastroparesis and previous abnormal GES within 2 years were enrolled in the study. Subjects underwent simultaneous GES and WMC to assess gastric transit. Gastric and small bowel pressure profiles were measured by WMC to determine the contribution of pressure to diagnostic gain realized with WMC. Key Results Fifty-one percent of subjects had abnormal GES while 70% of subjects had either abnormal gastric emptying time (GET) or antroduodenal pressure. Gastric emptying time was abnormal in 60% of subjects while gastric or small bowel pressure was abnormal in 47% of subjects. The overall diagnostic gain of WMC compared to GES was 19% (P = 0.04). Seven percent of subjects had abnormal small bowel pressure profiles when both GES and GET were normal. Conclusions & Inferences (i) Gastroparesis is a heterogeneous disorder and testing only solid food emptying by scintigraphy may miss a significant amount of pathology. (ii) Measuring complementary aspects of gastric and small bowel function simultaneously results in greater detection of physiologic abnormalities that may underlie patient symptoms. C1 [Kuo, B.] Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA. [Lee, A.] Tufts Med Ctr, Dept Med, Boston, MA USA. [Wilding, G.] SUNY Buffalo, Dept Biostat, Buffalo, NY 14260 USA. RP Kuo, B (reprint author), Massachusetts Gen Hosp, Dept Gastroenterol, 55 Fruit St,GRJ 724, Boston, MA 02114 USA. EM bkuo@partners.org FU International Foundation of Functional Gastrointestinal Disorders; NIH NIDDK [K23K069614] FX This work was supported by International Foundation of Functional Gastrointestinal Disorders and NIH NIDDK K23K069614. NR 43 TC 4 Z9 5 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1350-1925 J9 NEUROGASTROENT MOTIL JI Neurogastroenterol. Motil. PD JUL PY 2012 VL 24 IS 7 DI 10.1111/j.1365-2982.2012.01905.x PG 7 WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences SC Gastroenterology & Hepatology; Neurosciences & Neurology GA 962AG UT WOS:000305510800016 PM 22417117 ER PT J AU Kennedy, DN Haselgrove, C Hodge, SM Rane, PS Makris, N Frazier, JA AF Kennedy, David N. Haselgrove, Christian Hodge, Steven M. Rane, Pallavi S. Makris, Nikos Frazier, Jean A. TI CANDIShare: A Resource for Pediatric Neuroimaging Data SO NEUROINFORMATICS LA English DT Editorial Material DE MRI; Segmentation; Neuroanatomy; Childhood psychiatric disorders ID HUMAN BRAIN; SEGMENTATION C1 [Kennedy, David N.; Haselgrove, Christian; Hodge, Steven M.; Rane, Pallavi S.; Frazier, Jean A.] Univ Massachusetts, Sch Med, Div Neuroinformat, Worcester, MA 01605 USA. [Kennedy, David N.; Haselgrove, Christian; Hodge, Steven M.; Rane, Pallavi S.; Frazier, Jean A.] Univ Massachusetts, Sch Med, Child & Adolescent NeuroDev Initiat CANDI, Dept Psychiat, Worcester, MA 01605 USA. [Makris, Nikos] Massachusetts Gen Hosp, Dept Neurol, Ctr Morphometr Anal, Boston, MA 02114 USA. [Makris, Nikos] Massachusetts Gen Hosp, Dept Psychiat, Ctr Morphometr Anal, Boston, MA 02114 USA. RP Kennedy, DN (reprint author), Univ Massachusetts, Sch Med, Div Neuroinformat, 356 Plantat St,Suite 100, Worcester, MA 01605 USA. EM David.Kennedy@umassmed.edu RI Kennedy, David/H-3627-2012; OI Rane, Pallavi/0000-0002-8720-6807 FU NICHD NIH HHS [P30 HD004147]; NIMH NIH HHS [R01 MH083320] NR 8 TC 5 Z9 5 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1539-2791 J9 NEUROINFORMATICS JI Neuroinformatics PD JUL PY 2012 VL 10 IS 3 BP 319 EP 322 DI 10.1007/s12021-011-9133-y PG 4 WC Computer Science, Interdisciplinary Applications; Neurosciences SC Computer Science; Neurosciences & Neurology GA 960TY UT WOS:000305415000007 PM 22006352 ER PT J AU Sheth, SA Mian, MK Neal, J Tritos, NA Nachtigall, L Klibanski, A Biller, BMK Swearingen, B AF Sheth, Sameer A. Mian, Matthew K. Neal, Jonathan Tritos, Nicholas A. Nachtigall, Lisa Klibanski, Anne Biller, Beverly M. K. Swearingen, Brooke TI Transsphenoidal Surgery for Cushing Disease After Nondiagnostic Inferior Petrosal Sinus Sampling SO NEUROSURGERY LA English DT Article DE ACTH; Cushing disease; Inferior petrosal sinus; Pituitary gland; Transsphenoidal surgery ID CORTICOTROPIN-RELEASING HORMONE; DIFFERENTIAL-DIAGNOSIS; ITALIAN MULTICENTER; MANAGEMENT; MICROSURGERY; MORTALITY; OUTCOMES; TUMOR; ACTH AB BACKGROUND: Inferior petrosal sinus sampling (IPSS) is a useful technique for confirming a pituitary source of adrenocorticotropic hormone (ACTH) overproduction in Cushing disease. Uncertainty remains regarding the appropriate course of therapy when an ectopic tumor is predicted by IPSS but none can be found and in circumstances when the procedure cannot be successfully completed owing to technical or anatomic limitations. OBJECTIVE: To determine an appropriate course of action after nondiagnostic IPSS. METHODS: We reviewed 288 IPSS procedures in 283 patients between 1986 and 2010 at our center. An IPS: peripheral ACTH ratio >= 2 at baseline or >= 3 after corticotrophin-releasing hormone was considered predictive of a pituitary source of ACTH. A procedure was considered nondiagnostic if the procedure was successfully performed and the results predicted an ectopic source but none could be found despite extensive imaging or if the IPS could not be bilaterally cannulated because of technical difficulties or anatomic variants. RESULTS: The sensitivity, specificity, positive predictive value, and negative predictive value of IPSS for detecting a pituitary source in Cushing disease were 94%, 50%, 98%, and 29%, respectively. We identified 3 categories of nondiagnostic IPSS comprising 44 of the total procedures. These patients underwent exploratory transsphenoidal surgery, and in 42 of these patients (95%), a pituitary source was surgically proven, with a remission rate of 83%. CONCLUSION: Transsphenoidal surgery should be considered in cases of ACTH-dependent Cushing disease and noncentralized or technically unsuccessful IPSS without evidence of ectopic tumor. C1 [Sheth, Sameer A.; Mian, Matthew K.; Neal, Jonathan; Swearingen, Brooke] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Tritos, Nicholas A.; Nachtigall, Lisa; Klibanski, Anne; Biller, Beverly M. K.] Massachusetts Gen Hosp, Dept Med, Neuroendocrine Unit, Boston, MA 02114 USA. [Sheth, Sameer A.; Mian, Matthew K.; Neal, Jonathan; Tritos, Nicholas A.; Nachtigall, Lisa; Klibanski, Anne; Biller, Beverly M. K.; Swearingen, Brooke] Harvard Univ, Sch Med, Boston, MA USA. RP Sheth, SA (reprint author), 55 Fruit St,White 502, Boston, MA 02114 USA. EM sheth@post.harvard.edu FU Pfizer FX Dr Tritos has received research support from Pfizer for work unrelated to any of the results presented here. The other authors have no personal financial or institutional interest in any of the drugs, materials, or devices described in this article. NR 32 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD JUL PY 2012 VL 71 IS 1 BP 14 EP 22 DI 10.1227/NEU.0b013e31824f8e2e PG 9 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 961RX UT WOS:000305487000005 PM 22353796 ER PT J AU Niesten, MEF McKenna, MJ Grolman, W Lee, DJ AF Niesten, Marlien E. F. McKenna, Michael J. Grolman, Wilko Lee, Daniel J. TI Clinical Factors Associated With Prolonged Recovery After Superior Canal Dehiscence Surgery SO OTOLOGY & NEUROTOLOGY LA English DT Article DE Superior canal dehiscence surgery; Craniotomy; Transmastoid; Recovery ID PRESSURE-INDUCED VERTIGO; CONDUCTIVE HEARING-LOSS; DELAYED FACIAL PALSY; POSTOPERATIVE PERIOD; TRIGEMINAL NEURALGIA; BONE DEHISCENCE; MIGRAINE; MECHANISMS; MANIFESTATIONS; MANAGEMENT AB Objective: To identify clinical factors associated with prolonged recovery after superior canal dehiscence surgery. Study Design: Retrospective review. Setting: Tertiary care academic medical center. Patients: Thirty-three patients that underwent surgery for SCDS were identified from a database of 140 patients diagnosed with SCD (2000-2010) at the Massachusetts Eye and Ear Infirmary (U.S.A.). The diagnosis of SCDS was based on clinical signs and symptoms, audiometric and vestibular testing and high-resolution temporal bone computed tomography. Intervention: For the primary repair, the superior canal was plugged in 31 patients through a middle fossa craniotomy approach and in 1 patient through a transmastoid approach. In 1 patient, the SCD was resurfaced through a middle fossa craniotomy approach. Main Outcome Measures: Postoperative clinical signs and symptoms and factors that may influence duration of disequilibrium after surgery. Results: Thirty-three patients (15-71 yr; mean, 43 yr) underwent surgery for SCDS on 35 ears (2 bilateral). Mean follow-up was 28.7 months (range, 3 mo to 10 yr); 33 of 33 (100%) patients experienced initial improvement of the chief complaint. Three patients required revision surgery, improving symptoms in 2 patients. Six patients had dizziness lasting more than 4 months postoperatively, and all had bilateral SCD, migraines, and a dehiscence of 3 mm or greater. Conclusion: Surgical plugging of SCD is an effective management option to provide long-term improvement of the chief complaint in SCDS patients. Patients with bilateral SCD, a history of migraines, and larger defects may be at risk of prolonged recovery and should be appropriately counseled. C1 [Niesten, Marlien E. F.; McKenna, Michael J.; Lee, Daniel J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Niesten, Marlien E. F.; Grolman, Wilko] Univ Med Ctr, Dept Otorhinolaryngol Head & Neck Surg, Utrecht, Netherlands. [Niesten, Marlien E. F.; Grolman, Wilko] Rudolf Magnus Inst Neurosci, NL-3508 TA Utrecht, Netherlands. [Niesten, Marlien E. F.; McKenna, Michael J.; Lee, Daniel J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Lee, DJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM daniel_lee@meei.harvard.edu OI Grolman, Wilko/0000-0002-3524-3526 NR 37 TC 14 Z9 14 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD JUL PY 2012 VL 33 IS 5 BP 824 EP 831 DI 10.1097/MAO.0b013e3182544c9e PG 8 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 961SI UT WOS:000305488500029 PM 22664897 ER PT J AU Jensen, KB Kosek, E Wicksell, R Kemani, M Olsson, G Merle, JV Kadetoff, D Ingvar, M AF Jensen, Karin B. Kosek, Eva Wicksell, Rikard Kemani, Mike Olsson, Gunnar Merle, Julia V. Kadetoff, Diana Ingvar, Martin TI Cognitive Behavioral Therapy increases pain-evoked activation of the prefrontal cortex in patients with fibromyalgeia SO PAIN LA English DT Article DE Fibromyalgia; Cognitive Behavioral Therapy (CBT); Acceptance and Commitment Therapy (ACT); fMRI ID CEREBRAL BLOOD-FLOW; RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; ACCEPTANCE STRATEGIES; ANALGESIA; METAANALYSIS; DEPRESSION; EXPOSURE; ANXIETY AB Interventions based on Cognitive Behavioral Therapy (CBT) are widely used to treat chronic pain, but the brain mechanisms responsible for these treatment effects are poorly understood. The aim of this study was to validate the relevance of the cortical control theory in response to an exposure-based form of CBT, Acceptance and Commitment Therapy, in patients with chronic pain. Forty-three female patients diagnosed with fibromyalgia syndrome were enrolled in a randomized, 12-week, waiting-list controlled clinical trial (CBT n = 25; controls n = 18). CBT was administered in groups of six patients during 12 weekly sessions. Functional magnetic resonance imaging (fMRI) during pressure-evoked pain was assessed before and after treatment or the 12-week period. Self-report questionnaires of depression and anxiety were administered pre- and posttreatment as well as 3 months following end of treatment. Patients treated with CBT reported larger improvement of fibromyalgia on the Patient Global Impression of Change measure, and improved depression and anxiety symptoms, compared to the waiting-list controls. However, there were no effects on clinical pain or pain sensitivity measures. An analysis of fMRI scans revealed that CBT led to increased activations in the ventrolateral prefrontal/lateral orbitofrontal cortex; regions associated with executive cognitive control. We suggest that CBT changes the brain's processing of pain through an altered cerebral loop between pain signals, emotions, and cognitions; leading to increased access to executive regions for reappraisal of pain. Our data thereby support our hypothesis about the activation of a cortical control mechanism in response to CBT treatment in chronic pain. (C) 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 [Jensen, Karin B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. [Jensen, Karin B.] Athinoula A Martinos Ctr Biomed Imaging, Boston, MA USA. [Kosek, Eva; Wicksell, Rikard; Kemani, Mike; Kadetoff, Diana; Ingvar, Martin] Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden. [Kosek, Eva; Kadetoff, Diana; Ingvar, Martin] Karolinska Inst, Osher Ctr Integrat Med, Stockholm, Sweden. [Wicksell, Rikard; Kemani, Mike; Olsson, Gunnar] Karolinska Univ Hosp, Behav Med Pain Treatment Serv, Stockholm, Sweden. [Olsson, Gunnar] Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden. [Merle, Julia V.] Charite, Dept Child & Adolescent Psychiat, D-13353 Berlin, Germany. RP Jensen, KB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Psychiat Neuroimaging Bldg,120 2nd Ave, Charlestown, MA 02129 USA. EM karinj@nmr.mgh.harvard.edu RI Jensen, Karin/G-6360-2012; OI Ingvar, Martin/0000-0002-9041-5714; Jensen, Karin/0000-0003-2521-3160 FU Swedish Society for Medical Research (SSMF); Swedish Council for Working Life and Social Research; Swedish research council [K2009-53X-21070-01-3]; Stockholm County Council; Swedish Rheumatism Association FX We are grateful to the funding organizations that made this study possible: KJ received support from the Swedish Society for Medical Research (SSMF) and the Swedish Council for Working Life and Social Research. EK received support from the Swedish research council, project # K2009-53X-21070-01-3 and Stockholm County Council. Also, EK and GO were supported by the Swedish Rheumatism Association. We also wish to thank Jonathan Berrebi and Fredrik Lindstedt for help with MR scanning. NR 60 TC 58 Z9 58 U1 4 U2 25 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD JUL PY 2012 VL 153 IS 7 BP 1495 EP 1503 DI 10.1016/j.pain.2012.04.010 PG 9 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 960WN UT WOS:000305423700024 PM 22617632 ER PT J AU Mackey, K Parchman, ML Leykum, LK Lanham, HJ Noel, PH Zeber, JE AF Mackey, Katherine Parchman, Michael L. Leykum, Luci K. Lanham, Holly J. Noel, Polly H. Zeber, John E. TI Impact of the Chronic Care Model on medication adherence when patients perceive cost as a barrier SO PRIMARY CARE DIABETES LA English DT Article DE Diabetes; Medication adherence; Chronic care delivery; Out-of-pocket cost ID CHRONIC ILLNESS CARE; CONCEPTUALLY BASED APPROACH; SELF-MANAGEMENT; BIPOLAR DISORDER; RANDOMIZED-TRIAL; NONADHERENCE; PRESCRIPTIONS; VALIDATION; PRESSURES; OUTCOMES AB Aims: Cost burdens represent a significant barrier to medication adherence among chronically ill patients, yet financial pressures may be mitigated by clinical or organizational factors, such as treatment aligned with the Chronic Care Model (CCM). This study examines how perceptions of chronic illness care attenuate the relationship between adherence and cost burden. Methods: Surveys were administered to patients at 40 small community-based primary care practices. Medication adherence was assessed using the 4-item Morisky scale, while five cost-related items documented recent pharmacy restrictions. CCM experiences were assessed via the 20-item Patient Assessment of Chronic Illness Care (PACIC). Nested random effects models determined if chronic care perceptions modified the association between medication adherence and cost-related burden. Results: Of 1823 respondents reporting diabetes and other chronic diseases, one-quarter endorsed intrapersonal adherence barriers, while 23% restricted medication due of cost. Controlling for age and health status, the relationship between medication cost and CCM with adherence was significant; including PACIC scores attenuated cost-related problems patients with adequate or problematic adherence behavior. Conclusions: Patients experiencing treatment more consistent with the CCM reported better adherence and lower cost-related burden. Fostering highly activated patients and shared clinical decision making may help alleviate medication cost pressures and improve adherence. Published by Elsevier Ltd on behalf of Primary Care Diabetes Europe. C1 [Zeber, John E.] Scott & White Healthcare, Ctr Appl Hlth Res, Temple, TX 76502 USA. [Mackey, Katherine; Parchman, Michael L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Family & Community Med, San Antonio, TX 78229 USA. [Parchman, Michael L.; Leykum, Luci K.; Lanham, Holly J.; Noel, Polly H.] S Texas Vet Hlth Care Syst VERDICT HSR&D, Dept Vet Affairs, San Antonio, TX USA. [Leykum, Luci K.; Lanham, Holly J.; Noel, Polly H.] Univ Texas Hlth Sci Ctr San Antonio, Dept Internal Med, San Antonio, TX 78229 USA. [Zeber, John E.] Cent Texas Vet Hlth Care Syst, Temple, TX USA. RP Zeber, JE (reprint author), Scott & White Healthcare, Ctr Appl Hlth Res, 2102 Birdcreek DriveTemple, Temple, TX 76502 USA. EM zeber@uthscsa.edu OI Parchman, Michael/0000-0001-7129-2889 FU National Institute of Diabetes and Digestive and Kidney Diseases [NIH/NIDDK R18DK075692] FX The authors would like to thank Nedal Arar, Raymond Palmer, and Laurel Copeland for additional suggestions and contributions to this manuscript. This project was supported by funding provided through award number NIH/NIDDK R18DK075692 from the National Institute of Diabetes and Digestive and Kidney Diseases. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Diabetes and Digestive and Kidney Diseases or the National Institutes of Health. NR 30 TC 9 Z9 11 U1 0 U2 9 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1751-9918 EI 1878-0210 J9 PRIM CARE DIABETES JI Prim. Care Diabetes PD JUL PY 2012 VL 6 IS 2 BP 137 EP 142 DI 10.1016/j.pcd.2011.12.004 PG 6 WC Endocrinology & Metabolism; Primary Health Care SC Endocrinology & Metabolism; General & Internal Medicine GA 960HJ UT WOS:000305378300007 PM 22264426 ER PT J AU Sadaka, A Durand, ML Gilmore, MS AF Sadaka, Ama Durand, Marlene L. Gilmore, Michael S. TI Bacterial endophthalmitis in the age of outpatient intravitreal therapies and cataract surgeries: Host-microbe interactions in intraocular infection SO PROGRESS IN RETINAL AND EYE RESEARCH LA English DT Article DE Endophthalmitis; Staphylococcus aureus; Coagulase-negative staphylococci; Streptococcus pneumoniae; Enterococcus faecalis; Bacillus ID RESISTANT STAPHYLOCOCCUS-AUREUS; COAGULASE-NEGATIVE STAPHYLOCOCCI; BACILLUS-CEREUS ENDOPHTHALMITIS; VIRULENCE GENE-EXPRESSION; CASSETTE CHROMOSOME MEC; TUMOR-NECROSIS-FACTOR; ENTEROCOCCUS-FAECALIS ENDOPHTHALMITIS; BIOSYNTHESIS-ACTIVATING PHEROMONE; MELANOCYTE-STIMULATING HORMONE; ACUTE-ONSET ENDOPHTHALMITIS AB Bacterial endophthalmitis is a sight threatening infection of the interior structures of the eye. Incidence in the US has increased in recent years, which appears to be related to procedures being performed on an aging population. The advent of outpatient intravitreal therapy for management of age-related macular degeneration raises yet additional risks. Compounding the problem is the continuing progression of antibiotic resistance. Visual prognosis for endophthalmitis depends on the virulence of the causative organism, the severity of intraocular inflammation, and the timeliness of effective therapy. We review the current understanding of the pathogenesis of bacterial endophthalmitis, highlighting opportunities for the development of improved therapeutics and preventive strategies. (c) 2012 Elsevier Ltd. All rights reserved. C1 [Sadaka, Ama; Gilmore, Michael S.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Sadaka, Ama; Gilmore, Michael S.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. [Durand, Marlene L.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. [Gilmore, Michael S.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP Gilmore, MS (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM michael_gilmore@meei.harvard.edu FU NEI NIH HHS [R01 EY008289, R01 EY008289-22]; NIAID NIH HHS [P01 AI083214-05, P01 AI083214] NR 253 TC 18 Z9 21 U1 0 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1350-9462 J9 PROG RETIN EYE RES JI Prog. Retin. Eye Res. PD JUL PY 2012 VL 31 IS 4 BP 316 EP 331 DI 10.1016/j.preteyeres.2012.03.004 PG 16 WC Ophthalmology SC Ophthalmology GA 960IF UT WOS:000305380500003 PM 22521570 ER PT J AU Shih, YYI Muir, ER Li, G De La Garza, BH Duong, TQ AF Shih, Yen-Yu I. Muir, Eric R. Li, Guang De La Garza, Bryan H. Duong, Timothy Q. TI High-Resolution 3D MR Microangiography of the Rat Ocular Circulation SO RADIOLOGY LA English DT Article ID RETINAL BLOOD-FLOW; SCANNING LASER OPHTHALMOSCOPY; FUNCTIONAL MRI; CARBON-DIOXIDE; OXYGEN; HYPEROXIA AB Purpose: To develop high-spatial-resolution magnetic resonance (MR) microangiography techniques to image the rat ocular circulation. Materials and Methods: Animal experiments were performed with institutional Animal Care Committee approval. MR microangiography (resolution, 84 x 84 x 84 mu m or 42 x 42 x 84 mu m) of the rat eye (eight rats) was performed by using a custom-made small circular surface coil with an 11.7-T MR unit before and after monocrystalline iron oxide nanoparticle (MION) injection. MR microangiography measurements were made during air, oxygen, and carbogen inhalation. From three-dimensional MR microangiography, the retina was virtually flattened to enable en face views of various retinal depths, including the retinal and choroidal vascular layers. Signal intensity changes within the retinal or choroidal arteries and veins associated with gas challenges were analyzed. Statistical analysis was performed by using paired t tests, with P < .05 considered to indicate a significant difference. Bonferroni correction was used to adjust for multiple comparisons. Results: The central retinal artery, long posterior ciliary arteries, and choroidal vasculature could be distinguished on MR microangiograms of the eye. With MR microangiography, retinal arteries and veins could be distinguished on the basis of blood oxygen level-dependent contrast. Carbogen inhalation-enhanced MR microangiography signal intensity in both the retina (P = .001) and choroid (P = .027) compared with oxygen inhalation. Carbogen inhalation showed significantly higher signal intensity changes in the retinal arteries (P = .001, compared with oxygen inhalation), but not in the veins (P = .549). With MION administration, MR microangiography depicted retinal arterial vasoconstriction when the animals were breathing oxygen (P = .02, compared with animals breathing air). Conclusion: MR microangiography of the eye allows depth-resolved imaging of small angiographic details of the ocular circulation. This approach may prove useful in studying microvascular pathologic findings and neurovascular dysfunction in the eye and retina. (C) RSNA, 2012 C1 [Shih, Yen-Yu I.] Univ N Carolina, Dept Neurol, Biomed Res Imaging Ctr, Chapel Hill, NC 27599 USA. [Shih, Yen-Yu I.; Muir, Eric R.; Li, Guang; De La Garza, Bryan H.; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Ophthalmol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Shih, YYI (reprint author), Univ N Carolina, Dept Neurol, Biomed Res Imaging Ctr, 130 Mason Farm Rd,Bioinformat Bldg,CB 7513, Chapel Hill, NC 27599 USA. EM shihy@unc.edu RI Duong, Timothy/B-8525-2008; Li, Guang/C-9539-2011; Muir, Eric/H-8830-2013; OI Li, Guang/0000-0002-7648-0464; Shih, Yen-Yu Ian/0000-0001-6529-911X FU National Institutes of Health [5T32HL007446-29]; American Heart Association [10P0ST4290091]; Clinical Translational Science Award [UL1RR025767]; San Antonio Area Foundation; MERIT Award from the Department of Veterans Affairs and San Antonio Life Science Institute; National Eye Institute [R01 EY014211, EY018855]; National Institute of Neurological Disorders and Stroke [R01-NS45879] FX Y.Y.I.S. No potential conflicts of interest to disclose. E. R. M. Financial activities related to the present article: salary during some of the work has been partially paid by a stipend from the National Institutes of Health training grant 5T32HL007446-29. Financial activities not related to the present article: none to disclose. Other relationships: none to disclose. G. L. No potential conflicts of interest to disclose. B. H. D. L. G. No potential conflicts of interest to disclose. T. Q. D. No potential conflicts of interest to disclose.; From the Research Imaging Institute (Y.Y.I.S., E. R. M., G. L., B. H. D. L. G., T. Q. D.) and Departments of Ophthalmology, Radiology, and Physiology (T. Q. D.), University of Texas Health Science Center at San Antonio, San Antonio, Tex; and South Texas Veterans Health Care System, San Antonio, Tex (T. Q. D.). Received September 30, 2011; revision requested November 9; final revision received December 5; accepted December 29; final version accepted January 13, 2012. Supported in part by the American Heart Association (10P0ST4290091) and the Clinical Translational Science Award (parent grant UL1RR025767). Y.Y.I.S. supported in part by the San Antonio Area Foundation. E. R. M. supported in part by National Institutes of Health training grant T32HL007446-29. T. Q. D. supported in part by the MERIT Award from the Department of Veterans Affairs and San Antonio Life Science Institute.; This research was supported by the National Eye Institute (grants R01 EY014211, EY018855), the National Institute of Neurological Disorders and Stroke (grant R01-NS45879), and the National Institutes of Health (grant T32HL007446-29). NR 21 TC 14 Z9 14 U1 0 U2 4 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUL PY 2012 VL 264 IS 1 BP 234 EP 241 DI 10.1148/radiol.12112033 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 963NA UT WOS:000305626500028 PM 22523323 ER PT J AU Jin, G deMoya, MA Duggan, M Knightly, T Mejaddam, AY Hwabejire, J Lu, J Smith, WM Kasotakis, G Velmahos, GC Socrate, S Alam, HB AF Jin, Guang deMoya, Marc A. Duggan, Michael Knightly, Thomas Mejaddam, Ali Y. Hwabejire, John Lu, Jennifer Smith, William Michael Kasotakis, Georgios Velmahos, George C. Socrate, Simona Alam, Hasan B. TI TRAUMATIC BRAIN INJURY AND HEMORRHAGIC SHOCK: EVALUATION OF DIFFERENT RESUSCITATION STRATEGIES IN A LARGE ANIMAL MODEL OF COMBINED INSULTS SO SHOCK LA English DT Article DE Traumatic brain injury; hemorrhage; edema; swine; shock ID FOCAL CEREBRAL-ISCHEMIA; FRESH-FROZEN PLASMA; SEVERE HEAD-INJURY; INTRACRANIAL-PRESSURE; FLUID RESUSCITATION; POLYTRAUMA MODEL; HEMODILUTION; COAGULATION; HYPOTENSION; IMPACT AB Traumatic brain injury (TBI) and hemorrhagic shock (HS) are the leading causes of trauma-related mortality and morbidity. Combination of TBI and HS (TBI + HS) is highly lethal, and the optimal resuscitation strategy for this combined insult remains unclear. A critical limitation is the lack of suitable large animal models to test different treatment strategies. We have developed a clinically relevant large animal model of TBI + HS, which was used to evaluate the impact of different treatments on brain lesion size and associated edema. Yorkshire swine (42-50 kg) were instrumented to measure hemodynamic parameters and intracranial pressure. A computer-controlled cortical impact device was used to create a TBI through a 20-mm craniotomy: 15-mm cylindrical tip impactor at 4 m/s velocity, 100-ms dwell time, and 12-mm penetration depth. Volume-controlled hemorrhage was started (40% blood volume) concurrent with the TBI. After 2 h of shock, animals were randomized to one of three resuscitation groups (n = 5/group): (a) normal saline (NS); (b) 6% hetastarch, Hextend (Hex); and (c) fresh frozen plasma (FFP). Volumes of Hex and FFP matched the shed blood, whereas NS was three times the volume. After 6 h of postresuscitation monitoring, brains were sectioned into 5-mm slices and stained with TIC (2,3,5-triphenyltetrazolium chloride) to quantify the lesion size and brain swelling. Combination of 40% blood loss with cortical impact and a period of shock (2 h) resulted in a highly reproducible brain injury. Total fluid requirements were lower in the Hex and FFP groups. Lesion size and brain swelling in the FFP group (2,160 +/- 202.6 mm(3) and 22% +/- 1.0%, respectively) were significantly smaller than those in the NS group (3,285 +/- 130.8 mm(3) and 37% +/- 1.6%, respectively) (P < 0.05). Hex treatment decreased the swelling (29% +/- 1.6%) without reducing the lesion size. Early administration of FFP reduces the size of brain lesion and associated swelling in a large animal model of TBI + HS. In contrast, artificial colloid (Hex) decreases swelling without reducing the actual size of the brain lesion. C1 [Jin, Guang; deMoya, Marc A.; Duggan, Michael; Knightly, Thomas; Mejaddam, Ali Y.; Hwabejire, John; Lu, Jennifer; Smith, William Michael; Kasotakis, Georgios; Velmahos, George C.; Alam, Hasan B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Surg, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. [Socrate, Simona] MIT, Inst Soldier Nanotechnol, Cambridge, MA 02139 USA. RP Alam, HB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Surg, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM hbalam@partners.org OI Kasotakis, George/0000-0002-7630-0742 FU US Army Medical Research Material Command [GRANTT00521959]; U.S. Army Research Office [W911NF-07-D-0004] FX This study was funded by a pant from the US Army Medical Research Material Command GRANTT00521959 (to H.B.A.) and by the U.S. Army Research Office under contract number W911NF-07-D-0004 (to SS). NR 35 TC 39 Z9 40 U1 2 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1073-2322 J9 SHOCK JI Shock PD JUL PY 2012 VL 38 IS 1 BP 49 EP 56 DI 10.1097/SHK.0b013e3182574778 PG 8 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA 961WV UT WOS:000305501100009 PM 22575994 ER PT J AU Jiang, XL Xing, HY Kim, TM Jung, YC Huang, W Yang, HW Song, SY Park, PJ Carroll, RS Johnson, MD AF Jiang, Xiuli Xing, Hongyan Kim, Tae-Min Jung, Yuchae Huang, Wei Yang, Hong Wei Song, Shengye Park, Peter J. Carroll, Rona S. Johnson, Mark D. TI Numb Regulates Glioma Stem Cell Fate and Growth by Altering Epidermal Growth Factor Receptor and Skp1-Cullin-F-Box Ubiquitin Ligase Activity SO STEM CELLS LA English DT Article DE Glioma; Notch; Numb; Asymmetric division; Cancer stem cells ID PROGENITOR CELLS; GENE-EXPRESSION; INTRACELLULAR DOMAIN; SUBVENTRICULAR ZONE; TUMOR-SUPPRESSOR; GLIOBLASTOMA; PROTEIN; CANCER; DIFFERENTIATION; PROLIFERATION AB Glioblastoma contains a hierarchy of stem-like cancer cells, but how this hierarchy is established is unclear. Here, we show that asymmetric Numb localization specifies glioblastoma stem-like cell (GSC) fate in a manner that does not require Notch inhibition. Numb is asymmetrically localized to CD133-hi GSCs. The predominant Numb isoform, Numb4, decreases Notch and promotes a CD133-hi, radial glial-like phenotype. However, upregulation of a novel Numb isoform, Numb4 delta 7 (Numb4d7), increases Notch and AKT activation while nevertheless maintaining CD133-hi fate specification. Numb knockdown increases Notch and promotes growth while favoring a CD133-lo, glial progenitor-like phenotype. We report the novel finding that Numb4 (but not Numb4d7) promotes SCFFbw7 ubiquitin ligase assembly and activation to increase Notch degradation. However, both Numb isoforms decrease epidermal growth factor receptor (EGFR) expression, thereby regulating GSC fate. Small molecule inhibition of EGFR activity phenocopies the effect of Numb on CD133 and Pax6. Clinically, homozygous NUMB deletions and low Numb mRNA expression occur primarily in a subgroup of proneural glioblastomas. Higher Numb expression is found in classical and mesenchymal glioblastomas and correlates with decreased survival. Thus, decreased Numb promotes glioblastoma growth, but the remaining Numb establishes a phenotypically diverse stem-like cell hierarchy that increases tumor aggressiveness and therapeutic resistance. STEM CELLS 2012;30:1313-1326 C1 [Jiang, Xiuli; Xing, Hongyan; Jung, Yuchae; Huang, Wei; Yang, Hong Wei; Song, Shengye; Carroll, Rona S.; Johnson, Mark D.] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Kim, Tae-Min; Park, Peter J.] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA USA. [Johnson, Mark D.] Dana Farber Brigham & Womens Canc Ctr, Program Neurooncol, Boston, MA USA. RP Johnson, MD (reprint author), Brigham & Womens Hosp, Dept Neurosurg, 75 Francis St, Boston, MA 02115 USA. EM mjohnson27@partners.org FU American Brain Tumor Association Fellowship; Brain Science Foundation Research Award; Harvard Stem Cell Institute grant; Hagerty Fund Research Award; NIH New Innovator Award [DP2OD002319] FX This work was supported by an American Brain Tumor Association Fellowship to X.J. and by a Brain Science Foundation Research Award, a Harvard Stem Cell Institute grant, a Hagerty Fund Research Award, and an NIH Director's New Innovator Award (DP2OD002319) to M.D.J. NR 45 TC 20 Z9 20 U1 0 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PD JUL PY 2012 VL 30 IS 7 BP 1313 EP 1326 DI 10.1002/stem.1120 PG 14 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 961PB UT WOS:000305477000001 PM 22553175 ER PT J AU Ko, CY Merkow, RP AF Ko, Clifford Y. Merkow, Ryan P. TI Outcomes Research in Surgical Oncology Preface SO SURGICAL ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 [Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90095 USA. [Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. [Ko, Clifford Y.; Merkow, Ryan P.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL 60611 USA. [Merkow, Ryan P.] Northwestern Univ, Feinberg Sch Med, Dept Surg & Surg Outcomes, Chicago, IL 60611 USA. [Merkow, Ryan P.] Northwestern Univ, Feinberg Sch Med, Qual Improvement Ctr, Chicago, IL 60611 USA. [Merkow, Ryan P.] Univ Colorado, Sch Med, Dept Surg, Aurora, CO USA. RP Ko, CY (reprint author), Univ Calif Los Angeles, Dept Surg, 10833 LeConte Ave,72-215 CHS, Los Angeles, CA 90095 USA. EM CKo@mednet.ucla.edu; Ryan.Merkow@ucdenver.edu NR 0 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 1055-3207 J9 SURG ONCOL CLIN N AM JI Surg. Oncol. Clin. N. Am. PD JUL PY 2012 VL 21 IS 3 BP XV EP XVI DI 10.1016/j.soc.2012.04.001 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA 959YS UT WOS:000305354700002 PM 22583999 ER PT J AU Rochefort, MM Tomlinson, JS AF Rochefort, Matthew M. Tomlinson, James S. TI Unexpected Readmissions After Major Cancer Surgery An Evaluation of Readmissions as a Quality-of-Care Indicator SO SURGICAL ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Surgery; Readmission; Rehospitalization; Oncology; Quality care ID VALIDATION; MORTALITY AB Readmissions following major oncologic operation are common affecting patient treatment, outcome, and hospital resources. The Center for Medicare and Medicaid Services mandates reporting of certain disease-specific readmissions and Congress is considering using individual hospital readmission rates as a performance measure. Studies using administrative data demonstrate that readmission rates following major cancer surgery are high. Administrative data cannot determine causes. Single-institution studies demonstrate length of hospital stay and comorbidities as risk factors. Discharge processes and outpatient healthcare utilization can be improved. Until studies on readmission rate are conducted, using readmission rates as a measure of quality should be pursued cautiously. C1 [Rochefort, Matthew M.; Tomlinson, James S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Tomlinson, James S.] Greater Los Angeles VA Med Ctr, Los Angeles, CA 90073 USA. RP Tomlinson, JS (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, 10833 Le Conte Ave,Room 54-140 CHS,Box 9511782, Los Angeles, CA 90095 USA. EM jtomlinson@mednet.ucla.edu NR 16 TC 12 Z9 12 U1 0 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1055-3207 J9 SURG ONCOL CLIN N AM JI Surg. Oncol. Clin. N. Am. PD JUL PY 2012 VL 21 IS 3 BP 397 EP + DI 10.1016/j.soc.2012.03.004 PG 10 WC Oncology; Surgery SC Oncology; Surgery GA 959YS UT WOS:000305354700006 PM 22583989 ER PT J AU Lawson, EH Gibbons, MM Ko, CY AF Lawson, Elise H. Gibbons, Melinda Maggard Ko, Clifford Y. TI Appropriate Use of Surgical Procedures for Patients with Cancer SO SURGICAL ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Cancer; Appropriateness method; Surgery; Overuse; Underuse ID CAROTID-ENDARTERECTOMY; CORONARY REVASCULARIZATION; MEDICAL PROCEDURES; PHYSICIAN RATINGS; PANEL; CARE; GUIDELINES; HYSTERECTOMY; NECESSITY; UNDERUSE AB With increasing focus on improving quality and promoting patient-centered care, ensuring that patients receive appropriate surgical procedures is paramount. The appropriateness method was developed to determine which patients should and should not undergo surgical intervention versus medical therapy. This method combines the best available evidence in the literature with expert opinion to produce explicit guidance for clinicians on the relative risks and benefits of a procedure for specific clinical indications. A coordinated effort to produce appropriateness criteria for surgical oncology could improve the quality of surgical care for patients with cancer if these criteria are integrated into routine clinical practice. C1 [Lawson, Elise H.] Univ Calif Los Angeles, Med Ctr, Dept Surg, Los Angeles, CA 90095 USA. [Lawson, Elise H.; Gibbons, Melinda Maggard; Ko, Clifford Y.] VA Greater Angeles Healthcare Syst, Los Angeles, CA 90095 USA. [Ko, Clifford Y.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL 60611 USA. RP Lawson, EH (reprint author), Univ Calif Los Angeles, Med Ctr, Dept Surg, CHS 72-215,10833 LeConte Ave, Los Angeles, CA 90095 USA. EM elawson@mednet.ucla.edu NR 25 TC 2 Z9 2 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 1055-3207 J9 SURG ONCOL CLIN N AM JI Surg. Oncol. Clin. N. Am. PD JUL PY 2012 VL 21 IS 3 BP 479 EP + DI 10.1016/j.soc.2012.03.008 PG 9 WC Oncology; Surgery SC Oncology; Surgery GA 959YS UT WOS:000305354700012 PM 22583995 ER PT J AU Lok, J Zhao, S Leung, W Seo, JH Navaratna, D Wang, X Whalen, MJ Lo, EH AF Lok, Josephine Zhao, Song Leung, Wendy Seo, Ji Hae Navaratna, Deepti Wang, Xiaoying Whalen, Michael J. Lo, Eng H. TI Neuregulin-1 Effects on Endothelial and Blood-Brain Barrier Permeability After Experimental Injury SO TRANSLATIONAL STROKE RESEARCH LA English DT Article DE Neuregulin-1; Endothelial; Blood-brain barrier; Brain trauma; IL-1 beta; Permeability ID TISSUE-DAMAGE; UNITED-STATES; MICE; DISRUPTION; HEALTH; IMPACT AB Blood brain barrier (BBB) disruption occurs with a high incidence after traumatic brain injury, and is an important contributor to many pathological processes, including brain edema, inflammation, and neuronal cell death. Therefore, BBB integrity is an important potential therapeutic target in the treatment of the acute phase of brain trauma. In this short communication, we report our data showing that neuregulin-1 (NRG1), a growth factor with diverse functions in the central nervous system (CNS), ameliorates pathological increases in endothelial permeability and in BBB permeability in experimental models of injury. For in vitro studies, rat brain endothelial cells were incubated with the inflammatory cytokine IL-1 beta, which caused an increase in permeability of the cell layer. Co-incubation with NRG1 ameliorated this permeability increase. For in vivo studies, C57B1/6 mice were subjected to controlled cortical impact (CCI) under anesthesia, and BBB permeability was assessed by measuring the amount of Evans blue dye extravasation at 2 h. NRG1 administered by tail-vein injection 10 min after CCI resulted in a decrease in Evans blue dye extravasation by 35 %. Since Evans blue extravasation may result from an increase in BBB permeability or from bleeding due to trauma, hemoglobin ELISA was also performed at the same time point. There was a trend toward lower levels of hemoglobin extravasation in the NRG1 group, but the results did not reach statistical significance. MMP-9 activity was not different between groups at 2 h. These data suggest that NRG1 has beneficial effects on endothelial permeability and BBB permeability following experimental trauma, and may have neuroprotective potential during CNS injury. C1 [Lok, Josephine; Leung, Wendy; Whalen, Michael J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat, Boston, MA 02114 USA. [Lok, Josephine; Zhao, Song; Leung, Wendy; Seo, Ji Hae; Navaratna, Deepti; Wang, Xiaoying; Lo, Eng H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroprotect Res Lab, Charlestown, MA USA. [Zhao, Song] Jilin Univ, First Hosp, Dept Orthoped, Spine Div, Changchun 130023, Jilin, Peoples R China. [Lo, Eng H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. [Lo, Eng H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Whalen, Michael J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Neurosci, Charlestown, MA USA. RP Lok, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat, Boston, MA 02114 USA. EM jlok1@partners.org FU National Institute of Health [K08NS057339, R01NS53560, RO1NSO61255, R01-NS76694] FX This study was supported by National Institute of Health grants (K08NS057339 to JL, R01NS53560, RO1NSO61255 to MW, and R01-NS76694 to EHL). The authors declare no conflicts of interest. NR 19 TC 15 Z9 15 U1 3 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1868-4483 J9 TRANSL STROKE RES JI Transl. Stroke Res. PD JUL PY 2012 VL 3 SU 1 SI SI BP S119 EP S124 DI 10.1007/s12975-012-0157-x PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 961AT UT WOS:000305436500015 PM 22773936 ER PT J AU Valant, V Keenan, BT Anderson, CD Shulman, JM Devan, WJ Ayres, AM Schwab, K Goldstein, JN Viswanathan, A Greenberg, SM Bennett, DA De Jager, PL Rosand, J Biffi, A AF Valant, Valerie Keenan, Brendan T. Anderson, Christopher D. Shulman, Joshua M. Devan, William J. Ayres, Alison M. Schwab, Kristin Goldstein, Joshua N. Viswanathan, Anand Greenberg, Steven M. Bennett, David A. De Jager, Philip L. Rosand, Jonathan Biffi, Alessandro CA ADNI TI TOMM40 in Cerebral Amyloid Angiopathy Related Intracerebral Hemorrhage: Comparative Genetic Analysis with Alzheimer's Disease SO TRANSLATIONAL STROKE RESEARCH LA English DT Article DE TOMM40; APOE; Cerebral amyloid angiopathy; Alzheimer's disease; Linkage disequilibrium ID APOLIPOPROTEIN-E EPSILON-2; COGNITIVE IMPAIRMENT; CLINICAL-DIAGNOSIS; COMMON VARIANTS; ASSOCIATION; PATHOLOGY; DEMENTIA; GENOTYPE; LINKAGE; DESIGN AB Cerebral amyloid angiopathy (CAA) related intracerebral hemorrhage (ICH) is a devastating form of stroke with no known therapies. Clinical, neuropathological, and genetic studies have suggested both overlap and divergence between the pathogenesis of CAA and the biologically related condition of Alzheimer's disease (AD). Among the genetic loci associated with AD are APOE and TOMM40, a gene in close proximity to APOE. We investigate here whether variants within TOMM40 are associated with CAA-related ICH and CAA neuropathology. Using cohorts from the Massachusetts General Hospital (MGH) and the Alzheimer's Disease Neuroimaging Initiative (ADNI), we designed a comparative analysis of high-density SNP genotype data for CAA-related ICH and AD. APOE epsilon 4 was associated with CAA-related ICH and AD, while APOE epsilon 2 was protective in AD but a risk factor for CAA. A total of 14 SNPs within TOMM40 were associated with AD (p< 0.05 after multiple testing correction), but not CAA-related ICH (all p>0.20); as a result, all AD-associated SNPs within TOMM40 showed heterogeneity of effect in CAA-related ICH (BD p<0.001). Analysis of CAA neuropathology in the Religious Orders Study (ROS) and Rush Memory and Aging Project (MAP), however, found that neuritic plaque, diffuse plaque burden, and vascular amyloid burden associated with all TOMM40 SNPs (p<0.02). These results suggest that alterations in TOMM40 can promote vascular as well as plaque amyloid deposition, but not the full pathogenic pathway leading to CAA-related ICH. C1 [Valant, Valerie; Anderson, Christopher D.; Devan, William J.; Rosand, Jonathan; Biffi, Alessandro] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Valant, Valerie; Anderson, Christopher D.; Devan, William J.; Goldstein, Joshua N.; Rosand, Jonathan; Biffi, Alessandro] Massachusetts Gen Hosp, Dept Neurol, Div Neurocrit Care & Emergency Neurol, Boston, MA 02114 USA. [Valant, Valerie; Anderson, Christopher D.; Devan, William J.; Ayres, Alison M.; Schwab, Kristin; Goldstein, Joshua N.; Viswanathan, Anand; Greenberg, Steven M.; Rosand, Jonathan; Biffi, Alessandro] Massachusetts Gen Hosp, Hemorrhag Stroke Res Grp, Boston, MA 02114 USA. [Valant, Valerie; Keenan, Brendan T.; Anderson, Christopher D.; Shulman, Joshua M.; Devan, William J.; De Jager, Philip L.; Rosand, Jonathan; Biffi, Alessandro] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Keenan, Brendan T.; Shulman, Joshua M.; De Jager, Philip L.] Harvard Univ, Brigham & Womens Hosp, Program Translat NeuroPsychiat Genom, Inst Neurosci,Dept Neurol & Psychiat, Boston, MA 02115 USA. [Goldstein, Joshua N.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Bennett, David A.] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Dept Neurol Sci, Chicago, IL 60612 USA. [Keenan, Brendan T.; Shulman, Joshua M.; De Jager, Philip L.] Harvard Univ, Sch Med, Boston, MA USA. RP Rosand, J (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St,CPZN 6818, Boston, MA 02114 USA. EM jrosand@partners.org RI Goldstein, Joshua/H-8953-2016; OI Anderson, Christopher/0000-0002-0053-2002 FU John and Marilyn Keane Stroke Genetics Fund; Edward and Maybeth Sonn Research Fund; NINDS [R01 NS059727]; Alzheimer's Disease Neuroimaging Initiative (ADNI); National Institutes for Health (NIH) [U01 AG024904, P30 AG010129, K01 AG030514]; National Institute on Aging (NIA); National Institute of Biomedical Imaging and Bioengineering; Northern California Institute for Research and Education Inc; Dana Foundation; American Heart Association/Bugher Foundation Centers for Stroke Prevention Research [0775010 N]; Beth Israel Deaconess Medical Center and Harvard/MIT Health Sciences and Technology; Pfizer Inc.; Merck Co.; Parkinson's Study Group; Harvard Neuro Discovery Center/Massachusetts Alzheimer's Disease Research Center; Burroughs Wellcome Fund; Danone Research B.V.; Illinois Department of Public Health; Robert C. Borwell Endowment Fund; Biogen Idec; National Center for Research Resources; National Institute of Health-National Institute of Neurological Disorders and Stroke [K23NS059774] FX This work was supported by the John and Marilyn Keane Stroke Genetics Fund, the Edward and Maybeth Sonn Research Fund, NINDS R01 NS059727, the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the National Institutes for Health (NIH) (grant U01 AG024904). The ADNI is funded by the National Institute on Aging (NIA), the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abbott Laboratories, AstraZeneca AB, Bayer Schcring Pharma AG, Bristol-Myers Squibb, Eisai Global Clinical Development, Elan Corporation Plc, Genentech Inc, GE Healthcare, GlaxoSmithKline, Innogenetics, Johnson and Johnson Services Inc, Eli Lilly and Company, Medpace Inc, Merck and Co Inc, Novartis International AG, Pfizer Inc, F. Hoffman-La Roche Ltd, and Wyeth Pharmaceuticals, as well as nonprofit partners the Alzheimer's Association and the Alzheimer's Drug Discovery Foundation, with participation from the US Food and Drug Administration. Private sector contributions to the ADNI are facilitated by the Foundation for the NIH. The grantee organization is the Northern California Institute for Research and Education Inc, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. The ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of California, Los Angles. This research was also supported by the NIH (grants P30 AG010129 and K01 AG030514) and the Dana Foundation. Drs Biffi and Anderson receive research support from the American Heart Association/Bugher Foundation Centers for Stroke Prevention Research (grant 0775010 N). Dr. Shulman is supported by the Clinical Investigator Training Program: Beth Israel Deaconess Medical Center and Harvard/MIT Health Sciences and Technology, in collaboration with Pfizer Inc. and Merck & Co., Parkinson's Study Group, Harvard Neuro Discovery Center/Massachusetts Alzheimer's Disease Research Center, and Burroughs Wellcome Fund, Career Award for Medical Scientists. Dr Bennett receives research support from Danone Research B.V., the NIH, the Illinois Department of Public Health, and the Robert C. Borwell Endowment Fund. Dr DeJager receives research support from Biogen Idec and the NIH. Dr Rosand receives research support from the National Center for Research Resources. Dr Goldstein (grant K23NS059774) receives research support from the National Institute of Health-National Institute of Neurological Disorders and Stroke. NR 49 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1868-4483 J9 TRANSL STROKE RES JI Transl. Stroke Res. PD JUL PY 2012 VL 3 SU 1 SI SI BP S102 EP S112 DI 10.1007/s12975-012-0161-1 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 961AT UT WOS:000305436500013 ER PT J AU Ifediba, MA Moore, A AF Ifediba, Marytheresa A. Moore, Anna TI In vivo imaging of the systemic delivery of small interfering RNA SO WILEY INTERDISCIPLINARY REVIEWS-NANOMEDICINE AND NANOBIOTECHNOLOGY LA English DT Review ID LIPOSOME-MEDIATED DELIVERY; INHIBITS TUMOR-GROWTH; SIRNA DELIVERY; MAMMALIAN-CELLS; EFFICIENT DELIVERY; NONHUMAN-PRIMATES; GENE-EXPRESSION; CANCER-CELLS; ADULT MICE; BIODISTRIBUTION AB Short interfering RNAs (siRNAs) have emerged as a potent new class of therapeutics, which regulate gene expression through sequence-specific inhibition of mRNA translation. Human trials of siRNAs have highlighted the need for robust delivery and detection techniques that will enable the application of these therapeutics to increasingly complex disease and organ systems. Efforts to monitor the in vivo trafficking and efficacy of siRNAs have routinely involved bioluminescence imaging of naked siRNA molecules. More recently, siRNAs have been incorporated into a variety of molecular imaging probes to promote their detection with clinically relevant imaging modalities. Lipid-, polymer-, and nanoparticle-based siRNA delivery vehicles have proven effective in improving the stability, bioavailability, and target specificity of siRNAs following systemic administration in vivo. Additionally, these methods provide a platform to modify siRNAs with a variety of contrast agents and have enabled nuclear and magnetic resonance imaging of siRNA delivery in preclinical studies. These image-guided delivery approaches represent a crucial step in the transition of siRNA therapeutics to the clinic. WIREs Nanomed Nanobiotechnol 2012, 4:428437. doi: 10.1002/wnan.1158 For further resources related to this article, please visit the . C1 [Ifediba, Marytheresa A.; Moore, Anna] Massachusetts Gen Hosp, Mol Imaging Lab, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA 02129 USA. [Ifediba, Marytheresa A.; Moore, Anna] Harvard Univ, Sch Med, Charlestown, MA USA. [Ifediba, Marytheresa A.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Ifediba, Marytheresa A.] MIT, Harvard MIT Div Hlth Sci & Technol HST, Cambridge, MA 02139 USA. RP Moore, A (reprint author), Massachusetts Gen Hosp, Mol Imaging Lab, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA 02129 USA. EM amoore@helix.mgh.harvard.edu NR 57 TC 6 Z9 6 U1 0 U2 24 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1939-5116 J9 WIRES NANOMED NANOBI JI Wiley Interdiscip. Rev.-Nanomed. Nanobiotechnol. PD JUL-AUG PY 2012 VL 4 IS 4 BP 428 EP 437 DI 10.1002/wnan.1158 PG 10 WC Nanoscience & Nanotechnology; Medicine, Research & Experimental SC Science & Technology - Other Topics; Research & Experimental Medicine GA 961JO UT WOS:000305460900007 PM 22228711 ER PT J AU Batki, SL Lasher, BA Herbst, E Prathikanti, S Metzler, T Tarasovsky, G Waldrop, A Neylan, TC Petrakis, I Coetzee, J AF Batki, Steven L. Lasher, Brooke A. Herbst, Ellen Prathikanti, Sridhar Metzler, Thomas Tarasovsky, Gary Waldrop, Angela Neylan, Thomas C. Petrakis, Ismene Coetzee, John TI Topiramate Treatment of Alcohol Dependence in Veterans with PTSD: Baseline Alcohol Use and PTSD Severity SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Meeting Abstract C1 UCSF, Dept Psychiat, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD JUL-AUG PY 2012 VL 21 IS 4 MA 3 BP 382 EP 382 PG 1 WC Substance Abuse SC Substance Abuse GA 956XH UT WOS:000305122400015 ER PT J AU Yule, A Wilens, TE Martelon, MK Simon, A Biederman, J AF Yule, Amy Wilens, Timothy E. Martelon, Mary Kate Simon, Andrew Biederman, Joseph TI Does Exposure to Parental SUD Increase SUD Risk in Offspring: An Eleven Year Follow-up Study SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Meeting Abstract C1 [Yule, Amy; Wilens, Timothy E.; Martelon, Mary Kate; Simon, Andrew; Biederman, Joseph] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD JUL-AUG PY 2012 VL 21 IS 4 MA 21 BP 388 EP 388 PG 1 WC Substance Abuse SC Substance Abuse GA 956XH UT WOS:000305122400030 ER PT J AU Wilens, TE Martelon, MK Anderson, JP Shelley-Abrahamson, R Biederman, J AF Wilens, Timothy E. Martelon, Mary Kate Anderson, Jesse P. Shelley-Abrahamson, Rachel Biederman, Joseph TI Difficulties in Emotional Regulation and Substance Use Disorders: A Controlled Family Study of Bipolar Adolescents SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Meeting Abstract C1 [Wilens, Timothy E.; Martelon, Mary Kate; Anderson, Jesse P.; Shelley-Abrahamson, Rachel; Biederman, Joseph] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD JUL-AUG PY 2012 VL 21 IS 4 MA 24 BP 389 EP 389 PG 1 WC Substance Abuse SC Substance Abuse GA 956XH UT WOS:000305122400033 ER PT J AU Meszaros, ZS Abdul-Malak, Y Dimmock, JA Wang, DL Batki, SL AF Meszaros, Zsuzsa Szombathyne Abdul-Malak, Ynesse Dimmock, Jacqueline A. Wang, Dongliang Batki, Steven L. TI Varenicline Treatment of Alcohol and Nicotine Dependence in Schizophrenia: Problems Encountered in a Pilot Trial SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Meeting Abstract C1 [Batki, Steven L.] SUNY Upstate Med Univ, Dept Psychiat, San Francisco VA Med Ctr, Syracuse, NY 13210 USA. [Wang, Dongliang] SUNY Upstate Med Univ, Dept Publ Hlth & Prevent Med, Syracuse, NY 13210 USA. [Batki, Steven L.] UCSF, Dept Psychiat, San Francisco, CA 94143 USA. NR 0 TC 2 Z9 2 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD JUL-AUG PY 2012 VL 21 IS 4 MA 36 BP 393 EP 394 PG 2 WC Substance Abuse SC Substance Abuse GA 956XH UT WOS:000305122400044 ER PT J AU Wilens, TE Simon, A Martelon, MK AF Wilens, Timothy E. Simon, Andrew Martelon, Mary Kate TI A Midpoint Analysis of the Characteristics of Young Adults Who Misuse Stimulant Medications SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Meeting Abstract C1 [Wilens, Timothy E.; Simon, Andrew; Martelon, Mary Kate] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD JUL-AUG PY 2012 VL 21 IS 4 MA 46 BP 396 EP 397 PG 2 WC Substance Abuse SC Substance Abuse GA 956XH UT WOS:000305122400051 ER PT J AU Lu, ZY Li, YC Jin, JF Zhang, XM Lopes-Virella, MF Huang, Y AF Lu, Zhongyang Li, Yanchun Jin, Junfei Zhang, Xiaoming Lopes-Virella, Maria F. Huang, Yan TI Toll-Like Receptor 4 Activation in Microvascular Endothelial Cells Triggers a Robust Inflammatory Response and Cross Talk With Mononuclear Cells via Interleukin-6 SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE endothelial cells; gene expression; inflammation; interleukin-6; toll-like receptor ID HUMAN ATHEROSCLEROSIS; CORONARY ATHEROSCLEROSIS; CHLAMYDIA-PNEUMONIAE; PLAQUE VULNERABILITY; ADHESION MOLECULE-1; EXPRESSION; NEOVASCULARIZATION; ANGIOGENESIS; PATHOGENESIS; MACROPHAGES AB Objective-It is known that toll-like receptor 4 (TLR4) plays an important role in atherosclerosis. Because both microvascular (MIC) and macrovascular (MAC) endothelial cells (ECs) are present in atherosclerotic lesions, the present study compared TLR4-triggered inflammatory response and cross talk with mononuclear cells between MIC and MAC ECs. Methods and Results-ELISA, real-time polymerase chain reaction, and gene expression profiling showed that TLR4 activation by lipopolysaccharide stimulated a much higher expression of inflammatory genes including cytokines, chemokines, growth factors, and adhesion molecules in MIC ECs than MAC ECs. Furthermore, coculture studies showed that TLR4 activation in MIC ECs, but not MAC ECs, induced a cross talk with U937 mononuclear cells through MIC EC-released interleukin-6 to upregulate matrix metalloproteinase-1 expression in U937 cells. To explore molecular mechanisms underlying the different responses to TLR4 activation between MIC and MAC ECs, we showed that MIC ECs had a higher expression of TLR4 and CD14 and a higher TLR4-mediated nuclear factor-kappaB activity than MAC ECs. Conclusion-The present study showed that TLR4 activation triggers a more robust inflammatory response in MIC ECs than MAC ECs. Given the importance of inflammatory cytokines and matrix metalloproteinases in plaque rupture, MIC ECs may play a key role in plaque destabilization through a TLR4-dependent mechanism. (Arterioscler Thromb Vasc Biol. 2012;32:1696-1706) C1 [Lopes-Virella, Maria F.; Huang, Yan] Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29403 USA. [Lu, Zhongyang; Li, Yanchun; Jin, Junfei; Zhang, Xiaoming; Lopes-Virella, Maria F.; Huang, Yan] Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, Charleston, SC 29403 USA. RP Huang, Y (reprint author), Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, 114 Doughty St, Charleston, SC 29403 USA. EM huangyan@musc.edu FU Department of Veterans Affairs, National Institutes of Health [DE016353, DK081352] FX This work was supported by the Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs, National Institutes of Health grant DE016353 (to Y. Huang) and DK081352 (to M.F. Lopes-Virella). NR 50 TC 19 Z9 21 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUL PY 2012 VL 32 IS 7 BP 1696 EP 1706 DI 10.1161/ATVBAHA.112.251181 PG 11 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 959SK UT WOS:000305333100021 PM 22596222 ER PT J AU Lebron-Milad, K Graham, BM Milad, MR AF Lebron-Milad, Kelimer Graham, Bronwyn M. Milad, Mohammed R. TI Low Estradiol Levels: A Vulnerability Factor for the Development of Posttraumatic Stress Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material ID FEAR EXTINCTION; CIRCUITRY; ESTROGEN; CYCLE C1 [Lebron-Milad, Kelimer; Graham, Bronwyn M.; Milad, Mohammed R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Charlestown, MA 02129 USA. RP Milad, MR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Charlestown, MA 02129 USA. EM milad@nmr.mgh.harvard.edu NR 10 TC 19 Z9 19 U1 0 U2 10 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 JUL 1 PY 2012 VL 72 IS 1 BP 6 EP 7 DI 10.1016/j.biopsych.2012.04.029 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 958ZF UT WOS:000305278800004 PM 22682395 ER PT J AU Postupna, N Rose, SE Bird, TD Gonzalez-Cuyar, LF Sonnen, JA Larson, EB Keene, CD Montine, TJ AF Postupna, Nadia Rose, Shannon E. Bird, Thomas D. Gonzalez-Cuyar, Luis F. Sonnen, Joshua A. Larson, Eric B. Keene, C. Dirk Montine, Thomas J. TI Novel Antibody Capture Assay for Paraffin-Embedded Tissue Detects Wide-Ranging Amyloid Beta and Paired Helical Filament-Tau Accumulation in Cognitively Normal Older Adults SO BRAIN PATHOLOGY LA English DT Article DE aging; Alzheimer's disease; ELISA; immunohistochemistry ID ALZHEIMERS-DISEASE; SYNAPTIC PROTEINS; NATIONAL-INSTITUTE; DEMENTIA; PATHOLOGY; IMPAIRMENT; DIAGNOSIS; RECOMMENDATIONS; NEUROPATHOLOGY; QUANTITATION AB Quantifying antigens in formalin-fixed tissue is challenging and limits investigation in population-based studies of brain aging. To address this major limitation, we have developed a new technique that we call Histelide: immunohistochemistry (HIST-) and enzyme-linked immunosorbent assay (ELISA) (-EL-) performed on a glass slide (-IDE). We validated Histelide in sections of prefrontal cortex from 20 selected cases: 12 subjects with clinically and neuropathologically diagnosed Alzheimer's disease (AD), either autosomal dominant or late-onset forms, and 8 clinical and neuropathologic controls. AD cases had significantly increased amyloid beta (A beta) peptide and paired helical filament (PHF-) tau per area of neocortex that was proteinase K-sensitive, and significantly decreased amount of synaptophysin. We next investigated prefrontal cortex from 81 consecutive cases of high-cognitive performers from the Adult Changes in Thought (ACT) study, a population-based study of brain aging and incident dementia. As expected, latent AD was common in this group; however, our results quantified widely individually varying levels of A beta peptides and PHF-tau among these high-cognitive performers. This novel approach obtains quantitative data from population-based studies, and our initial studies with high-cognitive performers provide important quantitative insights into latent AD that should help guide expectations from neuroimaging and prevention studies. C1 [Postupna, Nadia; Rose, Shannon E.; Gonzalez-Cuyar, Luis F.; Sonnen, Joshua A.; Keene, C. Dirk; Montine, Thomas J.] Univ Washington, Dept Pathol, Seattle, WA 98104 USA. [Bird, Thomas D.] Univ Washington, Dept Med, Seattle, WA 98104 USA. [Bird, Thomas D.] Univ Washington, Dept Neurol, Seattle, WA 98104 USA. [Bird, Thomas D.] VA Puget Sound Hlth Care Syst, Geriatr Res Clin & Educ Ctr, Seattle, WA USA. [Larson, Eric B.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. RP Montine, TJ (reprint author), Univ Washington, Dept Pathol, 300 9th Ave,Roomm 703, Seattle, WA 98104 USA. EM tmontine@uw.edu RI Sonnen, 37382016/H-3738-2016; Keene, Christopher/N-1806-2015 OI Sonnen, 37382016/0000-0001-9267-8705; FU NIH [AG05136, AG23801, AG006781, NS62684, T32AG000258, T32ES007032]; Nancy and Buster Alvord Endowment FX This work was supported by grants from the NIH (AG05136, AG23801, AG006781, NS62684, T32AG000258, T32ES007032), and the Nancy and Buster Alvord Endowment. We thank Dr. Kathy Montine for editorial assistance. NR 41 TC 7 Z9 7 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD JUL PY 2012 VL 22 IS 4 BP 472 EP 484 DI 10.1111/j.1750-3639.2011.00542.x PG 13 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 958KH UT WOS:000305234900003 PM 21999410 ER PT J AU Troisi, R Altantsetseg, D Davaasambuu, G Rich-Edwards, J Davaalkham, D Tretli, S Hoover, RN Frazier, AL AF Troisi, Rebecca Altantsetseg, Dalkhjav Davaasambuu, Ganmaa Rich-Edwards, Janet Davaalkham, Dambadarjaa Tretli, Steinar Hoover, Robert N. Frazier, A. Lindsay TI Breast cancer incidence in Mongolia SO CANCER CAUSES & CONTROL LA English DT Article DE Mongolia; Breast cancer; Urban-rural; Asia; International ID ASIAN-AMERICAN WOMEN; HEPATITIS-C VIRUS; HORMONE LEVELS; VITAMIN-D; RISK; PREVALENCE; PATTERNS; BIRTH; RATES; AGE AB Data on international variation in breast cancer incidence may help to identify additional risk factors. Substantially lower breast cancer rates in Asia than in North America and Western Europe are established, but differences within Asia have been largely ignored despite heterogeneity in lifestyles and environments. Mongolia's breast cancer experience is of interest because of its shared genetics but vastly different diet compared with other parts of Asia. Age-standardized breast cancer incidence and mortality rates obtained from the International Association of Cancer Registries are presented for several Asian countries. Mongolian incidence rates obtained from its cancer registry describe incidence within the country. Breast cancer incidence in Mongolia (age standardized 8.0/100,000) is almost a third of rates in China (21.6/100,000), and over five times that of Japan (42.7/100,000) and Russia (43.2/100,000). Rates within Mongolia appear to have increased slightly over the last decade and are higher in urban than rural areas (annual percentage increase of age-standardized rates from 1998 to 2005 was 3.60 and 2.57 %, respectively). The increase in breast cancer incidence with age plateaus at menopause, as in other Asian populations. Mongolia's low breast cancer incidence is of particular interest because of their unusual diet (primarily red meat and dairy) compared with other Asian countries. More intensive study of potential dietary, reproductive and lifestyle factors in Mongolia with comparison to other Asian populations may provide more clarity in what drives the international breast cancer rate differences. C1 [Troisi, Rebecca] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03756 USA. [Troisi, Rebecca; Hoover, Robert N.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Altantsetseg, Dalkhjav] Mongolian Natl Oncol Ctr, Ulaanbaator, Mongol Peo Rep. [Davaasambuu, Ganmaa] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Rich-Edwards, Janet] Brigham & Womens Hosp, Connors Ctr Womens Hlth & Gender Biol, Boston, MA 02115 USA. [Davaalkham, Dambadarjaa] Hlth Sci Univ Mongolia, Ulaanbaator, Mongol Peo Rep. [Tretli, Steinar] Canc Registry Norway, Oslo, Norway. [Frazier, A. Lindsay] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Frazier, A. Lindsay] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Troisi, R (reprint author), Dartmouth Hitchcock Med Ctr, Room 854,7297 Rubin Bldg,1 Med Ctr Dr, Lebanon, NH 03756 USA. EM troisir@mail.nih.gov FU Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human Services FX We thank Ms. Narantuya Khad, senior officer and research fellow in the Public Health Sector Policy Research Unit of the Health Department, for her work at the Registry. This work was supported by the Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human Services. NR 35 TC 11 Z9 13 U1 4 U2 10 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JUL PY 2012 VL 23 IS 7 BP 1047 EP 1053 DI 10.1007/s10552-012-9973-2 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 953WW UT WOS:000304905400006 PM 22543542 ER PT J AU Sanchez, MA Vinson, CA La Porta, M Viswanath, K Kerner, JF Glasgow, RE AF Sanchez, Michael A. Vinson, Cynthia A. La Porta, Madeline Viswanath, Kasisomayajula Kerner, Jon F. Glasgow, Russell E. TI Evolution of Cancer Control PLANET: moving research into practice SO CANCER CAUSES & CONTROL LA English DT Article DE Dissemination; Implementation; Evidence-based; Cancer control; Program planning; Internet; Web resources ID EVIDENCE-BASED INTERVENTIONS; PROMOTE PHYSICAL-ACTIVITY; PUBLIC-HEALTH; PARTNERSHIPS; DEPARTMENTS; PREVENTION; DIFFUSION; EDUCATION; TRENDS; POLICY AB Evidence-based interventions (EBIs) are not broadly implemented, despite widespread availability of programs, policies, and guidelines. Systematic processes for integrating EBIs with community preference remain challenging for cancer control and prevention, as well as other areas. The Cancer Control P.L.A.N.E.T. (P.L.A.N.E.T) Web portal provides a platform to access data, EBIs, and resources to foster local partnerships and assist public health researchers and practitioners design, implement, and evaluate evidence-based cancer control programs. This article summarizes the evolution of P.L.A.N.E.T. and describes effective and innovative Web 2.0 strategies to increase Web visits, create more interactive platforms for researchers and practitioners to integrate evidence-based resources, community preferences, and the complex context in which programs and policies are implemented. Lessons learned could benefit public health settings and reach low-income, high-risk communities. Researchers, community practitioners, and government partnerships should continue to develop and test innovative ways to address pressing issues in cancer control, health disparities, and health delivery. C1 [Sanchez, Michael A.; Vinson, Cynthia A.; La Porta, Madeline; Glasgow, Russell E.] NCI, EPN, Rockville, MD 20852 USA. [Viswanath, Kasisomayajula] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Viswanath, Kasisomayajula] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kerner, Jon F.] Canadian Partnership Canc, Toronto, ON, Canada. RP Sanchez, MA (reprint author), NCI, EPN, 6130 Execut Blvd,Room 6131A, Rockville, MD 20852 USA. EM sanchezgarciama@mail.nih.gov OI Kerner, Jon/0000-0002-8792-3830 FU National Cancer Institute [CA132651] FX The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the National Cancer Institute or the Canadian Partnership Against Cancer. Viswanath's effort was funded by a grant from the National Cancer Institute, CA132651. Christopher Politis of the Primary Prevention Program of Canadian Partnership Against Cancer provided additional support for data analysis. NR 30 TC 7 Z9 8 U1 1 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JUL PY 2012 VL 23 IS 7 BP 1205 EP 1212 DI 10.1007/s10552-012-9987-9 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 953WW UT WOS:000304905400021 PM 22674294 ER PT J AU Lee, J Hong, YK Jeon, GS Hwang, YJ Kim, KY Seong, KH Jung, MK Picketts, DJ Kowall, NW Cho, KS Ryu, H AF Lee, J. Hong, Y. K. Jeon, G. S. Hwang, Y. J. Kim, K. Y. Seong, K. H. Jung, M-K Picketts, D. J. Kowall, N. W. Cho, K. S. Ryu, H. TI ATRX induction by mutant huntingtin via Cdx2 modulates heterochromatin condensation and pathology in Huntington's disease SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE ATRX; huntingtin; heterochromatin condensation; Huntington's disease; Cdx-2 ID CREB-BINDING PROTEIN; X SYNDROME; MENTAL-RETARDATION; TRANSGENIC MICE; MUTATIONS; TRANSCRIPTION; DROSOPHILA; EXPRESSION; GENE; CHROMOSOMES AB Aberrant chromatin remodeling is involved in the pathogenesis of Huntington's disease (HD) but the mechanism is not known. Herein, we report that mutant huntingtin (mtHtt) induces the transcription of alpha thalassemia/mental retardation X linked (ATRX), an ATPase/helicase and SWI/SNF-like chromatin remodeling protein via Cdx-2 activation. ATRX expression was elevated in both a cell line model and transgenic model of HD, and Cdx-2 occupancy of the ATRX promoter was increased in HD. Induction of ATRX expanded the size of promyelocytic leukemia nuclear body (PML-NB) and increased trimethylation of H3K9 (H3K9me3) and condensation of pericentromeric heterochromatin, while knockdown of ATRX decreased PML-NB and H3K9me3 levels. Knockdown of ATRX/dXNP improved the hatch rate of fly embryos expressing mtHtt (Q127). ATRX/dXNP overexpression exacerbated eye degeneration of eye-specific mtHtt (Q127) expressing flies. Our findings suggest that transcriptional alteration of ATRX by mtHtt is involved in pericentromeric heterochromatin condensation and contributes to the pathogenesis of HD. Cell Death and Differentiation (2012) 19, 1109-1116; doi: 10.1038/cdd.2011.196; published online 13 January 2012 C1 [Lee, J.; Kowall, N. W.; Ryu, H.] Boston Univ, Sch Med, Dept Neurol, VA Boston Healthcare Syst, Boston, MA 02130 USA. [Hong, Y. K.; Cho, K. S.] Konkuk Univ, Dept Biol Sci, Seoul, South Korea. [Jeon, G. S.; Hwang, Y. J.; Kim, K. Y.; Seong, K. H.; Jung, M-K; Ryu, H.] Seoul Natl Univ, World Class Univ, Coll Med, Dept Biomed Sci,Neurocyt Grp, Seoul, South Korea. [Picketts, D. J.] Univ Ottawa, Dept Med & Biochem, Ottawa, ON, Canada. [Picketts, D. J.] Univ Ottawa, Dept Microbiol, Ottawa, ON, Canada. [Picketts, D. J.] Univ Ottawa, Dept Immunol, Ottawa, ON, Canada. [Picketts, D. J.] Ottawa Hosp, Res Inst, Ottawa, ON, Canada. RP Ryu, H (reprint author), Boston Univ, Sch Med, Dept Neurol, VA Boston Healthcare Syst, 150 S Huntington Ave, Boston, MA 02130 USA. EM hoonryu@bu.edu RI Kowall, Neil/G-6364-2012 OI Kowall, Neil/0000-0002-6624-0213 FU NIH [NS 067283-01A1]; WCU [800-20080848]; SRC from NRF [2010-0029-403] FX We thank Dr. Marcy MacDonald for STHdhQ7/7 and STHdhQ111/111 cells and Soung Chan Kim for their technical assistance. This study was supported by NIH NS 067283-01A1 (HR), WCU Neurocytomics Program Grant (800-20080848) (HR), and SRC Grant (2010-0029-403) (HR) from NRF. NR 28 TC 11 Z9 11 U1 2 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD JUL PY 2012 VL 19 IS 7 BP 1109 EP 1116 DI 10.1038/cdd.2011.196 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 959EJ UT WOS:000305295300003 PM 22240898 ER PT J AU Sharma, C Rabinovitz, I Hemler, ME AF Sharma, Chandan Rabinovitz, Isaac Hemler, Martin E. TI Palmitoylation by DHHC3 is critical for the function, expression, and stability of integrin alpha 6 beta 4 SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Article DE Integrin; alpha 6 beta 4; DHHC3; Palmitoylation ID LAMININ-BINDING INTEGRINS; CYSTEINE-RICH DOMAIN; TETRASPANIN PROTEINS; EPIDERMOLYSIS-BULLOSA; MEMBRANE INTERACTIONS; GABA(A) RECEPTORS; BETA-4 INTEGRIN; CELLS; CD151; PHOSPHORYLATION AB The laminin-binding integrin alpha 6 beta 4 plays key roles in both normal epithelial and endothelial cells and during tumor cell progression, metastasis, and angiogenesis. Previous cysteine mutagenesis studies have suggested that palmitoylation of alpha 6 beta 4 protein supports a few integrin-dependent functions and molecular associations. Here we took another approach and obtained strikingly different results. We used overexpression and RNAi knockdown in multiple cell types to identify protein acyl transferase DHHC3 as the enzyme responsible for integrin beta 4 and alpha 6 palmitoylation. Ablation of DHHC3 markedly diminished integrin-dependent cellular cable formation on Matrigel, integrin signaling through Src, and beta 4 phosphorylation on key diagnostic amino acids (S1356 and 1424). However, unexpectedly, and in sharp contrast to prior alpha 6 beta 4 mutagenesis results, knockdown of DHHC3 accelerated the degradation of alpha 6 beta 4, likely due to an increase in endosomal exposure to cathepsin D. When proteolytic degradation was inhibited (by Pepstatin A), rescued alpha 6 beta 4 accumulated intracellularly, but was unable to reach the cell surface. DHHC3 ablation effects were strongly selective for alpha 6 beta 4. Cell-surface levels of similar to 10 other proteins (including alpha 3 beta 1) were not diminished, and the appearance of hundreds of other palmitoylated proteins was not altered. Results obtained here demonstrate a new substrate for the DHHC3 enzyme and provide novel opportunities for modulating alpha 6 beta 4 expression, distribution, and function. C1 [Sharma, Chandan; Hemler, Martin E.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA. [Rabinovitz, Isaac] Beth Israel Deaconess Med Ctr, Dept Pathol, Div Canc Biol & Angiogenesis, Boston, MA 02215 USA. [Rabinovitz, Isaac] Harvard Univ, Sch Med, Boston, MA USA. RP Hemler, ME (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Rm D1430,450 Brookline Ave, Boston, MA 02215 USA. EM martin_hemler@dfci.harvard.edu FU National Institutes of Health [GM38903] FX We thank Dr. Hong-Xing Wang for assistance with confocal microscopy and for providing a control vector. This work was supported by National Institutes of Health Grant GM38903 (to MEH). NR 55 TC 13 Z9 14 U1 0 U2 11 PU SPRINGER BASEL AG PI BASEL PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD JUL PY 2012 VL 69 IS 13 BP 2233 EP 2244 DI 10.1007/s00018-012-0924-6 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 958VH UT WOS:000305268300011 PM 22314500 ER PT J AU Qualls, ML Mooney, MM Camargo, CA Zucconi, T Hooper, DC Pallin, DJ AF Qualls, Munirih L. Mooney, Megan M. Camargo, Carlos A., Jr. Zucconi, Tanya Hooper, David C. Pallin, Daniel J. TI Emergency Department Visit Rates for Abscess Versus Other Skin Infections During the Emergence of Community-Associated Methicillin-Resistant Staphylococcus aureus, 1997-2007 SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID SOFT-TISSUE INFECTIONS; CELLULITIS AB Due to a flaw in the International Classification of Diseases, Ninth Revision, Clinical Modification coding system, epidemiology of skin and soft-tissue infections (SSTIs) has conflated abscess with other SSTIs. We analyzed emergency department visits during 1997-2007, finding that the odds of abscess relative to any other diagnosis increased 11% per year, or 3.1-fold, whereas other SSTIs increased minimally. C1 [Qualls, Munirih L.; Mooney, Megan M.; Pallin, Daniel J.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Zucconi, Tanya] Brigham & Womens Hosp, Ctr Clin Excellence, Boston, MA 02115 USA. [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Hooper, David C.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Pallin, Daniel J.] Childrens Hosp Boston, Div Emergency Med, Boston, MA USA. RP Pallin, DJ (reprint author), 75 Francis St, Boston, MA 02115 USA. EM dpallin@partners.org RI Pallin, Daniel/H-6382-2013 OI Pallin, Daniel/0000-0002-8517-9702 FU Department of Emergency Medicine of Brigham and Women's Hospital FX This study was supported by a seed grant from the Department of Emergency Medicine of Brigham and Women's Hospital. NR 11 TC 24 Z9 28 U1 0 U2 1 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 JUL 1 PY 2012 VL 55 IS 1 BP 103 EP 105 DI 10.1093/cid/cis342 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 956KM UT WOS:000305088500016 PM 22460965 ER PT J AU Armah, KA McGinnis, K Baker, J Gibert, C Butt, AA Bryant, KJ Goetz, M Tracy, R Oursler, KK Rimland, D Crothers, K Rodriguez-Barradas, M Crystal, S Gordon, A Kraemer, K Brown, S Gerschenson, M Leaf, DA Deeks, SG Rinaldo, C Kuller, LH Justice, A Freiberg, M AF Armah, Kaku A. McGinnis, Kathleen Baker, Jason Gibert, Cynthia Butt, Adeel A. Bryant, Kendall J. Goetz, Matthew Tracy, Russell Oursler, Krisann K. Rimland, David Crothers, Kristina Rodriguez-Barradas, Maria Crystal, Steve Gordon, Adam Kraemer, Kevin Brown, Sheldon Gerschenson, Mariana Leaf, David A. Deeks, Steven G. Rinaldo, Charles Kuller, Lewis H. Justice, Amy Freiberg, Matthew TI HIV Status, Burden of Comorbid Disease, and Biomarkers of Inflammation, Altered Coagulation, and Monocyte Activation SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID C-REACTIVE PROTEIN; APPARENTLY HEALTHY-MEN; T-CELL DEPLETION; MYOCARDIAL-INFARCTION; MICROBIAL TRANSLOCATION; DIABETES-MELLITUS; ANTIRETROVIRAL THERAPY; BLOOD-PRESSURE; SOLUBLE CD14; INFECTION AB Background. Biomarkers of inflammation, altered coagulation, and monocyte activation are associated with mortality and cardiovascular disease (CVD) in the general population and among human immunodeficiency virus (HIV)-infected people. We compared biomarkers for inflammation, altered coagulation, and monocyte activation between HIV-infected and uninfected people in the Veterans Aging Cohort Study (VACS). Methods. Biomarkers of inflammation (interleukin-6 [IL-6]), altered coagulation (D-dimer), and monocyte activation (soluble CD14 [sCD14]) were measured in blood samples from 1525 HIV-infected and 843 uninfected VACS participants. Logistic regression was used to determine the association between HIV infection and prevalence of elevated (>75th percentile) biomarkers, adjusting for confounding comorbidities. Results. HIV-infected veterans had less prevalent CVD, hypertension, diabetes, obesity, hazardous drinking, and renal disease, but more dyslipidemia, hepatitis C, and current smoking than uninfected veterans. Compared to uninfected veterans, HIV-infected veterans with HIV-1 RNA >= 500 copies/mL or CD4 count <200 cells/mu L had a significantly higher prevalence of elevated IL-6 (odds ratio [OR], 1.54; 95% confidence interval [CI], 1.14-2.09; OR, 2.25; 95% CI, 1.60-3.16, respectively) and D-dimer (OR, 1.97; 95% CI, 1.44-2.71, OR, 1.68; 95% CI, 1.22-2.32, respectively) after adjusting for comorbidities. HIV-infected veterans with a CD4 cell count <200 cells/mu L had significantly higher prevalence of elevated sCD14 compared to uninfected veterans (OR, 2.60; 95% CI, 1.64-4.14). These associations still persisted after restricting the analysis to veterans without known confounding comorbid conditions. Conclusions. These data suggest that ongoing HIV replication and immune depletion significantly contribute to increased prevalence of elevated biomarkers of inflammation, altered coagulation, and monocyte activation. This contribution is independent of and in addition to the substantial contribution from comorbid conditions. C1 [Armah, Kaku A.; Kuller, Lewis H.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. [Gordon, Adam] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Sch Med, Mental Illness Res Educ & Clin Ctr, Pittsburgh, PA 15260 USA. [Baker, Jason] Univ Minnesota, Dept Med, Hennepin Cty Med Ctr, Minneapolis, MN 55455 USA. [Gibert, Cynthia] VA Med Ctr, Washington, DC USA. [Gibert, Cynthia] George Washington Univ, Med Ctr, Washington, DC 20037 USA. [Butt, Adeel A.] Sheikh Khalifa Med City, Abu Dhabi, U Arab Emirates. [Bryant, Kendall J.] NIAAA, NIH, Bethesda, MD USA. [Goetz, Matthew; Leaf, David A.] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. [Tracy, Russell] Univ Vermont, Dept Pathol, Coll Med, Burlington, VT 05405 USA. [Tracy, Russell] Univ Vermont, Dept Biochem, Coll Med, Burlington, VT 05405 USA. [Oursler, Krisann K.] Univ Maryland, Baltimore VA Med Ctr, Sch Med, Baltimore, MD USA. [Rimland, David] Emory Univ, Sch Med, VA Med Ctr, Atlanta, GA USA. [Crothers, Kristina] Univ Washington, Div Pulm & Crit Care, Dept Internal Med, Seattle, WA 98195 USA. [Rodriguez-Barradas, Maria] Baylor Coll Med, Houston, TX 77030 USA. [Rodriguez-Barradas, Maria] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Crystal, Steve] Rutgers State Univ, Ctr Pharmacotherapy Chron Dis Management & Outcom, Inst Hlth, New Brunswick, NJ 08903 USA. [Crystal, Steve] Rutgers State Univ, Sch Social Work, New Brunswick, NJ 08903 USA. [Gordon, Adam] Univ Pittsburgh, Sch Med, Ctr Hlth Equity Res & Promot, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15260 USA. [Gordon, Adam] Univ Pittsburgh, Sch Med, Ctr Res Healthcare, Pittsburgh, PA 15260 USA. [Kraemer, Kevin] Univ Pittsburgh, Sch Med, Div Gen Internal Med, Pittsburgh, PA 15260 USA. [Brown, Sheldon] Mt Sinai Med Ctr, Dept Internal Med, New York, NY 10029 USA. [Brown, Sheldon] Bronx Vet Affairs Med Ctr, New York, NY USA. [Gerschenson, Mariana] Univ Hawaii Manoa, Hawaii AIDS Clin Res Program, Dept Med, Honolulu, HI 96822 USA. [Gerschenson, Mariana] Univ Hawaii Manoa, John A Burns Sch Med, Honolulu, HI 96822 USA. [Deeks, Steven G.] San Francisco Gen Hosp, Dept Med, Posit Hlth Program, San Francisco, CA 94110 USA. [Rinaldo, Charles] Presbyterian Univ Hosp, Dept Microbiol, Dept Pathol, Pittsburgh, PA USA. [Justice, Amy] Yale Univ, Sch Med, Sect Gen Med, New Haven, CT USA. [Justice, Amy] VA Connecticut Healthcare Syst, West Haven, CT USA. [Freiberg, Matthew] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA. RP Freiberg, M (reprint author), 230 McKee Pl,Ste 623, Pittsburgh, PA 15213 USA. EM freibergms@upmc.edu OI Goetz, Matthew/0000-0003-4542-992X FU National Institute on Alcohol Abuse and Alcoholism (NIAAA); National Heart Lung and Blood Institute (NHLBI) at the National Institutes of Health (NIH) [K23AA015914-0651, R01HC095136-04, 5R01HC095126-04, U10AA013566-10]; NIH/NHLBI/NIAAA; Yale University; US Department of Veterans Affairs (VA) through the University of Pittsburgh FX This work was supported by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and National Heart Lung and Blood Institute (NHLBI) at the National Institutes of Health (NIH; grant numbers K23AA015914-0651, R01HC095136-04, 5R01HC095126-04 to M. F.; and U10AA013566-10 to A. J.).; K. A., K. A. O., A. G., K. K., S. B., S. D., A. J., and M. F. received NIH/NHLBI/NIAAA grant funding for this work. M. G. has received grant funding and support from Yale University for this work. R. T. has received grant funding from the US Department of Veterans Affairs (VA) through the University of Pittsburgh for this work. R. T. owns Haematologic Technologies and has received funding from Tibotec, Merck, and Abbott, none of which pertain to this work. All other authors report no potential conflicts. NR 37 TC 94 Z9 94 U1 1 U2 13 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 JUL 1 PY 2012 VL 55 IS 1 BP 126 EP 136 DI 10.1093/cid/cis406 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 956KM UT WOS:000305088500020 PM 22534147 ER PT J AU Richardson, J Tjoelker, R AF Richardson, Jeannette Tjoelker, Rita TI Beyond the Central Line-Associated Bloodstream Infection Bundle The Value of the Clinical Nurse Specialist in Continuing Evidence-Based Practice Changes SO CLINICAL NURSE SPECIALIST LA English DT Article DE catheter-related infections; evidence-based practice; quality improvement ID NETWORK NHSN REPORT; CRITICALLY-ILL PATIENTS; MORTALITY AB Purpose: The purpose of this project was to demonstrate the value of clinical nurse specialist (CNS)-led efforts to optimize patient outcomes through continued monitoring and management of a previously implemented evidence-based practice project. Background: Central line-associated bloodstream infections (CLABSIs) significantly impact patient morbidity/mortality and cost of care. In 2006, the critical care unit (CCU) of the Portland VA Medical Center implemented national recommendations for the prevention of CLABSIs through use of the Institute of Healthcare Improvement Central Line Bundle. This practice change was led by the CCU and infection control CNSs, and compliance in the completion of bundle items has remained consistently high (>90%). Although the CCU has maintained CLABSI rates below the national benchmark, it experienced a 4-month period of increased incidence in late 2008. Description: Clinical nurse specialists in CCU and infection control organized a "Hot Team" of nurses from multiple departments throughout the hospital to evaluate processes/data related to the recent increase in infections. Using national guidelines, the team focused on interdisciplinary implementation of strategies beyond the Central Line Bundle components. Consideration of cost and workflow patterns was critical to decision making. Outcome: Infection rates in CCU decreased from a high of 1.5 per 1000 line days down to 0 in June 2011, with the last CLABSI occurring in May 2010. Conclusion: The formation and efforts of a CNS-led team of nurses has been successful in decreasing infection rates through implementation of multiple innovative strategies. Implications: Clinical nurse specialist surveillance, management, and leadership following project implementation are valuable strategies for continued optimal patient outcomes. C1 [Richardson, Jeannette; Tjoelker, Rita] Portland VA Med Ctr, Portland, OR 97239 USA. RP Richardson, J (reprint author), Portland VA Med Ctr, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM jeannette.richardson@va.gov NR 17 TC 8 Z9 10 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0887-6274 J9 CLIN NURSE SPEC JI Clin. Nurse Spec. PD JUL-AUG PY 2012 VL 26 IS 4 BP 205 EP 211 DI 10.1097/NUR.0b013e31825aebab PG 7 WC Nursing SC Nursing GA 958YU UT WOS:000305277700006 PM 22678186 ER PT J AU Isakoff, MS Barkauskas, DA Ebb, D Morris, C Letson, GD AF Isakoff, Michael S. Barkauskas, Donald A. Ebb, David Morris, Carol Letson, G. Douglas TI Poor Survival for Osteosarcoma of the Pelvis: A Report from the Children's Oncology Group SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID ADJUVANT CHEMOTHERAPY; MURAMYL TRIPEPTIDE; SURGERY; TRIAL; EXPERIENCE; WINDOW AB The pelvis is an infrequent site of osteosarcoma and treatment requires surgery plus systemic chemotherapy. Poor survival has been reported, but has not been confirmed previously by the Children's Oncology Group (COG). In addition, survival of patients with pelvic osteosarcomas has not been compared directly with that of patients with nonpelvic disease treated on the same clinical trials. First, we assessed the event-free (EFS) and overall survival (OS) of patients with pelvic osteosarcoma treated on COG clinical trials. We then asked whether patient survival compared with that of patients treated on the same clinical trials with nonpelvic disease. Finally, we asked whether patients with metastatic disease at initial diagnosis had worse survival. We retrospectively reviewed data from 1054 patients with osteosarcoma treated in four studies between 1993 and 2005. Twenty-six of the 1054 patients (2.5%) had a primary tumor of the pelvis. At diagnosis, nine patients had metastatic disease. The minimum followup was 2 months (mean, 34 months; range, 2-102 months). Two of the nine patients with metastatic disease at diagnosis and five of the 17 with localized disease were alive at last contact. Estimates of the 5-year EFS for localized versus metastatic disease of the pelvis were 22% versus 23%. OS for patients with localized versus metastatic disease was 47% versus 22%. Patients with osteosarcoma in all other locations had a 5-year EFS of 57% and OS of 69%. Our analysis confirms poor survival for patients with pelvic osteosarcoma. Survival with metastatic disease in the absence of a pelvic primary tumor is similar to that for localized or metastatic pelvic osteosarcoma. Improved surgical or medical therapy is needed, and patients with pelvic osteosarcoma may warrant alternate or experimental therapy. Level II, prognostic study. See Guidelines for Authors for a complete description of levels of evidence. C1 [Isakoff, Michael S.] Connecticut Childrens Med Ctr, Dept Hematol Oncol, Hartford, CT 06106 USA. [Barkauskas, Donald A.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Ebb, David] Massachusetts Gen Hosp, Dept Pediat Hematol Oncol, Boston, MA 02114 USA. [Morris, Carol] Mem Sloan Kettering Canc Ctr, Dept Orthoped Surg, New York, NY 10021 USA. [Letson, G. Douglas] Univ S Florida, H Lee Moffitt Canc Ctr, Div Sarcoma, Tampa, FL 33682 USA. RP Isakoff, MS (reprint author), Connecticut Childrens Med Ctr, Dept Hematol Oncol, 282 Washington St, Hartford, CT 06106 USA. EM misakoff@ccmckids.org FU Children's Oncology Group from the National Cancer Institute, National Institutes of Health, Bethesda, MD, USA [U10 CA98543, U24 CA114766]; WWWW (QuadW) Foundation, Inc FX This research was supported by the Chair's Grant U10 CA98543 and Human Specimen Banking Grant U24 CA114766 of the Children's Oncology Group from the National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Additional support for research is provided by a grant from the WWWW (QuadW) Foundation, Inc (www.QuadW.org) to the Children's Oncology Group. NR 20 TC 13 Z9 17 U1 0 U2 1 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 JUL PY 2012 VL 470 IS 7 BP 2007 EP 2013 DI 10.1007/s11999-012-2284-9 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 958BU UT WOS:000305211800026 PM 22354612 ER PT J AU Buijze, GA Guitton, TG van Dijk, CN Ring, D AF Buijze, Geert A. Guitton, Thierry G. van Dijk, C. Niek Ring, David CA Sci Variation Grp TI Training Improves Interobserver Reliability for the Diagnosis of Scaphoid Fracture Displacement SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID COMPUTED-TOMOGRAPHY; NEER SYSTEM; AGREEMENT; VARIABILITY; RADIOGRAPHS; DEFORMITY; FEATURES; IMPACT; PLANE AB The diagnosis of displacement in scaphoid fractures is notorious for poor interobserver reliability. We tested whether training can improve interobserver reliability and sensitivity, specificity, and accuracy for the diagnosis of scaphoid fracture displacement on radiographs and CT scans. Sixty-four orthopaedic surgeons rated a set of radiographs and CT scans of 10 displaced and 10 nondisplaced scaphoid fractures for the presence of displacement, using a web-based rating application. Before rating, observers were randomized to a training group (34 observers) and a nontraining group (30 observers). The training group received an online training module before the rating session, and the nontraining group did not. Interobserver reliability for training and nontraining was assessed by Siegel's multirater kappa and the Z-test was used to test for significance. There was a small, but significant difference in the interobserver reliability for displacement ratings in favor of the training group compared with the nontraining group. Ratings of radiographs and CT scans combined resulted in moderate agreement for both groups. The average sensitivity, specificity, and accuracy of diagnosing displacement of scaphoid fractures were, respectively, 83%, 85%, and 84% for the nontraining group and 87%, 86%, and 87% for the training group. Assuming a 5% prevalence of fracture displacement, the positive predictive value was 0.23 in the nontraining group and 0.25 in the training group. The negative predictive value was 0.99 in both groups. Our results suggest training can improve interobserver reliability and sensitivity, specificity and accuracy for the diagnosis of scaphoid fracture displacement, but the improvements are slight. These findings are encouraging for future research regarding interobserver variation and how to reduce it further. C1 [Ring, David] Harvard Univ, Orthopaed Hand & Upper Extrem Serv, Massachusetts Gen Hosp, Sch Med,Yawkey Ctr, Boston, MA 02114 USA. [Buijze, Geert A.; Guitton, Thierry G.; van Dijk, C. Niek] Univ Amsterdam, Acad Med Ctr, Orthopaed Res Ctr Amsterdam, Dept Orthopaed Surg, NL-1105 AZ Amsterdam, Netherlands. RP Ring, D (reprint author), Harvard Univ, Orthopaed Hand & Upper Extrem Serv, Massachusetts Gen Hosp, Sch Med,Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org RI Page, Richard/K-6327-2015; OI Page, Richard/0000-0002-2225-7144; Frihagen, Frede/0000-0002-4811-669X; Guitton, Thierry/0000-0002-2599-1985; Ladd, Amy/0000-0003-0948-1034; Soong, Maximillian/0000-0003-0333-8181 FU Netherlands Organisation for Scientific Research, The Hague, The Netherlands FX One of the authors (GAB) has received funding from the Netherlands Organisation for Scientific Research, The Hague, The Netherlands. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research editors and board members are on file with the publication and can be viewed on request. NR 25 TC 14 Z9 15 U1 1 U2 6 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 JUL PY 2012 VL 470 IS 7 BP 2029 EP 2034 DI 10.1007/s11999-012-2260-4 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 958BU UT WOS:000305211800029 PM 22290132 ER PT J AU Cai, WL Lee, JG Fikry, K Yoshida, H Novelline, R de Moya, M AF Cai, Wenli Lee, June-Goo Fikry, Karim Yoshida, Hiroyuki Novelline, Robert de Moya, Marc TI MDCT quantification is the dominant parameter in decision-making regarding chest tube drainage for stable patients with traumatic pneumothorax SO COMPUTERIZED MEDICAL IMAGING AND GRAPHICS LA English DT Article DE Computer-aided volumetry (CAV); Computer-aided diagnosis (CAD); Decision-making; Multi-detector computed tomography (MDCT); Pneumothorax; Chest tube drainage ID OCCULT PNEUMOTHORAX; COMPUTED-TOMOGRAPHY; COMPLICATIONS; THORACOSTOMY; MANAGEMENT AB It is commonly believed that the size of a pneumothorax is an important determinant of treatment decision, in particular regarding whether chest tube drainage (CTD) is required. However, the volumetric quantification of pneumothoraces has not routinely been performed in clinics. In this paper, we introduced an automated computer-aided volumetry (CAV) scheme for quantification of volume of pneumothoraces in chest multi-detect CT (MDCT) images. Moreover, we investigated the impact of accurate volume of pneumothoraces in the improvement of the performance in decision-making regarding CTD in the management of traumatic pneumothoraces. For this purpose, an occurrence frequency map was calculated for quantitative analysis of the importance of each clinical parameter in the decision-making regarding CTD by a computer simulation of decision-making using a genetic algorithm (GA) and a support vector machine (SVM). A total of 14 clinical parameters, including volume of pneumothorax calculated by our CAV scheme, was collected as parameters available for decision-making. The results showed that volume was the dominant parameter in decision-making regarding CTD, with an occurrence frequency value of 1.00. The results also indicated that the inclusion of volume provided the best performance that was statistically significant compared to the other tests in which volume was excluded from the clinical parameters. This study provides the scientific evidence for the application of CAV scheme in MDCT volumetric quantification of pneumothoraces in the management of clinically stable chest trauma patients with traumatic pneumothorax. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Cai, Wenli; Lee, June-Goo; Yoshida, Hiroyuki; Novelline, Robert] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Cai, Wenli; Lee, June-Goo; Fikry, Karim; Yoshida, Hiroyuki; Novelline, Robert; de Moya, Marc] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Fikry, Karim; de Moya, Marc] Massachusetts Gen Hosp, Dept Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. [Novelline, Robert] Massachusetts Gen Hosp, Div Emergency Radiol, Boston, MA 02114 USA. RP Cai, WL (reprint author), Massachusetts Gen Hosp, Dept Radiol, 25 New Chardon St,400C, Boston, MA 02114 USA. EM Cai.Wenli@mgh.harvard.edu FU Harvard Clinical and Translational Science Center [1 UL1 RR025758-01]; National Center for Research Resources FX This research was conducted with the support of grant number 1 UL1 RR025758-01, Harvard Clinical and Translational Science Center, from the National Center for Research Resources. NR 41 TC 4 Z9 4 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-6111 J9 COMPUT MED IMAG GRAP JI Comput. Med. Imaging Graph. PD JUL PY 2012 VL 36 IS 5 BP 375 EP 386 DI 10.1016/j.compmedimag.2012.03.005 PG 12 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 960EC UT WOS:000305369800004 PM 22560899 ER PT J AU Choi, SE Hur, C AF Choi, Sung E. Hur, Chin TI Screening and surveillance for Barrett's esophagus: current issues and future directions SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Review DE Barrett's esophagus; cost-effectiveness; esophageal adenocarcinoma; surveillance ID COST-UTILITY ANALYSIS; ENDOSCOPIC SURVEILLANCE; UPDATED GUIDELINES; ABLATIVE THERAPY; CANCER-RISK; ADENOCARCINOMA; PROGRESSION; DYSPLASIA; HETEROZYGOSITY; DIAGNOSIS AB Purpose of review Our article discusses the current understanding of screening and surveillance options for Barrett's esophagus and emerging concepts that have the potential to improve the effectiveness and cost-effectiveness of surveillance. Recent findings Although endoscopic surveillance of patients with Barrett's esophagus is commonly practiced in order to detect high-grade dysplasia and early esophageal adenocarcinoma ( EAC), the reported incidence of EAC in Barrett's esophagus patients varies widely. Recent studies found the risk of progression from Barrett's esophagus to EAC to be significantly lower than previously reported, raising concerns regarding the limitations of current surveillance strategies. Advances in imaging techniques and their enhanced diagnostic accuracy may improve the value of endoscopic surveillance. Additionally, various efforts are ongoing to identify biomarkers that identify individuals at higher risk of cancer, possibly allowing for individual risk stratification. Summary These new data highlight some of the opportunities to revise and improve surveillance in patients with Barrett's esophagus. The incorporation of new advances such as imaging techniques and biomarkers has the potential to improve the effectiveness and cost-effectiveness of new surveillance regimens. C1 [Choi, Sung E.; Hur, Chin] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Hur, Chin] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Hur, Chin] Harvard Univ, Sch Med, Boston, MA USA. RP Hur, C (reprint author), Massachusetts Gen Hosp, Inst Technol Assessment, 101 Merrimac St,10th Floor, Boston, MA 02114 USA. EM chur@partners.org FU NIH [R01-CA140574, U01-CA152926] FX NIH Grant Support: R01-CA140574 (C.H.); U01-CA152926 (C.H.). NR 35 TC 8 Z9 8 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD JUL PY 2012 VL 28 IS 4 BP 377 EP 381 DI 10.1097/MOG.0b013e328353d58e PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 959RF UT WOS:000305329800013 PM 22508325 ER PT J AU Kharbouch, A Shoeb, A Guttag, J Cash, SS AF Kharbouch, Alaa Shoeb, Ali Guttag, John Cash, Sydney S. TI An algorithm for seizure onset detection using intracranial EEG (vol 22, pg S29, 2011) SO EPILEPSY & BEHAVIOR LA English DT Correction C1 [Kharbouch, Alaa; Guttag, John] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Shoeb, Ali; Cash, Sydney S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Cash, Sydney S.] Harvard Univ, Sch Med, Boston, MA USA. RP Kharbouch, A (reprint author), MIT, Dept Elect Engn & Comp Sci, 32 Vassar St,Room 32-G915, Cambridge, MA 02139 USA. EM aak@mit.edu NR 1 TC 3 Z9 3 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 1525-5050 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD JUL PY 2012 VL 24 IS 3 BP 389 EP 389 DI 10.1016/j.yebeh.2012.04.118 PG 1 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA 958AS UT WOS:000305208900019 ER PT J AU Krajewski, KM Fougeray, R Bellmunt, J Pons, F Schutz, FAB Rosenberg, JE Salhi, Y Choueiri, TK AF Krajewski, Katherine M. Fougeray, Ronan Bellmunt, Joaquim Pons, Francesc Schutz, Fabio A. B. Rosenberg, Jonathan E. Salhi, Yacine Choueiri, Toni K. TI Optimisation of the size variation threshold for imaging evaluation of response in patients with platinum-refractory advanced transitional cell carcinoma of the urothelium treated with vinflunine SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE Advanced bladder cancer; Vinflunine; RECIST 1.0; Tumour shrinkage; Response evaluation ID COMPUTED-TOMOGRAPHY; BLADDER-CANCER; TARGETED THERAPY; SOLID TUMORS; CRITERIA; CT; CHEMOTHERAPY; ATTENUATION; SUNITINIB; RECIST AB Background: Vinflunine (VFL) has been approved in the European Union for second-line treatment of advanced transitional cell carcinoma of the urothelial tract (TCCU) in patients who progress after a platinum based regimen. However, very few patients achieve response by response evaluation criteria in solid tumours (RECIST). Therefore, another 'response' threshold may be more useful than RECIST 1.0 in this setting. Methods: One hundred and seventy nine patients with advanced TCCU treated with second-line VFL therapy had chest Computed Tomography (CT) and abdominal/pelvic CT or MRI performed at baseline and at first follow-up (6 weeks +/- 3 days) after therapy initiation. Tumour measurements and response by RECIST 1.0 were correlated with overall survival (OS). Kaplan-Meier and receiver operating characteristic (ROC) analysis were then used to determine the optimal size threshold to define 'responders'. Impact of adverse prognostic factors including Eastern Cooperative Oncology Group Performance Status (ECOG PS) >0, Hb <10 g/dL, and liver metastases was analysed. Results: Tumour response included 13 partial responses (PR) by RECIST 1.0 and 52 patients with >= 10% decrease in the sum of longest diameters. Responders by RECIST 1.0 did not have a statistically significant improvement in OS, while patients with sum long axis diameter (SLD) reduction of >= 10% had a longer OS than those with SLD reduction of <10%: 11.3 versus 6.9 months (log rank p = 0.0224). ROC analysis yielded >= 10% decrease in SLD as the optimal size change correlating with OS. These results persisted on multivariate analysis. Conclusion: In the study population, a >= 10% reduction in SLD at first follow-up imaging is a better early predictor of outcome than RECIST. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Krajewski, Katherine M.] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. [Krajewski, Katherine M.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Krajewski, Katherine M.; Schutz, Fabio A. B.; Rosenberg, Jonathan E.; Choueiri, Toni K.] Harvard Univ, Sch Med, Boston, MA USA. [Fougeray, Ronan; Salhi, Yacine] Inst Rech Pierre Fabre, Boulogne, France. [Bellmunt, Joaquim; Pons, Francesc] Univ Hosp del Mar, IMIM, Barcelona, Spain. RP Bellmunt, J (reprint author), Hosp del Mar, Med Oncol Serv, IMIM, Solid Tumor Oncol GU & GI, Paseo Maritimo 25-29, Barcelona 08003, Spain. EM JBellmunt@parcdesalutmar.cat FU Pierre-Fabre FX Ronan Fougeray and Yacine Salhi are employees of Pierre-Fabre. Joaquim Bellmunt received honoraria for consultancies and lecture fees from Pierre-Fabre. There are no financial disclosures for the other authors. NR 22 TC 8 Z9 8 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD JUL PY 2012 VL 48 IS 10 BP 1495 EP 1502 DI 10.1016/j.ejca.2011.11.018 PG 8 WC Oncology SC Oncology GA 958ZD UT WOS:000305278600009 PM 22176867 ER PT J AU Dabydeen, DA Jagannathan, JP Ramaiya, N Krajewski, K Schutz, FAB Cho, DC Pedrosa, I Choueiri, TK AF Dabydeen, Donnette A. Jagannathan, Jyothi P. Ramaiya, Nikhil Krajewski, Katherine Schutz, Fabio A. B. Cho, Daniel C. Pedrosa, Ivan Choueiri, Toni K. TI Pneumonitis associated with mTOR inhibitors therapy in patients with metastatic renal cell carcinoma: Incidence, radiographic findings and correlation with clinical outcome SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE Renal cell carcinoma; Temsirolimus; Everolimus; Mammalian target of rapamycin (mTOR) inhibitors; Lung toxicity ID MAMMALIAN TARGET; TEMSIROLIMUS; EVEROLIMUS; EFFICACY; TRIAL AB Background: Mammalian target of rapamycin (mTOR) inhibitors are approved for use in patients with metastatic renal cell carcinoma (mRCC) and are under investigation in several other malignancies. We assessed the incidence, clinical presentation and computed tomography (CT) findings of pneumonitis associated with mTOR inhibitors in mRCC. Correlation between radiological findings of pneumonitis and clinical outcome was also determined. Methods: We retrospectively reviewed the clinical data and serial CT scans from patients with mRCC treated with either temsirolimus or everolimus. Serial chest CT scans were reviewed in consensus, read by two independent radiologists for the presence of pneumonitis, and corresponding clinical data were reviewed for symptoms and clinical outcome. The baseline and follow up CTs were reviewed to assess outcome to therapy. Results: The study population consisted of 46 pts, 21 treated with temsirolimus and 25 with everolimus (M: F 2.5:1; median 63 years, range 31-79 years). CT evidence of pneumonitis was seen in 14/46 pts (30%), at a median of 56 days on mTOR inhibitor treatment (range 31-214 days). Respiratory symptoms at the time of radiographically detected pneumonitis, were observed in 7 pts. Stable disease (SD) by Response Evaluation Criteria in Solid Tumours (RECIST) was achieved in 12/14 pts (86%) who developed radiographic pneumonitis compared to 14/32 (44%) without pneumonitis (p = 0.01) The mean change of tumour long axis size for target lesions by RECIST, normalised for 30 days on therapy was -2.9% in the pneumonitis group and +4.3% in the non-pneumonitis group (p = .002). Conclusions: Preliminary data suggest that pneumonitis may be a marker of stable disease by RECIST and therefore, of therapeutic benefit. Careful patient assessment should be undertaken before the drug is discontinued. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Dabydeen, Donnette A.; Jagannathan, Jyothi P.; Ramaiya, Nikhil; Krajewski, Katherine; Schutz, Fabio A. B.; Choueiri, Toni K.] Harvard Univ, Dana Farber Canc Inst, Brigham & Womens Hosp, Sch Med, Boston, MA 02215 USA. [Cho, Daniel C.; Pedrosa, Ivan] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. RP Choueiri, TK (reprint author), Harvard Univ, Dana Farber Canc Inst, Brigham & Womens Hosp, Sch Med, 450 Brookline Ave, Boston, MA 02215 USA. EM toni_choueiri@dfci.harvard.edu NR 14 TC 37 Z9 39 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD JUL PY 2012 VL 48 IS 10 BP 1519 EP 1524 DI 10.1016/j.ejca.2012.03.012 PG 6 WC Oncology SC Oncology GA 958ZD UT WOS:000305278600012 PM 22483544 ER PT J AU Delforge, M Dhawan, R Robinson, D Meunier, J Regnault, A Esseltine, DL Cakana, A van de Velde, H Richardson, PG Miguel, JFS AF Delforge, Michel Dhawan, Ravinder Robinson, Don, Jr. Meunier, Juliette Regnault, Antoine Esseltine, Dixie-Lee Cakana, Andrew van de Velde, Helgi Richardson, Paul G. San Miguel, Jesus F. TI Health-related quality of life in elderly, newly diagnosed multiple myeloma patients treated with VMP vs. MP: results from the VISTA trial SO EUROPEAN JOURNAL OF HAEMATOLOGY LA English DT Article DE health-related quality of life; multiple myeloma; bortezomib; complete response; EORTC QLQ-C30 ID PREDNISONE PLUS THALIDOMIDE; RANDOMIZED CONTROLLED-TRIAL; LONG-TERM SURVIVAL; BORTEZOMIB-MELPHALAN-PREDNISONE; INTERNATIONAL STAGING SYSTEM; STEM-CELL TRANSPLANTATION; REPORTED OUTCOMES; INITIAL TREATMENT; COMPLETE RESPONSE; ORAL MELPHALAN AB Objectives The phase 3 VISTA study ( NCT00111319) in transplant-ineligible myeloma patients demonstrated superior efficacy with bortezomib-melphalan-prednisone (VMP; nine 6-wk cycles) vs. melphalan-prednisone (MP) but also increased toxicity. Health-related quality of life (HRQoL; exploratory endpoint) was evaluated using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30). The phase 3 VISTA study ( NCT00111319) in transplant-ineligible myeloma patients demonstrated superior efficacy with bortezomib-melphalan-prednisone (VMP; nine 6-wk cycles) vs. melphalan-prednisone (MP) but also increased toxicity. Health-related quality of life (HRQoL; exploratory endpoint) was evaluated using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30). Methods EORTC QLQ-C30 was administered at screening, on day 1 of each cycle, at the end-of-treatment visit, and every 8 wk until progression. EORTC QLQ-C30 scores were evaluated among patients with a valid baseline and at least one post-baseline HRQoL assessment. Results At baseline, domain scores were similar between arms. By cycle 4, mean differences were clinically meaningful for most domains, indicating poorer health status with VMP. From cycle 5 onwards, improvements relative to baseline/MP were observed for all domains with VMP. Mean scores were generally improved by the end-of-treatment assessment vs. baseline in both arms. Among responding patients, mean scores generally improved from time of response to end-of-treatment assessment, substantially driven by patients achieving complete response (CR). Multivariate analysis showed a significant impact of duration of response/CR on improving global health status, pain, and appetite loss scores. Analyses by bortezomib dose intensity indicated better HRQoL in patients receiving lower dose intensity. Conclusions These findings demonstrate clinically meaningful, transitory HRQoL decrements with VMP and relatively lower HRQoL vs. MP during early treatment cycles, associated with the expected additional toxicities. However, HRQoL is not compromised in the long term, recovering by the end-of-treatment visit to be comparable vs. MP. C1 [Delforge, Michel] Univ Hosp Leuven, Dept Hematol, B-3000 Louvain, Belgium. [Dhawan, Ravinder; Robinson, Don, Jr.] Janssen Global Serv, Raritan, NJ USA. [Meunier, Juliette; Regnault, Antoine] MAPI Consultancy, Lyon, France. [Esseltine, Dixie-Lee] Millennium Pharmaceut Inc, Cambridge, MA USA. [Cakana, Andrew] Janssen Res & Dev, Oncol R&D, High Wycombe, Bucks, England. [van de Velde, Helgi] Janssen Res & Dev, Oncol R&D, Beerse, Belgium. [Richardson, Paul G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [San Miguel, Jesus F.] Hosp Univ Salamanca, CIC, IBMCC USAL CSIC, Salamanca, Spain. RP Delforge, M (reprint author), Univ Hosp Leuven, Dept Hematol, Herestr 49, B-3000 Louvain, Belgium. EM michel.delforge@uzleuven.be OI SAN MIGUEL, JESUS/0000-0002-9183-4857 FU Millennium Pharmaceuticals, Inc.; Janssen Global Services; Millennium Pharmaceuticals; Janssen Research Development FX The authors would like to acknowledge Jane Saunders, Stephen Mosley, and Steve Hill of FireKite for writing assistance in the development of this manuscript, which was funded by Millennium Pharmaceuticals, Inc., and Janssen Global Services. Kathleen Rosa, PhD, from MAPI Values Boston MA (USA) provided valuable methodological guidance early in the analysis plan. Most of all, the authors thank the patients for their participation in the study and willingness to share their perceptions of health with the researchers.; MD: consultancy and honoraria with Janssen-Cilag, Celgene, and Novartis. RD: employment and ownership interest with Johnson & Johnson. DR: employment and ownership interest with Johnson & Johnson. JM: employment with MAPI Consultancy. AR: employment with MAPI Consultancy. D-LE: employment with Millennium Pharmaceuticals, and ownership interest with Johnson & Johnson and Millennium/Takeda. AC: employment with Johnson & Johnson. HvdV: employment and ownership interest with Johnson & Johnson. PGR: research funding from Millennium Pharmaceuticals, and membership of advisory boards for Millennium Pharmaceuticals, Celgene, Bristol-Myers Squibb, Johnson & Johnson, and Keryx Pharmaceuticals. JSM: honoraria and membership with Celgene, Millennium Pharmaceuticals, and Janssen-Cilag.; Research supported by Janssen Research & Development and Millennium Pharmaceuticals, Inc. Writing assistance was provided by Jane Saunders, Stephen Mosley, and Steve Hill of FireKite, who are professional medical writers, in the development of this manuscript, which was funded by Millennium Pharmaceuticals, Inc., and Janssen Global Services. NR 50 TC 22 Z9 23 U1 0 U2 4 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 JUL PY 2012 VL 89 IS 1 BP 16 EP 27 DI 10.1111/j.1600-0609.2012.01788.x PG 12 WC Hematology SC Hematology GA 958ZV UT WOS:000305280400003 PM 22469559 ER PT J AU Gopalakrishnan, L Kumar, V Kohli, P Singh, P Rastogi, U Gibson, CM AF Gopalakrishnan, Lakshmi Kumar, Varun Kohli, Payal Singh, Priyamvada Rastogi, Ujjwal Gibson, C. Michael TI Pharmacokinetic evaluation of rivaroxaban for the treatment of acute coronary syndromes SO EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY LA English DT Review DE acute coronary syndrome; BAY 59-7939; pharmacokinetics; rivaroxaban; venous thromboembolism ID FACTOR-XA INHIBITOR; TOTAL KNEE ARTHROPLASTY; TOTAL HIP-REPLACEMENT; DEEP-VEIN THROMBOSIS; VENOUS THROMBOEMBOLISM; ATRIAL-FIBRILLATION; HEALTHY-SUBJECTS; BAY 59-7939; MYOCARDIAL-INFARCTION; IN-VITRO AB Introduction: Arterial and venous thrombotic states, including myocardial infarction (MI), stroke and deep vein thrombosis with subsequent pulmonary embolism, are a significant cause of cardiovascular mortality and morbidity. Factor Xa (FXa) plays a pivotal role in thrombus formation. Its inhibition following acute coronary syndromes (ACS) blocks amplification of thrombin generation and subsequent clot formation, resulting in a risk reduction in recurrent MI, stroke and death. For this reason, a predictable form of oral anticoagulation continues to be an ongoing need. Rivaroxaban, the first oral FXa inhibitor, acts by direct inhibition of FXa and does not require an antithrombin cofactor for its activity. Areas covered: This paper describes the pharmacokinetics (PK) of low-dose rivaroxaban tested in patients with ACS. Age, gender, renal function and body weight have no clinically significant effects on the PK of the drug in treatment of ACS. Caution should be maintained during co-administration of strong CYP3A4 inducers and inhibitors. Among patients with moderate and severe hepatic impairment and in those with associated coagulopathies, rivaroxaban however is contraindicated. Expert opinion: The mortality benefit with low-dose rivaroxaban in ACS patients was first demonstrated in ATLAS ACS2 TIMI-51 trial. With its rapid oral bioavailability, predictable PK, low drug-drug interaction and no need for monitoring, the use of low-dose rivaroxaban in addition to dual antiplatelet therapy offers an appealing new option in improving outcomes following ACS in the modern era of novel oral FXa inhibitors. C1 [Gopalakrishnan, Lakshmi; Kumar, Varun; Singh, Priyamvada; Rastogi, Ujjwal; Gibson, C. Michael] Harvard Univ, Beth Israel Deaconess Med Ctr, PERFUSE Study Grp, Med Sch,Cardiovasc Div,Dept Med, Boston, MA 02115 USA. [Kohli, Payal] Harvard Univ, Brigham & Womens Hosp, TIMI Study Grp, Med Sch,Cardiovasc Div,Dept Med, Boston, MA 02115 USA. RP Gibson, CM (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, PERFUSE Study Grp, Med Sch,Cardiovasc Div,Dept Med, 185 Pilgrim Rd,Deaconess 319, Boston, MA 02115 USA. EM mgibson@perfuse.org FU Johnson Johnson; Bayer Corp.; Abbott; Angel Medical Corp.; Baxter Healthcare; Genentech, Inc.; Ikaria, Inc.; Lantheus Medical Imaging; Merck Co.; Roche Diagnostics; Sanofi-Aventis; Vocano Corp.; Walk Vascular; ActivBiotics, Inc.; Acusphere, Inc.; Ascenta Therapeutics; Angel Medical Systems; AstraZeneca; Atrium Medical Corp.; Bard Corp.; Biogen Idec; Boston Scientific Corp.; Bristol-Meyers-Squibb; British Biotech; Cardica, Inc.; CardioKinetix; Ciba Geigy Corp.; COR Therapeutics; Corgentech, Inc.; DVI Guidant Corp.; Eli Lilly Co.; FibroGen; FoldRx; Genentech; GlaxoSmithKline; Heartscape Technologies; INO Therapeutics LLC.; Jim Moran Heart and Vasc Research Institute; KAI Pharmaceuticals; Medicure, Inc.; Millennium Pharmaceuticals; Momenta Pharmaceuticals; NIH; Novartis; Nvelo; Otsuko Pharmaceuticals; PDL Pharmaceuticals; Percusurge, Inc.; Pfizer; Point Biomedical Corp.; Portola Pharmaceuticals, Inc.; SmithKlineBeecham; Sonus; St Jude Medical; Medicines Co.; Timi3 Systems, Inc.; Archemix Corp.; Schering-Plough Corp. FX This paper was funded by research grant support from Johnson & Johnson and Bayer Corp. CM Gibson also declares research grant funding from Abbott, Angel Medical Corp., Baxter Healthcare, Bayer Corp., Genentech, Inc., Ikaria, Inc., Johnson & Johnson, Lantheus Medical Imaging, Merck & Co., Roche Diagnostics, Sanofi-Aventis, Vocano Corp. and Walk Vascular. He also declares peer-to-peer communications with Daiichi Sankyo, Eli Lily & Co. and the Medicines Co. Furthermore, he is currently a consultant for Bayer Corp., Biogen Idec, Bristol-Meyer-Squibb, Daiichi Sankyo, CSL Behring, Eli Lilly & Co., GlaxoSmithKline, Genentech, Ischemix, Johnson & Johnson, Merck & Co., Ortho McNeil, Portola Pharmaceuticals, Inc., Regado Biosciences, Sanofi-Aventis, St Jude Medical and the Medicines Co. He has also received royalties from Pocket Medicine and UpToDate. In the past, he also received research/grant funding/speaker's bureau/consultancy funding from ActivBiotics, Inc., Acusphere, Inc., Ascenta Therapeutics, Angel Medical Systems, AstraZeneca, Atrium Medical Corp., Bard Corp., Biogen Idec, Boston Scientific Corp., Bristol-Meyers-Squibb, British Biotech, Cardica, Inc., CardioKinetix, Ciba Geigy Corp., COR Therapeutics, Corgentech, Inc., DVI Guidant Corp., Eli Lilly & Co., FibroGen, FoldRx, Genentech, GlaxoSmithKline, Heartscape Technologies, INO Therapeutics LLC., Jim Moran Heart and Vasc Research Institute, KAI Pharmaceuticals, Medicure, Inc., Merck & Co., Millennium Pharmaceuticals, Momenta Pharmaceuticals, NIH, Novartis, Nvelo, Otsuko Pharmaceuticals, PDL Pharmaceuticals, Percusurge, Inc., Pfizer, Point Biomedical Corp., Portola Pharmaceuticals, Inc., Sanofi-Aventis, SmithKlineBeecham, Sonus, St Jude Medical and the Medicines Co., Timi3 Systems, Inc. Archemix Corp. and Schering-Plough Corp. NR 72 TC 2 Z9 2 U1 0 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1742-5255 EI 1744-7607 J9 EXPERT OPIN DRUG MET JI Expert Opin. Drug Metab. Toxicol. PD JUL PY 2012 VL 8 IS 7 BP 889 EP 900 DI 10.1517/17425255.2012.688026 PG 12 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 959CB UT WOS:000305286600008 PM 22577900 ER PT J AU Kim, S Millard, SP Yu, CE Leong, L Radant, A Dobie, D Tsuang, DW Wijsman, EM AF Kim, Sulgi Millard, Steven P. Yu, Chang-En Leong, Lesley Radant, Allen Dobie, Dorcas Tsuang, Debby W. Wijsman, Ellen M. TI Inheritance Model Introduces Differential Bias in CNV Calls Between Parents and Offspring SO GENETIC EPIDEMIOLOGY LA English DT Article DE Schizophrenia; calling algorithm; family-based study; CNV burden ID COPY NUMBER VARIATION; BIPOLAR-DISORDER; INCREASE RISK; SCHIZOPHRENIA; ASSOCIATION; DELETIONS; DISEASE AB Copy Number Variation (CNV) is increasingly implicated in disease pathogenesis. CNVs are often identified by statistical models applied to data from single nucleotide polymorphism panels. Family information for samples provides additional information for CNV inference. Two modes of PennCNV (the Joint-call and Posterior-call), which are some of the most well-developed family-based CNV calling methods, use a Joint-model as a main component. This models all family members CNV states together with Mendelian inheritance. Methods based on the Joint-model are used to infer CNV calls of cases and controls in a pedigree, which may be compared to each other to test an association. Although benefits from the Joint-model have been shown elsewhere, equality of call rates in parents and offspring has not been evaluated previously. This can affect downstream analyses in studies that compare CNV rates in cases vs. controls in pedigrees. In this paper, we show that the Joint-model can introduce different CNV call rates among family members in the absence of a true difference. We show that the Joint-model may analytically introduce differential CNV calls because of asymmetry of the model. We demonstrate these differential call rates using single-marker simulations. We show that call rates using the two modes of PennCNV also differ between parents and offspring in one multimarker simulated dataset and two real datasets. Our results advise need for caution in use of the Joint-model calls in CNV association studies with family-based datasets. Genet. Epidemiol. 36:488-498, 2012. (C) 2012 Wiley Periodicals, Inc. C1 [Wijsman, Ellen M.] Univ Washington, Sch Med, Dept Med, Div Med Genet, Seattle, WA 98195 USA. [Millard, Steven P.; Tsuang, Debby W.] Vet Affairs Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. [Yu, Chang-En] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Yu, Chang-En] Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA USA. [Leong, Lesley; Radant, Allen; Dobie, Dorcas; Tsuang, Debby W.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Wijsman, Ellen M.] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA. [Wijsman, Ellen M.] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA USA. RP Wijsman, EM (reprint author), Univ Washington, Sch Med, Dept Med, Div Med Genet, Box 357720, Seattle, WA 98195 USA. EM wijsman@u.washington.edu RI Tsuang, Debby/L-7234-2016; OI Tsuang, Debby/0000-0002-4716-1894; Wijsman, Ellen/0000-0002-2725-6669 FU NIH [R01MH065558, R01MH065554]; U.S. Department of Veterans Affairs, Office of Research Development Biomedical Laboratory Research FX This work is supported by NIH: R01MH065558 and R01MH065554; the U.S. Department of Veterans Affairs, Office of Research Development Biomedical Laboratory Research: Merit Review; and VISN-20 MIRECC. We thank Jeremy Silverman and Larry Siever for contributing schizophrenia trios, and the NIMH Genetics Initiative on schizophrenia for providing DNA sample. The funding agencies did not play a role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 36 TC 2 Z9 2 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD JUL PY 2012 VL 36 IS 5 BP 488 EP 498 DI 10.1002/gepi.21643 PG 11 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 956YP UT WOS:000305125800008 PM 22628073 ER PT J AU Samson, F Mottron, L Soulieres, I Zeffiro, TA AF Samson, Fabienne Mottron, Laurent Soulieres, Isabelle Zeffiro, Thomas A. TI Enhanced visual functioning in autism: An ALE meta-analysis SO HUMAN BRAIN MAPPING LA English DT Review DE hyperlexia; reading; fMRI; vision; perception; enhanced perceptual functioning model; expertise; plasticity ID FUSIFORM FACE AREA; EVENT-RELATED FMRI; VENTROLATERAL PREFRONTAL CORTEX; POSITRON-EMISSION-TOMOGRAPHY; HUMAN EXTRASTRIATE CORTEX; FIGURES TASK-PERFORMANCE; PRIMATE FRONTAL-CORTEX; HUMAN NEURAL SYSTEM; SPECTRUM DISORDERS; WORKING-MEMORY AB Autistics often exhibit enhanced perceptual abilities when engaged in visual search, visual discrimination, and embedded figure detection. In similar fashion, while performing a range of perceptual or cognitive tasks, autistics display stronger physiological engagement of the visual system than do non-autistics. To account for these findings, the Enhanced Perceptual Functioning Model proposes that enhanced autistic performance in basic perceptual tasks results from stronger engagement of sensory processing mechanisms, a situation that may facilitate an atypically prominent role for perceptual mechanisms in supporting cognition. Using quantitative meta-analysis of published functional imaging studies from which Activation Likelihood Estimation maps were computed, we asked whether autism is associated with enhanced task-related activity for a broad range of visual tasks. To determine whether atypical engagement of visual processing is a general or domain-specific phenomenon, we examined three different visual processing domains: faces, objects, and words. Overall, we observed more activity in autistics compared to non-autistics in temporal, occipital, and parietal regions. In contrast, autistics exhibited less activity in frontal cortex. The spatial distribution of the observed differential between-group patterns varied across processing domains. Autism may be characterized by enhanced functional resource allocation in regions associated with visual processing and expertise. Atypical adult organizational patterns may reflect underlying differences in developmental neural plasticity that can result in aspects of the autistic phenotype, including enhanced visual skills, atypical face processing, and hyperlexia. Hum Brain Mapp, 2011 (C) 2011 Wiley-Liss, Inc. C1 [Samson, Fabienne; Mottron, Laurent; Soulieres, Isabelle] Univ Montreal CETEDUM, Ctr Excellence Troubles Envahissants Dev, Montreal, PQ, Canada. [Soulieres, Isabelle; Zeffiro, Thomas A.] Massachusetts Gen Hosp, Neural Syst Grp, Boston, MA 02114 USA. RP Zeffiro, TA (reprint author), Massachusetts Gen Hosp, Neural Syst Grp, Room 10-033,Bldg 149,13th St, Charlestown, MA 02119 USA. EM zeffiro@neurometrika.org FU Autism Speaks [2706]; Natural Sciences and Engineering Research Council of Canada; Canadian Institutes for Health Research; Fonds de la Recherche en Sante du Quebec FX Contract grant sponsor: Autism Speaks; Contract grant number: 2706; Contract grant sponsors: Natural Sciences and Engineering Research Council of Canada; Canadian Institutes for Health Research; Fonds de la Recherche en Sante du Quebec. NR 160 TC 83 Z9 84 U1 17 U2 67 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD JUL PY 2012 VL 33 IS 7 BP 1553 EP 1581 DI 10.1002/hbm.21307 PG 29 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 956ZK UT WOS:000305127900005 PM 21465627 ER PT J AU Zhang, XY Chen, DC Xiu, MH Haile, CN Luo, XG Xu, K Zhang, HP Zuo, LJ Zhang, ZJ Zhang, XR Kosten, TA Kosten, TR AF Zhang, Xiang Yang Chen, Da Chun Xiu, Mei Hong Haile, Colin N. Luo, Xingguang Xu, Ke Zhang, Hui Ping Zuo, Lingjun Zhang, Zhijun Zhang, Xiangrong Kosten, Therese A. Kosten, Thomas R. TI Cognitive and serum BDNF correlates of BDNF Val66Met gene polymorphism in patients with schizophrenia and normal controls SO HUMAN GENETICS LA English DT Article ID ACTIVITY-DEPENDENT SECRETION; NEUROTROPHIC FACTOR GENE; LONG-TERM-MEMORY; NEUROPSYCHOLOGICAL STATUS; REPEATABLE BATTERY; BIPOLAR DISORDER; CHINESE-HAN; MET ALLELE; BRAIN; ASSOCIATION AB Studies suggest that a functional polymorphism of the brain-derived neurotrophic factor gene (BDNF Val66Met) may mediate hippocampal-dependent cognitive functions. A few studies have reported its role in cognitive deficits in schizophrenia including its association with peripheral BDNF levels as a mediator of these cognitive deficits. We assessed 657 schizophrenic inpatients and 445 healthy controls on the repeatable battery for the assessment of neuropsychological status (RBANS), the presence of the BDNF Val66Met polymorphism and serum BDNF levels. We assessed patient psychopathology using the Positive and Negative Syndrome Scale. We showed that visuospatial/constructional abilities significantly differed by genotype but not genotype x diagnosis, and the Val allele was associated with better visuospatial/constructional performance in both schizophrenic patients and healthy controls. Attention performance showed a significant genotype by diagnosis effect. Met allele-associated attention impairment was specific to schizophrenic patients and not shown in healthy controls. In the patient group, partial correlation analysis showed a significant positive correlation between serum BDNF and the RBANS total score. Furthermore, the RBANS total score showed a statistically significant BDNF level x genotype interaction. We demonstrated an association between the BDNF Met variant and poor visuospatial/constructional performance. Furthermore, the BDNF Met variant may be specific to attentional decrements in schizophrenic patients. The association between decreased BDNF serum levels and cognitive impairment in schizophrenia is dependent on the BDNF Val66Met polymorphism. C1 [Zhang, Xiang Yang; Kosten, Thomas R.] VA Med Ctr, Houston, TX 77030 USA. [Zhang, Xiang Yang; Haile, Colin N.; Kosten, Therese A.; Kosten, Thomas R.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Chen, Da Chun; Xiu, Mei Hong] Beijing HuiLongGuan Hosp, Ctr Psychiat Res, Beijing, Peoples R China. [Luo, Xingguang; Xu, Ke; Zhang, Hui Ping; Zuo, Lingjun] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Zhang, Zhijun; Zhang, Xiangrong] Southeast Univ, Dept Neurol, Affiliated ZhongDa Hosp, Nanjing, Peoples R China. RP Zhang, XY (reprint author), VA Med Ctr, Res Bldg 109,Room 130,2002 Holcombe Blvd, Houston, TX 77030 USA. EM xyzhang@bcm.edu; kosten@bcm.edu OI Haile, Colin/0000-0001-8293-7291 FU Stanley Medical Research Institute [03T-459, 05T-726]; Department of Veterans Affairs, VISN 16, Mental Illness Research, Education and Clinical Center (MIRECC), United States National Institute of Health [K05-DA0454, P50-DA18827, U01-MH79639] FX This study was funded by the Stanley Medical Research Institute (03T-459 and 05T-726), and the Department of Veterans Affairs, VISN 16, Mental Illness Research, Education and Clinical Center (MIRECC), United States National Institute of Health K05-DA0454, P50-DA18827 and U01-MH79639. NR 51 TC 34 Z9 35 U1 2 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD JUL PY 2012 VL 131 IS 7 BP 1187 EP 1195 DI 10.1007/s00439-012-1150-x PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 957VV UT WOS:000305195400017 PM 22362486 ER PT J AU Sonnenberg, A Walker, JT AF Sonnenberg, Amnon Walker, James T. TI Occupational mortality associated with inflammatory bowel disease in the United States 1984-1998 SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE Crohn's disease; environmental risk factors; epidemiology; industry; occupation; occupational mortality statistics; proportional mortality ratio; ulcerative colitis ID CROHNS-DISEASE; ULCERATIVE-COLITIS AB Background: The occurrence of Crohn's disease (CD) and ulcerative colitis (UC) is shaped by environmental influences. Many such environmental risk factors vary potentially with occupational exposure. We used a large national database to study the occupational variation of mortality associated with CD and UC. Methods: The National Occupational Mortality Surveillance database contains data from the death certificate linked with information about the occupation and industry of each deceased individual. Deaths were grouped by gender, ethnicity, disease type, occupation, and industry. Mortality by occupation and industry were expressed as age-adjusted proportional mortality ratio. Results: A total of 3110 inflammatory bowel disease (IBD) patients were included in the present analysis. IBD mortality was low among blue collar workers and high among white collar workers. It was low among farming occupations, manufacturing occupations, and manual laborers. It was high among secretaries, professionals, sales workers, homemakers, managerial occupations, and teachers. There was a strong correlation between the occupational distribution of CD and UC that applied to men and women alike. The overall distribution among different industries corroborated the patterns observed with respect to the occupational distribution. Conclusions: The correlations between the occupational distribution of CD and UC support the contention that environmental influences shape the occurrence of both diseases. Such influence must vary by occupation and, to a lesser extent, also by industry. It must be similar for both types of IBD. (Inflamm Bowel Dis 2011;) C1 [Sonnenberg, Amnon] Dept Vet Affairs Med Ctr, Portland, OR USA. [Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Walker, James T.] NIOSH, Cincinnati, OH 45226 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 17 TC 4 Z9 4 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD JUL PY 2012 VL 18 IS 7 BP 1249 EP 1253 DI 10.1002/ibd.21807 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 956IP UT WOS:000305083600010 PM 21710539 ER PT J AU De Silva, P Ananthakrishnan, AN AF De Silva, Punyanganie Ananthakrishnan, Ashwin N. TI Vitamin D and IBD: More pieces to the puzzle, still no complete picture SO INFLAMMATORY BOWEL DISEASES LA English DT Editorial Material ID RECEPTOR GENE POLYMORPHISM; INFLAMMATORY-BOWEL-DISEASE; D-BINDING PROTEIN; CROHNS-DISEASE; ASSOCIATION C1 [De Silva, Punyanganie; Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA USA. RP De Silva, P (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 14 TC 1 Z9 1 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD JUL PY 2012 VL 18 IS 7 BP 1391 EP 1393 DI 10.1002/ibd.22854 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 956IP UT WOS:000305083600025 PM 22180018 ER PT J AU Bekelman, JE Deye, JA Vikram, B Bentzen, SM Bruner, D Curran, WJ Dignam, J Efstathiou, JA FitzGerald, TJ Hurkmans, C Ibbott, GS Lee, JJ Merchant, TE Michalski, J Palta, JR Simon, R Ten Haken, RK Timmerman, R Tunis, S Coleman, CN Purdy, J AF Bekelman, Justin E. Deye, James A. Vikram, Bhadrasain Bentzen, Soren M. Bruner, Deborah Curran, Walter J., Jr. Dignam, James Efstathiou, Jason A. FitzGerald, T. J. Hurkmans, Coen Ibbott, Geoffrey S. Lee, J. Jack Merchant, Thomas E. Michalski, Jeff Palta, Jatinder R. Simon, Richard Ten Haken, Randal K. Timmerman, Robert Tunis, Sean Coleman, C. Norman Purdy, James TI Redesigning Radiotherapy Quality Assurance: Opportunities to Develop an Efficient, Evidence-Based System to Support Clinical Trials-Report of the National Cancer Institute Work Group on Radiotherapy Quality Assurance SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Review DE Clinical trial design; Credentialing; Radiotherapy; Quality assurance ID PEDIATRIC-ONCOLOGY-GROUP; RADIATION-THERAPY; DOSIMETRY; IMPACT AB Purpose: In the context of national calls for reorganizing cancer clinical trials, the National Cancer Institute sponsored a 2-day workshop to examine challenges and opportunities for optimizing radiotherapy quality assurance (QA) in clinical trial design. Methods and Materials: Participants reviewed the current processes of clinical trial QA and noted the QA challenges presented by advanced technologies. The lessons learned from the radiotherapy QA programs of recent trials were discussed in detail. Four potential opportunities for optimizing radiotherapy QA were explored, including the use of normal tissue toxicity and tumor control metrics, biomarkers of radiation toxicity, new radiotherapy modalities such as proton beam therapy, and the international harmonization of clinical trial QA. Results: Four recommendations were made: (1) to develop a tiered (and more efficient) system for radiotherapy QA and tailor the intensity of QA to the clinical trial objectives (tiers include general credentialing, trial-specific credentialing, and individual case review); (2) to establish a case QA repository; (3) to develop an evidence base for clinical trial QA and introduce innovative prospective trial designs to evaluate radiotherapy QA in clinical trials; and (4) to explore the feasibility of consolidating clinical trial QA in the United States. Conclusion: Radiotherapy QA can affect clinical trial accrual, cost, outcomes, and generalizability. To achieve maximum benefit, QA programs must become more efficient and evidence-based. (C) 2012 Elsevier Inc. C1 [Bekelman, Justin E.; Bruner, Deborah] Univ Penn, Philadelphia, PA 19104 USA. [Deye, James A.; Vikram, Bhadrasain; Coleman, C. Norman] NCI, Bethesda, MD 20892 USA. [Bentzen, Soren M.] Univ Wisconsin, Madison, WI USA. [Curran, Walter J., Jr.] Emory Univ, Atlanta, GA 30322 USA. [Dignam, James] Univ Chicago, Chicago, IL 60637 USA. [Efstathiou, Jason A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [FitzGerald, T. J.] Univ Massachusetts, Boston, MA 02125 USA. [Hurkmans, Coen] European Org Res Treatment Canc, Brussels, Belgium. [Ibbott, Geoffrey S.; Lee, J. Jack] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Merchant, Thomas E.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. [Michalski, Jeff] Washington Univ, St Louis, MO USA. [Palta, Jatinder R.] Univ Florida, Miami, FL USA. [Simon, Richard] NIH, Bethesda, MD 20892 USA. [Ten Haken, Randal K.] Univ Michigan, Ann Arbor, MI 48109 USA. [Timmerman, Robert] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Tunis, Sean] Ctr Med Technol Policy, Baltimore, MD USA. [Purdy, James] Univ Calif Davis, Davis, CA 95616 USA. RP Bekelman, JE (reprint author), Univ Penn, 3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM bekelman@uphs.upenn.edu RI Bentzen, Soren/E-3997-2012; Timmerman, Robert/C-2222-2013 OI Bentzen, Soren/0000-0002-7444-7564; FU National Institutes of Health; National Cancer Institute Radiation Research Program FX Dr. Fitzgerald received National Institutes of Health funding to his institution to support the Quality Assurance Review Center. Dr. Michalski received National Institutes of Health funding to his institution to support the Advanced Technology Consortium.; We acknowledge the support of the National Cancer Institute Radiation Research Program in sponsoring the conference. We are grateful to the anonymous reviewers for constructive comments that improved the report. NR 21 TC 25 Z9 25 U1 0 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUL 1 PY 2012 VL 83 IS 3 BP 782 EP 790 DI 10.1016/j.ijrobp.2011.12.080 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 958QR UT WOS:000305256000025 PM 22425219 ER PT J AU Hattangadi, JA Powell, SN MacDonald, SM Mauceri, T Ancukiewicz, M Freer, P Lawenda, B El-Din, MAA Gadd, MA Smith, BL Taghian, AG AF Hattangadi, Jona A. Powell, Simon N. MacDonald, Shannon M. Mauceri, Thomas Ancukiewicz, Marek Freer, Phoebe Lawenda, Brian El-Din, Mohamed A. Alm Gadd, Michele A. Smith, Barbara L. Taghian, Alphonse G. TI Accelerated Partial Breast Irradiation With Low-Dose-Rate Interstitial Implant Brachytherapy After Wide Local Excision: 12-Year Outcomes From a Prospective Trial SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 53rd Annual Meeting of the American-Society-for-Radiation-Oncology CY OCT 01-06, 2011 CL Miami Beach, FL SP Amer Soc Radiat Oncol DE Accelerated partial breast irradiation; Implant brachytherapy; Early-stage breast cancer; Low-dose-rate; Long-term cosmesis ID PHASE-II TRIAL; RADIATION-THERAPY; LATE TOXICITY; FOLLOW-UP; CANCER; LUMPECTOMY; PATTERNS AB Purpose: To evaluate the long-term toxicity, cosmesis, and local control of accelerated partial breast irradiation with implant brachytherapy after wide local excision for Stage T1N0 breast cancer (BCa). Materials and Methods: Between 1997 and 2001, 50 patients with Stage T1N0M0 BCa were treated in a Phase I-II protocol using low-dose-rate accelerated partial breast irradiation with implant brachytherapy after wide local excision and lymph node surgery. The total dose was escalated in three groups: 50 Gy (n = 20), 55 Gy (n = 17), and 60 Gy (n = 13). Patient-and physician-assessed breast cosmesis, patient satisfaction, toxicity, mammographic abnormalities, repeat biopsies, and disease status were prospectively evaluated at each visit. Kendall's tau (iota(beta)) and logistic regression analyses were used to correlate outcomes with dose, implant volume, patient age, and systemic therapy. Results: The median follow-up period was 11.2 years (range, 4-14). The patient satisfaction rate was 67%, 67% reported good-excellent cosmesis, and 54% had moderate-severe fibrosis. Higher dose was correlated with worse cosmetic outcome (iota(beta) 0.6, p < .0001), lower patient satisfaction (iota(beta) 0.5, p < .001), and worse fibrosis (iota(beta) 0.4, p = .0024). Of the 50 patients, 35% had fat necrosis and 34% developed telangiectasias >= 1 cm(2). Grade 3-4 late skin and subcutaneous toxicities were seen in 4 patients (9%) and 6 patients (13%), respectively, and both correlated with higher dose (iota(beta) 0.3-0.5, p <= .01). One patient had Grade 4 skin ulceration and fat necrosis requiring surgery. Mammographic abnormalities were seen in 32% of the patients, and 30% underwent repeat biopsy, of which 73% were benign. Six patients had ipsilateral breast recurrence: five elsewhere in the breast, and one at the implant site. One patient died of metastatic BCa after recurrence. The 12- year actuarial local control, recurrence- free survival, and overall survival rate was 85% ( 95% confidence interval, 70-97%), 72% ( 95% confidence interval, 54-86%), and 87% ( 95% confidence interval, 73-99%), respectively. Conclusion: Low-dose-rate accelerated partial breast irradiation with implant brachytherapy provides acceptable local control in select early-stage BCa patients. However, treatment-related toxicity and cosmetic complications were significant with longer follow-up and at higher doses. (C) 2012 Elsevier Inc. C1 [MacDonald, Shannon M.; Mauceri, Thomas; Ancukiewicz, Marek; Taghian, Alphonse G.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Hattangadi, Jona A.] Harvard Radiat Oncol Program, Boston, MA USA. [Powell, Simon N.; El-Din, Mohamed A. Alm] Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10021 USA. [Freer, Phoebe] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Gadd, Michele A.; Smith, Barbara L.] Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02114 USA. [El-Din, Mohamed A. Alm] Tanta Univ Hosp, Dept Clin Oncol, Tanta, Egypt. [Lawenda, Brian] 21st Century Oncol, Las Vegas, NV USA. RP Taghian, AG (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St, Boston, MA 02114 USA. EM ataghian@partners.org OI Freer, Phoebe/0000-0001-6886-7100 FU NCI NIH HHS [P50 CA089393, P50CA089393, R01 CA139118, R01CA139118] NR 20 TC 22 Z9 22 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUL 1 PY 2012 VL 83 IS 3 BP 791 EP 800 DI 10.1016/j.ijrobp.2011.09.003 PG 10 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 958QR UT WOS:000305256000026 PM 22099046 ER PT J AU Hattangadi, JA Rombi, B Yock, TI Broussard, G Friedmann, AM Huang, M Chen, YLE Lu, HM Kooy, H MacDonald, SM AF Hattangadi, Jona A. Rombi, Barbara Yock, Torunn I. Broussard, George Friedmann, Alison M. Huang, Mary Chen, Yen-Lin E. Lu, Hsiao-Ming Kooy, Hanne MacDonald, Shannon M. TI Proton Radiotherapy for High-Risk Pediatric Neuroblastoma: Early Outcomes and Dose Comparison SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT Annual Meeting of the Pediatric-Radiation-Oncology-Society (PROS) CY JUN 21-24, 2011 CL Venice, ITALY SP Pediat Radiat Oncol Soc (PROS) DE High-risk neuroblastoma; Proton radiotherapy; Intensity-modulated proton radiotherapy; IMPT; Intensity-modulated radiotherapy; IMRT ID RESEARCH-HOSPITAL EXPERIENCE; RADIATION-THERAPY; LOCAL-CONTROL; TRANSPLANTATION; SURVIVAL; INFANTS; IMPACT AB Purpose: To report the early outcomes for children with high-risk neuroblastoma treated with proton radiotherapy (RT) and to compare the dose distributions for intensity-modulated photon RT (IMRT), three-dimensional conformal proton RT (3D-CPT), and intensity-modulated proton RT to the postoperative tumor bed. Methods and Materials: All patients with high-risk (International Neuroblastoma Staging System Stage III or IV) neuroblastoma treated between 2005 and 2010 at our institution were included. All patients received induction chemotherapy, surgical resection of residual disease, high-dose chemotherapy with stem cell rescue, and adjuvant 3D-CPT to the primary tumor sites. The patients were followed with clinical examinations, imaging, and laboratory testing every 6 months to monitor disease control and side effects. IMRT, 3D-CPT, and intensity-modulated proton RT plans were generated and compared for a representative case of adjuvant RT to the primary tumor bed followed by a boost. Results: Nine patients were treated with 3D-CPT. The median age at diagnosis was 2 years (range 10 months to 4 years), and all patients had Stage IV disease. All patients had unfavorable histologic characteristics (poorly differentiated histologic features in 8, N-Myc amplification in 6, and 1p/11q chromosomal abnormalities in 4). The median tumor size at diagnosis was 11.4 cm (range 7-16) in maximal dimension. At a median follow-up of 38 months (range 11-70), there were no local failures. Four patients developed distant failure, and, of these, two died of disease. Acute side effects included Grade 1 skin erythema in 5 patients and Grade 2 anorexia in 2 patients. Although comparable target coverage was achieved with all three modalities, proton therapy achieved substantial normal tissue sparing compared with IMRT. Intensity-modulated proton RT allowed additional sparing of the kidneys, lungs, and heart. Conclusions: Preliminary outcomes reveal excellent local control with proton therapy for high-risk neuroblastoma, although distant failures continu to occur. Dosimetric comparisons demonstrate the advantage of proton RT compared with IMRT in this setting, allowing more conformal treatment and better normal tissue sparing. (C) 2012 Elsevier Inc. C1 [Rombi, Barbara; Yock, Torunn I.; Broussard, George; Chen, Yen-Lin E.; Lu, Hsiao-Ming; Kooy, Hanne; MacDonald, Shannon M.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Hattangadi, Jona A.] Harvard Radiat Oncol Program, Boston, MA USA. [Friedmann, Alison M.; Huang, Mary] Massachusetts Gen Hosp, Dept Pediat Hematol Oncol, Boston, MA 02114 USA. [Rombi, Barbara] Prov Agcy Proton Therapy, Trento, Italy. RP MacDonald, SM (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St, Boston, MA 02114 USA. EM smacdonald@partners.org NR 20 TC 14 Z9 15 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 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUL 1 PY 2012 VL 83 IS 3 BP 1015 EP 1022 DI 10.1016/j.ijrobp.2011.08.035 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 958QR UT WOS:000305256000058 PM 22138463 ER PT J AU Arvold, ND Willett, CG Fernandez-del Castillo, C Ryan, DP Ferrone, CR Clark, JW Blaszkowsky, LS Deshpande, V Niemierko, A Allen, JN Kwak, EL Wadlow, RC Zhu, AX Warshaw, AL Hong, TS AF Arvold, Nils D. Willett, Christopher G. Fernandez-del Castillo, Carlos Ryan, David P. Ferrone, Cristina R. Clark, Jeffrey W. Blaszkowsky, Lawrence S. Deshpande, Vikram Niemierko, Andrzej Allen, Jill N. Kwak, Eunice L. Wadlow, Raymond C. Zhu, Andrew X. Warshaw, Andrew L. Hong, Theodore S. TI Pancreatic Neuroendocrine Tumors With Involved Surgical Margins: Prognostic Factors and the Role of Adjuvant Radiotherapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Adjuvant radiotherapy; Local control; Margin positive; Pancreatic neuroendocrine tumor; Survival ID ENDOCRINE TUMORS; SURVIVAL; EXPERIENCE; NEOPLASMS; SURGERY AB Purpose: Pancreatic neuroendocrine tumors (pNET) are rare neoplasms associated with poor outcomes without resection, and involved surgical margins are associated with a worse prognosis. The role of adjuvant radiotherapy (RT) in these patients has not been characterized. Methods and Materials: We retrospectively evaluated 46 consecutive patients with positive or close (<1 mm) margins after pNET resection, treated from 1983 to 2010, 16 of whom received adjuvant RT. Median RT dose was 50.4 Gy in 1.8-Gy fractions; half the patients received concurrent chemotherapy with 5-fluorouracil or capecitabine. No patients received adjuvant chemotherapy. Cox multivariate analysis (MVA) was used to analyze factors associated with overall survival (OS). Results: Median age at diagnosis was 56 years, and 52% of patients were female. Median tumor size was 38 mm, 57% of patients were node-positive, and 11% had a resected solitary liver metastasis. Patients who received RT were more likely to have larger tumors (median, 54 mm vs. 30 mm, respectively, p = 0.002) and node positivity (81% vs. 33%, respectively, p = 0.002) than those not receiving RT. Median follow-up was 39 months. Actuarial 5-year OS was 62% (95% confidence interval [CI], 41%-77%). In the group that did not receive RT, 3 patients (10%) experienced local recurrence (LR) and 5 patients (18%) developed new distant metastases, while in the RT group, 1 patient (6%) experienced LR and 5 patients (38%) developed distant metastases. Of all recurrences, 29% were LR. On MVA, male gender (adjusted hazard ratio [AHR] = 3.81; 95% CI, 1.21-11.92; p = 0.02) and increasing tumor size (AHR = 1.02; 95% CI, 1.01-1.04; p = 0.007) were associated with decreased OS. Conclusions: Long-term survival is common among patients with involved-margin pNET. Despite significantly worse pathologic features among patients receiving adjuvant RT, rates of LR between groups were similar, suggesting that RT might aid local control, and merits further evaluation. (C) 2012 Elsevier Inc. C1 [Niemierko, Andrzej; Hong, Theodore S.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Arvold, Nils D.] Harvard Univ, Sch Med, Harvard Radiat Oncol Program, Boston, MA USA. [Willett, Christopher G.] Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC USA. [Fernandez-del Castillo, Carlos; Ferrone, Cristina R.; Warshaw, Andrew L.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Ryan, David P.; Clark, Jeffrey W.; Blaszkowsky, Lawrence S.; Allen, Jill N.; Kwak, Eunice L.; Wadlow, Raymond C.; Zhu, Andrew X.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Deshpande, Vikram] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Hong, TS (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St, Boston, MA 02114 USA. EM Tshong1@partners.org NR 20 TC 3 Z9 4 U1 0 U2 2 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 JUL 1 PY 2012 VL 83 IS 3 BP E337 EP E343 DI 10.1016/j.ijrobp.2011.12.068 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 958QR UT WOS:000305256000006 PM 22414286 ER PT J AU Gay, HA Barthold, HJ O'Meara, E Bosch, WR El Naqa, I Al-Lozi, R Rosenthal, SA Lawton, C Lee, WR Sandler, H Zietman, A Myerson, R Dawson, LA Willett, C Kachnic, LA Jhingran, A Portelance, L Ryu, J Small, W Gaffney, D Viswanathan, AN Michalski, JM AF Gay, Hiram A. Barthold, H. Joseph O'Meara, Elizabeth Bosch, Walter R. El Naqa, Issam Al-Lozi, Rawan Rosenthal, Seth A. Lawton, Colleen Lee, W. Robert Sandler, Howard Zietman, Anthony Myerson, Robert Dawson, Laura A. Willett, Christopher Kachnic, Lisa A. Jhingran, Anuja Portelance, Lorraine Ryu, Janice Small, William, Jr. Gaffney, David Viswanathan, Akila N. Michalski, Jeff M. TI Pelvic Normal Tissue Contouring Guidelines for Radiation Therapy: A Radiation Therapy Oncology Group Consensus Panel Atlas SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Radiation therapy atlas; Pelvic contouring atlas; Normal tissue volumes; Male pelvis; Female pelvis ID COMPLICATION PROBABILITY-MODELS; LATE RECTAL TOXICITY; PROSTATE-CANCER; CONFORMAL RADIOTHERAPY; RANDOMIZED-TRIAL; HISTOGRAMS; GY AB Purpose: To define a male and female pelvic normal tissue contouring atlas for Radiation Therapy Oncology Group (RTOG) trials. Methods and Materials: One male pelvis computed tomography (CT) data set and one female pelvis CT data set were shared via the Image-Guided Therapy QA Center. A total of 16 radiation oncologists participated. The following organs at risk were contoured in both CT sets: anus, anorectum, rectum (gastrointestinal and genitourinary definitions), bowel NOS (not otherwise specified), small bowel, large bowel, and proximal femurs. The following were contoured in the male set only: bladder, prostate, seminal vesicles, and penile bulb. The following were contoured in the female set only: uterus, cervix, and ovaries. A computer program used the binomial distribution to generate 95% group consensus contours. These contours and definitions were then reviewed by the group and modified. Results: The panel achieved consensus definitions for pelvic normal tissue contouring in RTOG trials with these standardized names: Rectum, AnoRectum, SmallBowel, Colon, BowelBag, Bladder, UteroCervix, Adnexa_R, Adnexa_L, Prostate, SeminalVesc, PenileBulb, Femur_R, and Femur_L. Two additional normal structures whose purpose is to serve as targets in anal and rectal cancer were defined: AnoRectumSig and Mesorectum. Detailed target volume contouring guidelines and images are discussed. Conclusions: Consensus guidelines for pelvic normal tissue contouring were reached and are available as a CT image atlas on the RTOG Web site. This will allow uniformity in defining normal tissues for clinical trials delivering pelvic radiation and will facilitate future normal tissue complication research. (C) 2012 Elsevier Inc. C1 [Gay, Hiram A.] Washington Univ, Sch Med, Dept Radiat Oncol, St Louis, MO 63110 USA. [Barthold, H. Joseph] Commonwealth Hematol & Oncol, Weymouth, MA USA. [Barthold, H. Joseph] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [O'Meara, Elizabeth] Radiat Therapy Oncol Grp, Philadelphia, PA USA. [El Naqa, Issam] McGill Univ, Dept Radiat Oncol, Ctr Hlth, Montreal, PQ H3A 2T5, Canada. [Rosenthal, Seth A.; Ryu, Janice] Radiol Associates Sacramento, Radiat Oncol Ctr, Sacramento, CA USA. [Lawton, Colleen] Med Coll Wisconsin, Dept Radiat Oncol, Milwaukee, WI 53226 USA. [Lee, W. Robert; Willett, Christopher] Duke Univ, Med Ctr, Div Radiat Oncol, Durham, NC 27710 USA. [Sandler, Howard] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Zietman, Anthony] Harvard Univ, Sch Med, Boston, MA USA. [Zietman, Anthony] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Dawson, Laura A.] Univ Toronto, Princess Margaret Hosp, Dept Radiat Oncol, Toronto, ON, Canada. [Kachnic, Lisa A.] Boston Univ, Sch Med, Boston Med Ctr, Dept Radiat Oncol, Boston, MA 02118 USA. [Jhingran, Anuja] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. [Portelance, Lorraine] Univ Miami, Miami, FL USA. [Small, William, Jr.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Dept Radiat Oncol, Chicago, IL 60611 USA. [Gaffney, David] Univ Utah, Huntsman Canc Inst, Dept Radiat Oncol, Salt Lake City, UT USA. [Viswanathan, Akila N.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Gay, HA (reprint author), Washington Univ, Sch Med, Dept Radiat Oncol, 4921 Parkview Pl,Campus Box 8224, St Louis, MO 63110 USA. EM hgay@radonc.wustl.edu OI Gay, Hiram/0000-0001-9766-3537; Viswanathan, Akila/0000-0002-2003-0392 FU National Cancer Institute [CA81647, CA21661, CA32115, CA37422] FX Supported by Grants CA81647, CA21661, CA32115, and CA37422 from the National Cancer Institute. NR 20 TC 86 Z9 90 U1 1 U2 16 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 JUL 1 PY 2012 VL 83 IS 3 BP E353 EP E362 DI 10.1016/j.ijrobp.2012.01.023 PG 10 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 958QR UT WOS:000305256000008 PM 22483697 ER PT J AU Duncan, K Uwimpuhwe, H Czibere, A Sarkar, D Libermann, TA Fisher, PB Zerbini, LF AF Duncan, Kristal Uwimpuhwe, Henriette Czibere, Akos Sarkar, Devanand Libermann, Towia A. Fisher, Paul B. Zerbini, Luiz F. TI NSAIDs induce apoptosis in nonproliferating ovarian cancer cells and inhibit tumor growth in vivo SO IUBMB LIFE LA English DT Article DE NSAIDs; ovarian cancer; apoptosis; nonproliferating; quiescence ID ANTIINFLAMMATORY DRUGS; PROSTATE-CANCER; BREAST-CANCER; COLON-CANCER; CYCLOOXYGENASE-2; EXPRESSION; FINASTERIDE; RESISTANCE; CELECOXIB; SURVIVAL AB Ovarian cancer (OC) is one of the most lethal gynaecological cancers, which usually has a poor prognosis due to late diagnosis. A large percentage of the OC cell population is in a nonproliferating and quiescent stage, which poses a barrier to success when using most chemotherapeutic agents. Recent studies have shown that several nonsteroidal anti-inflammatory drugs (NSAIDs) are effective in the treatment of OC. Furthermore, we have previously described the molecular mechanisms of NSAIDs' induction of cancer apoptosis. In this report, we evaluated various structurally distinct NSAIDs for their efficacies in inducing apoptosis in nonproliferating OC cells. Although several NSAIDs-induced apoptosis, Flufenamic Acid, Flurbiprofen, Finasteride, Celocoxib, and Ibuprofen were the most potent NSAIDs inducing apoptosis. A combination of these agents resulted in an enhanced effect. Furthermore, we demonstrate that the combination of Flurbiprofen, which targets nonproliferative cells, and Sulindac Sulfide, that affects proliferative cells, strongly reduced tumor growth when compared with a single agent treatment. Our data strongly support the hypothesis that drug treatment regimens that target nonproliferating and proliferating cells may have significant efficacy against OC. These results also provide a rationale for employing compounds or even chemically modified NSAIDs, which selectively and efficiently induce apoptosis in cells during different stages of the cell cycle, to design more potent anticancer drugs. (c) 2012 IUBMB IUBMB Life, 64(7): 636643, 2012 C1 [Duncan, Kristal; Uwimpuhwe, Henriette; Zerbini, Luiz F.] ICGEB, Canc Genom Grp, ZA-7925 Cape Town, South Africa. [Uwimpuhwe, Henriette; Zerbini, Luiz F.] Univ Cape Town, Fac Hlth Sci, Med Biochem Div, ZA-7925 Cape Town, South Africa. [Czibere, Akos] Univ Dusseldorf, Dept Haematol Oncol & Clin Immunol, D-40225 Dusseldorf, Germany. [Czibere, Akos; Libermann, Towia A.] Beth Israel Deaconess Med Ctr, BIDMC Genom & Prote Ctr, Boston, MA 02215 USA. [Czibere, Akos; Libermann, Towia A.] Harvard Univ, Sch Med, Boston, MA USA. [Sarkar, Devanand; Fisher, Paul B.] Virginia Commonwealth Univ, Dept Human & Mol Genet, VCU Massey Canc Ctr, VCU Inst Mol Med,Sch Med, Richmond, VA USA. RP Zerbini, LF (reprint author), ICGEB, Canc Genom Grp, Werner & Beit Bldg S,Anzio Rd,UCT Campus, ZA-7925 Cape Town, South Africa. EM luiz.zerbini@icgeb.org RI Zerbini, Luiz /B-7720-2015; OI Libermann, Towia/0000-0002-4006-8179 FU National Institutes of Health (NIH) [1R01 CA85467, R01 CA138540, 1R01 CA097318, 1R01 CA127641, 1R01 CA134721, P01 CA104177]; Samuel Waxman Cancer Research Foundation; National Foundation for Cancer Research; Department of Defence [OC0060439]; ICGEB FX This work was supported with grants from the National Institutes of Health (NIH) grants 1R01 CA85467 (TAL); NIH grant R01 CA138540 (DS); NIH grants 1R01 CA097318, 1R01 CA127641, 1R01 CA134721, and P01 CA104177, and the Samuel Waxman Cancer Research Foundation and the National Foundation for Cancer Research (PBF); and Department of Defence grant OC0060439 and ICGEB (LFZ). We are thankful to Dr. Rodrigo E. Tamura for his guidance and insight. DS is the Harrison Endowed Scholar in Cancer Research and a Blick scholar. PBF holds the Thelma Newmeyer Corman Chair in Cancer Research and is a Samuel Waxman Cancer Research Foundation (SWCRF) Investigator and a National Foundation for Cancer Research (NFCR) Investigator. NR 40 TC 7 Z9 8 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1521-6543 J9 IUBMB LIFE JI IUBMB Life PD JUL PY 2012 VL 64 IS 7 BP 636 EP 643 DI 10.1002/iub.1035 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 959SL UT WOS:000305333200008 PM 22576850 ER PT J AU Shaw, TJ Addae, L Bridger, C Pepin, D AF Shaw, T. J. Addae, L. Bridger, C. Pepin, D. TI The ovary is poised to heal ovulation-induced wounds SO JOURNAL OF ANATOMY LA English DT Meeting Abstract C1 [Shaw, T. J.; Addae, L.; Bridger, C.] Univ London, Div Biomed Sci, London, England. [Pepin, D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-8782 J9 J ANAT JI J. Anat. PD JUL PY 2012 VL 221 IS 1 BP 91 EP 92 PG 2 WC Anatomy & Morphology SC Anatomy & Morphology GA 957TM UT WOS:000305185900064 ER PT J AU Rubinow, KB Vaisar, T Tang, CR Matsumoto, AM Heinecke, JW Page, ST AF Rubinow, Katya B. Vaisar, Tomas Tang, Chongren Matsumoto, Alvin M. Heinecke, Jay W. Page, Stephanie T. TI Testosterone replacement in hypogonadal men alters the HDL proteome but not HDL cholesterol efflux capacity SO JOURNAL OF LIPID RESEARCH LA English DT Article DE cardiovascular disease; lipoproteins; lipids; atherosclerosis; androgens ID HIGH-DENSITY-LIPOPROTEIN; CORONARY-ARTERY-DISEASE; APOLIPOPROTEIN-A-I; CARDIOVASCULAR-DISEASE; HEPATIC LIPASE; APOC-I; ANTIINFLAMMATORY PROPERTIES; POSTMENOPAUSAL WOMEN; MASS-SPECTROMETRY; THERAPY AB The effects of androgens on cardiovascular disease (CVD) risk in men remain unclear. To better characterize the relationship between androgens and HDL, we investigated the effects of testosterone replacement on HDL protein composition and serum HDL-mediated cholesterol efflux in hypogonadal men. Twenty-three older hypogonadal men (ages 51-83, baseline testosterone < 280 ng/dl) were administered replacement testosterone therapy (1% transdermal gel) with or without the 5 alpha-reductase inhibitor dutasteride. At baseline and after three months of treatment, we determined fasting lipid concentrations, HDL protein composition, and the cholesterol efflux capacity of serum HDL. Testosterone replacement did not affect HDL cholesterol (HDL-C) concentrations but conferred significant increases in HDL-associated paraoxonase 1 (PON1) and fibrinogen alpha chain (FGA) (P = 0.022 and P = 0.023, respectively) and a decrease in apolipoprotein A-IV (apoA-IV) (P = 0.016). Exogenous testosterone did not affect the cholesterol efflux capacity of serum HDL. No differences were observed between men who received testosterone alone and those who also received dutasteride.(Jlr) Testosterone replacement in older hypogonadal men alters the protein composition of HDL but does not significantly change serum HDL-mediated cholesterol efflux. These effects appear independent of testosterone conversion to dihydrotestosterone. Further research is needed to determine how changes in HDL protein content affect CVD risk in men. Rubinow, K. B., T. Vaisar, C. Tang, A. M. Matsumoto, J. W. Heinecke, and S. T. Page. Testosterone replacement in hy C1 [Rubinow, Katya B.; Page, Stephanie T.] Univ Washington, Sch Med, Ctr Res Reprod & Contracept, Seattle, WA 98195 USA. [Vaisar, Tomas; Tang, Chongren; Heinecke, Jay W.] Univ Washington, Sch Med, Diabet & Obes Ctr Excellence, Seattle, WA USA. [Matsumoto, Alvin M.] Univ Washington, Sch Med, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. [Matsumoto, Alvin M.] Univ Washington, Sch Med, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. [Matsumoto, Alvin M.] VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. RP Rubinow, KB (reprint author), Univ Washington, Sch Med, Ctr Res Reprod & Contracept, Seattle, WA 98195 USA. EM rubinow@uw.edu FU National Institutes of Health [RO1-AG-037603, U54-HD-42454, P50-CA-097186, DK-017047, T32-DK-007247, P30-DK-035816, R01-HL-089504, P30-DK-017047, P01-HL-112625, R01-HL-086798, P01-HL-092969]; Department of Veterans Affairs Puget Sound Health Care System; American Heart Association [083-0231N] FX This work was supported by National Institutes of Health Grants RO1-AG-037603, U54-HD-42454, P50-CA-097186, DK-017047, T32-DK-007247 (K. B. R.), P30-DK-035816 (T. V.), R01-HL-089504 (T. V.), P30-DK-017047, P01-HL-112625 (J. W. H.), R01-HL-086798 (J. W. H.), and P01-HL-092969 (J. W. H.); by the Department of Veterans Affairs Puget Sound Health Care System (A. M. M.); and by American Heart Association Grant 083-0231N (T. V.). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health. Transdermal placebo and testosterone gels were provided by Abbott Laboratories (formerly Solvay Pharmaceuticals), and dutasteride and oral placebo were provided by GlaxoSmithKline, neither of which had any input into the study design, analyses, or manuscript preparation. NR 47 TC 12 Z9 12 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 EI 1539-7262 J9 J LIPID RES JI J. Lipid Res. PD JUL PY 2012 VL 53 IS 7 BP 1376 EP 1383 DI 10.1194/jlr.P026005 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 957IZ UT WOS:000305156400014 PM 22504910 ER PT J AU Glover, GH Mueller, BA Turner, JA van Erp, TGM Liu, TT Greve, DN Voyvodic, JT Rasmussen, J Brown, GG Keator, DB Calhoun, VD Lee, HJ Ford, JM Mathalon, DH Diaz, M O'Leary, DS Gadde, S Preda, A Lim, KO Wible, CG Stern, HS Belger, A McCarthy, G Ozyurt, B Potkin, SG AF Glover, Gary H. Mueller, Bryon A. Turner, Jessica A. van Erp, Theo G. M. Liu, Thomas T. Greve, Douglas N. Voyvodic, James T. Rasmussen, Jerod Brown, Gregory G. Keator, David B. Calhoun, Vince D. Lee, Hyo Jong Ford, Judith M. Mathalon, Daniel H. Diaz, Michele O'Leary, Daniel S. Gadde, Syam Preda, Adrian Lim, Kelvin O. Wible, Cynthia G. Stern, Hal S. Belger, Aysenil McCarthy, Gregory Ozyurt, Burak Potkin, Steven G. TI Function biomedical informatics research network recommendations for prospective multicenter functional MRI studies SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Review DE functional magnetic resonance imaging; fMRI; multicenter; multisite; FIRST Biomedical Informatics Research Network; FBIRN ID INDEPENDENT COMPONENT ANALYSIS; WORKING-MEMORY TASK; MULTIPLE-SCLEROSIS; QUALITY-ASSURANCE; MULTISITE FMRI; AUDITORY HALLUCINATIONS; SCHIZOPHRENIA-PATIENTS; MOTOR TASK; BOLD FMRI; REPRODUCIBILITY AB This report provides practical recommendations for the design and execution of multicenter functional MRI (MC-fMRI) studies based on the collective experience of the Function Biomedical Informatics Research Network (FBIRN). The study was inspired by many requests from the fMRI community to FBIRN group members for advice on how to conduct MC-fMRI studies. The introduction briefly discusses the advantages and complexities of MC-fMRI studies. Prerequisites for MC-fMRI studies are addressed before delving into the practical aspects of carefully and efficiently setting up a MC-fMRI study. Practical multisite aspects include: (i) establishing and verifying scan parameters including scanner types and magnetic fields, (ii) establishing and monitoring of a scanner quality program, (iii) developing task paradigms and scan session documentation, (iv) establishing clinical and scanner training to ensure consistency over time, (v) developing means for uploading, storing, and monitoring of imaging and other data, (vi) the use of a traveling fMRI expert, and (vii) collectively analyzing imaging data and disseminating results. We conclude that when MC-fMRI studies are organized well with careful attention to unification of hardware, software and procedural aspects, the process can be a highly effective means for accessing a desired participant demographics while accelerating scientific discovery. J. Magn. Reson. Imaging 2012;36:3954. (c) 2012 Wiley Periodicals, Inc. C1 [Glover, Gary H.] Stanford Univ, Dept Radiol, Stanford, CA 94305 USA. [Mueller, Bryon A.; Lim, Kelvin O.] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA. [Turner, Jessica A.; Calhoun, Vince D.] Mind Res Network, Albuquerque, NM USA. [Turner, Jessica A.] Univ New Mexico, Dept Psychiat, Albuquerque, NM 87131 USA. [van Erp, Theo G. M.; Rasmussen, Jerod; Keator, David B.; Preda, Adrian; Potkin, Steven G.] Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92717 USA. [Liu, Thomas T.] Univ Calif San Diego, Ctr Funct MRI, San Diego, CA 92103 USA. [Greve, Douglas N.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Voyvodic, James T.; Diaz, Michele; Gadde, Syam] Duke Univ, Med Ctr, Brain Imaging & Anal Ctr, Durham, NC USA. [Brown, Gregory G.] Univ Calif San Diego, VA San Diego Healthcare Syst, San Diego, CA 92103 USA. [Calhoun, Vince D.] Univ New Mexico, Dept ECE, Albuquerque, NM 87131 USA. [Lee, Hyo Jong] Chonbuk Natl Univ, Dept Comp Sci & Engn, Jeonju, South Korea. [Ford, Judith M.; Mathalon, Daniel H.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Ford, Judith M.; Mathalon, Daniel H.] Univ Calif San Francisco, Brain Imaging & EEG Lab, San Francisco, CA 94143 USA. [Ford, Judith M.; Mathalon, Daniel H.] San Francisco VA Med Ctr, San Francisco, CA USA. [O'Leary, Daniel S.] Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA. [Wible, Cynthia G.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Wible, Cynthia G.] Brockton VAMC, Boston, MA USA. [Stern, Hal S.] Univ Calif Irvine, Dept Stat, Irvine, CA USA. [Belger, Aysenil] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. [Belger, Aysenil] Univ N Carolina, Deportment Psychol, Chapel Hill, NC USA. [McCarthy, Gregory] Yale Univ, Dept Psychol, New Haven, CT 06520 USA. [Brown, Gregory G.; Ozyurt, Burak] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Potkin, Steven G.] Funct Biomed Informat Res Network, Iowa City, IA USA. RP Glover, GH (reprint author), Stanford Univ, Dept Radiol, Stanford, CA 94305 USA. EM gary.glover@stanford.edu RI Potkin, Steven/A-2021-2013; Calhoun, Vince/H-7146-2013; Preda, Adrian /K-8889-2013; Turner, Jessica/H-7282-2015; OI Calhoun, Vince/0000-0001-9058-0747; Preda, Adrian /0000-0003-3373-2438; Turner, Jessica/0000-0003-0076-8434; Belger, Aysenil/0000-0003-2687-1966; Mathalon, Daniel/0000-0001-6090-4974 FU National Institutes of Health (NIH) [U24-RR025736, U24-RR021992, U24-RR021760, P41-RR009784, R01NS051661, R01MH084796, RO1 MH067080-01A2]; Department of Veterans Affairs; VA Medical Center of Excellence FX Contract grant sponsor: National Institutes of Health (NIH); Contract grant numbers: U24-RR025736, U24-RR021992, U24-RR021760, P41-RR009784, R01NS051661, R01MH084796, RO1 MH067080-01A2; Contract grant sponsor: Department of Veterans Affairs Research Enhancement Award Program; Contract grant sponsor: VA Medical Center of Excellence. NR 55 TC 64 Z9 64 U1 2 U2 24 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD JUL PY 2012 VL 36 IS 1 BP 39 EP 54 DI 10.1002/jmri.23572 PG 16 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 957TK UT WOS:000305185700003 PM 22314879 ER PT J AU Cardo, LF Coto, E de Mena, L Ribacoba, R Lorenzo-Betancor, O Pastor, P Samaranch, L Mata, IF Diaz, M Moris, G Menendez, M Corao, AI Alvarez, V AF Cardo, Lucia F. Coto, Eliecer de Mena, Lorena Ribacoba, Rene Lorenzo-Betancor, Oswaldo Pastor, Pau Samaranch, LLuis Mata, Ignacio F. Diaz, Marta Moris, German Menendez, Manuel Corao, Ana I. Alvarez, Victoria TI A Search for SNCA 3 ' UTR Variants Identified SNP rs356165 as a Determinant of Disease Risk and Onset Age in Parkinson's Disease SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE Parkinson's disease; Alpha-synuclein; DNA polymorphisms; Genetic risk ID ALPHA-SYNUCLEIN GENE; GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY; MUTATION; POPULATION; EXPRESSION; REGIONS AB Alpha-synuclein gene (SNCA) polymorphisms have been associated with the common sporadic form of Parkinson's disease (PD). We searched for DNA variants at the SNCA 3' UTR through single strand conformation analysis and direct sequencing in a cohort of Spanish PD patients and controls. We have genotyped the rs356165 SNCA 3' UTR polymorphism in a total of 1,135 PD patients and 772 healthy controls from two Spanish cohorts (Asturias and Navarre). We identified six SNCA 3' UTR variants. Single nucleotide polymorphism (SNP) rs356165 was significantly associated with PD risk in the Spanish cohort (p = 0.0001; odd ratio = 1.37, 95%CI = 1.19-1.58). This SNP was also significantly associated with early age at onset of PD. Our work highlights rs356165 as an important determinant of the risk of developing PD and early age at onset and encourages future research to identify a functional effect on SNCA expression. C1 [Cardo, Lucia F.; Coto, Eliecer; de Mena, Lorena; Diaz, Marta; Corao, Ana I.; Alvarez, Victoria] Hosp Univ Cent Asturias, Genet Mol Lab Med, Oviedo 33006, Spain. [Ribacoba, Rene; Moris, German; Menendez, Manuel] Hosp Univ Cent Asturias, Asturias, Spain. [Lorenzo-Betancor, Oswaldo; Pastor, Pau; Samaranch, LLuis] Univ Navarra Clin, Ctr Appl Med Res, Div Neurosci, Neurogenet Lab, Pamplona, Spain. [Ribacoba, Rene; Moris, German; Menendez, Manuel] Alvarez Buylla Mieres, Asturias, Spain. [Coto, Eliecer] Univ Oviedo, Dept Med, Oviedo, Spain. [Lorenzo-Betancor, Oswaldo; Pastor, Pau] Univ Navarra Clin, Dept Neurol, Pamplona, Spain. [Mata, Ignacio F.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Mata, Ignacio F.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA. RP Alvarez, V (reprint author), Hosp Univ Cent Asturias, Genet Mol Lab Med, Oviedo 33006, Spain. EM victoria.alvarez@sespa.princast.es RI Pastor, Pau/C-9834-2009; OI Pastor, Pau/0000-0002-7493-8777; Fernandez Mata, Ignacio/0000-0003-1198-0633; Moris, German/0000-0001-7608-2194 FU Fundacion Parkinson Asturias; Obra Social Cajastur; Spanish European Union [FIS-05/008, 08/0915]; FICYT-Principado de Asturias; Spanish Ministry of Science and Technology; European Social Fund; Spanish Ministry of Education and Science [SAF2006-10126]; Fundacio La Marato de TV3 [061131]; UTE, Spain FX Authors thank the "Fundacion Parkinson Asturias" and "Obra Social Cajastur" for their support. This work was supported by grants from the Spanish "Fondo de Investigaciones Sanitarias-Fondos FEDER" European Union (FIS-05/008 and 08/0915). LFC and LDM are predoctoral fellowships of FICYT-Principado de Asturias. LS held a "Torres Quevedo" fellowship from the Spanish Ministry of Science and Technology, co-financed by the European Social Fund. This study was supported by a grant from the Spanish Ministry of Education and Science (SAF2006-10126, 2006-2009) by the project 061131 from the "Fundacio La Marato de TV3" and by the UTE project FIMA, Spain to PP. NR 26 TC 14 Z9 17 U1 0 U2 4 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 JUL PY 2012 VL 47 IS 3 BP 425 EP 430 DI 10.1007/s12031-011-9669-1 PG 6 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 958DV UT WOS:000305217600002 PM 22076805 ER PT J AU Pope, WB Qiao, XJ Kim, HJ Lai, A Nghiemphu, P Xue, X Ellingson, BM Schiff, D Aregawi, D Cha, S Puduvalli, VK Wu, J Yung, WKA Young, GS Vredenburgh, J Barboriak, D Abrey, LE Mikkelsen, T Jain, R Paleologos, NA Lada, P Prados, M Goldin, J Wen, PY Cloughesy, T AF Pope, Whitney B. Qiao, Xin Joe Kim, Hyun J. Lai, Albert Nghiemphu, Phioanh Xue, Xi Ellingson, Benjamin M. Schiff, David Aregawi, Dawit Cha, Soonmee Puduvalli, Vinay K. Wu, Jing Yung, Wai-Kwan A. Young, Geoffrey S. Vredenburgh, James Barboriak, Dan Abrey, Lauren E. Mikkelsen, Tom Jain, Rajan Paleologos, Nina A. Lada, Patricia Prados, Michael Goldin, Jonathan Wen, Patrick Y. Cloughesy, Timothy TI Apparent diffusion coefficient histogram analysis stratifies progression-free and overall survival in patients with recurrent GBM treated with bevacizumab: a multi-center study SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Apparent diffusion coefficient; Glioblastoma multiforme; Progression-free survival ID HIGH-GRADE GLIOMAS; GLIOBLASTOMA-MULTIFORME; RESPONSE CRITERIA; BIOMARKER; PSEUDOPROGRESSION; MAPS AB We have tested the predictive value of apparent diffusion coefficient (ADC) histogram analysis in stratifying progression-free survival (PFS) and overall survival (OS) in bevacizumab-treated patients with recurrent glioblastoma multiforme (GBM) from the multi-center BRAIN study. Available MRI's from patients enrolled in the BRAIN study (n = 97) were examined by generating ADC histograms from areas of enhancing tumor on T1 weighted post-contrast images fitted to a two normal distribution mixture curve. ADC classifiers including the mean ADC from the lower curve (ADC-L) and the mean lower curve proportion (LCP) were tested for their ability to stratify PFS and OS by using Cox proportional hazard ratios and the Kaplan-Meier method with log-rank test. Mean ADC-L was 1,209 x 10(-6)mm(2)/s +/- A 224 (SD), and mean LCP was 0.71 +/- A 0.23 (SD). Low ADC-L was associated with worse outcome. The hazard ratios for 6-month PFS, overall PFS, and OS in patients with less versus greater than mean ADC-L were 3.1 (95 % confidence interval: 1.6, 6.1; P = 0.001), 2.3 (95 % CI: 1.3, 4.0; P = 0.002), and 2.4 (95 % CI: 1.4, 4.2; P = 0.002), respectively. In patients with ADC-L < 1,209 and LCP > 0.71 versus ADC-L > 1,209 and LCP < 0.71, there was a 2.28-fold reduction in the median time to progression, and a 1.42-fold decrease in the median OS. The predictive value of ADC histogram analysis, in which low ADC-L was associated with poor outcome, was confirmed in bevacizumab-treated patients with recurrent GBM in a post hoc analysis from the multi-center (BRAIN) study. C1 [Pope, Whitney B.; Qiao, Xin Joe; Kim, Hyun J.; Xue, Xi; Ellingson, Benjamin M.; Goldin, Jonathan] Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiol, Los Angeles, CA 90095 USA. [Lai, Albert; Nghiemphu, Phioanh; Cloughesy, Timothy] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Schiff, David] Virginia Commonwealth Univ Hlth Syst, Dept Neurol, Richmond, VA 23298 USA. [Aregawi, Dawit] Univ Virginia Hlth Syst, Dept Radiol, Charlottesville, VA 22908 USA. [Cha, Soonmee] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Puduvalli, Vinay K.; Wu, Jing; Yung, Wai-Kwan A.] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. [Young, Geoffrey S.] Harvard Univ, Dept Radiol, Sch Med, Boston, MA 02115 USA. [Vredenburgh, James] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Barboriak, Dan] Duke Univ, Med Ctr, Dept Radiol, Durham, NC 27710 USA. [Abrey, Lauren E.] Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10065 USA. [Mikkelsen, Tom] Henry Ford Hosp, Dept Neurol & Neurol Surg, Detroit, MI 48202 USA. [Jain, Rajan] Henry Ford Hosp, Dept Radiol, Detroit, MI 48202 USA. [Paleologos, Nina A.; Lada, Patricia] Northshore Univ Hlth Syst, Dept Neurol, Evanston, IL 60201 USA. [Prados, Michael] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. [Wen, Patrick Y.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. RP Pope, WB (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiol, Los Angeles, CA 90095 USA. EM wpope@mednet.ucla.edu RI Puduvalli, Vinay/A-2411-2016 FU Genentech/Roche FX Whitney B. Pope, Albert Lai, David Schiff, Lauren Abrey, Tom Mikkelsen, Nina A. Paleologos, and Timothy Cloughesy served on the Genentech/Roche advisory board; Albert Lai, Vinay K. Puduvalli, Tom Mikkelsen, and Patrick Y. Wen were supported by research funds from Genentech/Roche; Nina A. Paleologos, Lauren Abrey, and Tom Mikkelsen received honoraria from Genentech/Roche; All other authors declare no conflict of interest. NR 24 TC 66 Z9 66 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD JUL PY 2012 VL 108 IS 3 BP 491 EP 498 DI 10.1007/s11060-012-0847-y PG 8 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 956XV UT WOS:000305123800018 PM 22426926 ER PT J AU Reardon, DA Vredenburgh, JJ Desjardins, A Peters, KB Sathornsumetee, S Threatt, S Sampson, JH Herndon, JE Coan, A McSherry, F Rich, JN McLendon, RE Zhang, S Friedman, HS AF Reardon, David A. Vredenburgh, James J. Desjardins, Annick Peters, Katherine B. Sathornsumetee, Sith Threatt, Stevie Sampson, John H. Herndon, James E., II Coan, April McSherry, Frances Rich, Jeremy N. McLendon, Roger E. Zhang, Steven Friedman, Henry S. TI Phase 1 trial of dasatinib plus erlotinib in adults with recurrent malignant glioma SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Malignant glioma; Glioblastoma; Dasatinib; Erlotinib; Epidermal growth factor receptor (EGFR) ID PROGRESSION-FREE SURVIVAL; GLIOBLASTOMA-MULTIFORME; II TRIAL; IMATINIB MESYLATE; TEMOZOLOMIDE; THERAPY; CANCER; SRC; CCI-779; KINASES AB To determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of dasatinib, an inhibitor of the Src family kinase proteins, with erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor, among recurrent malignant glioma patients. Once daily dasatinib was escalated in successive cohorts while erlotinib was administered daily at established doses based on concurrent CYP3A-inducing anticonvulsant (EIAEDS) use. Dasatinib pharmacokinetic analyzes were performed. Forty-seven patients enrolled including 37 (79 %) with grade IV and 10 (21 %) with grade III malignant glioma. Thirty patients (64 %) were at a parts per thousand yensecond recurrence, while 27 (57 %) had received prior bevacizumab. The dasatinib MTD was 180 mg when combined with either 150 mg of erlotinib for patients not on EIAEDs, or 450 mg of erlotinib for patients on EIAEDs. The most common DLTs were diarrhea and fatigue, while most adverse events were grade 2. Pharmacokinetic data suggests that dasatinib exposure increased with increased dasatinib dose and concurrent erlotinib administration, while concurrent EIAED use diminished dasatinib exposure. No radiographic responses were observed, and only one patient (2 %) remained progression-free at 6 months. We demonstrate that dasatinib plus erlotinib can be safely co-administered on a continuous, daily dosing schedule with erlotinib, and established the recommended dose level of this combination. C1 [Reardon, David A.] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02215 USA. [Reardon, David A.; Threatt, Stevie; Sampson, John H.; Friedman, Henry S.] Duke Univ, Med Ctr, Dept Surg, Preston Robert Tisch Brain Tumor Ctr, Durham, NC 27710 USA. [Reardon, David A.; Friedman, Henry S.] Duke Univ, Med Ctr, Dept Pediat, Preston Robert Tisch Brain Tumor Ctr, Durham, NC 27710 USA. [Vredenburgh, James J.; Desjardins, Annick; Peters, Katherine B.] Duke Univ, Med Ctr, Dept Med, Preston Robert Tisch Brain Tumor Ctr, Durham, NC 27710 USA. [Sathornsumetee, Sith] Mahidol Univ, Siriraj Hosp, Fac Med, Dept Med Neurol, Bangkok 10700, Thailand. [Herndon, James E., II; Coan, April; McSherry, Frances] Duke Univ, Med Ctr, Dept Canc Ctr Biostat, Preston Robert Tisch Brain Tumor Ctr, Durham, NC USA. [Rich, Jeremy N.] Cleveland Clin, Dept Stem Cell Biol & Regenerat Med, Cleveland, OH 44106 USA. [McLendon, Roger E.] Duke Univ, Med Ctr, Dept Pathol, Preston Robert Tisch Brain Tumor Ctr, Durham, NC 27710 USA. [Zhang, Steven] Bristol Myers Squibb Co, Dept Clin Pharmacol & Pharmacometr, Princeton, NJ USA. RP Reardon, DA (reprint author), Dana Farber Canc Inst, Ctr Neurooncol, 450 Brookline Ave,SW 430, Boston, MA 02215 USA. EM David_Reardon@DFCI.HARVARD.EDU OI Sykes, April/0000-0002-7667-8155 FU NIH [P50 NS20023, CA11898, MO1 RR 30]; GCRC; NCRR; SPORE in Brain Cancer [2 P50 CA108786] FX This work was supported by NIH Grants P50 NS20023 and CA11898; NIH Grant MO1 RR 30, GCRC Program, NCRR and SPORE in Brain Cancer 2 P50 CA108786. The authors thank Wendy Gentry for her excellent secretarial support in the development of this manuscript. NR 33 TC 19 Z9 19 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD JUL PY 2012 VL 108 IS 3 BP 499 EP 506 DI 10.1007/s11060-012-0848-x PG 8 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 956XV UT WOS:000305123800019 PM 22407177 ER PT J AU Manley, PE McKendrick, K McGillicudy, M Chi, SN Kieran, MW Cohen, LE Kothare, S Scott, RM Goumnerova, LC Sun, PL London, W Marcus, KJ Pomeroy, SL Ullrich, NJ AF Manley, Peter E. McKendrick, Kiera McGillicudy, Megan Chi, Susan N. Kieran, Mark W. Cohen, Laurie E. Kothare, Sanjeev Scott, R. Michael Goumnerova, Liliana C. Sun, Pengling London, Wendy Marcus, Karen J. Pomeroy, Scott L. Ullrich, Nicole J. TI Sleep dysfunction in long term survivors of craniopharyngioma SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Craniopharyngioma; Pediatric; Survivorship; Fatigue; Sleep dysfunction ID QUALITY-OF-LIFE; INCREASED DAYTIME SLEEPINESS; CHILDHOOD CRANIOPHARYNGIOMA; PEDIATRIC SURVIVORS; CIRCADIAN-RHYTHMS; MELATONIN; CHILDREN AB Craniopharyngiomas are slow growing tumors of the sellar and parasellar region and may also involve the hypothalamus. Treatment involves maximal surgical excision or subtotal resection followed by focal radiation therapy. Late effects of treatment include endocrinopathies, cognitive deficits, behavioral changes, obesity and sleep dysfunction. We conducted a retrospective review of all patients with craniopharyngioma more than 2 years off treatment and who were evaluated in the neuro-oncology survivorship clinic between 2003 and 2007. Clinical data, extent of resection, treatment modalities, endocrine status, patient symptom report and sleep study results were collected to evaluate the presence of patient reported daytime sleepiness and sleep disturbance and to determine possible risk factors. 28 patients were identified (25 %) female. 19/28 self-reported daytime fatigue or sleep disturbance; this included 4/6 patients with gross total resection and 15/22 with subtotal resection. 16/22 patients treated with cranial irradiation reported sleep-related abnormalities, compared to 3/6 patients who did not receive radiation. All but one patient had pituitary dysfunction requiring hormonal replacement. Patients with more than a parts per thousand yen2 sleep related complaints had a higher BMI (44.6 vs. 32.6, p = 0.0192). 8 patients underwent formal sleep evaluation. 3 patients had documented central or obstructive sleep apnea. The mean arousal index was 11.0/h (normal < 5). Two patients were treated with melatonin for sleep disturbance and 2 were treated with stimulants for excessive daytime sleepiness. A majority of patients with craniopharyngioma have self-reported daytime fatigue and/or sleep dysfunction after treatment. Extent of resection did not increase the likelihood of patient-reported daytime sleepiness and/sleep dysfunction; however, patients who received radiation more frequently reported daytime sleepiness and/or sleep dysfunction. Patients with a higher BMI were more likely to experience sleep disturbance. Formal sleep evaluations should be considered in all patients with craniopharyngioma. C1 [Manley, Peter E.; McKendrick, Kiera; McGillicudy, Megan; Chi, Susan N.; Kieran, Mark W.; London, Wendy; Pomeroy, Scott L.; Ullrich, Nicole J.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Manley, Peter E.; Chi, Susan N.; Kieran, Mark W.; Cohen, Laurie E.; Sun, Pengling] Childrens Hosp Boston, Dept Med, Boston, MA USA. [Kothare, Sanjeev; Pomeroy, Scott L.; Ullrich, Nicole J.] Childrens Hosp Boston, Dept Neurol, Boston, MA USA. [Scott, R. Michael; Goumnerova, Liliana C.] Childrens Hosp Boston, Dept Neurosurg, Boston, MA USA. [Marcus, Karen J.] Childrens Hosp Boston, Dept Radiat Oncol, Boston, MA USA. RP Manley, PE (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM peter_manley@dfci.harvard.edu RI Sun, Pengling/G-1403-2011; OI Kothare, Sanjeev/0000-0001-7849-6649; Kieran, Mark/0000-0003-2184-7692 NR 18 TC 10 Z9 10 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD JUL PY 2012 VL 108 IS 3 BP 543 EP 549 DI 10.1007/s11060-012-0859-7 PG 7 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 956XV UT WOS:000305123800025 PM 22528788 ER PT J AU Winter, H Gunasekaran, T Tolia, V Gottrand, F Barker, PN Illueca, M AF Winter, Harland Gunasekaran, Thirumazhisai Tolia, Vasundhara Gottrand, Frederic Barker, Peter N. Illueca, Marta TI Esomeprazole for the Treatment of GERD in Infants Ages 1-11 Months SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article DE efficacy; gastroesophageal reflux; pediatrics; proton pump inhibitor; safety ID GASTROESOPHAGEAL-REFLUX DISEASE; NORTH-AMERICAN-SOCIETY; PEDIATRIC-GASTROENTEROLOGY; SYMPTOMS; RECOMMENDATIONS; QUESTIONNAIRE; LANSOPRAZOLE; PREVALENCE; GUIDELINES; CHILDHOOD AB Objectives: Gastroesophageal reflux disease (GERD) is present in pediatric patients when reflux of gastric contents causes troublesome symptoms and/or complications. The present study evaluates the efficacy and safety of esomeprazole in infants ages 1 to 11 months with GERD. Methods: In this multicenter randomized, double-blind, placebo-controlled, parallel-group, treatment-withdrawal study, infants received open-label, weight-adjusted doses of esomeprazole (2.5-10 mg) once daily for 2 weeks. Infants with symptom improvement were randomized to esomeprazole (weight-adjusted doses [2.5-10 mg]) or placebo for 4 weeks. The primary endpoint was time to discontinuation owing to symptom worsening based on global assessments by the parent/guardian and physician. Adverse events were recorded. Results: Of the 98 patients enrolled, 81 (82.7%) experienced symptom improvement determined by physician global assessment (PGA) during open-label esomeprazole treatment; 80 entered the double-blind phase. During this phase, discontinuation rates owing to symptom worsening were 48.8% (20/41) for placebo-treated versus 38.5% (15/39) for esomeprazole-treated patients (hazard ratio 0.69; P = 0.28). Posthoc analysis of infants with symptomatic GERD (ie, no diagnostic procedure performed) revealed that time to discontinuation was significantly longer with esomeprazole than placebo (hazard ratio 0.24; P = 0.01); the complementary subgroup difference was not significant (hazard ratio 1.39; P = 0.48). Esomeprazole was well tolerated. Conclusions: The discontinuation rate owing to symptom worsening did not differ significantly between infants receiving esomeprazole versus those receiving placebo. Improved diagnostic criteria in this age group are needed to identify infants with GERD who may benefit from acid suppression therapy. C1 [Winter, Harland] MassGen Hosp Children, Pediat GI Unit, Boston, MA 02114 USA. [Gunasekaran, Thirumazhisai] Advocate Lutheran Gen Childrens Hosp, Esophageal Ctr, Park Ridge, IL USA. [Gunasekaran, Thirumazhisai] Loyola Univ, Med Ctr, Maywood, IL 60153 USA. [Tolia, Vasundhara] Providence Hosp, Southfield, MI 48037 USA. [Gottrand, Frederic] Jeanne de Flandre Univ Hosp, Dept Pediat Gastroenterol Hepatol & Nutr, Lille, France. [Barker, Peter N.; Illueca, Marta] AstraZeneca LP, Wilmington, DE USA. RP Winter, H (reprint author), MassGen Hosp Children, Pediat GI Unit, CRPZ 5-560,175 Cambridge St, Boston, MA 02114 USA. EM hwinter@partners.org RI gottrand, frederic/G-7370-2015 OI gottrand, frederic/0000-0002-5290-0436 FU AstraZeneca LP; AstraZeneca; Johnson Johnson; Centocor; Proctor Gamble FX The present study was supported by AstraZeneca LP. Medical writing and editorial services were provided by Bret Fulton, freelance medical writer, and Stella Chow, Judy Fallon, Anny Wu, and Colleen Hedge from Scientific Connexions, Newtown, PA (all funded by AstraZeneca LP).; H.W. has been a consultant and investigator for AstraZeneca, Centocor, P & G, Takeda Pharmaceuticals, UCB, Salix, and Wyeth. T.G. has received grant/research support from and is a consultant for AstraZeneca. V.T. receives grant/research support from AstraZeneca, Johnson & Johnson, Centocor, and Proctor & Gamble. F.G. has no conflicts of interest. P.N.B. and M. I. are employees of and own stock in AstraZeneca. NR 23 TC 16 Z9 19 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD JUL PY 2012 VL 55 IS 1 BP 14 EP 20 DI 10.1097/MPG.0b013e3182496b35 PG 7 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 959TR UT WOS:000305337000005 PM 22241513 ER PT J AU Kochanek, AR Fukudome, EY Li, Y Smith, EJ Liu, B Velmahos, GC DeMoya, M King, D Alam, HB AF Kochanek, Ashley R. Fukudome, Eugene Y. Li, Yongqing Smith, Eleanor J. Liu, Baoling Velmahos, George C. deMoya, Marc King, David Alam, Hasan B. TI Histone Deacetylase Inhibitor Treatment Attenuates MAP Kinase Pathway Activation and Pulmonary Inflammation Following Hemorrhagic Shock in a Rodent Model SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE acute lung injury; inflammation; hemorrhage; valproic acid; histone deacetylase inhibitors; stress signals ID NF-KAPPA-B; INDUCED CELL-DEATH; FOCAL CEREBRAL-ISCHEMIA; ACUTE LUNG INJURY; REACTIVE OXYGEN; TERMINAL KINASE; PHYSIOLOGICAL FUNCTIONS; SIGNALING PATHWAY; PROTEIN-KINASES; VALPROIC ACID AB Background. Hemorrhagic shock activates cellular stress signals and can lead to systemic inflammatory response, organ injury, and death. We have previously shown that treatment with histone deacetylase inhibitors (HDACIs) significantly improves survival in lethal models (60% blood loss) of hemorrhage. The aim of the current study was to examine whether these protective effects were due to attenuation of mitogen activated protein kinase (MAPK) signaling pathways, which are known to promote inflammation and apoptosis. Methods. Wistar-Kyoto rats (250-300 g) were subjected to 40% blood loss and randomized to treatment with: (1) HDACI valproic acid (VPA 300 mg/kg i.v.; volume = 0.75 mL/kg), or (2) vehicle control (0.75 mL/kg of 0.9% saline). Animals were sacrificed at 1, 4, and 20 h (n = 3-4/group/timepoint), and lung samples were analyzed by Western blotting for expression of active (phosphorylated) and inactive forms of c-Jun N-terminal Kinase (JNK) and p38 MAPK. Myeloperoxidase (MPO) activity was measured in lung tissue 20 h after hemorrhage as a marker of neutrophil infiltration. Normal animals (n = 3) served as shams. Results. Hemorrhaged animals demonstrated significant increases in phosphorylated p38 at 1 h, phosphorylated JNK at 4 h, and increased MPO activity at 20 h (P < 0.05 compared with sham). VPA treatment significantly (P < 0.05) attenuated all of these changes. Conclusions. Hemorrhagic shock activates proinflammatory MAPK signaling pathways and promotes pulmonary neutrophil infiltration, affects that are significantly attenuated by VPA treatment. This may represent a key mechanism through which HDACIs decrease organ damage and promote survival in hemorrhagic shock. (C) 2012 Elsevier Inc. All rights reserved. C1 [Kochanek, Ashley R.; Fukudome, Eugene Y.; Li, Yongqing; Smith, Eleanor J.; Liu, Baoling; Velmahos, George C.; deMoya, Marc; King, David; Alam, Hasan B.] Harvard Univ, Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Dept Surg,Med Sch, Boston, MA 02114 USA. RP Alam, HB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Dept Surg,Med Sch, Boston, MA 02114 USA. EM hbalam@partners.org OI King, David/0000-0003-1028-1478 FU NIH [RO1 GM084127] FX The authors acknowledge support for this work by NIH RO1 GM084127 (HBA). NR 60 TC 13 Z9 15 U1 3 U2 7 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 JUL PY 2012 VL 176 IS 1 BP 185 EP 194 DI 10.1016/j.jss.2011.06.007 PG 10 WC Surgery SC Surgery GA 958BD UT WOS:000305210100036 PM 21816439 ER PT J AU Ono, S Obara, H Takayanagi, A Tanabe, M Kawachi, S Itano, O Shinoda, M Kitago, M Hibi, T Chiba, T Du, WL Matsumoto, K Tilles, AW Yarmush, ML Aiso, S Shimizu, N Sakamoto, M Kitagawa, Y AF Ono, Shigeshi Obara, Hideaki Takayanagi, Atsushi Tanabe, Minoru Kawachi, Shigeyuki Itano, Osamu Shinoda, Masahiro Kitago, Minoru Hibi, Taizo Chiba, Tomohiro Du, Wenlin Matsumoto, Kenji Tilles, Arno W. Yarmush, Martin L. Aiso, Sadakazu Shimizu, Nobuyoshi Sakamoto, Michiie Kitagawa, Yuko TI Suppressive Effects of Interleukin-18 on Liver Function in Rat Liver Allografts SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE adenovirus vector; interferon-gamma; interleukin-18; liver allograft ID IFN-GAMMA; IL-18-DEFICIENT MICE; CYTOKINE EXPRESSION; KIDNEY ALLOGRAFT; BINDING-PROTEIN; FAS-LIGAND; T-CELLS; REJECTION; TRANSPLANTATION; IL-18 AB Background. Interleukin-18 (IL-18) is a potent proinflammatory cytokine that augments both innate and acquired immune responses. It is also a crucial regulator of lymphocyte production of interferon-gamma (IFN-gamma), which can promote acute cellular rejection of transplanted solid organs. Methods. To evaluate the role of IL-18 in liver transplantation, we constructed an adenoviral vector encoding IL-18 binding protein (Adex-IL18bp), which specifically suppressed the biologic activity of IL-18, and examined the effect of this suppression on liver allografts by using a high-responder rat model (ACI to Lewis) of orthotopic liver transplantation (OLTx). Donor rats were given one intravenous injection of Adex-IL18bp or Adex-LacZ (control vector) 2 d before OLTx. Results. Seven days after OLTx, overexpression of IL-18bp resulting from the adenovirus gene transfer was associated with significantly decreased serum alanine aminotransferase levels and less histologic hepatic injury in recipient rats with Adex-IL18bp-pretreated donors compared with Adex-LacZ controls. Adex-IL18bp pretreatment also significantly prolonged rat/allograft survival, inhibited expression of IFN-gamma, and reduced levels (versus control values) of both CXCL10 and CX3CL1, which can be induced by IFN-gamma. Conclusion. These results suggest that IL-18 has an important role in liver allograft rejection through IFN-gamma and chemokines and that specific suppression of IL-18 may improve liver function early after transplantation. (C) 2012 Elsevier Inc. All rights reserved. C1 [Obara, Hideaki] Keio Univ, Sch Med, Dept Surg, Shinjuku Ku, Tokyo 1608582, Japan. [Takayanagi, Atsushi; Shimizu, Nobuyoshi] Keio Univ, Sch Med, Dept Mol Biol, Tokyo 1608582, Japan. [Chiba, Tomohiro; Aiso, Sadakazu] Keio Univ, Sch Med, Dept Anat, Tokyo 1608582, Japan. [Du, Wenlin; Sakamoto, Michiie] Keio Univ, Sch Med, Dept Pathol, Tokyo 1608582, Japan. [Shinoda, Masahiro; Tilles, Arno W.; Yarmush, Martin L.] Shriners Hosp Children, Massachusetts Gen Hosp, Ctr Engn Med & Surg Serv, Boston, MA USA. [Shinoda, Masahiro; Tilles, Arno W.; Yarmush, Martin L.] Harvard Univ, Sch Med, Boston, MA USA. RP Obara, H (reprint author), Keio Univ, Sch Med, Dept Surg, Shinjuku Ku, 35 Shinanomachi, Tokyo 1608582, Japan. EM obara@z3.keio.jp RI Obara, Hideaki/B-3174-2014 NR 39 TC 7 Z9 8 U1 1 U2 2 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 JUL PY 2012 VL 176 IS 1 BP 293 EP 300 DI 10.1016/j.jss.2011.07.053 PG 8 WC Surgery SC Surgery GA 958BD UT WOS:000305210100049 PM 21962809 ER PT J AU Latham, L MacDonald, A Kimball, AB Langley, RG AF Latham, Lesley MacDonald, Aimee Kimball, Alexa B. Langley, Richard G. TI Teaching empathy to undergraduate medical students using a temporary tattoo simulating psoriasis SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE disease burden; empathy; medical education; morbidity; psoriasis; quality of life; skin disease ID QUALITY-OF-LIFE; SKIN-DISEASE; DERMATOLOGY AB Background: Psoriasis has a profound negative effect on quality of life that is often underappreciated by health care professionals and the public. Objective: We sought to assess the perception of the burden of psoriasis relative to other medical conditions in first-year medical students, and to determine if wearing a temporary tattoo simulating psoriasis during a teaching exercise would change their perceptions. Methods: Participants completed a questionnaire assessing their perception of the impact of psoriasis and other common medical conditions (visual analog scale). Participants then wore a temporary tattoo of a psoriatic lesion for 24 hours and completed the same questionnaire after this exercise. Results: Of 91 students approached, 61 completed the study. At baseline, psoriasis (mean = 23.6) and eczema (mean = 23.3) were perceived as having the lowest physical burden of diseases queried (P < .0001), whereas the mental impact of psoriasis was scored comparably with arthritis, heart disease, and diabetes (mean = 45.1-56.7), but lower than cancer (mean = 82.2) and depression (mean = 93.8). After the exercise, the perception of the impact of eczema (physical: mean = 37.3, P < .0001; mental: mean = 66.6, P = .0005) and psoriasis (physical: mean = 37.8, P = .0014; mental: mean = 68.6, P = .0293) was significantly increased. Limitations: The exercise did not simulate the chronic nature of psoriasis or the scaling and pruritic characteristics of psoriatic lesions. The survey instrument used to assess empathy has not been previously validated and statistical analysis was limited by small sample size and the absence of a control group. Conclusions: Temporary tattoos are a novel and effective method of teaching medical students about the psychological burden of psoriasis. (J Am Acad Dermatol 2012;67:93-9.) C1 [Latham, Lesley; Langley, Richard G.] Dalhousie Univ, Div Dermatol, Dept Med, Halifax, NS B3H 2Y9, Canada. [MacDonald, Aimee] Dalhousie Univ, Sch Med, Halifax, NS B3H 2Y9, Canada. [Kimball, Alexa B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Clin Unit Res Trials Skin,Dept Dermatol, Cambridge, MA 02138 USA. RP Langley, RG (reprint author), Dalhousie Univ, Div Dermatol, Dept Med, Room 4-195,Dickson Bldg,QE 2 Hlth Sci Ctr, Halifax, NS B3H 2Y9, Canada. EM richardgblangley@gmail.com FU Canadian Dermatology Foundation FX Dr Langley receives funding from the Canadian Dermatology Foundation for his research on melanoma. NR 17 TC 3 Z9 3 U1 4 U2 16 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 JUL PY 2012 VL 67 IS 1 BP 93 EP 99 DI 10.1016/j.jaad.2011.07.023 PG 7 WC Dermatology SC Dermatology GA 959TI UT WOS:000305335900023 PM 21982056 ER PT J AU Hanchate, AD Lasser, KE Kapoor, A Rosen, J McCormick, D D'Amore, MM Kressin, NR AF Hanchate, Amresh D. Lasser, Karen E. Kapoor, Alok Rosen, Jennifer McCormick, Danny D'Amore, Meredith M. Kressin, Nancy R. TI Massachusetts Reform and Disparities in Inpatient Care Utilization SO MEDICAL CARE LA English DT Article; Proceedings Paper CT Meeting of the Society-of-General-Internal-Medicine CY MAY 05, 2011 CL Phoenix, AZ SP Soc Gen Internal Med DE health reform; disparities; utilization; inpatient care; access to care; socioeconomic status; race; ethnicity ID HEALTH-CARE; SOCIOECONOMIC-STATUS; MEDICAL-CARE; UNIVERSAL COVERAGE; ACCESS REFORM; INSURANCE; CANCER; PROGRESS; REMAIN; IMPACT AB Background: The 2006 Massachusetts health reform substantially decreased uninsurance rates. Yet, little is known about the reform's impact on actual health care utilization among poor and minority populations, particularly for receipt of inpatient surgical procedures that are commonly initiated by outpatient physician referral. Methods: Using discharge data on Massachusetts hospitalizations for 21 months before and after health reform implementation (7/1/2006-12/31/2007), we identified all nonobstetrical major therapeutic procedures for patients aged 40 or older and for which >= 70% of hospitalizations were initiated by outpatient physician referral. Stratifying by race/ethnicity and patient residential zip code median (area) income, we estimated prereform and postreform procedure rates, and their changes, for those aged 40-64 (nonelderly), adjusting for secular changes unrelated to reform by comparing to corresponding procedure rate changes for those aged 70 years and above (elderly), whose coverage (Medicare) was not affected by reform. Results: Overall increases in procedure rates (among 17 procedures identified) between prereform and postreform periods were higher for nonelderly low area income (8%, P = 0.04) and medium area income (8%, P < 0.001) cohorts than for the high area income cohort (4%); and for Hispanics and blacks (23% and 21%, respectively; P < 0.001) than for whites (7%). Adjusting for secular changes unrelated to reform, postreform increases in procedure utilization among nonelderly were: by area income, low = 13% (95% confidence interval (CI) = [9%, 17%]), medium = 15% (95% CI [6%, 24%]), and high = 2% (95% CI [-3%, 8%]); and by race/ethnicity, Hispanics = 22% (95% CI [5%, 38%]), blacks = 5% (95% CI [-20%, 30%]), and whites = 7% (95% CI [5%, 10%]). Conclusions: Postreform use of major inpatient procedures increased more among nonelderly lower and medium area income populations, Hispanics, and whites, suggesting potential improvements in access to outpatient care for these vulnerable subpopulations. C1 [Hanchate, Amresh D.] Boston Univ, Sch Med, Gen Internal Med Sect, Hlth Care Dispar Res Program, Boston, MA 02118 USA. [Hanchate, Amresh D.; Kressin, Nancy R.] VA Boston Healthcare Syst, Boston, MA USA. [Lasser, Karen E.] Boston Univ, Sch Publ Hlth, Dept Community Hlth Sci, Boston, MA 02118 USA. [Rosen, Jennifer] Boston Univ, Sch Med, Dept Surg, Boston, MA 02118 USA. [McCormick, Danny] Harvard Univ, Sch Med, Dept Med, Cambridge Hlth Alliance, Cambridge, MA 02138 USA. RP Hanchate, AD (reprint author), Boston Univ, Sch Med, Gen Internal Med Sect, Hlth Care Dispar Res Program, 801 Massachusetts Ave,2092, Boston, MA 02118 USA. EM hanchate@bu.edu OI Hanchate, Amresh/0000-0002-7038-4463; Kapoor, Alok/0000-0003-1300-7124; Kressin, Nancy/0000-0003-2767-4286; Lasser, Karen/0000-0003-3777-6075 FU NHLBI NIH HHS [1U01HL105342-01, U01 HL105342, U01 HL105342-01]; NINDS NIH HHS [1R21NS062677, R21 NS062677, R21 NS062677-02] NR 49 TC 23 Z9 23 U1 1 U2 12 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 JUL PY 2012 VL 50 IS 7 BP 569 EP 577 DI 10.1097/MLR.0b013e31824e319f PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 959DT UT WOS:000305292900003 PM 22683590 ER PT J AU Reed, M Graetz, I Wang, HH Fung, V Newhouse, JP Hsu, J AF Reed, Mary Graetz, Ilana Wang, Huihui Fung, Vicki Newhouse, Joseph P. Hsu, John TI Consumer-directed Health Plans With Health Savings Accounts Whose Skin is in the Game and How do Costs Affect Care Seeking? SO MEDICAL CARE LA English DT Article DE cost sharing; consumer directed; health savings account (HSA); health care benefits; financial burden ID COPAYMENTS; KNOWLEDGE; QUALITY AB Background: Employers are increasingly offering high-deductible health insurance plans with associated health savings accounts (HSAs), but there is limited information on account contributions or effects on patient care seeking. Objective: We examined HSA contributions and their source, patient-reported effects of costs on care seeking, and reports of financial burden. Research Design: We conducted telephone interviews with 488 adult members of small group of employer-sponsored HSA-eligible plans within an integrated delivery system. Principal Findings: HSA contribution sources and amounts varied with 32% receiving an employer contribution and also making their own employee contribution, 35% only receiving an employer contribution (no employee contribution), 19% only making their own contribution (no employer contribution), and 14% with no HSA contribution from either source. After adjustment for respondent characteristics, those who made their own HSA contributions in addition to their employer's contribution were significantly more likely to report that costs affected their care-seeking behavior, compared with those with only employer contributions (39% vs. 31% for emergency department and 60% vs. 49% for office visits, all P < 0.05). Respondents who contributed to their HSA or who paid out-of-pocket for care were significantly more likely to report financial burdens than those with only employer contributions (P < 0.05). Conclusions: The majority of consumers receive employer contributions to their HSA, but few have fully funded accounts. Those with only an employer contribution reported fewer changes in their care-seeking behavior and were less likely to report experiencing financial burdens. C1 [Reed, Mary; Graetz, Ilana] Kaiser Permanente Med Care Program, Div Res, Oakland, CA 94610 USA. [Wang, Huihui] World Bank, Nutr & Populat AFTHE, Africa Hlth, Washington, DC 20433 USA. [Fung, Vicki] Midatlantic Permanente Med Grp, Midatlantic Permanente Res Inst, Rockville, MD USA. [Newhouse, Joseph P.; Hsu, John] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Newhouse, Joseph P.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Newhouse, Joseph P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, John F Kennedy Sch Govt, Boston, MA USA. [Hsu, John] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Clin Econ & Policy Anal Program,Mongan Inst Hlth, Boston, MA USA. RP Reed, M (reprint author), Kaiser Permanente Med Care Program, Div Res, 2000 Broadway, Oakland, CA 94610 USA. EM Mary.E.Reed@kp.org RI Graetz, Ilana/N-1189-2016 OI Graetz, Ilana/0000-0003-3664-5815 NR 16 TC 3 Z9 3 U1 2 U2 14 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 JUL PY 2012 VL 50 IS 7 BP 585 EP 590 DI 10.1097/MLR.0b013e3182495cb3 PG 6 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 959DT UT WOS:000305292900005 PM 22322099 ER PT J AU Wong, ES Piette, JD Liu, CF Perkins, M Maciejewski, ML Jackson, GL Blough, DK Fihn, SD Au, DH Bryson, CL AF Wong, Edwin S. Piette, John D. Liu, Chuan-Fen Perkins, Mark Maciejewski, Matthew L. Jackson, George L. Blough, David K. Fihn, Stephan D. Au, David H. Bryson, Chris L. TI Measures of Adherence to Oral Hypoglycemic Agents at the Primary Care Clinic Level The Role of Risk Adjustment SO MEDICAL CARE LA English DT Article DE risk adjustment; adherence; diabetes; organization of care; veterans ID MEDICATION ADHERENCE; PERFORMANCE-MEASURES; MEANINGFUL VARIATION; VETERANS-AFFAIRS; THERAPY; QUALITY; PERSISTENCE; MORTALITY; DISEASE; COSTS AB Background: Prior research found that in the Veterans Affairs health care system (VA), the proportion of patients adherent to oral hypoglycemic agents varies from 50% to 80% across primary care clinics. This study examined whether variation in patient and facility characteristics determined those differences. Methods: Retrospective cohort study of 444,418 VA primary care patients with diabetes treated in 559 clinics in fiscal year (FY) 2006-2007. Patients' adherence to each oral hypoglycemic agent was computed for the first 3 months of FY2007, and averaged across agents to produce an adherence score for the patient's overall regimen. Patients with an adherence score over 0.8 were defined as adherent. Risk adjustment used hierarchical logistic regression accounting for patient factors and facility effects by clustering patients within clinics and clinics within parent VA medical centers. We then assessed the influence of risk adjustment using observed-to-expected (O/E) ratios computed for each clinic. Results: The mean unadjusted proportion of adherent patients in clinics was 0.715 (interdecile range 0.559-0.826). The percent variation in patient's likelihood of being adherent explained at the patient, clinic, and parent VA medical center levels was 2.94%, 0.27%, and 0.76%, respectively. The mean clinic-level observed-to-expected ratio was 1.001 (interdecile range 0.975-1.027). Conclusions: The variation in the proportion of patients adherent across clinics remained large after risk adjustment. As patient and facility effects explained only 4% of the variance in adherence, comparing clinics based on unadjusted scores is a reasonable starting point unless more predictive patient, provider, and facility factors are identified. C1 [Wong, Edwin S.; Liu, Chuan-Fen; Perkins, Mark] VA Puget Sound Hlth Care Syst, NW Ctr Outcomes Res Older Adults, Seattle, WA 98101 USA. [Wong, Edwin S.; Liu, Chuan-Fen] Univ Washington, Sch Publ Hlth & Community Med, Dept Hlth Serv, Seattle, WA 98195 USA. [Piette, John D.] VA Ann Arbor Healthcare Syst, Vet Affairs Ctr Clin Management Res, Ann Arbor, MI USA. [Piette, John D.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA. [Maciejewski, Matthew L.; Jackson, George L.] Durham VA Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC USA. [Maciejewski, Matthew L.; Jackson, George L.] Duke Univ, Med Ctr, Dept Med, Div Gen Internal Med, Durham, NC 27710 USA. [Blough, David K.] Univ Washington, Sch Pharm, Pharmaceut Outcomes Res & Policy Program, Seattle, WA 98195 USA. [Fihn, Stephan D.; Au, David H.; Bryson, Chris L.] Univ Washington, Dept Med, Seattle, WA USA. RP Wong, ES (reprint author), VA Puget Sound Hlth Care Syst, NW Ctr Outcomes Res Older Adults, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM eswong@uw.edu FU Department of Veterans Affairs, Health Services Research and Development [IIR 07-068-2]; VA Health Services Research and Development Postdoctoral Fellowship [TPP 61-024]; VA Career Development Award [03-177]; Gilead Sciences FX This research was supported by an Investigator Initiated Research Award (IIR 07-068-2) from the Department of Veterans Affairs, Health Services Research and Development. Dr Wong is supported by VA Health Services Research and Development Postdoctoral Fellowship TPP 61-024. Dr Bryson was supported by VA Career Development Award 03-177. An earlier version of this manuscript was presented as a poster at the Academy Health's Annual Research Meeting in Boston, MA in 2010.; Dr. Wong reports owning stock in Merck & Co., Inc. and the SPDR Health Care Select Sector Exchange Traded Fund. Dr. Fihn reports receiving travel/accomodations/meeting expenses from the Alliance for Academic Internal Medicine. Dr. Au reports serving as a consultant for Bosch Inc. and receiving grants from Gilead Sciences. All other authors declare no conflict of interest. NR 49 TC 11 Z9 11 U1 0 U2 4 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 JUL PY 2012 VL 50 IS 7 BP 591 EP 598 DI 10.1097/MLR.0b013e318249cb74 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 959DT UT WOS:000305292900006 PM 22354208 ER PT J AU Misra, M AF Misra, Madhusmita TI Effects of hypogonadism on bone metabolism in female adolescents and young adults SO NATURE REVIEWS ENDOCRINOLOGY LA English DT Review ID DEPOT MEDROXYPROGESTERONE ACETATE; TOTAL-BODY IRRADIATION; GROWTH-FACTOR-I; TRABECULAR STRUCTURE-ANALYSIS; ESTROGEN REPLACEMENT THERAPY; PREMENOPAUSAL BREAST-CANCER; ADJUVANT ENDOCRINE THERAPY; ORAL-CONTRACEPTIVE USE; PANEL VOLUME CT; ANOREXIA-NERVOSA AB Gonadal steroids, including androgens and oestrogens, play a critical part in bone metabolism, and conditions associated with a deficiency of gonadal steroids can reduce BMD in adults and impair bone accrual in adolescents. In addition, other associated hormone alterations, for example, insulin-like growth factor 1 deficiency or high cortisol levels, can further exacerbate the effect of hypogonadism on bone metabolism, as can factors such as calcium and vitamin D deficiency, low body weight and exercise status. This Review discusses the effects of different hypogonadal states on bone metabolism in female adolescents and young adults, with particular emphasis on conditions associated with low energy availability, such as anorexia nervosa and athletic amenorrhoea, in which many factors other than hypogonadism affect bone. In contrast to most hypogonadal conditions, in which replacement of gonadal steroids is sufficient to normalize bone accrual rates and BMD, gonadal steroid replacement may not be sufficient to normalize bone metabolism in these states of energy deficit. C1 [Misra, Madhusmita] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Misra, Madhusmita] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Misra, M (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, BUL 457,55 Fruit St, Boston, MA 02114 USA. EM mmisra@partners.org FU [1 R01 HD060827-01A1] FX The author's work is supported in part by grant 1 R01 HD060827-01A1. NR 145 TC 5 Z9 5 U1 2 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5029 EI 1759-5037 J9 NAT REV ENDOCRINOL JI Nat. Rev. Endocrinol. PD JUL PY 2012 VL 8 IS 7 BP 395 EP 404 DI 10.1038/nrendo.2011.238 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 959UE UT WOS:000305339300006 PM 22271187 ER PT J AU Lyall, K Pauls, DL Spiegelman, D Santangelo, SL Ascherio, A AF Lyall, Kristen Pauls, David L. Spiegelman, Donna Santangelo, Susan L. Ascherio, Alberto TI Fertility Therapies, Infertility and Autism Spectrum Disorders in the Nurses' Health Study II SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Article DE autism; infertility; fertility treatments; assisted reproductive technology (ART); ovulation-inducing drugs ID ASSISTED REPRODUCTIVE TECHNOLOGY; IN-VITRO FERTILIZATION; CHILDREN BORN; RISK-FACTORS; NEUROLOGICAL SEQUELAE; DIAGNOSTIC INTERVIEW; OVULATION INDUCTION; NATIONAL COHORT; CONCEPTION; MODELS AB Background: An increasing number of women are utilizing fertility treatments, but little is known about their relation to autism spectrum disorders (ASD). Methods: To determine the association between maternal fertility therapy use and risk of having a child with ASD, we conducted a nested case-control study within the Nurses' Health Study II (n = 116,430). Maternally reported diagnoses of ASD were confirmed through a supplementary questionnaire and, in a subgroup, the Autism Diagnostic Interview-Revised. Controls were randomly selected by frequency matching to case children's year of birth. Associations were examined by self-reported infertility and type of therapy using conditional logistic regression. Results: In all, 9% of the 507 cases and 7% of 2,529 controls indicated fertility therapy use for the index pregnancy. No significant associations with self-reported fertility therapies or history of infertility were seen in primary analyses. In subgroup analyses of women with maternal age =35 years (n = 1,020), artificial insemination was significantly associated with ASD; ovulation inducing drug (OID) use was significantly associated in crude but not adjusted analyses (odds ratio 1.81, 95% CI 0.963.42). Results were similar by diagnostic subgroup, though within the advanced maternal age group, OID and artificial insemination were significantly associated with Asperger syndrome and pervasive developmental disorder not-otherwise specified, but not autistic disorder. Conculsion: Assisted reproductive therapy and history of infertility did not increase risk of having a child with ASD in this study. However, the associations observed with OID and artificial insemination among older mothers, for whom these exposures are more common, warrant further investigation. C1 [Lyall, Kristen; Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Pauls, David L.; Spiegelman, Donna; Santangelo, Susan L.; Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Spiegelman, Donna] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Pauls, David L.; Santangelo, Susan L.] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Pauls, David L.; Santangelo, Susan L.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Ascherio, Alberto] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. RP Lyall, K (reprint author), 1616 Da Vinci Court, Davis, CA 95618 USA. EM klyall@hsph.harvard.edu FU NHS; Autism Speaks Foundation [1788]; US Army Medical Research and Material Command (USAMRMC) [A-14917]; [CA50385] FX The work reported in this manuscript was funded in part by CA50385, the main NHS II grant, #1788 from the Autism Speaks Foundation, and A-14917 from the US Army Medical Research and Material Command (USAMRMC). The first author, Dr Lyall, is currently affiliated with the M.I.N.D. Institute, University of California, Davis. NR 38 TC 25 Z9 25 U1 1 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0269-5022 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD JUL PY 2012 VL 26 IS 4 BP 361 EP 372 DI 10.1111/j.1365-3016.2012.01294.x PG 12 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA 956WY UT WOS:000305121500014 PM 22686388 ER PT J AU Moy, ML Danilack, VA Weston, NA Garshick, E AF Moy, Marilyn L. Danilack, Valery A. Weston, Nicole A. Garshick, Eric TI Daily step counts in a US cohort with COPD SO RESPIRATORY MEDICINE LA English DT Article DE Accelerometer; Exercise; Outcomes; Pulmonary disease ID OBSTRUCTIVE PULMONARY-DISEASE; PHYSICAL-ACTIVITY; LONG-TERM; ACCELEROMETER; POPULATION AB Background: Baseline values for daily step counts in US adults with COPD and knowledge of its accurate measurement, natural change over time, and independent relationships with measures of COPD severity are limited. Methods: 127 persons with stable COPD wore the StepWatch Activity Monitor (SAM) for 14 days, and 102 of them wore it a median 3.9 months later. SAM counts were compared to manual counts in the clinic. We assessed change over time, the effect of season, and relationships with forced expiratory volume in 1 s (FEV1) % predicted, 6-min walk test (6MWT) distance, the modified Medical Research Council (MMRC) dyspnea score, and the St. George's Respiratory Questionnaire Total Score (SGRQ-TS). Results: 98% of subjects were males, with mean age 71 +/- 8 years and FEV1 1.48 +/- 0.54 L (52 +/- 19% predicted). All 4 GOLD stages were represented, with the most subjects in GOLD 11(44%) and GOLD III (37%). The SAM had >90% accuracy in 99% of subjects. Average step count was 5680 steps/day, which decreased with increasing GOLD stage (p = 0.0046). Subjects walked 645 fewer steps/day at follow-up, which was partly explained by season of monitoring (p = 0.013). In a multivariate model, FEV1 % predicted, 6MWT distance and MMRC score were weakly associated with daily step counts, while SGRQ-TS was not. Conclusions: These findings will aid the design of future studies using daily step counts in COPD. Accurately measured, daily step counts decline over time partly due to season and capture unique information about COPD status. Published by Elsevier Ltd. C1 [Moy, Marilyn L.; Danilack, Valery A.; Weston, Nicole A.; Garshick, Eric] VA Boston Healthcare Syst, Pulm & Crit Care Med Sect, W Roxbury, MA 02132 USA. [Moy, Marilyn L.] Brigham & Womens Hosp, Div Pulm & Crit Care Med, Boston, MA 02115 USA. [Garshick, Eric] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. [Moy, Marilyn L.; Danilack, Valery A.; Garshick, Eric] Harvard Univ, Sch Med, Boston, MA USA. RP Moy, ML (reprint author), VA Boston Healthcare Syst, Pulm & Crit Care Sect, 1400 VFW Pkwy,Mail Code 111PI, W Roxbury, MA 02132 USA. EM marilyn.moy@va.gov FU Department of Veteran Affairs, Veterans Health Administration, Rehabilitation Research and Development Service; CIMIT: Center for Integration of Medicine and Innovative Technology; NIH/NICHD [RO1 HD42141]; VA Rehabilitation Research and Development Merit Review Grant [B6618R] FX The research reported here was supported by the Department of Veteran Affairs, Veterans Health Administration, Rehabilitation Research and Development Service through a VA Career Development Award to Dr. Moy.; Supported in part by CIMIT: Center for Integration of Medicine and Innovative Technology (Dr. Moy).; Supported in part by NIH/NICHD RO1 HD42141 and VA Rehabilitation Research and Development Merit Review Grant B6618R (Dr. Garshick). NR 30 TC 23 Z9 24 U1 0 U2 2 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0954-6111 J9 RESP MED JI Respir. Med. PD JUL PY 2012 VL 106 IS 7 BP 962 EP 969 DI 10.1016/j.rmed.2012.03.016 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System SC Cardiovascular System & Cardiology; Respiratory System GA 957LM UT WOS:000305164500007 PM 22521225 ER PT J AU Donohue, JF Anzueto, A Brooks, J Mehta, R Kalberg, C Crater, G AF Donohue, James F. Anzueto, Antonio Brooks, Jean Mehta, Rashmi Kalberg, Christopher Crater, Glenn TI A randomized, double-blind dose-ranging study of the novel LAMA GSK573719 in patients with COPD SO RESPIRATORY MEDICINE LA English DT Article DE Long-acting muscarinic receptor antagonist; Long-acting bronchodilator; Anticholinergic; Chronic obstructive pulmonary disease; G5K573719 ID OBSTRUCTIVE PULMONARY-DISEASE; MUSCARINIC ANTAGONIST; IPRATROPIUM; TIOTROPIUM; ACLIDINIUM AB Background: This study evaluated the dose-response and dosing interval of the novel long-acting muscarinic receptor antagonist (LAMA) GSK573719 in patients with COPD. Methods: This randomized, double-blind, placebo-controlled, 3-way cross-over, incomplete block study evaluated 5 once-daily doses of GSK573719 (62.5-1000 mu g), 3 twice-daily doses (62.5-250 mu g), and open-label tiotropium for 14 days in patients (N = 176) with COPD (FEV1 of 35-70% predicted). The primary endpoint was morning trough FEV1 at Day 15. Secondary endpoints included 0-24 h weighted mean FEV1 and serial FEV1 values over 28 h. Safety measures and pharmacokinetics were assessed. Results: All once-daily doses of GSK573719 significantly increased trough FEV1 at Day 15 with improvements ranging from 95 to 186 mL over placebo (p <= 0.006), from 79 to 172 mL with twice-daily dosing (p <= 0.03), and 105 mL with tiotropium (p = 0.003). No clear dose ordering was observed. Once-daily doses significantly (p < 0.001) increased 0-24 h weighted mean FEV1 at Day 14 by 131-143 mL over placebo, comparable to increases with the twice-daily doses (120-142 mL) and tiotropium (127 mL). Significant reductions in rescue albuterol use and improvements in FVC were also observed with once-daily dosing. Plasma C-max occurred within 5-15 min of dosing after which the drug was rapidly cleared and eliminated. GSK573719 was well tolerated, with no apparent treatment-related changes in vital signs, ECG and Hotter assessments, or clinical laboratory parameters. Conclusion: Once-daily dosing with GSK573719 in COPD provides clinically significant and sustained improvement in lung function over 24 h with similar efficacy to twice-daily dosing. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Donohue, James F.] Univ N Carolina, Coll Med, Dept Med, Chapel Hill, NC 27599 USA. [Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Anzueto, Antonio] Audie L Murphy Hosp, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Brooks, Jean] GlaxoSmithKline, Resp Med Dev Ctr, Stockley Pk UB11 1BT, England. [Mehta, Rashmi; Kalberg, Christopher; Crater, Glenn] GlaxoSmithKline, Resp Med Dev Ctr, Res Triangle Pk, NC 27709 USA. RP Donohue, JF (reprint author), Univ N Carolina, Coll Med, Dept Med, 4125 Bioinformat Bldg, Chapel Hill, NC 27599 USA. EM james_donohue@med.unc.edu; Anzueto@uthscsa.edu; jean.2.brooks@gsk.com; rashmi.s.mehta@gsk.com; chris.j.kalberg@gsk.com; glenn.d.crater@gsk.com OI Crater, Glenn/0000-0002-1159-1323 FU Boehringer Ingelheim; GlaxoSmithKline; Novartis; NHLBI; Lilly; Pfizer; Pneuma pharmaceuticals FX J.F.D. has served as consultant to Almirall, AstraZeneca, Boehringer Ingelheim, Dey, Elevation Pharmaceuticals, Forest Laboratories, GlaxoSmithKline, Novartis, Pearl Pharmaceuticals, Pfizer and Sunovion; and has received research grants from Boehringer Ingelheim, GlaxoSmithKline and Novartis. A.A. is an advisor, consultant, and speaker for Boehringer Ingelheim, GlaxoSmithKline, Pfizer, Merck, Bayer-Schering Pharma, Dey Pharma, Forest laboratories and has investigational grants with the NHLBI, GlaxoSmithKline, Lilly, Pfizer, and Pneuma pharmaceuticals. J.B., R.M., C.K., G.C. are employees of and hold stocks/shares in GlaxoSmithKline. NR 16 TC 46 Z9 48 U1 0 U2 5 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0954-6111 J9 RESP MED JI Respir. Med. PD JUL PY 2012 VL 106 IS 7 BP 970 EP 979 DI 10.1016/j.rmed.2012.03.012 PG 10 WC Cardiac & Cardiovascular Systems; Respiratory System SC Cardiovascular System & Cardiology; Respiratory System GA 957LM UT WOS:000305164500008 PM 22498110 ER PT J AU Cecere, LM Williams, EC Sun, H Bryson, CL Clark, BJ Bradley, KA Au, DH AF Cecere, Laura M. Williams, Emily C. Sun, Haili Bryson, Chris L. Clark, Brendan J. Bradley, Katharine A. Au, David H. TI Smoking cessation and the risk of hospitalization for pneumonia SO RESPIRATORY MEDICINE LA English DT Article DE Pneumonia; Smoking cessation; COPD ID COMMUNITY-ACQUIRED PNEUMONIA; OBSTRUCTIVE PULMONARY-DISEASE; ALCOHOL SCREENING SCORES; UNITED-STATES; HEALTH-STATUS; OLDER-ADULTS; MORTALITY; CARE; POPULATION; VETERANS AB Background: Smoking increases the risk of hospitalization for pneumonia, yet it is unknown if smoking cessation changes this risk. We sought to determine if smoking cessation and the duration of abstinence from tobacco reduce the risk of pneumonia hospitalization. Methods: We performed secondary analysis of data collected from male United States Veterans participating in a randomized trial. We used Cox proportional-hazard models to estimate risk of hospitalization for pneumonia within one year of enrollment. We adjusted for confounders, including: demographics, comorbidity, alcohol use, prior pneumonia, inhaled corticosteroid use, and intensity of tobacco exposure. Among a restricted cohort excluding never smokers, we assessed for effect modification by a diagnosis of chronic obstructive pulmonary disease (COPD). Results: Of the 25,235 participants, we identified 6720 current, 13,625 former, and 4890 never smokers. Compared to current smokers, never smokers had a decreased (adjusted HR 0.48, 95% Cl 0.31-0.74), while former smokers had no difference in (adjusted HR 0.83, 95% Cl 0.63-1.09) risk of hospitalization for pneumonia. Among participants without COPD, former smokers had a lower risk of hospitalization (adjusted HR 0.65, 95% Cl 0.45-0.95). However, this lower risk was isolated to those who quit tobacco more than 10 years previously (adjusted HR 0.62, 95% CI 0.41-0.93). Among those with COPD, there was no difference in risk with smoking cessation or duration of remaining tobacco-free. Conclusions: Tobacco cessation is likely important in reducing hospital admissions for pneumonia, but its benefit depends on duration of smoking cessation and is likely attenuated in the presence of COPD. Published by Elsevier Ltd. C1 [Cecere, Laura M.; Williams, Emily C.; Sun, Haili; Bryson, Chris L.; Bradley, Katharine A.; Au, David H.] Puget Sound Hlth Care Syst, Dept Vet Affairs, NW Ctr Excellence, HSR&D, Seattle, WA USA. [Cecere, Laura M.; Au, David H.] Univ Washington, Div Pulm & Crit Care Med, Dept Med, Seattle, WA USA. [Williams, Emily C.; Bradley, Katharine A.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Bryson, Chris L.; Bradley, Katharine A.] Univ Washington, Dept Med, Div Gen Internal Med, Seattle, WA USA. [Clark, Brendan J.] Univ Colorado Denver, Div Pulm Sci & Crit Care Med, Aurora, CO USA. [Bradley, Katharine A.] Grp Hlth Res Inst, Seattle, WA USA. RP Cecere, LM (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM lcecere@uw.edu FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development (HSRD) [IAC 05-206-1]; VA HSRD [TPM 61-037]; Giliad Sciences FX This study was supported by a Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development (HSR&D) grant [IAC 05-206-1]. Dr. Cecere is supported by a VA HSR&D fellowship [TPM 61-037]. 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.; Drs. Au and Bryson are co-investigators on a grant from Giliad Sciences for work which is unrelated to this manuscript. Dr. Au is a research consultant for Bosch LLC. Drs. Cecere, Williams, Sun, Clark, and Bradley have no potential conflicts of interest to disclose. NR 44 TC 5 Z9 6 U1 1 U2 3 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0954-6111 J9 RESP MED JI Respir. Med. PD JUL PY 2012 VL 106 IS 7 BP 1055 EP 1062 DI 10.1016/j.rmed.2012.03.018 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System SC Cardiovascular System & Cardiology; Respiratory System GA 957LM UT WOS:000305164500018 PM 22541719 ER PT J AU Onozato, M Merren, M Yagi, Y AF Onozato, Maristela Merren, Mark Yagi, Yukako TI Automated 3D-Reconstruction of Histological Sections SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Meeting Abstract C1 [Onozato, Maristela; Merren, Mark; Yagi, Yukako] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9173 EI 1943-7722 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD JUL 1 PY 2012 VL 138 SU 1 MA 311 BP A311 EP A311 PG 1 WC Pathology SC Pathology GA V45XG UT WOS:000209848700289 ER PT J AU Yagi, Y Hashimoto, N Bautista, PA AF Yagi, Yukako Hashimoto, Noriaki Bautista, Pinky A. TI Multispectral Imaging and Digital Staining of Pathology Images SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Meeting Abstract C1 [Yagi, Yukako; Bautista, Pinky A.] Harvard Med Sch, Boston, MA USA. [Yagi, Yukako; Hashimoto, Noriaki; Bautista, Pinky A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9173 EI 1943-7722 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD JUL 1 PY 2012 VL 138 SU 1 MA 73 BP A073 EP A073 PG 1 WC Pathology SC Pathology GA V45XG UT WOS:000209848700069 ER PT J AU Richman, JS Hosokawa, PW Min, SJ Tomeh, MG Neumayer, L Campbell, DA Henderson, WG Hawn, MT AF Richman, Joshua S. Hosokawa, Patrick W. Min, Sung-Joon Tomeh, Majed G. Neumayer, Leigh Campbell, Darrell A., Jr. Henderson, William G. Hawn, Mary T. TI Toward Prospective Identification of High-Risk Surgical Patients SO AMERICAN SURGEON LA English DT Article AB The purpose of this study was to explore the feasibility of prospectively identifying patients at high risk for surgical complications using automatable methods focused on patient characteristics. We used data from the Michigan Surgical Quality Collaborative (60,411 elective surgeries) performed between 2003 and 2008. Regression models for postoperative mortality, overall morbidity, cardiac, thromboembolic, pulmonary, renal, and surgical site infection complications were developed using preoperative patient and planned procedure data. Risk was categorized by quartiles of predicted probability: "low'' risk corresponding to the bottom quartile, "average'' to the middle two quartiles, and "high'' to the top quartile. C-indices were calculated to measure discrimination; model validity was assessed by cross-validation. Models were repeated using only patient characteristics. Risk category was closely related to event rates; 80 to 90 per cent of mortality and cardiac, renal, and pulmonary complications occurred among the 25 per cent of "high-risk" patients. Although thromboembolisms and surgical site infections were less predictable, 60 to 70 per cent of events occurred among high-risk patients. Cross-validation results were consistent and only slightly attenuated when predictors were restricted to patient characteristics alone. Adverse postoperative events are concentrated among patients identifiable preoperatively as high risk. Preoperative risk assessment could allow for efficient interventions targeted to high-risk patients. C1 [Richman, Joshua S.; Hawn, Mary T.] Birmingham Vet Affairs Med Ctr, C SMART, Birmingham, AL USA. [Richman, Joshua S.; Hawn, Mary T.] Univ Alabama Birmingham, Sch Med, Gastrointestinal Sect, Div Gen Surg, Birmingham, AL USA. [Hosokawa, Patrick W.; Min, Sung-Joon; Henderson, William G.] Univ Colorado, Sch Med, Colorado Hlth Outcomes Program, Denver, CO USA. [Tomeh, Majed G.] QCMetrix, Waltham, MA USA. [Neumayer, Leigh] Univ Utah, Salt Lake City, UT USA. [Campbell, Darrell A., Jr.] Univ Michigan Hlth Syst, Ann Arbor, MI USA. [Henderson, William G.] Univ Colorado, Sch Publ Hlth, Dept Biostat & Informat, Denver, CO 80202 USA. RP Richman, JS (reprint author), BVAMC, 700 South 19th St,REAP Mail Stop 151, Birmingham, AL 35222 USA. EM jrichman@uab.edu NR 17 TC 4 Z9 4 U1 2 U2 2 PU SOUTHEASTERN SURGICAL CONGRESS PI CUMMING PA 115 SAMARITAN DR, #200, CUMMING, GA 30040-2354 USA SN 0003-1348 EI 1555-9823 J9 AM SURGEON JI Am. Surg. PD JUL PY 2012 VL 78 IS 7 BP 755 EP 760 PG 6 WC Surgery SC Surgery GA V32LX UT WOS:000208953800013 PM 22748533 ER PT J AU Reslan, OM Ebaugh, JL Gupta, N Brecher, SM Itani, KMF Raffetto, JD AF Reslan, Ossama M. Ebaugh, James L. Gupta, Naren Brecher, Stephen M. Itani, Kamal M. F. Raffetto, Joseph D. TI Acute Expansion of a Hospital-Acquired Methicillin-Resistant Staphylococcus aureus-Infected Abdominal Aortic Aneurysm SO ANNALS OF VASCULAR SURGERY LA English DT Article ID CRYOPRESERVED ARTERIAL ALLOGRAFTS; IN-SITU REPLACEMENT; MYCOTIC-ANEURYSMS; STREPTOCOCCUS-PNEUMONIAE; VASCULAR INFECTION; RECONSTRUCTION; REPAIR; EXPERIENCE; GRAFT; PSEUDOANEURYSM AB Infected aortic aneurysms (IAAs) are rare but can have devastating outcomes, particularly if diagnosis and treatment are delayed.(1) The incidence of IAA is between 0.65% and 2% of all aortic aneurysms.(2) The disease has a poor prognosis because these aneurysms have an increased tendency to grow rapidly and to rupture,(3) and patients often have severe comorbidities and coexisting sepsis.(1) Typical microorganisms associated with IAA are Salmonella, Streptococci, and Staphylococcus aureus. Methicillin-resistant Staphylococcus aureus (MRSA) continues to emerge as a cause of serious infections, but its association with IAA is extremely rare. We present a rare case of infected abdominal aortic aneurysm caused by hospital-acquired (HA) MRSA. This case adds another presentation to the clinical spectrum of HA MRSA infections, and it highlights the problems encountered in the choice of the therapy of serious HA or health care-acquired infections in an era of increasing MRSA infections. We will discuss the clinical spectrum of HA MRSA infections as well as the problems encountered in the management of IAA, and will review the relevant literature. C1 [Raffetto, Joseph D.] VA Boston HCS, Div Vasc Surg, Dept Surg, W Roxbury, MA 02132 USA. [Reslan, Ossama M.; Ebaugh, James L.; Gupta, Naren; Itani, Kamal M. F.; Raffetto, Joseph D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Surg, Boston, MA 02115 USA. [Reslan, Ossama M.; Ebaugh, James L.; Gupta, Naren; Itani, Kamal M. F.; Raffetto, Joseph D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Vasc Surg, Boston, MA 02115 USA. [Brecher, Stephen M.; Itani, Kamal M. F.] Boston Univ, Sch Med, Dept Surg, Boston, MA 02118 USA. [Brecher, Stephen M.] VA Boston HCS, Dept Pathol & Lab Med, W Roxbury, MA 02132 USA. RP Raffetto, JD (reprint author), VA Boston HCS, Div Vasc Surg, Dept Surg, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM joseph.raffetto@med.va.gov NR 42 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0890-5096 J9 ANN VASC SURG JI Ann. Vasc. Surg. PD JUL PY 2012 VL 26 IS 5 AR 732.e1 DI 10.1016/j.avsg.2011.08.030 PG 6 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 953VO UT WOS:000304901500028 PM 22664293 ER PT J AU Goh, AC Kowalkowski, MA Bailey, DE Kazer, MW Knight, SJ Latini, DM AF Goh, Alvin C. Kowalkowski, Marc A. Bailey, Donald E., Jr. Kazer, Meredith W. Knight, Sara J. Latini, David M. TI Perception of cancer and inconsistency in medical information are associated with decisional conflict: a pilot study of men with prostate cancer who undergo active surveillance SO BJU INTERNATIONAL LA English DT Article DE prostate cancer; decision-making; active surveillance; quality of life; uncertainty AB OBJECTIVE To understand the factors associated with decision-making, we conducted a telephone-based survey as part of a pilot study to develop a psychoeducational intervention for men with prostate cancer who undergo active surveillance. PATIENTS AND METHODS From 2007 to 2008, we conducted a cross-sectional study of 34 individuals on active surveillance for prostate cancer. We examined how specific mental health, quality of life and sociodemographic characteristics relate to decision-making. Five validated decision-making scales were used as primary outcomes reflecting the amount of satisfaction, regret and conflict a participant experienced about his decision to undergo active surveillance. A multivariate regression model was developed to identify specific psychosocial factors related to the decision-making outcomes. RESULTS Primary analyses focused on the decisional satisfaction and conflict measures, as the decisional regret measure showed poor reliability (alpha < 0.70) in this sample. Four psychosocial measures showed strong associations across the decision-making subscales, including the Fife Constructed Meaning Scale (Pearson r > 0.26), Mishel Uncertainty in Illness Scale - Inconsistency (r > 0.32), Mental Health Index-5 (r > 0.33), and Lepore self-efficacy for prostate symptom management scale (r > 0.33). Individuals with higher self-efficacy for prostate cancer symptom management (P = 0.02) and higher positive meaning for cancer (P = 0.03) were less likely to express decision-making conflict as the result of uncertainty. Individuals reporting higher positive meaning for cancer (P = 0.01) and less uncertainty in illness attributed to inconsistency (P = 0.02) were less likely to exhibit decision-making conflict related to the perceived effectiveness of treatment. CONCLUSIONS Men choosing active surveillance represent a patient group with unique vulnerabilities that require new psychoeducational interventions to provide information and support that will maintain and improve quality of life. We describe specific characteristics that may put patients at higher risk during the decision-making process and indicate their increased need for such interventions. C1 [Goh, Alvin C.; Latini, David M.] Baylor Coll Med, Scott Dept Urol, Houston, TX 77030 USA. [Kowalkowski, Marc A.; Latini, David M.] Michael E DeBakey VA Med Ctr, VA Hlth Serv Res, Houston, TX USA. [Kowalkowski, Marc A.; Latini, David M.] Michael E DeBakey VA Med Ctr, Dev Ctr Excellence, Houston, TX USA. [Kowalkowski, Marc A.; Latini, David M.] Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. [Bailey, Donald E., Jr.] Duke Univ, Sch Nursing, Durham, NC USA. [Kazer, Meredith W.] Fairfield Univ, Fairfield, CT 06430 USA. [Knight, Sara J.] Univ Calif San Francisco, Dept Urol, San Francisco VA Med Ctr, San Francisco, CA USA. [Knight, Sara J.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Latini, David M.] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA. RP Goh, AC (reprint author), Baylor Coll Med, Scott Dept Urol, 6620 Main St Ste 1325, Houston, TX 77030 USA. EM acg622@gmail.com OI Kowalkowski, Marc/0000-0003-2624-4209; Latini, David/0000-0002-6161-4861 FU American Cancer Society [06-083-01-CPPB] FX This material is partly the result of work supported with resources and the use of facilities at the Health Services Research & Development Center of Excellence (HFP90-020), Michael E. DeBakey Veterans Affairs Medical Center. Dr Latini is supported by Mentored Research Scholar Grant 06-083-01-CPPB from the American Cancer Society. The views expressed reflect those of the authors and not necessarily those of the Department of Veterans Affairs or Baylor College of Medicine. NR 25 TC 16 Z9 16 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 EI 1464-410X J9 BJU INT JI BJU Int. PD JUL PY 2012 VL 110 IS 2B BP E50 EP E56 DI 10.1111/j.1464-410X.2011.10791.x PG 7 WC Urology & Nephrology SC Urology & Nephrology GA V31JY UT WOS:000208881100008 PM 22145791 ER PT J AU Robbins, CS Swirski, FK AF Robbins, Clinton S. Swirski, Filip K. TI Newly discovered innate response activator B cells: crucial responders against microbial sepsis SO EXPERT REVIEW OF CLINICAL IMMUNOLOGY LA English DT Editorial Material DE B cells; B lymphocytes; granulocyte-macrophage colony-stimulating factor; infection; innate immunity; sepsis C1 [Robbins, Clinton S.; Swirski, Filip K.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Robbins, Clinton S.; Swirski, Filip K.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Robbins, CS (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA. EM robbins.clinton@mgh.harvard.edu FU NCI NIH HHS [P50 CA86355, R24 CA69246]; NHLBI NIH HHS [U01 HL080731, 1R01HL095612, R01 HL095612]; PHS HHS [P01-A154904] NR 15 TC 5 Z9 5 U1 0 U2 9 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1744-666X EI 1744-8409 J9 EXPERT REV CLIN IMMU JI Expert Rev. Clin. Immunol. PD JUL PY 2012 VL 8 IS 5 BP 405 EP 407 DI 10.1586/ECI.12.32 PG 3 WC Immunology SC Immunology GA V32NY UT WOS:000208959100003 PM 22882214 ER PT J AU Huang, YY Tanaka, M Vecchio, D Garcia-Diaz, M Chang, J Morimoto, Y Hamblin, MR AF Huang, Ying-Ying Tanaka, Masamitsu Vecchio, Daniela Garcia-Diaz, Maria Chang, Julie Morimoto, Yuji Hamblin, Michael R. TI Photodynamic therapy induces an immune response against a bacterial pathogen SO EXPERT REVIEW OF CLINICAL IMMUNOLOGY LA English DT Review DE bacterial arthritis; bioluminescence imaging; methicillin-resistant Staphylococcus aureus; methylene blue; neutrophils; photodynamic therapy; Photofrin (R); preventative PDT AB Photodynamic therapy (PDT) employs the triple combination of photosensitizers, visible light and ambient oxygen. When PDT is used for cancer, it has been observed that both arms of the host immune system (innate and adaptive) are activated. When PDT is used for infectious disease, however, it has been assumed that the direct antimicrobial PDT effect dominates. Murine arthritis caused by methicillin-resistant Staphylococcus aureus in the knee failed to respond to PDT with intravenously injected Photofrin (R). PDT with intra-articular Photofrin produced a biphasic dose response that killed bacteria without destroying host neutrophils. Methylene blue was the optimum photosensitizer to kill bacteria while preserving neutrophils. We used bioluminescence imaging to noninvasively monitor murine bacterial arthritis and found that PDT with intra-articular methylene blue was not only effective, but when used before infection, could protect the mice against a subsequent bacterial challenge. The data emphasize the importance of considering the host immune response in PDT for infectious disease. C1 [Huang, Ying-Ying; Tanaka, Masamitsu; Vecchio, Daniela; Garcia-Diaz, Maria; Chang, Julie; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Huang, Ying-Ying; Tanaka, Masamitsu; Vecchio, Daniela; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Huang, Ying-Ying] Guangxi Med Univ, Dept Pathol, Guangxi 530027, Peoples R China. [Tanaka, Masamitsu] Natl Def Med Coll, Dept Orthoped Surg, Tokorozawa, Saitama 3598513, Japan. [Tanaka, Masamitsu; Morimoto, Yuji] Natl Def Med Coll, Dept Integrated Physiol & Bionano Med, Tokorozawa, Saitama 3598513, Japan. [Garcia-Diaz, Maria] Univ Ramon Llull, Inst Quim Sarria, Barcelona 08017, Spain. [Chang, Julie] Harvard Univ, Dept Chem, Cambridge, MA 02138 USA. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu RI Garcia-Diaz, Maria/J-9202-2014; OI Garcia-Diaz, Maria/0000-0002-4794-5437; Hamblin, Michael/0000-0001-6431-4605 FU US NIH [R01AI050875 M]; Ministry of Education, Culture, Sports, Science and Technology of Japan [23659628] FX Research in the Hamblin laboratory is supported by US NIH grant R01AI050875 M. Tanaka and Y Morimoto were supported by a Grant-in-Aid for Challenging Exploratory Research (23659628) from the Ministry of Education, Culture, Sports, Science and Technology of Japan. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 142 TC 11 Z9 11 U1 1 U2 11 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1744-666X EI 1744-8409 J9 EXPERT REV CLIN IMMU JI Expert Rev. Clin. Immunol. PD JUL PY 2012 VL 8 IS 5 BP 479 EP 494 DI 10.1586/ECI.12.37 PG 16 WC Immunology SC Immunology GA V32NY UT WOS:000208959100016 PM 22882222 ER PT J AU Fernandez, JF Sibila, O Restrepo, MI AF Fernandez, Juan F. Sibila, Oriol Restrepo, Marcos I. TI Predicting ICU admission in community-acquired pneumonia: clinical scores and biomarkers SO EXPERT REVIEW OF CLINICAL PHARMACOLOGY LA English DT Article DE biomarkers; community-acquired infections; ICU; pneumonia; score; severity AB Community-acquired pneumonia (CAP) remains a common and serious worldwide health problem. Despite all the advances in therapy, significant interest has focused on the identification of patients with CAP who require intensive care unit admission to improve their outcomes. The severity assessment of CAP provides an important guide to clinicians in deciding the site of care and the use of empiric antibiotics and adjuvant therapy. For years, several clinical assessment scores have been suggested and validated to achieve this goal. The recent introduction of biomarkers as prognostic indicators of severe CAP, whether used alone or in conjunction with other clinical severity of illness scores, has been investigated. An objective scoring system with a high level of sensitivity and specificity to predict the severity of CAP and the need for high levels of care do not exist. Today, the addition of clinical scores and biomarkers to clinical judgment is the best approach to optimize the care of severe CAP. Future research will allow validation of these and newer tools to improve the prognosis of patients with CAP. C1 [Fernandez, Juan F.; Sibila, Oriol; Restrepo, Marcos I.] Univ Texas Hlth Sci Ctr San Antonio, Div Pulm Crit Care Med, San Antonio, TX 78229 USA. [Sibila, Oriol] Hosp Santa Creu & Sant Pau, Serv Pneumol, Barcelona, Spain. [Restrepo, Marcos I.] South Texas Vet Hlth Care Syst, Div Pulm Crit Care Med, San Antonio, TX 78229 USA. [Restrepo, Marcos I.] South Texas Vet Hlth Care Syst ALMD, Vet Evidence Based Res Disseminat & Implementat C, San Antonio, TX 78229 USA. RP Restrepo, MI (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Div Pulm Crit Care Med, San Antonio, TX 78229 USA. EM restrepom@uthscsa.edu RI Restrepo, Marcos/H-4442-2014 FU National Heart, Lung and Blood Institute [K23HL096054]; Instituto de Salud Carlos III [BAE11/00102]; Sociedad Espanola de Neumologia y Cirugia Toracica (SEPAR); Societat Catalana de Pneumologia (SOCAP) FX MI Restrepo has participated in advisory boards for Ortho-McNeil-Janssen, Theravan, Forest Laboratories, Johnson & Johnson, Trius and Novartis. He is a former speaker for Covidien, BARD, Inc, Johnson & Johnson (Ortho-McNeil-Janssen) and Pfizer, and is also a consultant for Theravan, Trius and Pfizer (Wyeth). His time is partially protected by Award Number K23HL096054 from the National Heart, Lung and Blood Institute. O Sibila is supported by Instituto de Salud Carlos III (BAE11/00102), Sociedad Espanola de Neumologia y Cirugia Toracica (SEPAR) and Societat Catalana de Pneumologia (SOCAP). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 119 TC 3 Z9 4 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1751-2441 J9 EXPERT REV CLIN PHAR JI Expert Rev. Clin. Pharmacol. PD JUL PY 2012 VL 5 IS 4 BP 445 EP 458 DI 10.1586/ECP.12.28 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA V37PS UT WOS:000209288300016 PM 22943124 ER PT J AU Thompson, DA Kass, N Holzmueller, C Marsteller, JA Martinez, EA Gurses, AP Kanchuger, M Schwann, N Gibson, CS Bauer, L Pronovost, PJ AF Thompson, David A. Kass, Nancy Holzmueller, Christine Marsteller, Jill A. Martinez, Elizabeth A. Gurses, Ayse P. Kanchuger, Marc Schwann, Nanette Gibson, Charles S. Bauer, Laura Pronovost, Peter J. TI Variation in Local Institutional Review Board Evaluations of a Multicenter Patient Safety Study SO JOURNAL FOR HEALTHCARE QUALITY LA English DT Article DE cardiac surgery services; institutional review board; patient safety; quality improvement; research oversight AB Several highly visible quality improvement (QI) projects led to controversy over their ethical oversight, attracting attention from institutional review boards (IRBs) and the Office for Human Research Protection. While QI research has increased dramatically, there is limited empirical evidence regarding how multiple IRBs review the same study. This paper describes the variations in local IRB reviews for the same a multicenter QI study. The study, entitled "Locating Errors through Networked Surveillance", used multiple data collection methods to identify patient safety risks in cardiovascular operating room services. This study involved 2-day site visits to 5 hospitals by the research team to observe cardiac surgery procedures and interview staff regarding clinical practice and hazards. Surveys were self-administered. The IRB process varied widely across the 5 hospitals. Reviews ranged from full committee review and approval with verbal consent required from patients and operating room staff, to an IRB determining the study exempt from review and participant consent. The time to IRB approval ranged from 6 weeks to 6 months. This variation suggests there is wide interpretation of the Federal regulations put in place to guide IRBs. The adoption of uniformity would not only reduce inefficiencies but also attenuate the perceived arbitrary nature of current IRB review processes that often inappropriately influence hypothesis-generation and study design. C1 [Thompson, David A.] Johns Hopkins Univ, Sch Med, Dept Anesthesiol, Baltimore, MD 21218 USA. [Thompson, David A.] Johns Hopkins Univ, Sch Med, Dept Crit Care Med, Baltimore, MD 21218 USA. [Thompson, David A.] Johns Hopkins Univ, Sch Nursing, Div Acute & Chron Care, Baltimore, MD USA. [Thompson, David A.] Johns Hopkins Univ, Patient Safety Curriculum, Dept Anesthesiol & Crit Care Med, Baltimore, MD USA. [Kass, Nancy] Johns Hopkins, Berman Bioeth Inst, Bioeth & Publ Hlth, Baltimore, MD USA. [Kass, Nancy] Johns Hopkins, Berman Bioeth Inst, Publ Hlth, Baltimore, MD USA. [Kass, Nancy; Marsteller, Jill A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD USA. [Holzmueller, Christine] Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, Qual & Safety Res Grp, Baltimore, MD 21205 USA. [Marsteller, Jill A.] Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21205 USA. [Martinez, Elizabeth A.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Martinez, Elizabeth A.] Johns Hopkins Univ, ICU, Baltimore, MD 21218 USA. [Gurses, Ayse P.] Johns Hopkins Univ, Sch Med, Bloomberg Sch Publ Hlth, Baltimore, MD 21218 USA. [Kanchuger, Marc] NYU, Sch Med, New York, NY 10003 USA. [Kanchuger, Marc] NYU, Langone Med Ctr, Dept Anesthesia, New York, NY 10003 USA. [Schwann, Nanette] Penn State Hershey Coll Med, Hershey, PA USA. [Schwann, Nanette] Lehigh Valley Hosp & Hlth Network, Allentown, PA USA. [Schwann, Nanette] Drexel Univ, Coll Med, Philadelphia, PA USA. [Schwann, Nanette] Inst Womens Hlth & Leadership, Philadelphia, PA USA. [Gibson, Charles S.] Baystate Med Ctr, Dept Anesthesiol, Springfield, MA USA. [Bauer, Laura] Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, QSRG, Baltimore, MD 21205 USA. [Pronovost, Peter J.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD 21205 USA. [Pronovost, Peter J.] Johns Hopkins Univ, Sch Nursing, Baltimore, MD 21205 USA. RP Thompson, DA (reprint author), Johns Hopkins Univ, Sch Med, Dept Anesthesiol, Baltimore, MD 21218 USA. EM dthomps1@jhmi.edu FU Society of Cardiovascular Anesthesiologists (SCA); SCA Foundation; Agency for Healthcare Research and Quality [K01HS018762] FX The LENS study was funded by the Society of Cardiovascular Anesthesiologists (SCA). The FOCUS Initiative is a collaborative project of the Society of Cardiovascular Anesthesiologists, the SCA Foundation, and the Johns Hopkins University Quality and Safety Research Group. FOCUS is funded exclusively by the SCA Foundation. Dr. Gurses was supported by a grant from the Agency for Healthcare Research and Quality (K01HS018762). None of the authors have a financial stake in the funding agency described here. NR 16 TC 9 Z9 9 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1062-2551 EI 1945-1474 J9 J HEALTHC QUAL JI J. Healthc. Qual. PD JUL-AUG PY 2012 VL 34 IS 4 BP 33 EP 39 DI 10.1111/j.1945-1474.2011.00150.x PG 7 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA V36OO UT WOS:000209221200004 PM 22060010 ER PT J AU Ferencik, M Brady, TJ Hoffmann, U AF Ferencik, Maros Brady, Thomas J. Hoffmann, Udo TI Computed tomography imaging of cardiac allograft vasculopathy SO JOURNAL OF CARDIOVASCULAR COMPUTED TOMOGRAPHY LA English DT Review DE Cardiac computed tomography; Coronary computed tomography angiography; Heart transplantation; Cardiac allograft vasculopathy AB Cardiac allograft vasculopathy (CAV) is the main cause of morbidity and mortality beyond 1 year after heart transplantation. Ischemic symptoms are usually not present because of the denervated allograft and diffuse nature of the disease. Patients present with heart failure, ventricular arrhythmia, or sudden cardiac death as a result of advanced CAV. Therefore, clinical evaluation includes routine annual invasive coronary angiography (ICA) and transthoracic echocardiography to screen for CAV. Noninvasive imaging methods for the detection of CAV have not been widely adopted. Computed tomography (CT) permits detection of coronary stenoses and plaque in the nontransplant population. The strength of CT is its high negative predictive value. These attributes predispose CT to a role of a gatekeeper for further invasive testing in heart transplant recipients. We reviewed the available literature on CT evaluation of CAV. Technical challenges (eg, high heart rates, need for contrast and radiation, image quality) specific for patients who have received a heart transplant are emphasized, and solutions, including appropriate protocols and advances through the new CT technology, are summarized. We systematically analyze the results of studies that report the diagnostic performance of cardiac CT for the detection of coronary stenoses compared with ICA. Similar analysis is performed for the comparison between CT and intravascular ultrasound scanning for the detection of nonobstructive CAV. Finally, we suggest future directions in cardiac CT imaging research of CAV. (C) 2012 Society of Cardiovascular Computed Tomography. All rights reserved. C1 [Ferencik, Maros] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Ferencik, Maros; Brady, Thomas J.; Hoffmann, Udo] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Brady, Thomas J.; Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Ferencik, M (reprint author), Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St, Boston, MA 02114 USA. EM maros_ferencik@hms.harvard.edu NR 44 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-5925 J9 J CARDIOVASC COMPUT JI J. Cardiovasc. Comput. Tomogr. PD JUL-AUG PY 2012 VL 6 IS 4 BP 223 EP 231 DI 10.1016/j.jcct.2011.11.007 PG 9 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA V34CJ UT WOS:000209064200002 PM 22732195 ER PT J AU Meyer, JD Stegner, AJ Natelson, BH Cook, DB AF Meyer, Jacob D. Stegner, Aaron J. Natelson, Benjamin H. Cook, Dane B. TI Psychobiological Response To Exercise Differs Between Chronic Fatigue Syndrome (CFS) And CFS With Comorbid Fibromyalgia SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Meyer, Jacob D.; Stegner, Aaron J.] Univ Wisconsin, Madison, WI USA. [Natelson, Benjamin H.] Beth Israel Deaconess Med Ctr, New York, NY 10003 USA. [Cook, Dane B.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. EM jdmeyer3@wisc.edu NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 MA 1496 BP 325 EP 326 PG 3 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142901253 ER PT J AU Allsup, K Lecker, S Zavin, A Joseph, J Lazzari, A Vokonas, P Forman, DE AF Allsup, Kelly Lecker, Stewart Zavin, Alexandra Joseph, Jacob Lazzari, Antonio Vokonas, Pantel Forman, Daniel E. TI Comparing Physical And Funcational Measures In Heart Failure Patients And Healthy Controls SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Allsup, Kelly; Zavin, Alexandra; Joseph, Jacob; Lazzari, Antonio; Vokonas, Pantel; Forman, Daniel E.] VA Boston Healthcare Syst, Boston, MA USA. [Lecker, Stewart] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. EM Kelly.Allsup@VA.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 MA 2430 BP 658 EP 658 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142902532 ER PT J AU Ahluwalia, S AF Ahluwalia, Sangeeta TI IMPROVING THE STATE OF QUALITY MEASUREMENT: LESSONS FROM "DOWN UNDER" SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Ahluwalia, Sangeeta] Vet Adm Greater Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S226 EP S226 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900296 ER PT J AU Ashburner, JM Ward, CE Chang, YC Fosburgh, BW Atlas, SJ AF Ashburner, Jeffrey M. Ward, Charlotte E. Chang, Yuchiao Fosburgh, Blair W. Atlas, Steven J. TI DIFFERENCES IN PATIENT PERCEPTIONS OF THE QUALITY OF COMMUNICATION AMONG STAFF AND RESIDENT PRIMARY CARE PHYSICIANS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Ashburner, Jeffrey M.; Ward, Charlotte E.; Chang, Yuchiao; Fosburgh, Blair W.; Atlas, Steven J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S162 EP S163 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900154 ER PT J AU Benner, C Chabner, B Lui, R Aldrich, L Oo, S Rodgers, N Percac-Lima, S AF Benner, Carly Chabner, Bruce Lui, Raymond Aldrich, Leslie Oo, Sarah Rodgers, Nessa Percac-Lima, Sanja TI PATIENT NAVIGATION TO IMPROVE COLPOSCOPY FOLLOW UP AFTER AN ABNORMAL PAP SMEAR AMONG LATINA WOMEN SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Benner, Carly; Chabner, Bruce; Lui, Raymond; Percac-Lima, Sanja] Harvard Univ, Sch Med, Boston, MA USA. [Chabner, Bruce; Lui, Raymond] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Oo, Sarah; Percac-Lima, Sanja] Massachusetts Gen Hosp, Chelsea HealthCare Ctr, Boston, MA 02114 USA. [Aldrich, Leslie; Oo, Sarah; Rodgers, Nessa] Massachusetts Gen Hosp, Ctr Community Hlth Improvement, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S262 EP S263 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900383 ER PT J AU Bitton, A Schiff, G Yu, T Henderson, D Lipsitz, SR Simon, SR Flier, LA Keohane, C Bates, DW AF Bitton, Asaf Schiff, Gordon Yu, Tony Henderson, Daniel Lipsitz, Stuart R. Simon, Steven R. Flier, Lydia A. Keohane, Carol Bates, David W. TI CHANGES IN PATIENT EXPERIENCE IN A PAYMENT-LINKED PATIENT CENTERED MEDICAL HOME DEMONSTRATION PROJECT SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Bitton, Asaf; Schiff, Gordon; Yu, Tony; Henderson, Daniel; Lipsitz, Stuart R.; Simon, Steven R.; Flier, Lydia A.; Keohane, Carol; Bates, David W.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Bitton, Asaf] Harvard Univ, Sch Med, Boston, MA USA. [Bates, David W.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Henderson, Daniel] Univ Connecticut, Sch Med, Farmington, CT USA. [Simon, Steven R.] VA Boston HealthCare Syst, Jamaica Plain, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S138 EP S138 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900096 ER PT J AU Caverly, T Richlie, D Prochazka, AV Cook-Shimanek, MK Pawlak, M Woodward, J Stickrath, C AF Caverly, Tanner Richlie, Daniel Prochazka, Allan V. Cook-Shimanek, Margaret K. Pawlak, Mary Woodward, Jennifer Stickrath, Chad TI RISK-BENEFIT DISCUSSION PRIOR TO COMPUTED TOMOGRAPHY IMAGING - INFREQUENT AND INEFFECTIVE? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Caverly, Tanner; Prochazka, Allan V.; Cook-Shimanek, Margaret K.; Pawlak, Mary; Woodward, Jennifer; Stickrath, Chad] Univ Colorado, Denver, CO 80202 USA. [Caverly, Tanner; Richlie, Daniel; Prochazka, Allan V.; Stickrath, Chad] Denver Vet Affairs Med Ctr, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S302 EP S303 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900484 ER PT J AU Chang, E Rose, D Yano, EM Wells, K Lee, M Rubenstein, LV AF Chang, Evelyn Rose, Danielle Yano, Elizabeth M. Wells, Kenneth Lee, Martin Rubenstein, Lisa V. TI DETERMINANTS OF READINESS FOR PRIMARY CARE-MENTAL HEALTH INTEGRATION (PC-MHI) IN THE VA HEALTH CARE SYSTEM SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Chang, Evelyn] VA Greater Los Angeles, Los Angeles, CA USA. [Rose, Danielle; Yano, Elizabeth M.; Lee, Martin; Rubenstein, Lisa V.] VA HSR&D Ctr Excellence Study Healthcare Provider, North Hills, CA USA. [Wells, Kenneth] Univ Calif Los Angeles, Los Angeles, CA USA. [Wells, Kenneth; Rubenstein, Lisa V.] RAND Corp, Santa Monica, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S158 EP S158 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900143 ER PT J AU Chen, LM Birkmeyer, JD Saint, S Jha, AK AF Chen, Lena M. Birkmeyer, John D. Saint, Sanjay Jha, Ashish K. TI HOSPITALIST STAFFING AND PATIENT SATISFACTION IN THE NATIONAL MEDICARE POPULATION SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Chen, Lena M.; Saint, Sanjay] VA Ann Arbor Healthcare Syst, Ann Arbor, MI USA. [Chen, Lena M.; Birkmeyer, John D.; Saint, Sanjay] Univ Michigan, Ann Arbor, MI 48109 USA. [Jha, Ashish K.] VA Boston Healthcare Syst, Boston, MA USA. [Jha, Ashish K.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S211 EP S212 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900264 ER PT J AU Clair, C Cohen, MJ Eichler, FS Rigotti, NA AF Clair, Carole Cohen, Marya J. Eichler, Florian S. Rigotti, Nancy A. TI THE EFFECT OF CIGARETTE SMOKING ON DIABETIC PERIPHERAL NEUROPATHY: A SYSTEMATIC REVIEW AND META-ANALYSIS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Clair, Carole] Univ Lausanne, Lausanne, Switzerland. [Clair, Carole; Cohen, Marya J.; Eichler, Florian S.; Rigotti, Nancy A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Clair, Carole/D-9786-2014 OI Clair, Carole/0000-0001-5281-0943 NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S320 EP S320 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900527 ER PT J AU Cordasco, KM Zephyrin, LC Canelo, I Kessler, C Mallard, M Rubenstein, LV Yano, EM AF Cordasco, Kristina M. Zephyrin, Laurie C. Canelo, Ismelda Kessler, Chad Mallard, Merri Rubenstein, Lisa V. Yano, Elizabeth M. TI 2011 VETERANS' HEALTH ADMINISTRATION EMERGENCY SERVICES FOR WOMEN (ESW) SURVEY SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Cordasco, Kristina M.; Canelo, Ismelda; Rubenstein, Lisa V.; Yano, Elizabeth M.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Cordasco, Kristina M.; Rubenstein, Lisa V.] Univ Calif Los Angeles, David Geffin Sch Med, Los Angeles, CA USA. [Zephyrin, Laurie C.; Mallard, Merri] Vet Hlth Adm, Washington, DC USA. [Zephyrin, Laurie C.] VA New York Harbor Healthcare Syst, New York, NY USA. [Kessler, Chad] Jesse Brown VA Hosp, Chicago, IL USA. [Kessler, Chad] Univ Illinois, Chicago, IL USA. [Yano, Elizabeth M.] UCLA Sch Publ Hlth, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S99 EP S99 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900002 ER PT J AU Durant, RW Redmond, N You, ZY Hullett, S Sheppard, AR Scarinci, I AF Durant, Raegan W. Redmond, Nicole You, Zhiying Hullett, Sandral Sheppard, A. Robert Scarinci, Isabel TI RACIAL DIFFERENCES IN SELF-EFFICACY AMONG AFRICAN-AMERICANS AND WHITES WITH HEART FAILURE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Durant, Raegan W.; Redmond, Nicole; You, Zhiying; Sheppard, A. Robert; Scarinci, Isabel] Univ Alabama Birmingham, Birmingham, AL USA. [Durant, Raegan W.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Redmond, Nicole; Hullett, Sandral] Cooper Green Mercy Hosp, Birmingham, AL USA. [Sheppard, A. Robert] DCH Reg Med Ctr, Tuscaloosa, AL USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S292 EP S292 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900457 ER PT J AU Edelman, EJ Gordon, KS Becker, W Goulet, JL Skanderson, M Gaither, JR Braden, JB Gordon, A Kerns, R Justice, AC Fiellin, DA AF Edelman, E. J. Gordon, Kirsha S. Becker, William Goulet, Joseph L. Skanderson, Melissa Gaither, Julie R. Braden, Jennifer B. Gordon, Adam Kerns, Robert Justice, Amy C. Fiellin, David A. TI HIV STATUS IS AN INDEPENDENT PREDICTOR OF RECEIVING OPIOID ANALGESICS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Edelman, E. J.; Becker, William; Justice, Amy C.; Fiellin, David A.] Yale Univ, Sch Med, New Haven, CT USA. [Gordon, Kirsha S.; Becker, William; Goulet, Joseph L.; Skanderson, Melissa; Kerns, Robert; Justice, Amy C.] VA Connecticut Healthcare Syst, West Haven, CT USA. [Gordon, Kirsha S.] Columbia Univ, Sch Publ Hlth, New York, NY USA. [Gaither, Julie R.] Yale Univ, Sch Publ Hlth, New Haven, CT USA. [Braden, Jennifer B.] Univ Washington, Seattle, WA 98195 USA. [Gordon, Adam] Univ Pittsburgh, Pittsburgh, PA USA. [Gordon, Adam] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S203 EP S204 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900247 ER PT J AU Hanchate, AD Zheng, X Lasser, KE McCormick, D D'Amore, M Kapoor, A Kressin, NR AF Hanchate, Amresh D. Zheng, Xin Lasser, Karen E. McCormick, Danny D'Amore, Meredith Kapoor, Alok Kressin, Nancy R. TI IMPACT OF MASSACHUSETTS HEALTH REFORM ON RACIAL AND ETHNIC DISPARITIES IN USE OF INPATIENT CARDIOVASCULAR SURGERIES SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Hanchate, Amresh D.; Kressin, Nancy R.] VA Boston Healthcare Syst, Boston, MA USA. [Hanchate, Amresh D.; Zheng, Xin; Lasser, Karen E.; D'Amore, Meredith; Kapoor, Alok; Kressin, Nancy R.] Boston Univ, Sch Med, Boston Med Ctr, Boston, MA 02118 USA. [McCormick, Danny] Cambridge Hlth Alliance, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S219 EP S219 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900279 ER PT J AU Heyworth, L Rozenblum, R Meterko, M Prescott, D Neuwirth, Z Simon, SR AF Heyworth, Leonie Rozenblum, Ronen Meterko, Mark Prescott, Debra Neuwirth, Zeev Simon, Steven R. TI GROUP MEDICAL VISITS VERSUS USUAL CARE ON SATISFACTION AND PATIENT-CENTERED CARE EXPERIENCES: RESULTS FROM A THREE-YEAR STUDY. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Heyworth, Leonie; Rozenblum, Ronen; Simon, Steven R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Meterko, Mark; Simon, Steven R.] VA Boston Hlth Care Syst, Boston, MA USA. [Prescott, Debra; Neuwirth, Zeev] Atrius Hlth, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S202 EP S202 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900244 ER PT J AU Hong, CS Chang, YC Grant, RW Ashburner, JM Ferris, T Atlas, SJ AF Hong, Clemens S. Chang, Yuchiao Grant, Richard W. Ashburner, Jeffrey M. Ferris, Timothy Atlas, Steven J. TI Y DEVELOPMENT AND VALIDATION OF A PREDICTIVE MODEL TO IDENTIFY PATIENTS WHO PHYSICIANS DEFINE AS COMPLEX SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Hong, Clemens S.; Chang, Yuchiao; Grant, Richard W.; Ashburner, Jeffrey M.; Ferris, Timothy; Atlas, Steven J.] Massachusetts Gen Hosp, Brookline, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S160 EP S160 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900149 ER PT J AU Kangovi, S Grande, D Ryan, DA Meehan, P Mitra, N Shannon, R Long, JA AF Kangovi, Shreya Grande, David Ryan, Daniel A. Meehan, Patricia Mitra, Nandita Shannon, Richard Long, Judith A. TI PERCEPTIONS OF READMITTED PATIENTS ON THE TRANSITION FROM HOSPITAL TO HOME SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Kangovi, Shreya; Long, Judith A.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Kangovi, Shreya; Ryan, Daniel A.] Robert Wood Johnson Fdn Clin Scholars Program, Philadelphia, PA USA. [Grande, David; Shannon, Richard; Long, Judith A.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Grande, David; Mitra, Nandita] Univ Penn, Philadelphia, PA 19104 USA. [Meehan, Patricia] Univ Penn Hlth Syst, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S271 EP S271 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900405 ER PT J AU Kertesz, S Pollio, DE Holt, C Steward, JL Gordon, A Kim, TW Stringfellow, E Austin, E Golden, J Johnson, N Davis, LL AF Kertesz, Stefan Pollio, David E. Holt, Cheryl Steward, Jocelyn L. Gordon, Adam Kim, Theresa W. Stringfellow, Erin Austin, Erika Golden, Joya Johnson, Nancy Davis, Lori L. TI COMPARISON OF TAILORED VERSUS MAINSTREAM PRIMARY CARE DELIVERY FOR HOMELESS PERSONS: A NEW, VALIDATED PATIENT ASSESSMENT TOOL SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Kertesz, Stefan; Austin, Erika; Johnson, Nancy] Birmingham VAMC, Homewood, AL USA. [Kertesz, Stefan; Pollio, David E.; Steward, Jocelyn L.; Davis, Lori L.] Univ Alabama Birmingham, Birmingham, AL USA. [Kim, Theresa W.; Stringfellow, Erin] Boston Hlth Care Homeless, Boston, MA USA. [Holt, Cheryl] Univ Maryland, Baltimore, MD 21201 USA. [Golden, Joya] VA Greater Los Angeles, Los Angeles, CA USA. [Gordon, Adam] VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S147 EP S147 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900118 ER PT J AU Korthuis, T Marshall, R Beach, MC Saha, S Mori, T Loveless, MO Hibbard, JH Cohn, JA Sharp, VL AF Korthuis, Todd Marshall, Rebecca Beach, Mary Catherine Saha, Somnath Mori, Tomi Loveless, Mark O. Hibbard, Judith H. Cohn, Jonathan A. Sharp, Victoria L. TI PATIENT ACTIVATION AND IMPROVED OUTCOMES IN HIV-INFECTED PATIENTS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Korthuis, Todd; Marshall, Rebecca; Saha, Somnath; Mori, Tomi; Loveless, Mark O.; Hibbard, Judith H.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Beach, Mary Catherine] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Saha, Somnath] Portland VA Med Ctr, Portland, OR USA. [Hibbard, Judith H.] Univ Oregon, Eugene, OR 97403 USA. [Cohn, Jonathan A.] Wayne State Univ, Detroit, MI USA. [Sharp, Victoria L.] St Lukes Roosevelt Hosp, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S261 EP S262 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900381 ER PT J AU Kruse, GR Kelley, JH Linder, JA Park, ER Rigotti, NA AF Kruse, Gina R. Kelley, Jennifer H. Linder, Jeffrey A. Park, Elyse R. Rigotti, Nancy A. TI IMPLEMENTATION OF AN ELECTRONIC HEALTH-RECORD-BASED TOBACCO CARE MANAGEMENT SYSTEM FOR IMPROVING TREATMENT IN PRIMARY CARE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Kruse, Gina R.; Kelley, Jennifer H.; Park, Elyse R.; Rigotti, Nancy A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kruse, Gina R.; Linder, Jeffrey A.; Rigotti, Nancy A.] Harvard Univ, Sch Med, Boston, MA USA. [Linder, Jeffrey A.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S223 EP S224 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900290 ER PT J AU Kruse, GR Chang, YC Kelley, JH Linder, JA Rigotti, NA AF Kruse, Gina R. Chang, Yuchiao Kelley, Jennifer H. Linder, Jeffrey A. Rigotti, Nancy A. TI EFFECT OF A PAY-FOR-PERFORMANCE INCENTIVE TO INCREASE TOBACCO USE DOCUMENTATION IN AN ELECTRONIC HEALTH RECORD SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Kruse, Gina R.; Chang, Yuchiao; Kelley, Jennifer H.; Rigotti, Nancy A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kruse, Gina R.; Chang, Yuchiao; Linder, Jeffrey A.; Rigotti, Nancy A.] Harvard Univ, Sch Med, Boston, MA USA. [Kelley, Jennifer H.] Partners Hlth Care, Boston, MA USA. [Linder, Jeffrey A.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S176 EP S176 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900185 ER PT J AU Kullgren, JT Loewenstein, G Troxel, AB Norton, L Wesby, L Zhu, JS Tao, YY Volpp, KG AF Kullgren, Jeffrey T. Loewenstein, George Troxel, Andrea B. Norton, Laurie Wesby, Lisa Zhu, Jingsan Tao, Yuanyuan Volpp, Kevin G. TI A RANDOMIZED CONTROLLED TRIAL OF FINANCIAL INCENTIVES TO PROMOTE WEIGHT LOSS AMONG OBESE EMPLOYEES SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Kullgren, Jeffrey T.; Norton, Laurie; Volpp, Kevin G.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Kullgren, Jeffrey T.; Troxel, Andrea B.; Norton, Laurie; Wesby, Lisa; Zhu, Jingsan; Tao, Yuanyuan; Volpp, Kevin G.] Univ Penn, Philadelphia, PA 19104 USA. [Loewenstein, George] Carnegie Mellon Univ, Pittsburgh, PA 15213 USA. NR 0 TC 0 Z9 0 U1 1 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S102 EP S103 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900010 ER PT J AU Lam, KD Miao, YH Steinman, MA AF Lam, Khoa D. Miao, Yinghui Steinman, Michael A. TI CUMULATIVE CHANGES IN USE OF CHRONIC MEDICATIONS: A NEW MEASURE OF PRESCRIBING INTENSITY SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Lam, Khoa D.; Steinman, Michael A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Miao, Yinghui; Steinman, Michael A.] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S151 EP S151 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900128 ER PT J AU Larue, NM Pang, LD Paasche-Orlow, MK Volandes, AE AF Larue, Nicole M. Pang, Linda Paasche-Orlow, Michael K. Volandes, Angelo E. TI THE SYMPTOM BURDEN OF PATIENTS CONSULTED ON BY PALLIATIVE CARE IS UNDERESTIMATED BY THE PRIMARY INPATIENT CARE TEAM SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Larue, Nicole M.; Pang, Linda; Paasche-Orlow, Michael K.] Boston Univ, Med Ctr, Boston, MA USA. [Volandes, Angelo E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S327 EP S328 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900546 ER PT J AU Lasser, KE Pizer, SD Legler, A D'Amore, M Ash, AS Allison, J Shanahan, CW Adams, WG Berlowitz, D Kressin, NR AF Lasser, Karen E. Pizer, Steven D. Legler, Aaron D'Amore, Meredith Ash, Arlene S. Allison, Jeroan Shanahan, Christopher W. Adams, William G. Berlowitz, Dan Kressin, Nancy R. TI PRIMARY CARE WORKLOAD AND BLOOD PRESSURE MANAGEMENT DID NOT WORSEN AT AN URBAN SAFETY-NET HOSPITAL IN MASSACHUSETTS FOLLOWING HEALTH REFORM SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Lasser, Karen E.; Legler, Aaron; D'Amore, Meredith; Shanahan, Christopher W.; Adams, William G.; Kressin, Nancy R.] Boston Univ, Sch Med, Boston Med Ctr, Boston, MA 02118 USA. [Pizer, Steven D.; Kressin, Nancy R.] VA Boston Healthcare Syst, Boston, MA USA. [Lasser, Karen E.; Pizer, Steven D.; Berlowitz, Dan] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Ash, Arlene S.; Allison, Jeroan] Univ Massachusetts, Sch Med, Boston, MA 02125 USA. [Berlowitz, Dan] Bedford VA Med Ctr, Bedford, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S287 EP S287 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900444 ER PT J AU Lasser, KE Chu, C McCormick, D Kressin, NR D'Amore, M Cabral, H Kapoor, A Rose, A Hanchate, A AF Lasser, Karen E. Chu, Chieh McCormick, Danny Kressin, Nancy R. D'Amore, Meredith Cabral, Howard Kapoor, Alok Rose, Adam Hanchate, Amresh TI MASSACHUSETTS HEALTH REFORM DID NOT REDUCE 30-DAY READMISSIONS FOR ACUTE MYOCARDIAL INFARCTION AMONG MASSACHUSETTS RESIDENTS OVERALL OR AMONG RACIAL/ETHNIC MINORITIES. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Lasser, Karen E.; Chu, Chieh; Kressin, Nancy R.; D'Amore, Meredith; Kapoor, Alok; Rose, Adam; Hanchate, Amresh] Boston Univ, Sch Med, Boston Med Ctr, Boston, MA 02118 USA. [McCormick, Danny] Harvard Univ, Sch Med, Cambridge Hlth Alliance, Cambridge, MA 02138 USA. [Kressin, Nancy R.; Hanchate, Amresh] VA Boston Healthcare Syst, Boston, MA USA. [Lasser, Karen E.; Cabral, Howard] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Rose, Adam] Bedford VA Med Ctr, Bedford, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S243 EP S244 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900340 ER PT J AU Lawrence, V Noel, PH Yoder, LH Cornell, JE Johnson, AE Hsu, JR Wolf, SE AF Lawrence, Valerie Noel, Polly H. Yoder, Linda H. Cornell, John E. Johnson, Anthony E. Hsu, Joseph R. Wolf, Steven E. TI MENTAL HEALTH STATUS AND PHYSICAL FUNCTION OF COMBAT-INJURED MILITARY PERSONNEL AT HOSPITAL DISCHARGE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Lawrence, Valerie; Noel, Polly H.; Cornell, John E.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Lawrence, Valerie; Noel, Polly H.; Cornell, John E.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Yoder, Linda H.] Univ Texas Austin, Austin, TX 78712 USA. [Yoder, Linda H.; Hsu, Joseph R.] US Army Inst Surg Res, Ft Sam Houston, TX USA. [Johnson, Anthony E.; Hsu, Joseph R.] San Antonio Mil Med Ctr, Ft Sam Houston, TX USA. [Wolf, Steven E.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S246 EP S247 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900347 ER PT J AU Linsky, A Simon, SR AF Linsky, Amy Simon, Steven R. TI PATIENT IDENTIFICATION OF THEIR "MOST" AND "LEAST" IMPORTANT MEDICATION SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Linsky, Amy; Simon, Steven R.] VA Boston Healthcare Syst, Boston, MA USA. [Linsky, Amy] Boston Univ, Sch Med, Boston, MA 02118 USA. [Simon, Steven R.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S262 EP S262 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900382 ER PT J AU Linsky, A Simon, SR AF Linsky, Amy Simon, Steven R. TI MEDICATION DISCREPANCIES IN INTEGRATED ELECTRONIC HEALTH RECORDS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Linsky, Amy; Simon, Steven R.] VA Boston Healthcare Syst, Boston, MA USA. [Linsky, Amy] Boston Univ, Sch Med, Boston, MA 02118 USA. [Simon, Steven R.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S246 EP S246 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900345 ER PT J AU Liu, CF Perkins, M Wong, E Bryson, CL AF Liu, Chuan-Fen Perkins, Mark Wong, Edwin Bryson, Christopher L. TI SURVEY RESPONSES AND MEDICATION ADHERENCE AMONG DIABETIC PATIENTS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Liu, Chuan-Fen; Perkins, Mark; Wong, Edwin; Bryson, Christopher L.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Liu, Chuan-Fen; Bryson, Christopher L.] Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S312 EP S312 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900507 ER PT J AU Lynch, CP Gebregziabher, M Hunt, KJ Echols, C Gilbert, G Egede, LE AF Lynch, Cheryl P. Gebregziabher, Mulugeta Hunt, Kelly J. Echols, Carrae Gilbert, Gregory Egede, Leonard E. TI IMPACT OF MEDICAL AND PSYCHIATRIC COMORBIDITY BURDEN AND MORTALITY IN VETERANS WITH TYPE 2 DIABETES SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Lynch, Cheryl P.; Gebregziabher, Mulugeta; Hunt, Kelly J.; Echols, Carrae; Gilbert, Gregory; Egede, Leonard E.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Lynch, Cheryl P.; Gebregziabher, Mulugeta; Hunt, Kelly J.; Egede, Leonard E.] Med Univ S Carolina, Charleston, SC 29425 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S219 EP S220 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900280 ER PT J AU Lynch, CP Gebregziabher, M Axon, RN Hunt, KJ Echols, C Egede, LE AF Lynch, Cheryl P. Gebregziabher, Mulugeta Axon, R. Neal Hunt, Kelly J. Echols, Carrae Egede, Leonard E. TI COMPARISON OF COMORBIDITY RISK ADJUSTMENT METHODS IN A NATIONAL COHORT OF VETERANS WITH DIABETES SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Lynch, Cheryl P.; Gebregziabher, Mulugeta; Axon, R. Neal; Hunt, Kelly J.; Egede, Leonard E.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Lynch, Cheryl P.; Gebregziabher, Mulugeta; Axon, R. Neal; Hunt, Kelly J.; Echols, Carrae; Egede, Leonard E.] Med Univ S Carolina, Charleston, SC 29425 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S146 EP S147 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900117 ER PT J AU McCormick, D Hanchate, AD Kressin, NR Lin, MY D'Amore, M Lasser, KE AF McCormick, Danny Hanchate, Amresh D. Kressin, Nancy R. Lin, Mengyun D'Amore, Meredith Lasser, Karen E. TI IMPACT OF MASSACHUSETTS HEALTH CARE REFORM ON THE RISK OF HOSPITALIZATION FOR CARDIOVASCULAR AMBULATORY CARE SENSITIVE CONDITIONS. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [McCormick, Danny] Harvard Univ, Sch Med, Cambridge Hlth Alliance, Cambridge, MA USA. [Hanchate, Amresh D.; Kressin, Nancy R.] VA Boston Healthcare Syst, Boston, MA USA. [Hanchate, Amresh D.; Kressin, Nancy R.; Lin, Mengyun; D'Amore, Meredith; Lasser, Karen E.] Boston Univ, Sch Med, Boston Med Ctr, Boston, MA 02118 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S219 EP S219 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900278 ER PT J AU Percac-Lima, S Lopez, L Ashburner, JM Green, A Atlas, SJ AF Percac-Lima, Sanja Lopez, Lenny Ashburner, Jeffrey M. Green, Alexander Atlas, Steven J. TI DECREASING DISPARITIES IN COLORECTAL CANCER PREVENTION USING A CULTURALLY TAILORED PATIENT NAVIGATOR PROGRAM SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Percac-Lima, Sanja] Massachussetts Gen Hosp, Chelsea, MA USA. [Lopez, Lenny; Ashburner, Jeffrey M.; Green, Alexander; Atlas, Steven J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S154 EP S154 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900135 ER PT J AU Percac-Lima, S Bond, B Ashburner, J Oo, S Atlas, S AF Percac-Lima, Sanja Bond, Barbara Ashburner, Jeffrey Oo, Sarah Atlas, Steven TI DECREASING DISPARITIES IN BREAST CANCER SCREENING IN REFUGEE WOMEN USING CULTURALLY TAILORED PATIENT NAVIGATION SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Percac-Lima, Sanja; Oo, Sarah] Massachussetts Gen Hosp, Chelsea, MA USA. [Percac-Lima, Sanja; Bond, Barbara; Ashburner, Jeffrey; Oo, Sarah; Atlas, Steven] Massachusets Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S154 EP S154 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900134 ER PT J AU Richter, JM Lown, B Gareis, K Kormos, W Kriegel, G Leffler, DA Manning, C Meyer, G Puopolo, AL Sands, K Ship, A Weil, EM AF Richter, James M. Lown, Beth Gareis, Karen Kormos, William Kriegel, Gila Leffler, Daniel A. Manning, Colleen Meyer, Gregg Puopolo, Ann Louise Sands, Kenneth Ship, Amy Weil, Eric M. TI SCHWARTZ CENTER CONNECTIONS: QUALITY WITH COMPASSION SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Lown, Beth] Schwartz Ctr Compassionate Healthcare, Boston, MA USA. [Richter, James M.; Kormos, William; Meyer, Gregg; Weil, Eric M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gareis, Karen; Manning, Colleen] Goodman Res Grp Inc, Cambridge, MA USA. [Kriegel, Gila; Leffler, Daniel A.; Sands, Kenneth; Ship, Amy] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Puopolo, Ann Louise] CRICO RMF, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S305 EP S305 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900491 ER PT J AU Schnipper, JL Karson, AS Morash, SK Glotzbecker, B Milone, MJ Raley, DSY Nolido, NV Horsky, J Leinen, L Bhan, I Dankers, C Church, KL Minahan, JA Yoon, C AF Schnipper, Jeffrey L. Karson, Andrew S. Morash, Susan K. Glotzbecker, Brett Milone, Marsha J. Raley, Deborah S. Yolin Nolido, Nyryan V. Horsky, Jan Leinen, Laura Bhan, Ishir Dankers, Christian Church, Kendra L. Minahan, Jacquelyn A. Yoon, Catherine TI DESIGN AND EVALUATION OF A MULTI-DISCIPLINARY WEB-BASED HANDOFF TOOL SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Schnipper, Jeffrey L.; Glotzbecker, Brett; Milone, Marsha J.; Raley, Deborah S. Yolin; Nolido, Nyryan V.; Horsky, Jan; Church, Kendra L.; Minahan, Jacquelyn A.; Yoon, Catherine] Brigham & Womens Hosp, Boston, MA 02115 USA. [Schnipper, Jeffrey L.; Karson, Andrew S.; Glotzbecker, Brett; Bhan, Ishir; Dankers, Christian] Harvard Univ, Sch Med, Boston, MA USA. [Karson, Andrew S.; Morash, Susan K.; Bhan, Ishir; Dankers, Christian] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Horsky, Jan; Leinen, Laura] Partners Healthcare, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S156 EP S157 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900141 ER PT J AU Simmons, LH Leavitt, L Greipp, C Sepucha, KR AF Simmons, Leigh H. Leavitt, Lauren Greipp, Christine Sepucha, Karen R. TI A SURVEY OF PRIMARY CARE CLINICIANS ON USE OF DECISION AIDS AND CONFIDENCE IN SHARED DECISION MAKING SKILLS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Simmons, Leigh H.; Leavitt, Lauren; Greipp, Christine; Sepucha, Karen R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S104 EP S105 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900015 ER PT J AU Simon, SR Fix, G Archambeault, C Stewart, MD McInnes, K Hogan, TP Grochow, R AF Simon, Steven R. Fix, Gemmae Archambeault, Cliona Stewart, Max D. McInnes, Keith Hogan, Timothy P. Grochow, Rebecca TI BARRIERS TO ADOPTION AND USE OF A NATIONWIDE WEB-BASED PERSONAL HEALTH RECORD AND PATIENT PORTAL: A QUALITATIVE STUDY OF VA'S MYHEALTHEVET SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Simon, Steven R.; Archambeault, Cliona; Stewart, Max D.; Grochow, Rebecca] VA Boston Healthcare Syst, Boston, MA USA. [Simon, Steven R.; Stewart, Max D.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Fix, Gemmae; McInnes, Keith; Hogan, Timothy P.] VA Med Ctr ENRM, Bedford, MA USA. [Hogan, Timothy P.] Univ Massachusetts, Sch Med, Worcester, MA USA. [Fix, Gemmae; McInnes, Keith] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Grochow, Rebecca] Boston Univ, Sch Med, Boston, MA 02118 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S131 EP S132 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900080 ER PT J AU Simonetti, JA Fine, MJ Simak, DM Chen, YF Hess, R AF Simonetti, Joseph A. Fine, Michael J. Simak, Deborah M. Chen, Yi-Fan Hess, Rachel TI RACIAL DISPARITIES IN INTERMEDIATE OUTCOMES OF DIABETES CARE IN A PATIENT-CENTERED MEDICAL HOME SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Simonetti, Joseph A.; Fine, Michael J.; Simak, Deborah M.; Hess, Rachel] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Fine, Michael J.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Chen, Yi-Fan] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S291 EP S291 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900455 ER PT J AU Snyder, E Castiglioni, A Estrada, C You, ZY Kertesz, S Schumacher, JE AF Snyder, Erin Castiglioni, Analia Estrada, Carlos You, Zhiying Kertesz, Stefan Schumacher, Joseph E. TI AN EDUCATIONAL INTERVENTION TO IMPROVE OPIATE PRESCRIBING PRACTICES IN RESIDENT CLINIC SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Snyder, Erin; Castiglioni, Analia; Estrada, Carlos; You, Zhiying; Kertesz, Stefan; Schumacher, Joseph E.] Univ Alabama Birmingham, Birmingham, AL USA. [Snyder, Erin; Castiglioni, Analia; Estrada, Carlos; Kertesz, Stefan] Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S119 EP S120 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900050 ER PT J AU Stickrath, C Griffiths, M Prochazka, AV Aagaard, EM Anderson, M Deloughry, MN AF Stickrath, Chad Griffiths, Megan Prochazka, Allan V. Aagaard, Eva M. Anderson, Melver Deloughry, Melissa N. TI MAXIMIZING TEACHING EFFECTIVENESS: PREDICTORS OF LEARNER SATISFACTION WITH TEACHING ON ROUNDS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Stickrath, Chad; Prochazka, Allan V.; Anderson, Melver] Denver VA Med Ctr, Denver, CO USA. [Stickrath, Chad; Griffiths, Megan; Prochazka, Allan V.; Aagaard, Eva M.; Anderson, Melver; Deloughry, Melissa N.] Univ Colorado Denver, Aurora, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S244 EP S244 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900341 ER PT J AU Thompson, R Immen, E Litvak, A Ward, C Desroches, C Torchiana, D Ferris, T AF Thompson, Ryan Immen, Elizabeth Litvak, Andrea Ward, Cathleen Desroches, Catherine Torchiana, David Ferris, Timothy TI AN ANALYSIS TO DETERMINE DRIVERS OF SATISFACTION AND DISSATISFACTION IN THE PATIENT EXPERIENCE OF INPATIENT CONTINUITY OF CARE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Thompson, Ryan; Immen, Elizabeth; Litvak, Andrea; Ward, Cathleen; Desroches, Catherine; Torchiana, David; Ferris, Timothy] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S115 EP S115 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900039 ER PT J AU Vassy, JL Donelan, K Hivert, MF O'Brien, KE Grant, RW AF Vassy, Jason L. Donelan, Karen Hivert, Marie-France O'Brien, Kelsey E. Grant, Richard W. TI CHRONIC DISEASE RISK FACTORS AND ANTICIPATED BEHAVIOR CHANGE FROM GENETIC RISK TESTING IN YOUNG ADULTS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Vassy, Jason L.; Donelan, Karen; O'Brien, Kelsey E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Vassy, Jason L.; Donelan, Karen] Harvard Univ, Sch Med, Boston, MA USA. [Hivert, Marie-France] Univ Sherbrooke, Sherbrooke, PQ J1K 2R1, Canada. [Grant, Richard W.] Kaiser Permanente, Div Res, Oakland, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S141 EP S142 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900105 ER PT J AU Volpp, KG Norton, L Shea, JA Zhu, JS Small, D Basner, M Ecker, A Dinges, D Mollicone, D Novak, C Bellini, L AF Volpp, Kevin G. Norton, Laurie Shea, Judy A. Zhu, Jingsan Small, Dylan Basner, Mathias Ecker, Adrian Dinges, David Mollicone, Daniel Novak, Cristina Bellini, Lisa TI A RANDOMIZED CONTROLLED TRIAL OF THE FEASIBILITY OF A PROTECTED SLEEP PERIOD FOR MEDICAL INTERNS IN THE HOSPITAL FOR PROLONGED DUTY SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Volpp, Kevin G.; Norton, Laurie; Shea, Judy A.; Zhu, Jingsan; Small, Dylan; Basner, Mathias; Ecker, Adrian; Dinges, David; Novak, Cristina; Bellini, Lisa] Univ Penn, Philadelphia, PA 19104 USA. [Volpp, Kevin G.; Norton, Laurie; Novak, Cristina] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Mollicone, Daniel] Pulsar Informat, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S103 EP S103 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900011 ER PT J AU Wamsley, MA Batki, SL Dunlop, M Julian, K McCance-Katz, E O'Sullivan, PS Satterfield, J AF Wamsley, Maria A. Batki, Steven L. Dunlop, Miranda Julian, Katherine McCance-Katz, Elinore O'Sullivan, Patricia S. Satterfield, Jason TI A BRIEF CURRICULAR INTERVENTION TO IMPROVE SCREENING AND BRIEF INTERVENTIONS FOR SUBSTANCE ABUSE IN THE PRIMARY CARE SETTING DOES NOT IMPROVE PERFORMANCE ON A STANDARDIZED PATIENT ASSESSMENT SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Wamsley, Maria A.; Batki, Steven L.; Dunlop, Miranda; Julian, Katherine; McCance-Katz, Elinore; O'Sullivan, Patricia S.; Satterfield, Jason] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Batki, Steven L.] San Francisco Vet Adm Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S100 EP S100 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900003 ER PT J AU Ward, CE Ashburner, JM Chang, YC Atlas, SJ AF Ward, Charlotte E. Ashburner, Jeffrey M. Chang, Yuchiao Atlas, Steven J. TI RELATIONSHIP BETWEEN PATIENT EXPERIENCE OF CARE AND PHYSICIAN PRODUCTIVITY MEASURES SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Ward, Charlotte E.; Ashburner, Jeffrey M.; Chang, Yuchiao; Atlas, Steven J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S296 EP S296 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900467 ER PT J AU Ward, CE Hong, CS Ashburner, JM Chang, YC Atlas, SJ AF Ward, Charlotte E. Hong, Clemens S. Ashburner, Jeffrey M. Chang, Yuchiao Atlas, Steven J. TI HOW MUCH DOES PATIENT PANEL COMPOSITION INFLUENCE PHYSICIAN PERFORMANCE RANKING ON PATIENT EXPERIENCE OF CARE QUALITY MEASURES? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Ward, Charlotte E.; Hong, Clemens S.; Ashburner, Jeffrey M.; Chang, Yuchiao; Atlas, Steven J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S212 EP S213 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900266 ER PT J AU Williams, B Ahalt, C AF Williams, Brie Ahalt, Cyrus TI PAYING THE PRICE: THE DEARTH OF PUBLICALLY AVAILABLE PRISON HEALTHCARE COST DATA SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Williams, Brie; Ahalt, Cyrus] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Williams, Brie] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2012 VL 27 SU 2 BP S269 EP S269 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V35IG UT WOS:000209142900400 ER PT J AU Lam, J Simpson, PC Yang, PC Dash, R AF Lam, Justin Simpson, Paul C. Yang, Phillip C. Dash, Rajesh TI Synthesis of an In vivo MRI-detectable Apoptosis Probe SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE Molecular Biology; Issue 65; Biomedical Engineering; conjugation; annexin; iron oxide; nanoparticle; MRI; molecular imaging AB Cellular apoptosis is a prominent feature of many diseases, and this programmed cell death typically occurs before clinical manifestations of disease are evident. A means to detect apoptosis in its earliest, reversible stages would afford a pre-clinical 'window' during which preventive or therapeutic measures could be taken to protect the heart from permanent damage. We present herein a simple and robust method to conjugate human Annexin V (ANX), which avidly binds to cells in the earliest, reversible stages of apoptosis, to superparamagnetic iron oxide (SPIO) nanoparticles, which serve as an MRI-detectable contrast agent. The conjugation method begins with an oxidation of the SPIO nanoparticles, which oxidizes carboxyl groups on the polysaccharide shell of SPIO. Purified ANX protein is then added in the setting of a sodium borate solution to facilitate covalent interaction of ANX with SPIO in a reducing buffer. A final reduction step with sodium borohydride is performed to complete the reduction, and then the reaction is quenched. Unconjugated ANX is removed from the mix by microcentrifuge filtration. The size and purity of the ANX-SPIO product is verified by dynamic light scattering (DLS). This method does not require addition to, or modification of, the polysaccharide SPIO shell, as opposed to cross-linked iron oxide particle conjugation methods or biotin-labeled nanoparticles. As a result, this method represents a simple, robust approach that may be extended to conjugation of other proteins of interest. C1 [Lam, Justin; Yang, Phillip C.; Dash, Rajesh] Stanford Univ, Med Ctr, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA. [Simpson, Paul C.] Univ Calif San Francisco, Dept Med, Div Cardiol, San Francisco, CA 94143 USA. [Simpson, Paul C.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Dash, R (reprint author), Stanford Univ, Med Ctr, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA. EM rdash@cvmed.stanford.edu FU National Institutes of Health, NHLBI; American Heart Association; Stanford University, VPUE Grant FX National Institutes of Health, NHLBI (RD, PY, PS).; American Heart Association (JL).; Stanford University, VPUE Grant (JL). NR 12 TC 1 Z9 1 U1 1 U2 2 PU JOURNAL OF VISUALIZED EXPERIMENTS PI CAMBRIDGE PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA SN 1940-087X J9 JOVE-J VIS EXP JI J. Vis. Exp. PD JUL PY 2012 IS 65 AR UNSP e3775 DI 10.3791/3775 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V36PJ UT WOS:000209223200011 ER PT J AU Maguen, S Lau, KM Madden, E Seal, K AF Maguen, Shira Lau, Karen M. Madden, Erin Seal, Karen TI Factors Associated With Completing Comprehensive Traumatic Brain Injury Evaluation SO MILITARY MEDICINE LA English DT Article AB This study examined factors associated with Iraq and Afghanistan Veterans following up with the Department of Veterans Affairs (VA) comprehensive traumatic brain injury (TBI) evaluation after a positive first-level VA TBI screen. Participants included 465 Iraq and Afghanistan Veterans at one VA Medical Center and its five affiliated community-based outpatient clinics, with a positive initial TBI screen between April 1, 2007 and June 1, 2010. We found that 75% of Veterans completed the comprehensive TBI evaluation. Women were three times less likely to complete the comprehensive TBI evaluation than men, and those who endorsed post-traumatic stress disorder avoidance symptoms were nearly two times less likely to complete the comprehensive TBI evaluation. In contrast, headaches, Hispanic ethnicity, and the season of the initial TBI screen (summer vs. winter) were positively associated with completing a comprehensive TBI evaluation. A substantial minority of Veterans who screen positive on the VA initial TBI screen fail to present for the comprehensive TBI evaluation. Addressing specific gender-related issues, avoidance, and the timing of referrals in the context of VA polytrauma programs may increase the likelihood that Veterans receive further assessment, education, and early intervention for TBI or other mental health problems to prevent chronic postdeployment disability. C1 [Maguen, Shira; Lau, Karen M.; Madden, Erin; Seal, Karen] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Maguen, Shira; Seal, Karen] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Maguen, Shira; Seal, Karen] Hlth Serv Res, Dev Res Enhancement Award Program, San Francisco, CA 94121 USA. RP Maguen, S (reprint author), San Francisco VA Med Ctr, 4150 Clement St, San Francisco, CA 94121 USA. FU Department of Defense Psychological Health and Traumatic Brain Injury (PH/TBI) Research Program [W81XWH-05-2-0094]; VA Health Sciences Research and Development Career Development Award [RCD06042A] FX We thank Gary Abrams, MD; Don Donati; Thomas Neylan, MD; Richard Pham, PhD; and Guiomar Scheid for their contributions. This research was supported by grants to Shira Maguen, PhD, by the Department of Defense Psychological Health and Traumatic Brain Injury (PH/TBI) Research Program (W81XWH-05-2-0094) and VA Health Sciences Research and Development Career Development Award (RCD06042A). NR 20 TC 3 Z9 3 U1 1 U2 1 PU ASSOC MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 EI 1930-613X J9 MIL MED JI Milit. Med. PD JUL PY 2012 VL 177 IS 7 BP 797 EP 803 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA V33NZ UT WOS:000209026800007 PM 22808886 ER PT J AU Feinbaum, RL Urbach, JM Liberati, NT Djonovic, S Adonizio, A Carvunis, AR Ausubel, FM AF Feinbaum, Rhonda L. Urbach, Jonathan M. Liberati, Nicole T. Djonovic, Slavica Adonizio, Allison Carvunis, Anne-Ruxandra Ausubel, Frederick M. TI Genome-Wide Identification of Pseudomonas aeruginosa Virulence-Related Genes Using a Caenorhabditis elegans Infection Model SO PLOS PATHOGENS LA English DT Article ID ARGININE SUCCINYLTRANSFERASE PATHWAY; DROSOPHILA-MELANOGASTER; MYCOBACTERIUM-TUBERCULOSIS; TRANSLATIONAL INHIBITION; BACTERIAL PATHOGENICITY; STAPHYLOCOCCUS-AUREUS; AUXOTROPHIC MUTANTS; FUNCTIONAL GENOMICS; TWITCHING MOTILITY; CELL COMMUNICATION AB Pseudomonas aeruginosa strain PA14 is an opportunistic human pathogen capable of infecting a wide range of organisms including the nematode Caenorhabditis elegans. We used a non-redundant transposon mutant library consisting of 5,850 clones corresponding to 75% of the total and approximately 80% of the non-essential PA14 ORFs to carry out a genome-wide screen for attenuation of PA14 virulence in C. elegans. We defined a functionally diverse 180 mutant set (representing 170 unique genes) necessary for normal levels of virulence that included both known and novel virulence factors. Seven previously uncharacterized virulence genes (ABC transporters PchH and PchI, aminopeptidase PepP, ATPase/molecular chaperone ClpA, cold shock domain protein PA0456, putative enoyl-CoA hydratase/isomerase PA0745, and putative transcriptional regulator PA14_27700) were characterized with respect to pigment production and motility and all but one of these mutants exhibited pleiotropic defects in addition to their avirulent phenotype. We examined the collection of genes required for normal levels of PA14 virulence with respect to occurrence in P. aeruginosa strain-specific genomic regions, location on putative and known genomic islands, and phylogenetic distribution across prokaryotes. Genes predominantly contributing to virulence in C. elegans showed neither a bias for strain-specific regions of the P. aeruginosa genome nor for putatively horizontally transferred genomic islands. Instead, within the collection of virulence-related PA14 genes, there was an overrepresentation of genes with a broad phylogenetic distribution that also occur with high frequency in many prokaryotic clades, suggesting that in aggregate the genes required for PA14 virulence in C. elegans are biased towards evolutionarily conserved genes. C1 [Feinbaum, Rhonda L.; Urbach, Jonathan M.; Liberati, Nicole T.; Djonovic, Slavica; Adonizio, Allison; Carvunis, Anne-Ruxandra; Ausubel, Frederick M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Feinbaum, Rhonda L.; Urbach, Jonathan M.; Liberati, Nicole T.; Djonovic, Slavica; Adonizio, Allison; Ausubel, Frederick M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Carvunis, Anne-Ruxandra] Harvard Univ, Sch Med, CCSB, Boston, MA 02115 USA. [Carvunis, Anne-Ruxandra] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Feinbaum, RL (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. EM feinbaum@molbio.mgh.harvard.edu OI Carvunis, Anne-Ruxandra/0000-0002-6474-6413 FU NIH [R01 AI085581, R01 AI064332, P01 AI044220] FX This work was supported by NIH grants R01 AI085581, R01 AI064332, and P01 AI044220. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 117 TC 37 Z9 39 U1 1 U2 28 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD JUL PY 2012 VL 8 IS 7 AR e1002813 DI 10.1371/journal.ppat.1002813 PG 22 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 979RO UT WOS:000306837700034 PM 22911607 ER PT J AU Tran, K Brun, R Kuo, B AF Khoa Tran Brun, Rita Kuo, Braden TI Evaluation of regional and whole gut motility using the wireless motility capsule: relevance in clinical practice SO THERAPEUTIC ADVANCES IN GASTROENTEROLOGY LA English DT Review DE constipation; diffuse gastrointestinal dysmotility; gastroparesis; transit time; wireless motility capsule AB The wireless motility capsule (WMC) is an ambulatory noninvasive and nonradioactive diagnostic sensor that continuously samples intraluminal pH, temperature, and pressure as it moves through the gastrointestinal (GI) tract. This review summarizes the data obtained in clinical trials with the WMC and discusses its role in clinical practice. The United States Food and Drug Administration has approved the SmartPill GI monitoring system for the evaluation of gastric emptying time in patients with suspected gastroparesis, the evaluation of colonic transit time in patients with suspected chronic constipation, and for the characterization of pressure profiles from the antrum and duodenum. Clinical studies have shown that WMC-measured GI transit times can distinguish patients with motility abnormalities similarly to conventional testing. However, the WMC offers the advantage of providing a full GI-tract profile, enabling the detection of multiregional GI transit abnormalities in patients with suspected upper or lower GI dysmotility. The WMC also characterizes pressure profiles of the GI tract and impaired pressure profile limits are reported for the antrum and duodenum. In comparison with manometry, interpretations of pressure measurements obtained by the WMC are limited by an inability to detect a peristaltic pressure wave front, and further investigation is required to develop clinical applications. Clinical studies with the WMC indicated that it should be considered for the evaluation of regional and whole gut transit time in patients with suspected upper or lower dysmotility, particularly if there are concerns about multiregional dysmotility. C1 [Brun, Rita; Kuo, Braden] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Khoa Tran] Massachusetts Gen Hosp Children, Pediat GI, Boston, MA USA. RP Kuo, B (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St,GRJ 724, Boston, MA 02114 USA. EM bkuo@partners.org NR 38 TC 25 Z9 27 U1 4 U2 10 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1756-283X EI 1756-2848 J9 THER ADV GASTROENTER JI Ther. Adv. Gastroenterol. PD JUL PY 2012 VL 5 IS 4 BP 249 EP 260 DI 10.1177/1756283X12437874 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA V31ZP UT WOS:000208921800004 PM 22778790 ER PT J AU Zhao, X Bichara, DA Ballyns, FP Yoo, JJ Ong, W Randolph, MA Bonassar, LJ Gill, TJ AF Zhao, Xing Bichara, David A. Ballyns, Frederick P. Yoo, Jeong J. Ong, Winnie Randolph, Mark A. Bonassar, Lawrence J. Gill, Thomas J. TI Properties of Cartilage Engineered from Elderly Human Chondrocytes for Articular Surface Repair SO TISSUE ENGINEERING PART A LA English DT Article ID GROWTH PLATE CHONDROCYTES; TERM-FOLLOW-UP; BIOMECHANICAL ANALYSIS; INJECTABLE CARTILAGE; INVITRO CULTURE; MENISCAL REPAIR; TISSUE; POLYMER; IMPLANTATION; MATRIX AB Numerous studies on engineering cartilage utilizing chondrocytes from juvenile animal sources have been reported. However, there are many unknown aspects of engineering cartilage using human chondrocytes-especially from middle-aged or elderly adults-which are critical for clinical application of tissue engineering in the field of orthopedic surgery. The primary aim of this study was to engineer neocartilage tissue from 50-60-year-old human chondrocytes in comparison to engineered cartilage made from juvenile swine chondrocytes (JSCs). Articular chondrocytes from middle-aged, nonarthritic humans and juvenile swine were isolated and placed in culture for expansion. The chondrocytes (passage 1) were mixed in fibrin gel at 40-60x10(6) cells/mL until polymerization. Cells/nodule constructs and devitalized cartilage-cells/hydrogel-devitalized cartilage constructs (three-layered model) were implanted into subcutaneous pockets of nude mice for 12, 18, and 24 weeks. The specimens were evaluated histologically, biochemically, and biomechanically. This allowed for direct comparison of the cartilage engineered from human versus swine cells. Histological analysis demonstrated that samples engineered utilizing chondrocytes from middle-aged adults accumulated basophilic, sulfated glycosaminoglycans (sGAG), and abundant type II collagen around the cells in a manner similar to that seen in samples engineered using JSCs at all time points. Biochemical analysis revealed that samples made with human cells had about 40%-60% of the amount hydroxyproline of native human cartilage, a trend parallel to that observed in the specimens made with swine chondrocytes. The amount of sGAG in the human chondrocyte specimens was about one-and-a-half times the amount in native human cartilage, whereas the amount in the samples made with swine chondrocytes was always less than native cartilage. The biomechanical analysis revealed that the stiffness and tensile of samples made with human cells were in a pattern similar to that seen with swine chondrocytes. This study demonstrates that chondrogenesis using articular chondrocytes from middle-aged adults can be achieved in a predictable and reliable manner similar to that shown in studies using cells from juvenile animals and can form the basis of engineering cartilage with degradable scaffolds in this patient population. C1 [Zhao, Xing; Bichara, David A.; Yoo, Jeong J.; Ong, Winnie; Randolph, Mark A.; Gill, Thomas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lab Musculoskeletal Tissue Engn,Dept Orthopaed Su, Boston, MA 02114 USA. [Ballyns, Frederick P.; Bonassar, Lawrence J.] Cornell Univ, Dept Biomed Engn, Ithaca, NY USA. [Ballyns, Frederick P.; Bonassar, Lawrence J.] Cornell Univ, Sibley Sch Mech & Aerosp Engn, Ithaca, NY 14853 USA. RP Randolph, MA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lab Musculoskeletal Tissue Engn,Dept Orthopaed Su, Room WAC 435,15 Parkman St, Boston, MA 02114 USA. EM marandolph@partners.org RI Yoo, Jeong Joon/J-5553-2012; Bonassar, Lawrence/C-2103-2016 OI Bonassar, Lawrence/0000-0003-1094-6433 FU National Football League Charities FX This work was supported by a grant from National Football League Charities. Special thanks to Dr. Xing Zhao's wife Ying Zhou, Ph.D., candidate at the Boston University School of Medicine, for assistance on the statistical analysis. NR 29 TC 2 Z9 2 U1 1 U2 5 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3341 J9 TISSUE ENG PT A JI Tissue Eng. Part A PD JUL PY 2012 VL 18 IS 13-14 BP 1490 EP 1499 DI 10.1089/ten.tea.2011.0445 PG 10 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA 974YR UT WOS:000306474000017 PM 22435677 ER PT J AU Kearney, CJ Hsu, HPP Spector, M AF Kearney, Cathal J. Hsu, Huping P. Spector, Myron TI The Use of Extracorporeal Shock Wave-Stimulated Periosteal Cells for Orthotopic Bone Generation SO TISSUE ENGINEERING PART A LA English DT Article ID GENE-EXPRESSION; TISSUE; GROWTH; DIFFERENTIATION; CARTILAGE; THERAPY; PROLIFERATION; MULTIPOTENCY; OSTEOGENESIS; TGF-BETA-1 AB The cambium cells of the periosteum, which are known osteoprogenitor cells, have limited suitability for clinical applications of tissue engineering in their native state due to their low cell number (2-5 cells thick). Extracorporeal shock waves (ESWs) have been shown to cause rapid periosteal cambium cell proliferation and subsequent periosteal osteogenesis. This work investigates a novel strategy for orthotopic bone generation: applying ESW therapy as a noninvasive, inexpensive, and rapid method for stimulating cambium cell proliferation, and combining these cells with a bioactive scaffold for bone growth. ESWs applied to the rabbit medial tibia resulted in a significant 2.7-fold increase in cambium cell number and a 4-fold increase in cambium cell thickness at 4 days post-ESW. ESW-stimulated, or nontreated control, periosteal cells were elevated in situ and overlaid on an anorganic bovine bone scaffold to interrogate their ability to form bone. At 2 weeks post-surgery, there was a significant increase in all key outcome variables for the ESW-stimulated group when compared with controls: a 4-fold increase in osseous tissue in the upper half of the scaffold underlying the periosteum; a 12-fold increase in osseous tissue overlying the scaffold; and a 2-fold increase in callus size. These results successfully demonstrated the efficacy of ESW-stimulated periosteum for orthotopic bone generation. C1 [Kearney, Cathal J.; Hsu, Huping P.; Spector, Myron] Vet Adm Boston Healthcare Syst, Tissue Engn Lab, Boston, MA USA. [Kearney, Cathal J.; Spector, Myron] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Hsu, Huping P.; Spector, Myron] Harvard Univ, Brigham & Womens Hosp, Orthopaed Res Lab, Sch Med, Boston, MA 02115 USA. RP Spector, M (reprint author), VA Boston Healthcare Syst, Dept Tissue Engn, MS 151,150 S Huntington Ave, Boston, MA 02130 USA. EM mspector@rics.bwh.harvard.edu OI Kearney, Cathal/0000-0002-9514-6517 FU U.S. Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service FX The research reported here was supported by the U.S. Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service. The authors would like to acknowledge SANUWAVE Health, Inc. (Alpharetta, GA) and Geistlich Pharma (Wolhusen, Switzerland) for providing equipment and materials, respectively, for this project. NR 33 TC 5 Z9 7 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3341 J9 TISSUE ENG PT A JI Tissue Eng. Part A PD JUL PY 2012 VL 18 IS 13-14 BP 1500 EP 1508 DI 10.1089/ten.tea.2011.0573 PG 9 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA 974YR UT WOS:000306474000018 PM 22519654 ER PT J AU Maguen, S Cohen, B Cohen, G Madden, E Bertenthal, D Seal, K AF Maguen, Shira Cohen, Beth Cohen, Greg Madden, Erin Bertenthal, Daniel Seal, Karen TI Eating Disorders and Psychiatric Comorbidity among Iraq and Afghanistan Veterans SO WOMENS HEALTH ISSUES LA English DT Article AB Objective: Individuals with mental health problems are at elevated risk for eating disorders. Veterans serving in support of the conflicts in Afghanistan and Iraq (OEF/OIF) have a high prevalence of deployment-related mental health problems, but little is known about their risk for eating disorders. Our aim was to determine rates of eating disorder diagnoses among OEF/OIF veterans with mental health problems, particularly among those with comorbid mental health problems. Methods: This retrospective, cross-sectional analysis of nationwide VA healthcare facilities used descriptive statistics and regression analyses to determine eating disorder rates in OEF/OIF veterans who were new users of VA healthcare from October 7, 2001 to December 31, 2010 (N = 593,739). Results: Although the prevalence of eating disorder diagnoses was 0.007% (n = 465) in women and <0.001% (n = 192) in men, veterans diagnosed with mental health problems were significantly more likely to have an eating disorder than those without mental health diagnoses. Eating disorders were significantly more common in women with depression, posttraumatic stress disorder, and alcohol and/or drug use disorders than in women veterans without these mental health disorders. Among men, the associations between eating disorder diagnoses and comorbid mental health diagnoses closely paralleled those observed in women. Conclusions: Rates of eating disorders are significantly higher among returning veterans with comorbid mental health problems compared with those without mental health diagnoses. Further research should examine methods to improve detection and treatment of eating disorders in this population. C1 [Maguen, Shira; Cohen, Beth; Cohen, Greg; Madden, Erin] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Bertenthal, Daniel] San Francisco VA Med Ctr, Mental Illness Res Educ & Clin Ctr, San Francisco, CA 94121 USA. [Seal, Karen] San Francisco VA Med Ctr, Iraq Afghanistan Vet Integrated Care Clin, San Francisco, CA 94121 USA. [Maguen, Shira; Cohen, Beth; Seal, Karen] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. RP Maguen, S (reprint author), San Francisco VA Med Ctr, 4150 Clement St,116-P, San Francisco, CA 94121 USA. EM Shira.Maguen@va.gov FU NHLBI NIH HHS [K23 HL 094765-01] NR 19 TC 11 Z9 11 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 EI 1878-4321 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD JUL-AUG PY 2012 VL 22 IS 4 BP E403 EP E406 DI 10.1016/j.whi.2012.04.005 PG 4 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA V33SS UT WOS:000209039100009 PM 22749199 ER PT J AU Jeng, L Olsen, BR Spector, M AF Jeng, Lily Olsen, Bjorn R. Spector, Myron TI Engineering endostatin-expressing cartilaginous constructs using injectable biopolymer hydrogels SO ACTA BIOMATERIALIA LA English DT Article DE Cartilage tissue engineering; Gene therapy; Scaffold; Mesenchymal stem cell ID MESENCHYMAL STEM-CELLS; ANGIOGENESIS INHIBITOR ENDOSTATIN; COLLAGEN-GAG SCAFFOLDS; HEPARAN-SULFATE; MECHANICAL-PROPERTIES; CRYSTAL-STRUCTURE; GENE DELIVERY; SOLUBLE FLT-1; GROWTH-FACTOR; TUMOR-GROWTH AB The release of an anti-angiogenic agent, such as type XVIII/endostatin, from an implantable scaffold may be of benefit in the repair of articular cartilage. The objectives of this study are to develop an injectable mesenchymal stem cell (MSC)-incorporating collagen-based hydrogel capable of undergoing covalent cross-linking in vivo and overexpressing endostatin using nonviral transfection, and to investigate methods for the retention of the endostatin protein within the scaffolds. The effects of different cross-linking agents (genipin, transglutaminase-2, and microbial transglutaminase) and different binding molecules for endostatin retention (heparin, heparan sulfate, and chondroitin sulfate) are evaluated. Cartilaginous constructs that overexpress endostatin for 3 weeks are successfully engineered. Most of the endostatin is released into the surrounding media and is not retained within the constructs. The presence of two common basement membrane molecules, laminin and type IV collagen, which have been reported in developing and mature articular cartilage and are generally associated with type XVIII collagen in vivo, is also observed in the engineered cartilaginous constructs. Endostatin-producing cartilaginous constructs can be formulated by growing nonvirally transfected mesenchymal stem cells in collagen gels covalently cross-linked using genipin, transglutaminase-2, and microbial transglutaminase. These constructs warrant further investigation for cartilage repair procedures. The novel finding of laminin and type IV collagen in the engineered cartilage constructs may be of importance for future work toward understanding the role of basement membrane molecules in chondrogenesis and in the physiology and pathology of articular cartilage. (C) 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. C1 [Jeng, Lily; Spector, Myron] VA Boston Healthcare System, Tissue Engn, Boston, MA 02130 USA. [Jeng, Lily] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Olsen, Bjorn R.] Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. [Spector, Myron] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02115 USA. RP Spector, M (reprint author), VA Boston Healthcare System, Tissue Engn, Boston, MA 02130 USA. EM mspector@rics.bwh.harvard.edu FU Rehabilitation Research and Development Service of the US Department of Veterans Affairs; Department of Defense; National Science Foundation; Siebel Scholarship FX This work was supported by the Rehabilitation Research and Development Service of the US Department of Veterans Affairs, the Department of Defense, the National Science Foundation Graduate Research Fellowship (L. Jeng), and the Siebel Scholarship (L. Jeng). M. Spector is a VA Research Career Scientist. The funding sources had no involvement in study design, data collection and analysis, or report writing. The authors are grateful for the assistance of Alix Weaver, and would like to thank Ajinomoto Food Ingredients LLC (Chicago, Illinois) for providing the microbial transglutaminase. NR 45 TC 4 Z9 5 U1 3 U2 21 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1742-7061 J9 ACTA BIOMATER JI Acta Biomater. PD JUL PY 2012 VL 8 IS 6 BP 2203 EP 2212 DI 10.1016/j.actbio.2012.02.015 PG 10 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 955QN UT WOS:000305036100021 PM 22370447 ER PT J AU Monzani, B Rijsdijk, F Cherkas, L Harris, J Keuthen, N Mataix-Cols, D AF Monzani, Benedetta Rijsdijk, Fruhling Cherkas, Lynn Harris, Juliette Keuthen, Nancy Mataix-Cols, David TI Prevalence and heritability of skin picking in an adult community sample: A twin study SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE pathological skin picking; psychogenic excoriation; dermatillomania; etiology; genetics; twins ID OBSESSIVE-COMPULSIVE DISORDER; CLINICAL CHARACTERISTICS; PSYCHOGENIC EXCORIATION; COMORBIDITY; TRICHOTILLOMANIA; BEHAVIORS; FAMILY AB Skin-picking disorder (SPD) is a disabling psychiatric condition that can lead to skin damage and other medical complications. Epidemiological data is scarce and its causes are unknown. The present study examined the prevalence and heritability of skin-picking symptoms in a large sample of twins. A total of 2,518 twins completed a valid and reliable self-report measure of skin-picking behavior. The prevalence of clinically significant skin picking was established using empirically derived cut-offs. Twin modeling methods were employed to decompose the variance in the liability to skin picking into additive genetic and shared and non-shared environmental factors. A total of 1.2% of twins scored above the cut-off, indicative of clinically significant skin picking. All these participants were women. Univariate model-fitting analyses (female twins only, N?=?2,191) showed that genetic factors accounted for approximately 40% (95% CI 1958%) of the variance in skin picking, with non-shared environmental factors and measurement error accounting for the remaining variance (60% [95% CI 4281%]). Shared environmental factors were negligible. It is concluded that pathological skin picking is relatively prevalent problem, particularly among women, and that it tends to run in families primarily due to genetic factors. Non-shared environmental factors are also likely to play an important role in its etiology. (C) 2012 Wiley Periodicals, Inc. C1 [Monzani, Benedetta; Mataix-Cols, David] Kings Coll London, Inst Psychiat, Dept Psychosis Studies, London SE5 8AF, England. [Rijsdijk, Fruhling] Inst Psychiat, Social Genet & Dev Psychiat Res Ctr SDGP, London, England. [Cherkas, Lynn; Harris, Juliette] Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE5 8AF, England. [Keuthen, Nancy] Harvard Univ, Sch Med, Boston, MA USA. [Keuthen, Nancy] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Mataix-Cols, David] Kings Coll London, Inst Psychiat, Dept Psychol, London SE5 8AF, England. RP Monzani, B (reprint author), Kings Coll London, Inst Psychiat, Dept Psychosis Studies, PO 69,De Crespigny Pk Rd, London SE5 8AF, England. EM benedetta.monzani@kcl.ac.uk RI Mataix-Cols, David/G-3843-2010 OI Mataix-Cols, David/0000-0002-4545-0924 FU Welcome Trust; Department of Health via the National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre; St Thomas' NHS Foundation Trust; King's College London FX Grant sponsor: Welcome Trust; Grant sponsor: Department of Health via the National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre Award; Grant sponsor: St Thomas' NHS Foundation Trust in partnership with King's College London. NR 32 TC 15 Z9 16 U1 1 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD JUL PY 2012 VL 159B IS 5 BP 605 EP 610 DI 10.1002/ajmg.b.32067 PG 6 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 952SJ UT WOS:000304812300015 PM 22619132 ER PT J AU Demay, MB AF Demay, Marie B. TI The hair cycle and Vitamin D receptor SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Review DE Keratinocyte stem cell; Vitamin D receptor; Hair cycle ID EPITHELIAL-MESENCHYMAL INTERACTIONS; BETA-CATENIN; KNOCKOUT MICE; 25-HYDROXYVITAMIN-D 1-ALPHA-HYDROXYLASE; EPIDERMAL DIFFERENTIATION; FOLLICLE MORPHOGENESIS; MOUSE EPIDERMIS; SONIC-HEDGEHOG; TARGETED ABLATION; BINDING DOMAIN AB The Vitamin D receptor (VDR) plays a critical role in epidermal homeostasis. The ligand-dependent actions of the VDR attenuate epidermal keratinocyte proliferation and promote keratinocyte differentiation. Calcium can compensate for the absence of the VDR in maintaining a normal program of epidermal keratinocyte differentiation both in vitro and in vivo. In contrast, the effects of VDR ablation on the hair follicle cannot be prevented by maintaining normal calcium levels and are independent of 1,25-dihydroxyvitamin D. These actions of the VDR are critical in the keratinocyte stem cell population that resides in the bulge region of the hair follicle. Absence of a functional VDR leads to a self-renewal and lineage progression defect in this population of stem cells, resulting in the absence of post-morphogenic hair cycles. The molecular partners and downstream target genes of thc VDR in this unique population of cells have not yet been identified. (C) 2011 Published by Elsevier Inc. C1 [Demay, Marie B.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Demay, Marie B.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Demay, MB (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 50 Blossom St,Thier 11, Boston, MA 02114 USA. EM demay@helix.mgh.harvard.edu FU NIDDK NIH HHS [R01 DK046974] NR 44 TC 8 Z9 9 U1 1 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 EI 1096-0384 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JUL 1 PY 2012 VL 523 IS 1 SI SI BP 19 EP 21 DI 10.1016/j.abb.2011.10.002 PG 3 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 955UA UT WOS:000305045200004 PM 22008469 ER PT J AU Sanchez-Ortiga, R Klibanski, A Tritos, NA AF Sanchez-Ortiga, Ruth Klibanski, Anne Tritos, Nicholas A. TI Effects of recombinant human growth hormone therapy in adults with Prader-Willi syndrome: a meta-analysis SO CLINICAL ENDOCRINOLOGY LA English DT Article ID BODY-COMPOSITION; GH TREATMENT; SHORT-TERM; CHILDREN; OBESITY; SLEEP; FAT; ENDOCRINE; SECRETION; TRIALS AB Objective PraderWilli syndrome (PWS) is associated with GH deficiency, deleterious changes in body composition and function. As the effects of recombinant human GH (rhGH) in PWS adults have not been well established, we sought to conduct a meta-analysis of pertinent studies. Design Meta-analysis of studies examining the effects of rhGH therapy in PWS adults. Patients One hundred and thirty four PWS adults (75 men, 59 women). Measurements Literature searches, including publications (PubMed, EMBASE and the Cochrane Register), and abstracts presented at meetings through July 2011 describing studies of rhGH therapy in PWS adults; 8/1194 articles, describing unique cohorts, were included. Two authors independently extracted data and examined study quality. Results rhGH therapy for 12 months led to [weighted mean difference (95% CI)] decreased body fat [-2.91% (-3.90, -1.91)], visceral [-32.97 cm2 (-55.67, -10.26)] and subcutaneous adiposity [-55.24 cm2 (-89.05, -21.44)], and increased lean body mass (LBM) [2.41 Kg (1.32, 3.49)]. Similar changes in body fat [-2.89% (-4.69, -1.07)] and LBM [2.82 Kg (1.31, 4.33)] were found in longer studies. There were no changes in body mass index (BMI) or lipids. There was a small increase in fasting glucose [0.27 mmol/l (0.05, 0.49)] and trends towards higher fasting insulin [20.24 pmol/l (-0.55, 41.02)] and insulin resistance [HOMA: 0.60 (-0.04, 1.24)] after rhGH therapy for 12 months. Conclusions In PWS adults, rhGH therapy led to decreased body adiposity and increased LBM without changes in BMI or lipids. There was a small increase in fasting glucose and trends towards higher insulin and insulin resistance. C1 [Sanchez-Ortiga, Ruth; Klibanski, Anne; Tritos, Nicholas A.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Sanchez-Ortiga, Ruth] Hosp Gen Univ Alicante, Dept Endocrinol, Alicante, Spain. [Klibanski, Anne; Tritos, Nicholas A.] Harvard Univ, Sch Med, Boston, MA USA. RP Tritos, NA (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Zero Emerson Pl 112, Boston, MA 02114 USA. EM ntritos@partners.org FU Pfizer, Inc. FX RSO and AK have nothing to disclose. NAT is the recipient of research support and consulting honoraria from Pfizer, Inc., for work unrelated to the present manuscript. NR 35 TC 22 Z9 22 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD JUL PY 2012 VL 77 IS 1 BP 86 EP 93 DI 10.1111/j.1365-2265.2011.04303.x PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 953JZ UT WOS:000304864700016 PM 22117629 ER PT J AU Lindsley, RC LaCasce, AS AF Lindsley, R. Coleman LaCasce, Ann S. TI Biology of double-hit B-cell lymphomas SO CURRENT OPINION IN HEMATOLOGY LA English DT Review DE BCL2; BCL6; double hit; lymphoma; MYC ID NON-HODGKINS-LYMPHOMA; FOLLICULAR LYMPHOMA; BURKITTS-LYMPHOMA; POOR-PROGNOSIS; CLINICAL PRESENTATION; PEDIATRIC-PATIENTS; MYC TRANSLOCATION; REARRANGEMENTS; FEATURES; T(14/18) AB Purpose of review Mature B-cell lymphomas bearing concurrent chromosomal rearrangement of MYC/8q24 and BCL2/18q21 are associated with an aggressive clinical course and resistance to conventional chemotherapy. This review summarizes the recent literature regarding the clinical and pathologic features of double-hit lymphomas and outlines current questions about the most accurate and inclusive definition of the disease. Recent findings Comprehensive evaluation of large series of aggressive mature B-cell neoplasms reveals recurrent chromosomal aberrations in the majority of cases. A subset of these lymphomas harbors multiple rearrangements, including MYC/8q24 in combination with BCL2/18q21 and/or BCL6/3q27, and displays a particularly aggressive clinical course. Recent data suggest that consideration of additional features, such as copy number alteration, quantitative protein expression, and biologic pathway activation may be important in deriving a more accurate definition of double-hit lymphoma. Despite the poor prognosis associated with this subset of lymphomas, there remains no evidence for a risk-adapted treatment strategy and no clinical, pathologic, or genetic factors that predict response to therapy. Summary Double-hit lymphoma remains an incompletely characterized disease entity. Large, multicenter studies are needed to define relevant clinical, genetic, and pathologic variables and to characterize appropriate risk-adapted treatment strategies. C1 [Lindsley, R. Coleman; LaCasce, Ann S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Lindsley, R. Coleman] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. RP LaCasce, AS (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave M227, Boston, MA 02215 USA. EM ann_lacasce@dfci.harvard.edu OI Lindsley, Coleman/0000-0001-9822-806X FU National Institutes of Health [T32 CA009172-37] FX RCL is supported by the National Institutes of Health (T32 CA009172-37). NR 36 TC 13 Z9 15 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1065-6251 J9 CURR OPIN HEMATOL JI Curr. Opin. Hematol. PD JUL PY 2012 VL 19 IS 4 BP 299 EP 304 DI 10.1097/MOH.0b013e328353bbbd PG 6 WC Hematology SC Hematology GA 955PG UT WOS:000305032600010 PM 22504522 ER PT J AU Ding, J Sullivan, DA AF Ding, Juan Sullivan, David A. TI Aging and dry eye disease SO EXPERIMENTAL GERONTOLOGY LA English DT Review DE Aging; Meibomian gland dysfunction (MGD); Dry eye disease; FOXO; Retinoic acid; Androgens; Stem cell; Growth hormone; Insulin-like growth factor-1 (IGF-1); Insulin sensitivity ID MEIBOMIAN GLAND DYSFUNCTION; HUMAN SEBACEOUS GLAND; PROLIFERATOR-ACTIVATED RECEPTORS; FOXO TRANSCRIPTION FACTORS; TRANS-RETINOIC ACID; GROWTH-HORMONE; STEM-CELLS; INTERNATIONAL WORKSHOP; ANDROGEN RECEPTOR; OCULAR SURFACE AB Dry eye disease is a prevalent eye disorder that in particular affects the elderly population. One of the major causes of dry eye, meibomian gland dysfunction (MGD), shows increased prevalence with aging. MGD is caused by hyperkeratinization of the ductal epithelium of meibomian gland and reduced quantity and/or quality of meibum, the holocrine product that stabilizes and prevents the evaporation of the tear film. Of note, retinoids which are used in current anti-aging cosmetics may promote the development of MGD and dry eye disease. In this review, we will discuss the possible mechanisms of age-related MGD. (C) 2012 Elsevier Inc. All rights reserved. C1 [Ding, Juan; Sullivan, David A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Dept Ophthalmol,Med Sch, Boston, MA 02114 USA. RP Ding, J (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Dept Ophthalmol,Med Sch, 20 Staniford St, Boston, MA 02114 USA. EM Juan.ding@schepens.harvard.edu RI Ding, Juan/L-5149-2013 FU National Institutes of Health (NIH) [R01 EY05612]; AFER FX We thank the funding support from the National Institutes of Health (NIH R01 EY05612); JD is also supported by AFER/Vistakon Dry Eye Fellowship. NR 115 TC 21 Z9 24 U1 2 U2 22 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0531-5565 EI 1873-6815 J9 EXP GERONTOL JI Exp. Gerontol. PD JUL PY 2012 VL 47 IS 7 BP 483 EP 490 DI 10.1016/j.exger.2012.03.020 PG 8 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 952SR UT WOS:000304813200001 PM 22569356 ER PT J AU Lambrechts, D Truong, T Justenhoven, C Humphreys, MK Wang, J Hopper, JL Dite, GS Apicella, C Southey, MC Schmidt, MK Broeks, A Cornelissen, S van Hien, R Sawyer, E Tomlinson, I Kerin, M Miller, N Milne, RL Zamora, MP Perez, JIA Benitez, J Hamann, U Ko, YD Bruning, T Chang-Claude, J Eilber, U Hein, R Nickels, S Flesch-Janys, D Wang-Gohrke, S John, EM Miron, A Winqvist, R Pylkas, K Jukkola-Vuorinen, A Grip, M Chenevix-Trench, G Beesley, J Chen, XQ Menegaux, F Cordina-Duverger, E Shen, CY Yu, JC Wu, PE Hou, MF Andrulis, IL Selander, T Glendon, G Mulligan, AM Anton-Culver, H Ziogas, A Muir, KR Lophatananon, A Rattanamongkongul, S Puttawibul, P Jones, M Orr, N Ashworth, A Swerdlow, A Severi, G Baglietto, L Giles, G Southey, M Marme, F Schneeweiss, A Sohn, C Burwinkel, B Yesilyurt, BT Neven, P Paridaens, R Wildiers, H Brenner, H Muller, H Arndt, V Stegmaier, C Meindl, A Schott, S Bartram, CR Schmutzler, RK Cox, A Brock, IW Elliott, G Cross, SS Fasching, PA Schulz-Wendtland, R Ekici, AB Beckmann, MW Fletcher, O Johnson, N Silva, ID Peto, J Nevanlinna, H Muranen, TA Aittomaki, K Blomqvist, C Dork, T Schurmann, P Bremer, M Hillemanns, P Bogdanova, NV Antonenkova, NN Rogov, YI Karstens, JH Khusnutdinova, E Bermisheva, M Prokofieva, D Gancev, S Jakubowska, A Lubinski, J Jaworska, K Durda, K Nordestgaard, BG Bojesen, SE Lanng, C Mannermaa, A Kataja, V Kosma, VM Hartikainen, JM Radice, P Peterlongo, P Manoukian, S Bernard, L Couch, FJ Olson, JE Wang, XS Fredericksen, Z Alnaes, GG Kristensen, V Borresen-Dale, AL Devilee, P Tollenaar, RAEM Seynaeve, CM Hooning, MJ Garcia-Closas, M Chanock, SJ Lissowska, J Sherman, ME Hall, P Liu, JJ Czene, K Kang, D Yoo, KY Noh, DY Lindblom, A Margolin, S Dunning, AM Pharoah, PDP Easton, DF Guenel, P Brauch, H AF Lambrechts, Diether Truong, Therese Justenhoven, Christina Humphreys, Manjeet K. Wang, Jean Hopper, John L. Dite, Gillian S. Apicella, Carmel Southey, Melissa C. Schmidt, Marjanka K. Broeks, Annegien Cornelissen, Sten van Hien, Richard Sawyer, Elinor Tomlinson, Ian Kerin, Michael Miller, Nicola Milne, Roger L. Pilar Zamora, M. Arias Perez, Jose Ignacio Benitez, Javier Hamann, Ute Ko, Yon-Dschun Bruening, Thomas Chang-Claude, Jenny Eilber, Ursel Hein, Rebecca Nickels, Stefan Flesch-Janys, Dieter Wang-Gohrke, Shan John, Esther M. Miron, Alexander Winqvist, Robert Pylkas, Katri Jukkola-Vuorinen, Arja Grip, Mervi Chenevix-Trench, Georgia Beesley, Jonathan Chen, Xiaoqing Menegaux, Florence Cordina-Duverger, Emilie Shen, Chen-Yang Yu, Jyh-Cherng Wu, Pei-Ei Hou, Ming-Feng Andrulis, Irene L. Selander, Teresa Glendon, Gord Mulligan, Anna Marie Anton-Culver, Hoda Ziogas, Argyrios Muir, Kenneth R. Lophatananon, Artitaya Rattanamongkongul, Suthee Puttawibul, Puttisak Jones, Michael Orr, Nicholas Ashworth, Alan Swerdlow, Anthony Severi, Gianluca Baglietto, Laura Giles, Graham Southey, Melissa Marme, Federik Schneeweiss, Andreas Sohn, Christof Burwinkel, Barbara Yesilyurt, Betul T. Neven, Patrick Paridaens, Robert Wildiers, Hans Brenner, Hermann Mueller, Heiko Arndt, Volker Stegmaier, Christa Meindl, Alfons Schott, Sarah Bartram, Claus R. Schmutzler, Rita K. Cox, Angela Brock, Ian W. Elliott, Graeme Cross, Simon S. Fasching, Peter A. Schulz-Wendtland, Ruediger Ekici, Arif B. Beckmann, Matthias W. Fletcher, Olivia Johnson, Nichola Silva, Isabel dos Santos Peto, Julian Nevanlinna, Heli Muranen, Taru A. Aittomaki, Kristiina Blomqvist, Carl Doerk, Thilo Schuermann, Peter Bremer, Michael Hillemanns, Peter Bogdanova, Natalia V. Antonenkova, Natalia N. Rogov, Yuri I. Karstens, Johann H. Khusnutdinova, Elza Bermisheva, Marina Prokofieva, Darya Gancev, Shamil Jakubowska, Anna Lubinski, Jan Jaworska, Katarzyna Durda, Katarzyna Nordestgaard, Borge G. Bojesen, Stig E. Lanng, Charlotte Mannermaa, Arto Kataja, Vesa Kosma, Veli-Matti Hartikainen, Jaana M. Radice, Paolo Peterlongo, Paolo Manoukian, Siranoush Bernard, Loris Couch, Fergus J. Olson, Janet E. Wang, Xianshu Fredericksen, Zachary Alnaes, Grethe Grenaker Kristensen, Vessela Borresen-Dale, Anne-Lise Devilee, Peter Tollenaar, Robert A. E. M. Seynaeve, Caroline M. Hooning, Maartje J. Garcia-Closas, Montserrat Chanock, Stephen J. Lissowska, Jolanta Sherman, Mark E. Hall, Per Liu, Jianjun Czene, Kamila Kang, Daehee Yoo, Keun-Young Noh, Dong-Young Lindblom, Annika Margolin, Sara Dunning, Alison M. Pharoah, Paul D. P. Easton, Douglas F. Guenel, Pascal Brauch, Hiltrud CA GENICA Network KConFab Investigators Australian Ovarian Canc Study Grp TI 11q13 is a susceptibility locus for hormone receptor positive breast cancer SO HUMAN MUTATION LA English DT Article DE breast cancer susceptibility; polymorphisms; genome-wide association; risk factors; hormone receptor status; 11q13 ID GENOME-WIDE ASSOCIATION; SINGLE-NUCLEOTIDE POLYMORPHISMS; TUMOR CHARACTERISTICS; OVARIAN-CANCER; CONFER SUSCEPTIBILITY; FAMILY REGISTRY; COMMON VARIANTS; BRCA1 MUTATIONS; REPAIR GENES; IDENTIFIES 5 AB A recent two-stage genome-wide association study (GWAS) identified five novel breast cancer susceptibility loci on chromosomes 9, 10, and 11. To provide more reliable estimates of the relative risk associated with these loci and investigate possible heterogeneity by subtype of breast cancer, we genotyped the variants rs2380205, rs1011970, rs704010, rs614367, and rs10995190 in 39 studies from the Breast Cancer Association Consortium (BCAC), involving 49,608 cases and 48,772 controls of predominantly European ancestry. Four of the variants showed clear evidence of association (P = 3 X 10-9) and weak evidence was observed for rs2380205 (P = 0.06). The strongest evidence was obtained for rs614367, located on 11q13 (per-allele odds ratio 1.21, P = 4 X 10-39). The association for rs614367 was specific to estrogen receptor (ER)-positive disease and strongest for ER plus progesterone receptor (PR)-positive breast cancer, whereas the associations for the other three loci did not differ by tumor subtype. Hum Mutat 33:11231132, 2012. (c) 2012 Wiley Periodicals, Inc. 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[Winqvist, Robert; Pylkas, Katri] Univ Oulu, Canc Genet Lab, Dept Clin Genet, Oulu, Finland. [Winqvist, Robert; Pylkas, Katri] Univ Oulu, Bioctr Oulu, Oulu, Finland. [Jukkola-Vuorinen, Arja] Univ Oulu, Dept Oncol, Oulu Univ Hosp, Oulu, Finland. [Grip, Mervi] Univ Oulu, Dept Surg, Oulu Univ Hosp, Oulu, Finland. [Chenevix-Trench, Georgia; Beesley, Jonathan; Chen, Xiaoqing] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [KConFab Investigators; Australian Ovarian Canc Study Grp] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Shen, Chen-Yang; Wu, Pei-Ei] Acad Sinica, Inst Biomed Sci, Taipei, Taiwan. [Shen, Chen-Yang; Wu, Pei-Ei] Taiwan Biobank, Taipei, Taiwan. [Yu, Jyh-Cherng] Tri Serv Gen Hosp, Dept Surg, Taipei, Taiwan. [Hou, Ming-Feng] Kaohsiung Med Univ, Ctr Canc, Chung Ho Mem Hosp, Kaohsiung, Taiwan. [Hou, Ming-Feng] Kaohsiung Med Univ, Dept Surg, Chung Ho Mem Hosp, Kaohsiung, Taiwan. [Andrulis, Irene L.] Canc Care Ontario, Ontario Canc Genet Network, Toronto, ON, Canada. [Andrulis, Irene L.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Fred A Litwin Ctr Canc Genet, Toronto, ON M5G 1X5, Canada. [Andrulis, Irene L.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. [Mulligan, Anna Marie] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada. [Anton-Culver, Hoda; Ziogas, Argyrios] Univ Calif Irvine, Dept Epidemiol, Irvine, CA USA. [Muir, Kenneth R.; Lophatananon, Artitaya] Univ Warwick, Hlth Sci Res Inst, Warwick Med Sch, Coventry CV4 7AL, W Midlands, England. [Rattanamongkongul, Suthee] Srinakhrainwirot Univ, Dept Prevent Med, Ongkharak, Nakhon Nayok, Thailand. [Puttawibul, Puttisak] Prince Songkla Univ, Dept Surg, Sch Med, Hat Yai, Thailand. [Jones, Michael; Swerdlow, Anthony] Inst Canc Res, Epidemiol Sect, Sutton, Surrey, England. [Orr, Nicholas; Ashworth, Alan] Inst Canc Res, Chester Beatty Labs, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England. [Severi, Gianluca; Baglietto, Laura; Giles, Graham; Southey, Melissa] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia. [Marme, Federik; Schneeweiss, Andreas] Univ Heidelberg, Natl Ctr Tumor Dis, Heidelberg, Germany. [Burwinkel, Barbara] German Canc Res Ctr, Mol Epidemiol Grp, Heidelberg, Germany. [Neven, Patrick; Paridaens, Robert; Wildiers, Hans] Univ Hosp Gasthuisberg, Multidisciplinary Breast Ctr, B-3000 Louvain, Belgium. [Brenner, Hermann; Mueller, Heiko; Arndt, Volker] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, D-6900 Heidelberg, Germany. [Stegmaier, Christa] Saarland Canc Registry, Saarbrucken, Germany. [Meindl, Alfons] Tech Univ Munich, Div Gynaecol & Obstet, Munich, Germany. [Schott, Sarah] Univ Heidelberg, Dept Obstet & Gynecol, Heidelberg, Germany. [Bartram, Claus R.] Univ Heidelberg, Inst Human Genet, Heidelberg, Germany. [Schmutzler, Rita K.] Univ Hosp Cologne, Div Mol Gynecooncol, Dept Obstet & Gynaecol, Ctr Mol Med Cologne CMMC, Cologne, Germany. [Cox, Angela; Brock, Ian W.; Elliott, Graeme] Univ Sheffield, Inst Canc Studies, Dept Oncol, Sheffield S10 2TN, S Yorkshire, England. [Cross, Simon S.] Univ Sheffield, Acad Unit Pathol, Dept Neurosci, Sheffield S10 2TN, S Yorkshire, England. [Fasching, Peter A.; Beckmann, Matthias W.] Univ Hosp Erlangen, Univ Breast Ctr, Dept Obstet & Gynecol, Erlangen, Germany. [Fasching, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA. [Schulz-Wendtland, Ruediger] Univ Hosp Erlangen, Inst Diagnost Radiol, Erlangen, Germany. [Ekici, Arif B.] Univ Erlangen Nurnberg, Inst Human Genet, Erlangen, Germany. [Silva, Isabel dos Santos; Peto, Julian] London Sch Hyg & Trop Med, London WC1, England. [Nevanlinna, Heli; Muranen, Taru A.] Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, Biomedicum Helsinki, FIN-00290 Helsinki, Finland. [Aittomaki, Kristiina] Univ Helsinki, Cent Hosp, Dept Clin Genet, Helsinki, Finland. [Blomqvist, Carl] Univ Helsinki, Cent Hosp, Dept Oncol, Helsinki, Finland. [Doerk, Thilo; Schuermann, Peter; Hillemanns, Peter; Bogdanova, Natalia V.; Karstens, Johann H.] Hannover Med Sch, Dept Obstet & Gynaecol, D-3000 Hannover, Germany. [Bremer, Michael; Bogdanova, Natalia V.] Hannover Med Sch, Dept Radiat Oncol, D-3000 Hannover, Germany. [Antonenkova, Natalia N.; Rogov, Yuri I.] NN Alexandrov Res Inst Oncol & Med Radiol, Minsk, Byelarus. [Khusnutdinova, Elza; Bermisheva, Marina; Prokofieva, Darya] Russian Acad Sci, Inst Biochem & Genet, Ufa Sci Ctr, Ufa 450001, Russia. [Gancev, Shamil] Bashkirian Med Univ, Ufa, Russia. [Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna] Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland. [Jaworska, Katarzyna] Warsaw Med Univ, Postgrad Sch Mol Med, Warsaw, Poland. [Nordestgaard, Borge G.; Bojesen, Stig E.] Univ Copenhagen, Copenhagen Gen Populat Study, Herlev Univ Hosp, Copenhagen, Denmark. [Nordestgaard, Borge G.; Bojesen, Stig E.] Univ Copenhagen, Dept Clin Biochem, Herlev Univ Hosp, Copenhagen, Denmark. [Lanng, Charlotte] Univ Copenhagen, Dept Breast Surg, Herlev Univ Hosp, Copenhagen, Denmark. [Mannermaa, Arto; Kosma, Veli-Matti; Hartikainen, Jaana M.] Univ Eastern Finland, Sch Med, Inst Clin Med Pathol & Forens Med, Kuopio, Finland. [Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.] Kuopio Univ Hosp, Bioctr Kuopio, SF-70210 Kuopio, Finland. [Mannermaa, Arto; Kosma, Veli-Matti; Hartikainen, Jaana M.] Kuopio Univ Hosp, Dept Clin Pathol, SF-70210 Kuopio, Finland. [Kataja, Vesa] Kuopio Univ Hosp, Dept Oncol, SF-70210 Kuopio, Finland. [Kataja, Vesa] Univ Eastern Finland, Sch Med, Inst Clin Med, Kuopio, Finland. [Radice, Paolo; Peterlongo, Paolo] Fdn IRCCS Ist Nazl Tumori INT, Unit Mol Bases Genet Risk & Genet Testing, Dept Prevent & Predicted Med, Milan, Italy. [Manoukian, Siranoush] Fdn IRCCS Ist Nazl Tumori INT, Unit Med Genet, Dept Prevent & Predicted Med, Milan, Italy. [Radice, Paolo; Peterlongo, Paolo] Fdn Ist FIRC Oncol Mol, IFOM, Milan, Italy. [Bernard, Loris] Ist Europeo Oncol IEO, Dept Expt Oncol, Milan, Italy. [Bernard, Loris] Consortium Genom Technol Cogentech, Milan, Italy. [Couch, Fergus J.; Wang, Xianshu] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Olson, Janet E.; Fredericksen, Zachary] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Alnaes, Grethe Grenaker; Kristensen, Vessela; Borresen-Dale, Anne-Lise] Radiumhosp, Dept Genet, Inst Canc Res, Oslo Univ Hosp, Oslo, Norway. [Kristensen, Vessela; Borresen-Dale, Anne-Lise] Univ Oslo, Fac Med, Fac Div Ahus, N-0316 Oslo, Norway. [Devilee, Peter] Leiden Univ, Dept Pathol, Med Ctr, Leiden, Netherlands. [Devilee, Peter] Leiden Univ, Dept Human Genet, Med Ctr, NL-2300 RA Leiden, Netherlands. [Tollenaar, Robert A. E. M.] Leiden Univ, Dept Surg, Med Ctr, Leiden, Netherlands. [Seynaeve, Caroline M.; Hooning, Maartje J.] MC Daniel den Hoed Canc Ctr, Dept Med Oncol, Rotterdam Family Canc Clin, Rotterdam, Netherlands. [Garcia-Closas, Montserrat; Chanock, Stephen J.; Sherman, Mark E.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. [Garcia-Closas, Montserrat] Inst Canc Res, Div Genet & Epidemiol, London SW3 6JB, England. [Lissowska, Jolanta] M Sklodowska Curie Mem Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland. [Lissowska, Jolanta] Inst Oncol, Warsaw, Poland. [Hall, Per; Liu, Jianjun; Czene, Kamila] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Kang, Daehee; Yoo, Keun-Young; Noh, Dong-Young] Seoul Natl Univ, Coll Med, Seoul, South Korea. [Lindblom, Annika] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden. [Margolin, Sara] Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden. RP Brauch, H (reprint author), Dr Margarete Fischer Bosch Inst Clin Pharmacol, Auerbachstr 112, D-70376 Stuttgart, Germany. EM hiltrud.brauch@ikp-stuttgart.de RI Jakubowska, Anna/O-8050-2014; Garcia-Closas, Montserrat /F-3871-2015; Hartikainen, Jaana/E-6256-2015; Bowtell, David/H-1007-2016; Bruning, Thomas/G-8120-2015; Khusnutdinova, Elza/A-4810-2013; Brenner, Hermann/B-4627-2017; manoukian, siranoush/E-7132-2017; Bernard, Loris/K-5953-2014; Shen, CY/F-6271-2010; Verdrengh, Evelien/H-4571-2012; Noh, Dong-Young/G-5531-2011; Kang, Dae Hee/E-8631-2012; Yoo, Keun-Young/J-5548-2012; truong, therese/A-2837-2013; Kerin, Michael/D-6748-2013; Ekici, Arif/C-3971-2013; Andrulis, Irene/E-7267-2013; Dzhemileva, Lilya/K-8636-2013; Radice, Paolo/O-3119-2013; Dork, Thilo/J-8620-2012 OI Nevanlinna, Heli/0000-0002-0916-2976; dos Santos Silva, Isabel/0000-0002-6596-8798; Cox, Angela/0000-0002-5138-1099; Dunning, Alison Margaret/0000-0001-6651-7166; Giles, Graham/0000-0003-4946-9099; Muranen, Taru/0000-0002-5895-1808; Arndt, Volker/0000-0001-9320-8684; Garcia-Closas, Montserrat /0000-0003-1033-2650; Bowtell, David/0000-0001-9089-7525; Bruning, Thomas/0000-0001-9560-5464; Brenner, Hermann/0000-0002-6129-1572; manoukian, siranoush/0000-0002-6034-7562; Dite, Gillian/0000-0002-2448-2548; Czene, Kamila/0000-0002-3233-5695; Cross, Simon/0000-0003-2044-1754; Lissowska, Jolanta/0000-0003-2695-5799; Dzhemileva, Lilya/0000-0003-3315-4746; FU European Community [223175, HEALTH-F2-2009-223175]; Cancer Research UK [C1287/A10118, C1287/A12014]; European Union COST [BM0606]; United States National Cancer Institute, National Institutes of Health (NIH) [RFA-CA-06-503]; Cancer Prevention Institute of California [U01 CA69417]; University of Melbourne [U01 CA69638]; National Health and Medical Research Council of Australia; New South Wales Cancer Council; Victorian Health Promotion Foundation (Australia); Victorian Breast Cancer Research Consortium; Dutch Cancer Society [NKI DCS 2007-3839, 2009-4363, UL1997-1505]; Dutch National Genomics Initiative; Breast Cancer Research Trust; ELAN of the University Hospital of Erlangen; Cancer Research UK; Breakthrough Breast Cancer; NHS; National Cancer Research Network (NCRN); NIHR Comprehensive Biomedical Research Centre, Guy's and St. Thomas' NHS Foundation Trust; King's College London; Oxford Biomedical Research Centre; Dietmar-Hopp Foundation; Helmholtz Society; German Cancer Research Center (DKFZ); Fondation de France [2004012618, 2007005156]; Institut National du Cancer (INCa) [2007-1 SPC2, 2008-1-CP-4, 2009-1-SHS SP-04]; Association pour la Recherche contre le Cancer (ARC) [2008-1-CP-4]; Genome Spain Foundation; Red Tematica de Investigacion Cooperativa en Cancer; Asociacion Espanola Contra el Cancer; Fondo de Investigacion Sanitario [PI081583, PI081120]; Chief Physician Johan Boserup and Lise Boserup Fund; Danish Medical Research Council; Herlev Hospital; Baden Wurttemberg Ministry of Science, Research and Arts; German Cancer Aid (Deutsche Krebshilfe) [107054]; Federal Ministry of Education and Research (BMBF), Germany [01KW9975/5, 01KW9976/8, 01KW9977/0, 01KW0114]; Robert Bosch Foundation, Stuttgart; Deutsches Krebsforschungszentrum (DKFZ), Heidelberg; Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn; Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Bochum, Germany; "Stichting tegen Kanker" [232-2008, 196-2010]; German Cancer Research Centre (DKFZ); Rudolf Bartling Foundation; Hannover Medical School; Helsinki University Central Hospital; Academy of Finland [132473]; Finnish Cancer Society; Sigrid Juselius Foundation; German Academic Exchange Program; Friends of Hannover Medical School; German Federal Ministry of Research and Education [RUS08/017]; Swedish Cancer Society; Gustav V Jubilee Foundation; National Breast Cancer Foundation; NHMRC; Queensland Cancer Fund; Cancer Council of New South Wales; Cancer Council of Victoria; Cancer Council of Tasmania; Cancer Council of South Australia; Cancer Foundation of Western Australia; NHMRC [145684, 288704, 454508, 199600, 209057, 251533, 396414, 504711, 504715]; United States Army Medical Research and Materiel Command [DAMD17-01-1-0729]; Kuopio University Hospital; Cancer Fund of North Savo; Finnish Cancer Organizations; Academy of Finland; University of Eastern Finland; Deutsche Krebshilfe e.V. [70-2892-BR I]; Hamburg Cancer Society; German Cancer Research Center; Federal Ministry of Education and Research (BMBF) Germany [01KH0402]; Ministero della Salute; Ministero dell'Universita' e Ricerca [RBLAO3-BETH]; Fondazione Italiana per la Ricerca sul Cancro; Associazione Italiana per la Ricerca sul Cancro [4017]; NIH [CA122340, CA128978, CA58860, CA92044]; Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201]; Cancer Council Victoria; Norwegian Research council [155218/V40, 175240/S10]; FUGE-NFR [181600/V11]; Swizz Bridge Award; Finnish Cancer Foundation; University of Oulu; Oulu University Hospital; National Cancer Institute, Department of Health and Human Services, USA; Yorkshire Cancer Research; Breast Cancer Campaign; Ministry of Health and Welfare, Republic of Korea [AO30001]; Polish Foundation of Science; Institute of Biomedical Sciences, Academia Sinica, Taiwan; Lon V Smith Foundation [LVS39420]; Dutch Cancer Society d [UL1997-1505]; Biobanking and Biomolecular Resources Research Infrastructure [BBMRI-NL CP16]; Institute of Cancer Research; [PBZ_KBN_122/P05/2004] FX Contract grant sponsors: Part of this work was supported by the European Community's Seventh Framework Programme under grant agreement number 223175 (grant number HEALTH-F2-2009-223175) (COGS). The BCAC is funded by Cancer Research UK (C1287/A10118 and C1287/A12014). Meetings of the BCAC have been funded by the European Union COST program (BM0606). D. F. E. is a Principal Research Fellow of Cancer Research UK. The ABCFS, NC-BCFR, and OFBCR work was supported by the United States National Cancer Institute, National Institutes of Health (NIH) under RFA-CA-06-503, and through cooperative agreements with members of the Breast Cancer Family Registry (BCFR) and Principal Investigators, including Cancer Care Ontario (U01 CA69467), Cancer Prevention Institute of California (U01 CA69417), and University of Melbourne (U01 CA69638). Samples from the NC-BCFR were processed and distributed by the Coriell Institute for Medical Research. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the BCFR, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the BCFR. The ABCFS was also supported by the National Health and Medical Research Council of Australia, the New South Wales Cancer Council, the Victorian Health Promotion Foundation (Australia) and the Victorian Breast Cancer Research Consortium. J.L.H. is a National Health and Medical Research Council (NHMRC) Australia Fellow and a Victorian Breast Cancer Research Consortium Group Leader. M. C. S. is a NHMRC Senior Research Fellow and a Victorian Breast Cancer Research Consortium Group Leader. The ABCS study was supported by the Dutch Cancer Society (grants NKI DCS 2007-3839 and 2009-4363) and the Dutch National Genomics Initiative. The ACP is funded by the Breast Cancer Research Trust. The work of the BBCC was partly funded by ELAN Fond of the University Hospital of Erlangen. The BBCS is funded by Cancer Research UK and Breakthrough Breast Cancer and acknowledges NHS funding to the NIHR Biomedical Research Centre, and the National Cancer Research Network (NCRN). BIGGS: E. S. is supported by NIHR Comprehensive Biomedical Research Centre, Guy's and St. Thomas' NHS Foundation Trust in partnership with King's College London. I. T. is supported by the Oxford Biomedical Research Centre. The BSUCH study was supported by the Dietmar-Hopp Foundation, the Helmholtz Society and the German Cancer Research Center (DKFZ). CECILE study was funded by Fondation de France (grant 2004012618; 2007005156), Institut National du Cancer (INCa grant 2007-1 SPC2; 2008-1-CP-4; 2009-1-SHS SP-04), Association pour la Recherche contre le Cancer (ARC grant 2008-1-CP-4). The CNIO-BCS was supported by the Genome Spain Foundation, the Red Tematica de Investigacion Cooperativa en Cancer and grants from the Asociacion Espanola Contra el Cancer and the Fondo de Investigacion Sanitario (PI081583 and PI081120). The CGPS was supported by the Chief Physician Johan Boserup and Lise Boserup Fund, the Danish Medical Research Council and Herlev Hospital. The ESTHER study was supported by a grant from the Baden Wurttemberg Ministry of Science, Research and Arts. Additional cases were recruited in the context of the VERDI study, which was supported by a grant from the German Cancer Aid (Deutsche Krebshilfe).; The GENICA Network was funded by the Federal Ministry of Education and Research (BMBF), Germany, grants 01KW9975/5, 01KW9976/8, 01KW9977/0, and 01KW0114; the Robert Bosch Foundation, Stuttgart; Deutsches Krebsforschungszentrum (DKFZ), Heidelberg; Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn; Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Bochum, Germany. The LMBC was supported by the "Stichting tegen Kanker" (grants 232-2008 and 196-2010). The GC-HBOC was supported by Deutsche Krebshilfe (107054), the Dietmar-Hopp Foundation, the Helmholtz society, and the German Cancer Research Centre (DKFZ). The HABCS study was supported by the Rudolf Bartling Foundation and by an intramural grant from Hannover Medical School. 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 HM-BCS was supported by short-term fellowships from the German Academic Exchange Program (to N.B), and the Friends of Hannover Medical School (to N.B.). The HUBCS was supported by a grant from the German Federal Ministry of Research and Education (RUS08/017). The KARBAC work was supported by the Swedish Cancer Society and the Gustav V Jubilee Foundation. kConFab is supported by grants from the National Breast Cancer Foundation; the NHMRC; the Queensland Cancer Fund; the Cancer Councils of New South Wales, Victoria, Tasmania, and South Australia; and the Cancer Foundation of Western Australia. The kConFab Clinical Follow Up Study was funded by the NHMRC (145684, 288704, and 454508). Financial support for the AOCS was provided by the United States Army Medical Research and Materiel Command (DAMD17-01-1-0729), the Cancer Council of Tasmania and Cancer Foundation of Western Australia and the NHMRC (199600). G. C. T. and P. W. are supported by the NHMRC. The KBCP was financially supported by the special Government Funding (EVO) of Kuopio University Hospital grants, Cancer Fund of North Savo, the Finnish Cancer Organizations, the Academy of Finland, and by the strategic funding of the University of Eastern Finland. The MARIE study was supported by the Deutsche Krebshilfe e. V. (70-2892-BR I), the Hamburg Cancer Society, the German Cancer Research Center, and the genotype work in part by the Federal Ministry of Education and Research (BMBF) Germany (01KH0402). MBCSG is supported by grants from Ministero della Salute (Extraordinary National Cancer Program 2006 "Alleanza contro il Cancro", and "Progetto Tumori Femminili" to P. R.), Ministero dell'Universita' e Ricerca (RBLAO3-BETH to PR), Fondazione Italiana per la Ricerca sul Cancro (Special Project "Hereditary tumors"), Associazione Italiana per la Ricerca sul Cancro (4017 and by funds from Italian citizens who allocated the 5/1000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects "5 x 1000"). The MCBCS was supported by the NIH grants [CA122340, CA128978] and a Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201]. MCCS is supported by Cancer Council Victoria and by NHMRC (grants 209057, 251533, 396414, 504711, and 504715). The NBCS was supported by grants from the Norwegian Research council, 155218/V40, 175240/S10 to ALBD, FUGE-NFR 181600/V11 to VNK and a Swizz Bridge Award to ALBD.; The OBCS was supported by research grants from the Finnish Cancer Foundation, the Sigrid Juselius Foundation, the Academy of Finland, the University of Oulu, and the Oulu University Hospital. The PBCS was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. The SBCS was supported by Yorkshire Cancer Research and the Breast Cancer Campaign. The SEBCS was supported by the Korea Health 21 R&D Project [AO30001], Ministry of Health and Welfare, Republic of Korea. The SZBCS was supported by Grant PBZ_KBN_122/P05/2004; Katarzyna Jaworska is a fellow of International Ph.D. program, Postgraduate School of Molecular Medicine, Warsaw Medical University, supported by the Polish Foundation of Science. The TWBCS is supported by the Taiwan Biobank project of the Institute of Biomedical Sciences, Academia Sinica, Taiwan. The UCIBCS component of this research was supported by the NIH [CA58860, CA92044] and the Lon V Smith Foundation (LVS39420). ORIGO were funded by grants from the Dutch Cancer Society (UL1997-1505) and the Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL CP16). The UKBGS thank Breakthrough Breast Cancer and the Institute of Cancer Research for funding. The ICR acknowledge NHS funding to the NIHR Biomedical Research Centre. NR 73 TC 22 Z9 24 U1 4 U2 23 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD JUL PY 2012 VL 33 IS 7 BP 1123 EP 1132 DI 10.1002/humu.22089 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 952TK UT WOS:000304815100017 PM 22461340 ER PT J AU Bartek, J Ng, K Bartek, J Fischer, W Carter, B Chen, CC AF Bartek, Jiri, Jr. Ng, Kimberly Bartek, Jiri Fischer, Walter Carter, Bob Chen, Clark C. TI Key concepts in glioblastoma therapy SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Review ID GROWTH-FACTOR RECEPTOR; DNA-DAMAGE RESPONSE; BEVACIZUMAB PLUS IRINOTECAN; MGMT PROMOTER METHYLATION; TUMOR-INITIATING CELLS; CENTRAL-NERVOUS-SYSTEM; STEM-CELLS; RECURRENT GLIOBLASTOMA; ADJUVANT TEMOZOLOMIDE; IMMUNE SURVEILLANCE AB Glioblastoma is the most common form of primary brain cancer and remains one of the most aggressive forms of human cancer. Current standard of care involves maximal surgical resection followed by concurrent therapy with radiation and the DNA alkylating agent temozolomide. Despite this aggressive regimen, the median survival remains approximately 14 months. Meaningful strategies for therapeutic intervention are desperately needed. Development of such strategies will require an understanding of the therapeutic concepts that have evolved over the past three decades. This article reviews the key principles that drive the formulation of therapeutic strategies in glioblastoma. Specifically, the concepts of tumour heterogeneity, oncogene addiction, non-oncogene addiction, tumour initiating cells, tumour microenvironment, non-coding sequences and DNA damage response will be reviewed. C1 [Chen, Clark C.] Dana Farber Canc Inst, Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Div Genom Stabil & DNA Repair, Boston, MA 02115 USA. [Bartek, Jiri, Jr.] Karolinska Univ Hosp, Dept Neurosurg, Stockholm, Sweden. [Bartek, Jiri] Danish Canc Soc, Res Ctr, Copenhagen, Denmark. [Bartek, Jiri] Palacky Univ, Lab Genome Integr, CR-77147 Olomouc, Czech Republic. [Bartek, Jiri] Palacky Univ, Inst Mol & Translat Med, CR-77147 Olomouc, Czech Republic. [Fischer, Walter] Rigshosp, Dept Neurosurg, DK-2100 Copenhagen, Denmark. [Carter, Bob; Chen, Clark C.] Univ Calif San Diego, Ctr Theoret & Appl Neurosurg, San Diego, CA USA. [Chen, Clark C.] Beth Israel Deaconess Med Ctr, Div Neurosurg, Boston, MA 02215 USA. RP Chen, CC (reprint author), Dana Farber Canc Inst, Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Div Genom Stabil & DNA Repair, Jimmy Fund 620A,44 Binney St, Boston, MA 02115 USA. EM clarkchen@ucsd.edu RI Bartek, Jiri/G-5870-2014; OI Bartek Jr., Jiri/0000-0002-2911-1914 FU Doris Duke Charitable Foundation; Sontag Foundation; Burroughs Wellcome Fund Career Awards for Medical Sciences; Kimmel Scholar award; American Brain Tumour Association; National Cancer Institute; Danish National Research Foundation; Czech Ministry of Health [NT/11065-5/2010]; European Commission [CZ.1.05/2.1.00/01.0030] FX This work was supported by the Doris Duke Charitable Foundation Clinical Scientist Development Award, the Sontag Foundation Distinguished Scientist Award, the Burroughs Wellcome Fund Career Awards for Medical Sciences, the Kimmel Scholar award, a Discovery Grant from the American Brain Tumour Association, a National Cancer Institute K12 award, the Danish National Research Foundation, the Czech Ministry of Health (NT/11065-5/2010), and the European Commission (projects DDResponse, CZ.1.05/2.1.00/01.0030, and Infla-Care). NR 111 TC 28 Z9 29 U1 2 U2 13 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD JUL PY 2012 VL 83 IS 7 BP 753 EP 760 DI 10.1136/jnnp-2011-300709 PG 8 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 953XQ UT WOS:000304907500017 PM 22396442 ER PT J AU Eisner, B AF Eisner, Brian TI Imaging Calculi in Pregnancy-Is the Future Ultra Low Dose Computerized Tomography with Iterative Reconstruction Technique? SO JOURNAL OF UROLOGY LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02215 USA. RP Eisner, B (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02215 USA. NR 10 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JUL PY 2012 VL 188 IS 1 BP 12 EP 13 DI 10.1016/j.juro.2012.04.034 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 957GT UT WOS:000305148900003 PM 22583642 ER PT J AU Lu, J Wirth, GJ Wu, SL Chen, JX Dahl, DM Olumi, AF Young, RH McDougal, WS Wu, CL AF Lu, Jian Wirth, Gregory J. Wu, Shulin Chen, Junxing Dahl, Douglas M. Olumi, Aria F. Young, Robert H. McDougal, W. Scott Wu, Chin-Lee TI A Close Surgical Margin After Radical Prostatectomy is an Independent Predictor of Recurrence SO JOURNAL OF UROLOGY LA English DT Article DE prostatectomy; prostatic neoplasms; prostate-specific antigen; recurrence ID SPECIMENS; RESECTION; CANCER; TUMOR AB Purpose: The term close surgical margin refers to a tumor extending to the inked margin of the specimen without reaching it. Current guidelines state that a close surgical margin should simply be reported as negative. However, this recommendation remains controversial and relies on limited evidence. We evaluated the impact of close surgical margins on the long-term risk of biochemical recurrence after radical prostatectomy. Materials and Methods: We identified 1,195 consecutive patients who underwent radical prostatectomy and lymphadenectomy for localized prostate cancer at our institution from 1993 to 1999. In 894 of these patients associations between margin status and location, Gleason score, pathological stage, preoperative prostate specific antigen, prostate weight and age with the risk of biochemical recurrence were examined. Results: Of these 894 patients 644 (72%) had negative margins and of these patients 100 (15.5%) had close surgical margins. In the group with prostate specific antigen failure, median time to recurrence was 3.5 years. In the group without recurrence median followup was 9.9 years. Cumulative recurrence-free survival differed significantly among positive, negative and close surgical margins (p < 0.001). On multivariate analysis a close surgical margin constituted a significant, independent predictor of recurrence (HR 2.1, 95% CI 1.04-4.33). Gleason score and positive margins were the strongest prognostic factors. Conclusions: In this cohort close surgical margins were independently associated with a twofold risk of postoperative biochemical recurrence. Further evaluation of the clinical significance of close surgical margins is indicated as they might be an indicator of local recurrence and of relevance when considering salvage therapy. C1 [Lu, Jian; Wirth, Gregory J.; Chen, Junxing; Dahl, Douglas M.; Olumi, Aria F.; McDougal, W. Scott; Wu, Chin-Lee] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Wu, Shulin; Young, Robert H.; Wu, Chin-Lee] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. [Lu, Jian] Peking Univ, Hosp 3, Dept Urol, Beijing 100871, Peoples R China. RP Wu, CL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Urol, 55 Fruit St, Boston, MA 02114 USA. EM cwu2@partners.org OI Wirth, Gregory J./0000-0003-0636-3438 NR 18 TC 9 Z9 9 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JUL PY 2012 VL 188 IS 1 BP 91 EP 97 DI 10.1016/j.juro.2012.02.2565 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 957GT UT WOS:000305148900029 PM 22578729 ER PT J AU Yang, QR Ma, Y Zhu, RY Huang, GQ Guan, M Avram, MM Lu, Z AF Yang, Qiaorong Ma, Ying Zhu, Rongyi Huang, Guiqing Guan, Ming Avram, Mathew M. Lu, Zhong TI The effect of flashlamp pulsed dye laser on the expression of connective tissue growth factor in keloids SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE connective tissue growth factor; keloid; pulsed dye laser ID HYPERTROPHIC STERNOTOMY SCARS; TREATMENT RESPONSE; MANAGEMENT AB Objective To investigate connective tissue growth factor (CTGF) expression before and after pulsed dye laser (PDL, 595?nm) treatment, and to better understand the mechanism of PDL treatment of keloids. Method Twenty-six patients with keloids were recruited for this study. For each patient, two keloids of similar anatomic location, duration, texture, and appearance were chosen for study; one of these keloids was treated and the other served as a control. Three sessions of PDL treatment, with pulse duration of 1.5?milliseconds, spot size 7?mm, DCD duration 20?milliseconds/delay 10?milliseconds and fluence of 10?J/cm2, were performed on the keloids at 3- to 4-week intervals. Punch biopsies were performed both on the treated and untreated keloids prior to the first treatment and after the final treatment. The specimens underwent realtime polymerase chain reaction (PCR) and immunohistochemistry (IHC) to investigate the CTGF mRNA and protein expression after PDL treatment. Results According to realtime PCR, the CTGF mRNA was significantly down-regulated after PDL treatment in 80.77% of patients as compared to the control group. IHC investigation showed that after treatment the CTGF positive cells also significantly decreased in number as compared to the control group in 80.77% of patients. Using the Vancouver scar scale (VSS), there was an average decrease of 20.85?+/-?12.33% after PDL treatment. Conclusions Pulsed dye laser treatment of keloids significantly down-regulates the expression of CTGF in most cases. This may partially explain the mechanism of action of PDL treatment of keloids. Lasers Surg. Med. 44: 377383, 2012. (c) 2012 Wiley Periodicals, Inc. C1 [Yang, Qiaorong; Ma, Ying; Zhu, Rongyi; Huang, Guiqing; Lu, Zhong] Fudan Univ, Huashan Hosp, Dept Dermatol, Shanghai 200040, Peoples R China. [Yang, Qiaorong] Fudan Univ, Zhongshan Hosp, Dept Dermatol, Shanghai 200032, Peoples R China. [Guan, Ming] Fudan Univ, Huashan Hosp, Dept Lab, Shanghai 200040, Peoples R China. [Avram, Mathew M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Dermatol Laser & Cosmet Ctr,Dept Dermatol, Boston, MA 02114 USA. RP Lu, Z (reprint author), Fudan Univ, Huashan Hosp, Dept Dermatol, Shanghai 200040, Peoples R China. EM luzhong20100806@qq.com FU Shanghai Science and Technology Committee [10411961100] FX Contract grant sponsor: Shanghai Science and Technology Committee Medical Guidance Programme; Contract grant number: 10411961100. NR 20 TC 6 Z9 8 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD JUL PY 2012 VL 44 IS 5 BP 377 EP 383 DI 10.1002/lsm.22031 PG 7 WC Dermatology; Surgery SC Dermatology; Surgery GA 953VT UT WOS:000304902000003 PM 22539077 ER PT J AU Muhammed, M Fuchs, BB Wu, MP Breger, J Coleman, JJ Mylonakis, E AF Muhammed, Maged Fuchs, Beth Burgwyn Wu, Michael P. Breger, Julia Coleman, Jeffrey J. Mylonakis, Eleftherios TI The role of mycelium production and a MAPK-mediated immune response in the C. elegans-Fusarium model system SO MEDICAL MYCOLOGY LA English DT Article DE Caenorhabditis elegans; Fusarium; host; mancozeb ID ANTIMICROBIAL PEPTIDE EXPRESSION; ANIMAL INFECTION MODEL; TOLL-LIKE RECEPTOR; CAENORHABDITIS-ELEGANS; INNATE IMMUNITY; IMMUNOCOMPROMISED PATIENTS; SIGNAL-TRANSDUCTION; PROTEIN; VIRULENCE; OXYSPORUM AB Fusariosis is an emerging infectious complication of immune deficiency, but models to study this infection are lacking. The use of the soil nematode Caenorhabditis elegans as a model host to study the pathogenesis of Fusarium spp. was investigated. We observed that Fusarium conidia consumed by C. elegans can cause a lethal infection and result in more than 90% killing of the host within 120 hours, and the nematode had a significantly longer survival when challenged with Fusarium proliferatum compared to other species. Interestingly, mycelium production appears to be a major contributor in nematode killing in this model system, and C. elegans mutant strains with the immune response genes, tir-1 (encoding a protein containing a TIR domain that functions upstream of PMK-1) and pmk-1 (the homolog of the mammalian p38 MAPK) lived significantly shorter when challenged with Fusarium compared to the wild type strain. Furthermore, we used the C. elegans model to assess the efficacy and toxicity of various compounds against Fusarium. We demonstrated that amphotericin B, voriconazole, mancozeb, and phenyl mercury acetate significantly prolonged the survival of Fusarium-infected C. elegans, although mancozeb was toxic at higher concentrations. In conclusion, we describe a new model system for the study of Fusarium pathogenesis and evolutionarily preserved host responses to this important fungal pathogen. C1 [Muhammed, Maged; Fuchs, Beth Burgwyn; Wu, Michael P.; Breger, Julia; Coleman, Jeffrey J.; Mylonakis, Eleftherios] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA. RP Coleman, JJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, 55 Fruit St,Gray Jackson Room 504, Boston, MA 02114 USA. EM jjcoleman@partners.org; emylonakis@partners.org RI Coleman, Jeffrey/E-2981-2015; OI Coleman, Jeffrey/0000-0001-8579-1996 FU National Institutes of Health [P01 AI 083214, AI075286, AI079569, T32 AI007061] FX We would like to thank Evan Mojica in the MGH clinical mycology laboratory for kindly providing Fusarium isolates and Read Pukkila-Worley for insightful discussions. This research was supported by a National Institutes of Health grants P01 AI 083214, a R01 award AI075286 and a R21 award AI079569 to EM, and a T32 AI007061 to JJC. NR 60 TC 10 Z9 14 U1 2 U2 9 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1369-3786 J9 MED MYCOL JI Med. Mycol. PD JUL PY 2012 VL 50 IS 5 BP 488 EP 496 DI 10.3109/13693786.2011.648217 PG 9 WC Infectious Diseases; Mycology; Veterinary Sciences SC Infectious Diseases; Mycology; Veterinary Sciences GA 956FT UT WOS:000305076200005 PM 22225407 ER PT J AU Seo, SW Lee, JM Im, K Park, JS Kim, SH Kim, ST Ahn, HJ Chin, J Cheong, HK Weiner, MW Na, DL AF Seo, Sang Won Lee, Jong-Min Im, Kiho Park, Jun-Sung Kim, Sook-Hui Kim, Sung Tae Ahn, Hyun-Jung Chin, Juhee Cheong, Hae-Kwan Weiner, Michael W. Na, Duk L. TI Cortical thinning related to periventricular and deep white matter hyperintensities SO NEUROBIOLOGY OF AGING LA English DT Article DE White matter hyperintensities; Periventricle white matter hyperintensities; Deep white matter hyperintensities; Cortical thickness; Cognitive impairment; Dementia; Mild cognitive impairment ID MILD COGNITIVE IMPAIRMENT; SUBCORTICAL VASCULAR DEMENTIA; ALZHEIMERS-DISEASE; CEREBRAL MICROANGIOPATHY; CEREBROVASCULAR-DISEASE; CHOLINERGIC PATHWAYS; LESIONS; BRAIN; MRI; DECLINE AB Previous studies showed that white matter hyperintensities (WMH) are related to cognitive decline in patients with mild cognitive impairment (MCI) or dementia. Moreover, periventricular WMH (periventricular white matter hyperintensities (PWMH)) and deep WMH (deep white matter hyperintensities (DWMH)) may have different effects on cognition. The purpose of this study is to investigate the contributions of PWMH and DWMH to the topography of cortical thinning and to investigate the relationship among WMH, cortical thinning, and cognitive impairments. Participants included 226 patients with Alzheimer's disease or subcortical vascular dementia, and 135 patients with amnestic MCI or subcortical vascular MCI. Cortical thickness was measured using the surface based method. The topography of cortical thinning related to WMH was distributed in the frontal and perisylvian regions, which was similar to that of PWMH. In contrast, there were only small areas of cortical thinning inversely associated with DWMH, which were distributed in medial frontal and lingual gyrus. PWMH, but not DWMH, were associated with the frontal thinning and executive dysfunction; where both PWMH and frontal thinning were independently associated with executive dysfunction. Our results suggest that PWMH are associated with frontal thinning, which is further associated with frontal executive dysfunction. (C) 2012 Elsevier Inc. All rights reserved. C1 [Seo, Sang Won; Ahn, Hyun-Jung; Chin, Juhee; Na, Duk L.] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Neurol, Seoul, South Korea. [Lee, Jong-Min] Hanyang Univ, Dept Biomed Engn, Seoul 133791, South Korea. [Im, Kiho; Park, Jun-Sung] Harvard Univ, Div Newborn Med, Childrens Hosp Boston, Sch Med, Cambridge, MA 02138 USA. [Kim, Sook-Hui] Konkuk Univ, Dept Neurol, Konkuk Univ Hosp, Sch Med, Seoul, South Korea. [Kim, Sung Tae] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Radiol, Seoul, South Korea. [Cheong, Hae-Kwan] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Social & Prevent Med, Seoul, South Korea. [Weiner, Michael W.] San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA USA. RP Na, DL (reprint author), Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Neurol, Seoul, South Korea. EM dukna@skku.edu RI Na, Duk Lyul/C-9598-2011; OI Cheong, Hae-Kwan/0000-0003-2758-9399 FU Ministry for Health, Welfare and family Affairs, Republic of Korea [A050079]; Korean Science and Engineering Foundation (KOSEF) NRL; Korean government (MEST) [R0A-2007-000-20068-0]; Samsung Medical Center [CRL-108011, CRS 110-14-1] FX This study was supported by a grant from the Korean Healthcare Technology R&D Project, Ministry for Health, Welfare and family Affairs, Republic of Korea (A050079), a Korean Science and Engineering Foundation (KOSEF) NRL program grant funded by the Korean government (MEST; R0A-2007-000-20068-0), and a Samsung Medical Center Clinical Research Development Program grant (CRL-108011 and CRS 110-14-1). NR 55 TC 33 Z9 34 U1 1 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2012 VL 33 IS 7 BP 1156 EP + DI 10.1016/j.neurobiolaging.2010.12.003 PG 13 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 953GG UT WOS:000304854300006 PM 21316813 ER PT J AU Vannini, P Hedden, T Becker, JA Sullivan, C Putcha, D Rentz, D Johnson, KA Sperling, RA AF Vannini, Patrizia Hedden, Trey Becker, John A. Sullivan, Caroline Putcha, Deepti Rentz, Dorene Johnson, Keith A. Sperling, Reisa A. TI Age and amyloid-related alterations in default network habituation to stimulus repetition SO NEUROBIOLOGY OF AGING LA English DT Article DE Episodic memory; Functional MRI; Hippocampus; Amyloid; Aging ID MILD COGNITIVE IMPAIRMENT; PITTSBURGH COMPOUND-B; PRECLINICAL ALZHEIMERS-DISEASE; NEURAL RESPONSE SUPPRESSION; FUNCTIONAL CONNECTIVITY; OLDER PERSONS; HEALTHY-INDIVIDUALS; FUSIFORM CORTEX; CEREBRAL-CORTEX; MEMORY AB The neural networks supporting encoding of new information are thought to decline with age, although mnemonic techniques such as repetition may enhance performance in older individuals. Accumulation of amyloid-beta, one hallmark pathology of Alzheimer's disease (AD), may contribute to functional alterations in memory networks measured with functional magnetic resonance imaging (fMRI) prior to onset of cognitive impairment. We investigated the effects of age and amyloid burden on fMRI activity in the default network and hippocampus during repetitive encoding. Older individuals, particularly those with high amyloid burden, demonstrated decreased task-induced deactivation in the posteromedial cortices during initial stimulus presentation and failed to modulate fMRI activity in response to repeated trials, whereas young subjects demonstrated a stepwise decrease in deactivation with repetition. The hippocampus demonstrated similar patterns across the groups, showing task-induced activity that decreased in response to repetition. These findings demonstrate that age and amyloid have dissociable functional effects on specific nodes within a distributed memory network, and suggest that functional brain changes may begin far in advance of symptomatic Alzheimer's disease. (C) 2012 Elsevier Inc. All rights reserved. C1 [Vannini, Patrizia; Sperling, Reisa A.] Harvard Univ, Athinoula A Martinos Ctr Biomed Imaging, Dept Psychiat, Massachusetts Gen Hosp,Med Sch, Charlestown, MA USA. [Vannini, Patrizia; Rentz, Dorene; Johnson, Keith A.; Sperling, Reisa A.] Harvard Univ, Brigham & Womens Hosp, Ctr Alzheimer Res & Treatment, Dept Neurol,Med Sch, Boston, MA 02115 USA. [Vannini, Patrizia] Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Clin Geriatr, Karolinska Univ Hosp, Stockholm, Sweden. [Hedden, Trey; Becker, John A.; Johnson, Keith A.] Harvard Univ, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Massachusetts Gen Hosp,Med Sch, Charlestown, MA USA. [Sullivan, Caroline; Putcha, Deepti; Rentz, Dorene; Johnson, Keith A.; Sperling, Reisa A.] Harvard Univ, Athinoula A Martinos Ctr Biomed Imaging, Dept Neurol, Massachusetts Gen Hosp,Med Sch, Charlestown, MA USA. RP Vannini, P (reprint author), Massachusetts Gen Hosp, Gerontol Res Unit, 149 13th St,Suite 2691, Boston, MA 02129 USA. EM patrizia@nmr.mgh.harvard.edu OI Kennedy, Kristen/0000-0001-5373-9026 FU Karolinska Institutet foundations [Fobi0794]; Swedish Research Council; Royal Swedish Academy of Sciences [FOAO7L501]; European Union [FP7-PEOPLE-2007-4-1-IOF]; National Institutes of Health [K24 AG035007, R01 AG027435-S1, P01AG036694, P50AG00513421]; Alzheimer's Association [IIRG-06-27374, IIRG-08-90934] FX We are indebted to the volunteers who participated in this study. We thank Janice Fairhurst, George Chiuo, Seung-Schik Yoo, and Istvan Akos Morocz for their help with scan acquisition at the Center for Advanced Imaging at Brigham and Women's Hospital and Meghan Frey for collecting the neuropsychological data. This work was supported by Karolinska Institutet foundations (Fobi0794) (PV), the Swedish Research Council (PV); the Royal Swedish Academy of Sciences: FOAO7L501 (PV); and Marie Curie Fellowship: FP7-PEOPLE-2007-4-1-IOF from the European Union (PV), National Institutes of Health: K24 AG035007 (RS), R01 AG027435-S1 [RS and KJ], P01AG036694 [RS and KJ], P50AG00513421 [RS and KJ], and the Alzheimer's Association: IIRG-06-27374 (RS) and IIRG-08-90934 (DR). NR 94 TC 27 Z9 27 U1 1 U2 10 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 JUL PY 2012 VL 33 IS 7 BP 1237 EP 1252 DI 10.1016/j.neurobiolaging.2011.01.003 PG 16 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 953GG UT WOS:000304854300014 PM 21334099 ER PT J AU Beeri, MS Schmeidler, J Lesser, GT Maroukian, M West, R Leung, S Wysocki, M Perl, DP Purohit, DP Haroutunian, V AF Beeri, Michal Schnaider Schmeidler, James Lesser, Gerson T. Maroukian, Maria West, Rebecca Leung, Stephanie Wysocki, Michael Perl, Daniel P. Purohit, Dushyant P. Haroutunian, Vahram TI Corticosteroids, but not NSAIDs, are associated with less Alzheimer neuropathology SO NEUROBIOLOGY OF AGING LA English DT Article DE Glucocorticoids; Corticosteroids; Nonsteroidal anti-inflammatory drugs (NSAIDs); Neuritic plaques; Neurofibrillary tangles ID RANDOMIZED CONTROLLED-TRIAL; COGNITIVE FUNCTION; P-GLYCOPROTEIN; CACHE COUNTY; DISEASE; BRAIN; INFLAMMATION; DEMENTIA; GLUCOCORTICOIDS; PREDNISOLONE AB The objective of this study was to test the hypothesis that corticosteroid and nonsteroidal anti-inflammatory drug (NSAID) medications are associated with less global and regional Alzheimer's disease (AD) neuropathology. This postmortem study was based on 694 brains of subjects from the Mount Sinai School of Medicine Brain Bank who did not have neuropathologies other than neuritic plaques (NPs), neurofibrillary tangles (NFTs), or cerebrovascular disease. Densities of NPs and of NFTs were assessed in several neocortical regions and in the hippocampus, entorhinal cortex, and amygdala. Counts of NPs in several neocortical regions were also assessed. For each neuropathology measure, analyses of covariance controlling for age at death and sex compared subjects who received only corticosteroids (n = 54) or those who received only NSAIDs (n = 56) to the same comparison group, subjects who received neither (n = 576). Subjects receiving corticosteroids had significantly lower ratings and counts of NPs for all neuropathological measures, and NFTs overall and in the cerebral cortex and amygdala. In contrast, no measures were significant for subjects who received NSAIDs. Use of corticosteroids was associated with approximately 50% fewer NPs and NFTs in most brain regions examined, compared with nonmedicated subjects. In contrast, use of NSAIDs was not substantially associated with the reductions in hallmark lesions of AD. Because corticosteroids have anti-inflammatory as well as a myriad of other neurobiological effects, more direct studies in model systems could reveal novel therapeutic targets and mechanisms for AD lesion reduction. (C) 2012 Elsevier Inc. All rights reserved. C1 [Beeri, Michal Schnaider; Schmeidler, James; Maroukian, Maria; West, Rebecca; Leung, Stephanie; Wysocki, Michael; Haroutunian, Vahram] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Lesser, Gerson T.] Jewish Home & Hosp, New York, NY USA. [Perl, Daniel P.; Purohit, Dushyant P.] Mt Sinai Sch Med, Dept Pathol, New York, NY 10029 USA. [Haroutunian, Vahram] James J Peters VA Med Ctr, Bronx, NY USA. RP Beeri, MS (reprint author), Mt Sinai Sch Med, Dept Psychiat, 1 Gustave Levy Pl,Box 1230, New York, NY 10029 USA. EM michal.beeri@mssm.edu FU NIA [K01 AG023515-01, R01 AG034087, P01 AG02219]; Graubard Fund; Berkman Trust; Leir Foundation; ADRC [P50 AG05138] FX Study funding: supported by NIA grants K01 AG023515-01 and R01 AG034087 (MSB), P01 AG02219 (VH), and P50 AG05138 (ADRC- Dr. M. Sano), as well as by the Graubard Fund (MSB) and the Berkman Trust and Leir Foundation (VH). NR 43 TC 9 Z9 9 U1 2 U2 10 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 JUL PY 2012 VL 33 IS 7 BP 1258 EP 1264 DI 10.1016/j.neurobiolaging.2011.02.011 PG 7 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 953GG UT WOS:000304854300016 PM 21458888 ER PT J AU Wu, X Lu, Y Dong, YL Zhang, GH Zhang, YY Xu, ZP Culley, DJ Crosby, G Marcantonio, ER Tanzi, RE Xie, ZC AF Wu, Xu Lu, Yan Dong, Yuanlin Zhang, Guohua Zhang, Yiying Xu, Zhipeng Culley, Deborah J. Crosby, Gregory Marcantonio, Edward R. Tanzi, Rudolph E. Xie, Zhongcong TI The inhalation anesthetic isoflurane increases levels of proinflammatory TNF-alpha, IL-6, and IL-1 beta SO NEUROBIOLOGY OF AGING LA English DT Article DE Alzheimer's disease; Anesthesia; Isoflurane; TNF-alpha; IL-6; IL-1 beta ID FOCAL CEREBRAL-ISCHEMIA; ONSET ALZHEIMER-DISEASE; AMYLOID PROTEIN-LEVELS; TUMOR-NECROSIS-FACTOR; INFLAMMATORY PROCESSES; COGNITIVE DECLINE; INDUCED APOPTOSIS; GLOBAL-ISCHEMIA; IN-VIVO; EXPRESSION AB Anesthetics have been reported to promote Alzheimer's disease (AD) neuropathogenesis by inducing beta-amyloid protein accumulation and apoptosis. Neuroinflammation is associated with the emergence of AD. We therefore set out to determine the effects of the common anesthetic isoflurane on the levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-1 beta, the proinflammatory cytokines, in vitro and in vivo, employing Western blot, immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), and reverse transcriptase polymerase chain reaction (RT-PCR). Here, we show that a clinically relevant isoflurane anesthesia increased the protein and messenger ribonucleic acid (mRNA) levels of TNF-alpha, IL-6, and IL-1 beta in the brain tissues of mice. The isoflurane anesthesia increased the amounts of TNF-alpha immunostaining positive cells in the brain tissues of mice, the majority of which were neurons. Furthermore, isoflurane increased TNF-alpha levels in primary neurons, but not microglia cells, of mice. Finally, isoflurane induced a greater degree of TNF-alpha increase in the AD transgenic mice than in the wild-type mice. These results suggest that isoflurane may increase the levels of proinflammatory cytokines, which may cause neuroinflammation, leading to promotion of AD neuropathogenesis. (C) 2012 Elsevier Inc. All rights reserved. C1 [Wu, Xu; Lu, Yan; Dong, Yuanlin; Zhang, Yiying; Xu, Zhipeng; Xie, Zhongcong] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Geriatr Anesthesia Res Unit, Charlestown, MA 02129 USA. [Wu, Xu; Lu, Yan; Dong, Yuanlin; Zhang, Yiying; Xu, Zhipeng; Tanzi, Rudolph E.; Xie, Zhongcong] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Wu, Xu; Lu, Yan; Dong, Yuanlin; Zhang, Yiying; Xu, Zhipeng; Tanzi, Rudolph E.; Xie, Zhongcong] Massachusetts Gen Hosp, Genet & Aging Res Unit, MassGeneral Inst Neurodegenerat Dis, Dept Neurol, Charlestown, MA 02129 USA. [Wu, Xu; Zhang, Guohua] China Med Univ, Fac Forens Med, Dept Forens Pathol, Shenyang, Peoples R China. [Lu, Yan] China Med Univ, Shengjing Hosp, Key Lab Hlth Minist Congenital Malformat, Shenyang, Peoples R China. [Culley, Deborah J.; Crosby, Gregory] Brigham & Womens Hosp, Dept Anesthesia, Boston, MA 02115 USA. [Culley, Deborah J.; Crosby, Gregory; Marcantonio, Edward R.] Harvard Univ, Sch Med, Boston, MA USA. [Marcantonio, Edward R.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. RP Xie, ZC (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Geriatr Anesthesia Res Unit, 149 13th St,Room 4310, Charlestown, MA 02129 USA. EM zxie@partners.org FU National Institutes of Health [K08NS048140, R21AG029856, R01 GM088801, K08GM077057, RO1 GM088817, R37MH 60009]; American Geriatrics Society; Alzheimer's Association; Cure Alzheimer's Fund FX This research was supported by K08NS048140, R21AG029856, and R01 GM088801 (National Institutes of Health), Jahnigen Career Development Award (American Geriatrics Society), Investigator Initiated Research Grant (Alzheimer's Association) (to ZX); K08GM077057 (National Institutes of Health) (to DJC); RO1 GM088817 (National Institutes of Health) (to GC); R37MH 60009 (National Institutes of Health), and the Cure Alzheimer's Fund (to RET). The cost of anesthetic isoflurane was generously provided by the Department of Anesthesia, Critical Care and Pain Medicine in Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. NR 52 TC 70 Z9 86 U1 3 U2 20 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 JUL PY 2012 VL 33 IS 7 BP 1364 EP 1378 DI 10.1016/j.neurobiolaging.2010.11.002 PG 15 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 953GG UT WOS:000304854300028 PM 21190757 ER PT J AU Ksiezak-Reding, H Ho, L Santa-Maria, I Diaz-Ruiz, C Wang, J Pasinetti, GM AF Ksiezak-Reding, Hanna Ho, Lap Santa-Maria, Ismael Diaz-Ruiz, Carmen Wang, Jun Pasinetti, Giulio Maria TI Ultrastructural alterations of Alzheimer's disease paired helical filaments by grape seed-derived polyphenols SO NEUROBIOLOGY OF AGING LA English DT Article DE Alzheimer's disease; Paired helical filaments; Tau protein; Ultrastructure; Grape seed polyphenols; Immunogold labeling ID AMYLOID FIBRIL FORMATION; CROSS-BETA-STRUCTURE; IN-VITRO; TAU AGGREGATION; NEUROFIBRILLARY TANGLES; CORE DOMAIN; PROTEIN-TAU; BINDING; INHIBITION; EXTRACT AB Abnormal folding of the microtubule-associated protein tau leads to aggregation of tau into paired helical filaments (PHFs) and neurofibrillary tangles, the major hallmark of Alzheimer's disease (AD). We have recently shown that grape seed polyphenol extract (GSPE) reduces tau pathology in the TMHT mouse model of tauopathy (Wang et al., 2010). In the present studies we assessed the impact of GSPE exposure on the ultrastructure of PHFs isolated from Alzheimer's disease brain. Transmission electron microscopy revealed that GSPE induced profound dose-and time-dependent alterations in the morphology of PHFs with partial disintegration of filaments. Filaments showed similar to 2-fold enlargement in width and displayed numerous protrusions and splayed ends consistent with unfolding of tau and diminished structural stability. In addition, GSPE induced a reduction in immunogold labeling with antibodies against the C-terminal half (12E8, PHF-1) and the middle region of tau (AT8, Tau5, pSer214 tau, and AT180) but not the C-terminal end (Tau46). In comparison, labeling of N-terminus (Alz50) was enhanced. It is unlikely that alterations in immunogold labeling were due to biochemical alterations, e. g., protein phosphatase or proteolytic activities potentially stimulated by GSPE, because western blotting studies have shown the preservation of full length polypeptides of tau and their phospho-epitopes in GSPE-treated samples. The GSPE mechanism may include a noncovalent interaction of polyphenols with proline residues in the proline-rich domain of tau, with Pin1 sites at P213 and P232 most seriously affected as judged by suppression of labeling. Collectively, our results suggest that GSPE has a significant potential for therapeutic development by neutralizing phospho-epitopes and disrupting fibrillary conformation leading to disintegration of PHFs. (C) 2012 Elsevier Inc. All rights reserved. C1 [Ksiezak-Reding, Hanna; Ho, Lap; Santa-Maria, Ismael; Diaz-Ruiz, Carmen; Wang, Jun; Pasinetti, Giulio Maria] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. [Ksiezak-Reding, Hanna; Ho, Lap; Pasinetti, Giulio Maria] James J Peters Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. [Santa-Maria, Ismael] Queen Sofia Fdn, CIEN Fdn, Alzheimer Dis Res Unit, Madrid, Spain. RP Ksiezak-Reding, H (reprint author), Mt Sinai Sch Med, Dept Neurol, 1 Gustave L Levy Pl,Box 1137, New York, NY 10029 USA. EM hanna.reding@mssm.edu OI Diaz-Ruiz, Carmen/0000-0002-0112-0595 FU Society for Progressive Supranuclar Palsy; NIH [PO1 AT004511]; Veterans Administration FX The authors gratefully acknowledge the financial support from the Society for Progressive Supranuclar Palsy, NIH PO1 AT004511, and support in part from MERIT Review grant from Veterans Administration to GMP. NR 52 TC 22 Z9 25 U1 2 U2 24 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2012 VL 33 IS 7 BP 1427 EP 1439 DI 10.1016/j.neurobiolaging.2010.11.006 PG 13 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 953GG UT WOS:000304854300033 PM 21196065 ER PT J AU Kashino, SS Abeijon, C Qin, L Kanunfre, KA Kubrusly, FS Silva, FO Costa, DL Campos, D Costa, CHN Raw, I Campos-Neto, A AF Kashino, S. S. Abeijon, C. Qin, L. Kanunfre, K. A. Kubrusly, F. S. Silva, F. O. Costa, D. L. Campos, D., Jr. Costa, C. H. N. Raw, I. Campos-Neto, A. TI Identification of Leishmania infantum chagasi proteins in urine of patients with visceral leishmaniasis: a promising antigen discovery approach of vaccine candidates SO PARASITE IMMUNOLOGY LA English DT Article DE kala-azar; Leishmania infantum chagasi; ntf2; urine; vaccine; visceral leishmaniasis ID LATEX AGGLUTINATION-TEST; T-CELL RESPONSES; CUTANEOUS LEISHMANIASIS; MEGLUMINE ANTIMONIATE; RECOMBINANT ANTIGENS; PROTECTIVE IMMUNITY; FML-VACCINE; A2 PROTEIN; FOLLOW-UP; IMMUNIZATION AB Visceral leishmaniasis (VL) is a serious lethal parasitic disease caused by Leishmania donovani in Asia and by Leishmania infantum chagasi in southern Europe and South America. VL is endemic in 47 countries with an annual incidence estimated to be 500 000 cases. This high incidence is due in part to the lack of an efficacious vaccine. Here, we introduce an innovative approach to directly identify parasite vaccine candidate antigens that are abundantly produced in vivo in humans with VL. We combined RP-HPLC and mass spectrometry and categorized three L. infantum chagasi proteins, presumably produced in spleen, liver and bone marrow lesions and excreted in the patients urine. Specifically, these proteins were the following: Li-isd1 (XP_001467866.1), Li-txn1 (XP_001466642.1) and Li-ntf2 (XP_001463738.1). Initial vaccine validation studies were performed with the rLi-ntf2 protein produced in Escherichia coli mixed with the adjuvant BpMPLA-SE. This formulation stimulated potent Th1 response in BALB/c mice. Compared to control animals, mice immunized with Li-ntf2+ BpMPLA-SE had a marked parasite burden reduction in spleens at 40 days post-challenge with virulent L. infantum chagasi. These results strongly support the proposed antigen discovery strategy of vaccine candidates to VL and opens novel possibilities for vaccine development to other serious infectious diseases. C1 [Campos-Neto, A.] Forsyth Inst, Global Infect Dis Res Ctr, Cambridge, MA 02142 USA. [Abeijon, C.; Campos-Neto, A.] DetectoGen Inc, Grafton, MA USA. [Kanunfre, K. A.] Univ Sao Paulo, Inst Trop Med, Sao Paulo, Brazil. [Kubrusly, F. S.; Raw, I.] Butantan Inst Fdn, BioInd Div, Sao Paulo, Brazil. [Silva, F. O.; Costa, D. L.; Costa, C. H. N.] Univ Fed Piaui, Lab Leishmaniasis, Natan Portella Inst Trop Med, Teresina, PI, Brazil. [Campos, D., Jr.] Univ Brasilia, Dept Pediat, Brasilia, DF, Brazil. RP Campos-Neto, A (reprint author), Forsyth Inst, Global Infect Dis Res Ctr, 245 1st St, Cambridge, MA 02142 USA. EM acampos@forsyth.org RI Kashino, Suely/F-4171-2012; OI Kubrusly, Flavia/0000-0003-0646-583X FU NIH [R43AI084259-01] FX This work was supported in part by NIH grant R43AI084259-01 awarded to CA. NR 62 TC 1 Z9 1 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0141-9838 J9 PARASITE IMMUNOL JI Parasite Immunol. PD JUL PY 2012 VL 34 IS 7 BP 360 EP 371 DI 10.1111/j.1365-3024.2012.01365.x PG 12 WC Immunology; Parasitology SC Immunology; Parasitology GA 953WU UT WOS:000304905200002 PM 22443237 ER PT J AU Wu, RH Liu, CM Liu, PK Sun, PZ AF Wu, Renhua Liu, Charng-Ming Liu, Philip K. Sun, Phillip Zhe TI Improved measurement of labile proton concentration-weighted chemical exchange rate (kws) with experimental factor-compensated and T1-normalized quantitative chemical exchange saturation transfer (CEST) MRI SO CONTRAST MEDIA & MOLECULAR IMAGING LA English DT Article DE amide proton transfer (APT); chemical exchange saturation transfer (CEST); MRI ID KIDNEYS IN-VIVO; CONTRAST AGENT; MAGNETIZATION-TRANSFER; PARACEST AGENTS; 7 T; PH; RELAXATION; IOPAMIDOL; PEPTIDES; ISCHEMIA AB Chemical exchange saturation transfer (CEST) MRI enables measurement of dilute CEST agents and microenvironment properties such as pH and temperature, holding great promise for in vivo applications. However, because of confounding concomitant radio frequency (RF) irradiation and relaxation effects, the CEST-weighted MRI contrast may not fully characterize the underlying CEST phenomenon. We postulated that the accuracy of quantitative CEST MRI could be improved if the experimental factors (labeling efficiency and RF spillover effect) were estimated and taken into account. Specifically, the experimental factor was evaluated as a function of exchange rate and CEST agent concentration ratio, which remained relatively constant for intermediate RF irradiation power levels. Hence, the experimental factors can be calculated based on the reasonably estimated exchange rate and labile proton concentration ratio, which significantly improved quantification. The simulation was confirmed with creatine phantoms of serially varied concentration titrated to the same pH, whose reverse exchange rate (kws) was found to be linearly correlated with the concentration. In summary, the proposed solution provides simplified yet reasonably accurate quantification of the underlying CEST system, which may help guide the ongoing development of quantitative CEST MRI. Copyright (c) 2012 John Wiley & Sons, Ltd. C1 [Sun, Phillip Zhe] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula Martinos Ctr Biomed Imaging,Dept Radiol, Charlestown, MA 02129 USA. [Wu, Renhua] Shantou Univ, Coll Med, Dept Radiol, Affiliated Hosp 2, Shantou 515063, Guangdong, Peoples R China. [Wu, Renhua] Prov Key Lab Med Mol Imaging, Shantou, Guangdong, Peoples R China. [Liu, Charng-Ming; Liu, Philip K.; Sun, Phillip Zhe] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Sun, PZ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula Martinos Ctr Biomed Imaging,Dept Radiol, 149 13th St,Rm 2301, Charlestown, MA 02129 USA. EM pzhesun@nmr.mgh.harvard.edu FU National Natural Science Foundation of China [NSFC 30930027]; AHA/SDG [0835384N]; NIH/NIBIB [1K01EB009771]; NIH/NIDA/EUREKA [RO1026108]; NIH/NCRR [P41RR14075] FX This study was supported in part by grants from National Natural Science Foundation of China (NSFC 30930027, R. H. Wu), AHA/SDG 0835384N (P. Z. Sun), NIH/NIBIB 1K01EB009771 (P. Z. Sun), NIH/NIDA/EUREKA RO1026108 (P. K. Liu) and NIH/NCRR-P41RR14075. The authors would like to thank Ms Nichole Eusemann for editorial assistance. NR 38 TC 17 Z9 17 U1 0 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1555-4309 J9 CONTRAST MEDIA MOL I JI Contrast Media Mol. Imaging PD JUL-AUG PY 2012 VL 7 IS 4 BP 384 EP 389 DI 10.1002/cmmi.505 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 950QZ UT WOS:000304665100004 PM 22649044 ER PT J AU Bedimo, R Kyriakides, T Brown, S Weidler, J Lie, Y Coakley, E Holodniy, M AF Bedimo, R. Kyriakides, T. Brown, S. Weidler, J. Lie, Y. Coakley, E. Holodniy, M. TI Predictive value of HIV-1 replication capacity and phenotypic susceptibility scores in antiretroviral treatment-experienced patients SO HIV MEDICINE LA English DT Article DE antiretroviral therapy; HIV; phenotypic susceptibility score; replication capacity; resistance ID HUMAN-IMMUNODEFICIENCY-VIRUS; DISEASE PROGRESSION; REVERSE-TRANSCRIPTASE; RESISTANCE MUTATIONS; VIROLOGICAL FAILURE; DRUG SUSCEPTIBILITY; INFECTED PATIENTS; CLINICAL-TRIAL; EX-VIVO; THERAPY AB Objectives The aim of the study was to determine the prognostic value of HIV replication capacity (RC) for subsequent antiretroviral (ARV) treatment response in ARV-experienced patients. Methods RC and phenotypic resistance testing were performed at baseline and week 12 on plasma samples from patients randomized to undergo a 12-week ARV drug-free period (ARDFP) or initiate immediate salvage therapy (no-ARDFP group) in the Options in Management with Antiretrovirals (OPTIMA) trial. Dichotomous and incremental phenotypic susceptibility scores (dPSSs and iPSSs, respectively) were calculated. The predictive value of RC and PSS for ARV therapy response and/or ARDFP was evaluated using multivariate regression analysis and Pearson correlations. Results In 146 no-ARDFP subjects, baseline RC (50.8%) did not change at week 12 and was not correlated with CD4 cell count or viral load changes at week 12 (P?=?0.33 and P?=?0.79, respectively) or at week 24 (P?=?0.96 and P?=?0.14, respectively). dPSS predicted virological but not CD4 cell count response to ARV therapy at weeks 12, 24 and 48 (P?=?0.002, P?c, Mr. Rene Costello, Dr. Omer Bonne, Dr. Gyorgy Csako, Dr. Alan Remaley, Dr. Alexander Neumeister, and Dr. Mitchel A. King have no conflicts to disclose. Dr. Wayne C. Drevets has reported that the research support for this project was provided entirely by the NIMH DIRP. Although Dr. Drevets has no financial conflicts that are relevant to the subject matter of the manuscript, during the past two years he has served as a consultant for the following companies: Pfizer, Eisai, Rules Based Medicine, Johnson and Johnson. Dr. Drevets also is named as co-inventor for a Use Patent filed by the NIMH for Scopolamine in the Treatment of Depression. Dr. Dennis S. Charney has reported that he and Mount Sinai School of Medicine have been named on a use patent of Ketamine for the treatment of depression. If Ketamine were shown to be effective in the treatment of depression and received approval from the Food and Drug Administration (FDA) for this indication, Dr. Charney and Mount Sinai School of Medicine could benefit financially. Dr. Charney has also disclosed that he is not currently engaged in any consulting activity and has had no activity for the past three years. NR 32 TC 7 Z9 7 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD JUN 27 PY 2012 VL 520 IS 1 BP 1 EP 5 DI 10.1016/j.neulet.2012.04.072 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 969AE UT WOS:000306027300001 PM 22579817 ER PT J AU Schlippe, YVG Hartman, MCT Josephson, K Szostak, JW AF Schlippe, Yollete V. Guillen Hartman, Matthew C. T. Josephson, Kristopher Szostak, Jack W. TI In Vitro Selection of Highly Modified Cyclic Peptides That Act as Tight Binding Inhibitors SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID UNNATURAL AMINO-ACIDS; MESSENGER-RNA DISPLAY; HUMAN ALPHA-THROMBIN; DEHYDROALANINE-CONTAINING PEPTIDES; RIBOSOMAL SYNTHESIS; GENETIC-CODE; PROTEIN SURFACES; ALIGNMENT EDITOR; DRUG DISCOVERY; DE-NOVO AB There is a great demand for the discovery of new therapeutic molecules that combine the high specificity and affinity of biologic drugs with the bioavailability and lower cost of small molecules. Small, natural-product-like peptides hold great promise in bridging this gap; however, access to libraries of these compounds has been a limitation. Since ribosomal peptides may be subjected to in vitro selection techniques, the generation of extremely large libraries (>10(13)) of highly modified macrocyclic peptides may provide a powerful alternative for the generation and selection of new useful bioactive molecules. Moreover, the incorporation of many non-proteinogenic amino acids into ribosomal peptides in conjunction with macrocyclization should enhance the drug-like features of these libraries. Here we show that mRNA-display, a technique that allows the in vitro selection of peptides, can be applied to the evolution of macrocyclic peptides that contain a majority of unnatural amino acids. We describe the isolation and characterization of two such unnatural cyclic peptides that bind the protease thrombin with low nanomolar affinity, and we show that the unnatural residues in these peptides are essential for the observed high-affinity binding. We demonstrate that the selected peptides are tight-binding inhibitors of thrombin, with K-i(aPP) values in the low nanomolar range. The ability to evolve highly modified macrocyclic peptides in the laboratory is the first crucial step toward the facile generation of useful molecular reagents and therapeutic lead molecules that combine the advantageous features of biologics with those of small-molecule drugs. C1 [Szostak, Jack W.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. RP Szostak, JW (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Dept Mol Biol, 185 Cambridge St, Boston, MA 02114 USA. EM szostak@molbio.mgh.harvard.edu FU Ra Pharmaceuticals; Howard Hughes Medical Institute FX The authors declare the following competing financial interest(s): Employment: K. Josephson is employed by Ra Pharmaceuticals, which is further developing the technology described in this paper. Ra Pharmaceuticals may benefit from the publication of this paper. Personal financial interests: J. W. Szostak, K Josephson, and M. C. T. Hartman hold shares in Ra Pharmaceuticals; J. W. Szostak and M. C. T. Hartman receive consulting fees from Ra Pharmaceuticals.; This research was supported by the Howard Hughes Medical Institute. J.W.S. is an investigator of the Howard Hughes Medical Institute. We thank Florian Seebeck, Buckhard Seelig, Chi-Wang Lin, Doug Treco, Alonso Ricardo, Craig Blain, Matt Simon, Jason Schrum, Christian Hentrich, and Katarzyna Adamala for helpful discussions. NR 55 TC 75 Z9 75 U1 5 U2 95 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD JUN 27 PY 2012 VL 134 IS 25 BP 10469 EP 10477 DI 10.1021/ja301017y PG 9 WC Chemistry, Multidisciplinary SC Chemistry GA 964SJ UT WOS:000305716700031 PM 22428867 ER PT J AU Fagenholz, PJ Fernandez-del Castillo, C AF Fagenholz, Peter J. Fernandez-del Castillo, Carlos TI Necrosectomy for Infected Necrotizing Pancreatitis SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 [Fagenholz, Peter J.; Fernandez-del Castillo, Carlos] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Fagenholz, PJ (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. EM pfagenholz@partners.org NR 4 TC 0 Z9 0 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 27 PY 2012 VL 307 IS 24 BP 2584 EP 2584 DI 10.1001/jama.2012.5970 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 964KF UT WOS:000305692600011 PM 22735412 ER PT J AU Scemama, P Lee, B Guimaraes, E AF Scemama, Pascal Lee, Brian Guimaraes, Emily TI Anesthesia Care for Low-Risk Patients Undergoing Gastrointestinal Endoscopies SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 [Scemama, Pascal; Lee, Brian; Guimaraes, Emily] Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. RP Scemama, P (reprint author), Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. EM pscemamadegialluly@partners.org NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 27 PY 2012 VL 307 IS 24 BP 2585 EP 2585 DI 10.1001/jama.2012.6539 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 964KF UT WOS:000305692600013 PM 22735414 ER PT J AU Yu, EW Finkelstein, JS AF Yu, Elaine W. Finkelstein, Joel S. TI Bone Density Screening Intervals for Osteoporosis One Size Does Not Fit All SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID FRACTURE RISK; FEMORAL-NECK; OLDER WOMEN C1 [Yu, Elaine W.; Finkelstein, Joel S.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Yu, EW (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 50 Blossom St,Thier 1051, Boston, MA 02114 USA. NR 10 TC 14 Z9 14 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 27 PY 2012 VL 307 IS 24 BP 2591 EP 2592 DI 10.1001/jama.2012.6977 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 964KF UT WOS:000305692600024 PM 22735425 ER PT J AU Bitton, A Flier, LA Jha, AK AF Bitton, Asaf Flier, Lydia A. Jha, Ashish K. TI Health Information Technology in the Era of Care Delivery Reform To What End? SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID SYSTEM C1 [Jha, Ashish K.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Bitton, Asaf; Flier, Lydia A.; Jha, Ashish K.] Brigham & Womens Hosp, Div Gen Med, Boston, MA 02115 USA. [Bitton, Asaf] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Jha, Ashish K.] VA Boston Healthcare Syst, Boston, MA USA. RP Jha, AK (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, 677 Huntington Ave, Boston, MA 02115 USA. EM ajha@hsph.harvard.edu NR 9 TC 29 Z9 29 U1 2 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 27 PY 2012 VL 307 IS 24 BP 2593 EP 2594 DI 10.1001/jama.2012.6663 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 964KF UT WOS:000305692600025 PM 22735426 ER PT J AU Xian, Y Liang, L Smith, EE Schwamm, LH Reeves, MJ Olson, DM Hernandez, AF Fonarow, GC Peterson, ED AF Xian, Ying Liang, Li Smith, Eric E. Schwamm, Lee H. Reeves, Mathew J. Olson, DaiWai M. Hernandez, Adrian F. Fonarow, Gregg C. Peterson, Eric D. TI Risks of Intracranial Hemorrhage Among Patients With Acute Ischemic Stroke Receiving Warfarin and Treated With Intravenous Tissue Plasminogen Activator SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID SYMPTOMATIC INTRACEREBRAL HEMORRHAGE; GUIDELINES-STROKE; ATRIAL-FIBRILLATION; CLINICAL-PRACTICE; THROMBOLYSIS; ALTEPLASE; THERAPY; ASSOCIATION; DABIGATRAN; ATTACK AB Context Intravenous tissue plasminogen activator (tPA) is known to improve outcomes in ischemic stroke; however, patients receiving long-term chronic warfarin therapy may face an increased risk for intracranial hemorrhage when treated with tPA. Although current guidelines endorse administering intravenous tPA to warfarin-treated patients if their international normalized ratio (INR) is 1.7 or lower, there are few data on safety of intravenous tPA in warfarin-treated patients in clinical practice. Objectives To determine the risk of symptomatic intracranial hemorrhage (sICH) among patients with ischemic stroke treated with intravenous tPA who were receiving warfarin vs those who were not and to determine this risk as a function of INR. Design, Setting, and Patients Observational study, using data from the American Heart Association Get With The Guidelines-Stroke Registry, of 23 437 patients with ischemic stroke and with INR of 1.7 or lower, treated with intravenous tPA in 1203 registry hospitals from April 2009 through June 2011. Main Outcome Measure Symptomatic intracranial hemorrhage. Secondary end points include life-threatening/serious systemic hemorrhage, any tPA complications, and in-hospital mortality. Results Overall, 1802 (7.7%) patients with stroke treated with tPA were receiving warfarin (median INR, 1.20; interquartile range [IQR], 1.07-1.40). Warfarin-treated patients were older, had more comorbid conditions, and had more severe strokes. The unadjusted sICH rate in warfarin-treated patients was higher than in non-warfarin-treated patients (5.7% vs 4.6%, P < .001), but these differences were not significantly different after adjustment for baseline clinical factors (adjusted odds ratio [OR], 1.01 [95% CI, 0.82-1.25]). Similarly, there were no significant differences between warfarin-treated and non-warfarin-treated patients for serious systemic hemorrhage (0.9% vs 0.9%; adjusted OR, 0.78 [95% CI, 0.49-1.24]), any tPA complications (10.6% vs 8.4%; adjusted OR, 1.09 [95% CI, 0.93-1.29]), or in-hospital mortality (11.4% vs 7.9%; adjusted OR, 0.94 [95% CI, 0.79-1.13]). Among warfarin-treated patients with INRs of 1.7 or lower, the degree of anticoagulation was not statistically significantly associated with sICH risk (adjusted OR, 1.10 per 0.1-unit increase in INR [95% CI, 1.00-1.20]; P = .06). Conclusion Among patients with ischemic stroke, the use of intravenous tPA among warfarin-treated patients (INR <= 1.7) was not associated with increased sICH risk compared with non-warfarin-treated patients. C1 [Xian, Ying; Liang, Li; Olson, DaiWai M.; Hernandez, Adrian F.; Peterson, Eric D.] Duke Clin Res Inst, Durham, NC 27715 USA. [Smith, Eric E.] Univ Calgary, Dept Clin Neurosci, Calgary, AB, Canada. [Schwamm, Lee H.] Massachusetts Gen Hosp, Div Neurol, Boston, MA 02114 USA. [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. RP Peterson, ED (reprint author), Duke Clin Res Inst, POB 17969, Durham, NC 27715 USA. EM peter016@mc.duke.edu RI Hernandez, Adrian F./A-7818-2016; OI Schwamm, Lee/0000-0003-0592-9145; Hernandez, Adrian F./0000-0003-3387-9616; Smith, Eric/0000-0003-3956-1668 FU American Heart Association; Johnson Johnson; Amylin; Portola; Preventis; National Institutes of Health; Eli Lilly; Janssen Pharmaceuticals; American Heart Association-Pharmaceutical Roundtable; David and Stevie Spina; Janssen Pharmaceutical Companies of Johnson Johnson; Boehringer Ingelheim; Merck; Bristol-Myers Squibb/Sanofi Pharmaceutical Partnership; AHA Pharmaceutical Roundtable FX All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Smith reported serving as a volunteer for the American Heart Association (AHA) Get With The Guidelines (GWTG) Steering Committee and serving on the advisory board for Genentech. Dr Schwamm reported serving as the chair of the AHA GWTG Steering Committee; serving as a consultant to the Massachusetts Department of Public Health; providing expert review of medical records for malpractice claims against neurologists regarding care of acute stroke; and serving as principal investigator of a phase 2 multicenter study of extended-window intravenous thrombolysis (alteplase provided at no cost to Massachusetts General Hospital). Dr Olson reported receiving a grant from the American Heart Association (Duke Clinical Research Institute serves as the statistical coordinating center for AHA GWTG). Dr Hernandez reported serving as a consultant for Johnson & Johnson, AstraZeneca, sanofi, and Corthera; receiving research grants or grants pending from Johnson & Johnson, Amylin, Portola, and Preventis; and serving as a consultant to Corthera. Dr Fonarow reported serving as a consultant to Pfizer, Merck, Schering-Plough, Bristol-Myers Squibb, and sanofi-aventis; receiving research grants or grants pending from the National Institutes of Health; receiving speakers honoraria from Pfizer, Merck, Schering-Plough, Bristol-Myers Squibb, and sanofi-aventis; and that he is an employee of the University of California, which holds a patent on retriever devices for stroke. Dr Peterson reported receiving research grants from Johnson & Johnson, Eli Lilly, and Janssen Pharmaceuticals and serving as a consultant to Boehringer Ingelheim, Johnson & Johnson, Medscape, Merck, Novartis, Ortho-McNeil-Janssen, Pfizer, Westat, the Cardiovascular Research Foundation, WebMD, and United Healthcare. No other authors reported disclosures.; This study received an award from the American Heart Association-Pharmaceutical Roundtable and from David and Stevie Spina. The Get With The Guidelines-Stroke (GWTG-Stroke) program is provided by the American Heart Association/American Stroke Association. The GWTG-Stroke Program is currently supported in part by a charitable contribution from Janssen Pharmaceutical Companies of Johnson & Johnson. GWTG-Stroke has been funded in the past through support from Boehringer Ingelheim, Merck, Bristol-Myers Squibb/Sanofi Pharmaceutical Partnership, and the AHA Pharmaceutical Roundtable. NR 34 TC 77 Z9 81 U1 1 U2 9 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 27 PY 2012 VL 307 IS 24 BP 2600 EP 2608 DI 10.1001/jama.2012.6756 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 964KF UT WOS:000305692600028 PM 22735429 ER PT J AU Metzger, ML Weinstein, HJ Hudson, MM Billett, AL Larsen, EC Friedmann, A Howard, SC Donaldson, SS Krasin, MJ Kun, LE Marcus, KJ Yock, TI Tarbell, N Billups, CA Wu, JR Link, MP AF Metzger, Monika L. Weinstein, Howard J. Hudson, Melissa M. Billett, Amy L. Larsen, Eric C. Friedmann, Alison Howard, Scott C. Donaldson, Sarah S. Krasin, Matthew J. Kun, Larry E. Marcus, Karen J. Yock, Torunn I. Tarbell, Nancy Billups, Catherine A. Wu, Jianrong Link, Michael P. TI Association Between Radiotherapy vs No Radiotherapy Based on Early Response to VAMP Chemotherapy and Survival Among Children With Favorable-Risk Hodgkin Lymphoma SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID INVOLVED-FIELD RADIOTHERAPY; PEDIATRIC-ONCOLOGY-GROUP; COMBINED-MODALITY TREATMENT; PROSPECTIVE CLINICAL-TRIAL; LONG-TERM SURVIVORS; LOW-DOSE RADIATION; STAGE-I; CHILDHOOD-CANCER; DISEASE; ADOLESCENTS AB Context More than 90% of children with favorable-risk Hodgkin lymphoma can achieve long-term survival, yet many will experience toxic effects from radiation therapy. Pediatric oncologists strive for maintaining excellent cure rates while minimizing toxic effects. Objective To evaluate the efficacy of 4 cycles of vinblastine, Adriamycin (doxorubicin), methotrexate, and prednisone(VAMP) in patients with favorable-risk Hodgkin lymphoma who achieve a complete response after 2 cycles and do not receive radiotherapy. Design, Setting, and Patients Multi-institutional, unblinded, nonrandomized single group phase 2 clinical trial to assess the need for radiotherapy based on early response to chemotherapy. Eighty-eight eligible patients with Hodgkin lymphoma stage I and II (<3 nodal sites, no B symptoms, mediastinal bulk, or extranodal extension) enrolled between March 3, 2000, and December 9, 2008. Follow-up data are current to March 12, 2012. Interventions The 47 patients who achieved a complete response after 2 cycles received no radiotherapy, and the 41 with less than a complete response were given 25.5 Gy-involved-field radiotherapy. Main Outcome Measures Two-year event-free survival was the primary outcome measure. A 2-year event-free survival of greater than 90% was desired, and 80% was considered to be unacceptably low. Results Two-year event-free survival was 90.8% (95% CI, 84.7% - 96.9%). For patients who did not require radiotherapy, it was 89.4% (95% CI, 80.8%-98.0%) compared with 92.5% (95% CI, 84.5%-100%) for those who did (P = .61). Most common acute adverse effects were neuropathic pain (2% of patients), nausea or vomiting (3% of patients), neutropenia (32% of cycles), and febrile neutropenia (2% of patients). Nine patients (10%) were hospitalized 11 times (3% of cycles) for febrile neutropenia or nonneutropenic infection. Long-term adverse effects after radiotherapy were asymptomatic compensated hypothyroidism in 9 patients (10%), osteonecrosis and moderate osteopenia in 2 patients each (2%), subclinical pulmonary dysfunction in 12 patients (14%), and asymptomatic left ventricular dysfunction in 4 patients (5%). No second malignant neoplasms were observed. Conclusions Among patients with favorable-risk Hodgkin lymphoma and a complete early response to chemotherapy, the use of limited radiotherapy resulted in a high rate of 2-year event-free survival. C1 [Metzger, Monika L.; Hudson, Melissa M.; Howard, Scott C.] St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN 38105 USA. [Krasin, Matthew J.; Kun, Larry E.] St Jude Childrens Res Hosp, Dept Radiol Sci, Memphis, TN 38105 USA. [Billups, Catherine A.; Wu, Jianrong] St Jude Childrens Res Hosp, Dept Biostat, Memphis, TN 38105 USA. [Metzger, Monika L.; Hudson, Melissa M.; Howard, Scott C.] Univ Tennessee, Hlth Sci Ctr, Memphis, TN USA. [Weinstein, Howard J.; Friedmann, Alison] Massachusetts Gen Hosp, Dept Pediat Hematol & Oncol, Boston, MA 02114 USA. [Yock, Torunn I.; Tarbell, Nancy] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Billett, Amy L.] Childrens Hosp Boston, Dept Pediat Oncol, Boston, MA USA. [Marcus, Karen J.] Childrens Hosp Boston, Dept Radiat Oncol, Boston, MA USA. [Billett, Amy L.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Marcus, Karen J.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Larsen, Eric C.] Barbara Bush Childrens Hosp, Maine Med Ctr, Portland, Dorset, England. [Donaldson, Sarah S.] Stanford Univ, Dept Radiat Oncol, Stanford, CA 94305 USA. [Link, Michael P.] Dept Pediat Hematol & Oncol, Stanford, CA USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. RP Metzger, ML (reprint author), 262 Danny Thomas Pl,MS 260, Memphis, TN 38015 USA. EM monika.metzger@stjude.org RI Howard, Scott/K-3401-2013 OI Howard, Scott/0000-0003-2244-1686 FU Seattle Genetics; Amgen; Millennium; American Society for Clinical Oncology; St Jude Children's Research Hospital; Pfizer; National Institutes of Health [CA-21765]; American Lebanese Syrian Associated Charities FX The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Metzger reported that she has received funding for an international conference unrelated to the study from Seattle Genetics, Amgen, and Millennium. Dr Kun reported that he is a board member for the National Cancer Institute Brain Malignancies steering committee. Dr Link reported that he has received funding for his institution from American Society for Clinical Oncology for his role as president, and from St Jude Children's Research Hospital for patient enrollment on this study and for his roles on the Scientific Advisory Board and Cancer Center Advisory Board. Dr Link reported that he receives support from Seattle Genetics for clinical trial participation (unrelated to this study) and Pfizer (unrelated to this study). No other financial disclosures were reported.; Study supported by grant CA-21765 from the National Institutes of Health Cancer Support Core Grant and the American Lebanese Syrian Associated Charities. NR 37 TC 29 Z9 31 U1 0 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 27 PY 2012 VL 307 IS 24 BP 2609 EP 2616 DI 10.1001/jama.2012.5847 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 964KF UT WOS:000305692600029 PM 22735430 ER PT J AU Olin, JW Froehlich, J Gu, XK Bacharach, JM Eagle, K Gray, BH Jaff, MR Kim, ESH Mace, P Matsumoto, AH McBane, RD Kline-Rogers, E White, CJ Gornik, HL AF Olin, Jeffrey W. Froehlich, James Gu, Xiaokui Bacharach, J. Michael Eagle, Kim Gray, Bruce H. Jaff, Michael R. Kim, Esther S. H. Mace, Pam Matsumoto, Alan H. McBane, Robert D. Kline-Rogers, Eva White, Christopher J. Gornik, Heather L. TI The United States Registry for Fibromuscular Dysplasia Results in the First 447 Patients SO CIRCULATION LA English DT Article DE aneurysm; dissection; fibromuscular dysplasia; hypertension; renal; stroke ID RENAL ARTERIAL DISEASE; RENOVASCULAR HYPERTENSION; FIBRODYSPLASIA; ANGIOPLASTY; CLASSIFICATION; ANEURYSMS; FEATURES; THERAPY; DONORS; BRAIN AB Background-Fibromuscular dysplasia (FMD), a noninflammatory disease of medium-size arteries, may lead to stenosis, occlusion, dissection, and/or aneurysm. There has been little progress in understanding the epidemiology, pathogenesis, and outcomes since its first description in 1938. Methods and Results-Clinical features, presenting symptoms, and vascular events are reviewed for the first 447 patients enrolled in a national FMD registry from 9 US sites. Vascular beds were imaged selectively based on clinical presentation and local practice. The majority of patients were female (91%) with a mean age at diagnosis of 51.9 (SD 13.4 years; range, 5-83 years). Hypertension, headache, and pulsatile tinnitus were the most common presenting symptoms of the disease. Self-reported family history of stroke (53.5%), aneurysm (23.5%), and sudden death (19.8%) were common, but FMD in first-or second-degree relatives was reported only in 7.3%. FMD was identified in the renal artery in 294 patients, extracranial carotid arteries in 251 patients, and vertebral arteries in 82 patients. A past or presenting history of vascular events were common: 19.2% of patients had a transient ischemic attack or stroke, 19.7% had experienced arterial dissection(s), and 17% of patients had an aneurysm(s). The most frequent indications for therapy were hypertension, aneurysm, and dissection. Conclusions-In this registry, FMD occurred primarily in middle-aged women, although it presents across the lifespan. Cerebrovascular FMD occurred as frequently as renal FMD. Although a significant proportion of FMD patients may present with a serious vascular event, many present with nonspecific symptoms and a subsequent delay in diagnosis. (Circulation. 2012;125:3182-3190.) C1 [Olin, Jeffrey W.] Mt Sinai Sch Med, Zena & Michael A Wiener Cardiovasc Inst, New York, NY 10029 USA. [Froehlich, James; Gu, Xiaokui; Eagle, Kim; Kline-Rogers, Eva] Univ Michigan, Ann Arbor, MI 48109 USA. [Bacharach, J. Michael] N Cent Heart, Sioux Falls, SD USA. [Gray, Bruce H.] Vasc Hlth Alliance, Greenville, SC USA. [Jaff, Michael R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kim, Esther S. H.; Gornik, Heather L.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Mace, Pam] Fibromuscular Dysplasia Soc Amer, Rocky River, OH USA. [Matsumoto, Alan H.] Univ Virginia, Charlottesville, VA USA. [McBane, Robert D.] Mayo Clin, Rochester, MN USA. [White, Christopher J.] Ochsner Clin Fdn, New Orleans, LA USA. RP Olin, JW (reprint author), Mt Sinai Sch Med, Zena & Michael A Wiener Cardiovasc Inst, 1 Gustave L Levy Pl,Box 1033, New York, NY 10029 USA. EM jeffrey.olin@mountsinai.org RI White, Christopher/J-6686-2012 OI White, Christopher/0000-0001-8618-7539 FU Fibromuscular Dysplasia Study of America; Fibromuscular Dysplasia Society of America FX This work was supported by the Fibromuscular Dysplasia Study of America, a nonprofit organization.; The US FMD Patient Registry gratefully acknowledges the collaborative efforts of its clinical centers and coinvestigators, the support of the Fibromuscular Dysplasia Society of America, and the support and motivation provided by our community of FMD patients. NR 43 TC 108 Z9 117 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 26 PY 2012 VL 125 IS 25 BP 3182 EP + DI 10.1161/CIRCULATIONAHA.112.091223 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 981OF UT WOS:000306977000025 PM 22615343 ER PT J AU Palacios, IF AF Palacios, Igor F. TI Transcatheter Aortic Valve Implantation The Interventionist Vision SO CIRCULATION LA English DT Article DE cardiovascular surgical procedures; clinical trials as topic; percutaneous aortic valve replacement ID INOPERABLE PATIENTS; REPLACEMENT; STENOSIS; VALVULOPLASTY; PROSTHESIS C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Palacios, IF (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Bigelow 826,Fruit St, Boston, MA 02114 USA. NR 15 TC 4 Z9 4 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 26 PY 2012 VL 125 IS 25 BP 3233 EP 3236 DI 10.1161/CIRCULATIONAHA.112.093104 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 981OF UT WOS:000306977000031 PM 22733338 ER PT J AU Jo, H Mondal, S Tan, DW Nagata, E Takizawa, S Sharma, AK Hou, QM Shanmugasundaram, K Prasad, A Tung, JK Tejeda, AO Man, HY Rigby, AC Luo, HBR AF Jo, Hakryul Mondal, Subhanjan Tan, Dewar Nagata, Eiichiro Takizawa, Shunya Sharma, Alok K. Hou, Qingming Shanmugasundaram, Kumaran Prasad, Amit Tung, Joe K. Tejeda, Alexander O. Man, Hengye Rigby, Alan C. Luo, Hongbo R. TI Small molecule-induced cytosolic activation of protein kinase Akt rescues ischemia-elicited neuronal death SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE drug discovery; cell signaling ID PLECKSTRIN HOMOLOGY DOMAIN; CELL-DEATH; SIGNALING PATHWAY; APOPTOSIS; INHIBITOR; SURVIVAL; PHOSPHATIDYLINOSITOL-3,4,5-TRISPHOSPHATE; IDENTIFICATION; DISORDERS; TOLERANCE AB Elevating Akt activation is an obvious clinical strategy to prevent progressive neuronal death in neurological diseases. However, this endeavor has been hindered because of the lack of specific Akt activators. Here, from a cell-based high-throughput chemical genetic screening, we identified a small molecule SC79 that inhibits Akt membrane translocation, but paradoxically activates Akt in the cytosol. SC79 specifically binds to the PH domain of Akt. SC79-bound Akt adopts a conformation favorable for phosphorylation by upstream protein kinases. In a hippocampal neuronal culture system and a mouse model for ischemic stroke, the cytosolic activation of Akt by SC79 is sufficient to recapitulate the primary cellular function of Akt signaling, resulting in augmented neuronal survival. Thus, SC79 is a unique specific Akt activator that may be used to enhance Akt activity in various physiological and pathological conditions. C1 [Jo, Hakryul; Mondal, Subhanjan; Tan, Dewar; Prasad, Amit; Tung, Joe K.; Tejeda, Alexander O.; Luo, Hongbo R.] Harvard Univ, Sch Med, Dept Pathol, Dana Farber Harvard Canc Ctr, Boston, MA 02115 USA. [Jo, Hakryul; Mondal, Subhanjan; Tan, Dewar; Prasad, Amit; Tung, Joe K.; Tejeda, Alexander O.; Luo, Hongbo R.] Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA. [Nagata, Eiichiro; Takizawa, Shunya] Tokai Univ, Sch Med, Dept Neurol, Isehara, Kanagawa 2591193, Japan. [Sharma, Alok K.; Shanmugasundaram, Kumaran; Rigby, Alan C.] Harvard Univ, Sch Med, Dept Med, Beth Israel Deaconess Med Ctr,Div Mol & Vasc Med, Boston, MA 02115 USA. [Hou, Qingming; Man, Hengye] Boston Univ, Dept Biol, Boston, MA 02215 USA. RP Luo, HBR (reprint author), Harvard Univ, Sch Med, Dept Pathol, Dana Farber Harvard Canc Ctr, Boston, MA 02115 USA. EM hongbo.luo@childrens.harvard.edu FU National Institutes of Health [HL085100, AI076471, HL092020, GM076084] FX The authors thank Solomon H. Snyder, Sangwon Kim, and Lewis C. Cantley for very helpful comments and suggestions on the manuscript; Leslie Silberstein, John Manis, and Li Chai for helpful discussions; Natsuko Fujii, Yusuke Moriya, Yoko Takahari for help with middle cerebral artery occlusion model; and Bo Chen and Kai Yao for intraocular injections. H. L. is supported by National Institutes of Health Grants HL085100, AI076471, HL092020, and GM076084. NR 35 TC 47 Z9 47 U1 4 U2 13 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 26 PY 2012 VL 109 IS 26 BP 10581 EP 10586 DI 10.1073/pnas.1202810109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 972QE UT WOS:000306291400095 PM 22689977 ER PT J AU Kim, Y Li, ZM Apetri, M Luo, BB Settleman, JE Anderson, KS AF Kim, Youngjoo Li, Zhimin Apetri, Mihaela Luo, BeiBei Settleman, Jeffrey E. Anderson, Karen S. TI Temporal Resolution of Autophosphorylation for Normal and Oncogenic Forms of EGFR and Differential Effects of Gefitinib SO BIOCHEMISTRY LA English DT Article ID GROWTH-FACTOR RECEPTOR; SITE-SPECIFIC PHOSPHORYLATION; CELL LUNG-CANCER; KINASE DOMAIN; TYROSINE KINASE; INCREASED SENSITIVITY; ACTIVATION; MUTATIONS; INHIBITOR; MECHANISM AB Epidermal growth factor receptor (EGFR) is a member of the ErbB family of receptor tyrosine kinases (RTK). EGFR overexpression or mutation in many different forms of cancers has highlighted its role as an important therapeutic target. Gefitinib, the first small molecule inhibitor of EGFR kinase function to be approved for the treatment of nonsmall cell lung cancer (NSCLC) by the FDA, demonstrates clinical activity primarily in patients with tumors that harbor somatic kinase domain mutations in EGFR. Here, we compare wild-type EGFR autophosphorylation kinetics to the L834R (also called L858R) EGFR form, one of the most common mutations in lung cancer patients. Using rapid chemical quench, time-resolved electrospray mass spectrometry (ESI-MS), and Western blot analyses, we examined the order of autophosphorylation in wild-type (WT) and L834R EGFR and the effect of gefitinib (Iressa) on the phosphorylation of individual tyrosines. These studies establish that there is a temporal order of autophosphorylation of key tyrosines involved in downstream signaling for WT EGFR and a loss of order for the oncogenic L834R mutant. These studies also reveal unique signature patterns of drug sensitivity for inhibition of tyrosine autophosphorylation by gefitinib: distinct for WT and oncogenic L834R mutant forms of EGFR. Fluorescence studies show that for WT EGFR the binding affinity for gefitinib is weaker for the phosphorylated protein while for the oncogenic mutant, L834R EGFR, the binding affinity of gefitinib is substantially enhanced and likely contributes to the efficacy observed clinically. This mechanistic information is important in understanding the molecular details underpinning clinical observations as well as to aid in the design of more potent and selective EGFR inhibitors. C1 [Kim, Youngjoo; Li, Zhimin; Apetri, Mihaela; Luo, BeiBei; Anderson, Karen S.] Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06510 USA. [Settleman, Jeffrey E.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Settleman, Jeffrey E.] Massachusetts Gen Hosp, Ctr Mol Therapeut, Ctr Canc, Charlestown, MA 02129 USA. RP Anderson, KS (reprint author), Yale Univ, Sch Med, Dept Pharmacol, 333 Cedar St, New Haven, CT 06510 USA. EM karen.anderson@yale.edu RI Li, Zhimin/A-9671-2011 OI Li, Zhimin/0000-0001-7036-9282 FU National Institute of Health [NCI CA127580, CA125284] FX This research was supported by National Institute of Health grants NCI CA127580 and CA125284 to K.S.A. NR 45 TC 14 Z9 15 U1 1 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 EI 1943-295X J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 26 PY 2012 VL 51 IS 25 BP 5212 EP 5222 DI 10.1021/bi300476v PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 963YV UT WOS:000305661800022 PM 22657099 ER PT J AU Pietrzak, RH Tracy, M Galea, S Kilpatrick, DG Ruggiero, KJ Hamblen, JL Southwick, SM Norris, FH AF Pietrzak, Robert H. Tracy, Melissa Galea, Sandro Kilpatrick, Dean G. Ruggiero, Kenneth J. Hamblen, Jessica L. Southwick, Steven M. Norris, Fran H. TI Resilience in the Face of Disaster: Prevalence and Longitudinal Course of Mental Disorders following Hurricane Ike SO PLOS ONE LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; NEUROPSYCHIATRIC INTERVIEW MINI; NATIONAL COMORBIDITY SURVEY; INTIMATE PARTNER VIOLENCE; MASS TRAUMATIC EVENT; IV ALCOHOL-ABUSE; DSM-IV; PTSD CHECKLIST; PSYCHOLOGICAL RESILIENCE; PSYCHOMETRIC PROPERTIES AB Objectives: Natural disasters may increase risk for a broad range of psychiatric disorders, both in the short-and in the medium-term. We sought to determine the prevalence and longitudinal course of posttraumatic stress disorder (PTSD), generalized anxiety disorder (GAD), panic disorder (PD), depression, and suicidality in the first 18 months after Hurricane Ike. Methods: Six hundred fifty-eight adults representative of Galveston and Chambers Counties, Texas participated in a random, population-based survey. The initial assessment was conducted 2 to 5 months after Hurricane Ike struck Galveston Bay on September 13, 2008. Follow-up assessments were conducted at 5 to 9 and 14 to 18 months after Hurricane Ike. Results: Past-month prevalence of any mental disorder (20.6% to 10.9%) and hurricane-related PTSD (6.9% to 2.5%) decreased over time. Past-month prevalence of PTSD related to a non-disaster traumatic event (5.8% to 7.1%), GAD (3.1% to 1.8%), PD (0.8% to 0.7%), depression (5.0% to 5.6%), and suicidality (2.6% to 4.2%) remained relatively stable over time. Conclusions: PTSD, both due to the hurricane and due to other traumatic events, was the most prevalent psychiatric disorder 2 to 5 months after Hurricane Ike. Prevalence of psychiatric disorders declined rapidly over time, suggesting that the vast majority of individuals exposed to this natural disaster 'bounced back' and were resilient to long-term mental health consequences of this large-scale traumatic event. C1 [Pietrzak, Robert H.; Southwick, Steven M.] Vet Affairs Connecticut Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, West Haven, CT USA. [Pietrzak, Robert H.; Southwick, Steven M.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Pietrzak, Robert H.; Tracy, Melissa; Galea, Sandro; Kilpatrick, Dean G.; Ruggiero, Kenneth J.; Hamblen, Jessica L.; Southwick, Steven M.; Norris, Fran H.] Natl Ctr Disaster Mental Hlth Res, White River Jct, VT USA. [Tracy, Melissa; Galea, Sandro] Columbia Univ, Sch Publ Hlth, Dept Epidemiol, New York, NY USA. [Kilpatrick, Dean G.; Ruggiero, Kenneth J.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Kilpatrick, Dean G.; Ruggiero, Kenneth J.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Hamblen, Jessica L.; Norris, Fran H.] White River Junct Vet Affairs Med Ctr, Natl Ctr Posttraumat Stress Disorder, White River Jct, VT USA. [Norris, Fran H.] Geisel Sch Med Dartmouth, Hanover, NH USA. RP Pietrzak, RH (reprint author), Vet Affairs Connecticut Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, West Haven, CT USA. EM robert.pietrzak@yale.edu FU National Center for Disaster Mental Health Research (National Institute of Mental Health) [5 P60 MH082598]; National Center for Posttraumatic Stress Disorder; Claude D. Pepper Older Americans Independence Center at Yale University School of Medicine (NIA) [P30AG21342] FX This research was supported by the National Center for Disaster Mental Health Research (National Institute of Mental Health Grant 5 P60 MH082598), Fran H. Norris, Center Director, Sandro Galea, Research Director. Preparation of this report was supported in part by the National Center for Posttraumatic Stress Disorder and a Research Career Development Award to Dr. Pietrzak from the Claude D. Pepper Older Americans Independence Center at Yale University School of Medicine (NIA Grant P30AG21342). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 61 TC 23 Z9 23 U1 8 U2 26 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 26 PY 2012 VL 7 IS 6 AR e38964 DI 10.1371/journal.pone.0038964 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 966AK UT WOS:000305808700014 PM 22761716 ER PT J AU Siedner, MJ Lankowski, A Haberer, JE Kembabazi, A Emenyonu, N Tsai, AC Muzoora, C Geng, E Martin, JN Bangsberg, DR AF Siedner, Mark J. Lankowski, Alexander Haberer, Jessica E. Kembabazi, Annet Emenyonu, Nneka Tsai, Alexander C. Muzoora, Conrad Geng, Elvin Martin, Jeffrey N. Bangsberg, David R. TI Rethinking the "Pre" in Pre-Therapy Counseling: No Benefit of Additional Visits Prior to Therapy on Adherence or Viremia in Ugandans Initiating ARVs SO PLOS ONE LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; FOLLOW-UP; SOUTH-AFRICA; HIV CARE; PROGRAMS; BARRIERS; EFFICACY; DURBAN; ART; INTERVENTION AB Background: Many guidelines recommend adherence counseling prior to initiating antiretrovirals (ARVs), however the additional benefit of pre-therapy counseling visits on early adherence is not known. We sought to assess for a benefit of adherence counseling visits prior to ARV initiation versus adherence counseling during the early treatment period. Methods: We performed a secondary analysis of data from a prospective cohort of HIV-infected patients in Mbarara, Uganda. Adults were enrolled upon initiation of ARVs. Our primary exposure of interest was ARV adherence counseling prior to initiating therapy (versus concurrent with initiation of therapy). Our outcomes of interest were: 1) average adherence >90% in first three months; 2) absence of treatment interruptions >72 hours in first three months; and 3) Viral load >400 copies/ml at the three month visit. We fit univariable and multivariable regression models, adjusted for predictors of ARV adherence, to estimate the association between additional pre-therapy counseling visits and our outcomes. Results: 300 participants had records of counseling, of whom 231 (77%) completed visits prior to initiation of ARVs and 69 (23%) on or shortly after initiation. Median age was 33, 71% were female, and median CD4 was 133 cell/ml. Median 90-day adherence was 95%. Participants who completed pre-therapy counseling visits had longer delays from ARV eligibility to initiation (median 49 vs 14 days, p<0.01). In multivariable analyses, completing adherence counseling prior to ARV initiation was not associated with average adherence >90% (AOR 0.8, 95% CI 0.4-1.5), absence of treatment gaps (AOR 0.7, 95% CI 0.2-1.9), or HIV viremia (AOR 1.1, 95% CI 0.4-3.1). Conclusions: Completion of adherence counseling visits prior to ARV therapy was not associated with higher adherence in this cohort of HIV-infected patients in Uganda. Because mortality and loss-to-follow-up remain high in the pre-ARV period, policy makers should reconsider whether counseling can be delivered with ARV initiation, especially in patients with advanced disease. C1 [Siedner, Mark J.; Lankowski, Alexander; Haberer, Jessica E.; Bangsberg, David R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. [Lankowski, Alexander; Kembabazi, Annet; Emenyonu, Nneka; Muzoora, Conrad] Mbarara Univ Sci & Technol, Mbarara, Uganda. [Tsai, Alexander C.; Bangsberg, David R.] Harvard Univ, Robert Wood Johnson Hlth & Soc Scholars Program, Boston, MA 02115 USA. [Geng, Elvin; Martin, Jeffrey N.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Bangsberg, David R.] Massahusetts Gen Hosp, Ctr Global Hlth, Boston, MA USA. [Bangsberg, David R.] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Boston, MA USA. RP Siedner, MJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. EM msiedner@partners.org OI Tsai, Alexander/0000-0001-6397-7917 FU National Institutes of Health [R01 MH054907, K24 MH87227, P30 AI027793]; Mark and Lisa Schwartz Family Foundation; Robert Wood Johnson Health and Society Scholars Program; Doris Duke Charitable Foundation Clinical Research Fellowship at Harvard Medical School FX The study was funded by the National Institutes of Health (R01 MH054907, K24 MH87227, and P30 AI027793), and the Mark and Lisa Schwartz Family Foundation. Dr. Tsai received salary support from the Robert Wood Johnson Health and Society Scholars Program. Dr. Siedner received additional support from the Harvard Institute for Global Health and from the Fogarty International Clinical Research Scholars and Fellows Program at Vanderbilt University (R24 TW007988) and the American Relief and Recovery Act. Mr. Lankowski received support from the Doris Duke Charitable Foundation Clinical Research Fellowship at Harvard Medical School. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 37 TC 21 Z9 21 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 26 PY 2012 VL 7 IS 6 AR e39894 DI 10.1371/journal.pone.0039894 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 966AK UT WOS:000305808700053 PM 22761924 ER PT J AU Tanaka, M Mroz, P Dai, TH Huang, LY Morimoto, Y Kinoshita, M Yoshihara, Y Nemoto, K Shinomiya, N Seki, S Hamblin, MR AF Tanaka, Masamitsu Mroz, Pawel Dai, Tianhong Huang, Liyi Morimoto, Yuji Kinoshita, Manabu Yoshihara, Yasuo Nemoto, Koichi Shinomiya, Nariyoshi Seki, Suhji Hamblin, Michael R. TI Photodynamic Therapy Can Induce a Protective Innate Immune Response against Murine Bacterial Arthritis via Neutrophil Accumulation SO PLOS ONE LA English DT Article ID RESISTANT STAPHYLOCOCCUS-AUREUS; KAPPA-B ACTIVATION; IN-VIVO; ANTITUMOR IMMUNITY; CHOROIDAL NEOVASCULARIZATION; BIOFILM INFECTIONS; ENDOTHELIAL-CELLS; MRSA ARTHRITIS; SOLID TUMORS; MICE AB Background: Local microbial infections induced by multiple-drug-resistant bacteria in the orthopedic field can be intractable, therefore development of new therapeutic modalities is needed. Photodynamic therapy (PDT) is a promising alternative modality to antibiotics for intractable microbial infections, and we recently reported that PDT has the potential to accumulate neutrophils into the infected site which leads to resolution of the infection. PDT for cancer has long been known to be able to stimulate the innate and adaptive arms of the immune system. Methodology/Principal Findings: In the present study, a murine methicillin-resistant Staphylococcus aureus (MRSA) arthritis model using bioluminescent MRSA and polystyrene microparticles was established, and both the therapeutic (Th-PDT) and preventive (Pre-PDT) effects of PDT using methylene blue as photosensitizer were examined. Although Th-PDT could not demonstrate direct bacterial killing, neutrophils were accumulated into the infectious joint space after PDT and MRSA arthritis was reduced. With the preconditioning Pre-PDT regimen, neutrophils were quickly accumulated into the joint immediately after bacterial inoculation and bacterial growth was suppressed and the establishment of infection was inhibited. Conclusions/Significance: This is the first demonstration of a protective innate immune response against a bacterial pathogen produced by PDT. C1 [Tanaka, Masamitsu; Mroz, Pawel; Dai, Tianhong; Huang, Liyi; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Tanaka, Masamitsu; Mroz, Pawel; Dai, Tianhong; Huang, Liyi; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Tanaka, Masamitsu; Yoshihara, Yasuo; Nemoto, Koichi] Natl Def Med Coll, Dept Orthoped Surg, Tokorozawa, Saitama 359, Japan. [Morimoto, Yuji; Shinomiya, Nariyoshi] Natl Def Med Coll, Dept Integrated Physiol & Bionano Med, Tokorozawa, Saitama 359, Japan. [Kinoshita, Manabu; Seki, Suhji] Natl Def Med Coll, Dept Immunol & Microbiol, Tokorozawa, Saitama 359, Japan. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Tanaka, M (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM moyan@ndmc.ac.jp; hamblin@helix.mgh.harvard.edu OI Hamblin, Michael/0000-0001-6431-4605 FU Ministry of Education, Culture, Sports, Science and Technology of Japan [23659628]; U.S. National Institutes of Health [R01AI050875]; Airlift Research Foundation Extremity Trauma Research Grant [109421] FX This work was supported by a Grant-in-Aid for Challenging Exploratory Research (23659628) from the Ministry of Education, Culture, Sports, Science and Technology of Japan to Yuji Morimoto. Liyi Huang and Michael R. Hamblin were supported by U.S. National Institutes of Health grant R01AI050875 to Michael R. Hamblin, and Tianhong Dai by an Airlift Research Foundation Extremity Trauma Research Grant (grant 109421). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 52 TC 15 Z9 15 U1 1 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 26 PY 2012 VL 7 IS 6 AR e39823 DI 10.1371/journal.pone.0039823 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 966AK UT WOS:000305808700049 PM 22761911 ER PT J AU Dohgu, S Ryerse, JS Robinson, SM Banks, WA AF Dohgu, Shinya Ryerse, Jan S. Robinson, Sandra M. Banks, William A. TI Human Immunodeficiency Virus-1 Uses the Mannose-6-Phosphate Receptor to Cross the Blood-Brain Barrier SO PLOS ONE LA English DT Article ID MANNOSE 6-PHOSPHATE RECEPTOR; ENVELOPE GLYCOPROTEIN GP120; LYSOSOMAL-ENZYME; ADSORPTIVE ENDOCYTOSIS; MEDIATED TRANSPORT; ENDOTHELIAL-CELLS; SURFACE-PROTEINS; HIV-1 GP120; RAT-BRAIN; MOUSE AB HIV-1 circulates both as free virus and within immune cells, with the level of free virus being predictive of clinical course. Both forms of HIV-1 cross the blood-brain barrier (BBB) and much progress has been made in understanding the mechanisms by which infected immune cells cross the blood-brain barrier BBB. How HIV-1 as free virus crosses the BBB is less clear as brain endothelial cells are CD4 and galactosylceramide negative. Here, we found that HIV-1 can use the mannose-6 phosphate receptor (M6PR) to cross the BBB. Brain perfusion studies showed that HIV-1 crossed the BBB of all brain regions consistent with the uniform distribution of M6PR. Ultrastructural studies showed HIV-1 crossed by a transcytotic pathway consistent with transport by M6PR. An in vitro model of the BBB was used to show that transport of HIV-1 was inhibited by mannose, mannan, and mannose-6 phosphate and that enzymatic removal of high mannose oligosaccharide residues from HIV-1 reduced transport. Wheatgerm agglutinin and protamine sulfate, substances known to greatly increase transcytosis of HIV-1 across the BBB in vivo, were shown to be active in the in vitro model and to act through a mannose-dependent mechanism. Transport was also cAMP and calcium-dependent, the latter suggesting that the cation-dependent member of the M6PR family mediates HIV-1 transport across the BBB. We conclude that M6PR is an important receptor used by HIV-1 to cross the BBB. C1 [Dohgu, Shinya] Fukuoka Univ, Fac Pharmaceut Sci, Dept Pharmaceut Care & Hlth Sci, Fukuoka 81401, Japan. [Ryerse, Jan S.] St Louis Univ, Hlth Sci Ctr, Dept Pathol, St Louis, MO 63103 USA. [Robinson, Sandra M.] St Louis Univ, Sch Med, Div Geriatr Med, Dept Internal Med, St Louis, MO 63104 USA. [Banks, William A.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Banks, William A.] Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA USA. RP Dohgu, S (reprint author), Fukuoka Univ, Fac Pharmaceut Sci, Dept Pharmaceut Care & Hlth Sci, 8-19-1 Nanakuma, Fukuoka 81401, Japan. EM wabanks1@u.washington.edu FU Veterans Affairs merit review; National Institutes of Health [RO-1 AG029839] FX The funders were Veterans Affairs merit review (http://www.research.va.gov/programs/csrd/merit_review.cfm) and National Institutes of Health RO-1 AG029839. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 49 TC 14 Z9 14 U1 2 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 25 PY 2012 VL 7 IS 6 AR e39565 DI 10.1371/journal.pone.0039565 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 965QG UT WOS:000305781700049 PM 22761827 ER PT J AU Staropoli, JF Xin, WN Barone, R Cotman, SL Sims, KB AF Staropoli, John F. Xin, Winnie Barone, Rosemary Cotman, Susan L. Sims, Katherine B. TI An atypical case of neuronal ceroid lipofuscinosis with co-inheritance of a variably penetrant POLG1 mutation SO BMC MEDICAL GENETICS LA English DT Article DE Neuronal ceroid lipofuscinosis; CLN5; POLG1; mtDNA depletion; Oxidative phosphorylation ID MITOCHONDRIAL-DNA POLYMERASE; BATTEN-DISEASE; MODEL; GENE; MICE; NCL; PARKINSONISM; DELETIONS; JUVENILE; CELLS AB Background: The neuronal ceroid lipofuscinoses (NCLs, or Batten disease) comprise the most common Mendelian form of childhood-onset neurodegeneration, but the functions of the known underlying gene products remain poorly understood. The clinical heterogeneity of these disorders may shed light on genetic interactors that modify disease onset and progression. Case presentation: We describe a proband with congenital hypotonia and an atypical form of infantile-onset, biopsy-proven NCL. Pathologic and molecular work-up of this patient identified CLN5 mutations as well as a mutation-previously described as incompletely penetrant or a variant of unknown significance-in POLG1, a nuclear gene essential for maintenance of mitochondrial DNA (mtDNA) copy number. The congenital presentation of this patient is far earlier than that described for either CLN5 patients or affected carriers of the POLG1 variant (c.1550 G>T, p.Gly517Val). Assessment of relative mtDNA copy number and mitochondrial membrane potential in the proband and control subjects suggested a pathogenic effect of the POLG1 change as well as a possible functional interaction with CLN5 mutations. Conclusions: These findings suggest that an incompletely penetrant variant in POLG1 may modify the clinical phenotype in a case of CLN5 and are consistent with emerging evidence of interactions between NCL-related genes and mitochondrial physiology. C1 [Staropoli, John F.; Xin, Winnie; Cotman, Susan L.; Sims, Katherine B.] Massachusetts Gen Hosp, Ctr Human Genet Res, Mol Neurogenet Unit, Boston, MA 02114 USA. [Staropoli, John F.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Staropoli, John F.; Xin, Winnie; Barone, Rosemary; Sims, Katherine B.] Massachusetts Gen Hosp, Ctr Human Genet Res, Neurogenet DNA Diagnost Lab, Boston, MA 02114 USA. RP Cotman, SL (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Mol Neurogenet Unit, 185 Cambridge St, Boston, MA 02114 USA. EM cotman@helix.mgh.harvard.edu; ksims@partners.org FU Batten Disease Support and Research Association (BDSRA); National Institute of Neurological Disorders Stroke [R01NS073813]; Massachusetts General Hospital ECOR Tosteson award FX We thank the laboratory of Dr. Charles Lee in the Cytogenetics Core of the Dana Farber-Harvard Cancer Center (P30 CA006516) for the design of the tiling microarray. GM8330 fibroblasts were a kind gift from Dr. Stephen Haggarty. We thank members of Dr. Vamsi Mootha's laboratory for helpful discussion. We thank Yi Cao, Xin Feng, and Scott Coppel for expert technical support. This work was supported by grants from the Batten Disease Support and Research Association (BDSRA) to JFS and SLC and the National Institute of Neurological Disorders & Stroke to SLC (R01NS073813), and by a Massachusetts General Hospital ECOR Tosteson award to JFS. No funding source had a role in the study design; in the collection, analysis and interpretation data; in the writing of the report; or in the decision to submit the paper for publication. NR 30 TC 5 Z9 5 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2350 J9 BMC MED GENET JI BMC Med. Genet. PD JUN 24 PY 2012 VL 13 AR 50 DI 10.1186/1471-2350-13-50 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 009WV UT WOS:000309057000001 PM 22727047 ER PT J AU Derks, EM Vorstman, JAS Ripke, S Kahn, RS Ophoff, RA AF Derks, Eske M. Vorstman, Jacob A. S. Ripke, Stephan Kahn, Rene S. Ophoff, Roel A. CA Schizophrenia Psychiat Genomic Con TI Investigation of the Genetic Association between Quantitative Measures of Psychosis and Schizophrenia: A Polygenic Risk Score Analysis SO PLOS ONE LA English DT Article ID SYMPTOM DIMENSIONS; METAANALYSIS; POPULATION; CONTINUUM; DISORDER; COMMON AB The presence of subclinical levels of psychosis in the general population may imply that schizophrenia is the extreme expression of more or less continuously distributed traits in the population. In a previous study, we identified five quantitative measures of schizophrenia (positive, negative, disorganisation, mania, and depression scores). The aim of this study is to examine the association between a direct measure of genetic risk of schizophrenia and the five quantitative measures of psychosis. Estimates of the log of the odds ratios of case/control allelic association tests were obtained from the Psychiatric GWAS Consortium (PGC) (minus our sample) which included genome-wide genotype data of 8,690 schizophrenia cases and 11,831 controls. These data were used to calculate genetic risk scores in 314 schizophrenia cases and 148 controls from the Netherlands for whom genotype data and quantitative symptom scores were available. The genetic risk score of schizophrenia was significantly associated with case-control status (p<0.0001). In the case-control sample, the five psychosis dimensions were found to be significantly associated with genetic risk scores; the correlations ranged between. 15 and. 27 (all p<.001). However, these correlations were not significant in schizophrenia cases or controls separately. While this study confirms the presence of a genetic risk for schizophrenia as categorical diagnostic trait, we did not find evidence for the genetic risk underlying quantitative schizophrenia symptom dimensions. This does not necessarily imply that a genetic basis is nonexistent, but does suggest that it is distinct from the polygenic risk score for schizophrenia. C1 [Derks, Eske M.; Vorstman, Jacob A. S.; Kahn, Rene S.; Ophoff, Roel A.] Univ Med Ctr Utrecht, Rudolf Magnus Inst Neurosci, Dept Psychiat, Utrecht, Netherlands. [Derks, Eske M.] Univ Amsterdam, Acad Med Ctr, Dept Psychiat, NL-1105 AZ Amsterdam, Netherlands. [Ripke, Stephan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Ophoff, Roel A.] UCLA Ctr Neurobehav Genet, Semel Inst Neurosci & Human Behav, Los Angeles, CA USA. [Ophoff, Roel A.] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands. RP Derks, EM (reprint author), Univ Med Ctr Utrecht, Rudolf Magnus Inst Neurosci, Dept Psychiat, Utrecht, Netherlands. EM e.m.derks@amc.uva.nl RI Ruderfer, Douglas/M-5795-2016; McQuillin, Andrew/C-1623-2008; Derks, Eske/A-1652-2017; Cichon, Sven/H-8803-2013; Cichon, Sven/B-9618-2014; Myin-Germeys, Inez /L-5106-2014; Hansen, Thomas/O-5965-2014; Mattheisen, Manuel/B-4949-2012; Melle, Ingrid /B-4858-2011; OI Ruderfer, Douglas/0000-0002-2365-386X; McQuillin, Andrew/0000-0003-1567-2240; Derks, Eske/0000-0002-6292-6883; Cichon, Sven/0000-0002-9475-086X; Cichon, Sven/0000-0002-9475-086X; Hansen, Thomas/0000-0001-6703-7762; Mattheisen, Manuel/0000-0002-8442-493X; Melle, Ingrid /0000-0002-9783-548X; Bergen, Sarah/0000-0002-5888-0034; Zammit, Stanley/0000-0002-2647-9211; Myin-Germeys, Inez/0000-0002-3731-4930; lichtenstein, paul/0000-0003-3037-5287; Bruggeman, Richard/0000-0002-3238-8471; Agartz, Ingrid/0000-0002-9839-5391; Nothen, Markus/0000-0002-8770-2464; Andreassen, Ole A./0000-0002-4461-3568 FU Netherlands Scientific Organization (NWO) [451-080-010, 480-05-003]; Eli Lilly; Janssen Pharmaceutica; GlaxoSmithKline; Bristol-Myers Squibb; AstraZeneca Pharmaceuticals; Pfizer; Forest Pharmaceuticals; Novartis; Solvay; Generation Scotland; Genetics Health Initiative; Organon; Foundation for the National Institutes of Health; Shire; Forest; H. Lundbeck A/S; Eli Lilly Company; Merck; Bristol-Meyers Squibb; PGxHealth (a division of Clinical Data, Inc.); Roche Diagnostics; Vanda Pharmaceuticals; Golden Helix, Inc.; InforMed Insights; Johnson Johnson; Schering-Plough; Hospira (Mayne); AstraZeneca; Hospira; Janssen Cilag FX Over 40 United States National Institutes of Health grants and similar numbers of government grants from other countries, along with substantial private and foundation support, enabled this work. We greatly appreciate the sustained efforts of T. Lehner (National Institute of Mental Health) on behalf of the Schizophrenia Psychiatric Genome-Wide Association Study (GWAS) Consortium (PGC). Dr. E. M. Derks is supported by the Netherlands Scientific Organization (NWO; project number 451-080-010). Statistical analyses were carried out on the Genetic Cluster Computer (http://www.geneticcluster.org) which is financially supported by the Netherlands Scientific Organization (NWO 480-05-003). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; The authors declare the following interests: Eli Lilly funded portions of the genotyping for CATIE and TOP. P. F. S. received research funding from Eli Lilly in connection with CATIE. T. S. S. received research funding from Eli Lilly and consulting fees from Janssen Pharmaceutica, GlaxoSmithKline and Bristol-Myers Squibb. J.A.L. received research funding from AstraZeneca Pharmaceuticals, Bristol-Myers Squibb, GlaxoSmithKline, Janssen Pharmaceutica and Pfizer and consulting and educational fees from AstraZeneca Pharmaceuticals, Bristol-Myers Squibb, Eli Lilly, Forest Pharmaceuticals, GlaxoSmithKline, Janssen Pharmaceutica, Novartis, Pfizer and Solvay. D.St.C. received research funding from GlaxoSmithKline and Generation Scotland, Genetics Health Initiative. F. A. received funds from Pfizer, Organon and the Foundation for the National Institutes of Health. D. W. B. has received research support from Shire and Forest, has been on the speakers' bureau for Pfizer and has received consulting honoraria from Forest and Jazz. T. W. has received consulting and lecture fees from H. Lundbeck A/S. O.A.A. has received Speaker's honorarium from AstraZeneca, Janssen, Bristol-Myers Squibb and GlaxoSmithKline. I. M. has received a Speaker's honorarium from Janssen and AstraZeneca. A. K. M. has received consulting fees or honoraria from Eli Lilly & Company, Janssen Pharmaceutica, Merck, Bristol-Meyers Squibb, Pfizer, PGxHealth (a division of Clinical Data, Inc.), Roche Diagnostics and Vanda Pharmaceuticals and has received research support from Eli Lilly & Company. T. L. has received consulting fees or honoraria from Merck, Eli Lilly & Company, Golden Helix, Inc., InforMed Insights and PGxHealth (a division of Clinical Data, Inc.). I. B. has been an advisory board member, consultant and lecturer for AstraZeneca, Bristol-Myers Squibb, Eli Lilly, EGIS, Janssen, H. Lundbeck A/S, Novartis, Pfizer, Richter and Schering-Plough and received a grant for an investigator-initiated study from H. Lundbeck A/S. J.J.M. has received consulting and speaker's fees from Johnson & Johnson, Schering-Plough and Eli Lilly. C. P. has received grant support from Janssen-Cilag, Eli Lilly, Hospira (Mayne) and AstraZeneca, provided consultancy to Janssen-Cilag, Eli Lilly, Hospira (Mayne), AstraZeneca, Pfizer and Schering-Plough and has undertaken investigator-initiated studies supported by Eli Lilly, Hospira, Janssen Cilag and AstraZeneca. The Denmark-Aarhus group (The GEMS Stud with principal investigators A. D. B., O.M. and P. B. M.) received research funding from H. Lundbeck A/S. E.G.J. has served as an unpaid consultant for Eli Lilly. H. S., S. S., and K. S. are employed at deCODE Genetics, Reykjavik, Iceland. MH is employed at Illumina, Inc., La Jolla, California, USA. PM is employed at NeuroSearch A/S, Ballerup, Denmark. TFO is employed at ARoS Applied Biotechnology A/S, Skejby, Denmark. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials, as detailed online in the guide for authors. NR 22 TC 19 Z9 19 U1 0 U2 12 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 22 PY 2012 VL 7 IS 6 AR e37852 DI 10.1371/journal.pone.0037852 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 964XV UT WOS:000305730900005 PM 22761660 ER PT J AU Jutras-Aswad, D Jacobs, MM Yiannoulos, G Roussos, P Bitsios, P Nomura, Y Liu, X Hurd, YL AF Jutras-Aswad, Didier Jacobs, Michelle M. Yiannoulos, Georgia Roussos, Panos Bitsios, Panos Nomura, Yoko Liu, Xun Hurd, Yasmin L. TI Cannabis-Dependence Risk Relates to Synergism between Neuroticism and Proenkephalin SNPs Associated with Amygdala Gene Expression: Case-Control Study SO PLOS ONE LA English DT Article ID POPULATION-BASED SAMPLE; STOP SIGNAL INHIBITION; D2 RECEPTOR GENE; ENVIRONMENTAL-INFLUENCES; PRE-PROENKEPHALIN; NEGATIVE AFFECT; WORKING-MEMORY; SUBSTANCE USE; FEMALE TWINS; DRUG-USE AB Background: Many young people experiment with cannabis, yet only a subgroup progress to dependence suggesting individual differences that could relate to factors such as genetics and behavioral traits. Dopamine receptor D2 (DRD2) and proenkephalin (PENK) genes have been implicated in animal studies with cannabis exposure. Whether polymorphisms of these genes are associated with cannabis dependence and related behavioral traits is unknown. Methodology/Principal Findings: Healthy young adults (18-27 years) with cannabis dependence and without a dependence diagnosis were studied (N = 50/group) in relation to a priori-determined single nucleotide polymorphisms (SNPs) of the DRD2 and PENK genes. Negative affect, Impulsive Risk Taking and Neuroticism-Anxiety temperamental traits, positive and negative reward-learning performance and stop-signal reaction times were examined. The findings replicated the known association between the rs6277 DRD2 SNP and decisions associated with negative reinforcement outcomes. Moreover, PENK variants (rs2576573 and rs2609997) significantly related to Neuroticism and cannabis dependence. Cigarette smoking is common in cannabis users, but it was not associated to PENK SNPs as also validated in another cohort (N = 247 smokers, N = 312 non-smokers). Neuroticism mediated (15.3%-19.5%) the genetic risk to cannabis dependence and interacted with risk SNPs, resulting in a 9-fold increase risk for cannabis dependence. Molecular characterization of the postmortem human brain in a different population revealed an association between PENK SNPs and PENK mRNA expression in the central amygdala nucleus emphasizing the functional relevance of the SNPs in a brain region strongly linked to negative affect. Conclusions/Significance: Overall, the findings suggest an important role for Neuroticism as an endophenotype linking PENK polymorphisms to cannabis-dependence vulnerability synergistically amplifying the apparent genetic risk. C1 [Jutras-Aswad, Didier; Jacobs, Michelle M.; Yiannoulos, Georgia; Roussos, Panos; Nomura, Yoko; Liu, Xun; Hurd, Yasmin L.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Jacobs, Michelle M.] Mt Sinai Sch Med, Dept Pharmacol & Syst Therapeut, New York, NY USA. [Bitsios, Panos; Hurd, Yasmin L.] Univ Crete, Fac Med, Dept Psychiat & Behav Sci, Iraklion, Crete, Greece. [Liu, Xun] Chinese Acad Sci, Inst Psychol, Beijing 100101, Peoples R China. [Nomura, Yoko] Queens Coll, Dept Psychol, Queens, NY USA. [Hurd, Yasmin L.] Mt Sinai Sch Med, Dept Neurosci, New York, NY USA. [Hurd, Yasmin L.] James J Peters VA Med Ctr, New York, NY USA. RP Jutras-Aswad, D (reprint author), Univ Montreal, Dept Psychiat, Montreal, PQ H3C 3J7, Canada. EM Yasmin.hurd@mssm.edu RI Liu, Xun/C-2400-2009; Roussos, Panos/J-7090-2013 OI Liu, Xun/0000-0003-1366-8926; Roussos, Panos/0000-0002-4640-6239 FU Mount Sinai School of Medicine Fund; Centre Hospitalier de l'Universite de Montreal Research Fellowship Award; National Institutes of Health [DA15446, T32 DA007135] FX This research was supported by Mount Sinai School of Medicine Fund (YLH), Centre Hospitalier de l'Universite de Montreal Research Fellowship Award (DJA) and National Institutes of Health [DA15446 (YLH), T32 DA007135 (MMJ)]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 40 TC 15 Z9 16 U1 2 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 22 PY 2012 VL 7 IS 6 AR e39243 DI 10.1371/journal.pone.0039243 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 964XV UT WOS:000305730900038 PM 22745721 ER PT J AU Nahed, BV Babu, MA Smith, TR Heary, RF AF Nahed, Brian V. Babu, Maya A. Smith, Timothy R. Heary, Robert F. TI Malpractice Liability and Defensive Medicine: A National Survey of Neurosurgeons SO PLOS ONE LA English DT Article ID HEALTH-CARE SERVICES; UNITED-STATES; RISK; PHYSICIANS; OVERUSE; COST AB Background: Concern over rising healthcare expenditures has led to increased scrutiny of medical practices. As medical liability and malpractice risk rise to crisis levels, the medical-legal environment has contributed to the practice of defensive medicine as practitioners attempt to mitigate liability risk. High-risk specialties, such as neurosurgery, are particularly affected and neurosurgeons have altered their practices to lessen medical-legal risk. We present the first national survey of American neurosurgeons' perceptions of malpractice liability and defensive medicine practices. Methods: A validated, 51-question online-survey was sent to 3344 practicing U. S. neurosurgeon members of the American Association of Neurological Surgeons, which represents 76% of neurosurgeons in academic and private practices. Results: A total of 1028 surveys were completed (31% response rate) by neurosurgeons representing diverse sub-specialty practices. Respondents engaged in defensive medicine practices by ordering additional imaging studies (72%), laboratory tests (67%), referring patients to consultants (66%), or prescribing medications (40%). Malpractice premiums were considered a "major or extreme'' burden by 64% of respondents which resulted in 45% of respondents eliminating high-risk procedures from their practice due to liability concerns. Conclusions: Concerns and perceptions about medical liability lead practitioners to practice defensive medicine. As a result, diagnostic testing, consultations and imaging studies are ordered to satisfy a perceived legal risk, resulting in higher healthcare expenditures. To minimize malpractice risk, some neurosurgeons have eliminated high-risk procedures. Left unchecked, concerns over medical liability will further defensive medicine practices, limit patient access to care, and increase the cost of healthcare delivery in the United States. C1 [Nahed, Brian V.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Babu, Maya A.] Mayo Clin, Dept Neurol Surg, Rochester, MN USA. [Smith, Timothy R.] Northwestern Univ, Dept Neurol Surg, Chicago, IL 60611 USA. [Heary, Robert F.] Univ Med & Dent New Jersey, Dept Neurol Surg, Newark, NJ 07103 USA. RP Nahed, BV (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. EM bnahed@partners.org; babu.maya@mayo.edu FU Council of State Neurosurgical Societies (CSNS); Congress of Neurological Surgeons (CNS) FX The authors wish to thank Katie O. Orrico, J.D. and the American Association of Neurological Surgeons (AANS) for assistance with contacting members. Additionally, the authors wish to recognize the support of Deborah L. Benzil M. D., Christopher C. Getch M. D., the Council of State Neurosurgical Societies (CSNS), and the Congress of Neurological Surgeons (CNS). The authors had access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. NR 32 TC 37 Z9 37 U1 2 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 22 PY 2012 VL 7 IS 6 AR e39237 DI 10.1371/journal.pone.0039237 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 964XV UT WOS:000305730900037 PM 22761745 ER PT J AU Zhang, XH Ma, J Wu, KN Chan, AT Fuchs, CS Giovannucci, EL AF Zhang, Xuehong Ma, Jing Wu, Kana Chan, Andrew T. Fuchs, Charles S. Giovannucci, Edward L. TI Blood Donation and Colorectal Cancer Incidence and Mortality in Men SO PLOS ONE LA English DT Article ID BODY IRON STORES; COLON-CANCER; HEME IRON; ALCOHOL-CONSUMPTION; SERUM FERRITIN; GENE-MUTATIONS; RECTAL-CANCER; HEART-DISEASE; DIETARY IRON; RED MEAT AB Background: Although blood donations may reduce body iron stores, to date, prospective data on frequent blood donation and colorectal cancer risk are limited. Methodology/Principal Findings: We tested whether frequent blood donation is associated with a lower risk of colorectal cancer in the Health Professionals Follow-up Study. We prospectively followed 35,121 men who provide the information on lifetime number of blood donations in 1992 through 2008. Serum ferritin levels were measured in a random sample of 305 men. Cox proportional hazard regression models were used to calculate the multivariable relative risks (RRs, 95% CIs) after adjusting for age and other established colorectal cancer risk factors. We documented 684 incident colorectal cancer cases and 224 deaths from colorectal cancer. The mean serum ferritin levels varied from 178 mg/L for men who did not donate blood to 98 mg/L for men who had at least 30 donations. Age-adjusted results for both incidence and mortality were essentially the same as the multivariable-adjusted results. Comparing with non-donors, the multivariable RRs (95% CIs) for colorectal cancer incidence were 0.92 (0.77, 1.11) for 1-5 donation, 0.85 (0.64, 1.11) for 6-9 donations, 0.96 (0.73, 1.26) for 10-19 donations, 0.91 (0.63, 1.32) for 20-29 donations, and 0.97 (0.68, 1.38) for at least 30 donations (P-trend = 0.92). The multivariable RRs for colorectal cancer mortality were 0.99 (0.72, 1.36) for 1-5 donation, 0.93 (0.57, 1.51) for 6-9 donations, 0.85 (0.50, 1.42) for 10-19 donations, and 1.14 (0.72, 1.83) for at least 20 donations (P-trend = 0.82). The results did not vary by cancer sub-sites, intake levels of total iron, heme iron, or family history of colorectal cancer. Conclusions/Significance: Frequent blood donations were not associated with colorectal cancer incidence and mortality in men. Our results do not support an important role of body iron stores in colorectal carcinogenesis. C1 [Zhang, Xuehong; Ma, Jing; Chan, Andrew T.; Fuchs, Charles S.; Giovannucci, Edward L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA 02115 USA. [Wu, Kana; Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Chan, Andrew T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. [Fuchs, Charles S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Zhang, XH (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA 02115 USA. EM xuehong.zhang@channing.harvard.edu FU National Institutes of Health [CA55075] FX This work was supported by the National Institutes of Health grant CA55075. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 39 TC 1 Z9 1 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 22 PY 2012 VL 7 IS 6 AR e39319 DI 10.1371/journal.pone.0039319 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 964XV UT WOS:000305730900042 PM 22761761 ER PT J AU Chen, JX Krane, M Deutsch, MA Wang, L Rav-Acha, M Gregoire, S Engels, MC Rajarajan, K Karra, R Abel, ED Wu, JC Milan, D Wu, SM AF Chen, Jenny X. Krane, Markus Deutsch, Marcus-Andre Wang, Li Rav-Acha, Moshe Gregoire, Serge Engels, Marc C. Rajarajan, Kuppusamy Karra, Ravi Abel, E. Dale Wu, Joe C. Milan, David Wu, Sean M. TI Inefficient Reprogramming of Fibroblasts into Cardiomyocytes Using Gata4, Mef2c, and Tbx5 SO CIRCULATION RESEARCH LA English DT Article DE gene expression; Ca2+ channels; cardiac development; myocardial ischemia; myocyte regeneration ID EMBRYONIC STEM-CELLS; INFARCTED RAT HEARTS; MYOCARDIAL-INFARCTION; DIRECT CONVERSION; DEFINED FACTORS; MECHANISMS; SURVIVAL; ENHANCER; NKX2-5; MOUSE AB Rationale: Direct reprogramming of fibroblasts into cardiomyocytes is a novel strategy for cardiac regeneration. However, the key determinants involved in this process are unknown. Objective: To assess the efficiency of direct fibroblast reprogramming via viral overexpression of GATA4, Mef2c, and Tbx5 (GMT). Methods and Results: We induced GMT overexpression in murine tail tip fibroblasts (TTFs) and cardiac fibroblasts (CFs) from multiple lines of transgenic mice carrying different cardiomyocyte lineage reporters. We found that the induction of GMT overexpression in TTFs and CFs is inefficient at inducing molecular and electrophysiological phenotypes of mature cardiomyocytes. In addition, transplantation of GMT infected CFs into injured mouse hearts resulted in decreased cell survival with minimal induction of cardiomyocyte genes. Conclusions: Significant challenges remain in our ability to convert fibroblasts into cardiomyocyte-like cells and a greater understanding of cardiovascular epigenetics is needed to increase the translational potential of this strategy. (Circ Res. 2012;111:50-55.) C1 [Wu, Sean M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Dept Med,Cardiovasc Res Ctr, Boston, MA 02114 USA. [Krane, Markus; Deutsch, Marcus-Andre] Tech Univ Munich, German Heart Ctr Munich, Dept Cardiovasc Surg, Dept Expt Surg, Munich, Germany. [Wang, Li; Wu, Joe C.] Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA. [Karra, Ravi] Duke Univ, Sch Med, Dept Med, Div Cardiol, Durham, NC 27706 USA. [Abel, E. Dale] Univ Utah, Sch Med, Div Endocrinol Metab & Diabet, Salt Lake City, UT USA. [Abel, E. Dale] Univ Utah, Sch Med, Program Mol Med, Salt Lake City, UT USA. [Wu, Sean M.] Harvard Stem Cell Inst, Cambridge, MA USA. RP Wu, SM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Dept Med,Cardiovasc Res Ctr, 185 Cambridge St, Boston, MA 02114 USA. EM smwu@partners.org FU German Research Foundation [KR3770/1-1]; German Heart Foundation (Deutsche Herzstiftung e.V.); NIH [DA026982, HL109004]; NHLBI [HL081086, HL100408]; NIH/OD [004411]; Harvard Stem Cell Institute; [NIH-P50-NS40828]; [NIH-P30-HD18655] FX We thank Dr William Pu at Boston Children's Hospital for cTnt-Cre/ROSAmtmg reporter fibroblasts; Dr Robert Schwartz at University of Houston for Nkx2.5-Cre knock-in mice; Dr X.J. Yang at McGill University and Dr Qi Kenneth Wang at Cleveland Clinic and Case Western Reserve University for promoter constructs used in luciferase reporter assays; Drs Konrad Hochedlinger and Matthias Stadtfeld for the rtTA plasmid vector. Microarray studies were performed by the Molecular Genetics Core Facility at Children's Hospital Boston supported by NIH-P50-NS40828 and NIH-P30-HD18655. Ms Laura Prickett-Rice at the MGH-Center for Regenerative Medicine flow cytometry core facility provided assistance with FACS.; M. Krane was supported by the German Research Foundation (KR3770/1-1). M. A. Deutsch was supported by the German Heart Foundation (Deutsche Herzstiftung e.V.). D. Milan was supported by NIH grants DA026982 and HL109004. S. M. Wu was supported by NHLBI (HL081086, HL100408), NIH/OD (004411), and the Harvard Stem Cell Institute. NR 18 TC 109 Z9 115 U1 2 U2 21 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD JUN 22 PY 2012 VL 111 IS 1 BP 50 EP 55 DI 10.1161/CIRCRESAHA.112.270264 PG 6 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 969NF UT WOS:000306061700012 PM 22581928 ER PT J AU Zullo, JM Demarco, IA Pique-Regi, R Gaffney, DJ Epstein, CB Spooner, CJ Luperchio, TR Bernstein, BE Pritchard, JK Reddy, KL Singh, H AF Zullo, Joseph M. Demarco, Ignacio A. Pique-Regi, Roger Gaffney, Daniel J. Epstein, Charles B. Spooner, Chauncey J. Luperchio, Teresa R. Bernstein, Bradley E. Pritchard, Jonathan K. Reddy, Karen L. Singh, Harinder TI DNA Sequence-Dependent Compartmentalization and Silencing of Chromatin at the Nuclear Lamina SO CELL LA English DT Article ID TRANSCRIPTION FACTOR; MAMMALIAN-CELLS; GENE-EXPRESSION; GAGA FACTOR; PERIPHERY; PROTEIN; ORGANIZATION; LOCUS; DEACETYLATION; MAINTENANCE AB A large fraction of the mammalian genome is organized into inactive chromosomal domains along the nuclear lamina. The mechanism by which these lamina associated domains (LADs) are established remains to be elucidated. Using genomic repositioning assays, we show that LADs, spanning the developmentally regulated IgH and Cyp3a loci contain discrete DNA regions that associate chromatin with the nuclear lamina and repress gene activity in fibroblasts. Lamina interaction is established during mitosis and likely involves the localized recruitment of Lamin B during late anaphase. Fine-scale mapping of LADs reveals numerous lamina-associating sequences (LASs), which are enriched for a GAGA motif. This repeated motif directs lamina association and is bound by the transcriptional repressor cKrox, in a complex with HDAC3 and Lap2 beta. Knockdown of cKrox or HDAC3 results in dissociation of LASs/LADs from the nuclear lamina. These results reveal a mechanism that couples nuclear compartmentalization of chromatin domains with the control of gene activity. C1 [Zullo, Joseph M.; Singh, Harinder] Univ Chicago, Dept Mol Genet & Cell Biol, Chicago, IL 60637 USA. [Pique-Regi, Roger; Gaffney, Daniel J.; Pritchard, Jonathan K.] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. [Demarco, Ignacio A.; Spooner, Chauncey J.; Singh, Harinder] Genentech Inc, Dept Discovery Immunol, San Francisco, CA 94080 USA. [Pique-Regi, Roger; Gaffney, Daniel J.; Pritchard, Jonathan K.] Univ Chicago, Howard Hughes Med Inst, Chicago, IL 60637 USA. [Epstein, Charles B.; Bernstein, Bradley E.] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA 02142 USA. [Epstein, Charles B.; Bernstein, Bradley E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Epstein, Charles B.; Bernstein, Bradley E.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Luperchio, Teresa R.; Reddy, Karen L.] Johns Hopkins Univ, Sch Med, Dept Biol Chem, Ctr Epigenet, Baltimore, MD 21205 USA. RP Singh, H (reprint author), Univ Chicago, Dept Mol Genet & Cell Biol, 920 E 58Th St, Chicago, IL 60637 USA. EM harindsi@gene.com RI Pique-Regi, Roger/A-4110-2009; OI Pique-Regi, Roger/0000-0002-1262-2275; Luperchio, Teresa/0000-0001-8586-3101; Gaffney, Daniel/0000-0002-1529-1862; Reddy, Karen/0000-0003-4548-5999 FU NIH [GM086213]; Cancer Research Institute; Howard Hughes Medical Institute; Chicago Biomedical Consortium FX We acknowledge support from the University of Chicago Functional Genomics Facility for genome-wide expression and DamID analyses. We thank Lazlo Komuves and Allison Bruce at Genentech for assistance with confocal imaging and graphics art, respectively. We are grateful to members of the Singh laboratory for critical input. J.M.Z. was supported by an NIH training grant. I. A. D. acknowledges support by the Cancer Research Institute. H. S. acknowledges support by the Howard Hughes Medical Institute and the Chicago Biomedical Consortium and from NIH GM086213. H. S. and C.J.S. are employees of Genentech Inc. NR 43 TC 161 Z9 166 U1 2 U2 25 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD JUN 22 PY 2012 VL 149 IS 7 BP 1474 EP 1487 DI 10.1016/j.cell.2012.04.035 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 965FY UT WOS:000305753800014 PM 22726435 ER PT J AU Chung, HC Pamp, SJ Hill, JA Surana, NK Edelman, SM Troy, EB Reading, NC Villablanca, EJ Wang, S Mora, JR Umesaki, Y Mathis, D Benoist, C Relman, DA Kasper, DL AF Chung, Hachung Pamp, Suenje J. Hill, Jonathan A. Surana, Neeraj K. Edelman, Sanna M. Troy, Erin B. Reading, Nicola C. Villablanca, Eduardo J. Wang, Sen Mora, Jorge R. Umesaki, Yoshinori Mathis, Diane Benoist, Christophe Relman, David A. Kasper, Dennis L. TI Gut Immune Maturation Depends on Colonization with a Host-Specific Microbiota SO CELL LA English DT Article ID SEGMENTED FILAMENTOUS BACTERIA; ROR-GAMMA-T; INTESTINAL MICROBIOTA; CELLS; DISEASE; DIFFERENTIATION; RESPONSES; SYSTEM; HOMEOSTASIS; RECEPTORS AB Gut microbial induction of host immune maturation exemplifies host-microbe mutualism. We colonized germ-free (GF) mice with mouse microbiota (MMb) or human microbiota (HMb) to determine whether small intestinal immune maturation depends on a coevolved host-specific microbiota. Gut bacterial numbers and phylum abundance were similar in MMb and HMb mice, but bacterial species differed, especially the Firmicutes. HMb mouse intestines had low levels of CD4(+) and CD8(+) T cells, few proliferating T cells, few dendritic cells, and low antimicrobial peptide expression-all characteristics of GF mice. Rat microbiota also failed to fully expand intestinal T cell numbers in mice. Colonizing GF or HMb mice with mouse-segmented filamentous bacteria (SFB) partially restored T cell numbers, suggesting that SFB and other MMb organisms are required for full immune maturation in mice. Importantly, MMb conferred better protection against Salmonella infection than HMb. A host-specific microbiota appears to be critical for a healthy immune system. C1 [Chung, Hachung; Surana, Neeraj K.; Edelman, Sanna M.; Troy, Erin B.; Reading, Nicola C.; Kasper, Dennis L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab, Boston, MA 02115 USA. [Chung, Hachung; Hill, Jonathan A.; Surana, Neeraj K.; Edelman, Sanna M.; Troy, Erin B.; Reading, Nicola C.; Mathis, Diane; Benoist, Christophe; Kasper, Dennis L.] Harvard Univ, Sch Med, Dept Microbiol & Immunol, Boston, MA 02115 USA. [Pamp, Suenje J.; Relman, David A.] Stanford Univ, Sch Med, Dept Microbiol & Immunol, Stanford, CA 94305 USA. [Pamp, Suenje J.; Relman, David A.] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA. [Villablanca, Eduardo J.; Wang, Sen; Mora, Jorge R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Gastrointestinal Unit, Boston, MA 02114 USA. [Umesaki, Yoshinori] Yakult Cent Inst Microbiol Res, Kunitachi, Tokyo 1868650, Japan. [Pamp, Suenje J.; Relman, David A.] Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA 94304 USA. [Surana, Neeraj K.] Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA. RP Kasper, DL (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab, Boston, MA 02115 USA. EM dennis_kasper@hms.harvard.edu RI Pamp, Sunje/H-8787-2012; Villablanca, Eduardo/E-1380-2016 OI Pamp, Sunje/0000-0002-6236-1763; Villablanca, Eduardo/0000-0001-9522-9729 FU Crohn's & Colitis Foundation of America; Juvenile Diabetes Research Foundation; Danish Council for Independent Research Natural Sciences; National Institutes of Health [F32 AI091104]; Director's Pioneer Award [DP1OD000964]; Thomas C. and Joan M. Merigan Endowment at Stanford University FX We thank Shakir Edwards for gnotobiotic animal care, Julie B. McCoy for editing, Tom DiCesare for image design, Dr. Rod Bronson for pathology scoring, Jennifer Dinalo for ten human fecal samples, and Les Dethlefsen and Robert Edgar for helpful advice. This work was supported by a Senior Research Award from the Crohn's & Colitis Foundation of America (to D. L. K.), by the Juvenile Diabetes Research Foundation (to H. C.), by the Danish Council for Independent Research Natural Sciences (to S.J.P.), by National Institutes of Health Grant F32 AI091104 (to N.K.S.), and by Director's Pioneer Award DP1OD000964 (to D. A. R.). D. A. R. is supported by the Thomas C. and Joan M. Merigan Endowment at Stanford University. NR 58 TC 279 Z9 290 U1 11 U2 141 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD JUN 22 PY 2012 VL 149 IS 7 BP 1578 EP 1593 DI 10.1016/j.cell.2012.04.037 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 965FY UT WOS:000305753800022 PM 22726443 ER PT J AU Wible, CG AF Wible, Cynthia G. TI Hippocampal temporal-parietal junction interaction in the production of psychotic symptoms: a framework for understanding the schizophrenic syndrome SO FRONTIERS IN HUMAN NEUROSCIENCE LA English DT Article DE hippocampus; schizophrenia; parietal; biological motion; superior temporal sulcus; intraparietal sulcus; autism; social cognition ID ANTERIOR CINGULATE CORTEX; VOXEL-BASED MORPHOMETRY; INTRINSIC FUNCTIONAL CONNECTIVITY; DOPAMINE-GLUTAMATE INTERACTIONS; SOCIAL COGNITIVE NEUROSCIENCE; D-ASPARTATE RECEPTOR; FRONTAL-LOBE DAMAGE; GRAY-MATTER VOLUME; 2 VISUAL-SYSTEMS; WORKING-MEMORY AB A framework is described for understanding the schizophrenic syndrome at the brain systems level. It is hypothesized that over-activation of dynamic gesture and social perceptual processes in the temporal-parietal occipital junction (TPJ), posterior superior temporal sulcus (PSTS) and surrounding regions produce the syndrome (including positive and negative symptoms, their prevalence, prodromal signs, and cognitive deficits). Hippocampal system hyper-activity and atrophy have been consistently found in schizophrenia. Hippocampal activity is highly correlated with activity in the TPJ and may be a source of over-excitation of the TPJ and surrounding regions. Strong evidence for this comes from in-vivo recordings in humans during psychotic episodes. Many positive symptoms of schizophrenia can be reframed as the erroneous sense of a presence or other who is observing, acting, speaking, or controlling; these qualia are similar to those evoked during abnormal activation of the TPJ. The TPJ and PSTS play a key role in the perception (and production) of dynamic social, emotional, and attentional gestures for the self and others (e.g., body/face/eye gestures, audiovisual speech and prosody, and social attentional gestures such as eye gaze). The single cell representation of dynamic gestures is multimodal (auditory, visual, tactile), matching the predominant hallucinatory categories in schizophrenia. Inherent in the single cell perceptual signal of dynamic gesture representations is a computation of intention, agency, and anticipation or expectancy (for the self and others). Stimulation of the TPJ resulting in activation of the self representation has been shown to result a feeling of a presence or multiple presences (due to heautoscopy) and also bizarre tactile experiences. Neurons in the TPJ are also tuned, or biased to detect threat related emotions. Abnormal over-activation in this system could produce the conscious hallucination of a voice (audiovisual speech), a person or a touch. Over-activation could interfere with attentional/emotional gesture perception and production (negative symptoms). It could produce the unconscious feeling of being watched, followed, or of a social situation unfolding along with accompanying abnormal perception of intent and agency (delusions). Abnormal activity in the TPJ would also be predicted to create several cognitive disturbances that are characteristic of schizophrenia, including abnormalities in attention, predictive social processing, working memory, and a bias to erroneously perceive threat. C1 Harvard Univ, Sch Med, Dept Psychiat, Neurosci Lab,VA Boston Healthcare Syst, Brockton, MA 02301 USA. RP Wible, CG (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Neurosci Lab,VA Boston Healthcare Syst, 940 Belmont St, Brockton, MA 02301 USA. EM cindy@bwh.harvard.edu FU NIMH [1R01 MH067080-01A2, 1R01 MH52807]; Harvard Neuro-Discovery Center (formally HCNR); Biomedical Informatics Research Network [U24RR021992]; National Institute of Mental Health; NIH [MH40799]; Veteran's Administration (VA) Merit award; VA Research Enhancement Award Program (REAP); VA Medical Center of Excellence Award FX This work was supported by an NIMH grant: 1R01 MH067080-01A2 and by the Harvard Neuro-Discovery Center (formally HCNR). Funded also by the Biomedical Informatics Research Network (U24RR021992); National Institute of Mental Health. Support was also received from NIMH 1R01 MH52807, NIH MH40799, a Veteran's Administration (VA) Merit award, a VA Research Enhancement Award Program (REAP), and a VA Medical Center of Excellence Award (principal investigator for these grants: Robert W. McCarley). The author would like to thank Israel Molina for assembling the reference section. NR 303 TC 5 Z9 6 U1 8 U2 25 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-5161 J9 FRONT HUM NEUROSCI JI Front. Hum. Neurosci. PD JUN 22 PY 2012 VL 6 AR 180 DI 10.3389/fnhum.2012.00180 PG 30 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA 965TF UT WOS:000305789500001 PM 22737114 ER PT J AU Ryan, RJH Bernstein, BE AF Ryan, Russell J. H. Bernstein, Bradley E. TI Genetic Events That Shape the Cancer Epigenome SO SCIENCE LA English DT Editorial Material ID MUTATIONS; DIFFERENTIATION; EZH2 C1 [Ryan, Russell J. H.; Bernstein, Bradley E.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Dept Pathol, Boston, MA 02114 USA. [Ryan, Russell J. H.; Bernstein, Bradley E.] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. [Ryan, Russell J. H.; Bernstein, Bradley E.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Ryan, Russell J. H.; Bernstein, Bradley E.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. RP Ryan, RJH (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Dept Pathol, Boston, MA 02114 USA. EM bernstein.bradley@mgh.harvard.edu FU Howard Hughes Medical Institute NR 20 TC 36 Z9 36 U1 0 U2 12 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUN 22 PY 2012 VL 336 IS 6088 BP 1513 EP 1514 DI 10.1126/science.1223730 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 961ZE UT WOS:000305507500035 PM 22723401 ER PT J AU Siedner, MJ Haberer, JE Bwana, MB Ware, NC Bangsberg, DR AF Siedner, Mark J. Haberer, Jessica E. Bwana, Mwebesa Bosco Ware, Norma C. Bangsberg, David R. TI High acceptability for cell phone text messages to improve communication of laboratory results with HIV-infected patients in rural Uganda: a cross-sectional survey study SO BMC MEDICAL INFORMATICS AND DECISION MAKING LA English DT Article DE SMS; Cellular phones; HIV; Sub-Saharan Africa; Confidentiality; Privacy ID RANDOMIZED CONTROLLED-TRIAL; ANTIRETROVIRAL THERAPY; MOBILE PHONES; SOUTH-AFRICA; FOLLOW-UP; CHALLENGES; ADHERENCE; INTERVENTION; DISCLOSURE; REMINDERS AB Background: Patient-provider communication is a major challenge in resource-limited settings with large catchment areas. Though mobile phone usership increased 20-fold in Africa over the past decade, little is known about acceptability of, perceptions about disclosure and confidentiality, and preferences for cell phone communication of health information in the region. Methods: We performed structured interviews of fifty patients at the Immune Suppression Syndrome clinic in Mbarara, Uganda to assess four domains of health-related communication: a) cell phone use practices and literacy, b) preferences for laboratory results communication, c) privacy and confidentiality, and d) acceptability of and preferences for text messaging to notify patients of abnormal test results. Results: Participants had a median of 38 years, were 56% female, and were residents of a large catchment area throughout southwestern Uganda. All participants expressed interest in a service to receive information about laboratory results by cell phone text message, stating benefits of increased awareness of their health and decreased transportation costs. Ninety percent reported that they would not be concerned for unintended disclosure. A minority additionally expressed concerns about difficulty interpreting messages, discouragement upon learning bad news, and technical issues. Though all respondents expressed interest in password protection of messages, there was also a strong desire for direct messages to limit misinterpretation of information. Conclusions: Cell phone text messaging for communication of abnormal laboratory results is highly acceptable in this cohort of HIV-infected patients in rural Uganda. The feasibility of text messaging, including an optimal balance between privacy and comprehension, should be further studied. C1 [Siedner, Mark J.; Bangsberg, David R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Infect Dis, Boston, MA 02114 USA. [Bwana, Mwebesa Bosco; Bangsberg, David R.] Mbarara Univ Sci & Technol, Mbarara, Uganda. [Bangsberg, David R.] Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, Ctr Global Hlth, Boston, MA 02114 USA. RP Siedner, MJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Infect Dis, 55 Fruit St,GRJ-5, Boston, MA 02114 USA. EM msiedner@partners.org RI Emchi, Karma/Q-1952-2016; OI Siedner, Mark/0000-0003-3506-842X FU National Institutes of Health [RO-1 MH54907, K-24 MH87227, K23 MH087228]; National Institute of Health [R21 MH085550, K24 MH090894-01]; Harvard Global Health Institute and the Fogarty International Center [R24 TW007988]; NIH [1 UL1 RR024975] FX David Bangsberg receives support from the National Institutes of Health (RO-1 MH54907, K-24 MH87227).; Jessica Haberer receives support from the National Institutes of Health (K23 MH087228).; Norma Ware receives support from the National Institute of Health R21 MH085550, K24 MH090894-01).; Mark Siedner receives additional support from the Harvard Global Health Institute and the Fogarty International Center (R24 TW007988). The Redcap database tool is provided by the Vanderbilt Institute for Clinical and Translational Research with NIH grant support (1 UL1 RR024975). NR 25 TC 28 Z9 28 U1 2 U2 11 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6947 J9 BMC MED INFORM DECIS JI BMC Med. Inform. Decis. Mak. PD JUN 21 PY 2012 VL 12 AR 56 DI 10.1186/1472-6947-12-56 PG 7 WC Medical Informatics SC Medical Informatics GA 024YO UT WOS:000310148100001 PM 22720901 ER PT J AU Sumen, C Reddy, TE Alber, MS Lee, PP AF Sumen, Cenk Reddy, Timothy E. Alber, Mark S. Lee, Peter P. TI Agent-based modeling of the context dependency in T cell recognition (vol 236, pg 376, 2005) SO JOURNAL OF THEORETICAL BIOLOGY LA English DT Correction C1 [Alber, Mark S.] Univ Notre Dame, Dept Math, Notre Dame, IN 46556 USA. [Alber, Mark S.] Univ Notre Dame, Ctr Study Biocomplex, Notre Dame, IN 46556 USA. [Sumen, Cenk] Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. [Reddy, Timothy E.] Boston Univ, Program Bioinformat & Syst Biol, Boston, MA 02215 USA. [Lee, Peter P.] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Lee, Peter P.] Beckman Ctr, Beckman Res Inst, Duarte, CA 91010 USA. RP Alber, MS (reprint author), Univ Notre Dame, Dept Math, 255 Hurley Bldg, Notre Dame, IN 46556 USA. EM mark.s.alber.1@nd.edu; plee@coh.org NR 1 TC 0 Z9 0 U1 0 U2 3 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-5193 J9 J THEOR BIOL JI J. Theor. Biol. PD JUN 21 PY 2012 VL 303 BP 152 EP 153 DI 10.1016/j.jtbi.2012.03.018 PG 2 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 022UZ UT WOS:000309990600014 PM 22783551 ER PT J AU Elvington, M Huang, YX Morgan, BP Qiao, F van Rooijen, N Atkinson, C Tomlinson, S AF Elvington, Michelle Huang, Yuxiang Morgan, B. Paul Qiao, Fei van Rooijen, Nico Atkinson, Carl Tomlinson, Stephen TI Atargeted complement-dependent strategy to improve the outcome of mAb therapy, and characterization in a murine model of metastatic cancer SO BLOOD LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; CD20 MONOCLONAL-ANTIBODIES; DECAY-ACCELERATING FACTOR; IN-VIVO; TUMOR-CELLS; INHIBITORY PROTEINS; IMMUNE-RESPONSE; FACTOR-H; ACTIVATION; IMMUNOTHERAPY AB Complement inhibitors expressed on tumor cells provide an evasion mechanism against mAb therapy and may modulate the development of an acquired antitumor immune response. Here we investigate a strategy to amplify mAb-targeted complement activation on a tumor cell, independent of a requirement to target and block complement inhibitor expression or function, which is difficult to achieve in vivo. We constructed a murine fusion protein, CR2Fc, and demonstrated that the protein targets to C3 activation products deposited on a tumor cell by a specific mAb, and amplifies mAb-dependent complement activation and tumor cell lysis in vitro. In syngeneic models of metastatic lymphoma (EL4) and melanoma (B16), CR2Fc significantly enhanced the outcome of mAb therapy. Subsequent studies using the EL4 model with various genetically modified mice and macrophage-depleted mice revealed that CR2Fc enhanced the therapeutic effect of mAb therapy via both macrophage-dependent Fc gamma R-mediated antibody-dependent cellular cytotoxicity, and by direct complement-mediated lysis. Complement activation products can also modulate adaptive immunity, but we found no evidence that either mAb or CR2Fc treatment had any effect on an antitumor humoral or cellular immune response. CR2Fc represents a potential adjuvant treatment to increase the effectiveness of mAb therapy of cancer. (Blood. 2012; 119(25): 6043-6051) C1 [Elvington, Michelle; Huang, Yuxiang; Qiao, Fei; Atkinson, Carl; Tomlinson, Stephen] Med Univ S Carolina, Dept Microbiol & Immunol, Childrens Res Inst, Charleston, SC 29425 USA. [Morgan, B. Paul] Cardiff Univ, Dept Infect Immun & Biochem, Sch Med, Cardiff, S Glam, Wales. [van Rooijen, Nico] Free Univ Amsterdam, Dept Cell Biol & Immunol, Amsterdam, Netherlands. [Tomlinson, Stephen] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Tomlinson, S (reprint author), Med Univ S Carolina, Dept Microbiol & Immunol, Childrens Res Inst, 173 Ashley Ave,BSB 201, Charleston, SC 29425 USA. EM tomlinss@musc.edu FU National Institutes of Health [RO1CA158179]; Department of Defense [BC061523] FX This work was supported by the National Institutes of Health (grant RO1CA158179, S.T.) and the Department of Defense (BC061523 fellowship, M.E.). NR 44 TC 12 Z9 13 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 21 PY 2012 VL 119 IS 25 BP 6043 EP 6051 DI 10.1182/blood-2011-10-383232 PG 9 WC Hematology SC Hematology GA 987EG UT WOS:000307398700019 PM 22442351 ER PT J AU Konstantinidis, DG Pushkaran, S Johnson, JF Cancelas, JA Manganaris, S Harris, CE Williams, DA Zheng, Y Kalfa, TA AF Konstantinidis, Diamantis G. Pushkaran, Suvarnamala Johnson, James F. Cancelas, Jose A. Manganaris, Stefanos Harris, Chad E. Williams, David A. Zheng, Yi Kalfa, Theodosia A. TI Signaling and cytoskeletal requirements in erythroblast enucleation SO BLOOD LA English DT Article ID RED-BLOOD-CELLS; VESICLE TRAFFICKING; RAC GTPASES; GUANOSINE TRIPHOSPHATASES; MEMBRANE DOMAINS; RHO GTPASES; MYOSIN-II; CYTOKINESIS; DYNAMICS; RAFTS AB To understand the role of cytoskeleton and membrane signaling molecules in erythroblast enucleation, we developed a novel analysis protocol of multiparameter high-speed cell imaging in flow. This protocol enabled us to observe F-actin and phosphorylated myosin regulatory light chain (pMRLC) assembled into a contractile actomyosin ring (CAR) between nascent reticulocyte and nucleus, in a population of enucleating erythroblasts. CAR formation and subsequent enucleation were not affected in murine erythroblasts with genetic deletion of Rac1 and Rac2 GTPases because of compensation by Rac3. Pharmacologic inhibition or genetic deletion of all Rac GTPases altered the distribution of F-actin and pMRLC and inhibited enucleation. Erythroblasts treated with NSC23766, cytochalasin-D, colchicine, ML7, or filipin that inhibited Rac activity, actin or tubulin polymerization, MRLC phosphorylation, or lipid raft assembly, respectively, exhibited decreased enucleation efficiency, as quantified by flow cytometry. As assessed by high-speed flow-imaging analysis, colchicine inhibited erythroblast polarization, implicating microtubules during the preparatory stage of enucleation, whereas NSC23766 led to absence of lipid raft assembly in the reticulocyte-pyrenocyte border. In conclusion, enucleation is a multistep process that resembles cytokinesis, requiring establishment of cell polarity through microtubule function, followed by formation of a contractile actomyosin ring, and coalescence of lipid rafts between reticulocyte and pyrenocyte. (Blood. 2012;119(25):6118-6127) C1 [Kalfa, Theodosia A.] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Div Hematol Oncol, Canc & Blood Dis Inst,Coll Med, Cincinnati, OH 45229 USA. [Manganaris, Stefanos] IBM Corp, Armonk, NY USA. [Harris, Chad E.; Williams, David A.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Harris, Chad E.; Williams, David A.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kalfa, TA (reprint author), Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Div Hematol Oncol, Canc & Blood Dis Inst,Coll Med, 3333 Burnet Ave,MLC 7015, Cincinnati, OH 45229 USA. EM theodosia.kalfa@cchmc.org RI Zheng, Yi/J-7235-2015 OI Zheng, Yi/0000-0001-7089-6074 FU National Institutes of Health [K08 HL088126, R01 CA141341, 5R01DK062757-11] FX This work was supported by the National Institutes of Health (grants K08 HL088126, T.A.K.; R01 CA141341, Y.Z.; and 5R01DK062757-11, D.A.W.). NR 43 TC 37 Z9 37 U1 0 U2 6 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 21 PY 2012 VL 119 IS 25 BP 6118 EP 6127 DI 10.1182/blood-2011-09-379263 PG 10 WC Hematology SC Hematology GA 987EG UT WOS:000307398700027 PM 22461493 ER PT J AU Buckholtz, JW Meyer-Lindenberg, A AF Buckholtz, Joshua W. Meyer-Lindenberg, Andreas TI Psychopathology and the Human Connectome: Toward a Transdiagnostic Model of Risk For Mental Illness SO NEURON LA English DT Review ID CATECHOL-O-METHYLTRANSFERASE; MAJOR DEPRESSIVE DISORDER; FUNCTIONAL NETWORK CONNECTIVITY; OBSESSIVE-COMPULSIVE DISORDER; GENERALIZED ANXIETY DISORDER; WITHIN-FAMILY TESTS; WORKING-MEMORY; COGNITIVE CONTROL; INDIVIDUAL-DIFFERENCES; BIPOLAR DISORDER AB The panoply of cognitive, affective, motivational, and social functions that underpin everyday human experience requires precisely choreographed patterns of interaction between networked brain regions. Perhaps not surprisingly, diverse forms of psychopathology are characterized by breakdowns in these interregional relationships. Here, we discuss how functional brain imaging has provided insights into the nature of brain dysconnectivity in mental illness. Synthesizing work to date, we propose that genetic and environmental risk factors impinge upon systems-level circuits for several core dimensions of cognition, producing transdiagnostic symptoms. We argue that risk-associated disruption of these circuits mediates susceptibility to broad domains of psychopathology rather than discrete disorders. C1 [Buckholtz, Joshua W.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Buckholtz, Joshua W.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02115 USA. [Buckholtz, Joshua W.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA. [Meyer-Lindenberg, Andreas] Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, D-68159 Mannheim, Germany. RP Buckholtz, JW (reprint author), Harvard Univ, Dept Psychol, 33 Kirkland St, Cambridge, MA 02138 USA. EM joshua_buckholtz@harvard.edu; a.meyer-lindenberg@zi-mannheim.de RI Buckholtz, Joshua /E-7299-2010; Meyer-Lindenberg, Andreas/H-1076-2011 OI Buckholtz, Joshua /0000-0002-9418-8686; Meyer-Lindenberg, Andreas/0000-0001-5619-1123 NR 177 TC 93 Z9 94 U1 7 U2 53 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 EI 1097-4199 J9 NEURON JI Neuron PD JUN 21 PY 2012 VL 74 IS 6 BP 990 EP 1004 DI 10.1016/j.neuron.2012.06.002 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 963YA UT WOS:000305659700006 PM 22726830 ER PT J AU Kim, BM Thier, MC Oh, S Sherwood, R Kanellopoulou, C Edenhofer, F Choi, MY AF Kim, Byeong-Moo Thier, Marc-Christian Oh, Sangnam Sherwood, Richard Kanellopoulou, Chryssa Edenhofer, Frank Choi, Michael Y. TI MicroRNAs Are Indispensable for Reprogramming Mouse Embryonic Fibroblasts into Induced Stem Cell-Like Cells SO PLOS ONE LA English DT Article ID MICROPROCESSOR COMPLEX; RNA INTERFERENCE; NUCLEAR EXPORT; ENZYME DICER; BIOGENESIS; PLURIPOTENCY; EXPRESSION; GENERATION; DIFFERENTIATION; MIR-302 AB MicroRNAs play a pivotal role in cellular maintenance, proliferation, and differentiation. They have also been implicated to play a key role in disease pathogenesis, and more recently, cellular reprogramming. Certain microRNA clusters can enhance or even directly induce reprogramming, while repressing key proteins involved in microRNA processing decreases reprogramming efficiency. Although microRNAs clearly play important roles in cellular reprogramming, it remains unknown whether microRNAs are absolutely necessary. We endeavored to answer this fundamental question by attempting to reprogram Dicer-null mouse embryonic fibroblasts (MEFs) that lack almost all functional microRNAs using a defined set of transcription factors. Transduction of reprogramming factors using either lentiviral or piggyBac transposon vector into two, independently derived lines of Dicer-null MEFs failed to produce cells resembling embryonic stem cells (ESCs). However, expression of human Dicer in the Dicer-null MEFs restored their reprogramming potential. Our study demonstrates for the first time that microRNAs are indispensable for dedifferentiation reprogramming. C1 [Kim, Byeong-Moo; Oh, Sangnam; Choi, Michael Y.] Massachusetts Gen Hosp, Dept Med, GI Unit, Boston, MA 02114 USA. [Kim, Byeong-Moo; Oh, Sangnam; Sherwood, Richard; Choi, Michael Y.] Harvard Univ, Sch Med, Boston, MA USA. [Thier, Marc-Christian; Edenhofer, Frank] Univ Bonn, Life & Brain Ctr, Inst Reconstruct Neurobiol, Bonn, Germany. [Sherwood, Richard] Brigham & Womens Hosp, Boston, MA 02115 USA. [Kanellopoulou, Chryssa] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Kim, BM (reprint author), Massachusetts Gen Hosp, Dept Med, GI Unit, Boston, MA 02114 USA. EM mchoi@partners.org OI Edenhofer, Frank/0000-0002-6489-714X FU NIH [K08 DK078641] FX The research was supported by NIH grants to M.Y.C. (K08 DK078641). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 39 TC 14 Z9 15 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 21 PY 2012 VL 7 IS 6 AR e39239 DI 10.1371/journal.pone.0039239 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 964KY UT WOS:000305695100029 PM 22737231 ER PT J AU Pashai, N Hao, HP All, A Gupta, S Chaerkady, R De Los Angeles, A Gearhart, JD Kerr, CL AF Pashai, Nikta Hao, Haiping All, Angelo Gupta, Siddharth Chaerkady, Raghothama De Los Angeles, Alejandro Gearhart, John D. Kerr, Candace L. TI Genome-Wide Profiling of Pluripotent Cells Reveals a Unique Molecular Signature of Human Embryonic Germ Cells SO PLOS ONE LA English DT Article ID ADENOMATOUS POLYPOSIS-COLI; LEUKEMIA INHIBITORY FACTOR; GENE-EXPRESSION PROFILES; STEM-CELLS; DNA-DAMAGE; OVARIAN-CANCER; ES CELLS; HOMOLOGOUS RECOMBINATION; EXCISION-REPAIR; SOMATIC-CELLS AB Human embryonic germ cells (EGCs) provide a powerful model for identifying molecules involved in the pluripotent state when compared to their progenitors, primordial germ cells (PGCs), and other pluripotent stem cells. Microarray and Principal Component Analysis (PCA) reveals for the first time that human EGCs possess a transcription profile distinct from PGCs and other pluripotent stem cells. Validation with qRT-PCR confirms that human EGCs and PGCs express many pluripotency-associated genes but with quantifiable differences compared to pluripotent embryonic stem cells (ESCs), induced pluripotent stem cells (IPSCs), and embryonal carcinoma cells (ECCs). Analyses also identified a number of target genes that may be potentially associated with their unique pluripotent states. These include IPO7, MED7, RBM26, HSPD1, and KRAS which were upregulated in EGCs along with other pluripotent stem cells when compared to PGCs. Other potential target genes were also found which may contribute toward a primed ESC-like state. These genes were exclusively upregulated in ESCs, IPSCs and ECCs including PARP1, CCNE1, CDK6, AURKA, MAD2L1, CCNG1, and CCNB1 which are involved in cell cycle regulation, cellular metabolism and DNA repair and replication. Gene classification analysis also confirmed that the distinguishing feature of EGCs compared to ESCs, ECCs, and IPSCs lies primarily in their genetic contribution to cellular metabolism, cell cycle, and cell adhesion. In contrast, several genes were found upregulated in PGCs which may help distinguish their unipotent state including HBA1, DMRT1, SPANXA1, and EHD2. Together, these findings provide the first glimpse into a unique genomic signature of human germ cells and pluripotent stem cells and provide genes potentially involved in defining different states of germ-line pluripotency. C1 [Pashai, Nikta; All, Angelo; Gupta, Siddharth] Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21205 USA. [Hao, Haiping] Johns Hopkins Univ, High Throughput Biol Ctr, Deep Sequencing & Microarray Core, Baltimore, MD USA. [All, Angelo] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. [Kerr, Candace L.] Johns Hopkins Univ, Stem Cell Program, Inst Cell Engn, Baltimore, MD USA. [Gearhart, John D.] Univ Penn, Dept Cell & Dev Biol, Inst Regenerat Med, Philadelphia, PA 19104 USA. [Gearhart, John D.] Univ Penn, Dept Anim Biol, Inst Regenerat Med, Philadelphia, PA 19104 USA. [Kerr, Candace L.] Johns Hopkins Univ, Inst Cell Engn, Dept Gynecol & Obstet, Baltimore, MD USA. [Chaerkady, Raghothama] Johns Hopkins Univ, Sch Med, Dept Biol Chem, Baltimore, MD 21205 USA. [De Los Angeles, Alejandro] Childrens Hosp Boston, Div Pediat Hematol Oncol, Stem Cell Transplantat Program, Boston, MA USA. [De Los Angeles, Alejandro] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [De Los Angeles, Alejandro] Harvard Stem Cell Inst, Cambridge, MA USA. RP Pashai, N (reprint author), Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21205 USA. EM ckerr@jhmi.edu OI Hao, Haiping/0000-0002-8826-1568 FU National Institute of Child Health and Human Development (NICHD) [R21 HD057487]; Maryland Stem Cell Research Funds [2007-MSCRFE-0210-01, 2008-MSCRFE-0129-00] FX This work was graciously supported by National Institute of Child Health and Human Development (NICHD) R21 HD057487 (CK) and Maryland Stem Cell Research Funds 2007-MSCRFE-0210-01 (CK) and by 2008-MSCRFE-0129-00 (CK). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 112 TC 8 Z9 9 U1 0 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 21 PY 2012 VL 7 IS 6 AR e39088 DI 10.1371/journal.pone.0039088 PG 19 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 964KY UT WOS:000305695100026 PM 22737227 ER PT J AU Sholukh, AM Mukhtar, MM Humbert, M Essono, SS Watkins, JD Vyas, HK Shanmuganathan, V Hemashettar, G Kahn, M Hu, SL Montefiori, DC Polonis, VR Schur, PH Ruprecht, RM AF Sholukh, Anton M. Mukhtar, Muhammad M. Humbert, Michael Essono, Sosthene S. Watkins, Jennifer D. Vyas, Hemant K. Shanmuganathan, Vivekanandan Hemashettar, Girish Kahn, Maria Hu, Shiu-Lok Montefiori, David C. Polonis, Victoria R. Schur, Peter H. Ruprecht, Ruth M. TI Isolation of Monoclonal Antibodies with Predetermined Conformational Epitope Specificity SO PLOS ONE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN IMMUNE-RESPONSE; CLADE-C ENV; NEUTRALIZING ANTIBODIES; REPLICATION-COMPETENT; RHESUS MACAQUES; CD4 BINDING; B-CELLS; HIV-1; INFECTION AB Existing technologies allow isolating antigen-specific monoclonal antibodies (mAbs) from B cells. We devised a direct approach to isolate mAbs with predetermined conformational epitope specificity, using epitope mimetics (mimotopes) that reflect the three-dimensional structure of given antigen subdomains. We performed differential biopanning using bacteriophages encoding random peptide libraries and polyclonal antibodies (Abs) that had been affinity-purified with either native or denatured antigen. This strategy yielded conformational mimotopes. We then generated mimotope-fluorescent protein fusions, which were used as baits to isolate single memory B cells from rhesus monkeys (RMs). To amplify RM immunoglobulin variable regions, we developed RM-specific PCR primers and generated chimeric simian-human mAbs with predicted epitope specificity. We established proof-of-concept of our strategy by isolating mAbs targeting the conformational V3 loop crown of HIV Env; the new mAbs cross-neutralized viruses of different clades. The novel technology allows isolating mAbs from RMs or other hosts given experimental immunogens or infectious agents. C1 [Sholukh, Anton M.; Mukhtar, Muhammad M.; Humbert, Michael; Essono, Sosthene S.; Watkins, Jennifer D.; Vyas, Hemant K.; Shanmuganathan, Vivekanandan; Hemashettar, Girish; Ruprecht, Ruth M.] Dana Farber Canc Inst, Dept Canc Immunol, Boston, MA 02115 USA. [Sholukh, Anton M.; Mukhtar, Muhammad M.; Humbert, Michael; Essono, Sosthene S.; Watkins, Jennifer D.; Vyas, Hemant K.; Shanmuganathan, Vivekanandan; Hemashettar, Girish; Ruprecht, Ruth M.] Dana Farber Canc Inst, AIDS, Boston, MA 02115 USA. [Sholukh, Anton M.; Mukhtar, Muhammad M.; Humbert, Michael; Essono, Sosthene S.; Watkins, Jennifer D.; Vyas, Hemant K.; Schur, Peter H.; Ruprecht, Ruth M.] Harvard Univ, Sch Med, Boston, MA USA. [Kahn, Maria; Hu, Shiu-Lok] Univ Washington, Dept Pharmaceut, Seattle, WA 98195 USA. [Hu, Shiu-Lok] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. [Montefiori, David C.] Duke Univ, Sch Med, Dept Surg, Durham, NC USA. [Polonis, Victoria R.] Walter Reed Army Inst Res, Mil HIV Res Program, Silver Spring, MD USA. [Schur, Peter H.] Brigham & Womens Hosp, Dept Rheumatol Immunol & Allergy, Boston, MA 02115 USA. RP Sholukh, AM (reprint author), Dana Farber Canc Inst, Dept Canc Immunol, Boston, MA 02115 USA. EM ruth_ruprecht@dfci.harvard.edu RI Hu, Shiu-Lok/A-3196-2008 OI Hu, Shiu-Lok/0000-0003-4336-7964 FU NIH [P01 AI048240, P01 AI048240-08s1, R37 AI034266, P30 AI060354] FX This work was supported by NIH grants P01 AI048240, P01 AI048240-08s1, R37 AI034266, and P30 AI060354. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 37 TC 4 Z9 4 U1 0 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 21 PY 2012 VL 7 IS 6 AR e38943 DI 10.1371/journal.pone.0038943 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 964KY UT WOS:000305695100023 PM 22737224 ER PT J AU Stephens, PJ Tarpey, PS Davies, H Van Loo, P Greenman, C Wedge, DC Nik-Zainal, S Martin, S Varela, I Bignell, GR Yates, LR Papaemmanuil, E Beare, D Butler, A Cheverton, A Gamble, J Hinton, J Jia, MM Jayakumar, A Jones, D Latimer, C Lau, KW McLaren, S McBride, DJ Menzies, A Mudie, L Raine, K Rad, R Chapman, MS Teague, J Easton, D Langerod, A Lee, MTM Shen, CY Tee, BTK Huimin, BW Broeks, A Vargas, AC Turashvili, G Martens, J Fatima, A Miron, P Chin, SF Thomas, G Boyault, S Mariani, O Lakhani, SR van de Vijver, M Van 'Tveer, L Foekens, J Desmedt, C Sotiriou, C Tutt, A Caldas, C Reis, JS Aparicio, SAJR Salomon, AV Borresen-Dale, AL Richardson, AL Campbell, PJ Futreal, PA Stratton, MR AF Stephens, Philip J. Tarpey, Patrick S. Davies, Helen Van Loo, Peter Greenman, Chris Wedge, David C. Nik-Zainal, Serena Martin, Sancha Varela, Ignacio Bignell, Graham R. Yates, Lucy R. Papaemmanuil, Elli Beare, David Butler, Adam Cheverton, Angela Gamble, John Hinton, Jonathan Jia, Mingming Jayakumar, Alagu Jones, David Latimer, Calli Lau, King Wai McLaren, Stuart McBride, David J. Menzies, Andrew Mudie, Laura Raine, Keiran Rad, Roland Chapman, Michael Spencer Teague, Jon Easton, Douglas Langerod, Anita Lee, Ming Ta Michael Shen, Chen-Yang Tee, Benita Tan Kiat Huimin, Bernice Wong Broeks, Annegien Vargas, Ana Cristina Turashvili, Gulisa Martens, John Fatima, Aquila Miron, Penelope Chin, Suet-Feung Thomas, Gilles Boyault, Sandrine Mariani, Odette Lakhani, Sunil R. van de Vijver, Marc Van 'tVeer, Laura Foekens, John Desmedt, Christine Sotiriou, Christos Tutt, Andrew Caldas, Carlos Reis-Filho, Jorge S. Aparicio, Samuel A. J. R. Salomon, Anne Vincent Borresen-Dale, Anne-Lise Richardson, Andrea L. Campbell, Peter J. Futreal, P. Andrew Stratton, Michael R. CA OSBREAC TI The landscape of cancer genes and mutational processes in breast cancer SO NATURE LA English DT Article ID NUCLEOTIDE EXCISION-REPAIR; GENOME-WIDE ASSOCIATION; SWI/SNF COMPLEX; CELLS; SUSCEPTIBILITY; CARCINOMAS; MECHANISMS; MODELS; ARID1A AB All cancers carry somatic mutations in their genomes. A subset, known as driver mutations, confer clonal selective advantage on cancer cells and are causally implicated in oncogenesis(1), and the remainder are passenger mutations. The driver mutations and mutational processes operative in breast cancer have not yet been comprehensively explored. Here we examine the genomes of 100 tumours for somatic copy number changes and mutations in the coding exons of protein-coding genes. The number of somatic mutations varied markedly between individual tumours. We found strong correlations between mutation number, age at which cancer was diagnosed and cancer histological grade, and observed multiple mutational signatures, including one present in about ten per cent of tumours characterized by numerous mutations of cytosine at TpC dinucleotides. Driver mutations were identified in several new cancer genes including AKT2, ARID1B, CASP8, CDKN1B, MAP3K1, MAP3K13, NCOR1, SMARCD1 and TBX3. Among the 100 tumours, we found driver mutations in at least 40 cancer genes and 73 different combinations of mutated cancer genes. The results highlight the substantial genetic diversity underlying this common disease. C1 [Stephens, Philip J.; Tarpey, Patrick S.; Davies, Helen; Van Loo, Peter; Greenman, Chris; Wedge, David C.; Nik-Zainal, Serena; Martin, Sancha; Varela, Ignacio; Bignell, Graham R.; Yates, Lucy R.; Papaemmanuil, Elli; Beare, David; Butler, Adam; Cheverton, Angela; Gamble, John; Hinton, Jonathan; Jia, Mingming; Jayakumar, Alagu; Jones, David; Latimer, Calli; Lau, King Wai; McLaren, Stuart; McBride, David J.; Menzies, Andrew; Mudie, Laura; Raine, Keiran; Rad, Roland; Chapman, Michael Spencer; Teague, Jon; Campbell, Peter J.; Futreal, P. Andrew; Stratton, Michael R.] Wellcome Trust Sanger Inst, Canc Genome Project, Hinxton CB10 1SA, England. [Van Loo, Peter] VIB, Human Genome Lab, Dept Human Genet, B-3000 Louvain, Belgium. [Van Loo, Peter] Katholieke Univ Leuven, B-3000 Louvain, Belgium. [Greenman, Chris] Univ E Anglia, Sch Comp Sci, Norwich NR4 7TJ, Norfolk, England. [Greenman, Chris] Genome Anal Ctr, Norwich NR4 7TJ, Norfolk, England. [Yates, Lucy R.; Tutt, Andrew] Kings Coll London, Breakthrough Breast Canc Res Unit, Sch Med, London SE1 9RT, England. [Yates, Lucy R.] Guys & St Thomas NHS Trust, Dept Clin Oncol, London SE1 7EH, England. [Easton, Douglas] Ctr Canc Genet Epidemiol, Dept Oncol, Strangeways Res Lab, Cambridge CB1 8RN, England. [Easton, Douglas] Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Strangeways Res Lab, Cambridge CB1 8RN, England. [Langerod, Anita; Borresen-Dale, Anne-Lise] Oslo Univ Hosp, Dept Genet, Inst Canc Res, Norwegian Radium Hosp, N-0310 Oslo, Norway. [Lee, Ming Ta Michael; Shen, Chen-Yang] Acad Sinica, Natl Genotyping Ctr, Inst Biomed Sci, Taipei 115, Taiwan. [Tee, Benita Tan Kiat] Singapore Gen Hosp, Dept Gen Surg, Singapore 169608, Singapore. [Huimin, Bernice Wong] Natl Canc Ctr Singapore, NCCS VARI Translat Res Lab, Singapore 169610, Singapore. [Broeks, Annegien; Van 'tVeer, Laura] Netherlands Canc Inst, Dept Expt Therapy, NL-1066 CX Amsterdam, Netherlands. [Vargas, Ana Cristina; Lakhani, Sunil R.] Univ Queensland, Clin Res Ctr, Royal Brisbane & Womens Hosp, Brisbane, Qld 4029, Australia. [Turashvili, Gulisa; Aparicio, Samuel A. J. R.] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V6T 2B5, Canada. [Turashvili, Gulisa; Aparicio, Samuel A. J. R.] British Columbia Canc Res Ctr, Vancouver, BC V5Z 1L3, Canada. [Martens, John; Foekens, John] Erasmus Univ, Dept Med Oncol, Med Ctr, Daniel den Hoed Canc Ctr, NL-3000 CA Rotterdam, Netherlands. [Martens, John; Foekens, John] Canc Genom Ctr, NL-3000 CA Rotterdam, Netherlands. [Fatima, Aquila; Miron, Penelope; Richardson, Andrea L.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Chin, Suet-Feung; Caldas, Carlos] Univ Cambridge, Dept Oncol, Cambridge CB2 0RE, England. [Chin, Suet-Feung; Caldas, Carlos] Canc Res UK, Cambridge Res Inst, Li Ka Shin Ctr, Cambridge CB2 0RE, England. [Thomas, Gilles; Boyault, Sandrine] Univ Lyon 1, INCa Synergie, Ctr Leon Berard, F-69365 Lyon 08, France. [Mariani, Odette; Salomon, Anne Vincent] Inst Curie, Dept Tumor Biol, F-75248 Paris 05, France. [Lakhani, Sunil R.] Univ Queensland, Sch Med, Brisbane, Qld 4006, Australia. [Lakhani, Sunil R.] Royal Brisbane & Womens Hosp, Brisbane, Qld 4029, Australia. [van de Vijver, Marc] Univ Amsterdam, Acad Med Ctr, Dept Pathol, NL-1105 AZ Amsterdam, Netherlands. [Desmedt, Christine; Sotiriou, Christos] Univ Libre Brussels, Breast Canc Translat Lab, Inst Jules Bordet, B-1000 Brussels, Belgium. [Caldas, Carlos] Cambridge Univ Hosp NHS Fdn Trust, NIHR Cambridge Biomed Res Ctr, Cambridge CB2 2QQ, England. [Caldas, Carlos] Cambridge Univ Hosp NHS Fdn Trust, Cambridge Expt Canc Med Ctr, Cambridge CB2 2QQ, England. [Reis-Filho, Jorge S.] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England. [Salomon, Anne Vincent] INSERM, U830, Inst Curie, F-75248 Paris 05, France. [Borresen-Dale, Anne-Lise] Univ Oslo, KG Jebsen Ctr Breast Canc Res, Inst Clin Med, Fac Med, N-0318 Oslo, Norway. [Richardson, Andrea L.] Harvard Univ, Dept Pathol, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Campbell, Peter J.] Addenbrookes Hosp, Dept Haematol, Cambridge CB2 0QQ, England. [Campbell, Peter J.] Univ Cambridge, Dept Haematol, Cambridge CB2 2XY, England. RP Stratton, MR (reprint author), Wellcome Trust Sanger Inst, Canc Genome Project, Wellcome Trust Genome Campus, Hinxton CB10 1SA, England. EM mrs@sanger.ac.uk RI Van Loo, Peter/A-3287-2012; Shen, CY/F-6271-2010; Caldas, Carlos/A-7543-2008; Lee, Ming Ta Michael/N-5396-2015; Varela, Ignacio/G-1699-2016; OI Lee, Ming Ta Michael/0000-0003-2510-8977; Varela, Ignacio/0000-0002-0969-506X; chin, suet-feung/0000-0001-5697-1082; Van Loo, Peter/0000-0003-0292-1949; Wedge, David/0000-0002-7572-3196; Desmedt, Christine/0000-0002-5223-5579; Martin, Sancha/0000-0001-6213-5259 FU Wellcome Trust [077012/Z/05/Z]; Breakthrough Breast Cancer; Wellcome Trust Senior Clinical Research Fellowship [WT088340MA]; Research Foundation - Flanders (FWO); travel grant from the FWO; International Human Frontier Science Program Organization; Norwegian Research Council; Norwegian Cancer Society; Radium Hospital Foundation; Health Region SO; 'Interface INSERM' grant; Department of Health via the National Institute for Health Research comprehensive Biomedical Research Centre award; St Thomas' NHS Foundation Trust; King's College London; King's College Hospital NHS Foundation Trust; Cancer Research UK; National Institute for Health Research; Welsh Assembly Government; HSC R&D Office for Northern Ireland and the Chief Scientist Office, Scotland; MEDIC foundation; Fonds National de Recherche Scientifique; Netherlands Genomics Initiative/Netherlands Organization for Scientific Research; Institut National du Cancer; Fondation Synergie-Lyon-Cancer; Canceropole Lyon Auverge Rhone Alpes; Centre Leon Berard; Ludwig Institute for Cancer Research; Dutch Genomics Initiative-Cancer Genomics Center FX This work was supported by the Wellcome Trust (grant reference 077012/Z/05/Z) and Breakthrough Breast Cancer. P.J.C. is personally funded through a Wellcome Trust Senior Clinical Research Fellowship (grant reference WT088340MA). P. V. L. is a postdoctoral researcher at the Research Foundation - Flanders (FWO) and is a visiting scientist at the Wellcome Trust Sanger Institute, supported by a travel grant from the FWO. I. V. is supported by a fellowship from The International Human Frontier Science Program Organization. A.-L.B.-D. and A. L. are funded by the Norwegian Research Council, The Norwegian Cancer Society, The Radium Hospital Foundation and Health Region SO. A. V. S. was supported by an 'Interface INSERM' grant. J.S.R.-F. is funded in part by Breakthrough Breast Cancer and is a recipient of the 2010 CRUK Future Leaders Prize. D. E. is a Principal Research Fellow of Cancer Research UK. A. T. receives financial support from the Department of Health via the National Institute for Health Research comprehensive Biomedical Research Centre award to Guy's and St Thomas' NHS Foundation Trust in partnership with King's College London, and from King's College Hospital NHS Foundation Trust in conjunction with The Experimental Cancer Medicine Centre Initiative jointly funded by Cancer Research UK, the National Institute for Health Research, the Welsh Assembly Government, the HSC R&D Office for Northern Ireland and the Chief Scientist Office, Scotland. C. D. and C. S. received partial funding from the MEDIC foundation and the Fonds National de Recherche Scientifique. J.M. and J.F. are funded in part by a research grant from the Netherlands Genomics Initiative/Netherlands Organization for Scientific Research. The INCa-Synergie facility received support from the Institut National du Cancer, the Fondation Synergie-Lyon-Cancer, the Canceropole Lyon Auverge Rhone Alpes and the Centre Leon Berard. A. C. V. is funded by The Ludwig Institute for Cancer Research. L.v.'t.V. and A. Broeks receive funding from the Dutch Genomics Initiative-Cancer Genomics Center. We also acknowledge support for sample collection, banking and processing from the Biological Resource Center of Institut Curie; the Breakthrough Breast Cancer Unit; P. Watson and the BCCA Tumour Tissue Repository; the Centre for Translational Genomics; A. Lane and P. T. Simpson; the Australian Biospecimens Network; the Breast Unit at Royal Brisbane and Women's Hospital; the Dana-Farber/Harvard SPORE in breast cancer (reference CA089393); A. M. Sieuwerts; and the Singhealth Tissue Repository, Singapore. We are grateful also for the support of T. B. Tean, and acknowledge the input and guidance of P. Spellman and A. Ashworth. NR 34 TC 670 Z9 682 U1 9 U2 135 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUN 21 PY 2012 VL 486 IS 7403 BP 400 EP + DI 10.1038/nature11017 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 961LV UT WOS:000305466800043 PM 22722201 ER PT J AU Banerji, S Cibulskis, K Rangel-Escareno, C Brown, KK Carter, SL Frederick, AM Lawrence, MS Sivachenko, AY Sougnez, C Zou, LH Cortes, ML Fernandez-Lopez, JC Peng, SY Ardlie, KG Auclair, D Bautista-Pina, V Duke, F Francis, J Jung, J Maffuz-Aziz, A Onofrio, RC Parkin, M Pho, NH Quintanar-Jurado, V Ramos, AH Rebollar-Vega, R Rodriguez-Cuevas, S Romero-Cordoba, SL Schumacher, SE Stransky, N Thompson, KM Uribe-Figueroa, L Baselga, J Beroukhim, R Polyak, K Sgroi, DC Richardson, AL Jimenez-Sanchez, G Lander, ES Gabriel, SB Garraway, LA Golub, TR Melendez-Zajgla, J Toker, A Getz, G Hidalgo-Miranda, A Meyerson, M AF Banerji, Shantanu Cibulskis, Kristian Rangel-Escareno, Claudia Brown, Kristin K. Carter, Scott L. Frederick, Abbie M. Lawrence, Michael S. Sivachenko, Andrey Y. Sougnez, Carrie Zou, Lihua Cortes, Maria L. Fernandez-Lopez, Juan C. Peng, Shouyong Ardlie, Kristin G. Auclair, Daniel Bautista-Pina, Veronica Duke, Fujiko Francis, Joshua Jung, Joonil Maffuz-Aziz, Antonio Onofrio, Robert C. Parkin, Melissa Pho, Nam H. Quintanar-Jurado, Valeria Ramos, Alex H. Rebollar-Vega, Rosa Rodriguez-Cuevas, Sergio Romero-Cordoba, Sandra L. Schumacher, Steven E. Stransky, Nicolas Thompson, Kristin M. Uribe-Figueroa, Laura Baselga, Jose Beroukhim, Rameen Polyak, Kornelia Sgroi, Dennis C. Richardson, Andrea L. Jimenez-Sanchez, Gerardo Lander, Eric S. Gabriel, Stacey B. Garraway, Levi A. Golub, Todd R. Melendez-Zajgla, Jorge Toker, Alex Getz, Gad Hidalgo-Miranda, Alfredo Meyerson, Matthew TI Sequence analysis of mutations and translocations across breast cancer subtypes SO NATURE LA English DT Article ID CELL LUNG-CANCER; PROSTATE-CANCER; COLORECTAL CANCERS; HIGH-FREQUENCY; PIK3CA GENE; GENOME; KINASE; LANDSCAPES; PATTERNS; FUSION AB Breast carcinoma is the leading cause of cancer-related mortality in women worldwide, with an estimated 1.38 million new cases and 458,000 deaths in 2008 alone(1). This malignancy represents a heterogeneous group of tumours with characteristic molecular features, prognosis and responses to available therapy(2-4). Recurrent somatic alterations in breast cancer have been described, including mutations and copy number alterations, notably ERBB2 amplifications, the first successful therapy target defined by a genomic aberration(5). Previous DNA sequencing studies of breast cancer genomes have revealed additional candidate mutations and gene rearrangements(6-10). Here we report the whole-exome sequences of DNA from 103 human breast cancers of diverse subtypes from patients in Mexico and Vietnam compared to matched-normal DNA, together with whole-genome sequences of 22 breast cancer/normal pairs. Beyond confirming recurrent somatic mutations in PIK3CA(11), TP53(6), AKT1(12), GATA3(13) and MAP3K1(10), we discovered recurrent mutations in the CBFB transcription factor gene and deletions of its partner RUNX1. Furthermore, we have identified a recurrent MAGI3-AKT3 fusion enriched in triple-negative breast cancer lacking oestrogen and progesterone receptors and ERBB2 expression. The MAGI3-AKT3 fusion leads to constitutive activation of AKT kinase, which is abolished by treatment with an ATP-competitive AKT small-molecule inhibitor. C1 [Banerji, Shantanu; Cibulskis, Kristian; Carter, Scott L.; Frederick, Abbie M.; Lawrence, Michael S.; Sivachenko, Andrey Y.; Sougnez, Carrie; Zou, Lihua; Cortes, Maria L.; Ardlie, Kristin G.; Auclair, Daniel; Duke, Fujiko; Francis, Joshua; Jung, Joonil; Onofrio, Robert C.; Parkin, Melissa; Pho, Nam H.; Ramos, Alex H.; Schumacher, Steven E.; Stransky, Nicolas; Thompson, Kristin M.; Beroukhim, Rameen; Lander, Eric S.; Gabriel, Stacey B.; Garraway, Levi A.; Golub, Todd R.; Getz, Gad; Meyerson, Matthew] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Banerji, Shantanu; Peng, Shouyong; Schumacher, Steven E.; Beroukhim, Rameen; Polyak, Kornelia; Richardson, Andrea L.; Garraway, Levi A.; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Banerji, Shantanu; Baselga, Jose; Beroukhim, Rameen; Polyak, Kornelia; Sgroi, Dennis C.; Richardson, Andrea L.; Lander, Eric S.; Garraway, Levi A.; Golub, Todd R.; Toker, Alex; Meyerson, Matthew] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Rangel-Escareno, Claudia; Fernandez-Lopez, Juan C.; Quintanar-Jurado, Valeria; Rebollar-Vega, Rosa; Romero-Cordoba, Sandra L.; Uribe-Figueroa, Laura; Jimenez-Sanchez, Gerardo; Melendez-Zajgla, Jorge; Hidalgo-Miranda, Alfredo] Inst Nacl Med Genom, Mexico City 01900, DF, Mexico. [Brown, Kristin K.; Toker, Alex] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [Bautista-Pina, Veronica; Maffuz-Aziz, Antonio; Rodriguez-Cuevas, Sergio] FUCAM, Inst Enfermedades Mama, Mexico City 04980, DF, Mexico. [Baselga, Jose] Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. [Beroukhim, Rameen; Meyerson, Matthew] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Polyak, Kornelia] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Sgroi, Dennis C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Richardson, Andrea L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Lander, Eric S.] MIT, Cambridge, MA 02139 USA. [Golub, Todd R.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. [Golub, Todd R.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Meyerson, M (reprint author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. EM atoker@bidmc.harvard.edu; gadgetz@broadinstitute.org; ahidalgo@inmegen.gob.mx; matthew_meyerson@dfci.harvard.edu RI Meyerson, Matthew/E-7123-2012; Hidalgo-Miranda, Alfredo/B-2123-2010; Romero-Cordoba, Sandra Lorena/A-2246-2014; Schumacher, Steven/E-9821-2013; Rangel-Escareno, Claudia/F-4587-2012; Fernandez, Juan Carlos/C-4976-2013 OI Hidalgo-Miranda, Alfredo/0000-0003-2315-3977; Romero-Cordoba, Sandra Lorena/0000-0002-5591-696X; Schumacher, Steven/0000-0002-6819-5647; Rangel-Escareno, Claudia/0000-0003-1303-0834; Fernandez, Juan Carlos/0000-0003-3680-4193 FU Carlos Slim Health Institute in Mexico; CancerCare Manitoba; University of Manitoba; John Gavin Post-doctoral Fellowship; Genesis Oncology Trust of New Zealand; Mexican Council of Science and Technology (CONACyT); NIH [CA122099]; Dana-Farber/Harvard SPORE in breast cancer under NCI grant [CA089393] FX We would like to thank all patients who contributed samples to this study. This study was a collaboration of the Broad Institute in Cambridge, Massachusetts, USA, and the National Institute of Genomic Medicine (INMEGEN) in Mexico City, Mexico. The work was conducted as part of the Slim Initiative for Genomic Medicine, a project funded by the Carlos Slim Health Institute in Mexico. This work is part of a global effort in collaboration with the International Cancer Genome Consortium (ICGC). The authors would also like to acknowledge J. Barretina and H. Greulich for their critical review of the manuscript. In addition, we would like to acknowledge the technical expertise and data generation efforts of The Broad Institute Biological Samples, Genome Sequencing, and Genetic Analysis Platforms. S. B. has received fellowship support co-sponsored by CancerCare Manitoba and the University of Manitoba. K. K. B. is a recipient of the John Gavin Post-doctoral Fellowship, Genesis Oncology Trust of New Zealand. R. R.-V. and S. L. R.-C. received a scholarship from the Mexican Council of Science and Technology (CONACyT). R. B. is a V Foundation Scholar. A. T. is funded by NIH grant CA122099. This work was partially supported by the Dana-Farber/Harvard SPORE in breast cancer under NCI grant reference CA089393. NR 29 TC 475 Z9 487 U1 18 U2 121 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD JUN 21 PY 2012 VL 486 IS 7403 BP 405 EP 409 DI 10.1038/nature11154 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 961LV UT WOS:000305466800044 PM 22722202 ER PT J AU Catlin, EA Warren, HS Shailam, R Lahoud-Rahme, M Lew, M AF Catlin, Elizabeth A. Warren, H. Shaw Shailam, Randheer Lahoud-Rahme, Manuella Lew, Madelyn TI Case 19-2012: A Premature Newborn Boy with Respiratory Distress SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID HERPES-SIMPLEX-VIRUS; GENITAL HERPES; INFECTION; PREGNANCY C1 [Catlin, Elizabeth A.; Warren, H. Shaw] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Warren, H. Shaw; Lahoud-Rahme, Manuella] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Shailam, Randheer] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Lew, Madelyn] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Catlin, Elizabeth A.; Warren, H. Shaw] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Warren, H. Shaw; Lahoud-Rahme, Manuella] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Shailam, Randheer] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Lew, Madelyn] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Catlin, EA (reprint author), Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. NR 22 TC 4 Z9 4 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 21 PY 2012 VL 366 IS 25 BP 2409 EP 2419 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 961GH UT WOS:000305451700013 PM 22716980 ER PT J AU Dong, YL Wu, X Xu, ZP Zhang, YY Xie, ZC AF Dong, Yuanlin Wu, Xu Xu, Zhipeng Zhang, Yiying Xie, Zhongcong TI Anesthetic Isoflurane Increases Phosphorylated Tau Levels Mediated by Caspase Activation and A beta Generation SO PLOS ONE LA English DT Article ID ALZHEIMERS-DISEASE; INDUCED APOPTOSIS; PROTEIN-LEVELS; MOUSE MODEL; IN-VIVO; MICROTUBULES; HYPERPHOSPHORYLATION; SEVOFLURANE; IMPAIRMENT; EXPOSURE AB Anesthetic isoflurane has been shown to promote Alzheimer's disease (AD) neuropathogenesis by inducing caspase activation and accumulation of beta-amyloid (A beta). Phosphorylation of tau protein is another important feature of AD neuropathogenesis. However, the effects of isoflurane on phosphorylated tau levels remain largely to be determined. We therefore set out to determine whether isoflurane can increase phosphorylated tau levels. 5 to 8 month-old wild-type and AD transgenic mice [B6. Cg-Tg (APPswe, PSEN1dE9) 85Dbo/J] were treated with 1.4% isoflurane for two hours. The mice brain tissues were harvested at six, 12 and 24 hours after the anesthesia. For the in vitro studies, primary neurons from wild-type and the AD transgenic mice were exposed to 2% isoflurane for six hours, and were harvested at the end of anesthesia. The harvested brain tissues and neurons were subjected to Western blot analysis by which the levels of phosphorylated tau protein at Serine 262 (Tau-PS262) were determined. Here we show that the isoflurane anesthesia increased Tau-PS262 levels in brain tissues and primary neurons from the wild-type and AD transgenic mice. Moreover, the isoflurane anesthesia may induce a greater increase in Tau-PS262 levels in primary neurons and brain tissues from the AD transgenic mice. Finally, caspase activation inhibitor Z-VAD and A beta generation inhibitor L-685,458 attenuated the isoflurane-induced increases in Tau-PS262 levels. In conclusion, clinically relevant isoflurane anesthesia increases phosphorylated tau levels, which may result from the isoflurane-induced caspase activation and A beta generation. These findings will promote more studies to determine the effects of anesthetics on tau phosphorylation. C1 [Dong, Yuanlin; Wu, Xu; Xu, Zhipeng; Zhang, Yiying; Xie, Zhongcong] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Geriatr Anesthesia Res Unit, Charlestown, MA USA. [Dong, Yuanlin; Wu, Xu; Xu, Zhipeng; Zhang, Yiying; Xie, Zhongcong] Harvard Univ, Sch Med, Charlestown, MA USA. [Wu, Xu] China Med Univ, Fac Forens Med, Dept Forens Pathol, Shenyang, Peoples R China. RP Dong, YL (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Geriatr Anesthesia Res Unit, Charlestown, MA USA. EM zxie@partners.org FU (National Institutes of Health), USA, Jahnigen Career Development Award (American Geriatrics Society), USA [K08NS048140, R21AG029856, R21AG038994, R01 GM088801]; Investigator Initiated Research Grant (Alzheimer's Association) USA; Cure Alzheimer's Fund, USA FX This research was supported by K08NS048140, R21AG029856, R21AG038994 and R01 GM088801 (National Institutes of Health), USA, Jahnigen Career Development Award (American Geriatrics Society), USA; Investigator Initiated Research Grant (Alzheimer's Association) USA; Cure Alzheimer's Fund, USA (to ZX). The cost of anesthetic isoflurane was generously provided by the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General and Hospital and Harvard Medical School, Boston, MA, USA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 48 TC 26 Z9 28 U1 0 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 20 PY 2012 VL 7 IS 6 AR e39386 DI 10.1371/journal.pone.0039386 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 964KK UT WOS:000305693200072 PM 22745746 ER PT J AU Kessler, DA Maruvka, YE Ouren, J Shnerb, NM AF Kessler, David A. Maruvka, Yosi E. Ouren, Joergen Shnerb, Nadav M. TI You Name It - How Memory and Delay Govern First Name Dynamics SO PLOS ONE LA English DT Article ID DRIFT AB The adoption and abandonment of first names through time is a fascinating phenomenon that may shed light on social dynamics and the forces that determine cultural taste in general. Here we show that baby name dynamics is governed almost solely by deterministic forces, even though the emerging abundance statistics resembles the one obtained from a pure drift model. Exogenous events are shown to affect the name dynamics very rarely, and most of the year-to-year fluctuations around the deterministic trend may be attributed solely to demographic noise. We suggest that the rise and fall of a name reflect an "infection" process with delay and memory. The symmetry between adoption and abandonment speed emerges from our model without further assumptions. C1 [Kessler, David A.; Shnerb, Nadav M.] Bar Ilan Univ, Dept Phys, Ramat Gan, Israel. [Maruvka, Yosi E.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Maruvka, Yosi E.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Ouren, Joergen] Stat Norway, Res Dept, Oslo, Norway. RP Kessler, DA (reprint author), Bar Ilan Univ, Dept Phys, Ramat Gan, Israel. EM nadav.shnerb@gmail.com RI Kessler, David/B-1391-2008 OI Kessler, David/0000-0002-5279-1655 FU Israeli Science Foundation BIKURA [1026/11] FX The work was supported by Israeli Science Foundation BIKURA grant no. 1026/11. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 16 TC 5 Z9 5 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 20 PY 2012 VL 7 IS 6 AR e38790 DI 10.1371/journal.pone.0038790 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 964KK UT WOS:000305693200023 PM 22745679 ER PT J AU Canellos, GP AF Canellos, George P. TI Brentuximab Vedotin and Panobinostat: New Drugs for Hodgkin's Lymphoma-Can They Make One of Medical Oncology's Chemotherapy Success Stories More Successful? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID DISEASE; ABVD; GEMCITABINE; BEACOPP C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Canellos, GP (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 15 TC 8 Z9 8 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2012 VL 30 IS 18 BP 2171 EP 2172 DI 10.1200/JCO.2011.39.6416 PG 2 WC Oncology SC Oncology GA 960TJ UT WOS:000305413200004 PM 22547611 ER PT J AU Burstein, HJ Piccart-Gebhart, MJ Perez, EA Hortobagyi, GN Wolmark, N Albain, KS Norton, L Winer, EP Hudis, CA AF Burstein, Harold J. Piccart-Gebhart, Martine J. Perez, Edith A. Hortobagyi, Gabriel N. Wolmark, Norman Albain, Kathy S. Norton, Larry Winer, Eric P. Hudis, Clifford A. TI Choosing the Best Trastuzumab-Based Adjuvant Chemotherapy Regimen: Should We Abandon Anthracyclines? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID HER2-POSITIVE BREAST-CANCER; NSABP B-31; PACLITAXEL; CONCURRENT; EFFICACY; THERAPY; TRIAL; HER2 C1 [Burstein, Harold J.; Winer, Eric P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Piccart-Gebhart, Martine J.] Inst Jules Bordet, B-1000 Brussels, Belgium. [Perez, Edith A.] Mayo Clin, Jacksonville, FL 32224 USA. [Hortobagyi, Gabriel N.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Wolmark, Norman] Allegheny Gen Hosp, Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA 15212 USA. [Albain, Kathy S.] Loyola Univ, Chicago Stritch Sch Med, Maywood, IL 60153 USA. [Norton, Larry; Hudis, Clifford A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Burstein, HJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. OI Norton, Larry/0000-0003-3701-9250 NR 19 TC 22 Z9 22 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2012 VL 30 IS 18 BP 2179 EP 2182 DI 10.1200/JCO.2012.42.0695 PG 4 WC Oncology SC Oncology GA 960TJ UT WOS:000305413200008 PM 22614986 ER PT J AU Hassett, MJ Silver, SM Hughes, ME Blayney, DW Edge, SB Herman, JG Hudis, CA Marcom, PK Pettinga, JE Share, D Theriault, R Wong, YN Vandergrift, JL Niland, JC Weeks, JC AF Hassett, Michael J. Silver, Samuel M. Hughes, Melissa E. Blayney, Douglas W. Edge, Stephen B. Herman, James G. Hudis, Clifford A. Marcom, P. Kelly Pettinga, Jane E. Share, David Theriault, Richard Wong, Yu-Ning Vandergrift, Jonathan L. Niland, Joyce C. Weeks, Jane C. TI Adoption of Gene Expression Profile Testing and Association With Use of Chemotherapy Among Women With Breast Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RT-PCR ASSAY; ECONOMIC-ANALYSIS; ADJUVANT TREATMENT; PREDICT SURVIVAL; HORMONAL-THERAPY; VALIDATION; RECURRENCE; TAMOXIFEN; UPDATE; TRENDS AB Purpose Gene expression profile (GEP) testing is a relatively new technology that offers the potential of personalized medicine to patients, yet little is known about its adoption into routine practice. One of the first commercially available GEP tests, a 21-gene profile, was developed to estimate the benefit of adjuvant chemotherapy for hormone receptor-positive breast cancer (HR-positive BC). Patients and Methods By using a prospective registry data set outlining the routine care provided to women diagnosed from 2006 to 2008 with HR-positive BC at 17 comprehensive and community-based cancer centers, we assessed GEP test adoption and the association between testing and chemotherapy use. Results Of 7,375 women, 20.4% had GEP testing and 50.2% received chemotherapy. Over time, testing increased (14.7% in 2006 to 27.5% in 2008; P < .01) and use of chemotherapy decreased (53.9% in 2006 to 47.0% in 2008; P < .01). Characteristics independently associated with lower odds of testing included African American versus white race (odds ratio [OR], 0.70; 95% CI, 0.54 to 0.92) and high school or less versus more than high school education (OR, 0.63; 95% CI, 0.52 to 0.76). Overall, testing was associated with lower odds of chemotherapy use (OR, 0.70; 95% CI, 0.62 to 0.80). Stratified analyses demonstrated that for small, node-negative cancers, testing was associated with higher odds of chemotherapy use (OR, 11.13; 95% CI, 5.39 to 22.99), whereas for node-positive and large node-negative cancers, testing was associated with lower odds of chemotherapy use (OR, 0.11; 95% CI, 0.07 to 0.17). Conclusion There has been a progressive increase in use of this GEP test and an associated shift in the characteristics of and overall reduction in the proportion of women with HR-positive BC receiving adjuvant chemotherapy. J Clin Oncol 30:2218-2226. (c) 2012 by American Society of Clinical Oncology C1 [Hassett, Michael J.] Dana Farber Canc Inst, Dept Med Oncol, Ctr Outcomes & Policy Res, Boston, MA 02215 USA. [Silver, Samuel M.] Univ Michigan, Ctr Canc, Ann Arbor, MI 48109 USA. [Herman, James G.] Sparrow Reg Canc Ctr, Lansing, MI USA. [Pettinga, Jane E.] Spectrum Hlth, Grand Rapids, MI USA. [Share, David] BlueCross BlueShield Michigan, Detroit, MI USA. [Blayney, Douglas W.] Stanford Canc Ctr, Stanford, CA USA. [Niland, Joyce C.] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Edge, Stephen B.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Hudis, Clifford A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Marcom, P. Kelly] Duke Univ, Med Ctr, Duke Comprehens Canc Ctr, Durham, NC 27710 USA. [Theriault, Richard] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Wong, Yu-Ning] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Vandergrift, Jonathan L.] Natl Comprehens Canc Network, Ft Washington, MD USA. RP Hassett, MJ (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Ctr Outcomes & Policy Res, 450 Brookline Ave, Boston, MA 02215 USA. EM michael_hassett@dfci.harvard.edu FU National Cancer Institute to Dana-Farber Cancer Institute [CA89393]; BlueCross BlueShield of Michigan; American Society of Clinical Oncology Career Development Award; Susan G. Komen for the Cure Career Catalyst Award FX Supported by Grant No. CA89393 from the National Cancer Institute to Dana-Farber Cancer Institute and BlueCross BlueShield of Michigan and by an American Society of Clinical Oncology Career Development Award (M.J.H.) and a Susan G. Komen for the Cure Career Catalyst Award (M.J.H.). NR 42 TC 55 Z9 55 U1 1 U2 8 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2012 VL 30 IS 18 BP 2218 EP 2226 DI 10.1200/JCO.2011.38.5740 PG 9 WC Oncology SC Oncology GA 960TJ UT WOS:000305413200014 PM 22585699 ER PT J AU Neal, JW Sequist, LV AF Neal, Joel W. Sequist, Lecia V. TI Complex Role of Histone Deacetylase Inhibitors in the Treatment of Non-Small-Cell Lung Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID MESENCHYMAL TRANSITION; GROWTH; SENSITIVITY; EXPRESSION; ERLOTINIB; LINES; VORINOSTAT; MUTATIONS; GEFITINIB; MECHANISMS C1 [Neal, Joel W.] Stanford Canc Inst, Stanford, CA 94305 USA. [Sequist, Lecia V.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Neal, JW (reprint author), Stanford Canc Inst, Stanford, CA 94305 USA. NR 28 TC 7 Z9 7 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2012 VL 30 IS 18 BP 2280 EP 2282 DI 10.1200/JCO.2011.41.0860 PG 3 WC Oncology SC Oncology GA 960TJ UT WOS:000305413200022 PM 22508823 ER PT J AU Barry, MJ Gallagher, PM Skinner, JS Fowler, FJ AF Barry, Michael J. Gallagher, Patricia M. Skinner, Jonathan S. Fowler, Floyd J., Jr. TI Are Medicare-Based Findings Applicable to All Prostatectomy Patients? Reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter C1 [Barry, Michael J.] Massachusetts Gen Hosp, Med Practices Evaluat Ctr, Boston, MA 02114 USA. [Barry, Michael J.; Fowler, Floyd J., Jr.] Fdn Informed Med Decis Making, Boston, MA USA. [Gallagher, Patricia M.; Fowler, Floyd J., Jr.] Univ Massachusetts, Survey Res Ctr, Boston, MA 02125 USA. [Skinner, Jonathan S.] Dartmouth Coll, Hanover, NH 03755 USA. [Skinner, Jonathan S.] Dartmouth Inst Hlth Policy & Clin Practice, Hanover, NH USA. RP Barry, MJ (reprint author), Massachusetts Gen Hosp, Med Practices Evaluat Ctr, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2012 VL 30 IS 18 BP 2287 EP 2287 DI 10.1200/JCO.2012.42.1305 PG 1 WC Oncology SC Oncology GA 960TJ UT WOS:000305413200025 ER PT J AU Hermos, JA AF Hermos, John A. TI Posttraumatic Stress Disorder and Opioid Use Among US Veterans SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID LONG-TERM; BENZODIAZEPINE; PRESCRIPTIONS C1 VA Boston Healthcare Syst, VA Cooperat Studies Program, Boston, MA USA. RP Hermos, JA (reprint author), VA Boston Healthcare Syst, VA Cooperat Studies Program, Boston, MA USA. EM john.hermos@va.gov NR 3 TC 0 Z9 0 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 20 PY 2012 VL 307 IS 23 BP 2485 EP 2485 DI 10.1001/jama.2012.6234 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 960MB UT WOS:000305391400013 PM 22797438 ER PT J AU Seal, K Krebs, E Neylan, T AF Seal, Karen Krebs, Erin Neylan, Thomas TI Posttraumatic Stress Disorder and Opioid Use Among US Veterans Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID CHRONIC NONCANCER PAIN C1 [Seal, Karen; Neylan, Thomas] San Francisco VA Med Ctr, San Francisco, CA USA. [Krebs, Erin] Minneapolis Vet Affairs Hlth Care Syst, Minneapolis, MN USA. RP Seal, K (reprint author), San Francisco VA Med Ctr, San Francisco, CA USA. EM karen.seal@ucsf.edu NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 20 PY 2012 VL 307 IS 23 BP 2485 EP 2486 DI 10.1001/jama.2012.6236 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 960MB UT WOS:000305391400014 ER PT J AU Ranieri, VM Rubenfeld, GD Thompson, BT Ferguson, ND Caldwell, E Fan, E Camporota, L Slutsky, AS AF Ranieri, V. Marco Rubenfeld, Gordon D. Thompson, B. Taylor Ferguson, Niall D. Caldwell, Ellen Fan, Eddy Camporota, Luigi Slutsky, Arthur S. CA ARDS Definition Task Force TI Acute Respiratory Distress Syndrome The Berlin Definition SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ACUTE LUNG INJURY; PULMONARY-ARTERY; INTEROBSERVER VARIABILITY; CLINICAL-TRIAL; MORTALITY; ARDS; EPIDEMIOLOGY; PRESSURE; CATHETER; OUTCOMES AB The acute respiratory distress syndrome (ARDS) was defined in 1994 by the American-European Consensus Conference (AECC); since then, issues regarding the reliability and validity of this definition have emerged. Using a consensus process, a panel of experts convened in 2011 (an initiative of the European Society of Intensive Care Medicine endorsed by the American Thoracic Society and the Society of Critical Care Medicine) developed the Berlin Definition, focusing on feasibility, reliability, validity, and objective evaluation of its performance. A draft definition proposed 3 mutually exclusive categories of ARDS based on degree of hypoxemia: mild (200 mm Hg= 10 cm H2O), and corrected expired volume per minute (>= 10 L/min). The draft Berlin Definition was empirically evaluated using patient-level meta-analysis of 4188 patients with ARDS from 4 multicenter clinical data sets and 269 patients with ARDS from 3 single-center data sets containing physiologic information. The 4 ancillary variables did not contribute to the predictive validity of severe ARDS for mortality and were removed from the definition. Using the Berlin Definition, stages of mild, moderate, and severe ARDS were associated with increased mortality (27%; 95% CI, 24%-30%; 32%; 95% CI, 29%-34%; and 45%; 95% CI, 42%-48%, respectively; P < .001) and increased median duration of mechanical ventilation in survivors (5 days; inter-quartile [IQR], 2-11; 7 days; IQR, 4-14; and 9 days; IQR, 5-17, respectively; P < .001). Compared with the AECC definition, the final Berlin Definition had better predictive validity for mortality, with an area under the receiver operating curve of 0.577 (95% CI, 0.561-0.593) vs 0.536 (95% CI, 0.520-0.553; P < .001). This updated and revised Berlin Definition for ARDS addresses a number of the limitations of the AECC definition. The approach of combining consensus discussions with empirical evaluation may serve as a model to create more accurate, evidence-based, critical illness syndrome definitions and to better inform clinical care, research, and health services planning. JAMA. 2012; 307(23):2526-2533 Published online May 21, 2012. doi: 10.1001/jama.2012.5669 www.jama.com C1 [Rubenfeld, Gordon D.] Univ Toronto, Program Trauma Emergency & Crit Care, Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. [Ranieri, V. Marco] Univ Turin, Dept Anesthesia & Intens Care Med, Turin, Italy. [Thompson, B. Taylor; Caldwell, Ellen] Univ Toronto, Interdept Div Crit Care Med, Toronto, ON M4N 3M5, Canada. [Ferguson, Niall D.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Ferguson, Niall D.] Harvard Univ, Sch Med, Boston, MA USA. [Caldwell, Ellen; Camporota, Luigi] Univ Hlth Network, Dept Med, Toronto, ON, Canada. [Caldwell, Ellen; Camporota, Luigi] Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. [Fan, Eddy] Univ Washington, Div Pulm & Crit Care Med, Seattle, WA USA. [Camporota, Luigi] Guys & St Thomas NHS Fdn Trust, Dept Crit Care, Kings Hlth Partners, London, England. [Slutsky, Arthur S.] Univ Toronto, Keenan Res Ctr, Li Ka Shing Knowledge Inst, Interdept Div Crit Care Med,St Michaels Hosp, Toronto, ON M4N 3M5, Canada. RP Rubenfeld, GD (reprint author), Univ Toronto, Program Trauma Emergency & Crit Care, Sunnybrook Hlth Sci Ctr, 2075 Bayview Ave, Toronto, ON M4N 3M5, Canada. EM gordon.rubenfeld@sunnybrook.ca OI Ferguson, Niall/0000-0002-6213-5264 FU Maquet; Hemodec; Ikaria; Faron; Cerus; US Biotest; Sirius Genetics; sanofi-aventis; Immunetrics; Abbott; Eli Lilly; National Heart, Lung, and Blood Institute; GlaxoSmithKline; Tarix; European Society of Intensive Care Medicine; National Institutes of Health [R01HL067939]; Canadian Institutes of Health Research New Investigator Award (Ottawa, Canada) FX All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Ranieri reported receiving consulting fees or honoraria from Maquet and Hemodec and board membership from Faron. Dr Rubenfeld reported receiving consulting fees or honoraria from Ikaria, Faron, and Cerus. Dr Thompson reported receiving support for travel from European Society of Intensive Care Medicine; being an advisory board member of Hemodec and AstraZeneca; receiving consultancy fees from US Biotest, Sirius Genetics, sanofi-aventis, Immunetrics, Abbott, and Eli Lilly; and receiving grants from the National Heart, Lung, and Blood Institute. Dr Slutsky reported receiving support for travel expenses from European Society of Intensive Care Medicine; board membership from Ikaria; receiving consultancy fees from GlaxoSmithKline and Tarix; having stock/stock options with Apeiron and Tarix; and sitting on advisory boards for Maquet Medical and NovaLung and steering committees for HemoDec and Eli Lilly. No other authors reported any financial disclosures.; This work was supported by the European Society of Intensive Care Medicine and grant R01HL067939 from the National Institutes of Health (Dr Rubenfeld). Dr Ferguson is supported by a Canadian Institutes of Health Research New Investigator Award (Ottawa, Canada). NR 33 TC 1146 Z9 1238 U1 17 U2 136 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 20 PY 2012 VL 307 IS 23 BP 2526 EP 2533 DI 10.1001/jama.2012.5669 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 960MB UT WOS:000305391400029 ER PT J AU Blinderman, CD Krakauer, EL Solomon, MZ AF Blinderman, Craig D. Krakauer, Eric L. Solomon, Mildred Z. TI Challenges of Do-Not-Attempt-Resuscitation Orders Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID CARDIAC MASSAGE C1 [Blinderman, Craig D.] Columbia Univ, Med Ctr, New York, NY 10027 USA. [Krakauer, Eric L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Solomon, Mildred Z.] Harvard Univ, Sch Med, Boston, MA USA. RP Blinderman, CD (reprint author), Columbia Univ, Med Ctr, New York, NY 10027 USA. EM cdb21@columbia.edu NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 20 PY 2012 VL 307 IS 23 BP 2488 EP 2489 DI 10.1001/jama.2012.5607 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 960MB UT WOS:000305391400020 ER PT J AU Prabhakar, H Cooper, JB Sabel, A Weckbach, S Mehler, PS Stahel, PF AF Prabhakar, Hari Cooper, Jeffrey B. Sabel, Allison Weckbach, Sebastian Mehler, Philip S. Stahel, Philip F. TI Introducing standardized "readbacks" to improve patient safety in surgery: a prospective survey in 92 providers at a public safety-net hospital SO BMC SURGERY LA English DT Article ID OPERATING-ROOM; UNIVERSAL PROTOCOL; MEDICAL ERRORS; WRONG-SITE; MORTALITY; AVIATION; IMPLEMENTATION; COMMUNICATION; PHYSICIANS; MORBIDITY AB Background: Communication breakdowns represent the main root cause of preventable complications which lead to harm to surgical patients. Standardized readbacks have been successfully implemented as a main pillar of professional aviation safety for decades, to ensure a safe closed-loop communication between air traffic control and individual pilots. The present study was designed to determine the perception of staff in perioperative services regarding the role of standardized readbacks for improving patient safety in surgery at a single public safety-net hospital and level 1 trauma center. Methods: A 12-item questionnaire was sent to 180 providers in perioperative services at Denver Health Medical Center. The survey was designed to determine the individual participants' perception of (1) appropriateness of current readback processes; (2) willingness to attend a future training module on this topic; (3) specific scenarios in which readbacks may be effective; and (4) perceived major barriers to the implementation of standardized readbacks. Survey results were compared between departments (surgery versus anesthesia) and between specific staff roles (attending or midlevel provider, resident physician, nursing staff), using non-parametric tests. Results: The response rate to the survey was 50.1 % (n = 92). Respondents overwhelmingly recognized the role of readbacks in reducing communication errors and improving patient safety. There was a strong agreement among respondents to support participation in a readbacks training program. There was no difference in the responses between the surgery and anesthesia departments. There was a statistically significant difference in the healthcare providers willingness to attend a short training module on readbacks (p < 0.001). Resident physicians were less likely to endorse the importance of readbacks in reducing communication errors (p = 0.01) and less willing to attend a short training module on readbacks (p < 0.001), as compared to staff providers and nursing staff. The main challenge for respondents, which emanated from their responses, appeared to relate to determining the ideal scenarios in which readbacks may be most appropriately used. Overall, respondents strongly felt that readbacks had an important role in patient handoffs, patient orders regarding critical results, counting and verifying surgical instruments, and delegating multiple perioperative tasks. Conclusion: The majority of all respondents appear to perceive standardized readbacks as an effective tool for reducing and/or preventing adverse events in the care of surgical patients, derived from a breakdown in communication among perioperative caregivers. Further work needs to be done to define the exact clinical scenarios in which readbacks may be most efficiently implemented, including the definition of a uniform set of scripted quotes and phrases, which should likely be standardized in concert with the aviation safety model. C1 [Weckbach, Sebastian; Stahel, Philip F.] Univ Colorado, Dept Orthopaed, Sch Med, Denver, CO 80204 USA. [Stahel, Philip F.] Univ Colorado, Sch Med, Denver Hlth Med Ctr, Dept Orthopaed Surg, Denver, CO 80204 USA. [Stahel, Philip F.] Univ Colorado, Sch Med, Denver Hlth Med Ctr, Dept Neurosurg, Denver, CO 80204 USA. [Prabhakar, Hari; Cooper, Jeffrey B.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Cooper, Jeffrey B.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Cambridge, MA 02139 USA. [Sabel, Allison] Univ Colorado, Dept Biostat & Informat, Sch Publ Hlth, Denver, CO 80204 USA. [Sabel, Allison; Mehler, Philip S.] Univ Colorado, Dept Patient Safety & Qual, Sch Publ Hlth, Denver, CO 80204 USA. [Mehler, Philip S.] Univ Colorado, Dept Internal Med, Sch Publ Hlth, Denver, CO 80204 USA. [Cooper, Jeffrey B.] Ctr Med Simulat, Cambridge, MA 02139 USA. RP Stahel, PF (reprint author), Univ Colorado, Dept Orthopaed, Sch Med, 777 Bannock St, Denver, CO 80204 USA. EM philip.stahel@dhha.org NR 37 TC 5 Z9 5 U1 2 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2482 J9 BMC SURG JI BMC Surg. PD JUN 19 PY 2012 VL 12 AR 8 DI 10.1186/1471-2482-12-8 PG 8 WC Surgery SC Surgery GA 993YF UT WOS:000307895300001 PM 22713158 ER PT J AU Fong, TG Jones, RN Marcantonio, ER Tommet, D Gross, AL Habtemariam, D Schmitt, E Yap, L Inouye, SK AF Fong, Tamara G. Jones, Richard N. Marcantonio, Edward R. Tommet, Douglas Gross, Alden L. Habtemariam, Daniel Schmitt, Eva Yap, Liang Inouye, Sharon K. TI Adverse Outcomes After Hospitalization and Delirium in Persons With Alzheimer Disease SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID CONFUSION ASSESSMENT METHOD; COGNITIVE IMPAIRMENT; ELDERLY-PATIENTS; DEMENTIA; CARE; DECLINE; ASSOCIATION; VALIDATION; FREQUENCY; DATABASES AB Background: Hospitalization, frequently complicated by delirium, can be a life-changing event for patients with Alzheimer disease (AD). Objective: To determine risks for institutionalization, cognitive decline, or death associated with hospitalization and delirium in patients with AD. Design: Prospective cohort enrolled between 1991 and 2006 into the Massachusetts Alzheimer's Disease Research Center (MADRC) patient registry. Setting: Community-based. Participants: 771 persons aged 65 years or older with a clinical diagnosis of AD. Measurements: Hospitalization, delirium, death, and institutionalization were identified through administrative databases. Cognitive decline was defined as a decrease of 4 or more points on the Blessed Information-Memory-Concentration test score. Multivariate analysis was used to calculate adjusted relative risks (RRs). Results: Of 771 participants with AD, 367 (48%) were hospitalized and 194 (25%) developed delirium. Hospitalized patients who did not have delirium had an increased risk for death (adjusted RR, 4.7 95% CI, 1.9 to 11.6]) and institutionalization (adjusted RR, 6.9 [ CI, 4.0 to 11.7]). With delirium, risk for death (adjusted RR, 5.4 [CI, 2.3 to 12.5]) and institutionalization (adjusted RR, 9.3 [CI, 5.5 to 15.7]) increased further. With hospitalization and delirium, the adjusted RR for cognitive decline for patients with AD was 1.6 (CI, 1.2 to 2.3). Among hospitalized patients with AD, 21% of the incidences of cognitive decline, 15% of institutionalization, and 6% of deaths were associated with delirium. Limitations: Cognitive outcome was missing in 291 patients. Sensitivity analysis was performed to test the effect of missing data, and a composite outcome was used to decrease the effect of missing data. Conclusion: Approximately 1 in 8 hospitalized patients with AD who develop delirium will have at least 1 adverse outcome, including death, institutionalization, or cognitive decline, associated with delirium. Delirium prevention may represent an important strategy for reducing adverse outcomes in this population. C1 [Fong, Tamara G.] Hebrew SeniorLife, Aging Brain Ctr, Inst Aging Res, Boston, MA 02131 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Fong, TG (reprint author), Hebrew SeniorLife, Aging Brain Ctr, Inst Aging Res, 1200 Ctr St, Boston, MA 02131 USA. EM tfong@bidmc.harvard.edu RI Jones, Richard/J-3488-2013 OI Jones, Richard/0000-0002-1049-218X FU National Institute on Aging; MADRC; Alzheimer's Association [IIRG-08-88737]; National Institute on Aging [P50AG005134, P01AG031720, K24AG035075]; Aging Brain Center, Institute for Aging Research, Hebrew SeniorLife FX National Institute on Aging and the MADRC.; Funded in part by grant IIRG-08-88737 to Dr. Inouye from the Alzheimer's Association and grants P50AG005134 to Drs. Inouye and Yap, P01AG031720 to Dr. Inouye, and K24AG035075 to Dr. Marcantonio from the National Institute on Aging, as well as the Aging Brain Center, Institute for Aging Research, Hebrew SeniorLife. NR 32 TC 50 Z9 52 U1 1 U2 10 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUN 19 PY 2012 VL 156 IS 12 BP 848 EP U121 DI 10.7326/0003-4819-156-12-201206190-00005 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 992NF UT WOS:000307783200014 PM 22711077 ER PT J AU Maselli, DJ Anzueto, A AF Maselli, Diego J. Anzueto, Antonio TI The need to further understand who gets hospitalized for a COPD exacerbation SO MULTIDISCIPLINARY RESPIRATORY MEDICINE LA English DT Editorial Material ID OBSTRUCTIVE PULMONARY-DISEASE; MORTALITY; PREVENTION C1 [Maselli, Diego J.; Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, S Texas Vet Hlth Care Syst, Audie L Murphy Div, Dept Med,Div Pulm Crit Care Med, San Antonio, TX 78229 USA. RP Maselli, DJ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, S Texas Vet Hlth Care Syst, Audie L Murphy Div, Dept Med,Div Pulm Crit Care Med, San Antonio, TX 78229 USA. EM masellicacer@uthscsa.edu NR 12 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 2049-6958 J9 MULTIDISCIP RESP MED JI Multidscip. Respir. Med. PD JUN 19 PY 2012 VL 7 AR 7 DI 10.1186/2049-6958-7-7 PG 2 WC Respiratory System SC Respiratory System GA 984YL UT WOS:000307229700002 PM 22958418 ER PT J AU Farbota, KD Bendlin, BB Alexander, AL Rowley, HA Dempsey, RJ Johnson, SC AF Farbota, Kimberly D. Bendlin, Barbara B. Alexander, Andrew L. Rowley, Howard A. Dempsey, Robert J. Johnson, Sterling C. TI Longitudinal diffusion tensor imaging and neuropsychological correlates in traumatic brain injury patients SO FRONTIERS IN HUMAN NEUROSCIENCE LA English DT Article DE traumatic brain injury; diffusion tensor imaging; longitudinal; neuropsychology; recovery; DTI; TBI ID CORPUS-CALLOSUM MICROSTRUCTURE; WHITE-MATTER INTEGRITY; AXONAL INJURY; DAMAGE; MODEL; MRI; ADOLESCENTS; ACTIVATION; PLASTICITY; FASCICULUS AB Traumatic brain injury (TBI) often involves focal cortical injury and white matter (WM) damage that can be measured shortly after injury. Additionally, slowly evolving WM change can be observed but there is a paucity of research on the duration and spatial pattern of long-term changes several years post-injury. The current study utilized diffusion tensor imaging to identify regional WM changes in 12 TBI patients and nine healthy controls at three time points over a four year period. Neuropsychological testing was also administered to each participant at each time point. Results indicate that TBI patients exhibit longitudinal changes to WM indexed by reductions in fractional anisotropy (FA) in the corpus callosum, as well as FA increases in bilateral regions of the superior longitudinal fasciculus (SLF) and portions of the optic radiation (OR). FA changes appear to be driven by changes in radial (not axial) diffusivity, suggesting that observed longitudinal FA changes may be related to changes in myelin rather than to axons. Neuropsychological correlations indicate that regional FA values in the corpus callosum and sagittal stratum (SS) correlate with performance on finger tapping and visuomotor speed tasks (respectively) in TBI patients, and that longitudinal increases in FA in the SS, SLF, and OR correlate with improved performance on the visuomotor speed (SS) task as well as a derived measure of cognitive control (SLF, OR). The results of this study showing progressive WM deterioration for several years post-injury contribute to a growing literature supporting the hypothesis that TBI should be viewed not as an isolated incident but as a prolonged disease state. The observations of long-term neurological and functional improvement provide evidence that some ameliorative change may be occurring concurrently with progressive degeneration. C1 [Farbota, Kimberly D.; Bendlin, Barbara B.; Johnson, Sterling C.] William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Madison, WI USA. [Farbota, Kimberly D.] Univ Wisconsin, Neurosci Training Program, Madison, WI 53705 USA. [Bendlin, Barbara B.; Johnson, Sterling C.] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI 53705 USA. [Alexander, Andrew L.] Univ Wisconsin, Dept Med Phys, Sch Med & Publ Hlth, Madison, WI 53705 USA. [Rowley, Howard A.] Univ Wisconsin, Dept Radiol, Sch Med & Publ Hlth, Madison, WI 53705 USA. [Dempsey, Robert J.] Univ Wisconsin, Dept Neurol Surg, Sch Med & Publ Hlth, Madison, WI 53705 USA. RP Johnson, SC (reprint author), Univ Wisconsin, William S Middleton Mem VA Hosp, Dept Med, 2500 Overlook Terrace, Madison, WI 53705 USA. EM scj@medicine.wisc.edu OI Bendlin, Barbara/0000-0002-0580-9875 FU Department of Veterans Affairs; NIH [MH65723, AG000213] FX This study was supported by a Merit Review Grant from the Department of Veterans Affairs, the NIH MH65723 (SCJ), NIH AG000213 and by the facilities and resources of the William S. Middleton Memorial Veterans Hospital. The assistance of Lisa Newman, Amy Hawley, Donald McLaren, and Erik Kastman is greatly appreciated. We would also like to acknowledge the support of researchers and staff at the Waisman Center , University of Wisconsin, Madison, where MR imaging took place . Finally, we thank all the patients who took part in this study . The contents of this report do not necessarily represent the views of the Department of Veterans Affairs or the United States Government. NR 59 TC 33 Z9 35 U1 2 U2 14 PU FRONTIERS RES FOUND PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-5161 J9 FRONT HUM NEUROSCI JI Front. Hum. Neurosci. PD JUN 19 PY 2012 VL 6 AR 160 DI 10.3389/fnhum.2012.00160 PG 15 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA 965SK UT WOS:000305787400001 PM 22723773 ER PT J AU Chen, LJ Tam, POS Leung, DYL Fan, AH Zhang, MZ Tham, CCY Chiang, SWY Fan, BJ Wang, NL Pang, CP AF Chen, Li Jia Tam, Pancy O. S. Leung, Dexter Y. L. Fan, Alex H. Zhang, Mingzhi Tham, Clement C. Y. Chiang, Sylvia W. Y. Fan, Bao Jian Wang, Ningli Pang, Chi Pui TI SNP rs1533428 at 2p16.3 as a marker for late-onset primary open-angle glaucoma SO MOLECULAR VISION LA English DT Article ID GENOME-WIDE ASSOCIATION; NORMAL-TENSION GLAUCOMA; GENE POLYMORPHISMS; MUTATION PATTERN; COMMON VARIANTS; POPULATION; OPTINEURIN; LOCUS; SUSCEPTIBILITY; IDENTIFICATION AB Purpose: To investigate the associations between gene variants in cholesterol 24S-hydroxylase (CYP46A1), LIM homeobox transcription factor 1-beta (LMX1B), plexin domain containing 2 (PLXDC2), toll-like receptor 4 (TLR4), transmembrane and tetratricopeptide repeat containing 2 (TMTC2), zona pellucida glycoprotein 4 (ZP4), chromosome 2p16.3, and primary open-angle glaucoma (POAG). Methods: We studied 462 POAG patients and 577 controls from three cohorts (Hong Kong, Shantou, and Beijing, China). Twelve single-nucleotide polymorphisms (SNPs) were genotyped in the Hong Kong cohort using TaqMan genotyping assay. Significant associations were validated in the Shantou and Beijing cohorts. Results: Association of POAG with TLR4 rs7037117, in a recessive model, was identified in the Hong Kong and Shantou cohorts (both southern Chinese, p(rec)=0.0019) but not the Beijing cohort (northern Chinese). rs1533428 at chromosome 2p16.3 showed a consistent trend of age-specific association in all three cohorts. Genotypes TT + CT conferred a 2.16 fold of significantly increased risk to late-onset POAG (p(dom)=0.00025), but no significant risk to POAG of younger ages of onset in the combined cohort. A joint effect was found between rs7037117 and rs1533428, with carriers of both higher-risk genotypes having a 4.53 fold of increased disease risk (p=0.00028). Conclusions: Our study reveals discrepant association patterns of 12 candidate SNPs in 7 genes/loci with POAG in Chinese, provides positive replications for POAG markers rs1533428 at 2p16.3 and TLR4 rs7037117, and suggests that rs1533428 is a putative risk variant for late-onset POAG. The identification of an age-specific association between rs1533428 and late-onset POAG highlights a new genotype-phenotype association in POAG. Further studies are warranted to confirm the age-specific association. C1 [Chen, Li Jia; Leung, Dexter Y. L.] Hosp Author, Hong Kong Eye Hosp, Hong Kong, Hong Kong, Peoples R China. [Chen, Li Jia; Fan, Alex H.] Hosp Author, Prince Wales Hosp, Hong Kong, Hong Kong, Peoples R China. [Zhang, Mingzhi] Chinese Univ Hong Kong, Shantou, Peoples R China. [Zhang, Mingzhi] Shantou Univ, Joint Shantou Int Eye Ctr, Shantou, Peoples R China. [Fan, Bao Jian] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA. [Wang, Ningli] Capital Med Univ, Beijing Tongren Eye Ctr, Beijing Tongren Hosp, Beijing, Peoples R China. [Chen, Li Jia; Tam, Pancy O. S.; Leung, Dexter Y. L.; Fan, Alex H.; Tham, Clement C. Y.; Chiang, Sylvia W. Y.; Pang, Chi Pui] Chinese Univ Hong Kong, Dept Ophthalmol & Visual Sci, Hong Kong, Peoples R China. RP Pang, CP (reprint author), Chinese Univ Hong Kong, Hong Kong Eye Hosp, Dept Ophthalmol & Visual Sci, 147K Argyle St, Kowloon, Hong Kong, Peoples R China. EM cppang@cuhk.edu.hk RI Chen, Li Jia/I-5078-2014; Pang, Chi/I-5388-2014; OI Chen, Li Jia/0000-0003-3500-5840; Leung, Dexter/0000-0002-9830-3143; Fan, Baojian/0000-0002-6851-2737 FU Endowment Fund for Lim Por-Yen Eye Genetics Research Centre, Hong Kong; General Research Fund, Hong Kong [2140597] FX We express our greatest gratitude to all participants in this study. The work in this paper was supported in part by the Endowment Fund for Lim Por-Yen Eye Genetics Research Centre, Hong Kong, and research grant 2140597 from the General Research Fund, Hong Kong. NR 38 TC 12 Z9 12 U1 0 U2 2 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD JUN 19 PY 2012 VL 18 IS 167-68 BP 1629 EP 1639 PG 11 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 962OT UT WOS:000305555300002 PM 22773901 ER PT J AU Zhu, TF Adamala, K Zhang, N Szostak, JW AF Zhu, Ting F. Adamala, Katarzyna Zhang, Na Szostak, Jack W. TI Photochemically driven redox chemistry induces protocell membrane pearling and division SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE origin of life; vesicles ID TRANSFER DIFFERENCE NMR; VESICLES; MODELS; INSTABILITY; COMPETITION; CURVATURE; TENSION; LIFE AB Prior to the evolution of complex biochemical machinery, the growth and division of simple primitive cells (protocells) must have been driven by environmental factors. We have previously demonstrated two pathways for fatty acid vesicle growth in which initially spherical vesicles grow into long filamentous vesicles; division is then mediated by fluid shear forces. Here we describe a different pathway for division that is independent of external mechanical forces. We show that the illumination of filamentous fatty acid vesicles containing either a fluorescent dye in the encapsulated aqueous phase, or hydroxypyrene in the membrane, rapidly induces pearling and subsequent division in the presence of thiols. The mechanism of this photochemically driven pathway most likely involves the generation of reactive oxygen species, which oxidize thiols to disulfide-containing compounds that associate with fatty acid membranes, inducing a change in surface tension and causing pearling and subsequent division. This vesicle division pathway provides an alternative route for the emergence of early self-replicating cell-like structures, particularly in thiol-rich surface environments where UV-absorbing polycyclic aromatic hydrocarbons (PAHs) could have facilitated protocell division. The subsequent evolution of cellular metabolic processes controlling the thiol: disulfide redox state would have enabled autonomous cellular control of the timing of cell division, a major step in the origin of cellular life. C1 [Szostak, Jack W.] Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Howard Hughes Med Inst, Boston, MA 02114 USA. RP Szostak, JW (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, Boston, MA 02114 USA. EM szostak@molbio.mgh.harvard.edu OI Adamala, Kate/0000-0003-1066-7207 FU NASA Exobiology Program [EXB02-0031-0018] FX We thank R. Bruckner, I. Budin, I. Chen, C. Hentrich, and S. Mansy for discussions and comments on the manuscript. J.W.S. is an investigator of the Howard Hughes Medical Institute. This work was supported in part by grant EXB02-0031-0018 from the NASA Exobiology Program to J.W.S. NR 24 TC 35 Z9 37 U1 6 U2 56 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 19 PY 2012 VL 109 IS 25 BP 9828 EP 9832 DI 10.1073/pnas.1203212109 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 969NC UT WOS:000306061400040 PM 22665773 ER PT J AU Cypess, AM Chen, YC Sze, C Wang, K English, J Chan, O Holman, AR Tal, I Palmer, MR Kolodny, GM Kahn, CR AF Cypess, Aaron M. Chen, Yih-Chieh Sze, Cathy Wang, Ke English, Jeffrey Chan, Onyee Holman, Ashley R. Tal, Ilan Palmer, Matthew R. Kolodny, Gerald M. Kahn, C. Ronald TI Cold but not sympathomimetics activates human brown adipose tissue in vivo SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE metabolism; thermogenesis; respiratory quotient; norepinephrine; white adipose tissue ID ENERGY-EXPENDITURE; BETA(3)-ADRENOCEPTOR AGONIST; NONSHIVERING THERMOGENESIS; SKELETAL-MUSCLE; HEALTHY-ADULTS; EPHEDRINE; EXPOSURE; NOREPINEPHRINE; PROPRANOLOL; METABOLISM AB As potential activators of brown adipose tissue (BAT), mild cold exposure and sympathomimetic drugs have been considered as treatments for obesity and diabetes, but whether they activate the same pathways is unknown. In 10 healthy human volunteers, we found that the sympathomimetic ephedrine raised blood pressure, heart rate, and energy expenditure, and increased multiple circulating metabolites, including glucose, insulin, and thyroid hormones. Cold exposure also increased blood pressure and energy expenditure, but decreased heart rate and had little effect on metabolites. Importantly, cold increased BAT activity as measured by F-18-fluorodeoxyglucose PET-CT in every volunteer, whereas ephedrine failed to stimulate BAT. Thus, at doses leading to broad activation of the sympathetic nervous system, ephedrine does not stimulate BAT in humans. In contrast, mild cold exposure stimulates BAT energy expenditure with fewer other systemic effects, suggesting that cold activates specific sympathetic pathways. Agents that mimic cold activation of BAT could provide a promising approach to treating obesity while minimizing systemic effects. C1 [Cypess, Aaron M.; Sze, Cathy; Chan, Onyee; Holman, Ashley R.; Kahn, C. Ronald] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Integrat Physiol & Metab,Res Div, Boston, MA 02215 USA. [Chen, Yih-Chieh; Wang, Ke; English, Jeffrey; Tal, Ilan; Palmer, Matthew R.; Kolodny, Gerald M.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Radiol,Div Nucl Med, Boston, MA 02215 USA. RP Kahn, CR (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Integrat Physiol & Metab,Res Div, Boston, MA 02215 USA. EM c.ronald.kahn@joslin.harvard.edu FU National Institutes of Health (NIH) [DK087317, DK055545, DK033201, DK081604, DK046200, RR025757]; National Institute of Diabetes and Digestive and Kidney Diseases [P30 DK036836]; Clinical Translational Science Award [UL1RR025758]; BIDMC from the National Center for Research Resources; Harvard Catalyst/The Harvard Clinical and Translational Science Center (NIH [UL1 RR 025758]; Harvard University; Eli Lilly Foundation FX We thank the Beth Israel Deaconess Medical Center (BIDMC) Clinical Research Center nursing team, Bionutrition Core, research pharmacy, and nuclear medicine technologists for the excellent support they provided; Y. Iris Chen, Ken Kwong, Anna-Liisa Brownell, Cecile Vernochet, Christina Sass, and Ross Smith for their input in preparing this manuscript; Murray Mittleman, Hillary Keenan, and Elissa Wilker for their biostatistical advice; and our volunteers for their commitment to the studies. This work was supported by National Institutes of Health (NIH) Grants DK087317, DK055545, and DK033201 (to C. R. K.); DK081604 and DK046200 (to A. M. C.); RR025757; Grant P30 DK036836 from the National Institute of Diabetes and Digestive and Kidney Diseases; Clinical Translational Science Award UL1RR025758 to Harvard University and the BIDMC from the National Center for Research Resources, Harvard Catalyst/The Harvard Clinical and Translational Science Center (NIH Award UL1 RR 025758 and financial contributions from Harvard University and its affiliated academic health care centers); and the Eli Lilly Foundation. NR 35 TC 110 Z9 110 U1 2 U2 18 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 19 PY 2012 VL 109 IS 25 BP 10001 EP 10005 DI 10.1073/pnas.1207911109 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 969NC UT WOS:000306061400069 PM 22665804 ER PT J AU Ndung'u, T Weiss, RA AF Ndung'u, Thumbi Weiss, Robin A. TI On HIV diversity SO AIDS LA English DT Review DE antigenic diversity; evolution; genetic diversity; HIV ID HUMAN-IMMUNODEFICIENCY-VIRUS; DISEASE PROGRESSION; SUBTYPE-C; ANTIRETROVIRAL THERAPY; INFECTION; NEUTRALIZATION; TRANSMISSION; PATHOGENESIS; BROAD; AIDS AB HIV type 1 (HIV-1) displays a greater degree of genetic and antigenic variability than any other virus studied. This diversity reflects a high mutation rate during viral replication with a large turnover of virus, and a high tolerance of variation while maintaining reproductive capacity. Generation of diversity is a common property of lentiviruses such as HIV. Differences in virulence and in transmissibility are seen between different HIV-1 strains which may have clinical implications. The great degree of HIV diversity presents challenges to maintaining sensitivity to antiretroviral therapy and to the development of preventive strategies such as microbicides and vaccines. (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins C1 [Weiss, Robin A.] UCL, Div Infect & Immun, Wohl Vir Ctr, London WC1E 6BT, England. [Ndung'u, Thumbi] Univ KwaZulu Natal, Nelson R Mandela Sch Med, Doris Duke Med Res Inst, HIV Pathogenesis Programme, Durban, South Africa. [Ndung'u, Thumbi] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Boston, MA USA. RP Weiss, RA (reprint author), UCL, Div Infect & Immun, Wohl Vir Ctr, Cruciform Bldg,Gower St, London WC1E 6BT, England. EM r.weiss@ucl.ac.uk OI Ndung'u, Thumbi/0000-0003-2962-3992 FU Medical Research Council [G0801176] NR 63 TC 24 Z9 24 U1 0 U2 18 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD JUN 19 PY 2012 VL 26 IS 10 BP 1255 EP 1260 DI 10.1097/QAD.0b013e32835461b5 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 961NF UT WOS:000305471000014 PM 22706010 ER PT J AU Adachi, MS Taylor, AB Hart, PJ Fitzpatrick, PF AF Adachi, Mariya S. Taylor, Alexander B. Hart, P. John Fitzpatrick, Paul F. TI Mechanistic and Structural Analyses of the Role of His67 in the Yeast Polyarnine Oxidase Fmsl SO BIOCHEMISTRY LA English DT Article ID MONOMERIC SARCOSINE OXIDASE; AMINO-ACID OXIDASE; N-METHYLTRYPTOPHAN OXIDASE; OXYGEN ACTIVATION SITE; POLYAMINE OXIDASE; SUBSTRATE-SPECIFICITY; CRYSTAL-STRUCTURE; TRYPTOPHAN 2-MONOOXYGENASE; HETEROLOGOUS EXPRESSION; KINETIC MECHANISM AB The flavoprotein oxidase Fms1 from Saccharomyces cerevisiae catalyzes the oxidation of spermine and N-1-acetylspermine to spermidine and 3-aminopropanal or N-acetyl-3-aminopropanal. Within the active site of Fms1, His67 is positioned to form hydrogen bonds with the polyamine substrate. This residue is also conserved in other polyamine oxidases. The catalytic properties of H67Q, H67N, and H67A Fms1 have been characterized to evaluate the role of this residue in catalysis. With both spermine and N-1-acetylspermine as the amine substrate, the value of the first-order rate constant for flavin reduction decreases 2-3 orders of magnitude, with the H67Q mutation having the smallest effect and H67N the largest. The k(cat)/K-O2 value changes very little upon mutation with N-1-acetylspermine as the amine substrate and decreases only an order of magnitude with spermine. The k(cat)/K-M-pH profiles with N-1-acetylspermine are bell-shaped for all the mutants; the similarity to the profile of the wild-type enzyme rules out His67 as being responsible for either of the pK(a) values. The pH profiles for the rate constant for flavin reduction for all the mutant enzymes similarly show the same pK(a) as wild-type Fms1, about similar to 7.4; this pK(a) is assigned to the substrate N4. The k(cat)/K-O2-pH profiles for wild-type Fms1 and the H67A enzyme both show a pK(a) of about similar to 6.9; this suggests His67 is not responsible for this pH behavior. With the H67Q, H67N, and H67A enzymes the k(cat) value decreases when a single residue is protonated, as is the case with the wild-type enzyme. The structure of H67Q Fms1 has been determined at a resolution of 2.4 angstrom. The structure shows that the mutation disrupts a hydrogen bond network in the active site, suggesting that His67 is important both for direct interactions with the substrate and to maintain the overall active site structure. C1 [Adachi, Mariya S.; Taylor, Alexander B.; Hart, P. John; Fitzpatrick, Paul F.] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. [Hart, P. John] S Texas Vet Hlth Care Syst, Dept Vet Affairs, Audie Murphy Div, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA. RP Fitzpatrick, PF (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. EM fitzpatrick@biochem.uthscsa.edu FU NIH [GM058698]; The Welch Foundation [AQ-1399, AQ1245]; National Center for Research Resources [5P41RR015301-10]; National Institute of General Medical Sciences from the National Institutes of Health [8 P41 GM103403-10]; U.S. DOE [DE-AC02-06CH11357]; Department of Veterans Affairs; Veterans Health Administration; Office of Research Development; Biomedical Laboratory Research and Development; UTHSCSA Executive Research Committee; Cancer Therapy Research Center FX This work was supported in part by the NIH, grant GM058698 (to P.F.F.), and The Welch Foundation, grants AQ-1399 (to P.J.H.) and AQ1245 (to P.F.F.). This work is based upon research conducted at the Advanced Photon Source on the Northeastern Collaborative Access Team beamlines, which are supported by grants from the National Center for Research Resources (5P41RR015301-10) and the National Institute of General Medical Sciences (8 P41 GM103403-10) from the National Institutes of Health. Use of the Advanced Photon Source, an Office of Science User Facility operated for the U.S. Department of Energy (DOE) Office of Science by Argonne National Laboratory, was supported by the U.S. DOE under Contract DE-AC02-06CH11357.; This material is based upon work supported in part by the Department of Veterans Affairs, Veterans Health Administration, Office of Research Development, Biomedical Laboratory Research and Development. Support for the X-ray Crystallography Core Laboratory by the UTHSCSA Executive Research Committee and the Cancer Therapy Research Center is gratefully acknowledged. NR 44 TC 4 Z9 4 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 19 PY 2012 VL 51 IS 24 BP 4888 EP 4897 DI 10.1021/bi300517s PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 959NZ UT WOS:000305320800012 PM 22642831 ER PT J AU Shahian, DM Normand, SLT AF Shahian, David M. Normand, Sharon-Lise T. TI Autonomy, Beneficence, Justice, and the Limits of Provider Profiling SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material DE ethics; informed consent; mortality rate; outcomes; profiling ID HOSPITAL OUTCOMES; SURGERY; CARE; CONSEQUENCES; CHOICE C1 [Shahian, David M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Qual & Safety, Boston, MA 02114 USA. [Shahian, David M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Normand, Sharon-Lise T.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Harvard Med Sch,Dept Hlth Care Policy, Boston, MA 02114 USA. RP Shahian, DM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Qual & Safety, Bulfinch 270,55 Fruit St, Boston, MA 02114 USA. EM dshahian@partners.org NR 19 TC 2 Z9 2 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUN 19 PY 2012 VL 59 IS 25 BP 2383 EP 2386 DI 10.1016/j.jacc.2011.12.050 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 958YK UT WOS:000305276700012 PM 22698493 ER PT J AU Dzamko, N Inesta-Vaquera, F Zhang, JZ Xie, CS Cai, HB Arthur, S Tan, L Choi, H Gray, N Cohen, P Pedrioli, P Clark, K Alessi, DR AF Dzamko, Nicolas Inesta-Vaquera, Francisco Zhang, Jiazhen Xie, Chengsong Cai, Huaibin Arthur, Simon Tan, Li Choi, Hwanguen Gray, Nathanael Cohen, Philip Pedrioli, Patrick Clark, Kristopher Alessi, Dario R. TI The IkappaB Kinase Family Phosphorylates the Parkinson's Disease Kinase LRRK2 at Ser935 and Ser910 during Toll-Like Receptor Signaling SO PLOS ONE LA English DT Article ID INNATE IMMUNE-RESPONSE; TUMOR-NECROSIS-FACTOR; CYTOPLASMIC LOCALIZATION; CROHNS-DISEASE; 14-3-3 BINDING; CROSS-TALK; MUTATIONS; AUTOPHAGY; ALPHA; INFLAMMATION AB Mutations in leucine-rich repeat kinase 2 (LRRK2) are strongly associated with late-onset autosomal dominant Parkinson's disease. LRRK2 is highly expressed in immune cells and recent work points towards a link between LRRK2 and innate immunity. Here we demonstrate that stimulation of the Toll-Like Receptor (TLR) pathway by MyD88-dependent agonists in bone marrow-derived macrophages (BMDMs) or RAW264.7 macrophages induces marked phosphorylation of LRRK2 at Ser910 and Ser935, the phosphorylation sites that regulate the binding of 14-3-3 to LRRK2. Phosphorylation of these residues is prevented by knock-out of MyD88 in BMDMs, but not the alternative TLR adaptor protein TRIF. Utilising both pharmacological inhibitors, including a new TAK1 inhibitor, NG25, and genetic models, we provide evidence that both the canonical (IKK alpha and IKK beta) and IKK-related (IKK epsilon and TBK1) kinases mediate TLR agonist induced phosphorylation of LRRK2 in vivo. Moreover, all four IKK members directly phosphorylate LRRK2 at Ser910 and Ser935 in vitro. Consistent with previous work describing Ser910 and Ser935 as pharmacodynamic biomarkers of LRRK2 activity, we find that the TLR independent basal phosphorylation of LRRK2 at Ser910 and Ser935 is abolished following treatment of macrophages with LRRK2 kinase inhibitors. However, the increased phosphorylation of Ser910 and Ser935 induced by activation of the MyD88 pathway is insensitive to LRRK2 kinase inhibitors. Finally, employing LRRK2-deficient BMDMs, we present data indicating that LRRK2 does not play a major role in regulating the secretion of inflammatory cytokines induced by activation of the MyD88 pathway. Our findings provide the first direct link between LRRK2 and the IKKs that mediate many immune responses. Further work is required to uncover the physiological roles that phosphorylation of LRRK2 by IKKs play in controlling macrophage biology and to determine how phosphorylation of LRRK2 by IKKs impacts upon the use of Ser910 and Ser935 as pharmacodynamic biomarkers. C1 [Dzamko, Nicolas; Inesta-Vaquera, Francisco; Zhang, Jiazhen; Arthur, Simon; Cohen, Philip; Clark, Kristopher; Alessi, Dario R.] Univ Dundee, Coll Life Sci, MRC Prot Phosphorylat Unit, Dundee, Scotland. [Xie, Chengsong; Cai, Huaibin] NIMH, Transgen Sect, Neurogenet Lab, Natl Inst Aging,Natl Inst Hlth, Bethesda, MD 20892 USA. [Tan, Li; Choi, Hwanguen; Gray, Nathanael] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Tan, Li; Choi, Hwanguen; Gray, Nathanael] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Pedrioli, Patrick] Univ Dundee, Coll Life Sci, Scottish Inst Life Sci, Dundee, Scotland. RP Dzamko, N (reprint author), Univ Dundee, Coll Life Sci, MRC Prot Phosphorylat Unit, Dow St, Dundee, Scotland. EM n.dzamko@neura.edu.au; d.r.alessi@dundee.ac.uk RI Arthur, J. Simon/B-8058-2010; Cai, Huaibin/H-3359-2013; OI Arthur, J. Simon/0000-0002-8135-1958; Cai, Huaibin/0000-0002-8596-6108; Alessi, Dario/0000-0002-2140-9185; Dzamko, Nicolas/0000-0002-9121-0294 FU Medical Research Council; Wellcome Trust UK Parkinsona(TM)s Disease Consortium; Michael J Fox Foundation; National Institute on Aging; NIH [1ZIAAG000944-04]; AstraZeneca; Boehringer-Ingelheim; GlaxoSmithKline; Janssen Pharmaceutica; Merck KgaA; Pfizer FX This work was supported by the Medical Research Council (DRA, PC and SA), Wellcome Trust UK Parkinsona(sic)(TM) s Disease Consortium (DRA), Michael J Fox Foundation (DRA), the Intramural Research Program of National Institute on Aging, NIH (1ZIAAG000944-04 to HC). We also thank the pharmaceutical companies supporting the Division of Signal Transduction Therapy Unit (AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Janssen Pharmaceutica; Merck KgaA and Pfizer) for financial support. I can also confirm that the funders listed above had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 63 TC 59 Z9 59 U1 0 U2 16 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 18 PY 2012 VL 7 IS 6 AR e39132 DI 10.1371/journal.pone.0039132 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 962XO UT WOS:000305583300099 PM 22723946 ER PT J AU Koo, JE Hong, HJ Dearth, A Kobayashi, KS Koh, YS AF Koo, Jung-Eun Hong, Hye-Jin Dearth, Andrea Kobayashi, Koichi S. Koh, Young-Sang TI Intracellular Invasion of Orientia tsutsugamushi Activates Inflammasome in ASC-Dependent Manner SO PLOS ONE LA English DT Article ID INNATE IMMUNE RECOGNITION; POLYMERASE-CHAIN-REACTION; SCRUB TYPHUS; CELL-DEATH; RICKETTSIA-TSUTSUGAMUSHI; AIM2 INFLAMMASOME; FRANCISELLA-TULARENSIS; HOST-DEFENSE; CASPASE-1; RECEPTORS AB Orientia tsutsugamushi, a causative agent of scrub typhus, is an obligate intracellular bacterium, which escapes from the endo/phagosome and replicates in the host cytoplasm. O. tsutsugamushi infection induces production of pro-inflammatory mediators including interleukin-1 beta (IL-1 beta), which is secreted mainly from macrophages upon cytosolic stimuli by activating cysteine protease caspase-1 within a complex called the inflammasome, and is a key player in initiating and maintaining the inflammatory response. However, the mechanism for IL-1 beta maturation upon O. tsutsugamushi infection has not been identified. In this study, we show that IL-1 receptor signaling is required for efficient host protection from O. tsutsugamushi infection. Live Orientia, but not heat-or UV-inactivated Orientia, activates the inflammasome through active bacterial uptake and endo/phagosomal maturation. Furthermore, Orientia-stimulated secretion of IL-1 beta and activation of caspase-1 are ASC- and caspase-1- dependent since IL-1 beta production was impaired in Asc- and caspase-1-deficient macrophages but not in Nlrp3-, Nlrc4- and Aim2-deficient macrophages. Therefore, live O. tsutsugamushi triggers ASC inflammasome activation leading to IL-1 beta production, which is a critical innate immune response for effective host defense. C1 [Koo, Jung-Eun; Hong, Hye-Jin; Koh, Young-Sang] Jeju Natl Univ, Sch Med, Dept Microbiol & Immunol, Brain Korea Program 21, Cheju, Jeju Do, South Korea. [Koo, Jung-Eun; Hong, Hye-Jin; Koh, Young-Sang] Jeju Natl Univ, Inst Med Sci, Cheju, Jeju Do, South Korea. [Dearth, Andrea; Kobayashi, Koichi S.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Kobayashi, Koichi S.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA. RP Koo, JE (reprint author), Jeju Natl Univ, Sch Med, Dept Microbiol & Immunol, Brain Korea Program 21, Cheju, Jeju Do, South Korea. EM Koichi_Kobayashi@dfci.harvard.edu; yskoh7@jejunu.ac.kr FU National Research Foundation of Korea (NRF); Ministry of Education, Science and Technology [2010-0023645]; NIH [R01DK074738]; Cancer Research Institute; Claudia Adams Barr Award FX This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2010-0023645) to YSK and a grant from the NIH (R01DK074738) to KSK. KSK is a recipient of the Investigator Award from the Cancer Research Institute and the Claudia Adams Barr Award. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 53 TC 17 Z9 18 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 18 PY 2012 VL 7 IS 6 AR e39042 DI 10.1371/journal.pone.0039042 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 962XO UT WOS:000305583300082 PM 22723924 ER PT J AU Lee, J van Hummelen, P Go, C Palescandolo, E Jang, J Park, HY Kang, SY Park, JO Kang, WK MacConaill, L Kim, KM AF Lee, Jeeyun van Hummelen, Paul Go, Christina Palescandolo, Emanuele Jang, Jiryeon Park, Ha Young Kang, So Young Park, Joon Oh Kang, Won Ki MacConaill, Laura Kim, Kyoung-Mee TI High-Throughput Mutation Profiling Identifies Frequent Somatic Mutations in Advanced Gastric Adenocarcinoma SO PLOS ONE LA English DT Article ID CANCER; GENE; PIK3CA; P53 AB Background: Gastric cancer is one of the leading cancer types in incidence and mortality, especially in Asia. In order to improve survival, identification of a catalogue of molecular alterations underlying gastric cancer is a critical step for developing and designing genome-directed therapies. Methodology/Principal Findings: The Center for Cancer Genome Discovery (CCGD) at the Dana-Farber Cancer Institute (DFCI) has adapted a high-throughput genotyping platform to determine the mutation status of a large panel of known cancer genes. The mutation detection platform, termed OncoMap v4, interrogates 474 "hotspot'' mutations in 41 genes that are relevant for cancer. We performed OncoMap v4 in formalin-fixed paraffin-embedded (FFPE) tissue specimens from 237 gastric adenocarcinomas. Using OncoMap v4, we found that 34 (14.4%) of 237 gastric cancer patients harbored mutations. Among mutations we screened, PIK3CA mutations were the most frequent (5.1%) followed by p53 (4.6%), APC (2.5%), STK11 (2.1%), CTNNB1 (1.7%), and CDKN2A (0.8%). Six samples harbored concomitant somatic mutations. Mutations of CTNNB1 were significantly more frequent in EBV-associated gastric carcinoma (P=0.046). Our study led to the detection of potentially druggable mutations in gastric cancer which may guide novel therapies in subsets of gastric cancer patients. Conclusions/Significance: Using high throughput mutation screening platform, we identified that PIK3CA mutations were the most frequently observed target for gastric adenocarcinoma. C1 [Lee, Jeeyun; Jang, Jiryeon; Park, Joon Oh; Kang, Won Ki] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Div Hematol Oncol,Dept Med, Seoul, South Korea. [van Hummelen, Paul; Go, Christina; Palescandolo, Emanuele; MacConaill, Laura] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [van Hummelen, Paul; Go, Christina; Palescandolo, Emanuele; MacConaill, Laura] Harvard Univ, Sch Med, Boston, MA USA. [Park, Ha Young; Kang, So Young; Kim, Kyoung-Mee] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Pathol, Seoul, South Korea. RP Lee, J (reprint author), Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Div Hematol Oncol,Dept Med, Seoul, South Korea. EM kkmkys@skku.edu RI Lee, Jee Yun/C-9646-2011; Lee, Jeeyun/I-7171-2015 FU Korea Healthcare Technology RD Project; Ministry for Health & Welfare Affairs, Republic of Korea [A092255, A101130]; Samsung Biomedical Research Institute [SBRI-CB11031, SBRICB02202]; Sungkyunkwan University [S-2009-1181-000] FX This paper was supported by the grant from the Korea Healthcare Technology R&D Project, Ministry for Health & Welfare Affairs, Republic of Korea (A092255 & A101130), Samsung Biomedical Research Institute grant (# SBRI-CB11031, SBRICB02202) & Sungkyunkwan University grant (# S-2009-1181-000). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 19 TC 40 Z9 43 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 18 PY 2012 VL 7 IS 6 AR e38892 DI 10.1371/journal.pone.0038892 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 962XO UT WOS:000305583300065 PM 22723903 ER PT J AU Li, YH Wang, XX Pan, YF Lee, DH Chowdhury, D Kimmelman, AC AF Li, Ying-Hua Wang, Xiaoxu Pan, Yunfeng Lee, Dong-Hyun Chowdhury, Dipanjan Kimmelman, Alec C. TI Inhibition of Non-Homologous End Joining Repair Impairs Pancreatic Cancer Growth and Enhances Radiation Response SO PLOS ONE LA English DT Article ID DNA-DAMAGE; UP-REGULATION; BREAK REPAIR; PROTEIN; RECRUITMENT; CHECKPOINT; HALLMARKS; PATHWAY; PKCS AB Pancreatic ductal adenocarcinoma (PDAC) is amongst the deadliest of human cancers, due to its late diagnosis as well as its intense resistance to currently available therapeutics. To identify mechanisms as to why PDAC are refractory to DNA damaging cytoxic chemotherapy and radiation, we performed a global interrogation of the DNA damage response of PDAC. We find that PDAC cells generally harbor high levels of spontaneous DNA damage. Inhibition of Non-Homologous End Joining (NHEJ) repair either pharmacologically or by RNAi resulted in a further accumulation of DNA damage, inhibition of growth, and ultimately apoptosis even in the absence of exogenous DNA damaging agents. In response to radiation, PDAC cells rely on the NHEJ pathway to rapidly repair DNA double strand breaks. Mechanistically, when NHEJ is inhibited there is a compensatory increase in Homologous Recombination (HR). Despite this upregulation of HR, DNA damage persists and cells are significantly more sensitive to radiation. Together, these findings support the incorporation of NHEJ inhibition into PDAC therapeutic approaches, either alone, or in combination with DNA damaging therapies such as radiation. C1 [Li, Ying-Hua; Wang, Xiaoxu; Pan, Yunfeng; Lee, Dong-Hyun; Chowdhury, Dipanjan; Kimmelman, Alec C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Genom Stabil & DNA Repair,Dept Radiat Oncol, Boston, MA 02115 USA. RP Li, YH (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Genom Stabil & DNA Repair,Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. EM Alec_Kimmelman@DFCI.HARVARD.EDU FU National Cancer Institute Grant [R01CA157490]; Kimmel Scholar Award; AACR-PanCAN Career Development Award; Karyopharm therapeutics FX ACK is supported by the National Cancer Institute Grant R01CA157490, Kimmel Scholar Award, and AACR-PanCAN Career Development Award. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding was received for this study.; ACK is a Consultant for Forma Therapeutics and for Dainippon Pharma. He has received research funding from Karyopharm therapeutics for an unrelated project and has received a speaking honorarium from Pfizer. There are no patents, products in development or marketed products to declare. This does not alter our adherence to all the PLoS ONE policies on sharing data and materials, as detailed online in the guide for authors. NR 35 TC 20 Z9 20 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 18 PY 2012 VL 7 IS 6 AR e39588 DI 10.1371/journal.pone.0039588 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 962XO UT WOS:000305583300144 PM 22724027 ER EF